PYRAZOLONES, PYRAZOLIDONES, AND DERIVATIVES Richard H. Wiley Uw'ver5i~of Louimille, Louisville, Kentidzy
Paul Wiley Upjobn Laboratories, Kalamqoo, Micbigan
1964
INTERSCIENCE PUBLISHERS a division of
J O H N WILEY & SONS
N E W YORK
LONDON
SYDNEY
PYRAZOLONES, PYRAZOLIDONES, A N D DERIVATIVES
This is the tiwn?ietll volume in the series
T H E C H E M I S T R Y OF H E T E R O C Y C L I C C O M P O U N D S
T H E C H E M I S T R Y OF H E T E R O C Y C L I C C O M P O U N D S A S E R I E S OF M O N O G R A P H S
A R N 0 LD W EI S S B E R GE R, Consdting Editor
PYRAZOLONES, PYRAZOLIDONES, AND DERIVATIVES Richard H. Wiley Uw'ver5i~of Louimille, Louisville, Kentidzy
Paul Wiley Upjobn Laboratories, Kalamqoo, Micbigan
1964
INTERSCIENCE PUBLISHERS a division of
J O H N WILEY & SONS
N E W YORK
LONDON
SYDNEY
First published by John Wiley t Sons, 1964
All Itight,s Reserved Library of Congress Cat,alog Card Number 63-20237
The Chemistry of Heterocyclic Compounds The Chemistry of heterocyclic compounda is one of the most complex branches of organic chemistry. It is equally interesting for its theoretical implications, for the diversity of its synthetic procedures, and for the physiological and industrial significance of heterocyclic compounds. A field of such importance and intrinsic difficulty should be made as readily accessible as possible, and the lack of a modern detailed and comprehensivepresentation of heterocyclic chemistry is therefore keenly felt. It is the intention of the present aeries to fill this gap by expert presentations of the various branches of heterocyclic chemistry. The subdivisions have been designed to cover the field in its entirety by monographs which reflect the importance and the interrelations of the various compounds and accommodate the specific interests of the authors.
ARNOLD WEISSBERGER Research Laboratories Eastman Rodak Company Rochester, New York
V
Preface Perhaps one of the most unusual facets of pyrazole chemistry is the extensive literatim on the pyrazolin-5-ones. Although this will probably come as no surprise to those who have had any interest in this class of compounds, the basic chemical reasons underlying this extensive literature, and the man-hours of chemical research which have gone into producing it,, deserve careful consideration. There are very real practical and theoretical bases for the situation. Historically, dyes and pharmaceuticals derived from pyrazolin-5-ones were among the first successful commercial synthetic organic chemicals in which interest has continued actively until thc present. Ludwig Knorr’s discovery in 1883 of antipyrine (%,3-dimetliyl-l-phenyl-3-pyrazolin-5-one) and Ziegler’s discovery in 1884 of the yellow dyestuff tsrtrazine: 4-(4sulfophenylazo)-l-(4-sulfophenyl)-5-oxo-2-p~ra~olin-3-car~ox~lic acid gave useful compounds before their structures were known. The value of these materials was immediately recognized and both are still in use. Much of the voluminous literature has resulted from studies directed toward modification of t.hese structures t o enhance thcir useful Characteristics. A group of widely used pharmaceuticals including aminopyrine (4-dimethylamino-2,3-dimcthyll-phenyl-3-pyrazolin-5-onc); dipyrone (2,3-dimethyl-l-pheny1-5-0~0-2-pyrozolin-4-methylaminomethanesdfonic acid sodium salt); and sulfamipyrine (a dipyrone analog) were developed. This research has recently culminated in the discovery of the useful anti-inflammatory properties of I n spite of the phenylbutazone (4-butyl-l,2-diphenyl-3,5-pyrazolidinedione). problems encountered in the undesirable side-reactions, principally agranulocytosiu, produced by these drugs, interest in them has never abated and one feels confident in predicting the discovery of additional useful and improved drugs in this structural classification. The development of new and improved dyes based on pyrazolinone structures has likewise led t o modern developments of no inconsidcrable magnitude. The use of tartrazine as an approved color for foodstuffs is of significance. The development of pyrazolinone dyes for use as magenta couplers and sensitizers in color photography and in metal chelate dye structures has established a renewed, modern interest in these dyes. The chclating characteristics, which will be of continuing toheoreticalstructurc interest in coordination chemistry, have been used in developing picrolonates (salts of 3-methyl-4-nitro-l-~-nitrophengl-~-pyrazolin-5-one) of possible utility in analytical procedures. vii
viii
Preface
The overwhelming deluge of chemical research arising from these utilitarian values has probably obscured the possibilities for fundamental research with these compounds. For the most part the structural problems that have been encountered are not complex. This is probably due in part to the fact that modern organic reaction techniques, such as radiationinduced transformations, modern structural concepts, such as molecular orbital theory and conformational analysis, and modern physical instrumentation, such as n.m.r., have not as yet been applied to the possibilities inherent in the chemistry of these compounds. It is also perhaps unusual that no pyrazolinone has been found to occur in nature. With the discovery in 1959 of /?-(l-pyrazolyl)alaninein the seeds of Gitrullus vulgaris, it would now appear probable that a pyrazolinone may likewise be found in some living tissue. This would certainly provide a new type of fundamental interest in the bio-organic chemistry of these materials. It might lead ultimately t o a clue as t o the mode of action of the pharmaceuticals-a problem about which there appears t o be little or no current available information. With the hope that the availability of the information on pyrazolinones presented in this volume might be of value in the furtherance of both fundamental and applied studies, the publishers and authors have considered i t best to present this material as promptly as possible in the present volume rather than as part of the pyrazole volume for which it was originally intended. The authors are appreciative of this cooperation on the part of the publishers and i t is hoped that users of this book will be aware that the immensity and sheer bulk of the literature has posed an unusual, but altogether interesting, challenge to all concerned in the preparation of this volume. The authors also wish especially to thank Miss Ollidene Weaver who did much of the typing of the manuscript in her spare time.
RICHARD H. WILEY
PAULWILEY
Contents
.
Part 1 Chemistry
.
Chapter I General 1 Introduction ............................................... 2 . Historical .................................................. 3. Structure ................................................. 4 . Synthesis ................................................. 5 Physical Properties ......................................... 6. Chemical Properties .........................................
. .
. . . . .
.
5 9 10 11
.
Chapter II Pyrazolin-5-ones 1 Introduction ............................................... 2 Unsubstituted Alkyl, Alicyclic, Aralkyl, Aryl and Heterocyclic Substituted Derivatives ..................................... A. 2-Pyrazolin-5-ones ....................................... (1) Syntheses .......................................... (2) Physical Properties ................................. (3) Chemical Properties ................................. (4) Hydroxyalkyl Types ................................. (5) AminoalkylTypes ................................... (6) Bis(2-pyrazolin-5-ones)............................... B 2-Pyrazolin.5.thiones ..................................... C 6-Imino-2-pyrazolines .................................... D 3-Pyrazolin-5-ones ....................................... (1) Syntheses .......................................... (2) Properties ......................................... (3) Bis(3-pyrazolin-5-ones)............................... E 3-Pyrazolin-5-thiones and -5-selenones . ..................... F 5-Imino-3-pyrazolines .................................... 3. Hydroxy and Mercapto Derivatives ........................... A . 2-Pyrazolin-5-ones ....................................... B 3-Pyrazolin-5-ones ....................................... 4 Amino, Imino, Hydrazino, Azo and Related Derivatives . . . . . . . . . A 2-Pyrazolin-5-ones ....................................... B 3-Pyrazolin-5-ones ....................................... 5. Halogen Substituted Derivatives ............................. A. 2-Pyrazolin-5-ones ....................................... B . 3-Pyrazolin-5-ones ....................................... 6 . Nitroso Substituted Derivatives .............................. A 2 -Pyrazolin-5-ones ....................................... B 3-Pyrazolin-5-ones ....................................... 1* ix
. .
3 4
. . .
. .
13
13 13 13 18
19 29 30
31 40 41 46 46
49 56
58 59 61 61 63 65 65
76 81 81 83 85 85
87
Contents
9
.
7 Nitro Substituted Derivatives ................................ A 2-Pyrazolin-5-ones ....................................... B 3-Pyrazolin-5-ones ....................................... 8 Aldehydes and Ketones ..................................... A . 2-Pyrazolin-5-ones ....................................... B 3-Pyrazolin-5-ones ....................................... 9 Carboxylic Acids and Derivatives ............................. A 2-Pyrazolin-5-ones ....................................... B 3-Pyrazolin-5-ones ....................................... 10 Sulfonic Acids and Derivatives ............................... A 2 -Pyrazolin-5-ones ....................................... B. 3-Pyrazolin-5-ones ....................................... 11 Functional Group Substituents on Nitrogen ................... A. 2-Pyrazolin-5-ones ....................................... B 3-Pyrazolin-5-ones ....................................... 12 Mercury Substituted Derivatives . . . . . . . . . . . . . . . . A 2-Pyrazolin-5-ones ....................................... B 3-Pyrazolin.5 -ones ....................................... 13 Metallic and Non-metallic Complexes .......................... A 2-Pyrazolin-5-ones ....................................... B 3-Pyrazolin-5-ones ....................................... 14. Miscellaneous Derivatives ....................................
.
. .
. . . . . . . . . . . . .
.
.
88 88
89 89 89 92 95 95 100
101 101 102 102 102 104
104 104 105 105 106 107 108
Chapter 111 2-Pyrazolin-4-ones ......................................
111
. Chapter V . 3-Pyrazolidinones ....................................... Chapter VZ. 3,4-Pyrazolidinediones ................................... Chapter MI. 3,5-Pyrazolidinediones 1. Introduction ............................................... 2 . Alkyl, Aralkyl, Heterocyclicalkyl and Aryl Substituted Derivatives 3. Hydroxy and Alkoxy Substituted Derivatives ................. 4. Amino and Azo Substituted Derivatives ....................... 5 . Halogen Substituted Derivatives ............................. 6 . Nitroso Substituted Derivatives .............................. 7 . C-Acyl Substituted Derivatives ............................... 8. N-Acyl Substituted Derivatives ............................... Chapter VIII. 5-Imino-3-pyrazolidinones 1. Introduction ............................................... 2 . Alkyl, Alicyclic, Aralkyl, Heterocyclicalkyl, Heterocyclic and Aryl
114
Chapter IV 2-Pyrazolin-4, 5-diones ...................................
Substituted Derivatives ..................................... 3. Functional Group Derivatives ................................
.
Chapter IX Miscellaneous 3,5-Pyrazolidinediones and Analogs
...........
115 120 123 124
128 128 129 129 129 130 131
132 137 139
Part 2 . Applications
. Chapter II. Color Photography......................................
Chapter I Medical .................................................
143 148
xi
Contents
.
................................. Chapter IV. Analytical Reagents ..................................... ChapterV.Miscellaneous ........................................... Chapter I11 Textile and Fabric Dyes
.
Appendix Systematic Tables of Pyrazolones and their Derivatives
.......
....................................................... ............................................................
152
155 157 161
References
483
Index
525
Systematic Tables of Pyrazolones and their Derivatives Physical Properties of Antipyrine Investigated . . . . . . . . . . 2-Pyrazolin.5-ones ................................... Section A Alkyl and Alicyclic Substituents ...................... Section B Monoaryl, Alkyl. and Alicyclic Substituents ............ Section C Aralkyl. Heterocyclicalkyl. Aryl. and Alkyl Substituents Section D Polyaryl Substituents ................................ Section E Heterocyclic. Alkyl. and Aryl Substituents ............. Section F a-Hydroxy- and a.Alkoxyalky1. Alkyl. Aralkyl. Aromatic. and Heterocyclic Substituents ........................ Section G. a-Amino- and a.Iminoalky1. Alkyl. and Aryl Substituents . TABLE 111 4.4'.Bis(2.pyrazolin. 5.ones) Linked by a Single Bond ..... TABLE I V 4.4'.Bis(2.pyrazolin. &ones) Linked by a Double Bond .... TABLE V 4.4'.Bis(2.pyrazolin. &ones) Linked by a Carbon Chain Section A. l.l'.Phenyl.3.3 '.methyl Substituents................... Section B Alkyl and Aryl Substituents. ......................... TABLE VI Miscellaneous 4.4 '.Bis( 2.pyrazolin.5.ones) ............... TABLE VII 4.4'.Bis(Z.pyrazolin. 5.ones) Linked by Chains Containing N a n d S ........................................... TABLE MII 3.3'.Bis(2.pyrazolin. 5.ones) ........................... TABLE IX l.l'.Bis(2.pyrazolin. &ones) ........................... TABLE 3 Furlones ........................................... TABLE XI 2 -Pyrszolin-5-thiones ................................ TABLE XII 5-Imino-2-pyrazolines ............................... TABLE XI11 N . N '.Big( 5-imino-2-pyrazolines)....................... TABLE XIV 3-Pyrazolin-5-ones................................... Section A. Alkyl and Alicyclic Substituents ...................... Section B Alkyl and Aryl Substituents .......................... Section C Alkyl. Aralkyl. Heterocyclicalkyl and Aryl Subatituents Section D . Alkyl. Aryl and Heterocyclic Substituents ............. Section E a.Hydroxy.. wdcyloxy.. and a.Alkylthioalky1. Alkyl and Aryl Substituents ................................... Section F a.Amino.. a.Imino.. a.Oximio.. a-Amido- and a-Hydrazinoalkyl. Alkyl and Aryl Substituents................. 4.4'.Bis(3.pyrazolin. 5.ones) Linked by a Single Bond . . . . . TABLE xv 4.4 '.Bis( 3-pyrazolin-5-ones)Linked by Carbon or HeteroTABLE XVI atoms ............................................. Miscellaneous Bis(3-pyrazolin-5-ones) and B i s ( 5 - i h o - 8 TABLE XVII pyrazolines) ........................................ xiii TABLE I
TABLE I1
. . . . . .
.
...
.
.
. . .
..
11 161 161 165 178 185 189
200 202 207 210 211 211 214 217 218 222 224 231 233 234 245 246 246 247 255 263 268 273 278 278 281
xiv
List of Tables 3-Pyrazolin-5-thiones and -5-selenones ................. 5-Imino-3-pyrazolines ............................... 2.Pyrazolin.5.ones . Hydroxy and Mercapto Derivatives . 3.Pyrazolin.B.ones . Alkoxy, Aryloxy, Acyloxy, and Alkylthio Substituents .................................... 2.Pyrazolin.5.ones . Amino, Imino, Hydrazino, Azo. and Related Derivatives ................................. 4-Arylazo-2-pyrazolin-5-ones .........................
TABLE XVIII TABLE XlX
.
TABLE XX TABLE XXI TABLE XXII TABLE XXIII
283 284 288 291 293 303
. . .
303 Section A Alkyl and Aralkyl Substituents ....................... Section B Alkyl, Aryl, and Heterocyclic Substituents ............. 307 Section C Arylazo Substituted with Functional Groups ........... 330 TABLE
xxw
I.Pyrazolin.5.ones . Imino, Amino. Amido. Azo. Aminoazo. 334 and Hydrszido Substituents ..........................
2.Pyrazok.5.ones . Halogen Substituted ................ TABLE XXVI 3.Pyrazolin.5.ones . Halogen and Halogen Combined with Carboxylic Acid and Derivatives ...................... Z.Pyrazolin.5.ones 4-Nitroso Derivatives ............... TABLE XXVII TABLE xxvm 3.Pyrazolin.5.ones Nitroso and Nitro Substituted Dcrivafives ............................................... TABLE XXIX 8.Pyrazolin.B.ones . 4-Nitro Derivatives ................. 2.Pyrazolin.5.ones . Aldehydes and Ketones ............. TABLE xxx TABLE XXXI 3.Pyrazolin.5.ones Acyl Substituents on Carbon . . . . . . . . TABLE XXXII 2-Pyrazolin-5-one-(3 or 4)-carboxylic Acids ............. TABLE xxxm 2.Pyrazolin.5.ones Carboxyl Derivatives Combined with Other Functional Substituents ........................ TABLE XXXIV 3.Pyrazolin.5.ones . Carboxylic Acids and Thiocarboxylic Acids and Derivatives ................................ TABLE w x v 2.Pyrazolin.B.ones . Sulfonic Acids ..................... TABLE x x x v ~ 3.Pyrazolin.6.ones Sdf'onic Acids ..................... TABLE X X X ~ I 2.Pyrazolin.B.ones Acyl and Carboxyl Derivatives and Sulfonyl Substituents on N-1 ......................... TABLE XXXVIII t.Pyrazolin.5.ones Acyl Substituents on Nitrogen ....... TABLE xxx~x Mercurated 3-Pyrazolin-&ones ........................ TABLE XL 2-Pyrazolin-4-ones and 4-Imino-2-pyrazohes ........... TABLE XLI 2.Pyrazolin.4,5.diones ................................ TABLE XLII 3-Pyrazolidinones ................................... Section A All Substituents Except Mercury ..................... Section B Mercury Substitucnts ................................ TABLE xsm 3.Iminopyrazolidines ................................. TDLE XLIV 4-Imino-3-pyrazolidinones ............................ TABLE x L V 4,47Bis(4.imino. 3.pyrazolidinones) ..................... TABLE XLVI Miscellaneous Bis(3,5.pyrazolidinediones), Bis(5-imino-3pyrazolidinones), and Bis(4-imino-3-pyrazolidinones) ..... TABLE
xxv
. . .
344 345 347 3g1
353 354 356 359
.
. .
.
. .
366 366 373 373 374 380 381 382 387 388 388 391 393 394 405 406
List of Tables
xv
3. 5.Pyrazolidinediones ............................... Section A Alkyl and Aralkyl Substituents ....................... Section B Alkyl. Aralkyl. Heterocyclicalkyl. Aryl and Acyl on Carbon Substituents ....................................... TABLE xLvm 3.5.Pyrazolidinediones . Acyl on Nitrogen and Oxygen. Nitrogen. and Halogen Substituents ................... TABLE XLIX 5-1mino.3.pyrazolidinones ............................ Section A . Blkyl. Alicyclic. Aralkyl. Heterocyclicalkyl. Heterocyclic. and Aryl Substituents ............................... Section B Acyl. Carboxyl. and Carboxyl Derivatives .............. Section C . Halogen. Nitroso. Amino. Imino. Azo. and Amido Substituents ........................................... 4.4 '.Bis( 5-imino-3-pyrazolidinones)..................... TABLE L 3-Methyl-1-phenyl-2-pyrazolin-5.ones Dyes . . . . . . . . . . . . TABLE LI 2.Pyrazolin.5.ones . Dyes ............................. TABLE LII 3.PyrazoUn.5.ones Dyes ............................. TABLE LIII 4.Arylazo.3.pyrazolin.5.ones . Dyes .................... TABLE LIV TABLE XLWI
. .
.
.
.
408 408 409 422 424 424 441 443 445 448 461 475 482
PART
I
CHEMISTRY
CHAPTER I
1. Introduction
Pyrazolinones and pyrazolidinones are 0x0 derivatives of pyrazolines and pyrazolidines, respectively, and are so named in Chemical Abstracts at present. However, the usual method of naming in the earlier literature is the pyrazolone-pyrazolidone system. Although a large number of tautomeric structures are possible for pyrazolinones, the usual assignment of ring structures is as shown in (I),(11)and (111). The ChemicaE Abstracts names for these are: (I)%pyrazolin-5-one, (11) HC
-
N2 113
~
N ‘’
46
HC-CH 3
=Or
HC-C=O 4
H./Jz
6/k=O
N ‘’
Na 113
I
J
H2
‘N’
H
H
H
(1)
(11)
(111)
3-pyrazolin-&one and (111) 2-pyrazolin-4-one. The names most frequently used in the literature for (I) and (11) are 5-pyrazolone and 3pyrazolone, respectively. In many cases there has been no certain identification of a compound as a 2-pyrazolin-5-oneor a 3-pyrazolin-5one. Because of this it will be assumed that all pyrazolin-5-ones having no substituent at N-2 are 2-pyrazolin-5-ones unless thfs has been definitely shown to be incorrect. The basic ring structures for pyrazolidinones are (IV) and (V) but no compounds of type (V) have been
4
Part 1. Chapter I
reported. Compounds of type (IV) are usually called pyrazolidones in the literature. The nomenclature used in this discussion will generally be in accordance with Chemical Abstracts, although some trivial names will be used since these are very common among pyrazolinones and are frequently well known. Examples of such names are antipyrine, pyrazole blue and aminopyrine. The numbering is as shown in formulas
WV). As an aid t o classification all compounds in which the tautomerism 1
>CH--C=X
>&XI3
I
can theoretically exist will be considered as > CH-C=X compounds (X=O, S, Se, Te, NH, N l t or NCOK). It is recognized that this will frequently be in disagreement with the actual structure which, if known, will be indicated in the discussion. This review will cover all pyrazolinoncs and pyrazolidinones reported up to and including the 1956 Chemical Abstracts and will cover the morc important publications which have appeared since. However, a number of publications dealing with applications, biological activities and analysis were omitted as they were regarded as being of insufficient significance for coverage. A rather extensive list of the compounds of these types which have been reported is included, although here again there are many omissions. A number of dyes were not included as their structure was uncertain. Some very complex dyes which would require considerable space for inclusion are omitted and a reference t o them is given. I n general, the large number of salts reported were not included and in particular all picrolonates were omitted. However, many of the complexes which pyrazolin-5-ones form so readily are discussed, although in some cases these may be of a salt-like nature. Compounds in which the 0x0 substituents are replaced by such groups as imino, thiono and seleno are considered in this review. The early literature, which is available from standard sources (Beilstein, Meyer-Jacobson) has not been exhaustively compiled. 2. Historical
The well-known German chemist, Ludwig Knorr, reported the preparation of the first pyrazolinone in 1883.*05This compound was 3-methyl-l-phenyl-2-pyrazolin-5-one prepared by the reaction of ethyl acetoacetate with phenylhydrazine. I n the first publication no structure was proposed, but in a, later publication806structure (VI)was suggested.
General
5
I n this same article synthesis of the widely used analgesic and antipyretic, antipyrine, was reported. This was one of the first synthetic
(W organic drugs. It was marketed and used before the correct structure for pyrazolinones was suggested by Knorreo9in 1887 and the name by Ruhemann .Iz3 O 3. Structure
A short time after the discovery of pyrazolin-&ones K n ~ r r ~ ~ ~ proposed the 2-pyrazolin-5-one and the 3-pyrazolin-&one structures on the basis of analyses, methods of preparation and reactions. These structures in the main approximate the correct ones and in some cases are correct. However, a large number of structures are theoretically possible for most pyrazolin-5-ones and in many cases no one structure can be said to fit completely. The tautomeric isomers (VI1)-(XIII) are possible for unsubstituted pyrazolin-5-ones: HC
-
g..
I1
N
H& -
HC =CH
l
c=o
I T " "
l
c=o
HN
N
'N/
H
H
(VW
(VIII)
HC -- CH
1
\N/ H
(XI
I
S O H
HC -
g..
il
N
S O H
\ / N
(XI)
C=O
\N/ (IX)
lii'"
H&-
N \N/
(XIS)
C-OH
HC-CH
I
I
HN
C-OH
\" (XIII)
I n addition a number of ionic tautomeric isomers can be envisaged which could make very important contributions to the over-all structure. These are (X1V)-(XVIII). Substitutions at N-1, N-2 and disubstitntion at G 4 substantially alter the possibilities for various tautomeric
6
Part 1. Chapter I
and resonance forms. Of the possible tautomeric forms shown, only (VII), (VIII) and (X) appear to exist to any extent although Valyashko
H
(XVXI)
(XVIII)
and B l i z n y k ~ v report ~ ~ l ~ diazo structures as present on the basis of rather complex ultraviolet absorption spectra. There is extensive evidence, both chemical and physical for these three structures. The presence of enolic forms is shown by the fact that one of the most common tests for 2-pyrazolin-5-ones is the use of ferric chloride to form a colored complex809~1551 and by the ready formation of 5-alkoxypyrazoles from p y r a z ~ l i n o n e s . ~ ~Dmowska ~~ and St. Weil 376 have claimed the isolation of the keto and enol forms of 4,4'-(3-nitrobenzyliand keto and enol forms dene)bis(3-methyl-l-phenyl-2-pyrazolin-5-one) of similar compounds have been i s 0 1 a t e d . l ~1135 ~ ~ . Existence of the form (VIII) is shown by alkylation of 3-phenyl-2-pyrazolin-5-one to give 2-methy1-3-phenyl-3-pyrazolin-5-0ne.~~ The structures of pyrazolin-5-ones have been very extensively studied using ultraviolet and infrared absorption spectra and such techniques have established unequivocally that (VII), (VIII) and (X) are the chief tautomeric contributors. Most of the workers in this field have emphasized the complexity of ultraviolet spectra due to the existence of tautomeric mixtures. GomezSa4has stated that no deduction can be drawn from the ultraviolet spectra of l-methyl-3-phenyl-2and its 4pyrazolin-ti-one, 2,3-dimethyl-l-phenyl-3-pyrazolin-5-one dimethylamino analog because of the tautomeric equilibria present. The existence of an equilibrium between 2-pyrazolin-5-one and 3pyrazolin-5-one structures has been proposed by Biquard and Grammaticakis 95 for 3-alkyl- 1-aryl- and 1-aryl-3,4-dialkyl-2-pyrazolin-5-ones on the basis of ultraviolet absorptions. Gagnon and
General
7
have been most active in this field and have drawn several conclusions from ultraviolet studies, some of which were in disagreement with infrared absorption spectra interpretations. These workers have found that pyrazolin-5-onesabsorb ultraviolet light either in the neighborhood of 240-260 mp with a log E value of 4.0-4.4 or at 295-325 mp with a, log E value of 3.3-4.0, or in both regions. The shorter wave length absorption is believed to be due to > &C< absorption while the longer is due to > C=N-. Thus type (VII) would show the longer wave length absorption, type (VIII) the shorter, and type (X) both, or a mixture of any two would show absorption at both wave lengths. 4-Alkyl-3-aryl-2pyrazolin-5-ones absorb at the lower wave length only, indicating that they possess only structure (VIII). However, this conclusion was in disagreement with the finding that these compounds exhibited absorption in the infrared at 1600 cm.-l due to >C=Nand at 3300 cm.-l 605 and showed no absorption attributable to carbonyl. Thus they must actually be of type (X). From the ultraviolet spectra 4-alkyl1,3-diaryl-Z-pyrazolin-5-0nes were concluded to be a mixture of types, but the infrared spectra very clearly showed them to be type (VII) as there was only carbonyl and > G=N- absorption. It would appear that the 1-arylpyrazolin-5-oneswith no N-2 substituent are usually of type (VII), since Glauert and Mann578found no imino or hydroxyl absorption in the infrared spectra of 1,4-diaryl-2-pyrazolin-5-ones. Recently 366a the infrared spectra of 3-methyl-, 3-trifluoromethyl-, 1,3-dimethyl-, I-methyl-3-trifluoromethyl- and 1-phenyl-3-trifluoromethyl-2-pyrazolin-5-one have been studied. The presence of absorption bands at 2400-2700 cm. believed due to zwitterionic forms indicated that these compounds exist largely as form (XIV). The effect of substitution on the structure of pyrazolinones is a very important one, because certain of the tautomeric forms then become impossible. For example, substitution at N-1 allows only structures (VII), (VIII) and (X). Substitution at N-2 would make (VIII) and (XIII) the only possible tautomers. A combination of N-1 and N-2 substitution leaves (VIII) as the only possibility. If there is substitution at N-1 and disubstitution at C-4, then only isomer (VII) is possible. There has been little investigation of the possibilities for tautomeric structures of N-2 substituted pyrazolinones. However, K i t a m ~ r a has ?~~ suggested that such compounds exist as a mixture of forms (VIII)and (XIII). There has been considerable discussion of the situation in regard to the ionic structures. About fifty years ago Michaelis 978* 983. Q84.1002~1003 proposed (XIX) as the structure for 1,2-disubstituted pyrazolinones. I n modern terminology this could correspond to structure (XIV).
8
Part 1. Chapter I
Koma.da844-846 recently has used this structure to explain the structure of the tetrabromides of this type of pyrazolinones. l i i t a m ~ r a ~ ~ ~
I
R’ (XIW
has used rather inconclusive chemical evidence in support of the exis tence of 3-pyrazolin-5-ones in form (XVII). Somewhat better evidence for the structural contributions of these resonance forms has been given in the form of dipole moments, ultraviolet data and bond lengths. Jensen and Friedinger715 and Brown et aZ.246have found abnormally high dipole moments for 2,3-dimethyl-l-phenyl-3-pyrazolin-6-one and its thiono analog. This waa considered to be due to contributions by forms (XIV) and (XVII) to the extent of about 35 per cent. A structure analogous to (XVII) has been proposed for 2-pyrazolin-5-thionesalso on the bwis of dipole moments.934Valyashko and Bliznykov1509have found that 4-amino-2,3-dimethyl-I-phenyl-3-pyrazolin-5-ones have ultraviolet spectra very similar to that of 5-chloro-3-methyl-1-phenylpyrazole methochloride, indicating a considerable contribution by form (XIV). Krohs860has demonstrated a considerablc contribution from the carbonyl form, as shown by infiared absorption in the carbonyl region. This has been confirmed by other infrared studies, and it has been proposed on the basis of iliis that form (VIII)is the predominating one in some cases.366aItomain120Ehas studied the bond lengths in 4-bromo-2,3-dimethyl- 1-phenyl-3-pyrazolin-5-one. These bond lengths indicate a resonance hybrid structure composed of forms (VIII) and (XIV) with some contribution from (XVII). Chattaway and co-workers287 -290* 294 have synthesized a number of 1-aryl-2-pyrazolin-4-ones which, as a rule, have been considered to have the 4-hydroxypyrazole structures. However, some of these must have the 2-pyrazolin-4-one structure due to digubstitution at (2-5. Emerson and Beegle 425 have synthesized some 2-pyrazolin-4-ones unsubstituted at N-1 permitting more possibilities for isomerism. These will be discussed later. The pyrazolidinones (IV) present a number of possibilities for structural isomerism, but very little study of their structure has been made. It is generally assumed that they have the classical form (IV).
General
9
Certainly they would not be expected to have the tendency of 2pyrazolin-&ones to enolize, since they could not achieve an aromaticlike structure. 4. Synthesis
Only a few of the principal synthetic methods for pyrazolinones and pyrazolidinones will be discussed at this point. Other methods will be mcntioned in connection with various classes of compounds. The procedures mentioned here will be discussed in greater detail at the appropriate places. By far the most widely used synthesis for 2-pyrazolin-5-onesis the condensation of a B-ketoester with a hydrazine (eq. 1).6,11.64,269.303*805
---I, /_ 1
Ra
IV-
RZ
I I
+
I ~ ~ C O C - - C O O R ~R ~ X H R ’ H ~
R3
---it3
N
\,=o
(1)
N
I
R5
The R groups in this reaction can be almost anything, H, alkyl, aralkyl, aryl, heterocyclic and many others. Nodifications of this procedure have employed /3-thionoesters,1006* loo8 /I-oximinoesters1555 and /3ketoamide~.~Q. Perhaps the most common procedure for preparing 3-pyrazolin-5ones is alkylation of a 2-pyrazolin-&one at N-3 a.s shown for the synthesis of antipyrine (ey. 2).806 Other alkylating agents such as dimethyl
LaH,
JeH,
sulfate781 can be used, and almost any 2-pyrazolin-5-one can be alkylated, although frequently 0-alkylation occurs and also alkylation at N-1 if it has no substituent. Another useful synthesis of 3-pyrazolin5-Ones is the condensation of a /3-ketoester with acetylphenylhydrazine (eq. 3). The acetyl group is lost and the phenyl group appears a t R1COCH2COORa
+ CaH,NHNHCOCH3
---+
\N r H
(3)
Part 1. Chapter I
10
N-2.9s4*g8s*993 A modification of this consists of using a symmetrically
substituted hydrazine to give 1 ,2-disubstituted-3-pyrazolin-5-ones.54 The synthesis of pyrazolidinones is readily achieved by condensaester1209.1569 or amide758with a tion of an cqB-unsaturated hydrazine. In eq. 4 is shown the reaction for an amide. Ra R'R2C=CCOXHR'
I R3
+ RWHNHS
___+
(4)
H
The reaction of a malonic ester or chloride with hydrazines gives 3,5-pyrazolidinediones(eq. 5).1*8.222* 24*. 252.1234
cox I
RWH
I
+ RaNHNHR3 +
O=l-IR'
cox
5. Physical Properties
Most pyrazolinones and pyrazolidinones are solids, although many, some very complex, can be distilled as high-boiling liquids. 2-Pyrazolinlowers 5-one is a liquid boiling at 163". Reduction of the >&Nthis to 132'. Substitution on N-1 and N-2 gives a low-melting solid. However, substitution at C-3 or C-4 has a more pronounced effect, as which melts at 215". Alkyl for example in 3-methyl-2-pyrazolin-5-one, substitution in pyrazolidinones does not have such a marked effect but does raise boiling and melting points. Almost all aryl substituted pyrazolinones and pyrazolidinones are solids, but many can be distilled. The solubility of pyrazolinones and pyrazolidinones is so varied M to make generalizations of little value. The simpler ones, of lower molecular weight, are soluble in hot water and a few are even soluble in cold water. Almost all are soluble in polar organic solvents and many are soluble in ether and benzene. However, most are insoluble in petroleum ether. Ultraviolet and infrared spectra have been considered in some detail in the section dealing with structure. Concerning the ultraviolet spectra it can be stated that, while there is considerable absorption by pryazolinones and some pyrazolidinones, these absorptions are so complex, owing to tautomerism, that little can be deduced from them.
General
11
The infrared spectra are as would be expected. In some cases there are clear bands due to carbonyl and > C=N- and in others the carbonyl band is missing but hydroxyl bands are present. Raman spectra of 116' antipyrine and aminopyrine have been investigated.273* DipoIe moments have already been discussed in the section dealing with structure. They have been found to be quite high for the few 3-pyrazolin-5-ones studied. The only value reported for a 2-pyrazolin5 - 0 is~ considerably ~ lower, being 2.54 for 3-methyl-2-pyrazolin-5-one. A number of miscellaneous physical properties of antipyrine and a few of its derivatives have been studied. These are listed with references in Table I. TABLEI . Physical Properties of Antipyrine Investigated
___
Physical Property
Crystal Form Dielectric Constant Dielectric Coefficient Heat Capacity Latent Heat Phase Diagram Surface Activity
Refercncc
___ - _-
- -__ 844 367 367 1466 668 669 561
6. Chemical Properties
Only a few of the more important chemical properties of pyrazolinones and pyrazolidinones will be discussed in this section, since these will be covered more thoroughly in connection with the different classes. The pyrazolinones are in general weak acids805 and many can be titrated with strong bases. The 2-pyrazolin-5-ones are stronger acids than the 3-pyrazolin-5-oneslSz3which are very weak. Most pyrazolinones are readily soluble in bases. The pyrazolidinones are not acidic, unless some special feature makes them so. The most extensive data on basicity have been provided by Veibel and ~ o - w o r k e r slSz2* ~ ~ 1525 ~ ~ who * have titrated a number of pyrazolinones with perchloric acid in acetic acid. The pK, values range from 10.3 to 12.3, except for 4,4-disubstituted and 4-halogen substituted 2-pyrazolin-&ones. The 4,4-disubstituted 2-pyrazolin-5-ones are so weak that they are essentially neutral, while the halogenated compounds have pK, values of about 13.2. Both 2-pyrazolin-5-ones and 3-pyrazolin-5-ones undergo substitution at G 4 in an aromatic faahion. Halogenation, nitration and coupling with diazonium salts occur readily. In 2-pyrazolin-&onessuch reactions
12
Part 1. Chapter I
as condensation with aldehydes and ketones and alkylations occur readily at (2-4. The pyrazolinone and pyrazolidinone rings do not have aromatic stability, although in many cases they can assume an aromaticlike structure. The ring is readily destroyed by acid or base hydrolysis and by oxidation. Pyrazolidinones react very much aa do aliphatic hydrazides .
C H A P T E R I1
Pyrazolin-5-ones 1. Introduction
The pyrazolin-5-ones are classified and discussed according t o their functional groups. Compounds having more than one pyrazolinone ring will be classified similarly to the monocyclic ones and discussed in thc same section. All compounds which can theoretically assume the 2-pyrazolin-5-one structure, except those classified as 3,5-pyrazolidinedione derivatives will be considered to be such. Only those for which this is impossible, i.c. 2-substituted pyrazolin-5-ones, will be considered 3-pyrazolin-&ones. A number of compounds having no functional group on the pyrazolinone ring, which have been synthesized for study as coloring agents are listed in connection with the discussion of pyrazolinones used in photography. A number of very complex compounds of similar type are not included in this review, but references to them are given in the dye section. All compounds having no functional group attached t o the pyrazolinone ring will be considered in the section dealing with alkyl, alicyclic, aralkyl, aryl and heterocyclic substituted pyrazolin-5-ones. All oximes are classified as nitroso compounds unless i t is manifestly impossible to do so as in a case having the substituent =NOR. This would be listed in the section concerning amino-2-pyrazolin-5-ones. The 5-iminopyrazolines and the aminopyrazoles which in this discussion are classified as 5-iminopyrazolines are considered with the 2-pyrazolin-5-ones appropriate to their substitution, as are the 2-pyrazolin-5-thiones. 2. Unsubstituted Alkyl, Alicyclic, Aralkyl, Aryl and Heterocyclic
Substituted Derivatives A. 2-PyrazoLin-5-ones
(1) Syntheses
Syntheses of the 4-pyrazolin-5-one ring will be discussed in this section. Those syntheses of this cla.ss which depend upon introduction 13
Part1. ChapterII
14
of a substituent into the already formed ring will be discussed under reactions. Compounds of this type are listed in Table I1 (see Appendix). Methods for synthesis of 2-pyrazolin-5-onesare extremely numerous but the one most frequently used is that shown in eq. 1, the condensation of a /?-aldehydo-or /?-kcto-esterwith a hydrazine. The substituents on the ester and the hydrazine have been greatly varied. All types of alkyl, alicyclic, aralkyl, aryl and heterocyclic substituted esters have been used. In general the yields are the better the smaller the substituents R2,R3 and R4.I n the case in which R2 and R3 are benzyl, . ~ ~ if ~ pyrazolinone formation does not occur when R4 is p h e n ~ l Also, lt2and R3 are aryl, pyrazolinone formation fails. When R3 is larger than methyl, formation of pyrazolinones is more difficult, although many more complex esters having one a-substituent or none have been Ethyl a,a-diethylacetoacetate does not form a pyrazolinone with hydrazine hydrate, but the corresponding methyl ester does.61 R1 may be hydrogen, in which case the ester would be a #I-aldehydoester,303.813. 1636 or it may be alky1,42,53,61,97,135.572.805.1582 a r ~ 1 469.505 , ~ ~ . heterocyclic,lO.307*682 a l i c ~ c l i c , ~or~ *of other types.12* It has been reported that cyclization of benzoylacetic esters to pyrazolinones is easier than is that of acetoacetic esters.777Almost any monosubstituted hydrazine can be used to prepare a pyrazolinone. The simpler the substituent the better the yield usually is,505 though alky1,250.788a1icyclic,lo1 a r a l k ~ 1 , ~ ~arylZ5. O 136*229* 1251 and heterocyclic 7 4 - 91 833 hydrazines have been successfully employed. The conditions used in condensing /?-ketoesters and hydrazines to form pyrazolinones are quite varied. The most widely used method is simply heating the ester and the hydrazine together without added catalysts. The temperatures used are most frequently 100-200°.250.505*805 Quite frequently the hydrazine is condensed with the ketoester to form a hydrazone under milder conditions than are used in the final cyclization step.505A modification of this is to use an already prepared hydra1490 Acidic 2 5 * 1372 and basic conditions are frequently used, particularly in the cyclization step. Under favorable circumstances the yields are very good. Gagnon and c o - w o r k e r ~have ~ ~ ~prepared a series in yields of 83-96 per cent, of 4-alkyl-3-phenyl-2-pyrazolin-5-ones although yields of corresponding 1-phenyl compounds were much lower, varying from 50 to 81 per cent. I n summarizing this method of synthesis it can be said that it is so extremely general that almost any non-substituted or monosubstituted /3-ketoester will react with almost any monosubstituted hydrazine to form a 2-pyrazolin-5-one. A number of niodifications of the /I-ketoester-hydrazine synthesis 413u
Pyrazolin-5-ones
15
of pyrazolinones has been used. One of these modifications is the use of acid hydrazides (eq. 6).6. 360 Under mild conditions the pyrazolinone 960
CH3COCH&OOC~H,+ RCONHNH,
5 c H 3 ~ . - 0
" H
(6)
obtained has the acyl substituent on N-1, but at temperatures of 25' to 100" this substituent is lost. I n addition to 8-ketoesters, the corresponding amides and anilides have been employed in a number of caaes lg7* 378. 872,1030.1276 under very similar conditions. The amides may or may not be substituted on the nitrogen atom. Mitra1006.1007 has reported the use of /3-thionoacetoacetatesinstead of acetoacetic esters to form pyrazolinones. The use of p-ketoesters in which R1or R2of eq. 1 is CH,CO or C2H500C165.358 gives pyrazolinones with elimination of the acyl substituent. A further modification of this synthesis is shown in eq. 7.
NNHCOCH,
H
A number of syntheses of 2-pyrazolin-5-onesdepend on the reaction of compounds, other than /3-ketoesters, substituted in the p-position or of a,P-unsaturated acids, esters and amides. The most frequently used unsaturated compounds are those having a triple bond in the a,/?position~1023,1024.1075.1548.1680R2 can be H0,1652 RO 1023.1024.1686 or H2N (eq. S).1023-1024 A similar reaction is the condensation of ethyl
H
a-chlorocinnamnte with hydrazine t o give 3-phenyl-2-pyrazolin-Sone.610 This probably goes through an acetylenic intermediate. The condensation of methyl crotonate, isocrotonic esters and methyl methacrylate with hydrazines gives as a side-product small yields of 2-pyrazolin-5-ones, the main products being p y r a z o l i d i n o n e ~ . ~ ~ ~ . ~ ~ ~ ~ The pyrazolidinones are probably dehydrogenated to a slight extent to give the pyrazolinones. The reaction of p-alkoxy-a,/3-unsaturated esters 1023.1024 and /I-alkylthio-and/?-acylthio-a,8-unsaturated esters loo7 with hydrazines to give pyrazolinones (eq. 9) proceeds quite readily. The
Part 1. Chapter I1
16
reaction of ketene with arylhydrazines forms 2-pyrazolin-5-ones.723* 885 R*C=CHCOOCzH,
+ HzNNHz
---+
R1- 11
XRa I
'
?.N,J=o H
X =0 or S;Ra=alkyl or acyl
(9)
The first product formed is the hydrazone of the corresponding acetoacethydrazide (XX). This then cyolizes to the desired product at eleCH,-CCH&ONHNHAr
II
NNHAr (XX)
vated temperatures. The reaction of phenylhydrazine with j?-halogenated acids to give pyrazolinones as shown in eqs. 10 and 11 has been 858 These reactions probably occur by removal of water reported.446*
ClCH,CHCOOH
I
+ C,H5NHNH,
-+
I!
3
\x,
OH
'70
(11)
t'& or hydrogen bromide to give an unsaturated intermediate. It has been shown that such an intermediate, methyl j?-chloroisocrotonate, reacts with hydrazine hydrate to give 3-methyl-2-pyrazolin-5-0ne.~~~ A number of heterocyclic systems react with hydrazine to give pyrazolinones. These are shown in eqs. 12-17 and are of little synthetic utility.
ij K=CH, or C,H,
Pyrazolin-5-ones HOOC--/
O\=O
I1vI
17
-
(14)1553
,N/J=o H CHa-
4,NJ=o
(15)laZ2
H
I
CH3
Ho-,iN'i"" -
R
N v - R
(16)457
H
R = H or CH3
Various pyrazole systems having appropriate substituents in the 6-position can be converted into pyrazolinones. The most frequently used synthesis of this type is hydrolysis of 5-alkoxypyrazoles which is shown with others in eqs. 18-21.
v
N
\
N/-OCZHS
-7 ,i=o HCl
N
\
(18) 1360
(19)460
2 + C.H.C. 20
18
Part 1. Chapter I1
The oxidation of 2-arylpyrazolidinones (eq. 2 2 ) to pyrazolinones occurs readily and yields as high as 95 per cent have been reported.68 or calcium The reagents used were ferric chloride,68.1351 bromine 816 hypoch10rite.l~~~
The decarboxylation of 5-0x0-2-pyrazolin-3-and 4-carboxylicacids has been used frequently to prepare 2-pyrazolin-5-ones. I n the case of the 4-carboxylic acids decarboxylation usually occurs in boiling 532*1228* 1230 The 3-carboxylic acids decarboxylate by pyrowater.308* lysis, at somewhat higher temperatures, or by heating with sodium carbonate or calcium carbonate.506* 1544- 1546 A rather unusual synthesis of pyrazolinoiles from a cyclobutane
derivative has been reported (eq. 23).1277This probably involves cleavage of the 1,3-dione to a p-ketohydrazide which cyclizes. (2) Physical Properties
The 2-pyrazolin-5-ones are almost all solids, but a few are liquids. Their melting points vary a great deal and many melt with deconiposition although some are sufficiently thermally stable to be distilled at temperatures above 200". For many, more than one melting point has been reported and it is usualIy impossible to decide from the published data which is the correct one. The solubilities of these compounds vary greatly, but in general they are insoluble in nonpolar solvents and soluble in polar ones and frequently can be crystallized from hot water. Both acidic and basic properties are possessed by 2-pyrazolin-5They dissolve readily in ammonia and sodium carbonate solutions. The pK, values reported505 are 6.2-1 1.0, compounds unsubstituted at N-1 being somewhat stronger acids than are those
Pyrszolin-5-ones
19
substituted at N-1. Veibel and c o - w ~ r k e r s l1524 ~ ~ ~have . reported that 2-pyrazolin-5-ones have pK, values of 10-13, indicating very weak basicity. Only those compounds which can assume the betaine form shown in (XIV) (p. 6) can be titrated with acid. No basic properties are shown by those compounds in which &substitution at (2-4 precludes the existence of this form. A number of studies of ultraviolet and infrared absorption spectra of 2-pyrazolin-5-ones have been made.95.505-506*578 The ultraviolet spectra show maxima in the neighborhood of 250 mp with log E values of 4.10-4.40 and at about 310 mp with log 6 values of 3.90, or in both of these regions of the spectrum. The shorter wave length absorption is attributed t o the presence of >C==N-- and the longer wave length absorption t o > C==C<. Infrared absorption occurs at 1600 cm.-l in all cases owing to the > 6 N - absorption and either at 3300 cm.-l for compounds existing in the enol form, or at 1700-1710 cm.-l for compounds having the carbonyl form. From the spectral data it has been concluded that 2-pyrazolin-5-ones having aryl substitution a t N-1 generally exist in the 0x0 forms (VII) and (VIII) (p. 5 ) unless substitution prevents format.ion of the (VIII) type. If N-1 is unsubstituted, the form (X) predominates. However, recently de Stevens and coworkers 366a have reported somewhat different findings for infrared spectra of 2-pyrazolin-5-ones having H, alkyl and aryl a t N-1 and alkyl groups at G-3. Their results led them t o suggest the form (XIV) as the principal one for these compounds. A study of the absorption of 2-pyrazolin-5-ones by silver bromide has been made by Stolyarova and C h e 1 ’ t ~ o v . lThese ~ ~ ~ workers found that there was absorption of a unimolecular layer of pyrazolinones with the heterocyclic rings parallel to the absorbent surface.
(3) Chemical Properties
The most outstanding chemical property of 2-pyrazolin-5-ones is the activity of the hydrogen atoms at G 4 . This position is very reactive, undergoing the characteristic condensations and substitutions of the active methylene group. Aldehydes and ketones react readily at this position, giving in the simpler cases a mixture of products as shown in eq~~44.22.34.110.296.311,333,633.702.809.980.1123.1241.1250.1263.1288.1351~~s
type of reaction is generally true of aldehydes, but in the case of ketones where one R is aryl only the monopyrazolinone product is obtained.1128 ~ ~ chlora1107*895 Some more active aldehydes such as f ~ r m a l d e h y d eand do not eliminate water but form, as one of the products, a hydroxyalkyl
Part 1.
20
Chapter I1
compound, as shown for formaldehyde in eq. 25. This type of reaction listed is used for synthesis of the 4-(a-hydroxyalkyl)-2-pyrazolin-5-ones RZ-
J- . N J=O
-
+ R3COR4
I
Rl
R3
I
R3
1
R'
I
Rl
Rl
in Table 11, Section F. The formation of the bispyrazolinone can be suppressed by use of acetic acid as the condensing agent.1036.1123 Other condensing agents, such as potassium hydroxide,22 piperidine311 and
I
C6H5
hydrochloric acid 22 have been used, although these are not necessary. This type of reaction has been used extensively to form 4-alkyl- and 4-benzyl-2-pyrazolin-5-ones. The unsaturated product first formed is reduced catalytically to the desired product (eq. 26). Condensation of
I
R'
an aldehyde or ketone with pyrazolinones is the most common method of synthesis for bispyrazolinones of the type shown as a product in eq. 24. A modification of this synthesis which gives d-benzylpyrazolinones is condensation of a pyrazolinone with formaldehyde in the In the presence of an activated aromatic compound such as guaia~ol.~* undergoes presence of piperidine, 3-methyl-l-phenyl-2-pyrazolin-5-one an intermolecular aldol condensation (eq. 27). The carbonyl compounds
..
Pyrazolin-5-onas
el
which have been most frequently condensed with 2-pyrazol?~w5-one8 have been aromatic ones and a very large number of these hav6 Gsen used. Ridi and Checchi l l a 81189 * have studied the condensation-of formamides with 2-pyrazolin-5-ones. This condensation occurs at a' temperature of 160-200" and appears to be an aldol condensation followed by dehydration (eq. 28). R l may be hydrogen, alkyl or aryl, while R2
has been only alkyl and aryl. It3 has been either hydrogen or aryl. Acetamide and other amides also react in this way with 2-pyrazolin5 - 0 n e s . ~ ~1192. * ~ l.l g 3 The compounds synthesized in this manner are shown in Table 11, Section G. It is not completely certain that the 4-substituent is as shown in eq. 28. It may bo the isomeric form, R3N=CH. One of the products frequently obtained in this reaction is a 4,4'-metliylidynebispyrazolinone,formed by the reaction of the first product with the starting material with elimination of ammonia or an amine. A reaction analogous to the condensation of amides with 2pyrazolin-5-ones is the reaction of amidines first reported by Dains This has been extended by Ogata, Tauno and Nishida'O'O (eq. 29).348*349 to vinylogs of amidines of the type CBH,NH(CH=CH),CH=NC,H5.
If a,/3-unsrtturated ketones are condensed with 2-pyrazolin-5-ones the reaction is a Michael addition (eq. 30)686*721resulting in alkylation.
Part 1. Chapter I1
22
The alkylation of 2-pyrazolin-&ones a t (2-4 occurs retl.dily (eq. 31) ‘I3* 1321 with compounds having reactive halogen atoms. An example R
I
I
I C,H,
I
COH,
C,H5
of this is the alkylation of 3-methyl-1-phenyl-?-pyrazolin-5-one with methyl iodide and sodium methoxide to give the corresponding 4,4dimethyl compound.809However, this reaction may give alkylation a t N-2 or 0-alkylation and as a rule it is easier to alkylate at these positions than it is at C-4 when aliphatic halides are used. Indeed, in the N-2 alkylation the case of 3-methyl-1-phenyl-2-pyrazolin-5-one occurs to a much greater extent than does exclusive alkylation at C-4, the products being 2,3-dimethyl-l-phenyl-3-pyrazolin-5-one and 1phenyl-2,3,4-trimethyl-3-pyrazolin-5-one. Various triaryl carbinols and ethers of such carbinols alkylate 2-pyrazolin-5-ones in the presence of acids t o give 4-triarylrnethyl-2-pyra~olin-5-ones.~~~~~~~ A somewhat similar reaction is that of orthoesters (eq. 32).764 2-Xethyl-4-chloroquinoline also alkylates 2-pyrazolin-5-ones at C-4.971 R2--
iI \N
I
/Lo
4 R3C(OR4)3 +
RZ
/
,
=
, ! A
\E;
y
4
(32)
I
R’
R’
A very important reaction in the synthesis of merocyanine dyes is the alkylation of 2-pyrazolin-5-ones with various heterocyclic rings as illustrated in eqs. 33-35.166.238,239 2-Pyrazoljn-5-ones other than the C
H
.. 3
~
E,=o
i
+
c:\’s+lIs
-:,,
N, I
----,
X-
one shown here can be used, and a large variety of heterocyclic compounds such as quinolines, benzoxazoles and numerous others have been employed. The anion may be halogen or p-tosyl.
Pyrazolin-5-ones
23
The hydrazones of 5-formylbarbituric acid react with 2-pyrazolin5-ones in a fashion rather similar to that of aldehydes and ket$ones
+ I
(35)
CBH5
I
CsH5
C6HS
(eqs. 36 and 37).11**Apparently it cannot be predicted which of these two types of reaction will occur.
Part 1. Chapter I1
24
2-Pyrazolin-5-ones can be readily acylated at C-4 with acid chlorides,l1° esters1641 and anhydrides.1279Very few reactions with acid chlorides and esters have been reported but the product is the ketone (XXI), as expected. Phthalic anhydride reacts with two moles
I
It' (XXI)
of 2-pyrazolin-5-one according to eq. 38. Perhaps the first step in this 0
i
I
C,H,
C.3,
reaction is acylation, followed by reaction of a second molecule of pyrazolinone with the ketone first formed. Another reagent which alkylates 2-pyrazolin-5-ones is ethyl isoformanilide, the products being 4-anilinomethylidyne-2-pyrazolin-5ones (eq. 39).823*824 Similar products have been obtained by Losco and Passerini 1089 by reaction of isonitriles with 2-pyrazolin-5-ones.
I JBH6
w
5
As would be expected, 2-pyrazolin-5-ones undergo the lllannich reaction readily (eq. 4O).log8
Pyrazolin-6-ones
25
A variety of functional groups can be introduced directly into the 4-position of 2-pyrazolin-&ones. Perhaps the most important of these is the arylazo group which is introduced by reaction with diazonium This reaction has been used t o prepare a vast salts (eq. 41).333*8090813 R2-__II h\'N J = O
+
ArNaCl
-
I
R2-
(41)
Ig:=Nh
I
R'
R'
number of azo dyes, many of which have been of considerable commercial importance. It will be discussed in more detail in connection with pyrazolinone dyes and preparation of azo derivatives. Another reaction of commercial importance is that of 2-pyrazolin-5-ones with aromatic amines in the presence of oxidizing agents t o form color couplers which (eq. 172).244* 1538 The same kind of are 4-arylimino-2-pyrazolin-5-ones product is obtained by the reaction of 4-arylidene-2-pyrazolin-5-ones with aromatic amines. The net result is replacement of the arylidene group with the arylimino Halogenation at the 4-position also occurs readily with phosphorus p e n t a ~ h l o r i d e , phosphorus ~ ~ ~ . ~ ~ ~ tribromide 333 or bromine.333*809*816 The phosphorus halides form 4,4-dihalogenated derivatives. Direct bromination with a n equivalent but excess of bromine of bromine gives 4-bromo-2-pyrazolin-5-ones, gives the 4,4-dibromo and even some tribromo compound. 2-Pyrazolin5-ones react with nitrous acid to give nitroso derivatives which exist Nitration with usually as the corresponding oximes (XXII).333*809.816
kl
(XXII)
dilute nitric acid forms 4-nitr0-2-pyrazolin-5-ones.~~ 333*806 A 4-formyl group can be introduced by using the Reimer-Tiemann reaction. Sulwith 20 per cent oleuni fonation of 3-methyl-l-phenyl-2-pyrazolin-5-one at 10-15" results in formation of the corresponding 4-sulfonic Higher temperatures cause not only sulfonation of the heterocyclic ring, but sulfonation of the phenyl group. A cyano group can be introduced into the 4-position of 2-pyrazolin-5-ones by reaction with cyanogen bromide in the presence of aluminum chloride.24 These substitutions are much more difficult if an alkyl substituent is present in the 4position, although in some cases such a group is eliminated. 4-Triarylmethyl-2-pyrazolin-6-ones react with diazonium salts with replacement 2*
Part 1. Chapter I1
26
of the triarylmethyl substituent by the arylazo Of course, 4,4-dialkyl-2-pyrazolin-5-ones do not react with these substituting reagents. These reactions are discussed further in sections devoted to preparation of the various types of compounds arising from such reactions. As already mentioned, it is possible for 2-pyrazolin-5-ones to react with alkylating agents at N-2 and at the oxygen atom in addition to (3-4. If there is no substituent at N-1, this position can also be alkylated. Moat alkylations give a mixture of the possible products. However, by alkylation at temperatures of 100-130", with or without basic catalysts, in 2-pyrazolin-5-ones can be converted to 2-alkyl-3-pyrazolin-5-ones excellent yields (eq. 42). This reaction has been extensively studied
I
R1
I
RI
because, in the case of 3-methyl-l-phenyl-2-pyrazolin-5-0ne and methyl iodide, the product is the commercially important analgesic and antipyretic, antipyrine. The most widely used procedure for carrying out this reaction is the use of methyl iodide and methanol at 100".806 Methylation has also been accomplished by use of methyl sulfate and sodium hydroxide,l1° methyl p-toluenesulfonate and sodium meth985 methyl iodide at 130°,1475diazooxide,54 dimethyl methane,94 and methyl iodide and sodium m e t 1 i o ~ i d e . lAlkylation ~~~ under similar conditions with alkylating agents having longer carbon chains, such as ethyl iodide,1205propyl bromide,1321benzyl chloride and 2-dialkylaminoethyl chlorides249 has been successful. Nef 1056 has reported that alkylation of 3-methyl-l-phenyl-2-pyrazolin-5-one with methyl iodide and sodium methoxide occurs at C-4 with no N-2 alkylation, at N-2 with no C-4 alkylation, and at both positions. In 2-pyrazolin-5-ones lacking a 1-substituent alkylation occurs to give 1205 usually with little or no 1-substituted 2-pyra~olin-ti-ones,~~0-alkylation, and alkylation with alkylchloroformates leads to subSomewhat more drastic conditions form stitution only at N-1 5-alko~ypyrazolea.~~ 1331 Acylation of 2-pyrazolin-5-ones having no substituent at N-1 1598 acetic occurs readily with such agents as acetyl chloride,1499* anhydride,1499-1598 benzoyl chloride 1056.1598 and aryl sulfonyl chlorbut acylation ides.1199The usual product is a l-acyl-2-pyrazolin-5-one, may also occur on oxygen, or both on oxygen and at N-2.1598
-
Pyrazolin-5-ones
27
The reaction of 2-pyrazolin-5-oneswith phosphorus oxychloride to ~ . ~ ~loo3. ~ . lZo5 give5-chloropyrazoles(eq.43) is a ~ e r y g e n e r a l o n e . ~985*992.
- RzT-J:;
R2-lr
Y J - R3
POCla
I
(43)
I
R1
R'
The reaction requires temperatures of 100-150" and all pyrazolinones of this type undergo it. The oxygen of 2-pyrazolin-5-ones can also be replaced by sulfur if phosphorus pentasulfide a t about 130-150" is used This reaction is widely used for preparation of 2(eq. 44).759*1343 pyrazolin-5-thiones. R3
R3
I
I
R'
R'
The hydrogen atoms on C-4 of 2-pyrazolin-5-ones are readily attacked by mild oxidizing agent.s. The products of this reaction are bispyrazolinones (eq. 45) when such oxidizing agents as phenyl
I R'
I
R'
I
Rl
(45)
hydrazine333~636.809,818-991 or nitrous acid are used.809 The use of ferric chloride in limited amounts gives the bispyrazolinones in which the two rings are connected by a single bond,1582but larger amounts of ferric chloride give further oxidation and in the product the two pyrazolinone rings are attached to each other by double bondssog as shown in eq. 45. Oxidation of 2-pyrazolin-5-oneshaving a 1-aryl substituent with t-butylhydroperoxidelSz6or oxygen in neutral solution1528 leads to bispyrazolinoncs, as shown in the first step of eq. 45. I n contrast to this, the use of t-butylhydroperoxide in the presence of sodium a l k o x i d e ~ or ' ~ of ~ ~oxygen in acid media1528converts the 2-pyrazolin5-One to the corresponding hydroxy compound. These are excellent
Part 1. Chapt.er I1
28
preparative methods for 4-hydroxy-2-pyrazolin-5-ones. Shirai and Yashiro 1299 have found that some 2-pyrazolin-5-ones can be converted t o bispyrazolinones merely by recrystallization from hot water. 4,4Disubstituted-2-pyrazolin-5-onesdo not undergo the oxidative dimerization, except in the cases of those substituted with a 4-arylidene group which are oxidized by p h e n y l h y d r a ~ i n e .These ~ ~ ~ ~compounds apparently react by replacement of the ArCH= by hydrogen from the phenylhydrazine and the unsubstituted pyrazolinone thus arising is oxidized. Strong oxidizing agents, such as potassium permanganate, completely destroy the 2-pyrazolin-5-one ring, forming pyruvic acid, water, nitrogen and carbon dioxide.154g The heterocyclic ring of 2-pyrazolin-5-ones is quite stable t o catalytic reduction. Aromatic substituents present can be reduced t o cyclohexyl groups by means of various hydrogenation cata,lysts without reduction of the heterocyclic ring.161*859*l m 0The carbonyl function of 2-pyrazolin-5-ones is subject to reduction by various chemical reagents. with zinc results in Treatment of 3-methyl-l-phenyl-2-pyrazolin-5-ones reduction to the corresponding p y r a z ~ l ebut , ~ ~somewhat ~ more drastic conditions cause complete decomposition of the heterocyclic ring, giving aniline and a c e t ~ n i t r i l e .Reduction ~~~ of the same compound with sodium and alcohol forms the corresponding pyrazoline (eq. 46).809The
use of sodium and amyl alcohol on 2-pyrazolin-5-ones forms 5-hydroxyp y r a ~ o l i n e sas , ~ does ~ reduction with 1it.hium aluminum hydride.1505 Although 2-pyrazolin-5-ones are relatively stable t o acid hydrolysis, those having 1-(dinitrophenyl) or 1 -( trinitrophenyl) substituents are decomposed, forming arylhydrazones (eq. 47).777
I
R'
Hydrolysis of 2-pyrazolin-5-ones with 33 per cent sodium hydroxide solution also destroys the ring.1286The hydrolysis products were not identified with certainty, but it was thought that acetic and propionic acids were among them. 2-Pyrazolin-5-ones form a variety of complexes with various metals
Pyrazolin-5-ones
29
and metal salts.393~394~482 3-Methyl-1-phenyl-2-pyrazolin-5-one has been reported to form complexes with iron, cobalt, silver, cupric oxide, cupric iodide, silver iodide, ferric iodide, cobalt iodide and beryllium chloride. These complexes actually are salts of the enolic form of the py-razolinone in many cases, although in others the only bonds may be those formed by donation of the electrons by the C===N-N< group.394 I n some cases both types of linkages are present. The compounds formed usually have the number of molecules of 2-pyrazolin-5-one corresponding to the valence of the metal atom present. (4) Hydroxyalkyl Types
Most of the syntheses of a-hydroxyalkyl and a-alkoxyalkyl-2pyrazolin-5-ones have been discussed in connection with the reactions of 2-pyrazolin-5-ones. However, there is one synthesis by which compounds of this type are obtained directly. This is by reaction of the appropriate alkoxy- or phenoxymethylacetoacetic esters with hydra1562 The reactions of these compounds zines (eq. 48).532*1314.1315,1316.
I
R3
.(4W
HOCH2-------Rz HCI
+
4--. 1 N/ I
R3
are the general ones for 2-pyrazolin-5-onesand for hydroxy and alkoxy functions except for the condensation of 4-hydroxymethyl-2-pyrazolin5-ones with another pyrazolinone to give bis(2-pyrazolin-5-ones) (eq. 49).24
Part 1. Chapter I1
30
The a-hydroxyalkyl and a-alkoxyalkyl-2-pyazolin-5-ones are listed in Table 11, Section F. ( 5 ) Aminoalkyl Types
A number of syntheses of compounds having nitrogen on a carbon attached to 2-pyrazolin-5-one rings have already been mentioned, but several others are known. The most important of these is the reaction with hydroxylamine, hydraof 4-formyl- or 4-acyl-2-pyrazolin-5-ones 1641 These compounds zines, semicarbazide and similar chemicals.559can also be obtained by direct synthesis from an appropriate ,9-ketoester or derivative and a hydrazine (eq. 50).138.51a*1100 An interesting syn-
+
R1-NCHZCOCH,COOC2HS
I
R'-N-CH,-
R3NHNH,
Ra I
RZ
?'I, = O
I
(50)
I H3
thesis of this type of compound is that shown in eq. 51.1179Presumably condensation of one molecule of semicarbazide with the ketone carbonyl NHNHCONH2 CE3COONB
C6H,COCH=CHCOOC,H,
l- H,NHNCONH, -----+
I
C'H
CHCOOCaH5 (51)
I
H
is followed by cyclization to the C-3 of the ester with elimination of ammonia after addition of a second molecule of semicarbazide. Two other syntheses of these compounds are shown in eqs. 52 and 53.9a5-l a o 6 CH,
NH20B~ECI
CHS-JTCH=NOH
\N
'N
=O
(62)
I
C*H,
(XXII-B)
+ H,NNH,.H,O 'N
+ cH3-'N
1
68%
(53)
I GH,
The reactions of these derivatives are typical of the functional groups present.
Pyrazolin-5-ones
31
Compounds having nitrogen on a carbon atom which is attached to a 2-pyrazolin-5-onering are listed in Table 11, Section G . ( 6 ) Bis(2-~yrazoZin-5-0~#)
A large number of 2-pyrazolin-5-ones exist in which two or more such rings are combined. These are almost all combined symmetrically, that is Dhe same positions in the two rings are linked, and the vast majority are combined in the 4,4‘-positions, although many are connected at the 3,3’-positions and some by way of the 1,l‘-positions. Those 4,4’-bispyrazolinones in which the two rings are directly connected are listed in Tables I11 and IV. Those having atoms between the rings are listed in Tables V-VII. The 3,3’-bispyrazolinones are listed in Table VIII and the 1,l’-bispyrazolinones in Table IX. The most widely used synthesis of 4,4’-bis(2-pyrazolin-&ones) is mild oxidation of monocyclic 2-pyrazolin-5-ones, which has already been discussed in the section devoted to reactions of 2-pyrazolin-5-ones (eq. 45). These. compounds can also be synthesized by reaction of a,a’-diacylsuccinic esters with hydrazines (eq. 54).357. *15 A number
I
I
R2
R”
of miscellaneous dimerizations of 2-pyrazolin-5-ones and 3-pyrazolin5-ones have been reported to give 4,4’-bis(2-pyrazolin-5-ones).3-Methyl1 -phenyl-2-pyrazolin-5-one reacts with various acylanilidesI1O2 and with sodium ethoxide1s45to give dimers. Ethyl groups are introduced at the 4,4‘-positions by the use of sodium ethoxide. Heating a, 4oximino-2-pyrazolin-5-one has been reported to give a dimer in which the 4-substituent has been eliminated (eq. 55).925 According t o van C H 3 r - Y O H ‘N $0 I
&
CH,-
”--) P---~CH~ -
=o
,N
0-
I
I
I
C6H6
(XXII-C)
N/ I
(55)
&EHS
Alphen 1513it is also obtained by the reductive cyclization of a crotonic ester (eq. 56). The replacement of a 4-imino function in a 2-pyrazolin&one by a 2-pyrazolin-5-one lacking a 4-substituent also leads to a
Part 1. Chapter I1
32
dimer.1538Hydrazines react with various heterocyclic compounds to give 4,4’-bis(2-pyrazolin-&ones). These reactions are shown in eqs. 57-59.129p725*729 Ridi and co-workersllS4have treated various pyrazoloCBH5C=CHCOSS + C6HSNHNH2 --+
u
‘OH5
ik
CBHS (57)
I
I
CsH5
CeHS
R
I
,
I
’I
kJ=o
GHS
R
I
CBH5
2-pyrones and phenylmethyltartonylurea and imide with phenylhydraA variety of zine to give 4,4’-bis(3-methyl-1-phenyl-2-pyrazolin-5-one). other 4,4’-bis(2-pyrazolin-5-ones) can be converted into the type being
I
&fiH5
GH5
I (kH5
(XXII-D)
discussed here. 4-Benzylidene-4,4‘-bis(3-methyl-l-phenyl-2-pyrazolin5-one) reacts with azobenzene or phenylhydrazine to give 4,4’-bis(3methyl-l-phenyl-2-pyrazolin-5-one).10go~1091 Of particular interest is
33
Pyrazolin-5-ones
the addition of various compounds having active methylene to the 4,4‘-bis(2-pyrazolin-5-ones) connected by a double bond since this leads This reaction is shown in in some cases t o trimers.1607.160g.1613.1614 eq. 60. Only a very few 4,4’-bis(2-pyrazolin-5-ones) linked by a double bond have been prepared. The parent compound of this series, 443methyl - 1-phenyl-5-oxo-2 - pyrazolin-4-ylidene)-3-methyl-l-phenyl-2pyrazolin-5-one (XXII-D), is known as pyrazole b l ~ e . ~ ~ ~ . ~ ~ ~ * 1090*1091It was so named by Knorr because of its great resemblance t o indigo blue. All these compounds are strongly colored. The usual synthesis is by ferric chloride oxidation of monomeric 2-pyrazolin-5-ones or by oxidation of the corresponding bis compounds (eq. 61)296*809
C H 3 ~ i \
N/”O
I
FeCI3
(xXI1-D)
(61)
CBH,
linked by a single bond with ferric chloride, nitrous acid, nitric acid or various nitriles.296.333.1090 The product in eq. 61 is pyrazole blue. Other methods of synthesis are treatment of 4-(3-methyl-l-phenyl-Zpyrazolin-5-ylidene)-3-methyl1-phenyl-2-pyrazolin-5-one with bromine in alkali,323 heating of 4-bromo-3-methyl-l-phenyl-2-pyrazolin-5-one CH, I
L-I. with alcohol80Band degradation of trimers.1s07*1e08The trimer degradation procedure gives unsymmetrical compounds of the pyrazole blue type (eq. 62). The double bond connecting the rings in these
34
Part 1. Chapter I1
compounds reacts m do normal olefins and in addition undergoes additions with compounds having active hydrogenlso7.1608 or with such compounds as hydrogen cyanide.lsla 4,4'-bis(Z-pyrazolin-5-0nes)linked by carbon chains have been prepared in a multitude of ways, several of which have been mentioned in the discussion concerning reactions of 2-pyrazolin-&ones. The only method of any importance is the condensation of 2-pyrazolin-&ones with aldehydes and ketones (eq. 24, p. 20) and this has already been discussed. An interesting modification of this is the use of an anil as a substitute for the aldehyde.log4The a d functions similarly to the aldehyde. A second modification in which the aldehyde is generated in the course of the reaction has also been used (eq. 63).1351Another C,H,NHNH,
+
HOHC=CHCOOC,H,
-
C,H,NHXHCH=CHCOOC,H,
I
I
C6H6
C6H5
method used to some extent for the synthesis of 4,4'-bis(Z-pyrazolin&ones) is the reaction of bis-/3-ketoesters with hydrazines (eq. 64).451* 513*514*1154The reaction of 2-pyrazolin-&oneswith amidines to CHaCOCHhOOCzH6
R'-CHCOCHB
I
+
RWHNH,
COOC,H,
I
I
R"
Ra
give substitution at the 4-position has already been mentioned. I n addition to such products this reaction often gives 4,4'-methylidynebis(2-pyrazolin-5-ones) (eq 65).1070~11aa A reaction which appears
I
R'
I
R'
to be very similar to this and gives the same type of product is the condensation of 2-pyrazolin-5-ones with l-phenyl-l,2-dihydro-4,6diamin0-1,3,5-triazines.3~~ The synthesis of 4,4'-methylidynebis(2pyrazolin-&ones) has usually been achieved by condensation of
Pyrazolin-6-ones
36
2-pyrazolin-&ones with ethyl orthoformate 611*1188*1669(eq. 66) or by the condensation of 5-oxo-2-pyrazolin-4-carboxaldehydeswith RZ-
+
R2---CH--gI HC(@&H6)3
_ _ f
{ N K
I
dN)
k'
R' I
R'
(6e)
2-pyrazolin-5-ones (eq. 67).92s,1093,1185The latter condensation can be modified by boiling the aldehyde alone in water which causes partial R2
'N
N
'N
I
R'
I
I
R'
R'
41
hydrolysis of the formyl group. The reactants shown in eq. 67 are then present and can react to form the bis compound. A variety of miscellaneous methods of preparing such compounds is given in eqs. 68-81. CH3
CH3
'N4 I0
0 &aH,
CBH5
(68)"O
CH,C-------CHCOOC2HB
II
NNHCeHs
I
__I,
CH,
\-.....-
d" AI
! *
C,HS
+
(69)117
0€I3CO~H
CHZSCH,
(XXII-A)
C2H60Na
CICHaSCH,
(XXII-A)
(70)"'
36
Part 1. Chapter I1 N C0H,N’
-
1
CCH,
\C - C d H
(7 1) 187
Pyrazolin-5 -ones
37
(78)s77
I
(79) low
OC2H,
OHCHNPI'HCHO
+
CH,COOH
'1
-CH-------
___f
CH3-7---
'h'
\
1
H
0
/LN,?
II
~
O
I
H
CH3 (80)1185
38
Part 1.
Chapter I1
(XXII-B) (81) lla7
4,4’-Arylidenebis(2-pyrazolin-5-ones) can be decomposed by heat or acid to give 4,4’-methylidynebis(2-pyrazolin-5-ones).g3~ lo3* In one was recwe 4,4’-methenylbis(3-methyl-l-phenyl-2-pyrazolin-5-one) ported as the product.22 The melting point given was 177”. This was undoubtedly the 4,4’-methylidyne compound which melts at 185”. The 4,4’-methenylbis compound, which melts at 220”, has been repeatedly reported as melting at 180-185O owing to its easy loss of hydrogen to give the 4,4‘-methylidynebis compound. In some cases this heat degradation of 4,4’-arylidenebispyrazolinonesconverts them back into the mono-2-pyrazolin-5-ones.1036 The degradation of bis(2-pyrazolin-5ones) to mono compounds is also brought about by heating with 4,4’-Methylidynebis-(2-pyrazolin-5-ones) are readily f~rmamide.ll~ ~ converted by treatment with hydroxylamine into the corresponding B-oxo-2-pyrazolin-4-carboxaldehyde oxime 925 or by hydrolysis with base to the 4-carboxaldehyde (eq. S2).926 The bromination of 4,4‘(XXII-B)
H20 __j
NaOH
I
CBH5
methylidynebis(3-methyl-1-phenyl-2-pyrazolin-5-one) has been reported by Ziegler and Sauermilch.les2Bromination replaced the only remaining G 4 hydrogen by bromine. Hydrogen bromide could not be eliminated, but heating with alcohol replaced the halogen by hydrogen. The condensation of a series of 2-pyrazolin-&ones with aryl aldehydes in 70 per cent acetic acid at elevated temperatures has been described as giving the enol form of 4,4’-arylidenebis(2-pyrazolin-5-0nes).~~~~ The corresponding keto forms can be converted into the enols by heating in alcohol. A few 4,4‘-bis(2-pyrazolin-5-ones)are known in which t>helinking chain contains nitrogen atoms. These are Schiff bases and amides. ~-0xo-2-pyrazolin-4-carboxaldehydes react with diamines having two The amides primary amino groups to form 4,4’-bispyrazolinone~.~~~~ are synthesized by reaction of bisisocyanates with 2-pyrazolin-5-ones
Pyrezolin-6-ones
39
(eq. t33).l1l1 This reaction is of particular interest because it illustrates the great activity of the hydrogen atoms at C-4. CH3-
+
LJ\
(CH&H&HzNCO)a
I
CsHs
--..-.+
m-,/ P
CONH(CH&HNOC J
\ ' "
(83) ~
I
CeHs ! O
0
The 3,3'-bis(2-pyrazolin-5-ones)in which the rings are connected by carbon chains (Table VIII) are usually prepared by condensation of a hydrazine with an appropriate j?,/3'-dioxodiester (eq. 84).41s* 462* 1222-1225 Such bispyrazolinones linked by a carbonyl group have been prepared by pyrolysis of the calcium salt of 8-0~0-2-pyrazolin-S-one.~~~~ RIOOCCHaCORCOCHICOOR*
The 1,l'-bis(2-pyrazolin-5-ones) (Table IX)have been prepared by three methods. Two of these are variants on the familiar j?-ketoester condensation with hydrazines but in these cases compounds having two hydrazine moieties are used.lls*zlz-255-4 5 9 - 1037 These two methods are illustrated in eq. 85. The R in the hydrazines used in the direct conR1COCHCOOR3
I
It2
+
K2NHNRNHKH2
u
I
densation is usually aryl. The commonly used hydrazine when going through the bishydrazone has been ~ a r b a z i d e or l~a ~ ~similar com-
Part 1.
40
Chapter I1
The reaction of phosgene with 1-(X-amino-phenyl)-% pyrazolin-&ones also forms l,l'-bis(2-pyrazolin-5-ones) (eq. 86).152* 511 R
tN
+
COCl,
--+
R
J=o
The 1, 1'-bispyrazolines undergo the usual reactions of 2-pyrazolin-6ones. West06 has reported the synthesis of complex bispyrazolinones which he has called furlones.1608.1610*1611These have two 2-pyrazolin5-one rings connected through a dihydrofuran ring which in turn is fused with a pyrazole ring. These were prepared by condensation of 4-ha1ogentted22-pyrazolin-5-ones, together, with l-aryl-2-pyrazolin-5ones, or with pyrazole blue (XXII-D) in the presence of a base and copper sulfate (eq. 87). These compounds are listed in Table X.
B. 2-Pyrazolin-5-thiones
The reaction of 2-pyrazolin-5-ones with phosphorus pentasulfide forms 2-pyrazolin-5-thiones (eq. 44).759* 1343 The reactants are usually heated at the temperature of boiling xylene. A second method used in the preparation of such compounds is the reaction of 5-chloro990.loo3 pyrazoles with potassium hydrogen sulfide (eq. 88).977* 990e
CsHs
CoH,
The properties of these compounds are very similar to those of the 50x0 analogs. They are usually colorless but are yellow if substituted
Pyrazolin-5-ones
41
in the 4-position. Acidic and basic properties are both present. Kendall exist as and Ruffin 759 claim that 3,4,4-trialkyl-2-pyrazolin-5-thiones mercapto pyrazoles having the structure (XXIII). R2
(XXIII)
Reactions of 2-pyrazolin-5-thiones at the 4-position are quite similar to those of the 5-0x0 analogs. Condensation of one mole of the pyrazolinthione with one mole of ketone or aldehyde to form 4-alkylidene- or arylidene-2-pyrazolin-5-thionesoccurs.99o Coupling with diazonium salts forms 4-azo compounds 990 and nitrosation occurs.ggoAlkylation or acylation ordinarily attacks the sulfur atom 990 Oxidation with mild oxidizing to give 5-rnercaptopyra~oles.~~~~ , ~ ~the ~ use of agents such as iodine or nitrous acid forms a d i s ~ l f i d ebut hydrogen peroxide gives a sulfonic acid, according to illichaelis,990or replacement of the sulfur by oxygen, according to K i t a m ~ r a . ~ ~ ~ Mercaptides are formed with mercuric oxide or mercuric salts.990The 4,4'-bis(2-pyrazolin-ti-thiones) cyclize very readily to form a tricyclic compound with elimination of hydrogen sulfide (eq. S9).990 The 2pyrazolin-5-thiones are listed in Table XI.
C. 5-Imino-2-pyramlines
It is probable that most of the 5-imino-2-pyrazolinesexist as the corresponding aminopyrazoles (XXIV). Gagnon, Boivin and Trem-
(XXW
bley50s have studied the ultraviolet absorption spectra of these compounds and concluded that the usual structure is the aminopyrazole
Part 1. Chapter I1
42
one, although frequently more than one isomer is present. The chemical literature usually refers to what are here called 5-imino-2-pyrazolines as 5-aminopyrazoles. The principal methods of preparation of these compounds are very similar to those used for the 5-0x0-compounds, except that nitriles, and in some cases amides, are used instead of esters, acids or acid derivatives. /I-Ketonit_rile~,~~~* 344. 1562 B-aldehydonit,rile~,~27Bi m i n o n i t r i l e ~ ,324*g96* ~ ~ * 1010.1285*1542 +unsaturated trithiones12g and +acetylenic nitrilesloZ5are condensed with hydrazines. I n many caaes the intermediate hydrazones have been isolated and cyclized.86-132*310996*1011*1285-1287 These reactions are shown in eqs. 90 and 91. Worrall and co-workers 1655* 1656 have reported the condensation of aromatic acetylenic amides with hydrazines to give 5-imino-2-pyrazolines (eq. 92). Presumably the amides react like the iminothioacids, hydrogen R'
R'CXCHaCN
+
R'NHNH,
-+
X=O or N H
\II N / J a: '
i
(90)
\H
R'
AT'
sulfide being eliminated. Bottcher and BauerIz9 have condensed a,/?unsaturated trithiones with hydrazines to form ti-imino-2-pyrazolines (eq. 93). CeH5CdHCSSS
+ COHBNHNH,
u
----+
CGHS--I1 N \N'\
I
I
(93) NH
C6H5
Several methods for the synthesis of 5-imino-2-pyrazolines depend upon the amination of a pyrazole ring. 5-Chloropyrazoles react with aniline to give the corresponding 5-amino compound.826-loo2 The chloropyrazoles can be prepared and amination accomplished in one
Pyrazol-in5-onw
43
step by treatment of 2-pyrazolin-5-one with phosphorus oxychloride and aryl amines a t the same time.827*828 Also reduction of a 5-nitrohas pyrazole has been used.1086Ethyl 3-phenylpyrazole-5-carboxylate been converted into a hydrazide, then t o an azide, and finally, by a Curtius rearrangement, to the amino compound (eq. 94).loE6Also amides can be rearranged to give iminopyrazolines.104s
+
CH
4
I/
' N-"\
'K'\
H
HJNH,
COOC2H,
H 1. N s N 0 2 - W C I
CONHNH, (94)
Cusmano 340*3 4 1 * 3 4 5 has converted 5-alkyl- and 5-arylisoxazole-3carboxylic acids into 5-imino-2-pyrazolines by treatment with phenyl hydrazine. Musante has also used this procedure.1043-1045 This reaction goes by way of 8-ketonitrile intermediates and gives very poor yields.86 The decarboxylation of 1,3-diphenyl-5-imino-2-pyrazolin-3carboxylic acid gives 1,3-diphenyl-5-irnin0-2-pyrazoline.~~~ Druey and Schmidt 391 have taken advantage of the selective replacement of an 0x0 group by chlorine over that of an imino group to prepare 5-imino2-pyrazolines (eq. 95).
The reactions of 5-imino-2-pyrazolines are very similar t o those of the 5-0x0 analogs, except for reactions specifically involving the 5-imino group as its amino tautomer. For example, condensations with aromatic aldehydes occur t o form 4,4'-arylidenebis(5-imino-S-pyrazolincs). Michaelis996 has prepared compounds of this type from in which the arylidene groups 3-methyl-1-phenyl-5-imino-2-pyrazoline and melting points are respectively: C6H5CH, 66"; 2-NO2C6H,CH, 89"; X-HOC6H4CH, 120"; 4-CH3C6H,CH, 219'. However, reaction with aldehydes or ketones can also occur at the amino group to give Schiff bases or alkylation.lOll Ketones such as acetoacetic ester used in vigorous conditions give pyra~olopyrimidines.~~~ Halogenation, Qgs.1666
Part 1. Chapter I1
44
nitration,165s n i t r o ~ a t i o n ,loo2* ~~~ l o.l o and coupling with diazonium saltsgg6occur at (2-4 as expected. The nitrosation products are usually oximes. The condensation of phenyl isocyanate with the 5-imino-2pyrazolines occurs to give the 4-carboxyanilides (eq. 96).82s These comCHa-
+
NIi
C,H5SC() --
I
CH3-l
CoKHCSHS
k
i
‘ K ’ \
WHS
CBH5
I I
hC6H5
C6H5
pounds then readily cyclize to quinoline derivatives. Phenyl isothiocyanate, N,N’-diphenylurea and N,N’-diphenylthiourea also react in this way. pNitrophenylsulfeny1 chloride reacts with 3-methyl-1-phenyl 5-imino-2-pyrazoline to give 3-methyl-4-(4-nitropheny1mercapto)-1 phenyl-5-imin0-2-pyrazoline.~~~ Druey and Schmidt391 have reported that alkylation of N-1 unwith dimethyl sulfate substituted 4,4-dialkyl-5-imino-2-pyrazolines occurs at the N-1 position. As illustrated in eq. 97, the acylation of 5-imino-2-pyrazolines
R’
NH
occurs on the 5-imino group rather than at C-4 as in the &ox0 analogs. However, the use of diethylmalonyl chloride gives acylation at both positions.322Aliphatic acid chlorides,391aliphatic anhydrides,325 aromatic acid chlorides340and sulfonyl chlorides325have been used as acylating agents. Carbon disulfide reacts with the imino group to give a bispyrazolylthi~urea.~~~ Nitrous acid diazotizes the 5-imino another argument for its existence in the tautomeric amino form. If insufficient nitrous acid to diazotize all of the 5-imino-2-pyrazolines is used, the resulting diazonium salt couples with undiazotized material, giving an iminoazo compound (XXV). The diazonium salt also couples with phenols. Moureu and Lazennec loZ5were unable to hydrolyze 3-alkyl-5~ ~ ~ to imino-2-pyrazolines to the 5 - O X 0 analogs, but C u ~ r n a n oclaims
Pyrazolin-5-ones
45
have hydrolyzed the imino group of 4-nitroso-l,3-diphenyl-5-imino-2pyrazoline to an 0x0 group using acid conditions.
I
RZ
(XXV)
Michaelis 996 has reported that oxidation of various 5-imino-2 pyrazolines with hydrogen peroxide or nitrous acid gives what were called azipyrazoles of type (XXVI). It seems highly unlikely that these
I
It' (XXVI)
products actually had the structure proposed. It may be that the conipounds formed were 5,5'-bis(5-imino-2-pyrazolines), as indicated in eq. 98, although the evidence is not completely consistent wit.h this interpretation. 5-Imino-2-pyrazolinesare listed in Table XII.
A few bis(2-pyrazolin-5-ones)having one or both 5-0x0 groups replaced by imino groups have been preparcd. The preparation of those having one imino group is shown in eqs. 99 and 100. Those linked
46
Part 1. Chapter I1
through the nitrogen atoms of the 5-imino group are listed in Table XIII. The usual preparation is reaction of a 5-imino-2-pyrazolinehaving no substituent on the 5-imino nitrogen with oxalic or phosgene.301 D. 3-Pyrazolin-5-ones
( 1) Syntheses
As has been mentioned previously (eq. 42, p. 26) the method most frequently used to synthesize 3-pyrazolin-5-ones is alkylation of 2pyrazolin-5-ones at N-2. I n general this can be used only for synthesis The earliest of 2-alkyl-, 2-aralkyl- and 2-heteroalkyl-3-pyrazolin-5-ones. workers used methyl iodide in methanol at temperatures of 1001 30°.806.818* 99a Other methylating agents used have been dimethyl 1173 dimethyl sulfate sulfate at temperatures of 100-130°,113*362~781~ with base,l1° d i a ~ o m e t h a n e methyl ,~~ iodide,141*1475 methyl iodide in the presence of sodium methoxide,1205methanol and dry hydrogen chloride at 140' 1508 and methyl p-toluenesulfonate in the presence of b ; t ~ e . ~A number ~ ~ * of~ other ~ ~short-chain ~ * ~ ~alkyl ~ halides, ~ such as ethyl iodide, ally1 chloride and isopropyl chloride with and without added base have been ~ s e d . ~Benzyl ~ ~ c . h l~ ~ ~ r i d~ e and ~ ~ *' ~ ~~ ~~ ~ ~ xanthhydrol 457 give 2-aralkyl-3-pyrazolin-5-ones. A variety of heteroalkyl chlorides have been condensed with 2-pyrazolin-5-ones using sodamide as the condensing agent.249The yields in these alkylations vary considerably, but in general the more complex the alkyl or aralkyl halide used the lower the yields. Methylation has been reported in yields of 85 per cent,781b u t benzylation occurs only to the extent of 15 per cent.250The usual yields appear to be 40-65 per cent. The chief side reaction occurring is 0-alkylation to give 5-alkoxypyrazoles. Of course, if there is only hydrogen at N-1, alkylation frequently occurs there ais0.54
As shown in eq. 3 (p. 9) the reaction of acyl arylhydrazines with *40*984* l o o l The /3-ketoesters forms 2-ary1-3-pyrazolin-5-0nes.~~~~ acyl group is lost in the cyclization and these products have no N-1 substituent. Formyl-, acetyl- and benzoylhydrazines may be used. This is a very frequently employed method for preparation of 2-aryl-3pyrazolin-5-ones. The condensing agents generally used have been phosphorus trichloride, phosphorus oxychloride and phosphorus pentachloride. A modification of this, also mentioned earlier, has been the condensation of a symmetrically substituted hydrazine with a 8ketoester to give 1,2-disubstituted-3-pyrazolin-5-0nes.~~~ 370 The sub9889
Pyrazolin-5-ones
47
stituents on N-1 and N-2 may be both alkyl or both aryl, although very few 1,2-diaryl-3-pyrazolin-5-ones are known. A large number of other syntheses of 3-pyrazolin-5-oneshave been reported, although most are not of importance as practical methods of preparation. These are illustrated in eqs. 101-113.
R’
R1C€I=CHCOOR2 + CeHSNHNH2 +
(102)EOS.
1568
R2=H or CH3
CH3 CeHsNHNHCOCH,
+
CHaOK
CH,CCH,CONHNHAr
II
R”HA4r
mso
+ 300.
(J6H)-i
(103)a47
‘H”\
CH, ,lL‘l
ArN
(106)sSs
Lecher, Parker and C ~ n n * report *~ that the cyclization of the hydrazone hydrazide, as in eq. 106, is the preferred synthesis for 2-aryl-3-rnethyl-3-pyrazolin-5-ones. A number of 4-heterocyclic-3-pyrazolin-5-ones have been prepared using the appropriate 4-substituted pyrazolinone in the usual reactions
48
Part 1.
Chapter I1
to form the particular heterocyclic ring. For example, 4-amino-2,3dimethyl-l-phenyl-3-pyrazolin-5-one has been condensed with 1,4diketones to form pyrazolinones substituted by p y r r o l e ~ Isatin . ~ ~ ~ has Ar
)--'-7
ArCH=CHCONHKHAr
h \N/\ N
H CeHsNCHaCH2CN
1. KOE. E,O
O
-I
c 6 H 5 N 7
7
(107)1333
H
(106)11aa
O
R
1. 140'
COOH
R= H or CH3
R3
CHO
)=(
R=-X
+
"A I R'
0
'3
CH=CCOR6
it3
R4CH2COR5 +
I
R2-N
I N I
R.1
\
(113)316. BBO
R'
0
been used in the Pfitzinger reaction with 4-acetyl-2,3-dimethyl-lphenyl-3-pyrazolin-5-one to give pyrazolinones substituted by quinolines.903
Pyrazolin-5-ones
49
(2) Properties
Like the 2-pyrazolin-5-ones, most of the 3-pyrazolin-5-ones are solids with a wide range of melting points. Among the 3-pyrazolin-5ones having only alkyl, heterocyclicalkyl and aryl substituents a number having four substituents are very high boiling liquids. Those having fewer substituents are all solids, as are those substituted by aralkyl and heterocyclic groups. Solubility varies greatly and no generalizations can be made. I n contrast to the 2-pyrazolin-5-ones, the 3-pyrazolin-5-ones are It does basic, but usually are not acidiceo7or only very weakly appear that 3-pyrazolin-5-oneshaving no M-1 substituent are more acid than those substituted at N-l,885presumably because they can tautomerize to the lactim structure (XIII). The basic nature of 3-pyrazolin&ones is demonstrated by their ability to form stable hydrochlorides, picrates, methiodides and other salts.B01* 818*984 The infrared and ultraviolet absorption of 3-pyrazolin-5-ones has been discussed previously in connection with the structures of these compounds. The vast majority of reactions undergone by 3-pyrazolin-5-ones occur at the 4-position. These pyrazolinones react by direct substitution, very much aa do activated benzene rings. Such reactions as halogenation, nitrosation, sulfonation, acylation, the Mannich reaction and many others give 4-substituted-3-pyrazolin-5-ones. 3-Pyrazolin-5-ones react with formaldehyde to give 4-hydroxymethyl-3-pyrazolin-5-ones(eq. 114).17 I n the presence of phenols
(eq. further condensation occurs, forming 4-benzyl-3-pyrazolin-5-ones 1 15).20.21 The phenol condenses in the para position. A similar reaction occurs with dia1k~lanilines.l~~~ The Mannich reaction is also a reaction
+
“’I\
CBH,
C,H,OH
+
CH,O
-
&OH
cH3---cHz-
CHJ-1
“’AO
\=z/
(115)
I
C,H,
with formaldehyde, but in the presence of amines and is readily undergone by 3-pyrazolin-5-ones. With aliphatic amines the products are 4-dialkylaminomethyl-3-pyrazolin-5-ones,110~ 637. 945 but aniline gives a 3 + c.a.c. 20
Part 1. Chapter I1
60
4-arylaminomethyl derivative.1483 When methylaniline is used a bispyrazolinone is also obtained by reaction at the amino group and at the 4-position of the aromatic ring.1483Hydroxylamines react analogously to dialkylamines with 3-pyrazolin-5-ones and f0rrna1dehyde.l~~~ Reactions of 3-pyrazolin-5-ones with chloral902*1190 are entirely analogous to their reactions with formaldehyde. This is illustrated in eq. 116. The reaction of aromatic aldehydes with 3-pyrazolin-5-onesis OH
analogous to the reaction of such aldehydes with 2-pyrazolin-5-ones, 988. 99a as except that the products are always bispyrazolinones,21*809. shown in eq. 117. Ar
+ 1
R'
ArCHO +
0 dl
O
0
1
It'
Nitrosation of 3-pyrazolin-5-ones is quite easy, commonly occurring in the 4-position (eq. 118). The usual reagent is nitrous a ~ i d1174 prepared , in~ situ by ~the use ~of sodium ~
I
Rl
~
~
-
nitrite and acid. However, nitrogen trioxide has also been used successfully.1oo1If a substituent is present in the 4-position and the 3-position is vacant, nitrosation occurs to give a 3-nitros0-3-pyrazolin-5-one.~~~ Halogenation of 3-pyrazolin-&ones with elemental chlorine, bromine, and iodine occurs readily t o form the corresponding halogenated ~ ~ m p ~ ~In thencase of d bromine, s .addition ~ ~ frequently occurs to give the 3,4-dibromo derivatives (eq. 119) which lose hydrogen bromide very readily and the usual product is the 4 - b r 0 m o - 3 - p y r a z o l i n - 5 - o n e . ~ O 9Various ~ ~ ~ ~ .other ~~~~~ agents ~ ~ ~ ~ also react with 3-pyrazolin-Ei-onesto introduce halogen at G 4 . Chlorination occurs with sodium h y p o ~ h l o r i t eand ~ ~phosphorus ~ pentachloride.'Ool
~
~
-
Pyrazolin &ones
51
N-Bromosuccinimide brominates 3-pyrazolin-5-onesbut an excess brominates alkyl groups in the 3 - p o ~ i t i o n . Iodination ~ ~ ~ . ~ ~ ~occurs by treatment of 3-pyrazolin-5-ones with mercuric chloride followed by iodine.lool R3--
R
R2A-i
3
q
7
R*N N/\ 1
R’
Y’b R1
0
__f R;yA-i-Br
“’\I
(119)
El
3-Pyrazolin-5-ones react with concentrated nitric acid809*860.888* or an excess of nitrous acidg84-992.1001 to form 4-nitro-3pyrazolin-6-ones. Presumably the excess of nitrous acid first nitrosates and this product is oxidized to the nitro compound. A variety of miscellaneous reactions which occur by substitution at C-4 are illustrated in the following equations. None of these reactions 992.1001
CH31=~
+
CI
has been used, or investigated, extensively. Benzyl chloride has also been used in reaction (121) and only one benzyl moiety is introduced. Reaction (125) may also give 3-substitution if the 4-position is blocked.972
Part 1 .
52
Chapter I1
Those 3-pyrazolin-5-ones which have no X-1 substituent can be alkylated at this position by use of methyl iodide in ~ i i e t h a n o l ~ ~ ~ ~ ~ ~ ~ or dimethyl sulfate (eq. 126).10010-Methylation occurs as a side-
CH3T=-I CH,N
"'\
+ (&H,NHCONHC&
I
+ CH31__1rCONHC6H, CH3N
-..Pi I 0
I 0 CBHJ
(124)828
CsH,
CH,
reaction. Krohs 860 has reported that halogenated pyridines, pyrimidines and thiazoles in the presence of sodamide react with the oxygen rather than the nitrogen (eq. 127). An analogous reaction occurs between such
3-pyrazolin-5-ones and benzenesulfonyl chloride and acyl chlorides to give O-acylpyrazoles.988~1001 The reaction of phosphorus oxychloride with 3-pyrazolin-&ones is rather similar t o the reaction with 2-pyrazolin-5-ones in that oxygen is replaced by halogen. I n those cases in which there is no substitution at N-1 and aryl substitution occurs at N-2, chloropyrazoles are formed,
+
RT===l Ar-N \
N'\ H
POCI,
-*r-L'--(, ,'. N F
O
(128)
C1
as shown in eq. 128.984-988*1001 This reaction takes a different course In these cases t.he when the N-2 substituent is alkyl or aralky1.700-795 N-2 substituent is eliminated (eq. 129). I n cases in which both nitrogen
Pyrazolin-5-ones
53
atoms are substituted, the 3-pyrazolin-5-oneis converted to a quaternary salt of a 5-chloropyrazole (eq. 130).789 The 3-pyrazolin-&one ring is stable to mild catalytic reductions, such as reduction with low pressure hydrogen in the presence of platinum or palladium catalyst.532.860 However, under extremely drastic conditions, hydrogen at-a pressure of 1000 atmospheres and a tem-
(130)
perature of 180" and nickel catalyst, ring cleavage occurs859 with elimination of one nitrogen atom and formation ofanilides (eq. 131). R3CH,CHC0NHR1
I
(131)
R4
Hot acid destroys the ring system of 3-pyrazolin-5-0nes.~~~~~~~ Various products have been reported from this reaction, depending upon substituents in the pyrazolinone ring and conditions. Destruction of the 3-pyrazolin-5-onering system with base 700 leads to a j?-ketoanilide. The reaction of zinc with 2,3-dimethyl-l-phenyl-3-pyrazolin-5-one has been reported by Knorr807to give benzene, aniline and unidentified products. Heymons and R ~ h l a n dtreated ~ ~ ~ 1,2-diphenyl-3-methy1-3pyrazolin-5-one with metallic sodium, obtaining addition of sodium a t the 1,4-position of the conjugated system present (eq. 132). CH,-
-I
lk
~
C'eHsN \
hT-
1%
CBH5
*
5
Na
cH3J--
'
CeHsN
"'\
I'
1
(132)
(IN&
C,H,
The compounds discussed in the previous sections are listed in Sections A, B, C , and D of Table XTV. 3-Pyrazolin-&ones having 3- and 4-a-hydroxyalkyl substituents are prepared in a number of ways. Two of these, alkylation of the corresponding 2-pyrazolin-5-one at N-2 and reaction of 3-pyrazolin-5ones with aliphatic aldehydes, have already been mentioned. The
Part 1. Chapter I1
54
reduction of 4-acyl substituents will be discussed in the section dealing with such 3-pyrazolin-&ones. A fourth method used has been the at elevated temperhydrolysis of 3-bromomethyl-3-pyrazolin-5-ones atures (eq. 133).532*s97 The reactions of these compounds are those of ZcHOCH,7=rC2H,
BrCHZ---C,H5 CH,NJ
HZO
"'\ I
'"\I
CH3N
4-N02C&,
0
I
(133)
0
4-NOPC,H4
alcohols and esters and of 3-pyrazolin-5-ones,except for a few special in mild acid solution form ones. 4-Hydroxymethyl-3-pyrazolin-5-ones 4,4'-bis( 3-pyrazolin-5-ones) (eq. 134).970The alcohols obtained by con-
-
---CH,OH %-N-I
"'\
I
CBH,
CH,-------CHT j,-l
" 4
0
CHz
PH3
P"
NCH3 (134)
0
I 0 Ct3H6
JBH6
densing chloral with 3-pyrazolin-5-ones decompose in the presence of potassium carbonate to give the corresponding 4-carboxaldehydes (eq. 135).107*196~889 This is the principal method used for preparation
of such aldehydes. These compounds are listed in Table XIV, Section E. Bodendorf and Ziegler 113 have reported the conversion of a 4-(1-hydroxy-2-methylaminopropyl)-3-pyrazolin-5-one into a 4-( 2oxopropyl)-3-pyrazolin-5-onein the presence of acid (eq. 13G).
CH,-----CH,I$-/
-:rcHcH,
HCI
CH3----CHZCOCHB
AHCHiHC1~~~4-1
';;"'.\ CBH,
(136)
"'\
I 0 CeHs
Only a few ol-alkylthiomethyl-3-pyrazolin-5-ones are known.1127 These have been prepared by reaction of mercaptans with 4-dimethylaminomethyl-2,3-dimethyl-l-phenyl-3-pyrazolin-5-one (eq. 137). These compounds are listed in Table XlV, Section E.
Pyrazolin-5-ones
55
The most frequently used method of preparation of compounds having nitrogen attached to a carbon atom which is substituted on the 3-pyrazolin-5-one ring is reaction of hydroxylamine, amines, hydrazines, hydrazides, etc., with 5-oxo-3-pyrazolin-4-carboxaldehydes.
This will be discussed in more detail in the section devoted to the reactions of the 4-carboxaldehydes. A frequently used method for preparing 4-dialkylaminomethyl-3-pyrazolin-5-onesis the Hoffmann A rather interesting method for preparing amines (eq. 138).697.1318.1319
synthesis of 4-benzsmidomethyl-3-pyrazolin-5-ones has been published by Monti.1°14N-Methylolbenzamide was condensed with 2,3-dimethyll-phenyl-3-pyrazolin-5-one (eq. 139).
The reactions of these compounds are for the most part normal for such functional groups. The only unusual one reported is the rearrangement shown in eq. 140.110*1483Hellmann and Schumachers3* have
reported that 4-dimethylaminomethy1-3-pyrazolin-5-ones can react ;t8 alkylating agents. Nitro- and formamidomalonic esters react with these
Part 1.
58
Chapter I1
pyrazolinones by elimination of dimethylamine and introduction of the 5-oxo-3-pyrazolin-4-methyl system into the ma,lonic ester (eq. 141).
I
AH3
CHq=---CH,K CH,N " \ '
- CH,I
+
OHCNHCH(COOCH,),
hH3
I 0 C,Hs
C830Ns
,CH,--CH&(COOCH3)a
cH3'EL AHCHO
(141)
ha& 0 This reaction is quite analogous to such alkylations with gramine. These compounds are listed in Table XIV, Section F. (3) Bis(3-pyrazolin-5-onea) Only a very few 4,4'-bis(3-pyrazolin-&ones) are known in which the rings are linked directly. These are prepared by methylation of 4,4'-bis(2-pyrazolin-5-ones) 807.809 or by treatment of the methiodides of 4-(5-chloropyrazol-4-y1)-3-pyrazolin-5-ones with alkali .99 These compounds are listed in Table XV. Bis(3-pyrazolin-5-ones)in which the linking chain is not attached to the pyrazolinone nucleus by functional groups are listed in Tables XVI and XVII. Most of these compounds have as the linking chain an arylidene group and are prepared by the reaction of 3-pyrazolin-5-ones as shown in eq. 117 (p. 50). with aryl aldehydes,66g~668~669~80'~1001~1133 Some aliphatic aldehydes have also been used in this reaction.409 3-Pyrazolin-5-ones react with formaldehyde or formamide to form the llS2 Under basic conditions corresponding bis compounds (eq. 142).910.
4-hydroxymethyl-3-pyrazolin-5-ones condense to form bispyrazolinones apparently by partial elimination of the 4-hydroxy(eq. 134),107*481 methyl group and the condensation of this product with unchanged starting material. Bis(2-pyrazolin-5-ones) can be converted into the as is done so corresponding 3-pyrazolin-5-onesby alkylation at N--2,ll6 frequently in the mononuclear series. 4,4'-Methylenebis(3-pyrazolin-5ones) have been prepared by reduction of the corresponding ketone with pEg6
Pyrazolin-5-ones
57
zinc and acid.740A variety of 3-pyrazolin-5-oneshaving a 4-acyl substituent react with various reagents to form bis(3-pyrazolin-5ones).31a~79g~90a These preparations are illustrated in eqs. 143-145. The
R'
R '
R'
Mannich reaction using primary amincs, when applied to 3-pyrazolin-5ones, forms bispyrazolinone~.~~~ Two more preparations of such compounds are shown in eqs. 146 and 147.
+
C6H&kCCOOCzH,
CH&H~CHXNNHC,H~ CzHs __f
CeHS--COHS-N
1\x/\ H
I
//'X/
O
O
PJ-C,H,
H
(146)
C6H5
C6H5
I
I
n
3*
rArCeH
CA-
(147)Ioe4 CH3K
Part 1. Chapter I1
58
Very little investigation of the reactions of bis(3-pyrazolin-&ones) has been done, but presumably the typical reactions occurring at C-4 in the mononuclear compounds would not occur. Ginzburg and cow o r k e r ~5 6~8 *~6sg~ have * published a number of papers concerned with oxidation of 4,4'-arylidenebis(3-pyrazolin-5-ones).A mixture of nitrous and nitric acids was used as the oxidant and the tertiary carbon atom connecting the pyrazolinone rings was oxidized to a carbinol (eq. 148). Pyrolysis of 4,4'- (4-dimethylaminobenzylidene)bis(2,3 -dimethyl-1phenyl-3-pyrazolin-5-one) in the presence of carbon dioxide at 175-1 80" has been reported1133to cause loss of hydrogen. AT
AT
E. 3-Pyrazolin-5-thiones and -5-selenones
A large number of 3-pyrazolin-5-thiones and a few 5-seleno analogs (Table XVIII) have been prepared. Almost all of these have been synthesized by reaction of the methochloride or methiodide of a 3- or 5halogenated pyrazole with potassium hydrogen 984. 988. gga potassium sulfide, sodium sulfide 981 or potassium hydrogen ~ e l e n i d e . ~ ~ ~ This method of synthesis is illustrated in eq. 149 for a 5-halopyrazole.
I n one case the substituents on the nitrogen atoms were both p h e n ~ 1 . ' ~ ~ Two other methods of synthesis of the 3-pyrazolin-5-thioneshave been reported. Michaelis 99a has claimed the conversion of 1,2-dimethyl-3phenyl-3-pyrazolin-5-one to the thione analog by reaction with potassium hydrogen sulfide. Worrall 1663 has reported the synthesis shown in eq. 150. Although comparatively little has been published concerning the properties and reactions of 3-pyrazolin-5-thionesand -5-selenones,it is apparent that in general they are very similar to the comparable 0x0
Pyrazolin-5-ones
59
compounds. These compounds are basic, forming stable salts with mineral acids.978.984* 986 They undergo nitration at C-4 and presumably would react similarly in other electrophilic substitutions. Reaction with CEH6-C.H,WCSNHR
+
H,NNH,
+
c6H57i-
(rN
HN
(150)
H N/\ S
'NY
halogens gives a perhalide having four atoms of halogen per molecule of p y r a z o l i n ~ n eThese . ~ ~ ~then ~ ~lose ~ ~ halogen readily to leave a dihalo derivative, which is probably the corresponding 4,5-dihalo-3-pyrazolidinethione or -3-pyrazolidineselenone.Alkylation of the sulfur or selenium or other atom occurs by heating the methiodide (eq. 151)984*988*992 .CHJ
"')
b
R2-_-
R I T I "P\
(151)
SCH,
AH3
alkyl iodides. The 3-pyrazolin-5-thionesare capable of oxidation at the sulfur atom and several such oxidation products have been reported. K i t a m ~ r a ' ~has ~* found ~ ~ ~that oxidation of 2,3-dimethyl-l-phenyl-3pyrazolin-5-thione with hydrogen peroxide gives 2,3-dimethyl-lphenyl-3-pyrazolin-5-one. K ~ r n a d a has ~ * oxidized ~ the same compound with chlorine, hydrogen peroxide, sodium hypochloride and perbenzoic acid to give what was called a dioxide, the structure of which was not reported. The oxidation of various 3-pyrazolin-5-thiones with gives what was called a p e r o ~ i d e ' ~or~with . ~ ~chloririe978~985~988~1001 ~ trioxide. It is possible that this is a zwitterion a9 shown in eq. 152. A
few 5-oxo-5'-thiono-,5,5'-thiono- and 5,5'-selenobis(3-pyrazolines)have been prepared by methods used for the mono compounds and they are listed in Table XV.785*986.gg1 F. 5-Imino-3-pyrazoliies
A number of 5-imino-3-pyrazolines are known and are listed in Table XIX. Those which have no subst,ituent at N-1 can exist as
Part 1.
60
Chapter IT
aminopyrazoles and probably are in this tautomeric form. Most preparative methods for these compounds depend upon conversion of chloropyrazoles or 3-pyrazolin-5-ones t o 5-imino-3-pyrazolines, although they can be formed directly from noncyclic compounds. This is shown in eq. 153.1025Michaelis has prepared 5-imino-3-pyrazolines by R'CEXCK
+
R'NHNHZ +
(153)
H
NH
reaction of the methochlorides of chloropyrazoles with ammonia or amines (eq. 154).985*996*1352 From an analogous reaction with aryl-
amines RiIichaelis1002suggested that the products were of the type (XXVII). It seems much more likely that these were 5-arylimino-3
-4r (XXBII)
pyrazolines. 5-Imino-3-pyrazolines can also be prepared by treatment of 5-imino-2-pyrazolino methiodides with sodium hydroxide.996 3-Pyrazolin-5-one hydrochlorides react with hydrazines a t about 100" to form 5-imino compounds (eq. 155).983 A similar reaction has
R'l=l.HCl + RZN
'x'g
ArNHKHz
R3-___f
R k1-'
I
R'
0
"'\I ?rNHAr
(155)
R'
been reported for 3-pyrazolin-5-thion~s.'~~~ Other syntheses are shown in equations 156826and 157.*02Very little has been published concerning reactions and properties of these compounds.
Pyrazolin -5-0110s
61
A few Fi-imino- and 5,5'-iminobis(3-pyrazolines) are listed in Table XV. These are prepared by reaction of the appropriate chloropyrazole inethiodide with
3. Hydroxy and Mercapfo Derivatives A. 2-Pyrazolin-5-ones
Both 3-hydroxy- and 4-hydroxy-2-pyrazolin-5-ones can exist theoretically and quite a number of 4-hydroxy compounds are known. are tautomeric with 3,5-pyrazoliThe 3-hydroxy-2-pyrazolin-5-ones dinediones which probably exist principally as the 3-hydroxy isomers. However, for the purposes of this discussion these compounds will be considered as diones. The most widely used and certainly most general procedure for is that developed by preparation of 4-hydroxy-2-pyrazolin-5-ones Veibel, Linholt and W e s t o ~ . ~ ~ Usually ~ ~ oxidations of 2-pyrazolin5-ones lead to formation of bispyrazolinones. These workers found that in alkaline solutions gave oxidation of 1-substituted-2-pyra.zolin-5-ones very good yields of the 4-hydroxy analogs (eq. 158). Oxidizing agents R3
used were hydroperoxides and oxygen. Acid media were also found to suppress the formation of bis(2-pyrazolin-&ones). Various other methods have been used for preparation of 4-hydroxy-2-pyrazolin-5ones but none extensively. Thoms and SchmuppI49' have used catalytic reduction of 2-pyrazolin-4,5-diones. The &OX0 group is reduced to hydroxyl in preference to other unsaturated centers. Bulow and Haas,262 with zinc and in reducing 4-phenylazo- and 4-nitro-2-pyrazolin-5-ones acetic acid, obtained as side-products 4-hydroxy-2-pyrazolin-5-ones. The oxidation of 4,4'-bis[3-methyl-1-(4-nitropheny1)-2-pyrazolin-5-one] with ferric chloride forms the corresponding mononuclear 4,4'-dihydroxy compound.690The condensation of a-acyloxy-/3-ketoesterswith
62
Part 1.
Chapter I1
an equivalent of phenylhydrazine gives rise to a 4-acyloxypyrazolinone, but excess phenylhydrazine forms the 4-hydroxy analog (eq. 159).372 CH3COCHCOOC,Hs f CeHsNHNH,
__f
cH3-
4
AO’
“\
bR R =H or acyl
I
(159)
c8H6
3-Alkoxy-2-pyrazolin-5-ones have been prepared by two methods. I n one of these a hydrazine is condensed with a /3-substituted ester (eq. 160).698.1143 The second is 0-alkylation of a 4,4-disubstituted-l-
substituted-3,5-pyrazolidinedione(eq. 161). The reagents used have R’
R’ (161)
CeH,
been diazomethane 41 and methyl iodide and potassium hydroxide.g94 With diazomethane N-alkylation also occurs. The only example with an alkoxy group in the 4-position found in the literature is 4-hydroxy-4methoxy-3-methyl-l-(4-nitrophenyl)-2-pyr~zo~n-5-one, obtained by repeated crystallization of the corresponding 4,4-dihydroxy compound from methanol.6s0 One method of preparing acyloxy-2-pyrazolin-5-oneshaa already been mentioned (eq. 159). The second method is acylation of 3,5pyrazolidinediones having no N-2 substituent (eq. 162). The acylations R2
OHN = ’ I -
R’
R3Co”_
R3COO--
\N
\
(162)
bl
have been achieved by use of acetic anhydride,1234benzoyl chloridegg8 and by trans-esterification.Zo0
Pyrazolin-5-ones
63
A number of 4-arylmercapto-2-pyrazolin-5-ones have been prepared by reaction of a 2-pyrazolin-5-one with aryl mercaptans (eq. It wa8 concluded that the first reaction was oxidation of the 163).27*28 CH3
4 I
+
ArSH
___+
cH3p
4
”’\
ySAr (163)
I
Ce.&
CBH5
mercaptan to a disulfide which then reacted with the pyrazolin-5-one. I n support of this theory it was found that disulfides give the same reaction. The same types of compounds were also prepared by reaction of 4-bromo-3-methyl-l-phenyl-2-pyrazolin-5-one with the sodium salts of various rnercaptan~.~’* 28 Takahashi and Yoshii 14?* have treated 6-ethoxy-5-methyl-6-carbethoxypyrido-[2,3 :2’,3’J-p-thiazine with hydrazine and obtained a 4-arylmercapto-2-pyazolin-5-one.This is scarcely a practical synthetic method. a-Arylmercapto- and a-acylmercaptoacetoacetic esters react with hydrazines to give sulfurcontaining substituents at G4.27 This group of compounds is listed in Table XX. A few bis(2-pyrazolin-5-ones) having alkoxy substituents are known and are listed in Table 111. These are prepared by addition of alcohols to the double bond connecting the pyrazolinone rings in pyrazole blue. A few 4,4’-bis(2-pyrazolin-5-ones) in which the rings are linked by sulfur atoms are known. The linking group is almost always disulfide and is prepared by oxidation of 2-pyrazolin-5-onessubstituted in the 4-position with mercaptoaryl groups.578These compounds are listed in Table VII. The few 3-acyloxy-5-imino-2-pyrazolines known are prepared by acylation of 5-imin0-3-pyrazolidinones.~~~. 5 9 4 * 1599 Crippa and Gaumeri 32 have treated 3-methyl-l-phenyl-5-imino-2-pyrazoline with p nitrophenylsulfenyl chloride to obtain a 4-arylmercapto compound. These compounds are listed in Table XII. B. 3-Pyrazolin-5-ones
The two possible hydroxy-3-pyrazolin-5-ones (3-hydroxy and 4hydroxy) are isomeric with pyrazolidinediones, the former with 3,S-pyrazolidinediones and the latter with 3,4-pyrazolidinediones. In conformity with the usage of this discussion the hydroxy-3-pyrazolin5-ones will be considered as the isomeric diones. However, the derivatives of the hydroxyl groups will be considered in this section. Konek
Part 1. Chapt.er I1
64
and Szasz 7 0 3 have methylated 4-acyloxy-3-methyl-1-phenyl-Z-pyrazolin-5-ones a t N-2 with methyl iodide t o give the 4-acyloxy-3-pyrazolin-5-ones. Treatment of 3,5-pyrazolidinediones having no substihent at the 4-position with diazomethane has been used by Arndt and cow o r k e r ~t o~give ~ 3-methoxy-3-pyrazolin-5-ones. It is necessary t o have a 2-substituent. 3-Acyloxy-3-pyrazolin-5-ones have been prepared in a similar fashion by acylation of 3,5-pyrazolidinediones.200~1048 A number have been synthesized by the reaction of 4-acyloxy-3-pyrazolin-5-ones of 2,3-dimethyl- 1-phenyl-3,4-pyrazolidinedione with various chlorinated aromatic compounds (eq. 164). The halogen in the aromatic halide waa C & - n i = O CH,N
+
Iir~l
C,H,
CHzl----CH,N- T O A r
(164)
X ‘ \’
‘Xi\
I
-
0
I
0
C,H5
usually quite active, for example picryl chloride. The preparation of sulfur analogs of these compounds according to eq. 165 has been CH,SC,H,
OH
reported by Poppelsdorf and Holt. 1127 These compounds are listed in Table XXI. The only bis(3-pyrazolin-5-one) having alkoxy or aryloxy substituents has been prepared as shown in eq. 164, except that a disubstituted aromatic compound was This compound is included in Table XVI. Bis(3-pyrazolin-5-ones) having the 4,4‘-positions connected by a disulfide bridge have been prepared by the action of sulfur dichloride (eq. 166).8.848The same on 2,3-dimethyl-l-phenyl-3-pyrazolin-5-one
type of compound is formed as a by-product in the reaction of 4-bromo2,3-dimethyl-l-phenyl-3-pyrazolin-5-one with potassium thiocyanate to form the 4-thiocyano compound742 and also by treatment of the 4thiocyano compound with acid, base or heat.742The disulfides shown as
Pyrazolin-5-onee
65
products in eq. 166 have been reported by K ~ n e to k ~react ~ ~with mercury to give products of the type (XXVIII). A few bis(3-pyrazolinNR
CHC--S-H~*--J~~==~CAI
‘7
”
/
0 ‘ C*H,
0
&HE
(XXVIII)
5-ones) in which the pyrazolinone rings are linked by selenium in the 4,4’-positions are known. Preparation of these is by the reaction of mono-3-pyrazolin-5-ones with selenium,545selenium selet e t r a ~ h l o r i d eIn . ~the ~ ~ first two cases the nium d i ~ h l o r i d or e ~selenium ~~ bridge is one selenium atom; in the third there is a mixture of selenide
-Se-
4 . In the last case the bridge Se is a dichloroselenide function. These last two types of bridge systems and a two-atom bridge of the type
CH3--
rCH,
p
C € 1‘N3 k - I ’ T C H 3 N/ I 0 C8HS X =C1, or Se
~
CH3-CH3&-CseATZ N ‘\’
d*H,
/
I , O CBHl
0
N’
(167)
1 CsH,
can be converted into monoselenides by base, acid or heat treatment (eq. 167). These bispyrazolinones are listed in Table XVI. 4. Amino, Imino, Hydrazino, Azo and Related Derivatives A. 2-Pyrazolii-5-ones
All functional groups having nitrogen attached to the pyrazolinone nucleus are considered in this section except nitroso, nitro and some oximes. Only those oximes which cannot be considered as tautomeric with the nitroso group are discussed here. Hydrazones are in this section. These compounds are listed in Tables XXII and XXIII. All of these derivatives of 2-pyrazolin-5-oneshave a nitrogen atom substituted at the 4-position as the 3-nitrogen-substituted-2-pyrazolin5-ones are tautomeric with the 5-imino-3-pyrazolidinonesand are considered as such in this discussion. The 4-nitrogen-substituted-2pyrazolin-5-ones are not usually prepared by cyclization directly to the desired pyrazolinone ring but rather by modification of already formed pyrazolinones. The methods used are usually those employed in
Part 1. Chapter I1
66
preparing such derivatives in aliphatic or aromatic compounds. For example, 4-amino-2-pyrazolin-5-ones in which the amine is primary are prepared by reduction of 4-oximino-, 4-nitro- or 4-azo-2-pyrazolin5-ones. For the reduction of 0 x i m e ~ Og2 ~ 8 and n i t r o - g r o ~ p s * ~ * ~ ~ ~ ~ stannous chloride has been commonly used. Azo compounds have been reduced catalytically with hydrogen"O and with a zinc and acid mixture.307Michaelis and co-workers~gshave reported the oxidation of 4-phenylazo-3-methyl-I-phenyl-5-imino-2-pyrazoline to a fused pyrazolinone-azirane system aa shown in eq. 168 and subsequent CHS-1-
4 I
N=NCd%
NaNOa __j
"ANH
cH331N:.,,, "
c H 3 ~ ~ + , H 54 N'
'I
CeH5
&BH5
\
I 0 CsH5
reduction of this to the 4-amino-2-pyrazolin-5-one which was isolated only aa its oxidation product, rubazonic acid. The structure proposed for the intermediate seems most unlikely. Four methods have been reported for the direct preparation (i.e., with no amino intermediate) of secondary and tertiary 4-amino-2-pyrazolin-5-ones. Only one product has been synthesized by each of these routes. M a e d ~ Ohas ~ ~heated 2,3-dimethyl-4-dimethylamino-l-phenyl-3-pyrazolin-5-one (aminopyrine) in the presence of salicylic acid or barbital causing rearrangement of the 2-methyl substituent to the 4-position (eq. 169). I n the
oxidation of 3-methyl-l-phenyl-2-pyrazolin-5-one with nitrobenzene P e r r o n ~ i t o has l ~ ~found ~ that the principal product is the expected is bispyrazolinone, but 4-snilino-3-methyl-l-phenyl-2-pyrazolin-5-one also formed. This may occur through reaction of nitrobenzene reduction products formed by oxidation of some of the 3-pyrazolin-5-one. The cyclization of a tertiary amino /?-aldehydoester to a pyrazolinone has Itanosg5has used a method for preparation been reported (eq. 170).1537 OHCCHCOOC,H5 CH3AcHCOOC,H,
1
CHO
+
C,H,NHNH,
+
EIICH=NNHCoH5
' "'1I &OOC,H,
JsH5
(170)
Pyrazolin-5-ones
67
of such compounds that may be fundamentally the same as that of Perroncito, the reaction of an amine with a 2-pyrazolin-&one in the presence of an oxidant (eq. 171).
4-Imino-2-pyrazolin-5-ones of the type (XXIX) have become very important in the field of color photography and will be discussed in
ANR3
R 2 7 -
"\ dl
(XXIX)
more detail in respect to this use. They have been particularly investigated at Eastman Kodak by Weissberger and Vittum who oxidized an alkaline solution of a 2-pyrazolin-&one and 2-amino-5-diethylaminotoluene with silver nitrate or silver chloride (eq. 172) to obtain the
CH3
(172)
desired 4-iminopyrazolinones. Gerbeaux519 has used the same procedure and in addition has used potassium ferricyanide and sodium hypochlorite as oxidizing agents. Mann rand HaworthgP3and Gerbeaux519 have taken advantage of the active hydrogen atoms in the 4-position of 2-pyrazolin-5-ones for the preparation of the imino derivatives. Various aromatic nitroso compounds were condensed with X-pyrazolin5-ones (eq. 173). Brooker and White240have prepared this same type R
+
J 2
'K
\
dl
O
R~~ K O --+
"=T " \o
I
R'
(173)
Part 1.
68
Chapter I1
of compound by reaction of 4-nitroso (or oximino)-2-pyrazolin-5-ones with quaternary salts of heterocyclic compounds having active hydrogen on a methyl substituent (eq. 174).Similar products are obtained by
+
q '7 a
R'--NO
n
R3
C-CHa \ NP,
---+
R4 I X-
' 'N
R1
n '
R2-------- NCH=C
R3
N'
I
dl
R4
\
(174)
O
the reaction of 4-benzylidene-2-pyrazolin-5-oneswith aromatic a r n i n e ~ . 'The ~ ~ ~benzylidene group is replaced by an arylimino group (eq. 175). CH,
4 1A \=/
OCH3 i- (C2H&XQ-NH2
-CH
\N
I
CH'S
(173)
CBIh
Synthesis of 4-amino-2-pyrazolin-5-ones is usually achieved by treatment of an a-amido-/3-aldehydo- or /3-ketoester with hydrazines according to the classical method for preparation of %-pyrazolin-5-ones. Variants on this procedure consist of using an a-amidoester which has /+substituents whose reaction is equivalent to that of a ,!I-carbonyl substituent. Such compounds are D-benzylpenicilloic acid a-methyl ester,lo2' ethyl ~ h e n y l p e n a l d a t eand ~ ~ ~the acetal of an a-amido-pformyl ester.59*243 Cornforth has isomerized 2-phenyl-4-hydrazinoThe same methylidyneoxazolidone to d-benzamido-2-pyrazolin-5-one. compound was obtained by treatment of 1-ethoxyvinyl-2-phenyloxazolidone with p h e n y l h y d r a ~ i n e . ~ ~ ~ The synthesis of 4-azo-3-methyl-l-phenyl-2-pyrazolin-5-one is shown in eq. 176.114* The +hydrazones of 2-pyrazolin-4,5-diones have .OH
+
__j
I so,
CH3-
+
.
Pyrazolin-5-ones
69
been prepared by Auwers and c o - ~ o r k e r who s ~ ~ used the reaction of a hydrazine with the 4,Fi-diOne (eq. 177). This same compound was CH,
F\"\r o
+
C,H,N?JH2
N
+
4
CH3r=N (177) \Iv
AH3
AeH,
\
AH3
h a 6
synthesized by methylation of 3-methyl-4-phenylazo-l-phenyl-2pyrazolin-5-one and by cyclization of the bis(phenylmethy1hydrazone) of ethyl a,P-diketobutyrate. These compounds are listed in Table XXI. The 4-amino-2-pyrazolin-5-ones react as do other arnines. They can be alkylated with alkyl halidesgg2and react with aldehydes to form Schiff base^."^.^^^ Oxidation of these amino compounds with ferric chloride leads to the rubazonic acids (eq. 178) in which two 2-pyrazolin-
R2i--r..H, "b' I
R'
R2/,N--,j?R2 N
"-% 1
R'
0
A N / 0 A 1
(178)
5-one rings are connected at the 4,4'-position by nitrogen having no hydrogen. Rubazonic acid itself is 4-(3-methyl-1-phenyl-5-0x0-2-pyrazolin-4ylideneamino)-3-methyl-l-phenyl-2-pyrazolin-5-one. 4-Arylimino-2pyrazolin-&ones are readily reduced to the corresponding 4-arylamino2-pyrazolin-5-0nes.~~~~ 2-Pyrazolin-5-ones react with 4-arylimino-2pyrazolin-5-ones to give bispyrazolinones (eq. 179).1538
4-Arylazo-2-pyrazolin-5-ones are strongly colored and have good dyeing properties. These compounds have been prepared in vast numbers for use in dyeing all types of fabrics and are of great importance in the dye industry. They will be discussed fully from this viewpoint in the section dealing with pyrazolinone dyes. The 4-arylazo-2-pyrazolin5-ones are listed in Table XXIII. Of the many methods which have been used for preparing 4arylazo-2-pyrazolin-5-onesby far the most important is the direct coupling of a diazonium salt with a 2-pyrazolin-&one (eq. 41).77.809.813.818.980~1251 This reaction goes extremely readily with
Chapter I1
Pert 1.
70
practically all 2-pyrazolin-4-ones having no 4-substituent. Coupling occurs with any aromatic amine capable of forming a diazonium salt and under a wide variety of conditions. Even 4-substituted-2-pyrazolin5-ones have been reported to react with diazonium salts by replacement of the 4-substituent to form a 4-arylazo-2-pyrazolin-5-one. Substituents replaced have been t r i a r ~ l m e t h y l , ~a~ ~ ' y l and ~ ~ halogen.1514 l 4,4'Arylidenebis(2-pyrazolin-5-ones)react with diazonium salts to form 4-arylazo compounds (eq. 180).1255.1351 A variation of this procedure is Ar'
I
+
&N,X
-
R'
R'
reaction of a 5-acyloxypyrazole with a diazonium salt.5g1This reaction hydrolyzes the ester linkage and, if an acyl substituent is present at the 4-position, replaces it to form 4-arylazo-2-pyrazolin-5-ones (eq. 181).
R*rxR3 +
\N
I
R'
OCOR'
ArNaX
__f
N=NAr
RaJr-J\ "
I
(181)
R'
R3= H or R'CO
A method frequently used and capable of a large number of variations is the cyclization of a-substituted-p-ketoesters,amides or hydrazides with hydrazinea to 4-arylazo-2-pyrazolin-5-ones. One variant of this is the treatment of an a,p-diketoester with hydrazine (eq. 182).627* l w 3 -1574.1 5 ' ~ Instead of the ester, hydrazides of a$-diketoacids
Ar
have been used.99A very similar synthesis is the use of an a-oximinop-ketoester and a h y d r a ~ i n eAlso . ~ ~ quite similar is the cyclization of an or or$-diketoa-hydrazone of an a,/?-diketoestera55.259'262.314.732 amideZ6lwith a hydrazine. The bishydrazones of a,/?-diketoestersalso 257 It is react with hydrazines to form 4-arylaz0-2-pyrazolin-5-ones.~~~~ not necessary that the a-substituent be unsaturated. a-Amino-p-ketoesters,1535a-chloro-p-ketoesters1513.1514 and a-acyloxyesters372 have
71
Pyrazolin-5-ones
also been used (eq. 183). Apparently an oxidation of a hydrazino to an azo function occurs in the course of the reaction. RCOCHCOOC2HS
I X
+ 2ArNHNH2
4
(183)
"\
X=CI, Br, NH, or CH,COO
h
Cyclization of a variety of bishydrazones of a,B-diketoacid~,~~* 285 a,/3-diketoester~~~*~~~* 397-732. 782 and a , / M i k e t o a r n i d e ~ ,using ~ ~ ~ either acid, base or heat, to 4-arylazo-2-pyrazolin-5-ones has been reported (eq. 184). I n this reaction the aryl groups have usually been the same
Ra=OH, WDH6or NH,
1r1 b
although Kleene 782 has used different aryl groups. Another modification of this reaction is due to Chargaff and M a g a ~ a n i k , ~ who * ~ report that oxidation of the 1,2-bisphenylhydrazoneof mesoxaldehyde gave rise to 4-phen ylazo - 1-pheny1-2-pyrazolin-5-one. F i ~ h t e has r ~ reported ~~ an arylazopyrazolinone as one of the products from the reaction of a,a'-dibromo-a-methylsuccinicacid with p-bromophenylhydrazine (eq. 185). Br
4-BksH4
Huebner and Links70 have prepared 4-arylazo-2-pyrazolin-5-ones by the reaction of hydrazines with 4-hydroxycoumarin, 3,3'-methylenebis(4-hydroxycoumarin) and with 2,3,4-triketochroman derivatives. In the case of the 4-hydroxycoumarins oxidation by phenylhydrazine occurs to give the bisphenylhydrazone of an a,@-ketoester.The reaction then proceeds rm previously discussed for such compounds. Bulow and Hecking 263 have treated 4-arylazoisoxazolidoneswith hydrazines to form 4-arylazo-2-pyrazolin-5-ones (eq. 186) and other heterocycles undergo similar transformations.l18
i)
R
b
Part 1.
72
Chapter I1
A number of 2-pyrazolin-5-ones having substituents at C-4 react with arylhydrezines by replacement of the substituent to give 4-arylazo derivatives. These syntheses are illustrated in eqs. 187 and 188. xa---.-O
L
" \o
I
iArNHNH2
1%'
+
CH3-,--C1
CBH$"HNHs
4% deH,
__f
]tZ-----
"J\
N-=Nh (187) 12s.680
I
R' cH3--p
J J " I
N=NCBH,
\
( 188)151*
CBH,
Ridi llE5has reported that the reaction of 2,3-dimethyl-l-phenyl4-nitroso-3-pyrazolin-5-one with phenylhydrazine gives 4-phenylazo-3methyl-l-phenyl-2-pyrazolin-5-one. This may occur by replacement of the methylphenylhydrazine moiety in the 3-pyrazolin-5-oneby phenylhydrazine. The 4-oximino-2-pyrazolin-4-one could then react with phenylhydrazine t o give the reported product. Although in this discussion the 4-arylazo-2-pyrazolin-5-ones have been written as &OX0 compounds, it is likely that they exist largely in the tautomeric en01 form.262 The methylation of 4-arylazo-2-pyrazolin-5-ones has already been mentioned.52 Nitration occurs with replacement of the 4-arylazo group.262Reduction occurs readily but two different paths are followed. As mentioned earlier, 4-amino-2-pyrazolin-5-ones can be obtained by catalytic reduction 670 and with zinc and hydrochloric acid.397However, reduction with zinc and acetic acid leads to rubazonic acids (eq. 189).
The conditions which determine the course of this reduction are not known. The most important reactions of 4-arylazo-2-pyrazolin-5-ones are those with various salts to form metal complexes. These products are of great importance in the dye industry and will be discussed more completely in the section devoted to dyes. Chromium complexes are prepared by reaction of a 4-arylazo-2-pyrazolin-5-one with inorganic compounds213- 1457 including chromium sulfate 475 and chromium trifluoride,l*l6 with organic chromium compounds, such as chromium
73
Pyrazolin-5-ones
f ~ r m a t and e~~ chromium ~ complexes with salicylic acid.207Copper,213 lead,213 zinc 1616 and cobalt l 6 O 0 have also been used. The aromatic moiety of the arylazo group usually has a hydroxyl or carboxyl group ortho to the azo linkage. The complexes thus obtained with chromium contain either one or two molecules of the dye per atom of
-
I-
Na+
SOeNH,
(XXXI)
metal. The metal atoms react with the (2-5 oxygen of the pyrazolinone ring in its enol form and with the hydroxyl group of the aromatic ring to form more or less covalent bonds. There is also electron donation by other oxygen atoms and by the azo nitrogen atoms to the metal atom. The structure (XXX) has been proposed for 1 : 1 ~ o m p l e x e sand ' ~ ~ ~ ~ ~ ~ ~ ~ (XXXI) for 2 : 1 c0mplexes.~~59
Part 1. Chapter I1
74
Amino-substituted bis(2-pyrazolin-5-ones)have been prepared in which the rings are linked by carbon chains or by nitrogen atoms. The former are listed in Tables VIII and I X and the latter in Tables V I I and VIII. In most of those cases in which carbon chains link the two rings the amino substituents are introduced as they are in monop y r a z ~ l i n o n e s . ~ Eisner, ~ ~ * * ~Elvidge ~ and Linstead419 have prepared some amino bis(2-pyrazolin-5-ones) by direct cyclization (eq. 190). (CaH~OOC)~CHCOCH~HCOCH(COOC2Hs)l + C,H,NHNHz
Some 1,1'-bis(4-arylideneamino-2-pyrazolin-5-ones) have been prepared by Furuya and Ueno 494 by treating bis(2-pyrazolin-5-ones) with oxidizing agents in the presence of arylamines. The best known series of amino bis(2-pyrazolin-5-ones) is the rubazonic acid series. I n this case the two rings are linked by a single nitrogen atom. The preparation of rubazonic acid itself by oxidation with ferric chloride of 4-amino-3-methyl-l-phenyl-2-pyrazolin-5-one has already been mentioned (eq. 178).809 This is a general method for the preparation of rubazonic 397*611 although other oxidizing agents are sometimes used.480Votocek and Wichterle 15~' have reported the isolation of a rubazonic acid analog as a side-product in the reduction of 4-oximino-3-phenyl-l-(2-phenethyl)-2-pyrazolin-5-one to the corresponding amine using zinc and acetic acid. The reduction of 4-phenylazo-2-pyrazolin-5-one haa also been found to give a rubazonic acid.1552Wohl and Doll1676have prepared rubazonic acid analogs by the reaction of an a,P-diketoester with hydrazine (eq. 191) and a someR'COCOCOORa
+ H2NNH2
- RIJ-,,-/B"l 'z'
/
0
"
(191)
H
what analogous method has been reported by Wislicenus and Moureu, Choivin and Petitloz2 have obtained a very low yield of a rubazonic acid by the reaction of ethyl cr-bromocinnamate with phenylhydrazine. 4,4'-Bis(2-pyrazolin-5-ones) linked by a single azo group and by --N=N-R-N=Nhave been reported, although these compounds are very few. Diazotization of 4-amino-2-pyrazolin-5-ones
Pyrazolin-5-ones
76
followed by coupling with an appropriate acetoacetic ester derivative and cyclization gives 4,4'-azobis(2-pyrazolin-5-0nes).~~~~ von Walther and R o t h a ~ k e have r ~ ~ claimed ~~ that the reaction of 4,4-dichloro-3methyl-l-phenyl-2-pyrazolin-5-one and 3-methyl-1-phenyl-2-pyrazolin5-one in the presence of hydrazine gives the same type of product. The compounds having two azo groups in the chain are prepared by coupling of tetrazotized diamines with acetoacetic esters followed by cyclization to 2-pyrazolin-5-0nes,~~~ coupling of tetrazotized diamines with pyraz~linones,~~'. 1245*1359 or a combination of these.259 Priewe and Poljak114' reduced 5-oxo-2-pyrazolin-4-oximeswith hydrogen or sodium hyposulfite and obtained 4,4'-bis(5-0~0-2-pyrazolin-4-yl)hydrazines. Oxidation of these compounds gave 4,4'-aZO derivatives. 3,3'Tmino bis(2-pyrazolin-&ones) have been prepared by condensation of 3-amino-1-aryl-2-pyrazolin-5-ones ( 1-aryl-5-imino-2-pyrazolidinones) with ammonia or amines (eq. 192).595*59e R
The most interesting of the aminobispyrazolinones are the rubazonic acids having the =N- linkage. These compounds are quite strong acids, although no quantitative data on this are available. As would be expected, reduction of the extranuclear C=Noccurs readily with stannous chloride to give the corresponding tertiary amine. Rubazonic acid is decomposed completely by sodium hydroxide and reverts to a monomer (eq. 193) upon treatment with phenylhydrazine.809.992The NaOR
- I
CH,CCOCOOH II
~HC,H, (193)
3,3'-iminobia(2-pyrazolin-5-ones)react with formaldehyde and ethyl orthoformate at the reactive 4,4'-positions to give tricyclic comp o u n d ~ If . ~there ~ ~ is no substituent on the linking nitrogen atom, reaction with dimethyl sulfate causes methylation at this nitrogen.705
76
Part 1.
Chapter TI
Treatment with chlorosulfonic acid gives sulfonation in the benzene ring, when present.705 Michaelis and co-workersggOhave prepared 3-methyl- l-phenyl-4phenylazo-2-pyrazolin-5-thioneby coupling of the corresponding pyrazolinthione with phenyldiazonium chloride. 5-Imino-2-pyrazolines having nitrogen substituents a t the 4position have been reported by Michaelis and c o - w o r k e r ~ 996. ~ ~Ioo2 ~* The 4-amino compounds have been prepared by reduction of 4-oximino analogs1002and by reduction of arylazopyrazoles 995 (eq. 194) with
mild reducing agents, such as sodium hydrosulfite. These amino compounds react with ketones and isocyanates as do other amines. 4Arylazo-5-imino-2-pyrazolines have been prepared ;19 are the 5-Ox0 analogs.ggsThese compounds are listed in Table XII. B. 3-Pyrazolin-5-ones
3-Pyrazolin-5-ones having nitrogen substituents in the 3- or 4-positions, except primary amino, secondary amino, amido having hydrogen on the nitrogen, nitroso and nitro are discussed in this section. Although primary and secondary amino- and amido-3-pyrazolin-5-ones undoubtedly exist as the 3-pyrazolin-5-one tautomer, they are discussed under the heading of the 4-imino-3-pyrazolidinone and 5 imino-3-pyrazolidinone tautomers because of the convention adopted in this discussion regarding compounds having such tautomeric possibilities. These compounds are listed in Table XXIV. The most important amino-3-pyrazolin-5-one is aminopyrine, which is 4-dimethylamino-2,3-dimethyl-l-phenyl-3-pyrazolin-5-one. This compound has been widely used as an antipyretic and analgesic, particularly in Europe, and as a consequence its preparation and chemistry have been studied extensively. Most of the methods used have been those for synthesizing 4-dialkylamino-2-pyrazolin-5-ones used for the 4-dimethylamino compounds. Most syntheses of tertiary amino-3-pyrazolin-5-ones are based on an alkylation by one means or another of the primary or secondary amino analogs. I n some cases simultaneous reduction of a nitroso or nitro compound or of a Schiff base and alkylation of the amine so formed is carried out . 4-Dimethy lamino-3-pyrazolin-5-ones (amino-
Pyrazolin-5-ones
77
pyrine and analogs) have been synthesized by application of the Eschweiler-Clarke procedure to 4-amino-3-pyrazolin-5-ones(eq. 195).548,860.941Other alkylating agents used have been alkyl CHZO
___, HCOOH
(195)
halides,130* dimethyl sulfate 984. 992 and methyl-p-toluenesulf ~ n a t e . l 3-Pyrazolin-5-ones l~~ dialkylated a t N-4 have frequently been prepared by alkylation of the primary amine by such means as treatment with an aldehyde111s172and reduction of the Schiff base followed by alkylation. The final alkylation has been achieved by treatment with an alkyl halide,524*1298 by heating with an amine hydrochloride'll and by treatment with an aldehyde followed by reduction.860 A special type of alkylation of secondary amines is that reported by Bochmiihl and Stein.lo5 Secondary amines were treated with formaldehyde and sulfur dioxide or an alkali bisulfite to give an aminomethanesulfonic acid (eq. 196). Several patents have reported the synthesis of amino-
-
R2 C H 3 - q - N HI
CH3N 'X'\
L
RS
C H 3 7 - w ~I NCH2SOJH CH3N
(196)
"/'\ I Rl
O
0
pyrine starting with reduction of 4-nitroso-2,3-dimethyl-3-pyrazolin-5one with sodium bisulfite to give the 4-sulfamino analog (eq. 197). This CH~T---?IO CH3--N 'X/\ I 0 C6H5
1
-
CH3~--rNHS03H
CHa-N
\ ' y
CeH5
-
cH37==/N,LH, CH3
CH3-N
\n
3
(197)
is then methylated by various means. The most common method is use of formaldehyde and formic a ~ i d . ~ ~ 1174 ~ .Alkylation ~ ~ ~ ,with ~ ~ ~ . ~ ~ ~ . dimethyl sulfate 144. 1256 and electrolysis in the presence of formaldehyde and sulfuric acid691have also been used. Reduction of 4-nitroso-2,3-dimethyl-l-phenyl-3-pyrazolin-5-one with zinc or iron and a ~ i d or ~ catalytically551 ~ ~ * ~ in ~ the ~ presence * ~ ~ ~ of formaldehyde also gives aminopyrine. The analogous 4-nitro compound can also be reduced catalytically in the presence of formaldehyde
78
Part 1. Chapter I1
to form arnin~pyrine.~~O* 1356 Sonn and Litten 1320 have replaced the bromine atom in 4-bromo-3-benzyl-2-methyl-l-phenyl-3-pyrazolin-5one with dimethylamine. A variety of 4-amino-5-alkoxy- and acyloxy-1,3-disubstitutedpyrazoles have been treated with alkylating agents such as alkyl halides to give 4-dialkylamin0-3-pyrazolin-5-ones.~~~ There is a simultaneous alkylation of ring nitrogen and extranuclear nitrogen. The reported decomposition of 4-dimethyltriazeno-2,3-dimethyl-lphenyl-3-pyrazolin-5-oneto a r n i n ~ p y r i n e has ~ ~ ~ been shown by Stoltz 1353 to be incorrect. Most 4-amido-3-pyrazolin-5-ones have been prepared either by acylation of secondary amines 537* 1471 (4-alkylimino-3-pyrazolidinones) or by acylation of the primary amine 1471 followed by a l k y l a t i ~ n Shimidzu . ~ ~ ~ 1297 has reported the replacement of a methyl group by a cyan0 group and conversion of this to a thiourea (eq. 198). 618n
CH,
I
CsHs
4-Amino-3-pyrazolin-5-ones (4-imino-3-pyrazolidinones) react with aldehydes and ketones to form 4-alkylidene- and arylideneamino-3pyrazoIin-5-0nes.~~~. 984* 1365*1592 Formaldehyde,172aromatic aldeh y d e ~heterocyclic ,~~~ aldehydes lm4*1186 and aromatic ketones g92 have been used. Eisenstaedt 417 and Emerson and Kelly426have prepared somewhat similar compounds by condensation of 4-amino-3-pyrazolin5-ones with phenols and various amines in the presence of oxidizing agents, such as ferric chloride and potrtssium ferricyanide (eq. 199).
.99)
The same type of condensation occurs with 2-pyrazolin-5-ones having no substituent in the 4 - p o ~ i t i o nHere, . ~ ~ ~of course, it is unnecessary for
Pyrazolin-5-onea
79
the aromatic ring to assume a quinnooid form, as the 3-pyrazolin-$one analogs do, since two active hydrogen atoms are present on the C-4. 4-Amino-2-pyrazolin-5-onesreact with Schiff bases to form the 4arylideneamin0-3-pyrazolin-5-ones.~~~ R u b t s o ~reports ~ ~ ~ the ~ condensation of this amine with sodium 1,2-naphthoquinone-4-sulfonab to give a quinoncimine by replacement of the sulfonate group. The 4-arylideneamino substituent has been introduced by condensation of a 4-nitroso-3-pyrazolin-5-one with f l u o r e n e ~The . ~ ~condensation ~ occurs at the active methylene group of the fluorene. Michaelis and coworkerslOol have prepared a compound which they believe to have a sulfur-nitrogen double bond at least formally similar to the > C-Nsubstituents discussed here. This was prepared by condensation of a 4-amino-3-pyrazolin-5-one with thionyl chloride and supposedly gave a 4-OS-Nsubstituent. However, it appears unlikely that this type of compound W M actually prepared. The only amino 4,4’-bis(3-pyrazolin-5-one) reported is N,N’[bis(2,3-dimethyl-1-phenyl- 5 - 0x0 -3-pyrazolin- 4-yl)l -N,8’dimethylmethylenediamine prepared by acid treatment of the sodium salt of N-sulfomethyl-N-methylaminoantipyrine with 4-Amino-3-pyrazolin-5-ones (4-imino-3-pyrrtzolidinones)react with nitrous acid as do ordinary aromatic amines to form diazonium salts.426.984~ 1353 These then couple readily with aromatic 1323 and aliphatic compounds having amines,1017.1018.lo60 phenolssg2~ active hydrogen atom,426~1017 such aa acetoacetic esters. The products are 4-azo-3-pyrazolin-5-ones (eq. 200). The diazonium salts also couple
CaH,
with 2-pyrazolin-5-onesin the 4 - p o ~ i t i o nSimilar . ~ ~ ~ compounds can be prepared by the coupling of an aromatic diazonium salt with a 3pyrazolin-5-one. Coupling occurs in these cases either at the 3- or the 4-position, whichever is u n s u b ~ t i t u t e d .loo4 ~ ~ ~Huebner * and Linka70 prepared 4-arylazo-3-pyrazolin-5-onesby reaction of 2,3,4-trioxochromane-3,4-bis(phenylhydrazone) and 3-arylhydrazone with phenylhydrazine. The 3-arylhydrazone group becomes the 4-arylazo group in the final product.
Parb I.
80
Chapter I1
The preparation of l-(2,3-dimethyl-l-phenyl-5-oxo-3-pyrazolin-4yl)-3,3-dialkyltriazeneshas been accomplished by reaction of 2,3dimethyl-l-phenyl-5-oxo-3-pyrazolin-4-diazoniumchloride with dialkylamines (eq. 201).1353 The previously reported method of preparation527was found to be in error.
I
CeH3
2,3-Dimethyl-l-phenyl-5-oxo-3-pyrazolin-4-diazonium chloride reacts with hydrazoic acid to form the corresponding 4 - a ~ i d eT.h~ is~ ~ azide decomposed to form 4-(2,3-dimethyl-l-phenyl-5-oxo-3-pyrazolin4-yl)azo-2,3-dimethyl-l-phenyl-3-pyrazolin-5-one. Dihlmann3'l has determined the R, values of 4-amino- and 4amido-3-pyrazolin-5-ones by using butanol-acetic acitf-water as solvent and ferric chloride or p-dimethylaminobenzaldehydeas developer. The rearrangement of 4-dimethylamino-2,3-dimethyl-l-phenyl-3pyrazolin-5-one to a 2-pyrazolin-5-onehas already been mentioned (eq. 169). 4-Benzylideneamino-2,3-dimethyl-l-phenyl-3-pyrazolin-~-one reacts with dimethyl sulfate in aqueous media to give the 4-methylamino analog.940Presumably the Schiff base is hydrolyzed and the resulting amino group is methylated. 4-Dimethylamino-3-pyolin-5ones react with phosphorus oxychloride by conversion to the methochloride of a pyrazole.looO 4-Arylazo-3-pyrazo,oln-5-ones have been used as dyes. They form complexos with chromium which have good dyeing properties.1060 Michaelis, Kotelmann and Drewsga4report the reduction of 4-aryl-azo3-pyrazolin-5-ones having no 1-substituent to pyrazoles by use of phosphoma pentasulfide (eq. 202). Reaction of such azo compounds
pa88_
R31R1-N
(202)
H
with phosphorus oxychloride leads to the corresponding 5-chloropyra~ole.~~~
Pyrazolin-5-ones
81
The only 4-dialkylamino-3-pyrazolin-5-thionereported in the l i t e r a t ~ r e was ~ ~ prepared ~ - ~ ~ ~by ~ the action of sodium sulfide or potassium hydrogen sulfide on the methochloride of the corresponding 5-chloropyrazole. A very few bis(3-pyrazolin-5-ones) in which the two rings are connected by the azo group have been prepared. The preparation of these via the 4-azid0-3-pyrazolin-5-ones~~~ haa already been mentioned. These bispyrazolinones have also been prepared by coupling diazonium salts with 3-pyrazolin-5-ones (eq. 203).gs4.loolScott and c o - w ~ r k e r s ~ ~ ~ *
have reported a bis(3-pyrazolin-5-one)having a very extended bridge system prepared by reaction of a 3-pyrazolin-5-one diazonium chloride with N,N'-dibenzylidenediaminoguanidine. 5. Halogen Substituted Derivatives A. 2-Pyrazolin-5-ones
Halogenated 2-pyrazolin-5-ones having halogen a t N-1, C-3 and C-4 are known, but by far the largest number of such compounds have the halogen atom at C-4. Such compounds are usually prepared by direct halogenation with elemental halogen. Chlorination or bromination of 2-pyrazolin-5-ones having no 4-substituent with one equivalent of halogen gives the 4-monohalogeno product (eq. 204), but an excess 809* 1605 of halogen gives the 4,4-dihalo derivative.355* X
I
R'
I
R'
I
R'
4-Iodo- and 4,4-di-iodo-2-pyrazolin-5-ones can be prepared by treatment of 2-pyrazolin-5-ones with iodine-potassium iodide in an alkaline s01ution.l~~~ Here, again, either the mono or the dihalogeno product is formed, depending upon the amount, of halogen used. 4
+ C.H.C.
20
Part 1.
82
Chapter I1
Extremely good yields have been reported in these ha10genations.l~~~ 4-Alkyl-2-pyrazolin-5-ones react with halogens readily, but even with an excess only monohalogenated products have been obtained.lBo5 Smith and co-workers1309 have found that 1,3-dimethyl-2-pyrazolin-5one reacts with bromine to give both the expected 4-bromo product and also l-bromo-3-methyl-2-pyrazolin-5-one. This same compound ww obtained by bromination of 3-methyl-2-pyrazolin-5-one with N-bromos u c ~ i n i m i d e . ' ~4-Bromo-2-pyrazolin-5-ones ~~ have been prepared 1209 (eq. 205) with by bromination of 2-nitroso-3-pyrazolin-5-ones
I
I
H
H
bromine. Treatment of 3-pyrazolidinones with bromine results in oxidation of the pyrazolidinone to a pyrazolinone followed by bromination.818.1028Unless the temperature is controlled this reaction leads to a mixture of mono-, di- and tribromo-2-pyrazolin-5-ones. However, Muckermann1028WM able to obtain the monobromo derivative at 0" and the dibromo at room temperature. A number of reagents other than elemental halogen have been used for the introduction of halogen into 2-pyrazolin-5-ones.Treatment of 2-pyrazolin-5-ones with phosphorus p e n t a ~ h l o r i d e809= ~ ~ g80 ~ . or with sodium hypochloriteloo4 forms 4,4-dichloro-2-pyrazolin-5-ones. An analogous reaction is the formation of 4,4-dibromo analogs by use of phosphorus t r i b r ~ m i d e The . ~ ~ ~methods already discussed for halogenation of 2-pyrazolin-5-ones lead exclusively to the 4-substituted products, but 3-halogenated-2-pyrazolin-5-ones are known. These have been prepared by Michaelis and co-workersgg4.gg8 by reaction of one molar equivalent of phosphorus oxychloride with l-phenyl-3,5-pyrazolidinediones (eq. 206) or with 3-methoxy-1-phenyl-2-pyrazolin-5-ones. R'
O,-LIP
..i,/L0 dsH,
+
P0Cl3
-
R' LR2
C I I / N'N
Jz0
(206)
I
GHs
Some halogenated 2-pyrazolin-5-ones have been prepared by cyclization of various aliphatic compounds. Darapsky, Berger and a @-hydrazinohydrazide with bromine to N e ~ h a u shave ~ ~ treated ~ achieve cyclization, oxidation and halogenation in one step (eq. 207).
Pyrazolin-5-ones
83
The cyclization of a P-phenylazo-a$-unsaturated ester with hydrochloric acid has been reported by van A l ~ h e n ll5I4 ~ ~to~give . a 4-chloro2-pyrazolin-5-one. Br
R'CHCH&ONHNH,
(207)
I
NHNH, H
These compounds are listed in Table XXV. are reduced with hydriodic The 4,4-dichloro-2-pyrazolin-5-ones acid to the corresponding monochloro compound.1605The 4-monohalogenated-2-pyrazolin-5-ones react readily with another mole of the same compound or with unhalogenated 2-pyrazolin-5-ones to give bis(2-pyrazolin-5-ones).In the former case the two rings are linked by a double bond,1307and in the latter by a single bond.1528 Only two halogenated bis(2-pyrazolin-5-ones)have been reported (Table VI). One of these is prepared by bromination of 4,4'-methylidynebis(3-methyl-l-phenyl-2-pyrazolin-5-one) with bromine to give the 4-bromo analog.lsa2 I n the second case1109 bromine is added to a diolefinic system connecting two 2-pyrazolin-5-onerings. A number of halogenated 5-imino-2-pyrazolineshave beenreported. These are included in Table XII. They are usually prepared by direct halogenation.996* 1655 Another preparative method which has been used is treatment of a 5-imino-3-pyrazolidinonewith phosphorus oxychloride.391Micha,elishas reported the treatment of a compound, which he believed to have the azipyrazole structure (XXVI, p. 45), with 4-Chloro-3halogen acids to give halogenated 5-imin0-2-pyrazolines.~~~ has been prepared dichloromethyl-1-phenyl-5-phenylimino-2-pyrazoline with by treatment of l,l-bisanilino-2,4,4-trichloro-l-buten-3-one phenylhydrazine.lZo1The reactions of halogenated iminopyrazolinones are essentially the same as of those having no halogen. B. 3-Pyrszolin-5-ones
These compounds are listed in Table XXVI. As is the case with 2-pyrazolin-5-ones7direct bromination of 3pyrazolin-5-ones can be used to prepare the 4-bromo derivatives. This bromination is not complicated by substitution of a second bromine at the same carbon atom, but further bromination occurs to give 3pyrazolin-5-ones containing two or three atoms of bromine. I n spite of considerable investigation of these polybrominated 3-pyrazolin-5ones, their structures have not been conclusively established and several
84
Part 1. Chapter I1
very bizarre suggestions as to their nature have been made. Knorrso9 and other early w ~ r k e r found ~ ~ ~ that~ reaction * ~ ~ of ~ one mole of bromine with one mole of a 3-pyrazolin-5-onegave a compound whose molecular formula was that to be expected from addition of the bromine to the ring double bond to give 4,5-dibromo-3-pyrazolidinonesand it was suggested that this was the structure of the products. This view was held for many years1320 until Kitamura and S ~ n a g a w a ~ g ~ . ~ s ~ suggested that these compounds might be the hydrobromides of 4bromo-3-pyrazolin-5-ones in the betaine form. The ready conversion of these dibromo-3-pyrazolin-5-ones t o the corresponding 4-bromo-3pyrazolin-5-ones by treatment with base and the reaction of the monobromo compounds with hydrogen bromide to give the dibromo derivatives make the argument of Kitamura and Sunagawa very compelling. Westoo1605has agreed with this proposal and it seems very likely to be correct. Reaction of excess of bromine with 3-pyrazolin-5ones leads to the compounds called perbromides, generally considered to be tribromo compounds, although K ~ m a d aclaimed ~ ~ ~ to have obtained tetrabromo derivatives also. These claims have been discounted by others.794These perbromides have usually been considered as a molecular complex of the halogen and 4-bromo-3-pyrazolin-5-ones. Kitamura and S ~ n a g a w ahave ~ ~ ~proposed more definite structures involving dimerization, with the dimers bound by resonance. However, their suggested structure seems inherently improbable. Whatever may be the structures of these compounds, two of the bromine atoms must be very loosely held, as they are lost by treatment with ~ a t e r , ~ ~ ~ ~ ~ giving a 4-bromo-3-pyrazolin-5-one. Direct chlorinationgaa and iodination 540* with the elemental halogens to give 4-halogeno-3pyrazolin-5-ones have also been reported. Ledrut and co-workers362* a99 have found that bromination of 3-pyrazolin-&ones having hydroxymethyl, formyl and carboxyl groups at C-4 results in replacement of the 4-substituent by bromine. M i c h a e l i ~earlier ~ ~ ~ had reported this replacement if a 4-nitro group was present. A variety of other halogenating agents have been used to prepare 4-halogeno-3-pyrazolin-5-ones.N-Bromosuccinimide362~a99 replaces hydrogen or other substituents in the 4-position with bromine. Hydrobromic acid in the presence of peroxide g07 and bromocyanogen1491 also bring about bromination. 4-Chloro-2,3-dimethyl-l-phenyl-3-pyrazolin6-one is obtained in excellent yield by chlorination of 2,3-dimethyl-lphenyl-3-pyrazolin-5-onewith sodium h y p o c h l ~ r i t e . gOa ~ ~ ~5,5.~~~Dimethyl-l,3-dichlorohydantoinalso gives 4-chlorination of 3-pyrazolin-5-0nes.~6~4-Iodo-3-pyrazolin-5-oneshave been obtained by replacement of a 4-chloromercuri group with iodine.loO'*1155 3,4-
Pyrazolin &on@
85
Dichloro-2-phenyl-3-pyrazolin-5-one has been prepared by treatment of perchloro-1-penten-$-onewith phenylhydrazine.laol The halogen in these 3-pyrazolin-5-ones is readily replaced with hydrogen by catalytic reduction 697, 698 or by treatment with acetone.793 A few halogenated 3-pyrazolin-5-thionesare known (Table XVIII). These are prepared from the methyl chlorides of 3- or 4,5-dichloropyrazole by reaction with sodium sulfide or potassium hydrogen 981 Michaelis988-992 has reported that 3-pyrazolin-5-selenones sulfide.795* form dichlorides and di- and tetrabromides when treated with chlorine or bromine. No specific structures were suggested. 6. Nitroso Substituted Derivatives A. 2-Pyrazolin-5-ones
Although the compounds obtained by introduction of a nitroso group at G-4 in 2-pyrazolin-5-ones are considered as 4-nitroso-2pyrazolin-5-ones for purposes of classification in this discussion, they actually exist aa the oximino isomers (eq. 208) and are usually so
considered in the literature. These compounds are always strongly colored, being light yellow to deep red. Such compounds are listed in Table XXVII. by treatment Knorr 809 first prepared 4-oximino-2-pyrazolin-5-ones of 2-pyrazolin-&ones with nitrous acid (eq. 208) and this has remained If an excess the standard method of preparation.Z5*413*446*818*1004*1549 of nitrous acid is used, the nitroso substituent introduced is oxidized further to a nitro s u b s t i t ~ e n t Amy1 . ~ ~ ~ nitriteg and nitrogen trioxide355*406 have also been used as nitrosating agents, though not extensively . The standard p-ketoester-hydrazine reaction for preparation of 2-pyrazolin-5-oneshas been used for direct synthesis of the 4-oximino derivatives by starting with an a-oximino-j?-ket~ester.~~~*~~~~* 1534. 1536 I n a modification of this by Biilow and B o ~ e n h a r d at ~hydrazone ~~ of the a-oximino-j?-ketoesterwas used. Ponzio and Ruggeri 1125 have used a-oximino-8-hydrazonohydroxamicacids and hydrazines, and other oximino compounds, as illustrated in eq. 209.
86
Part 1. Chapter I1
It has been claimed that 3-pyrazolidinones can be converted to 4-oxiniino-2-pyrazolin-5-ones by treatment with nitrous acid.816.1550 However, later 1491 report that this reaction gives Ar I --=NOH ArCOCCHzKOz
1
I1
RNHNHZ
?r'
-__f
\N,
RNHNHa
=O
II
I
AOH
A r C O b C C O A r NOCOCH,
(209)
II
NOCOCH,
It
nitrosation at N-1.Since neither Knorr and Duden816nor von Rothenburg1550give sufficient physical data to identify their products, it may well be that they were actually 1-nitroso-3-pyrazolidinones. Curtius and Bleicher 335 have isomerized 1-nitroso-3-pyrazolidinones by boiling with dilute sulfuric acid, thus causing rearrangement of the nitroso group to the 4-position and oxidation to a pyrazolinone (eq. 210). Qvist 1153 has (210) I
I
H
H
rearranged 3-hydrazino-4-nitroso-5-arylisoxazoles to 4-oximino - 2 pyrazolin-5-ones by heating in aqueous sodium hydroxide. Freri 480 has reported a very interesting synthesis of 4-oximino3-methyl-2-pyrazolin-5-one. This consisted in the treatment of citraconic acid hydrazide with nitrous acid (eq. 21 1).The physical data which 4780
CHCONHNH, CH34CONHNHz II
+ HNOz
C'H,--r----NOH I/
YNi=o
('11)
H
were reported for the product were consistent with those reported by other workers for the same compound. The reaction may go by preferential Curtius rearrangement of one hydrazide to form /3-aminocrotonic acid hydrazide which cyclizes and is nitrosated. Treatment with nitrous acid of a 4-substituted-2-pyrazolin-&one having no substituent on N-1 gives the 1-nitroso derivative.262 I n the section dealing with 4-amino-2-pyrazolin-5-ones the reduction of 4-oximino-2-pyrazolin-5-ones and their reaction with active hydrogen atoms of heterocyclic compounds (eq. 174, p. 6s) have been discussed. The oximino group is readily oxidized to the nitro group by ozone478.480 or nitric a ~ i d . *The ~ ~hydrogen * ~ ~ ~of the oximino group can be replaced by silver by use of silver nitrate866.1553 and the silver salt thus formed can be alkylated to form an 0-alkyl oxime. The oximino group can be replaced by a hydrazino group.1549
Pyrazolin-5-ones
87
Only one oximinobis(2-pyrazolin-5-one) is known.459 This is 2,3-bis(4-oximino-3-phenyl-5-oxo-2-pyrazolin-l-yl)naphthalene prepared by nitrosation with nitrous acid. 4-Nitroso-5-imino-2-pyrazolines are capable of existing in several tautomeric forms, (XXXII), (XXXIII) and (XXXIV). Although there -NOH
R Z -
N ‘
I
1
,!=NH
‘N
I
R1
R’
R’
(XXXII)
(XXXIII)
(XXrn)
is little experimental evidence concerning structures, these compounds have usually been considered to exist in the oximino-imino form loo2 (XXXIII).996@ Preparation has usually been by the nitrosation of the 5-imino-2pyrazolines with nitrous acid.340.996*1002*lolo Qvist 1153 has prepared them by thermal rearrangement of nitrosoisoxazoles (eq. 212). The C,HSNHNHqN
~
\o
N -R
O
+
R =,,NO€I
=NH
NN ,
(212)
J6H6
4-oximino-5-imino-2-pyrazolines may be reduced to amines or oxidized with potassium permanganate to nitro compounds, similarly to their &OX0 analogs.lO10However, oxidation with sodium hypochlorite forms furoxazans (eq. 213).1010
B. 8-Pyrszolin-5-ones
3- and 4-Nitroso-3-pyrazolin-5-ones can only exist as the nitroso compounds. They are green, aa would be expected, and somewhat unstable to heat. In many cases they melt with deflagration. They are basic enough to form stabIe hydrochlorides, which are usually red. This probably means that these hydrochlorides are actually alkyl chloride salts of 4-oximino-2-pyrazolin-5-ones. The 4-nitroso-3-pyrazolin-5-ones have been of great commercial interest because 4-nitroso-2,3-dimethyl1-phenyl-3-pyrazolin-5-one is an intermediate in the preparation of the
Part 1. Chapter I1
88
analgesic, aminopyrine. The 4-nitroso33-pyrazolin-5-ones are listed in Table XXVIII. are alwaysprepared by nitrosation The 4-nitroso-3-pyrazolin-5-ones of 3-pyrazolin-5-oneswith nitrous aCid.99.103.145.647.781.807.809.854,888. 972.978. 984 Only one 3-nitroso-3-pyrazolin-5-one has been This was prepared by nitrosation of 3-pyrazolin-5-one having a 4methyl substituent and no substituent at C-3. has already been The reduction of 4-nitroso-3-pyrazolin-5-ones discussed in connection with the synthesis of 4-dialkylamino-3-pyrazolin-5-ones. This reduction occurs readily to give the corresponding amine when catalytic hydrogenation or various chemical combinations461.99a*'174~1175 are used. Oxidation of nitroso to nitro occurs in the presence of excess of nitrous acid or by use of nitric a ~ i d . ~ ~ ~ * ~ ~ ~ 7. Nitro Substituted Derivatives A. 2-Pyrazolin-Ci-ones
Only a few 4-nitro-Z-pyrazolin-5-0nes are known. They are listed in Table XXIX. The best-known of these compounds is picrolonic acid, This which is 4-nitro-3-methyl-l-(4-nitrophenyl)-2-pyrazolin-5-one. compound is widely used to form salts of basic compounds for isolation or identification. The hydrogen atom at C-4 is acidic in the 4-nitro-2pyrazolin-5-ones because of the two adjacent electron-withdrawing groups. This hydrogen is easily replaced by metals when treated with metal a l k o x i d e ~and l ~ ~reacts ~ with dia~omethane.~'~ is by nitration The usual synthesis of the 4-nitro-2-pyrazolin-fi-ones of 2-pyrazolin-5-onesunder mild conditions (eq, 214).61~872~690.1004.1683
I
Rl
I
R'
In the case of picrolonic acid further nitration can be brought about to give the 4,4-dinitro compound.6g0The oxidation of 4-nitroso-2-pyrazolin-5-ones has already been mentioned in the section dealing with the nitroso compounds. Ajellog has been able to nitrate 3-methyl-2pyrazolin-5-one using amyl nitrite in acetone or ether for several days. Hill and Blacks53 have reported the cyclization of N,N'-diacetylnitromalondialdimine with base to give 4-nitro-2-pyrazolin-5-one7 but such a course for this reaction seems unlikely. The reaction of furlones with sodium nitrite and sulfuric acid to give as one of the products 4-nitro-2pyrazolin-5-0nes~ has ~ ~already ~ been illustrated in eq. 62 (p. 33).
89
Pyrazolin-5-ones
The alkylation of 4-nitro-2-pyrazolin-5-ones at C-4 with diazomethane478has already been mentioned. This hydrogen atom is also replaceable with bromine.1642 Reduction of the nitro group with stannous chloride forms the corresponding amine.478* 480 Picrolonic acid condenses with itself to form a bis(2-pyrazolin-5-one) connected by a double bond at the 4,4'-position, with elimination of two moles of nitrous acid.690Condensat,ion also occurs in the presence of phenylhydrazine, but 4,4'-bis[3-methyl-1-(4-nitrophenyl)-2-pyrazolin-5-one] is formed.690 Two 4-nitro-5-imino-2-pyrazolines are listed in Table XII. One of these was prepared by permanganate oxidation of the 4-oximino compound1010and the other by direct nitration.1656These compounds were believed to be aminopyrazoles rather than 5-imino-2-pyrazolines. B. 3-PyrazoIin-5-ones
The 4-nitro-3-pyrazolin-5-ones are listed in Table XXVIII. They have been prepared most frequently by direct nitration of 3-pyrazolin~ i d 1320 . 5-ones, usually with concentrated nitric a The oxidation of 4-nitroso-3-pyrazolin-5-onesto give the 4-nitro compounds has been mentioned in connection with reactions of the 4-nitroso compounds. Nitration of 3-pyrazolin-5-ones with nitrogen tetroxide has been acc~rnplished.'~~~ The nitro group of 4-nitro-3-pyrazolin-5-ones is readily reduced to an amino group by metal-acid combinations.g84* lool 8
8. Aldehydes and Ketones A. 2-Pyrazolin-5-ones
A large number of 2-pyrazolin-5-one aldehydes and ketones are known. These are listed in Table XXX. It is possible to have both 3and 4-formyl and acyl substituents and both are known, although only one 5-oxo-2-pyrazoline-3-carboxaldehyde has been reported. There has been very little study of the effect of 4-acyl substituents on the structure of 2-pyrazolin-5-ones, but it seems probable that such compounds would tend to exist to a large extent as the 5-hydroxypyrazoles since they would be 1,3-dicarbonyl compounds. The preparation of the 5-0x0-2-pyrazolinecarboxaldehydesis usually done by procedures which are not applicable to preparation of the acyl homologues. The most extensively used method for preparing the aIdehydes is hydrolysis of their Schiff bases,824.1089*1092*1186,1188 4*
~
~
Part 1. Chapter I1
90
illustrated in eq. 215. R3 is usually aromatic, although it may be hydrogen.586-lI8* This hydrolysis occurs in the presence either of base or of acids. A second method of preparation is treatment of 4-(2,2,2trichloro-l-hydroxyethyl)-2-pyrazolin-5-ones, obtained by reaction of
I
R'
2-pyrazolin-5-ones with chloral, with potassium ~arb0nate.l~'von R o t h e n b ~ r g has ' ~ ~reported ~ that heating of the calcium salt of 5-0x02-pyrazolin-3-carboxylicacid in the presence of calcium oxide and Howcalcium formate formed 5-oxo-2-pyrazolin-3-carboxaldehyde. ever, his product was not well characterized and the work has not been confirmed. 4-Acyl-2-pyrazolin-5-ones have been synthesized by three general methods. These are cyclization of aliphatic compounds, conversion of other 2-pyrazolin-5-onesand conversion of other heterocycles. As might be expected the reaction of 13-ketoesters with hydrazines has been ~ t i l i z e d . l ~ 1532.1533 * . ~ ~ ~ ~I n* this case the p-ketoester has an a-acyl substituent (eq. 216). Both Borsche and LewinsohnlZ4 and Vila1533 R2COCHCOOR3
+ R4NFKNHa
R1roRa Y&-
+
-0
R'bO
(216)
A4
have used a-hydrocinnamoylacetoacetic ester in this reaction. The former workers claim that the 4-acetyl products are obtained, while Vila 4reported the products were 4-hydrocinnamoyl-2-pyrazolin-5-ones. Acetyl-2-pyrazolin-5-oneshave been obtained by cyclization of hydrazones of 8-ketoesters with acetic anhydride.1oo9Kendall and Fry767 have obtained 3-acyl-2-pyrazolin-5-ones by the reaction sequence shown in eq. 217. The reaction of P,y-diketoesters with hydrazines also forms 3-aoyl-2-pyrazolin-5-0nes.~~~ (CH3CO)2CHCH2COOC2H5 + CeH5NzCl
CH3COCHCHzCOOC2H,
1
N=NCeHS
Pyrazolin- 5 -ones
91
Acylation of 2-pyrazolin-5-ones leads to 4-acyl-2-pyrazolin-5-ones. This has been done by treatment with aromatic acid chloridesl10 and with ethyl oxalate in the presence of potassium. A modification of this procedure is acylation of 2-pyrazolin-5-onesto give 4-acyl-5-acyloxy1056 followed by hydropyrazoles 591.977 or 2,4-diacyl-3-pyrazolin-5-ones lytic removal of the N-acyl or 0-acyl groups. The 4-acyl compounds can also be prepared by hydrolysis of their Schiff bases as shown in eq. 215. The reaction of hydrazine with appropriately substituted isoxazo(eq. lones or isoxazolinones also forms 4-acyl-2-pyrazolin-5-ones 218).947.1295 R2 I
5-Qxo-2-pyrazolin-4-carboxaldehydes are oxidized to the corresponding acid by perrnanganate.lo7 These aldehydes under various and heating conditions form 4,4'-methylidynebis(2-pyrazolin-5-ones), This same type alone brings about this reaction (eq. 219).1089*1093.1188
I
R'
I
R,'
I
R'
of product is obtained by the reaction of the 2-pyrazolin-5-one aldehydes with 2-pyrazolin-5-0nes.~~~~ Reaction of these aldehydes with Such alde%methylindole also gives the bis(2-pyrazolin-5-0nes).~~~~ hydes react normally with amines and hydroxylamines to give Schiff undergo the Manbases and oximes.lla8 The 4-acyl-2-pyrazolin-5-ones nich reaction.log8Treatment of acylpyrazolinones with diazonium salts results in replacement of the acyl group by an arylazo Kendall and Fry7a8.770 have prepared 3-acetyl-4-phenylazo-2pyrazolin-5-one by the reaction of ethyl 8-acetyl-8-oxovalerate with two equivalents of phenyldiazonium chloride. 4-Benzoyl-3-methyl-l-phenyl-2-pyrazolin-5-thione has been prepared by Michaelis and co-workers977~990 by the reaction of sodium and 1-phenylpotassium hydrogen sulfide with 4-benzoyl-5-chloro-3-methylpyrazole. The thiono compound forms a methiodide and gives the characteristic reactions of both ketones and 2-pyrazolin-5-thiones.
Part 1. Chapter I1
92
B. a-Pyrazolin-5-ones
There has been considerable interest in the preparation of 5-0x0-3pyrazolin-4-carboxaldehydes(listed in Table XXXI) because of their close relationship to antipyrine (2,3-dimethyl-l-phenyl-3-pyrazolin-5one). The most frequently used preparation of these compounds has already been mentioned (eq. 135, p. 54). This consists of treating the condensation products of 3-pyrazoIin-5-ones and chloral with b a ~ e The McFadyen-Stevens . ~ aldehyde ~ syn~ thesis has been applied to the preparation of both 5-0x0-3-pyrazolin-3892*1634 This is illuscarboxaldehydes 698 and -4-~arboxaldehydes.~~~* trated in eq. 220. The final step is usually carried out in glycerol at C!HS---CH:,-S
1-‘ -..x
=o i
CsH580zNHNHa
CHa----I--/ CHJ--1U
--
COiiHSHS02C,H,
“/Lo
L‘,H,
elevated temperatures in the presence of sodium carbonate. The acylsulfonylhydrazide has been prepared alternatively by reaction of the acid chloride with hydrazine followed by treatment of the hydrazide so produced with benzenesulfonyl chloride. A group of Italian workers has claimed that 1,3-disubstituted-% methyl-5-oxo-3-pyrazolin-4-carboxaldehydes can be prepared through methylation of the Schiff bases derived from aromatic amines and 1,3-disubstituted-2-pyrazolin-5-0nes.~~~~ The methylation is carried out with methyl iodide which methylates the ring at N-2, and this is followed by hydrolysis of the Schiff bases with alkaline solutions (eq. 221). Passerini and Losco1092~1093~1097 and Ridi118’ claimed to have
I
1%‘
I lil
prepared 2,3-dimethyl-2-phenyI-5-oxo-2-pyrazol~-4-carboxaldehyde in this fashion. Ridi1la0 has also reported the preparation of similar compounds by the same procedure. However, various other workers 108*696. 897.902 have reported that in the presence of base 2,3-dimethyl-l-phenyl5-oxo-2-pyrazolin-4-carboxaldehyde isomerized to 4-acetyl-2-methyl-
~
~
Pyrazolin-5-ones
93
1 -phenyl-3-pyrazolin-Ci-one (eq. 2%), presumably by hydrolytic ring
cleavage and reclosure. Ledrut, Combes and Sweikertgo2have shown that the reaction depicted in eq. 221, in which R1= C,H, and R2 = CH,, does lead to the acetyl derivative, although other substituents give the expected product. A British patent 201 has appeared claiming that alkaline hydrolysis of the presumed 2-methyl intermediate in eq. 221 actually can be made to give the aldehyde by using dilute base and mild conditions. In summary it would appear that the various claims of Passerini, Losco and Ridi are largely correct. A few miscellaneous preparations of 5-0x0-3-pyrazolincarboxaldehydes have been reported. It0 698 has prepared 3-carboxaldehydes and 3,4-dicarboxaldehydes by manganese dioxide oxidation of the corresponding alcohols. The 4-carboxaldehydes have also been prepared in this Treatment of antipyrine with dimethylformamide in the presence of phosphorus oxychloride has also been used.696 Passerini and L o s c o ~ Ohave ~ ~ reported methylation of 3-methyl-1phenyl-5-oxo-2-pyrazolin-4-carboxaldehydeto the corresponding 3pyrazolin-4-carboxaldehyde.However, the melting point given for their product is that of 4-acetyl-2-methyl-1-phenyl-3-pyrazolin-5-one, so it is probable that isomerization occurred. are known. Most of those preOnly 4-acetyl-3-pyrazolin-5-ones pared are antipyrine derivatives. The most common method for preparing these is by a Friedel-Crafts reaction on 3-pyrazolin-5-ones with acid chlorides and aluminum chloride,88 zinc or no condensing agent.737 2,3-Dimethyl-l-phenyl-5-oxo-3-pyrazolin-4-carboxylic acid and its acid chloride have been condensed with various aromatic compounds to give ketones.740Treatment of 4-benzoyl-5chloro-3-methyl-1-phenylpyrazoleor 4-benzoyl-3-methyl-l-phenyl-2pyrazolin-&one with dimethyl sulfate gives rise to 4-benzoyl-2,3dirnethyl-l-phenyl-3-pyrazolin-5-0ne.~~~ Phenylhydrazine reacts with isoxazolidones to give what may be 4-acetyl-2-phenyl-3-pyrazolin-50118.1295
The 4-formyl and 4-acyl-3-pyrazolin-5-onesreact like normal carbonyl compounds with active methylene groups,896.llgo amines,107*1190 hydroxylamine,lg8 hydrazines1gs*201and semicarbazide,201although some fail to react with t h i o s e m i ~ a r b a z i d e They .~~~
Part 1. Chapter I1
94
also form bisulfite addition compounds.107 Isomerization of 5-0x0-3pyrazolin-4-carboxaldehydes to 4-acyl-3-pyrazolin-5-onesby base can be treatment has already been discussed. 4-Acyl-3-pyrazolin-5-ones reduced t o the corresponding alcohol by sodium-mercury amalgam. leads to replaceBromination of 5-oxo-3-pyrazolin-4-carboxaldehydes ment of the formyl group with bromine.362 Bodendorf, Mildner and Lehman lo7 have reported the condensation of 2,3-dimethyl-I-phenyl5-oxo-3-pyrazolin-4-carboxaldehyde with itself and with 2,3-dimethylCHqCH3N
c
I+
HO
\.x,
J6H5
CH37-~ CH,N \N,. =o I
+
CEi;iN=T
CeH, HO
7
CH3------cH3'~:
(223)
3
\ "-0
I 1-phenyl-3-pyrazolin-5-one(eq. 223) to form a trimeric 3-pyrszolin-5one. Passerini and co-workers log3.log?have reported that the reaction of 4-acetyl-2-methyl-l-phenyl-3-pyrazolin-5-one with 3-methyl-lphenyl-2-pyrazolin-5-onegives, in addition to 4,4'-methylidynebis(3methyl-l-phenyl-2-pyrazolin-5-one),some 2,3-dimethyl-l-phenyl-3pyrazolin-5-one (eq. 224) and this has been confirmed by Clurato10.~~~
I
I
C,H,
CeHs
I
I
It may be that there is a transfer of the CH3N-N-C6H, moiety of the 3-pyrazolin-&one molecule to the 2-pyrazolh-6-one, or it may be that the N-2 methyl group acts as a methylating agent. Various bis( 3-pyrazolin-5-ones) having acyl substituents are known. I n all cases the acyl group is part of a 4,4'-bridge between the 3-
Pyrazolin-5-ones
95
pyrazolin-5-one rings. The condensation of 2,3-dimethyl-l-pheny1-5oxo-3-pyrazolin-4-carboxaldehydewith 4-acetyl-2-methyl-1-phenyl3-pyrazolin-&onegives rise to such a compound.lo8.696.902 Antipyrine and its 4-carboxyl derivative condense to form diantipyryl ketone.740 Sodium 2,3-dimethyl-l-phenyl-5-oxo-3-pyrazolin-4-carboxyla~ reacts with 4-chloroacetyl-3-pyrazolin-5-onesto give bis compounds.741 4-Acyl-3-pyrazolin-5-ones dimerize by an aldol c o n d e n s a t i ~ n . ~ ~ ~ 4-Benzoyl-2,3-dimethyl-l-phenyl-5-imino-3-pyrazoline is prepared by treating the methiodide of 4-benzoyl-3-methyl-1-phenyl-5-imino-2pyrazoline with base.977 9. Carboxylic Acids and Derivatives A. 2-Pgramh-5-ones
A large number of 5-0x0-2-pyrazolin-3-and 4-carboxylic acids and their derivatives have been prepared. These are listed in Tables XXIII, X X X I I and XXXIII. These compounds have been of considerable commercial interest because they are the basis for many azo and azomethine dyes. The usual procedure for preparing the 5-oxo-2-pyrazolin-3carboxylic acids is reaction of oxaloacetic acid or esters with hydrazines (eq. 225). Several modifications of this reaction have been used. The 0
I
R3
common method is to use the ester in which R = R2= CH, or C6H, and either hydrolyze the ester first obtained (R2=CH, or C,H, to R 2 = H ) with base to give the acid498.1544.1547 or to use base for the cyclization with concomitant hydrolysis of the ester to give acid d i r e ~ t l y . ~ ~ + ~ ~ ~ * 837*1635 The acid ester in which R = H and R2=C2H5 as starting material gives the acid d i r e ~ t l y .Oxaloacetic ~ ~ ~ . ~ ~ acid ~ has been used and i t also gives the acid.43 Of course, hydrolysis of alkyl 5-oxo-2pyrazolin-3-carboxylates obtained by other means can also be used, as can the hydrolysis of the h y d r a ~ i d e . ~5-0xo-2-pyrazolin-4-carboxylic ,~ acids are most frequently prepared by hydrolysis of the corresponding e ~ t e r s . ~Oxidation ~ ~ * of ~ 4-hydroxymethyl-2-pyrazolin-5-o1~es~~ ~ ~ ~ . ~ ~ ~ ~ and 5-oxo-2-pyra~olin-4-carboxaldehydes~~~ with permanganate also gives the acid.
96
Part 1. Chapter I1
Esters of 5-oxo-2-pyrazolin-3-carboxylicacid are prepared by treatment of the esters of four-carbon dicarboxylic acids with hydrazines or diazonium salts. By far the most frequently used method has been the condensation of oxaloacetic esters (esters of a-oxoauccinicacid) with This is of course merely various hydrazines, as shown in eq. 225.35a*1544 a variation of the classical 2-pyrazolin-5-onesynthesis. The ester can be s ~ b s t i t u t e dto~give ~ various 4-substituents in the product and various hydrazines2*153* 499 can be used. The reaction mixture can be heated594 or mild bases can be used as condensing agents.414The hydrazone can first be prepared and then cyclized with acid.43Usually the 3-carboxylic As is the case with other acid hydrazide is obtained as a a,$-acetylenic esters, the condensation of diethyl acetylenedicarboxylate with hydrazine forms 2-pyrazolin-5-ones but the dicarboxylic esters give products having 3-carbethoxy s u b s t i t ~ e n t s . '1549 ~ ~ ~In * a very similar type of reaction diethyl chlorofumarate and hydrazines are used.1220 Treatment of diethyl cr-acetylsuccinatewith phenyldiazonium chloride (eq. 226).37* 767 forms ethyl l-phenyl-5-oxo-2-pyrazolin-3-carboxylates
The synthesis of alkyl 5-oxo-2-pyrazolin-4-carboxylates is carried out by reaction of hydrazines with various esters having $-substituents or a$-unsaturation and also an a-carbalkoxy substituent. These methods are quite analogous to ones used generally for this type of ring formation, being modified only t o introduce the carboxylate function at the appropriate place. The reaction of acylmalonic esters 138*418. 419-563. 1222* 1223 and their thiono analogs1008with hydrazines (eq. 1, p. 9, R2=COOR and R3= H ) gives this type of pyrazolinone and is the most frequently used synthesis. Ethoxymethylenemalonic also react with esters 306 and aminomethylidynemalonic esters804*1231 hydrazines to form alkyl 6-oxo-2-pyrazolin-4-carboxylates. Further syntheses are illustrated in eqs. 227a, 227b and 228. The thio analogsa9 RNHNH2
( H5Cz00C)2C=CHCH(COOCzH&
(227a)
RNHNB,
[HNCH=CH(COOC,H,),],
---+
1
R
(227b)
Pyrazolin-5-ones
91
of these esters are synthesized by reaction of 2-pyrazolin-&ones with carbon disulfide and ethyl bromide (eq. 229). 0
II
COOCZH,
RNHNH2
, CHs-i-COOC2H, I1
(228)
Tu'
\N/'OI
H5c2:~0~c.,
R
The usual acid derivatives of 5-0x0-2-pyrazolin-3-and 4-carboxylic acids are known. Amides are prepared by reaction of esters and ammonia,1339by the reaction of urea with 2-pyrazolin-5-ones, and by the reaction of azides with ammonia and amines. Hydrolysis of nitriles C€I3-----
+
I1
CS,
JE0
N'N
+
AICI3
C2H,Br
CH,a--71~2C2H5
__f
\K/-
I
(229)
I
CBHs
CeH5
also gives a m i d e ~ . ~The ~ * reaction of oxaloacetic esters with excess of hydrazine leads to formation of the h ydrazide of 6-oxo-2-pyrazolin-3carboxylic Fenton and Jones 443 have reported the same product obtained from oxaloacetic acid, but their melting point differs from the melting point reported by others for this compound. The 3-hydrazide is also obtained by the reaction of hydrazine with diethyl of hydrazides have been prepared by b r o m o s ~ c c i n a t e .A~ ~number ~ standard reactions, such as reaction of esters594and acid chlorides498 with hydrazine. Acid chlorides are prepared by reaction of acids with thionyl chlorides.498Azides have been synthesized by treatment of hydrazides with nitrous acid498and by reaction of acid chlorides with are prepared by sodium a ~ i d e s . ~5-0xo-2-pyrazolin-4-carbonitriles ~* condensation of acylcyanoacetic esters with hydrazine,1310 by dee ~ by ~ ~direct introduchydration of the 4-carboxaldehyde ~ x i m and tion of a nitrile group. The nitrilegroup has been introduced by treatment of 2-pyrazolin-5-ones with either cyanogen bromide in the presence of 118* Ridi aluminum chloridez4or with mercuric fulminate (eq. 230).924*
I
R'
I
R1
and ChecchillQO described a similar reaction but claimed obtained the isonitrile.
Part 1. Chapt,or I1
98
A variety of 2-pyrazolin-5-ones having carboxyl or carboxyl derivatives as substituents and a second functional group are known (Table XXXIII). Such compounds are usually prepared by methods already described, and only those compounds having an arylazo substituent as the second functional group will bc discussed. These compounds have been extensively investigated because of their commercial importance as dyes. The important dye tartrazine is of this class. It is the trisodium salt of 4-(4-~ulfophenylazo)-1-( 4-sulfophenyl)-5-oxo-2pyrazolin-3-carboxylic acid. These dyes exist largely as enol isomers. The principal means of preparation is coupling of a diazonium salt with a 5-oxo-2-pyrazolin-3-carboxylic acid or its derivatives. Another important preparation of these compounds (eq. 231) is by the reaction of CH3COCHCOOC2H5
+ 2ArN2 C1+
__f
,I H6czooc___
CH2COOC2HG I
N '
N==NAr
Lo
(231)
I Ar
diazonium salts with dialkyl a c e t y l ~ u c c i n a t e s . ~ ~ ~ ~ ~ ~ ~ 1661 In this method the two aryl groups are the same. Various derivatives of succinic acid or its esters such as a-keto-a'-hydro~y,~~ a,a'-diketo 291-293 or their hydrates (dihydroxytartaric acid and esters)71*1628- 1662 react with hydrazines to give the 4-arylazo-5-oxo-2-pyrazolin-3-carboxylic acid derivatives. Treatment of various oxaloacetic acid derivatives 26* 285* with diazonium salts, followed by treatment with hydrazines is another method of preparation (eq. 232). 768.770r1240*
HSC200CCH2COCOOC2H,
+ Ar2NZ CI+
___t
HsCzOOCCCOCOOC,H,
II
NNHAr2 AT~NBNH~ ~
H.&aOOC7-IV=Nha N\N/=ol
(232)
I
Ar'
The 5-0x0-2-pyrazolin-3- and 4-carboxylic acids give the normal reactions of 2-pyrazolin-5-ones and of acids. Their derivatives also react as would be expected. Decarboxylation of the 4-carboxylic acids heating occurs in boiling ~ a t e r ,or~upon ~ ~ ~ * with ~ ~acid306 ~ ~ to give the corresponding 2-pyrazolin-5-ones.The 3-carboxylicacids have been decarboxylated by heating their salts.1544+1549 This gives, in addition to simple loss of carbon dioxide, the bis(5-0~0-2-pyrazolin-4-yl) ketone. 5-Imino-2-pyrazolin-4-carbonitriles and 4-carboxamideshave been prepared by Taylor by reaction of hydrazines with ma10nonitrile.l~~~
Pyrazolin-5-ones
99
This presumably goes by dimerization of the malononitrile to give a substituted p-amino-crotononitrile. This dimer also reacts with hydrazines to give 5-imino-2-pyrazolin-4-carbonitriles. These can be hydrolyzed to amides. A number of bis(2-pyrazolin-5-ones) having carboxyl groups or carboxyl derivatives as substituents have been prepared. Compounds linked at the 4,4’-positions by a single bond are usually formed by oxidation of a 5-oxo-2-pyrazolin-3-carboxylate with hydrazines (eq. 45).1082a1229The usual process is to start with a compound, such as an oxaloacetic ester, and treat this with excess of hydrazine. The monomeric pyrazolinone is formed and oxidized to the dimer by the excess of hydrazine present. Another cyclization procedure resulting in dimeric pyrazolinones containing carbethoxy groups is the reaction of hydrazines with cu,a’-dicarbethoxy-p,p‘-doxoglutaricesters.1222 Dimerization of 5-oxo-2-pyrazolin-3-carboxylic acids or their derivatives has been achieved by reaction with formamide to give 4,4’-methylidynebis(5-oxo-2-pyrazolin-3-carboxylic acids).126z 5-0xo-2-pyrazolin-3carboxylic acids having a I-(X-aminopheny1)-substituenthave been dimerized by reaction with phosgene to give a urea which links the two monomers.152* 511 Some 4,4’-bis(2-pyrazolin-5-ones) of the pyrazole blue type, i.e. having an olefin linkage at the 4,4’-positions, have been converted to nitriles by treatment with hydrogen cyanide which adds across the double bond.ls12 Bis compounds having both carboxyl or carboxyl derivatives and arylazo substituents have been prepared analogously to the mono compounds, except for the use of tetrazonium salts.727.767 Only a few 6-imino-2-pyrazolinecarboxylicacid derivatives are known. One rather interesting synthesis is oxidation of the 3-methyl group of a 2-pyrazolin-5-one to a 3-carboxyl group with potassium ~ e r m a n g a n a t e ,illustrating ~~~ the stability of the 2-pyrazolin-5-one ring to oxidation. Treatment of 3-methyl-l-phenyl-5-phenylimino-2pymzoline with phenyl isocyanate gives the corresponding 4-carboxamide.826The third method for synthesizing such compounds is shown in eq. 233. CeHsNENHz
CsHSN2CJ
NCCH,COCOOC,H,
--
+ NCCHCOCOOC2Hs
I
N=NCeH5
Part 1 .
100
Chaptor I1
B. 3-Pyrazolin-6-ones
A large number of 5-0x0-3-pyrazolin-3- and 4-carboxylic acids, acid derivatives and their sulfur analogs are known and are listed in Tables XXXIV and XXVI. The acids are synthesized by methylation acids lo8or by conversion of the N-2 of 5-oxo-2-pyrazolin-3-carboxylic of 4-substituents to 4-carboxyl groups. These conversions involve oxidation of h y d r o ~ y l , ' ~formyl ~ ' ~ lo7 ~ ~ and ~~~ carbon chain suband hydrolysis of a stituents,lo8 hydrolysis of esters109*370*993 4-trichloroacetyl Esters have been prepared by reaction of N,N'-diphenylhydrazine with ethyl o x a l ~ a c e t a t eand ~ ~with ~ dimethyl acetylenedicarb~xylate,~~~ similarly to the previously mentioned S-oxo2-pyrazolin-3-carboxylate analogs. Diethyl ethoxymethylenemalonate and N-phenyl-N'-acetylhydrazinereact to form ethyl 2-phenyl-5-0x03-pyra~olin-4-carboxylate.~~~ Methylation of 2-pyrazolin-5-one esters at N-2, as expected, gives the 3-pyrazoline analogs.1228.1230 These esters are also obtained by direct esterification of the a ~ i d s ~ ~ and by reaction of acid chlorides with alcohols.741 The 6-0x0-2pyrazolin-3- and 4-carboxamides are synthesized by treatment of the or ester697*826*1339 with appropriate acid ~ h l o r i d e , l ~anhydridez3 ~*~~l an amine. Partial hydrolysis of nitriles has also given the a r n i d e ~ . ~ ~ ~ Treatment of 3-pyrazolin-&ones with ureas or isocyanates gives the 4 - c a r b o ~ a m i d e s .Hydrazides ~~~ have been prepared from 5-0x043pyrazolinecarboxylic acid chlorides204-8g2.1634 or esters 697*898 and hydrazines. Azides are obtained by treatment of hydrazides with nitrous 1387 Various dehydrations of 5-oxo-3-pyrazolin-4carboxaldehyde oximes have been used to prepare nit rile^.^^^."^^. The N-2 methylation of 5-0x0-2-pyrazolin-carbonitrileshas also been ernp10yed.l'~~ Acid chlorides,l8,loganhydrides741and acyl n i t r i l e ~ ~ ~ l have been synthesized by the usual procedures. acids, esters and Sulfur analogs of 5-oxo-3-pyrazolin-4-carboxylic amides are known. The usual synthesis of both thio and dithio acids ~~ shown ~.~~ in~eq. 234. is by alkaline hydrolysis of the d i t h i o e s t e r ~ ,as
I
'
11.
I
R'
-
~
~
Pyrazol in-5-ones
101
Also shown in the same equation is the synthesis of esters by the reaction of 3-pyrazolin-5-ones with carbon disulfide and either ethyl bromide or ethyl chloroformate in the presence of aluminum chloride.89* The monothio acids have been synthesized by reaction of acid chlorides with hydrogen sulfide.'09 Kocwa826.829-830.831 has studied the preparation of amides and hydrazides of these thio acids and found that two types exist. In one type the compounds are thioamides but in the other they are iminothiolic acids. Treatment SH
S
II
(-GNHR)
I
(--c=NR)
of dithioesters and monothio acids with amines results in a mixture of products. The reaction of 3-pyrazolin-5-ones with N,N'-diphenylthiourea or thioisocyanates forms the tllioamides.826Hydrolysis of the iniinothiolic acids with base gives amides no longer containing sulfur.826 Mixed anhydrides of sulfonic acids and 5-oxo-3-pyrazolin-4-carboxylic acids have been prepared by the reaction of the sodium salt of the carboxylic acid with benzenesulfonyl chloride.741 The 5-0x0-3-pyrazolincarboxylicacids react normally. A number of their reactions have already been discussed in connection with the synthesis of analogous aldehydes and ketones. The Curtius rearrangement of the azide will be discussed in more detail in the section conBoth the 3- and I-carboxylic acids cerning 5-imino-3-pyrazolidinones. ~ ~ . Hydrolysis ~~~of decarboxylate at elevated t e m p e r a t u r e ~ . l 370 4-carboxanilides with hydrochloric acid first forms the acid which then loses carbon dioxide.826 A few 5-phenylimino-3-pyrazolin-4-carboxanilides and thioanilides are known (Table XIX).These were prepared by the reaction of phenylisothiocyanates or N,N-diphenylthiourea with the corresponding Ei-iniin0-3-pyrazoline~~~ or by methylation at N-3 of a 5imin0-2-pyrazolin-4-carboxanilide.~~~
10. Sulfonic Acids and Derivatives A. 2-Pyrazolin-5-ones
The only compounds of this kind which have been reported are 5-oxo-2-pyrazolin-4-sulfonic acids (Table XXXV). They are prepared by direct sulfonation, usually with fuming sulfuric 685*lg71* 1672.1674 Sulfonation occurs at temperatures as low as 10-15°,684 but it takes place much more rapidly at higher temperatures. If an aryl
102
Part 1. Chapter I1
group is present as a 1-substituent, this too may be sulfonated at higher temperatures. The sulfonic acid group is readily replaced by a number of reagents, such as nitrous acidsa4and aryldiazonium salts. It is readily removed by acid hydrolysis.684 B. 3-Pyrazolin-5-ones
5-0xo-3-pyrazolin-4-sulfonic acids (Table XXXVI) are prepared by direct s u l f o n a t i ~ nwith ~~~ sulfuric - ~ ~ ~acid and acetic anhydride or by chlorosulfonation with chlorosulfonic acid, followed by hydrolysis to the a ~ i d . The ~ ~ reaction ~ ~ of. 2,3-dimethyl-l-phenyl-5-oxo-3~ ~ ~ ~ pyrazolin-4sulfonyl chloride with urea forms a bis(5-0x0-2-pyrazolin-4sulfonic acid) derivative,1249 the only such bis derivative reported. Reduction of the sulfonic acid chlorides with zinc and acid forms the corresponding mercapto compound.1249 11. Functional Group Substituents on Nitrogen
A. 2-Pyrazolin-5-ones
Functional group substituents on N-1 of 2-pyrazolin-5-ones(Table
XXXVII) are acyl, sulfonyl and various carboxyl derivatives, such as carbalkoxy, amides, thioamides, hydrazides, thiohydrazides and amidines. The usual synthesis of these compounds is by the classical 2-pyrazolin-5-onesynthesis, reaction of a p-ketoester with a hydrazine. I n these cases the hydrazines are special types such as hydrazide, semicarbazide, carbazide or their imino or thio analog^.^^.^^, 97*275.357. 358,359.497.602,716.71~,719,720.1012,1013,1067,1222,1345.1568.1632 This synthesis is illustrated in eq. 235. Hydrazides of sulfonic acids can also be R*COCH,COORa + R3CXNHNH2 +
I1 I N‘X )=O
I
(235)
CXR3 R3 = alkyl, mdkyl, aryl, NH,, NH,NH, C,H,NHNH X = 0, S , N H
used.716 Sometimes the hydrazone intermediates are isolated and cyclized by heating.264*355.358 If R3is aralkyl or aryl it is necessary to operate at room temperature, otherwise deacylation OCCUTS.~ A /3-ketoamide can be used instead of a / 3 - k e t o e ~ t e r2-Pyrazolin-5-ones .~~~ having
Pyrazolin-5-ones
103
no N-1 substituent have been acylated by various procedures (eq. 236). Weissberger and Porter 1598 have studied such acylations using acetic anhydride and found that a side-product is formed by acylation of both
N-1 and 0. Other acylating agents used have been arylsulfonyl chloridesllg9 and alkylchloroformates."" Isocyanattes react with N-1 of 2-pyrazolin-5-oneshaving no 1 -substituent to form 5-0x0-2-pyrazolin1 -carboxanilides. Treatment of 1-acyl-5-acyloxypyrazoles with piperidine in ethanol removes the 0-acyl to give 1-acyl-2-pyrazolin-5-0nes.~~~~ A number of such compounds having a functional group on carbon atoms of the ring are known. Compounds having nitro61and c a r b ~ x y l ~ ~ ~ substituents are prepared by the above procedures with appropriate substituents in the starting materials. Those compounds having bromine,355.357 nitroso355.357.1296 and phenylazo 355*1499 substituents are prepared by the usual methods for introducing such substituents into the 2-pyrazolin-&one ring. The N-1 acyl substituted 2-pyrazolin-&ones react as do the other classes of 2-pyrazolin-5-ones since the hydrogen atoms a t C-4 are active.519*1296 The N-acyl substituents are readily removed by hydrolysis26**355 or treatment with aniline.6 Pyridine and acetic acid cause a rearrangement of N-acetyl groups to the oxygen atom.159B A few bis(l-acyl-2-pyrazolin-5-ones) are known. Those linked through N-1 have been prepared by reaction of carbazide with two equivalents of a p-ketoester lo3-I* 1632 either with255or without isolation of the intermediate hydrazone. The bis compounds linked at G 3 or G 4 are prepared by reaction of bis(p-ketoesters)with s e m i c a r b a ~ i d e .1222 ~~~. The 5-imino-2-pyrazolines having no N-1 substituents can be acylated with acetic anhydride to form the 1-acyl derivatives,301* 342*391 as can their 5-0x0 analogs. Compounds of this type having a 3-acetoxy substituent have been prepared by reaction of 3-amino-2-pyrazolin-5with acetic anhydride (eq. 237).5941508 ones (5-imino-3-pyrazolidinones) Cusmano and Sprio343*344 have treated a-benzylidene-p-ketonitriles
Pwt 1. C'lutpter T I
104
(eq. 238) with semicarbazide to give products which may be 5-iminoA T - ]
YN,==XH CBH,CH=CCOAr
+
HzNCONHNH,
I
__f
HzNCO
AN
(238)
or
ArC=NNHCONH, I dH&E
2-pyrazolin-l-carboxamides, although they may be isomeric open-chain compounds, B. %Pyra~Oh-5-0n0~
Many 3-pyrazolin-5-ones having acyl substituents on N-1 or N-2 or on both have been reported and are listed in Table XXXVIII. Most of these compounds have been prepared by acylation of 2-pyrazolin-6ones with acyl chlorides or anhydrides. Usually it was assumed that acylation occurred on one or the other of the nitrogen atoms and 0-acylation was not considered. However, Weissberger and Porter 1598 have found that acylation occurs quite readily on the oxygen, and have shown that the compound reported by von R ~ t h e n b u r g lto~ ~be~ 1,2-diacetyl-3-phenyl-3-pyrazolin-5-one was actually 1-acetyl-3-phenyl5-acetoxypyrazole. In view of this work it is probable that many of the compounda believed to be 1- or 2-acyl-3-pyrazolin-6-onesare 5acetoxypyrazoles. Henry and Dehn643have obtained a product from 3-methyl-l-phenyl-2-pyrazolin-5-one and phenylisocyanate which may be 3-methyl-l-phenyl-2-phenylcarbamyl-3-pyrazolin-5-one but it may be a product of reaction of the enolic hydroxyl group. 4,4'-Bis(3-methyl-2-benzoyl-l-phenyl-3-pyrazolin-5-one) has been reported as the product obtained from treatment of 4,4'-bis(3-methyl-lphenyl-2-pyrazolin-5-one) with benzoyl chloride.1o56 The reaction of 5-imino-3-pyrazolidinoneswith acetic anhydride forms 2-acetyl-3-acetoxy-5-acetimido-3-pyrazolin-5-ones as well as the 5-imino-2-pyrazolinederivatives already mentioned.5941599 12. Mercury Substituted Derivatives A. 8-Pyrazolin-5-ones
Only one mercurated 2-pyrazolin-5-one has been reported. This was prepared by Schrauth and B a u e r s ~ h m i d t 'and ~ ~ ~its structure is not completely known (eq. 239).
Pyrazolin-5-ones
105
B. 3-Pyrazolin-5-ones A few mercurated 3-pyrazolin-5-ones have been prepared by R a g n ~ (Table ' ~ ~ ~XXXIX). Antipyrine was treated with mercuric acetate or mercuric ammonobasic chloride, giving mercury-containing substituents in the 4-position. The chloromercuri and acetoxymercuri compounds obtained were converted into others by treatment with hydrochloric acid, potassium bromide, potassium iodide, iodine or sodium hydroxide. More vigorous treatment with mercuric acetate introduced a second acetoxymercuri substituent which waa in the phenyl ring,
13. Metallic and Non-metallic Complexes A, 2-Pyrazolin-5-ones
2-Pyrazolin-5-ones react with salts of various metals to form compounds in which the pyrazolinone has reacted in its enolic form with replacement of the enolic hydrogen to give B salt and having semipolar bonds formed by donation of electrons to the metal by the nitrogen atoms393,394 Usually these compounds contain the number of pyrazolinone residues corresponding to the valence of the metal atom. Such salts as cuprous iodide, ferric iodide, cobaltous iodide, silver iodide and silver diiodide participate in such reaction^.^^^.^^^ I n addition, complexes may be formed in which there has been no elimination of a small molecule between the reactants and no formation of ionic Various substituted 2-pyrazolin-5-onesreact with metal salts with replacement of hydrogen and formation of semipolar bonds with electron donating atoms. The most important of these compounds are These complexes the metal complexes of 4-arylazo-2-pyrazolin-5-ones. are widely used in the dye industry to give desired properties to 4arylazo-2-pyrazolin-5-one dyes. Although a large number of metal-dye complexes have been used in dyeing, only a few such compounds have been characterized and reported in the literature. Usually a solution of the azo compound and an appropriate salt such as cupric chloride or nickel sulfate are mixed in solution and heated.32BThe reaction is
106
Part 1. Chapter I1
shown in eq. 240 together with the structure of the final product. In some cwes the formation of an intermediate, aa shown in eq. 240, has been reported.1038-1040The structures of complexes with chromium are shown in formulas (XXX) and (XXXI). Brady and Porter13* have
c1-
CBH.5 I
" Pi \J
N-
I
OCH,
reported complexes of 4-oximino-2-pyrazolin-B-oneswith lithium, sodium, pohasium, rubidium, ceaium, thallium and nickel. These complexes have the struoture (XXXV) if they are derived from an atom having a valence of one. If the metal has a valence of two, the
(XXXV)
complex is a dimer of (XXXV).G i ~ a has ~ ' ~prepared the thallous salt of picrolonic acid, 4-nitro-3-methyl-l-(4-nitrophenyl)-2-pyrazolin5-one. This is reported t o have a structure similar t o (XXXV), with the metal replacing the hydrogen of the pseudo-acid form of the nitro group.
Pyrazolin-6-ones
107
Dains, O'Brien and Johnson351 have added bromine to various 4-arylaminomethylidyne-1-aryl-3-alkyland 3-aryl-Z-pyrazolin-5-ones. Whether this is a complex or an addition to a carbon-nitrogen double bond is uncertain. The bromine is very loosely held and is probably not bound covalently. The formation of various complexes between 1-methyl-3-phenyl-2pyrazolin-5-one and organic compounds has been reported.lls4 These were 1: 1 complexes &withm- and p-nitrophenol, o-cresol, picric acid, trinitrobenzene, a-naphthol, hydroquinone, hydroxy- and halogenoaliphatic acids and aromatic acids. It was claimed that these did not behave as salts. Similar complexes of other 2-pyrazolin-&ones with trinitrobenzene have been r e ~ 0 r t e d . l ~ ~ ~ B. 3-Pyrazolin-5-ones
3-Pyrazolin-5-onesform complexes with both inorganic and organic compounds much more readily than do the 2-pyrazolin-5-ones. The most extensive series of complexes is that formed with a variety of metallic salts. Antipyrine (2,3-dimethyl-l-phenyl-3-pyrazolin-5-one) forms a series of complexes with salts of divalent, trivalent and tetravalent metals. Two molecules of antipyrine form a complex with one molecule of copper, cadmium, cobalt and zinc salts.2ss*8se*111a Complexes prepared from metallic nitrates are usually hydrated. 1322 There also exists a series of complexes in which three molecules of antipyrine form a complex with one or two molecules of metallic salts. Such complexes form with two molecules of simple ferric salts27aor with one of complex iron cyanides.608Nitrates of thorium, lanthanum, cerium and samarium also give such This ratio also occurs in some antipyrine complexes with cadmium and zinc thiocyanate.26s A number of salts of rare earths and iron which have complex anions such w thiosulfate, thiocyanate, dithionic acid and complex iron cyanides form complexes in which six molecules of antipyrine are present.405.408-s08*841* 950 Stannic chloride forms salts containing three or four molecules of antipyrine and hydrochloric acid.46 Aminopyrine (4-dimethylamino-2,3-dimethyl-l-phenyl-3-pyrazolin-5-one) forms complexes similar to those of antipyrine, but usually containing fewer molecules of the 3-pyrazolin-5-one. Complexes with mercury, cadmium, antimony, zinc and cobalt salts include only one molecule of aminopyrine. A number of complexes with cobalt, zinc and calcium salts have two molecules of aminopyrine, some also containing ~ . complex ~ ~ ~ ~ with cerous nitrate acid and water of h y d r a t i ~ n . ' ~The few contains three molecules of a m i n 0 ~ y r i n e . lA~ ~ ~ other substituted
108
Part 1. Chptsr I1
antipyrine-metal salt complexes of a similar nature have been reported.869.1158.1322 These metallic salt complexes are decomposed by sodium hydroxide 868 or by boiling with water.1158 Several complexes of 3-pyrazolin-5-ones with iodine are 429 These contain varying proportions of the pyrazolinones and iodine and always contain hydrogen iodide. The iodine is readily lost by heating or by recrystallization. Iodine complexes with bis(2,3dimethyl-l-phenyl-5-oxo-3-pyrazolin-4-yl)merc~iry have been reported.433 A number of organic compounds form complexes with antipyrine and aminopyrine. Usually these are in a 1 :1 ratio, although those with diethylbarbituric acid,1112phenylethylbarbituric and diphenylh y d a n t ~ i n *may ~ l contain two molecules of pyrazolinone, and a complex having two molecules of diphenylhydantoin to one of antipyrine has been reported.1021A series of complexes with phenols, aromatic acids, and hydroxy and halogeno aliphatic acids have been reported.lle4 These products do not behave like salts. Benzenesulfonyl chloride forms a complex with antipyrine in a 2 :1 ratio.1281Pfeiffer and Seydell1l5 claim that complexes of antipyrine and aminopyrine with 2,2,2-trichloroethyl carbamate and its N-phenyl homologue involve bonding a t l ~ ~ ~ the same the amide group in the pyrazolinone. T a b o ~ r y reaches conclusion regarding the chloral-antipyrine complex on the basis of Raman spectra. 14. Miscellaneous Derivatives
This section comprises a few 3-pyrazolin-5-ones which do not fit well in other sections and some polymeric 2-pyrazolin-5-ones. 2-Pyrazolin-5-ones have been incorporated into a number of polymers for use in color photography. Many of these are prepared by reaction of a functional group in a polymer with some reactive group in a pyrazolinone. Some are prepared by linking polymers with pyrazolinones through aldehydes, and frequently bifunctional pyrazolinones are made to react with aldehydes t o give condensation polymers. I n one case a hydrazino group is formed in a copolymer of p-aminostyrene and inaleic acid and this polymer is condensed with ethyl acetoacetate giving a polymeric pyrazolinone.16 Several pyrazolinone polymers have been prepared by linking polymers and pyrazolinones by amide linkages. This has been done by treating copolymers containing maleic anhydride with 1-(amjnophenyl)2-pyrazolin-5-ones162* 1273 and by treating the acid chloride of l-(3-carboxyphenyl)-3-methyl-2-pyrazdin-5-onewith polymeric
Pyrazolin-5-ones
109
A similar type of polymer is that obtained from poly-pexcept that chlorosulfostyrene and l-(aminophenyl)-2-pyrazolin-5-one, a sulfonamide linkage is obtained.loo5 Quite a variety of polymeric pyrazolinones have been prepared by reaction of polymers having amide or hydroxyl groups with aldehydes and pyrazolinones. Some of the pyrazolinones have contained amino groups. The linkages involved are probably acetal for the most part. In one of these cases the aldehyde group is incorporated in the 1-aryl group of the pyrazolinone and the polymer is a polyvinyl a l c h o h 0 1 . ~ ~ ~ Presumably the polyvinyl alcohol forms an acetal of the formyl group. Woodward 1647.1648 has prepared polymers from polyhydroxy compounds such as polyvinyl alcohols and methyl cellulose combined with aldehydes and pyrazolinones. The linkages here are no doubt formed by conversion of the aldehydes to acetals and may be derived from the enolic form of the 2-pyrazolin-5-ones.Jennings 708 and McQueen g66 have prepared similar polymers. Condensation of polyvinyl alcohol with 1-(3-arninophenyl)-3-methyl-2-pyrazolin-5-one in the presence of dialdehydes such as glyoxal and terephthaldehyde has given polymeric p y r a z o l i n ~ n e s .The ~ ~ ~linkage is probably a combination of Schiff’s base and acetal formation. A polymer has been prepared by reaction of a polyaniide with formaldehyde, 3-methyl-1-phenyl-2-pyrazolin-5-one and b u t a n 0 1 . ~It~seems ~ likely that the aniide nitrogen of the polymer is connected by a methylene group with C-4 of the pyrazolinone. Jennings, Murray and White712have obtained a polymer of uncertain structure from polyvinyl alcohol, m-aminobenzaldehyde and 1 -phenyl5-oxo-2-pyrazolin-3-carboxylic acid. There are a number of possibilities for linking groups which may be present in this polymer but, in any case, some must be of acetal or ether type. Bisamides of amino-2-pyrazolin-5-01ies react with aldehydes such as formaldehyde and p-hydroxybenzaldehyde to give p ~ l y r n e r sl o. 4~I ~ ~ ~ Presumably the linking group is > NdH-N< . Bisamides of 1-(aminophenyl)-2-pyrazolin-5-onesand of 3-amino-2-pyrazolin-5-ones have reacts with been used. 1-(3-Aminopheiiy1)-3-methy1-2-pyrazolin-5-one many aldehydes and ketones to form Probably condensation occurs a t C-4 and the amino group. The product of reaction of p-cresol with formaldehyde has been found to react with 1-(4-hydroxyphenyl)-3-methyl-2-pyrazolin-5-one to give a polymer that must have the aromatic and pyrazolinone rings connected by ether linkages.1269 Kirby 780 has linked a polymer with a pyrazolinone by forming the quaternary salt of l-(3-bromoacetamidophenyl)-3-methyl-2-pyrazolin5-0110 with a polyamine.
Part 1. Chapter I1
110
Jennings709 has linked pyrazolinones with zein by means of formaldehyde and dimethylolurea. It was suggested that a linkage is formed from amino groups in the zein to 6 4 or an amino group in the pyrazolinone. Verkade and Dhont 1531 have treated 3,4-dimethyl-2-pyrazolin-5one and 4-methyl-3-phenyl-2-pyrazolin-5-one with phenyldiazonium chloride, forming respectively 3,4-dimethyl-2-phenylazo-3-pyrazolin-5one, m.p. 273O, and 4-methyl-3-phenyl-2-phenylazo-3-pyr~zolin-5-one, m.p. 212 '. 2,3-Dimethyl-1-phenyl-3-pyrazolin-S-one reacts with thiooyanogen to give its thiocyanate salt and 2,3-dimethyl-l-phenyl-4thiocyanato-3-pyrazolin-5-one, m.p, 125°.742 2,3-Dimethyl-l-phenyl-5-oxo-3-pyrazolin-4-carboxaldehydereacts with 2,3-dimethyl-l-phenyl-3-pyrazolin-5-one to give tris(2,3dimethyl-l-phenyl-5-oxo-3-pyrazolin-4-yl)methane.1o7 Mannich and Krosche948have treated 2,3-dimethyl-l-aryl-2-pyrazolin-5-ones with hexamethylenetetramine to give compounds of the type shown in eq. 241. The aryl groups were phenyl and p-tolyl. The reaction of 2,3-
+
cH37=l
CH3-N \N/=O
I
Ar
(cH,),N,
-(
cH 1-" 3-3" CH,-A-Lo
(241) 3
dimethyl- l-phenyl-3-pyrazolin-5-one with ethylene diamine and formaldehyde gives (XXXVI).945 2,3-Dimethyl- 1-phenyl-3-pyrazolin-5-one reacts with mercuric oxide to give bis(2,3-dimethyl-l-phenyl-5-0~0-3pyrazolin-4-yl) mercury, m.p. 1S0°,433 and with selenium or selenium dioxide to give the corresponding selenide, m.p. 240°.545
CHAPTER I11
2-P yrazolin-+ones Relatively few 2-pyrazolin-4-ones are known, and most of our knowledge of these compounds has been furnished by Chattaway, Ashworth and co-workers who published an extensive series of papers on this subject in the thirties. These compounds are basic, forming salts with acids and alkyl halides, and they are also acids, giving salts with bases. They form colored complexes with ferric chloride. Four structures are possible for 2-pyrazolin-kone, (XXXVII), (XXXVIII), (XXXIX) and (XL), but substitution at G 3 and C-5 makes possible
H (XXXVII)
H (XXSVIII)
(XXXIX)
(XU
several more isomers. If a substituent is present at N-1, only two isomers, (XXXVII) and (XXXVIII), are possible. It has usually been considered that 2-pyrazolin-5-ones have the hydroxypyrazole structure (XXXVIII).266-290 has postulated this structure on the baais of the alcohol derivatives formed by these compounds. However, Emerson and Beegle 425 have found that 4-oxo-2-pyrazolin-3-carboxylic acid forms two derivatives by reaction with 4-amino-2,3-dimethyl-lphenyl-3-pyrazolin-5-one (2,3-dimethyl-l-phenyl-4-imino-3-pyazolidinone). This was interpreted to mean that the 2-pyrazolin-4-ones exist in two forms. One of these would be either (XXXVII) or (XXXVIII) with a carboxyl group at C-3, or a mixture of these two forms, and the other would be either (XLI) or (XLII), or a mixture of these. Bertho HOOC--
'N'
J0 &To" "*OC1
'N'
(XLII)
(XLI) 111
112
Part 1.
Chapter I11
and NUsselg2have argued that 2-pyrazolin-4-ones exist as keto-enol tautomers. 2-Pyrazolin-4-ones having substituents at N-1 and C-3 and disubstituted at C-5 would necessarily exist in the 0x0-form (XXXVII). The 2-pyrazolin-4-onesare listed in Table XL. Only two procedures are known for direct synthesis of the 2pyrazolin-4-one ring system and one of these has been used very little. The chief method employed has been cyclization of the 1-arylhydrazone of 3-substituted-l,2-dioxo compounds (eq. 242) using basic cyclizing XCH,COC=NNHR
I
---+
Y
‘N’
k
X = halogen or RCOO Y = COOC2H, or R’CO R = Ar or S0,Na
agents.286-290-295.1292*1644 I n the case in which R=SO,Na, the R is lost and in the final product R = H . The only other method of ring formation is that reported by Bertho and Pu’iissel92 in which malonic esters are t,reated with ethyl diazoacetate (eq. 243). If R1 is H, the substituent R2in the product is carbethoxyl, but otherwise R1= R2. R’CH(COOC2H,),
+ NZCHCOOC2H6 + “ ‘ ~ ~ ~ O O C z € 1 (243) 6 H
Treatment of 2-pyrazolin-4-oneswith chlorine results in formation of 5,5-dichloro-2-pyrazolin-4-ones.2a7~288~290 Reaction of the 5,5dichloro compound with hydrogen iodide 287 or potassium iodide 288.290 removes one chlorine atom to give 5-chloro-2-pyrazolin-4-ones. Bromination does not follow the same course as chlorination, but instead Carboxyl-containing 2forms 5-bromo-2-pyrazolin-4-ones.2a6~290~1292 pyrazolin-4-ones can be obtained by hydrolysis of the esters obtained, as shown in eq. 243, or directly by the cyclization procedure of eq. 242. These acids can then be decarboxylated at elevated temperature^.^^. 1644 Heating the methiodide of 2-pyrazolin-4-onegives methylation at N-1. 2-Pyrazolin-&ones couple with diazonium salts to give 5-arylazo sub~tituents.’~~* The 0x0 group in 2-pyrazolin-4-onesreacts as a hydroxyl group, forming acetates,286 benzoates 1644 and urethanes.164* Reaction of 2-pyrazolin-4-oneswith phosphorus oxychloride results in replacement
2-Pyrazolin-4-ones
113
of the oxygen to give 4 - c h l o r o p y r a ~ o l e sTreatment .~~~~ of 2-pyrazolin-4ones with nitrous acid gives substitution of an oximino group at (2-5. Ethyl 1-aryl-5,5-dichloro-4-oxo-2-pyrazolin-3-carboxylates react with alcohols and alkali by cleavage of the ring and formation of monoarylhydrazones of diketosuccinic acid and its esters.287.290 For purposes of classification the 4-aminopyrazoles'are considered to be 4-imino-2-pyrazolines and analogs of 2-pyrazolin-4-ones. These compounds are listed in Table XL. Such compounds can be prepared by direct cyclization using ethyl diazoacetate and ethyl c y a n o a ~ e t a t e . ~ ~ This is the same as eq. 243, except that the malonic ester is replaced by ethyl cyanoacetate. Purines can be hydrolyzed to 4-imino-21646 By far the most frequently pyrazolines by using strong used preparation is reduction of appropriately substituted pyrazoles, such as 4-nitro,368.812.819.1015.1019.1049 $-nitroso 1165 or 4-aryl974. 995 The hydrolysis of the carbethoxy 4-imino-2-pyrazolines derived from ethyl cyanoacetate and ethyl diazoacetate forms 4imino-2-pyrazolin-3-carboxylic acid which is readily decarboxylated to the parent compound.92 The 4-imino-2-pyrazolines react as would be expected of 4-ami1-10pyrazoles. For example, acylation 368-1043 and diazotization 812*819 occur readily. Only two bis(4-imino-2-pyrazolines)have been prepared. These were reported by Michaelis and S ~ h a f e r . ~ ~ ~
CHAPTER I V
z-Pyraxolin-4,5 -diones Only half-a-dozen of these compounds are known (Table XLI) and at least this number of methods of preparing them have been reported. Borsche and Manteuffel lZ5 have found that 2-pyrazolin-4,5-diones are formed aa the by-products when a-ketoesters are treated with aryldiazonium salts. The principal products are 4-arylazo-2-pyrazolin-5ones. Nitric acid oxidation of 3-methyl-l-phenyl-2-pyrazolin-5-one forms the corresponding 4 , 5 - d i 0 n e . ~Wislicenus ~~ and Goz 1642 heated 4 - bromo - 4 -nitro - 1- (4- bromophenyl) - 3 -methyl - 2 -pyrazolin - 5 - one in water and obtained the analogous 4-0x0compound. Acid hydrolysis of rubazonic acids, which are 4-imino-2-pyrazolin-5-ones, leads to 2pyra~olin-4,5-diones.~~~. *09 Oxidation of 4,4’-bis(2-pyrazolin-5-ones)or of rubazonic acids with nitric acidao9forms the 4,5-diones.
114
CHAPTER V
3 -Pyrazolidinones In recent years there has been extensive work in the field of 3-pyrazolidinones because of their use as photographic develop e r ~ . ~ ~ This~ phase . ~of ~3-pyrazolidinone ~ . ~ ~ ~chemistry ~ . ~will~be~ considered in more detail in a later section. The 3-pyrazolidinones are monoacidic basesgll*1550 forming various salts. They are not acidic,1550 in contrast to the 2-pyrazolin-5-ones. They reduce Fehling's solution and give colors with ferric chloride.1550Jensen '13 found that 5-phenyl3-pyrazolidinone absorbs infrared light in the carbonyl region at 5.83 p. and at 5.91 p in solution or at 5.97 p. in the solid state. The absorption was markedly different from that of noncyclic hydrazides. These compounds are listed in Table XLII. As was mentioned previously (eq. 4,p. lo), the principal method used for synthesis of 3-pyrazolidinones is the reaction of hydrazines with a,/?-unsaturated acids,446* 816*911-1342*1550 a$-unsaturated esters581.762.911.1209* 1569 and a,/?-unsaturateda m i d e ~I .n~many ~ ~ cases as shown these reactions do not give l-substituted-3-pyrazolidinoneaJ in eq. 4,but the isomeric 2-substituted-3-pyrazolidinones7 as shown for one particular case in eq. 244. Most frequently aryl hydrazines have CH,CH=CHCOOH
+ C6H6NHNH2
-
cH3-- I HNJ=O
(24)
&H6
been used in this synthesis, but in a few cases hydrazine has been ~ s e d . QIn this ~ ~situation ~ ~ isomerism ~ ~ ~ is* not ~ a~problem. ~ ~ Only a few acids have been used in these reactions, but these have all given the 1650 Acrylamide, methacrylamide, crotonamide 2-isomer (eq. 244).446 and fl,fi-dirnethylacrylamide and various aryl hydrazines have been condensed in anhydrous solvents in the presence of strong bases. In all cases the 1-isomer (eq. 4) has been obtained.758 Kendall, Duffin and 115
~
116
Part 1. Chapter V
Axford762have found that the reaction of various esters with phenylhydrazine in the presence of sodium ethoxide led to the 1-isomers (eq. 4). Under somewhat similar conditions, but using sodium methoxide as the condensing agent, VystrEil and Stejskal 1569 found that methyl crotonate and phenylhydrazine did not give a 3-pyrazolidinone but rather pyrazolinones. These latter authors studied the condensation of methyl methacrylate and methyl crotonate with phenylhydrazine in the presence of hydroquinone. The chief products were the %isomers (eq. 244), but I-isomers were usually formed in very small yields. Another widely used procedure for the preparation of 3-pyrazolidinones is one closely related to the preceding one. This method is treatment of a p-substituted acid, lactone, amide or acid chloride with an aryl hydrazine. Substituted p-chloropropionyl chlorides have been used, giving 1-aryl-3-pyra~olidinones.'~ The same kind of product was obtained with a 8-bromopropionic Condensation of P,Bdimethylglycidamide with phenylhydrazine at 150" gave 5,5-dimethyl4-hydroxyl-2-phenyl-3-pyrazolidinone.'56~ 1260, lZ6l Kendall 750 has claimed that arylhydrazines react with 8-propiolactoneto give 1-aryl-3pyrazolidinones. Reynolds and Tinker '17? have stated that this reaction does not occur. However, Gresham and c o - w o r k e r ~have ~ ~ ~reported that p-propiolactone and phenylhydrazine form the phenylhydrazide of /3-hydroxypropionic acid, and Reynolds and Tinker have converted this compound into 1-phenyl-3-pyrazolidinone.Furthermore, the physical constants claimed by Kendall for his products are the same as those reported by others for the same compounds. From these facts it seems likely that Kendall did obtain 3-pyrazolidinones by the procedure claimed. Cyclization of a,P-unsaturated acid hydrazides319 or 8-hydroxypropionic acid hydrazides 1177* 1327 forms 3-pyrazolidinones. The p hydroxy acid derivatives have usually been cyclized with acid a t elevated temperatures. If the hydrazides of aryl hydrazines are used, that a,Bunsaturated N-1 substitution occurs. It has been reported . acid hydrazines cyclize by treatment of the hydrazide with nitrous leading to formation of l-nitrosoacid (eq. 245),335.479.1028*1029 HNOZ
RCHLSCHCONHNH, --+
' 7
" 0
\h'/=o
(245)
H
pyrazolidinones. However, Godtfredsen and Vangeda1581have shown that in some cases the starting materials were pyrazolidinones, rather than hydrazides, and this may be true in all cases, so that cyclization by this procedure probably does not occur.
3-Pyrazolidinones
117
Cyclization of /3-hydrazino acids under acid conditions has been used by Lederer888 and by S t o l ~ ' ~to ~ ' obtain 3-pyrazolidinones. Treatment of an analogous nitrile with concentrated hydrochloric acid also gives a 3-pyraz01idinone.l~~~ VystriEil and Stejskal 1569 have reported that heating a mixture of methyl a-piperidinobutyrate and phenylhydrazine at 170' gave 4-methyl-2-phenyl-3-pyrazolidinone. The reaction of 2-phenyl-4-benzylidene-5-oxazolone with hydrazine 1342 Both 2-pyrazolinforms 4-benzamido-5-phenyl-3-pyrazolidinone.31g~ 6-ones and 3-pyrazolin-5-ones have been reduced catalytically to 3-pyra~olidinones.'~~~* 15g2 Heymons and Rohland"' have treated 3methyl-172-diphenyl-3-pyrazolin-5-one with sodium and carbon dioxide and claimed to have obtained a carboxylic acid, presumably by intermediate addition of sodium to the double bond (eq. 246). A number of
I
CBH,
I C6H5
conversions of variously modified ring systems into 3-pyrazolidinones have been reported. 3-Iminopyrazolidines have been hydrolyzed with acid to the analogous 0x0 compounds. Rondestvedt and ChangI2O9have found that treatment of N,N-diethyl-l-pyrazolin-3-sulfonamide with bromine forms 3-pyrazolidinones. The first step is probably the replacement of the sulfonamide portion by bromine; the bromopyrazoline could then go to the pyrazolidinone by hydrolysis. 3-Pyrazolidinone was also obtained by the reaction of ethylenesulfonyl chloride with diazomethane,1209 which also probably passes through a halogenated pyrazoline stage. T ~ u m a k i ~has ~ O claimed ~ that acid hydrolysis of 172-diphenyl-3,5-pyrazolidinedione formed 3,4-dihydroxy-l,2-diphenyl3-pyrazolidinone. The oxidation of 3-pyrazolidinones to 2-pyrazolin-5-oneshas been mentioned (eq. 23). The 3-pyrazolidinones are also oxidized by Fehling's and cupric sulfate.681 The oxidation of l-aryl-3888 pyrazolidinones to 3-pyrazolin-5-oneshas been Substitution in the 3-pyrazolidinone-- molecule occurspreferentiallx ----on one of €lie nitrogen iL@ms,-ifthish possible, although reagents such ~m o-m _ me_ may _oxidize the 3-pyrazolidinone to a 2-pyrazolin-5-one, and then substitute at G 4 . Alkylation of 3-pyrazolidinones with alkyl halides - - and alkyl sulfates and bases usually occurs at N-2,335.1029 but 8 substituents are present here, alkylatioaat, N-L 888.1261 _ _ I -
Part 1. Chapter V
118
Alkylation of 4-methyl-3-pyrazolidinonewith butyl ethylenesulfonate gave alkylation at N-1 with addition of nitrogen at the ,&position of the a$-unsaturated system.1209 Earlier workers have claimed that nitrosation of 3-pyrazolidinones leads to either substitution at C-4 446 or oxidation to 2-pyrazolin-5-ones followed by substitution at C-4.816* 1550 However, later workers uniformly report that nitrosation 1491 Treatment of 3-pyrazolidinones occurs at N-1 (eq. 247).911-1342.
I
I
GHt5
C,H5
with bromine results in oxidation to 2-pyrazolin-5-ones followed by 8 substitution of one or two bromine atoms at G 4 . 3 3 6 ~ 1 0 aAcetic anhydride reacts with 3-pyrazolidinones t o give 1-acetyl derivatives.888.1569Aldehydes react with 3-pyrazolidinones a t N-1, giving products which are ~ w i t t e r i o n s . ~ ~ ' In the presence of sulfuric acid 1-nitroso-3-pyrazolidinones lose nitrous acid by elimination, giving 2-pyrazolin-5-ones which are then nitrosated at C-4.335*1028The amino group in 4-amino-3-pyrazolidinones is diazotizable and the resulting diazonium salt undergoes coup1ing.l A number of mercury-containing 3-pyrazolidinones have been prepared by Schrauth and B a u e r s ~ h m i d tTreatment . ~ ~ ~ ~ of l-aryl-3pyrazolin-5-ones having no substituent at C-4 with mercuric acetate in methanol causes addition of acetoxymercuri and methoxy groups at the 3,4-double bond, substitution of acetoxymercuri at G 4 and mercuration in the aryl rings (eq. 248). 2-Pyrazolin-5-ones also undergo Hg0C0CH (248)
I
C,H,
I
C,H,(HgOCOCH,)2
this reaction, behaving as if they were 3-pyrazolin-5-ones.Substituents at G 4 change the course of the seaction. In these cases reaction does not occur at low temperatures but does at 160" to give addition of acetoxymercuri and hydroxyl at the 3,4-double bond. The 4-acetoxymercuri substituents are replaced by hydrogen in the presence of hydrochloric acid, but the same substituents at C-5 are converted to chloromercuri.
3-Pyrazolidinones
119
Only three bis(3-pyrazolidinones) have been reported in the literature. These are 5,5’-bis(4,4-dimethyl-l-phenyl-3-pyrazolidinone),I5 4,4’-bis(3-oxopyrazolidin-1-yl)dibenzyl ether1177 and 1,4bis(2-nitroso-3-oxopyrazolidin-5-yl)benzene.1226 These are made by procedures already discussed. A number of 3-iminopyrazolidines have been reported and are listed in Table XLIII. It has generally been believed that these compounds exist as 3-aminopyrazolines, although equilibrium between the two forms has been suggested.757Actually the correct structure of these compounds has not been established and it may well be that they exist primarily as the imino isomer. The reaction of a,,!l-unsaturated nitriles 396.7 5 7 * ‘13~ or 8-alkoxypropionitriles767 with hydrazines gives 3-iminopyrazolidines. If the hydrazine is substituted, the substituent appears at N-1 (eq. 249). The Ra
same type of product is obtained by cyclization of a /3-hydrazinopropionitrile.1122Reduction of 3-arylazopyrazolinesalso forms 3-iminop y r a z ~ l i d i n e s . The ~ ~ ~imino . ~ ~ ~group of these compounds is readily acylated, and the acyl derivatives can be reduced with lithium diiminum hydride to 3-alkyliminopyrazolidines.The acid hydrolysis of 3-iminopyrazolidines has already been discussed.
CHAPTER VI
For purposes of classification, 4-hydroxy-, 4-mercapto- and 4amino-3-pyrazolin-5-ones, except 4-amino having no hydrogen on the nitrogen, have been considered to be 3,4-pyrazolidinediones or derivatives thereof. These compounds could theoretically exist as the 4-0x0, 4-thiono or 4-imino forms but do exist largely, if not exclusively, as the hydroxy , mercapto and amino isomers. The amino compounds will be named as 4-amino-3-pyrazolin-5-ones. They are listed in Table XLIV. 1,5-Dimethyl-2-pheny1-3,4-pyrazolidinedione and its 1,5-diphenyl2-methyl analog are the only compounds of their class known. The former has been synt,hesized by treatment of 1 -(2,3-dioxobutyryl)-Iphenyl-2-methyl-2-nitrosohydrazine hydrate with sodium bisulfiteg9 and by methylation of 4-hydroxy-3-methyl-1-phenyl-2-pyrazolin-5one.82oThe latter compound has been prepared in the same way.1243 The dimethyl phenyl compound has also been isolated from urine as a metabolic product of 4-dimethylamino-2,3-dimethyl-l-phenyl-3-pyrazolin-5-ones1' and it is formed by treatment of the same compound with sulfuric acid.618 The 4-thiono analog is also known. Reduction of 2-3-dimethyl-l-phenyl-5-oxo-3-pyrazolin-4-sulfonic acid using zinc in acid gives 1,5-dimethyl-2-phenyl-4-thiono-3-pyrazolidinone. 249 There has been a great deal of interest in 4-amino-3-pyrazolin-5ones because of their pharmacological activity. These compounds are closely related to antipyrine and aminopyrine and a great many of them have considerable antipyretic and analgesic activity. By far the most widely used method of preparation of 4-amino-3-pyrazolin-5-ones has been reduction of the corresponding nitroso compounds (eq. 250). (250)
I
I
R'
R' 120
3,4-Pyrazolidinediones
121
Catalytic 1491 zinc-acetic lool. 1504 zincsodium b i s ~ l f i t e , ~ and ' ~ ~a. ~mixture ~ ~ ~ of sodium sulfide, sodium hydrogen sulfide and sodium 461 have been used. Reduction of 4-nitroso3-pyrazolin-5-ones with sodium bisulfite forms the 4-sulfamino acid or its sodium salt (eq. 197). The reduction of 4-nitro-3-pyrazolin-5-ones with zinc and acetic acid also gives the 4-amino compounds.984~992~1001 with hydrogens70 and of Reduction of 4-arylazo-3-pyrazolin-5-ones iminoquinones in which the imino nitrogen is substituted by a 5-0x0-3pyrazolin-4-yl 417 are means of obtaining 4-amino-3-pyrazolin-5-ones. A few other methods of preparing 4-amino-3-pyrazolin-5-ones have been reported but none has been used extensively. Methylation of the N-2 of 2-pyrazolin-5-ones, the classical 3-pyrazolin-5-one synthesis, has been reported only once.536 Emerson and co-workers 426 have hydrolyzed iminotoluquinone substituted by antipyrine to give the 4-amino compound. A rather similar reaction, hydrolysis of 4-benzylideneamino-2,3-dimethyl-l -phenyl-3-pyrazolin-5-one in the presence of dimethyl sulfate, forms the 4-methylamino analog.940 3-Pyrazolin-5ones react with urea and acylureas a t elevated temperatures, introduc4-Aminoing the urea moiety as a substituent a t C-4 (eq. 251).1300n1367
(251)
I
R1
I
R'
antipyrino has been isolated as one of the metabolic products of __ anti~yrine.~~~ reacts normally. The amino group of 4-amino-3-pyrazolin-5-ones Acylation occurs readily with a wide variety of acylating agents. Amides 1473 are formed by reaction with acid ~ h l o r i d e s , ~ 1414* ~.~ ~~.~~~* acidss18-g84~ 1471 and esters in the presence of phosphorus p ~ n t o r r i d e . ' ~ ~ ~ Thioformamides have been prepared by reaction with dithioformic acid and its salt^.^'^^ 556*1374 Sulfonyl chlorides react t o form sulfon984- 1249*1504 Chlorophosphates react with 4-amino-3pyrazolin-5-ones to form phosphoramide derivatives.509-1 4 ~ * The alkylation of 4-amino-3-pyrazolin-5-ones has already been discussed to a considerable extent in connection with the preparation of such compounds having two substituents on the extranuclear nitrogen atom (see p. 76). The most straightforward alkylation is that with alkyl h a l i d e ~ . l Alkylation ~ l ~ ~ ~ ~ by means of formation of the Schiff base with aldehydes or ketones followed by catalytic reduction has 1303 Treatment of 4-amino-2,3-dimethyl-lfrequently been used.111*131* phenyl-3-pyrazolin-5-one with formaldehyde and sodium bisulfite in 5"
Part 1. Chapter VI
122
basic solution forms sulfamipyrine ( M e l ~ b r i n ) , l 641 ~ ~ formerly + ’ ~ ~ ~ used as an antipyretic and analgesic (eq. 252). The 4-methylamino derivative
CH3mm2 Lo CHaO
NSHSO~
cH3-
\Ni=o
deH,
CH~T=NHCH,SO~H
CH3-N
‘N-
(262)
ha,
gives Dypyrone (Novalgin) used outside the U.S.A. Other aldehydes have also been used in this reaction to give analogous If sulfurous acid and formaldehyde are used in this reaction, the product is the sulfinic acid.ls4 The use of formaldehyde and hydrogen cyanide introduces a cyanomethyl substituent on the nitrogen.524A number of acridine and quinoline substituents have been introduced into the 4amino group by reaction of 4-amino-3-pyrazolin-5-ones with chlorinated These compounds were studied acridines and q u i n o l i n e ~ 390~547*717 .~~* for their antimalarial activity. The amino group of 4-amino-3-pyrazolin-5-ones can be diazotized easily and the resulting diazoniuin salt couples with the usual reagents. Other diazonium salts couple with 4-amino-3-pyrazolin-5-ones at the amino group. Mercuric halides replace the amino hydrogen in 2,3dimethyl-l-phenyl-4-sulfamino-3-pyrazolin-S-one.543 The 4-amino groups react normally with isothiocyanate~,~~ epoxides,1261ureas 1367 and n i t r ~ s a m i n e s . ~ ~ ” Only a few bis(4-imino-3-pyrazolidinones) are known and most of these are linked through the imino nitrogen atoms. The only exceptions to this are three compounds (Table XLVI) which are linked through arsenic atoms in the p,p‘-positions of 1,l’-aryl s u b s t i t u ~ n t ~ . ~ ~ ~ ~ ~ ~ ~ These compounds are prepared by way of 1-(4-arsinopheny1)-2,3dimethyl-4-nitroso-3-pg~azolin-5-one. This compound is reduced, giving 4,4’-amino groups and reducing the arsenic atoms to give the -As=Aslinkage connecting the two rings. The amino groups are then alkylated. The type formula and the remaining bis(4-imino-3p-yrazolidinones) are listed in Table XLV. These have been prepared by reaction of 4-amino-3-pyrazolin-5-ones with dihalides such as phosgene,58g ethylene dibromidegg2and /3,/3’-dichloromethyl ether, with carbon d i s ~ l f i d eand ~ ~with ~ . ~ketones.984 ~~~ The only 3,4-di-iminopyrazolidineknown is the 5-(3-pyridyl) compound prepared by chemical reduction of 3-(3-pyridyl)-4,S-dinitropyraz0le.9~~
CHAPTER VII
3,s -Pyraaolidinediones 1. Introduction The 3,5-pyrazolidinediones have become of increasing importance in recent years owing to the medical use of 4-butyl-l,2-diphenyl-3,5pyrazolidinedione which is marketed as Butazolidin (phenylbutazone) and used widely in the treatment of rheumatoid arthritis and various other diseases. A large number of analogs have been prepared for further investigation of their pharmacological and therapeutic properties. 3,Fi-Pyrazolidinediones have also been of interest as color contrary formers in color photography. The 5-imino-3-pyrazolidinones, to usual practice in this discussion, will be treated separately in the next chapter. This is due to the very large number that are known and the extensive knowledge concerning them and also t o the fact that they exist much more as 3-aminopyrazolino~iesthan as 5-imino-3-pyrazolidinones.
I
I
R'
R'
(XLITI)
(XLIV)
HO--
HO--R2 HL-L \N/-o
4
\N
I
I R1
R'
(XLVI)
(XLVII)
Five isomeric forms of 3,5-pyrazolidinediones are theoretically possible. These are (XLIII), (XLIV), (XLV), (XLVI) and (XLVII) 123
124
Part 1.
Chapter V I I
when R1is not hydrogen. When R1= H (XLV) and (XLVI) are identical but the fifth isomer, 3,5-dihydroxypyrazole, is still possible. In those instances in which there are substituents on both nitrogen atoms, only forms (XLIII) and (XLV), which would be identical with (XLVI), are possible if both substituents are the same. Different substituents on the nitrogen atoms would then make possible a third form (XLVI). Compounds having four substituents could exist only in form (XLIII). I n view of the acidity of 3,5-pyrazolidinediones1501.1512 and the ready 0-alkylation which they undergo, it was suggested by Michaelis and ROhmergg4that they must exist in form (XLV). Gagnon and cow o r k e r ~from ~ ~ a~ study * ~ ~of~their ultraviolet spectra proposed that a mixture of tautomers (XLIV), (XLV) and (XLVI) occurs. The strong absorption of infrared light in the carbonyl regions by 3,5-pyrazolidinedionesglgis indicative of the presence of only a very small amount of form (XLVII) or perhaps of its complete absence. In summary, it would appear that the 3,5-pyrazolidinediones tend to exist as an equilibrium mixture of 2-pyrazolin-5-one forms and 3-pyrazolin-5-oneforms if the existence of such forms is possible. 2. Alkyl, Aralkyl, Heterocyclicalkyl and Aryl Substituted Derivatives
By far the most widely used synthesis of 3,5-pyrazolidinediones is the condensation of malonic acids or esters or acid chlorides with hydrazines (eq. 5, p. 10). A large variety of malonic esters have been 969 monoary1,222a r a l k ~ l ,di~~~ used. Esters having monoa1kyl,lB8a l k ~ l d, i~a r~a~l k ~ l ,alkyl ~ ~ ~ and aralkyl 504 and alkyl and ary1388 substituents have been used. The larger the substituents the lower the yields. The hydrazines used have had alky1,222ary1506and diary1 substituents.lB8,1338 Those hydrazines having less bulky substituents react the more readily the smaller the malonic ester substituents. The usual 1339 condensing agents have been sodium a l k o x i d e ~ .1312* ~~~ * Substituted malonic acid chlorides condense with hydrazines under milder conditions than do the esters. The malonic acid chlorides used have had r n o n ~ a l k y1032 l ~ ~or~m ~ ~ n o a r y l1032 ~ ~substituents. ~~, Only symmetrical 1338 In most cases involving diarylhydrazines have been used.1032* condensation of malonic acids with hydrazines, N-aryl-N-acylhydrazines have been used with phosphorus trichloride222~997 or phosphorus oxychloridegg8as the condensing agent. However, a Swiss patent has The malonic acid may reported the use of ~yrn-diphenylhydrazine.~'~~ be u n s ~ b s t i t u t e d or , ~ ~m~o n ~ a l k y l dialkyl , ~ ~ ~ 997 or monoaryl 222 substit'uted. A modification of these methods is the use of carbon suboxide instead of the malonic acid derivatives.1512Although Tsumaki lSo1 has
3,5-Pyrazolidinediones
u5
reported poor yields from carbon suboxide, Quintilla 1150 claimed yields of 80-90 per cent. Phenylhydrazine and sym-diphenylhydmaurt-clPsve been condensed with carbon suboxide. The use of N,N'-diphenyl-Nb~tylhydrazine"~ led ~ to the formation of 4-butyl-l,2-diphenyl-3,5pyrazolidinedione (eq. 253).
Three other methods of forming the 3,5-pyrazolidinedione ring system have been reported. One of these involves oxidation of malonic acid amides with potassium h y p o c h l ~ r i t eor ~ ~with ~ sulfur and aluminum chloride (eq. 254).1324The second method is cyclization of R1
CONHAr
I
Ar
malonic acid half-ester hydrazitles with base.976 A rather similar method, published recently, is that of Hallman, Ringhardtz and F i s ~ h e r . ~This ' ~ involves the sequence of reactions shown in eq. 254a. RCH2COXNHC6HS &HI
CICO0C*B6
--*
1
RCH&ONNCOOC,H5 A6H6
C,H,
=
O=-------
..H..,,,L,I
R
(254a)
iLH5
Modification of this synthesis can be achieved by treating the hydrazide with diethyl carbonate or diethyl thiocarbonate. I n the latter case the products are 5-thiono-3-pyrazolidinones. Synthetic methods involving conversion of other, but similar, ring systems to 3,5-pyrazolidinediones have been reduction of 1,2diphenyl-3,4,5-pyrazolidinetrione with tin and hydrochloric acid 63 and hydrolysis of 5-imino-3-pyrazolidinones(3-amino-2-pyrazolin-5-ones) with acid.1339.1596 A variety of 4-substituted-3,5-pyrazolidinediones has been prepared by alkylation of 3,5-pyrazolidinediones in various ways. The
126
Part 1 .
Chapter VII
hydrogen atoms at the 4-position are active and direct alkylation with alkyl halides and a base is possible (eq. 255).222Usually the lower alkyl
bromides and benzyl bromide have been used. Sodium e t h ~ x i d e , ~ ~ sodium hydroxide 1437 and sodium304have been the reagents employed. Either monoalkylation or dialkylation at C-4 can be achieved. I n all cases in which this procedure has been used for alkylation, both nitrogen atoms have been substituted. A Wurtz-Fittig reaction on 4-bromo-3,5-pyrazolidinedione using alkyl halides and sodium, zinc or magnesium gives the same type of Probably the most widely used method for preparing 4-alkyl and 4-aralkyl-3,5-pyrazolidinediones is condensation of the parent 3,5-pyrazolidinedione with aldehydes or ketones 1501 followed by reduction.lE8The first product is a 4-alkylidene- or 4-arylidene-3,5-pyrazolidinedione. Catalytic reducor nickel1430as catalyst gives alkyl tion using either or aralkyl analogs. A large number of aliphatic aldehydes and ketones: cycloalkanones and such aromatic carbonyl compounds as benzaldehyde, acetophenone and benzophenone188~615*g76~1439*1501~1502 give aldol condensations with 3,5-pyrazolidinedioncs. l-Aryl-3,5-pyrazolidinediones having two substituents at C-4 can be alkylated a t N-2 with benzyl bromide248or methyl iodidegg8and a base. If only one substituent is present at C-4, a second group is introduced at (2-4 in addition to the one at N-2.222*998 Dyes can be derived from 3,5-pyrazolidinediones by introduction at the 4-position of heterocyclic rings connected through a conjugated unsaturated system to the pyrazolidinediones. This is done in a way very similar to the preparation of the 2-pyrazolin-5-one analogs (eq. 256).1330,1670
The 3,5-pyrazolidinediones undergo the Mannich reactiong19 and can be readily alkylated in this way. These compounds are listed in Table XLVII. Owing to the active hydrogen atoms at C-4 in 3,5-pyrazolidinediones various substitutions at C-4 can be accomplished. Reaction with acid chlorides in the presence of aluminum chloride gives 4-acyl-3,5976 However, if two groups are already present pyra~olidinediones.~~~* at G 4 ,the enolic form of the dione is acylated on the oxygen atom to give 3-acyloxy-2-pyrazoIin-6-ones.gg8 Treatment of 3,ii-pyrazolidinediones with nitrous acid gives nitrosation at G 4 . 9 7 6 The nitroso
3,5-Pyrazoliuinediones
127
derivative is thought to exist as the oximino isomer. Reaction with aryldiazonium salts 976 results in introduction of a 4-arylazo group.
+ ‘X
’\ //
I
-x
, &\i L X /
+ \--CH=CHW~H, I-
I
I
R’
or
LOCH,
GH,
(256)
-,
Bromination occurs readily with formation of 4-bromo-3,5-pyrazolidine1032*1048 A 4-phenyliminomethinyl substituent can be introducedllgOby reaction with N,N’-diphenylformamidine(eq. 257).
I
CeH,
I
CBHS
3,5-Pyrazolidinedioneshaving either no substituent at N-2 or at least one hydrogen atom at C-4 form 3-alkoxy-2- or 3-pyrazolin-5-ones by reaction with potassium hydroxide and methyl iodide.gg4I n addition, alkylation occurs at G-4. Arndt, Loewe and Ergener41 have studied alkylation of 3,5-pyrazolidinediones with diazomethane. 1Phenyl-3,5-pyrazolidinedionereacted to give 3-methoxy-Z-phenyl-3pyrazolin-5-one. However, if two substituents were present at G-4, the product waa a 3-methoxy-2-pyrazolin-5-one in addition to methylation of the unsubstituted nitrogen atom. Similarly, treatment of 4-ethyl-4phenyl-3,5-pyrazolidinedionewith hot acetic anhydride gave 3-acetoxy4-ethyl-4-phenyl-Z-pymzolin-5-0ne.~~3~ One or both of the nuclear oxygen atoms in 3,5-pyrazolidine&ones are replaced by chlorine upon reaction with phosphorus o x y c h l ~ r i d e .998 ~ ~Reaction ~* of l-phenyl-3,5pyrazolidinedione with one mole of phosphorus oxychloride forms 3-chloro-1-phenyl-Z-pyrazolin-5-0ne.A second mole of phosphorus oxychloride gives l-phenyl-2,4-dichloropyrazole.
128
Part 1. Chapter VII
Acid hydrolysis of 3,5-pyrazolidinediones opens the ring: giving under mild conditions a half-hydrazide of malonic acid. Under more vigorous conditions degradation goes further.9764-Ethyl-4-phenyl-3,5pyrazolidinedione undergoes an interesting d i m e r i z a t i ~ nunder ~~~~ oxidative conditions to form a bicyclic compound (eq. 258).
3. Hydroxy and Alkoxy Substituted Derivatives
Only two hydroxy- and alkoxy-3,5-pyrazolidinedionesare known (Table XLVIII). 4-Butyl-4-hydroxy-1,2-dipheny1-3,5-pyrazolidinedione is formed as a by-product in the synthesis of 4-butyl-l,2-diphenyl3,5-pyrazolidinedione by condensation of diethyl butylmalonate with sym-diphenylhydrazine in the presence of sodium e t h 0 ~ i d e . l ~ ~ ~ The reaction of 4-bromo-1,2-diphenyl-3~5-pyrazolidinedione with 2dimethylaminoethanol forms 4-(2-dimethylaminoethoxy)-1,2-diphenyl 3,5-pyra~olidinedione.~~*~ 4. Amino and AZQSubstituted Derivatives These compounds are listed in Table XLVIII. 4-Amino-3,5pyrazolidinediones have been prepared by reduction of the corresponding 4-oximino compounds.981.1048.1339 The preparation of 4-arylazo-3,5pyrazolidinediones by direct introduction of this substituent has already ~ ~ . ' ~and ~~ been mentioned in Section 2 of this ~ h a p t e r . ~ Bulow B o ~ e n h a r d thave ~ ~ ~ prepared 4-phenylazo-3,5-pyrazolidinedioneby cyclization of the phenylhydrazone of mesoxalic acid hydrazide in acetic acid (eq. 250). Stepanov and Kuzi11'~~O ham suggested that the
product obtained in the reaction of chloral hydrate with p-nitrophenylbut there hydrrtzine is 1,4-bis(4-nitrophenylazo)-3,5-pyrazolidinedione, is very little evidence for this and it seems highly unlikely.
-
3,5 Pyrazolidinediones
129
5. Halogen Substituted Derivatives
4-Halogeno-3,5-pyrazolidinedionesare listed in Table XLVIII. Preparation by direct halogenation has already been discussed. This has been done with bromine and chlorine458*1031*1032.1048 and only monohalogeno products have been obtained. A number of 4-halogeno-3,5pyrazolidinediones have been prepared by condensation of halogenomalonylchloride with sym-diphenylhydrazine. The replacement of halogen by alkoxy was mentioned in Section 3. The halogen atom is readily replaced by hydrogen upon treatment with sym-diphenylhydrazinelo31 1032 thus reversing halogenation. 6. Nitroso Substituted Derivatives
These are listed in Table XLVIII. The nitrosation of 3,5-pyrazolidinediones has already been mentioned (Section 2). A second method of preparation of the 4-nitroso-3,5-pyrazolidinediones (which are usually considered to have the tautomeric oximino form) has been used by Michaelis and K i r ~ t e i n . ~This ~ ' involves treatment of 3-chloro-3pyrazolin-5-ones with nitrous acid (eq. 260). A third method of syn-
(260)
I
I
CsH,
66H5
thesis is hydrolysis of 3-amino-4-oximino-2-pyrazolin-5-ones (4oximino-5-imino-3-pyrazolidinones).1339 The reduction of these nitroso compounds has already been discussed (Section 4).
7. C-Acyl Substituted Derivatives The structure of 4-acyl-3,5-pyrazolidinedioneshas been studied by use of infrared absorption spectra.919These studies indicate that one nuclear oxygen exists in its enolic form and the hydrogen is bonded to acyl oxygen in a chelate ring (XLVIII). These compounds are listed in Tables XLVII and XLVIII. R I
&HI (XLVIII)
130
Part 1.
Chapter VII
The preparation of 4-acyl-3,5-pyrazolidinediones by acylation of 3,5-pyrazolidinedioneshas already been discussed in Section 2. 4-Acetyl-1-methyl-2-phenyl-5-thiono-3-pyrazolidinone 89 ,log has been prepared by hydrolysis of ethyl 2,3-dimethyl-l-phenyl-5-oxo-3pyrazolin-4-thiocarboxylate with alcoholic potassium hydroxide. This presumably involves ring opening and reclosure. 8. N-Acyl Substituted Derivatives
These compounds are listed in Table XLVIII. N-Acyl-3,5-pyrazolidinediones are prepared either by acylation with acid chlorides,976 in which case acylation at G 4 occurs, or by cyclization.506~976 Cyclization involves condensation of semicarbazides with malonic esters or cyclization of 3-acylsemicarbazides.
CHAPTER VIII
5 -Imino-3-pyrazolidinones 1. Introduction The compounds considered in this section aa 5-imino-3-pyrazolidinones can, at least t,heoretically,have a number of tautomers. Of this number the four structures shown here, (XLIX), (L), (LI) and (LII),
H (XLIX)
H
H
(L)
(LI)
(LW
are those usually considered to describe adequately the isomers actually occurring. In most cases the structure has not been determined but has form (L). I n those been considered to be the 3-amino-2-pyrazolin-5-one cases which have been studied the form (L)and the 3-amino-3-pyrazolin5-One form (LI) have usually been the ones occurring. Gagnon, Boivin and others,120~497~499*507 as a part of their general investigation of the ultraviolet absorption spectra of Z-pyrazolin-5-ones, have studied 5-imino-3-pyrazolidinones.No generalization as to structure can be drawn from their findings, but they show the existence of forms (XLIX), (L) and (LI). Weissberger, Porter and Graham594*1597*1599 have shown that some 5-imino-3-pyrazolidinonesactually exist as the isomeric hydroxyiminopyrazolineform (LII). I n some cases1597the two isomeric forms (L) and (LII) have been isolated. Of course, various combinations of substituents make certain of these tautomeric forms impossible. Four substituents on N-1, N-2 and G - 4 would make form (XLIX) the only possible one. Two substituents a t N-1 and N-2 would preclude forms (L) and (LII). Two C-4 substituents would likewise eliminate form (LT). In recent years a great deal of research on 5-imino-3-pyrazolidinones has been done because of their use as color couplers in color 131
132
Pa,rt 1.
Chapter VIII
photography. Weissberger, Porter, Graham and others at the Kodak Research Laboratories have been particularly active in this field. This point will be discussed in more detail in the section devoted to dyes. 2. Alkyl, Alicyclic, Aralkyl, Heterocyclicalkyl, Heterocyclic and
Aryl Substituted Derivatives The most frequently used procedures for preparation of 6-imino-3pyrazolidines can all be considered as variations of cyclization of malonic acid derivatives. Various hydrazines react with ethyl /3-amino/3-ethoxyacrylate to form 2-substituted-5-imino-3-pyrazolidinones (eq. 261). Coniplex alkyl groups,7o5 aryl g r o ~ p s and~
~
~
~
heterocyclic groups 1142 have been used. This reaction can theoretically lead to the isomeric 1-substituted compound and actually does give such a compound as the principal product when methylhydrazine is used.594A variation of this procedure is to isolate the product resulting from replacement of the ethoxyl group by the hydrazine and cyclization of this product to the 5-irnin0-3-pyrazolidinone.~~~. 1142* 1603*1604 A somewhat similar method is that used by Weissberger, Porter and Gregory1597.1601 and by Worrall.1649.1651In this method phenylisothiocyanate is condensed with ethyl acetoacetate and the resulting thioamide is treated with hydrazine, giving the 5-imino-3-pyrazolidinone (eq. 262). Other isocyanates can be used in this s y n t h e s i ~ ' ~ ~ ~ . ~ ~ ~ ~ and both aliphatic and aromatic hydrazines have been used. CeHsNCS
+
CH,COCH&OOC2H5
----+ C,H,NHCSCHCOOCZH5 I COCH,
RNHNHZZ
CeH5X=R-N
1
H
In the preceding methods only compounds having substituents on the nitrogen atoms can be obtained. In order to introduce substituents at (2-4, substituted cyanoacetic esters and cyanoacetic hydrazides have been used (eq. 263). Two isomeric products are possible in this reaction,
*
5-Imino-3-pyrazolidinones
133
R3 being either at N-1 or N-2. Gagnon and c o - w o r k e r ~report ~ ~ ~ that unsubstituted cyanoacetic esters yield the N-2 isomers, while substituted esters give N-1 substituents. Other workers have also found
I
R3
that unsubstituted cyanoacetic esters give the 2-substituted-5-imino-3p y r a z o l i d i n ~ n e s .1141* ~ ~ ~ * Hydrazine ,391 arylhydrazines 496.872*1141 and heterocyclic h y d r a z i n e ~ ~ ~ have ~ ~ . been used. Monoalkyl, monoaryl and d i a l k ~ l cyanoacetic ~~l esters undergo this reaction. The usual condensing agents have been sodium alkoxides. A modification of this procedure is isolation of the intermediate cyanoacetic hydrazide and ~~~. cyclization of this with base 498*1138 or acid.506 U n s u b ~ t i t u t e d ,644 mono-substituted120*5 0 0 * 5 0 8 or d j s u b ~ t i t u t e dcyanoacetic ~~~ esters can be used and either hydrazine 594 or p h e n y 1 h y d r a ~ i n e . l ~ ~ ~ One of the most widely used methods for the preparation of 5-imino-3-pyrazolidinones is from 5-oxo-3-pyrazolin-3-carboxylic acids or their derivatives by use of the H ~ f r n a n n lor ~C ~ u. ~r t~ i~~ s1 3~8 7~* 1395 ~* rearrangements (eq. 264). A similar synthesis is from the analogous
I
I
R'
I
R'
t
(264)
I
R'
2-pyrazolin-5-ones by way of the Curtius rearrangement.497*499*594-1595 The amides and azides are formed by the usual procedures. The usual Hofmann and Curtius conditions are employed and the yields are frequently quite good. The azide rearrangement is usually carried out in ethanol and the carbamate derivatives of 5-imino-3-pyrazolidinones, 3-(5-oxo-2- or 3-pyrazolin-3-yl) carbamates are prepared a5 interm e d i a t e ~ . ~1387. ~ ~1395*1595 - ~ ~ ~ If. 3-pyrazolin-5-ones are used as starting mat,erials in this synthesis, the products can have only one substituent
Part 1.
134
Chapter VIII
at C-4 and are actually 3-amino-3-pyrazolin-5-ones. Use of 2-pyrazolin5-ones leads to compounds unsubstituted at N-1. In all cases the products obtained by these syntheses have had substituents at N-2. A number of 5-substituted imino-3-pyrazolidinones have been prepared by reaction of various reagents with 5-imino-3-pyrazolidinone. For example, 5-alkylimino compounds can be prepared by reduction of 3-benzylideneimin0-3-pyrazolin-5-ones.~~~~ The benzylidene derivatives are prepared by reaction of benzaldehyde with 5-imino-3-pyrazoliThe same products can be obtained by direct alkylation of 5-imino-3-pyrazolidinone with benzyl chloride and an analogous reaction has been reported by Jennen704.705with halogenated heterocycles. Various 5-substituted imino-3-pyrazolidinones have been prepared by reaction of the corresponding 5-iminO compounds with various amines.595*596.1597 This reaction must occur by way of the 5-imino form rather than an amino form and the compounds involved must be at least partially in the 5-imino, rather than the amino, forms. and ethylThis reaction has been carried out with aniline1595*1597 amine,595although in the latter case a 4,4'-ethyliminobis(2-pyrazolin-5one) is the chief product. A variation of this is the condensation of 2-phenyl-5-imino-3-pyrazolidinone with a r n m ~ n i a , " ~as * ~shown ~ ~ in eq. 265. The reaction of phenylisocyanate with 2-phenyl-5-imino-3-
I
CBH,
I
C,H,
I
CsHs
pyrazolidinono leads to the corresponding 5-phenylcarbamyl derivat i ~ e . 'Phenylisothiocyanate ~~~ reacts in the same may but p-tolylisothiocyanate in the presence of pyridine has been reported to cyclize to give 2-phenyl-5-[2-(5-methylbenzothiazolyl)imino]-3-pyrazolidinone.7o5 Acylation of 5-imino-3-pyrazolidinonecan occur at several places. Most commonly reaction occurs at the 5-imino group and further reaction then may occur by acylation of the en01 form of the 50x0 !PUP* In compounds which have no substituents at N-1 or N-2 nuclear acylation also occurs and under some conditions acylation occurs at G4. The use of 2-alkyl- or aryl-5-imino-3-pyrazolidinones, which exist as the 3-amino-2-pyrazolin-5-one isomer, with an equivalent of acid chloride, either aliphatic or aryl, leads to 3-acylamides (eq. 206),14~67~594.6s5.1247.1594~1595 although in some cases a side-reaction . ~ ~ ~ ~the same conditions 3gives both N - and O - a ~ y l a t i o n Under hydroxy-5-imino-2-pyrazolinones give 0 - a ~ y l a t i o n . The l~~~ reaction of
5-Imho-3-pyrawlidinones
136
aromatic acid chlorides in e x c ~ 8 ors of ~ acetic ~ ~anhy~ dridee93*1595 with the same toea of compounds leads to both N- and H Z N N III
+
RaCOCl
___f
Rzco*-
\pJ,=o
dl
t,L
(266)
A1
0-acylation. These amide-esters can be hydrolyzed with base to the N-acyl derivatives (eq. 267). Hepner and F a j e r s ~ t e j nhave ~~~ reported
I
R'
that acetic anhydride and benzoyl chloride react with 5-imho-3pyrazolidinones to give acylation on nuclear nitrogen and diacylation at G 4 . Graham, Porter and Weissberger594 have investigated this reaction and have found that acylation does not occur at G 4 but at the 5-imino group and the &OX0 group (eq. 268). A similar acylation occurs
I
H
CH,CONH-
+ I
COCH,
with l-phenyl-5-imino-3-pyrazolidinone to give 2-acetyl-3-acetoxy-1phenyl-5-acetimido-3-pyrazoline if pyridine is present.15ggOtherwise a mixture is obtained, but the chief product is 3-acetoxy-4-acetyl-1phenyl-5-imino-2-pyrazoline. 1599 The reactions undergone by 5-imino-3-pyrazolidinones are in general very similar to those of 2-pyrazolin-5-ones. The hydrogen atoms at C-4 axe active and this position is the reactive center in the nucleus of these molecules. Condensation with aldehydes and ketones occurs with formation of benzylidene6 4 4 * loS3 or 4,4'-beneylidenebis
~
~
~
~
136
Part 1.
Chapter VIII
compounds1603rather than Schiff bases which are formed with the amino substituent. However, when ,t?-ketoestersor 8-ketoacids are used the carbonyl group does react with the amino group and then cyclizes a t the C-4 position (eq. 269).1085Reaction with nitrous acid forms, at OH
0
least in compounds having no substituents at C-4,4-oximino-5-imino-3p y r a z o l i d i n o n e ~ .In ~ ~compounds ~ substituted at C-4 reaction with nitrous acid leads to loss of nitrogen.501 Coupling occurs with arylPapini diazonium salts to give 4-arylazo-5-imino-3-pyrazolidinones.594 reacts with and Venturini1OE5have found that 5-imino-3-pyrazolidinone N,N’-diphenylformamidine a t 150’ to introduce at C-4 the phenyliminomethylidyne group. 5-Imino-3-pyrazolidinones react with sulfur dichloride to give the 4,4’-bis sulfide.6g3* 921 Sulfur monochloride reacts to give the analogous d i s ~ l f i d eAs . ~is~ the ~ case with 2-pyrazolin-5-ones, the 5-imino-3-pyrazolidinonesundergo condensation at C-4 with p-amino-N,N-dimethylaniline in the presence of an oxidizing agent to form a magenta dye. Those 5-imino-3-pyrazolidinoneswhich have no N-2 substituent react as enols with phosphorus oxychloride to give 3-chloro-5-imino-2-pyrazolines.391 They also give positive color tests They are methylated at N-2 by dimethyl with ferric sulfate.391As mentioned previously, the 5-imino group can be hydro15g6 lyzed with acid to give 3,5-py;a~olidinediones.~~~~~ The known bis(5-imino-3-pyrazolidinones)are listed in Tables XLVI and L and are of three types: (1) linked at the 4,4’-positions directly, (2) linked at the 4,4‘-positions by a carbon chain, and (3) linked through the nitrogen of the 5-imino group. The compounds of the first type are prepared by reaction of 3-acylamido-1-aryl-4-arylimino-2-pyrazolin-5-ones with the corresponding 3-acylamido-l-aryl-2pyrazolin-&ones, the 5-imino-3-pyrazolidinonesbeing considered to tautomers (eq. exist in this case as their 3-amino-2-pyrazolin-5-one 270).1538The second type is usually synthesized by reaction of a 3-amido-2-pyrazolin-5-one with an aromatic aldehyde to give a 4arylidene derivative, followed either by addition of a second mole of the original pyrazolinone to give a symmetrical bis compound (eq. 68)1255.1603 or by addition of a different pyrazolinonc to give an unsymmetrical bis compound.1254Most of those compounds which are
-
5 - Imino 3-p yrazolidinones
137
linked through the 5-imino nitrogen are prepared by reaction of 5imino-3-pyrazolidinones with the acid chloride of a dibasic However, a bis compound connected only by a carbonyl group has been
__j
RacoNH~ (270)
I
R’
N’
I
R’
obtained as a by-product in the Curtius rearrangement of an azide to give a 5-imin0-3-pyrazolidinone.’~~~ It would appear that part of the intermediate isocyanate reacts with some of the final product.
3. Functional Group Derivatives 5-Imino-3-pyrazolidinoneshaving functional group substituents are listed in Sections B and C of Table XLIX. These compounds are usually synthesized by procedures which are used for introduction of the same substituents into previously discussed pyrazolinone and pyrazolidinone systems. 4-Bromo-6-imino-3-pyrazolidinones are synthesized by Curtius rearrangement of the azides of 4-bromo-5-oxo-3-pyrazolin-3-carboxylic 4-Nitroso-5-imino-3-pyrazolidinones are believed to exist as the oximino t a ~ t o m e r s They . ~ ~ ~are usually prepared by direct nitroof 4sation with nitrous a ~ i d . 1649 ~ ~A ~Curtius * ~ ~rearrangement ~ ~ * oximino-5-oxo-2-pyrazolin-3-carboxylic acid azide has also been 4-Amino-5-imino-3-pyrazolidinoneshave been synthesized by ~ ~Such ~ . amines form ureas reduction of the corresponding ~ x i m e s .1339 and thiourea5 by reaction with potassium cyanate in acid solution and with phenyl i s o t h i ~ c y a n a t e 4-Arylimino-5-imino-3-pyrazolidinones .~~~ have been prepared by reaction of the 5-imino-3-pyrazolidinoneswith p-amino-N,N-diethylaniline in the presence of silver salts as oxidizing agents (eq. 172).244-519, l2S5. 1538 4-Arylazo-5-imino-3-pyrazolidinones have most frequently been prepared by reaction of 5-imino-3-pyrazolidinones with aryldiazonium chlorides, as is usual for the preparation of One such cornsimilar compounds.~91.594.920,1087.1255.1339.1539.1649 pound has been prepared by the Curtius rearrangement of the corresponding 4-arylazo a~ide.5~4
Part 1. Chapter VIII
138
The preparation of C-4 acyl and N-1 and N-2 acyl 5-imino-3pyrazolidinones has been partially discussed in the preccding section. 4-Acetyl-5-imino-3-pyrazolidinones have been prepared by reaction of ethyl acetylcyanoacetate with phenylhydrazine (eq. 263, R1= CH,CO, R2= H).4984-Carbethoxy derivatives of 5-imino-3-pyrazolidinones have been prepared in two ways. One of these was by the cyclization procedure shown in eq. 271.1650The second method is direct introduction
by using ethyl chloroformate.loe3 In addition to the 3-acylations have been prepared already discussed, 1-acyl-5-imino-3-pyrazolidinones by treatment of l-acyl-3-acyloxy-6-imino-2-pyrazolines with piperidine.1598The acyl group on oxygen is preferentially removed. l-Acyl-5imino-3-pyrazolidinones also have been prepared by reaction of oyanoacetic esters with aoylhydrazines such as benzoyl hydrazide 497 or semicarbazides (eq. 263, R3= C,H&O, HzNCOor C,H,NHC0).498*506 Such compounds can also be prepared by the Curtius rearrangement.497 4-Amino-5-imino-3-pyrazolidinones react with formaldehyde at the 4-amino group giving methylol derivatives.644The 4-arylimino derivatives are reduced catalytically to give 4-arylamino a n a 1 0 g s . l ~ ~ ~ An interesting reaction of the 4-arylazo-5-imino-3-pyrazolidinones is the replacement of the 4-arylazo group by arylimino (eq. 272).1255.1296
I
R'
- R"oNa7==N w
(272)
J - L V W d Z
\Ni'O
I
CH3
Rl
It seems likely that this occurs by way of the hydrazono tautomer of the azo compound. linked at the 4,4'-positions by one Bis(6-imino-3-pyrazolidinones) or two atoms of sulfur are known (Table L) and their preparation was mentioned in the previous section.
CHAPTER IX
Miscellaneous 3,5 -Pyrazolidinediones and Analogs 3,4,5-Pyrazolidinetrionehas been prepared by oxidation of the anilide of mesoxalic acid with hydrogen peroxide in alkaline solution.63 Six 3,5-di-iminopyrazolidineshave been prepared. These compounds are usually considered to exist as diaminopyrazoles, although their structure has not been investigated. The parent compound, 3,5-di-iminopyrazolidine or 3,5-diaminopyrazole7 has been reported 473. 1561 as the product obtained by reaction of malononitrile and hydrazine. However, Taylor 1478 has claimed that these same reactants give a different product, derived from dimerization of the malononitrile followed by reaction with hydrazine. Knorr 819 has prepared 3,5-diiminopyrazolidine by the Curtius rearrangement starting with diethyl pyrazole-3,5-dicarboxylate. Two acyl derivatives and the intermediate carbamates were also prepared. Phenylhydrazine and malononitrile do not give a diaminopyrazole as reported.1478* 1561 2-Methyl-1-phenyl3,5-bis(phenylimino)pyrazolidineresults from the action o f aniline on the methiodide of 2,6-dichloro-l-phenylpyrazole.g61
139
PART
2
APPLICATIONS
CHAPTER I
Medical Since the synthesis of antipyrine (Z,$-dimethyl-l-phenyl-3pyrazolin-5-one) by Knorr in 1883 pyrazolinones have been widely used in medicine as analgesics and antipyretics. The discovery of this drug led to a widespread search for other pyrazolinones, having the same type of action but more satisfactory properties, and to a very intensive investigation of the biological properties of pyrazolinones. This investigation resulted in the discovery of aminopyrine, which is the 4-dimethylamino analog of antipyrine, and phenylbutazone (4butyl-1,2-diphenyl-3,5-pyrazolidinedione) and their employment in medicine. Many other pyrazolinones have been synthesized and studied and a number of these have been used as drugs, but these three have been by far the most important and most of this discussion will be concerned with them. Although antipyrine has been used ;t8 an antipyretic and analgesic for many years, i t finds very little use today. I n part this h a been due to the introduction of the more effective aminopyrine, but largely it has been due to replacement by the salicylates. At the present time it is used chiefly in Europe, South America and the Near East where approximately 50,000lb. per year is consumed. Antipyrine definitely has analgesic activity84abut this appears to be of a rather low order.2s5 It is absorbed rapidly from the gastrointestinal tract and blood plasma levels are at a maximum in 1-2 hours. Metabolism is rather rapid, with disappearance occurring at the rate of 6 per cent per hour. Water solubility is high and distribution in the tissues is in proportion to their water content. This property has been used as a basis for determining the water content of various tissues. About 30-40 per cent of ingested antipyrine is converted to 4-hydroxyantipyrine and excretmd in the urine conjugated with glucuronic At present aminopyrine is little used in the United States but is still widely used in Europe, South America and the Near East. World 143
144
Part 2.
Chapter I
production is 250,000-300,000 lb. per year. I t is somewhat more effective than antipyrine and is administered in doses of 0.3 or 0.6 g. every four hours. Absorption occurs from the gastrointestinal tract and blood levels reach a maximum in 1-2 hours and then the drug disappears at the rate of 10-30 per cent per hour. A large proportion of it is demethylated in the liver to 4 - a m i n 0 a n t i p y r i n e ~ ~and ~ . ~this ~~.~~~ is acetylated and excreted in the ~ r i n e . * ~A~ small * ~ ' ~amount, about 9 per cent, is excreted as 4-aminopyrine and about 5 per cent as 4hydr~xyantipyrine."'*~l~ As is the case with antipyrine the fate of about half of the aminopyrine ingested is unknown. Its primary effect is on the autonomic nervous system which it depresses1235*1495 and its analgesic action is exerted through this system.1479The mechanism of action of aminopyrine is not known. It does not appear to act through its metabolite, 4 - a m i n o a n t i ~ y r i n ebut , ~ ~it ~ may act through some as yet unknown metabolite. The action of aminopyrine in rheumatic fever is equal to that of the salicylates567and it is effective in reduction of inflammation due to edema and necrosis.1625The chief toxic manifestation of aminopyrine is agranulocytosis. This occurs only in a small minority of those taking the drug, but it may be extremely severe and there is a high death rate among those in whom agranulocytosis occurs. I n some individuals there seems to be a hypersensitivity to this drug. Other toxic effects are central nervous system involvement, rash and hemoglobin alterations. Aminopyrine forms complexes with barbiturates containing one or two molecules of aminopyrine for each molecule of barbiturate. These complexes have a synergistic action on the analgesic activity of the p y r a z o l i n ~ n e .Two ~ ~ ~ of these complexes have been marketed as analgesics under the names Allonal and Veramon. The former is a 1 :1 complex with phenylisopropylbarbituric acid and the latter is a 2 : 1 complex with diethylbarbituric acid. A complex of aminopyrine with trichloroethylurethan has been sold as an analgesic under the trade name Compral. A tremendous number of 3-pyrazolin-5-oneshave been tested for activity as antipyretics and analgesics. Of these many have been found to have such activity, most of them being rather closely related to antipyrine.5a.249.490.530.532.859.1337.1476 Many of these have been claimed to be superior to anipyrine and aminopyrine, but only a few have been used to any extent. Dypyrone (Novalgin)is perhaps the most widely used of these, although on a small scale and almost exclusively outside the U.S.A. This compound has the antipyrine nucleus, but the 4-substituent is Na03SCH2(CH,)N. Sulphamipyrine (Melubrin) is similar to this but lacks the methyl group attached to the side-chain
Medical
145
nitrogen atom and is very little used a t present. A pyrazolinone which has enjoyed some use as an analgesic is 2,3-dimethyl-4-isopropyl-lphenyl-3-pyrazolin-5-one. This compound is very closely analogous to aminopyrine and is of the same order of activity.842 The most interesting of the pyrazolinones and pyrazolidinones from the medical standpoint at the present time is phenylbutazone. This was synthesized by H. Stenzl in the laboratories of J. R. Geigy, S.A. in 1946 and was shortly found to have activity in various rheumatoid and arthritic conditions. Phenylbutazone was then marketed as the sodium salt under the trade name of Butazolidin. It has also been marketed as a mixture with aminopyrine under the name Irgapyrine. Since then practically every aspect of the biological activity of phenylbutazone has been investigated and a large number of analogs have been synthesized. Hemming and KuzellB3*have published an excellent review of the biological properties and medical uses of phenylbutazone and most of the material reported here is drawn from that publication. After oral administration phenylbutazone is completely absorbed in a short time and high plasma, concentrations are reached in about two hours. Intramuscular injection gives a much slower peak concentration in the plasma, requiring six to eight hours. The usual dose is about 800 mg. per day and under this regime a stable plasma concentration is reached in three or four days. A considerable amount of phenylbutazone is bound by plasma protein and this acts as a reservoir. The drug is metabolized at a rate of 15-25 per cent per day in the human but dogs and rats metabolize it much more rapidly. The metabolic products are 4-(3-hydroxybutyl)-l,%diphenyl-3,5-pyrazolidinedione and 4-butyl-l(4-hydroxyphenyl)-2-phenyl-3,5-pyrazolidinedi0ne.~~~ It has been suggested that the former metabolite is responsible for the effect of phenylbutazone on uric acid excretion and the latter metabolite has the antirheumatic effect and causes sodium chloride retention.1663Some phenylbutazone is excreted in the urine.1335 Several workers have found that phenylbutazone has a pronounced effect upon electrolyte balance.435* 5 9 7 * 1626 A decrease in urine volume occurs with retention of sodium and chloride ions. This is apparently caused by increased reabsorption in the renal tubules.1B26 After discontinuance of the drug diuresis occurs and the edema disappears. Phenylbutazone brings about a number of changes in the blood. In rabbits it decreases total protein albumin, but increases g10bulin.l~~~ There is frequently a drop in the platelet count, mild anemia, occasionally hemorrhage from the gastrointestinal tract and sometimes granulocytopenia. The most serious blood reaction is the occurrence of 6+C.H.C.
20
146
Part 2.
Chapter I
a g r a n u l o c y t ~ s i s906 . ~ ~This ~ ~ occurs infrequently but may result from moderately low doses and therefore must be kept constantly in mind. It has been reported that concurrent administration of ferrous iron reverses the a g r a n u l o c y t o ~ i s .Some ~ ~ ~ physicians have regarded this toxic manifestation as being so serious that they recommend the complete discontinuance of the use of phenylbutazone. The principal action of phenylbutazone is its inhibition of inflammatory action, although it is also a mild analgesic and antipyretic. It has a very striking clinical effect in many arthritic cases, giving rapid and complete relief from pain. There is also significant improvement of joint function and objective remission of the arthitic condition. Its field of usefulness is very similar to that of the corticosteroids, and as a consequence it has been suggested that i t may be a stimulant of the pituitary-adrenal system. However, its failure to affect urinary ketosteroid excretion, eosinophil count and the erythrocyte sedimentation rate make this action unlikely. It may be that it acts by a cortisonesparing mechanism. Korns and others852have suggested this because of their h d i n g that phenylbutazone prevents the inactivation of cortisone by rat liver slices. Wallenfels and Sund1587believe that phenylbutazone may be transported to inflamed tissue as a complex with the zinc attached to dehydrogenase systems. I n these tissues the complex may be broken down owing to the relatively acid conditions and phenylbutazone enter the intracellular space where it inhibits dehydrogenases. Phenylbutazone has been found to be clinically useful in several forms of arthritis. It is particularly effective in acute gouty arthritis, in which i t is superior to any other drug. I n several series of patients it has been claimed that nearly all patients are improved by phenylbutazone treatment. This is probably a result of its ability to increase mate clearances.1664I n such diseases as rheumatoid arthritis, osteoarthritis and rheumatoid spondylitis phenylbutazone affords prompt relief of pain in something like 76 per cent of cmes in which it is used. Although there is considerable disagreement as to the incidence of measurable objective improvement, it is probable that this occurs in at least 50 per cent of patients using phenylbutazone. The objective improvement is reduction in swelling and increased mobility. Some have claimed that improvement is due to analgesic effect, but the beneficial effect is too pronounced for mere analgesia and must be due to a specific antirheumatic effect of phenylbutazone. An amazing number of other conditions, usually arthritic, have been reported to be improved by phenylbutazone, although its use is as yet not completely established in many of these. Some of these diseases are psoriatic
Medical
147
arthritis, osteoporosis of the spine, acute peritendonitis, acute myofibritis, degenerative diseases of the hip, bursitis, fibrositis, postmenopausal arthralgia, scleroderma with arthropathy and lumbrosacral sprain. Phenylbutazone has also been used in arthritic conditions in veterinary medicine. The clinical efficacy of phenylbutazone haa been well established but the high percentage of side-effects resulting from it has severely curtailed its usefulness. In many of the arthritic conditions for which it is used treatment for long periods of time is necessary and drug toxicity is particularly disadvantageous. It has been found that 25 per cent of patients taking phenylbutazone are subject to toxic reaction, many so severe as to prevent further use of the drug. The most common of these are gastrointestinal upset, edema and drug rash. Of other side-effects, as already mentioned, the most dangerous is agranulocytosis. A number of phenylbutazone analogs have been studied in attempts to decrease side-effects and retain p o t e n ~ y , ~ ~and ~ .itl ~is ~to* be hoped that these studies will be successful. I n the case of phenylbutazone it seems that the drug can be used effectively, but only with great care and conservatively. Its tendency to reactivate peptic ulcers contraindicates its use in patients who have ulcers. Periodic blood counts should be made, and the patient should be under close supervision of a physician. I n order to overcome some of these side-effects phenylbutazone has been marketed mixed with aluminum hydroxide, magnesium trisilicate and homatropine methyl bromide. Various publications have appeared in which pyrazolinones, either alone or as mixtures with other materials, have been claimed to be , ~antimicrobial ~~ agents,571as effective as germicides,2s in i n t l ~ e n z aas fungicides,676 as a n t i a ~ t i n i c s , ' ~and ~ ~ as anti diuretic^."^. 1078 At present it appears that none of these claims have led to clinical use.
CHAPTER I1
Color Photography The pyrazolinones and pyrazolidinones are extensively employed in photography as color couplers, sensitizers, supersensitizers, developers and antihalation agents. A number of pyrazolinones which have been prepared for use as sensitizers are listed in Tables LI and LII. The most important use of pyrazolinones in photography is their utilization as color couplers. The reaction of p-phenylenediamines with 2-pyrazolin-5-ones in the presence of oxidizing agents, in this case silver ions, forms magenta azomethine dyes (eq. 172, p. 67). These magenta dyes are then used to reproduce the green component in pictures. Two processes have been devised to form the magenta dye at the appropriate place on the developed film. In one process one coating of a three-coated film contains a substance sensitizing that coating to green light. After the film has been exposed it is developed in a solution containing a p-phenylenediamine developer, usually a p-amino-N,Ndiethylaniline, and a 2-pyrazolin-5-one. The silver halide which has been affected by light acts as an oxidizing agent to couple the two compounds, hence the name color coupler, and a magenta color appears at those points where green light has been absorbed. This can then be reprinted as green. I n the second method, which is now much more extensively used, a three-layer film is used. The middle layer contains a green-sensitized emulsion and a 2-pyrazolin-5-one. Upon exposure to a developer an azomethine magenta dye is formed. The chemistry involved in the formation of these azomethine dyes has been extensively investigated by Vittum and others.244* 1538*1539a The present interpretation of the reactions involved is that the primary amino group of the developer is oxidized to give a quinonediimine cation which then reacts with the anion of the coupler to form a leuco dye. Subsequent oxidation converts the leuco dye to a colored form (LIII). This may be done by silver ion or by the oxidized form of the developer. The over-all reaction requires the reduction of four silver ions. 148
Color Photography
149
The azomethine dyes have two absorption bands in the visible region.244*519 One, of much higher intensity, is in the green region at wave lengths of 510-560 mp. A lower intensity band occurs in the blue region a t 420-450 mp. The second band is undesirable in photographic applications and can be suppressed to a certain extent by modifications in the group at C-3. Amide substitutions at this position are effective for this purpose. The structures contributing to the resonance hybrid responsible for the absorption of the dyes are considered to be (LII1)(LVII). The forms (LIII) and (LV) represent the ground state. Transitions of these to the forms (LVI) and (LVII) are responsible for absorption at the longer wave lengths, while transitions to form (LIV) give rise to the shorter wave length, less intense band. Electropositive and electronegative substituents at C-3 have considerable effect upon the electron density a t N-2 and thus alter the light absorption of the 2-pyrazolin-5-ones. R1---=N-(3-N(R3)).
4
\N
Ra--Jq-o-
-_
N<)=&(R3)2 =
N '
I
I
R'
R'
(LIII)
(LIV)
I
I
R'
R'
(LV)
(LW RZ---X i=\-k( - 'Nh ' T J 0 - V
R3)2
I
R' (LVII)
A very large number of compounds have been claimed to be useful color ~~~p~~~~~492~493.634,705,766,769,797~870,921,922,965,966.1041.1138 11*0*1142. 1684 Weissberger and Edens have reported very complex amides which are useful as color couplers, but are so complex that they are listed in none of the tables. In the color photography process employing the 2-pyrazolin-&one in solution in the developer, low 1247s
160
Part 2. Chapter I1
molecular weight compounds were used. These, being acidic, are soluble in the alkaline developer solution. When the 2-pyrazolin-&one is incorporated in one layer of the film, diffusion from layer to layer is a serious problem. I n order to prevent this, large groups are introduced in the molecule, usually at N-1 or at (3-3. The substituent at N-1 is always aromatic and may have very complex substituents. Frequently it has a carboxyl or sulfonic acid group to assist in dispersion in the gelatin. One of the most successful approaches to the problem of diffusion is that developed by Weissberger and co-workers. Their solution to the problem was use of l-aryl-3-amino-2-pyrazolin-5-ones (2-aryl-Simino-3-pyrazolidinones). I n order to increase the bulk of the molecule the amino group was a ~ y l a t e d870*921* ~ ~ ~ .922 or carried a heterocyclic s u b ~ t i t u e n t . "2-Pyrazolin-5-ones ~~ having a carboxyl substituent aa an have amide at G 3 are also satisfactory. Kendall and Fry766*789 suggested the use of 3,5-pyrazolidinedionesas color couplers. Although by far the majority of 2-pyrazolin-5-ones used aa color couplers have no substituent a t (7-4, this is not a necessary condition. 4,4'-Bis(2-pyrazolin-5-ones) can be used for this purpose since the 4-substituents can be eliminated and an azomethine dye formed. Such couplers may offer certain advantages. It is claimed that they are more stable and also they make i t possible to form two azomethine dyes if the two portions of the molecule are different. Weissberger, Vittum and Porter 1540*1603 have patented a number of 4,4'-arylidenebis(2-pyrazolin-5-ones) for use as color couplers. G l ~ c k ~has ~ Osuggested 4,4'-bis(2-pyrazolin-5-ones)linked by sulfur which he prepared. Another approach to prevention of diffusion of color couplers has been the incorporation of 2-pyrazolin-&onesinto some type of polymer. The pyrazolone can he incorporated directly in the polymer by utilizing a polymer-forming derivative such as a 1-(amino or hydroxypheny1)pyrazolone in a phenol (or aniline)-formaldehyde polymerization. Alternatively, the pyrazolone nucleus can be combined with a synthetic or natural polymer by reaction of a functional group in the pyrazolone with the polymer. Thus, a 1-formylphenyl type is used to form a polyvinyl acetal. A compilation of such reactions is given in Part 1, Chapter 11, Section 14, pp. 108-110. In many photographic processes it has been found advantageous to use a colored coupler. In these processes a 4-arylazo-2-pyrazolin-5-one is the coupler and it reacts with a developer as shown in eq. 272 (p. 138).1539This results in the formation of an azomethine dye which counteracts the overlapping absorption of the negative image dyes present and leads to improved color reproduction. These compounds usually have a negative substituent at N-1 1058.1305 88 this enhances the
Color Photography
151
rate of r e a ~ t i 0 n . Amide l ~ ~ ~ substituents at G 3 have the same effect. Another important use for pyrazolinones in photography is a,s sensitizers and supersensitizers. Addition of certain dyes to silver halide gelatin emulsions increases the sensitivity of the silver halide to the green or red regions of the spectrum and a number of methine dyes derived from pyrazolinones have been used for this purpose. These compounds sensitize at 475-700 mp, although their maximum absorption is at somewhat shorter wave lengths. Both 2-pyrazolin-5~~~~488.707.747.749.765,771,772,1069.1195 and 3-pyrazolin-5-ones7655’1516. 1517 have been used. These nuclei are connected through one or more unsaturated groups to heterocyclic rings such as benzoxazoline, benzimidoazoline or benzothiazoline rings.747.749* 771 Frequently the pyrazolinone is a substituent on the unsaturated chain of acyanine dye (Table LIII).765,1516The more extended the unsaturated chain is the longer are the wave lengths at which sensitization occurs. A variety of substituents have been used at C-3. Among these are methy1,488*747 ~ a r b e t h o x yamino , ~ ~ ~1330 and h y d r o ~ y 1 . Supersensitization l~~~ occurs in some cases by addition of a second dye which is synergistic with the first. Brooker and White have patented a number of azomethine 2-pyrazolin-5-onesfor this purpose.240 There has been a great deal of interest in Great Britain in I-phenyl3-pyrazolidinone (phenidone) and some of its analogs as photographic developers. I n combination with various weak developers, pyrazolinones greatly enhance their developing powers. Such compounds aa ascorbic acid, gallic acid, glucose, dihydropyrogallol and various reductones show this property.57*640*641*1630 Reynolds1176in the United States has also reported such a phenomenon with iminoascorbic acid. A number of 3-pyrazolidinoneshaving various aryl substituents at N-1 and hydrogen or alkyl groups at G 4 have been reported to be effective.701* 750*756*7 5 8 . 1176.1630.1631 It has been claimed by Kendal157*751 that in the course of development 1-phenyl-3-pyrazolidinoneis oxidized to 2-phenyl-3pyrazolin-5-one. A number of compounds having two alkyl substituents at CL4701.1176*1630 or at C-5758 have been reported to be photographic developers and these could not undergo such an oxidation. A number of 2-pyrazolin-5-ones have been reported in patents to be useful as color filters and for antihalation. Most of these are colored compounds, in two cases merocyanine dyes1301 and in others various methine dyes having heterocyclic rings at the end of unsaturated chains.776van Dormael and van der Aurwa1518 have reported that a mixture of the product of reaction between aromatic amines and furfural with 3-methyl-1-phenyl-2-pyrazolin-5-one is useful for antihalation.
CHAPTER I11
Textile and Fabric Dyes The most important commercial use for pyrazolinones is as dyes. They have been extensively employed for this purpose since tartrazine (Table LIV) was synthesized by Ziegler and Locher in 18841681aand this dye is still widely used today as an approved coloring for foodstuffs. Almost all pyrazoline dyes are azo dyes having an arylazo group substituted at the 4-position of a 2-pyrazolin-5-oneand frequently having two, three or four azo groups in the entire molecule. The preparation of these compounds has already been discussed in the section dealing with 4-arylazo-2-pyrazolin-5-ones. A tremendous variety of l-aryl-2pyrazolin-5-ones have been used to prepare azo dyes, although most of the commercially important dyes have been derived from l-aryl-2pyrazolin-5-oneshaving methyl, carboxyl groups or carboxylderivatives substituted at C-3. The I-aryl substituents have been so greatly varied that no generalizations can be made. Most dyes contain at N-I substituted phenyl groups which frequently have sulfonic groups as substituents. The arylazo groups also have been extremely varied and in many cases are very complex. The majority of pyrazolinone azo dyes are either acid dyes or dyes which are complexed with metals. The acid dyes are compounds having carboxylic and/or sulfonic acid functions and can be used to dye fabrics directly, while the metal complexes are formed with various metals either before or after deposition on the material to be dyed. The outstanding feature of the pyrazolinone dyes is their excellent fastness to light and to severe wet treatments. A number of pyrazolinone dyes are produced in very large quantities. I n the U.S.A. the production of tartrazine in 1960 was 437,000 lb. and the production of many more is in the tens of thousands of pounds. I n Table LIV are listed the trade names and structures of a number of representative commercially important dyes. It is generally considered that pyrazolinone azo dyes have one or more of the structures (LVIII), 152
Textile and Fabric Dyes
153
(LIX) and (LX) but other structures are theoretically possible. Little research has been published to indicate which of these structures is the correct one, although the usual methods of preparation would allow
I
I
Arl
Ar'
I
Ar' (LX)
any of the three. In the case of dyes complexed with various metals it is believed that (LIX) is the usual structure. I n these cases it is probable that the metal reacts with the enol form of the pyrazolinone and with a hydroxyl group at the ortho-position in the arylazo group-formulas (XXX) and (XXXI).1259This is then stabilized by electron donation by the nitrogen atoms of the azo However, in most uncomplexed dyes it has not been established which form is the correct one. A few 4-arylazo-3-pyrazolin-5-ones have been patented for use as dyes.lo60 The earlier pyrazolinone azo dyes were used to dye wool yellow,81,214,217.312~5a2~1384~ 1424 but this situation has changed so that by use of suitable complexes almost any color can be obtained with almost any material it is desired to dye. A very large variety of orange dyes are available199.207.475.622.840,1449.1459,1617 as well as brown,169.576,856.1446 red7312.803.839.1119green,630,1060.1291 violet,186.189 gray205and intermediate shades.190.208,221.577 I n addition to wool other materials which can be dyed with pyrazolinone azo dyes are cotton and its derivatives such a ~~y0~,169,177.205.215.453,877.963,1326.1449.1451 synthetic polyamides,216.865,1117silk,453.582.1117.1457 leather39.1117.1457 577 Complexed metal dyes are not suitable for polyesters and and polyacrylonitriles. As already mentioned, numerous pyrazolinone azo dyes form complexes with metals. This can be done either before or after deposition but is usually done after the azo dye has been used to treat the fabric. I n those dyes which are applied to wool the usual metal employed is c~o~um.77~177.213.441.935.1061.1259.1421.1448For cotton dyes it is more common to use copper.38.177.276.622.879.1429.1619 Cobalt 207.276 lead > 213 3
6*
154
Part 2.
Chapter I11
nicke1213*276 and iron177*276 have also been used. Many metal salts and oxides can be used for the metallizing operation, In the case of chromium, various salts of chromosalicylic acid have been widely ~ s e d ~ as ~ well ~ as. sulfates, ~ ~ fluorides ~ . and ~ others. ~ ~ ~ . ~ The polymethine dyes derived from pyrazolinones have not been of importance in dyeing fabrics because of their lack of fastness to light. However, methylidyne bispyrazolinones are suitable for dyeing polyester fabrics. The following list of references is made up of those reporting azo dyes having structures so complex that i t was considered inadvisable to include them in the tables: 168, 174, 177, 179, 182, 203, 205, 209, 215, 218, 220, 221, 224, 227, 477, 486, 487, 635, 657, 782, 839, 840, 863, 886, 904, 958, 1020, 1062, 1121, 1267, 1326, 1358, 1361, 1366, 1381, 1394, 1398, 1403, 1408, 1412, 1415, 1416, 1419, 1420, 1429, 1449, 1451, 1465.
~
~
~
CHAPTER I V
Analytical Reagents The use of various pyrazolinones as reagents in qualitative and quantitative analysis has been proposed, although these procedures have not been widely applied. Calcium ions form an insoluble precipitate with picrolonic acid. They can therefore be determined by using excess of the acid and back t i t r a t i ~ nSodium, . ~ ~ ~ potassium, ammonium, copper, zinc and strontium ions form crystalline salts with picrolonic acid and these salts can be used for identification of the Trivalent, and tetravalent plutonium ions form insoluble salts of picrolonic acid and can be isolated as such.1o99Hovorka and Sykora665*666 have studied the use of various 4-nitroso-2-pyrazolin-5-onesin the gravimetric determination of a number of metal ions. It was found that the 3methyl, 3-phenyl and 1,3-diphenyl compounds give precipitates with silver, mercuric, cuprous, cupric, plumbous, cadmium, ferrous, ferric, manganous, nickel and cobalt ions. However, only silver waa precipitated quantitatively. The cupric ion could also be precipitated quantitatively by use of 3-methyl- or 3-phenyl-4-nitroso-1-(2-phenethyl)-2pyrazolin-5-one. I n the presence of ammonium thiocyanate cobalt gives a blue color with antipyrine1369or 4,4'-methylenebis(2,3-dimethyl-lphenyl-3-pyrazolin-6-one) 1678 which can then be used to determine the cobalt colorimetrically. It is claimed that cobalt can be determined in concentrations of one part per million,1369but iron, copper and bismuth interfere. 4,4'-Methylenebis(2,3-dimethyl-l-phenyl-3-pyrazolin-6-one) also forms insoluble complexes with various ions and this can be used to determine the ions gravimetrically. Cadmium forms such a complex in the presence of bromide i ~ nand cobalt, ~ ~ copper, ~ zinc, ~ ferric, * ~ cadmium and mercury ions form such complexes in the presence of ammonium thiocyanate.la79 Cyanides and cyanogen halides in the presence of pyridine and 3-methyl-l-phenyI-2-pyrazolin-5-one give a color which can be used for 165
~
~
~
156
Part 2.
Chapter IV
their determinati~n.'~~ The cyanides must be converted to cyanogen halides. The determination depends on conversion of pyridine to glutaconaldehyde which reacts with the pyrazolinone t o form a colored compound. The ferricyanide ion forms an insoluble complex with 4,4'-benzylidene-bis(2,3-dimethyl-l-phenyl-3-pyrazolin-5-one). This complex can be used to determine the ion gravimetrically if other complex ions are not present.609A green color is formed by the ferricyanide ion in the presence of aminopyrine and can be used for determination because of its fluorescence.1212The ferrocyanide ion does not interfere. Emerson, Kelly, Beegle and B e a ~ h a m425*427 ~ ~ ~ have . studied the coupling of various phenols with 4-aminoantipyrine and suggest the use of this reaction as a volumetric test for phenols. Phenols having no para-substituent or such para-substituents aa carboxyl, sulfo, hydroxy or methoxy groups couple, in the presence of mild oxidizing agents such as potassium ferricyanide, with the pyrazolinone t o give a color which can be used i ~ (the basis for determination of the phenol.
CHAPTER V
Miscellaneous Various pyrazolinones have been reported in patents and publications to have a variety of applications and activities. For example, both 2-pyrazolin-5-ones and 3-pyrazolin-5-oneshave been reported to cause abnormal mitosis in plants and to inhibit their growth.lqeg* 1665 Howland 667 has reported that a number of 2-pyrazolin-5-ones are effective antioxidants for rubber and linseed oil. The same property is probably responsible for their inhibition of odor formation in synthetic deterg e n t ~The . ~ perchlorate ~ ~ of antipyrine has been patented for use ~ E Ian explosive.933Matsumoto 953 has found that aminoantipyrine (probably the &amino) is an effective catalyst for decarboxylation. 5-Methyl-2-(3-sulfophenyl-and 2-chloro-3-sulfophenyl)-3-pyrazolidinone forms complexes with choromethylcumene to give surfaceactive textile assistants.13e8 The use of antipyrine as an agent for the concentration of tannin in tannin extracts has been proposed.66 Antipyrine forms a waterinsoluble complex with tannin and the complex is eaxiily decomposed by treating an aqueous suspension with organic solvents. These properties can be utilized for tannin concentration.
187
APPENDIX
SYSTEMATIC TABLES OF PYRAZOLONES AND THEIR DERIVATIVES
H H H
H
CtlH,,
CBHlB
CSHIl
H H H
C3H7
H
~Bo-C~H~ t-C,H,
H
H
H
H
CH3
H
CH3 H H H
H
H
H
R"
R=
.RI
Section A. Alkyl and Alicyclic Substituents
TABLE 11. 2-Pyrazolin-5-0nea
R1
p
" 9 I
R1 NII
R3
R H H
H
H H H
H
H
R'
216'
226" 207" 183' 2100 1980 2010 187O
1666 6,64,61,338,
(Tobbcontinued)
364,369,479, 480,1047, 1076, 1086, 1199, 1485, 1553,1622 61,467 360,1012 1012 364, 1522 1024 1024 856
1232, 1622, 1644,1648, 1647,1648, 16W,1563,
457, 813, 1228,
1660
Reference
M.P.
c3
I
% 7-
<
3.
t,
$
ec
P.
5
8;
9
.s"
%
5I
H
8.
8 3
m
3
H H H H H H H CzH6OOCCHz H H H
CHB
m 3
H
H
H H H H H H H H H H H H H H H H H H H H H H H H
H H H H H H CzH6OOCCHa H H H H H H H H H H H H H H H . H
CiiH13
(CH3)&CH&H, CzHSOOCCHz H H$?"NCOCHa C,H,CH=NNHCOCH2 2.HOC~H~CH=NNHCOCH, 3-NOpC,H,CH=NNHCOCHZ CBH,CH=CHCH=KNHCOCHz HOOCCHZCHZ CII,OOCCH&H. H2NHNOCCHZCHz CH3 CH3 CH3 CH3 CH3 CH3 CH3
R4
Ra
R"
TABLE 11, Seotion A (eonfin&)
167'
-
164O 166" 52' 106"
209'
67O 108" 149' 208" 203" 189' 167' 180" z 190" > 200" > 145' > 145' 222a 168' 178' 117' 109O 115" 99O 56". 86" 120° 59O 650
M.P.
1119 962 1118,1119 1118,1119 1119 1119
135 1480 96 564 1317 866 962 866 866 866 866 866 1221 1221 1221 $88,985, 1622 250 250 250 206,250, 1681 250 206 206 1118,1119
Reference
--
B$
* w
El
aa
c
CH3
188O
240"
H H
182' 193' 197" 158' 198" 178' 182O 273" H H H H H H H H
H H H H H H H H
I
232' 211°
H H
H H
H H
229"
H
H
CizHa, HOCH&Hz CH3CH I OH HOOCCHS C,H,OOCCH=C
272'
1288
349
513,514,516
So, 1171
0
5 $
2.
?
P
93
I 1645 81,358,359,660, 729,1012. 1645 730 359, 720, 1522, 1646 250 883, 1522, 1648 1526 917 1012 6. 1606 U
c3 61,358,359,892, 1012, 1631, a
B
m
3
1684
1119 1684 1884 1884
1119
-
-
-
-
liquid
146"
H
H
H H H H
11
H
bH HOaSCH2CHCHS I bH H
H H H H
AH3 ~so-C,H,~OOCCH&H, H03SCH2CH1 HO,SCH&H2 HO3SCHSCHCHS
I
H
NCCHCHS
CH3
H
H
H H
0
CH3 CH3
CH3
H
H
R=
RI
TABLE 11, Section A (contind) _____
_.-___
H
NO&HzC
\ CH3
/
AH3 CH,
NHaNHCOCH
_^_.______
R3
-
-
H
H H H H H H H H H CH3
H
H
3%.
224"
76" 105"
74" 109'. 268"
840 71' 113' 850 84" 83"
94"
133"
-
212"
M.p.
1579
1522 1522 250 260 260 250 250 61,368,359, 769, 1012, 1531,1560 81 61,769,1522
51, 1531 1522
64
1277
Referenee
- + r
c1
* ;-
a
37
.a
GJ
Systematic Tables of Pyrazolones and their Derivatives
x
X
X
I
165
R'
R=
TABLE 11, Section B (eonlind) R3
I1
H H
H
H H
H H H H H
H H H H H
H H H H
110"
100' 99" 165' 110.5" 186' 81" 182" 191' 83' 180" 79'. 107'
-
142' 207' 127", 213'
127'
-
177O 126' 217' 210° 225' 290' (dec.) 233' 205'
H H H H H
H
M.P.
R'
181 835 1577 1675 622 68,95,629, 723, 788, 805,806, 809,811,816, 838 1569 64,992, 1660 64,1531, 1680 564 1686 303 505 1688 505 1588 1294 1640 1686 506 97, 448, 1589, 1590 1582, 1689, 1590
467
798
446
1004
Reference
3
01 01
Y
LLPI
1221
'PLZ
8LL
OZLI
0911
0921
'H@3
H
'H33
0
H
H
-\ H
H
H e'H83 H LlH83 H Q'HLD
~
H H H H H H H H H H H H
'Hb
e
H
H crH83
'H%
909 €PI
909 €FI
909 €*I M)9
bl MM 'PZOI '€201
0691 '6891
0011
-
r,OPZ 0 96 OL9 0001
09L
O B I
09'LOI 09XL
099
H H
H
'HQ3
06SI
1ZH0l3
€I
H H H H
0801 028 0911
H
H
H
8111 9EQ
0%
H
"H93
SH@:,
ZP
e8EI
H
H 0
H
H
'6891 '88!2l
06EI
H
1x3 IZZI
'H@D 'HQ3 EHQ3 9 ~ 'Hg3 'HQ3 H EHQ3 H 'H*3 H 'Hg3
9013
96
9891 '069T '6891 '8207
3
3
~
~
~
R'
__
1
Fe I
hJ
R=
____
TABLE 11, Section B (continued)
H H H
H
H H
H H H H
H H
H
H
H
H
H
R4
H
R=
172'
131'
182", 199'
132'
1494 296.838 296,838, 1002
192, 296, 838,
492 863
470
192
197
838 902 1149
122O
-
68,723,806, a38 1477
806, 838, 1524, 1584 723, 838 1477
628
F W erenee
91.50,1400 104"
104" 103"
143", 183'
186"
M.P.
1
* %
0, 00
Y
bH 4-(4-C6HsCO)C& 2-HOOCC6H4 3-HOOCCeH4 4-HOOCC,H, 4-CaH500CCeH4 4-(3-HOOC-4HOC~H,NHCO)CBH, 2-HO3SCBH4 3-HO3SCeHI 3-HO,SCeH, 4-HOSSCeH4
I
H
H H
H
H H H
CZHl H H
H
H H H H H H
212"
H H H
248'
237O
-
> 3Oo0
306"
-
205O
-
-
278" 145'
-
170' 189"
-
134" 233" 170" 196" 185' 220"
H H H H H H
26
1306 593 1348 191. 356,684, 1163 694 1481 324, 328, 356, 695, 1475, 1476, 1628
1497 1004, 1520 165, 1270 356 1490 1361
1683 1569 303 446 837 777,838,1282, 1372 303 1684 1684
?. %
%
<
U 3_.
g
e P.
3
a
P
Fs
[
v
'd
0 %
25
If.
d 3 9,
Y,
R'
R'
TABLE 11, Section B (coratinued) R4
H H H I3 H
H
H
H
R3
H H H H H
H
H
H
198"
-
-
194O
-
51i
1160
163
141 I97 163,1377
546
150°
Reference
M.P.
._
r
2
H H H H H H H H H H H H H H H H H H H H H H H H
H
H H H H H H H H H H H H H H H H H H H H H H H H
H
211" 190° 190" -
-
163O 144O, 126'
-
164"
178'
-
> 300"
-
-
164" 194"
238.239 534 534 71
808
123 312 1393 777 806
446 723, 777. 1207 197
1348
679 446 1389 539 1162 364 694 1348 296, 885 80
g.
i 3
6 a
i
0
%
2i
%
i3
!2
s. 0
%
m
3
R1
R'
TABLE 11, Seotion B (continued) R3 127" 107' 111.5' 1Ol0 116"
-
b0.006
H H
H H H H H
95 O 118' 92 114.5' 80.4" 133'
130"
94" 1900
H H H H H H
H H H
148-151°
M.P.
H'
1171 583
1336
1239
63,560 560, 1336 1338 1582 277
1477
95, 809, 811, 814, 1056, 1299 95, 814, 1007, 1522, 1624 1277,1589,1590 53, 1622 53, 249, 1336 1477
Rcference
c
t3
4
CH3
CH&OOCaHs
I
CH3k
CH,
OH
AH3 (CH3)2C= -CHaCH2-
CH,CCH=CH HOOCCHa CsHaOOCH2 C2H,OOCCH&H2 CSH6OOCCHd
I1
0
I
CH3!CH2 0 CH, CHJCHaCI
NOH
H H
98O
1100
117" 94O, 138' (2forms)
1810 178O 138" b3215' 246"
1347
753
809 872
721 814 309 814 1288
686
142"
H
H H
113
674 113
106"
146" 114"
H
H H
3
m
<
$ -. !
4
C.
U 4
s2.
n
a
Appendix
174
0
14
5:
1130 1130, 1131 1130 1130, 1131 1130 1130, 1131
185"
235" 226" 118' 214'
231'
166
1130
235"
B
a
0,
w
cd
&
m
2
0
5 Ec.
u)
'c
176
Appendix
4-NH2C6H4 4-FCpHs 4-NOaCeH4 4-NOzCeH4
CZH5
CH3 H H
1004 1524
1188
> 300"
1188
159' 82.5"
308"
TABLE I1 (continzled) _ _ _ -
__
- -__
___ -
C6H,CHz H
CH3 CH3
H H
H H
C,H,CH=CH C,HsCH2CH,CHz
Section C. Aralkyl, Heterocyclicalkyl, Aryl, and Alkyl Substituents
__- .-. -- -
H H
CZH, C3H, CBH7 CSHS C3H7 CH3 CH3
174' 134" 82O 155' 213", 218', 230' 214' 176'
883 883
181
54, 250, 333 1566 334 334 302,660, 729
21e'
180'
-
5'
3a
3. CF;
.__
1320 813
538
538
53, 95 53 53 53, 1321 53
197"
-
39', 51' b,,181" bia184" b,,192" b3,203" -
H
H
c6w5
H
C6H6
CeH5CH=
H H H H
H
I
CeH5 HOOCC=C
I
H H H H H H
CEH5CH= CEH5CH=
H H H H H
H H
H
H
H
H H H H H C6HsCH
C6H5
NO2 CeHS CeH&H2 ~o-C~H, CEH5CH= H C,H&H, H CEHsCHz
I
I
C2H5 CeH6CH-CH
H
I
CH=CH2 CsH5CH
I
CEBsCH
H
H
162" 144.5" 176' 171' 280'
145"
334 334 1236 1334 835
1050
1552, 1560 1534 1567 124, 1334 246 246 1639
306
1200 170" > 250' 133' 145.5' 148" 115' 118.5' 220"
505
172O
302 250 333 1320 1236, 1320 333
383
882, 883
882
146' 204' 184"
-
177' 74" 111O
235"
193"
184"
H'
TABLE 11, Section C ( c d i n u e d ) M.p.
H H H
H
1128
150"
1320 818 505 1200 1227 1284, 1255
1131
185"
139' 147" 178O 229" 163" 127"
1131
1131
1308 1128 1321, 1584 1148 686, 809, 1260 809 1522
1Leierence
1810
227"
235"
208"
143' 106" 139" 220"
H H
140'
H
116'
~,~,~-(CH~)~-~-HO-~.CH&OOC~CH~(CH~).& 208" =Z
R'
0
0;
c.'
CHzCH&l
I
dH&HzC1 4-(C2HSN)CeH,CH=
4-HzNC&CHz CCH&ONHCeH,CHz 34CH&NCeH,CH= 4-(CH&NC,H,CH= 4-(CH,N)Ce&CH=
H
H
H H
162"
1220 169' 240" 157' 181" 205" 208' 141'
180". 209'
162"
167"
-
117'
185O 117' 196" 154"
(Table continued)
570
570
34 633 633 110.376, 633 832 22 24 22 1241 1123 956 965 702 1073 836 1114 567 570
34
311 376 34
110 110
oil
r
Appendix
182
hl N 0
x
X
+
0 N
x
v 0 =u,
x
d
u
s u)
kY
Y
%
V
Systematic Tables of Pyrazolones and t.heir Derivatives
E
x"
V
Appendix
184
oa
.%
w
X
II
G
i)
c
V
x
X
X
Systematic Tables of Pyrazolones and their Derivatives I
i
!
I1 I
i
X
X
! I
i
I
I
I !
I j
7'
185
CeH, C6H5 2-CH&H, 3-CH,0C6H4 4-CH30C6H, 4-BrC6H4 3-X02C6H4 4-NO2C6H, 2-HOOCCeH4 4-HOOCC6H4 2-HO3SCsH4 3-HO3SCeH4 4-H03SC6H4 4-H2NO2SCeH,
C6H6
CsH5
C6H5
C6H5
C6HS
CeH,
C6H5
C6HS
C6HS
CBHS
C6H5
C6H5
c6H5
C6H6
H H H H H H H H
H H
H H
H H H H H H
H
H H H
H
H H H H H
H H
H H
11
2GH7 H
H
H H H
H H
2-HSCeH4 2-HS-4-C,H,OC,H,
H H H H
H H H H
H H H
H H
CsHs H
236"
-
230" 215' 191" 124" 137" 154O 174' 207.5' 196' -
195' 140" 152' 113" 144" 140°, 161' 209 195' 243" 199" 127.5O 219" 235" 128" 1225 455 1004, 1524 1581 1581 351 777, 1003 777 1520 857 469, 857 857 857 695
506, 1636 673 1588,1589,1590 1580 1580 1580, 1589 340 857 578 578 1577 1577 1640 1575 1585
E'
3a
ccr3.
H H H H H H H H H H H H H H H H H H H H H H H
H H H H H H H H H H H H H H H H H H H H H H H
H H H H H H
K
H H H H H H H H H
H H
a57 1581 1580 1580 1580 a57 1577 1577 1575 694 694 694 857 694 857 469 a57 469, 857 229
857 857 777 857
163 857 a57 857 777 469, 857 857 857 857
f
I
$
P
z.P
2. v
s
a
J
P
2
0
0,
K
%
2
%
EO
;
6 4
50
m Y,
H
H
'Hg3
'Hs3
'H%
0602
8LE
H
8L8
8LE
*H~~~OOH-P
'H93 'H@~~OOH-P
'Hg3 'Hs3 H "3
LHe3-OB!
'H@3
~ H V ~ O B !
'H'3 'H'3 'H@3 'H93 'H@3 'Hg3
GO9 90s 90!2 909 909 909
9LZ1 909
om1
H
CH3 H H H
H
H H H H H H H H H H H
9LZ1 GO9 909
w 1
ZZBI 909 LB8
L4%
sH932ON-P
sHs3cH3-P
'H'3
'Hb
'HS
'h53
'He3 'H'3 'H'3 'H93 'H'3 "Hg3 'Hg3 'H@3
'H'3 'H'3
9H93
'Hb
sHo13-Z-SCOH-I 'H83SE0H -9-300H-E-OH-Z
H
H
H
/I
S
1
/-
O
\/
N
wII
0
vil
/-
y v H
H
H
204"
46 > 266 241°
H CH,
H
H
H
265"
205"
223'
-
-
H
4-(4-H03SCeR*CH~NH).J-CH&H&H=
2-HO3S-4-(4-NO&H*CONH)C6H5 C6HS CH3 CeH,CH= CeHsCH=
358
662
1498. 1499
1361 3, 1640 1343 351 1004 1371
Appendix
cd m
CD
m
2
d
m
FD rn CI
X
X
x
z
X
X
x
X
X
X
l . 3
x
x
Syst,ematic Tables of Pyrazolories and their Derivatives
191
W
W m
i ~
0
W
2
X
X
iI I
3;
I
x
x
X
rl
192
Appendix
X
2
X
x
X
$1
x
X
X
51
$1
Systematic Tables o f Pyrazolones and their Derivatives
193
%
2 m
s2
i2
8
z
w
w
W
W
w
X
w
w
W n
*
5
z!
Q)
0, a
X
W
W
w
PI
w
E
V
f
mi
cu
3
0,
i Y
t 3
Appendix
X
w
X
X
z
$:
X
X
Systematic Tables of Pyrazolones and t.heir Derivatives
W
(D W
r-
m -8 d
X
8
x
X
V
0e 0 4
u"
x4
G
8
x
d
2
I4
V
m cv m
Appendix
Q)
rg
0 Q,
El *)
*
c-
$1
X
bx
-V
4
V
Systematic Tables of Pyrazolonea and their Derivatives
lw
E:
m v)
v)
2
3
(d
rch
k
c1
X
d
V
197
Appendix
rm m
ac,
1n
x
"
m
m m t-
E
X
I
I
x
X
Systematic Tables of Pyrazolones and their Derivatives
199
l -
2
00 r’ m
CI
0
P
8
0
8
X
X
X
==!\
I-
/
0
X
i
I
a V
H
H
H H H
H H H
Section F. a-Hydroxy- and a-Uoxyalkyl, Alkyl, Aralkyl, Aromatic, and Heterocyclic Substituents
TABLE I1 (condinwd)
0
H
0
TABLE 11, Section E (colatinued)
H CH3 CZH,
H
H
148' 135" 99"
216'
m2o
1315 1314 1314
1147
1147
Es
8
191°
bH CI,CCH
I
OH
C6H8
I
CZH, CZHSOC=
130"
120"
CH:, C2HsOC=
I
129O
CzH50C=
H
184O
OH C1,CCH
I
1316 532 24 895
82O 158' 189O
H H HOCH, CIaCCH
764
764
1190
1194
254O
I
lalo
-
H
i? ;i'
B
-9
0
8
E
2
a c .
8
m
3
_ _ _ ~
CH, CH3
H
H
co
2-HOOCCEH,CONHCH,
CH3
Ra
H
_____-_-___
R'
-
__
-
H
H
NNHC,H,
/I
NH CsH5.C
I/
H
N
H
192"
1tX0
230°
> 300" H
NH C,H,C
II
280'
H
__
CH3C
-
145' 166'
h1.p.
_
-
H H
90"
R4
R"
Section G. a-Amino- and a-Iminoalkyl Alkyl, and Aryl Substituents
T A B L E I1 (continued)
I / \o /-
TABLE 11. Section F (continued)
-
138
138
1193
1193
1193
Reference
1562 1562
764
* x
E
31
CD
N
N 0
II
NH
NH C*H&
II
CH,C
NCH,
c
137" 201 184O
110"
H H H
H
68"
172'
H H
224"
210" 221" 221O
H
H
H
170"
H H H 1550
171O
H
H
283' 863" 240" 172O
H H H H
H H H H
(Table COJr(inWd)
1206 348, 823, 824, 923, 1070, 1088, 1089, 1090 1189
1193
1193
1192, 1193
1W8
925 1189 1189 1008 1098
1179
1188, 1189 1188 1188 1179
53
N
*
CBH5
H'
CH3
It2
TABLE 11, Section G (continued)
I 2-ROOk&H,
<,,LNH-C= CeH, I
C6H&HN=C I
cir,
I
C,H5NHN----C
it3
162" 173"
H H H H H H H H H H H H
H
H
183"
H
186"
168"
197', 210'
2420
161O
164O 175' 170" 181' 203" 122" 171'
-
144"
170'
N.P.
R'
1193
1193
559, 1192
1202
351 351 1092 1190 348 351 351 350 923 348 348 947
348
947, 1192
Referonce
z.2'
3
9 3
c
ts 0
P-C,H,OC,H, 4-C,H,OC6H,
HON=CH CeHsN=CH
COOCzHs
I
H
XI
4-CH3C6H4
4-CH,CeH,
H
LOOH C6H6NHN=S &OOC,H, C6H,NHNHC=
H H H H
H H H H
H
H
H
k00C2Hs CeH5NSH 3-CH3CeH,N----CH 4-CZH,OCeH,N=CH 3-CH3CeH4NSH 2,5-(CH3)&eH3NdH 2-C2H50C6H4N=CH 4-BrCeHaN=CH CeH5NHh'=C
bo0cpH6 (CeHs)pNNHC=
COOH 4-BrCeHINHN=C
I
COOC2Hj CEH6NHN=C
I
H
2-CH4C8H4 2-CH,C6H4 S-CH3C6H4 4-CH3CeH4 Q-CH,C,H, 4-CH,C6H, 4-CH3CEH4 4-CH3CeHI
ca5
CeHs
C6HS CeH5NHX=C
C6H5
I
CBH,NHX==C
C6H5
182" 155'
209"
195"
122" 249' 133' 196' 217O
160°
140' 232'
137'
213"
205'
182"
204"
1186 902
1641
1641
351 351 351 351 349 351 351 lG41
1641
1641
1193
z
I
A
i5.
2'
U 9
z6'
cc
Be.
m 8
0
r'd
%
3e P
__
R=
__
T A B L E 11, Section G (continued)
H H H H H H H H H H H H H CH3
AOOCaHs C6H5N-CH S94-(CH3),CeH3N=CH 4-C1CeH4N=CH 3-BrCeH4N==CH 4-BrCtiH4N=CH C,H,N=CH CH,
H
142" 188" 77"
148O
169" 142O 181
254' 195", 140' 146' 215" 184' 192" 208O
190a 175'
177"
132' 235"
H H
H
B1.P. - ___
R'
! I HONAH CeH6N=CH 2-CHJ&H,N=CH 2-NHaCeH4NdH 4-BrCeH4NdH 2-CloH,N=CH CsHsNHNd
NH 2-NHaCeHIN4H NH&=
II
C6HSC
NH
II
CH&
~~
351 351 351 351 351 351 512
1190 600 348 1641
348
902 348,902
1190 1189
1193
1186 1193
.
Reference
E3
U s
C
I
I
R3
/\
__ -
__- -
H H H H H H H H H H H
H H H H H H H H H H H -
H H H H H H
H H H H H H
TABLE 111. 4,4'-Bia(3-pyrazolin-5-ones)Linkcd by a Singlc Bond
K1
\N
X I/
~Z-..-L-I-.-..-
I
s/I
RZ
R6
ps/
i
R4
-
-
265" (doc.)
dec.
-
-
-
238'
> 290"
290". 320'
melting,
dec. without
-
> 3759
-
> 360' > 360'
___
(Table continued)
12 12 72 72 296 690 72 72 72
636
725 1485 12,725 12 114,807,809,815, 886, 925, 1090, 1091, 1096, 1185, 1192, 1513, 1522, 1638, 1612 1582
v
U
9.
cc b
2
g
J
3R
Y,
0,
R1
-
R"
T X R L E I I I (continued)
CEH5
160' (dcc.)
I
COCH3
COX H, C2H50 CH30 C3H?O NC H H H
(CN),CH NCCH
COOH HOOCCH, NCCHZ H,C,OOCCH
H
COOC,H, NCHC
I
149", 161" 215' 161" 116'
-
1289 197'
94' (dec.)
-
230' (dec.)
-
213" (dec.) 160' 106"
>280" > 330"
CaH5 CEHSCH2 CaH5 NCHC
-
M.P.
166'
I
H5
-
R4
-
._.
CH3
__
.
_.
H H H H H
R3
-.
1609 1609 1609 1612 73, 367 73, 357 73
1614 1614
1613 1613 1613
1613
72 72 333 72, 129, 818, 1022 129 729,809,1299,1528, 1606, 1611 809,1526,1528,1645 849 1522 1613
Reicrcncc
to
0 00
Systematic Tables of Pyrazolones and their Derivatives
wwww w
xwww x" w
w
209
210
Appendix
111
I
R'
TABLE IV. 4,4'-Bis(2-pyrnzolin-S-ones)Linked by a Double Bond Xp. -..
-
IieCereiire
__ -
-
1560
230'
323, 807, 809, 816,
300"
1090, 1091 298
296
219'
1607, 1608
142"
333
Systematic Tables of Pyrazolones and their Derivatives
1 3 Y
mom
d W
il
w
4
h
dt 0 -
0
10d *
tm El
T A B L E V , Section A (continued)
CH<
2200
I
=cH-H=
II
4-?U'O&H,CH< 2-HOOCC8H,CH< 2-CH,OOCCeH,CH < 2-CZH,OOCCHzOC~H4CH< 4-HO-3-CH,OCeH&H< 3,4-(CH,O)&,H,CH< 2,4,6-(CH,O)&,HzCH< 3-CH,0-4-HO-5-H0,SC,H2CH<
118-140"
212O
181O
228'
93, 1135 1135 162" 1135 175' 1094, 1255 231' 1135 1135 149' 208O 1135 146' (dec.), 203" 633, 1135 150"(deo.), 227" 376, 633, 1134 (164' enol) 226O 110 208' 1279 178" 1279 204' 832 191O 22 1220 22 204" 1036 22
ReKorenco
-
93
297
1224
-____.
2-HOCeH,CH< 3-HOCBH,CH< 4-HOC,H*CH< 4-CH,OCeH*CH< 2-CICeH,CH< 3-ClC,H,CH< 4-CIC,H,CH< 2-NOzC,H,CH < 3-XOzC,H,CH<
-
a1.p.
- --___
R
___~
FJ
c
-
~ - _ _ta
Systematic Tables of Pyrazolones and their Derivatives
w
oa
2
0
m
I
I
2
2
m
2
213
0
2 3
0 Q)
8
g/ \g V
214
Appendix
x xxw
w warn
Systematic Tables of Pyrazolones and their Derivatives
t-
2
4
e
V
215
Appendix
216
cr)
i3 lm d
2 m
r-d 00
d(r(
mul
mm
I
5
2 2 E$ Y
x"
V
3
0
H 4
I
Systematic Tables of Pyrazolones and their Derivatives
217
B'
K.3
I
I
It'
R'
TABLE VI. Miscellaneous 4,4'-Bie(2-pyrazolin-B-ones) - __--. - __-
__
~
R
111
-C- '
c I-
Br
Br
I
It3
12 3
M.D.
Reference
138"
1682
Br
80°
1109
H
267"
513
CH, CH,
178' 129'
1134
R4
C6HS
CH3
Br
H
CH,
CH3CH-
I
CH,CH<
I
3-NOzC,H,CH< C,H&H<
CoH, H
CH, CH3
OH CH3 CH,
1560
I
CeH5CH2CHz H
C,H5cH2
H H
H H
S
It
-__. . _ _ I
TABLE VII. 4,4'-Bie(2-pyrazolin-5-onee)Linked by Chaine Conteining N and S
R'
-
578
281'
160°
95O lHO, 267' (dec.)
1576 1576 333 1566 1552, 1576
262 480
578 270'
238" (dec.) 247' (deo.) (HCU 235" (dec.) 260' (dec.)
579,580
Ref ercnce
181'
3Z.p.
t3
m
L
Systematic Tables of Pyrazolonea and their Derivatives
> 270"
259
1359
Systematic Tables of Pyrazolones and their Derivatives
I
8
8
8
@
0,
u, w
221
222
Appendix
I m
A W
2
I
Systematic Tables of Pyrazolones and their Derivatives
X
$ V
X
X
X
X
X
X
5 X
4 V
3 w 4
223
I
I
~
Ri
(continued)
II -c-
0
I
L
-
R
H
H
L
H
H
R3
Ra
TABLE IX. I,l'.Bis(2-pyrazolin-5-ones)
-N-
CH3
-N-
R
---
TABLE VIII
CH3
H
I
H
H
C6H.S
4-(4-t-QHJ&R40) CeH4
CeH,
R'
656
TO6
183" 1037,1632
-
-
595,696
595, 596
245"
260"
Retercnoe
M.D.
Ip
El El
Systematic Tables of Pyrazolones and their Derivatives
ZX
x
X
w
X
X
X
225
Appendix
3 I
,
X
$
X
w
X
X
Systematic Tables of Pyrazolones and their Derivatives
6 X
z
8
227
Appendix
228
co
3
m W
w
cc) W L1
I
I
I
x
x
s
x
x
x
x
V
V
0 0
x
G
-0
G
--u
0
:
Systematic Tables of Pyrazolonen and their Derivatives
x
229
8 W
W u3 W
Q, d
*
x
4
$
8
1
I
I
I
I
I
I
X
x
d
Q,
230
Appendix
Q,
b,
s:
8
I
I
Systematic Tables of Pyrazolones and their Derivatives
23 1
TABLE X . Furlone8 Compounds
M.P.
Reference
158"
1608, 1611
151"
1608
134O
1808
161'
1608
/AN /
O
-CH, CH3
(Table conlinued)
Appendix
232
T A B L E X (wnlinued) -
- I _ _
Conlpounds
-
--
_ B1.D.
Helerencc
147'
1608
164O
1608
162.5" (dec.)
1010
172' (dec.)
1610
I
2-CH,deH, 2-CH3CeHi I
A N/
O
k
4-CHaCeH4
I N
I
\/ \ N
CH3O
N
I
4-CH3CeHl
_
~
Systcniatic Tahlcs of Pyrazolones and thcir Derivatives
233
166' 174'
157'
1652, 1656 1666 1655,1656
1086
342,344, 1025 299
125"
H H H
391 172"
391 1543
391
368 1026,1026 1025,1026 1065
368.1049 368, 1049
819, 1266 819 714
Reference
b,,,9l0
H H H
-
115"
H
172O 232O
-
253" 41' 32'
168O
b1,140" 163" 235O 94O
M.p.
H
H
H C2HSOOC 4-HsNCeH4SOj H CSHSOOC 4-HzNCaH4SOs H H H H
Rs
H
CZH5
H
H H CH3 C A
11 H H
C2H5
H H H H H H H H H C4Hn
H H H H
R4
-_ R3
CsH6 H
Ra
CHCX CH3 H H
ll
H H H H H H CH&
H
H H H H
R'
TABLE XII. 5-hhO-Z-pyrSZOhW
I
R'
R3
T
3
t3 c1: P
zoo1 'Hz3
H H H
H
H H H
EH3
EH3
'H'3
'H'3 'H'O 'H'3
'0101 *8&8
EH3 EH3
.PT€9
H
H
'LZ8 'QZ8 09Pl 'oOZI 08Z2z19
H
H
9L6 9L6
0011
03'H3
e m ' I W 'ZZE
o80E
"3
H H H H H H H H H
'H93
H H
H
H
H
186
H
%'3'H3-P H QHb 'H'3 'H@3 SH93 'H*3 'Hg3 'He3 'H'3 'H'3
*~93~0Nt
'H'3
H
H H H H H H H H H H H H
H
H H H H H 'H'3 H 03030sH'H5 H 030'H23 H 0 3 ~ ~ 9 3H 03'H3 H 0 3H H Hg3-'H'3.P H *H~~I:v H 'HgP3'P H 'H'N8-8 H
H
o 8'3
-
10E '66Z
I E6
*B '2% ZWI 1%
ZOOT IOE 10E
TOE TOE OBI
9991 W9T
9BT
.-x
2a 4
0
0901 008 I OL91 OlEI 0 EG 1EZ9
OOCK
-
98 Z00I 966 966 zooI 966 9201 %zor
ZZE 0
COZ
9GG
0081
OSTZ 00zz OOL1 OEIt 0011
0"EI OLE1 OEEI
.8&I
o9EI 0661 .GO1
09L 00PI
Zoo1
zoo1 'LZ8
OZL
'dm
ZOO1
966 966 'Z?;& 828 ZOO" zoo1 966 9GG 2001
9GG
EZC 4'ZE 966
966
966
___
I
'H93
H 'H93 H 03'H3 'H93 H H
H3=NVN\
H H H H H H H
I b E H 3 H 3SNH"Hg3 H 30NHsHg3 H 30N'H H z ~ ~ ~ ~ gH 3 2 ~ N ~ '0S'H03NZH-P H e ~ ~ S ~H 9 3 0 3 ~ ~ H ~ 3 H H H 0DCH3 03H H013 1
L
P.)I
.% I ._.____. -~
._ .
+ H ~ ~ Z O N - PH v ~ 9 3 Z ~ H ~ - ~ ~ ~ ~ 3 3 0 0 H~ ~ ~ 3 - ~ * ~ ~ 3 3 0 0 HH~ 'Hg3-Ttl-p H '~~313-v H t B E H H 3 H3-P ' ~ 9 3 ~ ~ 3 -H 2 -
H H H H H H H H H H H H
H H
H H H H H CX
CH3 CH3
'H3 'H3 EH3
EH3 rrH'3
CH3 CH3 EH3 EH3 CH3 €H3 CH3 EH3 "3
"3 EHO
CH3 EH3 "3 CH3 CH3 =H3 CH3 =H3
C 8
__
~
*x9~13-z
'H93EH3-t **Hg3'H3-P H Q3CH3-Z *P Q~r FQ 3 C ~ 3 - ~ H d'H3-Z 9HQ3
'H5 'H80 'H93 3 ' " "'3 'H03 'Hg3 'H93 'H93 *H93 "Q3 'H93 'H'3 'H83 sHQ3
-
'H'3 'HQ3 "'3
__IU
(panu??uoo)IIX 3 7 8 V J
-
C6HJ
C6H5
CGH5
H CH,CO H H H CH,CO H
340 1543
340
(Table c o n f i n d )
188" 127' 110" 236' 137' __
-
1287 1287 90, 129 1543
1690
H H H H H H H
CH3CO
340
153'
149"
H
CHCOOC2H, CBHS
217"
H H
H H
/I
H CHaC-
H
I1 H
CBHS H
1002 976 324 86 184O 1207 2044" 1207 286" 1207 190° 1207 166" 1207 216' (dec.) 1207 122O 976 146" 975 128O 129, 340, 342, 345 606 125" 299
106" 98O 246'
1652 1287
H H H H H H H H H H H H H
H €I H H H H H H H H H H H
4
ta
m
c 6
i5
c
$ ".
v
U
5
@
Ei; E
3
%
5 2 %
?
c'
2
m 6
3
TABLE XI1 (continued)
H CeH6CO H H CeH5CO H CeH5CO H CH3 CeH6C0 CeHs 4*CH&*H, CBH5 4-CHaCeH, H H CH,CO
H H H H H H H H H H
H H H
H
H
H
H
H H CH,CO CeHSCO H CHaCO
RE
4-CICsHI 4-CICeH4 H H
H
3-ClCeH4 4-CICeH, H H 4-N01C8H4 4-NO&H4
R4
H H H H H H
R3
122
174"
77" 1200 184O 164O 163" 295" I84O 10" 120"
160°
102O 196" 81 53O 233" 55"
127
-
975, 1011 1011 132 1011 1011 1011 1011 976, 1011 975 975,1011 1002 102 1002 102 918 1562 1562
340,342
1543 1562 1562 340
1543
Iloferoncc
108" 185' 219" 219" 185" 218"
M.P.
m
ts
u
TABLE XI1 (codinued)
CH2COOC2HS C,H5CH=N 4-CH3OCeH,CH=K CpHSCONH HzNOCHN C6HBNHOCHN CBHSNHSCHN
I
H 4-NO&H,S 4-NOzC&3 H,N HzN HzN HzN H2N CH3C=N
H
H
H
H H H H H H H H CzHs QHS H H H H H H
H
R*
163" 149" 127' 140' 114' 155" 175' 155' 150' 183" 202 105' 193" 170' 201"
CBHsCO H H H H H H H CeH5CO H CH&O H CeHsCO H CH3C0 H H CsH5 4-CH3CaHS 3-Pu'0,-4-CH,CeH, C6H5 147' l9l0 187" 201O 220' 160"
140' 131" 97 127'
-
M.P.
H6
995 995 995 995 1002 1002
391 1699 1599 325 325 1044 1043,1044 995,1002 1002 1002 995
594 391
1562 1563 310 310 310 310 310 310
Reference
B
(D (D
3
.:
U $
[
rc
e
6
0
5-
%
2 e1
1 g.
5
m
3
0181
08Ll ot61 oZOIITq 0991 ow1
I91
0281 0
O L E
8CZ
0091
L8Zl
OLIT
o
199 966 966
068
9991 9991 599I 16E 16E 16E 16E IBE 168 9WI
OFOX
OEEZ
OOPI
oE6
a811
-
6EOI 966 '9L6 Z*91
C B E H3H3-P-38-Z H 'H03.'a*E H "H0318-P-D-Z H H 'HZ3 H 'HZ3 H 'H'3 03"H3 'Reg H 'H'3 H 'H'3 H H
I
'H03
'H03
'H03
H H H
H H H H
e€lz3
13
H
H
J8
3 8
13
D
38
"H3
*H93
'H03
'H93'H3-P
H
I
'Hg3
'H'3
'H93
Y\ H
EH3 "3 "H3
EHHn
"H3
"H3 *HO3EH3-P
'HQ3SGOeH3cH3SeOH-P 'H93'H3-Z "Q3 'H83 'H03 'H03 H H H H H H H H
H
H H H
H H H H H H H
NO NO NO NO
NO
__
H H H H
NO NO2 NO2 NO2
Ii
NO
NO
NO KO NO
NO
NO
NO
c1
H
H H H H
Br Hr
Br Br I c1 Br I
C1 C1
H H H H H H H H H H H H
Br Br Br C1
H CH3C0 CeH,CO C6H50COC0 CeH5 H 4-CH3CEH. H H H H H H H CH3C0 H
2-Br-4-C1CeH, 2,4-Br2CeH3 2-Br-4-ICeH3 H CH3C0 C6H5 H CeH5CO H H H H H 4-BrC'gHs H H
340,1153 1152, 1153 1153 340 1043 1043 1044,1045 228" 180" 225"
-
996
198'
301 301 301 301 1002 1002, 1010 1002 996
1002 975 1643
996
1665, 1656 1652, 1654 1656 975 975 1201 975 996 975 996 996 996
207 ' 230" 208"
270" (dec.) 237" 271O 240a(dec.) 113" 168O, 199' 117' 195"
167'
-
131"
128'
172" 75O 114" 134" 141
106O
198O 206" (dec.) 201 O 118" 132' 138'
Lw
s 8. !2 2' g. $
a
a1
0
la
0
-
3 t0
%
%
5. e a g
f
m Y
4 8
01
2
SLPT 8LPI 9611 LZ8
828 828 828 928 8LPI
8LPI 8LP1
909 909 99zt 9921 EL6 LL6'EL6 wo1 '&fa1'0101
ZS6
ZE6
9"l
6POI
&PZ OOOZ
w 9 1 'Z99I ( * D a d 09%
H H H LHOr$I 'He3 LH0'3.1 LHoTO-I "Hb H H H H H H H 'H'3 H
H
03'H3
H
3N
3N
3N S3HNEH03 S3HN9Ha3 o ~ H P H O ~ - I
03HN*H03 0 3 ~ ~ ODN'H O ~ N ~ H 0 3 ~
"Hb 'H93
'HCON 'HEKIN H EH3 =Ha "H3
"H3 ~
3
~ ~ "H3 ~ 3 'H~OOH C
3
~' ~ 3~3 0 0 ~ 300~~5
~
~
~
'H3
H H
"Hb
'H03
'H93 'H03
'He0
'H'3 EH3 H 'He3 cH5
H H 'H'3 'H93
3 0 0 ~ ~ ~ 3 300H
"H3
'He3
300H H H "H3
EH3
H
039~03
CON
-0
0 3 ~ ~ ~ 3
H
20s
H
H H H H H H H H H H H H H H H H H
H
-\
'Hb 'H93 EH3
0 'ON
'ON
ZON 'ON
H H H
H zHHg3EH3-9-G(z00K)-f'ZH E ~ e 3 G ( G ~H~ ) - ~ ' ~ 3 0 0 ~ ~ 3H
I
Ctl& C*Hs
C6H6
OH CsH6NHCS CBHSNHCS CBH5
CeH5N&
OH
1 H
H
CH,CO
H
H
Br Br H
CH,CO
CH,CO H
H H H H H
H
H
H H H H H H H H H H H
187" 196' 124' 125" 174" 210'
184"
170' 180' 338' 168' 173' 161' 206'
-
H H
H H H H H H H H H 4-ClCeH4 H H H
CHaCO CH$O CH&O CH&O C,H,CO CeH5C0 HaNCO HJCO H,NCO H,NCO CeH5NHC0 CeH,NHCO CeHsN=C
1440 221" 163' 203O 159'
H
H
CH,CO C2H500CC0 H CH&O CH&O CH&O CsH6CO H H H H
159O
CHCOOCaHs CH,CO
It
162' 148"
NC NC H H
-
186' 153' 168'
H H H H H CHSC
H H H H H H
HZNCO CH,HNCO
1542 1542 996 996 325 325
1542
301, 342, 344 301 1542 1542 344 301 301 343,344 1542 343 918 1542 1542 1542
726 726 726 1478 1542 299
8
g.
%
U
?ti.
E.
I¶
1 c
T
0
96
%
:
2
m 3cc
ClHB
CEH,N=N H H
HsC200C CH,COO CH,COO c1
CBHS CH&O CH&O CH&O
-.-___--
R3
RS
R'
TABLE XI1 (&inwd) R'
Re
131' 5oo
-
105"
M.p.
Reference
126 1598 594 39 1
I _ -
El 4
Systematic Tables of Pyrazolones and their Derivatives
,
248
R N a ~ ~ E R R 33 - u R 2 ,-N-R-N=
N
N
I
I R' iV,N'.Bis(5-imino-$.pyrazolines)
TABLE XIII. R'
R'
ILa
R3
K
M.P.
Reference
0
II
H
CEH,
H
-c-
310" (dec.)
301
H
CL3H6
H
II II --c--c
> 310'
301
CeH,
CH3
H
184O
998
cd&
CH,
-
322
CH&O
CeH, CH3
243'
301 973
CEH6
H
0 0
40 0
JjJ0
H C,H,CO
II
-cnone
-
0-
iso-C3H7 iao-C3H, ~o-C~H, iso-C,H, iso-C,H,
H
H
850
66"
b3161"
H
c-
135" 40"
H
H CH3 H
174"
H
It2
H
___--~-___
M.P.
R3
_R4
Section A. Alkyl and Alicyclic Substituents
T A B LE X I V. 3-Pyrazolin-5-ones
"'
250 250 250 250 260
101
101, 103, 859
101
1205 1205 54, 788, 789, 985
54, 788, 860.
Reference
x
32:
> CJ
H
166"
-
CH3
H H
H
H
CH3
H H
CH3
H
CH3
H H
H
280' 270' 169O 196' 217" 227' 245O 239" 233' 266" 180" 231O 240" 130"
165'
H H
CeHs CH3
H
126" 117'
H
H
H
155'
H
H
H
H
M.P.
H
R'
R2
RJ
R'
Section B.Alkyl and Aryl Substituents
TABLE X I V (continued)
_ .-
.$ -
1001
( Tabk ccmtinuld)
679 885 885 370
448
446 1001 885
Ei,
P 4
P
c
!2
460, 858, 993, 5: 9. 1122, l&S, P, 1559 446 e a 108 64, 1205 0 95, 247, 788, 826, 885, 888, 988. 1522, 1624, 1559,1669 972, 1569 1023, 1024 1023. 1024 P, 988, 1524 988 446
Referonce
R'
-_
R=
TABLE XIV, Section B (Con6inued) RJ
______--
H
R'
95, 808, 1023, 1024, 1042, 1071, 1333, 1522,1524 1524 670
256'
1477 115O
9oo 219'
113" lOS0 256" 65" 121" 172"
781, 785, 801, 806, 807, 1173, 1174, 1198,1508 95, 888, 1522 992 95,984 1252 303 95, 984, 1522, 1524 1321 250
113"
207 O 222"
Reference
M.p.
_ _ _ __
t4 P
W
b,.o,201
137' 98'
-
b0.061850
H
H H H H
O
96 ' 169' 161.5' H H CZH,
NO,
I
NHCHO (Hp,C,OOC)2CCH,
-
1430
NHCHO ( H,C,0C)C)2CCH,
I
181'
NO2 (H,COOC),CCHg
I
-
I
NHCOC6H5 H5C200CCHCNz
I
228'
-
86' b2.,178' 115" 186" 147"
NH, HOOCCHCHz
I
H H HOCHzCHz HOOCCHz H,C,OOCCHZ H$IOCCHZ HOOCCHCH,
1477
988 145
806
1477
806 988 1524
638
638
638
638
638
636 1252 1171 638 638 638 638
1
E.
50
E:
T A B L E X I V , Section B (continued)
H
H H H H H
H
H H H H H H
H
H
540 1001 446 978 978 978 1475, 1476 361
150' 126' 188' 98" 132' 248' 239'
296
645 296 296
-
113' 89 126'
-
-
-
167" 119" 199" 221O 261 251O 266'
H H H H H H
H
-
541 978 978 978 978 978 978 674, 1290 674 645
146 1149 978 978 978 978
902
chloroplatiate)
165" 148' 210' 270' (dec.,
56 '
81'
-
H
H H H H H H
E3
CH3 BrCH2
H
CHP
-
129" 175' 130" 150'
H H H
H
147' (racemic)
97.5" 143'
H
H
H H H
95, 362, 809. 814, 1056, 1252
806 899 647,789 818
141
546 679 296
-
td
% f: 0
Systematic Tables of Pyrazolones and their Derivatives
2 3
x"
8--0x" 4
"
II
sR z
0 =o ? i
X
8
3T
0
x"
V
g
G
d
253
264
Appendix
Systematic Tables of Pyrazolones and their Derivatives
*
m fl
I
255
CH3
CH,
C6H5
R'
CEH,
-
R'
__
TABLE XIV, Section C (continued)
H
H
H
R3 .I
-~
_____
i'
L'-CH2
R' ~
-__ ___
149"
110
99" 152" 2209 114"
110
110, 1483 110 110
2.50 1321 21,563 110, 1483
87 128.5' 204" 140"
897
___-
378
-
Reference
118'
2580
N.P. -
7,
K i h
C8H5
C6H5
c8H5
CeHs
CH,
,c=o
\
C6H5
L-NH
o=c/
H
N-C=CH
378 89"
224' (dec.)
263'
696
696
195" (dec., HBr) 799
700
192'
110
110 21 107, 316
152"
1910
2-CH3-4-HO-5-iso-C3H,C,HnCH,
C8H,COCH=CH CeHsCHz
CsHlCHa 199"
165'
20
20
270"
139" 171"
\-coo-
a-' 7CH3CCH3 7:L02H)
21 21 20
155'
218"
2-HzN-5-CH3CeH3CHS 2-CH,CONH-5-CH3C6H&HS
3-CH30-4-
(
2,4-(HO)&,H3CHZ 3,4-(HO)&,H&Hz 3-CH,O.4-HOCsH&Ha 3-CH30-4-CaH&OOC6H&H2 v1
-.c -.3 C P
9'
5
ec
a
1
Q
(LI
s z3
3
cd
%
(LI
B
4 Q
c)
.l:?
Y, %
258
Appendix
m 0, m
2 a2
0
8 hl
0 (0 W
c3
d
w"
U
G
U
Syskmatic Tables of Pyrazolones and their Derivatives
w"
V
@V
8
259
260
Appendix
rl
*
W
::
#T
V
Systematic Tables of Pyrazolones and their Derivatives
3
-f W
261
Appendix
262
m m t-
t-
2
3
X
Systematic Tables of Pyrazolones and their Derivatives
3
u3
5:
w
dr
m
0
5:
X
x"
V
x"
V
a
263
X
R'
94
231"
CH3
NHh'HCOCH3
94
152"
CH,
s
94
130"
CH3
Reference
94
I
COOH
h1.D.
236'
R'
903
R3
- _ - .-__ ___
284"
R'
T A B L E XIV, Section D (continued) Q,
N I&
Systematic Tables of Pyrazolones and their Derivatives
< V
265
CH3
CH3
N
N
f J ) -
H
194O
202O, 280°
220"
799
799, llao
991
991
Systematic Tables of Pyrazolones and their Derivatives
c 4, a 00
El -Y 0
267
It=
(3%
-___._
CH3
R3
C H . ! ,
HOOC-
114
1
N
,!LH3
4OOH
-
R'
R3
HOCH, HOCH, HOCH, CH3 HOCH, HOCH2
R=
CH3 CHs CH3 CH3 CHa CHB
__
17
CH3
CH,
H
-
528 532
158 170 HOCH,
-
698 538 532 H
145 223
Hcference
378
452
Reference
H
__
144"
2560
M.P.
M.p.
-
li'
Section E.a-Hydroxy-,a-Acyloxy-,and a-Alkylthioalkyl,Alkyl and Aryl Substituents
TABLE XIV (continued)
C6HB
Rl
T A B L E XIV, Section D ( d i n a e d )
N
g:x
T
ab
%
CBH6
I-CH&&
CH,
CEH6
HOCHS HOCH, HOCHa HOCHa CH3
HOCHS HOCH, HOCH,
190 173 156" 191" 140'
AH C13CCH AH C13CCH
AH C13CCH OH Cl,CCH
OH C13CCH
188"
OH Br3CCH
OH
I
OH NCCH
I
188"
I
OH CI,CCH
I
I
I
244 183 109 197
CH3 CzHs C9H6 CoH, C13CCH
-
186
-
107
889,902
902
889
901
532 532 532 532 107, 196, 889. 895
532 532 532
-.
U
z.
cc 3-
5a
P
0
2s.
u)
x8
R'
-___--
CH3
Ha
T A B L E X I V , Section E (continued)
CH3
CH3
CH3
H3
-___
I
AH
CBH,CH
iso-C,H,NH
bH
CH,CHCH
I
AH CaHeNH
I
CH3CHCH
NHCH3
bH
CH,CHCH( HCl)
1
OH h'H2
I
CH,CHCH( HCI)
R' -
173'
165'
162'
123"
103" (threo) 220" (erythro)
M.p.
977
112
112
112
112, 113
113
Reforence
0
-.I
le
H
i)H
970 970 895
895
154O
141
1194
800
-
-
164'
227'
240'
152'
P
0
3' F
s
U
m
6r
R=
TABLE XIV, Section E (eonfinued) Ra
-~
135"
im-C+H,COOCH
C,H,NHCOOCHa CZHSSCH, CdHVSCHB CIHVSCHP CBH,CH,SCH, CBH~SCH:,
CBr,
1
C6HsCOOCH
Cur3
I
CH,COOCH
&I3
3 HO,SC,H,COOCH
1127
53 O 1000
102"
1127 1127
1127 1127 640
402 97"
895
895
891i
895
a05
Reference
271.5'
170"
13ao
230'
160'
4-NO&H~COOCH
bl3
214'
C6HGCOOCH
Ll,
(333
136'
I
__
M.p.
C,H,COOCH
H'
_....- -_
m
-1
ts
w
M 0
C6H6
C6H0
P HI
i:
RZ
I
I
.._
CH, CH3
CHaCHNHCHB
CH3
RJ -
-
I
CaHs C6H,NHCH
I
C6H6NHCHa 4-CH3C6HSNHCHa CH3NHCH
H H HJCH, CHaNHCHZ(HNO3) CaH5KHCHa
R4
__--
945 1318 68"
(Table conlinued)
945 945
93O 66' 132'
1094
110,111,1483 110 112 185O
17l0,143' 140" 105"
107
88"
1319
697 697 901 107 107
Reference
70' 83" 168'
b1.p.
$ Section F. a-Amino-, a-Imino-, a-Oximino-,a-Amido- and a-Hydrazinoalkyl, Alkyl a.nd Aryl Substituents
0
-w a
ts
k2
Ef.
8.
U
r 2.
ct
Ea
8
I
E
s
cd
: F
i.
u1
5
274
Appendix
4
Y
g g
an
6
n
6
6
CH3
CH3
CH3 CH3
CH,
CH3
CHa
192' 163' 215'
Z-CHJ&H,N=CH 4-C2HSOC6H*N=CH 2-HZNCeH4NdH 4-OHCCSHJVdH
232
152"
148'
CBHsN----CH
K=CH
0
-
-
S03Xa CzHsN=CH CH,N=CH
I
120" (dec.)
C6HsPiHCH
S03Na
I
150' (dec.)
S03Na 4-CZH,OCGH*NHCH
202, 891
1700
107, 202, 891, 897 891 891 1190 891
107,891
107 107
203, 891
202, 891
202, 891, 894
110, 1483
128"
-
I
107
165'
I S0,Na I-H,NO&X,H,NHCH
107
167"
$, d 8
5 ?.
ti
a
3
a
B
3
0
E
21
%
c3
3 H
13
u1
2
R'
____
R=
TABLE XIV, Section F (catinued) R3
211O
215"
hH2CI HaNXS
I
C,H5NHN=CH 4-hTOaCEH4NHN=CH 2,4-(XOz)~C~H,XHNdH CBHbNHN=C
C6H5N€IN=CH
C6H6
I
_
_
_
_
~
Reference
_
977
902, 1186 201, 1183 698 799
202 891 891 1190 1186 202. 891, 902 1183 196, 201, 889, 1092,1181 1190 977
_
225", 236", 255" 196,201, 889. 1181, 1182 230" 1190 2720 201,1181 260' 201 260" 977
210" 239O 227"
C6Hs HON=CH HON=CH H Ha"=€!
I
2210 197"
HON=CH HON=C
I
190" 97O 135' 161" 140a 220"
-
Y.P.
^
4-HaN02SC6HINdH 3-HO-4-HOOCCaH,N=CH l-CloH,h'-l=H 4-C&OC6HdNH=CH 4-'&H60C,H,N=CH CEHsN=CH C&N==CH HON=CH
R*
.
;e
s
t3:
t.3
4 -7
CH3
I
256" 210°, 256' 226", 246" 238' (dec.) 246" 215" 233" 233"
HZXCONHNdH HZNCONHNdH HZNCSNHNdH HaNCSNHN=CH C2H5NHCSNHNSH CBH*NHCSNHTT=CH HZNCSNHNdH H~NCSNHNdH
235"
216' (dec.) 204O, 223", 245'
I
160"
-
260"
900
900
698 201,204, 892, 1181 1186 201,1180 510, 818, 799, 900 1190 900 900
799
1186 1186 799
412
270"
AH3 CH2Cl CeHeNHNdH HZNCONHNSH
I
hHaCl 3-CH30-4-HOCeH&H=NN&
CeHsNHNSH 4-C2HsOCeH*NHN&H C,H,CH=CHCH"---C
696
263"
-1
t3
P
p,
s2.
U
g.
3-
8
EL e
rd
P
e
0
rT.
BP
r/,
3ct
Appendix
278
:-rp:;l =x
y=
N
I
I
R1
R'
T A B L E X V . 4,4'-Bis(3-pyrazolin-5-ones) Linked by a Single Bond H'
S
Y
0
0
25.4"
S
237" 270' 250" 225" 269O 215' 240' 203"
S Se NH 0 0 0 0 0
0
0
It
R3---.-.
Rz-$----l
\
Se HN S HN C6H5,N
/==o
N
I
T A B L E XVI.
=-R3
I
-j
4N
R1
785, 807, 809,991 785,991 986 991 991 991 991 807 1056
N-R2 /
I
It'
4,4'Bis(3-pyrazolin-5-onea)Linked by Carbon or Heteroatoma
R
Xp.
Reference
CH3CH,CH < CH2
180" 192O 155". 178'
902 1042 19, 740, 910, 1192, 1483 107,896 107 107
239" 204O 92"
HOOCCH< H3COOCH< C,H,OOCH< 0
II
CH=CHCCH=CH (CH&CHCH&H< CeH,CH< 4-CH30CeH4CH< CeHSCH < 4-CH30CeH,CH<
CH3
CeHs H H H H
CH3 CEHJ C6H5
4-CHaCeH4 4-CH,CeH,
CH3 CH3 CH, CH3 CH3 CH3
270' 160" 270' 287' 278* 270°
316 409 988 988 988
988
Systematic Tables of Pyrazolones and their Derivativea
279
TABLE X V I (continued) R
____
--
-
It1
R'
-
Rs
C6H5CH< C6H,CH< 2-HOC,H,CH< 2-CH3OC6H4CH< 3-CHzOCeH4CH< 4-(CH3),NC,H,CH< 2-C1C6H+CH< 4-ClC,H,CH< 2-NOZC,H,CH< 3-N0,C6H,CH< 4-N0,C6H4CH< 2-HO,SC6H,CH< 4-HO3SC6H,CH< 3-CH3-4-HOC6H,CH< 3-CH30-4-HOCeH3CH< 3,4-(CH30)&H&H< l-C,,H,CH< C6H5COH 3-CH,OC,H,COH 4-(CH3)zNC6H4COH %-CICeH+COH 4-CIC6HdCOH 2-NO&H4COH 3-NOzC6H,COH C-NO&&COH 2-H03SC6H4COH I-HO,SCeH,COH 3,4-(CH30)aC6H3COH
II I
II
-&=CHC-
201O 213' 193' 216" 186" 260" 169" 214' 214" 232' 288" (dec.) 300" (dec.) 119" 146' 200" 254' 172" 111O (picrate) 135" logo (picrate) 137" 130' (picrate) 148" (picrate) 180"
807,809,1133 992 21 568 569 1133 568 566 566, 568 566 566 568 568 21 566 569 566 569 569
-
118O (picrate) 235" (picrate) 246"
0
-CCHdHCH3 0
Reference
-
1-CloH7COH -0
M.P.
569 568 566 568 569 566, 569 568 568 569 566, 569 740
H
256"
902
H
266'
901
CH3
269O(dec.)
481
280
Appendix
T A B L E XVT
(continued)
R1
R
Ra
113
icp.
Rctcrcnco
CH,
221"
481
CH3
2-56'
740, 741
CH,
243"
744
CH3 CH, CH3 CH3 CH3
256' 199"
8, 742, 848 848 848 848 545, 850 850 850 696 945
H
c3H6
4OOCH&O-
ssss4-Hg-4-
4-Hg-4-
-
Se 4- Se<
CH3
Cl&e < CONHNdH CHaNCH2
CH3
CH, CH3
230" 240" 215' 225" 232' 111"
CH, CHaNCHa
CH3
143"
945
CH,
163"
945
CH,
174'
945
CH3
217'
945
CH3
93"
945
CH3
163'
1483
S e -
I
I
CaH5 CHaNCHa
I
C3H.5
(4H2COCeH6
(Table conlinued)
281
Systematic Tables of Pyrazolones and their Derivatives T A B L E X V I (continued) K
-N
I
H'
R'
I<"
3l.p.
Reference
C6H5
CH3
CH3
262"
927
CH,
248'
945
CH3 CH3 CH3 CH,
275' 175O
745 1001
160" 165O
456
CH3
154'
1284
CH3
224'
891
CH3
312'
589
C6H,
1
CH3
984
X-
I,' 0
T A B L E X V I I . Miscellaneous Bis(3-pyrazolin-5-ones) and Bia(5-imino-3-pyrazolincs) Structure
M.P.
Reference
258"
108, 696
(hydrate)
I C6H5
1 o*
I C6H5
(Table milinued)
Appendix
282 TABLE XVII (continued) Structure
Reference
M.p. -
~
-
______
177"
116
300"
116
I
TABLE X V I T I .
H
x=s
R'
R=
3-Pyrazolin-5-thioneeand -5-selcnones ._
\
I
R'
/
h'
c6H6
R3
H
R'
136' 178' 133" 223" 172' 199" 255' 271' 265O 97O 238' 190' 204O 242"
789, 986
147O 182'
988 992 988 988 978 978 978 978 978 1001 1001 978 978 1001
785,844, 845
1053
Reierence
169"
11.p.
1
$
5 1'
U
E, 1
r
?+
5a,
E
e
Y
cd
P
e
0
2z.
H
-
R'
-.
-
-
5-Imino-3-pyrazolincs _- - - .- __
C5H5
Rl
TABLE X I X .
H
R3
H
it4
___ -
RaN
I
R1
N
H
Et 5
-.-__
930
M.P.
__
398
Iteferencc
H H
2-CH3CeH4 C-CH&H, 3-HZNCeHd 3-CHaCOHNCeH4
C6H5
H
H H
C6H5CH2
H
985 975, 1352 1352 1352
H H CH:, C2HS
63", 211" 131O
H H H H
212O
45O
69' 106"
79O
Oil
-
155'
827, 975 1002 1002 1002 1002
975
398, 1025
1025
1653
176"
112O 146O 116' 128"
398 398 398 398 398 826 826 1002 1002 1002
234O
100O 124" 108'
398
H
H
124' bla 231" 135'
H
H H H H H H H c6H5 CeH, c6H5 H H
H
R'
TABLE
XIX
R=
(&inued) R3
1002
-
H
H H H H H H H H H H H H H H H H
128O
Oil
161O 7oo 176' 211O
-
81° 114' 129O 150' 155O 100O
1002 1002 1002 1002 1002 996 996 1002 1002 976 976 1352 1352 983 983
1002
169'
H H H H
780 205O
1002 1002 1002 1002 1002 1002
172" 112O 143' 120° 196' 142'
H
H
Reference
R5
n1.p.
R'
rn
E
3
*
+a
oa
OD
66'21 WB 928 928 116
L16 L16
oE8 0202
OPIZ OPZZ
08LI .,69I 0991. 0011 0161
0881 ow1 OPZI -
966 966 966 916 916 $16
OZZI 0281
08.4
-
00.41:
0811
.BE
06LI 0981 c6ZI
OLLI
0901
o€OZ
0611 096
-
-
&PI
9.6 ZBSI 2911 9t6 C16
zoo1 zoo1 966 zoo1 966 966 966 ZOO1 966 PL6 9L6 ZP&I €86
03'H3 03'H3 SHe3 'Hg3
N'H%
/I
H H O~NH'H'~ S~NH~H% 'H'DHNN
H
CH3 EH3 "3 EH3 %H3 EH3 CH3 EH3
03'HD 03'HD CH3 'H'3
QHe3 gHS "H3
t H93 1 :H3-Z 'H03 'He3
'He3 H 'Hg3 H
003"H3 EH3 "3
QHe3
EHe3
"3
EH3 "H3 "H3
CH3 EH3
0h3
"H3 "H3 CH3 CH3 "H3 EH3
0h3 5hz3
'HgDEH3-Z
+He 3n8 3 - Z
*H83.'WP 'H'313-P t Q E H 3 H3-f i 0 8 H 3 H3-P %lg3CH3-P +He3eH3-Z 'H'3'HD-Z
LHo'3-Z
QHe3 gH'3 CHe3 LH013-Z
kHslr3-P
'He:, 'Hg3 'H'3 'H'3
eH3 EH3 CH3 EH3 EH3 OH3 CH3 "3 EH3 "H3 'H3 "3 CH3 EH3 "3 EH3 =H3 "3 EH3 EH3 EH3 EH3 EH3 EH3 CH3 EH3
CH3
"h13
EH3
003'HD
SH'3 3SHe3 SHB3 03~~93 H 0 3 9 ~ 9 3 1 'H~~~oo~H~-P .'a H N=N~H"~ N=N'Hg3 H e ~ ~ 9 ~ s 3 Z~3s~e3 0DSHe3 'H~'H% "3 zH3'He3 H e~3s~e3 CH3 EHH3 H CH3 L 01 H 3-2 H QHe3 H 'He3 H 'H93 H %SPHQ3 H 'He3 H H H H t ~ ~ 9 ~ e 3 0 3 ~ ~ ~ 3 H H H H H H H "OS'H'3 H H
'Hzv
TABLE X X , 2-Pyrazolin-5-onea. Hydroxp and Mercapto Derivatives
lW", 225" 143" 185' 39O 126" 143", 155O 106", 113" 117". 130° 116' 115' 95 145' lloo
OH OH OH OH OH OH OH OH OH
OH OH OH OH OH OH
OH
OH
OH
205" 96' 128' 117" 103' 101" 140'
OH OH
''
262 1526 1526 1526 's w 1526 T3 1.526 1.526 Q 99,372, 1491 1526 1526 1525, 1526 1527 1525, 1526 1525, 1526, 1828 1525, 1526, 1528 1525, 1526 1525 1525, 1526 1525, 1526 1525
QI3-
1234 320 998
159.5'
son 115'
110"
97
( Table W i n w e d )
317 315 200
783
162'
-
1143 185'
1143 59"
1143
1143
152'
59"
1143
200"
1143
598
41, 317 1143
598, 1143
157' 116.5'
H
994
151" 197'
70 a 94
C6H5
C6HS
a, cg
Lu
NH,
4-CHaC,H,S 2-NH2CeH,S 4-NHzCeH4S 4-ClCeH4S 4*BrCeH,S 2,4-C&H3S 2-NO&eH,S 4-NOaCe&S OH OH
--\
<,--L3-
I
H H H OH CH,O
H
1810
690
690
192'
28 28 28 28 28 28 28 27
1474
1243 1243 1243 1243 1243
185O
217' 205" 221" 225O 207' 238'
212O H H H
226' (dec.)
165O
-
82O
2o0°
H
H
CaH5O Na0,S
OH OH OCaH5
H H OH
OH C8H&O0 OH
f
%1
291
Systematic Tables of Pyrazolones and their Derivatives R2-N
I
R'
TABLE XXI. 3-Pyrazolin-5,onea. Alkoxy, Aryloxy, Acyloxy, and Alkylthio SubR'
-
M.P.
_____
_
Relerence
~
_
H
92"
41
H
188'
200
H
314"
1048
H
337O
1048
75 60"
820 820 820 744 744 744 744
139'
176" 174O 191"
250' 171" 205'
744
744
195
744
267' (dec.) 240' 246O
744
150"
744
142'
744
744 744
Xppondix
292
T A B L E X X I (continued)
__ ~. HI
H2
CH, CH3 C6H5 C6H5
CH3
C6H5 C6H5
H3
R4
11.p.
Reference
194" 143' 135" 201
783 783 887 200 1127
133"
1127
-
1243 1243
Systemut,ic Tables of Pyrazolones and their Derivatives
.f
Q E l: 6
I
293
R'
-
H H H
CH3
R"
TABLE X X I I (continued)
1
C6HBCONH CeH&H&ONH H 44C*H6)2NCeH5N= 2-CH,-4-(CZH5)aNCEH3N;= NH2 HOOCCH2NHCaHSOOCNH CaHSCONH Xa CBHaNH 4-(CH&NCeH,N= 4-(CaHsN)CeHdN=
H H H H H H
C,H,ON= CHSCOON= CBHSCOON=
I
COOCZHS
CH3
102O
168', 187'
198"
-
183'
-
-
-
192' 209"
153' 82" 142" 198' 173' 111°
224"
134O
152' 165"
519 244 809, 996 525 526 52 1144 1107 519, 1242 519
,595
1560 1560 1660 319 1102
1083 1560 1560 519 244 1537
> 245"
-
I QAg 2-HOCeH&H= ;"JHB C,H,CH=X 44C~HS)~NCEH,N= 2-CH3-4-(CsH&,NCeHJ= COHONHXSHCHN-
333
-
(CEH,NH)2;?I=
-~
Reference
ALP.
H4
H H H
H
H
H
R3
-
c. 5'
s
b 5
rp
w
N
Systematic Tables of Pyrazolones and their Derivatives
X XX
295
Appendix
296
2 El
% w
0 cd., l
0
c4 d
-
c
ci
a,
a, W
0
U3 2
4 V
4 u
H H H
H
H
4-(CaH&KCeH41C== O-HOCeH*CH=N 4-CHsOC,HdCH=N 4-N02C6H,CH=N
CH3 NH,
Br
CCHCONH
/ I
\
240
52 52 536
225" (dec.)
183"
992 519 992 992 992
> 175' (HCl salt) 96" 230' (dec.) 220" (dec.) 250" (dec.)
-
536
240
186' (.. c.)
-
240
220" (dec.)
G'
4-CH3CeH4
R'
Ra
TABLE S X I I (eatinued)
-.
R=
-
R'
144' 1890 148" 169' iiao
-
246' (dec.)
b1.p.
494 494,519 244 244 244 519
240
Hcference
t3
m
0,
Sysbmatic Tables of Pyrazolones and their Derivatives
3
E)
z
x
299
300
Appendix
% El
3
3
C
0
8A
d
0
*
0 CI
0
t 0) -
E3
i?
N
d
V
A
c o R
0
4
A
Systematic Tables of Pyrazolones and their Derivatives
A
d
a,
d
a,
30 1
Appendix
302
3
rn
4
V
Systematic Tables of Pyrazolones and their Derivatives
0
c1
Ig2
X
X
td*
m
B
303
314
-
> 250"
866
152"
238"
247"
-
865 865 263, 264 283, 264
582 582 582 963
-
27TQ
-
190°
234" 267' (dec.) > 280" 268" > 250' > 250" 223' (dec.) 235"
Reference
263,264 262,263, 264 263,264 262,264 263, 264 314 314 314 260 262 260 1467 263 223'
x.p.
H
Ar
1251
R*
H
H H H H H H H H H H H H H H H H H H H H H H
R'
__.____I
T A B L E X X I I I , Section A (continued)
Z'
E.
B
b Lcr
4 0
W
I
HOOCCH~CH, C2HsOOCCH2CH2 ~EO-C~H~OOCCH&H~ CIHeOOCCH2CH2 CiHBOOCCH2CHz iso-C4HsOOCCHzCH2 iso-C7Hl500CCH2CH2 CH,CHOOCCH&Hz
(Table continued)
1118 1118 1118
206 208 228, 1681 206 253 253 253 253 253 253 253, 1463 283, 1469 253 253,1463 206 206 206 1118 1118 1118 1118 1118 1118 1118 1118 1118 1118
1560
UI
w
C.
f
Ea
Appendix
306
2 ,-I 4
b) l-
31"
38
$
x"
8 0
6'-9. 0
Systematic Tables of Pyrazolones and their Derivatives
gg g ggg
407
__-
_.
-
308" (dec.)
H
-
-
-
-
__
-
-
__
-
-
-
-
-
___ -
_.
-
H H
H H H H H
H
H
H
H
H
H H H
H H H H
H H
H H H H
H
-
-
-
H
_________
M.R.
-
_______
dr
H
H H
R=
_ I _
782 782 782 782 782 782 782 782 782 782 782 782 782 782 782 782 782 782 782 782 782 782 782 782 782 782 782 782 782 782 285
Reference
0
00
R'
__
w --
___
-~
TABLE X X I I I , Section B (confinued)
Systematic Tables of Pymzolones and their Derivatives
c61 t.l
309
T A B L E X X I I I , Section B (continued)
1591
1591
255O
1691 1591 1591 1591 1591
280
-
243"
192" 154'
2470
150"
-
-
240"
280
327 864 1677
-
260"
4-CH3CCgHa 2-(C,H,SO,NHOC)CeH4 4-(4-PSO&H,SO2)CsH, 3-Ka03SC6H4 4-Na03SC6H, 4-CIO,SC6H, 4-H&02SC6H4 4-C€I,NHO2SC,H, 4-(C2H5)2NO,SCeH4 4-C6H,NHO2SC6H4
II
327
278.327 278, 327 278, 327 278, 327 263, 278, 732 327 327
148'
187"
136"
198"
183O
209'
140' 151'
4-CHSCCeH4 NKHCOKH2
/I
NOH NNHU,H,
/I
4-C1C6H4 4-BrC6H, 2-N0,C6H* 3-NOzCgHd 4-KOZC6H4 4-CH3COC6H4 4-CHSCCeH4
W w
(Table wntinued)
649 374 211 228, 1681 278 280 278 180 278 278 263 263 1462 203 625 625 626 180 142
648
864 327 327 280 1462 1461 211, 1446, 1461 211 219 650 225 650
c
R'
--
__
TABLE X X I I I , Section B (continued) Iil
-
__I
._
M.P.
T',]l/k\,
1_ -i
2-HO-4-HO&l-C1,H, 2-C~Ii~C00-4-HO~S-6-NOa-1-C,,H,
2-HO-4-HO3S-6-CH3O-1-Cl0HS
3,4-(CH3)2-2-H03SC6Hz 3-NO2-4-CH3-5-HO3SCBHZ 2-HO-4-HS-5-C1C6Hz 2-HO-4-N02-5-CH3OJXsH, 2-KO-3-H03S-S-ClCeH, 2-H0-3-H2NO$-S-N02CBH2 2,5-(CZH,O)2-4-CeH&ONHCeHz 2-CeH,C00-3-HO&5-NO,C,H, 2-CeH&O0-3-H0&5-ClCeHz 2-CBH,CO0-3-HOOC-4-H03SCsH, 2-(~ - N O & ~ H ~ C O O ) - ~ - H O ~ S - ~ - N O Z C ~ H ~ 2-HO-3-H0&5-[2,2,4-(CH3)3C5BalCBH, 2-HO-3,6-C12-5-H03SCBH 2-HO-3,5-ClZ-4-HSC,H 1*C10H7 2-CioH7 2-h'OZ- 1-C,oH, 4-XOz-l-C1oHe 1-NaO3S-2-C,,-,H, 2-C3H,C00.4-HO,S-l-C,oHs 2-CeHsCO0.4-H038C1oHs
Ir
- .-
327
214 885 442 442 442 442 1386 276 879 263,278, 327 263,278, 327 327 327 280 442 442 189, 1616 441, 1618 442
1444
523 123 879 1445
Referonce
H
32
b W
ha
i
t3
Systematic Tables of Pyrazolones and their Derivatives
ED
0, m
c4 0.1 P-
I
g
11*
313
R' RZ
__-
TABLE X X I I I , Section B ( d i n u e d )
Ar Reference
1493
281
281
281
281
M.p.
-
160"
206'
215'
248'
x
3E
ab
lb
Y
w
1535 1576 403 397 397 397 627 1118 1118 1398 1398 1398 397 1462 1462 1462 987 625 625 02.5 180 1458, 1402 1383 125 403, 576 79 878 878 877, 878 878 878 209 878
R1
_-
342-HO-l-CIoHeCONH)Ce& 4-(2-HO-l-C~oH&ONH)C6H+ 3-!2-HO-l-C1~CON)CeH, 4-(2-HO.l-CloH&ONH)CeH, 3-(2-HO- 1-CioH&ONH)CBH, C-CH,OC& 4-CH3OCeH, 4-CzH,OCeH4 4-CzH60CeH4 2-CICeH, 2-CICeH4 2-CICeH, 2-CICeH4 2-CICeH4 2-ClCEH4 2-CICeHa 2-CICeH4 3-CICeH, 3-CICeH4 3-CICeH4 3-ClCeHd 3-ClC6Ha 3-ClCBH4 3-C1C6H, 3-CICeH4 3-ClCgH4
3-(2-HO-l-CloHeCONH)C6H,
4-NHgCeH4 ~-C~H$~OZNHC~H~ 4-(4-HOOCCeHQSO,NH)CpHI 34~ - H O - I - C ~ O H & O N H ) C ~ H ~
I _ _
__ .
-
2-(5-CH3-2-iso-C3H,CeH3SOzNHSOz)CBH4
2-(4-CICeH&02NHSO~)-5-ClC~H~
180 180
180
397 217
442
1456
1398
877 877 1456 1456 1456 1456 296 1034 1398 1398
877
226 465 160 857 877 877 877
_ _ _ _ ~
Reference .
2-(5,6,7,8-H4-1-CIoH#O&HSO&pH,
ALP.
2-(l-CloH7S02NHSOZ)C~H4 2-(2-CloH,SOzNHSOa)CBH, 2-(~-CH~-~-~BO-C~H,C~H~SOZNHSO~)C~H,
.
180 180 180 180 180
4-HO,SOCH&H&OzCBH, 2-HO-6-HsC2SOzCeH3 2-C,H~C00-4-HO,S-l-C~oC~ 2-CIC6HI 2-Hz,C,oOOCCeH, 2-(3,4-Cl,CeH,S0,NHSOz)Ce~ 2 42,4,5-CI~CeH2SOJiESO2)CBH(
4-Na00CCHzCHzCOOCHzCHzSOzC~H4 4-Na00CH=CHC00CH2CHzSOzCeH,
-
2-HOOC-4-HO3SC6H3 4-HO3S-2-CloHe 2,3,5-C13-6-HOOCC,H 2-CH30-5-CICBH, 2-CH30-4-CICaH3 2-CH3.4-C1C6H, 2-CH3-4-CIC6H3 2-CF3-4-C1CeH3 3-ClCBH4 l-CioH, 2-HO-5-CICeH3 2-HO-4-HzNOzSC6H3 ~-HO-~-H~NOZSC~H~ 2-HO-6-HZNO&!,H3 2-CICeH4 4-HOOCCH~CHzCOOCH&HzSO~CeH~
Ar
% 2.
* z
'Q
2 CQ
.I
$
la
* .-I
2
(pmU?lUaJYW,z)
19PI 'WI I IZ 11z og9 9W.I "IZ 802 962 0%I 08I OBI
5
08I 0%I
-3
9
a
08 I
08I 08I OBI 08 I 08 I
081 08 I 081
rn a,
-8 ! pc
ru 0
m
08I
0
3 08I 081
8 081
0
di
4
.I
A
B
c3
m
08I 081 081 08I 08 I OBI 08 r 08 I 08I
'H3 "H3 'H3 EH3 'H3 "H3 EH3
"H3 "H3 "H3 'H3 CH3 "3
"3 'H3 CH3 CH3 CH3 =H3 "H3 "H3 "H3
EH3 "H3 "3
"HD
CH3
"3 eH3 'H3 "H3 EH3 "H3 "H3
TABLE X X I I I , Section B ( d i n z c e d )
-.-
2,4.(h'On)CeH3 2,4-(KOa)CeH, 2-HO-5-C1CeH, 2-HO-5-H&"ZSC& CeHs 2-ClCSH4 4-NOzCeH, 2,5-CI&eHa 2-HO-5-ClCBHa 2-HO-PH$JO&&H3 2-Cl-5-(3,4-CI~C~H~SO,NHSO~)C,H3 CsHs
2-(5,6,7,8-H+-l-CioH@O~NIISOa)Ce& 2-(8,G,7,8-Hl-2-C1,H,SOaNHSO,IC,H,
2-HO-4-CH3HKOaCeH3 2-HO-5-CH3OaSCeH3 4-BTCeH4 2 4 2-CH3-5-iso-C3H,CeH3SOzNHSOz)C~H4 2-(5-CH,-2-iao.C3H,CeH3S0,h'HS02)CeH4 2-(l-C,oH$3OzNHSOn)CsH, 2-(2-C,oH,SOaNHSO&&HI
2-HO-5-C2H50&&H3 2-HO-5-ClCHgO&&€I3 2-HOOC-5-ClCHz02SCeH3 2-HO-4-NOa-5-CH3SO&pH, 2-HO-3-Pu'Oa-5-ClCHaOoSC,K, 4-ClCeH, 2-HO-5-CH3HNO&Y&H3
2-HO-3-CH3CONH-5-CH3O$CeHa
2-H0*4-(C,H&NOpSCeH3
-____-______ x p .
1004
1466 1456 180
591
125 125 1456 1453, 1456 690, 732 268 732
180
180
180 180 180
180
446
254
225, 1460, 1681 228
296
211 211 219 223 223 1445 223
Reference
x
3E
* 21
z
W
(Tabla continued)
1617 1444
1680 1444 1617
1680
1616 180 195,1617 195 207
189
1460 203 189
864 864 864
1293 1619
661
651 651 651 648 651 651
661
356 1461
980
980
W
R'
-RZ
T A B L E X X I I I , Section B (continued) Ar
___________.____
31.p.
____-
279, 913. 914 279 279 279 279 279 1062 324 324 324 324 324, 356
1062
217, 935 356 173 217 1620 475 1620 716 623 1392 1421 442 1059 1616 1060 1060
.
Refcrence
2 FL z.
b
.a
0
to
w
CeH, Z-HO~S-4,.5-(CH3)&6H3 2-HOOC-4-C,H&ONHC6H3
2-(5,6,7,8-H4-1-CloH~SO~NHSO2)C6H~ 2-(5,6,7,8-H*-2-CloH&lO,NHSO1)CgH,
2-(l-C1oH$3OgNHSOz)CeH4 2-(2-CloH,SOzNHSO,)CeH4
2-CH3-5-(CeH,SO2NHSOs)C,H3
2-HO-3-NO2-5-HO3SC6HZ Z-HO-3-HO3S-5-CH3CeHz 3-(4-CH3CeH4SOzNHSOZ)CsH, 3-[X,Y-(CH3)zCeH3SOaNHSOz]CeHI 3-(4-CH3CeH,SO2NHSO2)-4-CH,CBH3 2-CH3-5-(4-CH3CeH4SO&HSOz)CBH, 2-C1-544-CH3CeH4SOzNHS02)CeH3
2-HOOC-4-(2-HOC2H4NHOzS)CeH3
Z-HOOC-4-H,NO2SCeH3
2-(5-CH3-2-iso-C3H,CeH3S02NHS02)CeH3
Z-HOOCCeH, 2-F,C-4-ClC,H, 2-HO-5-CH3NH02SCeH3 2-HO3S-4-ClCeH3 2-CICeH4 CeHs 2,4-(CH3)zCeH3 2-Cl-B-(C~H,SOZNHSO~)C,H~ 2-HO-5-HO3SCeHg 2-(2-CH3-5-i~o-C3H,CeH3S0,NHSOa)CeH4
180 180 180 180 651 523 176
180 180 180
180
180 180
80
80
180 208 208
80 180
160 651 1460 651 651 296 1438 180
1629
8
3. F
U
Ei'
0
r
c+
6a
m
2
3 0
1
+d
%
g
8 c5. 2
5 !
m v
R=
T A B L E X X I I I , Section B (eontind)
651 913 40 173 173 173 1486 1486 1382 1382 1382 1382 1382 180
2.H03SCeH4 4-H03SCeH, 4-HO3SCsHI 3-C17H35CONHSOJ&H4 3-C15H31CONHSOzCeH4
3-CF3C6H. 3-CF&H* 2-HOOCCOH, 2-HOOC-4(or 5)-H03SCeH3 2(0r 6)-HO-3-H03S-5-NOaC6H2 2-HOOCC,H, %HO-P(or5)-N02C,H3 2-C1-5-(4-ClC6H4SO&HSOa)CeH3
3-C17H36CONHS02-4-CH30C6H3
652 1331
3-CH,=CHSOaCeHI 4-(CaHj)&CeH,
1486 217 176 176 173 1486 1620 173 263 1620 1488
180
1361
Itelerence
a 2.
P3
* a
M
E3
w
Systematic Tables of Pyrazolones and their Derivatives
.t r( c1
I
d
L3
2
I
32 3
-_____
Fl1
0
H'
~-
TABLE X X I I I , Section B (continued) Ar
-_____
2-CH3C6H4 3-CH&H, 4-CH3CeHt Z-CHaOCeH, 4-CH30C,H, 2-C,HsOC,H,
0
.____
__
-
179' 193", 242" 209" 187" 206"
183', 226"
173'
413
237"
278, 1552 278 278, 1552 278 278 278
1673
129, 278, 372, 818, 1003, 1514, 1652,
413
1251
Reference
-
M.P.
x
N It-
w
N
\ /--
ii-7
203
176"
-
238", 196' 175'. 225"
-
206O 244"
-
2M" 220'
-
-
281
280 280 278 278 280 278 278 280 180 278, 1662 278. 1662 280
269
177' 193" 216" 231O 204O 203" 2450 195'
-
278 259 269 278 278 278 278 278 278 278 259
177" 208O
R1
_-
R'
- .
TABLE X X I I I , Section B (continued) Ar
_____ -
281
281
281
1145
212"
271'
265'
141O 189" 205 a 285' 139', 149" 267" 137' 236" 177' 213'
670 670 670, 1581 1581 1581 1581 129, 1581 1581
670
Reference
31.p.
___
a
f3
W
201' 227' 231O 223" 103" 260'
200"
165" 195" 187' 190" 193" 164" 198' 173"
-
I
-
-
-
-
194"
2250
179" 290" 200" 239"
-
-
-
-
77 278, 1499 278 278 278 278 278 278 278 278 278 278 278 278 278 278
77 77
1580 1580 1580 180 1003 1574 1581 1581 1004 1004 279 279 279 279 279 279
32L
Appendix
3
0.1 4,
0
m
3
I
/'\a
(R
0,
x
x,
4-NaO3SC,H, 4-Na03SC6H, 4-Na03SC6H, 4-Na0,SC6H, 4-Na0,SC,H4 4-Na0,SC6H4 2-C,H30 2-C4H30 2-C4H,O 2-C,H,O 2-C4H30 2-C4H30
2-C,H30
693
180"
lMO
C.H&ON=-
4-(CH3),CCBH*OCHCON=
593
-
279 279 279 279 279 279
281
Ce& 2-NO&,H4 4-NO&eH+ 2-CH3-4-CIC6H.g 2-CH3-5-ClC,H3 2,5-C1aC6H3
-
287"
c!
eB
Ca
.;
B
m
%
HOOC
CBH6 2-CH3CaHS 4-CH,C6H4 3-HZ?r'C,H, 3-ClC,H* 3-CIC,H4 3-CICSH4 4-ClCBH4 4-BSeHa 3-?JO,C,H* 2-H03SC6HI 4-H03SC,H,
4-HO3SCeHS
C6H5
H
H
H
C6HS
CH&O HOOC HOOC HOOC HOOC HOOC HOOC HOOC HOOC HOOC HOOC HOOC HOOC HOOC HOOC HOOC HOOC
TABLE XXIII
C&s C6H5 3-CH3C,H4 2-HOOCCG11, CaH6 4 - BrC,H, 2-CH3C6H, 4-CH3CBHd 4-[3-H038-4-(4-H03SC,H,PI'=.-N)CBH,NHCO]C!eH* 2-HO-3-NO2-5-CeHllC6H~ 2-IIO-3-N02-5-t-C,H,,C,Ha 2-HO-3-NOo-5-CBH,C6Ho 4-CICnHa
1'. 1
323' (dec.)
-
-
-
254' (dec.) 260" (dec.)
-
-
229' (dec.) 233' [dec.) . .
-
227 O 230'
-
182" (dec.) > 250"
1629
768, 770 449, 1545 449 1552 292, 1082 292 293 293 215 873 873 873 29 1 291 276 1079 57 1
0
w w
H H H CH3 C8H5 2-CH,CVH,
H H H H H H
4-HzNOaSCsH, 2-CH3-4-H03SCeH3 2,4-ClzCeH, 3,4-ClzCeH3 3,4-CI&eH, 3,6-ClZCeH, 3,6-C1,C,H3 2,4-BraC6H, 2-CH3-4-HO3S-6-ClCsHa 4-Ns03SCeH4 5-HO-7-Na0,S-2-CloH, H H H H H H 4-BrCOH, 2,4-Br1C6H3 H H H
HOOC HOOC HOOC HOOC HOOC HOOC HOOC HOOC HOOC NaOOC NaOOC H3COOC H3COOC HaCOOC H,COOC H,COOC HaCOOC H3COOC H&OOC C2HSOOC CzHsOOC C2H500C C2HsOOC C2HSOOC CzH500C CaH5OOC CpHSOOC C2H,00C C2HsOOC CzHSOOC CzHsOOC CZHSOOC CzH,OOC C,H,OOC 2-CH3C,H,
C6HS
4-H,XOZSC,H* 2-HO3S-4,5-(CHj)&eHz 2,4-C1&H4 2-HO-3-N02-G-CeH,,C6Ha 2-HO-3-NOz-5-L-CsHllC6H~ 2-HO-3-NOp-5-t-CSHllCeHz ~.HO-~-NO~-~-C~H,,CBH~ 2,4-Br2C6H3 3-CF,C6H, 4-Na038CeH4 5-H0-7-Ka0&2-CloH, CeH5 2--UOz-4-CH30C6H3 2-NO2-4-CzHEOC6H3 2-N0,-4-CIC6H3 2-N02-4-CH,COCsH3 2-~0z-.1-C4HgNH02SC,H3 4-Br(!,H4 2,4-Br2C6H3 2-HOOCC,H, CsH, 2-x0&&4 2-N02-4-F3CC6H3 2-NO2-4-CH3OCeH3 2-KO2-4-ClCBH3 2-P102-4-C2HsOOCCeH3 2-N0+4-HOCH&HsNHCOC6H3 2-N02-4-CH30CH&HzNHCOC,H3 2-iYOz-4-CzH6NHSOZC6H3 2-NOZ-4-C,H,NHSO&6H3 2-NO2-4-SCNCeHa 4-CH3OCeH4 209" 243' 244O 225' 254' 230" 213' 233" 255" 241" 256' 186" 246' 228' 205" 154" 226' 251' 230" 125" 152' 145'
-
-
248"
-
continued)
369 369 369 369 369 369 369 1357 594 37,44.1240 293,445
1549 369 369 369 369 369 291 291 1552 1544,1546 369 369
71
1628, 1662 523 291 873 873 873 873 291 1486 768,770,1066
( Tnble
252" (dec.)
-
-
5
c
La
0 m
2.
E
?'
8
U
EG.
c
3
?
6
0
2
'+'d
L?
0
n
c
0
2=. 4
u1
3 g
~-
R'
-
C2HsOOC C,H,OOC CpH600C CzH500C CzHsOOC CpHBOOC CZHSOOC C2H500C C2H500C CZHSOOC CaHsOOC C,H500C CoH5OOC CpHSOOC CZHSOOC CzHsOOC C,H,OOC C,H,OOC C2H500C CzH,OOC CzH500C CzH500C C,HsOOC C2H600C C2Hs00C C2H600C C2H500C C,HSOOC CzH600C C2H500C CzH,OOC
Ra
T A B L E X X I I I , Section C (cmtinued)
-~~
-
170" (dec.)
216' (dec.) 2-C10H7
158' 213" 229'
165'
-
-
190" 160' 260" 246O, 260" 224' (dac.) 132' 228"
-
143' 198" 228' 179'
-
146' 143" 177' 152' 195' 146"
h1.p.
1-C10H7
-
2-HO-3-h'0~-~-t-CsHl1C~Hz
2-HO-3-NOp-5-t-CsH,lC,H1 3,4-( CH3)aCeHa 2-CH,-4-NOzCeH, 2,5-CI,C6H3 2,4-BrzC6H3
2-HO-3-n'0,-5-t-C,H,,CeH2
3.CH&H4 4-CH3CeH4 2-CH40C6H* 2-CzH,OCeH* 2-HzNC6HI 3*H,PU'CeH, 2-CH3-4-ClCeH, 4-HzNCeH, 4-CeHJ=NCpH, 2-CH3-4-ClC6H3 Z-ClCeH, 2-C1-5-(2,4,B-C13CBH,SO*NHSO2)C~H3 4-ClCeHI 3-BrCsH4 I-BJC~H, 4-NO&H, 4-HOOCC6H4 3-C,H,OOCCeH, 4-(2-CioH,OCO)CgH, 4-H03SCeH4 CeH5 2-HO-3-n'Oz-5-t-C5H11C,Ha
Ar _ _ -
-
874 1450 1450 1661 1661 285 291 874 768, 770 768, 770
661
878 444 770 a77 1661 180 291, I661 1661 291 444, 770 768, 770 1661 I661 444
444
445 293,445 1661 1661 444
Referenoe
-
j?'
%
3*
ci,
W
W
l-NaO3S-2-CloH~
4-BIC,H4 CH3 CH&O CsH5CO C6HsCO CeHSCO CEHSCO HZNCO HZNCS
CH, CeH5
2-CHaOCeH4 3-CIC6H5 3-HZK02SCEH4 2-CI-5-HzNO2SC6H, 3-H,NOZS-4-ClCEH3 H 3-H,N0,SC6H, 3-HOCHzCHzNHOgSCeH,
C6t1.5
C8H6
C6H3
2,4.BrzC!,H3 H H
a$-( HO3S)z-2-C,oH,
CZH5OOC C H 00C C,H,OOC H,NOC C4H,NHOC HzNOC H,NOC HZNOC HzNOC HZNOC HZNOC HaNOC HZNOC C4H,HNOC CH3NHOC CH3NHOC HOCH&HzNHOC H,NHNOC ONC CN 180
768, 770 770 291 369 226 1218 1218 1218 1218
-
-
1450 874 874 1464 1450 1450 1450 212' 594 253' 594 152' (dec.), 126, 768 189' 203" 126 120' (exp.) 594 199" 1560 209" 264 171" 264 412" 264 224" 264 355 217" 355
-
-
I
-
200" (dec.) 260' 178" 218'
W
w
w
P
5
b 3.e P
5a
It'
I
N
/1=0
,
4-CH&Ha P-CH&,H, 4-CH3CBH4 4-CHJ&H,
4-CH3CeHI 4-BrC,H4
H H H H
H H
-
CeH5 CeH, CeH, 4 CH3C6H+
CeH5CHaN
CHJ
CH3 CH3
CH, CH3 CH3 CH3
CH3 CH3 CH3 CH3
CH3
CH,
/ \
I CHa I CHl I N
CH3
CH3
I
305" 190°
CH, (CeHB),C=N (CH3)zN
I
233" 235' 217" 302O
232' 303"
245O
248'
216"
-
C,H,CH=N 4-CH,0CoH4CH=N C,H,CH=CHCH=N C,H,C=N
coow
CeIT,CH=lc' 4-CH30CsH,CH=N C,H,CH=CHCH=N CH3C=li
H
(CHJAJ
____I
3-Pyrazolin-5-ones. Imino, Amino, Amido, Azo, Aminoazo, and Hydrazido Substituenta __ - -_ -_ - - H* R3 R' b1.p. - .__
H H H H
C6H5
H
--_____I_
R=
_-
TABLE X X I V .
--
Ra--?i
984 1001
984 984 984
984
984 984 984 984
1052
860
Rcfcrcwe -
--
__
+
w w
4-BrC,HI
H
CH3 CH, CH3
4-BrC6H, 4-BrCeHI 4-BrC,H4 4-BrCeH4 4.BrC6H4
H H H H H
CH3
HO,SCHpY
lOl0 105'
102O
Oil
74' 118'
106"
130,743 130
134,172 133,144,160,172, 371, 463, 526, 527, 560, 561, 554, 603, 661, 691, 781, 915, 938, 941. 1198, 1256, 1356 984 992 992 431
860
74"
-
105
1001 1001 1001 1001 1001
153' (dec.)
199O
274"
249" 303" 340"
ti' 0
CT
P
g-
9
'
k
-7
0
2 F rn
C6H5
R'
H3
1184
157O 151' 206"
155"
198" 173" 177' 213' 230'
151'
173"
821,940,1592 992 430,954 992 992 821 430 992 430, 821 992
I
COOC,H, CeH,CH=N CBH,CH=N 2-HOCeH,CH=N 2-HOCeH*CH=N 4-CH,OCgH,CH=N 3-N OpCeHaCH=N 2,3-(OCH,O)C,H,CK=N 4-NOpC6H,CH=N CeH,CH=CHCH=N CeH6CH=CHCH=N
101
94'
a21
101
Reference
84"
M.P.
CH3C=N
n*
Q,
R'
-.
w
W
TABLE X X I V (continued)
ts 0
CEH5
CH, (HOCH,CH,),N (HOCH&H&H,),N (HOCH2CH,CHzCHz)zN (CH,)ZNCHzCH,N I
460 460 460 111, 1298 111
-
213" (HCI) Oil
-
-
993
1217
167"
227' (dec.)
4
Appendix
338
" 2
d -
l-
I
d
T
9
9
3 P
-$
*
I
I
r(
0
Syatematic Tables of Pyrazolones and their Derivatives
r0
cv
0
0
2
0
n
cv La
d
V
B w
339
Appendix
340
d o 0
M
d
oocn
t-
b b 20,
$
V
Syst!ematicTables of Pyrazolones and their Derivatives
3
3
mQ eO 4 C O
gg
gg
gv gv
t-
2
3
34 1
1017 1017
1018
999 1323
181" 199"
142'
174' 266"
426, 1017
1149 1149 1320 1365 984 1001 426, 1353 992 972 885 984 1060 1060 1001 1004 670 670 174"
253' 210" 189" 205"
-
99 O 236" 215' -
-
-
120"
-
111"
82' 139"
Systematic Tables of Pyrazolones and their Derivatives
0" d
I
t6" 0
0 0 1 1 0 0
w vw wv wv wo v
v6'
343
31.p.
68" 83"
-
116' 171" 202O 116'
-
65' 800
-
170' (HBr salt) 132" 59 81O 143' 198" 178' 188' 153" 128'
78'
182'
-~
980 1309 1522,1528, 1605 1605
1004
1028,1029 1309 1309 355,1028,1029 333 333 981,994 1028, 1560 353 335 1513, 1514 809,818, 1056, 1307, 1605 1605 809, 816,1605 809,816, 1605 1605 351 1513
Reference
-
__ __
c1
__ - --
It2-L-I
\/ I
fi3---R4
_ _ ~
C,H&H=
____I__
H Br H Br Br Br H
I CH3 H H 225' 220" 250" 144O 130' (dec.) 146"
160'
70' bza170" 210° 110' 108"
~
~
_.
CH3 H H H
CSHS
H H
~
R'
--
-_----____
4-BrCeHI
Ce&
C6H5
C6H6
CH3 C2H6 CH,
RZ
CH3 CH3 c1 c1 CHa CH3 CH3
R3
~
__-
C1
Br Br H H Ci Br
R'
218" 39" 67 O 117O 261' 241" (deo.) 220"
J1.p.
R' TABLE XXVI . 3-Pyrazolin-5-ones. Halogen and Halogen Combined with Carboxylic Acid and Derivatives
- ___
C6H5
-
CH3 CH3 CH3 cH3 CeHs CeHs
.
Br Br Br Br Br Br NO
CeHs CeHK.
2-CH3CeHd C6HS CH3CO H,NOC H,NSC H,NSC H,NOC H,NSC
c1
c1 Br
C1
* 2-HOOCCeH4
CH3 CHB
CH3
C6H6
E CeH5
-
(Table contenued)
1205 981 981 988 988 1001
1205
Reference
-~-
1605 994,998 1004 351 994 1309 355 355 355 357 357 994
%
W
z. -4 8
T.
5. <
t:
5 &'
e
5. c
8
Y
.2
R
7
+d
-2
0
- P5
5i;' 2
s
re
TJI
3
It'
T A B L E X X V I (continued)
Br
Br Br Br Br
c1
Br Br
Br
Br Br Br Br Br
I
Br Br
Br
Br Br
I
Br Br
CI Br
Br I
c1
Br
I
184" 173' 2000 181' 224' (dec.) 143' 135' 249O 112' 186' 128" 192' 104' (exp.)
-
116' 217' 240 " 237' 236" 163'
179' -
231' 207' (dec.) 253' 246' 221 126' 115' 888 992 1155 1320 978 978 978 978 540,1354 540 978 978 1001 362, 697, 698 697 697 362, 697, 698, 899 1201 981 697,698 697,698 697 107
1605
1001 1001 1001 1001 795,907,908, 362, 793, 794, 809, 1297, 1320, 1491,
1001
's-
1
8 z K
9
%
Systcmatic Tables of I'yrazolones and their Derivatives
I
6
ii"
x"
XV
347
1125
1004 334 269
2410
213" 162" 253 '
H
157' 244"
202 O
593 9, 676, 818, 1123. 1153, 1852 1125, 1152 1581 1581
296
446 334
25
237"
181' 161" l66O == 250" 19Y0
296 296,676 446 9 1004 980 980
173" 180" 189' 215' 2009 242 253O
4-CH3C6H4 2-HOOCCeH4 3,4-( OCH,0)CBH3
ca5
C6H6
2-CH,-4-ICsH3 3,4-( OCHBO)CpH3 2,4-C1&HtI, 3-HO,SCaH+
TABLE X X V I I (continued)
2
Systematic Tables of Pyrazolones and their Derivat.ives
8 *
3
0, CI W
r-
2 c
349
350
Appendix
TABLE X X V I I I (continu~d)
161" 273' 2100 143' (dec.) 193" 221" 2440 203" (dec.) 271" (exp.) 276'
1640
217' 222" 190° 211"
-
163' (dec.) 237" 214' 211" 188O 225' (deo.) 188"
-
978 978 1001 978
1320 1001
978 1003 978 546 860 984 984 1001 670 333 807. 809, 1491 888 992
647 146 541 146 1149 978 978 978
licferoncc
__
-
-
R' R=
TABLE XXIX. 2-Pyrazolin-5-ones. 4-Nitro Derivatives
I
R=
R1
R3
157"
172'
-
85' (dec.)
128" 288" (dec.) 84" (dec.)
-
1004 1642 1642 6W 61 61
1683
9,809,1607 1642 672
333
663 9, 61, 478,480 478
136" 276" 127" 144" (dee.) 129' (dec.) 260"
__.___-
Reference
-
M.P.
._
W
cn
W
5p.
d,
R1
TABLE X X X .
H CH&O C,H,CO
HCO
H
H H
HCO CH,CO CzH5C0 C,H,CO C&CHZCH&O (CH3)zNCHzCHZCO
CHa CH, CH3 CHB CH3
H
H
H H H H
H H H H
H
H
H
H
CH,CO CH&O
HCO H H H H H H H H
H H H H H H H
R'
CH3 CsH5 CH&O H CeH5 HsCzOOCCHzCO H5C2OOCCH2CO H,CzOOCCHzCO H,CzOOCCHzCO H6C200CCHzC0 H,CaOOCCH2C0 H,C200CCHzC0 HEC2OOCCHZCO HEC,00CCH2C0 CH3
H
R3
_.-_.___.
R'
Z-Pyr~zolin-5-ones. Aldehydes and Ketones
I
-"
N \ /=O
RzrP
R3
68' 35 131' 220"
66'
173'
-
178' 184' 189O 180' 1090 lBO 227O
182'
191O 204"
225' 261°, 280" (dec.) 215' (doc.) 180'
-
M.p.
837 837 837 837 837 837 837 837 837 586, 824, 1089, 1092, 1093 591, 1192 1193 1193 1532, 1533 1098
1188
1546 1295 947, 1193 1188 767 1295
Reference
*en
W
.k! 5 -cl d G
9811
PZ I 916
'216
s IP9I
16'2
o6PI
OFlOT
OLCZ
zzz
08LI 0
OZ91
.L61 0861 OP11
8 EBKI
do 981I
08KZ
A
s IWT
I
r,
zoz I
OK1
9901 'LL6 '6L6
0
0
ow
II H
03300Z3'H 03H
0DEH3 0DEH3 03H 03300E3gH 03300H 03H
03OH3
03'H3
=H3'He30H-P =HD'He30H-P
=H3'HeDOH-P
H
H H H H H H H
03'Hn3
03"He13 03SEHL13 O3*H9D300H-Z O~*H~D~ON-P
&OZ
-
/ 7
'He3 'H'3
0
'H'3 QH*3
*H~~ZOK-P
EHH83z(z0hI;r)-P'Z *H%S~OH-V *H03zON-P
*H~~OZ~~H-P *H~~OYPH-P 'H9DEH3-P 'He3'H3-P HL3l cH3'P
t
'H'3 'He3 "H'3
'He3
'H'3 'H'3 'H93
ch03 5h03
H H H H H H H
"H3 'H93 03ZH3zH3xd
eH3zH3PH'3 03EEHQb 03"EH'r3 "3 EH3 "H3 "3 EH3 EH3 03ECHar3 cv 10 H 3 seHLI 3 "3 EH3 EH3 €H3 EH3 a 8 1 1 'oZOK '098 0 18 hap) 09CZ
H
03ZH3eH3NZ(sHz3)
03300~~~3 03300H
IP91 If91
cozz
H
PZK K HI1
0801
pc
LO1 9KE
0991 ,8PI Z9
3 0
.C
id
c,
$
A
4
r/2
8601
oZIt
"H3 8601
NI
I
138' 165" 166' 146' 113", 148' 104O
HCO HCO CH3C0 CSHSCO C3H,C0 C,H,CO iao-C*H,CO CSHUCO (C2H5)&HC0 HOCH&O CH3COOCH,C0 2-HOC,H5COOCH,C0 CH3CHC0 CH3CO0
I
169' 206" 190", 234' (dec.) 161O
CSHSCO HOOCCO C,H,CH=CHCO HCO
88
737 736.740 362, 740 88, 740 740 112
103'
1296 698 108, 109, 331, 696, 901, 902, 1097 901 10s 696,902 196, 201, 204, 889, 892. 893, 896, 897, 1092, 1093, 1097, 1181, 1634 1190 1190 799 112, 740 88, 737 737 94O 133" 121° 173" 196' 148"
llQO
216"
191"
CH3C0 H CH3C0
TABLE XXXI. 3-Pyrazolin-6-ones. Aayl Subetituenta on Carbon
\ /-
R1-N '
3f
b-
'cj
C!6H5
CH3
CH,
CH,
I
/
?U'CH,CO
CH,h'H
I
(CH3)2N HzNCHzCHzCO CH,CHCO
I
iso-C,H,NH CH,CHCO
I
C2H,NH CH,CHCO
I
NH, CH,COCO CH3CHC0
C6H,CH,NHCH,C0 C5H5NHCHzC0 4-CaH,OCBHINHCH&O CH,CHCO
\
,'\ -
CH3CO0 H2NCHzC0 CH,NHCH,CO C2H5NHCH2C0 (CzH&NCH&O
I
CH,CH,CHCO
23 23, 112
130"
112
162'
203"
112
112
238'
112
221
23. 88
315'
224"
740 740
740
88
88 740 740 371
88
2220 152' 185"
1250
-
177'
139' 242"
141'
P
5.
7'
tl 2
5a
P
2 P
c6H5
TABLE X X X I (continued)
156' 206 149" 194' 144O 260' 217' 216' 423' 210" 172" 166*, 209"
Br CKl'H,CO HOOC'C'O C6H,C0 4-C,H,OC,H,CO 3-H,ZI;C6H,CO 4-H,1VC6H,C0 4-(CH3),3CeH4CO 4-CH3CONHCeH4C0 4-H,XCOKHC,H4CO 4-CeHSNHCONHCeH,CO 2-NOaCeHkCO I-NO,C,H,CO
I
129"
170' 13.5' 140" 181" 146' 127" 162O
Br (CH,),CHCHCO
ClCH,CO BrCH,CO ICH,CO CI3CC0 CH3CHBrCO C2HSCHBrCO
125'
740 108 737, 740 740 740 88, 740 740 740 740 740 740 88, 110, 740
88
88
88
362 88 88 88. 112
88, 737, 799
88
W 01
Systematic Tables of Pyrazolones and their Derivatives cva 0 9 0; m
u
359
R'
206"
HOOC
H H H H H H H H HOOC &,He HOOC iso-C3H, C,H,CHa CBH,
H H
H
H H
H
H H H H H H H H H H H H H
144"
110" 19S0, 233"
96" 187'
189"
264" (dec.) 264" (dec.) -
-
-
233'
260" (dec.) -
-
SO0
H
H H
H
91" (dec.) 188"
H H
HOW
H H
H
HOW HOOC HOOC HOOC HOOC HOW HOOC HOOC HOW HOW HOW HOOC HOOC HOOC CH, HOOC CH, HOW HOOC HOOC
948
1546 626, 767, 837, 1304,1635 306,1230 167, 1162, 1304 87 152, 347 a73 624 1162 1628 a73 873 312 518 767 767 1379 24 107 107 167 167, 498 167,506
1228 43
241
Reference
_________ M.P.
-
R4
HOW
R"
HOW
H HOOC
R'
TABLE X X X I I (CORtinued) 0 -
w m
-
oL61
oL61
0882 eE8Z
0081
H
H H
.
H H H H H H
’H03 3 0 0 ~ ~ ~ 3
^^
.. - .
H
.______-
”H’D
SH% EH3 H
%I3
“HD
TI
H H H H H H H
DOOsHz3
H
H OOOsHz3 D00SHE3 EHD =H3’H03 300’Hz3 Z ~ ; ~ ~ ~ ~ S ~ Z 3 300’Hz3 CE 91 30OSHz3 H 3 6 2 *I 30OSHZ3 H 3 SZH”13 3 0 0 ~ ~ ~ 3 300SHe3 300’HZ3 H rzHor 3 O‘HL3 CH3 DOOSHZ3 H
H
H H H H H H 300’HZ3 H H
300SHZ3
”‘3 H H
‘Hg3 ’H93SCOH-P *H~DOO~H~-V
1I
H
H H ZH39H’3 H
H
H CHD H H H H H
300sHz3 300CH3 300CH3 300’HD DOO’H3 300CH3 300EH3 H
Appendix
m
2
0
2
N
37 XX3loWXXX:x
w
w
a
2
3
9
F, 0
C& CeH5CH=NHNOC CeH5CONHXHOC H2NHNOC
H H CH3
I
C,H5OOCCH,C=NHNOC
H
C2HsOCH, .~ CH, CzHsOOC (CzH5)2NCH,CH200C H
H
H R
H
H H H H
H
H H H H H H H H H H H H
11 H H
H H H H,XW H H H H H,NOC HzNOC H,NOC! H
C,H.S,C
252' 269" (dec.) 253" (HCI)
182" (dec.)
82 223O 140" 227" 196O, 238 ', 253"
-
219' 246 > 230' 255' 233
a1 0
( Tnble
-_ eonIinued)
337, 1645 337 594
1549 225" 594 1193 194, 1595 194 194 767 924, 1193 1193 924 282, 337, 443, 1544, 1646, 1547 337
89
532 563 506 574 89 89
135' 176" 142' 200" (2HC1) 184O 186"
H
C,H500C C2H500C CeHs H C*H,S,C CzH&C CH3 H
1223
-
H
CZHSOOC
&5
' 1 3
J?i
z . <
P,
?.
8
b
29'
3.
3
fD
G:
81
'3 R
'd
r:
2
!4
z.
;i; 3 a
M
3
HzNHNOC HZNHNOC HzNHNOC H,NHNOC HZNHXOC N,OC X,OC NaOC NaOC CH3 CH3 C61f,CH, CH3 C6H5CHZ
C6H5
ClOC
C6H5
C6H5
C6H5
CH,
C6H5
4-CzHsOC,H,
C6H5
C6H5
CBH5 H
C6H5
C6H5
CH,
C6H5
C6H5
C6H5
C6H5
C,H,
-_ -~
It2
___-
R'
T A B L E X X X I I (continued) ~
-
CN
C6H5CH2
CN Cp?' CK
H H C6H,CHz CGH5 CN CN CN
C6H5
C6H5CH2
H CH, CZH,
HJ
--
_ _
--
H H H H H H H H H C2H5 H H H
H H
H H
R4
281" > 316". 218' 173' 198" 167' 232 ' liquid 225O
134' (def.)
213" 113' (def.)
-
235' 179' 144"
ALP.
1595 499 499 498 506 594 1595 498 506 924 24, 924.925 1310 1186 1310 924 498 1190
Refcrencc
w 0, Ip
Systematic Tables of Pyrazoloncs and their Derivatives
365
R3
TABLE XXXIII, 2-Pyrazolin-5-ones. Carboxyl Derivatives Combined with Other Functional Substituents R'
. RZ
-_
-
-
R3
H'
-
H H
C6H5CH=X HOOC
HOOC SO
H H
C6H5 CBH5 4-HOaSC6H4
HOOC HOOC HOOC HOOC H,COOC C,H500C C,H500C CzH500C C2H,OOC CzH,OOC CzH5OOC CzH500C CzH5OOC C,H,OOC C2H,00C H,NOC
SO H2N
H H H H H H H H H H H H
cPH6
H H H H HzNOC H,NOC CeH5 C6H5
C6H5 CfiH5 C,H,CO C,H5
H2N CH,CONH XO
C',H,O C,H,S
YO
HOOCCHzCHL UN C,H&O?rT H C6H5S 4-(C211[5)zNC,H,S= 2-CH3-4-(C2H&SC,H3K= C,H,CH, 2-CH,-4-(~,H,),SC,H,S~-
Xp.
___
H
-
>280° 215O (dec.)
-
22.50
216"
-
Reference 557 1545
1036 292 36 292
1549
213' 213' 1820 170"
G77 675
195"
366
183.5' l5O0 161' 217'
077 519 244 497
210°
-044
1545 1252 292
(tlr.c..)
H CH3
H,NHSOC I3,KHXOC
SO
H
CPH5C0 C6H5C0
H,NHNOC N,OC
C,H,CH2 C6H5CH2
H
H
C,H,CONHNHCO
C,H5C0
H
H,S?;-E
178"
H
112O (exIJ.1 203' 135' (def.) 214'
1549 594 497 497
337
Rl
I
=
O
CH, C,H, CH3 CH3 CH, CH3 CH, CH, CH,
CoHs CeHs CsHs 4-CHSCeH4 CeHs CeH5
C6H5
C6HJ
CH,
CH,
CHJ
HOOC
C6H5
HOOC CH, HOOC HOOC
CH3
CeH,
C6H5
CH,
C6H5
HOOC H HOOC
H
-
R3
CsHo
C6H5
CH, CH,
c6H5
H
C6H5
-
HZ
-
It'
__
HOOC
H HOOC H
-
(dec.) 121" 138' 15p' la70 oil
189O
73Q 110" 186' 107" 187' 189"
178O
72"
-
C'& HOOC iso-C3H, C6H5CH, HOOC COHS HOOC HSOC HSSC
__
216" (dec.) 198O 220" 205O (dec.) 214'
--
___ J1.p.
HOOC
__
R'
T A B L E XXXIV. 3-Pyrazolin-5-oncs. Carboxylic Acids and Thiooarboxylic Acida and Derivatives -____
y
1 1
R3 ___- R4 R2-N
la. 741 993 1228
109
698 370
17, 107, 741, as6 167 741 167 167 107. 196 167 196 107,109 109, 831
108 370
ioa
993
Ncfcrenee
W
3
3 sf
aa
0,
CH, H,SCSHCH,CH,OOC (',H,C'H,OOC C,H500C Z-CH3OC,H,OOC 2-CH,OOCCaH,OOC 2-C,H,OOCC,H,OOC 1-C,,H,OOC 2-C1,H,OOC
Il
0
4-C,H5OC~H,NHCH&H,OOC 4-C,H,OOCIC',H,NHCH,CHaOOC (C6Hs)2XCH,CHz00C 1-C,HsOC6H,NHCHOOC
C'H, ('€1,
I
186"
C6HSSHCH2CHZOOC
CH,
CH, CH,
2420 (dec.)
H,SCH,CH,OOC VH3NHCH2CH,00C (C€13)2XCH2CHz00C
coniinued)
74 1 74 1 74 1 741 741 741 74 1 ( Tabk
74 1 126" 198' 163" 138" 179' 175" 188'
74 1
160'
130"
741 741 741
741 175" 134"
(dec.)
208" 202"
(dcc.) ,260'
741 74 1 741
74 1
144"
230'
99"
152" 960 73" 101" 1110
CH, CH, "H,
1230 370 107, 741 167 1339 167 741 74 1 741
71'
-
ko-C1,H7 ieo-C,H, iso-C,HgOOC iso-CSH,,OOC CICH,CH200C NCCH,CH,OOC
CH,
C2HsOOC H C2HjOOC
H C2H,00C CH3 C,H,OOC C,H500C C2H500C CH, CH3 CH, CH,
4
368
Appendix
u3 W m
V
0
C6H6
C6H5
\/
i B o c
Br
I
Br H,NCONHOC (CH3)&H&HOCNHOCNHOC
I
CH3CONHCONHOC (CZH5)zCOCPU'HOCNHOC
197"
169"
203" 261 26" 174' 304" 172" 210" 230"
194"
741
741
74 1
741 741 74 1 74 1
741 74 1 741 741 541 74 1 741 741 741
74 1
180"
74 1 74 1 74 1
74 1 74 1
741 741
370" (dec.) 260" 246' 230" 228O
250 O 208"
141'
-
250"
182'
249"
$. 4 R 2. 8
U
2.
e 1
5$a.
8
1
e0
R
Go
370
Appendix
CH,
H,NHNOC H,XHNOC
CgH5
CH, CH,
H,NHNOC
HJHXOC HzNHNOC H,NHNOC H,NHNOC HJHR'OC
H,NHPU'OC CH,
H,NHNOC CH,
C6HSSOzMHNHOC
CH3
CsHj
I
H
H H
SH
I
8H 1-C1oHTX=C
I
SH C,HSHNSC C8H,X=C
HN=C 830 829
830
698
183"
167
(CZHSOH)
229' 698 (dec.) . . 171' 167 200", 270' 696, 892, 1634 158' 167 262" 892, 204, 1634 175' 167 113' 167, 1387 145' 167 191O 167 75" 167
247"
233", 147' 167,698, 1387
l52O 206"
197'
q
1, m
0
0,
h
$f m r
SH
ClCH2COOOc CeHSCOOOC CeHjS030C C-CH,CeH$O3OC
ChT CN ClOC NCOC CH,COOOC (C2H5)&HCOOOC
CeHs iso-C3HT CN
ieo.C3H, s.C4H, CeHsCHz
H H
H
(exp.1 97" (dec.) 167 92" (dec.) 167 224' 741, 928, 1181 188" 1183 186O 1180 171" 18,107,741 174' 741 154O 741 74 1 218O (dec.) 122" 23 185" 741 103" 74 1 102O 741
90" lloo(dec.) 167 167
167 (exp.) 95O (dec.) 167, 1387 117O 167 (dec.) 88' (dec.) 167, 1387 110"
b
z.
3 %
cb
w
Systematic Tables of Pyrazoloncs and their nerivat,ives
37 3
I
R' TABLE XXXV.
2-Pyrazolin-5-ones. Sulfonic Acids R'
Referanca
n1.p.
1671 684,685,738,745, 1671, 1672 1674 1671, 1672, 1674 1674 1671 684,685 1671
i
R' TABLE XXXVI.
3-Pyrazolin-&ones. Sulfonic Acids
R'
HO HO CI H2N CH3HN (C2H5)2N C,H5NH 4-C2HsOCeH,NH 4*H,NOZSCpHINH CoH5CONH
M.p.
___ - __
276O (dec.)
-
1Ol0 228" 193" 153O 203" 93 213O 242'
-
-
Reference 738,745,1249 738 745, 1248, 1249 745, 1248, 1219 745, 1248 745, 1248 746 745 1248 745
\/\"
co
q
CH3CO
CH3C0 CH3C0 CH,CO CH3CO CHaCO
R'
TABLE X X X V I I .
A1
/ I 1 \/-
H
H
H
H
H H
H H
R'
2-Pyrazolin-5-ones. Acyl and Carboxyl Derivatives and Sulfonyl Subatituenta on N-1
R3
> 3w0
237'
719
718
6
6
1498, 1499
866 1531 1557, 1560 302 1598
116' 126" 168O 128' 127' 153"
Rcfcrence
3r.p.
jjl.
1
*
v
2
w
Systematic Tables of Pyrazolones and their Derivatives
0
5
I
I
W
X
W
8
V
0
2
m
3
X
w
a
X
W
<
u
u
4
375
H
R' ._
CZH, ieo-C6Hll 2-CHzCIHg H
H H H H
H
R=
H,NOC HINOC H,NOC HQNOC
Ra
H H H H H H H H H H H H H H H H H
co
~
(continued)
4-CH3CONHC~H4SO~ 4-CH,OOCNHCeH,SOa 4-XOaCeH4SOz CHaOOC CeH5OOC C,H,OOC CzH,OOC C,H,OOC C3H,00C C3H700C H,NOC H,KOC HzNOC H,NOC H,NOC HJOC HZNOC
-
R'
TABLE X X X V I I
716, 1197, 1199 356 1199 1627 61 61 61 61 61 61 61 61,275,355 97 275 1221 1221 61,358,692 61,358, 1012 1013 65 65 357
l52O, 166O
145' 157' 156" 179"
203" 184O 170" 1200 149' 126' 170'. 192" 165' 185" 195O (dec.) 172' 180", 194" 168'
-
167' 158'
1050
__ -
Reference
182"
M.P.
4
W
2+
E x
31
.eel
Q)
NH
H2NC
II
NH
H2NC
II
(HN03 salt)
(HNO,d t )
H2NC (HN03salt) NH
II
NH
4-CH&H+NHOC 4-(l-C,,H,)NHOC
CEHSNHOC
H
262"
202"
369
369
643 643
234" 195' 235' (dec.)
1498. 1600
192"
H
C,H,NHOC
1067
1012 1640 1345
> 300"
237"
H
CgHsNHOC
HpNOC
C,H,CH=
192'
H
HZNOC
H 181" 318' 131'
CaH6 CeH, CBHsCHZCHp
H H
H2NOC
E; H,NOC
d
W
-.
9e. 2
p.
1
3 8s
3g
r:
378
Appendix
X
X
X
X
Z
$
e
:
X
X
X
'
X
X
X
I
.
-
-
C2H,00CCH=CNHCS CeH5SHCS C6H,NHCS 4-CH3C,H,NHCS 4-CH3CsH4NHCS C,H,NHNHCS
CH,
H H H H H H H H H H H H
H H H
H H H
H,WS CH,?;HCS C,H,SHCS
HJCS H
H
H H
C,H,OOCCH,C=NSHCO
I
175' 117' 127" 1210 10F" -
179"
161" 84"
230' (dcc.) 180"
355 357 357 357 357 GO2
~- ..
1037, 1632 355, 358, 421 357 357 357
359
180'
CH,
H
H
2-CloH,lTHC
I/
359
249
H
H
4-CH,CsH,NHC ?U'-2-C1,H7
I!
K'-4-CH3CeH,
u
4
w
2.
5
8
i! 83
w Y
a
5
Y P
Bc, 0
Ft
m Y
Appendix
380
R"N
\ /=o h'
I
I<,* TABLE X X X V I I I .
3.Pyrazolin-5-ones. Acyl Substituenta on Nitrogen
Rl
R'
R3
H
CH&O
CsH6
H
R4
M .p.
Reference
144'
1598
CH,
H
169'
356
H
4 - C H 3 C O B H ~ - S O z
CH,
H
195'
3.56
CeH5 C5H6
CeHSCO C6H,NHC0
CH3 CH,
H H
75" 142O
1056 043
C*&
CH&O
CH&O
CH,CO
CHjCO
CH&O
CsHs CBH6 CH&O CH&O CHDCO CH,CO CH,CO
CeHSCO CSH6CO C,H,N=N CH,CO CHaCO CH,CO CH&O C6H6C0
C6H6
1056 1056 1531 44",86' 1531,1587 57" 729 40" 729 69" 729 157" 973, 1056 99O
82.5'
Systematic Tables of Pyrazolones and their Derivatives
I
CH,-N \J=O
I
C,H,
T A I3 LE X X XI X . Mercuratd 3-Pyrazolin-5-ones _
_
.
_
__-
__-
~
x
M.P.
Reference
c1
95O 130"
1155 1185 1185 1155 1155
Br
I OH CH,COO
-
-
-
381
_______I__
2-NO&H, 4-NOzC6H4 4-Hz 03dsCeH4 Z-CH3-4-KOzCeH3
C6H5
____
R3
___R4
Rip
CeH5 CZHeOOC CzH500C CZHSOOC CZHSOOC C,H,OOC
C6H5CH2
H H H
H HOOC HOOC H C2H500C CzH500C C,H500C H H
H
HOOC C6H5XIN SO
H
H H H H H
I
H H H H H H H H
n
185' 157"
H H H H H H H H H H H
177"
-
153" 220°
84O
92 1644 286 286 129.2 290
92
92
423, 16-44
115' 169" 162'
153'
288 288
92 1644 1644
425, 1644
425
1644 1644 92 92
Reference
~
__
92 92
_
- --
211" 186' 183"
121
1YO"
122O
208" 204"
-
118" -
H H
h1.p.
_
____ -~
_____--______-
___I__ ~ ~ ___
H H (CH,)&HCHzCHz C&CHz H HOOC H H H C&CO C6H5C0 (CH3)zCHCH&Hz CsHsCHz HOOC (CH3)&HCH,CH2
H*
__ _____
2-Pyrazolin-4-ones and 4-Imino-2-pyra.zolines _______-__ _ -_
I___I-__
2-NOzC6H4 4-?iO&H4 H H CdL H H H
C6H5
C6H5
H CH3 H H CoHs H H
--
H'
-
TABLE XL. -S=O
I
R1
W W
52
b
I I
c3
CeH,
2,4,6-Br3C6H2 2,4-C1,-4-NOzC,Hz 2,6-Br2-4-N02C6Hz
2,4,0-CI&H2
2-CH3-5-Pi02C6H3 3,5-CIzC,H3 3,5-Br2C6H3 2-Br-4-NOzC6H3 2,4-(XOz)zC~H3 2-CH3-6-NO2CpH3 2-XO2-4-CH3CsHa 3-KOZ-4-CH3C6H3 3-CH3-4-Br-6-NOzC6H, 2-CH3-4-h'Oz-6-BrC6H, 2-KOz-4-CH3-6-BrC,H, 2,6-Br,-3-P40z.4-CH3C,H
.
O O o C
CH300C CaH500C C6H5C0 C6H5C0 HOOC C,H500C CzH500C C2H500C C2H500C C,H,OOC C2H,O0C
C6H5
I
\/
K' T
C2H,00C CZH500C CzH500C CZHSOOC C,H,OOC CzH500C C,H500C C,H,OOC C2H,00C C2H500C CZHSOOC C,H,OOC C,H500C C,H,OOC C,HaOOC CzH500C
c1
c1 C1 H c1
C,H,N=N c1
H H H H H H H H H (4-NOH) H H
120° 17i" 209" (dec.) 143" 109" 146' 222" 181O 101"
151"
232"
177"
H
H
CH300C C,H,OOC Cl C1
160' 150"
1.58"
H
H
H H H H H
H H
H H
H H H
114" 154" 154' 189" 150° 99O 119" 183" 162O 183" 165" 1fH0
H H
H H H H H H H H H H H H H H H H
92 92 288 288 1644 287 287 287 287 290 290
1644
% b
8
a.
1
2'
t
2.
5
0.
is
2
Y
8
F:
2
m
1
0
P
cl
3 4n z.
b
286
u1
2
290 295 295 286 289 290 290 290 290 290 290 290 294 294 287
R'
TABLE X L (continued)
CzHBOOC CZHSOOC CaH500C C2H500C C2H500C C2H500C CQHSOOC CZHSOOC C,H,OOC CzH500C CZH,OOC CZHSOOC C2H500C C,H,OOC C,H500C CzHSOOC C2H500C CzH500C C,H,OOC C1H500C CzHsOOC CaH500C HOOC C,H5C0 C,H,CO CzHSOOC CpHSOOC CZHSOOC C2HSOOC C2H500C
R=
---
c1
c1
CI
c1
Br Br Br Br Br Br SO CI GI CI
Br Br Br Br Br Br
c1
Cl c1
a
CI CI CI GI
c1
Cl
c1
H H H H H H H H H H H H H H
H H H H H
H
H H H
c1 Cl C1 c1 c1 GI
R'
H3
.___
166" 145O 98 135" 124' 131 O
-
288 287 287 287 290 287
1644 288
190O
208" 209O
190°
133' 146" 143" 156" 218'
290 290 287 290 290 290 294 285 290 290 286 286 286 1292 290 290 290 295 286 294 291 286
UJ
W
.FI _-
Reference
135" 128" 191" 164O 202" 168' 178", 19.5' 2oO0 165" 169" 161' 167' 163"
-
M.R.
-___
Systematic Tables of Pyraeolones and their Derivatives
El Q,
2
m El v) &
I
z
ZZXXXXDI
X
x
XXXXXXX
X
X
385
TABLE XL (continued)
H
H H H H H H
c1 HOOC HOOC CZHSOOC CH3 c1
c1 c1
CI
Br CI CI CI
GI
c1
H H H H H H H H H H H H H H H H H H H H H
CH, H H H H H H H H CH3 CH3 CH3 CH3
4-H2XC6H4 4-CH3CONHCBH, HCO CH3C0 HSNCO C,H5NHC0 CeH,SHCS H H CH3C0 C&CO H CH,CO H HCO CH3C0 C,H,CO CeH5SO* HJWO CeH5NHC0 COHjKHCS H H H CH,CO CH3C0
1044
1048
186'
974 974 92, 1210 1049 92
974
974
974, 995 974 974 974
1048
1157 995 995 995 995 995 995 995 995 812 1043 1043 1165 1045
176"
182" 212O 208' 144"
2160
154O 230"
233" 88O 188" 239' 81" 120" 198" 193' 173' 102O 38" 130" 153O 182" 185' 227' 137 123* 148"
W W
Systemat,ic Tables of Pyrazolones and their Derivatives
C6H5
CH,
118'
4-BrCGH4 4-N02CeH, .I.CHjOC,H* 4-BK6H4 4-BrC,H4
CH3 CH, C,H,OOCCH=CHCH-CH C2H500CCH=CH CZHSOOCCH=CHCHrCH C,H5
171"
c6H5
m0
164"
91" 159"
-
387
52, 424, 809, 1242 1642 690 125 125 125 1243
H H H €3 H H H
H
H H
H
H
H
H
H H H
C,H, H H H H
H CH3
H
-
H
H
H
Section A. All Substituents Except Mercury
TABLE X L I I . 3-Pyrazolidinones
H H
H
H
H H
H H H H H
H
H
H
I
RIN\)=O
R5 Re-!,-LR3
--
- -~
H 3-NOzCeH4 H H
H H
H H
H
CBHS
H
H H
H
R4
H
H
H H
H
H
H H H H H
H
H
H
132"
139" 195' 109"
212O
146" 117'
101O 195' 178" 163"
78"
120"
b,, 162'
t),60
__
.
1177, 1630
1177
386, 750, 756, 758, 1177, 1631 758 396,750, 756, 758 1177 335, 581
1177
1209, 1550 911,1209 57, 396, 750, 756, 758, 1122, 1177, 1550,1630 1381, 1491 581, 1028 1177
-_____l_l_ I _ -
'
8 35
09 CQ
W
KO
NO
C8H6CH2
H 4-HOCH,CHzCeH4 H H C,H5
4-CIC8H,
H H
4-CH3SOzNHCH,CH,C,H,
135"
H H H H H H H H H H H H H H H
H H H H H H H H H H H H H H
H H H H H H
CH3
CH3 H CH3 H H CH3 H CH3 H H H
H CH3 H H H H C,H5CONH H CH, H H
CH,
H CH3
215'
H
H
H
H
143"
H H H H CH3 H H
H
114" 116' 131" (dec.), 173" 127' (dec.) 126" 108" 228" 160" 164O 166" 107'
107" 159"
-
-
117'
-
84"
127" lloa
142"
H
H
H
H
319* 888 1342 15, 701 758, 762 26, 816, 1491, 1592 15, 1630
335
396, 701, 758. 762, 1669 758, 762, 888 911, 1569 68, 816, 1569 68 768 1388 1631 1388 849 396, 758, 762, 1327 581 911 479, 1028, 1029 1028 353
1177
1177
0
2'
3
U
?G.
G
1
Eo
s8
2
cd
%
8
e
2
ij.
8
m
2
Section B. Mercury Substituents
J-CHaCGH, C,H,
C6HS
C6H5 CeH5 C8HS
KO HO
pi0
HO H H
Br
H H H
H H HO CH, CH3 CH, CH, CH3
(clec.)
> 200"
-
-200" (dcc.)
_._____--
--
CH,COOHg H CH3COOHg H CH,COOHg
_________ J1.p.
-.__-
218"
__
-
160" 122' (dcc.) 130'
RS
-- ._ -
HOOC H,COOC HOOC HOOC Br
H
1275 1275
127.5 1275 1275
Ibfcrence
1501 647 647 446 446 820
-
P' 3
z
7.
8
U
;i'
cc
m
X ,Y-( CIHg),C6H, 4-CH,-X,Y-(CH&00)2CeH, 2-CH,-X,Y-( CH,COO)&eH, 2-CH,-X,Y -(CIHg)&sHz X-CH3COOHgCeH, X-CIHgC6HI X,Y-(CH3COOHg),C6H, X,Y -(CH,COOHg)2C6H, X,Y -(CH3COOHg)&gH, X,Y-(CIHg)&H,
Rl R'
TABLE XLII, Section I3 (contin&)
ClHg CH,COOHg CH3COOHg ClHg CH,COOHg ClHg CH3COOHg CH,COOHg CH,COOHg ClHg
R3
n* CH,O CH,O CH30 CH,O CH,O CH,O CH,O HO HO HO
_ I
H CH,COOHg CH&OOHg H CHaCOOHg If CH,COOHg Br CH, CH,
R5
225" 225' (dec.) 237' (dec.) 245" (dec.)
-
167"
-
-
-
xp,
1275 1275 1275 1275 1275 127.5 127.5 1275 1275 1275
Hefercnce
;o CD KJ
393
Systematic Tablea of Pyrazolones and their Derivatives
I
H TABLE B L I I I .
3-Irninopyrazolidincs
€i'
R'
R3
It4
H
H
H
H
757
C6H3
H
H
H
H H H I€ H H H H H H H H CH3 CH3
H H H H H H H H H H CH3 CH, H CH3 H H H H H H HaN C,H,OOCHN
H H H H
396, 757, 1122 396, 757 396, 757 396, 757 757 '160 757 760 760 396, 760 760 760 396, 757 396, 757
2-CH3C6HI 3-CH&H, 4-CHSCeHI 4-CH30C,H, 4-C,HsOC,H, 4-CH,CON HC,H4 4-(4-CH&H,S)C,H, 3-CIC6H4 4-C1C6H, 4-BrCOH4 Z,S-(CH3)2C,HS CsH, C,H5 3-CH3CSH4 4-CH3CBHI 4-CICBH4 C6H5
C6H, CsH5 H H
C6H5 C6H5
C,H, H H H
H H H H H H H H H
H H H H GHs CH3C0 CBHSNHSC H CZHSOOC
3i.p.
74 110' 143" 179' 192' 2040 123" 142' 132" 121° 99 82" 106O
172" 152' 195O 129' 74O 192' 196"
-
Reference
760
396, 757 396, 757 396, 760 396 396 396 336 336
101
101
102" CH3
cr
i"i
\/
H H H H H H H
H H
H
H
670
1001
984 984 984 984 984 984 984 1001
1001
1001
1001
1001 1001
b, 178"
litin
Reference
H
-
n1.p.
238" 240" 289" > 350' 282O 1820 197" 233" 221" 249' 244" 220" 155' 199" 255i
~
R'
H H HCO CH3C0 HaNCO C6HsNHCS H HCO CH&O CSHSNHCS H CH&O C6H5NHCS H CH3C0 H
H H H H H
T A B E X L I V. 4-Imino-3.pyrazoiidionee
I
H'
x
Bf:
*
a
P
w w
CH,
CH3
(1CH,
CH3
CH3
-
H
H HCI
1590
44O
61" 82" 80" 67' 7u0 83.5" 61" 100" 37 a
63"
108"
205"
99, 420, 461, 527, 617, 1174, 1175, 1491 172, 431,637, 940, 1303 1303 1303 164,431,1303 1303 104,431,1303 1303 1303 1303 1303
101
101
c1
.5 :
3.
1
13
8
9
2
8
ccw
c3 P
5'
aR
Fi:
m
2
396
Appendix
Systematic Tables of I'yrazolonee arid their Derivatives
c, m rn
397
398
Appendix
r. 0, OD
l-
4
M
OD 0.1
l-
o t-
3
B
Systematic Tables of Pyrazolones and their Derivatives
a
m
x
I
I
I
u
d
8
si
0
U
399
1470, 1471, 1473 1470, 1473
181"
79"
N(CHdz CH CHC0
N(CH3)Z
I
CzH5CHC0
N(C2H5)2
I
I
168"
1470, 1473
1471
175'
HNCH, CH3CHC0
I
CH3CHC0
260" 151'
Ill0
618 617,618 536 68,533 58,731 1470, 1473 371, 1470, 1473
1890 198"
-
69
276'
HCO CHaCO iso-C,H,CO iso-C,H,CO Hz;?c'CHzCO(HCI) (CH,)ZNCH&O (CZHS)&CH~CO
69
278'
2 r!
* j
CH3 130'
N(C&)a C H CHCO
186'
x(CaH.dz iso-C H CHCO
187". 198' 218'
N(C,H,), ClCHZCO CH3CHC0
Br 2-CH&OOCsH,CO 3,5-Br&6H3C0 COCH=P;OH HOOC
I
-
219' 252' 190'
205"
Br im-C3H,CHC0
I
185a
Br C3H7CHCO
1346 1414 731 549
533, 1470, 1473
1470, 1473
1470, 1473
208'
Br CZHSCHCO
I
1470. 1471, 1473
I
206" (dec.)
1470,1473 1471
50, 1156,
1470, 1473
1470, 1473
1470, 1473
1470. 1473
1470, 1473
CH,CHCO
I c1
177'
I
N(CH3)2 iso-C3H7CHC0
'
7~
80"
I
N(CJ33)2 CBH&HCO
'I
119"
I
CzHbCHCO
C6H5
TABLE XLIV (continued)
CH3 CH3 C'H, CH3
N
\ /=o
I
CHzCOOC2H,
I
4-CPHSOOCC,H,NHCO 3-HO-4-CH300CCoH3NHCS C6HSHh'CO H,NHNCO C2HSCH=NNHCO CH,C=NNHCO
Br
I
H&CO iso-C3H,CHCONHC0
CH3-k
2m0 207 '
135"
200' (dec.) 236"
-
70"
-
242'
198" lMO 208" 213". 269"
175' 249O, 260"
4-HzNC,H*S02
HCS
-
206' oil
C2H6OOC ClCO CH3COOC0
1367 49 929 929 929 929
929 1300
589 589 371 472,556,1374 70, 98, 356, 1105, 1197, 1504, 1633 489 489 98 98, 356, 1108,
E3
Ip
0
C2H5
CH, C2H5 CH3 CH,
I>H H H H03SCH, H
H
-
117" 129" 118' 125' (dcc.)
12SC
245" 210° 117" 150" 186'
190°
176" 109' 209' 233" 234"
-
102" 156" 105" 113' 85 __
-
186'
2259 214"
521 521 541 145,521
521
1477
992 520 50 50
Eg
992 992 992 992
U
B
F
@
9. <
Y
T 8.
rt
5
5
i!
cd
%
e8
P,
5. H
Y
5c
cr
1496 1496 1496 1496 1496 1496 1496 1496 1496 509 992 992
928
929 929
Systematic Tables of Pyrazolones and their Derivatives
405
406
Appendix
T A B L E XLVI. Miscellaneous Bis(3,6-pyrazolidinei~nes), Bis(S-irniiro-3-~~razolidinConipourid
-
ones), and Bis(4-imino-3-p~razolidinones) __ __ __
___
-
__
._
-
3r.p.
-
-
-
Ik~ferenc'c
646
, r
i
'\
I
:
546
(Table eonlirrtted)
Systematic Tables of Pyrazolones and their Derivatives TABLE X L V I (conttnued) __ -- - on~pouncl
.
-
-
.
___
_________-
..
__
407
-
1r.p.
Reference -
____-
260c (dec.)
797
281"
797
I
I C6H5
C6H5
I
I
3-CHJGH4
3-CH3C,H,
797
I
C,H,
251
797
165'
1387
0
I
C6H5
H
C6H13
CgH13
H H H H H H H H H H H H H H H H
H H H
CH3
H
Ha
R'
Section A. Alkyl and Aralkyl Substituents
TABLE XLVII . 3,5-Pyrazolidmdionea
HJ
H H H H H
R'
182' 83' 94" 93" 93' 81"
-
301'
232' 254' 280" 186' 220' 228" 289'
250" 270'
-
Xp.
604
504 504
504 504
388
504
769 504 248, 388, 1234 1234 388,1234 1234 388 248, 388 388 388 497 504
Reference
*
-
-___-_
H
H ___--
H H H H H H CH3
H H H H H CH3 H H
2-ClCeH4 3-ClCeH4 4-CICSHI 4-BrCeH4 4-NO2CsHd CeH, C,H6 CBHS
__-
H
H
CeHs
--
-
CBHS
(385
It 9
R' H=
- .._--
_-
-
I
CZH,
H H
H
H H H
198'
177' 108'
84"
217'
181" 174' 207'
M.p.
-
H H
-
192"
_
H
____
-__
H '
Section B. AlkyI, Aralkyl, Heterocyclicelkyl, Aryl and Acyl on Carbon Substituents
TABLE XLVII (continued) -
128' 74O
155' 134'
_-
504 997 997 1339 496 388,496, 998 381, 388, 1234
5oQ
504
248, 317, 496, 681, 976, 994, 997, 1512, 1596
Reference
-
~
(Tablecmtmucd)
-
504 248 248 248. 734
J
(0
8
2' a
R
2.
s
s2.
a
E
8
E
2
%
3 m 5
B t.
u2
3
H H H
H
H
H H H H
H H H
H
H H H H H H H H H H H H H H H H H H H H H It H H H H H H 220" 2029 193" 193" 174" 147" 1600
181' 1840 169" 172' 157O 155' 147 1890
H H H H H H
H H H H H H H H
H
I87O
H
313'
504 504 504 504
1330
506 506 506 506 506
506 506
504
501
504
%
5
a
?
8
3
FF-
2
3
w
3
8
2
+d
% 504 504
8 504 504
a E
4
Bz.
rn 3cc
504
504
jo4
1550
504
504 504 504 504 504 504
239O
1960
131' 197" 210°
154"
132' 110" 106'
169O 150"
H H H H H H H H H H H H
CEH5
C6H5CHP
CH3 €I H H H H
H H
)-Ji-rX -
4-(C6HI)CEH4
4-CICeH4 3-NOaCeHa
N
H H
496 496 248
182" 211" 136' 98' b0.3
116' 106'
113O
bo.1 148"
248
769
769 769
248, 681, 766, 969, 1150, 1234, 1501 222, 506, 612 612 769 769 339 339 766
Rcfcrcnce
997 248, 388, 496 1339 317,496 248
176"
-
H H H 4-HsNCEHI 288" (dec.) ~ - ( ~ - C E H ~ C H = N ) C ~ H271' ~ 177' H H H
H X-CH&H4 4-CH3OCEH+ H
H
172O, 233'
H
H
__
178O
H
3l.p.
H
T A B L E X L V I I , Section B (continued)
x
3E
* a
H H H c6H.S H
H H H H H
135' lO5O
H H
118' 127' 128O 104" 137' 107'
168'
143'
H
172' 108'
171" 258' 243O 114" 168" 114' 108'
(Table continued)
133891440 1338 1338 1338 1338 1338
1437, 1439. 1440 619,1338 63, 188, 612, 952, 1032, 1150, 1312, 13% 1325. 1430, 1439 222
188, 1338,
248 496 506 1338 222,612 222 1033, 1150, 1338 222, 612 188, 619, 1440
t w
5-%
9. 1 U
5tL 9
0
3
2
'c
%
c:
5
2
5-
g
3
3
m
R1
__
R'
TABLE XLVII, Section B (continued)
CH,
R3
222 188
136'
176"
-
184'
H
CBH,CH, H H
77O 85 '
H H
H
-
-
H
H
-
177O
H
H
222, 612 188
172'
H
188, 1338 188 919 919
188
1440
188, 619, 1338, 1430, 1440 188, 619, 1338, 1437, 1439,
188,1338
1338
95
H
Reference
M.P.
It'
P
2-
a
2
w
~
c P
__
-
CH&OOCHzCO CICH C0 CH3SCHZCO C4HgSCHZCO 3-HOC4H, CzHSOCH&HP CaH,OCH&Hz iso-C3H,0CHzCHz C4H,0CHZCHz C3H,0CH&HLCHzCH2 CEHSOCH2CHz C~H50CHzCHzCH2CH2 CEHsCH,OCHzCHzCHZCHz XaO,SCH, CH3SCHzCHz CzHSSCHzCH2 C3H7SCHzCH, iso-C3H7SCHzCH2 C3H5SCHzCHzCH2 CEHSSCH2CHz 4-CH&EH$3CH&HZ 2,4-(CH3)&6H3SCH&Hz 4-CIC,H&CH&H2 4-BrC,H,SCHzCH2 4*CH30CEH,SCH&Hz CEH~CH~SCH&H, C6H,SCH,CH&Hz CEH5SCH2CHZCH&H2 CBHsCHzSCH&HzCH2CHz C2H,SOCH,CH, CzH550zCHzCHz CEH5SOCHzCHz CEHSSOzCHzCHz 4-CH30CGH,SOzCH&H2 H H H H H H H H H H H H H H H H H H H H H H H H H
93"
H
-
-
-
18l0
-
112O 121"
-
-
-
101" 104O 117'
-
250" 120° 92" 94 = 105'
-
147' -
90 O 104"
-
173" 149' 1540 149'
H H H H H H H H
615 615 615 615 615 615 615 615 615 615 615 61 5 615
615 615 615 615 233 615
1454
919
615
919 919 919 919 267 615 615 61 5 616 615 615 615
m
2'
R
8. d
U
E j.
?
1 e.
a
8
1
i;
0
N
5
v
8 0,
@ a
4
0-
c+
B
lil
3
416
Appendix
Systematic Tables of Pyrazolones and their Derivatives
417
Appendix
d
3,
I
lB I
I
!
1
1-
2
14
El G,
SystematsicTables of Pyrazolones and their Derivatives
2 W
?i 2
?i
-# N 3
C1 0
a
a
2
2222
m w w w
d
"J
m
8
x
xs:
XXEX
x I1
V
x"
-V
5
v),
x X
U
4
I I I I
<
0, X
9
/--\R -Vs
0 /
4-CH&SCeH4
R1
___
Ra
TABLE XLVII, Section B (eontinuel)
-
H H
158"
H H H
H
H
H H H H
H
H
H
283"
244"
272' (dec.) 280" (dcc.) 258" (dec.) 270' (dec.) 220' (dec.) 255' (dec.) 225' (dec.)
132'
198O
200" 180"
250" (dec.) 228' (dec.) 275" (dec.) 222' (dec.) 245' (dec.)
H H H H H H
H
__
H
I
CH3 CHsCHCH2
I
-
H H
iso-C4HoSCH2CH2 CHSSCHCHZ
-
M.P.
R'
113
__..
251 252 252 252 252 252 253 262 252 252 252
1289
615 252 252 252 252 252 252 252 252
615
615 615
Rcference
.
x
3&
> 3
0
P ba
bo.2 130" b0.m 106* 42' 93 bo.00 155O 99" b0.01 175O bo.01 144O b0.05 l8Oo 121O 115" lloo 159"
570
164" 186O 1540 180" 123' 143' 243 70" 620 94 b0.15 l23' b0.03 lg"
222
222 222
304
248
252 252 252 252 252 252 506 248, 998 998 41,248 248 248 248 248 248 248, 734 248 248 248 248 248
m
U
g
e
Be
z
gE
5 5 3
8
z
a
C-I
-.g.
M Y
422
Appendix
C6H5NHCO HCO CH&O C6H&O H H H H H H H H CH3
l3r
Br Br
H H Cl
198" 1990 194' 243" 81
217'
160" 119O 166" 1100 96" 111O 170"(doc.) 160' (doc.) 150'
106" 98O loo" 116"
51a
-
5n
P
w 3
-¶
0
eco0
e
0
z.
3
3 F
P, w
B _ _ _ ~ g.
89, 109
506 506
506 506
606 506 506 506
1340 1048 458 1033 1033 458, 1032, 1033 1031, 1033 1031 976 734 734 976
~
-~ ~
I
kl
H
H H H H H
H H
H
H H
H H
H
H
H
H
H
H
H
H
H
H
H H
H
H
H
H
CH3 CH3 CH3
H
H H H H H H
H
H
H H
H
H
H H H
H H H H
H H H
H H
H H H
H
H H
H H
H
H
H H H H H H
H H H
H
H
H
H4
H
R3
R'
R' R'
Section A. Alkyl, Alicyclic, Aralkyl, Heterocyclicalkyl, Heterocyclic, and Aryl Substituents
~~~~~
TABLE XLIX . 5-Imino-3-p~~azo~dinones
1-0
\ Nr -
R6NL-LlV I R2-N
R3
Reference
214'
594, 644. 1083 255O 1597, 1649 223' (dec.) 1651 250" (dec.) 1651 246' (dec.) 1649 200' 1651 2120 1651 205" (dec.) 1651 198' (dec.) 1651 271" (dec.) 1651 234O 1649 242" (dec.) 1651 249" (dec.) 1651 214' 1651 239" (dec.) 1651 227O 594 594 227a 192' 694 220" 1597 215' 594
M.P.
R'
3a
*
P N P
I
H
H H
H H
H H
H H
COOH
CH3
I
CeH5CH
C0H6CH2
COHsCH= C,H,CH=
H H
H
H HOOC
H H
H
COOH CSHiiCH
H
H
H
H
CaHiiCH
I
H
H
H
H
H H
H H H
H H H H
H
H
H H H
CaHsCO H H H H H H H H
c6H5
H
H
H H H H H H H H H H H
H
H
CH3 CH3 CH3 H H H H H H H H
H H H H H H H H H 182'
705
-
567
644,1085
497,501 120
(Table continued)
> 280'
244'
202" 80'
-
705
507
239"
200'
507 500 498
498
594 1597 594 501 501 508 508 507 507 507 507
152"
234'
2220
208' 243' 242' 247" 128" 145' 133" 190' 136' 131'
01
426
Appendix
xxxxxxxxxxxxxxxx
xxzx?i
x
xxxxxxxxxxxxzxxx
z
Systematic Tables of Pyrazolones and their Derivatives
0
I-
cc.4 l
I
I
88 /\
/\
a
xxx
X
X
X
x
X
X
xxx
X
X
X
X
X
X
xxx
W
X
X
X
w
427
CEH5
H H H
H H H H
H
H H H H
H H H H
H
H
H H H H
H H H H
H H
H
H H H H
H H H
H H H
H H
H H H
H H H H
H H H
H
H
H
R4
R3
Ha
CEH5
R'
TABLE XLIX, Section A ( h i n d )
I
188O
215" -
220° 220"
195"
-
170'
-
-
co
3-HzN-4-Ci8H370CeH3CO 3-NO,-4-C1,H,,OCeH,CO 3-{2-[2,4-(t-C5H11),C,H30]-5-H,NCeH3CO)CBH,CO 3-{2-[2,4-(t)C5H11)&H,O]-5-[2,5-(CH,OOC)2C~H3XHCOCONH]C,H3CONH}CeH4CO 3-(3-CIO&K&H4CONH)-4-Cl~H3~OCBH,CO 3-(3-C120~SCeH4CONH)-4-Cl~H~~OC6H~CO
-
152'
205"
-
1380 155'
1246 1246
1246 1246 1087 1087
776 1602 693, 1595 67, 1139, 1247 67, 1247 1139 67 1602
693, 1139, 1595 1594 1602 1255
595,596
290"
218'
Reference
M.P.
3-{[4-(4-t-C5H11C6H4O)C6H4NHCO]C~H4SOaNH)CGH,-
3-OzNC6H5CO 2-HzNOCCeH4CO 3-(3-C102SC~H4NH)C,H4CO
CH3COSCH,C0 CeH6HNCHZCO CEH5C0 3-H2NCBH4CO
C6H5
I
HSCH,CO BICH&O CH,CH.&HCO
CEHS CH&O
R'
~
6
m _.
H H H H H H H H H H H H
H H H H H
H
H H H H H H H
H H
H
H
H H H H H
H
H H H H
CBH5 CeHs C6H6
CfiH5
CeH5
H H
H H H H H 11 H
H H H H
H H H H
H H
H H
H H
H H
1247
1247 1347 1247
1246 591
1246 1246 1246 1246
1246 1246
(?'able continued)
E3
P
c <
(D
2.
Y
v
;j.
?
G
3
eJ
a 1 m
0
0,
%
1
w
5
B
3 E
c5 .
3
2
r+
U-
2
(0
- I @ .
1247 1247 1247 198O 1595 1595 235" 227" 705 142', 160" 1138, 1596, 1599 168" 1597 233" 1599 237" 1136, 1138, 1599 1138
-
-
__
-
-
204O
1480
142' 210° 128'
-
-
Append i zc
XXX
xxx X X X X x x x
xxx
4-N02CeH4 4-NOzCeH4 4-P;OzCeH, 3-HOOCCeH4 3-NCCeH4 4-KCCBH4 4-h'CCbH, I-SCCeH, 4-h'CCeH4 I-XCCeH, 4-NCCeH4 4-ICCCeH4 4-riCCeH4 4-NCCeH4 4-NCCeHs 4-NCC6H4 4-NCCeH4 4-NCCeH4 4-NCCBH4
H H H H H H H H H H H H H H
H H H H H
H H H H H H H H H H H 4-[3-(4-C5H,,CsH,0)CeH4COXH]CeH4 H H 3-ClCeH4 4-BICgH4 H 4-S0,CeH, H
4-(3-CIO.SCeH4CONH)CsH, 4 4 2-HO,SCeH,CONH)CeH, 4-(3-H03SCGH&ONH)CeH, 4-(2-H03SC6H,COICH)CeH4 4-(2-HO3SC6H4CONH)CgHa 4-(2-H03SC6H,CONH)CeH4 4 4 2*HOJSC6H4CONH)CeH4 4-(Z-HO,SCeH,CONH)CeH, 4-(2-HO&&H4CONH)CgH, 442-H03SC,H,CONH)CeH4 44 2-H03SCeH4CONH)CeH4
H H H H H H H H
H H H H H H H H H H H H H H H H H H H H H H H H H H
H H H H H
H H H H H H H H H H H H H H H
H H H H H H H H H H H
H
H
H
CeH5C0 H
-
(Tahle c o n t l a w d )
220' (dec.) 592 130" 592 592 1247 1247 1247 124i 592 592 592 592 117O 592 205" 870, 1600 850 248" (dec.) 1140. 1601 186" 592 592 195" 592 273' (dec.) 871 1604 224' 1601, 1601 1604 1604 1604 16M 1604 1604 1604 1604 254O 591. 1601 1604 1604 1604 1604 3
P W c
5z. P
1.
U
$.
3.
e
P . 4
J
e,
Q
3 6
'd
5 P 0,
3
g.
* 3
'i:
R' R3
H H H H H H H H H H H H H H H H H H H H H H H H H H
RX
H H H H H H H H H H H H H H H H H H H H H H H H H
H
TABLE XLIX, Section A ( u m t i n d )
H
H H H H H H H H H H H H H H H H H H H H H H H H H
R'
H5
______ .______I_-
M.P.
~_
1601
1604 1604 1604 1604 1604 1604 1604 1604 1601, 1604 1604
1604 1604
1604 1604
1604 1604 1604 1604 1604 1604 1604 1604 1604 1604
Reference
x
3a
P a
hl
W
*
Systemat>icTables of Pyrazolones and their Derivatives
s
3
5 : s" 3
I
8
0 0 0 0
I
iz>
i , =x \
z
x "% uov
0
I/
x
x
X
xxxx
x
xxxxxxxxxx
x
x
x
xxxx
x
XXXXXXXXmx
x
x
2
xxxx
x
x2xxxxxxxx
413
N
H
0-
R'
H
H
Q-
H
H H
H H
H H H H H H H H H H
H
H H H
H H H
H
H H H H H H H H
H H H
H H H H H
R'
H H H H H H H H H H H H H H H H H H
R3
R=
TABLE X L I X , Seotion A (continued)
-
Xp.
Refereuce
H
H
H CeH&H&O CBH5C0 3-HgNCeH*CO 3-NOzCeH*CO
188"
277O
-
1600
1142, 1601
1254 922 932 1254 12.54 922 ~-[~,~.(S-C~H,)&H~OCH&'ONH]C~E[,CO 13S0, 220" 922, 1603 342.44 t-C~H1l)&eH30CH&ONH]C~H4CO 922 H 922 C,H&H&O 274' 922 CeH,CO 270' 922 3-(4-t'CjH1IC~H,O)CeH4CO 922 ~-[~,~-(s-C,H,)&~H~OCH&ONH]C~H+CO 922 225' ~.[~,~(~-CSH~~)~C~H~OCH~CONH]C~H,CO 1604 2,4-(t-C,H11)zC6H,OCH&H&O CeHSCO 1604 1604 3-[2,4-(t-C5H11)2CeH30CH2CO]CsH&O H 223' 13, 14 13, 14 234" CBH5C0
RU
--
&
.FI w
Systematic Tables of Pyrazolones and their Derivatives
0
435
0
2
r; CJ
N
X
X
X
24
X
x
x
X
X
X
X
24
x
E
X
X
x
X
ez L/ I
x
x
H
H
R'
\
'\/-
B
H
H
H
Qq
H
H3
€1
R'
T A B L E X L I X , Section A (continued) _-_ --. --
H
€1
H H CH,OOC H H H
H CH3 H
H H H
H CSHSOOC
H
H
CBH,CO
H
CH3C0
H'
H
H
H
H
H
R'
1601
1600
Reference
196' 85" 1010 79" 86"
200"
140' 2800 223 ' 249'
499 507 167 391 499 499 499 499
499
499
218" (dec.) 1600
196O
252'
M.P.
0,
w
b b
H H H H H CH,
H
H
H H H
H
H H H
H
H H
H
H H H H H H H H H H
H H H H H H CH3 CH, CH3 H
H CBH5 H
CeH5
H H H H
H
H
H
H CZHSOOC CeHsCO
H
H
iso-C3H,00C H H
CzH,OOC
H H
C6HSC0 CZHSOOC C4HBOOC HOCH,CH,OOC H CZHSOOC
498 498 498
498
(Table continued)
206" 178' 225'
154"
208" 391 192' 391 175'. 236" 391, 507 223 507 200" 507 242 ' 501 230" 167, 697, 1339, 1387 69" 1052 257" 1339 233" 1339 167,1387 222O 194" 167 212" 167 137' 499 242 ' 499 227 ' 501 145', 226' 167, 499, 1398 213" 167,499, 1395 211O 167 213' 501 215" 391 167" 498
W 4
Ip
8
5.
3. F
U
2z.
?L
P
R
3
'd
%
3 eD
5.
'D
2
m
2
H
H
CHSCOSCHZCO
H
H
219"
165"
H
H
H H 238'
C6H50CHaCHz CeHsOCH2CHzCHz H
CeHa
I
100' 397" 102
H CeH5CO CH&H&HCO c6H5
M.P.
RS
H
H
R'
136" lOS0
C,HS C@HJ
H H
____-
R3
H H
Ra
R'
._
TABLE X L I X , Section A (continued)
776
776
501
801
60 1
498, 501 498 1255
Reference
Systematic Tables of Pyrazoiones and their Derivatives
w
'$$$ \ W
Ma5 x
/
I
X
x
439
H H H
CH300C CzH500C iso-C3H700C C3HSOOC CICH,CH,OOC HOCH,CH,OOC HZNOC H CH3OOC H CH300C H H H CH300C CzH500C
H H CH&O C,H5C0 H H H H CH,OOC iso-C,H,OOC H CH300C H H
140" 190" 206j" 178" 141' 188" 135" 186" 155" 1570 157' 144' 141' 204"
391 391 391 391 499 499 499 167 167 167 167 167 391 167, 1395, 1400 126" 167 167 141O 167 139" 167 102') 167 135" 167 136" 167 166' 2049 167 109O 167 137' 167 158' 167 138' 391 105O 391 204", 230' 1395, 1400 126" 1395 141' 1395
Reference
E
3
b
f
H CBHd
H H
H H H H
NNHC~H~
2,4(t-C,H,,)2C8H,OCH&O
H
H
CH3CO HOOC CzH,OOC C2HsOOC C,H,OOC C2H,00C C2HsOOC CHaC I/
CeH.5 H H H R H H
__
R3
R1
Scction B. Acyl, Carboxyl. and Carboxyl Derivatives ~- - _ _ _ -____ -
T A B L E X L I X (continued)
H
R'
H
2,4-(t-C5H11)2CeH~OCH&O
H
CeH5 2-CHaCeH, 4-CH,CeH, HOOC
H
140"
-
Refereucc
-__
187 167 167 167 391 391 391
501
1395 1395 317
591
498,1599 557 1083 194O 1650 215' 1650 200" 1650 187' 557 185' (dec.)557
233' >3Oo0
-
H
~
B1.p.
~
204" 126' 211° 259O 241O 124O 205" 191" 76' b13 173' b0.* 155"
R'
CHaOOC H CpH6QOC H
H
CH,OOC H H H CHaOOC
H
e
@
CEH&O C,H,CO C,H,CO C&,CO C,H,CO CeHSCO H,NOC HaNOC H,KOC
H H H
H
H kl H H H H
H H H H H
H,NOC HpNOC H,NOC H,NOC HzNOC C,HSNHOC
H CH,CO H H H H C,H&O C,H,CO CEHeCO CgHsCO CEH&O C&.CO CeHSCO
CHZCO H CH3C0 CEH~CO CeH,CO C&CO H
H H H H H H
R=
Rl R'
H
Ra
H
TABLE XLIX, Section B (continued)
H H H H H H
273" 261O 270" 266' 259' 117"
300"
498 498 498 498 498 506
497 497 497 497 497 497 498 498 498
236' 235" 238' 236' 237' 238' 304" 278'
H H H H H H H H H
Reference
207' (dec.) 1598 203' 1598 594 195" 198' 1598 171" 594 160' 497 234' 497 232" 497 233' 497 235' 497 234" 497 236' 497 236' 497
M.p.
CEHS CiH, CH3C0 CeHs CEH&O CpH6OOC H H H H H H H
R4
g
3
* ?
rp,
IP
C6H5
CEHL
--____
lt1
- -
H H
C,H, CH3 CH3 H H CH, H H H
__
R'
I
HOE=
CZHB 2-CH3-4-(C2H&NCeH,X= 2-CH3-4-(CZH&NCeHaN=
H2IS HOCH2NH HaN 4-(CsH5)2NCeHdN= 4- (CaH&NCsHIN= 4-(HOCH&H2N)CeH,N=
Br
BK
K3
H H H H H
R'
-
I
C6H5
H
H CHaOOC CeH5CHzOOC H H H H CH,CO H
- - -_
_Re
Section C. Halogen, Nitroso, Amino, Imino, Azo, and Amido Substituents
TABLE X L I S (continued)
CeH,NHOC CeH5NHOC C,H,NHOC CeH,NHOC CeH5NHOC CeHSNHOC CeH6NHOC C,H&HOC CeHSXHOC
__
-
__
-
__
._
.-
Reference
506 506 506 506 506 506 506
____-
-
506 506
148', 169" 244, 519 173' 244
180" 78' 125' 180"
644 1339 519 519 519
644
223" 317 102O 167 212' (dec.) 697
-
M.p.
- ^
167'
loo0
234" 95"
264O 240"
115' 113" 110"
P
E <
<
U s -.
;i'
E
c
rn
2
7
g
2-
H H H H H H
H
4-CH30C8H4K=S 2-HOOC-5-H03SCeHSS=K 2-HOOC-4-H03SCeH3N=N 2-HOOC-4-HO,SC,H,N=N 2-HO-3-NO2-5-H03SCeH,N=N 2,5-(CH300C)2CeH,N=N 4-HOOCCH~OCeH~K=z=N
H
C6H5
I€
H H H CH3 H
H
H CH3 CH, H CBHI
H H H H H H H H H
H H
KO KO KO KO CBH5N=X 4-H2NO~SC6H4N=S 2-HO-4-H03S-l-CIoHJ=X 2-HO-4-HO3S-1-C,oH5K=X 2-HO-4-HO3S-l-CloHJ=N 4-CH30CeH,h'=N 4-CH,OC,H,X=X 4-CH,0CBH,S=N C,H5N=N
H H H
2-CH3-4-(CsH,)zNC6H3N= 2-CH,-4-(CZH5)d?iCeH3~=
H H H H H H CH, H H H
CeH.5 CeH5 H H H H reH, H H H KO
2-CH3-4-(CaH5)zNCeH,N=
H
CeH5
T A B L E X L I X , Section C (continued) --
___
-
1255, 1539
Reference
1920
O
1087
920 920 920 920 1247
1255, 1539
1838 1538 >3m0 644 218' (dee.) 337 174' (dec.) 337 1649 193" (dee.) 1339 21 1 (dec.) 1649 2740 356 920 __ 920 920 172' 594 181" 594 2.100 594 175" .591 2180
207'
168'
Xp.
CsH5 H H CH,CO H 3-{2-[2,4(t-C~Hl1)2C,H,0]*5-(2-H03SCeH,CONH)CBH3CONH}CeH4C0 3-(2-[2,4-(t-C5Hll)~CeH30]-5-[3,5-(CH30OC)z205' CeH,NHCOCONH]CeH,CONH}CeH4C0
I
CH3CHzCHC0
H CeH5 CH&O H CzH,OOC H 2,4-(5-C,H,l)zCoH,OCH&O
H
C6H5
CBH5C0 4-CICsHaCO H CH300C CzH,OOC CeH5 H
CeH5
I
CH,CH,CHCO
R6
x
TE
*
v
lb
lb rp
Systematic Tables of Pyrazolones and their Derivatives
445
4-CH,OSHC,
\
1
-iq
$-
o-'
CeH5
4-CH30CoH4CH
C-CH,OCeH,
Rl
R
TABLE L (continued)
CeHli
K'
- _
CEHS
Reference
1254
198" 170"
1603
1603 1603 1603 203" 192O
1603
I603
1603 1603
1254
215'
150'
120" 1254
145'
*
lb
+P
% x
31
Y?
___-aa
142" 1255
N.p.
~
218O
173'
170"
~-[~-(~-CIH,)C~H,O]C~H~ 4-[4-(C+H,)CeH4OICeHICO
CeHs
I
CH,CH&HCO
R=
___
4-{4-[3-(t-CsH11)CeHdO]C6- CH,CH&HCO H4CONH}C6H4(CHz)4C0 I CeHs
C6H5
I
CH&H&HCO
CeH5
I
CH3CHzCHCO
R2
-_
Systematic Tables of Pyrazolones and their Derivatives
03 u)
447
m
In
2
a a x x A
0
0
2
h
Appendix
448
CH3
I
CII,
257" (dec.)
754
290"
761
449
Systematic Tables of Pyrazolones and their Derivatives TABLE L I ( d i n u e d )
234"
776
256"
776
188"
776
1516
287"
488
238"
235
Appendix
450
T A B L E LI ( m t i n d ) R
M.p.
Reference
210"
236, 1667
218
237
184",212"
747. 237, 772.773
216" (dec.)
620, 772, 1668
205"
620
-
707
257"
747
CH,
(Tubls continued)
Systematic Tables of Pyrazolones and their Derivatives
461
T A B L E LI (continua?) R
M.p.
Reference
248'. 281'
741, 764, 172
254'
147, 764, 765
130" (dec.)
741
183"
747.712
IOO0
141
197"
741
209"
747
180"
747. It34
(Tabla m i n u & )
Appendix
452 T AB L E LI (continued)
222O
747
251
747
loOD
764
238"
764
260"
764
208'
771
226'
771
CHCH=
N I
Systematic Tables of Pyrazolones and their Derivatives
453
T A B L E LI (continued)
233"
771
145' (dec.) i 7 1
I
CH,
'Jon,171"
772, 1668
(dcc.)
171"
772
162"
1069
224'
1110
CHCH=
OCH, I
454
Appendix
TABLE LI (continued)
258"
1213
258"
1214
156"
1328
239"
1328
1616
178" (dec.)
1668
287" (dec.)
1670
Systematic Tables of Pyrazolones and their Derivatives
455
TABLE L I (continued)
I-C,H,OC,H, I N-f
,
II1.p.
Reference
141"
776
248O
776
165'
78
194'
776
0
4-C2H,0C,H4 1488
I
CzH6
I-
I CBHs 30
29,30,31
(Tuble confinued)
456
Appendix
TABLE LI (conlinmd)
204"
748
219O
749
293' (dec.)
241
194'
765
258'
755
Systematic Tables of Pyrszolonea and their Derivatives
457
TABLE LI (contiad) 31.p.
Heference
236'
755
212O
755
260"
755
193"
755
257 O
382
Appendix
458
TABLE LI (continued) R
M.P.
Reference
OH -/-CH=CHCH=CHCH=
-
382
ti""" S
C H 3 - P CH=CHCH=CHCH=
382
N
382
L
139' (dec.)
775
139"
775
242'
775
225"
776
0 CN
(Table cotuinued)
Systematic Tables of Pyrazolones and their Derivatives
459
T A B L E LI ( c o n l i n d ) - __ __ R
__
~
-
~
-
y
I
CH,N
.
____
M.p.
Reference
169"
776
-
776
185"
1519
230' (dec.)
1519
242
1472
240" (dec.)
1519
-
382
216'
763
154'
1129
S
CHCHdHCHdH-
(Table continued)
460
Appendis
T A B L E LI (eonlinued)
178'
1129
171'
1129
-
1129
150'
1129
TTO
1129
210Q
1129
167"
1129
146'
1129
194O
1129
218'
1129
155'
1129
2203
1129
Systematic Tables of Pyrazolones and their Derivatives eu
8 n
$2
m" 0) cu
M
*
w
I
I 4i
L?
n w
I
j
I i
i
21
s;"
u
i
i3
I I
i
I 1
i
I I
..
n
5
461
Appendix
462
4
2
0
I ?
cv
Q,
Systematic Tables of Pyrazolones and their Derivatives
v)
t-
a
n El dl
x
X
x
x"
4
483
464
Appendix
0
v)
10 C-i m
m
A
8
8
0 CI
V
A
Systematic Tables of PyrazoloneR and their Derivatives
*
e 4 El
*
El
me4
m-
ei N
2 m
d u
4
It
x
V
Q
rn
/\
16+C.H.C.
2-
20
486
Appendix
466
El El -#
eJ El
m^
3 m
El m
g
* El
Systematic Tables of Pyrazolones and their Derivatives
*
-
El
N
!-I
Po-
0
rn
N rn
e
u3 Po El
$!
i=( \< a
&
x
467
Appendix
468
c.l n Q,
0)
LEl
B
I
Systematic TableR of Pyrazolones and hheir Derivatives
2 m
tt-
In
rg
0
o
8
(0
2
W W ,-I
m A
3?
8
8
It-
W t-
0
0
3?
u
V
*
?i Y
4 Y
L3 *
3
0
4.
4
469
470
Appendix m
x
a e4n
a0
3
01
N
n
rg
tt-
N
n
t-
L-JI
v) N d
N
x"
V
@
-V
x"
--u
Systematic Tables of Pyrazolones and their Derivatives
47 1
e4
5: s?
z
co"
e4 n
0-4
l-
0
2A
e 1.3
2
I
I d =\
0
472
Appendix
tf-$
r(
tt-
I
1 2
J!0-UII
A
Systematic Tables of Pyrazolones and their Derivat,ives
3
1-
16*
*
t1-
L1 fc-
CI 1 1--
473
Appendix
474
7 0.1
X
X
X
u II
m
/\ z
x"
-0
uI1
N
Systematic Tables of Pyrazolones and their Derivatives
l
In CD t-
I
475
lp
d
I+
1!: &
, a
b
8
iI I
X
476
Appendix
I-
?!
m
8
Systemat.ic Tables of Pyrazolones and their Derivatives
-
m
El
a3:
Y
&
8 /\
/\
(=J
6 x"
i)
s
V
g
7;-0
d u
477
Appendix I3 4 10
0
0 W tl
s
u
s
0
Systematic Tables of Pyrazolones and t,heir Derivatives
:: 10
3
8 w
B?
V
8
0
x"
0
1 0
tW
479
480
Appendix
10 cn L-
V
k 0 cn L-
Systeiiiat,icTables of I'yrezolones atid tlioir Derivat,ivev
u2
(D I ' .
*
m ea m
kz
V
481
NaOOC HOOC HBC2OOC CH3 H5C,00C CH3 CH3 HOW NaOOC H,XOC CH3 CH3 CH, CH3 CH3 CH3 CH, CH3
Supramine Yellow 3G Polar Yellow 5G Diamond Red G Acid Alizarin Flarin CF Metachrome Red 5G Pigment F a s t Yellow G
4-Arylazo-3-pyrazolin-5-onea. Dyes
Tartrazine Kiton Yellow S Wool Silk Yellow G F a s t Light Yellow G Saturn Yellow GG Wool Fast Yellow 3GL Xylene Light Yellow Normal Ycllow 3GL Pyrazole Orange Acid Alizarin Bordeaux B Anthralan Yellow G Eriochrome Red B
T A B L E LIV.
2-C'H3-4-?ia0,S-6-C1C,H, CH,
C6H5
4-Na03SC,H4 4-HO,SC,H, 4-Xa0,SC6H, 4-Pia03SC,H, 2-CI-4-Na03S-6-CH3C,H2 2-Cl-5-Na03SC,H3 2,.i-CI,-4-Na03SC6HI, 4-H03SC,H4 4-9a0,SC6H,
I
2-CH3-5-(CH,COh')C,H, 4-(4-CH3C~H,8020)C~H4 Z-HO-4-KOZC6Hd 2-NaOOCCeH, Z-H0-3-HO~S-5-CIC,H2 2-HOOC-5-HO3SCeH3
4-Na03SC6H4 CBH6 2-ClCsH4 CsH5 2-CH3-3-ClCGH3 CeH5 4-?;a03SC6H4 2,4-(CH3)2-5-HO$iX&HZ 4-C4-(2-NaOOC-4-HOC,H,S=~')C,H,]U,H, 2-HO-3-h'aO3S-5-C1CsH2 4-Sa03SC6H4 Z-HO-4-Sa0,S-1-C,oH, CZH,
x
Y
2 -.
b
%r:
References 1. A d a m and Fawthrop, U.S. Pat., 2,584,314 (1952). 2. Adiokes, J. prukt. Claem., 161, 271 (1943). 3. Adickes and Meister, Ber., 68, 2191 (1935). 4. Adler and Adler, Fr. Pat., 697,881 (1930). 5. Adler and Adler, U.S. Pat., 1,954,909 (1934). 6. Aggarwal and Ray, J. Chena. Soc., 1930, 492. 7. Ahuja and Dutt, J . Indian Chem. Soc., 28, 12 (1951). 8. Airan and Wagle, .J. Univ. Bombay, 23, Pt. 3, Sci. A'o., Sect. A, No. 36, 29 (1954); through Chem. Abstracts, 49, 10272 (1955). 9. Ajello, Guzz. chim. ital., 70, 401 (1940). 10. Albanese, auzz. chim. ital., 60, 21 (1930). 11. Albertson, Tullar, King, Fishburn and Archer, J. Am. Chem. SOC.. 70, 1150
(1948). 12. Allan and Xizik, Che~n.Lidy, 47, 380 (1953); through Chem. Abstracts, 49, 207 (1955). 13. Allen, U.S. Pat., 2,550,661 (1951). 14. Allen, Buniess, Edens, Kibler and Salminon, J. Org. Chem., 14, 169 (1949). 15. Allen and Byers, U.S. Pat., 2,772,282 (1956). 16. Allen and Laakso, U.S. Pat., 2,646,421 (1953). 17. Amill, Rev. facultk sci. univ. Istanbul, Ser. A, 5 , 237 (1940); through Clwm. Abstracts, 37, 3091 (1943). 18. AmM, Rev. fucultk sci. uiiiv. Istuitbul, 14, 44 (1949); through Chem. Abatracta, 45, 611 (1951). 19. Amll, Rev. facultt! sci. univ. Istatcbul, 14, 90 (1949); through Chem. Abstracts, 44, 6414 (1950). 20. Amill, Rev. facultt! sci. m i v . Istanbul, 14, 311 (1949); throughchem. Abstracts, 45, 611 (1951). 21. Amill, Rev. faculG sci. uwiv.Istairbul, 14, 317 (1949); throughclbem. Abstracts, 44, 6853 (1950). 22. Amill and Kapuano, Phurm. Acta IIelv., 26, 379 (1951); through Chem. Abstracts 47, 5933 (1953). 23. AmAl and Kapuano, Pharm. Acta Helv., 28, 87 (1953); through Claem. Abstracts, 48, 5181 (1954). 24. AmAl and Ozgor, Rev. jaculG sci. univ. Istuptbul, 16, 7 1 (1951); through Chm. Abstracts, 46, 4534 (1952). 25. Amorosa, Aim. chim. jurm. (Suppl. to Farm. itd.), May 1940, 54; through Chem. Abstracts, 34, 7910 (1940). 26. Anderson, U.S. Pat., 2,107,321 (1938). 483
484
References
27. Angelhi and Riartani, A ~ I H Chinr. . (Rome), 45, 64 (19%); through C k n r . Abstracis, 50, 1649 (1956). 28. Angelini and Martani, A ~ HChirrr. . (lioar~),45, 156 (1955); through Chem. Abstracts, 50, 3416 (1956). 29. Anish, U.8. Pat., 2,450,390 (1948). 30. Anish, Brit. Pat., 620,482 (1949). 31. Anish, U.S. Pat., 2,496,843 (1950). 32. Anish, U.8. Pat., 2,504,615 (1950). 33. Anish and Hensley, U.S. Pat., 2,500,111 (1950). 34. Anker and Cook, J. C k m . SOC.,1944, 489. 35. Anschutz, Ann., 306, 1 (1899). 36. Arbuzov, zhur. Priklrul. Khim.,23, 866 (1950); through Cheni. Abstracts, 45, 10105 (1951). 37. h e n s and Tiang, Idonesicz J. Xat. Sci., 109, 215 (1953); through Chem. Absbracls, 49, 8305 (1955). 38. Armatys, U.S. Pat., 2,454,766 (1948). 39. Armento, U.S. Pat., 2,607,769 (1952). 40. Armento, U.S. Pat., 2,746,955 (1956). 41. Arndt, Loewe and Ergener, Rev. facult6 sci. univ. Istanbul, 13, 103 (1948); through C k m . Abstracts, 43, 579 (1949). 42. Asahha, Yanagita and Sakurai, Ber., 70, 227 (1937). 43. Asano, Arata and Ban, J. Pharm. Soc. Japan, 61, 220 (1941); through rhem. Abstracts, 45, 1518 (1951). 44. &tin and Riley, J. C h m . SOC.,1934, 844. 45. Astre and Aubouy, Bull. soc. chim. France, [3], 35, 856 (1906). 46. Astre and Vidal, Bull. soc. chin&.France, [4], 9, 309 (1911). 47. Astre and Vidal, Bull. SOC. chim. Prance, [4], 9, 836 (1911). 48. Auboy, Bull. soc. chim. France, [4], 3, 388 (1908). 49. Aumiiller, Hoimor, Kimmig, Meyor-Rohn, Junghahns and Pohl, Cltem. Ber.. 85, 760 (1952). 50. Austrian Pat., 86,136; through Chem. Abstracts, 17, 1305 (1923). 51. Auwers and Bbhr, J . prakt. Chem., 116, 65 (1927). 52. Auwers, Dannehl and Boennecke, Ann., 378, 210 (1911). 53. Auwers and Dersch, Ann., 462, 104 (1928). 54. Auwers, h-iemeyer, Prfauss and Daniel, J . prakt. Chem., 110, 153 (1925). 55. Awe and Stog, ~aturwissensc?M~terr, 37, 452 (1950). 56. Axford, Brit. J. Phot., 103, 88 (1956). 57. Axford and Kendall, Science and Inds. phot., 24, 467 (1953); through Clwrn. Abstracts, 48, 484 (1954). 58. Bachem, Therap. Momtah., 23, 588 (1909). 59. Bachmann and Cronyn, Chem. of Penicillin, 1949, 849. 60. Backman and Heisey, J. Am. Chem. Soc., 71, 1985 (1949). 61. Backer and Meyer, Rec. Iran chim., 45, 82 (1926). 62. Backer and Meyer, Rec. traw. chim., 45, 428 (1926). 63. Badia, Span. Pat., 219,066 (1955). 64. Bahner, U.S. Pat., 2,425,270 (1947). 65. Baker, J. Chem. Soc., 1950, 1302. 66. Barnes, U.S. Pat., 2,753,371 (1956). 67. Barr, Salminen and Weissberger, J. Am. Chem. SOC.,73, 4131 (1951). 88. Basel and Kaufler, Ger. Pat., 524,638 (1926).
References
485
H a m and L)w Giipta, .I. IdiaiL CIN5m. SOC.,15, 160 (1938). I3ttsi1 and Bas Uupta, J . I t i d ~ u rC'hem. ~ Soc., 18, 167 (1941). Battegay and Wolff, BzdZ. soc. Chi?& France, [4], 33, 1481 (1923). Havely, US. Pat., 2,411,915 (1946). Bavely, U S . Pat., 2,435,550 (1948). Bayer, Heidirckerhoff and Schindhelm, Ger. Pat. 614,327 (1936). Bayer, Heidieckerhoff and Schindhelm, U.S. Pat., 2,073,600 (1937). Bayley, U.S. Pat., 2,425,503 (1947). Beech and Mendoza, Brit. Pat., 560,892 (1944). Beech and Mondoza, Brit. Pat., 587,334 (1947). Beech and Mendoza, U.S. Pat., 2,429,600 (1947). Beech and Mendoza, Brit. Pat., 594,925 (1947). Beech and Mendoza, J3rit. Pat., 624,247 (1947). Beersmans, Brit. Pat., 626,470 (1949). Belg. Pat., 447,815 (1942). Belg. Pat., 445,959 (1942). Belg. Pat., 450,727 (1943). Bell, J . Chern. SOC.,1941, 285. Be11 and Lindwall, J . Org. Chem., 13, 647 (1948). Benary, Ber., 66, 924 (1933). Benary and Schmidt, Ber., 57, 517 (1924). Benary and Schwoch, Ber., 57, 332 (1924). Bernstein, S t e a m , Shaw and Lott. J . A m . Chem. Soc., 69, 1151 (1947). Bertho and Nussel, Ann., 457, 278 (1927). Betti and Mundici, Gazz. chim. ital., 36, I, 178 (1906). Beyer and Stehwein, Arch. Pharm., 286, 13 (1953). Biquard and Grammaticakis, Bull. SOC. chim. Prance, [5], 8, 246 (1941). Birkhofer and Storch, Chem. Ber., 86, 32 (1953). Blaise and Cornillot, C m p t . rend., 178, 1186 (1924). Blanc, Ann. pharna. ji-am., 10, 40 (1952). Bockmiihl, Med. u. Chem. Abhandl. med-chem. ForscAungsskitten I . G . Furbenind., 3, 294 (1936); through Chem. Abstracts, 31, 5796 (1937). 100. Bockmuhl and Ebert, U.S. Pat., 1,056,881 (1913). 101. Bockmiihl and Krohs, Ger. Pat., 611,003 (1935). 102. Bockmiihl and Krohs, U.S. Pat., 2,068,790 (1937). 103. Bockmiihl and Krohs, Can. Pat., 374,822 (1938). 104. Bockmiihl, Krohs, Racke and Windisch, U.S. Pat., 2,193,788 (1940). 105. BockmuN and Stein,Ger. Pat., 617,237 (1935). 106. Bockmiihl and Stein, Ger. Pat., 644,647 (1937). 107. Bodendorf, Mildner and Lehman, Ann., 563, 1 (1949). 108. Bodendorf and Popelak, Ann., 566, 84 (1950). 109. Bodendorf and Popclak, Arch. Pharm., 285, 310 (1952). 110. Bodendorf and ICaaf, Ann., 592, 26 (1955). 111. Bodendorf and Raaf, ~4aneiwaitteZ-Forsch.,5, 695 (1955). 112. Bodendorf and Ziegler, Arch. Pharm., 288, 500 (1955). 113. Bodendorf and Ziegler, Ber., 88, 1197 (1955). 114. Boesc, U.S. Pat., 2,165,445 (1939). 115. Boese, Ind. Erg. Chem., 32, 16 (1940). 116. Boeseken and Roos, Rec. trav. chim., 58, 58 (1939). 117, Bohme and Mundlos, Chem. Ber., 86, 1414 (1953). 69. 50. 51. 72. 73. 74. 75. 76. 77. 78. 79. 80. 81. 82. 83. 84. 85. 86. 87. 88. 89. 90. 91. 92. 93. 94. 95. 96. 97. 98. 99.
486 118. 119. 120. 121. 122. 123. 124. 125. 126. 127. 128. 129. 130. 131. 132. 133. 134. 135. 136. 137. 138. 139. 140. 141.
References Bohme, Freimuth and Mundlos, C h i n . Ber., 87, 1661 (1954). Boie and Wulzinger, U.S. Pat., 2,323,193 (1944). Boivin, Gagnon, Renaud and Bridgeo, Can. J. Chem., 30, 994 (1952). Bonfils, Hardouin and Delbaue, Compt. rend. soc. bioZ., 148, 881 (1954). Bonhote and Schmid, U.S. Pat., 1,991,312 (1935). Boniger, Brit. Pat., 266,533 (1926). Borsche and Lewinsohn, Ber., 66, 1792 (1933). Borsche and Manteuffel, Ann., 505, 177 (1933). Borsche and Mankuffol, Ann., 512, 97 (1934). Borsche and Mantcuffel, Ann., 526, 22 (1936). Bossard and Reding, U.S. Pat., 2,545,872 (1951). Bottcher and Bauor, Ann., 568, 227 (1950). Bottcher and Stoltz, Ger. Pat., 489,363 (1923). Bougealt, Cattelain and Chabrier, Compt. rend., 225, 876 (1947). Bouvealt, BdZ. ~ O C .chim. Fmnce, [3], 4, 647 (1890). Bouvier, U.S. Pat., 2,499,265 (1950). Bouvier, U.S. Pat., 2,525,518 (1950). Bowman, J. Chem. Soc., 1950, 322. Bowman and Fordham, J. Chem. Soc., 1952, 3945. Boyd and Walter, U.S. Pat., 2,631,991 (1953). Bradshaw, Stephen and Weizmann, J . Chem. Soc., 107, 803 (1915). Brady and Porter, J. Chem. SOC.,1933, 840. Brandstatter, 2.p l y s i k . Chem., 192, 260 (1943). Braun, Anton, Haensel, Innische, Michaelis and Teuffert, Ann., 507, 14
(1933). 142. Breig, Glietenberg and Xussler, Ger. Pat., 927,705 (1956). 143. Breusch and Keskin, Rev. facultd sci. univ. Istanbul, 11, 24 (1946); through Chem. Abstracts, 40, 5400 (1946). 144. Brit. Pat., 13,383 (1907). 145. Brit. Pat., 15,759 (1912). 146. Brit. Pat., 27,485 (1907). 147. Brit. Pat., 28,583 (1910). 148. Brit. Pat., 118,448 (1917). 149. Brit. Pat., 146,870 (1920). 150. Brit. Pat., 198.615 (1922). 151. Brit. Pat., 210,669 (1923). 152. Brit. Pat., 219,653 1923). 153. Brit. Pat., 243,758 1924). 154. Brit. Pat., 245,107 1924). 155. Brit. Pat., 255,434 1925). 150. Brit. Pat., 389,310 1933). 157. Brit. Pat., 414,684 1934). 158. Brit. Pat., 433,053 1935). 159. Brit. Pat., 452,868 1936). 160. Brit. Pat., 458,417 1936). 161. Brit. Pat., 468,375 1937). 162. Brit. Pat., 468,916 1935). 163. Brit. Pat., 486,747 1938). 164. Brit. Pat., 500,284 1939). 165. Brit. Pat., 502,664 1939).
Referencee 166. Brit. Pat., 556,266 (1943). 167. Brit. Pat., 563,279 (1944). 168. Brit. Pat., 578,014 (1946). 169. Brit. Pat., 578,964 (1946). 170. Brit. Pat., 684,255 (1947). 171. Brit. Pat., 592,614 (1947). 172. Brit. Pat., 595,703 (1947). 173. Brit. Pat., 597,131 (1948). 174. Brit. Pat., 597,414 (1948). 175. Brit. Pat., 600,739 (1948). 176. Brit. Pat., 602,170 (1948). 177. Brit. Pat., 604,921 (1948). 178. Brit. Pat., 611,320 (1948). 179. Brit. Pat., 619,373 (1949). 180. Brit. Pat., 621,642 (1949). 181. Brit. Pat., 632,832 (1949). 182. Brit. Pat., 632,944 (1949). 183. Brit. Pat., 633,790 (1949). 184. Brit. Pat., 633,824 (1949). 185. Brit. Pat., 636,681 (1950). 186. Brit. Pat., 637,404 (1950). 187. Brit. Pat., 646,123 (1950). 188. Brit. Pat., 646,597 (1950). 189. Brit. Pat., 648,364 (1951). 190. Brit. Pat., 648,715 (1951). 191. Brit. Pat., 649,856 (1951). 192. Brit. Pat., 649,674 (1951). 193. IJrit. Pat., 654,495 (1951). 194, Brit. Pat., 665,627 (1952). 195. Brit. Pat., 666,258 (1952). 196. Brit. Pat., 666,578 (1952). 197. Brit. Pat., 673,623 (1952). 198, Brit. Pat., 676,270 (1952). 199. Brit. Pat., 678,492 (1952). 200. Brit. Pat., 681,376 (1952). 201. Brit. Pat., 686,614 (1953). 202. Brit. Pat., 688,225 (1953). 203. Brit. Pat., 688,850 (1953). 204. Brit. Pat., 694,204 (1953). 205. Brit. Fat,., 695,534 (1953). 206. Brit. Pat., 697,056 (1953). 207. Brit. Pat., 6'39,976 (1953). 208. firit. I'at., 701,140 1953). 209. Brit. Pat., 701,241 1953). 210. Brit. Pat., 702,016 19.54). 211. Brit. Pat., 706,370 1954). 212. Brit. Pat., 707,337 1954). 213. Brit. Pat., 708,681 1954). 214. Brit. Pat., 709,495 1954). 315. Brit. Pat., 717,000 1954).
481
488
References
Brit. Pat., 723,719 (1955). Brit. Pat., 727,199 (1955). Brit. Pat., 727,528 (1955). Brit. Pat., 730,036 (1955). Brit. Pat., 730,384 (1955). Brit. Pat., 730,647 (1955). Brit. Pat., 732,820 (1955). Brit. Pat., 737,019 (1955). Brit. Pat., 741,002 (1955). Brit. Pat., 743,907 (1956). Brit. Pat., 744,441 (1956). Brit. Pat., 744,829 (1956). Brit. Pat., 746,944 (1956). Broadbent and Chu, J . Am. C i ~ mSOC., . 7 5 , 226 (1953). Brodie and Axelrod, J . Pharmacol. and Exptl. Therap., 99, 171 (1950). Brodie, Axelrod, Shore and Udenfriod, J. Biol. Chem., 208, 741 (1954). Brodie, Lowman, Burns, Lee, Chenkin, Goldman, Weiner and Stoele, Am. J. Med., 16, 181 (1954). 233. Brodie, Yu, Burns, Chenkin, Paton, Stecle and Gutman, Proc. SOC.Exptl. Biol. Med., 86, 884 (1954). 234. Bromberg and Vilemkii, Zhur. PrikEarl. Khim., 22, 128 (1949); through Chem. Abstracts, 44, 465 (1950). 235. Urooker and Cressman, U.S. Pat., 2,398,999 (1946). 236. Brooker, Keyes, Sprague, Van Dyke, Van Lare, Tan Zandt and White, J . Am. Chem. SOC.,73, 5326 (1951). 237. Brooker, Keyes, Spragtie, Van Dyke, Van Lare, Van Zandt, White, Cressman and Dent, J. Am. Chem. Soc., 73, 5332 (1951). 238. Brookor and White, U.S.Pat., 2,493,747 (1950). 239. Brooker and Whito, U.S. Pat.., 2,526,632 (1950). 240. Brooker and White, U.S. Pat., 2,646,409 (1953). 241. Brooker and White, U.S.Pat., 2,730,964 (1956). 242. Brooker, White and Keyes, Brit. Pat., 006,141 (1948). 243. Brown, Chemistry of Penicillin, 1949, 473. 244. Brown, Graham, Vittum and Weissborger, J. Am. C b m . SOC.,73,919 (1951). 245. Brown, Hukins, Le Fevre, Northcott and Wilson, J. Chom. Soc., 1949, 2812. 246. Brown and Partridgo, J. Am. Chem. SOC.,67, 1423 (1945). 247. Bruner and Moser, Monaatsh., 53 and 54, 682 (1929). 248. Biichi, Ammon, Lieberherr and Eichenberger, H d u . Chim. Actu, 36, 75 (1953). 249. Buchi, Meyer, Hirt, Hunziker, Eichenberger and Lieborhorr, Helv. Chim. Acta, 38, 1670 (1955). 250. Buchi, Ursprung and Lauener, Helv. Chim. Acta, 32, 984 (1949). 251. Buck, Feadey, Meanoclr and Patley, Lancet, 266, 225 (1954). 252. Budziarek, Drain, Macrae, McLean, Il'ewbold, Seymour, Spring and Stansfield, J. Chem. Soc., 1955, 3158. 253. Buehler and Mosor, Brit. Pat., 709,401 (1954). 254. Buohler and Zickendraht, U.S. Pot., 2,727,032 (1955). 255. Biilow, Ber., 40, 3787 (1907). 256. Riilow, Ber., 42, 4429 (1909). 257. Bulow and Bozenhardt, Ber., 43, 234 (1910). 216. 217. 218. 219. 220. 221. 222. 223. 224. 225. 226. 227. 228. 229. 230. 231. 232.
References 258. 259. 260. 281. 262. 283. 264. 265. 266. 267. 268. 269. 270. 271. 272. 273. 274. 275. 276. 277. 278. 279. 280. 281. 282. 283. 284. 285. 286. 287. 288. 289. 290. 291. 292. 293. 294. 295. 296. 297.
489
Biilow and Bozenhardt, Ber., 43, 551 (1910). Biilow and Buaso, Ber., 39, 3861 (1906). Biilow and Engler, Ber., 51, 1246 (1918). Bulow antl Dick, Ber., 57, 1281 (1924). Biilow and Haas, Ber., 43, 2647 (1910). Biiluw and Hecking, Ber., 44, 467 (1911). Biilow arid Schauf, Ber., 41, 2355 (1908). Burger, “Medicinal Chemistry”, New York, Interscience Publishers Inc., 1951, Vol. 1, p. 191. Burkat, Zhur. ObshcheZ, Khim., 26, 1379 (1956);through Chem. A6stracts, 50, 14432 (1956). Burns, Rose, Goodwin, Reichental, Hornung and Urodie, J. IlibarmczcoE. ExptE. Thrup., 113, 481 (1955). Burr and Rowe, J. SOC.Dyers and Colourists, 44, 205 (1928). Burrus and Powell, J . Am. Chem. SOC.,67, 1468 (1945). Calderon and Perez, Anales usoc. quim. Argentina, 28, 5 (1940); through Chem. Abstracts, 34, 5430 (1940). Calken, Can. Pat., 269,837 (1927). Cafiolari, Boll. chim. j a m . , 50, 763 (1911); through Chem. Abstracts, 6 , 1809 (1912). Canals and Peyrot, Compt. rend., 206, 1179 (1958). Cannon and Whiddun, * J . Org. Ghem., 17, 685 (1952). Carribre, Aria. chim., 17, 38 (1921);through Chem. Abstracts, 16, 2478 (1922). Carson, U.S. Pat., 2,443,226 (1948). Cason, Rinehart and Thornton, J. Org. Clwm., 18, 1594 (1953). Caaoni, Boll. sci. fucoltd chim. itid. Bologna, 9, 4 (1951); through Ghem. Abstructs, 45, 7353 (1951). Casoni, Boll. sci. fucoltd chim. ird. Bologna, 9, 9 (1951); through Chem. Abstracts, 45, 7355 (1951). Casoni, Boll. sci. fucoltd chim. ind. BoEogrm, 9, 13 (1951); through Chem. Abstracts, 45, 7355 (1951). Caaoni, auzz. chim. ital., 85, 404 (1955). Cavallini, Massarani, Mazzucohi and Ravenna, Farm. x i . e. tec., 7, 397 (1952); through Chem. Abstracts, 47, 8015 (1953). Chargaff and Magasanik, J. A m . Chem. SOC.,69, 1459 (1947). Charonnat and Delaby, Compt. rend., 189, 850 (1929). Chattaway and Adair, J. Chem. SOC., 1932, 1022. Chattaway and Ashworth, J. Chem. SOC.,1933, 475. Chattaway and Ashworth, J. Chem. Soc., 1933, 1389. Chattaway and Ashworth, J. C h m . Soc., 1933, 1624. Chattaway and Ashworth, .J. Chem. SOC.,1934, 1985. Chattaway, Ashworth antl Grimwade, J . Chem. SOC.,1935, 117. Chattaway and Humphrey, J . Chem. A’oc., 1927, 1323. Chattaway and Humphrey, J . Chem. Soc., 1927, 2133. Chattaway and Humphrey, J. C l ~ mSoc., . 1927, 2793. Chattaway antl Lye, Proc. Roy. Soe. (Lortdoti),A135, 282 (1933). Chattaway and Parkes, J. Chem. Soc., 1935, 1005. Chattaway and Strouts, J. Chem. Sot., 125, 2423 (1924). Chatterjee and Das, J . Am. Chem. SOC.,41, 707 (1919).
490
References
298. Chatterjeo and Ghosh, Proc. A s i d i c SOC. BenguE, 15, CXXXII (1919); through Chem. Abslruct.9, 14, 1674 (1920). 299. Checchi, Papini and Ridi, Guzz. chim. itul., 85, 1160 (1955). 300. Checchi, Ridi and Papini, Aim. chim. (Rome), 44, 522 (1954); through Clwm. Abstracts, 49, 14774 (1955). 301. Checchi, Ridi and Papini, Cfuzz. chim. itul., 85, I558 (1955). 302. Cherchi, Guzz. chirn. ital., 50, 120 (1920). 303. Chi and Yang, J. A m . Chem. SOC.,58, 1152 (1936). 304. Chrzczonowicz, Zwierzak and Achmatowicz, Zeazyty ,Vuuk. Polite&. Zrddz., No. 2, Clam., KO. 1, 97 (1954); through Chem. Abstruch, 49, 14742 (1955). 305. Ciusa, Atti e relazioni uccad. pugliese sci., 6, 3 pp. (1948); through Chem. Abstracb, 43, 2316 (1949). 306. Ciaisen and Haase, Ber., 28, 35 (1895). 307. Clemo and Holmes, J. Chem. Soc., 1934, 1739. 308. Clemo, Holmes and h i t c h , J. Chem. SOC.,1938, 753. 309. Clemo and Welch, J. Chem. Soc., 1928, 2621. 310. Coan and Becker, J . A m . C k m . SOC.,76, 501 (1954). 311. Cocker and Turner, J. Chem. Soc., 1940, 57. 312. Coffey and Everatt, Brit. Pat., 405,003 (1934). 313. Cohn and Kolthoff, J . Biol. Chem., 148, 711 (1943). 314. Cobs and Hamilton, J. A m . Chenc. s'oc., 68, 2588 (1946). 315. Collins, Robinson and Fry, Brit. Pat., 674,356 (1952). 316. Combs, Hebbelynck and Ledrut, Bull. soc. chim. France, 1953, 315. 317. Conrad and Zart, Ber., 39, 2282 (1906). 318. Cook and Heilbron, Chemistry of Penicillin, 1949, 921. 319. Cornforth, Chemistry of Penicillin, 1949, 688. 320. Cornforth and Cornforth, J. Chem. Soc., 1953, 93. 321. Cousin, Bdl. soc. chim. France, [4], 5, 121 (1909). 322. Crippa and Uaracci, Gazz. chim. ital., 70, 389 (1940). 323. Crippa and Caracci, Guzz. chim. ital., 71, 574 (1941). 324. Crippa and Cuarneri, IZ Furmuco (Pavia), Ed. Sci., 10, 691 (1955);through Chem. Abstracts, 50, 8605 (1956). 325. Crippa and Guarneri, Guzz. chim. ital., 85, 199 (1985). 326. Crippa and Long, Buzz. chim. ita2., 61, 99 (1931). 327. Crippa, Long and Perroncito, Guzz. chim. ital., 62, 944 (1932). 328. Crippa and Maffei, Guzz. chin,. i d . , 72, 97 (1942). 329. Crippa and Perroncito, auzz. chim. ital., 66, 649 (1936). 330. Cudkowicz and Jacobs, Lancet, 264, 223 (1953). 331. Curatolo, Worn. med. militare, 101, 283 (1951); through Chem. Abstracts, 47, 2169 (1953). 332. Currie, Lancet, $63, 15 (1952). 333. Curtius, J. p u k t . Chem., 85, 37 (1912). 334. Curtius, J. prukt. Chem., 85, 137, 393 (1912). 335. Curtius and Bleicher, J . prukt. Chem., 107, 86 (1924). 336. Curtius and Bourcart, J. p u k t . Chem., 91, 39 (1915). 337. Curtius and Cockel, J. prukt. Chem., 83, 279 (1911). 338. Chrtius and Jay, J. prukt. Chem., 39, 43 (1889). 339. Curtius and Miihlhausser, J . prukt. Chem., 125, 211 (1930). 340. Cusmano, G u n . chim. ital., 69, 594 (1939). 341. Cusmano, Gazz. chim. itul., 70, 86 (1940).
References
49 1
Cusmano, Gazz. chim. ihl., 81, 380 (1951). Cusmano and Sprio, Uazz. chim. W.,82, 191 (1952). Cusmano and Sprio, Gazz. chim. it& 82, 373 (1952). Cusmano and Tiberio, Gazz. cArn~.itnl., 78, 896 (1948). Cusmano and l'iberio, Uazt. c h n . itad., 80, 229 (1950). Dahlen and Friedrich, U.S. Pat., 2,153,615 (1939). Dains and Brown, J. Aim. Cheiii. ~Soc.,31, 1148 (1909). Dains and Daily, Univ. of Kansas S c i . Bulletin, 19, 215 (1930); through Ghem. Abstracts, 26, 427 (1932). 350. Dains, Malleis and Meyers, J. Am. C?wm.LSOC.,35, 970 (1913). 351. Dains, O'Bricn and Johnson, J . A m . C k m . SOC.,38, 1510 (1916). 352. Dakin, Biocbm. J., 11, 79 (1917). 353. Darapsky, Borger and Seuharie, J. prczkt. Ciiein., 147, 145 (1936). 354. Dayton, Gonip. rend., 237, 185 (1953). 355. De, Quurt. J . I?rclzai~Clirrn. Soc., 3, 30 [ 1926). 356. De and n a t t a , S c i e c~o d~ Cullure, 11, 150 (1945); through Clwn. Abstracts, 40, 1804 (1946). 367. De and Dutt, J . Indictrr C/ierir. Sue., 5, 459 (I!#%). 358. De and Dutt, J. I m f h Ghem. Soc., 7, 473 (1950). 359. De and ltakshit, J . Iwliuti Chem. Soc., 13, 509 (1936). 360. Decombo, Airri. chiin., 18, 81 (1932); through Clwm. Abstracts, 27, 2136 (1933). 361. Deeving, Gray, l'latt anti S t t q ~ h e n . J. ~ ~Ctwn. ~ ~ , SOC.,1942, 239. 362. DeGraef, Lodrut and I'ornbes, Hull. SOC. chirn. Belges, 61, 331 (1952); through Chem. Abstracts, 47, 12363 (1933). 363. Dolaby and Charomat, Compt. rend., 190,59 (1930). 364. Demers and Lynn, J. A m . Pharm. Assoc., 30, 327 (1941). 365. Dent and Rrooker, TJ.S. Pat., 2,533,206 (19.50). 366. Desai, J . Chem. Soc., 1932, 1088. 366a. UeStevens, Halamandaris, W'enli arid Dorfinan, J . Am. Chem. Soc., 81, 8292 (1959). 367. Devoto, Atti accad. Liiicei, 21, 819 (1935); through CAem. Abstracts, 30, 3290 (1936). 368. Dewar and King, J. Chem. Soc., 1945, 114. 369. Dickey, Byers and McNrtlly, U.S. Pat., 2,439,798 (1948). 370. Diels and Reese, Ann., 511, 168 (1934). 371. Dihlmann, Natun~se?i,qchften, 40, 510 (1953). 372. Dimroth and Schweizer, Ber., 56, 1375 (1923). 373. Dinets, Sovet. Med., 1940, S o . 18, 26; through C h m . Abstructs, 38, ,5967 (1944). 374. Dittmar and Putter, Ger. Pat., 929,567 (1956). 375. Dittmar, Putter and Suckfull, U.8. Pat., 2,734,052 (1956). 376. Dmowska and Weil, RocznikiCiLem., 18, 170 (1938);through Chem. Ahtracts, 33, 592 (1939). 377. Dohrn and Diodrich, U.S. Pat., 2,345,385 (1944). 378. Dohrn and Hamann, Ger. Pat., 697,801 (1940). 379. Dohrn, Hamann and Hillemann, Gcr. Pat., 703,678 (1941). 380. Domenjoz, Intern. Record of Med., 165, 467 (1952). 381. Donatelli, Scarinci and Di Carlo, Arch. sci. biol. (Italy), 39, 257 (1955); through Chem. Abstrach, 50, 14971 (1956). 342. 343. 344. 345. 346. 347. 348. 349.
492 382. 383. 384. 385. 386. 387. 388. 389. 390. 391. 392. 393. 394. 395. 396. 397. 398. 399. 400. 401. 402. 403. 404. 405. 406. 407. 408. 409. 410. 411. 412. 413. 414. 415. 416. 417. 418. 419. 420. 421. 422. 423. 424. 425.
References Donnael and Uhys, Brit. Pat., 628,837 (194Y). Dornow and Roberg, Aim., 578, 94 (1952). Dornow and Theis. Attn., 581, 219 (1953). Dorough and McQoeen, U S . Pat., 2,310,943 (1943). Douglas, Parkinson and Wakefield, Brit. Pat ., 603,753 (1948). Douris, Compt. rend., 218, 514 (1944). Dox, J . Am. Chem. SOC.,54, 3674 (1932). Dreyfuss and Gaspar, U.S. Pat., 2,677,683 (1954). Drozdov and Chorntzov, J. Gen. Chem. (U.S.S.R.), 5, 1736 (1935); through Chem. Abstracts, 30, 3432 (1936). Druey and Schmidt, Helv. Clbim. Acta, 37, 1828 (1954). Drummond and Atlas, S. Ajrimn Med. J . , 27, 997 (1953). Dubsky, Winter and Mareth, Pub.jacu.Zt6 sci. univ. Masaryk, 271, 1 (1939); through Chem. Abstracts, 33, 7230 (1939). Dubsky and M'introva, Colkclioti Czech. Chena. Commun., 11, 526 (1939). Ducommun and I)ucommun-Lehmann, Rev.Can. biol., 11, 298 (1952). Duffin and Kendall, J. Chem. SOC.,1954, 408. Dufin and Kendall, J. Chem. Soc., 1955, 3969. Duffin and Kendall, Brit. Pat., 743,505 (1956). Duquhois, J. p k a m . chim., 26, 353 (1937). DuquBnois, Rev. facultk sci. univ. Istanbul, 6 , 116 (1941); through ClLenz. Abstructs, 37, 3.560 (1943). Duqubnois, Bull. soc. chim. E'mnce, 1946, 425. Duquhois and Amal, Bull. aoc. chim. France, [5], 9, 718 (1942). Dutch Pat., 71,532 (1953). Dutt, Proc. Lee& Phil. Lit. Soc., ~Sci.Sect., 1, 113 (1926); through Clmn. Abstracts, 21, 1118 (1927). Dutt, J . Indian Chem. Soc., 28, 533 (1951). Dutt and Dharam, Proc. Indian Auzd. S c i . , 10A, 55 (1939); through Chmwk. Abstracts, 34, 425 (1940). Dutt and Goswami, J . I d i a t t CIwm. Soc., 30, 275 (1953). Dutt and Mukherjee, J. Indian Chem. Soc., 30, 272 (1963). Eccles, J . Ant. Chem. Boc., 24, 1050 (1902). Eckmann, U.S. Pat., 1,347,083 (1920). Edwards and Kendall, U.S. Pat., 2,531,973 (1950). Efimovtlky and Rumpf, Bull. SOC. chim. France, 1954, 1401. Efros and Davidenkov, Zhur. ObslwheZ Khim., 21, 2046 (1951); tlirough C h m . Abstrach, 46, 8100 (1952). Eichwede and Fischcr, U.S.Pat., 1,766,813 (1930). Eisenberg and Keenan, J. Asmc. Omd Agr. ClLem., 27, 177 (1944). Eisenberg and Keenan, J. Assoc. Oficial: Agr. Chem., 27, 458 (1944). Eisenstaedt, J. Org. Chem., 3, 153 (1958). Eisner, Elvidge and Linstead, J. Chem. Soc., 1950, 2223. Eisnor, Elvidge and Linstead, J . Chem. ~Yoc.,1951, 1501. Eistcrt, Clwm. Ber., 80, 47 (1947). Ekstrand, Aetrc Chem. Scatrd., 2, 294 (1948). Emerson, U.S. Pat., 2,194,201 (1940). Emerson, Seacham and Beegle, J. Org. Clam., 8, 417 (1943). Emerson and Beegle, J. Org. Ckem., 8, 429 (1943). Emerson and Beegle, J . Org. CIam., 8, 433 (1943).
References
493
Emerson and Kelly, J. Org. Cllem., 13, 532 (1948). Emerson, Kelly, Beacham and Beagle, .I. Org. Chem., 9, 226 (1944). Emery, J. Am. Pharm. Assoc., 16, 932 (1927). Emery and Palkin, J. Am. Chem. SOC.,38, 2166 (1916). Erdos and Surii, Magyar Qydgysrirazlud. Tarsaaay lhesitijje, 10, 424 (1934); through Chem. Abstracts, 29, 1816 (1935). 431. Erlenbach ant1 Sieglite, Brit. Pat., 693,249 (1953). 432. Ershov, Lyashenko and Grachev, Anilinokra.9ochayu Prom., 4, 306 (1934); through Chem. Abstracts, 28, 7538 (1934). 433. Eury, Bull. sci. pharmacology, 15, 384 (1908); through C h m . Abetrack, 3,
426. 427. 428. 429. 430.
1862 (1909). 434. Fabre, Bull. soc. chim. France, [a], 33, 791 (1923). 435. Fabre and Mach, Schweiz. Med. Wochchr., 81, 473 (1951); through Cherr~. Abetracts, 45, 9731 (1951). 436. Palkof, Witten and Gehauf, U.S. Pat., 2,678,260 (1954). 437. Fand and Spoerri, J. Am. Ckmn. SOC.,74, 853 (1952). 438. Fargher and Fiirness, J. Chem. Soc., 107, 688 (1915). 439. Felix and Heckendorn, U.S. Pat., 2,495,243 (1950). 440. Felix, Heckendorn, Reich and Oesterlein, U.S. Pat., 2,496,386 (1950). 441. Felix, Heckendorn and Widmer, U.S. Pat., 2,478,185 (1949). 442. Felix, Heckendorn and Widmer, U.S. Pat., 2,570,052 (1951). 443. Fenton and Jones, J. Cltem. Soc., 79, 91 (1901). 444. Feofilaktov, Null. mad. sci. U.R.S.S., Clime sci. chim., 1941, 521; through Chem. Abstracts, 37, 2348 (1943). 445. Feofilaktov arid Ivanova, Xhur. O b ~ h h e Khim., i 25, 125 (1955); through C h m . AbRtracts, 50, 1781 (1956). 446. Fichter, J . p m k i . Chem., 74, 297 (1906). 447. Fichter and de Montmillon, Helw. Chim. Actu, 5, 256 (1922). 448. Fichter, Jetzer and Leepin, Ann., 395, 1 (1913). 449. Fierke and Barclay, U.S. Pat., 2,503,717 (1950). 450. Fischer and Knoevenagel, Ann., 239, 194 (1887). 451. Fischer and Niemann, 2.physiol. CfLein., 146, 196 (1925). 452. Fischer and Reinecke, 2. phpiol. Chem., 258, 243 (1939). 453. Fleischauer, Nuller and Schultis, U.H. Pat., 2,384,419 (1945). 454. Flett, U.S. Pat., 2,469,378 (1949). 455. Forrest, Fuller and Walker, J. Chem. SOC.,1948, 1501. 456. Forster and Muller, J. Chem. SOC.,95, 2072 (1909). 457. F o w , Hieulle and Bass, Compt. reid., 178, 811 (1924). 458. Franchi, I1 Fannaco (Pavia), E d . Sci., 10, 628, 1955; through Chena. Abstracts, 50, 8611 (1956). 459. Franzen, J. p u k t . Chem., 76, 205 (1907). 460. Freedman, U.S. Pat., 2,076,714 (1937). 461. Freedman and Sherndal, U.S. Pat., 1,877,166 (1932). 462. Fr. Pat., 44,843 (1935). 463. Fr. Pat., 362,465 (1906). 464. Fr. Pat., 377,130 (1907). 465. Fr. Pat., 378,486 (1907). 466. Fr. Pat...403,919 (1908). 467. Fr. Pat., 661,224 (1928). 468. Fr. Pat., 734,776 (1932).
494 469. 470. 471. 472. 473. 474. 475. 476. 477. 478. 479. 480. 481. 482. 483. 484. 485. 486. 487. 488. 489. 490. 491. 492. 493. 494. 495. 496. 497. 498. 499. 500. 501. 502. 603. 504. 505. 506. 507, 508. 509. 510. 511. 512.
References
Fr. Pat., 769,572 (1934). Fr. Pat., 771,486 (1934). Fr. Pat., 820,328 (1937). Fr. Pat., 822,533 (1937). Fr. Pat., 830,124 (1938). Fr. Pat., 848,896 (1939). Fr. Pat., 966,764 (1950). Fr. Pat., 983,719 (1951). Fr. Pat., 988,579 (1951). Freri, Atti Accad. Lincei, 22, 264 (1935); through Chem. Abstracts, 30, 6375 (1936). Freri, Atti VCorqr. Xatl. chim. pura applicah, Rome, 1935, F’t. I, 361 (1936); through Chem. Abstracts, 31, 3914 (1937). Freri, Gazz. ckim. ital., 66, 23 (1936). Fresenius, Arzneimittel-Forsch., 1, 128 (1951). Fricke, Z. anorg. Chem., 253, 173 (1947). Frohlich and Schneider, U.S. Pat., 2,307,399 (1943). Frohlich and Schneider, U.S. Pat., 2,357,393 (1944). FrOhlich, Schneider and Zeh, U.S. Pat., 2,348,463 (1944). Froning, U.S. Pat., 2,362,477 (1944). Froning, Brit. Pat., 581,305 (1946). Fry and Kendall, U.S. Pat., 2,388,963 (1945). Fuhrmann arid Degering, J. A m . Chem. SOC.,67, 1245 (1943). Fujimara, Bull. Inst. Chem. Researrh, Kyoto Univ., 30, 53 (1952); through Chem. Abstracts, 47, 9561 (1953). Pujinaga, Jap. Pat., 8048 (1954). Fujieawa et al., Jap. Pat., 3086 (1953). Furnya, BIujazawa and Komuro, J . SOC. Sci. Phot. J u p a ~ 12, , KO. 1, 8 (1949); through Cltem. Abstracts, 46, 2936 (1952). Furuya and Uono, ,7. Soc. Sci. I’hot. Japan, 13, No. 4, 27 (1951); through C k m . Abstmacts, 46, 7447 (1952). Gaglio, Reurnatisanto, 6, Suppl. N o . 2, 32 (1954); through Chem. Abstracts, 49, 1973 (1955). Gagnon, Boivin and Boivin, Can. J. Research, 28B, 720 (1956). Gagnon, Boivin, Hoivin and Craig, Can. J. Chem., 30, 52 (1952). Gagnon, Boivin, Boivin and Jones, Can. J . Chem., 29, 182 (1951). Gagnon, Boivin and Chisholm, Can. J. Chem., 30, 904 (1952). Gagnon, Boivin and Gigntre, Can. J . Chern., 29, 328 (1951). Gagnon, Boivin and Jones, CUH.J. Research, 27B, 190 (1949). Gagnon, Boivin and Jones, Can. J . Research, 28B, 34 (1950). Gagnon, Boivin and Laflamme, Can. J. Chem., 34, 530 (1956). Gagnon. Boivin, JIacDonald and Yoffe, Can. J . Chem., 32, 823 (1954). Gagnon, Boivin ancl Paquin, Cmt. J . Clwn., 31, 1025 (1953). Gagnon. IJoivin and Tremhlay, G ~ H J..Chem., 31, 673 (19.53). Chgnon. Nolin and Jones, Cali. .J. Cltem., 29, 843 (1981). Gagnon, Savard, Gaudry anti Hichardson, Caw. J. Research, 25B, 28 (1947). Gailliot and Debarre, U.S. Pat., 2,744,912 (1956). Gardner, Smith, \Venis and Lee, J . Org. Chenz., 16, 1121 (1951). Gasper, C.S. Pat., 2,470,769 (1949). Gault ancl Thirode, Compt. rend., 150, 1123 (1910).
References Gault and Wendling, Compt. rend., 199, 1052 (1934). Gault and Wendling, Uull. aoc. ckim. Frutice, r5], 3, 53 (1936). Gault and Wendling, BULLSOC. china. Fmrbce, [ 5 ] , 3, 369 (1936). Gautier, Compt. rend, soc. biol., 80, 672 (1917). Gebauer, Ger. Pat., 590,174 (1933). Goller, U.8. Pat., 856,413 (1932). Gerbaux, Bull. BOC. chim. Belges, 58, 498 (1949). Ger. Pat., 91,504; through Bed. I, 24, 277. Ger. Pat., 92,009; through Bed. I, 24, 277, 278. Ger. Pat., 131,537; through J. Chem. SOC.,82, 730 (1902). Ger. Pat., 176,954; through J. C h m . SOC.,92, 363 (1907). Ger. Pat., 184,850 (1906). Ger. Pat., 189,842 (1907). Ger. Pat., 193,632 (1907). Ger. Pat., 203,753 (1907). Ger. Pat., 206,637 (1907). Ger. Pat., 208,593 (1908). Ger. Pat., 214,716 (1908). Ger. Pat., 217,555 (1909); through J . Che7n. Soc., 98, 340 (1910). Ger. Pat., 217,558 (1909); through J . C'kam Soc., 98, 340 (1910). Gar. Pat., 227,013 (1908). Ger. Pat., 233,068 (1910). Ger. Pat., 238,256 (1910). Ger. Pat., 238,373 (1910). Ger. Pat., 243,197 (1910). Ger. Pat., 248,887 (1911). Ger. Pat., 249,626 (1911). Ger. Pat., 254,487 (1911). Uer. Pat., 254,711; through J . Chem. Soc., 104, 401 (1913). Ger. Pat.. 259,577 (1911). Ger. Pat., 261,081 (1911) and 261,082 (1912). Ger. Pat., 264,287; through J . Chem. Soc., 100, 93 (1914). 545. Ger. Pat., 299,610 (1917). 546. Ger. Pat., 313,320. 547. Ger. Pats., 360,421; 364,034; 364,032; 367,081.. 548. Ger. Pat., 360,423. 549, Ger. Pat., 360,424. 550. Ger. Pat., 469,285 (1923). 551. Ger. Pet., 479,348 (1927). 552. Ger. Pat., 484,763 (1927). 553. Ger. Pat., 496,647 (1928). 554. Ger. Pat., 499,823 (1923). 555. Ger. Pat., 582,806 (1933). 556. Ger. Pat., 675,881 (1939). 557. Ghosh, J. Iicdiari Chem. Soc., 13, 86 (1936). 558. Ghosh, .I. I t i f f i w t c!hein. soioc., 15, 89 (1938). 559. Ghoeh and Das Gupta, J . Indian Chem. Soc., 16, 63 (1939). 560. Giacalono, GUZZ.chirn. itaE., 67, 460 (1937). 561. Giacalone and IX Maggio, GUZZ.chim. itnl., 09, 122 (1039).
513. 514. 515. 616. 517. 618. 619. 520. 521. 522. 523. 524. 525. 526. 527. 528. 529. 530. 531. 532. 533. 534. 535. 536. 537. 538. 539. 540. 541. 542. 543. 544.
495
496
References
362. Ciiiltironi and C:rwsi, Boll. SOC.it&. b i d . ,?p(>r.,28, 1580 (1932); through Clwm. Abstrctx, 47, 4487 (1953). 563. Uidvani, Kon and Wright, J . Chenr. Soc.., 1932, 1027. 564. Gilman, Tolman, Yeoman, \Voods, Shirley and Avakiwi, J. An). Clwtu. SOC., 68, 426 (1946). 565. Ginzburg, Zhur. ~ b s h c / r K e ~h h r i . , 23, 1504 (1953); through Chem. Abstracts, 48, 1776 (1954). 566. Ginzburg, Zhur. Obahchei Kkim., 23, 1677 (1953); through Chem. Abatracts, 48, 13685 (1954). 567. Ginzburg, Zhur. Obahchd Khim., 23, 1890 (1953); through Chem. Abstracts, 49, 1049 (1955). 568. Ginzburg and Joffe, Bhur. Obshchei Rhim., 25, 1739 (1955); through Chem. Abstrmta, 50, 5645 (1956). 569. Ginzburg. Toffe and Mel’nikova, Zhur. Obshchei Khim., 25, 358 (1955) through G l ~ e mAbalracts, . 50, 2552 (1956). 570. Ginzburg and ’l’erushkin, Bhur. Obshchei Khim., 23, 1049 (1953); through Chem. Abstracta, 48, 8221 (1954). 571. Girard, U.S. Pat., 2,256,261 (1941). 572. Giua, Gazz. chim. i d . , 46, 11, 61 (1916). 573. Giua, Gazz. chim. itd.,54, 204 (1924). 574. Giuliano and Stein. I1 k’armclco (Priuia),Ed. sci., 11, 3 (1956); through Chem. Abstracts, 50, 12986 (1956). 575. Glas.., Vittiim and IVoissbcrgw, U.S. Pat., 2,455,170 (1948). 576. Glassman, U.S. Pat., 2,514,236 (1950). 577. Glassman and Sarfrtb, Brit. Pat., 633,218 (1949). 578. Glauert and Mann, J. Chmn. Soc., 1952, 2401. 579. Gluck, Brit. Pat., 566,520 (1945). 580. Cluck, U.S. Pat., 2,387,115 (1945). 581. Godtfredsen and I’angedal. A c h Chent. Scmid., 9, 1498 (1985). 582. Gold and Piopenbrink, Ger. Pat., 842,978 (1952). 583. Gol’mov, Zhur. Obshchei Khim., 20, 1881 (1950); through C h m . Abstracts, 45, 2411 (1951). 584. Gomez, Rev. aead. cienc. Madrid, 31, 563 (1934); through Chem. Abstracts, 29, 5422 (1935). 585. Goodings and Rogers, U.S. Pat., 2,410,604 (1946). 586. Goodings and Rogers, U.S. Pat., 2,437,465 (1948). 587. Goodman and Gilman, “The Pharmacological Basis of Therapeutics”, New York, The Macmillan Company, 1955, 2nd Edn., pp. 318, 322. 588. Coryainova and Gurevich, F a r W i y a i Fannakol., 1937, No. 11, 60; through Chem. Absfracts,34, 6192 (1940). 589. Gottler, Ber.. 48, 1765 (1915). 590. Grachev, ~nvodakayah b . , 11, 154 (1945); through Chem. Abstracts, 40, 1106 (1946). 591. Graham, U.S. Pat., 2,G94,703 (1954). 592. Graham, U.S. Pat., 2,710,871 (1955). 593. Oraham, U.S.Pat., 2,725,291 (195.5). 594. Graham, Porter and Weissberger, J. Am. Chem. SOC.,71, 983 (1949). 595. Graham, Reckhow md Weiasberger, J . Am. C h m . Soc., 76, 3993 (1954). 596. Graham and Wekbarger, U.S. Pat., 2,691,659 (1954). 597. Green and Williams, Lancet, 264, 575 (1953).
Heferences
497
598. Gregory, U.S. Pat., 2.472,581 (1949). 599. Gresham, Jansen, Shaver, Bankert and Kiedorp, J. Ant. Cham. Soc., 73, 3168 (1951). 600. Urothaus and Dains, J. Am. Chem. SOC.,58, 1334 (1936). 601. Grotowsky, Ger. Pat., 514,421 (1926). 602. Uuha and Roy-Choudhury, J. Indian Chem. SOC.,5, 149 (1928). 603. Gulinov, Gurarii and Pashchenka, Ituas. Pat., 46,924 (19M). 604. Gundermann, Ann., 578, 48 (1952). 606. Gunn, &wart. J . Phurm.and Phurmacol., 6, 643 (1933). 606. Gunst, U.8. Pet., 2,686,178 (1954). 607. Gurevich, Farmatsiya, 1940, No. 2-3, 5 ; throiigh Chem. ADstraets, 34, 6191 (1940). 608. Yusev and Beiles, Zlbur. OOskel~iKhim., 21, 1971 (1951); through C ' h p r r t . rlbstracts, 46, 3442 (1952). 609. Gusev and Beiles, zhur. A?tui!.Khim., 7, 219 (1962); thrc~itghChenf.A b s t m c f n , 47, 1532 (1953). 610. Gutsche and Hillman, J. Am. Chein. SOC.,76, 2236 (1964). 611. Gysling and Schwarzenbach, Helv. Chim. dcta, 32, 14x4 (1949). 612. Haas and Kraft, Arzneimitlel-Forscl., 4, 219 (19.54). 613. Hafliger, U.S. Pat., 2,674,600 (1954). 614. Hiifliger, U.S. Pat., 2,700,670 (1955). 615. Hafliger, U.S. Pat., 2,700,671 (1955). 616. Hagenbach and Gysin, Ezprieittin, 8, 184 (1952). 617. Halberkann and Fretwurst, Arquiuos. orsf.biol. ( S r r o I'rctclo), 11. 149 (1940): through Chem. Abstrach, 36, 101 (1942). 618. Halberkann and Fretwurst, 2.physiol. C h i n , , 285, 97 (ltf.30). 619. Hallman, Ringhardtz and Fischer, Phew. I k r . , 90, 547 (1957). 620. Hamer, J. Chem. SOC.,1951, 294. 621. Hanford, U.S. Pat., 2,495,000 (1950). 622. Hanhart, U.S. Pat., 2,709,166 (1955). 623. Harradence and Lions, J . Proc. Roy. SOC. A'S. ll'des. 72,233 (1939);through Chem. Abetrack, 33, 5856 (1939). 624. Harrington, U.S. Pat., 2,366,616 (1945). 626. Harrison and Twitchell, Brit. Pat., 691,475 (1953). 626. Hartmann, Kaegi and Isler, U.S. Pat., 1,886,481 (1932). G27. Hasselquist, Arkiu Kemi, 7, 121 (1954); through Chem. ADafrocta, 49, 826n (1955). 628. Hauser and Lindsay, J. Org. CILem., 22, 4H2 (1957). 629. Hauser, Shivcrs and Skell, J. Am. Chenz. Soc., 67, 400 (1945). 630. Hayashi, Oshima, Tsuruoka and Seo, Rept. Japan =lusoc. . 4 h . Sri., 17, 30 (1942); through C h m . Abslraets, 44, 3258 (1950). 631. Hazelton, "using and Holland, J . Pharmucol. ortd E.rptZ. Tiierap.. 109, 38; (1953). 632. Heiduschka and Rothacker, J. prakt. Chem., 80, 289 (1909). 633. Heiduschka and Rothacker, J. prakt. C h m . , 84, 533 (1911). 634. Heimbach, U.S. Pat., 2,584,349 (1952). 635. Hoin and Pierce, J . Am. Chem. Soc., 77, 4107 (1955). 636. Helferich and Koster, Ber., 56, 2088 (1923). 637. Hellmann and Opitz, C k m . Bet., 89, 81 (1956). 638. Hellmann and Schumrtcher, Chem. Ber., 89, 95 (1966). 17+C.H.C.
20
498
References
639. Hemming and Kuzell, Antibiotics and Chemotherapy, 3, 634 (1953). 640. Herin and King, H w t . Sci. a d Tech. ( I I ) , 1, 126 (1954). 641. HCM and Reynolds, U.S. Pat., 2,691,589 (1954). 642. Heime, K h . 1Vochsclw., 31, 522 (1953). 643. Henry and Dehn, J. Am. Chetn. SOC.,71, 2297 (1949). 644. Hepner and Fajersztejn, Hull. soc. chirn. 1.51, 4, 834 (1937). 645. Hermaim, Streitnoif and Yehrle, (ier. Pat.. 505,799 (19%). 646. Heseltine and Brookrr, U.S. Pat., 2,719,131 (1953). 647. Heymons and Eohland, Ber., 66, 1054 (1933). 648. Heyntt and Hensel, Ger. Pat., 938,143 (1956). 649. Heyna and Hensel, ( k r . Pat., 938,145 (1956). 650. Heyna, Hcilael and Schuniacher, <:car. Pat., 940,482 (1936). 651. Heyna, Hensel and Schiiorrenberg, Ger. Pat., 925,121 (1955). 652. Heyna and Schumacher, U.S. Pat., 2,657,205 (1953). 653. Hill and Black, Am. Clkent. J . , 33, 292 (1905). 654. Hiller and Strauss, Die Mefl~zirtisclt.e,1954, 613; through Chern. Absfrcrcts, 18. 8406 (1954). 655. Himmelbauer, J. prukt. Clmn. [2], 51, 532 (1895). 656. Hindermann, U.S.Pat., 2,472,109 (1949). 657. H i n d e m a m , U.S. Pat., 2,505,244 ( 1950). 658. Hmdemann, U.S. Pat., 2,517,312 (1950). 659. Hindermann, U.S. Pat., 2,544,087 (1951). 660. H m t , MacUeth and Traill, Pruc. Roy. Irish had., 37B, 47 (1923); throiigh C h m . Abs6rack7, 19, 2931 (1925). 661. Hoffmann, U.S. Pat., 1,531,286 (1925). 662. Homeyer, US.Pat., 2,630,437 (1953). 663. Horlin, Linke arid Rlossmur., Deut. Arch. kZh. &led., 201, 690 (1953). 664. Hovorku and Yykora, C u l l e c t i o ~Czech. Chetn. C o m i w t i . , 11, 70 (1939). 666. Hovorka and Sykora, Co&.xtku/t Czech. Chem. C O m T ~ k U l l . , 11, 124 (1939). 666. Hovorka and Sifrkora,Chem. listy, 35, 89 (1941); through Chem. Abstracts, 37, 3023 (1943). 667. Howland, U.S. Pat., 2,458,780 (1949). 608. Hrynakowski and Smoczkiewiczowa, RoczntkiChem., 17,165 (1937);through Chem. Abstracts, 31, 6096 (1937). 669. Hrynakowski and Szmyt, 2. physik. Chem., A181, 113 (1937). 650. Huebner and Link, J . Am. Che7n. SOC.,67, 102 (1945). 671. Huebner and Link, J. Am. Chmn. Soc., 72, 4812 (1950). 672. Hugounenq, Florence and Couture, Bull. SOC. chim. b~ol.,7, 58 (1925). 673. Humphlett, Woks and Hauser, J . Am. Cbem. SOC.,70, 4020 (1948). 674. Hung. Pctt., 135,432 (1949). 675. Hunig, Ann., 574, 106, 112 (1951). 676. Hunter and Sundholm, V.S. Pat., 2,510,696 (1950). 677. Huntress and Olsen, J . Am. CIwm SOC.,70, 2856 (1948). 678. Hurwitz and Thompson, Arch. Ophthalmol., 43, 712 (1950); A m .I. Oplblhtrlmol., 34, 130 (1951). 679. Huston, Sell and Brigham, J . Am. Chem. Soc., 55, 3407 (1933). 680. Hiittel. Buchole and Jochum, C h m . Ber., 88, 1577 (1958). 681. Imanishi, J . Chenz. Phys., 18, 1307 (1950). 682. Ingraffia, Guzz. chim. itnl., 64, 778 (1934).
References
499
683. Ioffe and Khavin, Zhur. Obshchei Khzm., 14, 882 (1944); through Chem. Abstracts, 40, 2847 (1946). 684. Ioffe and Khevin, Zhur. Obahchei Khzm., 17, 522 (1947); through Chem. Abstracts, 42, 903 (1948). 685. Ioffe end mavin, Zhur. Obshchei Khirn., 17, 528 (1945); through Cham. Abstracta, 42, 1933 (1948). 686. Ionescu, Bd. 8oc. stunk CZuj, 3, 381 (1927); throrigh Chem. Abstrncts, 22 1353 (1928). 687. Ionescu and Georgescu, Bull. YUC. chim. France, 141, 41, 881 (1927). 688. Jonoscu and Georgescu, Bull. soc. chim. fr’ruttce,[4], 41, 1514 (1927). 689. Ionescu and Popescu, BUZZ.soc. ehint. Frame, [a], 51, 1215 (1932). 690. Iseki, Sugiura, YaRunaga and Kakaaina, Ber., 74, 1420 (1941). 691. Ishihara and Ito, .Tap. Pat., 2665 (1950). 692. Ishikawa, Kano and Katayarna, J. Phurm. Soc. J n p m , 74, 138 (1954); t,hhrough Ohem. Abstracta, 49, 1707 (19.55). G93. Itano, J . Phann. SOC.Jaymi, 71, 540 (1951); through CIma. Abstmcb, 46, 4532 (1952). 694. Ttano, J. Phnrm. Soe. Japan, 71, 1456 (1951); through Clteirr. Abstrrtcts, 46, 5095 (1952). 6!t:’. Itano, , J . Plcnr~it.Sot.. Jupott, 75, 441 (195.5); through C / K ! / / Abstrmts, . 50, 2552 (1956). 6!)6. Tto, J . Pharni.SOC. Jupan, 76, 167 (1956);through C’Aenr. Absfrcicts, 50, 13939 ( 1956). 6’37. Tto. , I . l’liwm. 8oe. Juputt, 76, 820 (1!)56); through C’hent. Ab8/rad8, 51, 1148 (195i). 698. I t n , . J . I’hamn. SOC.Japan, 76, 822 (1956); through Chevt. Ahstruct.v, 51, 1149 (1957). 690. Jacobs, “Heterocyclic C‘ompoiin(ls”,Scw York. .Tolin \Yilry nncl Sons, Inc., 1957, Yo]. 5, p. 163. 700. .JecobRen and .Tost, Ann., 400, 19.5 (1913). 701. Jamer and Tanselow, P S A Jourttnl, Sect. 13. l’/tol. Sci. Tcdr., Scr. [I. I. 77 (1954); through Chem. Ahstrtrtts, 48, 112238 (1954). 702. Jamicka, Hiszpanska. ant1 \Veil, Roczrtikt Clwrit ., 18, 138 ( 1938); throiiph Cheni. Abstructa 33, 592 (1939). 703. .Jennen, U.H. Pat., 2,611,698 (1952). 704. Jennen, U.S. Pat., 2,619,419 (1952). 70.5. Jennen, U.S. Pat., 2,672,417 (19.54). 706. Jennnn and Michaelis, U.S. Pat., 2,485,260 (I!)>()). 5 0 7 . Jennnn and Michaelis, U.S. Pat., 2.544,422 (1951). 708. Jennings, LJ.S.Pat., 2.397,865 (1946). 709. Jnnnings, U.S. Pat., 2,397,867 (1946). 510. Jsnnings, U.8. Pat., 2,422,680 (1947). 7 11. Jcnnings R n d Jliddleton. U.R. Pat., 2.200,‘3?4 (1!)40). 712. .JcruiingN, JIiirray and ivhitc, U.S. Pat., 2,397,864 (1‘346). 7 13. Jenscn, Acta Chern. Scni~I.,9, 1498 (19.55). 514. Jensen, Dansk Ti&. Farm., 15, 299 (1941); t.hrough Chrijt. -4Datrncts, 36, 5593 (1942). 5 15. Jensen and Frietliger, l<$. Drmeke IYidert~knb.Selxkab, Mutk -fjJ8. Medrl., 20, ?To. 20, 1 (1943); through Chem. Abstrarts, 39, 2068 (1945). 716. Jensen and Hensen, Acta Chem. rScn~ul.,6, 196 (1952).
500
References
John, Swiss Pat., 183,197 (1936). John and Ottawa, J . prakt. Chew., 131, 346 (1931). John and Schmit. J . prakt. Chem., 132, 15 (1931). John and Schmit, J . prakt. Chem.. 133, 177 (1932). .Johnson, J. Chem. Soc., 1947, 1626. Johnson, J. Soc. Chem. Znd., 40, 176 (1921). Johnston, U.S. Pat., 2,017,815 (1935). .Jollw, 1Vardlewort.hand 1Vootl. Brit. Pat ., 650,850 (1951). .Jones, J. .4m. Chent. ,C;oc.. 78, 159 (l!Li6). .riistoni and Ihsco, Onzz. chi717. itid., 68, 59 (1038). Kaiser, U.S. Pat., 2,490,967 (1949). Kanao, .Tap. Pat., 5682 (1953). Kano, J . Phnrm. Soc. Jnpnrr, 73, 383 (1983); tlirougli CRetrt. Ahaqtrocts,48, 3342 (1954). 730. Kano and Makisiimi, I‘ltarwr. B i d . (Japrrt), 3, 250 (1953); through ChenL. Abstract.?, 50, 12061 (1956). 731. Karrer, Dieckmann and Haebler, Helv. Chitti. Ada, 7, 1031 (1924). 732. Karrer and Hershberger, Helv. Chim. Acta, 17, 1014 (1934). 733. Kartaschoff and Merian, U.S. Pat., 2,855,973 (1051). 734. Kaufrnann, 2. Angew. Chem., 40, 69 (1927). 736. Kaufmann, US.Pat., 2,109,445 (1938). 736. Kaufmann, Ger. Pat., 660,620 (1938). 737. Kaufmann, Ger. Pat., 668,387 (1938). 738. Kaufmann, U.S. Fat., 2,234,866 (1941). 739. Kaufmann, Ger. Pat., 735,266 (1943). 740. Kaufmann, Huang and Biickrnann, Bet., 7 5 , 1236 (1!142). 741. Kaufmann, Huang, Schnitz, Hultcnschmidt mid BiiclrmanIi, Be,., 75, 1214 (1942). 742. Kaiifrnann and Liepe, Rer., 56, 2514 (1923). 743. Kaufmann and Ritter, Arch. Pharm., 267, 212 (1929). 744. Kaufmann, Seher and Pankoke, Arch. Phrni., 284, 330 (19.51). 745. Kaufmarin and Steinhoff, Arch. PJuzrm., 278, 437 (1940). 746. Keller and Zwwicller, U.S. Pat., 2,462,403 (1949). 747. Kendall, Brit. Pat., 519,895 (1940). 748. Kendall, Brit. Pat., 555,936 (1943). 749. Kendall, US. Pat., 2,397,013 (1946). 750. Kendall. nrit,. Pat., 650,911 (1951). 751. Kendall, Brit. J . Phot., 100, 56 (1953); ttiroiigh (‘hein. Abs/rncta, 47, 3157 (1953). 752. Kendall and Collins, U.S. Pat., 2,213,986 (1940). 753. Kendall and Doyle, Brit. Pat., 595,785 (1947). 754. Kendall and Doyle, Brit. Pat., 604,217 (1948). 755. Kendall and Doyle, U.S. Pat., 2,518.476 (1950). 756. KendaU and DuRm, Brit. Pat., 679,677 (1952). 757. Kendall and Duffin, Brit. Fat., 679,678 (1952). 758. Kendall and Duffin, U.S. Pat., 2,704,762 (1955). 759, Kendall and Duffin, Brit. Pat., 730,489 (1955). 760. Kendall and Duffi, U.S. Pat., 2,726,248 (1955). 761. Kendall and Duffin, Brit. Pat., 749,192 (1966). 762. Kendall, Dufin and Axford, U.S. Pat., 2,688,024 (1954). 717. 718. 719. 720. 721. 722. 723. 724. 725. 726. 727. 728. 729.
References
50 1
Kendall and Edwards, C.S.Pat., 2,412,816 (1946). Kendall and Frye, Brit. Pat., 544,647 (1942). Kendall and Fry, U.S.Pat., 2,385,815 (1945). Kendall and Fry, Brit. Pat., 577,260 (1946). Kendall and Fry,Brit. Pat., 585,780 (1947). KendaIl and Fry,Brit. Pat., 585,781 (1947). Kendall and Fry, U.S.Pat., 2,427,911 (1947). Kendall and Fry, U.S. Pat., 2,457,823 (1949). Kendall, Fry and Morgan, Brit. Pat., 672,291 (1952). Kendall and Majer, U.S. Pat., 2,369,355 (1945). Kendall and Majer, J . Chem. Soc., 1948, 687. Kersley and Mandel, Lancet, 263, 1046 (1952). Keyes and Brooker, U.S. Pat., 2,533,472 (1950). Keyes and Brooker, U.S. Pat., 2,611,696 (1952). Khromov-Boueov, Zhur. Obshchei Khim., 25, 136 (1955); through Chem. Abstracts, 49, 8257 (1955). 778. Kidd, Robins and Walker, J. Chem. SOC.,1953, 3244. 779. Kiely and Stickney, Proc. StuflMeetings N a y 0 Clink, 28, 341 (1953). 780. Kirby, U.S.Pat., 2,396,275 (1946). 781. Klebanskii and Lemke, J . Applied Clten?. (U.S.S.R.),8, 269 (1935); through Chent. Abstracte, 29, 6891 (1935). 782. Kleene, U.S. Pat., 2,512,251 (1950). 783. Konak and Szasz, Weiii.Chem.-Ztg.,46, 266 (1944); through Chem. Abstracts, 40, 6063 (1946). 784. Kitamurit and Ishiwatari, J . Phurm. SOC.Japan, 57, 1011 (1937); through Chem. Abstracts, 32, 2534 (1938). 785. Kitarnura, J . Phurrn. Sac. Japan, 58, 445 (1938); through Chem. Abstracts, 32, 6648 (1938). 786. Kitamura, J . €’harm. SOC.Japan, 58, 613, 676 (1938); through Chem. Abstracts, 32, 8416 (1938). 787. Kitamura, J. Hiarm. SOC. Japai~,59, 84 (1939); through Chern. Abstracts, 33, 3791 (1939). 788. Kitamura, J . Pharm. Soc. J a p a ~ 60, , 45 (1940); through Chem. Abstract.9, 34, 3737 (1940). Japan, 61, 19 (1941);through Chem. Abstracts, 35, 789. Kitamura, J. I’harrn. SOC. 4770 (1941). . 61, 33 (1941);through Chem. Abstracts, 35, 790. Kitamura, J. l’harm. L ~ O CJupan, 3633 (1941). 791. Kitamura, .I. Pharm. SOC. Japan, 61, 94 (1941); throiigh Chem. Abstracts, 36, 473 (1942). 792. Kitntnura, Kept. Japan. Assoc. Adaanrernent h‘ci., 16, 541 (1942); through Chem. dhstract.9, 44, 3489 (1950). 793. Kitarnt1i-a and Sunagawa, J . f%rm. SOC.Jupan, 60, 60 (1940). 794. Kitamura and Srmagawa, J . Phnrm. Sor. .Japan, 60, 65 (1940). 795. Kitamura and Siinagawa, J . Phurm. SOC..lapin, 61, 26 (1941); through Chem. Abstracts, 35, 4770 (1941). 796. Kitamura, Bull. Inst. Phys. Chem. Research ( T o k y o ) ,20, 848 (1941); through Chem. Abstracts, 43, 8386 (1949). 797. Kleigcr and Hugos, U.S. Pat., 2,671,021 (1954). 798. Klosa, Arch. Pharm., 286, 391 (1953).
763. 764. 765. 766. 767. 768. 769. 770. 771. 772. 773. 774. 775. 776. 777.
17*
502
References
799. Klosa, Arch. €'harm., 288, 217 (1955). 800. Klosa, Arch. Pharm., 288, 545 (1955). 801. Knevel and Miller, Proc. X.Dakota A d . Sci., 7, 39 (1953);through Chem. Abstracts, 48, 13685 (1954). 802. Knight, US.Pat., 2,384,749 (1945). 803. Knight, Brit. Pat., 708,427 (1954). 804. Knight, Brit. Pat., 706,857 (1954). 805. Knorr, Ber., 16, 2597 (1883). 806. Knorr, Ber., 17, 546 (1884). 807. Knorr, Ber., 17, 2032 (1884). 808. Knorr, Ber., 20, 1107 (1887). 809. Knorr, Ann., 238, 137 (1887). 810. Knorr, Ber., 28, 701 (1895). 811. Knorr, Ber., 28, 706 (1895). 812. Knorr, Ber., 28, 714 (1895). 813. Knorr, Ber., 29, 249 (1896). 814. Knorr and Blank, Ber., 17,2049 (1884). 815. Knorr and Biilow, Ber., 17, 2057 (1884). 816. Knorr and Duden, Ber., 25, 759 (1892). 817. Knorr and Geuther, Ann., 293, 55 (1896). 818. Knorr and Klotz, Ber., 20, 2545 (1887). 819. Knorr, Pemsel and Morentz, Ber., 37, 3520 (1904). 820. Knorr and Pschorr, Ann., 293, 49 (1896). 821. Knorr and Stolz, Ann., 293, 58 (1896). 822. Knorr and Taufkirch, Ber., 25, 768 (1892). 823. Knott, Brit. Pat., 614,471 (1948). 824. Knott, U.S. Pat., 2,515,878(1950). 825. Knott, J . C k m . SOC., 1951, 3033. 826. Kocwa, Bull. intern. d. polon. sci., Cluaee sci. math. nut., 1936A, 766; through Chem. Abstracts, 31, 1803 (1937). 827. Kocwa, Bull. intern. d. polon. sci., Chsse sci.math. nut., 1936A,382, 390; through Chem. Abstracts, 31, 1804 (1937). polon. sci., Gluase sci. math. mt., 1937A, 571; 828. Kocwa, BuU. intern. d. through Chem. Abstracts, 32, 4986 (1938). 829. Kocwa, Polaka Akad.
[email protected],Prace Kom. Nauk Famuceut., Dissertationes Pharm., 1, 55 (1949);through Chem. Abstrach, 44, 1490 (1950). 830. Kocwa, Polaka Akad. Umiejftnodci, Prace Kom. Nauk F a m e & . , Dissertutiones P h r m . , 1, 143 (1949);through Chem. Abstracts, 44, 1491 (1950). 831. Kocwa, Polska A k d . UmiejqtnoSci, Prace Kom. Nauk F a m c e u t . , Dissertationes Pharm.. 2, 21 (1950);through C h m . Abstracts, 45, 9534 (1951). 67, 569 (1945). 832. Koelsch, J . Am. Chem. SOC., 833. Koenigs, Weiw and Zscharn, Ber., 59, 316 (1926). 834. Kohlbach, Arkiv. Hem. Farm., 11, 99 (1937);through Cliem. Abstracts, 33, 2897 (1939). 835. Kohler and Baltzly, J . Am. G k m . Soc., 54, 4016 (1932). 836. Kohlstadt, HeZv. Chem. Acta, 27, 685 (1944). 837. Koike, Iida and Kashioka, J . Chem. Soc. Japan, Ind. Chem. Sect., 57, 123 (1954);through Chem. Abstracts, 49, 11629 (1955). 838. Koike, Iida, Okawe and Kashioka, J . Chem. SOC.Japan, I t t d . CkPm. Sect., 57, 56 (1954);through Chem. Ab8tracts, 49, 11629 (195.5).
References
503
839. Koikc, Suzuki, Tanakadate and Ida, Hfpts. Oozy. Chem. I d . Research Inst. Tokyo, 49, 158 (1954); through Chem. Abstracts, 48, 11079 (1954). 840. Koike, Suzuki, Tanakadate, Iida and Okiwa, Repts. Ow.ClLem.Ind. Research Inat. Tokyo, 49, 153 (1954); through Chem. Abstracts, 48, 11079 (1954). 841. Kolb, 2. anorg. Chem., 83, 143 (1913). 842. Koll and Fleischmann, Arch. exptl. Path. I'harmakd., 198, 390 (1941); through Chem. Abstracts, 39, 3355 (1945). 843. Kolthoff, Rec. trae. claim., 41, 135 (1922). 844. Komada, J. Clwm. SOC.Japan, 58, 1091, 1096, 1193, 1295, 1305, 1315 (1937); through Chem. Abstracts, 32, 9082 (1938). 846. Komada, J. Chem. SOC.Japan, 59, 412, 477, 485 (1938); through Chem. Abstrncts, 32, 9083 (1938). 846. Komada, J. Chem. SOP.Japnm,~, 59, 490 (1938); through Chem. Abstracts, 32, 9081 (1938). 847. Kondo, J. Pharm. SOC.Japnn, 57, 832 (1937); through Chem. Abatracts, 32, 1239 (1938). 848. Konek, Ber., 53, 1666 (1920). 849. Konek and Mitterhauser, Ber., 51, 865 (1918). 850. Konek and Schleifer, Ber., 51, 842 (1918). 851. Kopp and Gangneux, U.S. Pat., 2,477,487 (1949). 852. Korns, Sohriebers and Dirscherl, ArzneimitteZ-~'orsch.,6 , 596 ( 1956). 853. Korolev and Rostovtseva, OTg. chen2. Ind. (U.S.S.R.), 4, 609 (1937); through Chem. Abstracts, 32, 6245 (1938). 854. Kosakada, Jap. Pat., 130 (1954). 855. Kosuge, Okeda, Abiiratani, Ito and Rosaka, J. Phaim. S O C ..Jupan, 74, 1086 (1954); through Chern. Abstracls, 49, 11628 (1955). 856. Krackcr, U.S. Pat., 2,688,613 (1954). 857. Kracker and Schmid, Ger. Pat., 622,113 (1935). 858. Krauth and Pfleger, Ccr. Pat., 71,253. 859. Krohs, Med.u. Chem. Abhandl. med.-cltem.Forschungsstatter?I.G. Farheniizd., 3, 310 (1936); through Chem. Abstracta, 31, 5795 (1937). 860. Krohs, Chem.. Ber., 88, 866 (1985). 861. Kropp, U.S. Pat., 1,151,885 (1915). 862. Kropp and Taub, U.S. Pat., 1,508,401 (1924). 863. Krzikalla, Eistert, Schmitt and Kraclrer, Ger. Pat., 597,589 (1934). 864. Krzikalla and Toepel, Ger. Pat., 821,977 (1951). 865. Krzikalla and Trofimov, Ger. Pat., 917,632 (1954). 866. Kufferath. J. prakt. Chem., 64, 334 (1901). 867. Kuga, J. Hiochem. ( J a y n ) ,35, 293 (1942);through Chon. Abstrnck, 45, 7960 (1951). 868. Kumov, Zhur. Obshcliei Khim.,21, 1765 (1951); through Chem. Abstracts. 47, 2622 (1953). 869. Kumov, Zhur. Anal. h-him.. 7,301 (1952);through Chem. Abstrurts, 47, 2629 (1953). Sci. Phot. (Japan), 14, 37 (1951);through Chem. Abstracts, 870. Kunimine, J.SOC. 47, 3155 (1953). 871. Kunimine and Itano, J . Pltarni. Soc. Japan, 74, 726 (1954); through Chem. Abstraeta, 49, 11627 (1955). 872. Kiistcr, 2.phyaiol. chem., 145, 53 (1925). 873. Kiister, U.S. Pat., 2,633,463 (1953).
504
References
874. Kiisitsr, U.S. Pat., 2,659,720 (1953). 875. Labes and Bergstermanri, Arch. exptl. Path. Phurniuko/., 187, 389 (1937); through Chem. Abstmcts, 33, 4594 (1939). 876. La Du, Gaudette, Trousof and Srodie, J . Uiol. Chem., 214, 741 (1955). 877. Langbein, Ger. Pat., 888,733 (1953). 878. Langbein, Ger. Pat., 906,063 (1954). 879. Lantz and Mingasson, U.S. Pat., 2,647,113 (1953). 880. La Parola, (Jazz. chin&.itel., 67, 645 (1937). 881. Larive and Collet, U.S. Pat., 2,708,669 (1955). 882. Lauer and Brodoway, J . Am. Chem. SOC.,75, 5406 (1953). 883. Lauer and Kilburn, J . Am. Chem. Soc., 59, 2586 (1937). 884. Lecher, Parker and Conn, U.S. Pat., 2,227,654 (1941). 885. Lecher, Parker and Conn, J . Am. Chem. SOC.,66, 1959 (1944). 886. Lecher, Parker and Denton, U.S. Pat., 2,385,088 (1945). 887. Lechleitner and Ritzer, Austrian Pat., 178,164 (1954). 888. Lederer, J. prukt. Chem. [2], 45, 83 (1892). 889. Ledrut, U.S.Pat., 2,622,086 (1962). 890. Ledrut, U.S. Pat., 2,628,233 (1953). 891. Ledrut, U.S. Pat., 2,650,219 (1953). 892. Ledrut, U.S. Pat., 2,651,638 (1953). 893. Lodrut, Can. Pat., 506,562 (1954). 894. Ledrut, Can. Pat., 510,619 (1956). 895. Ledrut and Combes, Bull. soc. chini. Frame, 1948, 674. china. France, 1950, 127. 896. Ledrut and Combes, Bull. SOC. 897. Ledrut and Combes, Bull. soc. chin. France, 1950, 228. 898. Ledrut and Combes, Bull. SOC. chim. France, 1950, 786. 899. Ledrut and Combes, Compt. rend., 231, 1513 (1950). 900. Ledrut and Combes, B d l . SOC. chim. Frame, 1952, 189. 901. Ledrut, Combes and Swierkot, Bull. soc. chim. France, 1952, 185. 902. Ledrut, Combes and Swierkot, Bull. soc. chim. France, 1950, 232. 903. Ledrut and Swierkot, Bull. SOC. chim. Belges, 59, 238 (1950); through Clbeirs. Abstracts, 45, 2486 (1951). 904, Legg, Brit. Pat., 738,999 (1955). 905. Lehr, Terranova and Boyd, Urol. and Cutawous Rev., 47,661 (1943); through Chem. Abstrcacts, 38, 5584 (1944). 906. Leonard, Brit. Med. J., 1953, I, 1311. 907. Leulier, J . p h u m . chim., 29, 447 (1924). 908. Leulier and Cohen, J. pharm. chim., 29, 24.5 (1939). 909. Levine and Hauser, J. Am. C h m . SOC.,66, 1768 (1944). 910. Lieberman and Wagner, J . Org. Chem., 14, 1001 (1949). 911. Lieser and Kemmer, Chem. Ber., 84, 4 (1951). 912. Linares, Bayes and Cardona, Pubs. 2 m t . quim. “&onso Barba”, 4,310 (1960); through Chem. Abstracts, 46, 8082 (1952). 913. Locke, U.S.Pat., 2,418,416 (1947). 914. Locke, U.S.Pat., 2,478,768 (1949). 915. Lockemann, Brit. Pat., 214,261 (1923). 910. Lockemann, Brit. Pat., 223,182 (1923). 917. Locquin, B d l . soc. chim. Fratace, [3], 35, 962 (1906). 918. Logemann, Almirante and Caprio, C’hern. Bet-., 87, 1175 (1954). 919. Logemann, Lauria and Zamboni, Chem. Ber., 88, 1353 (1955).
References
505
920. Long and Lewis,U.S. Pat., 2,437,645 (1948). 921. Loria, Vittum and Weissberger, U.S. Pat., 2,592,303 (1952). 922. Loria, Weissberger and Vittum, U.S.Pat., 2,600,788 (1952). 923. Losco, Gazz. chim. ital., 67, 553 (1937). 924. Losco, Gazz. chim. itul., 68, 474 (1938). 925. Losco, Guzz. chim. ital., 69, 639 (1939). 926. Losco, Qazz. chim. itol., 70, 284 (1940). 927. Luft, Ber., 38, 4044 (1905). 928. LumiPre, Lumikre and Perrin, Bull. 8or. ch?m. FrarLcr. [3], 33, 20.5 (1905). 029. Lumiere, Lumi6re and Barbier, Bull. soc. chin,. fi’mnce. [3], 33, 503 (1905). 030. Lumihe and Porrin, Bull. soc. rhim. Fratwe, [a], 30, 966 (1903). 931. h n d , .7. Chem. SOC.,1933, 686. 932. Lund, J . Ghem. Soc., 1935, 418. 933. Lundsgaard, Brit. Pat., 163,946 (1920). 934. Luttringhaus and Grohman, 27. iVuttwforsch., lob, 365 (19.55). 935. MacKenzie and Nestler, U.S. Pat., 2,434,173 (1948). 936. Mackir and Cutler, Rec. trav. chim.. 71, 1198 (19.54). 937. 3lndaus. Arzneimiltel-Forseh., 1, 375 (1951). 938. Maeda, Jap. Pat., 153,365 (1942). 939. Magidson. Zkur. Obshchei Khim., 26, 1137 ( 1 956); Lhrough Chcni. a4batrmfs, 50, 16764 (1936). 940. Magitlson and Gorhovitskii, Huss. Fat., 53,877 (1938). 941. JIagidson and Gorbovitskii, RUM.Pat., 52,991 (1940). 942. Mangini and Dal Monte, Chimie et indtcstrir, 63, No. 3 bis, 463 (1950); through Clwnt. Abstracts, 47, 868 (1953). 943. Mann and Haworth, J . Chew. SOC.,1944, 670. 944. Mannich and Heilner, Ber., 55, 365 (1922). 945. Mannich and Katler, Arch. Phum., 257, 18 (1919). 946. Mannich and Krosche, Arch. Pharm.. 250, 647 (1913). 947. Mansberg and Shaw, J . Ghem. SOC.,195.1,3467. 948. Marschall and Williams, U.S. Pat., 2.739,963 (1956). 949. Martin, U.S. Pat., 2,476,986 (1949). 950. Martini, Andes asoc. p i m . Argentirm, 31, 69 (1943); throrigh C’hrin. Abstrcrcts, 38, 531 (1944). 951. Marx, U.S. Pat., 2,718,487 (1955). 952. Massot, Span. Pat., 225,801 (1956). 953. Matsumot.o, Tech. BUZZ. Kaqawu Agr. PoU. (Jrrpcin), 5, 103 (1953-54), through CIwn, Absimcts, 49, 7493 (1955). 954. Mattu, Cnzz. china. { f d , 81, 891 (1951). 955. Mauthner, Ber., 41, 2530 (1908). 956. Mauthner, Ann., 395, 273 (1913). 957. Mauthner. , I . prakt. Chem., 116, 321 (1927). 958. Mayer and Widlmor, U.S. Pat., 2,476,259 (1049). 959. Mayer and Widmer. C . S . Pat., 2,476,261 (1949). 960. Mayhew, U.S. Pat.. 2,476,991 (1949). 961. McCormick, G P , 14, 95 (1956). 962. McMillan and King, J . Am. Chem. Soc., 77, 3376 (1955). 963. McNally and Dickey. U.S. Pat., 2,391,180 (1946). 964. McQueen, U.S. Pat., 2,367,036 (1945). 965. McQueen, U.8. Pat., 2,428,108 (1947).
306 966. 967. 968. 969. 970. 971. 952. 973. 974. 975. 976. $77. 978. 979. 980. 981. 982. 983. 084. 985. 986. 987. 988.
989. 990. 991. 992. 993. 994. 995. 996. 997. 998. 999. 1000. 1001. 1WZ. 1003. 1004. 1005. 1006. 1007. 1008. 1009. 1010. 1011. 1012. 1013.
References JIcQueen, U.S. Pat., 2,477,462 (1949). Mendoza, Brit. Pat., 300,321 (1927). Mendoza, U.S. Pat., 1,841,621 (1932). Mester, Span. Pat., 212,764 (1954). Mctais and Duquenois, Bull. SOC. chinl. Frcoirc, 1949, 515. JIeyer and Uouchet, Compt. rend., 227, 345 (1948). Michaelis, Rer., 38, 154 (1905). Jlichaelis and Bender, Ber., 36, 523 (1903). Michaelis and Bressel, Ann., 407, 274 (1913). Michaelis, Brust, Preuner, Blumc, Hepncr uncl Datidf'tiw, dtoc., 339, 1 1 7 (1905). Michaelis and Burmeister, Ber., 25, 1502 (1892). Mirhaelis and Engelhardt, Ber., 41, 2668 (1908). Michaelis, Graff, Gesing and Boie, Ann., 378, 293 (1911). Michaelis and Hepner, Ber., 36, 3271 (1903). Michaelis and Horn, Ann., 373, 213 (1910). Jlichaelis and Kirstein, Ber., 46, 3603 (1913). 3lichaelis and Klopstock, Ann., 354, 102 (1907). Michaalis and Kobert, Ber., 42, 2765 (1909). Michselis, Kotelmann and Drews, Ann., 350, 288 (1906). Xichaelis and Lachwitz, Ber., 43, 2106 (1910). Michaelis, Lagenkamp and Duntze, Ann., 404, 21 (1914). Michaelis, Leonhardt and Wohle, Ann., 338, 215 (190.7). Michaelis, Mayer, Behrem and Hahn, Anti., 338, 267 (1905). Michaelis and Mielecke, Ber., 40, 4482 (1907). Mcliaelis, Pandor, Lehmann and Drilk, =Inn.. 361, 2.51 (1906). JfIchselis, Rademacher and Schmiedenkitrnpf,- 4 ~ ) t . 354, , A5 (1907). Michaelis, Rassman, von der Hagen, Dorn and lVrc&>,A/i)i.,352,152 (1907). Michaelis and Renny, Ber., 40, 1020 (1907). Michaelis and Rohmer, Ber., 31, 3003 (1898). XIichaelis and Schafer, Ann., 407, 229 (191.5). Michaelis, Schafer, Klappert and Titius, Attfc.,397, 119 (1913). Michaelis and Schenk, Ber., 40, 3568 (1907). Michaslis and Schenk, Ber., 41, 386.5 (1908). Jlichaelis and Schlecht, Ber., 39, 1955 (1906). JIichaelis and Stau, Ber., 46, 3612 (1913). Michaelis, Stiegler and Willert, Antr., 358, 127 (1!107). Michaelis, Walter, Wurl, Doopinann. Thornas, Iscrt and Mentzel, A P I ~ I . , 385, l ( l 9 1 1 ) . Michaelis and Willert, A t t ~ i .358, , 171 (1907). 3fichaeliq Ziescl, Kriig, Leo and Katlinp, .4/0(..373, 129 (1910). Jfinqk, U.S. Pat., 2,759,816 (1956). Mitnt, J . 1)tdin)i C1te.m. ~S'oc..8, 471 (l!K
Monti, Guzz. chim. i h l . , 60, 39 (1930). Morgan and Ackerman, J. Chert&.SOC.,123, 1308 (1923). Morgan and Reilly, Proc. Chem. Soc., 28, 334 (1913). Morgan and Reilly, J. Ghem. Soc., 103, 808 (1913). Morgan and Reilly, J . CIwtt. Sor., 103, 1494 (1913). Morgan and Reilly, J . ChenL. *!oc.,105, 435 (1915). Moser, U.S. Pat., 2,399,447 (1946). Mossini and Guerci, BolE. chitrb. furm., 80, 443 (19.41): thntiigh (%em. Abstracts, 37, 3756 (1943). 1022. Moureu, Choivin and Petit, Gompt. rend., 241, 1954 (1955). 1023. Moureu and Lazennec., Conzpt. r e d . , 142, 1534 (1906). 1024. Moureu and Lazennec, Bull. soc. chitn. Fruwx, [3], 35, 843 (1906). 1025. Moureu and Lazennec, Cotnpt. r e d , 143, 1239 (1906). 1026. Moureu and Lazonncc, Hull. soc. chiin. Fratwe, [4], 1, 1071 (1907). 1027. Yozingo and Folkers, Chemistry uf Peti irilli/l. 1949, 535. 1028. Muckermann, Ber., 42, 3449 (1909). 1029. i?fuckermann, J . prukt. Chetn., 84, 278 (1911). 1030. Mueller, U.S. Pat., 2,616,915 (1952). 1031. Mitkherjee, Indian Pats., 49,798 and 50,925 (1955). 1032. Xukherjee, Gupta, Lasltar and Rayniaharsay, J . IwZiu/i Chem. S'or., 30, 841 (1953). 1033. Mukhorjce, Gupta, Laskar and Raymahassay, J . I t i d m j i ('hem. S U C . , 31, 835 (1954). 1034. Muller and Sclioidogger, U.S. Pat., 2,424,493 ( I 947). 1035. l i t 6 R C h . d. Wochschr., 59, 469; through Chent. . Z O x h c t s . 6, 1180 (1912). 1036. Nundici, Oazz. chrm. ituZ., 39, 11, 123 (1909). 1037. Yunro and Wilson, J. Ghent. SOL,1928, 1237. 1038. Mrw, Zhur. Obshchei Klbinr., 24, 572 (1954): tht'oiigh Chrni. Alisf~nrts, 49, 6198 (1955). 1039. Mur, Zhur. Obshchei Khirn., 25, 374 (1958); thrmigli C'hem. Abslmcts, 50, 2460 (1956). 1040. Blur, Zhur. Obshchei K l h n . , 26, 381 (1956); throiigh C'heni. Abstmcts, 50, 13881 (1956). 1041. Murray, U.8. Pat., 2,463,794 (1949). 1042. Musante, Guzz. chim. ztal., 67, 652 (1937). 1043. Musante, Guzz. chin&.iial., 72, ,537 (1942). 1044. Musante, G u m chin&.ital., 73, 355 (1943). 1046. Musante, Guzz. chim. i f d , 75, 109 (1945). 1046. Musante, Gazz. chim. itul., 78, 178 (1948). 1047. Vusante and Fabbrini, I1 Furrnico (Puviu),E d . S c i . , 8, 264 (1963); through Chem. Abstracls, 48, 4530 (1954). 1048. Musante and Fabbrini, Guzz. rbim. ital., 84. 595 (1954). 1049. Musante and Mubmaini. Gazz. chzm. itul., 77, 182 (1947). 1050. Musante and Parrini, Gazz. chim. id., 84, 209 (1954). 1051. Naito, Taki, Shioda, Fujikawa, il'akajima, Fujii, Tokuoka, Oltarmoto and Hitosa, J. Phann. Soc. Japan, 71, 811 (1951); through Ghem. Abstracts, 4G, 1615 (1952). 1052. Naito, Yoshida, and Smo, J . €'harm. SOC.Japan, 72, 346 (1952); through Chem. Abstrmts, 47, 6408 (1953). 1053. Nandi, J . Indiun Chem. Soc., 17, 449 (1940). 1014. 1015. 1016. 1017. 1018. 1019. 1020. 1021.
50s 1054. 1055. 1056. 1057. 1058. 1059. 1060. 1061. 1062. 1063. 1064. 1065. 1066. 1067. 1068. 1069. 1070. 1071. 1072. 1073. 1074. 1075. 1076. 1077. 1078.
1079. 1080. 1081. 1082. 1083. 1084. 1085. 1086. 1087. 1088.
References Xar&lli and Paolini, Gor. Pat., 180,120 (1906). h'assim and Pilkington, Brit. filed. J., 1953, I, 1310. Nef, Atan., 266, 52 (1891). Kesmeyanov and Ioffe, J . Gen. Chern. (V.S.S.R.),11, 392 (1941); through Chem. Abstracts, 35, 5869 (1941). Neugebauer, Barthenheier and Rebeiiatock, U.S. Pat., 2,702,242 (1955). Nios, U.S. Pat., 2,420,791 (1947). Nies, U.S. Pat., 2,432,034 (1947). Nies, U.S. Pat., 2,446,662 (1948). Nies, U.Y. Pat., 2,447,867 (1948). Nikolaiev, Khim. Farm. Prom., 1934, ?u'o. 1, 35; through ( : h e m Abstracts, 28, 5444 (1934). Nishikawa, Repts. Research Sci. Dept. Kyushu C r > t i i * . , 1, 58 (1950);through Chem. Abstracts, 46, 2497 (1952). Kogrichi, Okeda and Iahida, J. Pharm. SOC.Jupan, 76, 393 (1956); through Chem. Abstracts, 50, 13747 (1956). Norton, %. E'urbetL-Ind., 20, 8 (1928); through C h w . Abutrncts, 22, 2665 (1928). Oddo, Guzz. chim. ital., 50, 11, 258 (1920). Oddo and Acrito, Gatz. chim. ital., 66, 380 (1936). Ogata and Noguchi, J. Sci. Beseurch Inst. (Z'oByo), 45, 154 (1931); through C h m . Abstracts, 46, 2936 (1952). Ogata, Tauno and Nishida, Rep&. S c i . Research I w t . ( J u p w t ) , 28, 259 (1952); through Chem. Abstracts, 47, 5284 (1953). Ohta, J. Phumn. SOC.Japan, 64, 59 (1944); througli Chem. -46sfructs. 45, 7970 (1951). Oksengendler, Zliur. 0bshche.Z Khifn., 23, 135 (1'353); through CAem. Abstracts, 48, 672 (1954). Olrsengendler and Kiprianov, Ukraitt. K h h . Zhur., 16, 383 (1950); through Chem. Abstracts, 48, 1685 (1954). Orostano, Arch. ital. sci. fuwnacol., 8 , 353 (1939); throiigh Chwri. Abstracts, 39, 1926 (1945). Oakerko, M e m . Inst. Chem. Ubrairi. Bed. Sci., 4, 195 (1937); throiigh Chenh. Abstracts, 32, 3334 (1938). Ostromislensky, U.S. Pat., 2,011,255 (1935). Pacault, h t t . chim. [12], 1, 527 (1946); throiigh Chem. Abstracts, 42, 4409 (1948). Pacovsky and HolecBk, ~ a s o p i sLCkur't'c &slicjc.h, 95, 300 (1956): through Chern. Abstracts, 50, 7306 (1956). Peige, U.S. Pat.,2,490,703 (1949). Paige, U.S. Pttt., 2,490,704 (1949). Paluzzo and Liveraru, Atti nccarl. Littcei, 20, 11, 55 (1911); ttirnugh Chem. Abstracts, 5 , 3683 (1911). Panizzi, Gazz. chiin. ital., 7 0 , 738 (1940). Papini, Checchi and Ridi, Gazz. chini. itat., 84, 769 (1934). Papini and Franco, Guzz. chim. itnl., 81, 230 (19Sl). Papini and Venturini, Cfazz. chim. ital., 83, 861 (1953). Parharn and Bleasdale, J. A m . Chent. Aoc., 73, 4664 (1951). Pannorter, U.S. Pat., 2,710,802 (1955). Passerini, Qaz. chim. ital., 69, 480 (1938).
References
509
1089. Passorini and Casini, ffuzz. d i m . ital., 67, 332 (1937). 1090. Passerini and Casini, (Jazz.china. ital., 67, 785 (1937). 1091. Passerini and Losco, Qazz. china. ital., 68, 485 (1938). 1092. Paaserini and Losco, ffuzz. chim. ital., 69, 658 (1939). 1093. Passerini and Losco, Gazz. chim. ituZ., 70, 410 (1940). 1094. Passerini and Ragni, (Jazz. chim. dd.,66, 684 (1936). 1095. Passerini and Ridi, Gazz. chim. ital., 64, 931 (1934). 1096. Passerini and Ridi, Gazz. chim. ital., 65, 930 (1935). 1097. Paaserini, Ridi and Losco, Gazz. chim. if& 80, 803 (1950). 26, 371 (1949). 1098. Pathak and Chosh, J . Indian.Chem. SOC., 1099. Patton, Natl. Nuclear Energy Ser., Manhattan Project Tech. Sect. Div. I S ' , 14B, 851 (1949);through Chem. Abslracts, 45, 10192 (1951). 1100. Pauly, Gilmour and Will, Ann., 403, 119 (1914). 1101. Pechmann, Ber., 28, 1624 (1895). 1102. Peck and Folkers, Chemistmj of Penicillin, 1949, 52. 1103. Perekalin, Savost'yanova and Morozova, Zhur. Obshchei Khim., 22, 821 (1952);through Chem. Abstracts, 46, 10886 (1952). 1104. Perott, Boll. chim. farm., 77, 1 (1938);through Chem. Abstrmts, 32, 3240 (1938). 1105. Perotta and Mezzadra, Ann. chim. applicala, 30,307 (1940);through Chem. Abstracts, 35, 1773 (1941). 1106. Perroncito, cfazz. chim. ital., 65, 554 (1935). 1107. Perroncito, ffuzz.chim. ital., 65, 1254 (1935). 1108. Perroncito, Gazz. chim. ital., 66, 563 (1936). 1109. Perroncito, Gwz. chim. i d . , 67, 158 (1937). 1110. Peters, Pringle and Rowe, J . Chem. Soc., 1948, 597. 1111. Petersen, Ann., 562, 205 (1949). 1112. PfeXer, Brit. Pat., 231,512 (1924). 1113. Pfeiffer and Angern, 2. physiol. Chenz., 154, 276 (1926). 1114. Pfeiffer and Enders, Chem. Ber., 84, 313 (1951). 1115. Pfeiffer and Seydel, 2.physiol. Chem., 178, 81 (1928). 1116. PfeXer and Wittka, Ber., 48, 1289 (1915). 1117. Pfitzner and Kaufmann, U.S. Pat., 2,703,193(1955). 1118. Piepenbrink and Bayer, U.S. Pat., 2,634,262 (1953). 1119. Piepenbrink, Bayer and Petersen, Ger. Pat., 843,449 (1952). 1120. Pieroni, Atti accad. Lincei [6], 5, 303 (1927);through Chem. Abstracts, 21, 1814 (1927). 1121. Pieth, U.S. Pat., 2,427,534 (1947). 1122. Pietra, Boll. sci. fuc. chim. ind. Bologna, 11, 78 (1953);through Chem. Ab8tracts, 49, 13975 (1955). 1123. Pizzuti, Guzz. chim. ital., 40,11, 238 (1911). chim. France, 1954, 504. 1124. Polansky and Lederer, Bull. SOC. 1125. Ponzio and Ruggeri, Gazz. china. itul., 56, 733 (1926). 1126. Popkin, U.S. Pat., 2,431,889 (1947). 1127. Poppelsdorf and Holt, J . Chem. SOC.,1954, 1124, 4094. 1128. Porai-Roshits and Dinaburg, Zhur. Obshchei Khim., 24, 635 (1954); through Chem. Abstracts, 49, 5450 (1955). 1129. Poraf-Koshits and Dinaburg, Zhur. Ob8hcheZ KhinZ., 24, 1221 (1954); through Chem. Abstructs, 49, 12449 (1955). 18-c.1i.c. 20
610
References
1130. Porai-Koshits and Dinaburg, Zhur. Obshchei Khim., 24, 2208 (1954); through Chem. Abstracts, 50, 310 (1956). 1131. Porai-Koshits and Dinaburg, Zhur. ObshcheZ Khim., 25, 151 (1955); through Chem. Abstracts, 50, 1780 (1956). 1132. Pod-Koshits, Ginzburg and Porai-Koshits, Zhur. Obshchei Khim., 17, 1752 (1947); through Chem. Abstracts, 42, 6357 (1958). 1133. Porai-Koshits, Porai-Koshits and Ginzburg, Compt. rend. d. sci. U.R.S.S., 47, 407 (1945); through Chem. Abstracts, 40, 4217 (1946). 1134. Porai-Koshits, Porai-Koshits and Lipina, Zhur. Obshchei Khim., 25, 1604 (1955); through Chem. Abstracts, 50, 4917 (1956). 1135. Porai-Koshits, Porai-Koshits and Lipina, Zhur. ObshchZ Khinc., 26, 842 (1956); through Chem. Abstracls, 50, 14720 (1956). 1136. Porter and Weissberger, U.S. Pat., 2,343,702 (1944). 1137. Porter and Weissberger, U.S. Pat., 2,343,703 (1944). 1138. Porter and Weissberger, U.S. Pat., 2,367,523 (1945). 1139. Porter and Weissberger, U.S. Pat., 2,369,489 (1945). 1140. Porter and Weissberger, U.S. Pat., 2,376,380 (1945). 1141. Porter and Weissberger, Org. Syn., 28, 87 (1948). 1142. Porter and Weissberger, Brit. Pat., 599,919 (1948). 1143. Porter, Woissborger and Gregory, U S . Pat., 2,439,098 (1948). 1144. PoskoEil and Allan, Chem. listy, 47, 1801 (1953); through Chena. Abstrach, 48, 4221 (1954). 1145. Posner and Schreiber, Ber., 57, 1127 (1924). 1146. Prelog and Kohlbmh, Collection Czech. C k m . Commun., 8, 377 (1930). 1147. Priowo and Poljak, Chem. Ber., 88, 1932 (1955). 1148. Profft and Buchmann, Chem. Tech. (Berlin),7, 138 (1955); through Chem. Abstracts, 50, 7070 (1956). 1149. Profft, Runge and Blanke, J . prakt. chem. [4], 1, 110 (1954). 1150. Quintilla, Span, Pat., 211,285 (1955). 1151. Quiroga and nlagnin, Actas Dembibliog. (Madrid), 44, 397 (1953); Excerptu Med., Sect. XIII, 8, 135 (1954); through Chem. Abstracts, 49, 13593 (1955). 1152. Qvist, Acta A d . Aboensk Math. phys., 4, No. 3, 25 pp.; through Chem. Abstracts, 22, 4485 (1928). 1153. Qvist. Acta A d . Aboensia Math. phys., 5, No. 2, 16 pp.; through Chern. Abstracts, 24, 3788 (1930). 1154. Raho and Elm, Ann., 323, 83 (1902). 68, 741 (1938). 1155. Ragno, Guzz. chim. id., 1156. Raiziss and Clemenee, J . Am. Chem. SOC.,52, 2019 (1930). 1157. Raiziss, Clemonce and Freifolder, J. Am. Chem. SOC.,63, 2739 (1941). 1158. Rboanu, Ann. sci. univ. Jassy, 18, 72 (1933); through Chem. Abstracts, 28, 4677 (1934). 1159. Rath and Binz, Ger. Pat., 516,534 (1924). 1160. Rath and Gcbauer, Ger. Pat., 589,146 (1933). 1161. Rechenberg, Klin. Wocbchr., 29, 726 (1951). 1162. Reed, Brit. Pat., 644,897 (1950). 1163. Reeves, J. Chem. SOC.,127, 911 (1925). 1164. Regenbogen, Pharm. WelcbW,55, 1126 (1918); through Chem. Abstracts, 12, 2408 (1918).
References
511
1165. Reilly and MacSweeney, Proc. Roy. ITish A d . , 39B, 497 (1930); through Chem. Abatracle, 25, 1523 (1931). 1166. Reilly and Madden, J. Chern.Soc., 127, 2936 (1925). 1167. Reitz, 2. plsy&k. Chern., B46, 165 (1940). 1168. Remy and Kummell, 2. Ekktrochem., 15, 254 (1909). 1169. Renard, BuU. c h a e x i . , A d . TOY, Belg., 29, No. 719, 536 (1943); through Chem. Abstracts, 40, 6422 (1946). 1170. Renkin, A n . J. Physiol., 173, 125 (1953). 1171. Reppe el al., Ann., 596, 158 (1955). 1172. Reppe et ul., Ann., 596, 38 (1955). 1173. Reuter, U.S. Pat., 2,005,505 (1935). 1174. Keuter, U.8. Pat., 2,005,506 (1935). 1175. Reuter, Ger. Pat., 617,360 (1935). 1176. Reynolds, U.S. Pat., 2,688,548 (1954). 1177. Reynolds and Tinker, U.S. Pat., 2,743,279 (1956). 1178. Riat and Mayer, U.S. Pat., 2,536,957 (1951). 1179. Rice, J . Am, Chem. SOC.,45, 222 (1923). 1180. Ridi, Ann. chim. applieala, 30, 495 (1940); through Chem. Abslract~,35, 2890 (1941). 1181. Itidi, Guzz. chim. ital., 71, 95 (1941). 1182. Ridi, Gazz. chim. itul.,71, 100 (1941). 1183. Ridi, Gum. chim. ital., 71, 106 (1941). 1184. Ridi, Guzz. chim. ital., 71, 462 (1941). 1185. Kidi, Guzz. chim. ital., 71, 542 (1941). 1186. Ridi, Guza. chim. ital., 77, 3 (1947). 1187. Ridi, Gazz. chim. itul., 80, 633 (1950). 1188. Ridi, Guzz. chim. it'd., 82, 746 (1952). 1189. Ridi and Checchi, Guzz. chim. ilaE., 83, 36 (1953). 1190. Ridi and Checchi, Ann. chim. (Rome), 43, 816 (1953); through Chem. Abstracts, 49, 6234 (1955). 1191. Ridi and Feroci, Quzz. chim. ital., 79, 175 (1948). 1192. Ridi and Papini, Gazz. chim. itul., 77, 99 (1947). 1193. Ridi and Papini, Qazz. ehim. itul., 78, 3 (1948). 1194. Ridi, Papini, Checchi and Conti, Guzz. chim. ital., 84, 781 (1954). 1195. Ri&er, Ger. Pat., 821,524 (1951). 1196. Robins, J. Am. Chem. SOC.,78, 784 (1956). 1197. Roblin, Williams, Winnek and English, J. Am. Chem. SOC.,62, 2002 (1940). 1198. Rodionov, Bull. aoc. chim. France, [a], 39, 305 (1926). 1199. Rodionov and Fedorova, Izvest. Akad. llauk S.S.S.R., Oldel. Khim. &'auk, 1952, 1049; through Chern. Abstrmts, 48, 671 (1954). 1200. Rodionov and Suvorov, Zhur. Obshchei Khim., 20, 1273 (1950); through Chem. Abstracts, 45, 1543 (1951). 1201. Roedig, Becker, Fugrnann and Schoedel, Ann., 597, 214 (1955). 1202. Rohde, J. prukt. Chem., 143, 325 (1935). 1203. Rohde and Hartwick, Ger. Pat., 638,533 (1936). 1204. Rohde and Tenzer, J. prakt. Chem., 87, 541 (1913). 1205. Rojahn, Ber., 55, 2959 (1922). 1206. Rojahn and Fahr,Ann., 434, 252 (1923). 1207. Rojahu and Fegeler, Eer., 63, 2510 (1930). 1208. Romain, Bull. 80C. chim. FTance, 1957, 1417.
512
Refcrcnces
1209. Rondestvedt and Chang, J. Am. Chem. SOC., 77, 6532 (1955). 1210. Rose, J. Chem. SOC.,1952, 3448. 1211. Rosenthaler, Rev.facuZtd sci. univ. Istanbul, 9A, 132 (1944); through Chern. Abstracts, 40, 1755 (1946). 1212. Roura, Rev. Asoc. bioquim. Argentina, 19, 225 (1954); through Chem. Abstracts, 49, 6022 (1955). 1213. Rowe, Desai and Peters, J. Chem. SOC., 1948, 2811. 1936, 1704. 1214. Rowe and Twitchett, J. Chem. SOC., 1215. Royals, Hoppe, Jordan and Robitwon, J. Am. Chem. Soc., 73, 5857 (1951). 1216. Rozovskaye and Shterenson, Farmakol. i ToBihl., 8, No. 2, 46 (1945); through Chem. Abstracts, 40, 5845 (1946). 1217. Rubtaov, Zhur. Obshchei Khim., 16, 221 (1946); through Chem. Abstracts, 41, 431 (1947). 1218. Ruckstuhl, Senn and Wehrli, U.S. Pat., 2,572,394 (1951). 1219. Ruggli and Disler, Helv. Chim. Acta, 10, 938 (1927). 1220. Ruggli and Hartmann, Helv. Chim. Acta, 3, 493 (1920). 1221. Ruggli and Maader, Helv. Chim. Acta, 25, 936 (1942). 1222. Ruggli and Maeder, Helv. Chim. Acta, 26, 1476 (1943). 1223. Ruggli and Maeder, Helv. Chim. Acta, 27, 436 (1944). 1224. Ruggli and Schetty, Helv. Chim. A&, 23, 718 (1940). 1225. Ruggli and Staub, HeZv. Chim. Acta, 19, 962 (1936). 1226. Ruggli and Theilheimer, Helv. Chim. Acta, 24, 899 (1941). 1227. Ruggli, Weis and Rupe, Helv. Chim. Actu, 29, 1788 (1946). 1228. Ruhemann, Ber., 27, 1658 (1894). 1229. Ruhemann, J. Chem. Soc., 69, 1394 (1896). 1230. Ruhemann and Morrell, J. Chem. SOC., 61, 791 (1892). 1231. Ruhemann and Morrell, Ber., 27, 2743 (1894). 1232. Ruhemann and Morrell, Ber., 28, 987 (1895). 1233. Ruhemann and Orton, J. Chem. SOC.,67, 1002 (1895). 1234. Ruhkopf, Ber., 73, 820 (1940). 1236. Ruhnau, Deut. tierartzl. Wochschr., 59, 38 (1952); through Chem. Abstracts, 47, 781 (1953). 1236. Rupe and Heckendorn, Helv. Chim. Acfu, 9, 980 (1926). 1237. Rupe and Zickendraht, Relv. Chim. Acta, 29, 1529 (1946). 1238. Ryabchikov and Terent'eva, Compt. rend. a d . sci. U.S.S.R., 51, 291 (1946); through Chem. Abstracts, 40, 6362 (1946). 1939, 1544. 1239. Rydon, J. Chem. SOC., 1240. Rydon and Siddappa, J. Chem. Soc., 1951, 2462. 1241. Sachs and Appenzellen, Ber., 41, 91 (1908). 1242. Sachs and Barschall, Uer., 35, 1437 (1902). 1243. Sachs and Recheroscu, Ber., 36, 1132 (1903). 1244. Sachs and Kraft, Ber., 36, 757 (1903). 1245. Sah, Rec. trav. chim., 69, 1407 (1950). 1246. Salminen and Weiasborgor, U.S. Pat., 2,694,635 (1954). 1247. Salminon and Weissberger, U.S. Pat., 2,694, 718 (1954). 1248. Sanna, Rend. seminar. fac. sci. univ. Cagliari, 10, 54 (1940); through Chem. Abstracts, 37, 2356 (1943). 1249. Sama and Sollsi, Gazz. chim. ital., 72, 313 (1942). 1250. Sastry, J . Chem. SOC.,109, 270 (1916). 1251. Saunders, J. Chem. SOC., 117, 1264 (1920).
References
513
1252. Sawa, J. P h a m . SOC. Japan, 57, 953 (1937); through Chem. Abstracts, 32, 2533 (1938). 1253. Sawdey, U.S. Pat., 2,632,702 (1953). 1254. Sawdey, U.S. Pat., 2,706,683 (1955). 1255. Sawdey, Ruoff and Vittum, J. Am. Chem. SOC.,72, 4947 (1950). 1256. Scheitlin, Ger. Pat., 199,844 (1907). 1257. Scheitlin, Brit. Pat., 12,889 (1907). 1258. Scheitlin, Brit. Pat., 462,949 (1937). 1259. Schetty, J. Soc. Dyers and Colourists, 71, 705 (1955). 1260. Schickh, Ger. Pat,, 588,045 (1933). 1261. Schickh, Ber., 69, 967 (1936). 1262. Schiedt, J. prakt. Chern., 157, 203 (1941). 1263. Schiemann and Winkelmuller, Ber., 66, 727 (1933). 1264. Schmid, U.S. Pat., 2,211,293 (1940). 1265. Schmidt, Behnisch and Mietzsch, U.S. Pat., 2,664,425 (1953). 1266. Schmidt and Druoy, Helv. Chim. Actu, 39, 986 (1966). 1267. Schmid and Moser, U.S. Pat., 2,399,066 (1940). 1268. Schmid and Schetty, U.S. Pat., 2,494,969 (1950). 1269. Schneider, U.S. Pat., 2,186,734 (1940). 1270. Schneider and Frohlich, U.S. Pat., 2,200,306 (1940). 1271. Schneider and Frohlich, U.S. Pat., 2,437,063 (1948). 1272. Schneider, Frohlich and Zeh, Ger. Pat., 736,867 (1943). 1273. Schneider and Hagedorn, U.S. Pat., 2,178,612 (1939). 1274. Schoberl and Eck, Ann., 522, 97 (1936). 1275. Schrauth and Bauerachmidt, Ber., 47, 2736 (1914). 1276. Schreiber, Ann. china. [12], 2, 84 (1947); through Chem. Abstracts, 41, 6204 (1947). 1277. Schroeter, Kesseler, Liesche and Miiller, Ber., 49, 2697 (1916). 1278. Schultz and Mayor, Deut. Apoth.-Ztg., 92, 358 (1952); through Chem. Abstracts, 46, 11580 (1952). 1279. Sohultz and Rohde, J. prakt. Chem., 87, 119 (1913). 1280. Schuster and Krzikalla, U.S. Pat., 2,132,193 (1938). 1281. Schwartz and Dehn, J. Am. Chem. SOC.,39, 2444 (1917). 1282. Schwarz and Dossmann, Cer. Pat., 701,135 (1946). 1283. Schwoitzer and Bayer, Ger. Pat., 859,185 (1952). 1284. Scott, O’Sullivan and h i l l y , J. Am. Chem. SOC.,75, 5309 (1953). 1285. Searles and Kash, J. Org. Chem., 19, 928 (1954). 1286. Seibert, Chem. Ber., 80, 494 (1947). 1287. Seidel, J . prakt. Chem. [2], 58, 129 (1898). 1288. Seidel, Thier, Uber and Dittmer, Ber., 68, 1913 (1935). 1289. Selmiciu, Lupu and Ciretescu, Rev. chim. (Bucharest), 6, 578 (1955); through Chem. Abstracts, 50, 16958 (1956). 1290. Seppi, Bull. soc. ital. biol. sper., 16, 280 (1941); through Chem. Abstracts, 40, 6060 (1946). 1291. Seruto, U.S. Pats., 2,709,697 and 2,709,698 (1955). 1292. Sharp and Hamilton, J. Am. Chem. SOC.,68, 588 (1946). 1293. Sharvin, Arbuzov and Varshavaskie, J. Chem. I d . (Moscow),6, 1407 (1929); through Chem. Abstracts, 25, 502 (1931). 1294. Shave], Leonard, McMillan and King, J. Am. P h m . ASSOC., 42, 402 (1953). 1296. Shaw, J. Chem. SOC.,1952, 3428.
514
References
1296. Shestakov and Kazakov, J . Rms. P h p . Chem. SOC.,44, 1312; through Chem. Abatracts, 7 , 1984 (1913). 1297. Shimidzu, J . Phumn. SOC.Japan, KO.5 , 27, 12 (1926); through Chem. Abalracts, 20, 2857 (1926). 1298. Shinoda, Jap. Pat., 2779 (1952). 1299. Shirai and Yaahiro, Bull. Nagoya City Un.iv. Pharrn. School, No. 3, 30 (1955); through Chem. Abstracta, 50, 16754 (1956). 1300. Siegfried, Swiss Pat., 136, 848-50 (1928). 1301. Silberstein and Carroll, U.S. Pat., 2,527,583 (1950). 1302. Siminov, Zhur. Obshehei Khim., 10, 1220 (1940); through Chem. Abstracts, 35, 2868 (1941). 1303. Skita, Keil, Stiihmer, Jmschke, Ziegler, Kampmann, Arendts and Gerlach, Ber., 75, 1696 (1942). 1304. Slifkin, U.S. Pat., 2,536,398 (1951). 1305. Slifkin and Trojnar, U.S. Pat., 2,537,098 (1951). 1306. Sluzewska and Mazur, Roczniki Pahatwowego Zakladu Hig.,5 , 171 (1954); through Chem. Abstracts, 49, 8032 (1955). 1307. Smith, Kgl. Fysiograf. Sallskap. Lund., Forh., 18, No. 1, 3 (1948); through Chem. Abstracta, 44, 1490 (1950). 1308. Smith and Carlin, J. Am. Chem. Soc., 64, 433 (1942). 1309. Smith, Merits and Norlov, Kgl. Fysioyraf. Sallskup. Luiid., Forh., 23, 51 (1953); through Chem. Abstracts, 49. 15863 (1955). 1310. Smith and Thorpe, J . Chem. SOC.,91, 1899 (1907). 1311. Smyth and Clark, J . Chronic Diseases, 5, 734 (1957). 1312. Sokolova and Magidson, Zhur. Obshchei Khim., 26, 604 (1956); through Chem. Abstracts, 50, 13879 (1956). 1313. Soliman and Youssef, J. Chem. SOC.,1954, 4655. 1314. Sommolet, Bull. BOC. claim. France,[4], 9, 33 (1911). 1316. Sommelet, Compt. rend., 154, 706 (1912). 1316. Sommelet, Bull. SOC. chim., 29, 553 (1921). 1317. Sommer and Pioch, J . Am. Chem. SOC.,76, 1606 (1954). 1318. Somogyi and Hofstetter, Swiss Pat., 275,620 (1951). 1319. Somogyi and Hofstetter, Swiss Pat., 285,030 (1952). 1320. Sonn and Litten, Ber., 66, 1512 (1933). - 1321. Sonn and Litten, Ber., 66, 1582 (1933). 1322. Souchay, Bull. SOC. chim. France, [5], 7 , 797 (1940). 1323. Span. Pat., 208,830 (1954). 1324. Span. Pat., 211,291 (1954). 1325. Span. Pat., 216,773 (1964). 1326. Sparkes, Libby and Trepagnier, U.S. Pat., 2,448,158 (1948). 1327. Spasov and Kurtev, Annwlire univ. Sofca, Facult4 phys.-math.,43, Livre 2, 37 (1946-7); through Chem. Abstracts, 44, 1491 (1950). 1328. Sprague, U.S. Pat., 2,519,001 (1950). 1329. Sprague, U.S. Pat., 2,706,193 (1955). 1330. Sprague, Brooker and Dent, US. Pat., 2,639,282 (1953). 1331. Sprung, U.S. Pat., 2,687,957 (1954). 1332. Stallman and Langerak, U.S. Pat., 2,643,250 (1953). 1333. StanGk, Collection Czech. Chem. Commun., 13, 37 (1948). 1334. Stangk and Holub, Chem. listy, 47, 404 (1953); through Claern. Abstracts, 49, 232 (1955).
References 1335. 1336. 1337. 1338. 1339. 1340. 1341. 1342. 1343. 1344. 1345. 1346. 1347. 1348. 1349. 1350. 1351. 1352. 1353. 1354. 1355. 1356. 1357. 1358. 1359. 1360. 1361. 1362. 1363. 1364. 1366. 1366. 1367. 1368. 1369. 1370. 1371. 1372. 1373. 1374. 1375. 1376. 1377. 1378. 1379.
515
Stanfield, Brodio and Yeoman, Proc. SOC.Exptl. Biol. Ned., 83, 254 (1953). Stenzl, Ger. Pat., 565,799 (1931). Stenzl, U.S. Pat., 1,972,036 (1934). Stenzl, U.S. Pat., 2,562,830 (1951). Shnzl, Staub, Simon and Baumann, HeZw. Chim. Acta, 33, 1183 (1950). Stepanov and Kuzin, Ber., 65, 1239 (1932). Stevens and Beutel, J. Am. Chem. SOC.,65, 449 (1943). Stodola, J. Org. Chem., 13, 757 (1948). Stoerrner and Johmnsen, Ber., 40, 3701 (1907). Stoermer and Martinsen, Atan., 352, 322 (1907). Stoormer, Schonk and Bushmann, Ber., 61, 2312 (1928). Stoll, Morg. and Poyer, U.S. Pat., 2,401,522 (1946). StollB, Ber., 38, 3023 (1905). Stolyarova and Chel'tsov, Doklady A M . Xuuk S.S.S.R., 87, 1025 (1952); through Chem. Abatracts, 49, 5068 (195.5). Stolyarova and Chel'tsov, Zhur. Fiz. Khim., 27, 640 (1953); through Chem. Abstracts, 48, 2441 (1954). Stolz, Ber., 27, 407 (1894). Stolz, Ber., 28, 023 (1895). Stolz, Ber., 36, 3279 (1903). Stolz, Ber., 41, 3849 (1908). Stolz, U.S. Pat., 1,053,240 (1913). Stolz and Korndorfer, U.S. Pat., 990,310 (1911). Stolz and Kross, Ger. Pat., 500,521 (1929). Strain and Dickey, U.S. Pat., 2,430,484 (1947). Straub and Brassol, US. Pat., 2,404,198 (1946). Straub, Brassol and Pieth, U.S. Pat., 2,439,163 (1948). Straub, Brassel and Pieth, U.S. Pat., 2,557,057 (1951). Straub, Ranhart and Mannhart, U.S. Pat., 2,494,416 (1950). Streitwolf, Fehrle and Hallendeben, Gor. Pat., 540,700 (1928). Streitwolf, Fehrle and Herrmann, Ger. Pat., 581,329 (1933). Streitwolf, FehrIo and Herrmann, U.S. Pat., 2,161,538 (1939). Streitwolf, Fehrle, Hermann and Fritsche, Ger. Pat., 520,225 (1928). Stiisser and Petersen, Ger. Pat., 762,445 (1952). St. Weil and Zyngier, Roczniki Chem., 8, 177 (1928); through Chem. Abstracts, 22, 4506 (1928). Sudborough and Beard, J. Chem. SOC.,97, 773 (1910). Sudo, J. Chem. SOC. Japan, Pure Chem. Sect., 74, 658 (1953); through Chent. Abstracts, 48, 2510 (1954). Sugasawa and Mizukami, I'harm. Bull. (Japan), 3, 393 (1955); through Chem. Abstracts, 50, 15534 (1956). Sumio and Miyahara, Jap. Pat., 3082 (1953). Sumpter and Wilken, J . Am. Chem. Soc.. 70, 1980 (1948). Swiss Pats., 167,709-13 (1934). Swiss Pat., 199,648 (1935). Swiss Pat., 214,905 (1941). Swiss Pat., 216,108 (1941). Swiss Pat., 220,106 (1942). Swiss Pats., 220,411-15, 220,750-51 (1942). Swiss Pat., 220,748 (1942).
516 1380. 1381. 1382. 1383. 1384. 1385. 1386. 1387. 1388. 1389. 1390. 1391. 1392. 1393. 1394. 1395. 1396. 1397. 1398. 1399. 1400. 1401. 1402. 1403. 1404. 1405. 1406. 1407. 1408. 1409. 1410. 1411. 1412. 1413. 1414. 1415. 1416. 1417. 1418. 1419. 1420. 1421. 1422. 1423. 1424. 1425. 1426. 1427. 1428. 1429.
References
Swiss Pats., 222,139-48 (1942). Swiss Pats., 223,703-04 (1943). Swiss Pat., 224,118 (1943). Swiss Pat., 224,352 (1942). Swiss Pat., 224,647 (1943). Swiss Pat., 229,184 (1944). Swiss Pat., 230,906 (1944). Swiss Pat., 232,460 (1944). Swiss Pats., 232.270-71 (1944). Swiss Pat., 233,084 (1944). Swiss Pat., 233,085 (1944). Swiss Pat., 233,186 (1944). Swiss Pats., 233,353-54 (1944). Swiss Pat., 233,570 (1944). Swiss Pat., 234,937 (1945). Swiss Pats., 235,509-12 (1945). Swiss Pat., 236,764 (1945). Swiss Pats., 238,461-62 (1946). Swiss Pats., 238,463-66 (1946). Swiss Pats., 238,334-41 (1946). Swiss Pat., 239,883 (1946). Swiss Pats., 240,12%24 (1946). Swiss Pat., 240,994 (1946). Swiss Pat., 241,415 (1946). Swiss Pats., 244,510-15 (1947). Swiss Pat., 246,476 (1947). Swiss Pat., 248,694 (1948). Swiss Pat., 248,698 (1948). Swiss Pats., 248,805-6 (1948). Swiss Pats., 249,027-30 (1948). Swiss Pat., 249,551 (1948). Swiss Pat., 251,797 (1948). Swiss Pats., 252,949-51 (1948). Swiss Pats., 253,398-406 (1948). Swiss Pat., 253,641 (1948). Swiss Pats., 253,877-78 (1948). Swiss Pats., 253,879-83 (1948). Swiss Pat., 261,361 (1949). Swiss Pat., 255,314 (1949). Swiss Pats., 257,02&30 (1949). Swiss Pats., 259,723-27 (1950). Swiss Pats., 259,822 and 263,845 (1949). Swiss Pats., 261,056-57 (1949). Swiss Pat., 261,364 (1949). Swiss Pat., 263,284 (1949). Swiss Pats., 259,822 and 263,841 (1949). Swiss Pat., 265,105 (1950). Swiss Pat., 265,418 (1950). Swiss Pat., 265,720 (1950). Swiss Pat., 266,100 (1950).
References 1430. 1431. 1432. 1433. 1434. 1435. 1436. 1437. 1438. 1439. 1440. 1441. 1442. 1443. 1444. 1445. 1446. 1447. 1448. 1449. 1450. 1451. 1452. 1453. 1454. 1455. 1456. 1457. 1458. 1459. 1460. 1461. 1462. 1483. 1464. 1465. 1466. 1467. 1468. 1469. 1470. 1471. 1472, 1473. 1474.
517
Swiss Pate., 266,236-37 (1950). Swiss Pat., 266,368 (1950). Swiss Pat., 267,269 (1950). Swiss Pats., 267,30&12 (1950). Swiss Pat., 268,422 (1950). Swiss Pat., 268,512 (1950). Swiss Pat., 269,045 (1950). Swiss Pat., 269,087 (1950). Swiss Pat., 269,509 (1950). Swiss Pats., 269,980-82 (1950). Swiss Pats., 269,983-87 (1950). Swiss Pats., 270,539; 272,495-500 (1951). Swim Pat., 270,833 (1950). Swiss Pat., 273,078 (1951). Swiss Pat., 278,449 (1952). Swiss Pat., 281,647 (1952). Swiss Pat., 287,117 (1953). Swiss Pat., 287,198 (1953). Swiss Pat., 291,812 (1953). Swiss Pat., 292,087 (1953). Swiss Pats., 293,699; 293,901-04 (1953). Swiss Pats., 293,861-66; 293,888; 293,870 (1954). Swiss Pats., 294,228-29 (1954). Swiss Pat., 298,511 (1954). Swiss Pat., 299,099 (1954). Swiss Pat., 299,598 (1954). Swiss Pats., 300,457-65 (1954). Swiss Pat., 300,593 (1954). Swiss Pat., 301,439 (1954). Swiss Pat., 302,154 (1954). Swiss Pats., 302,544; 306,246-50 (1955). Swiss Pats., 303,280; 306,251; 306,261-62; 306,266-67 (1955). Swiss Pats., 303,855-93 (1955). Swiss Pats., 304,613-14 (1955). Swiss Pats., 305,714 (1955). Swiss Pats., 305,715 and 305,717 (1955). Sato and sogabo, Sci. Papers Inat. Phys. Chem. Research (Tokyo),38, 231 (1941); through Chem. Abstracts, 35, 4666 (1941). Taboury, Compt. rend., 214, 764 (1942). Taboury and Boureau, BUZZ.8oc. chim. France, [5], 12, 598 (1945). Taboury and Gray, BuU. SOC. chim. France, [5], 11, 435 (1944). Takahashi and Ogyu, JEP. Pat., 3683 (1954). Takahashi. Okada and Hori, J. €'harm. SOC.Japan, 75, 1431 (1955); through Chem. Abstraets, 50, 10086 (1956). Takahashi and Satake, J . Phurm.SOC. Japan, 75,14 (1955); through Chem. Abstracts, 50, 1005 (1956). Takahashi and Senda, J . Phurm. SOC. Japan, 72,614 (1952); through Chem. Abstracts, 47, 6406 (1953). Takahashi and Yoshii, P k m . Bull. (Japan),2, 382 (1954); through Chem. Abstracts, 50, 13032 (1956).
518
References
1475. Takeda, Jap. Pat., 1717 (1951). 1476. Takeda, Kurizuka, Okano and Majima, Yokohama &led. Bull., 3, 291 (1952);through Chem. Abstracts, 48, 3352 (1954). 1477. Taube, U.S. Pat., 2,731,473 (1956). 81, 2452, 2456 (1959). 1478. Taylor and Hartke, J . Am. Chem. SOC., 1479. Ten C a b and Knoppers, Arch. ncierland. physiol., 26, 329 (1942);through Chem. Abstracts, 38, 5587 (1944). 1480. Teramura, Itagaki and Oda, Bull. Inst. Chem. Research, Kyoto Univ.. 31, 223 (1953);through Chem. Abatracte, 48, 7551 (1954). 1481. Teramura, Itagaki and Oda, J . Chem. SOC.Japan, I d . Chem. Sect., 57, 126 (1954);through Chem. Abstracts, 49, 11625 (1955). 1482. Thesing, Uhrig and Miiller, Angew. Chem., 67, 31 (1955). 1483. Thesing, Zeig and Mayer, Chem. Ber., 88, 1978 (1955). 1484. ThieIe, U.S. Pat., 1,582,802(1926). 1485. Thielepape and Spreklesen, Ber., 55, 2929 (1922). 1486. Thieas, Ger. Pat., 831,716 (1952). 1487. Thiess, Ger. Pat., 832,178 (1952). 1488. Thompson, U.S. Pat., 2,518,730 (1950). 1489. Thompson, Swsnaon and Norman, Botan. (fuzz.,107, 476 (1946). 1490. Thoms and Ritsert, Ber. Pham. Qes., 31, 65 (1921); through Chem. Abstracts, 15, 2852 (1921). 1491. Thoms and Schnupp, Ann., 434, 296 (1923). 1492. Thurston, U.S. Pat., 2,309,679 (1943). 1493. Thurston, U.S. Pat., 2,444,013 (1948). 1494. Tomasik, Roczniki Chem., 8, 345 (1928);through Chem. Abstracts, 23, 2176 (1929). 1495. Tomek, Arzneimittel-Forssch.,5, 53 (1955). 1496. Tonutti, Schoeller and Jonaa, Brit. Pat., 691,800 (1953). 1497. Torrey and Rabsky, J . Am. C h m . SOC.,32, 1489 (1910). 1498. Torrey and Zanotti, J . Am. Chem. SOC.,30, 1241 (1908). 1499. Torrey and Zanetti, Am. Chem. J . , 44,391 (1910). 1500. Tripodo and Capaldo, Riv. bio2. (Peru&), 46, 501 (1954);through Chem. Abstracts, 49, 8501 (1955). 1501. Tsumaki, Bull. Chem. SOC. Japan, 6 , 1 (1931);through Chem. Abstracts, 25, 2145 (1931). 1502. Tsumaki, B d l . Chem. SOC.Japan, 7 , 45 (1932);through Chem. Abstracta, 16, 2977 (1932). 1503. Tsumaki and Hattori, J . Chem.SOC.Japan, 62, 1022 (1941);through Chem. Abstracts, 41, 3095 (1947). 1504. Terpeinen and Kallio, Suomen Kemktilehti, 14B, 8 (1941);through Chem. Abstracts, 36, 426 (1942). 1505. Twomey, Proc. Roy. Irish A d . , S7B, 39 (1954);thro.ugh Chem. Abstracta, 50, 340 (1956). 1506. U.S. Pat., 936,380(1909). 1507. Vaisman and Kogan. Aptechnoe Delo, 1952, No. 3, 17; through Chem. Abstracts, 47, 1006 (1953). 1508. Valysshko and Bliznyukov, Ukrainakii Khem. Zhur., Sci. Pt., 5, 47 (1930); through Chem. Abstracts, 24, 5751 (1930). 1509. Valyaahko and Bliznyukov, J. Uen. Chem. (U.S.S.R.), 10, 1343 (1940); through Chem. Abstracb, 35, 3633 (1941).
References
519
1510. Valyashko and Bliznyxkov, J. @en. Chem. (U.S.S.R.), 11, 23 (1941); through Chem. Abstracts, 35, 5496 (1941). 1511. Vdyashko and Bliznyukov, J. Gen. Chem. (U.S.S.R.), 11, 559 (1941); through Chem. Abstracts, 35, 7961 (1941). 1512. van Alphen, Rec. trav. chim., 43, 823 (1924). 1513. van Alphon, Rec. trav. chim., 64, 109 (1945). 1514. van Alphen, Rec. trav. chim., 64, 305 (1945). 1515. van do Straete and Schouwenaam, US. Pat., 2,557,806 (1951). 1516. vctn Domael, Chimie et indwtrie, 63, No. 3 bis, 478 (1950);through Chem. Abstracts, 47, 6285 (1953). 1517. van Domael and Nys, BdZ. soc. chim. Belges, 62, 199 (1953);through Chem. Abstracts, 48, 6295 (1954). 1518. van Domael and van der Aurwa, U.S. Pat., 2,566,814 (1951). 1519. van Domael and van der Auwem, U.S. Pat., 2,621,125 (1952). 1520. Veibel and Arnfred, Acta Chem. Scad., 2, 914 (1948). 1521. Veibel, Eggersen and Linholt, Acta Chem. Scad., 6, 1066 (1952). 1522. Veibel, Eggemen and Linholt, Acta Chem. Scad., 8, 768 (1954). 1523. Voibel and Kjaer, Proc. X l t h Inter. Congr. Pure and Applied Chem. (London),2, 329 (1947);through Chem. Abstracts, 45, 6128 (1951). 1524. Veibel, Kjmr and Plejl, Acta Chem. Scad., 5 , 1283 (1951). 1525. Veibel and Linholt, Acta Chem. Scand., 8, 1007 (1954). 1526. Veibel and Linholt, Acta Chem. Scad., 8, 1383 (1954). 1527. Veibel and Linholt, Acta Chem. Scad.,9, 963,970 (1955). 1528. Veibel and WestW, Acta Chem. Scad., 7, 119 (1953). 1529. Veldstra and Wiardi, Rec. trav. chim., 61, 627 (1942). 1530. Venus-Danilova and Fabritsy, Zhur. Obskhei Khim., 26, 884 (1956); through Chem. Abstracts, 50, 14721 (1956). 1531. Verkade and Dhont, Rec. traw. chim., 64, 165 (1945). 1532. Vila, Ion, 7, 150 (1947);through Chem. Abstracts, 42, 2933 (1948). 1533. Vila and Carreras, Analesfis. y quim. (Madrid), 41, 807 (1945);through Chem. Abatrackr, 41, 6549 (1947). 1534. Vila and Carreras, Am& fi.. y quim. (Madrid), 43, 51 (1947); through Chem. Abstracts, 41, 4469 (1947). 1535. Vila and Mass6, Anaka real SOC. e s p a f i . j a . y quuim.,48B, 155 (1952);through Chem. Abstracts, 47, 6871 (1953). 1536. Vila and Pulido, A&@. y quim. (Madrid),43, 389 (1947);through Chem. Abstracts, 42, 129 (1948). 1537. Visoontini, Bally and Meier, Nelv. Chim. Acta, 35, 451 (1952). 153s. Vittum and Uuennebier, J. Am. Chem. SOC.,72, 1536 (1950). 1539. Vittum, Sawdey, Hordle and Scholl, J. Am. Chem. SOC.,72, 1533 (1950). 1539a. Vittum and Woissberger, J . Phot. Sci., 6, 157 (1958). 1540. Vittum, Weissberger and Porter, U.S. Pat. Appl., 668,778,Offmid Gas., 631, 283 (1950). 1541. Voelkel, Arch. intern. phamnacedynamie, 102, 194 (1955);through Chem. Abstracts, 49, 15046 (1955). 1542. von Meyer, J. prakt. Clam., SO, 1 (1914). 1543. von Meyer and Spreckels, J. prukt. Chem., 92, 174 (1915). 1544. von Rothenburg, Ber., 25, 3441 (1892). 1545. von Rothenburg, Ber., 26, 415 (1893). 1546. von Rothenburg, Ber., 26, 868 (1893).
520
References
1547. von Rothenburg, Ber., 26, 1719 (1893). 1548. von Rothenburg, Ber., 26, 1722 (1893). 1549. von Rothenburg, Ber., 26, 2053 (1893). 1550. von Rothenburg, Ber., 26, 2972 (1893). 1551. von Rothenburg, Ber., 27, 782 (1894). 1552. von Rothenburg, Ber., 27, 783 (1894). 1553. von Rothenburg, Ber., 27, 790 (1894). 1554. von Rothenburg, Ber., 27, 946 (1894). 1555. von Rothenburg, Ber., 27, 1098 (1894). 1556. von Rothenburg, Ber., 27, 1099 (1894). 1557. von Rothenburg, J. prakt. Chem. [2], 50, 227 (1894). 1558. von Rothenburg, J. prakt. Chem. [2],51, 157 (1895). 1659. von Rothenburg, J. prakt. Chem. [2],51, 522 (1895). 1560. von Rothenburg, J. prakt. Chem. [2], 52, 23 (1895). 1561. von Rothenburg, J. prakt. Chem. [2],52, 45 (1895). 1562. von Walther, J. prakt. Chem., 83, 171 (1911). 1563. von Walther and Hirschberg, J. p a k t . Chem. [2], 67, 377 (1903). 1564. von Walther and Rothacker, J. prakt. Chem. [2], 74, 207 (1906). 1565. Vorbrodt, Bull. intern. acad.polon. sci., Ctasse sci. math. et nat., 103, I, 17i (1951);through Chem. Abstracts, 46, 8727 (1952). 1566. Votocek and Valentin, Collection Czechoslov. Chem. Commun., 5, 84 (1933). 1567. Votocek and Wichtarle, Collection Czechoslow.Chem. Cmmun., 7,388 (1935). 1568. VystrEil and ProkLSs, Chem. listy, 46, 670 (1952);through Chem. Abstracts, 48, 165 (1954). 1569. VystrEil and Stejskal, &~sopisCeskkho Ldkdrnictva, 63, 75 (1950);through Chem. Abstracts, 46, 7566 (1952). 1570. VystrEil and VidliEka, Chem. Eisty, 45, 407 (1951);through Chem. Abstracts, 46, 7567 (1952). 1571. Wachsmuth, J . Pharm. Chim. [9], 1, 383 (1941). 1572. Wagner, Arch. Plum., 289, 121 (1956). 1573. Wahl, Bull. soc. chim. France, El], 1, 726 (1907). 1574. WaN, Bull. soc. chirn. France, [4], 1, 729 (1907). 1575. Wahl, C m p t . rend., 206, 521 (1938). 1576. Wahl and Doll, BdZ. aoc. chim. France, [4], 13, 468 (1913). 1577. Wahl, Goedkoop and Heberlein, C m p t . rend., 206, 191 (1938). 1578. Wahl and Meyer, Compt. rend., 145, 192 (1907). 1579. Wahl and Meyer, B d l . soc. chim. Fi-ance, [4], 3, 957 (1908). 1580. Wahl and Rolland, Ann. Chim. [lo], 10, 5 (1928);through Chem. Abstracts, 23, 3218 (1929). 1581. Wahl and Silbenweig, Bull. 8oc. chim. France, [4]. 11, 61 (1912). 1582. Wahlberg, Ber., 44, 2071 (1911). 1583. Wales and Nelson, J. Am. Chem. SOC.,45, 1657 (1923). 1584. Walker, Am. Chem. J., 16, 430 (1894). 1585. Walker, J. Chem. SOC.,1942, 347. 1586. Wallenfels, Bep.., 74, 1598 (1941). 1587. Wallenfela and Sund, Arch. exptl. Pathol. Phannakol., 232, 338 (1957). 1588. Wallingford and Homeyer, U.S. Pat., 2,367,362 (1945). 1589. Wallingford and Homeyer, U.S.Pat., 2,407,942 (1946). 1590. Wallingford, Homeyer and Jones, J. Am. Chem. SOC.,63, 2252 (1941).
References
521
1591. Wang and Yuen, J . Chinese Chem. SOC.,15, 215 (1948); through Chem. Abstracts, 42, 7266 (1948). 1592. Wascr, Helv. Chim. Acta, 8, 117 (1925). 1593. Weissberger and Edens, U.S. Pat., 2,589,004 (1962). 1594. Weissberger, Kibler and Young, U.S. Pat., 2,412,700 (1946). 1595. Weissberger and Porter, J . Am. Chem. SOC.,64, 2133 (1942). 1596. Weiasberger and Porter, J . Am. Chem. SOC.,65, 52 (1943). 1597. Weissbergor and Porter, J . Am. Chem. Soc., 65, 732 (1943). 1598. Weissberger and Porter, J . Am. Chem. Soc., 65, 1495 (1943). 1599. Weissbergcr and Porter, J . Am. Chem. SOC.,65, 2180 (1943). 1600. Weissberger and Porter, J . Am. Clwm. SOC.,66, 1849 (1944). 1601. Weissberger, Porter and Gregory, J . Am. Chem. SOC.,66, 1851 (1944). 1602. Weissberger and Salminen, U.S. Pat., 2,484,477 (1949). 1603. Weissberger and Vittum, U S . Pat., 2,618,641 (1952). 1604. Weissborgcr, Vittum and Eden, U.S. Pat., 2,511,231 (1950). 1605. Westoo, Actu Chem. Scum€.,6, 1499 (1952). 1606. West.66, Acta Chem. Swznd., 7 , 352 (1953). 1607. Westoo, Acta Chem. Scand., 7 , 355 (1953). 1608. Westoo, Acta Chem. Scund., 7 , 360 (1953). 1609. Westoo, Acta Chem. Swnd., 7 , 449 (1953). 1610. Westoo, Actu Chem. Scad., 7 , 453 (1953). 1611. Westoo, Actu Chem. Scad., 7 , 456 (1953). 1612. West60, Acta Chem.Scad., 9, 797 (1955). 1613. Westod, Acta Chem. Scand., 10, 9 (1956). 1614. Westoo, Ackc Chem. Scand., 10, 587 (1956). 1615. Weygand, Grimbaeh, Kirchner and Haselhorat, Chem. BeT., 88,487 (1955). 1616. Widmor and Buehler, U.S. Pat., 2,570,085 (1951). 1617. Widmer, Fasciati and Reich, U.S. Pat., 2,606,185 (1952). 1618. Widmer and Heckendorn, U.S. Pat., 2,599,331 (1951). 1619. Widmer, Kaiser, Buehler and Zickendraht, U.S. Pat., 2,538,568 (1951). 1620. Widmer and Ruegg, US.Pat., 2,538,610 (1951). 1621. Widmer and Zickcndraht, U S . Pat., 2,665,898 (1951). 1622. Wiloy, Hart, Davies and Smith, J . Am. Chem. SOC.,76, 4931 (1954). 1623. Wilhelmi, Schweiz. med. woclwchr., SO, 936 (1950); through Chem. Abstracts, 45, 4823 (1951). 1624. Wilhelmi and Currie, Schweiz. med. wochchr., 84, 1315 (1954); through Chem. Abstracts, 49, 4868 (1955). 1625. Wilhelmi and Domenjoz, Arch. intem. pharmacodynamie, 85, 129 (1951); through Chem. Abstracts, 45, 3941 (1951). 1626. Wilkinson and Brown, Am. J . Med. Sci., 225, 163 (1953). 1627. Williams, U.S. Pat., 2,243,324 (1941). 1628. Willstaodt, Svenak Kim. Tid., 55, 214 (1943); through Chem. Abstracta, 39, 2059 (1945). 1629. Willstaedt, Borggard and RlyrbLck, Arkiv Kemi, 1 , 331 (1949); through Chem. Abstracts, 44, 3955 (1950). 1630. Wilson, U.S. Pat., 2,085,515 (1954). 1631. Wilson, U.S. Pat., 2,085,516 (1954). 1632. Wilson, Baird, Burns, Munro and Stephen, J . Roy. Tech. Coll. ( Q h g o w ) , 2, No. 1, 56 (1929); through Chem. Abstracts, 23, 5164 (1929). 1633. Winnek, U.S. Pat., 2,281,014 (1942).
622
References
Winternitz, Ledrut and Combes, Bull. SOC. chim. France, 1952, 398. Wislicenus, Ber., 19, 3225 (1886). Wislicenus, Ber., 20, 2930 (1887). Wislicenus, Ber., 24, 1261 (1891). Wislicenus and Bilfinger, Ber., 46, 3948 (1913). Wislicenus and Eble, Ber., 50, 250 (1917). Wislicenus, Eichert, Marquardt and Riethmuller, Ann., 436, 82, 88 (1924). Wislicenus, Elvert and Kurtz, Ber., 46, 3395 (1913). Wislicenus and Goz, Ber., 44, 3491 (1911). Wislicenus and Schrotter, Ann., 424. 215 (1921). Wolff, Luttringhaus and Fertig, Ann., 313, 1 (1900). WoH and Thielepape, Ann., 420, 275 (1920). Wollers and Behrend, Ann., 323, 279 (1902). Woodward, U.S. Pat., 2,415,381 (1947). Woodward, U.S. Pat., 2,415,382 (1947). Worrall, J. Am. Chem. SOC.,44, 1551 (1922). Worrall, J. Am. Chem. SOC.,45, 3092 (1923). Worrall, J . Am. Chem. SOC.,46, 2832 (1924). Worrall, J. Am. Chem. SOC.,59, 933 (1937). Worrall, J . Ant. Chem. SOC.,59, 1486 (1937). Worrall, J . Am. Chem. SOC.,60, 1198 (1938). Worrall and Lavin, J . Am. Chem. SOC.,61, 104 (1939). Worrall, Lerner and Washnock, J . Am. Chem. SOL,61, 105 (1939). Wyngaarden, J . Clin. Invest., 34, 256 (1955). Yagupol'skii and Kiprianov, Zhw. Obshchei Khim., 22, 2216 (1952); through Chem. Abstracts, 47, 4771 (1953). 1659. Yale, Losee, Martins, Hoking, Perry and Bernstein, J . Am. Chem. Sac., 75,
1634. 1635. 1636. 1637. 1638. 1639. 1640. 1641. 1642. 1643. 1644. 1645. 1646. 1647. 1648. 1649. 1650. 1651. 1652. 1653. 1654. 1655. 1656. 1657. 1658.
1933 (1953). 1660. Yano, Polio Phaarmncol. Japan, 23, 211 (1937); through C1te.m.Abstracts, 31, 2354 (1937). 1661. Yaauda, Rep&. Sci. Reaearch Inst. (Japan),30, 340 (1954); through Chem. Abstracts, 49, 12836 (1955). 1662. Yosida, Jap. Pat., 132,943 (1959). 1663. Yu, Burns, Paton, Gutman and Brodie, J. Phrm. Ezptl. Therapeutics, 123, 63 (1958). 1664. Yu, Sirota and Gutman, J . Clin. Invest., 32, 1121 (1953). 1665. Zeller, Verhandl. Ber. Schweiz. Physiol., 21, 43 (1942); through Chem. Abstrach, 38, 5509 (1944). 1666. Zeller and Bisseger, HeEv. Chim. Acta, 26, 1619 (1943). Sci. l'hot. Japan, 15, 37 (1952); through Chem. Abstracts, 49, 1667. Zenno. J . SOC. 300 (1955). 1668. Zenno, J . Pharm.SOC.Japan, 73, 589 (1953); through Chem. Abstracts, 48, 6858 (1954). 1669. Zenno, J . Pharm. SOC. Japan, 73, 1063 (1953); through Chem. Abstracts, 48, 8543 (1954). Sci. I'hot. Japan, 15, 99 (1953); through Chem. Abstracts, 48, 1670. Zenno, J . SOC. 11063 (1954). 1671. Zervas, Gcr. Pat., 745,625 (1943). 1672. Zervas, U.S. Pat., 2,315,836 (1943). 1673. Zervas, U.8. Pat., 2,322,907 (1944).
References
523
1674. ZeNaS, u.8.Pat., 2,337,845 (1943). 1675. Zerweck and Fleischharrer, Ger. Pat., 818,221 (1951). 1676. Zeuner, Zentr. Bakt. Parmitenk., I Orig., 150, 116 (1943); through Chem. Abstracts, 38, 414 (1944). 1677. Zhadek, Zhur. Priklad. Khim., 25, 109 (1952); through Chem. Abstracts, 47, 867 (1953). 1678. Zhivopistsev, Doklady Akad. Nauk S.S.S.R., 73, 1193 (1950); through Chem. Abstracts, 45, 492 (1951). 1679. Zhivopistsev, Zhw. Prikkzd. Khim., 26, 335 (1953); through Chem. Abalracls, 47, 12113 (1953). 1680. Zickendraht and Buehler, U.S. Pat., 2,673,201 (1954). 1681. Zickendraht and Buehler, US. Pat., 2,727,031 (1955). 168la. Ziegler and Locher, Ber., 20, 834 (1887). 1682. Ziegler and Sauennilch, Ber., 63, 1851 (1930). 1683. Zimmerman and Cuthbertson, 2. phy&oZ. Chem., 205, 38 (1932). 1684. Zischler, US. Pat., 2,265,221 (1941). 1685. Zorn and Schmidt, Hoppe-Zeyler’s 2. physiol. Chem., $98, 140 (1954). 1686. Zoas and Hennion, J. Am. Chem. SOC.,63, 1161 (1941). 1687. Zwart and Wibaut, Rec. trav. chim., 74, 1062 (1955).
Index Acetylphenylhydrazinc, reaction with Absorption spectre, of azomethine dycs, 149 /3-kotoestere, 9 of 3,5-pyrazolidinediones, 124, 129 4-Acetyl-3-pyrazolin-5-ones, eynthesis, 93 of 3-pyrazolidinones, 10, 11, 115 Acid Alizarin Bordeaux B, 482 of 2-pyrazolin-5-ones, 5, 6, 19 Acid Alizarin Flavin CF, 482 of 3-pyrazolin-B-ones,6 Acrylamide, reaction with aryl hydra3-Acotoxy-4-ethyl-4-phenyl-2zines, 115 pyrazolin-5-one, 127 6-Acetoxypyrazoles, 104 l-Acyl-5-acyloxypyrazoles, reaction with piperidine, 103 Acetamide, reaction with 2-pyrazolin5-ones, 21 4-Acyl-B-acyloxypyrazoles, synthesis, 91 Acetoacethydrazidos, cyclization to 2pyrazolin-5-ones, 16 3-Acylamido-l-acyl-4-arylimino-2pyrazolin-5-ones. 136 Acetoacetic estors Acyl arylhydrazines, reaction with @reaction with p-aminostyreneketoastors, 9, 46 malonic acid polymer, 108 reaction with hydrazines, 14 Acylation reaction with phenylisothiocyanate, of 5-imino-3-pyrazolidinones,63, 138 132 of 4-imino-2-pyrazolines, 113 2-Acetyl-3-acetoxy-B-acetimido-3pyrezolin-5-ones, 104 of 5-imino-2-pyrezolinos, 44 4-Acetyl-2,3-dimothyl-1-phenyl-3of 3,5-pyr~zolidinedioncs, 62, 126, pyrazolin-5-one, 48 129, 130 Acetylenic ester synthesis of pyrazolinof 2-pyrazolin-5-ones, 24, 26, 102, 103, 104 ones, 15 of 3-pyrttzolin-5-one.s,49, 104 a,@-Acetylenic nitrilo synthesis of 5 imino-2-pyrazolines, 42 of 2-pyrazolin-B-thionos,41 4-Acctyl-5-imino-3-pyrazolidinones, 3-Acylazopyrazolincs, reduction, 119 Acylcyanoacetic esters, reaction with 138 hydrazine, 97 4-AcetyI-2-mcthyl-1-phonyl-3Acylhydrazines, reaction with cyanopyrazolin-5-ones, 93, 94, 95 acetic estors, 138 4-Acetyl-l-methyl-2-phcnyl-5-thiono4-Acylidene-3,5-pyrazolidinediones, 3-pyrazoIidinone, 130 126 1-Acetyl-3-phenyl-5-acetoxypyrazolc, 104 l-Acyl-5-imino-2-pyrazolidinones, 138 3-Acctyl-4-phenylazo-2-pyrazolin-5- Acylmalonic esters, reaction with hydrazines, 9, 96 one, 91 525
526
Index
3-Acyloxy-5- imino - 2-pyrazolines, 63, a-Alkylthiomethyl-3-pyr~zolin-5-ones, 234-244 54 a-Acyloxy-8-ketocsters, reaction with Allonal, 144 phonylhydmzine, 61 Amides, reaction with 2-pyrazolin-5Acyloxy-Z-pyrazolin-5-onos, 62, 126 ones, 21 0-Acylpyrazoles, 52 Amidines, reaction with 2-pyrazolin-5Acyl-3,5-pyrazolidinediones,126, 129, ones, 21, 34 130, 409-423 3-.4mido- 2 .pyrazolin-5-ones, 136 4-Amido-3-~~yrazolin-5-ones, SO l-Acyl-Z-pyrazolin-5-ones, 103 Amination of pyrazole ring, 42 4-Acyl-2-pyrazolin-5-ones, 30, 89, 90Amines, reaction with 2-pyrazolin-591, 354-355 ones, 25 4-Acyl-8-pyrazolin-5-ones, 93 Agranulocytosis, 144, 145-146 4-Aminoantipyrine, 121, 144, 157 Aldehydes 8-Aniino-crotonitriles, reaction with reaction with 4-amino-Z-pyrazolin-5hydrazines, 99 ones, 69 Z-Amino-5-diethylaminotoluene, reacreaction with 5-imino-2-pyrazolinesnes, tion with 2-pyrazolin-5-ones, 43 67 reaction with 3,5-pyrazolidinediones, p-Amino-X,E-diethylaniline, reaction 126 with 2-pyrazolin-5-onas, 148 reaction with 2-pyrazolin-5-ones, 19, p-Amino-N,N-dimethylmiline, reac20, 34, 35 tion with 5-imino-3-pyrazolidinreaction with 3-pyrazolin-5-ones, 50, ones, 136 53, 56 &Amino-2,3-dimethyl-l-phenyl-3fi-Aldehycloesters,reaction with hydrapyrazolin-5-ono, 48, 111, 121 zines, 14, 66 4-Amino-5-imino-3-pyrazolidinones, 8-Aldehydonitriles, reaction with hy137, 138 drazines, 42 Aniinomethylidynemalonic caters, rea-Alkoxyalkyl-2-pyrazolin-5-ones, 29 action with hydrazines, 96 8-Alkoxypropionitriles, reaction with 4-Amino-3-methyl-1-phenyl-2hydrazines, 119 pyrazolin-5-one, oxidation, 74 5-Alkoxypyrazoles, 17, 26 1-( 3-Aminophenyl)-3-methyl-2Alkoxy-3,5-pyrazolidinediones, 128, pyrazolin-5-one, 109 422-423 1-(Aminophenyl)-Z-pyrazolin5-ones, 3-Alkoxy-2-pyrazolin-5-ones, 62 polymerization, 108 Alkylation Aminopyrazoles, 13, 41, 60, 89, 113, of 5-imino-2-pyrazolines,44 233, see also Iminopyrazolinas of 3,5-pyrazolidinedioncs, 62, 126, 4-Amino-3,5-pyrazolidinediones, 128, 127 422-423 of 3-pyrazolidinonos, 12, 118 4-Amino-3-pyrazolidinones, 118 of 2-pyrazolin-5-ones, 21, 22, 26, 46, 3-Aminopyrazolines, 119, see also 353 Iminopyrazolidinm of t-pyrazolin-5-ones, 12, 52, 76- Amino-2-pyrazolin-5-onebisamidea, 77 109 of 3-pyrazolin-5-selenones, 59 3-Amino-2-pyrazolin-5-ones, 136, see of 2-pyrazolin-5-thionas, 41 d o 5-Imino-3-pyrazolidinones of 3-pyrazolin-5-thiones. 59, 76-77 ~-Arnino-t-pyrazolin-5-ones 5-Alkylimino-3-pyrazolidinones, syndiazotization, 74 thesis, 134 Schiff base formation, 69 4-Alkyl-2-pyrazolin-5-ones, 20 synthesis, 68
Index
4-Amino-3-pyrazolin-5-ones, 80, 120, 394-404 acylation, 121 alkylation, 76, 121 biological activity, 120 diazotization, 79, 122 mercuration, 122 reaction with aldehydes, 78, 121 reaction with ketones, 78, 121 reaction with quinolines, 122 synthesis, 120-121 see &o 4-Imino-3-pyrazolidinones Aminopyrine, vii, 4, 11, 66, 76, 77, 80, 88, 107, 108, 120, 143, 144, 156 Analgesics, 5, 26, 76, 120, 122, 143, 144, 145 Analytical reagents, 156-156 4-Anilinomethylidyne-2-pyrazolin-5ones, 3, 24 4-Anilino-3-methyl-1-phenyl-2pyrazolin-5-0110, 66 Anils, reaction with 2-pyrazolin-5ones, 34 Anthralan Yellow G , 482 Antihalation agents, 151 Antimalarial agents, 122 Antioxidants, 157 Antipyretics, 5 , 26, 76, 120, 122, 143, 145 Antipyrine, vii, 4, 5, 6,9, 10, 11, 22, 26, 55, 84, 92, 93, 105, 107, 108, 110, 120, 121, 143, 165, 157 Antipyrine perchlorate, 157 1-(Arsinophenyl)-2,3-dimethyl-4nitroso-3-pyrazolin-5-one, 122 1-Aryl-3-amino-3-pyrazolin-5-ones, as color couplers, 150 4-Arylazo-5-imino-3-pyrazolidinones, 136, 137, 138 4-Arylazoisoxazolidones,7 1 4-Arylazo-5-0x0-2-pyrazolin-3carboxylie acids, 98 4-Arylazo-3,5-pyrazolidinediones, 128 4-Arylazo-2-pyrazolin-5-ones, 69, 7071, 72, 114, 150, 152, 303-333 4-Arylazo-3-pyrazolin-5-ones, 80, 121, 153, 482 Arylhydrazines reaction with ketene, 16
52 7
reaction with C-4 substituted 2pyrazolin-5-ones, 72 Arylhydrazones, from hydrolysis of 1(dinitropheny1)- and 1-(trinitrophenyl)-t-pyrazolin-5-onee, 28
4,4’-Arylidenebis(5-imino-2-
pyrazolines), 43 4,4’-Arylidenebis(2-pyrazolin-5-ones), 38, 150 4,4‘-Arylidenebis(3-pyrazolin-5-ones), 58 4-Arylidene-2-pyrazolin-5-ones, 25 2-Aryl-5-imino-3-pyrazolidinones, as color couplers, 150 4 -Arylimino-5-imino- 3-pyrazolidinones, 137, 138 4-Arylimino-2-pyrazolin-5-ones, 25, 69 4-AryImercapto-2-pyrazolin-5-onesy 63 2-Aryl-3-methyl-3-pyzolin-5-ones, 47 l-Aryl-3-pyrazolidinones, 116 2-Arylpyrrtzolidinones,oxidation, 18 l-Aryl-2-pyrazolin-4-ones, 8 Azides of 5-0x0-3-pyrazolin-carboxylic acids, 100, 101, 133 of 3-phenylpyrazole-5-carboxylic acid, 43 Azipyrazoles, 45, 83 Aziranes, 66 4,4’Azobis( 2 -pyrszolin-5-ones), synthesis, 75 Azo dyes, 25, 152-154, 482 Azomethine dyes, 67, 148, 149, 150 4-Azo-3-methyl-1-phenyl-2-pyrazolin&one, 68 4-Azo-2-pyrazolin-5-ones, reduction, 66 Barbiturates, complexes with aminopyrine, 144 4-Benzamido- 5-phenyl-3 pyrazolidinone, 117 Uenzimidazoline, 151 Benzothiazoline, 151 Benzoxazoles, reactions with 2pyrazolin-5-one, 22 Uenzoxazoline, 151 Benzoylacetic esters, reaction wit.h hydrazinos, 14
-
528
Index
Benzoyl hydrazide, reaction with cyanoacetic esters, 46, 138 4-Benzoyl-3-methyl-l-phenyl-2pyrazolin-5-thione, 91 4-Benzylideneamin0-2,3-dimethyl1phenyl-3-pyrazolin-5-one, 121 4,4‘-Benzylidenobis(2,3-dimethyl1phenyl - 3-p yrazolin-5 -one),156 a-Benzylidene$-ketonitriles, roaction with semicarbazide, 103 D-BenzylpeNcilloicacid, 68 Bis(1-acyl-2-pyrazolin-5-ones), 103 Bishydrazones of a,P-diketoesters, in synthesis of 4-arylazo-2-pyrazolin5-ones, 70-71 Bis(4-imino-3-pyrazolidinones), 122, 394-404, 405, 406-407 Bis(5-imino-3-pyrazolidinones), 136, 138, 406407, 445-447 Bis(4-imino-2-pyrazolinea), 113 5,5’-Bis(5-imino-2-pyrazolines),45, 245, 281-282 Bisisocyanates, reaction with 2pyrazolin-5-ones, 38 4,4‘-Bis(3-methyl-2-benzoyl-1-phenyl3-pyrazolin-5-one), 104 4,4’-Bis[3-methyl-1- (4-nitrophenyl)-2pyrazolin-5-one]. 89 4,4’-Bis( 3-methyl-1-phenyl-2pyrazolin-5-0no), 32, 104 Bis(5-oxo-2-pyrazolinn-4-sulfonic acid), 102 B is(phenylmethylhydrazone) of othy1 a,/?-diketobutyrate, cyclization, 69 Bis(3,5-pyrazolidinediones),406-407 Bis(3-pyrazolidinones), 119 l,l’-Bis(2-pyrazolin-5-ones), 31, 39, 224-230 3,3’-Bis(2-pyrazolin-5-onos), 31, 39, 222-224 4,4’-Bis(2-pyrazolin-5-ones), 207-222 addition reactions, 99 carboxyl substituted, 99 color couplers, 150 degradation, 38 linked by carbon chain, 34, 211-216 alkyl and aryl substituted, 214-210 linked by double bond, 210 linked by N atoms, 218-222 linked by S atoms, 63, 218-222
syntheses, 20, 27, 31, 34, 66, 169, 99 Bis(3-pyrmolin-5-ones). 50, 54, 56, 64, 65, 94-95, 278-282 Bromination, see Halogenation Bromo-compounds, see also Halogenocompounds 4-Bromo-2,3-dimethyl-l-phenyl-3pyrazolin-5-ones, 64 3-Bromomethyl-3-pyrazolin-5-one, 54 1-Bromo-3-methyl-2-pyrazolin-5-one, 82 4-Bromo-3,5-pyrazolidinediones, 126, 127 4-Bromo-2-pyrazolin-5-ones, 82 5-Bromo-2-pyrazolinn-4-ones, 112 4-Bromo-3-pyrazolin-5-ones, 84 N-Bromosuccinimide reaction with 3-methyl-2-pyrazolin5-ones, 82 reaction with 3-pyrazolin-5-ones, 51, 84 Butazolidin, see Phenylbutazone 4-Butyl-1,2-diphenyl-3,5-pyrazolidinedione, see Phenylbutazone t-Butylhydroperoxide, oxidation of 1aryl-2-pyrazolin.5-ones, 2 7 4-Butyl-4-hydroxy-1,2-tfiphonyl-3,5pyrazolidinedione, 128 Cadmium, reactionwith 4,4‘-methylenebis(2,3-dimethyl-l-phenyl-3pyrazolin-5-one), 155 Carbazide, reaction with ketoestors, 39, 105 Carbon disulfide, reaction with 5imino-2-pyrazolines, 44 Carbon suboxide reaction with N,N-diphenyl-Nbutylhydrazine, 126 reaction with qwa-diphenylhydrazine, 126 reaction with phenylhydrazine, 124 1 (3-Carboxypheny1)-3-methyl-2 pyrazolin-5-one, 108 Chemical Abstracts nomenclature, 3, 4 Chloral reaction with 2-pyrazolh-5-ones, 19,QO reaction with 3-pyrazolin-5-ones, 54
-
-
Index Chloral hydrate, reaction with p-nitrophenylhydrazine, 128 Chlorination, see Halogenation Chloro-compounds, 8ee d a o Halogenocompounds a-Chlorocinnamates, reaction with hydrazine, 15 4-Chloro-3-dichloromethyll-phenyl-5phenylimino-2-pyrazoline,83 3-Chloro-5-imino-2-pyrazolines, 136 Chloromethylcumene, complexes with 5-methyl-2-(3-sdfophonyl)-3pyrazolidinone, 157 3-Chloro-1-phenyl-2-pyrw~olin-5-one. 127 4-Chloropyrazolos, 113 5-Chloropyrazoles, 40, 42, 52, 53, 60, 61, 80 3-Chloro-3-pyrazolin-5-ones, 129 5-Chloro-2-pyrazolin-4-ones, 112 Chromium complexes of 4-arylazo-2-pyrazolin-5-ones, 7273 of 4-arylazo-3-pyrazolin-5-ones, 80 Citraconic acid hydrazide, in synthesis of 4-oximino-3-methyl-2pyrazolin-5-one, 86 Cleavage, see Ring cleavage Cobalt ions reaction with antipyrine, 155 reaction with 4,4’-methylenebis(2,3dimethyl- 1-phenyl-3-pyrazolin-5one), 155 Color couplers, 25, 131, 148, 150 Color fdters, 151 Color formers, 123 Colorphotography, 13,67,108,123,131 Complexes, 8ee Metallic complexes; ?Jon-metallic complexes Compral, 144 Condensation reactions of 5-imino-2-pyrazolines,43 of 2-pyrazolin-5-ones, 3 k 3 5 of 2-pymzolin-5-thiones, 41 ,Cmtonamide, reaction with arylhydrazinos, 115 Curtius rearrangement, 43, 86, 101, 133, 137, 138, 139 Cyanides, color reaction with 3-methyl1-phenyl-2-pyrazolin-5-one, 155
529
Cyanine dyes, 151 Cyanoacetic esters reaction with ethyl diazoacetate, 113 reaction with hydrazines, 97, 132133, 138 Cyanoacetic hydrazides, reaction with hydrazines, 132-133 Cyanogen halides, reaction with 2pyrazolin. 5-ones, 155 Cyclobutanone, in synthesis of pyrazolinones, 18 Decarboxylation catalysis by aminoantipyrine, 157 of 4-imino-2-pyrazolin-3-carboxylic acids, 113 of 5-0x0-2-pyrazolin-carboxylic acids, 18 of 5-0x0-3-pyrazolin-carboxylic acids, 101 Degradation of bis(2-pyrazolin-5-ones), 38 Developers, photographic, 151 1,2-Diacetyl-3-phenyl-3-pyrazolin5one, 104 2,4-Diacyl-3-pyrazolin-5-ones, 91 cc,a’-Diacylsuccinic esters, reaction with hydrazines, 31 Dialkyl acetyl succinatos, reaction with diazonium salts, 98 4-Dialkylaminomethyl- 3-pyrazolin-5ones, 49, 55 4,4‘-Dialkyl-2-pyrazolin-5-ones, 26 Diaminopyrazoles, 139 Diamond Red G, 482 Diazomethane reaction with ethylenesulfonyl chloride, 117 reaction with 4-nitro-2-pyrazolin-5ones, 88 reaction with 3,5-pyrazolidinediones, 62, 127 reaction with 2-pyrazolin-5-ones, 46 Diazonium salts of 4-amino-3-pyrazolidinones, 118 of 4-a~nino-2-pyrazolin-5-ones, 74 79, of 4-amino-3-pyrazolin-5-ones, 122 of 4-imino-2-pyrazoliness,113 of 5-imino-2-pyrazolines, 44
530
Index
reaction with acetoacetic esters, 75, a,P-Diketoesters, reaction with 79 hydrazines, 14 reaction with mylpyrazolinonee, 91 1,4-Diketones, reaction with 4-aminoreaction with dialkyl acetylsuccin2,3-dimethyl-1-phenyl-3ates, 95 pyrazolin-5-one, 48 reaction with dicarboxylic acids, 96 Dimerization reaction with 3,4-dimethyl-2of 2-pyrazolin-5-onea,28, 31 pyrazolin-5-one, 110 of 3-pyrazolin-5-ones,31 reaction with 5-hino-3~,/3-Dimethylacrylamide,reaction with pyrazolidinones, 136, 137 arylhydrazines, 115 reaction with 5-imino-24-Dimethylamino-2,3-dimethyl1pyrazolines, 44 phenyl-3-pyrazolin-5-one, ~ e e reaction with a-ketoesters, 114 Aminopyrine reaction with 4-mothyl-3-phonyl-2- 4-(2-dimethy1aminoethoxy)1,2pyrazolin-5-ono, 110 diphenyl-3.5-pyrazolidinedione, reaction with 5-0x0-2-pyrazolin-3128 carboxylic acids, 95 4-Dimethylaminomethyl-3-pyrazolinreaction with 3,5-pyrazolidinediones, 5-oncs, 55 127 2,3-Dhethyl-l-aryl-2-pyrazolin-5reaction with 2-pyrazolin-4-ones, 70, ones, 110 112 5,5-Dimethyl-4-hydroxyl-2-phenyl-3reaction with 2-pyrazolin-5-ones, 11, pyrazolidinediono, 116 25, 69 2,3-Dimethyl-4-isopropylI-phcnyl-3reaction with 3-pyrazolin-5-ones, 12, pyrazolin-5-one, 145 81 Dimethylolurea, reaction with pyrazoreaction with 2-pyrazolin-5-thiones, linones and zein, 110 41 3,4-Dimethyl-2-phenylazo-34,5-Dibromo-3- pyrazolidinones , 84 pyrazolin-5-one, 110 2,5-Dichloro-1-phonylpyrazolo, 139 2,3-Dimethyl-l-phenyl-.4-nitroso-34,4-Dichloro-2-pyrazolin-5-ones, 82, 83 pyrazolin-5-onc, 72 5,5-Dichloro-2-pyrazolin-4-one, 112 2,3-Dimethyl-1-phonyl-5-oxo-3Diethylbarbituric arid, complexes with pyrazolin-4-carboxaldehydc, 92, aminopyrine and antipyrine, 108 93, 95, 110 Diothyl ethoxymcthylenemalonate,re- 2,3-Dimethyl-1-phonyl-5-oxo-3action with N-phenyl-N’-acetylpyrazolin-4-carboxylic acid, 93 hydrazine, 100 2,3-Dimethyl-l-phenyl-5-oxo-fDiethyl pyrazole-3,6-dicarboxybte, pyrazolin-4-methylamino139 mothanesulfonic acid sodium salt, see Dypyrone N,N-Diethyl-1-pyrazolin-3-sulfonamide, 117 2,3-Dimethyl-1-phenyl-G-oxo-3pyrazolin-4-sulfonic acid, 120 Diethyl thiocarbonate, in synthesis of 2,f-Dimethyl-l-phenyl-5-oxo-33,5-pyrazolidinediones, 125 4,B-DihaIo-3-pyrazolidineselenonos,59 pyrazolin-4-sulfonyl chloride, 102 4,5-Dihalo-3-pyraeolidinethiones, 59 1, 5-uimothyl-2 -phenyl-3.4 3,4-Dihydroxy-1,2-diphenyl-3pyrazolidinedione, 120 pyrazolidinone, 117 2,3-Dimethyl-l-phenyl-3-pyrazolin-5Dihydroxytartaric acid, reaction with one, 8ee Antipyrine hydrazines, 98 2,3-Dimethyl-1-phenyl-4-thiocyanate3,4-Di-iminopyrazolidinos,122 t-pyrazoli-5-one, 110 3,fi-Di-iminopyrazolidines, 130 1,3-Dimethyl-2-pyrazolin-5-one, 82
Index
531
reacEthyl j3-amino-~-ethoxyacrylate, 3,4-Dimethyl-2-pyrazolin-5-one, 110 tion with hydrazines, 132 Dioxodiesters, reaction with hydraEthyl 1-aryl-5,5-dichloro-4-oxo-2zines, 39 N,N‘-Diphenylformamidine pyrazoh-3-carboxylates, 113 Ethyl a-bromocinnarnate, reaction with reaction with 5-hino-3phenylhydrazine, 74 pyrazolidinone, 136 reaction with 3,5-pyrazolidmediones, Ethyl a-chbrocinnamate, reaction with hydrazine, 15 127 Ethyl chloroformate, reaction with 5Diphenylhydantoin, complexes with imino-3-pyrazolidinones, 138 aminopyrine and antipyrine, 108 Ethyl cyanoacetate, reaction with ethyl Diphenylhydrazine diazoacetate, 113 reaction with carbon suboxide, 125 reaction with diethyl butylmalonate, Ethyl diazoacetate reaction with ethyl cyanoacetate, 113 128 reaction with malonic esters, 112 reaction with dimethyl acetylenediEthylene diamine, reaction with 2.3carboxylate, 100 dimethyl- 1-phenyl-3-pyrazolin-5reaction with ethyl oxaloacetate, 100 one, 110 reaction with halogenomalonyl Ethyl 2,3-dimethyl-l-pheny1-5-0~0-3chlorides, 129 pyrazolin-4-thiocarboxylate,130 reaction with malonic acids, 124 1,3-Diphenyl-5-irnino-2-pyrazolin-3- 4,4’-Ethyliminobis(2-pyrazolin-5-one), 134 carboxylic acid, 43 Ethyl isoformanilide, reaction with 21,3-Diphenyl-5-imino-2-pyrazoline, 43 pyrazolin-5-ones, 24 1,5-Diphenyl-t-rnethyl-3,4Ethyl orthoformate pyrazolidinedione, 120 I ,2-Diphenyl-3-methyl-3-pyrazolin-5- reaction with 3,3‘-iminobk(2pyrazolin-5-ones), 75 one, reaction with sodium, 53 reaction with 2-pyrazolin-5-ones, 35 1,2-Diphenyl-3,5-pyrazolidinedione, Ethy1 1-phenyl-5-oxo-2-pyrazolin-3acid hydrolysis, 117 carboxylates, 96 1,2-Diphenyl-3,4,5-pyrazolidmetrione, Ethyl 2-phenyl-5-0x0-3-pyrazolin-4reduction, 125 carboxylate, 100 N,N’-Diphenylthiourea, reaction with 4-Ethyl-4-phenyl-3,5-pyrazolidine5-imino-3-pyrazolines, 101 dione, dimerization, 128 Dipole moments 3-pyrazolidinones, 11 pyrazolin-5-ones, 8, 11 Dyes, vii, 4, 13, 22, 25, 67, 72, 80, 95, Fast Light Yellow G, 482 98, 105, 126, 136, 148, 151, 152- Fluorenes, reaction with 4-nitroso-3154, 448-482 pyrtazolin-5-one, 79 Formaldehyde Dypyrone, vii, 122, 144 reaction with 4-amino-3-pyrazolin5-ones, 77 Eriochrome Red B, 482 reaction with 3,3’-iminobis(2Ethoxymethylenemalonic esters, reacpyrazolin-5-ones), 7 5 tion with hydrazines, 96 reaction with 2-pyrazolin-li-onea, 19, Ethyl acetoacetate react ion with p -amhostyrene-maleic 20 acid copolymer, 108 reaction with 3-pyrazolin-5-ones, 49 Formamides, reaction with phenylhydrazine, 138 reaction with phenylisothiocyanate, reaction with 2-pyrazolin-5-ones, 21 132 reaction with 3-pyrazolin-5-ones, 56
532
Index
Formylation of 2-pyrazolin-5-ones, 25 6-Formylbarbituric acid hydrazones, reaction with 2-pyrazolii-5-ones, 23 Furlones, 33, 40, 88, 231-232 Furoxazans, 87 Glyoxal, in synthesis of polymeric 2pyrszolin-5-ones. 109 Gramine, 56 Growth inhibitors, 157 Halogenation of antipyrine, 84 of 1,3-dirnethyl-2-pyrazolin-5-ones, 82 of 5-imin0-2-pyrazoline, 43 82 of 2-nitroso-3-pyrezolin-5-ones, of 3,5-pyrazolidinediones, 126, 129 of 3-pyrazolidinones, 11, 82, 118 of 2-pyrazolin-5-ones, 11, 25, 27, 30, 81 of 3-pyrazolin-5-ones, 11, 49, 50, 51, 83, 84 58-59, 85 of 3-pyrazolin-5-selenones, of 3-pyrazolin-5-thiones, 68-59 Halogenopyrazolos, 58 4-Halogeno-3,5-pyrazolidinediones, 129, 422-423 Hofmann reaction, 55 Hofmann rearrangement, 133 Hydrazides, preparativo uses, 15, 47, 70, 82, 86 Hydrazines reaction with acotyl cyanoacetates, 138 reaction with aoryiamidos, 115 reaction with 8-aldohydoesters, 14 reaction with /?-aldehydonitriles, 42 reaction with alkoxymethylacetoacetic esters, 29 reaction with /?-dkoxypropionitrile, 119 reaction with /?-amino-/?ethoxyscrylates, 132 reaction with 4-aryiazoisoxazolidonos, 7 1 reaction with arylisoxazole-3carboxylic acids, 43
reaction with a-bromocinnamates, 74 reaction with /?-bromopropionicacid, 116 reaction with carbon suboxide, 125 reaction with a-chlorocjnnaxnic esters, 15 reaction with chlorofumaric esters, 96 reaction with /?-chloroisocrotonic esters, 16 reaction with /3-chloropropionyl chlorides, 116 reaction with cyanoacetic esters, 97, 132-133, 138 reaction with cyanoacetic hydrazides, 132-133 reaction with a,a'-diacylauccinic esters, 31 reaction with dicarbethoxy-j?,& dioxoglutario esters, 99 reaction with dihydroxytartaric acid, 98 reaction with 2,3-dimethyl-l-phenyl4-nitroso-3-pyrazolin-5-ono, 72 reaction with dioxodiesters, 39 reaction with esters, /?-substituted, 62 reaction with 6-ethoxy-5-methyl-Bcarbethoxypyrido[2,3: 2',3']-pthiazine, 63 reaction with l-othoxyvinyl-2phenyloxazolidone, 68 reaction with ethyl acetylcyanoacetate, 138 reaction with heterocyclic compounds, 32 reaction with 4-hydroxycoumarin, 7 1 reaction with /?-iminonitriles, 42 reaction with isoxalidones, 93 reaction with isoxazolones, 91 reaction with ketene, 16 reaction with j3-ketoamides, 70, 102 reaction with /?-ketoesters, 9, 14, 34, 61, 62, 68, 70, 85, 90, 102 reaction with j3-ketonitriles, 42 reaction with malonic acid chlorides, 124 reaction with malonic esters, 10, 96, 100, 124 reaction with malononitrile, 98, 139
Index
’
reaction with oxaloacetic esters, 95, 97,99, 100 reaction with 5-0x0-3-pyrazolincarboxylic acid chlorides, 92 reaction with perchloro-l-penten-3one, 85 reaction with phenoxymethylacetoacetic esters, 29 reaction with /3-propiolactone, 116 reaction with 2-pyrazolin-4,5-diones, 69 reaction with 2-pyrazolin-5-ones, 27, 28, 30, 72 reaction with 3-pyrazolin-5-ones,60, 72 reaction with 3-pyrazolin-5-thiones, 60 reaction with pyrazolo-2-pyrones, 32 reaction with rubazonic acids, 75 reaction with 2,3,4-triketochroman, 71 reaction with a,p-unsaturated acids, 115 reaction with a,p-unsaturated amides, 42, 115 reaction with a,punsaturated eaters, 14, 116, 117 reaction with a$-unsaturated nitriles, 42, 119 reaction with a,j9-unsaturated trithiones, 42 3-Hydrazino-4-nitroso-5arylisoxazoles, 86 15-Hydrazinopropionitrile,cyclization, 119 Hydrazones cyclization, 14, 16, 42, 85, 90, 96 of 2-pyrazolin-4,6-diones,68-69,291, 292 of 2-pyrazolin-5-ones, 65, 293-333 Hydrolysis of li-imino-2-pyrazolinesnes, 44 of 3,5-pyrazolidinediones, 128 of 2-pyrazolin-5-ones,28 a-Hydroxyalkyl-2-pyazolin-5-ones, 20, 29, 201-202 a-Hydroxyalkyl-3-pyrazolin-5-0nes. 53, 268-272 4-Hydroxyantipyrine, 143, 144
533
Hydroxylaminea. reaction with 6-oxo-3-pyrazolin-4carboxaldehydes, 55 reaction with 2-pyrazolin-5-ones, 30, 38 reaction with 3-pyrazolin-5-ones, 50 4-Hydroxy-4-methoxy-3-methyl1(4-nitrophenyl)-2-pyrazolin-5-one, 62 4-Hydroxy-3-methyl-1-phenyl-2pyrazolin-6-one,120 4-Hydroxymethyl-2-pyrazolin-5-onos, 29 4-Hydroxymethyl-3-pyrazolin-5-onea, 49, 54, 56
1-(4-Hydroxyphenyl)-3-rnethyl-2pyrazolin-5-one, 109 f3.Hydroxypropionic acid phenylhydrazide, in synthesis of l-phenyl-3pyrazolidinone, 116 4-Hydroxypyrazoles, 8 Hydroxy-2-pyrazolin-5-ones, 61, see a180 Pyrazolidinediones Hydroxy-3-pyrazolin-8-ones, 63, see also Pyrazolidinediones
5,5’-Iminobis(3-pyrazolin~), 61, 278 3,3’-Iminobis(2-pyrazolin-5-ones), 76 /I-Iminonitriles, reaction with hydrazines, 42 3-Iminopyrazolidines, 117, 119, 393 4-Imino-3-pyrazolidinones, 394-404, see also 4-Amino-3-pyrazolin-5ones 5-Imino-3-pyrazolidinones, 65, 104, 131-132, 134-138, 424-445, 8.535 also 3-Amino-2-pyrazolin-5-onea 5-Imino-2-pyrazolin-4-carbonitriles, 98 5-Imino-2-pyrazolin-1-carboxamides, 104 5-Imino-2-pyrazolin-4-carboxamides, 98 5-Imino-2-pyrazolin-4--carbo~nilides, 101 5-Imino-2-pyrazolin-3-carboxylic acids, 99, 113 4-Imino-2-pyrazolines, 113, 382-386 5-Imino-2-pyrazolines, 13, 41-45, 103, 104, 234-244
534
Index
5-Imino-3-pyrazolines, 13, 46, 60, 101, 270, 284-287 4-Imino-2-pyrazolin-5-ones, 67, 114, see &o Rubazonic acids Iodination, 8ee Halogenation Irgapyrine, 145 Isocrotonic esters, reaction with hydrazines, 15 Isocyanates, reaction with 2-pyrazolin&ones, 103 Isonitriles, reaction with 2-pyrazolin5-0neS, 24 Isoxalidones, reaction with phenylhydrazine, 93 Isoxazolones, reaction with hydrazine, 91 Ketene, reaction with arylhydrazines, 16 Keto-enol tautomerism in pyrazolinones, 6 Ketoesters, preparative wes, 14, 15, 68, 70, 71, 90, 102 h-Ketohydrazides, in synthesis of pyrazolinones, 18 Ketones, preparative uses, 19, 20, 21, 34, 43, 126 8-Ketonitriles, preparative uses, 42, 43 Kiton Yellow S, 482 Lithium aluminum hydride, reaction with 2-pyrazolin-5-ones, 28 Magenta dyea, 148 Malonic acid amides, oxidation in synthesis of 3,5-pyrazolidinediones, 125 Malonic esters, 10 reaction with ethyl diazoacetate, 112 reaction with hydrazines, 96, 124 reaction with sernicarbszides. 130 Malononitrile, reaction with hydrazines, 98, 139 Mannich reaction 91 of 4-acyl-2-pyrazolin-5-ones, of 3,5-pyrazolidinediones, 126 of 2-pyrazolin-5-ones, 24 of 3-pyrazolin-5-ones, 49, 57
McFadyen-Stevens aldehyde synthesis of 5-0x0-3-pyrazolincarboxal. dehydes, 92 Yelubrin, 8ee Siilfamipyrine Mercaptans, reaction with 3-pyrazolin5-ones, 54 Mercaptopyrezolcs, 41 Mercury compounds of bis(3-pyrazolin-Ei-ones), 65, 110 of 3-pyrazolidinones, 118, 391-393 of 2-pyrazolin-5-ones,104 of 3-pyraxolin-5-ones,105, 381 Merocyanine dyes, 22, 151 Mesoxaldehyde, in synthesis of 4phenylazo-1-phenyl-2-pyrazolin-5 one, 71 Mesoxalie acid anilide, in synthesis of 3,4,.5-pyrazolidinetrione, 139 Mesoxalie acid hydrazide, in synthesis of 4-phenylazo-3,5-pyrazolidinedione, 128 Metachrome Hod, 5G, 482 Metallic complexes of 4-arylazo-2-pyrazolin-5-ones, 7273, 105 of azo dyes, 152-153 of 4-oxirr1ino-2-pyrazolin-5-ones, 106 of 2-pyrazolin-4-ones,111 of 2-pyrazolin-5-ones, 28, 29, 105106 of 3-pyrazolin-B-ones, 107-108 Methacrylamide, reaction with aq.1hydrazines, 115 Methine dyes, 151 4,4’-IMethenylbis(3-methyl-1-phenyl-2p yrazolin-5-one), 38 3-Nethoxy-1-phenyl-2-pyrazolin-5ones, 82 3-Methoxy- 2-phenyl-3-pyrazolin-5-0110, 127 3-Methoxy- 2-pyrt~zolin-5-one,127 4-Methoxy-3-pyrazolin-5-ones, 56-57 Methylation of 2-pyrazolin-5-ones. 26, 40, 56, 09 Methylcellulose in synthesis of polymeric pyrazolinones, 109 Methyl /3-chloroisocrotonate, reaction with hydrazine, 16 2-Methyl-4-chloroquinoline, reaction with 2-pyrazolin-5-ones,22
Index
535
of 3-pyrazolin-5-selenones, 59 Methyl c r o t o n a h , reaction wit.h hydrazines, 15, 116 of 3-pyrazolin-5-thiones,59 3-Methyl-1,2-diphenyl- 3-pyrazolin-5Nitriles in synthesis of 5-imino-2one, 117 pyrazolinoa, 42 4,4'-Methylenobis(3-pyrazolin-5-onea), Nitrogen trioxido, reaction with 356, 155 pyrazolin-5-ones. 50 Methylhydrazine, reaction with ethyl- 5-Nitro-5-imino-2-pyrazolines, 89 8-amino-8-ethoxyacrylate,132 P3itrosoisoxazoles, in synthesis of 44,4'-l\lethylidynebis(2-pyrazolin-5nitroso-5-imino-2-pyrazolines, 87 onee.), 21, 34, 38, 91, 94, 99, 154 4-Nitro-3-methyl-1-(4-nitrophenyl)-2Methyl methacrylate, reaction with hypyrazolin-5-one, 8ee Picrolonic drazines, 15, 110 acid 3-Methyl-4-nitro-1-(p-nitrophenyl)-2p-Nitrophenylhydrazine, reaction with pyrazolin-5-one,see Picrolonic acid chloral hydrate, 128 5-Xitropyrazoles, reduction, 43 3-Methyl-4-nitroso-1-( 2-phenethyl)- 24-Nitro-2-pyrazolin-5-onos, 25, 61, 66, pyrazolin-5-one, 155 88, 89, 353 2-Methyl-l-phenyl-3,5-bis(phenyl4-Nitro-3-pyrazolin-5-onea, 51, 121 imino)pyrazolidine, 139 Nitrosation 3-Methyl-1-phenyl-Ei-irnino2of B-imino-2-pyrazohos, 44 pyrazoline, 43' 3-Methyl-1-phenyl-5-oxo-2-pyrazolin- of 3,5-pyrazolidinones, 126, 129 4-carboxaldehyde, 93 of 2-pyrazolin-5-ones, 11, 25, 85 of 3-pyrazolin-5-onea, 49, 50, 51, 88 4-(3-Methyl-l-phonyl-5-0~0-2of 2-pyrazolin-5-thiones, 41 pyrazolin-4-ylidene)-f-rnethyl1Nitroso-compounds, 13, see also pheny1-2-pyrazolin-Ii-on0, see Oximino-compounds Pyrazole blue 4-Nitroso-2,3-dimethyl-1-phenyl-34-Methyl-3-phenyl-2-phenylazo-3pyrazolin-5-one, 77, 87 pyrazolin-5-one, 110 3-Methyl-1-phenyl-2-phenylcarbamyl- 4-Nitroso-5-imino-3-pyrazolidinones, 137 3-pyrazolin-5-one, 104 3-Methyl-1-phenyl-5-phenylimino-2- 4-Nitroso-5-imino-2-pyrazolinea, 87 pyrazoline, 99 4-K;itroso-3,5-pyrazolidinediones, 129, 422-423 4-Methyl-2-phenyl-3-pyrazolidinone, 117 2-~itroso-3-pyrazolin-5-ones, 82 3-,Methyl-1-phenyl-2-pyrazolin-ti-onas, 3-Nitroso-3-pyrazolin-5-ones, 88 4, 6, 16, 20, 22, 25, 26, 28, 29, 31, 4-Nitroso-2-pyrazolin-5-ones, 85, 88, 155, 347-350 66,104,109,114,151,155,448-460 4-Methyl-3-phonyl-2-pyrazolin-5-one, 4-Nitroso-3-pyrazol~-5-ones, 77, 87, 110 88, 121, 351-352 Methyl a-piperidinobutyrate, reaction Nitrous acid reaction with hydrazides, 86, 100, 116 with phenylhydrazine, 117 5-Methyl-2-(3-sulfophenyl)-3see also Diazonium saltt3; Yitration; pyrazolidinone, 157 Kitrosetion Michaol addition in 2-pyrazolin-5-ones, Nomenclature (Chemical Abstracts), 3 Non-metallic complexes 21 of aminopyrine, 144 Nitration of 5-methyl-2-(3-sulfopheny1)-3of 6-imino-2-pyr&zohwina9, 44 pyrazolidinone, 157 of 2-pyrazolin-5-ones,25, 88 of 2-pyrazolin-5-ones, 107 of 3-pyrazoh-5-0nes, 11, 51 of 3-pyrazolin-5-ones, 108
536
Index
Normal Yellow 3GL, 482 Novalgin, 8ee Dypyrone
5-0x0 3-pyrazolin-3-carboxaldehydeu, 92 5-0xo-3-pyrazolin-4. carboxclldehydos, 54, 55,92,94,268-272, 356-359 4-Oxo-2-pyrazolin-3-carboxylic acids, 111 5-0xo-2-pyrazolin-3-carboxylic acids, 90, 95, 96, 97, 98, 100, 101, 304329, 359-366 5-0xo-2-pyrazolin-4-carboxylic acids, 95,97, 98, 304-329, 359-364 5-0xo-3-pyrazolin-3-carboxylic acids, 100, 101, 133, 137, 366-372 5-0x0-3-pyrazolin-4-carboxylic acids, 92, 100, 101, 366-372 5-0xo-2-pyrazolin-4-sulfonic acids, 101, 102, 373 5 0x0-3-pyrazolin-4-sulfonicacids, 102,373 5-0~0-3-pyrazolin-4-thioacid~, 100
Orthoesters reaction with 3,3'-iminobis(2pyrazolin-5-ones), 75 reaction with 2-pyrazolin-S-ones, 22, 35 Oxalic acid, reaction with 5 - h h o - 2 pyrezolines, 46 Oxaloacotic acid, reaction with hydrazines, 95, 97, 99, 100 Oxidation of 4,4'-arylidenebis(t-pyrazolin-5ones), 58 of 4-arylmercapto 2-pyrazolin-5ones, 63 of 4,4'-bh( 5-0x02-pyrazolin-4-yl) hydrazines, 75 of 5-imino-2-pyrazolines, 45 of mesoxaldehyde 1,2-bisphonylPalladium catalyst, 53 hydrazone, 7 1 of 3-methyl-1-phenyl-Z-pyrazolin-5- Perbcnzoic acid, reaction with 3pyrazolin-5-thiones, 59 ones, 66 Perbromo-3-pyrazolin-5-ones, 84 of 4-phenylazo-3-methyl-l-phenyl5-imino 2-pyrazoline, 66 Pfitzinger reaction for synthesis of of 3-pyrazolidinones, 18, 82, 117 quinoline-substituted 3-pyrazolinof 2-pyrazolin-5-ones, 27, 31, 33, 61, &ones, 48 99 Phenidone, 8ee l-Phenyl-3of 2-pyrazolin-5-thiones, 41 pyrazolidinone of 3-pyrazolin-5-thionos, 59 Phenols reaction with 4-aminoantipyrine, 156 Oximes, 13,aee alao Nitroso-compounds Oximinobis(2-pyrazolin-5-one),87 reaction with 3-pyrazolin-5-ones, 49 cr-Oximino-~-ketoesters,reaction with Phenoxymethylacetoacotic esters, in hydrazines, 85 synthesis of 2-pyrazolin-5-ones,29 4-Oximino-5-imino-3-pyrazoIidinones, N-Phenyl-N'-acetylhydrazine,reaction 128, 129, 137 with diethyl ethoxy4-Oximino-5-0x0-2-pyrwzolin-3methylenomalonate, 100 carboxylic acid, 137 4-Phenylazo-3-methyl-l-phenyl-54-Oximino-5-imino-2-pyrazolines, 44, imino-2-pyrazoline, 66 76, 87 4-Phenylazo-3-methyl-1-phenyl-24-Oximino-2-pyrazolin-5-ones, 25, 31, pyrazolin-5-0ne. 72 65, 66, 75, 85, 86, 347-350 1-Phenylazo-1-phenyl-2-pyrazolin-65- Oximino- 2 - pyrazolin-4-0~1~3, 113 one, 7 1 5-0xo-2-pyrazolin-4-carbonitriles, 97, 4-Phenylazo-2-pyrazolin-5-one, 61, 74 100 2-Phonyl-4-benzylidene-5-oxazolone, 5-0xo-2-pyrazolin-3-carboxaldehydes, reaction with hydxazine, 117 89 Phenylbutazone, vii, 123, 125, 143, 5-Oxo-2-pyrazolin-4-carboxaldehydes, 145-147 35, 38, 91, 95, 97 1-Phenyl-2,4-dichloropyrazole, 127 ~
-
-
-
Index
537
Phenylcthylbarbituric acid, complexes Pigment Fast Yellow G, 482 with aminopyrine and antipyrine, Piperidhe, reaction with l-acyl-3acyloxy 5-imino-2-pyrazolmes, 108 Phenylhydrazine, preparative uses, 27, 138 28, 32, 43, 61, 62, 68, 71, 72, 74, Platinum catalyst, 53 75, 83, 85, 89, 93, 115, 116, 117, Polar Yellow 5G, 482 125, 133, 138, 139 Polymeric 2-pyrazolin-5-oncs, 108-109, 2-Phenyl-5-imino-3-pyrazolidinone, 150 134 Potassium pennanganate, reaction 5-Phenylimino-3-pyrazolin-4with Z-pyrazolin-5-0nes, 28 carboxyanilides, 101 Purines, in synthosis of 4-imino-2Phenyl isocyanate pyrazolines, 113 reaction with 5-imino-2-pyrazolines, Pyrazole Blue, 4, 33, 34, 40, 63, 99 44 Pyrazole Orange, 482 reaction with 3-methyl-l-phenyl-5Pyrazoles, 17, 42, 80, 113 3,4-Pyrazolidinediones, 120 phenylimino-2-pyrazoline, 99 3,5-Pyrazolidinediones, 405-423 reaction with 2-phenyl-5 imino-3absorption spectra, 124 pyrazolidinone, 134 acybtion, 62, 126, 129, 130 Phenyl ieothiocyanate aldol condensation, 126 reaction with ethyl acetoacetate, 132 alkylation, 62, 126, 127 reaction with 2-phenyl-5-imino-3pyrazolidinone, 134 in color photography, 123, 150 Phenylmethyltartonylurea, reaction diazonium coupling, 127 with pyrazolo-2-pyrones, 32 dimerization, 128 3-Phenyl-4-nitroso-1-(2-phenethyl)-2dyes, 126 pyrazolin-5-one, 155 halogenation, 127, 129 1-Phenyl-5-0x0-2-pyrazolin-3Mannich reaction, 126 oarboxylic acid, 109 nitrosation, 126, 129 l-Phenyl-3,5-pyrazolidinedione, 82, reduction, 126 ring cleavage, 128 127 l-Phenyl-3-pyrazolidinone, 116, 151 structure, 13, 123-124 2-Phenyl-3-pyrazolin-5-one, 151 synthesis, 124-125 3-Phenyl-2-pyrazolin-5-one, 16 3,4,5-Pyrazolidinetrione,139 l-Phenyl-2,3,4-trimethyl-3-pyrazolin-3-Pyrazolidinones, 388-392 &one, 22 absorption spectra, 10, 11, 115 Phosgene acidic properties, 11, 115 in synthesis of l,l’-bis(2-pyrazolinalkylation, 12, 118 5-ones), 40 basic properties, 11, 115 in synthesis of ti-imino-2-pyrazolinbromination, 11, 82, 118 5-ones, 46 diazotization, 118 Phosphorus oxychloride, reaction with dipole moments, 11 2-pyrazolin-4-ones, 112 mercury compounds, 118, 391-392 Phosphorus pentasulfide, reaction with oxidation, 18, 82, 117 2-pyrazolin-5-ones,27, 40 ring cleavage, 12 Photographic reagents, 13, 67, 108, structure, 3, 8 115, 123, 131 synthesis, 10, 115, 119 Phthalic anhydride, reaction with 2- 2-Pyrazolin-4,5-dionm, 387 pyrazolin-5-ones, 24 reduction, 61 Picrolonic acid, viii, 4, 88, 89, 106, synthmis, 114 155 2-Pyrazolin-4-ones, 111, 112, 382-386
-
538
Index
2-Pyrazolin-5-ones absorption spectra, 6 acidic properties, 11, 18 acylation, 24, 26, 102, 103, 104 alkylation, 21, 22, 26, 46, 53 basic properties, 11, 19 condensation reactions, 19, 21, 3435, 90, 10&109 diazonium coupling, 11, 25, 69 dimerization, 28, 31 halogenation, 11, 25, 27, 30, 81 mercury compounds, 104, 118 nitration, 25, 88 nitrosation, 11, 25, 85 oxidation, 27, 31, 33, 61, 99 polymeric, 108-109, 150 reduction, 28 Reher-Tiemann reaction, 25 ring cleavage, 28 structure, 5, 6, 7, 19, 29 sulfonation, 25, 101 synthesis, 9, 14, 15 3-Pyrazolin-5-ones absorption spectra, 6, 49 acylation, 49 addition reactions, 50 alkylation, 12. 52, 76-77 basic properties, 49 diazonium coupling, 12, 81 dimerization, 31 halogenation, 11, 49, 50, 51, 83-84 Mannich reaction, 49 mercury compounds, 105 nitration, 11, 51 nitroation, 49, 50, 51, 88 oxygen replacement, 52 pyrolysis, 58 reduction, 28, 53, 85, 117 ring cleavage, 53 sulfonation, 49, 102 structure, 5, 6, 7, 13, 49, 76 substitution reactions, 49 synthesis, 9 trimerization, 94 3-Pyrazolin-5-selenones,58, 59, 85, 283-284 2-Pyrazolin-5-thiones, 13, 27, 40, 41, 59, 233 3-Pyrazolin-5-thiones, 58, 59. 293-284 Pyrazolopyrimidines, 43
Pyrazolo-2-pyrones, 32 Quinolines, 44, 48 reaction with 2-pyrazolin-5-ones, 22 reaction with 4-nmino-3-pyrazolin-5ones, 122 Quinonedi-imine, 148 Raman spoctra, 11 Reduction of 4-amino-3-pyrazolin-5-one Schiff base, 121 of 4-azo-2-pyrazolin-5-ones, 66 of 4-methoxy-3-pyrazolin-5-ones, 56-57 of 5-nitropyrazoles, 43 of 4-nitro-2-pyrazolin-5-ones, 66 of 4-nitro 3-pyrazolin-5-ones, 76 of 4-nitroso-3-pyrazolin-5-ones, 76, 88, 121 of 4-oximino-2-pyrazolin-5-ones, 66, 76 of 3,5-pyrazolidinediones, 126 of Z-pyrazolin-4,6-dione~,61 of 2-pyrazolin-5-ones,28 of 3-pyrazolin-5-ones,28, 53, 85, 117 Reimer-Tiemann reaction of 2pyrazolin-5-ones, 25 Rheumatoid conditions, drugs for, 123, 145 Ring cleavage in 2,3-dimethyl-1-phenyl-5-oxo-2pyrazolin-4-carboxaldehyde,93 in ethyl l-aryl-5,5-dichloro-4-oxo-2pyrazolin-3-carboxylates, 113 in 3,5-pyrazolidinediones, 128 in 3-pyrazolidinones, 12 in 2-pyrazolin-5-ones,28 in 3-pyrazolin-5-ones,53 Rubazonic acids, 66, 67, 69, 52, 74, 75, 114
-
Saturn Yellow GG, 482 Schiff bases from 4-amino-2-pyrazolin-5-ones, 69, 79 from 4-amino- 3-pyrazolin-5-ones, 77, 80, 121 from 5-imino-3-pyrazolidinones, 136 from 5-imino-2-pyrazolines,43
Index from 5-oxo-2-pyrazolin-4ctlrboxaldehydes. 89, 91 from polymeric pyrazolinonss, 109 Selenium-bridgodbis(3-pyrazolin-5ones), 65, 280 Semicartazides reaction with 4-myl-2-pyrazolin-5ones, 30 reaction with malonic esters, 130 Sensitizers, photographic, vii, 148, 151, 448-474 Silver nitrate oxidation of 2-pyrazolin5-ones, 67 Sodium, roaction with 1,2-diphenyl-3methyl-3-pyrazolin-5-onc, 53 Sulfamipyrine, vii, 122, 144 Sulfonation of 2-pyrazolin-5-ones, 25, 101 of 3-pyrazolin-5-ones, 49, 102 4-(4-Sulfophenylazo)- 1- (4-sulfopheny1)5-oxo-2-pyrazolin-3-carboxylic acid, see Tartrazine Supersensitizers, photographic, 151 Supramine Yellow 3G, 482 Surface-active textile assistants. 1.57 Tannin, complex with antipyrine, 157 Tartrazine, vii, 98, 152, 482 Tautomerism, 5 in 4-acyl-3,5-pyrazolidinediones, 129 in d-acyl-2-pyrazolin-5-ones, 89 in azo dyos, 153 in 3,5-di-iminopyrazolidines, 139 in 3-hydroxy-2-pyrazolinn-5-ones, 61 in 3-hydroxy-3-pyrazolinn-5-ones, 63 in 4-hydroxy-3-pyrazolin-5-ones, 63, 120 in 3-iminopyrazolidines, 119 in 5-imino-3-pyrazolidinonos, 131 in 5-imino-2-pyrazolines,44, 89 in 5-imino-3-pyrazolhes, 60 in 4-nitroso-5-imino-3pyrazolidinones, 137 in 4-nitroso-5-imino-2pyrazolines, 87 in 4-nitroso-3,5-pyrttzolidinediones, 129
539
in 4-nitroso-2-pyrazolin-5-oncs,85 in 3,4-pyrazolidinediones, 120 in 3,5-pyrazolidinediones, 61, 123124 in 2-pyrazolin-4-ones, 111 in 2-pyrazolin-5-ones, 6, 7, 29, 65 in 3-pyrazolm-5-ones, 49, 76, 120 Terephthaldehyde, in synthesis of polymeric pyrazolinones, 109 Tetrazonium salts, in synthesis of bis(2-pyrazolin-5-ones), 99 Thiocyanogen, reaction with 2,3dimethyl- 1-phenyl-3-pyrazolin-5one, 110 Thioisocyanates, reaction with 3pyrazolin-5-ones, 101 b-Thionoacetoacetates, reaction with hydrazines, 15 3,4,4-Trialkyl-2-pyrazolin-5-thiones, 41 Triazines, reaction with 2-pyrazolin-5ones, 34 Triazines of 3-pyrazolin-5-ones, 80 Trichloroethylurethan, complex with aminopyrine, 144 Tris(2,B-dimethyl-1-phenyl-5-oxo-3pyrazolin-4-yl)methano, 110 Tris(pyrazo1in-&ones),33 Trithiones, a,/l-umatiirated, reaction with hydrazines, 42 Urea, reaction with 3-pyrazolin-5-ones. 121 \‘eramon, 144 Wool Fast Yellow 3GL, 482 Wool Silk Yellow G, 482 Wurtz-Fittig reaction for synthesis of 4-substituted-3,5-pyrazolidinediones, 126 Xyleno Light Yellow, 482 Zein, reaction with pyrazolinones, 110 Zinc, &s reducing agent, 28, 53, 61, 66, 77,121
11 IIII III Il 11111ll~~
9 780470 381908
