Compendium of Organic Synthetic Methods
Compendium of Organic Synthetic Methods IAN T. HARRISON
and SHUYEN HARRISON ...
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Compendium of Organic Synthetic Methods
Compendium of Organic Synthetic Methods IAN T. HARRISON
and SHUYEN HARRISON SYNTEX RESEARCH P A L 0 ALTO, CALIFORNIA
A WILEY-INTERSCIENCE PUBLICATION
JOHN WILEY & SONS New York Chichester Brisbane Toronto Singapore
A NOTE TO THE READER This book has been electronically reproduced from digital information stored at John Wiley & Sons, Inc. We are pleased that the use of this new technology will enable us to keep works of enduring scholarly value in print as long as there is a reasonable demand for them. The content of this book is identical to previous printings.
Copyright @ 1971, by John Wiley & Sons, Inc. All rights reserved. Published simultaneously in Canada.
Reproduction or translation of any part of this work beyond that permitted by Sections 107 or 108 of the 1976 United States Copyright Act without the permission of the copyright owner is unlawful. Requests for permission or further information should be addressed to the Permissions Department, John Wiley & S o n s , lnc. Library of Congress Catalog Card Number: 71-162800 ISBN 0-471-35550-X
10
PREFACE Compendium of Organic Synthetic Methods is a systematic listing of functional group transformations designed for use by bench chemists, persons planning syntheses, students attending courses on synthetic chemistry, and teachers of these courses. The idea for this compilation came from the observation that organic chemists spend a large proportion of their time searching a formidable original literature for these hard-to-find synthetic methods. A key feature of this book is the classification of reactions on the basis of the functional group of the starting material and of the product, without reference to the reaction mechanism. We wished to produce as comprehensive a set of reactions as possible, covering all branches of organic chemistry. Reactions giving low yields or requiring exotic reagents are not omitted. Consequently reactions included cover the f u l l range of methods from boiling in oil to treatment with fluorine or orange-peel enzymes. The presentation of each synthetic method in the form of representative reactions without discussion follows the plan used successfully in Steroid Reactions (Djerassi, Holden-Day). The limitations of such compilations containing much information but few words are obvious: there is, however, a great need for a comprehensive one-volume listing of synthetic methods as an intermediary between the chemist and the literature. The reader interested in a detailed discussion of synthetic methods should consult Reagents for Organic Synthesis (Fieser and Fieser, Wiley) and Survey of Organic Syntheses (Buehler and Pearson, Wiley). We apologize to authors for the space-saving anonymity of references and for referring in many instances not to papers by the originators of a reaction but rather to subsequent articles by other authors. We make no apology, however, for omitting unnecessary reference punctuation, and avoiding the use of ibid. and other sources of confusion. Ian T. Harrison Shuyen Harrison Palo Alto, California March 1971
CONTENTS ABBREVIATIONS
ix
INDEX
xi
INTRODUCTION
xiii
1 PREPARATION OF ACETYLENES
1
2 PREPARATION OF CARBOXYLIC ACIDS, ACID HALIDES, AND ANHYDRIDES
16
3 PREPARATION OF ALCOHOLS AND PHENOLS
75
4 PREPARATION OF ALDEHYDES
132
5 PREPARATION OF ALKYLS, METHYLENES, AND ARYLS
177
6 PREPARATION OF AMIDES
203
7 PREPARATION OF AMINES
230
8 PREPARATION OF ESTERS
271
9 PREPARATION OF ETHERS AND EPOXIDES
309
10 PREPARATION OF HALIDES AND SULFONATES
329
11 PREPARATION OF HYDRIDES
357
12 PREPARATION OF KETONES
379
13 PREPARATION OF NITRILES
457
14 PREPARATION OF OLEFINS
479
vi i
Ac Bu DCC DDQ DMA DMF Et HMPA Me Ms N BA N BS NCS Ni Ph Pr PYr THF TH P
Ts
acetyl butyl d icyclohexy lcarbod iim ide 2,3-dichloro-5,6-dicyanobenzoquinone d imethylacetarnide d imethylformam ide ethyl hexarnethylphosphoramide methyl rnethanesulfonyl N-bromoacetamide N-bromosuccinimide N-chlorosuccinimide Raney nickel phenyl ProPYl pyridine tetra hyd rof u ran tetrahydropyranyl p to Iue nesuIf ony I
ix
x.
Miscellaneouscornpounds
Olefins
N itri les Nitriles
Ketones
Hydrides (RH)
Halides, sulfonates, sulfates
Ethers, epoxides
Esters
Arnines
Arnides
Alkyls. methylenes. aryls
Aldehydes
I
I
I
2 2 3 3 4 3
Carboxylic acids, acid halides, anhydrides Alcohols, phenols
14 13 15 13
12 10
10 6
7 5 8 6
1
1
Acetylenes
16 31 46 61 16 75 132 177 17 32 47 62 18 76 132 178 18 33 48 63 26 78 137 180 19 34 49 64 31 80 144 181 20 50 65 36 146 182 21 36 51 66 39 85 148 184 67 37 52 22 86 150 184 41 68 38 53 23 87 152 185 42 69 39 54 24 92 154 186 * 46 55 40 25 70 186 102 156 47 26 41 56 71 53 107 162 __ 191 27 42 57 72 56 110 164 193 58 28 73 62 166 198 44 59 74 29 119 168 198 64 45 60 75 30 122 172 202 68
76 203 77 204 78 208 79 209 80 210 81 211 82 213 83 218 84 220 85 220 86 222 87 223 88 225 89 227 90 229 96 236 97 240 98 249 99 249 100 250 101 255 102 LO2 258 103 262 104 264 105 266
91 230 92 230 93 232 94 233
111 289 112 290 113 291 114 293 115 295 116 299 117 302 118 304 119 305 120 307
106 271 107 272 108 280 109 287
134 325 135 328
127 318 128 318 129 320 130 320 131 322 132 323
122 309 123 310 124 316
149 354 150 356
136 329 137 329 138 331 139 338 140 338 141 338 142 339 143 342 144 343 145 345 146 349 147 353 __.
166 181 196 379 457 479 152 167 182 197 357 380 457 482 153 168 183 198 359 386 459 484 154 169 184 199 363 3% 460 489 155 170 185 200 365 400 464 493 156 171 186 201 366 403 464 495 157 172 187 202 367 404 465 4% 158 173 188 203 368 406 467 498 159 174 189 204 369 408 467 501 160 175 190 205 411 468 504 370 161 176 191 206 375 375 -. . 417 471 512 162 177 192 207 375 473 513 419 163 178 193 208 376 433 474 520 164 179 194 209 377 435 475 520 165 180 195 210 377 442 476 526
I Sect. 30A 45A 60A 105A 180A
Pg. 71 124 174 266 449
Blanks in the table correspond to sections for which no examples were found in the literature
Carboxylic acids Alcohols, phenols Aldehydes Amines Ketones
[PROTECTION
INTRODUCTION Classification and Organization. Compendium of Organic Synthetic Methods contains approximately 3000 examples of published chemical transformations classified according to the reacting functional group of the starting material and the functional group formed. Those reactions that give products with the same functional group form a chapter. The reactions in each chapter are further classified into sections on the basis of the functional group of the starting material. Within each section reactions are listed in a somewhat arbitrary order although an effort has been made to put chain lengthening processes before degradations. The classification is unaffected by allylic, vinylic, or acetylenic unsaturation, which appears in both starting material and product, or by increases or decreases in the length of carbon chains. For example, the reactions t-BuOH -+ t-BuCOOH, PhCH20H -+ PhCOOH, and PhCH = CHCH,OH + PhCH = CHCOOH are all found in Section 18 on carboxylic acids from alcohols. The terms hydrides, alkyls, and aryls classify compounds containing reacting hydrogens, alkyl groups, and aryl groups, respectively; for example, RCH2-H-+ RCH,COOH (carboxylic acids from hydrides), RMe -+ RCOOH (carboxylic acids from alkyls), RPh -+ RCOOH (carboxylic acids from aryls). Note the distinction between R,CO + R2CH2(methylenes from ketones) and RCOR’-+ RH (hydrides from ketones). The following examples illustrate the application of the classification scheme to some potentially confusing cases: RCH=CHCOOH -+ RCH=CHZ RCH=CH,-+ RCH=CHCOOH ArH -+ ArCOOH ArH --+ ArOAc RCHO -+ RH RCH=CHCHO -+ RCH=CH, RCHO --+ RCHI RZCHz-+ R2CO RCHQCOR-+ R2CHCOR RCH=CH,+ RCH&H, RBr RC=CH -+ RC-CR
+
(hydrides from carboxylic acids) (carboxylic acids from hydrides) (carboxyl ic acids from hydrides) (esters from hydrides) (hydrides from aldehydes) (hydrides from aldehydes) (alkyls from aldehydes) (ketones from methylenes) (ketones from ketones) (alkyls from olefins) (acetylenes from halides, also acetylenes from acetylenes) xiii
xiv
ROH
INTRODUCTION
+ RCOOH
--+
RCOOR
(esters from alcohols, also esters from carboxylic acids)
Sulfonic esters are grouped with halides. Hydrazines are listed with amines and hydrazides with amides. Yields quoted are overall, reduced to allow for incomplete conversion and impurities in the product. Trivial reactions not described in the given references b u t required to complete a sequence are indicated by a dashed arrow.
How to Use the Book. Examples of the preparation of one functional group from another are located via the index on p. xi, which gives the corresponding section and page. Thus Section 1 contains examples of the preparation of acetylenes from other acetylenes; Section 2, acetylenes from carboxylic acids; Section 3, acetylenes from alcohols; etc. Sections giving examples of the reactions of a functional group are found in horizontal rows of the index. Thus Section 1 gives examples of the reactions of acetylenes forming other acetylenes; Section 16, reactions of acetylenes forming carboxylic acids; Section 31, reactions of acetylenes forming alcohols; etc. Examples of alkylation, dealkylation, homologation, isomerization, transposition, etc. are found in Sections 1, 17, 33, and so forth, which lie close t o a diagonal of the index. These sections correspond to the preparation of acetylenes from acetylenes, carboxylic acids from carboxylic acids, alcohols and phenols from alcohols and phenols, etc. Examples of the protection of carboxylic acids, alcohols, phenols, aldehydes, amines, and ketones are also indexed on page xi. Examples of name reactions can be found by first considering the nature of the starting material and product. The Wittig reaction, for example, is to be found in Section 199 on olefins from aldehydes and Section 207 on olefins from ketones. The pairs of functional groups, alcohol-ester, carboxylic acid-ester, amineamide, carboxylic acid-amide, can be interconverted by quite trivial reactions. When a member of these groups is the desired product or starting material, t h e other member should of course also be consulted in the text. The original literature must be used to determine the generality of reactions. A reaction given in this book for a primary aliphatic substrate may in fact also be applicable to tertiary or aromatic compounds. The references given usually yield a further crop of references to previous work. Subsequent publications can be found through Science Citation Index. Reactions Included in the Book. Interconversions of monofunctional compounds form the major part of this compilation. Reactions of bifunctional compounds in which the two functions are identical and which give monofunctional
INTRO DU CTI 0 N
xv
products are also included; for example, R2C(COOH), RICO (ketones from carboxyl ic acids). Examples of the removal of one functional group from bifunctional compounds and the preparation of functional groups from groups not listed on the index are included in the miscellaneous sections; for example, RCH(Br)COR -+ RCH2COR, RCH(0H)COR -.+ RCHGOR and RCH=CHCOR -+ RCH,CH?COR (ketones from miscellaneous compounds), RCH2N02-+ RCHO (aldehydes from miscellaneous corn pou nds). Reactions are included even when full experimental details are lacking from the given reference. In some cases the quoted reaction is a minor part of a paper or may have been investigated from a purely mechanistic aspect. When several references are given, the first refers to the reaction illustrated; others give further examples, related reactions, or reviews. --f
Reactions Not Included in the Book. Reactions forming bifunctional products are not included, for example, RCH=CH, -.+ RCH(OH)CH,OH. Chain lengthening processes via unsaturated intermediates, for instance, RCHO --+ [RCH= CHCOOEtl + RCH,CH,COOEt, are only partially covered. Ring forming reactions and reactions that involve several functional centers (e.g., the Diels-Alder reaction) are represented by very few examples. These gaps will be filled by a second volume, presently under consideration, which will include reactions forming unsaturated and other bifunctional products. Reactions published after early 1971 are not included.
Compendium of Organic Synthetic Methods, Volume 1 Edited by Ian T. Harrison, Shuyen Harrison Copyright 0 1971 by John Wiley & Sons, Inc.
PR E PA RATIO N OF ACETYLENES
Chapter 1
Section 1
Acetylenes from Acetylenes 00000000000000000000000000
. . . . . . . . . . . . . . . . . . page ....................
A l k y l a t i o n o f acetylenes Isomerization o f acetylenes
Org React (1949) 2 1
Review: The S y n t h e s i s o f A c e t y l e n e s
C5H11CZCH
1 i-PrMgC1 2 BuI
Et20
*
HMPA
1-2 2
C5H11CfCBu
66%
Bull SOC Chim F r (1964) 2000
BuCiCH
1 EtMgBr
Et2O
2 Et2S04
Et20
BuCfCEt
w
70%
JACS (1936) 58 796
J O C (1959) g 8 4 0
1 Na THF c1
c1 Bull SOC Chim Fr (1965) 1525
1
36%
COMPENDIUM OF ORGANIC SYNTHETIC METHODS
2
SECTION 2
are included i n F u r t h e r examples o f t h e r e a c t i o n RCXH + R ' X -+RCECR' s e c t i o n 10 ( A c e t y l e n e s f r o m Hal i d e s , S u l f o n a t e s and S u l f a t e s )
PhCXH
CH212
Zn-Cu
Et20
37%
PhCXMe
P
Bull SOC Chim F r (1965) 1525 Tetrahedron (1958) 2 197
EtCH2C:CH
KOH
EtOH
170-180'
E t CXMe
P
~ 7 0 %
2 1273 Quart Rev (1970) 24 585 JACS (1951)
C5H11 CSCCH3
NaNH2
1,2,4-trimethylbenzene
150'
D
C5H11CH2CECH
Org React (1949)
BuCEC(CHZ)~CH~
NaNH2 m i n e r a l o i l
.
Bu(CH~)~CZCH
O r g React (1949)
Section 2
BuCXCOCl
21
S
1
A c e t y l e n e s f r o m C a r b o x y l i c A c i d s and A c i d H a l i d e s 0000000000000000000000000000000000000000000000000
1 Ph3P=CHPh Et3N 2 -280'
CgHg
b
BuCZC-CXPh JCS (1964) 543
80%
SECTION 4
ACETYLENES FROM ALDEHYDES 1 SOC12
PhCH2COOH
c
2 PhMgBr-CdC12
PhCH2COPh
1 PC15
2 NaNH2
Helv (1938)
3
PhCZCPh
34%
2 1356
Section 3
Na
BuOH
TsCl
NaCXH
BuOTs
NH3
BuCXH
37-47%
JACS (1937) 2 1490 Org React (1949) S 1
A c e t y l e n e s f r o m Aldehydes
Section 4
000000000000000000
Ber (1962)
t
AcOCH~CH=C(CH2)2CHO I
Me
1 Ph3PCH2C1 C1
Et20
*
lithium piperidide 2 MeONa MeOH 3 BuLi E t 2 0
95
2514
HOCH2CH=C(CH2)2CXH I
JACS (1969)
Me
91 4318
55%
COMPENDIUM OF ORGANIC SYNTHETIC METHODS
4
1 Ph,P=CHMe
THF
SECTION 4
NaNH-
3 N-Chlorosuccinimide
T e t r Lett (1970) 447
@CHO
N02QCHPO(OPh)2Cl
CN
NaH
@'"@.
*
Me2S0
N02 80%
CN
JACS (1965)
0
87 2777
CH=C(COOH)~ 1 Br2
CHC13
@
P
2 KpCO3 H 2 0 3 PhLi
Compt Rend (1949)
PhCHO
BrCHZCOOEt
Zn
C6H6
PhyHCH2COOEt
OH
'
229 6 6 0
N2H4
*
2 NaN02 HC1 H20 pet ether 3 NOCl P y r 4 KOH H20 J A C S (1951)
51 %
73 4199
PhCXH
5
No examples
Section 6
A c e t y l e n e s f r o m Amides
0000000000000000
No examples
Section 7
t
EtCHCH2NMe3 I
NMe3 2Br-
A c e t y l e n e0 s0 0 f0r0o0m0 0Amines 0 0 0 0 0 b
1 Ag20
H20
EtC-CH
____t
2 100-250'
t
JACS
61 1943
@ 8
CHZCECPh
CHzNMe31
Fe
(1939)
PhCXH
PhLi
E t 2 0 THF
*
Fe
J C S (1963) 2990
43%
6
COMPENDIUM OF ORGANIC SYNTHETIC METHODS
Section 8
SECTION 10
Acetylenes from Esters
000000000000000000 0 0 0 6
450"
MeFHCH20Ac OAc
MeCXH Izv
(1959) 4 3 54 75473
(Chem Abs
Section 9
Acetylenes from Ethers
0000000000000000000000
No examples
S e c t i o n 10
Review:
i-PrBr
A c e t y l e n e s f r o m H a l i d e s , S u l f o n a t e s and S u l f a t e s
J
The S y n t h e s i s o f A c e t y l e n e s
PhCECLi
150"
dioxane
*
Org React (1949)
21
i-PrCiCPh Annalen (1958)
65%
614 37
53%
JACS (1969) 91 4771 Angew (1959) 245
SECTION 10
7
ACETYLENES FROM HALIDES, SULFONATES AND SULFATES
1 LiCtl2CSCSiMe3
MezC=CH( CH2)2?=CHCHzBr
2 AgN03 3 NaCN
Me
*
M e 2 C = C H ( C H 2 ) 2 C =I C H C H 2 C H 2 C f C H Me
T e t r L e t t (1968) 5041 (1970) 2247
PhCZCNa
BuOTs
65-70%
PhECBu
To1 u e n e
O r g React (1949) 5 1 JACS (1937) 59 1450
Et2S04
NaCzCH
NH3
EtCXH
_____c
60% J A C S (1931)
NaCXH
li-PrzS04
NH3
29-50%
i-PrCECH JACS (1937)
1 Mg
EtBr
2 289
Et20
2 BrCH2CiCCHZBr
*
2 1490
EtCH2CZCCH2Et J C S (1946) 1009
I
PhCSCCu
Pyr b
Me0
Wl20"
Me0 JOC (1963) 28 3313 JACS (1964) 4358
98%
8
COMPENDIUM OF ORGANIC SYNTHETIC METHODS PhCXCu
PhCH=CHBr
DMF
w
SECTION 10
PhCH=CHCZCPh
75%
Chem C o r n (1967) 1259
PhI
1 CuCZCCH(OEt)2
pyr
2 Acid hydrolysis 3 NaOH MeOH H20
*
PhCXH
JCS
C
(1969) 2173
F u r t h e r examples of t h e r e a c t i o n RCiCH t R ' X + R C X R ' section 1 (Acetylenes from Acetylenes)
BuBr
1 Mg
Et20
2 PhCiC8r
+
CoC12
are included i n
BuCXPh
32%
JCS (1954) 1704
Br
Org Synth (1941) C o l l Vol 1 186 Org React (1949) 5 1
CH2CXH Me
1 Mg E t 2 0 t 2 ClCHgCH=CHCl 3 NaNH;
@Me
Compt Rend (1925)
181 555
ACETYLENES F R O M H Y D R I D E S ( R H )
SECTION 11
c1
1 CHZ=CHCl
9
CfCH
AlC13
36%
2 NaNH2 NH3 Rec Trav C h i m (1965)
1 Me3N P
2 Ag20 H20 3 100-250"
c
9%
EtCECH
JACS
NaNH2 Me2SO
fi 31
(1939)
61 1943
CgH17CZCH
54%
Tetrahedron (1970) 26 2127 JACS (1934)
EtCHzFH-FH2 i r Br
KOH
EtOH
2120-
EtCH2CXH Org React (1949)
5
1
F u r t h e r examples of t h e c o n v e r s i o n o f d i b r o m i d e s i n t o a c e t y l e n e s a r e i n c l u d e d i n s e c t i o n 14 ( A c e t y l e n e s f r o m O l e f i n s )
S e c t i o n 11
No examples
A c e t y l e n e s f r o m H y d r i d e s (RH)
DoDDoDoDooooDoooooooo~oo~o~oO
10
COMPENDIUM
SECTION 12
Acetylenes f r o m Ketones
S e c t i o n 12
Review:
OF ORGANIC SYNTHETIC METHODS
00000000000000000000000
The S y n t h e s i s o f Acetylenes
Org React (1949)
2 I 2 Et3N THF 3 KOH MeOH
5
1
HO
J O C (1969) 5il_ 3502
COCH3
f'r v
1 PCl5 ___)
2 KOH
CZCH
JACS (1932)
Q;rH3 OMe
2 NaNH2
-35%
2
1184
73% J
OMe T e t r a h e d r o n (1969)
@
COCH3
POCl3 _3
DMF
25
4249
- YCZCH NaOH H20 dioxane
Ber (1965) 98 3554 J O r g a n o m e t x l i c Chem (1966)
77%
a 173
SECTION 1 2
ACETYLENES FROM KETONES 1 N2H4aH20
PhCH2COMe
2 (CF3C00)2Hg2
Et20
11
PhCXMe
t
J O C (1966)
PhCOCH3
PhCOCH3
(PhO)3P
--*PhCOCH2Br
--*.
2 NaNH2
2 624
PhC-CH
163
Dokl (1965) 656 (Chem Abs 63 11338)
1 (Et0)3P
PhCOCH2C1
48%
t
Et20
NH3
PhCiCH
-75%
JCS (1963) 3712
PhyO Et
BrCH2COOEt Zn
'gH6
Ft
PhCCHZCOOEt I OH
N2H4 +
2 NaN02 HC1 H20 p e t e t h e r
3 KOH
EtOH
H20
JACS (1951)
COPh
PhC-CEt
73 4199
C-CPh N2H4
2 Mn02 3 CHC13 4 MeLi
t-BuOK
Chem Ind (1969) 1306
80%
COMPENDIUM OF ORGANIC SYNTHETIC METHODS
12
JACS (1952) N2H4*H20
PhCOCOPh
HgO
PrOH
C6H6
b
2 3636
SECTION 1 2
3643
PhCECPh
67-73%
O r g S y n t h (1963) Coll V o l 4 377
CoCoPh
1 N2H4 2 CF3COOAg
c1
80%
Et3N
C1
EtOH
JOC (1958)
2 665
26%
T e t r L e t t (1968) 4511
PhCOCOPh
(Et0)3P
215'
*
PhCZCPh
JOC (1964)
60%
29
2243
SECTION 15
ACETYLENES FROM MISCELLANEOUS COMPOUNDS
13
No examples
S e c t i o n 14
Li
BuCHECH~
THF
BuCXLi
___t
____
H20 +
BuCXH
w65% J O C (1967)
OH
1 Br2
32
105
CCl4
2 NaNH2
46%
HMPA
Tetr L e t t (1970) 4 1 T e t r a h e d r o n (1970) 26 2127
CgH17CH'CH(CH2)7COOH
1 Br2
2 NaNH2 NH3
*
Et20
C8H17CEC(CH2)7COOH
J Am O i l Chem SOC (1951) (Chem Abs 45 8449) Org Synth (1947) 27 76
S e c t i o n 15
Review:
A c e t y l e n e s f r o m M i s c e l l a n e o u s Compounds OOODOOOOoOOooOooDOoOOOODOODOODDOODOODD
The S y n t h e s i s o f A c e t y l e n e s
Org React (1949)
5
1
68%
27
14
COMPENDIUM OF ORGANIC SYNTHETIC METHODS
PhCH=CHBr
BuLi
Et20*
H- -2 0- - +
PhCXLi
JACS (1940)
PhCH=CHCl
PhLi
Et20
SECTIG,, 1 5
PhCfCH
62
2327
100%
PhCXH
Ber (1941) Z B 1474
PhCH=CHBr
NaH
HMPA
PhCXH Bull SOC Chim Fr (1966) 1293
CgH, 3 f = C H 2
NaH
HMPA
Bull SOC C h i m Fr (1966) 1293
PhC=CHBr I Me
CF3C = CCF3
dl
70%
CgH, 3CSCH
Br
L1
NaNH2
HMPA
CgHg
*
40%
PhCXMe Bull SOC Chim Fr (1966) 1293
Zn
EtOH
CF3CECCF3
54% JACS (1949)
298
SECTION 1 5
ACETYLENES FROM MISCELLANEOUS COMPOUNDS BuLi
--.---+
PhCH=CCl F
PhCECBu
-20% Angew (1963)
(Internat Ed
75 638 1. 477)
Helv (1967)
1 HC(OEt)3
PhCOy HPh OH
2 C6H13COOH
HOAc
t
500'
15
2101
PhCiCPh
40%
Chem Corn (1970) 206
C1 HN
Mes ityl e ne
- N"
____t
176"
PhCECH
59%
Tetr Lett (1966) 1663
h v dioxane
+
Ph
P
NTsLi
+
-
CH2=CHCH2NMe3Br
1 Ag2D
H20
2 310-325"
PhCZCPh Angew (1964) (Internat Ed
85%
76 144 3 138)
HC-CMe
JOC (1949) 2 1
<34%
Compendium of Organic Synthetic Methods, Volume 1 Edited by Ian T. Harrison, Shuyen Harrison Copyright 0 1971 by John Wiley & Sons, Inc.
PR E PARATI 0 N OF CARBOXYLIC ACIDS ACID HALIDES AND ANHYDRIDES
Chapter 2
S e c t i o n 16
BuCXH
Carboxylic Acids from Acetylenes
0000000000000000000000000000000
1 (i-Bu)zAlH 2 BuLi 3 c02
THF
w
BuCH2CH( COOH)2
*
---* BuCH~CH~COOH
62%
Tetr Lett (1966) 6021
CH
CCOOH
Ill
‘C I
(fH2)8 COOH
:H2COOH
111
1 NaNH2 2 CO2
I
NH3 EtpO
Hp
*
Ni
H20
y 2
*
(fH2)8 COOH
JACS (1945)
67 1171
Annales d e Chirnie (1931)
16
33%
(tH2)8 COOH
la
309
SECTION 16
BuC-CH
1 D i c y c l o h e x y l borane THF 2 m-Chloroperbenzoic a c i d
+ THF
BuCH~COOH
JACS (1967)
PhCECH
CF3C002H Na2HP04
*
CH2C12
+
PhCOOH
89 291
PhCH2COOH
38%
25% JACS (1964)
KMn04
C8Hl7C?C(CH2)7COOH
H20
pH 12
1 03 2 NaI
CCl4
HOAc
*
4866
HOOC(CH2)7COOH JOC (1952)
BuCXBu
17
CARBOXYLIC A C I D S FROM ACETYLENES
80%
11 1063
BuCOOH Annalen (1953)
35%
583
29
41%
1 0Ac
OAc Carbohydrate Res (1966)
2 315
C a r b o x y l i c a c i d s may a l s o be p r e p a r e d by c o n v e r s i o n o f a c e t y l e n e s i n t o e s t e r s o r amides, f o l l o w e d b y h y d r o l y s i s . See s e c t i o n 106 ( E s t e r s from A c e t y l e n e s ) and s e c t i o n 76 (Amides f r o m A c e t y l e n e s )
COMPENDIUM OF O R G A N I C SYNTHETIC METHODS
18 S e c t i o n 17
C a r b o x y l i c A c i d s , A c i d H a l i d e s and Anhydrides 5 f r o m C a r b o x y l i c A c i d s and A c i d H a l i d e s 0
0
0
0
0
0
0
0
0
0
... ............. ..... ..... ... . ..... 0
~
0
0
0
0
0
0
~
D
~
~
Chain e x t e n s i o n and a l k y l a t i o n o f c a r b o x y l i c a c i d s Degradation o f carboxylic acids Acid halides from carboxylic acids . . . Anhydrides from c a r b o x y l i c acids I
1 Cyclododecanone m o r p h o l i n e enamine C5H11C O C l
(YH2)8 CH II
CH2
Na I 1 MeCOCHCOOEt CgH6 2 MeONa MeOH 3 I(CH2)10COOEt 4 KOH MeOH
~
~
*
K2C03
~
~
(7H2)11
(CH2)8
KOH triethylene glycol
(tH2)8
I
~
~
FOOH N2H4
*-
FH
~
100 4 0 1 0
(fH2)11
F0
~
C5H11 (CH2) 12COOH -70%
TOOH -P
~
18-22 ... page . . . . 22 . .. .. 22-24 24-26
Et3N
2 NaOH EtOH 3 N2H4 KOH t r i e t h a n o l a m i n e Ber ( 1 9 6 7 )
YOCl
SECTION 17
7H2
iH CH2
CH2
Arkiv Kemi ( 1 9 4 9 ) 1 9 9 (Chem Abs
43 7 4 1 4 7
( H2 ) 6 COOC H2P h C5H1 C O C l
1 NaC(COOCH2Ph)2 2 H2 Pd-C 3 78" (decarbox) 4 H2SO4
*
C5HllCO(CH2)7COOH
N2H4
NaOH
J C S (1950) 1 7 4
JCS (1952) 3 9 4 5
C5H11 (CH2)8COOH 56%
~
~
~
~
0
~
~
SECTION 17
CgH13cOc1
CARBOXYLIC ACIDS, ACID HALIDES AND ANHYDRIDES FROM CARBOXYLIC ACIDS AND ACID HALIDES
1 Thiophene
SnC14
2 N2Hd*H20 KOH
C7H15
0
1
Succinic
an hydr i de AlC13 2 N2H4 KOH 3 Ni Na2C03
19
C7H15( CH2)7COOH
JCS (1954) 4162 ( 1 9 6 2 ) 350
EtCOOH
1 soc12
+ 2 CH2N2 Et2O 3 CH2=CO to1 uene 4 N2H4 NaOH diethylene glycol
Et(CH2)3CODH
Annalen ( 1 9 6 4 )
37%
2 Collidine PhCH201 3 KDH MeOH J O C (1948)
c1
678 113
1 EtCHN2
Me0 @Jcocl
HO''
1 DCC Et2O
*
13 7 6 3
c1
2 MeCHN2 Et20 3 PhNEt2 PhCH20H 4 Hydrolysis
JCS
28%
C
(1970) 971
17%
COMPENDIUM OF O R G A N I C SYNTHETIC METHODS
20
1 MeCHN2
PhCOCl
2 Ag2O
Et2O
PhfHCOOH
t
PhNH2
SECTION 17
Me
3 Acid hydrolysis
Chem Ind (1955) 1673
C14H29CH2COCl
1 CH2N2 2 HC1
Et20 Et2O
t
KOH
C14H2gCH2COCH2Cl
C14H2gCHCOOH 1 Me
Chem Phys L i p i d s (1968)
1 ClCOOEt 2 CH2N2 3 hv
Et3N
CH2C12
P
Et20
dioxane
70%
2 213
/-
1%34%
C H2 C 00 H
tI2@
C
JCS (1969) 1319 T e t r L e t t (1969) 4517
&
CH2COOH
21 Ag20 CH2N2 Na2C03 Et20 dioxane
Na2S203*
@@
1.74%
H20 Org React (1942) 1 3 8 JCS (1950) 926
0
cocl
t -
1 Me2SOCH2 2
hU
H20
CH2COOH
THF
t
%80%
JACS (1964)
86 1640
SECTION 17
BuCHdOOH
CARBOXYLIC ACIDS, ACID HALIDES AND ANHYDRIDES FROM CARBOXYLIC ACIDS AND ACID HALIDES 1 NaH
(i-Pr)zNH THF
BuCHCOOH
t
C6H13
1 BuLi
(i-Pr)2NH
hexane THF
t
2 HMPA 3 BuBr
JOC
C5H11FHCOOH Bu
92
1 BuLi
2 BuBr
(1970)
(i-Pr)*NH hexane THF *
1 Sodium-naphthalene
2 i-PrBr
THF
t
1 i-PrMgC1 HMP
?u
2 EtI
35
t
50%
262
PhFHCOOH i-Pr
Et2O
93%
2 262
C5H117COOH Bu
J O C (1967)
PhCH2COOH
1397
C5H11 FHCOOH Bu
J O C (1970)
PhCHzCOOH
86%
I
JACS (1970)
C5H11 CH2COOH
21
2 2797
PhfHCOOH Et B u l l SOC C h i m F r (1964) 2000
88%
SECTION 1 7
COMPENDIUM OF ORGANIC SYNTHETIC METHODS
22
COOH
1 (i-Pr)zNLi
C H ~
2 BuBr
heptane
THF
69-73%
JACS (1970)
92
1396
A l k y l a t i o n o f a c i d s may a l s o be accomplished v i a e s t e r o r amide i n t e r m e d i a t e s . See s e c t i o n 113 ( E s t e r s f r o m E s t e r s ) and s e c t i o n 81 (Amides f r o m Amides)
FOOH
COOMe
FOOH
FHMe
CMe
CHMe
p 2 FHMe y 2 FHMe
I
II
1 B r 2 P4
CH
___t
CHMe
2 MeOH 3 Pyr
KMn04 Me2CO
FH2
I
t
fH2 FHMe CH2R
CHMe I
CH2R
CH2R JCS (1963) 3081
PrCH2CH2COC1
1 Br2
2 i-PrCH20H 3 PhNEt2
PrCH=CHCOOCH2Pr-i
KOH
Biochem J (1951)
CC13COOH
SOCl2 __t
DMF
PrCOOH
300-340'
163
89%
CC1 3COCl Helv (1959) 42 1653 Org S y n t h (1932) C o l l Vol 1 1 2
SECTION 1 7
C A R B O X Y L I C A C I D S , A C I D H A L I D E S AND A N H Y D R I D E S FROM C A R B O X Y L I C A C I D S AND A C I D H A L I D E S
COOH
23
COCl
JCS (1963) 491
98% JACS (1920) 42 599 Can J Chem (1955) 33 1515
t-BuCOOH
PhCOCl
t-BuCOC1
92% JACS (1938)
PhCH2COOH
PCl3
60 1325
PhCH2COC1 Org Synth (1943) C o l l Vol 2 156
-
@‘O‘ H
PBr3
Me
$ODH
Ph3P
CCl4
acoBr 65%
Me
J C S (1934) 1406
FOC’
tHO
CH20
JACS (1966)
3440
24
COMPENDIUM OF ORGANIC S Y N T H E T I C METHODS
Annalen (1966)
C 1 5 H 3 1 COOH
N N ' - C a r b o n y 1 d i irni d a z o l e HC1
CHC13
*
*
MeCCl20Et
68%
694 78
PhCOCl Ber (1963)
MeCH=CHCOOH
693 132
C15H31COCl
Annalen (1966)
PhCOOH
SECTION 1 7
77%
96 1387
79%
MeCH-CHCOC1 Rec Trav Chim (1957)
76 969
50-80%
PhCOOH
TsCl
pyr
____t
97%
(PhCO)20 JACS (1955)
77 6214
SECTION 17
CARBOXYLIC ACIDS, ACID HALIDES AND ANHYDRIDES FROM CARBOXYLIC ACIDS AND ACID HALIDES
25
60% JCS (1964) 755
J Lipid Res (1966) 1 1 7 4
Me[CH2],~H-~H[CH2I7COOH OH OH
C1 COOEt
Et3N THF
(Me[CH,l,~H-~H[CH21,C0)20 OH OH JOC (1963)
CTSH31COOH
N-Trifluoroacetyl imidazole CgHg
(C15H31C0)zO
t
Ber (1962)
PhCOOAg
1905
cs2
95
54%
2073
( PhCO)20
98%
Proc Chem Soc (1957) 20
67%
COMPENDIUM
26
PhCOOH
1
CH2=CO
OF
ORGANIC SYNTHETIC METHODS (PhCO)20
t
2 Distillation
96%
54 3427
JACS (1932)
PrCOOH
PhCOCH=CHCOPh Bu3P CgH6
( PrCO) 2O
*
J O C (1964)
Section 18
SECTION 18
77%
29
1385
Carboxylic Acids from Alcohols and Phenols 000000000000000000000000000000000000000000
Carboxylation o f alcohols . . . . . . . . . . . . . . . . . page 26-27 Oxidation o f alcohols and phenols to carboxylic acids . . . . . 27-30 Oxidative cleavage o f diols . . . . . . . . . . . . . . . . . . . . 30
CH2COOH
CH2=CC12 H2SO4
*
Ber (1967)
PhfHOH Me
CH2=CC12 H2SO4 BF3
w
100 978
PhFHCH2COOH Me Angew (1965) ( I n t e r n a t Ed
t-BuOH
HCOOH H2SO4
*
24%
50%
77 967 5
956)
t- BuCOOH Org S y n t h (1966) 5 72 JACS (1961) 83 3980
75%
cJoH ocooH
SECTION 18
CARBOXYLIC ACIDS FROM ALCOHOLS AND PHENOLS
27
HCOOH H2SO4 t
75%
Ber (1966) 99 1149
MeOH
CO (400 p s i ) HI
H20 CsHs
RhC13.3H20
F
MeCOOH
99%
Chem Corn (1968) 1578
CrO3 HOAc
FCH2(CH2)8CH20H
H20
+
FCH2(CH2)8COOH JACS (1956) (1960)
1
0
L-u
(Jones' reagent)
93%
2255 6147
-u 0
77%
Helv (1967) 269 J Med Chem (1970) 13 926
C13C(CH2)3CH20H
KMn04 H20
P
C13C(CH2)3COOH Bull Chem SOC Jap (1963)
92%
5 1264
28
COMPENDIUM OF ORGANIC SYNTHETIC METHODS
KMnO4
Na2C03
H20
*
Br (CH2) &H20H
HNO3
8;'""" B u l l Acad Polon (1964) (Chem Abs 61 1895) JACS (1950) 72 2953
N204
2 5137
2 202
RuO4 CCl4
C5H11COOH
P
10%
80 6682
JACS (1958)
Ph(CH2)zCHzOH
Nickel peroxide NaOH H20
*
Ph ( CH2 ) 2 COOH J O C (1962)
PhCHzCHCH20H
Nickel peroxide NaOH H20
2 15
CgH1 gCOOH Ber (1956)
C5H11CH20H
66%
Br(CH2)5COOH JACS (1950)
CgH1 gCH20H
SECTION 18
t
27
70% 1597
PhCH=CHCOOH
J O C (1962)
27
81 %
1597
SECTION 18
29
CARBOXYLIC A C I D S FROM ALCOHOLS AND PHENOLS
100%
Me
Me T e t r L e t t (1968) 5685
O2
(HOCH2)3CCH20H
Pt
NaHC03
H20
*
(HOCH2)3CCOOH
Ber (1956)
&
Angew (1957)
t-Butyl chromate
Me ( CH2) 1 4CH20H
*
50%
1648
69 600
54%
Me (CH2) 14COOH
Bull Chem SOC J a p (1965)
PhCH20H
CC14
KOH
t-BUOH
H20
JACS (1969)
MeCH20H
Xenic acid
H20
-
@
91 7510
MeCOOH JACS (1964)
HO
893
75%
PhCOOH
t
38
86
2078
PICoo KOH
fusion
47%
HO Helv (1944) JACS (1948)
27 1727 2 3485
30
COMPENDIUM OF ORGANIC SYNTHETIC METHODS
SECTION 18
COOH
Me2F0H H202
HBr
NH4V03
H20
*
56%
COOH JCS (1961) 4082
5
&@
& - C O O H
55%
Zh Org Khim (1967) 3 1636 (Chem Abs 68 29874) T e t r L e t t (1967) 4729
0
JCS
CgH17CHCH20H I
02
cobalt laurate
PhCN
C
w
(1966) 1918
CgH1 ~ C O O H
OH T e t r L e t t (1968) 5689
70%
CARBOXYLIC A C I D S AND A C I D HALIDES FROM ALDEHYDES
SECTION 19 S e c t i o n 19
C a r b o x y l i c A c i d s a;d 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0
A c i d ~ a l ~ d e ~ o f rAldehydes om
0000000
1 [ ( Et0)2P0]2CHNMe2 2 HC1
L O '
00
00
00000000000000
NaH d i o x a n e
?
*
H20 Angew (1968)
( I n t e r n a t Ed
i-PrCHO
31
&
PcH
L
O
364
1. 391)
i-PrCH2COOH
2 Hydrolysis
T e t r L e t t (1967) 3201
QCHo
NaHS03
,
@OHfHCN H I
NaCN H20
OH
H20
OH
JOC (1956)
PhCHO
1 PhCONHCH2COOH 2 Base o r a c i d
*
PhCH2COCOOH
@cH2cooH
P4,
H202
OH
2
78%
1149
PhCH2COOH
Org React (1942) 1 2 1 0
0 CHO
1 Rhodanine 2 NaOH 3 NH20H 4 Ac20
5 KOH
NaOAc
HOAc CH2COOH
JACS (1940) 62 1512 Org React (1942) 1 2 1 0
74%
32
COMPENDIUM OF ORGANIC S Y N T H E T I C METHODS
S E C T I O N 19
0;;' ~ r 0 3 ~ 2 ~L 0 4 Me2CO
t-Bu
t-Bu
JCS
C (1970)
Br
Br CHo
Me0
1168
K M n 0 4 Me2CO
H20 Me0
OCH2Ph JCS
OHC
C
OCH2Ph
(1970) 1208
Hooc;iy'
v K M n 0 4 Pyr
0
0
Steroids (1964)
3
639
C6H1 3CH0
gc CHzCHO
76-78% O r g Synth (1943) C o l l Vol 2 315
@O:OH
93%
O
J
Tetrahedron (1968)
24
6583
SECTION 1 9
-
CARBOXYLIC A C I D S AND A C I D H A L I D E S FROM ALDEHYDES
M ~ ~ C = C H ( C H ~ ) ~ X ~ ~ ( C H ~ ) ~ ACgHo O THF
Me
33
Me2C=CH(CH2)2~=CH(CH2)3COOH
H20
Me
55%
T e t r L e t t (1969) 1837 JACS (1968) 90 5617
Argentic picolinate
PrCHO
PrCOOH
t
T e t r L e t t (1967) 415
(
,"DCt" H202
NaOH
90%
___f
Monatsh (1955)
CgH, 3CHO
MeC002H ___L
86
CgH1 ~ C O O H
88% Org React (1957)
PrCHO
?OH PhCMe2
325
OsO4 MeOH
*
9
73
PrCOOH JCS (1950) 2169
Se02
&-. CHO
H202
t-BuOH
t
-
A
Chem Comm (1969) 945
COOH
COMPENDIUM
34
OF ORGANIC SYNTHETIC METHODS
SECTION 19
c1 24% c1
c1
JCS (1951) 1208
OAc
T e t r L e t t (1966) 2507
(
>-
02 C ~ 2 0 - A g 2 0
CHO
NaOH
H20
*
QCOOH
86-90%
Org S y n t h (1963) C o l l Vol 4 493
02
Pd
p H 7.1
54-60%
HO HO OH
HO
Helv (1957)
40
2383
SECTION 19
CARBOXYLIC A C I D S AND A C I D HALIDES FROM ALDEHYDES
35
34% Org React (1944) 2 94 Org S y n t h (1963) C o l l Vol 4 974
BufHCHO
NaOH
H20
Et
i-PrCHO
Et
1 NH20H.HCl
20%
Bu7HCOOH
____t
NaOAc
Helv (1951)
EtOH
H20
+
2 KOH d i e t h y l e n e g l y c o l
?
MeOCHCHO
I2K I KHC03
K2CO3 H20
1211
i-PrCOOH
J O C (1962)
MeOf HCHO
34
2 629
MeOFHCOOH k
?
MeOCHCOOH J A C S (1954)
76 3188
70% Org S y n t h (1941) C o l l Vol 1 155
i-PrCHzCHO
Benzoyl p e r o x i d e
CC14
*
i-PrCH2COCl
J A C S (1947)
9 2916
60%
36
COMPENDIUM
OF
SECTION 20
ORGANIC SYNTHETIC METHODS
C a r b o x y l i c a c i d s may a l s o be p r e p a r e d b y c o n v e r s i o n of aldehydes i n t o e s t e r s , f o l l o w e d b y h y d r o l y s i s . See s e c t i o n 109 ( E s t e r s f r o m A l d e h y d e s ) . Some o f t h e methods l i s t e d i n s e c t i o n 27 ( C a r b o x y l i c A c i d s f r o m Ketones) may a l s o be a p p l i e d t o t h e p r e p a r a t i o n o f c a r b o x y l i c a c i d s f r o m aldehydes
S e c t i o n 20
C a r b o x y l i c A c i d s f r o m A l k y l s , Methylenes and A r y l s
Q
0 0 0 0 0 0 0 0 00 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0
CHMe2
COOH
V2O5
HNO3
HOAc
25%
Me
Me J Med Chem (1970)
0 ,
13 254
0 COOH 0.3%
v
v
Annalen (1933)
KMn04
500 270
H20,
76-78% Org Synth (1943) C o l l Vol 2 135
K3Fe(CN)6 CHJ
KOH
H20
GZYcooH COOH
Helv (1931)
14 233
SECTION 20
C A R B O X Y L I C A C I D S FRON A L K Y L S , METHYLENES AND A R Y L S
CrO3
H2S04
81 %
AczO HOAc
Ph3Si
JACS (1956)
H20
NO2
@
64%
Hg
H20
CH3 Br
t
*
HNO3
1759
76%
94 834
@
160-180' CH3
26
NO2 Ber (1961)
~
78 1689
250"
JOC (1961)
HNO3
COOH 0
0
JCS (1960) 3 4 1 JOC (1960) 25 668 PhCH3
37
Argentic p i c o l i n a t e
t
PhCOOH T e t r Lett (1967) 4 1 5
COMPENDIUM OF ORGANIC SYNTHETIC METHODS
38
PhCH3
C’2
T i 02
PhCC13
PhCOCl
PhCOOH
---+
J A C S (1958)
J A C S (1946)
3483
68
-70% 1840
100%
H20
QCH3
SECTION 20
COOH
COOH
JOC (1961)
SO2
PhCHMe2
H20
H202 H20
24%
PhCOOH
3 1 5’
PhCH2Me
J O C (1961)
NH4V03
26 2929
HBr
t
5
2929
PhCOOH
40%
J C S (1961) 4082
Ph
COOH
Ber (1960)
93 2521
S E C T I O N 21
39
CARBOXYLIC A C I D S FROM AMIDES
25% T e t r Lett (1967) 4729 Chem Comm (1970) 1420
S e c t i o n 21
KOH Me
CHMe
Me
diethylene glycol
94 %
CHMe
GJCONH2 J O C (1950)
CH2CONH2
HC1 HOAc
15 617
@&
H20
CH2COOH
90%
JACS (1941)
Me
145-1 50'
63 2494
70%
Me
Rec T r a v Chim (1927)
I o n exch r e s i n ( a c i d ) a
C
O
I
N
COPh
H
2
Me2CO H20
46 600
61% I
COPh
Chem Ind (1957) 736
COMPENDIUM
40
CONH2 OAc
OF ORGANIC SYNTHETIC METHOOS
. N2O4
OAc OAc
HOAc
OAc
i- P r
60
235
i- P r t -
NO B F 4
MeCN
Pr-i
i- P r J O C (1965)
Bu~CCONH~
58%
OAc JACS (1938)
i-Pr
SECTION 21
BuONO
HC1
HOAc
*
Pr-i
70%
30 2386
Bu3CCOOH
79%
JACS (1948) 70 3091 J hied Chem (1966) 9 603
JACS (1961)
PhCONHFHMe Et
1 NaN02 2 Pentane
Ac20 25'
*
5 1492
PhCOOH
JACS (1955)
64% 6011
SECTION 22
41
CARBOXYLIC A C I D S FROM AMINES
3
+
PhCON
PhCOOH Ber (1963)
MnOp
EtOOCCH2NHCOTH( CH2) 2CONHNHPh NHCOOCH2Ph
HOAc
67%
96 1387
EtOOCCH2NHCOfH (CH2) 2COOH
H20
JOC (1963)
THR’ RCHCONHNHPh
FeC13
HC1
*
c e l l osol ve
82%
NHCOOCHzPh 453
YHR‘ RCHCOOH
85%
H20
J A C S (1957)
19 637
645
C a r b o x y l i c a c i d s may a l s o be p r e p a r e d by c o n v e r s i o n o f amides i n t o e s t e r s , f o l l o w e d by h y d r o l y s i s . See s e c t i o n 111 ( E s t e r s f r o m Amides)
S e c t i o n 22
CH3CH2NEt2
6 COOEt
C a r b o x y l i c A c i d s f r o m Amines
0000000000000000000000000000
1 i-PrLi 2 c02
JACS (1969)
t
---+
25%
i-Pr(CH2)2COOH
91 6362
-
@
N2 BF4
Ni(CO)4
HOAc
COOEt
52%
COOEt
JCS (1962) 686
42
COMPENDIUM OF O R G A N I C SYNTHETIC METHODS
KMn04
NaOH H20
27% JACS (1951)
S e c t i o n 23
SECTION 23
3 4122
C a r b o x y l i c A c i d s and A c i d H a l i d e s f r o m E s t e r s
~ ~ ~ O O O O O ~ ~ O O O O O O O O O O O ~ O ~ O O O O O O O O O O O O O O O O O O O ~ O
. . . page 42-45
H y d r o l y s i s and c l e a v a g e o f e s t e r s t o c a r b o x y l i c a c i d s , , , , Degradation o f e s t e r s t o c a r b o x y l i c acids , , Acid halides from esters ,
. . . , . . 45 . . . . . . . . . . . . . . . . . . . . 46 I
CgH, 9CH=CCOOMe I
Me
KOH
EtOH
CgHlgCH=CCOOH I Me O r g S y n t h (1963) C o l l Vol 4 608
MeOOC( CH2)gCOOMe
Ba(OH)2
MeOH b
60%
MeOOC( CH2)gCOOH
Org S y n t h (1963) C o l l Vol 4 635
( i-Pr)3CCOOMe
t-BuOK
Me2SO
*
( i -Pr)$COOH
100%
T e t r Lett (1964) 2969 JCS (1965) 1290
Me
Me KOH-dicycl o h e x y l -
Me
18-crown-6
94%
Me JACS (1967)
7017
SECTION 23
CARBOXYLIC A C I D S AND A C I D HALIDES FROM ESTERS
43
59%
217
JACS (1958)
PhCOOMe
Me3N MeOH
PhCOOH
P
JACS (1933)
MeCOOPh
Guanidine
H20
EtOH
*
55 4079
MeCOOH B u l l Chem SOC J a p (1966) JACS (1964) 86 837
BrCH2yHCOOMe
Br
HBr
H20
852
72%
BrCH2FHCOOH
Br JACS (1940)
MeCOOCgH11
39
I o n exch r e s i n ( a c i d )
H20
*
62
3495
MeCOOH
JCS (1952) 1607
F u r t h e r examples o f t h e r e a c t i o n RCOOR' -+RCOOH + R'OH a r e i n c l u d e d i n s e c t i o n 38 ( A l c o h o l s f r o m E s t e r s ) and s e c t i o n 3DA ( P r o t e c t i o n o f Carboxyl ic Acids )
44
COMPENDIUM OF ORGANIC SYNTHETIC METHODS
PhCOOBu- t
MeOH
reflux
4 days
*
190-200"
Me0
__3
@'
23%
PhCOOH JACS (1941)
Me0
63 3382
@@'
COOH
@'
OMe J O C (1962)
-
HO
DMF
100%
OMe
2 519
$'
COOMe
LiI
SECTION 23
\
do
JCS (1965) 6655 F o r cleavage o f e t h y l e s t e r s see J O C (1963) 2184
AcO &COOMe
LiI
c o l l i d i n e tAcO
Helv (1960)
90%
43
113
SECTION 23
45
CARBOXYLIC A C I D S AND A C I D HALIDE7 FROM ESTERS
(i-Pr)3CCOOMe
PrSLi
H2
PhCOOCH2Ph
HMPA
Pd
Et20
99%
(i-Pr)3CCOOH Tetr Lett (1970) 4459
PhCODH
t
J O C (1958) 2 1700 Org React (1953) 7 263
H2
PhCOOCHPh
Pd
Et20
PhCOOH
t
JOC (1958)
2 1700
F u r t h e r examples of t h e c l e a v a g e o f b e n z y l e s t e r s a r e i n c l u d e d i n s e c t i o n 30A ( P r o t e c t i o n o f C a r b o x y l i c A c i d s )
@)@
, @ J @ ,
~ r 0 3 HOA~. CH20Ac
Ac20
COOH
0
0
26 979
-Ibi,
JOC (1961)
x -
CH=CPh2
RO
3
1 PhMgBr ___t
2 HOAc
1 03
EtOAc
2 H202
HOAc
~ u 0 4 ~a104 JACS (1963)
3419
46
COMPENDIUM OF ORGANIC SYNTHETIC METHODS
Me JOC
(1969)
34
SECTION 24
2486
~ O \ 0' P C I ~
*
PhCOOBu
PhCOCl
91 %
Ber (1963)
S e c t i o n 24
CH3CH20Et
Carboxylic Acids from Ethers
P
1 i-PrLi
2 co2
Et20
*
i-PrCH2CH2COOH JACS (1953) (1955)
CH2=CHCH20Ph
1387
1 Mg 2 co2
BrCHZCHzBr
THF
5%
15. 1 7 7 1 77 2806
CH2-CHCH2COOH
t
J
Organometallic Chem (1969)
63%
2
249
100% JACS (1967)
3550
55% JACS (1967)
3550
SECTION 25
47
CARBOXYLIC A C I D S AND A C I D HALIDES FROFl HALIDES CrO3
Me( CH2)14CH20Et
HOAc
CH2C12
*
55%
Me( CH2)14CDOH Chem Corn ( 1 9 6 6 )
752
C a r b o x y l i c a c i d s may a l s o be prepared b y o x i d a t i o n o f e t h e r s t o e s t e r s , f o l l o w e d by h y d r o l y s i s . See s e c t i o n 114 ( E s t e r s f r o m E t h e r s )
S e c t i o n 25
$' ('H2)4
t-Bu
1 Mg
Et2O
2 EtOOC(CH2),4CHOC 3 KOH
EtOH
H20
YOOH (fH2)14
yHOH
1 ~
~
r
2 KOH 3 H2 P t
I
y 2 YHMe
Et
1 Mg
FOOMe
Et20
*
2 CdC12 3 MeOOC(CH2)2COCl
(fH2)2
yo
'
"
2 N2H4
K1 H20* NaOH MeOH
(YH2)19 t-Bu
2 5139
___. Zn
FOOH
HC1
(YH2)4 FHMe
H20
46%
Et
y42 CHMe
it
PhCH2C1
*
MeOH
(;H2I4 t-Bu JACS ( 1 9 5 0 )
Br
fOOH
g
JACS ( 1 9 4 4 )
66
46
PhCH2(CH2)5COOH
Ber ( 1 9 5 2 )
6 1 1061
69%
COMPENDIUM
48
OF ORGANIC SYNTHETIC METHODS
JACS (1948)
SECTION 25
2 3352
n glycol J O C (1958)
CgH1 gYHCH2Br Me
1 Mg
Et20
*
QCHO
ocl-
CgH19yHCH2( CH2)4COOH
EtpO
2 P h y s i o l Chem (1951)
3 co2
1 NaCH(S02Et)z 2 CH2'CHCN KOH t - B u O H
*
287
65
(CH2)2COOH
2 CH2=CH2
PhCH2C1
584
Me
3 HC1 E t O H 4 N2H4 KOH
1 Li
23
JACS (1969)
47%
91 6362
"zEt I 1 HC1 H 2 0 PhCH2CCH2CH2CN v PhCH2(CH2)3COOH I HOAc "zEt 2 N i NaOH H20 JACS (1952)
74
1225
CARBOXYLIC A C I D S AND A C I D HALIDES FROM HALIDES
SECTION 25
BuBr
MeCOCH2COOEt
t
NaOEt
KOH H20
BuFHCOOEt COMe
49
BuCH~COOH
Org Synth (1941) C o l l Vol 1 248 JACS (1930) 5005
52
1 Mg THF 62% 3 BrCH2COOEt 4 NaOH
1 CH3CODBu-t C8H171
JOC (1968)
NaNH2 NH3
+
2 HC1 H20 d i o x a n e
2
CgH17CH2CDOH
g
JACS (1959)
PhCH2C1
1 EtCHzCOOBu-t 2 HC1
NaNH2 NH3
H20 d i o x a n e
1675
*
70%
5817
PhCHZfHCOOH
92%
Et
81 5817
JACS (1959)
F u r t h e r examples o f t h e a l k y l a t i o n o f e s t e r s w i t h h a l i d e s a r e i n c l u d e d i n s e c t i o n 113 ( E s t e r s f r o m E s t e r s ) . Examples o f t h e a l k y l a t i o n o f a c i d s w i t h h a l i d e s a r e i n c l u d e d i n s e c t i o n 17 ( C a r b o x y l i c A c i d s f r o m C a r b o x y l i c Acids)
PhCH2I
1 Ph3P=CHCOOMe EtOAc 2 KOH MeOH
*
PhCH2CH2COOH Tetr Lett (1960) ( 4 ) 5
Ber (1962)
95 2 9 2 1
75%
COMPENDIUM OF ORGANIC SYNTHETIC METHODS
50
1 EtCH(COOMe)2 C18H371
t-BuC1
Na
BuOH
2 NaOH H 2 0 3 160-170'
*
C18H37qHCOOH
JCS (1953) 3031 Org React (1957) f?. 107
CH2( COOEt 12
!?!*
t-BuCH(COOEt)2 50%
8F3* E t 2 0
G L C H 2 R
RBr
HBr
t-BuCH2COOH
NaBr H20
JACS (1969)
CH2zCC12
BF3
H2SO4
*
BrCH2CH2Br
2 288
RCH2COOH
85%
91 5886
78%
t-BuCH2COOH Angew (1965) ( I n t e r n a t Ed
1 Mg
83%
Et
Naturwiss (1964)
t-BuC1
SECTION 25
967
5 956)
*&
Et20
56%
( P r o c e d u r e for u n r e a c t i v e ha1 i d e s )
JOC (1959) Me I PrCCl I
Et
1 Mg 2 C02
Et20 (50 p s i )
*
24 SO4
Me I PrCCOOH
25%
it JACS (1949)
1877
SECTION 25
JACS (1939)
Angew (1967) ( I n t e r n a t Ed
RI
1
cl)
BuLi
2 02 3 HgC12
Angew (1965) ( I n t e r n a t Ed
CO (300 k g / c m 2 ) KOAC
61 1371
79 468 6
442)
5
1134 1075)
RCOOH
Helv (1935)
PhBr
51
CARBOXYLIC A C I D S AND A C I D H A L I D E S FROM H A L I D E S
N i (0Ac)p
H20
c
18 7 2 1
PhCOOH B u l l Chem SOC J a p (1967)
MeCH=CHCHzCl
CO (500 atmos)
(n-a1l y l - P d C l ) 2
t
MeCH=CHCH2COC1
J C S (1964) 1 5 8 8
40 2203
8 1%
52
S E C T I O N 25
COMPENDIUM OF ORGANIC S Y N T H E T I C METHODS CO (100 a t m o s )
PhCH2C1
PhCHZCOC1
#
(Ph3P)2Rh(CO)Cl
T e t r L e t t (1966) 4713 JACS (1968)
CO
Me2CC1
AgC104
PhN02
90 99
Me2FCOOH
t
100%
Et
Et
JACS (1960)
BuBr
--*
CO
(Bus12
(Et0)3P
d i -t-butyl peroxide
t
BuCOSBU
1261
NaOH
- - - - + BUCOOH
JACS (1960)
B uI
MepNLi
CHBt-3
HMPA
t
BuCBr3
NaOH
-----
2181
BuCOOH
Compt Rend (1967)
t-Bu
0
Cu(N03)~ air
H20
CH2Br
t
C264
1609
t-Bu JCS (1935) 1847
CH2C1
c1 HOOC
CH2C1
KMn04
NaOH
H20
t
HOOC
J Pharm SOC J a p (1950)
70 538
SECTION 26
53
CARBOXYLIC A C I D S FROM H Y D R I D E S (RH)
13% JACS (1966) 88 3318 JCS (1962) 186
C a r b o x y l i c a c i d s may a l s o be p r e p a r e d by c o n v e r s i o n o f h a l i d e s i n t o e s t e r s o r arnides f o l l o w e d by h y d r o l y s i s . See s e c t i o n 115 ( E s t e r s f r o m H a l i d e s ) and s e c t i o n 85 (Arnides f r o m H a l i d e s )
S e c t i o n 26
C a r b o x y l i c A c i d s f r o m H y d r i d e s (RHL 0000000000000000000000000000000000
-
R e a c t i o n s i n w h i c h a hydrogen i s r e p l a c e d b y c a r b o x y l o r a c a r b o x y l c o n t a i n i n g c h a i n , e . g . RH RCOOH o r RCH2COOH ( R - a l k y l , v i n y l o r a r y l ) , a r e i n c l u d e d i n t h i s s e c t i o n . F o r r e a c t i o n s i n which a l k y l o r a r y l groups a r e o x i d i z e d t o c a r b o x y l , e.g. RCH3 --+ RCOOH, see s e c t i o n 20 ( C a r b o x y l i c A c i d s f r o m A l k y l s , Methylenes and A r y l s )
0
ICH2COOH h g
0"'
CO
0
CH2COOH
ACS Div Petr Chem (1966) (Chem Abs 66 104510)
HF
SbF5
*
11 241
0 O:H:
Ber (1967)
100 984
63% JCS (1963) 3918
54
1 (7-Bu)zHg-K
CgH17COOH
t
24-35%
Monatsh (1967)
PhCH3
S E C T I O N 26
COMPENDIUM OF ORGANIC S Y N T H E T I C METHODS
1 Na
PhCl
98
763
77%
PhCH2COOH
2 co2
J A C S (1940) 62 1514 Chem Rev (1957) 867
QCH2
1 CO(CN)2
CH2COOH
2 H 2 0 dioxane Chem Ind (1961) 1116
JACS (1952)
ClCH2COOH
Fez03
74
1591
KBr
<45%
JACS (1950) 72 4302 Synthesis (1970) 628
PhCH2Me
1 B u L i -Me2NCH2CH2NMe2 * 2 co2
P h y HCOOH
t
QCOOH
Me J O C (1970) 35 10 Chimia (1970) 24 109
CH2Me
S E C T I O N 26
Me0
C A R B O X Y L I C A C I D S FROM H Y D R I D E S ( R H )
0
P d C 1 2 NaOAc * A c 2 0 HOAC
55
@JCooH Me0 T e t r L e t t (1969) 1019
PdC12 NO 2
Ac20
NaOAc HOAc
'@
COOH
t
NO2
T e t r L e t t (1969) 1019
PhH
CO2 ( o r C o C 1 2 )
~ 1 ~ 1 3 t
--- *
PhCOCl
PhCOOH
Chem Rev (1955)
~1 c 1 3
Me Me
CH2C12
l o w yield
55
229
Me
t
Ber (1963)
96
91 %
Me 1382
CH2C1 P a r a f o r m a 1de hyde
& COOMe
00
H2S04 HC1
KMn04
&
J Pharm Soc J a p (1950)
1 BuLi 2 c02
Et20 +
COOH
70 535
COOH
00
J O C (1970) 35 10 Org React (1954)
S
258
33%
56
COMPENDIUM
OF
O R G A N I C SYNTHETIC METHODS
OMe
SECTION 27
OMe
60% Ber (1964)
97
3098
C a r b o x y l i c a c i d s may a l s o be p r e p a r e d b y c o n v e r s i o n o f h y d r i d e s (RH) i n t o e s t e r s o r amides, f o l l o w e d by h y d r o l y s i s . See s e c t i o n 116 ( E s t e r s f r o m H y d r i d e s ) and s e c t i o n 86 (Amides f r o m H y d r i d e s )
S e c t i o n 27
CrjH11COCHMe2
C a r b o x y l i c A c i d s f r o m Ketones 00000000000000000000000000000
CHz=CHCN KOH t-BuOH
MeOH
t
1 KOH
C5H11COyMe2 CHzCHzCN
C5H11 CHzfMe2
N2H4 NaOH
CH2CH2COOH
JCS (1948) 1741
+ CN
FN 1 CH2COOEt
P
NH40Ac
2 Me2CuLi
Q -Q -0OH
COOEt
43%
T e t r L e t t (1967) 2893
21 MeMgI KOH
_____)
U
ethylene glycol
sy"^""""
\
T e t r L e t t (1964) 1763
oo SECTION 27
CARBOXYLIC A C I D S FROM KETONES
FN CH2COOEt NH40Ac
HOAc
oo Mg
6 OTHP
70 497
JACS (1948) (1959)
@
COOBu-t
_____f
CrC0OH
pto2,
2 KOH H20 3 A
C6H6
BrCH2COOBu- t
HZ
COOEt
57
57%
5397
COOH
A;i c~2*
Et20 H20
JOC (1966) 3 1 983 JACS (1946)-%
2339
B2H6 Et20
39%
2 H202 NaOH 3 CrO3 Me2CO
OTHP
OTHP
Chem C o r n (1968) 206 2498 JACS (1960)
82
.
Me0 R0@c0CH3
EtONa
MeO
H20
.
N2H4 H20
RO@COCOOH
Me
Monatsh (1952)
rn
1 S
morpholine
C0CH3 2 H2SO4
HOAc
H20
reflux
RCJ~~JHZCOOH
83 8 8 3
@Q-cooH 76%
Org R e a c t (1946)
3
83
Morpholine S DMF Acid PhCOCH3 ---------+ PhCzCH2 PhCH2CS - - - - + PhCH2COOH 15-20'
'
CB)
H20
Angew (1964)
( I n t e r n a t Ed
76 861 3 705)
58
COMPENDIUM OF ORGANIC SYNTHETIC METHODS OCH2Ph
Me0
@
@
OCH2Ph (CH2) 3COOH
CO(CH2)zCH3 1 S
OCH2Ph
morpholine
Me0
+
2 KOH
EtOH
CCl4
KOH
t-BuOH
H20
0
CC14
70%
JACS
flCOOH
__t
Et20
t o 1uene
V
C o m p t Rend (1939) 208 1020 JACS (1960) 4 3 0 7 Org React (1960) 11 261
NaOH
,/$?COOH
U
JACS (1952)
oo
Se02
60%
(1969) 91 7510
KOH
H202
91 7510
CHCOOH Ae
H20
( Y O M e
1996
0
KOH
P
t-BuOH
47
PhzCHCH2COOH JACS (1969)
CH2COCH3
37%
OCH2Ph
Helv (1964)
Ph2CHCOCH3
SECTION 27
51 %
74 5352
t-BuOH JOC (1957) 22 1680 C o m p t Rend C (1967) 265 578 Annalen (19c5) 681 3 0
< 27%
SECTION 27
CARBOXYLIC A C I D S FROM KETONES
59
T e t r Lett (1966) 1779
COOH
1 BuONO _____c
t-BuOK 2 ClNH2
34%
H20 E t 2 0 T e t r L e t t (1964) 2813
AcO
@’
h J dioxane
0
n
H20
*Acod
Ber (1964) 97 958 Angew (1965) 77 229 ( I n t e r n a t Ed 5 211)
KOH 350’
mineral o i l
c
Me ( CH2) 1OCOOH
Zh Org Khim (1967) 3 1418 (Chem Abs 67 1166187
JCS (1942) 488
55%
COMPENDIUM
60
OF ORGANIC S Y N T H E T I C METHODS
S E C T I O N 27
0 43% JACS (1969)
0
t-BuOK Me2SO room temp
H20
.
91 1009
&OOH
65%
T e t r L e t t (1964) 3251
Ph2CO
t-BuOK
30'
monoglyme H 2 0
.
90%
PhCOOH JACS (1967)
t- BuCOMe
CC14
t-BuOH
KOH
H20
89 946
t-BuCOOH
80% JACS (1969)
91 7510
cnnH
COMe
60-70%
COOMe
COOH JACS (1951)
Cl2
NaOH
H20
73 3803
87%
t
Org S y n t h (1943) C o l l Vol 2 428
61
CARBOXYLIC A C I D S FROM KETONES
S E C T I O N 27
Br2
NaOH
CH2COOH
H20
Aust J Chem (1967)
PhCOPr
1 NaOBr
H20
t
2 NaOH
HNO3
H20
2033
PhCOOH
48%
JACS (1950)
Et3CCOEt
2
1642
71%
Et3CCOOH B u l l SOC Chim F r (1967) 2011 JACS (1942) 64 2421
':fiOOH
H20
Tetrahedron (1962) 18 1351
JACS (1956)
0
C8H17co
1 m - C h l o r o p e r b e n z o i c acid
CF3COOH 2 KOH
CH2C12
*
1414-
7 9%
CgH17COOH
JACS (1967)
4530
JACS (1963)
1171
62
COMPENDIUM OF ORGANIC SYNTHETIC METHODS
PhCO COMe
NaOBr H20
PhCOOH
91% JACS (1950)
HoQcocoMe OH
COOH
Na 104
SECTION 28
72 1642
""Q OH
COOH
JCS (1935) 1467 Org React (1944)
2 341
100% Org React (1957)
9
73
Carboxylic acids may also be prepared by conversion of ketones into esters or amides, followed by hydrolysis. See section 117 (Esters from Ketones) and section 87 (Amides from Ketones)
Section 28
Carboxylic Acids from Nitriles
0DD00D0000000000000000000~~00~
Acidic hydrolysis of nitriles to carboxylic acids Basic hydrolysis of nitriles t o carboxylic acids Me Me
Me
H2SO4 H20
Me
@
. . . . . , page .,......
62-63 63-64
CH2COOH Me
Org S y n t h (1955) C o l l Vol 3 557
70-90% Rec Trav Chim (1927)
?a 600
S E C T I O N 28
CARBOXYLIC A C I D S FROM NITRILES
'HN
H$04
Nv
NaN02
63
NN%cooH NMe
H20 *
v
NMe
92%
JCS (1945) 751
CH2yHCN
c" PhCN
H2S
HCOOH H20
t
80%
Proc Chem SOC (1962) 117
o-Chlorobenzoic a c i d
300'
*
97%
Annalen (1968)
NH3
EtOH
NaOH Ph
HC1
b
EtOH
716 78
---- +
PhCOOH
Ber (1890) JOC (1951)
23 158 16 131
PhCSNH2
H20
*
81 -90%
Ph JCS
C
(1966) 840
64
COMPENDIUM
OF ORGANIC SYNTHETIC METHODS
Chem Pharm B u l l (1969)
SECTION 29
17 1564
C a r b o x y l i c a c i d s may a l s o be p r e p a r e d b y c o n v e r s i o n o f n i t r i l e s i n t o e s t e r s o r amides, f o l l o w e d by h y d r o l y s i s . See s e c t i o n 118 ( E s t e r s f r o m N i t r i l e s ) and s e c t i o n 88 ( Amides f r o m N i t r i l e s )
S e c t i o n 29
4 MezC=CH2
C6Hl3CH=CH2
Carboxylic Acids from O l e f i n s 000000000000000000 o O D o O o o O O o O
1 t-BuLi
Et3N
30-45%
2 c02
CH2=CC12 BF3
H2S04
-
CH3COOH di-t-butyl
peroxide
J O C (1965) 30 917 JACS (1969) 91 6362
Me3CCH2COOH Angew (1965) 7 7 967 ( I n t e r n a t Ed c 9 5 6 )
C6H13(CH2 )3COOH
75%
-70%
JCS (1965) 1918
BuCHzCH2
BrCH2COOH
hu
*
Bu(CH~)~COOH Chem Comm (1967) 435
80%
CARBOXYLIC A C I D S
SECTION 29
CH2( COOEt)2
CgH13CH=CH2
di-t-butyl peroxide
FROM OLEFINS
65
1 Hydrolysis
* C6Hi 3 (CH2) 3COOH
* C6H13CH2CH2CH(COOEt)2 2 A
Chem I n d (1961) 830
BuCH=CH~
. HC ( C O O E t ) 3
d i t-bu t y l peroxide
1 Hydrolysis
BUCH2CH2C(COOEt)3
Bu (CH2)3COOH
------------+
2
A
S y n t h e s i s (1970) 124
CgH13CH=CH2
1 Di-cyclohexyl
2
borane
*
co
m-Chloroperbenzoic *CtjH13CH2CH2COOH a c i d CF3COOH 79% CH2C12
6
CgH13CH2CH2CO
JACS (1967)
4530
a;::, acooH CO (200 atmos)
H2S04
*
)2COOEt
(CH2)2COOH
JACS (1960)
HCOOH H2SO4
1261
P COOH
T e t r a h e d r o n (1965)
2 2641
0 - OCOOH HCOOH H2SO4
Ber (1966)
80%
99
1149
9%
66
x
COMPENDIUM OF ORGANIC SYNTHETIC METHODS Me CO (300 a t m o s )
H2SO4
*
-
HC1
hP
Me2CO
H20
60%
97
3088
H2SO4
O C O O H
Ber (1968)
N i (C0)q
Me
ExCOOH t
Ber (1964)
F c1
SECTION 29
*
101 1291
(+ i s o m e r s )
CgH13CHCOOH I
Me
90%
43%
Angew (1965) 77 813 ( I n t e r n a t Ed c 7 9 0 )
0
CHzCH2
1 PrMgBr
TIC14
CH2CH2COOH
THF
49%
2 c02
JOC (1970)
2 392
Chem Corn (1968) 122
35%
JACS (1946)
68
2033
C A R B O X Y L I C A C I D S FROM OLEFINS
S E C T I O N 29
KMnO4
Me2CH ( CH2) 3CHCH=CH2
NaHC03
Me2CO
I
*
67
M e 2 C H (CH2)3FHCOOH
Me
Me JACS (1943)
KMn04
NaIO4
t-BUOH
H20
K2CO3
*
65
45%
745
8 COOMe
Can J C h e m ( 1 9 6 7 )
7OOMe
COOMe
(fH2)7
(yH2)7 COOH
1439
I
iH
K M ~ O ~a104
I
t-BuOH
CH
5
*
H20
(yH2)7 Me
98-99%
SJOOH (tH2)7 Me Can J C h e m ( 1 9 5 6 ) 3 4 1 4 1 3 J A C S (1961) 3 4 8 1 r
COOH
0 RUO~
~a104
89%
Ac 0 JACS (1963)
B e r (1942)
85
3419
75B 6 5 6
68
COMPENDIUM
OF ORGANIC SYNTHETIC METHODS
1 03
2 CrO3
HO
EtOAc H2SO4 Me2CO
SECTION 30
t
80%
Tetr Lett (1969) 1 7 3 3
C a r b o x y l i c a c i d s may a l s o be p r e p a r e d b y c o n v e r s i o n o f o l e f i n s i n t o e s t e r s o r amides, f o l l o w e d by h y d r o l y s i s . See s e c t i o n 119 ( E s t e r s from O l e f i n s ) and s e c t i o n 89 (Amides f r o m O l e f i n s )
CH=CHCOOH
CH2CH2COOH H2
MeNHCOO
Pt02
MeOH
*
70%
MeNHCOO
Chem Pharm Bull (1970)
2 243
Org S y n t h (1963) C o l l Vol 4 136
PhCH=CHCOOH
N2H4
Ni
H20
*
PhCH2CH2COOH A c t Chem Scand (1961)
85%
15 1200
SECTION 30 PhCH=CHCOOH
CARBOXYLIC ACIDS FROM MISCELLANEOUS COMPOUNDS Hp
(Ph3P)3RhCl
69
PhCHZCHzCOOH
b
75%
Compt Rend C (1966) 263 251 Chem Corn ( i 9 6 9 ) 1 3 6 5 -
/ COOH
95% JACS (1969) 9 1 1228 Compt Rend (1969) C
PhCH=CHCOOH
P4 KI H3PO4
P4 KI H3PO4
80%
22 601
PhCH2COOH
*
90%
Helv (1939) 22 6 0 1 Org Synth (1932) C o l l Vol 1 224
p4 I2
HOAC H20
CJ
CH2COOH
J O C (1966)
Phy HCOOH OAc
640
PhCH2CH2COOH Helv (1939)
Phf HCOOH OH
268
He Pd-Bas04 tetralin
2 983
PhCH2COOH Org React (1953) I 2 6 3
70
COMPENDIUM OF ORGANIC SYNTHETIC METHODS H2SO4 H20
PrCH2N02
SECTION 30
-
PrCOOH
P
Ind Eng Chem (1939)
H=CHCOMe
1 RuO4
e
COOMe
C
O
2
90%
118
O H COOMe
Tetr Lett (1968) 2681
0 0
AcO
1 6
KMn04 MeZCO AcO
H
Helv (1938)
CsHl 7COfH(CH2)7COOH OH
Ph C H COOH
6H
OH
KIO4 H2SO4 EtOH
Nickel peroxide
NaOH H20
*
<25%
2 828
CgH1 7COOH
92%
JCS (1936) 1788 (1935) 1467
*
PhCOOH Chem Pharm B u l l (1964)
90%
12 403
-
S e c t i o n 30A
P r o t e c t i o n o f Carboxylic Acids
RCOOH
--_--P
Zn
71
PROTECTION OF CARBOXYLIC A C I D S
SECTION 30A
HOAc
RCOOCH2CC13
H20
(Me3Si)p
JACS (1966)
CHC13
COOH
*
88 852
ACOOSiMe3
T -
Annalen (1964) 673 166 JACS (1966) 88 3390
H20
Me$=CHz
H2N0
CHzoAc COOH
CF3COOH
H2S04
*
-
Y COOCMe3
J Med Chem (1966)
2 444
-
SECTION 30A
COMPENDIUM OF ORGANIC SYNTHETIC METHODS
72
COOMe
@ ~ o ~ [ z c o o M e Me0
Di h y d r o p y r a n TsOH
TsOH
CgHg
*
HOAc
J A C S (1957) 79 1995 J C S (1952) 3945
HOCH2aOMe I _
0
R c o N H ~ > CCOOH H ~ R
RYH MeCHCOOH
L CF3COOH C6H6
Me0
a
Et3N
OOH H2
PhCONHCH2COOH
Y
HC(Octi2Bu-t)2NMe~
OMe J A C S (1969)
CH28r
CHC13 H20) OMe
MeOH THF
Chloromethylmesitylene Et3N
91 5674
RF;IH
*
( o r NaOH d i o x a n e Pd
COOCH2
*
JCS
C
(19701 964
PhCONHCHzCOOCH2
DMF
L 2N H B r HOAc Me Aust J Chem (1966) (1967)
19 1067 3 2243
F u r t h e r examples o f t h e p r e p a r a t i o n and c l e a v a g e o f b e n z y l e s t e r s a r e i n c l u d e d i n s e c t i o n 107 ( E s t e r s f r o m C a r b o x y l i c A c i d s ) and s e c t i o n 23 ( C a r b o x y l i c A c i d s f r o m E s t e r s )
SECTION 3 0 A
-
PROTECTION OF C A R B O X Y L I C A C I D S
Ph3CBr. CgHg
PhCH2CH2COONa
NaOH
Et3N
J O C (1962)
27
3595
RNHCH2COOCPh3
____f
HC1
PhCH2CH2COOCPh3
H20
Ph3CC1
RNHCH2COOH
73
d i o x a n e H20 JCS C (1966) 1191
PhCOCHZBr
RNHCHCOOH I
EtOAc
Me
H2
Pd
b
RNHCHCOOCH2COPh 1
Me
PhSNa
PhCH-CHCOOH
Et3N
DMF
JCS C (1966) 1191 JOC (1964) 29 2006
MeOH H 2 0
-
p B r o m o p he na cy 1 b r o m i d e
base Zn
t
PhCH=CHCOOCH2CO 1
HOAc
Br
Tetr Lett (1970) 343
J C S (1965) 3 5 7 1 JACS (1970) 2 6333
74
COMPENDIUM OF O R G A N I C SYNTHETIC METHODS
FH2CH2COOH yHCONHCH2COOMe NHCOOCH2Ph
----+
FH2CH2CONHNHPh CHCONHCH2COOMe NHCOOCH2Ph
yP2CONHCH2COOH
---- +
$H2CONHCHzCONHNH2
NHCOOCHZPh
u
NHCOOCH2Ph
NBS
RCHzCOOH
SECTION 30A
JOC (1965)
H20
RCH2COOMe
----t
-
----t
2 315
RCH2CONHOH
y 2 Me2CCH20H
R
u HC1
H20
EtOH
R
( S t a b l e t o RMgX and Cr03)
JACS (1970)
92 6646
Other reactions useful f o r the p r o t e c t i o n o f carboxylic acids are included i n s e c t i o n 107 ( E s t e r s f r o m C a r b o x y l i c A c i d s ) , s e c t i o n 23 ( C a r b o x y l i c A c i d s f r o m E s t e r s ) , s e c t i o n 77 (Amides f r o m C a r b o x y l i c A c i d s ) and s e c t i o n 21 ( C a r b o x y l i c A c i d s f r o m Amides)
Compendium of Organic Synthetic Methods, Volume 1 Edited by Ian T. Harrison, Shuyen Harrison Copyright 0 1971 by John Wiley & Sons, Inc.
Chapter 3
PREPARATION OF
ALCOHOLS AND PHENOLS
BuCXH
PrCZCH
BuCXH
BuCECH
1 EtMgBr 2 MeCOEt
Et20 Et20
\t
+
2 MeLi 3 EtBr 4 NaOH
THF
OH 92%
2 MeONa 3 Me1 4 02
1 B2Hg
Ft
BuCH2CH2:Me
OH JACS (1941) 63 186 T e t r Lett (1965) 1 6 1 9
PrCH2CHEt
90%
OH
T e t r Lett (1966) 2535 JACS (1967) 89 2 9 1
H20
1 (i-Bu)zAIH
Pt
-----+
I
1 B2Hg
H2
BuCZCCMe
THF
*
BuCH2FHOH
90%
Me T e t r Lett (1966) 6021
THF
*
2 H202 NaOH
BuCHzCH20H JACS (1967)
75
80%
89
291
76
COMPENDIUM OF ORGANIC SYNTHETIC METHODS
S e c t i o n 32
SECTION 32
A l c o h o l s and Phenols f r o m C a r b o x y l i c A c i d s , A c i d C h l o r i d e s and
kpl:::;
. . .. . . .
, , , page 76-77 Reduction o f c a r b o x y l i c acids t o alcohols , , , R e d u c t i o n o f a c i d c h l o r i d e s , a c i d a z i d e s and a n h y d r i d e s t o a l c o h o l s 77 , , , , , , , 77-78 D e g r a d a t i o n o f a c i d s t o a l c o h o l s and p h e n o l s
PhCOOH
HZ (205 atmos)
Re03
+
PhCH20H
H20
CgH1 gCOOH
J O C (1963)
H2 (173 atmos)
Rh2O7
43%
28
2345
CgH1 gCH20H
b
J O C (1959)
100%
24
1847
mLHcooH Me
Me0
Me
B2Hg THF
87%
Me0
J Med C h e m (1970)
BCooH NaBH4 A l C l 3
c1
diglyme
b
b
64%
c1
J A C S (1956)
Electrolysis H2S04 H20
13 203
18 2582
@JCH20H NH2 J C S (1942) 9 8
56%
SECTION 32
77
ALCOHOLS AND PHENOLS FROM C A R B O X Y L I C A C I D S , A C I D CHLORIDES AND ANHYDRIDES
Ph3CCOOH
1
Ph3CCOC1
LiAlH4
THF
LiAlH4
THF
LiAlH4
BrCH2CH2COCl
*
Ph3CCH20H
/
AlCl3
Org React (1951)
Et20
a 469
BrCH2CH2CHzOH
b
90%
JACS (1959) 1 6 1 0
C5H11 COOH
ClCOOEt
Et3N
THF
C5H11'? OCOOEt
NaBH4 THF
C5H11CH2OH H2° Chem Pharm Bull (1968) Ifi 492
1 Et3N PhCH2CONH
NaBH4
//
c0n3
-
C6H1 3
~
PYr
~
Ni
PhCH2SH
C15H31COSCH2Ph
483
Et20
Helv (1946)
1 m-Chloroperbenzoic a c i d * ~ 1 p y r hexane 2 Hexane cyclohexane r e f l u x 3 Base
78%
CH20H
J Med Chem (1964)
C15H31COCl
70%
29
C15H31CH20H 684
C6H130H
JOC (1965) 30 3760
66%
78
COMPENDIUM
'OC1
OF O R G A N I C
SECTION 33
SYNTHETIC METHODS
1 Sodium p - n i t r o p e r b e n z o a t e
Me0
*
2 SOC12
3 NaOH
Me0
2 67
J A C S (1950)
OH
J O C (1961)
'-"Q
-
t-BuQNHz
NaN3 H2SO4
1 NaN02
*
CHC13
t-Bu
a 3144
t-BuQoH
H2 so4 H20 2 H2SO4
t-Bu
t-Bu
H20
74%
41 1653
Can J Chem (1963)
A l c o h o l s may a l s o be prepared by e s t e r i f i c a t i o n o f c a r b o x y l i c a c i d s f o l l o w e d b y r e d u c t i o n . See s e c t i o n 38 ( A l c o h o l s f r o m E s t e r s )
S e c t i o n 33
A l c o h o l s from A l c o h o l s and Phenols 0
~
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
~
~
~
~
~
~
0
~
~
~
~
~
~
~
. . . . . . . . . . . . . . . . . . page 78-79 . . . . . . . . . . . . . . . 79-80
~
Epimerization of alcohols R e d u c t i o n o f phenols t o c y c l o h e x a n o l s
S t e r o i d s (1964)
3 359
30%
SECTION 3 3
79
ALCOHOLS FROM ALCOHOLS AND PHENOLS
1 TsCl
Pyr
2 Bu4NOAc HO
Me2CO
* HO$"'
3 LiA1H4 JCS
C
JCS
C (1969)
92%
(1969) 1605
969
0' Me
,CHOH
H2 R h - A t 2 0 3 MeOH YOAc
t
J O C (1962)
@I& H2
Rh-Al203
80%
2288
HOAct
90%
J O C (1964)
29
J O C (1958)
3 1404
3427
OH
80
SECTION 34
COMPENDIUM OF O R G A N I C SYNTHETIC METHODS
96% JACS (1949)
H Z copper chromi t e
QOH
MeO-@fH:i
Et
b
M e O ~ f t l ? l ~ O H
Et
JACS (1948)
Section 34
2 3889
Iv
2 4127
Alcohols and Phenols from Aldehydes
0000000000000000000000000000000000~
...... . ......... . . ......
Alcohols from aldehydes by Grignard r e a c t i o n s . page . . Hydrogenation of aldehydes t o a l c o h o l s , , , , Metal liydride reduction of aldehydes t o alcohols Reduction of aldehydes t o alcohols with miscellaneous reagents Degradation of aldehydes t o a l c o h o l s and phenols
80-81
. 81-82 . . 82-83 . 83-84 . . . . 84
OH
Y CHo BrMgCECCH20
THF
OH
Chem Pharm B u l l ( 1 9 6 9 ) Tetr Lett (1966) 3457
690
52%
SECTION 34
ALCOHOLS AND PHENOLS FROM ALDEHYDES
octio CHz=CHCHzBr
Mg
Et20
o!iCH2CH=CH2
*
72%
(Procedure f o r unstable Grignard reagents) JOC (1963)
Li
PhBr
PhCHO
THF
*
81
2 3269
Ph2CHOH
96% (One-step p r o c e d u r e ) Chem Corn (1970) 1160
Me MeMgBr
EtpO
P
76% JACS (1944)
Hp
Pt
FeC13
EtOH
b
@
CHo
Pt0p
1295
CgH13CHpOH JACS (1923)
ti2
66
5 1071
CH20H
FeS04
EtOH
OMe
OMe JACS (1940)
Me2C=CHCH2CH2!=CHCHO
H2
Pt
FeS04
*
62
1478
Me2C=CHCH2CH2F=CHCH20H
Me
Me JACS (1926) (1925)
48 477 47 3061
100%
82
CgH13CHO
COMPENDIUM OF ORGANIC SYNTHETIC METHODS H2 (50 a t m o s )
RhC13(Ph3P)3
+
SECTION 3 4
CgH13CH20H
100%
Chem Comm (1965) 17
PrCHO
H2
CO (240 a t m o s )
RhC13.3H20
*
PrCH20H Ber (1966)
70%
99
1086
75-81%
Org S y n t h (1932) C o l l Vol 1 304 JACS (1939) 61 2134
86%
a
Org React (1951) 469 JACS (1947) 69 1197
PhCHO
LiAl(OBu-t)jH
EtpO
*
PhCH20H JACS (1958)
aCHo NaBH4
5372
MeOH
82%
QJCH20H
JACS (1949)
2 122
S E C T I O N 34
ALCOHOLS AND PHENOLS LiBH3CN
PhCHO
MeOH
*
B2Hg
PrCHO
PhCH=CHCHD
THF
FROM
ALDEHYDES
PhCH20H
78% JACS ( 1 9 6 9 )
91 3 9 9 6
JACS ( 1 9 6 0 )
82 6 8 1
PrCH20H
C5H5NBH3
CgHg
b
PhCH=CHCH20H JOC ( 1 9 5 8 )
Ph3SnH
PhCHO
84%
5 1561
PhCH20H
___t
JACS ( 1 9 6 1 )
MeCH=CHCHO
Bu2SnH2
Et20
*
PrCHO
83 1 2 4 6
MeCH=CHCH20H JACS ( 1 9 6 1 )
59% 1246
PrCH201i
36%
Org React ( 1 9 4 4 )
Me0
83
aH0 HCHO
NaOH+
MeOH
H20
2 178
CH2DH Me0 JACS ( 1 9 3 5 ) 51 9 0 5 Org React ( 1 9 4 4 ) 1. 9 4
85-90%
84
SECTION 34
COMPENDIUM OF O R G A N I C SYNTHETIC METHODS
CHO
CH20H
NCOOK
HOAc
A r C = O > A1 iphC=O
MeOH 75%
&
02
Ac 0
hU
JCS
Aco&
loc xoH 21%
JACS (1958)
H202
20%
-
2 Zn
-
(1967) 1120
T e t r L e t t (1966) 2507
CH2C12
CgH11 CH2CHO
g
)
EtOAC
1 Pyridine oxide
0
(Rate o f r e d u c t i o n
NaOH
_3
MeOH
-
90 915
-
C5H11CH20CHO
Org React (1957) 9 7 3 Ber (1941) 74B 1552
H202
KOH
Pyr
*
Org React (1957) 9 7 3 Ber (1940) 73B 935 A l c o h o l s may a l s o be prepared f r o m aldehydes b y some o f t h e methods l i s t e d i n s e c t i o n 42 ( A l c o h o l s and Phenols f r o m Ketones)
80%
SECTION 36
Section 35
85
ALCOHOLS FROM AMIDES
Alcohols a n d Phenols from Alkyls, Flethylenes and Aryls
0 0 0 0 ~ 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 O O o O O D ~ 0 ~ ~ ~ 0 ~ ~ ~ ~ 0 0 ~ ~ ~ 0 ~ 0 0 0 0 0 0 0 ~
No examples of the r e a c t i o n RR' + R O H
( R ' = a l k y l , a r y l e t c . ) occur in the (R=alkyl o r a r y l ) see l i t e r a t u r e . For r e a c t i o n s of the type R H + R O H s e c t i o n 41 (Alcohols and Phenols from Hydrides)
Section 36
Alcohols from Amides
00000000000000000000
LiAlH4
THF
96%
_____)
Me
Me Me Ber (1955) LiAlH4
Et20
*
301
PhCH20H
80%
JOC (1953)
H2 (200-300 atmos) 250' Copper chromite
EtOH
1190
c1 1 H23CH20H
t
JACS (1934)
Electrolysis
LiCl
MeNH2
P
56
2419
c13H27CH20H
92%
J O C (1970) jS 1210
Electrolysis
Me4NC1
MeOH
*
Ber (1965)
PhCH20H
98
3462
69%
COMPENDIUM OF ORGANIC SYNTHETIC METHODS
86
CH2yH PhCO
1 N2O4
NaOAc
2 Na2C03
0
-
CH2? PhCO
HOAc
CCl4
SECTION 37
ch20h
NaDH
0
36%
0
JOC (1969)
2 3834
A l c o h o l s may a l s o be prepared b y c o n v e r s i o n o f amides i n t o e s t e r s , f o l l o w e d by h y d r o l y s i s . See s e c t i o n 111 ( E s t e r s from Amides)
S e c t i o n 37
Me
A l c o h o l s and Phenols f r o m Amines ooooooooooooooooooooOODDOOOooooaoo
NH2
1 NaN02
H2SO4
Br
2 H2SO4 Na2S04
H20
@
*
H20
OH Br
Me
80-92%
Org S y n t h (1955) C o l l Vol 3 130
n-BuNH2
NaN02
HC1
H20
*
n-BuOH
+ s-BuOH
25%
13%
JACS (1932)
54 3441
67% JOC (1965)
2 350
SECTION 38
a7
ALCOHOLS AND PHENOLS FROM ESTERS
NaN02
HOAc
H20
dioxane
96%
JCS (1959) 345
CH2CH2NH2 Ac2O
-
y C H 2 C H 2 N H A c 1 NaN02
&
Meo@ Me0
HOAc
Ac20
Me0
OH 82%
2 KOH MeOH Chem Pharm B u l l (1960)
S
266
S e c t i o n 111 c o n t a i n s f u r t h e r examples o f t h e c o n v e r s i o n o f N-acyl aniines i n t o e s t e r s f r o m which a l c o h o l s can be prepared by h y d r o l y s i s
S e c t i o n 38
A l c o h o l s and Phenols f r o m E s t e r s
EtMgBr
C15H31 COOMe
Et20
*
OH
JACS (1945)
PhCOOMe
Me1
Li
Ye
THF
96%
C15H31yEt2
PhyOH
5 2239
(One-step p r o c e d u r e )
74%
Me Chem Comm (1970) 1160
C11 H23COOEt
Na
EtOH
toluene
*
c11 H23CH2oH Org S y n t h (1943) C o l l Vol 2 372
65-75%
88
SECTION
COMPENDIUM OF ORGANIC SYNTHETIC METHODS Na
C7H15COOEt
NaOAc
H20
IlOAc
Et20
*
> 90%
C7H15CH20H Rec Trav Chim (1923)
Hp ( 2 0 0 a t m o s )
C5HllCOOMe
copper c h r o m i t e
250"
38
42
1050
92%
C5H11 CHpOH
t
JACS (1932) 54 1145 Org React (1954) 8 1
PrCOOBu
Hp ( 2 0 5 a t m o s )
Re03
2 1 80
PrCH20H
t
85%
28
JOC (1963)
PhCOOEt
Electrolysis
Me4NC1
MeOH
2345
89%
PliCH2OH
98 3462
Ber (1965)
69 1197 O r g React (1951) 6 469 JACS (1947)
pTA
Ye
Me
Me OH
NHAc
OCHCHzOH LiBH4
THF
____II
B OH
M
e NHAc
C a r b o h y d r a t e Res (1967)
4 504
91%
S E C T I O N 38
89
ALCOHOLS AND PHENOLS FROM ESTERS
NaBHq c1
AlCl3
diglyme
*
CH20H
84%
c1
78 2582
JACS (1956)
. NaBH4
Ph(CH2)zCOOMe
MeOH
73%
Ph(CH2)2CH20H
ref1 ux
J O C (1963)
28
3261
4
CHPh
92%
6Ac
OH T e t r a h e d r o n (1970)
6
395
Fle
J A C S (19.50)
@ PhCOO E t
CH20Ac
NaOH
MeOH
Me
H20 b
12. 1 4 7
@
CH20H
Me
95-97%
Org S y n t h (1963) C o l l Vol 4 582
NaOH
Me2SO
*
EtOH JCS (1965) 1290
90
COMPENDIUM
OF
ORGANIC SYNTHETIC METHODS
K2CO3
Mey=CH (CH2 ) 2y=CHCH20Ac COOEt Me
EtOH
MeC=CH ( CH2 ) 2C=CHCH20H I COOEt Me
JACS ( 1 9 6 9 )
OAC OAc
SECTION 38
98%
91 4318
MeONa
60%
MeOH
CHCl3
'
?
co I
CH CHPh
JCS (1967) 448
CHPh
Me0 MeOK
AcO OAc
MeOH 99%
P
OAc JACS (1948)
AcO
NH3
MeOH
_7
H
O
-
70 314
p
98% OAc
HCOOBu
OH
NaH
diglyme
JCS (1956) 2042
68%
BuOH Tetr L e t t (1965) 1713
HzNFH ( CHz ) 3CONH COOH
91
ALCOHOLS AND PHENOLS FROM ESTERS
SECTION 38
Orange p e e l a c e t y l
0L‘JCH20Ac COOH
esterase
H20 pH 6 . 6 *
Biochem J (1961)
Ber (1938)
hg
h’CH20H
50%
591
71B 2696
EtOH 34 %
t-Bu
t-Bu
JCS (1965) 5162
Ac 0
HC1 AcO’”
\ COOMe
kCOOMe
MeOH 88%
____t
H
Helv (1944)
21 713
F u r t h e r examples of t h e h y d r o l y s i s and c l e a v a g e o f e s t e r s a r e i n c l u d e d i n s e c t i o n 23 ( C a r b o x y l i c A c i d s f r o m E s t e r s ) and s e c t i o n 45A ( P r o t e c t i o n o f A l c o h o l s and Phenols)
92
COMPENDIUM
S e c t i o n 39
ALc;m;:,a~:
OF ORGANIC SYNTHETIC METHODS
SECTION 39
~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~
A l c o h o l s and phenols f r o m e t h e r s by rearrangements Cleavage o f e t h e r s t o a l c o h o l s and phenols , , , , Alcohols from epoxides , , , . , , , . . .
..
.
.
..
,
,
page
. . . . . , ,
,
.
. ...
,
92 92-100
100-102
73%
21
Org React (1944)
PhCH20Me
PhLi
Et20
Ye
35%
PhCHOH Annalen (1942)
JOC (1962)
t-BuLi
Me2C=CHCH20CH2CH=CMe2
THF
e
2
550 260
1933
Ye
Me2C=CHCHCCH=CH2 l
l
31%
HO Me Tetr Lett (1970) 353
Review: The C l e a v P y o f E t h e r s
COOH
54 615
COOH
HBr
&OMe
Chem Rev (1954)
HOAc
90% J O C (1941)
a 852
93
ALCOHOLS AND PHENOLS FROM ETHERS AND E P O X I D E S
S E C T I O N 39
HI
P4
Ac20
*
82%
@OMe CH2tHCOOH
CH2CHCOOH NHMe
NHMe
Org S y n t h ( 1 9 5 5 ) C o l l V o l 3 5 8 6
0
-
OCH2Ph
OH
CF3COOH
COOEt
COOEt JOC ( 1 9 6 5 )
2 2491
0
0
Low y i e l d HO
HO
0
0
OMe
JCS (1961) in08
AlCl3
OH
@
PhN02
*
Ber (1943)
50-6D%
2 900
CHO AlC13
CHzC12
*
AlBt-3
an
@OH
C&
pho@oH
OH
Ber (1960)
93
2761
COMPENDIUM OF ORGANIC S Y N T H E T I C METHODS
94
S E C T I O N 39
T e t r L e t t (1966) 4153 J C S (1962) 1260
-
CHO
BCl3
@JocHZph bCHePh
CHO
CHZC12
75%
@OH OH T e t r L e t t (1966) 4155
MeCHCH20Me
,
BBr3
CHZC12
J A C S (1968)
BBr3
CH2C12
90
1648
+
67% T e t r a h e d r o n (1968)
PhOEt
1 613
2 H20
24 2289
PhOH T e t r L e t t (1967) 4131
Pr$
BI3
(Pr0)zBI
---- t
PrOH T e t r L e t t (1967) 4131
EtpO
C5H5NBH2I
CgHg
EtpO
CtjHcjNBH20Et
@
HC1
OMe
H20
Pyr
21 0"
*
EtOH
----+
JACS (1968)
Et
95
ALCOHOLS AND PHENOLS FROFI ETHERS AND E P O X I D E S
SECTION 39
90
6260
97%
Et Chem I n d (1967) 1138
Pyridine hydrochloride
+
21 0"
NO2
J O C (1962)
AcDq CH20CPh3
HOAc
75%
&OH
2 4660
H20
AcO
AcO
OAc
OAc
Ber (1956)
80%
CH20H
g
898
F u r t h e r examples o f t h e c l e a v a g e o f t r i p h e n y l m e t h y l e t h e r s a r e i n c l u d e d i n s e c t i o n 45A ( P r o t e c t i o n o f A l c o h o l s and Phenols)
AcO.():,l AcO
CrO3
HOAc
~
b°CHo
Hydrolysis
HO
OH
OAc Carbohydrate Res (1970)
12 147
S E C T I O N 39
COMPENDIUM OF ORGANIC S Y N T H E T I C METHODS
96
&C8H17
Me0
BuOCHZPr
H
PhC002Bu-t cut'
‘gH6
BuOyHPr PhCOO
C
E tOCH2Me
PhN=NOAc
BuOyHPr NCOOEt 60% HkOOEt
EtO$HMe OAc
H2
Pd
____)
BuOH
a\
BuOH
A c t a Chem Scand (1961)
15 249
T e t r L e t t (1960) ( 2 ) 4 Arkiv Kemi (1960) 16 287
H20
BuOH C h e m Comm (1965) 259
H20
_--_+ JACS
BuOCHZPh
HO
BQ r -
----+
iCOOEt N C O O E t hu ------+
O
Chem Comm (1966) 752
50%
BuOCH2Pr
O
EtOH (1964)
86
3150
100%
L
Ore React (1953) 263 JACS (1954) 76 3158
J bled Chem (1969)
12 192
SECTION 39
97
ALCOHOLS AND PHENOLS FROM ETHERS AND E P O X I D E S
phcH20D HO
HO
OCH2Ph
Br2
hU
t e t r a m e t h y l e n e s u lfone
*
H
JOC (1968)
JCS
LiI
collidine
C
O
33
97%
D
4292
(1967) 2188
*
100%
Chem Corn (1969) 616 JACS (1950) 3396 F o r c l e a v a g e w i t h KCN see Ber (1933) 1623
+J
qeL EtS
DMF
94%
Me
Me T e t r L e t t (1970) 1327
PhOMe
PhOR
MeNH2
H20
185"
Ph2PLi
*
PhOH Chem I n d (1970) 1230 Aust J Chem (1970) 23 2539
THF
t
83% (R=Me) 88% (RZPhCH2)
PhOH
No r e a c t i o n (R-Et,
JCS (1965) 4120
T e t r L e t t (1967) 3661 JACS (1970) 92 7232
i-Pr)
COMPENDIUM OF ORGANIC SYNTHETIC METHODS
98
SECTION 39
OCH2CH=CH2
@@ PhOMe
LiAlH4
NiC12
THF
*
76% JACS (1957)
Lithium diphenyl
THF
t
BuMgBr
CoC12
EtzO
*
80%
PhOH JOC (1963)
PhOR
79 5463
2 707
PhOH
86% (RzPhCH2)
43% (R=Ph) No r e a c t i o n (R=Me) JOC (1952)
669
OH
OMe
MeMgI
175' J A C S (1956)
EtO
fyp7
78 6322
74%
hexane Na C 5 H l l C l JACS (1951)
73 1263
v EtNa
QoEt
Et4Pb
cyclohexane
*
72% +OH J P r a k t Chem (1938)
151 6 1
SECTION 39
ALCOHOLS AND PHENOLS FROM ETHERS AND E P O X I D E S 1 Mg
PhOCH2CH=CHZ
THF
99
86%
PhOH
____t
2 co2
J Organometallic C h e m (1969)
PhOR
NaNH2
piperidine
c
PhOH
Chem Ind (1957) 80 J A C S (1951) 73 1437
Li
PhCH20Et
THF
K
PhOMe
HMPA
Na
PhOMe
Pyr
Na
OPh
J O C (1961)
26 3723
76-80%
PhOH Bull SOC C h i m Fr (1966) 3344
94%
PhOH Ber (1943)
NH3
+
QH
___t
768 156
PhOH
Me J A C S (1937)
Li
82% (R=Me) 90% (R=PhCH2)
EtOH
Me
PhOMe
18 249
H~NCH~CH~NHZ
*
59
1488
54%
PhOH J O C (1957)
22
891
COMPENDIUM OF ORGANIC SYNTHETIC METHODS
100
OCHZPh
Li
SECTION 39
Et2NH
< 94% JACS (1970)
92
553
A l c o h o l s and phenols may a l s o be p r e p a r e d by c o n v e r s i o n o f e t h e r s i n t o e s t e r s , f o l l o w e d by h y d r o l y s i s . See s e c t i o n 114 ( E s t e r s f r o m E t h e r s ) F u r t h e r methods f o r t h e c l e a v a g e o f e t h e r s t o a l c o h o l s a r e i n c l u d e d i n s e c t i o n 45A ( P r o t e c t i o n o f A l c o h o l s and Phenols)
/O\
-
E t CH CH2
MeMgCl ___f
?H EtCHCH2Me 45%
F;1'
t
EtCHCH20H 22% 11%
Me2CuLi
88% JACS (1970)
92 4979
Chem Rev (1951)
49 4 1 3
JACS (1960) 82 3995 B u l l SOC C h i c F r (1969) 4414
1 2-Lithio-1 ,3-dithiane ,:,0;
THF 2 Ni EtOH
*
Me Host!'
Chem Comm (1970) 141 741
71%
SECTION 39
ALCOHOLS AND PHENOLS FROM ETHERS AND EPOXIDES
H2
Pt
HOAc
*
/O\ MeCH-CH2
Na
8 1%
HO"' Helv (1953) (1943)
101
36 26
1332 562
OH
NH3
MetHMe Quart Rev (1958)
12 1 7
7
AcO
@
Li
EtNH2
t-BuOH
HO JCS
Me$
/O\
-CH2
LiAlH4
'
\LiAlHq
Et20 AlCl3
1581
PH
t
Et20
C (1968)
*
Me2CMe
26%
Me 2 C HC H 2 0 H
55%
JACS (1956) 78 3226 Org R e a c t (1951) 5 469
/O\
PhCH-CH2
LiAlH4
Et20
+
PH
PhCHMe JACS (1948)
94% 3738
@yQTcHz COMPENDIUM
102
OF
@
A1HC12
~
Et20
Me
SECTION 40
O R G A N I C SYNTHETIC METHODS
~
~
c
H
z 72%o
Me
Tetr L e t t (1969) 901
JACS (1968)
90 2686
Chem Comm (1968) 1549
S e c t i o n 40
A l c o h o l s and Phenols from H a l i d E s and S u l f o n a t e s 000000000000000000000000000000
.
A l c o h o l s and phenols from h a l i d e s . A l c o h o l s and phenols f r o m s u l f o n a t e s
. .
,
.
. . . .
0000000000000000
. , . . . , page .,...., ..
JACS (1369)
BuBr
----+
BuLi
CH2=CHCH20H w
MezNCHzCHzNMe2
102-105 105-107
91 6362
BuCHCH~OH I
Me Tetr L e t t (1969) 325
72%
H
S E C T I O N 40
103
ALCOHOLS AND PHENOLS FROM H A L I D E S AND SULFONATES
CHz=CHCHzBr
Et20
1 Mg
(CH2=CHCH2)3COH
P
2 (Et0)zCO
30%
Compt Rend (1968) g 267 773 Org Synth ( 1 9 4 3 ) C o l l Vol 2 602
2 PhCOOEt
CgHg
PhBr
2 Ph2CO CgHg
*
89-93%
Ph3COH
c
Org Synth (1955) C o l l Vol 3 839
Br
1 Mg
Et20
82-88%
2 MeCHO
c1
c1
Org Synth (1955) C o l l Vol 3 200 BuBr
1 Mg
Et20
w
2 HCOOEt
Bu~CHOH
83435% Org Synth (1943) C o l l Vol 2 179
JACS (1970)
1 ocH2(
(
/O\ C H 2 - CH2
O c H 2 "
Mg E t p O
92 433
59%
0
CH2(CH2)30H
FH2-yH2 CH2 .O
THF
J O C (1968) 33 2991 Org Synth (1932) C o l l Vol 1 306
37%
104
COMPENDIUM OF ORGANIC SYNTHETIC METHODS
1 L i Et20 2 Paraformaldehyde
Me
SECTION 40
@JCH20H
L
95%
Me
R e c T r a v C h i m (1965) F o r G r i g n a r d r e a c t i o n w i t h HCHO gas see JACS (1933) 55 1119 and .JOC (1968) c 3 4 0 8
NaOH
Meo@J1
H20
68%
CHO
1 Mg E t 2 0
PhBr
CuSO4
CHO C a n J C h e m (1962) J O C (1939) 5 318
46% J A C S (1955)
Me
PhCl
91 %
1 Mg
Et20
2 HgC12
1 Mg
Et20
------+
2 (Me0)3B 3 H202
t-BuHgC1
J A C S (1955) (1943)
03
CH2C12
1 Mg
Et20
2 t-BuOOH
65
6032
501
t-BuOH
50%
78%
PhOH
H20
-
6032
T e t r L e t t (1970) 2679
J O C (1957)
PhBr
40 2175
PhOH
2 02
t-BuC1
84 1200
22
1001
98%
PhOH J A C S (1959)
81 4230
SECTION 40
ALCOHOLS AND PHENOLS FROM HALIDES AND SULFONATES 1 Mg
PhBr
Et2O
Acid
PhOCu-t
t
2 PhC002B~-t
105
PhOH
A r k i v Kemi (1961) 393 Org Synth (1963) 43 55
Org Synth (1955) C o l l Vol 3 650 652
Br
NaHC03
THF
ooH
H20
*
JACS (1961) (1946)
0 COOMe
AcO
83 198
68
751
COOMe 1 AgOAC
Br
HOAC H20
2 Hydrolysis
* HOO
OAc
O OH
Ber (1964)
CH2Br
AgN03
97
443
CH20H
H20
m e t h y l c e l losol ve
Ph3Si
H
t
76%
Ph3Si JACS (1956) 78 1639 J Biol Chern (1946) 164 569
//TT HCOPh
DMF
MeONa
NHCOPh
77% Ber (1970)
103 3 7
COMPENDIUM OF ORGANIC SYNTHETIC METHODS
106
OTs
Electrolysis
EtqNBr
H20
96%
JOC (1968)
TsO
Na-Hg
33 2716
MeOH H20
/O
PhCH ‘ 0
PhCH 0‘
Helv (1945)
PhOTs
Sodium-naphthalene
THF
t
SECTION 40
88%
1164
PhOH JACS (1966)
99% 1581
56%
JCS (1949) S178
SECTION 41
ALCOHOLS AND PHENOLS FROM HYDRIDES (RH)
107
C8H17
MsO"'
@;;tW
MezSO.
87%
HO"'
T e t r Lett (1964) 305
F u r t h e r examples o f t h e c l e a v a g e o f s u l f o n a t e s t o a l c o h o l s and phenols a r e i n c l u d e d i n s e c t i o n 45A ( P r o t e c t i o n o f A l c o h o l s and Phenols)
S e c t i o n 41
000000000000000000000000000000000000000
A l c o h o l s from h y d r i d e s Phenols f r o m h y d r i d e s
PhH
/O\ MeCH - CH2 C6H6
0
. . . . . . . . . . . . . . . . . page ....................
A l C13
*
Me PhCHCH20H
cs2
di-t-butyl
56%
Bull Chem SOC J a p (1967)
\I
peroxide.
CH2
F';;aformaldehyde
>
2 2980
38%
Neftekhimiya (1965) (Chem Abs 63 162231
0
107-109 109-110
2 554
0
CH2CH20H
J A C S (1950)
38%
2 2871
Chem Rev (1952)
2 505
108
COMPENDIUM OF O R G A N I C SYNTHETIC METHODS
QHp
Paraformaldehyde
AcpO
220"
1 (CF$00)4Pb C7H'6
2 NaOH H20
*
SECTION 41
* Q
CHCHpOH
3 2033
Aust J Chem (1967)
C7H150H
N45%
(isomer m i x t u r e ) J A C S (1967)
3662
COOH
Air
FeS04 H
ascorbic a c i d
HO'~' &H
ethylenediamine-
t e t r a a c e t i c a c i d EtOH EtOAc pH 5.5 S t e r o i d s (1965)
2
-61% 451
0
Cr03
HOAc
30%
AcO T e t r L e t t (1969) 1157 JCS 5 (1968) 2346 JACS (1948)
f!e BuCH I
Et
NazCt-207
HOAC
111 3237
HClO4
6%
H20 JACS (1961)
423
T e t r a h e d r o n (1968)
QoH JOC (1963)
2
2057
24
4667
1 H202 /
NaOCl
H20
63%
Ye
L
2 Reduction
MezC=CMeZ
CHZ=CyMeZ OH
/
\
02 h v r o s e bengal
MeOH JACS ( 1 9 6 8 )
LO
100%
90 9 7 5
'&
1 02 h v h e m a t o p o r p h y r i n 2 H2 N i Pyr
HO
55%
HO
618
Annalen ( 1 9 5 8 ) Argentic picolinate
PhCH3
109
ALCOHOLS AND PHENOLS FROM H Y D R I O E S (RH)
SECTION 41
Me2SO
*
OH
194 185
PhCH20H Tetr L e t t (1967) 415
1 (CF3C00)4Pb
RH
2 NaOH H20
c
ROH
-45%
(R=Ph o r PhCH?) JACS (1967)
Me
89 3 6 6 2
Me
89% JOC ( 1 9 6 4 ) (1966)
1 (CF3C00)3Tl Me
2 Pb(0Ac)q 4 HC1
CF3COOH
31
2397 153
*
3 Ph3P 5 Base
62%
Me JACS ( 1 9 7 0 )
92
3520
COMPENDIUM OF ORGANIC SYNTHETIC METHODS
110
PhH
H202
V2O5
t-BuOH
SECTION 42
PhOH
t
30%
59 2 3 4 2 Tetrahedron ( 1 9 6 8 ) 24 3475
JACS ( 1 9 3 7 )
KOH
i- P r
i- P r
35%
250-325" i - P r JACS ( 1 9 4 9 ) 7 1 3889 Org React ( 1 x 6 ) 5 141
A l c o h o l s may a l s o be prepared by c o n v e r s i o n o f h y d r i d e s i n t o e s t e r s , f o l l o w e d by h y d r o l y s i s . See s e c t i o n 116 ( E s t e r s f r o m H y d r i d e s )
S e c t i o n 42
A l c o h o l s and Phenols f r o m Ketones
0000000000000006
. . . . . .. . .
, page A l c o h o l s f r o m ketones b y G r i g n a r d and r e l a t e d r e a c t i o n s H y d r o g e n a t i o n o f ketones t o a l c o h o l s , , , , , , D i s s o l v i n g m e t a l and e l e c t r o l y t i c r e d u c t i o n o f ketones t o a l c o h o i s A l c o h o l s f r o m ketones by r e d u c t i o n w i t h m e t a l and o t h e r h y d r i d e s A l c o h o l s f r o m ketones by r e d u c t i o n w i t h m i s c e l l a n e o u s r e a g e n t s B a e y e r - V i l l i g e r d e g r a d a t i o n o f ketones t o a l c o h o l s and phenols ,
.
MeMgI
O+-
(i-Pr)p
PrMgBr Et20
Et20
t
.
0-1 11 1-112 2-113 3-116 6-1 18 118
71 %
JOC (1962)
LiC104
1 1 1 1 1
2107
%-
(i-Pr)zCOH
Pr
70% (Procedure f o r h i n d e r e d k e t o n e s )
Chem Comm ( 1 9 7 0 ) 4 7 0
SECTION 42 PhBr
Me2CO
111
ALCOHOLS AND PHENOLS FROM KETONES Li
THF
Me 2C OH
34%
6h
(One-step p r o c e d u r e ) Chem Comm ( 1 9 7 0 ) 1 1 6 0
4 4H 4H -
-
H2
KECMe
0
Pd
Pr
CXMe
Tetr Lett ( 1 9 6 5 ) 1 6 1 9 J O C ( 1 9 6 9 ) 34 3 7 5 4
OH
NaCZCH
CZCH
------*
LiAlH4 dioxane JCS (1954) 1854
- 0 0’
Pr-i OH
pentane i-PrLi
J H e t e r o c y c l i c Chem ( 1 9 6 9 )
i-PrCHzCOMe
H2
Pd-C
------+
?H
64%
5
139
i-PrCHZCHMe ( P t Rh o r Ru c a t a l y s t s may a l s o be used) J O C (1959)
24
1855
For s t e r e o c h e m i s t r y see Chem Rev ( 1 9 5 7 )
57 8 9 5
Helv ( 1 9 4 3 ) 26 5 6 2 JCS ( 1 9 5 4 ) 2 4 8 7
112
COMPENDIUM OF ORGANIC SYNTHETIC METHODS
SECTION 42
Chem Corn (1970) 567
Li
NH3
dioxane
0
Et2O
MeOH
*
65% HO
JACS (1958) 80 6115 (1968) 6486
Pr2CO
Li
NH~CH~CH~NHZ +
Pr2CHOH
30% J O C (1957)
‘sHl 7
0
@
Na
EtOH
P
22 891
Ho”’*g 1 93%
Bull S O C Chim F r (1964) 2236 JCS C (1969) 968
COOEt
Al-Hg
Et20 H20 COOEt
Arch Pharm (1942)
74%
280 361
Li
i-PrOH
JCS
C
(1969) 804 968
ALCOHOLS AND PHENOLS
SECTION 42
FROM KETONES
a 1
Electrolysis
*
Bu4NC1
0
100%
H
JOC (1961)
(1970)
2 1738 35 261
bCoMe LiAlH4
Me
113
Et201
Me
Me
JACS (1947) $ 9 - 1197 Org React (1951) 6 469
LiAlH4
AlCl3
isoborneol
70%
P
HO"'
0 JOC (1965)
PhCO
LiAlH4
30
3809
PhCHOH
Pyr
56% CHzCH2COMe
CHzCH2COMe
JACS (1962)
1756
OH
0
C o l l Czech (1959)
24
2284
114
SECTION 42
COMPENDIUM OF O R G A N I C SYNTHETIC METHODS
JCS
&
(1967) 581
83%
&-
JOC (1959) 4627 F o r r e d u c t i o n o f u n s a t u r a t e d ketones see Chem Comm (1970) 2 1 3
NaBH4
0
EtOH
76%
JACS (1953)
75 1286
J C S (1955) 3426
0 O
M
Lit
0:.
THF
cis/trans=99/1
e
0' ooH JACS (1970)
Li::3CNb
92
709
(LiBH3CN i s s t a b l e t o pH 3 )
77% JACS (1969)
91 3996
SECTION 42
oo
ALCOHOLS AND PHENOLS FROM KETONES 82H6
115
ooH
diglyme +
82 681
JACS (1960)
1 82H6
THF
2 H202
NaOH
b
T e t r L e t t (1968) 4937
82H6-a-pi nene
t
c i s / t r a n s = 92/8 U
M
e
s3 3166
JACS (1961)
~ 8 3 %
Ph2CHOH J O C (195
23 1561 -
OAc
66% Helv (1967)
2259
Tetr L e t t (1968) 5385
t-Bu
85-93%
t-Bu JACS (1958) (1961)
83
3798 1246
COMPENDIUM OF ORGANIC SYNTHETIC METHODS
116
EtgSiH
CF3COOH
74% T e t r a h e d r o n (1967)
PhZCO
NaH
xylene
*
& i-PrOH
i - P r O H*
At ol (l uOePnr e- i ) g
b
2235
83%
68 2647
&Q
J O C (1939) 5 456 Org React (1944)
i-PrOLi
2
PhZCHOH JACS (1946)
PhCOMe
SECTION 42
2 178 > 90%
PhFHOH Me JCS
C
(1969) 804
C
(1969) 1653 (1970) 785 Chem Corn (1970) 162
JCS
76%
Chem Comm (1970) 162
SECTION 4 2
Ph2CO
ALCOHOLS AN0 PHENOLS FROM KETONES KOH
HOCHzCH20H
*
117
93%
Ph2CHOH J O C (1967) (1960)
32 840 25 1707
Chem Corn (1969) 450
1 NH2CONHNH2.HOAc
2 EtONa EtOH
0
J3
JACS (1939)
$COONa PhCOMe
NCOONa
HOAc
MeOH
t
90%
HO
61 1992
Ye
PhCHOH
31 %
( R a t e of r e d u c t i o n ArC=O
> AliphC=O)
Chem Corn (1965) 71
Ph2CO
PhLi-Pyr
Et20
*
62%
Ph2CHOH Can J Chem (1963)
41 1961
COMPENDIUM OF O R G A N I C SYNTHETIC METHODS
118
SECTION 4 2
OH
0
&
71B 2696
Ber (1938)
:&
12 Monoperphthal KOH MeOH i c acid
Ho CN Gazz (1961)
(Chem 4bs
EtCOPh
PhC002H CHCl3
EtCOOPh
L
----+
73% JACS
-0
'OPh
Me0
1 MeC002H
HOAc
2 Hydrolysis
91 1250
56
(1949)
10211)
PhOH
2
14
*
86 %
Me0 JACS
(1950)
72 5515
F u r t h e r examples o f t h e B a e y e r - V i l l i g e r d e g r a d a t i o n o f ketones t o a l c o h o l s and phenols v i a e s t e r s a r e i n c l u d e d i n s e c t i o n 117 ( E s t e r s f r o m Ketones) Some of t h e methods l i s t e d i n s e c t i o n 34 ( A l c o h o l s and Phenols f r o m Aldehydes) may a l s o be a p p l i e d t o t h e p r e p a r a t i o n o f a l c o h o l s f r o m ketones
SECTION 44
S e c t i o n 43
119
ALCOHOLS FROM OLEFINS
A l c o h o l s and Phenols f r o m N i t r i l e s
0 0 0 0 0 0 0 ~ 0 ~ 0 0 0 0 0 0 0 0 0 0 ~ ~ ~ 0 ~ ~ ~ ~ 0 0 ~ ~ ~ ~
No examples
S e c t i o n 44
A l c o h o l s from O l e f i n s DDooDooooDooooDoooooo
1 NaBH4
CgH13CH=CH2
2
BF3 d i g l y m e
co
H202 NaoH
H20
(%Hi 3CH2CH2 )3COH
90%
JACS (1967) 89 2737 (1970) 6648
Di-t-butyl peroxide
C5H11 CH=CH2
t
+
CSH~~CH~CH~~HOH
MeCH20H
40-60%
Me I z v (1964) 894 (Chem Abs 61 5510)
PrCH-CH2
1 B2Hg
THF
*
2 MeOCHC12 MeLi E t 2 0 3 H202 NaOH H20
(PrCH2CH2)2CHOH t
PrCH2yHCH2CH2Pr
21 %
OH
28%
T e t r L e t t (1969) 2955
70%
3 KOH EtOH 4 H202
PhCH=CHZ
-
JACS (1967)
H2 (2,600 p s i )
HCHO
H2S04
0
copper c h r o m i t e
89 2740
t
Ph( CH2)30H
JACS (1950) 72 5314 Chem Rev (1952) 505
-74%
COMPENDIUM OF ORGANIC SYNTHETIC METHODS
120
SECTION 44 73%
Ber (1966)
CO H2 (450 atmos)
99
1086
CH20H
56%
JACS (1952)
BuCH=CH2
1 62116 2 CH2=SMe2 Me2SO
3 H202 NaOH
*
Bu(CH2)30H
THF
2 H202 NaOH H20
fH2 CH
vc>o
Bu(CH2)20H
+
Chem Corn (1967) 505
H20
1 NaBH4 BF3.Et20
i-PrCH2CH=CH2
4496
f
i -Pr(CH2)30H
Org React (1963)
13 1
1 LiBH4 H2SO4 THF
22%
H202 NaOH H20
2
0-L
I
80%
J O C (1963)
28
3551
Ye
1 (i-PrCH)zBH THF
CH2=CH( CH2)aCOOH
Me 7C=CHMe
2 H202
1
r
r
*
HOCH2CH2( CH2)gCOOH
82%
JACS (1961) 83 486
THF
Me 7 CHC HMe JACS (1968)
N95%
90
5281
SECTION 44
121
ALCOHOLS FROM OLEFINS
C10H21 CH=CHC11 H23
1 NaBH4 BF3-Et20 bis-2-ethoxyethyl ether 185-190" 2 H202 NaOH H20
t
c22H45CH20H
51%
J O C (1961) 5 3657 JACS (1967) 561 567
PhCH=CHMe
1 Et2AlCl 2 H202 NaOH
*
PhCH2CHMe I OH
75%
T e t r L e t t (1970) 3471
JACS (1966)
MeCO( CH2)2CH=CMe2
1 HCOOH
2 NaHC03 MeOH
S 3016
Me MeCO(CH2)2CH2bOH Me
*
Bol I n s t Quim U n i v Nac Aut blex (1965) (Chem Abs 65 8963)
JACS (1953)
MeCO( CH2)2CH=CMe2
1 H2SO4
H20
2 NaOH H20
t
1 Hg(0Ac)z
THF H20
2 NaOH H20 3 NaBH4 NaOH H20
*
11 181
2 6212
Ye
MeCO( CH2)2CH2COH Me
JACS (1955)
BuCH=CH2
80-95%
77
85%
1617
BuCHMe I OH
JACS (1967) 89 1522 J O C (1970) 5 1 8 4 4
96%
122
OF
COMPENDIUM
H20
hv
SECTION 45
ORGANIC SYNTHETIC METHODS
xylene
*
MeOCHZCHzOMe
50%
JACS (1967) 6788 Acc Chem Res (1969)
-
Me
1 03
I
Me2C=CH(CH2)2CHCH$OOMe
MeOH
2 NaBH4
PhCH=CHCHZOH
CHz=CHCH20H
PhCH=CHCH20H
Y?
HOCH2( CH2)2CHCH2COOMe
JACS (1968) Helv (1967)
S e c t i o n 45
2 33 72%
2 3525 2445
A l c o h o l s from M i s c e l l a n e o u s Compounds 0000000000000000000000000000000000000
H2
Pd
Ph(CH2)30H
ClCHzCONHNH2.HCl NaOH
LiAlH4
55%
Annalen (1924)
P
439
M e ( CH2)zOH
276
70%
Chem Ind (1964) 839
Et20
+
Ph(CH2)30H JACS (1948)
93% 3484
OH Ni
EtOH
___)
93 1028 (Chem Abs 60 3029) JACS (1953) 2 1700 G a z z (1963)
&
SECTION 45
Me2SO Cr(OAc)2
AcO
Ace@
123
ALCOHOLS FROM MISCELLANEOUS COMPOUNDS
BUSH
Br OH
OH
JACS (1966)
PhCH=CHCHO
65%
H2 Pt
3016
Ph( CH2)30H JACS (1925)
47
3061
T e t r L e t t (1970) 3219
MeCH=CHCOOH
B2H6
__f
Me (CH2)30H tlua Hsueh Hsueh Pao (1965) (Chem Abs 64 8 0 2 2 )
Li-naphthalene THF
I
nickel tetraphenylporphi ne
31 376
61 %
b
JACS (1970)
92
395
124
COMPENDIUM OF O R G A N I C SYNTHETIC METHODS
S e c t i o n 45A
SECTION 45A
P r o t e c t i o n o f A l c o h o l s and Phenols
0000000000000000000000000000000000
. .... ... ... .......... . ...... ... . .... ..... .. .. .
E s t e r s o f o r g a n i c and i n o r g a n i c a c i d s , , page 124-126 127-129 Ethers , , , , , T e t r a h y d r o p y r a n y l e t h e r s , a c e t a l s , k e t a l s and o r t h o e s t e r s , , 129-131 Miscellaneous derivatives , , , , , , , 131
&
cc13c00
*!"314"
*
AcO
NH3
EtOH
Aco&
CHC13 ( S t a b l e t o CrO3 and a c i d )
11
HO
&
C o l l Czech (1962) 2567 Tetr Lett (1968) 4681
(CF3CO)zO
KHC03
Pyr
*
a/ Ac
CF3COO
MeOH
( S t a b l e t o Cr03)
Helv (1954)
&*
HCOOH Ace0
AcO
KOH
*
MeOH
Me I
Mesitoyl chloride Pyr
CHC13
388
( S t a b l e t o CrO3)
Helv (1954)
R(CH2)2CH=CCH20H
37
31 443
t
Me
JACS (1969) (1967)
91 4318 89 2758
SECTION 45A
PROTECTION OF ALCOHOLS AND PHENOLS
125
Me MeCH=kCOCl
1 Os04 dioxane 2 pH 8 . 5
HO
MeCH=CCOO (Stable t o acid)
27 3103
(1962)
JOC
COCl
*
u hL,
J C S (1965) 3571
DCC PhCOCH2CH2COOH Pyr *
R o v y h y m i n e
OH
( S t a b l e t o CrO3 and a c i d )
Rowh ,
CgHg
*\
PhCOCH2CH2COO
N2H4
Pyr
HOAc
( S t a b l e t o CrO3 and a c i d ) JACS (1967)
7146
(C1 CH2C0)20 OAc
(NH2)zCS or HSCH2CH2NH2
35 1940
JOC (1970)
EoR u 1 Base
2 PhCH20COCl
OR
H2
Pd
C6Hg
OCOOCH2Ph
*
OR
( S t a b l e t o CrO3 and a c i d )
EtDH
JACS (1939)
61 3328
SECTION 45A
COMPENDIUM OF ORGANIC SYNTHETIC METHODS
126
CC13CH20COCl
Pyr
*
t -
Zn
HO
HOAc
CC13CH20C00 ( S t a b l e t o CrO3 and a c i d ) T e t r L e t t (1967) 2555 J O C (1968) 2 3589
Further examples of t h e preparation and cleavage o f e s t e r s a r e included in s e c t i o n 108 ( E s t e r s from Alcohols a n d Phenols) and s e c t i o n 38 (Alcohols a n d Phenols from E s t e r s )
&s
.,0\\\c13 ON02
H0.s’’
( S t a b l e t o CrO3, a c i d and base) Ber (1962)
95 1094 55 485
Chem Rev (1955) RICH211oCH20H
HgBO3 toluene
*
v H2O
MsCl
(RICH211 oCH20)3B ( S t a b l e t o Wittig r e a g e n t s , acid and base) Rec Tfav C h i m (1953) 72 41: T e t r L e t t (1969) 4155
Pyr ( S t a b l e t o CrO3 a n d a c i d )
P
R
NaOH H20
R
For cleavage of mesylates with PhLi see
2
JACS (1957) 717 JCS (1968) 2283
c
Further examples of the preparation and cleavage of s u l f o n a t e s a r e included in s e c t i o n 138 (Halides and Sulfonates from Alcohols and Phenols) a n d s e c t i o n 40 (Alcohols and Phenols from Halides and S u l f o n a t e s )
127
PROTECTION OF ALCOHOLS AND PHENOLS
SECTION 45A
Me2C-CH2
BF3
H3P04
0 1
*Me3CO
c CF3COOH ---
HO
( S t a b l e t o RMgX, L i A l H 4 , Cr03 and base) J C S (1963) 755
Ph3CC1
Pyr
c
R
HOAC
OH
H20
OH ( S t a b l e t o RMgX, L i A l H 4 , CrO3 and base)
J O C (1951) 2 349 (1950) 264 F o r h y d r o g e n o l y s i s o f t r i t y l e t h e r s see Rec Tra v Chim (1942)
i - P. r.
R&
1;
61 373
i- P r
PhCH2C1 4
H2
K2C03 Pd-C
EtoH EtOH
( S t a b l e t o RMgX, L i A l H 4 , CrOg
a c i d and base) J Med Chem (1967) 10 2 6 2
JACS (1954) 5 3 1 8 F Org Re a c t (1953) 1 2 6 3
F u r t h e r examples of t h e c l e a v a g e o f b e n z y l e t h e r s a r e i n c l u d e d i n s e c t i o n 39 ( A l c o h o l s and Phenols f r o m E t h e r s and Epoxides)
RCH20H
-
1 MsCl Pyr 2 Sodium p - c h l o r o p h e n o x i d e 1 L i NH3 2 Acid
EtDH
*.
RCH20 @ - Cl ( S t a b l e t o RMgX, L i A l H 4 , CrO3 a c i d and base) JACS (1968)
90 1090
SECTION 45A
COMPENDIUM OF O R G A N I C SYNTHETIC METHODS
128
OH
p-Bromophenacyl bromide
Zn
.
m C H 2 1 - - @ B r
( S t a b l e t o CrO3, a c i d and base)
HOAc
T e t r L e t t (1970) 343
CHzOCHzCH=CHz CHZ=CHCHzBr
NaH
CgHg
*
HzSO4
‘
Q
O
R
or KMn04 o r HgC12 o r 03
MezCO
NaOH H20
HgO
RO
JCS (1965) 2205
(1968) 1903
F u r t h e r examples o f t h e c l e a v a g e o f e t h e r s a r e i n c l u d e d i n s e c t i o n 39 ( A l c o h o l s and Phenols f r o m E t h e r s and Epoxides)
-_-_----
CH2=CHCH2Br ---*
CF3
PhCH20H
Se02
HOAc
MeCONHSiMej
---- - _ - _ _ - -
OCH2CH=CH2
dioxane
CF3 T e t r L e t t (1970) 2885
PhCHpOSiMe3
I _ - - -
H20 Ber (1964) 97 2196 F o r t r i m e t h y l s i l y l e t h e r s o f 3 r y a l c o h o l s see Chem Corn (1968) 466
SECTION 45A
129
PROTECTION O F ALCOHOLS AND PHENOLS Me3SiC1
Pyr
L w
@O:H
H20 For t r i m e t h y l s i l y l e t h e r s o f hindered phenols see
RCH20H
0
TsOH Et20
(1966)
JACS
22
592 3390
( S t a b l e t o RMgX, LiAlH4, CrO3 a n d base)
RCH20
\
J O C (1957)
TsOH MeOH
JACS (1969)
91 4318
For tetrahydropyranyl e t h e r s o f 3ry alcohols see T e t r a h e d r o n (1961) 13 2 4 1 a n d S t e r o i d s (1964) 5 229
Zn
PhC002Bu-t C6H130H HC1
*
HO
O P
S t e r o i d s (1965)
a 397
c~H~~oLOJ
( S t a b l e t o RMgX, LiAlH4, Cr03 and base)
H20
C8H1 7
EtOH
( S t a b l e t o CrO3 and base)
A c t Chem Scand (1960)
14 1854
(1961) j.5-
0
CF3COOH
CHCl3
AgN03 Me2CO H20 J O C (1966)
31
2333
249
130
COMPENDIUM OF ORGANIC SYNTHETIC METHODS
0
hymine
t
OH
HC1
AgN03
CHC13
*
MeCN J O C (1966)
1 EtONa
EtOH
2 MeOCH2C1 MeN
HOAc
31 2333
+
qCH2OMe
CHC13
( S t a b l e t o RMgX, L i A l H 4 , CrO3 and base)
J Med Chem (1966) JACS (1957)
-?Bu
t-BuOH
PhCOOCHPr
w-.
----_-_
SECTION 45A
9
79 5792
1
TBu t-BuOCHPr
( S t a b l e t o RMgX, I.iAlH4,
I -
13 2 4 1
T e t r a h e d r o n (1961)
Acid
CrO3 and base)
?Me CHZ=CMe TsOH
RO
c -
OH
H20
pH 4
RO
OfMe2 OMe
JACS (1967)
89 3366 26
T e t r a h e d r o n (1970)
Uracil
AcO
OH
M e O e TsOH t
pH 2.0
-
1023
AcOCH2
QUraci’ AcO
O
Me0
JACS (1967)
c
o
(Stab1 e t o RMgX , L i A1 H4, CrOg , and base)
89 3366
T e t r a h e d r o n (1970)
26
1023
PROTECTION OF ALCOHOLS AND PHENOLS
SECTION 4 5 A HCONH2
BuOH k.
PhCOCl
t
HC(OBU)~
( S t a b l e t o L i A 1 H 4 , C r O 3 and base)
-'._______________ *
Annalen (1968) 716 207 Rec Trav Chim (1969)
Acid
BuOH
131
HC(SEtj3
ZnC12
897
HC(OBU)~
\,..___--___-______~ Acid
HO H2 0
W
PhCOO
J A C S (1948)
racil
OCOPh
70 2268
Wraci1
CH20CH(OCH$H2C1)2 HC(OCH2CH$1)3 4
HOAc
H20
b
PhCOO
OCOPh
Tetr L e t t (1969) 4 4 4 3
Compendium of Organic Synthetic Methods, Volume 1 Edited by Ian T. Harrison, Shuyen Harrison Copyright 0 1971 by John Wiley & Sons, Inc.
Chapter 4
PREPARATION OF
ALDEHYDES
Section 46
Aldehydes from Acetylenes 0000000000000000000000000
1 Disiamylborane
2 H202 NaOH H20
THF
*+ CH2CH2CHO
Tetr Lett (1970) 41 JACS (1969) 91 4771 0rg React (1963) 13 1 C'H
Me0
2 NH2CONHNH2.HOAc
Section 47
Review:
1 MeCOSH
*
39%
JCS (1949) 619
Me 0
Aldehydes from Carboxylic Acids, Acid Halides and Anhydrides 0000u000000
0 0 0 0 0 00 0 0 0 0 0 u 0 0 0 - m
The Synthesis of Aldehydes from Carboxylic Acids Org React (1954) 132
S 218
61 %
ALDEHYDES FROM CARBOXYLIC A C I D S , A C I D H A L I D E S AND ANHYDRIDES
SECTION 47
[~ ) C H ( C H 2 ) 2 C 0 0 H PrCOOH
KOH
133
MeOH
*
electrolysis 2 HC1 H 2 0
P r (CH2)zCHO
B u l l Chem SOC J a p (1965)
-
2 922
Me
1 CH2N2
‘OC1
Et20
2 3,5-Dimethylpyrazole hJ E t 2 O
Me
b j c H 2 C o N M F L i A 1 Hq
Annalen (1961)
PhCH2COC1
1 CH2N2
2 EtSH
EtpO hU
CgH6
*
Me
Et20
PhCH2CH2COSEt
1 Ni
642
121
(PhNHCH2)z
2 HC1
H20
Et20
55%
PhCH2CH2CHO
Ber (1959) 92 528 Crg React (1954) 8 218
1 (i-Pr)pNLi
C6H13COOH
HMPA
THF
2 HCOOEt
*
C6H13CHO
65%
T e t r L e t t (1970) 699
BuCOOH
Li
MeNH2
BuCHO
66% JACS (1970)
HCOOH
c1
Ti02
*
92
5774
BCHO 36%
c1
JCS (1943) 84 JCC (1963) 3029
134
SECTION 47
COMPENDIUM OF ORGANIC SYNTHETIC METHODS
CgH1 ~ C O O H
Na-Hg
H3B03
Na2C03
NaHS03
H20
*
CgH17CHO
J SOC Chem Ind (1943)
p2 P h ( CH2)2COOH
36%
::
%$1 Me2CCH20H * 2 M e 1 MeN02 3 NaBH4 MeOH 4 NaOH
P h ( CH2)zCH
62 128
Ph(CH2)2CHO
Me
H20
J H e t e r o c y c l i c Chem (1966)
2 531
MeCHCOOH
1 N,N-Carbonyl THF 2 LiAl(OBu-t)3H
AcO
diimidazole THF
JOC (1970) 35 458 A n n a l e n (1962) 654 119
@@Jc'ooH
1 LkCHOgOEt N E t 3 Ic
y C o C H O( C O O J~ ~ ~ ; @4
@
w
2 EtOMgCH(COOEt)2 EtOH
MeOH B e r (1965)
yH20Ph
1 ClCOOEt c o N0H E X O O H
2 NaSH 3 N i (PhNHCH2)z HOAc
98 3040
Yh
NEt3
TsOH CH2C12
Ic
THF
JOC (1966)
79%
I
Ph
31
1922
<47%
SECTION 47
ALDEHYDES FROM CARBOXYLIC ACIDS, ACID HALIDES AND ANHYDRIDES
135
H2 Pd-Bas04
80%
xyl ene
4
Bu3SnH
PhCOCl
PhCHO J O C (1960)
Et20
hr/
PhCOBr
@
Me
JACS (1942) 64 928 (1940) 62 49 Org React (1948) 362
OMe
cot'
PhCHO
LiAl(0Bu-t)jH *
d ig 1 yme
25
284
80% Angew (1965) 77 169 ( I n t e r n a t Ed 6 1 4 6 )
Me
@
CHo
OMe
J Med Chem (1970) 1 3 26 JACS (1956) 78 252-
NH
/ \
t-BUCOC1
CH2-CH2
Et3N CgHg
,CH2 t-BuCON, I CH2
LiAlH4 Et20
JACS (1961)
t-BuCHO
83 4549
62%
COMPENDIUM OF ORGANIC SYNTHETIC METHODS
136
1 CH2N2 C15H31COCl
Et20
2 HOAc
1 Al(OPr-i)3
*
C15H31COCH20Ac
i-PrOH 2 Pb(OAc)4 HOAc
Org React (1954)
PhCOCl
EtSH
Pyr
Ni
PhCOSEt
____t
EtOH
H20
PhCOCl
N2H4
----+
SECTION 47
C15H31CHO 56%
218
PhCHO
4
62%
68 1455 T e t r L e t t (1964) 1763 Org React (1954) g 218 J A C S (1946)
1 PhS02C1
PhCONHNH2
S
*
Pyr +
2 Na2C03
-60%
PhCHO
ethylene glycol Org React (1954) 8 218 J O C (1961) 3667
BuCOCl
1 Q u i n o l i n e HCN CgH6 2 H2SO4
H20
F
JACS (1941) 63 2021 O r g R e a c t (1954) 8 218
[ OcH2''
P y r i d i n e N-oxide
Me0
chlorobenzene
CgH13CH2COC1
62%
BuCHO
1 BUSH ZnC12 C6H6
+
t
Me0
@J
CHo
T e t r L e t t (1965) 233
1 Perphthalic acid C~H~$H=C(SBU)~ 2 N2H4 MeOH
2 HC1 C6H13CH=NNH2
---- +
69%
CgH13CHO Rec Trav Chim (1959)
78 354
Et20
*
SECTION 48
ALDEHYDES FROM ALCOHOLS
iJ1-c^I ?H MeCHCH2CHCOOH
MeCHCH2CH2COOH 1
137
Bromination
MeCHCH2CHO
NaI04
t
Tetr Lett (1968) 1725
Aldehydes may also be prepared from carboxylic acids via amide or ester intermediates. See section 51 (Aldehydes from Amides) and section 53 (Aldehydes from Esters)
Section 48
BuOH
A1 dehydes from
A1 coho1 s
oooooooooooooooooooooo6
----+
BuOCH~CH=CH~
PrLi
BU (CH2)zCHO
29%
Tetr Lett (1969) 821
PH
i-PrCH2FCH=CH2 Me
CgHiiCH2CH(OEt)2 H3P04
t
i-PrCH2y=CHCH2CHCHO I Me CgH1 1
60%
Helv (1967) 2095 Tetr Lett (1961) 493
?H
MezCCH=CH2
C7H15CH20H
CH2zCHOEt
Me2C=CH(CH2)2CHO
Helv (1967) 50 2095 J A C S (1961) 198
H3P04
02 Pt EtOAc
+
C7H15CHO
J A C S (1955)
2
190 Angew (1957) 69 600 For application to allylic alcohols see Helv (1957) c 2 6 5
81%
21 %
138
COMPENDIUM OF ORGANIC SYNTHETIC METHODS
BuCH~OH
Li
NHzCH~CH~NH~ I
BuCHO
66%
Applicable t o benzyl i c alcohols J O C (1962)
Benzoquinone
SECTION 48
27
2662
A1 (OBu-t)g
\--I Chem C o r n (1969) 799
93% A p p l i c a b l e t o a l l y l i c and b e n z y l i c a l c o h o l s T e t r L e t t (1968) 3363 J O C (1961) 4814 (1970) 35 4000 OAc
a
CrO3
H2SO4
80%
P
DMF
0
H20
Helv (1968)
PhCHzCHCH20H
Na2Ct-207 Pyr.HC1
Pyr
*
772
PhCH-CHCHO
80%
Chem Ind (1969) 1594
EtCH20H
Kp-207
H2SO4
H20
EtCHO
45-49%
Org Synth (1943) C o l l Vol 2 541 F o r a p p l i c a t i o n t o a l l y l i c a l c o h o l s see B u l l SOC Chim Fr (1933) 53 301 and Ber (1947) 80 137
SECTION 48
139
ALDEHYDES FROM ALCOHOLS
CH20H
t-Butyl chromate CgHg
40%
Applicable to allylic and benzylic alcohols
B u l l Chem SOC Jap (1965)
Nickel peroxide
PhCH=CHCH20H
C6H6
CH20H Br
PhCH=CliCHO
+
J O C (1962) JCS (19'9)
(NHq)zCe(N03)6 HOAC H20
*
Br
38 1503
86%
27 C
1597 2173
@
CHo
JCS (1965) 5777 J O C (1967) 2 2349
@
893 1141
93% 3865
MeCH(CH2)2CHzOH Ag2C03-cel i te C6H6
Applicable to allylic alcohols
Compt Rend (1968)
i-PrCH20H
Ago H3PO4 HOAc
Argentic picolinate Me2SO H20
900
30%
i -PrCHO
w
Applicable to allylic alcohols
BuCH20H
C 267
*
T e t r L e t t (1967) 4193
BuCHO
Applicable to benzylic alcohols Can J Chem (1969)
74%
2 1649
dH0
COMPENDIUM OF ORGANIC SYNTHETIC METHODS
140
Me0 HO‘&
Mn02 MeCN
____t
PhCHzCHCH20H
PrCH20H
MnOp CCl4
Pb(OAc)4
Pyr
SECTION 48
Me0
76%
Proc Chem SOC (1964) 110 Chem Corn ( l C 5 6 ) 121
PhCH=CHCHO JCS (1952) 1094 JACS (1955) 4399 PrCHO
t
70%
Applicable to allylic and benzylic alcohols
T e t r L e t t (1964) 3071
C5H11 CH20H
INOj-Pyr CHC13
*
C5H11 CHO
Applicable t o benzylic alcohols
20%
JCS C
(1970) 676
95%
JCS
(1955) 1110
DCC CF3COOH Me2SO Pyr CgHg
-
1 0
MeCH(CH2)2CHO
Applicable t o benzylic alcohols JACS
(1965) 5670 Chem Rev (1967) 67 247
85%
141
ALDEHYDES FROM ALCOHOLS
SECTION 48
70%
----+
C7H15CH20H
C7H1 5CH20Ts
NaHC03 Me2SO
Applicable t o benzylic alcohols
C5H11 CH20H
COC12
Et2O
*
C7H15CHO
81 4113
JACS (1959)
C5H11CH20COCl
~ 7 8 %
1 MeZSO
C5H11CHO
68%
2 Et3N JCS (1964) 1855
KOCl
PhCH20H
MeOH H20
t
PhCHO J O C (1961)
CH20H
77%
26
1046
N-Chlorosuccinimide Me
71%
Bull SOC Chim Belg (1951) 60 54 Compt Rend (1954) 238 2538Chem Rev (1963) 63 2 1
i-PrCH20H
i-PrCHO
JACS (1954) 76 6345 For a p p l i c a t i o n t o b e n z y l i c a l c o h o l s see JCS (1960) 1332
31 %
142
COMPENDIUM OF ORGANIC SYNTHETIC METHODS
SECTION 48
lCOOEt
c11 H23CH20H
NCOOEt
t o 1 uene
t
Applicable t o benzylic alcohols
c11 H23CH0 J O C (1967)
4-Phenyl-1 , 2 , 4 - t r i a z o l i n e - 3 , 5 - d i o n e
PhCH20H
C6H6
20%
32
*
727
78%
PhCHO
Chem Corn (1966) 744 JCS C (1969) 1474
Yyp
2,3-Dichloro-5,6-
CH20H
d i c y a n o q u i n o n e (DDQ)
*
cvJ[
A p p l i c a b l e o n l y t o a l l y l i c and b e n z y l i c a l c o h o l s
S 409 61 153
J Med Chem (1962) Chem Rev (1967)
PhCH=CHCH20H
T e t r a c h l o r o - 1 ,2-benzoquinone
100%
PhCH=CHCHO
CCl4
A p p l i c a b l e o n l y t o a l l y l i c and b e n z y l i c a l c o h o l s JCS (1956) 3070
b1 MsCl
HO
OH
2 MeONa 3 NaN3
DIdF
DMF
1 Acetylation 2 hV
MeOH
Vg-J ~~0
OAc
Carbohydrate Res (1968)
Org React (1944)
2.
341
S
366
SECTION 48
143
ALDEHYDES FROM ALCOHOLS
57% HO
J A C S (1945) 6 7 39 J O C (1970) z 2 4 9
12 HgO
Ph( CH2)3FHyH( Cti2)3Ph HO OH
Ph:HCH20H
K2S208
CH2C12
JCS
AgN03
H20
*
OH
99%
Ph(CH2)3CHO
C
(1969) 383
61 %
PhCHO J A C S (1954)
76 6345
T e t r Lett (1968) 5689
MeFHFHMe HO OH
XeO3
H2O
MeCHO J A C S (1964)
2078
144
COMPENDIUM OF ORGANIC SYNTHETIC METHODS
S e c t i o n 49
Aldehydes from Aldehydes
. .
Chain e x t e n s i o n and a l k y l a t i o n o f aldehydes Degradation of aldehydes t o lower homologs
. . . . . . page ...... ... ,
SECTION 49
144-145 145-146
1 Ph3P-CHOGMe PhCHO
2 HC104 H20
PhCH2CHO
Et20
55%
Ber (1962)
HO
CHO
95
2514
CH2CHO
1 Ph3P=CHSPh Me2SO
'OtOH
2 HgC12 HgO H20
36%
OH T e t r L e t t (1969) 3665
CHO
CHzCHO
1 Ph3P=CHOMe
Et20
28%
Et2O
2 HClO4
Carbohydrate Res (1969)
1 C12CHCOOEt Mg-Hg 2 EtONa
ClCH20Et HgC12
THF
EtzO
Mg
*
CgH13CHCHCOOEt \I 0
1 NaOH
-----+
2
A
184
CgH13CH2CHO
Compt Rend (1937) 204 2 7 2 Org React (1949) 2 413
CgH13CHCH20Et I
OH
HCOOH
CgH13CH2CHO
B u l l SOC Chim F r (1959) 459
10%
SECTION 4 9
1 t-BuNH2
C5H11 CH2CHO
PrCH2CHO
145
ALDEHYDES FROM ALDEHYDES
2 EtMgBr 3 BuI
Acid
C5H11 YHCHZNBu-t Bu
H20
85
JACS (1963)
BuNHCHzPr-i
CgH] 1THCHO BU 2178
1 EtI
PrCH=CHNCH2Pr-i
PrCHCHO
2 A c i d H20
I
BU
50%
it
78%
Chem Corn (1967) 510
E t f HCHO
Pyrrolidine
*
1 CH2=CHCH$r
EtC-CHN3
CH2CH=CH2
*
EtfCHO
(tH2)2COOMe
(CH2)2COOMe
(CH2)2COOMe
Chem Comm (1965) 197 JACS (1963) 85 207 Angew (1960) 169
PhCH2CHO
1 PhNHNH2
2 KNH2 PhCH2C1
P h y HCHO
Me
1 Br2
2 CN-
PhCHCHZNNHPh I
---- +
PhCHCHO I
CHZPh
NH3
CH2Ph JACS (1967)
-
0
1 AlMe3
I \
PhC-CHCN I Me
2 A
463
Ye PhyCHO Me
T e t r L e t t (1970) 2947
HO OH Me HCH26HbHOEt
1 IBr
HBr
P
HOAc 2 KOH E t O H
A -
Na 104
HOAc Me2CO
Chem Comm (1968) 851 T e t r Lett (1970) 5229
MeCHCH2CHO
A. -
COMPENDIUM OF ORGANIC SYNTHETIC METHODS
146
2
Cu(0Ac)z
Pyr
Et3N
t
SECTION 50
MeCHO
Rec Trav Chim (1966)
437
Some o f t h e methods i n c l u d e d i n s e c t i o n 57 (Aldehydes f r o m Ketones) may a l s o be a p p l i e d t o t h e p r e p a r a t i o n o f aldehydes f r o m aldehydes
S e c t i o n 50 Reactions i n which methyl groups a r e c o n v e r t e d i n t o aldehyde (RMe +RCHO) a r e i n c l u d e d i n t h i s s e c t i o n . For r e a c t i o n s i n which a hydrogen i s r,eplaced by aldehyde, RH -+ RCHO ( R = a l k y l , v i n y l o r a r y l ) , see s e c t i o n 56 (Aldehydes f r o m H y d r i d e s )
50% JCS (1949) S230
CH3
1 Cr02C12
MezC=CHMe
2 H20
25% JACS (1951)
73 221
ACoQcH3 COOEt OAc
H2S04 HoAc
COOEt OAc
EtoH H20
COOEt OAc
33 4176 Org S y n t h (1943) C o l l Vol 2 441 J O C (1968)
50% JCS (1960) 1332
SECTION 50
ALDEHYDES FROM ALKYLS
CH3 Mn02 H2SO4
147
HzO 23%
t-Bu &cHo
t-Bu OMe
OMe
JOC (1951)
P
Me
CH2=CHi(CH2)$H=CCH3 OAc
-
Me
Se02
2 586
Ye
CH2=CHb(CH2)2CH=CCHO OAc Chem Corn (1968) 1277 Org React (1949) 2 331
73% J O C (1966) 2 2033 JCS 5 (1970) 1630
PhCH3
Argentic p i c o l i n a t e
Me2SO
*
PhCHO Tetr Lett (1967) 415
QCH3
@
NBS hV
benzoyl p e r o x i d e CC14
*
F
JACS (1966) 3318 (1956) 78 1689 Org React (1954) 197
S
COMPENDIUM OF ORGANIC SYNTHETIC METHODS
148
S e c t i o n 51
Aldehydes f r o m Amides
NaAlH4
THF
78%
c 1 5H31CH0
t
Tetrahedron (1969)
@
SECTION 5 1
15 5555
~ 7 0 %
CoNMe2 CONMe2 Ber (1951)
LiAlH4
Et20
84 625
PrCHO
t
JACS (1961)
*
Me
4549
57%
Me QCHO Me
Me
Ber (1955) 301 Org React (1954) S 218
@T@
LiA1H4
I
Et20b
PhCH=CHCO
BuCONMeZ
J O C (1953)
L i A l (OEt)3H
Et20
*
45%
PhCH=CHCHO
18 1190
BuCHO
92% JACS (1964)
1089
SECTION 51
( ~ - B u ) ~ A ~Et20 H
C71il5COyPh
C7H15CHO
t
Me
56%
I z v (1959) 2146
(Chem Abs
1 Na
C5H11CONHPh
NH3
Electrolysis
p2s5
PhCH=CHCONHPh
Pyr
LiCl
PC15
t o 1 uene
*
Q
Ni
EtOH
35
1210
PhCHO
74
JACS (1952) 3936 Org React (1962) 356
F’
PhCH=CHC=NPh
1 TsCl
SnC12
HC1
EtpO
@ONHNH2
12
PhCH=CHCHO
92%
I!218
Pyr
60%
2 NapC03 ethylene glycol
QCHO JOC (1961)
2
3664
Org React (1954)
NaIO4
53% 512
50%
Org React (1954)
CONHNH2
8
C5H11CHO JOC (1970)
PhCSNH2
-
10932)
A u s t J Chem (1955)
MeNH2 EtDH
-
54
C5H11CHO
2 HOAc
C5H1l CONHMe
PhCONHp
149
ALDEHYDES FROM AMIDES
NH3
H20 t
@ JACS (1952)
CHo
74 5796
218
60-70%
150
COMPENDIUM
OF
ORGANIC SYNTHETIC METHODS
Argentic picolinate
PhCHZNHAc
Me2SO
*
SECTION 52
PhCHO
T e t r L e t t (1967) 415
EtNHAc
K2S208
K2HP04
H20
MeCHO
t
48%
J O C (1964)
S e c t i o n 52
Aldehydes f r o m Amines
0 0 0 " " 8-0 0 0 0 0 0 0 0 0 0 0 0
gNH2 1 NaN02 NaOAc
3 HC1
QCHO
H20 *
H20
Me
JCS (1954) 1297
H20
Pyr
-
PhCHO
CgHg
2 D i a z a b i c y c l o n o n e n e Me2SO THF MeOH
*
THF
JACS (1969)
'gH1 1CH2NH2
63%
JCS (1954) 209
1 3,5-Dinitromesitylglyoxal 3 (COOH)2
41 %
CuSO4
1 2,4-Dinitrobenzaldehyde 2 HC1
c1 lH23CH2NH2
HC1
2 HCH=NOH NaOAc Na2S03
Me
PhCHzNHZ
29 3632
Hexami ne HCHO HOAc H20 *
c11 H23CHO
34%
91 1429
CgHilCHO
JCS (1953) 1737 O r g React (1954)
42%
S
197
Ja
SECTION 52
ALDEHYDES FROM AMINES
CH2NH2
Me
PhC H2 NE t 2
MeCH2NH2
NaN02 Me2SO
*
Me
BCHO 60%
Angew (1965) ( I n t e r n a t Ed
NaN02
NaOAc
HOAC H20
OF2
CF3COOH
151
+
811
5 787)
PhCHO JACS (1967)
f r e o n 11
MeCH=NOH
+
--+
1147
MeCHO
44%
JACS (1964)
1392
47% JCS (1964) 711
(PrCH213N
Br2
H20
pH 5
PrCHO
t
JACS (1968)
(EtCH2)3N
NBS
dioxane
H20
t
EtCHO
68%
JCS (1957) 4905 Chem Rev (1963)
PhCH2CHzNH2
1 t-Butyl hypochlorite NaHC03
Et2O
84 %
90 3502
t
63
PhCH2CHO
39%
2 EtONa E t O H 3 H2SO4 H20 JACS (1954)
21
5554
COMPENDIUM OF O R G A N I C SYNTHETIC METHODS
152
PrCHzNH2
H202 H20
PrCH2NH2
Na2W04 EtOH
*
PrCH=NOH
57%
KMn04 MSO4
---- + Ber (1960)
SECTION 53
PrCHO
93
132
PrCHO (M=Ca o r Zn) J O C (1967)
PhCH2NH2
PrCH2NH2
Mn02
PhCHO J A C S (1955)
Argentic picolinate
H20
*
2 3129
34%
77 4399
PrCHO
14%
J C S (1965) 4962 T e t r L e t t (1967) 415
Aldehydes may a l s o be prepared by o x i d a t i o n o f N-acyl amines. s e c t i o n 51 (Aldehydes f r o m Amides)
S e c t i o n 53
PrCOOMe
See
Aldehydes f r o m E s t e r s 000000000000000000000
NaAlH4
THF
*
81 %
PrCHO T e t r L e t t (1963) 2087
70%
J O C (1966)
2 283
SECTION 53 i-PrCOOEt
153
ALDEHYDES FROM ESTERS (i-Bu)zAlH
hexane Et2O
toluene
i-PrCHO
t
80%
T e t r L e t t (1962) 619
(1969) 1779
1 N2H4 H20
2 PhS02C1
*
Pyr
0 L
A
ethylene glycol
O
L
87%
O
J C S (1936) 584 JOC (1961) 3664 Org React (1954) 2 218
a
COOMe Me0
HO Me I 1
r!
280'
1 Me2CCOOMe
KBH4
Et (CH=CHCHz)3 (CH2)6COOMe
&
87%
B u l l SOC Chim F r ( 1 9 6 5 ) 1864
Na xylene
pcHo
Et (CH=CHCH2)3 (CH2)6fHOH E t (CH=CHCHz)3 (CH2)6CO
I
1 LiAlH4 2 Pb(OAc)4
Et(CH=CHCH2),(CH2)6CHO
PrCH(COOEt)2
N2H4
J Am O i l Chem SOC (1960) (Chem Abs 2 23373)
PrCH(CONHNH2 12
1 HN02
H20
2 H2SO4 H20
*
Org React (1946)
PrCHO
3
337
37
425
68%
46%
S e c t i o n 54
. . ...
, , . Aldehydes f r o m e t h e r s , Aldehydes by rearrangement o f epoxides
. . . . . page . ........ I
I
CUCl
hY
+
PrCH(OC&i13)2
154-155 155-156
---+
PrCHO
70% Angew Chem (1961) 73 65 Act Chem Scand (1961) 2 249 Tetrahedron (1961) 13 2 4 1
YCOOEt
NCOOEt
I
I
CgH130H t - b u t y l perbenzoate
(PrCH2 120
PrCH20Bu
S E C T I O N 54
COMPENDIUM OF ORGANIC SYNTHETIC METHODS
154
PryHOBu
NCOOEt
H20
PrCHO
HNCOOEt 60%
P b ( O A C ) ~ hV
PrCH20Bu
*
PryHOBu
OAc
-
Chem Corn (1965) 259
Acid
PrCHO
r
Annalen (1970)
735 47
fC
MeCHZOEt
1 PhNNO 2 Acid
MeOCH2CH20Me
MeCH20Et
MeCHO JACS
p-Chlorobenzendiazonium c h l o r i d e NaOAc
H20
PhIC12
hJ
50%
(1964)
*
3180
MeOCH2CHO
Angew (1958) 2 211
MeCHOEt
----+
MeCHO
61
79%
Annalen (1969)
728 12
SECTION 5 4
ALDEHYDES FROM ETHERS AND EPOXIDES Br2
PhCH20Me
HOAc
H20
83%
PhCHO
t
JACS ( 1 9 6 7 )
NBS
155
CHOMe
CCl4
89
HC1
3550
H20
JOC ( 1 9 5 8 ) 2 1 4 9 0 Angew ( 1 9 5 9 ) 349
.0:"";5%
NO2
2
SeOz
PhCH=CHCHzOMe
HOAc
dioxane
*
PhCH=CHCHO
66%
T e t r L e t t (1970) 2 8 8 5
1 02 Ph2CO h V
PrCH20Me
2 Acid
262'
MeCH20CPh3
PrCHO
b
Ber ( 1 9 6 3 )
MeCHO
JACS ( 1 9 3 0 ) (1924)
96 509
52
55%
753
5 2580
aiH2
A CHO
Me 0 I I\ i-PrCOOCH2CCH2C-CH2 I
Me
I
BF3.Et20
Me2SO
91 %
Ye
c
i-PrCOOCH2CCH2CHCHO
he h e
Me
JOC
(1965)
30
3480
64%
COMPENDIUM
156
OF
ORGANIC SYNTHETIC METHODS
SECTION 55 80%
Chern Corn (1968) 227
Ye
0
I\
(CH2CH2CH=C)2CH2CH2CHCMe2
(CH=CCHzCH2) I 2CH=CMe2 Me
Section 55
-
Me 1 (CH2CH2CH.C) 2CHzCH2CHO ( CH=CCH2CH2)2CH=CMe2 I Me
HI04
EtpO
Chem Comm (1968) 1067
Aldehydes from Halides and Sulfonates 0000000000000000000000000000000000000.
COCH20Me
2 MeOCH2CN
A -
- @@
MeCHCHO
21 MeMgCl KHS04
JACS (1939)
i -PrBr
BuBr
Mg Et2O * 2 MeOCH2COMe 1
-----
BuOCHzCH'CH2
CH2=CHC( CH2)2CH=yCH2Br Me CH2
(COOH)2
JACS (1946)
PrLi THF pentane
1 CH3CH-NBu-t ( i -Pr)2NLi
61 2134
-
VH
i-PrCCHzOMe I Me
59%
i-PrCHCHO Me
68
2339
Bu(CH2)2CHO
29%
Tetr Lett (1969) 8 2 1
+
Et20 2 (COOH)2 H20
Helv
CH2=CHC( CH2)2CH=C(CH2)2CHO 11 1 CH2 Me 61% (1967)
2440
P rI
2 NaBH4
THF
3 (COOH)2
EtOH
*
65%
PrCH2CHO
H2D JACS (1969)
(1970)
C"
BuLi,
D
C
H
JACS (1969)
Et2D
2 CHz=CHCHzBr
*
PhCHzCH=CH2
1 PhCOOAg 3 Pb(OAc)a
5886
36%
91 765 I2
PhCH2CHO
+
11 351
do
Et20
40-42%
____t
2 HC(OEt)3 3 HC1
92 6676
2 NaOH
Helv (1934)
1 Mg
2 763
O
NaBH4
1 Mg
PhBr
157
ALDEHYDES FROM HALIDES AND SULFONATES
SECTION 55
H20
Org Synth (1955) C o l l V o l 3 701 (1943) C o l l Vol 2 323 B e r (1970) 103 6 4 3
Br
@JBr
Me0
- OCHD 1 Mg
Et20
2 HCOOEt
Br
mBr
A n n a l e n (1912)
Me0
40%
393 215
JQ@
CHD
Chimia (1964) 18 141 JCS (1956) 4 6 9 F
80%
158
COMPENDIUM
OF
ORGANIC SYNTHETIC METHODS
J O C (1970)
2 PhN=CHOEt 3 HC1 H 2 0
Me
c1 zHEBr
1 Mg
Et20
3 HC1
H20
2 711
82%
Me
6
J O C (1941)
*
SECTION 5 5
489
73%
C12H25CH0
JACS (1955)
77 5118
Ye
1 t-BuCH2CNC I
EtCHBr Me
---- +
Me
EtCHLi I
Me
Et20 2 (COOH)2
*
EtFHCHO
92%
Me
H20
JACS (1969) 9 1 7778 (1970) 6675
1 Mg E t 2 0 CgH13Br
2 p-Dimethylaminobenzaldehyde *
75%
CgH13CHO
J O C (1960) (1962)
2 1691
2
279
SECTION 55
QBr
ALDEHYDES FROM HALIDES AND SULFONATES
HsScJ@
1 Mg Et20. Me 2 CS2
1 NH2CONHNH2.HCl Me
PYr 2 Hydrolysis JOC
( EtO)2CHCH2Br
C9H19Br
Ph3P THF
2 HOAc
*
QCHo
Me
60%
5 489
< 77%
(Et0)2CHCH2CHO
2 HgC12
1 Na2Fe(C0)4
(1941)
159
Angew (1965) 77 1134 ( I n t e r n a t Ed c l 0 7 5 )
*
CgH1 gCHO
77%
JACS (1970)
92 6080
PhCH2Br
CH2Br
@
COOMe
i-PrN02 EtONa
EtOH
72%
COOMe
JACS (1949) 1767 Org Synth (1963) C o l l Vol 4 932
EtC=CH(CH2)2C=CHCH2Br I Me Me
n i trocvc 1 ohexane
KOH i-PrOH H20
*
EtC=CH(CH2)2C=CHCHO I I Me Me
Zh Obshch Khim (1959) (Chem Abs
54 21170)
2 3965
COMPENDIUM OF ORGANIC SYNTHETIC METHODS
160
JACS (1961)
SECTION 5 5
193
t-
Me3NO CHC13 C7H15CH2X
b
C7H15CHO
50% ( X = I ) 55% (X=OTs) Ber (1961) 94 1360
74% JACS (1959)
Br
Me2SO
81 4113
65%
Br JACS (1959) 81 4113 Chem Rev (1967) 67 247
Me2C=CH( CH2CHpq-CH) 2CH2Br Me
1 Pyr
b
2 p-Nitrosodimethvlaniline
Me$=CH( CH2CH2C-CH) 2CHO
Helv (1941)
C6H13CH21
1 Hexamine HOAc
CHC13
c
Me
4
1039
CgH13CHO
Org React (1954)
41 %
S
197
ALDEHYDES FROM HALIDES AND SULFONATES
SECTION 5 5
CH2Br
C u ( N 0 3 ) ~ H20
t-Bu
+
t-Bu
161
@
CHo
JCS (1935) 1847
1 Mg
PhCHZC1
Et20
*
PhCHO
2 02 3 NaOH
JACS (1955)
NaN3 C7H15CH21
b u t y l carbi to1
*
C7H15CHzN3
6032
1 h9
2 Acid
C7H15CHO
T e t r a h e d r o n (1965)
CHBr2
HCOONa
EtOH
50%
11 2877
QCHO
tI20 *
70% OH
OA.:
JCS (1955) 1628
Ph3Si
CHBr2
AgN03 H20 c methyl c e l l o s o l v e
Ph3Si
@JCHO
JACS (1956)
Ber (1959)
78 1689
92 900
67%
162
COMPENDIUM OF ORGANIC SYNTHETIC METHODS
H20
MezYCHeBr Br
Section 56
MeZCHCHO
J A C S (1933)
(1 0
0 0
0
0
c)
0 0
75%
1136
~-
Aldehydes from Hydrides (RH) 0 0 0 00 0 0 0
SECTION 56
-
RCHO Reactions in which a hydrogen is replaced by CHO, e.g. RH (R-vinyl, ethinyl or aryl), are included in this section. For reactions in which alkyl groups are oxidized to aldehyde, e.g. RCH3 RCHO, see section 50 (Aldehydes from Alkyls)
Q
‘HZ
Me0
ii,b
0
CHCHO
POC13 HCONMe2
41 %
Z Chem (1967) 346 T e t r a h e d r o n (1969)
POCl
HCONMe2
Me0
*
Ph3P*Br2 HCONMe2 *
hCHO OMe
Ber (1964) 2 1252 JCS C (1969) 913
O
C
H
O
Annalen (1968)
Ye
POCl3 HCONPh
*
D
4535
C
H
45%
718 24
O Org Synth (1963) C o l l Vol 4 915 (1955) C o l l Vol 3 98
71%
SECTION 56
ALDEHYDES FROM HYDRIDES (RH)
i -Pr
i -Pr
Zn(CN)Z
i-Pr
163
AlC13
Pr-i HC1 C2HzC14
*
@
i -Pr
CHo Pr-i
J A C S (1942)
66%
64 30
73%
Ph Org React (1949) S 290 Org Synth (1943) C o l l Vol 2 5 8 3
HCOF
Me
BF3
CS2
Me
c
Me
Me
hCHO Me
JACS (1960)
Me
@
Ye
1 PhNCOCl
AlC13
2 LiAlH,
Me
t
T iC l 4
2380
S
301
CH2C12 +
Me Me
OMe
68%
Me QCHO Me Ber (1960)
93 8 8
OMe 1 PhLi
@M ,e
82
BCHO
Ber (1955)
BuOCHCl2
72%
Me
2 HCOYPh Me
Et20
t
Org React (1954)
8 258
164
COMPENDIUM OF ORGANIC SYNTHETIC METHODS
SECTION 5 7
L
JCS (1958) 1054
Section 57
0;
CH2=CHCH2SCHPO(OEt)2 L i t THF
VJHgO
160-180'
JACS (1970) 92 5522
1 Ph3PCH20Me C1 PhLi 2 HClO4
oo
1
Et20 Et20 JACS (1958) 80 6150 Org React ( 1 a S ) 14 2 7 0
P h j i C H p O D eb PhLi Et20
2 HClO4
1 ClCH20Et 2 HCOOH
Et20
0"" ~ 8 2 %
Ber (1962)
Mg
*
95
2514
tSH0
JACS (1968) 90 3282 Compt Rend (1963) 256 1996
51 %
SECTION 57 PhCOMe
-
0 / \ PhC-CHCOOEt I Me
ClCH2COOEt
NaNHz
C1 CHzCOOBu-t t-BuOK
165
ALDEHYDES FROM KETONES
1 NaOH
2
@HCOOBu-t
t
PhCHCHO I Me
looo
EtzCO
BrCHZCOOEt Zn C6H6
t
Et2:CHZCOOEt OH
O C H O
350-360: JACS (1963)
1 NZH4
2 NaN02 HC1 3 KOH
73 4199
BF3’EtzO JACS (1962)
1 LiCH2CH=N3 Et20 2 HOAc
&
*
84 867
OCHO
Me (CHz)2h=CHCHO 1 ~~0~
\I
79%
Et2CHCHO
+ -
Me3SO I NaH
65%
Me \--(CH2 )2LHCHO
SeO2 2 A1203
T e t r L e t t (1970) 381
KMn04
KOH
Pyr HzO
~
-
N ,N-Di methyl to1 u i d i ne
JACS (1965)
39%
955
JACS (1951)
42%
87 1 2 4 7
CHO
t
A -
COMPENDIUM OF ORGANIC SYNTHETIC METHODS
166
BuN3
PhCOCH2Me
H2SO4
toluene
t
PhCHO
+
SECTION 58
MeCHO
62%
50%
JACS (1959)
3369
Some o f t h e methods i n c l u d e d i n s e c t i o n 49 (Aldehydes f r o m Aldehydes) may a l s o be a p p l i e d t o t h e p r e p a r a t i o n o f aldehydes f r o m ketones
Aldehydes
S e c t i o n 58
from N i t r i l e s
oooo~ooubbbpbbb
Ph I
(PhNHCH2)z
Me0 OMe
HOAc
bh
MeOH
H20
Ber (1957)
PhCH2CN
1 H2
Ni
NaOAc
@$$
CN
NH2NHCONH2.HCl MeOH
H2
Ni
H20
*
c1
OMe
90 617
PhCH2CH=NNHCONH2 - - - + PhCH2CHO Angew (1955) 67 156 J O C (1962) 27 850
N2H4 \ y C H = N N H 2 D
EtOH Gazz (1955) (Chem Abs
CN
Me0
Et20
Ni HOAC
NaH2P02 H20
Pyr
t
c1
1705 10037)
aCHo
JCS (1962) 3961
80%
SECTION 5 8
ALDEHYDES FROM N I T R I L E S
CN
Ni-A1
HCOOH
167
H20 95%
@JCHO JCS (1965) 5775 (1964) 5880
LiAlH4
i- P r C N
L i A l (OEt)3H
EtpO
P C H O
t
Et20
NaA1(OEt)3H
48%
JACS (1951) 2 4047 Org React (1954) 8 252
i-PrCHO JACS (1964)
t
86
QCHO
THF w
88%
Me Annalen (1957)
PhCN
( ~ - B u ) ~ A ~ CgHg H
PhCHO
c
J O C (1959)
mCN %;l2
HC1
1085
607 24
90%
24 627
EtpOt
73-80%
Org S y n t h (1955) C o l l Vol 3 626
1 SnC12 c1 5 H 3 1 CN
2 H20
HC1
Et20
t
C15H31CHO
JCS (1925) j.2J
1874
168
COMPENDIUM OF ORGANIC SYNTHETIC METHODS
MeSCH2CHzCN
MeOH
HC1
1 LiA1H4
MeSCH2CH2C(OMe)3
C6H6 2 Acid JACS (1951)
---*
PhCH2CN
1 NaBH4
PhCH24
2 Base
THF
EtOH
SECTION 59
EtpO
MeSCH2CH2CH0
73 5005 *
PhCH2CHO
Chem Corn (1967) 1163
Me I
BrCCOOEt 1 Me
PhCN
Zn
CgHg
Me
*
1 H2
PhCOCCOOEt
tI2S
NH3
- - - - - - - - + PhCSNH2
Compt Rend (1953)
Ni
EtCH=CH2
fH2 CH I
(:H2)8 CN
t
PhCHO
236 826
PhCHO
EtOH
JACS (1952)
S e c t i o n 59
EtOH
2 260"
I
Me
PhCN
Ni
74 3936
Aldehydes f r o m O l e f i n s
000000000000'
1 B2Hg
THF
2 MeCH=CHCHO a i r i-PrOH
1 2 CO 3 H202
*
d
E t ( C H ) CHCH2CHO 2 2,
Me
JACS (1970)
2 714
C HD
THF L~A~(OBU-~)~H NaH2P04
90%
K2HP04
t
ti20
+2)2 (yH2)8 CN
JACS (1969)
91 4606
SECTION 59
Me2C=CH2
1 B2Hg
ALDEHYDES FROM O L E F I N S
169
MezCHCH2CHO
91%
THF P
LiAl(OMe)3H
2 CO
JACS (1968)
CsHl3CH=CH2
PrCHCH=CH2 I
Me
CO H 2
(100 p s i )
(Ph0)3P
toluene
co
H 2 (200 atmos)
c02(co)8
e0
Rh-C
90 499
818
89%
CgH13(CH2)2CHO
t
JOC (1969) 2 327 Chem Corn (19671 305
Pr?i(CH2)2CHO
b
CgHg
Me JACS (1968)
N
62%
90 6847
CH=CH2
k/
CH2CH2C$] 0
hJt
45%
Acid
_---*
T e t r L e t t (1969) 43 JOC (1968) 805
T e t r Lett (1968) 4339
86% Acc Chem Res (1970) 3 338 T e t r L e t t (1970) 5275
COMPENDIUM OF ORGANIC SYNTHETIC METHODS
170
1 CrOC12 CH2C12
(t-BuCH2) 2C=CH2
2
Zn
1 Hg(OAc)2
*
SECTION 59
(t-BuCH2)2CHCHO J O C (1968)
Me2CO
33
80%
3970
EtpO CgH6
2 NaBr 3 Br2 CCl4
J O C (1968)
33 3953
50% Chem Comm (1969) 773
1 03 MeOH
cgH17CH=CH(CH2)7COOMe
2 H2 Pd-C MeOH EtOAc (or Zn HOAc)
CgH17CHO
w
For reduction o f ozonides with tetracyanoethylene see )I ,I (Me0)3P " 4, (Me2N ) 3P " ,)
I!
It
I
'I
I,
I
'I
,I
I,
"
I'
I,
,I
I,
I,
'I
I1
I,
,I
4,
"
'I
selective ozonolysis
PhCHzCH2
Ph3P
J O C (1960) 2 618 JACS (1953) 75 4952 Ber (1963) 1564 J O C (1960) 2 1031 Helv (1967) 2387 JQC (1968) 33 787
" H e l v (1967) 2445 Me2S dinitrophenylhydrazine see JACS (1956) 2 5601 see J O C (1961) 26 4912 Na2S03
Bistriphenylsilyl chromate CCl4
"
78%
"
*
JACS (1958) (1969) (1958)
PhCHO 30C (1970)
2 774
80 915 91 4318 915
ALDEHYDES FROM OLEFINS
SECTION 59
171
Na2Ct-207
CH=CHMe
Sulfanilic acid
0
H20
86%
0
J SOC Chem Ind (1943) JCS (1937) 369 Org React (1959) lo 1
CgH13CH=CH2
Ru04
CCl4
12%
CgH13CHO
_____t
JACS (1958)
I
FN
HCONH
HCONH
CN (CH2)6
Me2Co
os04 ~ a 1 0 4 C ~ O H ~ ~ C H = C H_ ~ ___t dioxane
$HZ
FH
(tH2)8 COOMe
1 H202 2 MeONa
Me0 @cH=cHMe
62 90
JACS (1968)
6682
43%
90 3245
C1oH21CHO
68%
J O C (1956) 2 478 T e t r a h e d r o n (1968)
24
3095
HCOOH
MeOH'
E3;ctrolysis
Na2S04
*
Me0
@
Helv (1925)
CHo
5
332
52%
172
COMPENDIUM OF ORGANIC SYNTHETIC METHODS
CH=CHMe 1 C(N02)4 PYr 2 KOH
S e c t i o n 60
PrCH=yCHO
Et
Me2CO
\ y
t
H20
CH=fMe NO2 1 Phenylethylamine 2 HC1
H20
Can J Chem (1968)
*
79%
5 75
Aldehydes f r o m M i s c e l l a n e o u s Compounds 00000000000000000000000000000000000000
1 H2
y 2 EtCHCHZOH
Ni
2 HC1
PrCH2FHCHO
w
H20
Et J A C S (1955)
MeCH=CHCHO
SECTION 60
H2
(Ph3P)38hCl
CgH6
*
Me(CH2)zCHO JCS
C (1967)
-
~ ‘ H z c H 2 0 H
359
270
CH2CHO
Fe(C0)s
Chem C o r n (1968) 97
Me2C=CH( CH2)2y=CHCHO Me
PhCH-CHCN
2 Hydrolysis
*
0
I\
Me$-CH(CH2) 2tHCHO Me
Org React (1957) 9 73 T e t r L e t t (1970) 381
c02(co)8 MeOH
1 PhC002H
H20
HC1
+
Ph(CH2)2CHO Chem Comm (1967) 1140
50%
SECTION 60
PhCH=CHCONH*
ALDEHYDES FROM MISCELLANEOUS COMPOUNDS 1 NaOCl
MeOH H20
2 Acid
PhCH2CHO
-b
70%
;;I Org R e a c t (1946)
HO Hf'
1 NaOH
H20 c
2 H2SO4
H20
3
267
70%
OH
OH
OH
OH
PrCH2N02
173
OH
JACS (1951) 73 4662 JOC (1943) 8 10 Chem Rev (1955) 55 137
KMn04
KOH
MgS04
H20
PrCHO
97% J O C (1962)
2 3699
190-200" C10H21 YHCOOH OH
PhfHCOOH
OEt
CiOH21CHO
96%
J SOC C h e m Ind (1943)
Electrolysis
MeOH +
PhYHOMe OEt 71%
HC1
J O C (1962)
H20
2 281
62
PhCHO
128
COMPENDIUM OF ORGANIC SYNTHETIC METHODS
174 S e c t i o n 60A
i- P r C H O
SECTION 60A
P r o t e c t i o n o f Aldehydes
0000000D0DD0000000DD000
HC(OEt)3
i
NH4C1
1 - - - - - - - -- - - - -- -
EtOH ;
-PrCH(OEt)Z ( S t a b l e t o RMgX, LiA1H4, CrO3 and base) B u l l SOC Chim Fr (1965) 1007
Acid
CHo
PhS02NHOH MeOH
c1
*
PhS02NHOH H20 d i o x a n e
Me2S04 NaOH MeOH H20
c1 J O C (1970)
5 1962
t
Acid
( S t a b l e t o RMgX, L i A l H 4 , CrO3 and base) T e t r a h e d r o n (1959)
PhOCH2CH2CHO
2-Methyl -2,4-pentanediol
TsOH
+...................... Acid
J O C (1963)
28 594
217
PROTECTION OF ALDEHYDES
SECTION 6DA
HgC12 d i o x a n e
( S t a b l e t o L i A l H 4 and base) JCS C ( 1 9 6 6 ) 1 0 0 5
,
*
OH
EtOH
175
12
NaHC03 dioxane
OH
H20
JOC (1969)
For c l e a v a g e o f t h i o k e t a l s w i t h HgC12 see Ber
(PhNHCH2)2
PrCHO
c -
HC1
H20
(1958)
PrCGN]
Y' Ph
Ber (1953)
1463
do TsOH CgHg
+
~ . - - - - - - - - - - - - - - - - - - - -
Acid
H
JACS (1955)
1 HC(OEt)3
v
Me2CHCHO
1043
Yh
Piperidine
0
2 3618
91
NH4C1
EtOH
-
(Stable t o LiAlH4 and base)
77 1 2 1 6
Me$=CHOEt
-______________________ H3P04 /
( S t a b l e t o RMgX, L i A l H 4 , CrO3 and base)
Acid
Bull SOC Chim F r (1965) 1007
176
Me 2 C HC HO
COMPENDIUM 1 MeOH
HC1
2 PhNMe2
OF
ORGANIC SYNTHETIC METHODS
MeZC=CHOMe
t
Ber (1956)
Acid
H2SO4 H20
1468
pet ether
For c l e a v a g e of semicarbazones w i t h IIhICz see
YHO
( CHOAc ) I CH20Ac
NH20H ----------_----+
*
NaN02
HC1
SECTION 60A
EtOH
JCS (1950) 3361 JACS (1934) 56 1794
C,H=NOH
( FHOAc 14 CH20Ac JACS (1934)
1794
F o r c l e a v a g e o f oximes w i t h (NH4)2Ce(N03)6 see Can J Chem (1969) 47 145 I, I, ,I ,I 'I NaHS03 " J O C (1966) 31 3446 ,I I, It PI " Fe(C0)5 " J O C (1967) 32 2938
RCH=CHCHO
Ac20 H2SO4
H3P04 EtOH
*
RCH=CHCH(O A C ) ~ H20
JCS (1955) 1384
Some o f t h e methods i n c l u d e d i n s e c t i o n 180A ( P r o t e c t i o n o f Ketones) may a l s o be a p p l i e d t o t h e p r o t e c t i o n o f aldehydes
Compendium of Organic Synthetic Methods, Volume 1 Edited by Ian T. Harrison, Shuyen Harrison Copyright 0 1971 by John Wiley & Sons, Inc.
PR E PA RATI0 N
Chapter 5
OF ALKY LS M ETHYLEN ES AND ARYLS
This chapter CH2, Ph e t c .
; the conversion
Me, E t . . . ,
f f u n c t i n a l groups i n t
A l k y l s and M e t p l e n e s f r o m A c e t y l e n e s
S e c t i o n 61
BuCECH
15
0 0 0 0 0 0
1 (i-Bu)zAlH
THF
2 MeONa THF 3 Me1 4 Hydrolysis
oo"oooooooooooooooooob
Bu (CH2)zMe
t
74%
Tetr Lett (1966) 6021
71%
JACS (1952)
For hydrogenation w i t h N i II
I,
,I
I,
74 3636
c a t a l y s t see JCS (1952) 5032
, , R u ,, Re2S7
ii
,,
II
J O C (1959)
,,
JACS (1954)
and JACS (1959) 177
24
708
76
1519 3587
COMPENDIUM OF O R G A N I C SYNTHETIC NETHODS
178
BuCXH
Hp
Rh2(COOMe)4
Ph3P
CrjH11 CZCH
+
BuCH2Me
MeOH
Chem C o r n (1969) 8 2 5
(1965) 1 3 1
L i NH2CH 2 C H 2NH 2
*
C5H11CH2Me J O C (1957)
EtCXEt
Na
HMPA
t-BuOH
c
N2H4
air
2 891
EtCH2CH2Et J O C (1970)
PhCECPh
SECTION 62
Cu2+ MeOH
*
35
79% 3565
PhCH2CH2Ph
80%
Tetr L e t t (1961) 347
S e c t i o n 62
-
A l k y l s from Carboxylic Acids
0000000000000000000000000000
R e a c t i o n s i n w h i c h c a r b o x y l groups a r e c o n v e r t e d i n t o a l k y l e.g. RCOOH -+ RCH3, a r e i n c l u d e d i n t h i s s e c t i o n . For t h e c o n v e r s i o n RCOOH RH see s e c t i o n 152 ( H y d r i d e s f r o m C a r b o x y l i c A c i d s )
Electrolysis
Et3N
DMF
c
COOMe Chem C o r n (1967) 9 6 Advances i n O r g Chem (1960) 1 1
SECTION 6 2 YOOH (FH2)4
ALKYLS FROM CARBOXYLIC A C I D S Electrolysis
MeCOOH
MeOH
179
b1 e (FH2)4
t
COOMe
40%
COOMe JCS (1950) 3326
C17H35COOH
L i A1 H4
----+ C17H35CONHNHTs
C17H35Me
50-60%
T e t r a h e d r o n (1966) 22 487 Chim Ind (Milan) (1965) 47 6 2 (Chem Abs 62 10388)
Helv (1954) (1946)
.S:S;l3
@''OH Me
3 KOH
MeCN
MeOH
HI
P4
200-250"
82%
H20
Me
c17H35Me
b
Ber (1882)
RCOOH
H2 (120 atmos)
MoS2
1689 360
* JACS (1970)
C17H35COOH
37
29
350"
*
92
3232
15 1687
RMe Chem L i s t y (1956) 50 569 (Chem Abs 13854r
COMPENDIUM OF O R G A N I C SYNTHETIC METHODS
180 S e c t i o n 63
SECTION 63
-
A l k y l s and A r y l s f r o m A l c o h o l s
000000000000000000000000000000
R e a c t i o n s i n which h y d r o x y l groups a r e r e p l a c e d by a l k y l or a r y l e.g. ROH -+ RPh, a r e i n c l u d e d i n t h i s s e c t i o n . F o r t h e c o n v e r s i o n ROH see s e c t i o n 153 ( H y d r i d e s f r o m A l c o h o l s and Phenols)
1 NaH
51 % J A C S (1965)
87
3277
T i C13
1 J + J0 J
2 MeLi
U
PrOH
A1C13
J A C S (1968) 90 3284 C h e m Comm (1969) 53
CgHg
RH
H20
b
PrPh
JOC (1940)
J A C S (1942)
2
253
64 1576
O r g React (1946)
2
1
SECTION 64 S e c t i o n 64
ALKYLS FROM ALDEHYDES
181
A l k y l s f r o m Aldehydes
00D00000D000000000000
R e a c t i o n s w h i c h c o n v e r t t h e group CHO i n t o CH3 a r e i n c l u d e d i n t h i s s e c t i o n . F o r t h e c o n v e r s i o n RCHO -+RH see s e c t i o n 154 ( H y d r i d e s f r o m A1 dehydes)
C6H1~ C H O
H2
WS2
320-330"
H2
*
C6H13Me Chem Listy (1956) 50 565 (Chem Abs 13831r
PdC12
38%
86% JCS (1954) 4676 JACS (1956) 2 3769
PhCH20
@jJ$ H
CHo
NaBH4
LiAlH4
Pd-C
AlC13
Me0
+ &
i-PrOH PhCH20
H Can J Chem (1964)
Et20
t
89%
42 514
78%
Me0 JCS (1957) 3755 T e t r Lett (1967) 1849
AcO
&I-
CgH13CHO
H2SO4 E 1ec t r o dioxane l y s is JACS (1967)
Zn
HC1
H20
b
90%
Ac 0
89 4789
C6H13Me
72%
Org R e a c t (1942) 1 1 5 5
SECTION 65
COMPENDIUM OF ORGANIC SYNTHETIC METHODS
182
1 N2H4.HC1
N2H4
-
ethylene glycol 2 KOH
(21
48%
T e t r a h e d r o n (1969) 25 1335 Org React (1948) 4 378
1 TsNHNH~ C11H23CH0
2 NaBH4
c11 H23Me Chem Ind (1964) 153 1689 T e t r a h e d r o n (1963) 19 1127
MeOH-
OMe
OMe
C5H11 CHO
JCS (1962) 470
EtSH
ZnC12
NazS04
*
C5H11CH(SEt)2
Ni
EtOH
----+
C5H11Me
JACS (1944) 66 909 J O C (1968) 33 3551 Org React (1962) 12 356
F u r t h e r examples o f t h e c o n v e r s i o n C=O -+ CH2 a r e i n c l u d e d i n s e c t i o n 72 (A1 k y l s and Methylenes f r o m Ketones)
S e c t i o n 65
A l k y l s and A r y l s f r o m A l k y l s and A r y l s
-
ooooooooooooa~ooooooooooooooooooooooo
The c o n v e r s i o n R R ' + A r R ( R , R ' = a l k y l ) , t h e e p i m e r i z a t i o n , i s o m e r i z a t i o n and t r a n s p o s i t i o n o f a l k y l groups and t h e h y d r o g e n a t i o n o f a r y l groups a r e ArH i n c l u d e d i n t h i s s e c t i o n . f o r t h e c o n v e r s i o n s R R ' -+ RH and A r R ( R , R ' = a l k y l ) see s e c t i o n 155 ( H y d r i d e s f r o m A l k y l s )
t-BuCH2Pr-i
PhH AlC1-j ------+
t-BuPh JACS (1935)
57 2415
40%
SECTION 65
ALKYLS AND ARYLS FROM ALKYLS AND ARYLS BF3
EtFHCHzMe he
i-PrF
*
(
EtCH2FHMe Me
w t compds)
JACS (1951) 73 5013 J O C (1964) 9 94
OMe Me
+ h i g h e r mol
183
JACS (1948)
2 2773
-
@
BF3
Me
HF
100% Me JACS (1952) 74 6246 JCS (1952)
lm
OMe hV
Me
Pr- i
H2
HgBr2 cyclohexane
*J3 .$$*Me
Me
JACS (1970)
92
1094
Pr-i
Pt02
v
HC1
EtOH
JACS (1936)
He
1594
Rh-Al203
MeOH HOAc
* J O C (1962)
2 2288
184
COMPENDIUM OF O R G A N I C SYNTHETIC METHODS
S e c t i o n 66
SECTION 67
~~~~~~~~~~~~~~~~~~~~~~~~~~~
The c o n v e r s i o n s A r C O N R ' R " -+ ArMe and RCONHAr --+ A r A r ' a r e i n c l u d e d i n t h i s s e c t i o n . F o r t h e c o n v e r s i o n R C O N R ' R " -+ RH see s e c t i o n 156 ( H y d r i d e s f r o m Amides)
3
PhCON
H2 (200-300 atmos) copper c h r o m i t e
*
79%
PhMe
dioxane
JACS (1934)
1 HN02
2419
HOAc
2 CgH6 JCS (1940) 361 369 Org React (1944) 1. 224
S e c t i o n 67
A l k y l s and A r y l s f r o m Amines 0
0
0
0
~
0
~
~
0
0
0
0
~
~
~
~
0
0
0
0
~
~
~
~
R e a c t i o n s i n which an amine group i s r e p l a c e d by a l k y l o r a r y l a r e i n c l u d e d RH see s e c t i o n 157 ( H y d r i d e s i n t h i s s e c t i o n . F o r t h e c o n v e r s i o n RNH2 --+ f r o m Amines)
NH2 Br
1 NaN02
HC1
H20
2 NaOH CgHg
H20
*
34%
Br Org S y n t h (1932) C o l l Vol 1 113 Org React (1944) 1. 224 JCS (1962) 4257
&, HZ
NOCl
PhCl
_____)
F
C
l
JACS (1969)
15%
21 5073
SECTION 68
PhC HNHC H2 Ph I Me
FROM ESTERS
ALKYLS AND ARYLS 1 Nan02
2 LiAlH4
HC1
H20
Et20
y+
PhFHNCH2Ph Me
+
185
HgO
---+
EtOH
PhFHCH2Ph Me
Chem Pharm B u l l ( 1 9 7 0 )
S e c t i o n 68
18 1 1 3 7
A l k y l s and A r y l s f r o m E s t e r s 0000000000000000000000000000
T h i s s e c t i o n l i s t s t h e c o n v e r s i o n o f t h e group COOR t o a l k y l o r a r y l . F o r t h e c o n v e r s i o n RCOOR -+RH see s e c t i o n 158 ( H y d r i d e s f r o m E s t e r s )
!t
EtFlaBr
1 HCOOH
86%
JACS (1945)
67 2239
37% JACS ( 1 9 3 7 ) 59 1 2 0 4 Org R e a c t ( 1 9 4 6 ) 3 1
Me
EtMgBr
I
“QMe
I
Me MeCH=CCHzEt JCS (1965) 702
Me
H2 HO
Et20
+
MeCH=CCH20CO
MoS2 cyclohexane
260-300”
HO C o l l C z e c h (1958)
2
1322
1a6
COMPENDIUM OF ORGANIC SYNTHETIC METHODS
S e c t i o n 69
!l:yl0
00
SECTION 70
a ~0 d 0, A ~ ~ ~ '0 o0 0, ~ r o m , f ~ h o ~ ~ ~
0 0
The c o n v e r s i o n ROR -+ R R ' ( R ' = a l k y l o r a r y l ) i s i n c l u d e d i n t h i s s e c t i o n . For t h e h y d r o g e n o l y s i s o f e t h e r s (ROR ----t RH) see s e c t i o n 159 ( H y d r i d e s from Ethers)
EtpO
BF3
C6H6
EtPh
( + diethylbenzenes) Org React
OEt
EtNa
60 125 (1946) 3 1
JACS (1938)
cyclohexane
*
5.
25%
33%
J P r a k t Chem (1938) 1 5 1 6 1
S e c t i o n 70
A l k y l s and A r y l s f r o m H!lides
and S u l f o n a t e s
0 0 0 0 0 0 ~ 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0
The replacement of h a l o and t o s y l o x y groups by a l k y l o r a r y l groups i s i n c l u d e d i n t h i s s e c t i o n . F o r t h e c o n v e r s i o n RX -+ RH (X=halo o r OTs) see s e c t i o n 160 (Hydrides f r o m H a l i d e s and T o s y l a t e s )
Phi
PhCu
Pyr
JCS (1950) 711 Chem Rev (1946)
2 139
PhPh T e t r Lett (1968) 3307 JCS (1950) 7 ' 1
60%
SECTION 70
ALKYLS AND ARYLS FROM HALIDES AND SULFONATES
1 Li
Et20
2 CoC12
Et20
+
187
65%
Bull SOC Chim F r (1964) 1331
PhCl
PhLi
piperidine
Et20
PhPh
e
Angew (1957)
Me
69 267
61 %
91 %
MeM-e JACS (1968) 2423 T e t r a h e d r o n (1970) 2 4041
aPh
Me
Me
JOC (1965)
30 2493
1 Mg
75%
THF
56%
2 TlBr
JACS (1968)
90 2423
59% J O C (1970) (1954)
35
22
19 934
COMPENDIUM OF ORGANIC SYNTHETIC METHODS
188
THF HMPA
1 Mg Et2O
PhCH2C1
P
2 BuOTs
PhCH2Bu
t-BuC1
PrBr
(MeO)2CH(CH2)~~=CtlCH2CH2C=CH2 95% I Me Me Tetr Lett (1969) 1393
50-59%
Org Synth (1943) C o l l Vol 2 47 (1932) Coll V o l 1 4 7 1
Me JACS (1965)
Me
BuBr
-
CH2-CCH2MgCl
(MeO)zCH( CHz)z:=CHCH2Cl Me
1 Li
THF
1 Mg
Et20
a;. 5452
BuBu
t
2 (ICUPBU3)4 3 02
FeC13 CgHg
SECTION 70
84%
JACS (1967)
t-BuPh
t
*
2 t-BuC1 HgC12
5302
80%
Org React (1946) 3
PrBu-t
1
21% JACS (1929)
(1938)
60
1483 2598
SECTION 70
ALKYLS AN0 ARYLS FROM HALIDES AND SULFONATES
Ye
Me Me p C= CH ( C H2 ) 2b = CH ( C H2 ) 2C= CHCHp C 1
1
(NH2)zCS
------+
Base '2
3 Ph3P
4 Benzyne 5 Li NH3
Chem Conun (1969) 99
yH2fH(CHp)2I
JACS
N i (CO)4
MeCH=CHCHZCl
CHzCH2CH=CMe2
N i (CO)4
DMF
L i C3CMe
A
0 0
MeOH
+
(1967)
88%
2755
MeCH=CHCH2CHCH=CH2 I Me JACS (1951) 73 2654
fli2yH(CH2)2CXMe 0 0
H2 Pd
CHpFH(CH2)zPr 6 0
X
X
X
Ye
Me Me 2 C = CW ( CH2 ) 2b = CH ( CH2 ) 2 C = C H f H2 M~~C=CH(CH~)Z$=CH(CH~)~?=CHCH~ Me Me
gCH2* Me$=CHCHZBr
189
E . J . Corey, i n press
I (CH2)1oCOOH
RI
1 Me2CuLi
2 02
BupCuLi Et20
Etp0
b
*
RMe
BU (CH2)1 oCOOH JACS (1968)
90 5615
(R=C5H11 or P h ) JACS
(1969)
76%
98-99%
91 4871
190
S E C T I O N 70
COMPENDIUM OF ORGANIC S Y N T H E T I C METHODS MeZCuLi
PhCH=CHBr
EtpO
+
PhCH-CHMe
81%
JACS (1967)
Me2CC1 I
Pr
Me3A1
3911 4245
Me2fMe
100%
Pr
J O C (1970)
2 532
55%
T e t r Lett (1970) 315
PhCl
C11H23X
NaH
MeZSO
v
PhCH2SOMe 41 %
Me2SO
( X = B r o r OTs)
NaH
A1 -Hg
-------+ PhMe
C 1 1 H23CH2SOMe
JACS (1965)
Ni
EtOH
1345
C11H23Me
Aust J Chem (1966)
62%
19 521
65%
JACS (1967)
89 3911
4245
191
ALKYLS AN0 ARYLS FROM HYORIDES (RH)
SECTION 71
76%
S e c t i o n 71
A l k y l s and A r y l s f r o m H y d r i d e s
(R2k
000D00000000000000000000000000000
T h i s s e c t i o n l i s t s examples of t h e r e a c t i o n RH + R R ' ( R , R ' = a l k y l o r a r y l )
EtpO
1 PhLi
2 cuc12
*
19% Br
Br
PhH
PhH
1 T1 (OCOCF3)3 2 hV
n-PrC1
CF3COOH
CgH6
AlC13
EtBr
b
PhPr-n
Br
JACS (1940)
62
1963
JACS (1970)
92
6088
90%
PhPh
t
PhPr-i J O C (1940) S 253 Org R e a c t (1946)
2
1
AlCl3
86%
Et Org React (1946)
31
192
COMPENDIUM
OF
ORGANIC SYNTHETIC METHODS
*m
SECTION 71
i- P r
i-PrLi
decalin
165"
JACS (1963)
NaH
MeHgI
RH
hu
Me F- S bF3
33% (1966)
Proc Chem SOC (1961) 240
( R = a l k y l or a r y l ) JACS (1969)
OcH3 I \
PhCH=CHZ
HMPA
2 248
PhMe
RMe
------+
1356
Me2S0
JOC
PhH
85
20%
t-BuOK
*
91 2112
(CH2 12Ph
T e t r L e t t (1968) 3723
99% JACS (1957)
79 3142
SECTION 72
ALKYLS, METHYLENES AND ARYLS FROM IKETONES
PrCl
PhCH3
Na
CH2=CH2
Me2CHMe
PhCH2Pr
AlCl3
HCl
*
43%
Me 2 C HC HMe 2 JACS (1945)
S e c t i o n 72
63 327
JACS (1941)
193
67 1778
-
2
The c o n v e r s i o n s R2CO RR, R2CH2, R2CHR, e t c . ( R = a l k y l o r a r y l ) a r e i n c l u d e d i n t h i s s e c t i o n . For t h e c o n v e r s i o n R2CO -+RH see s e c t i o n 162 ( H y d r i d e s f r o m Ketones)
JACS (1968)
EtCO( CH2) 14COEt
Me2CO
1 BuMgBr
2 I2
1 c16H33C;CMgBr 2 HI
Et20
*
P4
270"
t
Me2C=CHPr
90
817
EtCH( CH2) 14CHEt I
C18H37 Helv (1937)
H2
catalyst
I
26%
C18H37 2 1179
Me2CHBu
JACS (1929) 51 1483 (1949) 71 819 J O C (1948) 13 239
F u r t h e r examples o f t h e c o n v e r s i o n o f ketones i n t o o l e f i n s and o f t h e h y d r o g e n a t i o n o f o l e f i n s a r e i n c l u d e d i n s e c t i o n 207 ( O l e f i n s f r o m Ketones) and s e c t i o n 74 ( A l k y l s and Methylenes f r o m O l e f i n s )
COMPENDIUM
194
mcHph -
OF O R G A N I C SYNTHETIC METHODS
SECTION 72
0
H2
PhCHO
EtOH
r
n
C
H
2
Pd-C HOAc
H20
”
,
88%
O r g Prep and P r o c e d u r e s (1970)
2 37
0 Chem Comm (1969) 1395
AcO
CtP
PhCOEt
N2H4
KOH
1 TsNHNH2 2 NaBH4
MeOH
dioxane.
\
60-70%
Chem I n d (1964) 153 T e t r a h e d r o n (1963) 19 1127
*
diethylene glycol
82%
PhCH2Et
68 2487 O r g React (1948) 4 378
J A C S (1946)
F o r r e d u c t i o n o f h i n d e r e d k e t o n e s w i t h N2H4’HCl e t c . see Chem Ind (1964) 1194
1 N2H4 2 t-BuOK
EtOH
-65%
toluene
0 J C S (1963)
1855 T e t r a h e d r o n (1970)
649
ALKYLS, METHYLENES AND ARYLS FROM KETONES
SECTION 72
oo
1 N2H4 2 t-6uOK
Me2SO 25"
195
0
*
80%
JACS (1962) 84 1734 For r e d u c t i o n o f hydrazones w i t h BuLi see JACS (1968) 90 7287
Do
----*
Ph
o:? N2H4'H20
Ph
KOH
ethylene glycol JACS (1959) (1962)
Ph
111 5834 84
JCS (1960) 4413
2938
50% JACS (1944) 909 Org React (1962) 2 356
32% Rec Trav Chim (1936) 55 903 Org React (1942) L 1 5 5 JACS (1947) 69 2350
Zn
HC1
Et2O
75%
0 Chem Comm (1969) 919
OH
OAc
T e t r a h e d r o n (1964)
20 957
196
COMPENDIUM
OF ORGANIC SYNTHETIC METHODS
w p n
n
21 L(Et0)2POC1 i NH3 E t 2 E0 t 2 0
0
SECTION 72
3 Li
EtNH2
50%
t-BuOH
Tetr L e t t (1969) 2145
T e t r a h e d r o n (1965)
F o r a p p l i c a t i o n t o p h e n y l k e t o n e s s e e JCS (1957) 3755
2
2641
75% JACS (1949) 2 1036 Org React (1953) 1 2 6 3
90% J O C (1970)
‘OEt HO
Ni-A1
NaOH
5 711
H20
*
78%
HO @cH2Et
Org R e a c t (1953) 1 2 6 3
94% Ber (1959)
92
1705
SECTION 72
197
ALKYLS, METHYLENES AND ARYLS FROM KETONES
JOC (1959)
Electrolysis dioxane
41964
H2SO4
97%
H20
0 JACS (1967)
PhCOMe
EtjSiH
CF3COOH
+
4789
P hCH2Me
70% Tetrahedron (1967)
(PhCH2)zCO
hv --+
3
2235
PhCH2CH2Ph
u-0
JACS (1970)
92 6076
JACS (1942)
64 80
hv
(1961)
4923
I
6077
198
S e c t i o n 73
COFIPENDIUM OF ORGANIC SYNTHETIC METHODS
SECTION 74
A l k y l s from N i t r i l e s 00000000000000000000
The c o n v e r s i o n RCN -+ RMe i s i n c l u d e d i n t h i s s e c t i o n . F o r t h e r e p l a c e m e n t o f CN b y hydrogen, RCN -+ RH, see s e c t i o n 163 ( H y d r i d e s from N i t r i l e s )
Tetr L e t t (1966) 4255 T e t r a h e d r o n (1961)
S e c t i o n 74
2 287
A l k y l s , Methylenes and A r y l s f r o m O l e f i n s 00000000000000000000000000000000000000000
The h y d r o g e n a t i o n , a l k y l a t i o n , a r y l a t i o n , d i m e r i z a t i o n e t c . o f o l e f i n s , forming alkanes o r a r y l - s u b s t i t u t e d alkanes, are included i n t h i s s e c t i o n . F o r t h e c o n v e r s i o n R2C=CR2 -+ RH o r R2CH2 see s e c t i o n 164 ( H y d r i d e s f r o m Olefins)
BUC H=CH2
EtCH=CHEt
1 NaBH4
BF3-Et20 d i g l y m e
2 KOH AgN03
C6H6 H2S04
H20
*
*
BU (CH2)4Bu
JACS (1961) 1002 Chem Corn (1968) 938
EtFHCH2Et Ph JACS (1939) 61 1002 Org React (1946) 3 1
66%
SECTION 74
ALKYLS, METHYLENES AND ARYLS FROM OLEFINS
-
1 Pr3A1 C~OH~~CH=CH~ 2 H20
t-BuLi
CioHzitHMe Pr
64 323
Angew (1952)
Et3N
J O C (1965)
C5H11CH=CHz
199
CHCl2S02Cl
*
benzoyl p e r o x i d e
C5H11 CHCH2CHC12 I
c1
30 917
L i A1 H4
dioxane
C5H11 (CH2)zMe C5H11C\H/H2
+
CH2
Tetrahedron (1964)
Br2 PhCH=CHZ ----+ PhCHCH2Br I
Br
1 NaBH4 2 EtCOOH
BF3.Et20
NaBH4
PhCH2Me
Me2SO
diglyme
0 1613
64%
T e t r L e t t (1969) 3495
b
BuCHpMe
91 %
JACS (1959)
81 4108
JACS (1970)
92
3221
200
COMPENDIUM OF O R G A N I C SYNTHETIC METHODS H2 (2000 p s i )
CgH13CH=CH2
(i-Bu)3B
225'
*
CgH13CH2Me J O C (1962)
JACS (1961)
1 Et2AlCl
PhzC=CHMe
SECTION 74
27
4368 4672
Ph2CHCH2Me
2 H20
T e t r L e t t (1970) 3471
H2
CgH13CH=CH2
Pt
CgH13CH2Me
F o r h y d r o g e n a t i o n w i t h Pd II
I,
I1
I,
,I
I,
PhSCH2CHzCH2
Hp
"
Ru
'I
Re2S7
"
Ni
(Ph3P)3RhCl
JACS (1962) 1495 Org Synth (1943) C o l l Vol 2 191
c a t a l y s t see JACS ,I
(1960)
J O C (1959)
"
I'
JACS
,I
"
CgHg
*
~2 6087
2 708 (1954) 76 1519
"
(1959) 1 3 5 8 7 J O C (1970) 2 1900
PhS(CH2)zMe
93%
T e t r L e t t (1967) 1935 J O C (1967) 32 2013 3074
F o r h y d r o g e n a t i o n w i t h Rh(COOMe)4 I1
I
I'
RuCl H( PPh3)3
c a t a l y s t see Chem Comm (1969) 825 "
"
Chem Corn (1967) 305
90% Chem Ind (1961) 433 J O C 119651 30 3980 Chem'Rev 11965) 65 5 1 F o r copper c a t a l y z e d d i i m i d e r e d u c t i o n see T e t r L e t t (1961) 347 and JACS (1970) 92 6635
SECTION 74
ALKYLS, METHYLENES AND ARYLS FROM OLEFINS TsNHNH2 diglyme
HOCH2CH=CH2
NCOONa [COONa
BuCHzCH2
Na
Pyr HOAc
NH3 MeOH
HOCH2CH2He
&
H20
99%
J A C S (1961)
83 3729
JACS (1963) (1961)
83 3725
c
BuCH2Me
*
201
3297
-41 % JACS (1954) 76 1258 JOC (1970) 35 3565
-
Na M~~C=CH(CH~)ZC=CHCH~CH=C-CH=CH~ M~~C=CH(CH~)~C=CHCH~CHZ?=CHM~ I I EtOH Me Me Me Me T e t r L e t t (1967) 2201 Ber (1956) 3j9- 1549
BuCH=CHMe
Li
NH~CH~CHZNH~ c
Bu( CH2)zMe
82%
J O C (1957) 22 891 JACS (1959) 1745
MezC=CHMe
Et3SiH CF3COOH
c
Me2CHCH2Me
(BuCH=CH2 i s not reduced) T e t r a h e d r o n (1967)
23 2235
COMPENDIUM OF ORGANIC SYNTHETIC METHODS
202
SECTION 7 5
50%
Chem C o r n (1968) 296
Me$HCH=CHCHMe2
S e c t i o n 75
1 03
2 hv
33%
MeZCHCHMe2 T e t r L e t t (1968) 3291
A l k y l s and M e t h y l e n e s f r o m M i s c e l l a n e o u s Compounds OOoOOeOOOOOOOOOOoOOOoooooooooooooooooooooooooooooo
PrCOyH( CHz), 2COOMe EtCOO
-
1 TSNHNH2 2 NaBH4
P~CH~CH~(CHZ)~~COOM~ Chem Ind (1967') 2150
Pt-glass
H Biochem J (1967)
105 4OP
70%
Compendium of Organic Synthetic Methods, Volume 1 Edited by Ian T. Harrison, Shuyen Harrison Copyright 0 1971 by John Wiley & Sons, Inc.
Chapter 6
PREPARATION OF AMIDES
N20 cyclohexylarnine
C5H11 CZCH
250"
C5H11 CH2CONH
c
N
94%
JCS (1951) 3016
S
C5H11 C X H
NH3 H20 Pyr
c
C5H11 CH2CONH2 JACS
PhCECMe
S
NH3 H20
(1946)
1 BuLi
S
2 Et2NH t-BuBr
68 2033
PhCH2CH2CONH2 J A C S (1946)
C5H11 CZCH
35%
*
CgH11CH2CSNEt2
68 2029
---.t
CgH11CH2CONEt2
Rec Trav C h i m (1968)
203
72%
38
COMPENDIUM OF O R G A N I C SYNTHETIC METHODS
204 S e c t i o n 77
SECTION 77
Amides f r o m C a r b o x y l i c A c i d s and A c i d H a l i d e s
00000000000000~00000000OODDDOOODDDODOODD~0~~0
. . . . . . page
A r n d t - E i s t e r t h o m o l o g a t i o n o f a c i d s t o amides Amides by r e a c t i o n o f c a r b o x y l i c a c i d s o r a c i d h a l i d e s w i t h amines, ammonia, e t c . M i s c e l l a n e o u s methods D e g r a d a t i o n o f a c i d s t o amides
.. .................... ...............
@cooH
1 DCC E t 2 0
c1
2 CH2N2
204 204-206 207 207
CH2CONHPh
Et20
c1
PhNH2 AgN03
EtoH
JCS
C
33%
(1970) 971
Me0@cH2coNH2 Me0 @cocl
2 NH3 CH2N2AgN03
57%
H20* Org React (1942) 1 3 8
PrCOCl
CH2N2
- - - - - + PrCOCHN2
CgH13COOH
NH3
190'
PhNHMe
hv
CgH6
*
PrCH2COyMe Ph Ber (1959) 92 528 JCS C (1970) 1208
45%
75%
CgH13CONH2 JACS (1931)
1879
Helv (1961) fi 1546 JCS (1969) 874
SECTION 7 7
AMIDES FROM CARBOXYLIC A C I D S AND A C I D H A L I D E S NHzCONHz
CgH1 ~ C O O H
170-180"
*
CgH13CONH2
205
68-74~
Org S y n t h (1963) C o l l Vol 4 513
HCONMe2
PhCOCl
150"
*
PhCONMe2
97% JACS (1954) (1949)
NH3
i-PrCOC1
H20
i-PrCONH2
70% Org Synth (1955) C o l l Vol 3 490 J O C (1954)
NH40Ac
MeCH=CHCOCl
Me$O
2 1372 2 2215
t
19 6 2 3
MeCH=CHCONH2
63%
JCS (1962) 2824
BuNH2 C ~ H ~ ~ C H = C H ( C H ~ ) ~ J C O -C-~---+
C8H17CH=CH(CH2)7CONHBu
pet ether
PhCH=CHCH2CHCOOH I
CH2Ph
1 ClCOOEt
JACS (1949) Helv (1959)
Et3N
CHC13
t
83%
2 2215 42 2073
PhCH=CHCH2yHCONH2
2 NH3
CH2Ph J Med Chem (1968)
2 534
94%
1 TsCl
Pyr
2 p-Toluidine
*
O
I C \O
N
JACS (1955)
Me0
a
SECTION 77
COMPENDIUM OF O R G A N I C SYNTHETIC METHODS
206
H
6214
Me
6
OMe DCC
90%
78%
JACS (1968) 90 4706 Compt Rend (1965) 260 2249 JACS (1968) 90 2 4 4 8
Amides by r e a c t i o n o f a c i d s with amines and HCECnMe
Rec T r a v Chim (1955)
I,
I,
,I
I,
I,
,I
11
I'
,I
4,
I,
I1
II
I!
I,
"
HCICCHZSMe2Br JCS
C (1969)
74 769
1904
Me$( OMe)2
Chim T h e r (1967) 195 (Chem Abs 61 108840) I,
I,
I,
!*
I,
I,
"
"
I,
I1
I,
1,
I,
1,
"
"
I,
I,
,,
I1
I1
I,
'I
'I
I,
I,
4,
,I
,I
I,
"
"
I,
,I
I,
1,
$1
I,
"
"
Sic14
J O C (1969)
Tic14
34
2766
Can J Chem (1970)
5 983
(PNC12)3 J O C (1968)
2 2979
2-iodo-1 -methyl pyridi nium iodide JCS (1964) 4650
S03.DMF J O C (1959)
Further examples o f the r e a c t i o n RCOOH s e c t i o n 82 (Amides from Amines)
+ R2NH
+
4368
RCONR2 a r e included i n
SECTION 77 C11 H23COOH
AMIDES FROM CARBOXYLIC ACIDS AN0 ACID HALIDES
207
(Me2N)3P0 180-200"
95%
*
C11 H23CONMe2 Chem I n d (1966) 1529
C 1 1 H23COONa
PhCH2COOH
)
-
-
(
BuZNCOC1
(B u N H ) ~ B
NaN3
ti20
C11 H23CONBu2 JOC (1963)
PhCHZCONHBu
Et20
.+
28 232
Tetrahedron (1970)
o C o N 3
78%
90% 1539
-0
JACS (1938)
NHCOPh
3 540
~50%
Amides may also be prepared from carboxylic acids via ester intermediates. See section 8 3 (Amides from Esters)
COMPENDIUM OF ORGANIC SYNTHETIC METHODS
208 S e c t i o n 78
Ad;e!: 0
0
0
SECTION 7 8
~ r o m o ~ ~ c o h !a;o l s Phy;ls 00000000
000
000
0
00
30% Tetr Lett (1968) 1899 Angew (1968) 626 (Internat Ed 1 6 2 9 )
Nickel peroxide
PhCH=CHCHZOH
Et20
NH3
( NH4)2Sx
PhCHCHMe2 I OH
*
Chem Corn (1966) 17
200"
*
PhCHzCHCONH2 I
Me JACS (1946)
CH20H
Me a
M
85%
PhCH=CHCONH2
MeCN
H2SO4
e
68 632
HOAc Me
5 331 O r g React (1969) JOC (1960)
Me PhCH2; OH Me
2033
NaCN
H2S04
HOAc
Me
+
92%
PhCHZtNHCHO Me JOC (1961)
213
a 3002
SECTION 79
AMIDES FROM ALDEHYDES
209
F1
1 PhN=CPh MeONa
PhOH
2 312-315"
Section 79
L
Ph2NCOPh
14 1
Org React (1965)
Amides f r o m Aldehydes
ooooooooooooooooou
PhCOO I
KCN
1 H2SO4
PhCOCl
2 Hp
Pd-Bas04
290
Arch Pharm (1957)
PhCHO
PhCHzCH2N3
H2SO4
b
PhCONHCH2CH2Ph
10%
JACS (1955)
PhCHO
1 SO2C12
benzoyl p e r o x i d e
CCl4
*
PhCOCl
PhNH2
951
PhCONHPh
Nippon Kagaku Z (1960) (Chem Abs 2370)
CgH13CHO
----*CgHl3CH=NOH
218
Ni
100"
J C S (1946) 599
JACS (1961)
2
1983
g
1450
100%
CgH13CONH2
Org React (1960)
67%
1
21 0
OF
COMPENDIUM
PhCH=CHCHO
Ph(CH2)zCHO
Nickel peroxide
ORGANIC SYNTHETIC METHODS
NH3
+
Et20
S
SECTION 80
PhCHzCHCONH2
85%
Chem Corn (1966) 17
NH3
Pyr
H20
t
Ph(CH2)zCONHz JACS (1946)
48%
68 2029
OcH2'@ Ac
HoAc c1 c1Me3N*BH3,
~~!Chloro-cl@cH=N@ c1
c1
aniline J O C (1962)
S e c t i o n 80
7 2640
Amides from A l k y l s
P
T h i s s e c t i o n l i s t s t h e c o n v e r s i o n o f a l k y l groups i n t o amide. F o r t h e c o n v e r s i o n RH -+RCONR2 see s e c t i o n 86 (Amides f r o m H y d r i d e s )
Et Et@:
Et NHZCOC1
AlCl3
CS2
c0nh2
Et@Et Et
Et
Et
Et Helv (1960)
5 1473
98%
S e c t i o n 81
Amides from Amides
000000000000000000
..... .. .. . ...... . ..... .. .
A l k y l a t i o n o f t h e a - c a r b o n o f amides A l k y l a t i o n of t h e n i t r o g e n o f amides D e a l k y l a t i o n o f N - a l k y l amides . D e g r a d a t i o n o f amides , ,
-
1 NaNH2
-
MeCH2CONMe2
NH3
MeCONH2
1 MeCH=CH2
Et
Na2HP04
2 H2
MeCH(OEt)2 H2SO4
MeCONH2
PdC12
HZ
Pd-C
I
. . . .
. . page 211 . . . . . . 211-212 . . . . . . . 212-213 , . . . . , . 213 . . I
+
62%
J O C (1966) 2 9 8 2 989 Ber ( 1 9 6 8 ) 101 3 1 1 3 JACS ( 1 9 6 7 ) 1647
14% Chem I n d ( 1 9 6 5 ) 7 6 8
*
MeCONHCHMe2 Proc Chem SOC ( 1 9 6 1 ) 3 7 0
MeCONHEt
HOAc
MeNHz.HC1 A
I
MeCHCONMe2
2 EtBr
C7H15 31%
MeCONH2
21 1
AMIDES FROM AMIDES
SECTION 81
JOC (1962)
45%
27 2 2 0 5
75%
MeCONHMe JACS ( 1 9 4 3 )
65
1566
21 2
COMPENDIUM OF ORGANIC SYNTHETIC METHODS
PhNH2
PhCHzCONH2
BF3 A
*
PhCH2CONHPh
99%
JACS (1937)
MeCONHZ
D i h y d r o p y r a n~tMeCONH H3P04
SECTION 81
03
59
1202
MeCOy C6H13
i Acid
1
MeCONHC6H13 B u l l SOC Chim F r (1964) 292
> 66% JACS (1961) 83 1492 J O C (1949) 1099 (1967) 32 3679
14
Examples o f t h e N - a l k y l a t i o n o f a c e t y l - and t r i f l u o r o a c e t y l - a m i n e s a r e i n c l u d e d i n s e c t i o n 97 (Amines f r o m Amines)
PhCONHPh
PhCONBu2
PCl5 __t
?'
PhC=NPh
PhONa
----+
Pyridine hydrochloride 190-200"
yPh
-
315" PhC=NPh PhCONPh2 Org R eact (1965) 14 1
t
30%
P hCONHBu Ber (1954)
87 1294
SECTION 82 K2S208
PrCONMe2
21 3
A M I D E S FROM A M I N E S K2HP04
H20
*
PrCONHMe J O C (1964)
Pb(OAc)4
0
CONHNH2
S e c t i o n 82
Ni
CgHg
HOAc
44%
L(?. 3632
c
CH2=CH(CH2)7NHAc Chem Corn (1965) 161 Aust J Chem (1968) 2 185
53%
CONH2
EtOH
____)
JACS (1954) 'a 5774 J O C (1957) 22 148
Amides f r o m Amines
000000000000000000
.... .. ... ...
Amides b y r e a c t i o n o f amines w i t h c a r b o x y l i c a c i d s , amides, e s t e r s and o t h e r d e r i v a t i v e s o f c a r b o x y l i c a c i d s page 213-217 D e a l k y l a t i o n o f amines b y c a r b o x y l i c a c i d s and a n h y d r i d e s 217 O x i d a t i o n o f amines t o amides , . , . 217-218
.... ...
MeCOCl
I
Pyr
80%
Me0
Me0
OMe
JOC (1970)
Me0@cH2cH2NH2
Ph2C=CHCOC1
Me0
NaOH H20
For
t
Et20
S
1219
M~O.@,CHZCH~NHCOCH=CP~~ Me0
J O C (1970) 35 825 Ber (1954) 2 1760 m i l d p r o c e d u r e see JCS (1962) 1445
COMPENDIUM OF ORGANIC SYNTHETIC METHODS
21 4
CH2CH2Pr-i 1 BuLi
, 2:' i-PrCH2CHz @
.
CH2CH2Pr-i
Me27C0C1
i-PrCH2CH2
Tetr Lett (1964) 1597
Et
HCOOH Ac20
i-PrCHNH2 COOH
85-90%
i-PrCHNHCHO
COOH JACS (1958) (1968)
PhNH2
PhCOOH PhSOzC1
Pyr
SECTION 82
*
90
1154 3245
94%
PhCONHPh JACS (1955)
6214
t
PhCOOH Me2SCH2CXH B r
PhCH2NH2
Me2SO
NH2
PhCHZNHCOPh
t
JCS
C
.
3,5-Dinitrobenzoic acid
DCC
THF
91 %
(1969) 1904
Compt Rend (1965) 260 2249 JACS (1968) 90 4 7 0 r
F u r t h e r examples o f t h e r e a c t i o n R2NH + RCOOH ---c RCONR2 a r e i n c l u d e d i n s e c t i o n 77 (Amides f r o m C a r b o x y l i c A c i d s and A c i d H a l i d e s ) and s e c t i o n 105A ( P r o t e c t i o n o f Amines)
93%
SECTION 82
MPY:
21 5
AMIDES FROM AMINES
HO
Me0
CH2=CO MeOH
Ber (1954) S;r 1138
Zh Org Khim (1967) 3 420 (Chem Abs 66 1155297
1 LiAlH4
PhNH2
2 PhCOOEt
THF
*
PhNHCOPh
2
J O C (1962) 1042 JCS (1954) 1188
Further examples o f t h e r e a c t i o n R 2 N H + RCOOR -+ RCONR2 a r e included i n s e c t i o n 83 (Arnides from E s t e r s )
-
NHCHO
HCONMe2 MeONa
Et
PhCH2NH2.HCl
HO
MeCONH2
A
J O C (1961)
JACS (1943)
j [ NHCOR
Et3N
RCoo0
- N 0 2 Me2SO
97%
2 2563
PhCH2NHAc
HO
- Ntlp
OH
@Et
HO
65
1566
80% (RZC17H35)
100% (R=Me) 100% ( R = P h )
OH
J O C (1970) 35 2042 Bull Chem SOC J a p (1963)
a 754
COMPENDIUM OF ORGANIC S Y N T H E T I C METHODS
21 6
CHz=bOAc
HOCHzCH2NH2
CHCl3
+
SECTION
a2
HOCH~CH~NHAC Chem Zvesti ( 1 9 6 4 ) 1 8 2 1 8 (Chem Abs 61 14773)-
CH20H
-
N A c e t o xy p h t ha 1 im i de Et3N
MeOH
NH2
HO0 J O C (1965)
NH2
3-Acetoxypyridine
Me
BuNH2
*
*
Me
2 448
-0";;
B u l l Chem SOC J a p ( 1 9 6 4 )
CC13CHO
CHCl3
*
70%
0H NHAc
88%
31 864
83%
BuNHCHO JACS ( 1 9 5 2 ) zL1_ 3 9 3 3
BuNH~
CO
RhC12(C0)4
Me3P
CgHg
t
BuNHCHO
96%
T e t r L e t t ( 1 9 6 9 ) 2329
Me2NH
co
CUCl
Me2NCHO B u l l Chem SOC J a p ( 1 9 6 9 )
42
73% 2610
SECTION 82
AMIDES FROM AMINES
217
H
72%
Chern I n d (1969) 493 JCS (1970) 1208 O r g React (1942) 1_ 38
P h ( CH2)2COOH
PhNMe2
2 1 0-2200
Ph(CH2)2COyMe
L
15%
Ph Ber (1930)
Pb(OAc)4
PhNEt2
Ac2O
CHC1-j
*
638 489
PhyAc
90%
Et Ber (1959)
92
288
LO 28% AC
B u l l SOC Chim Fr (1964) 234
Ph2NCH2Me
KMnOq
NaHC03
Me2CO
L
PhpNAc
70%
JCS (1946) 454 JACS (1968) 90 1648
PhyMe R
Mn02
CHC13
*
Phl;lCHO R
83% (R=H) 80% (R=Me) JCS (1957) 3032 (1966) 995
COMPENDIUM OF ORGANIC SYNTHETIC METHOOS
21 8
T e t r a h e d r o n (1967)
SECTION 83
3 4691
PhCH2yCHO
PhCH2NMe2
Me
PrCH2NBu2
85% T e t r Lett (1968) 4085 (1970) 5049 Chem Corn (1969) 639
PrCONBu2
44% JCS (1964) 711
PhCH2CH2NH2
S
(NH4)2Sx
dioxane
PhCH2CONH2
.b
75 740
JACS (1953)
S e c t i o n 83
32% 5392
Amides f r o m E s t e r s 0 -0
69% JACS (1949)
F o r c a t a l y s i s by 2 - h y d r o x y p y r i d i n e see JCS 1,
I,
I,
I,
"
NaNH2
'I
"
MeONa
"
c (1969)
2 2215 89
Chem Ind (1956) 277
J O C (1963)
2 2915
SECTION 8 3
21 9
AMIDES FROM ESTERS
CH2COOEt
CH2CONHMe
E]
MeNH2-LiA1 tl4
+
61 % (Procedure f o r h i n d e r e d e s t e r s ) T e t r L e t t (1969) 1573 JCS (1954) 1188 T e t r Lett (1970) 1791
i-PrCOOMe
HCONHR MeONa
i-PrCONHR J O C (1965)
NH3
BuCXCOOMe
PhCOOEt
MeOH
NH3
NH4C1
JACS (1941)
I,
I,
63
1151
PhCONH2
F o r c a t a l y s i s b y NaNH2 see I,
30 2376
BuCECCONH~
JACS (1938) It
53% R=H) 97% [R=Me)
JACS (1955)
60 579 77 469 59 1568
I'
MeONa
'I
JACS (1937)
"
BULi
I'
T e t r L e t t (1970) 1791
c1
c1
c1
c1 Helv (1944) 27 883 Org React (1946) 3 337
HCOOCPh3
MeCN
H2SO4
b
AcNHCPh3 JCS (1964) 5609
Org React (1969)
213
2 20
COMPENDIUM OF ORGANIC SYNTHETIC METHODS
S e c t i o n 84
Amides f r o m E t h e r s and Epoxides
~ 0 0 0 0 0 0 ~ 0 0 0 0 0 0 0 0 ~ 0 0 0 ~ ~ 0 0 ~ ~ ~ ~ ~ ~ ~
C1.l
-
t BuOMe
(hH2)4CN
HzS04
-
CONHBu t
HOAc
@J
.OMe
Et4NCN *
Electrolysis MeCN H20
S
(NH4)2Sx
dioxane
*
PhCH2CONH2 JACS (1953)
S e c t i o n 85
?ides
f r o m H;lidzs
000000000000
0 0 0
PhCH2C1
HMPA t
2 LiI
C5H11 B r
NaNH2
lutidine
D
91 4181
75 740
87%
Me PhCH2iHCONMe2
Ber (1968)
LiCHzCONMe2 THF
9%
0
FOOEt 1 MeCHCONMe2
213
@JCONH2 Me0
JACS (1969)
/ 0\ PhCHCHz
75%
(kH2)~coNHBu-t
t
Org React (1969)
Me0
SECTION 85
101 4230
64%
C5H11CH2CONMe2 Ber (1968) J O C (1966)
46%
101 3113 31 982 989
SECTION 85
PhCH2C1
221
AMIDES FROM HALIDES Li LiCHzCONPh
Et20
*
PhCH2CH2CONHPh
69%
JACS (1967)
PhCH=CHBr
C7H15Br
Pyrrolidine
PhCH=CHCON
f
1 M9
91 1233
JACS (1947) (1938)
69 2007 60 540
Mg * Me0 @JCONH2 2 Ethyl cyclohexylidenecarbama t e Bull Res Council Israel (1952) (Chem Abs 48 8727)
S
NH3
H20
170'
>
PhCH2CONH2 JACS (1953)
HCONH2 C8H17Br
82%
JACS (1969)
C7H15CONHPh
2 PhNCO
Me0@JBr
PhCHzCHzBr
3
N i (CO)4
MeOH
-
1647
NH3
h
5 740
2 72
80%
5395
CgH17NHCHO JOC (1969)
88%
3 3204
F o r examples of t h e r e a c t i o n RCONHR' + R"Ha1 -+ RCONR'R" (R'=H o r a l k y l ) see s e c t i o n 81 (Amides f r o m Amides)
91 %
COMPENDIUM OF ORGANIC SYNTHETIC METHODS
222 S e c t i o n 86
SECTION 8 6
Amides from Hydrides (RHL ~ 0 0 0 0 0 0 0 0 0 0 0 0 ~ 0 ~ 0 0 0 0 0 0
The c o n v e r s i o n s RH -+RCH2CONH2, section. For the r e a c t i o n RR' (Amides f r o m A l k y l s )
RCONR'R" o r RNHAc a r e i n c l u d e d i n t h i s (R=Ar, R ' = a l k y l ) see s e c t i o n 8 0
-+RCONH2
H20
ClCH2CONH2 hU
T e t r Lett (1969) 2387
Me PhNCOC1 A1 C l
(NH2)zCO
*
Me0 Ber (1955) 301 JCS (1931) 2323
A1 C13
27%
Ph J O C (1970)
5 2104
a3 CONH2
HCONH2 hV
Me2CO t
20%
T e t r Lett (1963) 77
PhCH3
HCONH2
hV
Me2CO
+
PhCH2CONH2 T e t r L e t t (1963) 7 7
23%
SECTION 87
AMIDES FROM KETONES
Electrolysis
PhCH3
LiC104
MeCN
*
H20
223
PhCH2NHAc T e t r L e t t (1968) 2411
MeCN
t-BuOH
H2S04 hexane
* Ber (1964)
3234
Org React (1969)
Section 87
11 213
Amides f r o m Ketones
0000000000000000000
C8H17
@rt-olidine+
0
2 ~
~
1
0
a[ :rNHzb a[ 0 ~
Helv (1967)
TsCl
Pyr
JACS (1962)
---+
Phy-NOH Me
CF3COOH
a CONH2
C104-
PhCOMe
36%
NHAc
1759
16%
-92%
1064
PhNHAc
Org React (1960)
-91 % 1
224
-
COMPENDIUM
PhCOyMe2
---+
!OH PhCFMe2
Ph
Ph
OF
SECTION 87
ORGANIC SYNTHETIC METHODS
Polyphosphoric a c i d
*
J O C (1963)
PhCONH2
-63%
8 278
0 oNoH ---~
hy
iPrOH
___t
(3
Can J Chem (1968)
Q0
-----+
3 A
00
PhNH2 ------+ ( Z N P i i
~ 8 1 %
n(CH2r8 H o Tetr Lett (1965) 4541
1 MeC002H
Et2O
2 Xylene r e f l u x Ber (1958) 91 1057 T e t r Lett (1969) 2281
NH3
Pyr
CH2CONH2
H20
40% Org React (1946)
R2CO
N2H4 * H20 EtOH
5 3381
QNoH 4 H20
S
44%
C5H11CONH2
R2C=NNH2
NaN02 ____t
H2SO4
H20
2
40% ( R = i - P r ) 72% (R=Ph)
RCONHR
JACS (1953)
83
2 5905
225
AMIDES FROM NITRILES
SECTION 88 NaN3
PhCH2COMe
polyphosphoric a c i d
L
PhCH2NHAc
J O C (1958)
23
50%
1330
JCS (1942) 6 1 O r g React (1946) J 3 0 7
88%
( Y O P h
JACS (1953) 75 369 Org React (1957) 9 1
Amides may a l s o be p r e p a r e d by c o n v e r s i o n o f ketones i n t o amines f o l l o w e d b y a c y l a t i o n . See s e c t i o n 102 (Amines f r o m Ketones)
S e c t i o n 88
Amides f r o m N i t r i l e s
0000000000000000000
Me$-CHEt
PhCH2CN
H2SO4
H20
*
69%
PhCH2CONHyMe2
Pr
JACS (1948) 70 4045 Org React (1969) 213
Me I
MeCN
EtCHOH
BF3
t
PhCN
(i-PrO)$H
*
-
BF4
Ye
65%
MeCONHCHEt Acta Chem Scand (1968)
CH2C12
L
PhCONHPr-i J O C (1969)
2 627
22
1787
226
COMPENDIUM OF ORGANIC SYNTHETIC METHODS
HC1
PhCHZCN
H20
B F 3 *AcOH
PhCH2CN
t -
BuCN
PhCHzCONHZ
E t 3 O BF4
Org Synth (1963) C o l l Vol 4 760 JACS (1948) 70 3091 Annalen (1968) 713 212
95%
PhCHZCONHz JOC (1955)
CHZC12
MnOp
CH2C12
20
1448
93%
BuCONHz
t
J O C (1969)
RC N
2 627
40% (R=Me) 72% (R=Ph)
RCONH2
&
SECTION 88
Chem Comm (1966) 1 2 1
Ni
Pyr
H20
89%
t
Bull Chem SOC J a p (1966) (1964)
CN
H202
NaOH
EtOH
H20
+
39 8 2 1325
9D-92%
@Me Org S y n t h (1943) C o l l Vol 2 586 J O C (1950) 800
CN
I o n exch r e s i n ( b a s i c )
H20
+
6JCONH2
J O C (1960)
2 560
89%
SECTION 89 PhCN
NaOH Me2SO
PhCHzCN
H2
Ni
NaOAc
AMIOES FROM OLEFINS
227
96%
PhCONH2 JCS (1965) 1290
Ac20
97%
PhCHzCH2NHAc J O C (1960)
25
1658
Amides may a l s o be p r e p a r e d b y r e d u c t i o n o f n i t r i l e s t o amines f o l l o w e d by a c y l a t i o n . See s e c t i o n 103 (Amines f r o m N i t r i l e s )
S e c t i o n 89
Amides f r o m O l e f i n s
P 0 0
1 62Hg BuCH=CH2
C5H11 CHzCH2
CgH13CH=CH2
+-
THF
*
BU (CH2)3CONEt2
2 Me2SCHCONEt2
JACS (1967)
CH3COONHEt di-t-butyl
HCONMe2 di-t-butyl
peroxide
*
t
-50%
S 6804
C5Hll (CH2)3CONHEt
Dokl (1964) 158 1127 (Chem Abs 62 2703) JCS ( 1 9 6 5 ) T 9 1 8
C6H13(CH2)2CONMe2
peroxide
T e t r L e t t (1961) 238
56%
228
COMPENDIUM
Me2CO
ORGANIC SYNTHETIC METHODS
SECTION 89
hu
HCONH2 BuCH=CH~
OF
t-BuOH
50%
BU(CH~)~CONH~
+
JOC (1964) 29 1855 (1965) 3361 Angew (1961) 73 621
70%
& BuCH=CH~
C] 2H25CH=CH2
JACS (1952)
74 4496
J A C S (1946)
68 632
2025 2029
1 ClS02NCO
66%
7
2 PhSH
Pyr
Me2CO JOC (1968) 33 370 (1970) 2 2043 A n n a l e n (1968) 718 94
1 H g ( N 0 3 ) ~ MeCN 2 NaBH4
NaCN
NaOH
H2SO4
H20
BuyHMe
70%
NHAc JACS (1969)
91 5647
MeCN
68%
C12H25CHMe I
NHAc O i l Chem SOC (1964) (Chem Abs 60 6733) JACS (1948) 70 4045 O r g R e a c t (1969) 213 J Am
fi 78
SECTION 90
MeCH=CH2
229
AMIDES FROM MISCELLANEOUS COMPOUNDS 1 MeCONH2
PdC12
Na2HP04
*
Me2CHNHAc Proc Chem SOC (1961) 370
2 H2
Amides may a l s o be p r e p a r e d b y c o n v e r s i o n o f o l e f i n s i n t o arnines f o l l o w e d by a c y l a t i o n . See s e c t i o n 104 (Amines f r o m O l e f i n s )
S e c t i o n 90
Amides f r o m M i s c e l l a n e y s CompounSfs
0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 ~ 0 0 0 0 0 0 0 0 ~ 0 00' ~ ~
* m
PhCOOCHCONH2
CH2CONH2
H2
Pd-Bas04
EtOH
Arch Pharm (1957)
CgH1sCH=CHCOOH
S
NH3
Pyr
H20 b
290
CI~H~~CH~CONH~ JOC (1947)
90%
218
41 %
12 76
71% JACS (1966)
3318
Compendium of Organic Synthetic Methods, Volume 1 Edited by Ian T. Harrison, Shuyen Harrison Copyright 0 1971 by John Wiley & Sons, Inc.
7
Chapter
S e c t i o n 91
MeCECH
PREPARATION OF AMINES
Amines f r o m A c e t y l e n e s
0000000000000000000000
Me2NH Cd(OAc)2
Zn(OAc) 2
H2
Me2CC:CMe
Pt
Me2CCHzCH2Me
--+
1
HOAc
I
NMe2
NMe2
JACS (1961)
Section 92
Amines f r o m C a r b o x y l i c A c i d s and A c i d H a l i d e s 000000000000000000000000000000000000000000000
C11H23COOH.NH3
Hp (300 atmos)
b
copper chromi t e
(CiiH23CH2)2NH JACS (1934)
CgH1gCOOH
213 216
Li
MeNH2
CgH1gCH=NMe
H2
Pd-C
MeNH2
5 2419
CgH1 gCH2NHMe
JACS (1970)
230
79%
92 5 7 7 4
68%
SECTION 92 C17H35COOH
PhCH2COCl
Ph
A COOH
HN3 H2SO4 CgHg
c17H35NH2
O r g React (1946)
1 NaN3 CgHg
2 HC1 H20
P
PhCH2NH2
Org React (1946) Nature (1963)
1 ClCOOEt Et3N Me2CO
-b
2 NaN3 3 Toluene 100" 4 HC1 H20
Ph
3
96% 307
5 337
J O C (1961)
5
94%
197 787
A NH2
Br
77%
3511
Br
3 HC1
H20
Rec Trav Chim (1921)
NH2OH * HC1
* polyphosphoric acid
C5H11COOH
231
AMINES FROM CARBOXYLIC ACIDS AND ACID HALIDES
NH20S03H mineral oil 170-180'
*
40 285
aNH2 Me
JACS (1653) 75 2014 Org React (1946) 3 337 Chem Rev (1943) 33 209
CgH11 NH2 J O C (1964)
76%
25%
29
2576
COMPENDIUM OF O R G A N I C SYNTHETIC METHODS
232 MeN02
PhCOOH
polyphosphoric a c i d
*
PhNH2
SECTION 93
68%
J O C (1964)
2
2576
Ber (1963) 96 3359 Org React (1969) 11. 213
Section 93
Amines from Aicohols and Phenols ooooooooooooo
H 2 (380 atmos)
Et3N
c1 2H250H
*
Cu-Ba-Cr oxide
c1 ZH25NEtZ JACS (1952)
74 4287
70%
mH mTs TsCl
HO
eooooooooooooooooo
Py;
NH3
_3
TsO
H 2 Nm H2
MeOH
JCS (1946) 393
JACS (1933)
345
Further examples of t h e preparation o f amines from t o s y l a t e s a r e included in s e c t i o n 100 (Amines from Halides and S u l f o n a t e s )
PhCHOH I
Me
KCN
H2SO4
Bu20
* PhCHNCHO I
Me
NaOH
PhCHNH2 I
Me
Org React (1969) 17 213 J O C (1961) 26 3 0 0 F
60%
SECTION 94
AMINES FROM ALDEHYDES
NaH
A
COH
233
Q A A
BrCN
LiA1H4
P C N C O
____)
BCNHMe
~ t 2 0
THF
J O C (1968) 33 4054 JACS (1964) 4732
1 NaH MeOCH2CH20Me
PhyHOH
PhCHNMe2 I
2 Me2NS02C1
Me
Me
3 60'
JACS (1965)
NH3
SO2
H20
5261
150"
94-96%
Org React (1942)
S e c t i o n 94
PhCHO
1. 105
Amines f r o m Aldehydes
000000000000000000000
MeNH2
PhCH=NMe
C6H6
PhCH2MgBr
Et20
PhCHNHMe
84%
I
CH2Ph
Org S y n t h (1963) C o l l Vol 4 605
PhCHO
HCN KOH
PhfHCN OH
Hq
Pd-C
L HC1
EtOH
52%
PhCH2CH2NH2 JACS ( 1 9 2 8 )
3370
234
(lQCHo(:@
COMPENDIUM OF ORGANIC SYNTHETIC METHODS
CH3N02
NH40Ac
CHzCHN02
*
HOAc
HC1
H20 Br
Br
Br
T e t r L e t t (1967) 1201
O r g React (1949)
CgH13CHO
PhCHO
PhNH2
Hz
Ni
NaOAc
EtOH
*
NH3
H2
Ni
EtOH
CgH13CH2NHPh
CH=NNHPh
PhNHNH2
CHO
Org React (1948)
2
2 H2
PdO
*
65%
89%
H2 N i EtOH H20
CH=NNHPh
1 NH2COOCHzPh
50%
301
4 174
174
1;: CH 2 NH 2
0
CHzNH2
JOC (1958)
PhCHO
5
Org React (1948)
PhCHZNHz
$: - $: CHO
0
SECTION 94
23
571
PhCH2NH2
63% JOC (1941)
5 878
SECTION 94
PhCHO
EtNH2 MeOH
PhCHO
235
AMINES FROM ALDEHYDES
PhNH2 HOAc
LiBH3CN pH 5 - 6
NaBH4
c
JACS (1969)
NaOAc
*
91 3996
83%
PhCH2NHPh
EtOH
J O C (1963)
Y
NH20H EtOH
H
72%
PhCH2NHEt
CH=NoH
3259
LiAlH4
___)
@TjcH2
Et2O
H
87%
211 7 2 5
J B i o l Chem (1954)
3370 F o r r e d u c t i o n o f o x i m e s w i t h H2 and Pd-C see J A C S (1928) I1 II I, I, Ni " JCS C (1966) 531 I' !I I, II " Na a n d EtOH " O r g S y n t h (1943) c o l l v o l 2 318 I,
PhCHO
I,
,I
NH20Me
II
PhCH=NOMe
'I
Na-Hg
1 B2H6 2 KOH
"
JACS (1949)
THF
11 2257
* PhCH2NH2 H20 J O C (1969) 34 1817
92%
22% JOC (1959)
24 561
COMPENDIUM OF ORGANIC SYNTHETIC METHODS
236 S e c t i o n 95
Amines f r o m A l k y l s , Methylenes and A r y l s
~
~
O
O
Q
O
O
O
O
O
O
O
O
O
O
O
O
O
D
O
~
O
~
O
O
~
O
~
~
~
~
SECTION 96
~
O
~
~
~
O
O
O
~
No examples o f t h e r e a c t i o n R R ' -+ RNR2 ( R , R ' = a l k y l , a r y l e t c . ) o c c u r i n t h e l i t e r a t u r e . F o r t h e c o n v e r s i o n RH --f RNR2 see s e c t i o n 101 (Amines f r o m H y d r i d e s )
S e c t i o n 96
Amines f r o m Amides
oooaooooooooooooo~
. . . page ................. ................ ................
T e r t i a r y amines f r o m formamides and G r i g n a r d r e a g e n t s R e d u c t i o n o f amides t o amines H y d r o l y s i s o f amides t o amines D e g r a d a t i o n o f amides t o amines
BuMgBr
(i-Pr)zNCHO
Et20
*
ICONS H2 (300 atmos)
C6H1
dioxane
Ac
( i-Pr)2NCHBu2 Monatsh (1951)
copper c h r o m i t e t
250'
E t p O+
LiAlH4
JACS (1934)
LiAlH4
Et20 t
82 330
CgH13 c H 2 N 3
56
67%
92%
2419
m E t Helv (1948)
PhOCH2CONH2
236 236-238 238-239 239-240
84%
31 1397
PhOCH2CH2NH2 Helv (1948) 31 1397 O r g React (1951) 469 Org S y n t h (1963) C o l l Vol 4 564
80%
SECTION 9 6 LiAlH4
i- P r ( C H 2 ) 2 C O N E t 2
PhNHAc
237
AMINES FROM AMIDES AlCl3
Et20
i-Pr(CH2)2CH2NEt? 2 . Chem (1966)
N a A l H2 (OCH2CH20Me )2
6
224
84%
PhNHEt
+
C6H6
PrCONH2
*
T e t r L e t t (1968) 3303
NaBH4
CoC12
MeOH
70%
PrCH2NH2
+
T e t r L e t t (1969) 4555
C7H15CONMe2
NaBH4
Pyr
t -
PhCONHEt
CgH13CONMe2
1 E t 3 O BF4
2 NaBH4
Chem Pharm B u l l (1969)
CH2C12
*
EtOH
i -Bu2A1 H
41 %
C7H15CH2NMe2
PhCH2NHEt
98
a 803
92%
T e t r L e t t (1968) 61 T e t r a h e d r o n (1970)
Et20
*
CgH13CH2NMe2
75-95%
I z v (1959) 2146 (Chem Abs 54 10932)
PrCONE t 2
Et3SiH
ZnClz
*
PrCH2NEt2
70% Compt Rend (1962)
254
2357
COMPENDIUM OF ORGANIC SYNTHETIC METHODS
238
B2Hg
C5H11 CONHMe
THF
CgHiiCH2NHMe JACS (1964) 3566 JOC (1968) 33 3637
-
1 ~ 2 ~ 5
QCoNEt2
2 Na2S
NaH
MeCHCONHCH2COOH HCO~H
diglyme
H202
QCHzNEt2
,Nio EtOH,
38%
dP
Et2NCHO
98%
acSNEt2 JOC (1951)
Me2N
SECTION 9 6
Ca
5
131
NH3
A
JACS ( 1 9 6 2 )
2018
EtZNH
40% Tetr Lett (1965) 1713
H20
------+ M~I?~CONHCH~COOH
NH2
Annalen (1960)
636
140
95-97%
Org Synth (1955) Coll Vol 3 661
239
A M I N E S FROM A M I D E S
SECTION 96
aMe CH20H
CH20H
HO
HO QMe
N2H4
__t
NH2 B u l l Chem SOC J a p (1966) 3F) 185
NHAc
Me
@'rC
55%
EtOH*
H20
HC1
Me
Br
Org Synth (1932) C o l l V o l 1 111
NHCoPh
ONH2
71 %
Electrolysis Me4NC1 MeOH
Ber (1965)
c1
t -
JII
1 Et3O BF4 mMe0 C
0 u
i nu W "3,
1 Br7
n B
u
"
-
0
2 dHOAc i o x a n eH20
*
JACS (1965) H e l v (1968)
MeONa
Pb(OAc)4
Iv CONHBu-t 87
0
933
11(
MeOH
L
'ONH2
t
98 3462
100%
Org React (1946)
3
267
EtjN
*
49%
DMF JACS (1965)
87
1141
T e t r L e t t (1965) 4039
240
COMPENDIUM OF ORGANIC SYNTHETIC METHODS
NH20H.HCl
PhCONHPh
*
PhNH2
polyphosphoric a c i d
S e c t i o n 97
SECTION 97
76%
JACS (1953)
75 2014
Amines f r o m Amines 000000000000000000
. ...... .......
a - A l k y l a t i o n o f 3 r y amines page A l k y l a t i o n o f amine d e r i v a t i v e s w i t h G r i g n a r d - t y p e r e a g e n t s R e d u c t i v e a l k y l a t i o n o f amines w i t h a l c o h o l s , aldehydes and ketones A l k y l a t i o n o f amines and amine d e r i v a t i v e s w i t h h a l i d e s and s u l f a t e s A l k y l a t i o n o f amines w i t h o l e f i n s and a c e t y l e n e s A l k y l a t i o n o f amines w i t h m i s c e l l a n e o u s r e a g e n t s I s o m e r i z a t i o n and c y c l i z a t i o n o f amines D e a l k y l a t i o n o f 2 r y and 3 r y amines D e a l k y l a t i o n of 4 r y amines I
I
. .
. . . ... ........ ............ I
Et2NCH2Me
BuLi
BuI
25%
Me
PrNH2
IiOAc
2 2061
MeMg I CN
2 HC104 EtOH 3 KCN H20
I
I
242-244 244-245 245-246 246 246-248 248
BU
J O C (1966)
OMe
I
241-242
Et2NFHMe
hexane
1 Hg(OAc)2
. ...... ...... . ... ...... ......
240 240-241
Me
---+
Et20
I
1
Me
JACS (1957) ,S 5279
PrCHO
----- +
PrN=CHPr
PhLi
Et20
PrNHCHPr I
Ph
Bull SOC Chim F r (1964) 952
Me
60%
SECTION 97
MeCHO
(i-Pr)ZNH.HCl
(i-Pr)*NH
KCN H20
HCOOH
AMINES FROM AMINES
(i-Pr)*NCHO
MeNHCO( CH2 ) 4NH2
93 476
Monatsh (1962)
EtpO
PhCH2NMe2
HCHO H2 Pd-C
*
H20
m EtNH
23%
(i-Pr)zNCHEtz
93 476
Monatsh (1962)
HCOOH HCHO
(i-Pr)2NCHMe2
Et20
EtMgCl
EtOH Ni
PhCH2NH2
MeMgCl
-
-
2 H NNH2 "
-
(i-Pr)zNCHCN I Me
241
N
H
E
t
60-67%
Org Synth (1963) C o l l Vol 4 2 8 3 JACS (1954)
76 6174
Org React (1949)
5
80%
301
MeNHCO ( CH2 ) 4NMe2 JCS
C
60%
(1969) 1358
0 NH2
Me
HCHO s u c c i n i m i d e H20 EtOH
*
N H c H 2 N 9 ti2 Ni.
@NHMe
EtOH Chem Pharm Bull (1967)
Me
15 1339
68%
242
PrNH2
COMPENDIUM OF O R G A N I C SYNTHETIC METHODS
KOH
PrCHO
1 PhCHO CgH6 C5H11NH2
H2 P t 0 2 E t O H
* PrNHCH2Pr O r g React (1948) 5 174 Tetr Lett (1968) 2639
PrN=CHPr
-----+
*
C5H11NBu I
2 H2 PtO2 HOAc 3
BuBr
CH2Ph
MeOH
0""' BuNH2
Me2CO
NaBH4
NaOAc
HOAc
H2
Pt02
HOAc
JACS (1941)
Cycl ohexanone HCOOH
HOAc
w
H20
SECTION 97
65%
C~H~~NHBU
63 1964
*
86%
Rev Chim (Bucharest) (1968) (Chem Abs 69 105967) Org React (1949) 5 301
19 360
63%
BuNHCHMe2 JOC (1963)
3259
F o r f u r t h e r examples o f t h e r e d u c t i v e a l k y l a t i o n o f amines w i t h aldehydes and ketones see s e c t i o n 94 (Amines f r o m Aldehydes) and s e c t i o n 102 (Amines f r o m Ketones)
1 Ph3PBrp
Et3N
2 NaNH2 NH3
N=PPh3
Etl
O N H E t
2 KOH EtOH J O C (1970)
2
2826
-67%
SECTION 97
AMINES FROM AMINES
243
NHPr-i 92%
@Me JACS (1960) 6163 Ber (1952) 85 1056
1 MeLi
NHPr-i
Et20
2 i-PrI
@Me
*
JACS (1960) (1964)
t-BuNH2
1 PhLi
Et20
2 Me2CCZCH tl
*
t-BuN=CHCH=CMeZ
H2
Ni
EtOH J O C (1961)
t-BuNHCH2CH2CHMe2 3772
n
J O C (1962)
Me1
2813
-a
0
PhCH2NH2
3 6163
NaHC03
*
MeOH
+
-
PhCHzNMe31
liA1H4
THF
2 3639
PhCH2NMe2
72%
JACS (1960) 82 4651 Ber (1957) 90 395
Ph2NH
PhI PhN02
Cu
K$O3
Ph2NPh
82%
Org S y n t h (1941) C o l l Vol 1 544 JCS (1946) 5
SECTION 97
COMPENDIUM OF ORGANIC SYNTHETIC METHODS
244
vhMe Ts
NH2 1 T s C l
HC1
*
2 Na t o l u e n e 3 Me2S04
PhCH=CH
BuNH2
Pyr
1 PhCOCH2S02C1 2 Me1
K$03
CH2C12
HOAC-
H20
PhCH-CH
56%
Annalen (1956) 598 174 J O C (1968) 2 1142 Ber (1953) 3 1246
Pyr +
Me2C0
-
Zn HC1 BUYSO~CH~COP~ HOAc Me
BuNHMe
T e t r L e t t (1970) 345
PhNH2
1 (CF3C0)20
2 EtI
*
KOH Me2CO
KOH
PhTCOCF3 Et
H20
C (1969)
JCS
83%
PhNHEt 2223
Me
NH2 1 A c 2 0 Me0
NaOH
H20*
pNAc
2 M e 2 S 0 4 NaNH2 toluene
I
KOH
@JNHMe
H20
___t
EtOH Ber (1954) J O C (1949)
Me0 1760
3 1099
Org Synth (1963) 43 45 B u l l Chem SOC J a p (1967)
BuNH2
1 MeCH=CH2 Na2HP04 2 H2
PdC12 THF
*
BuNHCHMe2 Proc Chem SOC (1961) 370
40 2991
SECTION 97
1 HgC12
PhNHMe
245
AMINES FROM AMINES CH2=CH2
2 LiAlH4
.
PhyMe
Et
Compt Rend (1966) C 262 1591 T e t r L e t t (1967) 5 i 6 r (1969) 2289
JACS (1961)
NH2 H C ( O E t ) 3
.iLiJ@J
H2SO4
213
2"0,
HC1
@"IiEt
c1
c1
c1
@2:'
(Et0)3P0,
Org Synth (1963) C o l l Vol 4 420 JACS (1956) 2 4778
@JNEt2 C1
ClCOOEt
NaOH
91 %
68 895
JACS (1946)
VLiAlH4 OH
MeO@":'H2NH2
bHCH2NHCOOMe Et20
?H MeOQCHCHzNHMe
.
Me0
Me0 H20
OMe
HCOOH
N74%
OMe J Med Chem (1963) 6 227 J O C (1965) 2 2483-
LiAlH4
THF
J Med Chem (1966)
~e
9
830
COMPENDIUM OF O R G A N I C SYNTHETIC METHODS
246
.
SECTION 97
F u r t h e r examples o f t h e p r e p a r a t i o n o f N - a l k y l amines by r e d u c t i o n o f amides a r e i n c l u d e d i n s e c t i o n 96 (Amines f r o m Amides)
CNH
1 L i A l H 4 THF 2 MeCOOEt
o
N
H
2
Ni
80%
t
JOC (1962)
27
1042
ONHQ
toluene+
82%
Annalen (1961) 644 23
PhNMe2
C5H11 Br
150-160”
1 C12
PhyMe
Ber (1881) 14 622 Org React (1953) 7 198
CgH11
NaOH H20
2 H2SO4 H20
*
70-80%
B u N 3
Org Synth (1955) Coll Vol 3 159 Chem Rev (1963) 63 55
JCS (1937) 1119
Tetrahedron (1961)
2 208 100%
Org React (1953) 7 263 JACS (1950) 3410 (1941) 63 1964
S E C T I O N 97
247
AMINES FROM AMINES
Me0 BrCN
L i A1 H4
K2C03
THF
c
JACS (1967) 89 1942 (1955) 71 4079 Org Synth (1955) C o l l Vol 3 608 198 Org React (1953)
Me0
L
Bu3N
C1 COOPh
CH2C12
*
Bu2NCOOPh
85%
i-PrONO
(i-Pr)2NEt
PhNMe2
Pr3N
02
CUCl
HBr
NBS
150"
dioxane
(i-Pr)2NN0
CXP
*
---- .t JCS
Bu2NH
C (1967)
--+
2015
(i-Pr)zNH
Angew (1970) 876 ( I n t e r n a t Ed 9 892) JACS (1967) 89 1147
PhNHMe
H20
Acid
J O C (1963)
Pr2NH
8 3144
JCS (1957) 4905 JACS (1968) 90 3502 Chem Rev (1963) 63 2 1
87%
MeCHNMe2 O2
hv m e t h y l e n e b l u e
MeOH Tetr L e t t (1970) 3649
80%
COMPENDIUM OF ORGANIC SYNTHETIC METHODS
248
1 14202 H20 2 Ac20
Me2N
CHC13t MeV
SECTION 97
a a --+ MeNH
70%
2 4681
T e t r a h e d r o n (1967)
t-BuOOH
(i-Pr)2NH
i-PrNH2 J O C (1960)
2 2114
88%
F u r t h e r r e a c t i o n s which may be used f o r t h e d e a l k y l a t i o n o f amines a r e i n c l u d e d i n s e c t i o n 82 (Amides f r o m Amines) and s e c t i o n 81 (Amides f r o m Amides)
+
Et3NCH2Ph
+
-
C1
PhSH NaOH
-
-
HOCHzCH2NH2
BuNMeg I
NMe3
LiA1H4
THF
Et3N
12
J bled Chem (1969) 694 T e t r L e t t (1966) 1375
BuNMe2 Ber (1957)
90 395
* JACS (1960)
4651
22%
SECTION 99 S e c t i o n 98
P hCH2COOR
249
AMINES FROM ETHERS
Amines f r o m E s t e r s 000000000000000000
1 NH20H base
2 PhCOCl
*
MeONa
PhCH2CONHOCOPh
LiAlH4
AlCl3
t PhCH2CH2NHz THF Bull SOC C h i m F r (1960) 509
Amines may a l s o be p r e p a r e d by c o n v e r s i o n o f e s t e r s i n t o amides f o l l o w e d by r e d u c t i o n . See s e c t i o n 83 (Amides f r o m E s t e r s ) and s e c t i o n 96 (Amines f r o m Amides)
PhCH2COOEt
1 N2H4*H20 E t O H 2 NaN02
t-BuOAc
S e c t i o n 99
HCN HzSO4
HC1
*
PhCHzCON3
H20
HC1
HOAc
H20 Org React (1946)
t-BuNH2
PhCH2NH2
-50%
2 337
Org React (1969)
213
Amines f r o m E t h e r s
000000000000000000
OMe
MeNH2 hU
H20
t
54%
NO2 @JNHMe Rec T r a v Chim (1966)
56
250
COMPENDIUM OF ORGANIC SYNTHETIC METHODS
S e c t i o n 100
SECTION 100
Amines f r o m H a l i d e s and S u l f o n a t e s
0000000000000000000000000000000000
...............
page 250-251 Amines by G r i g n a r d r e a c t i o n s Amines by a l k y l a t i o n o f ammonia, amines and amine d e r i v a t i v e s w i t h h a l i d e s and s u l f o n a t e s 251-254 254-255 M i s c e l l a n e o u s methods
................ ....................
PhBr
PhBr
1 Mg
Et20
PhCH2CH2NMez
t
2 ClCH2CH2NMe2
1 Mg
Et20
PhY-NH
2 EtCN
13%
J Med Chem (1966)
Et
LiAlH4
THF
MeCl
1 Mg
Et2O
*
2 (i-Pr)zNCHO
1 Mg
EtzD
Et
CN
C5H11Br
Et20
*
2 BuOCH2NEt2
1 Mg
Et20
2 NH20Me
75 5898
Monatsh (1951)
g
Monatsh (1962)
93 476
330
( i- P r ) 2NCHMe2
+
1 Mg
80%
( i-Pr)2NCHBu2
2 (i-Pr)zNFHMe
CH2=CHCH2Cl
790
PhFHNH2
JACS (1953)
BuBr
9
67%
54%
CH~SCHCH~CH~NE~~ J C S (1923) 123 532
C5H11NH2
65%
J C S (1946) 781
BuBr
1 Mg
Et20
dioxane
*
2 C1NH2
BuNH~
”I-*’ NaoN H2D
NH3
i-PrBr
Et2NH
JACS (1941) (1936)
+
1 Mg THF 2 TsN~
C7H15Br
JOC
PhNH2
63
97%
1692 27
QNH2
Me
(1969)
2 3430
82%
MeOH
C7H1 gNH2
HOCH2CHzOH
*
JACS (1932)
NH3
CuCl
Me
H20
195”
47% 3441
54 4457
60%
70%
PrNHPh
Me@Br
54 1499
Et2NPr- i JACS (1932)
PrBr
251
AMINES FROM H A L I D E S AND SULFONATES
SECTION 1 0 0
JCS (1930) 992
Cu,”
Me@JNH2 Me O r g Synth (1955) C o l l Vol 3 307
79%
COMPENDIUM OF O R G A N I C SYNTHETIC METHODS
252
NaNH2
NH3
60%
Ph
PhI
“2
Ph
PhLi
Me3N
SECTION 100
JOC (1957) 22 500 Ber (1964) 91 1994 Chem Rev (1962) 62 81
PhNMe2 Ber (1943)
76B 109
Further examples of t h e r e a c t i o n RHal + R2NH -+ R N R 2 (R=alkyl, a r y l e t c . ) a r e included in s e c t i o n 97 (Amines from Amines)
c1 gH330Ts
BuNH2
toluene
+
c1 tjH33NHBu 51 %
(C16H33)zNBU
+
33%
JACS (1933) 55 345 JCS (1955) 694
JCS (1961) 1643 Ber (1970) 103 475
0 Po t a s s ium
t-Bu
phthalimide
t-Bu JCS (1935) 1847 JACS (1950) 2787 Angew (1968) 986 (Internat Ed 919)
2
I.
60%
SECTION 100
Br
A M I N E S FROM H A L I D E S AND SULFONATES
Saccharin
PhCH2Br
RGNH'
1 Potassium p h t h a l i m i d e b
CuBr DMA 2 Hydrolysis
K$O3
*
253
Cheni C o r n (1969) 578
1 KOH
@)C lfH2Ph
2 BuOTs 3 HC1 H20
J Pharm SOC J a p (1953)
(1955)
I
N-Acetyl-p-anisidine copper bronze PhN02
74%
PhCH2NHBu
13 1319 75 153
159
gNHQ
K2CO3b
24%
OMe
c1
c1 JCS (1946) 5
C=CHCH2CHzBr
-1' TsNMeNa
/C=CHCH CH NMe
2+s
- 'I phenol HBr HOAc
C o l l Czech (1967)
BuX
PhCHoCl
1 (PhS)2NLi 2 HC1
H20
THF
BuNH~
Hexamethylenetetramine NaI
EtOH
*
C=CHCH2CH2NHMe
'
32
2826
60% (X=Br) 78% (X=OTs) T e t r L e t t (1970) 3411
PhCHoNH7 L L JACS (1939) 61 3585 Org React (1954) 197
82%
COMPENDIUM OF ORGANIC SYNTHETIC METHODS
254 C5H11Br
1 (NH2)2C=NH EtOH H20 NaOH *
-
t
1 NH2CN MeSOCH2 Na
Me2C=CH(CH2)3Br
2 KCN
MeOH 3 HOAC H20
C5H11NH2
T e t r L e t t (1969) 13
Me2SO
bBr C1
t-BuC1
[Me2C=CH(CH2)3]2NH
55%
LiAlH4 Et20
*
2
c
71 %
T e t r L e t t (1969) 3327 T e t r a h e d r o n (1970) 2 1275
NaN3 H20 CCl4
s@
SECTION 100
$N3
JACS (1970) (1951) Helv (1958)
Liiy4
___t
92 6302
5 5865 41 181
2@
34%
J O C (1962) 2 2925 JACS (1969) 91 2961
1 MeCN H2SO4
2 NaOH
65% J bled Chem (1963) 760 Org R e a c t (1969) 11 213
NCl3 AlC13
P t-BuNH2
J O C (1969)
3 911
90%
SECTION 1 0 1
AMINES FROM HYDRIDES (RH) NCO
I
Hydrolysis
*
I
---- +
I
aNH
C h e m Eng News (1970) March 9 39 J A C S (1964) 4732
hv THF B u ( C H ~ ) ~ N ~A
NaN3
Bu(CH2)4Cl
255
Bu
JCS (1962) 622
S e c t i o n 101
PhH
A m i n e s f r o m H y d r i d e s (RH)
0000000000000000000000000
CH2'CHCHzNHBu
A1 C 1 3
t
66%
PhFHCHZNHBu Me
J A C S (1943)
65
674 762
NH
/ \
PhH
MeCH-CH2
AlCl3
t
PhFHCHZNHz Me 12%
EtCHMe2
HCN
t-BuOH
HzS04
c
+
PhCH2fHNH2
Me 4 % J Heterocyclic Chem (1968)
EtCMe2
339
45%
NH2 Ber (1964) 97 3234 Org React (1969)
S
213
256
COMPENDIUM
OF ORGANIC SYNTHETIC METHODS
JACS (1967)
NCl3
36%
I
Me
JACS (1966) (1964)
Me2NC1
H2SO4
Na2SOq
PhNMe2 Ber (1966)
Me
3177
dichlorobenzene
Me
PhH
S E C T I O N 101
NH2OS03H A l C l 3*
@
NH2
JACS (1961)
88
99
100 1650
73% 1347 1361
50% 2 2 1 743
@ ;;;+f; C8Hl7
pb(oAc)41.0&~H2
AcO
2 LiAlH4
Et20 Tetrahedron (1970)
49%
26
1417
A M I N E S FROM H Y O R I D E S ( R H )
SECTION 101
JACS ( 1 9 5 3 )
B
N
0
2 koHHCl
257
369
H20*
i- P r
i-Pr
a
N
i- P r
H
2 52%
JCS (1939) 1 2 9 9
PhH
1 (CF3C00)3T1 2 NH3
CF3COOH
*
h9
@T@
PhNH2 Acc Chem Res (1970)
1 BuLi
0
hl/
2 NH20Me
t-BuOH
338
EteO
54%
* Org React (1954)
N2H4
3
S
NH2
258
45%
t
T e t r a h e d r o n (1966)
22 483
Amines may a l s o be p r e p a r e d by c o n v e r s i o n o f h y d r i d e s (RH) i n t o amides (EIIHCOR, RCONR2 e t c . ) f o l l o w e d by h y d r o l y s i s o r r e d u c t i o n . See s e c t i o n 86 (Amides f r o m H y d r i d e s ) and s e c t i o n 96 (Amines f r o m Amides)
COMPENDIUM OF ORGANIC SYNTHETIC METHODS
258 Section 102
Amines from K e t o y 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0
0-
&1 MeNH2
A
c
SECTION 102
O
W
,fl MeMgBr
1fiN
2 Me1
CH2C12
3 KCN
MeCN
EtpO
THF
J O C (1962) 27 2541 (1965) 3203
1 CH3N02
2 Ac20
t-BuOK Me2SO
1 NaBH4
t
CHN02
2 H2
Pd
CH2NH2
T e t r L e t t (1970) 1063
HCONH2
HCOOH
c1 @OMe
@JA:""' 5
c1
Cr'
HCONMe2
THF
CgHg
301
0""' J O C (1968)
1 PhCH2NH2 2 NaH
HCOOH
Org React (1949)
82%
33
-71 %
1647
O N z C H P h
O
N
+ Can J Chem (1970)
48 570
H
2
57%
SECTION 1 0 2 PhNHz
Me2C0
259
AMINES FROM KETONES
HOAc
NaBH4
NaOAc
EtOH
*
Me2CHNHPh
91 %
J O C (1963)
3259
96%
NH3
LiBH3CN
MeOH
48%
p H 5-6
0
0 &olidine
NH2 JACS (1969)
91 3996
aal
-----------*
1 B2H6
THF
2 MeOH
(3 NO"
T e t r L e t t (1970) 2849 J O C (1965) 30 3203
1 PhCH2NH2 ____t
0
2 NaBH4
PhCH2NH
EtOH
NH2
Bull SOC C h i m F r (1963) 798
25%
260
COMPENDIUM OF ORGANIC SYNTHETIC METHODS
Ph2CO
PhNH2
ZnC12
LiAlH4
PhzCZNPh
EtpO
SECTION 102
Ph2CHNHPh
)C
J O C (1958)
62%
2 535
For r e d u c t i o n o f i m i n e s w i t h HZ and P t see B u l l SOC Chim Fr (1964) 753 I,
I,
I!
I,
,I
I1
,I
I,
,I
,I
It
I,
Hp
"
I'
Pd
H2 " N i by e l e c t r o l y s i s "
" " I'
JCS
C
(1970) 1303
J O C (1962) JOC (1970)
27 35
2209 261
F o r r e v i e w o f r e d u c t i o n o f S c h i f f ' s bases see Org React (1948)
Ph2CO
Et2FIH
---+ PhzCN2
hJ
4
174
23%
Ph2CHNEt2 Annalen (1958)
614
19
Me2NNH2
1 Me1 MeCN ____)
2 NaH Me2SO 3 NaSIi 4 Ni
HO
Inz Et
Me C = NNMe2
J H e t e r o c y c l i c Chem (1964) 1 5 3
NH20H
PhCOEt
NaH2P02
Ni
PhC-NOH I
EtOH
Et
PhFHNH2
H20
Et
JCS
F o r r e d u c t i o n o f oximes w i t h Ni-A1 and NaOH see JCS I, I,
,
,I
I,
I!
I,
,I
I'
"
I,
I,
It
I,
I1
II
I1
II
I1
,I
II
I,
I,
II
II
II
'I
Zn
'I
NH3
"
78%
C
(1966) 531
c (1966)
655
Monatsh (1963)
94 677
Na and NH3 See Zh Obshch Khim (1965) (Chem Abs 62 13068) LiAlH4 see J O C (1952) 17 294
'I
62Hg
'I
H2
and
by e l e c t r o l y s i s
Rh
I'
JOC (1969)
'I
J O C (1962)
"
JACS (1967)
35
3 1817 2 2209 89
6374
125
SECTION 102
261
A M I N E S FROM KETONES
mcH2c I n
S
piperidine
*
N i H20 dioxane
3 @l$yH:f:" JOC
[)-COMe
NH20H
(CF3C0)20
-----+
+
I
Me
Ph2C0
NH2OH.HCl polyphosphoric a c i d
MeOCH2CH20Me
(1951)
16 131
D
JACS (1957)
- DNH2
NaOH NHCO~F~
2 6522
F77%
PhNH2
66% JACS (1953)
2014
Proc Chem SOC (1963) 2 2 4
Amines may a l s o be p r e p a r e d by c o n v e r s i o n o f ketones i n t o amides f o l l o w e d by h y d r o l y s i s o r r e d u c t i o n . See s e c t i o n 87 (Amides f r o m Ketones) and s e c t i o n 96 (Amines f r o m Amides)
Some o f t h e r e a c t i o n s l i s t e d i n s e c t i o n 94 (Amines f r o m Aldehydes) may a l s o be a p p l i e d t o t h e p r e p a r a t i o n of amines f r o m ketones
262
COMPENDIUM
S e c t i o n 103
C5H11CN
PhCN
00000000000000000000
1 PhMgBr
Et20
2 LiAlH4
THF
LLVll
J
IY, "3OH
HC1
*
54%
C5H11 yHNH2 Ph
JACS (1953)
OEt
H20
J O C (1969)
Hq
SECTION 103
Amines f r o m N i t r i l e s
L
'
OF ORGANIC SYNTHETIC METHODS
Pd-C
EtOH
PhCH2NH2
2
5898
2 627
JACS (1928) 3370 JCS (1942) 426
90%
& BuCN
Na
EtOH
Ni
NaH2P02
EtOH
H20
NaOH
*
82%
C
JCS (1966) 531 Bull Chem SOC J a p (1967)
toluene
5
1548
76%
BuCHzNH2 JACS (1934) Ber (1942)
56
1614
75B 991
SECTION 1 0 3
LiA1H4
LiA1H4
P I1C H 2 CN
PhCN
263
AMINES FROM N I T R I L E S
(i-Bu)*AlH
AlC13
C6H6
*
CH2NH2
Et20 *
@Me
88%
JACS (1948) 70 3738 Org React (1951) 5 469
-
EtzO
PhCH2CH2NH2 JACS (1955)
H2
PhCHZNH
Pd
83%
77 2544
57%
PhCH2NH2
J O C (1959)
2 627
C H 2 NH 2 85% Me
Me’ JACS (1956)
NaBH4
CoC12
MeOH
C7H1 gCN
B2H6
78 2582
*
80%
C7H1 5CH2NH2 T e t r L e t t (1969) 4555
C
CH2NH2
THF
85%
CH2NH2
H2S H
0
‘CN
H20
NaOH
HN
JACS (1960)
H2
0
681
Pd-C CH2NH2
CSNH2 Chern Pharm B u l l (1961) 16 131
J O C (1951)
0
9
119
PhCN
MeOH HC1 ------+
Electrolysis
PhC=NH*HCl
H2SO4
h e
PhCN
SECTION 104
COMPENDIUM OF ORGANIC SYNTHETIC METHODS
264
NH20H.HCl
*
PhNH2
polyphosphoric acid
* PhCH2NH2 H20 JACS (1935) 57 7 7 2
JACS (1953)
76%
2014
20%
Amines may a l s o be p r e p a r e d by c o n v e r s i o n o f n i t r i l e s i n t o amides f o l l o w e d b y h y d r o l y s i s o r r e d u c t i o n . See s e c t i o n 88 (Amides f r o m N i t r i l e s ) and s e c t i o n 96 (Amines f r o m Amides)
S e c t i o n 104
Ph
Amines f r o m O l e f i n s
P
dh(
THNEt2
MeCH2NEt2 h9 +
11%
Chem Comm (1969) 753
Me2NH paraformaldehyde H2SO4
CH2NMe2
19%
HOAc T e t r L e t t (1966) 6483
Me
1 NaBH4
BF3-Et20 diglyme
2 NH20S03H
*
(trans)
JACS (1966) 88 2870 JOC (1967) 2 3199
45%
SECTION 104
MeCH=CH2
A M I N E S FROM OLEFINS
I Hg(0Ac)Z
PhNH2
Ne2CHNHPh
t
2 NaBH4
265
70%
T e t r L e t t (1967) 5165 i m g j 2289 Compt Rend (1966) 262 1591
C
1 Hg(N03)2 MeCN 2 NaBH4
NaOH H20
t
JACS (1969)
91 5647
1 NaCN H2SO4 HOAc
58%
2 H20 T e t r a h e d r o n (1967) Org Re a c t (1969)
23
3563
17 213
1 AgCNO
I2
Et20t
-oNHc!3 eNH
~ ~ o o ~ ~ 2 0 H O A c
2 MeOH
JACS (1970)
MeCH=CH2
1 BuNH2
PdC12
Na2HP04 THF t
2 H2
92
1326
Me2CHNHBu
Proc Chem SOC (1961) 370
60%
Amines may a l s o be p r e p a r e d by c o n v e r s i o n o f o l e f i n s i n t o amides f o l l o w e d by h y d r o l y s i s o r r e d u c t i o n . See s e c t i o n 89 (Amides f r o m O l e f i n s ) and s e c t i o n 96 (Amines f r o m Amides)
COMPENDIUM OF ORGANIC SYNTHETIC METHODS
266 S e c t i o n 105
EtTHN02
Amines f r o m M i s c e l l a n e o u s Compounds
0 0 0 0 0 0 0 0 0 0 0 D 0 0 0 0 D 0 0 0 0 ~ ~ ~ ~ 0 0 0 0 0 0 ~ 0 0 0
LiAlH4
EtpO
EtyHNH2
t
Me
PrN02
SECTION 105A
Me
Pd
cyclohexene
Et20
*
JACS (1948) (1951)
70 3738 73 1293
PrNH2 JCS (1954) 3586
55%
F o r r e d u c t i o n o f n i t r o compounds w i t h H2 and Pd-C see Ber (1953) 86 939 I , I, ,, I, " H2 and N i seeOrg Synth (1955) C o l l Vol 3 59 I ,, I, I, I, " Fe and HC1 see Org Synth (1943) C o l l Vol 2 160 I, I1 I, I, !I " A1-Hg see JACS (1968) 90 3245
S e c t i o n 105A
P r o t e c t i o n o f Amines
0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 6
Amine p r o t e c t i n g groups which a r e g e n e r a l l y a p p l i c a b l e a r e i n c l u d e d i n t h i s s e c t i o n . F o r a r e v i e w o f t h e p r o t e c t i o n o f amino a c i d s and p e p t i d e s see Advances i n Org Chem (1963) 3 159 CF3CONMe
Me
K2CO3 MeOH
NH2CH2CONHR
k
H20
HCOOH A c ~ O
/
HC1 MeOH
Me
J O C (1965) 30 1287 JACS (1953) 3473
HCONHCH2CONHR Chem Ind (1953) 107 Helv (1960) 43 1751
S E C T I O N 105A
PROTECTION OF AMINES
NH2
ClCH2COCl
NHCOCH2C1
---------+
1 (NH2)zCS
EtOH
2 H20
HCl.NH2CHCONHCH2COOH I i-Bu
267
90 4508
JACS (1968)
Diketene
Et3N E t O H +
MeCOCH2CONtl~HCONHCH2COOH
4
i-Bu
PhNHNH2 HOAC
T e t r L e t t (1965) 605
F u r t h e r examples of t h e p r e p a r a t i o n and cleavage o f a c y l d e r i v a t i v e s o f amines a r e i n c l u d e d i n s e c t i o n 82 (Amides f r o m Amines) and s e c t i o n 96 (Amines f r o m Amides)
0 PhCH2fHNH2 COOH
P h t h a l i c anhydride p h c H 2 r N s (Stable t o acid)
4
N2H4'HzO
EtOH
0
CooH
2
J A C S (1952) 3822 Rec Trav C h i m (1960)
Cl
NaOH MeOH
n
-
C1 COOEt
HNWNH HC1 H20
( S t a b l e t o NBS)
c1 Can J Chem
NaOH H20
*
2 688
(1955)
33
n HNW N C O O E t J C S (1929) 39
JACS (1954)
2 1164
1819
268 PhNH2
COMPENDIUM OF ORGANIC SYNTHETIC METHODS ClCOOCH2Ph
SECTION 105A
PhNHCOOCH2Ph
____t
t--
HBr
11 1564
J O C (1952)
For the hydrogenolysis o f benzyloxycarbonyl groups see JACS (1957)
79
1636
and Org React (1953) 2 263 For the photolytic cleavage o f benzyloxycarbonyl groups see Tetr Lett (1962) 697
HCl-NH2CH2COOMe
@
NH2
Me
NjCOOBu-t Et3N EtOAc
*
\
HBr HOAc
Helv (1959) JACS (1957)
C1 COOCH2CH2I -*Me Zn MeOH
t-BuOCONHCH2COOMe
42 2622 79 4686
NHCOOCH2CH2I JCS (1965) 7136
C1 COOCH2CC13 Zn MeOH
PhNH2
C1 COOCH2CH2Ts
*
KOH EtOH
Tetr Lett
NHCOOCH2CCl-j (Stable to acid, base and Cr03) (1967) 2555
PhNHCOOCH2CH2Ts Proc Chem SOC
(1962) 363
PROTECTION OF A M I N E S
SECTION 105A
PhNH2
269
9-Fluorenylmethyl chloroformate -b
M o r p h o l i n e o r NH3 JACS (1970)
PhNH2
B i s - ( 8 - q u i n o l y l ) carbonate
---z---Cu
Me2CO
+
5748
6J?)
PhMHCOO
t
H20
JACS (1962)
(C6H13)2NH
92
84 4899
-------* ( C ~ H I ~ ) ~ N C H ~ P ~
H2
Pt
HOAc
( S t a b l e t o a c i d , base and RMgX) JCS (1940) 1307 Org React (1953) 263 3410 JACS (1950)
72
@--% ja COPh
PYr+
Me
1.
t -
1 Et3O BF4 32 NaBH4 NaOH
1
CN
H2
Pd
HC1
dioxane
EtOH
Tetrahedron (1970)
HC1 NH2CH2COOR
Ph3CC1
HOAC
/?,CHzPh
Et3N
CHC13
Ph3CNHCH2COOR
26
( S t a b l e t o base)
H20
or H2 Pd E t O H
JACS (1956)
803
2 1359
COMPENDIUM OF ORGANIC SYNTHETIC METHODS
270
N H ~
1 EtMgBr
Et20
*@J
2 ClSiMe3
Br
N ( S i Me3 ) (Stable to RLi)
Br
t -
JCS
MeOH
SECTION 1 0 5 A
C
(1966) 1706
Ts
BuNH~
TsCl
Pyr
HC1
HOAc
PhCOCH2S02C1
Pyr
JACS (1949) (1952)
CH2C12 +
Zn
HC1
2
1901
74 2006
BuNHS02CH2COPh ( S t a b l e t o a c i d , b a s e a n d Cr03) T e t r Lett (1970) 345
HOAc
opr CH2CH2COOH
NaN02
HBr
HC1
H20
CuCl
H20
+
I
NO
JACS (1946)
(1957)
CH20R
ROO
O NH2 R
Me0
*
HC1
68 146 79 2 2 1 5
+ Me2CO
%H-@)-OMe J A C S (1956)
78
1393
Compendium of Organic Synthetic Methods, Volume 1 Edited by Ian T. Harrison, Shuyen Harrison Copyright 0 1971 by John Wiley & Sons, Inc.
Chapter 8
S e c t i o n 106
BuCZCH
C5H11 C X H
C5H11 CZCH
PREPARATION OF ESTERS
Esters from Acetylenes
0000000000000000000000
1 LiNH2 d i o x a n e +
2 ClCOOEt
1 Na
2 TsCl
250"
MeOH
Pd
-----+ B u C H ~ C H ~ C O O E ~
25% Annalen (1958)
C5H11 CXC1
N20
H2
BuCZCCOOEt
EtONa
614 37
C5H11 CH2COOEt
Annalen (1931)
309
C5H11 CH2COOMe JCS (1951) 3016
!COOK
J O C (1965) 30 3985 JACS (1934) 56 1802
271
57%
COMPENDIUM OF ORGANIC SYNTHETIC METHODS
27 2 S e c t i o n 107
SECTION 107
E s t e r s f r o m C a r b o x y l i c A c i d s , A c i d H a l i d e s and Anhydrides o
o
o
o
o
o
o
o
o
o
o
o
o
o
o
o
o
o
~
o
~
~
~
~
... . . ....
~
A l k y l a t i o n and h o m o l o g a t i o n o f c a r b o x y l i c a c i d s , , page Esters by r e a c t i o n o f c a r b o x y l i c acids ( o r a c i d h a l i d e s ) w i t h a l c o h o l s and phenols E s t e r s b y r e a c t i o n o f c a r b o x y l i c a c i d s w i t h h a l i d e s and s u l f o n a t e s E s t e r s b y r e a c t i o n o f c a r b o x y l i c a c i d s w i t h d i a z o a l k a n e s and o t h e r 0-a1 k y l a t i n g agents , D e g r a d a t i o n o f c a r b o x y l i c a c i d s and a n h y d r i d e s t o e s t e r s , ,
. ..
~
272
a
~
~
~
273-276 276-277 277-279 279
COOH I
C5H11 COOH
(CH2)4COOMe
MeOH
H20
electrolysis
&
C5H11 (CH2)4COOMe
JCS (1950) 3326 Advances i n Org Chem (1960)
48%
1I
.@@
CH2COOEt
21 Ag2O CH2N2 E Et Ot 2H 0
ococl t -
1 MezSOCH2 THF
2 hV
CH3COOH
c
MeOH
y 2 Me2CCH20H
CH3C;:I
73-82%
O r g React (1942) 1 3 8
(\rCH2COOMe
v
80%
1640
J A C S (1964)
1 BuLi 2 BuBr 3 H2SO4
c
BuCH2COOEt
EtOH
JACS (1970)
92
6644
F u r t h e r methods f o r t h e a l k y l a t i o n and h o m o l o g a t i o n o f c a r b o x y l i c a c i d s and e s t e r s a r e i n c l u d e d i n s e c t i o n 17 ( C a r b o x y l i c A c i d s , A c i d H a l i d e s and A n h y d r i d e s f r o m C a r b o x y l i c A c i d s and A c i d H a l i d e s ) and s e c t i o n 113 (Esters from Esters)
~
~
~
~
~
~
SECTION 1 0 7
ESTERS FROM CARBOXYLIC ACIDS, A C I D H A L I D E S AND ANHYDRIDES
273
55% JACS (1951)
EtOH
t-BuCH2COOH
CgH17COOH
MeOH
H2SO4
H2SO4
i- P r
-
C12H25COOH
*
*
C12H250H
HO
xyl ene
OH
COOMe
i- P r
Pr-i
JACS (1941)
C12H25COOEt
Ho@CooH
Ja i -Pr
2 MeOH
HC1
TsOH
60 2790
CgH17COOMe Chem Ind (1968) 1568 (1967) 825
1 ~ 2 ~ 0 4
Pr-i
EtOH
JACS (1938)
-
'OH
77%
t-BuCH2COOEt
molecular sieves
i -Pr
73 5487
Org S y n t h (1943) C o l l Vol 2 292 (1932) C o l l Vol 1 246
HOQ.
*
63 2431
COOCl2H25
HO OH Rec Trav Chim (1951) 2 277 .JACS (1945) 67 902 Acta Chem Scand (1959) 13 1407
81%
ocooH ocooR
274
COMPENDIUM
ROH
OF
ORGANIC SYNTHETIC METHODS
EF3.Et20
*
F;H$OOH
PhOH
POC13
(R=Me, E t , i - P r ) Tetr Lett (1970) 4011 JCS (1965) 5770
FH2COOP h
______c
CHzCOOH
PhCOOH
CHZCOOPh
PhOH
P205-Et20
*
PhCH20H
SOCl2
t
62-67%
Org Synth (1963) Coll Vol 4 390 178
90%
Chem Ind (1964) 2102
Ph$HCOOCH2Ph
NH2
NH2
@
~ 8 1 %
PhCOOPh
CHCl3
PhtHCOOH
SECTION 1 0 7
90%
JOC (1965) 30 3575 Annalen (1961) 640 136
MeCHCHZCHzCOOH MeOH
MeCHCH2CHzCOOMe MeCOCl
100%
HO
Org Synth (1955) Coll Vol 3 237
C 1 5 H 3 1 COOH
(CF3C0)20
HOCH2CHCH2
bXb
C 1 5 H 3 1 COOCH2fHFH2
00
x
A p p l i c a b l e t o hindered a c i d s
JCS (1965) 4594 JOC (1965) 2 927
275
ESTERS FROM CARBOXYLIC A C I D S , A C I D H A L I D E S AND ANHYDRIDES
SECTION 1 0 7
1 TsCl
Pyr
2 EtOH
COOEt
* @ J NO2
OMe
90%
JACS (1955) LI_ 6214
OMe 1 ClCOOEt
Et3N
Et20
2 MeOH
OMe
Rev R o m a i n e Chim (1966) (Chem Abs 66 65249) JACS (1958) 5714 (1969) 91 3931
@cooH
MeOH
DCC
Et20
11 1237
COOMe 45%
HO
HO
MeOH
PhCH-CHCOOH
T e t r a h e d r o n (1965) 2 3531 Compt Rend (1963) 256 1804 (1962) 255 945
NN'-carbonyldiimidazole
MeONa
t
PhCH=CHCOOMe
Ber (1962) 1284 JCS C (1969) 1610
Ye
Me I
CH20CONHCHCOOCW2
HOCH20C12H25
,@
@
HC(OCH2Bu-t)2NMe2 o c 1 2H25
83%
CH2C12
OC1 2H25 Helv (1965) JACS (1969)
3
c1 2H25 1746
91 5674
83%
276
COMPENDIUM
( PhO) 2CHCOOH
OF
SECTION 107
ORGANIC SYNTHETIC METHODS
EtOH MezC(0Me)~
t
(Ph0)2CHCOOEt B u l l SOC Chim F r (1964) 381 J O C (1959) 261
2
F u r t h e r examples o f t h e r e a c t i o n RCOOH + ROH --t RCOOR a r e i n c l u d e d i n s e c t i o n 108 ( E s t e r s f r o m A l c o h o l s and Phenols) and s e c t i o n 30A ( P r o t e c t i o n o f Carboxyl i c A c i d s )
MeCHCOOH
MeCHCOOMe
Me1
NaHC03 DMA
HO
t
J O C (1968)
COONa
@
ijl
91 %
2 2143
COOCH2Ph PhCH2C1
EtOH
w
COOCHZPh
COONa
3 Med Chem (1967)
lo 706
84%
2
J O C (1962) 3595 JCS (1966) 1191
C
CH2C00H Et2S04
Na2 33
DMF
88%
*NO2 @cH2cooEt (Applicable t o hindered acids) Monatsh (1968) 2 103 H e l v (1943)
2 2283
277
ESTERS FROM CARBOXYLIC A C I D S , A C I D HALIDES AND ANHYDRIDES
SECTION 107
Et2S04
CH=CHCOOH
CH=CHCOOEt
N-ethyl d i cycl o-
hexylamine
92%
Me2CO OH
OH
(Applicable t o hindered acids) JOC (1964) 29 2490 JACS (1969)-% 3544
PhCOOH
CgH13C1
I
Bu3CCDONa
PhCOOCgH13
+
xyl ene
CH2=CCH2COOH Me
Et3N
1 NaOH H20
CH2=;CH2COOAg rlle
P
2 AgN03
EuOSOCl
CgHg
Bu~CCOOBU
b
C
47%
JOC (1961) j & 5180
Me1 Et20
JACS (1949) (1951) (1952)
JACS (1947)
47%
CH2=qCH2COOMe Me
71 3214
73 5487 fi 3944 82%
69 1046
COOEt
COOEt
(Applicable t o hindered acids)
89%
Chem Ind (1965) 349
COOBu HO
koH
COOEU
PhCOOH
MezNCH(OR)2 CgH6
*
PhCOOR
98% Zh Obshch Khim (1967) (Chem Abs 68 22157)
(R=Me, E t , CH2Ph) Helv (1965)
48
1746
37
1481
80-95%
278
COMPENDIUM OF ORGANIC SYNTHETIC METHODS t -
1 Me3N OH
Et
P
Et
2 200-250"
Et
&
SECTION 107
COOFle Et
63-90%
JACS (1939) 61 1290 Z P h y s i o l Chem (1936) 244 56
69% Tetr Lett (1964) 867
Me2C=CH2 H2S04
CH2( COOH),
CH2( COOBu-t)2 58-60% Org Synth (1963) C o l l Vol 4 261 JOC (1963) 28 1251
t -
PhCONHCHZCOOH
PhCOOH
PhCOOH
(Et0)3P
Et3O BF4 NaHC03 H20
/COOEt NCOOEt Et20
t
*
PhCONHCH2COOEt Tetr Lett (1969) 1819 Ber (1956) 209 2060
PhCOOEt
Bull Chem Soc Jap (1967)
CH2N2 Et20
PhCOOMe
JACS (1954)
76 4481
82%
40 2380
95%
SECTION 107
Ph2CN2
PhCOOH
279
ESTERS FROM CARBOXYLIC A C I D S , A C I D HALIDES AND ANHYDRIDES EtzO
+
PhCOOCHPh2
100% Org S y n t h (1955) C o l l Vol 3 351
see Org S y n t h (1943) C o l l Vol 2 165 and Org React (1942) 1. 50 see J C S (1966) 467
F o r p r e p a r a t i o n o f CH2N2 I!
1,
I,
I,
I,
!
" " 'I
PhCHN2 anthryldiazomethane
1 Pb(0Ac)q C15H31COOH
c
Me2CN2 and Pr2CN2
"
JACS (1964)
I'
Bull Chem Soc J a p (1967)
tetrachloroethane c1 5H31COOC15H31
2 I2
HgO
(PrCH$0)20
J O C (1963)
I2
BrCH$H$r
t
Et
m-Chloroperbenzoic a c i d Pyr
hexane
54%
50%
2 3167
COOYHBu
*
40 691
2 65
PrCHzCOOCtizPr J O C (1970)
BuYHCOCl
658
w73%
c1 J O C (1965) 30 3760 JACS (1950) 67
12
Ph2CHCOOH
E l ec t r o l y s is
HOAc
*
Ph2CHOAc JCS (1952) 3624
37%
COMPENDIUM OF ORGANIC SYNTHETIC METHODS
280 S e c t i o n 108
E s t e r s f r o m A l c o h o l s and Phenols 0
0
0
0
0
0
0
0
~
0
0
0
0
0
0
0
0
0
0
0
~
~
~
~
~
~
~
~
~
-
MeC(OEt)g C H ~ = ~ ( C H ~ ) Z C H = ~ ( COH H~)~ EtCODH Me Me
0
0
P
C H ~ = ~ ( C H Z ) ~ C H = ~ ( C H ~ ) ~> 9 1 %
Me Me JACS (1970) 92 741 Chem Comm (1970) 1512 1513
OH ?H
*
naphthalene-2-sulfonic a c i d
Me#
I
(CH2)2COOEt
?H ?H C8Hl7CH-CH( CH2)7COOH
Me
~
. . page 280 . . . 280-283 . . . . . . . . . . 283-284 . . . . . . . . . . . . . . . . . . . , 284-286 . .. ... . . . , 286
O r t h o e s t e r C l a i s e n rearrangement o f a l l y l i c a l c o h o l s . Esters by r e a c t i o n o f alcohols w i t h c a r b o x y l i c acids, a n h y d r i d e s and a c i d h a l i d e s , Preparation o f formate esters o f alcohols , F l i s c e l laneous methods , Oxidation o f alcohols t o esters , , , , , ,
C6H130H
SECTION 108
C8H,7~H-CH(CH2)7CooC6Hi~ JACS (1945) 67 902 Rec Trav Chim (1951)
3 277
COCl
* Me
Me
Annalen (1969)
JCS
C (1969)
726 216
2115
87-93% Org S y n t h (1941) C o l l Vol 1 285 JOC (1965) 2 3480
0' OH
281
ESTERS FROM ALCOHOLS AND PHENOLS
SECTION 108
(EtC0)20
Pyr
EtCOO
*
60%
NMe2
NMe2 J Med Chem (1970)
0OH
Ac20
13 125
OAc
H2SO4
96-98%
bH
OAc Org Synth (1955) Coll Vol 3 452
Ac20
HC104 JOC (1966)
2 324
@;;I:
Ye
ye
PhyOH
Phthalic anhydride
Et3N
Et
JCS (1957) 3148
@Me2
( Y O H
Ac20
Et3N
+
OOAC
Angew (1969)
(Internat Ed
t-BuOH
EtCOCl
PhNMe2 Et2O
*
81 1001 8 981)
EtCOOBu-t JACS (1943) 65 986 Helv (1944) 27 513 JCS (1952) 4883
86%
SECTION 108
COMPENDIUM OF ORGANIC SYNTHETIC METHODS
282
t-BuOH
MeCOCl
tetramethylurea
*
t-BuOAc
EtpO
Et3COH
50-60%
T e t r L e t t (1967) 3267
1 BuLi
THF
2 PhCOCl
94%
PhCOOCEt3
S 1198 28 582
J O C (1970)
E s t e r s f r o m a l c o h o l s , Ph3CNa and (RC0)20 J O C (1963) II
I,
,I
EtMgBr
It
I,
$8
K
I
I,
I,
CaC2
I,
I,
Mg
I,
I,
Na H
I,
"
"
$1
,I
"
"
and RCOCl "
3,5-Dinitrobenzoic a c i d C12H250H
TsCl
Pyr
"
*
JACS (1936) 1384 JCS (1963) 3578 JACS (1961)
423
blonatsh (1966)
62
Org Synth (1955) C o l l Vol 3 144 Chem Corn (1967) 259
N02@c00c1
2H25
82%
(Applicable t o hindered alcohols) JACS (1955) LI. 6214 (1963) 2446 PhOH
PhCOOH
(CF3CO)zO w
70%
PhCOOPh
( A p p l i c a b l e t o h i n d e r e d a l c o h o l s and p h e n o l s ) T e t r a h e d r o n (1965) 2 1 3531 T e t r L e t t (1964) 1 2 E JCS (1965) 4594 F o r s e l e c t i v e e s t e r i f i c a t i o n o f Pry-OH i n t h e presence o f l r y - O H see J O C (1961) 177
a
JACS (1969) (1958)
91 3931 5714
SECTION 108 PhCOOH DCC
PhOH
283
ESTERS FROM ALCOHOLS AND PHENOLS Et20
*
PhCOOPh T e t r a h e d r o n (1965) 2 3531 Compt Rend (1963) 256 1804 945 (1962)
255
PhCH20H
PhCOOH N,N'-carbonyl d i i m i d a z o l e
*
PhCOOCH2Ph
Ber (1962) 95 1284 J C S C (1969) 1610
F u r t h e r examples o f t h e r e a c t i o n ROH i.RCOOH --t RCOOR a r e i n c l u d e d i n s e c t i o n 107 ( E s t e r s f r o m C a r b o x y l i c Acids, A c i d H a l i d e s and Anhydrides) and s e c t i o n 45A ( P r o t e c t i o n o f A l c o h o l s and Phenols)
MeCHCH2CH2COOMe
@OH
HCOOH
HO\'''
HCOOi''
&
91 %
JACS (1954) 76 4915 (1945)
OH
Me2C=CH(CH2)2C=CH(CH2)&CH=CH2 I Me
Me
& 0
-
67
HCOOH
Ac20
740
HCO?
Me2C=CH(CH2)2~=CH(CH2)2~CH=CH2
Me
Me
Bull SOC Chim F r (1965) 484 Rec Trav Chim (1964) 83 1287 1294
TsC1-DMF
___L
1 5
Chem Comm (1965) 413 JACS (1958) 02906 Coll Czech (1961) 1723
79%
284
SECTION 108
COMPENDIUM OF ORGANIC SYNTHETIC METHODS HCOF
C8H170H
Et3N
Et20
*
HCOOCgH17
73%
JACS (1960) I)_z. 2380
Me
PhCH20CONH~HCOOCH2COOCH2
I?'
Me
Me
PhCH2OCONHCHCOOeNO2
Me
Imidazole
t
Me
Chem Ind (1967) 1960
COOMe
t-BUOH
Me@Me Me
@
COOMe
4
COOBu-t
t-BuOK
molecular s i e v e s CgH6
Me(CH2)7CH=CH(CH2)7CH20H
EtOAc
COOBu-t Chem Ind (1966) 1622
MeONa
t
Me(CH2)7CH=CH(CH,)7CH~OAc
Lipids (1967) 2 437 JACS (1956) 78 6347
JACS (1956)
2 6322
Me
Me
SECTION 108
ESTERS FROM ALCOHOLS AND PHENOLS
285
59% J Fled Chem (1969)
t
EtOH
12 563
-
MeCO SbF6 MeCN
*
EtOAc
(Applicable t o hindered alcohols)
84
JACS (1962) 2733 Gazz (1967) 2 442 (Chem Abs 67 117049)
95% I
I
Me
Me (Appl i c a b l e t o h i n d e r e d a1 co h o l s )
J Med Chem (1969) 12 432 J O C (1968) 33 3695Org React (1946) 2 108
For p r e p a r a t i o n o f CH2=CO see
,coo,
Me2C,CO0,C=CMe2 t-BuOH
K2CO3
*
MeZCHCOOBu-t
95%
Angew (1963) ( I n t e r n a t Ed
HOCH2
MeCN *
7s 8 4 1
2 608)
w91%
HOCH2 @OAC JACS (1969)
91 2162
286
BuOH
COMPENDIUM OF ORGANIC SYNTHETIC METHODS
QoAc
*
BuOAc
31 864
B u l l Chem SOC J a p (1964) Chem Ind (1965) 1498
( EtC0)2NH
HO
SECTION 108
HBr
85%
b
t o 1 uene
EtCOO
R o c z n i k i Chem (1952) (Chem Abs 49 2464)
0 1
93%
692
BuqNOAc
HO
TsO
MezCO
JCS (1969) 1605
i-PrCH2CH20H
t-Butylhypochlorite
CC14
*
i-PrCH2COOCH2CH2Pr-i
Helv (1953)
PrCH20H
NazCt-207 H2SO4 H20
+
AcO~"'
PrCOOCHZPr
89%
5 1763
41 -47%
Org S y n t h (1941) C o l l Vol 1 138
SECTION 109
ESTERS FROM ALDEHYDES
S e c t i o n 109
287
E s t e r s o t r o m Aldehydes 0000000000000
0 0 0 0 0 0
Me
NaCN Mn02
MezC=CH( CH2)2L=CHCHO
HOAc
MeOH
*
Ye
MezC=CH( CH2)2C=CHCOOMe
( A p p l i c a b l e t o u n s a t u r a t e d and a r o m a t i c aldehydes o n l y ) JACS (1968) 90 5616 Ber (1970) 3774
PrCHO
--*
PhCHO
MeC002H
PrCH(OEt)*
MeOH
(NH4)2S208
H2SO4
*
-
H2SO4
PrCOOEt J O C (1960)
PhCOOMe J O C (1968)
C7H15CHO
--+
-
hr/ Me2CO C ~ H ~ C ~ C H / ~ ~ 0' t-BuOH
3 1699
100%
2 2525
C7H15COOEt
T e t r L e t t (1963) 2189
C5H11CH2CHO
1 S02C12 2 NaI
CH2C12
Me2CO
*
C5H11CHCHO
f
EtOH
Ag'
C5H11CH2COOEt
Et20
T e t r L e t t (1968) 4415 JACS (1954) 76 2695
288
COMPENDIUM OF ORGANIC SYNTHETIC METHODS
SECTION 110
51 %
PrCHO
PhCHO
A1 (OEt ) 3
PrCOOCHzPr
NaH CgHg
J A C S (1947)
69 2605
JACS ( 1 9 4 6 )
68 2 6 4 7
92%
PhCOOCH2Ph
F o r examples o f t h e r e a c t i o n RCHO -+ HCOOR see page 84 ( S e c t i o n 34, A l c o h o l s and Phenols f r o m Aldehydes) E s t e r s may a l s o be prepared by o x i d a t i o n o f aldehydes t o c a r b o x y l i c a c i d s f o l l o w e d by e s t e r i f i c a t i o n . See s e c t i o n 19 ( C a r b o x y l i c Acids and A c i d Hal i d e s f r o m Aldehydes)
S e c t i o n 110
81 %
E s t e r s f r o m A l k y l s , blethylenes and A r y l s
o o D o o D o D o o o o D o o o o o a o o o a ~ o ~ o ~ ~ o o ~ ~ ~ o ~ o o o ~
No examples o f t h e r e a c t i o n RR -+ RCOOR' o r R ' C O O R ( R = a l k y l , a r y l e t c . ) o c c u r i n t h e l i t e r a t u r e . F o r t h e r e a c t i o n RH -+ RCOOR' o r R ' C O O R see s e c t i o n 116 ( E s t e r s f r o m H y d r i d e s )
SECTION 111
ESTERS FROM AMIDES
S e c t i o n 111
PhCONH2
289
E s t e r s f r o m Amides
000000000000000000
MeOH
BF3
105'
PhCOOMe
6 'ONH2
PhCONH2
EtOH
Me
GJcooit
HC1
CQH17Br 1i20
w
J O C (1960) 2 560 Arch Pharm (1957) J O C (1970) 35 125
PhCOOCgH17
170"
MeCONHBu
No2@coNHBu
J O C (1969)
1 HNO3 Ac20 2 CC14
100% Chem Comm (1969) 414
77"
w
MeCOOBu
1 NaN02 Ac20
34
290
85%
218
79% 3204
JACS (1955) 77 6011 J O C (1969) 2 3834
75%
COOBu 83%
2 Hexane r e f l u x NO? JACS (1955) 77 6008 6011 (1954) 2 4497 T e t r L e t t (1965) 2627
JCS (1965) 181
COMPENDIUM OF ORGANIC SYNTHETIC METHODS
290 S e c t i o n 112
BuNH2
E s t e r s f r o m Amines
000000000000000000
Ac20
HOAc
BuNHAc
1 NaN02 2 Hexane
NaN02
* BuOAc reflux JACS (1955) 6008 6011 (1954) 76 4497 JOC (1969) 3834 Chem Pharm B u l l (1960) 8 266
11 2
\
t
rearranged acetate
35%
T e t r L e t t (1968) 5145 T e t r a h e d r o n (1970) 2 147
-
Br
Br
JACS (1939) (1933)
p-Chlorobenzenediazonium hexafluorophosphate
83%
QOAc
18%
t
Br
Ac20
HOAc
@NH2 COOMe
BuNH:,
SECTION 112
*
DMF
BuN=NNH
61 143 55 4954
3,5-Dini t r o -
*
COOBu
benzoic a c i d
@)'
NO2
Cl T e t r L e t t (1961) 758
B u l l SOC Chim F r (1914)
63%
162
NO2
SECTION 113
ESTERS FROM ESTERS
S e c t i o n 113
291
Esters from Esters 000000000000000000
........ ...... ..... ..,.. ............... ...
A l k y l a t i o n and h o m o l o g a t i o n o f e s t e r s . . E s t e r exchange Epimerization o f esters E s t e r s o f monobasic a c i d s f r o m malonate e s t e r s I
BuBr
PhCH2COOBu-t
Me2CHCOOEt
NaH
MeCH2COOBu-t
C16H33CH2COOMe
t
1 NaNH2 NH3
2 PhBr
66%
58%
JACS (1940)
peroxide
2457
38%
Ph
J A C S (1959)
t
1627
C16H33FHCOOMe i- p r ( CH2)3yH( CH2)2 Me J Amer Oil Chem SOC (1968) (Chem Abs
1 Me2SOCH2 THF
62
MeFHCOOBu-t
Me i-Pr(CH2)&HCH=CH2
t -
291 292 293 293
Me2yCOOEt Et
di-t-butyl
. page , . . ... ...
30 2937 2 2990
J O C (1965) (1964)
BU
Et20
2 EtI
I
. . . .
PhyHCOOBu-t
monogl yme
1 Ph3CNa
. . .
2 3210)
42%
5 453
CH2COOMe
2 h v MeOH JACS (1964)
1640
F u r t h e r examples o f t h e a l k y l a t i o n and h o m o l o g a t i o n o f c a r b o x y l i c a c i d s and e s t e r s a r e i n c l u d e d i n s e c t i o n 17 ( C a r b o x y l i c A c i d s , A c i d H a l i d e s and Anhydrides f r o m C a r b o x y l i c A c i d s and A c i d H a l i d e s ) and s e c t i o n 107 ( E s t e r s f r o m C a r b o x y l i c A c i d s , A c i d H a l i d e s and A n h y d r i d e s )
S E C T I O N 113
COMPENDIUM OF ORGANIC S Y N T H E T I C METHODS
292
COOMe
@
-Q COOBu-t
t-BuOK
m o l e c u l a r sieves
t-BuOH
CgHg
> 90%
COOBu-t Chem Ind (1966) 1622
COOMe
I o n exch r e s i n ( b a s i c )
C17H35COOEt
*
MeOH
JOC (1969)
c1 O H 2 1 0 H
CH2=CHCOOMe
H2S04
*
80-90%
C17H35COOMe
2 2032
CH2=CHCOOCioH21
83%
JACS (1944) 66 1203 Org Synth (1955) C o l l Vol 3 146 605
RCOOBu
PhCOOBu-t
HBr
Et20
MeOH
r e f 1 ux
RCOOEt
PhCOOMe
PhCH2NMe2
3 Pharm S c i (1969)
JACS (1941)
58
63 3382
170'
949
62%
65%
JACS (1952)
74 547
SECTION 114 OAc
ESTERS
EtCH(COOEt)2
ETHERS
HgBr2 hJ
Me
470'
293
QAc
Me
PhCH(COOEt)2
FROM
JACS (1970)
PhCH2COOEt
NaCN Me2SO
J O C (1964)
92
29
1094
1249
EtCH2COOEt
36%
80% T e t r L e t t (1967) 215
Section 114 PhCH20Bu- t
PrCH20Bu
PrCH2OBu
Esters from Eth:rs
dOODDOOOODDOOOO
03 Freon 1 1
*
PhCooBu-t
Trichloroisocyanuric acid
JACS (1968) 90 6777 Annalen (1929) 476 233
H20
*
PrCOOBu
62%
100%
T e t r L e t t (1968) 5819
RuO4
CCl4
PrCOOBu
100% JACS (1958)
6682
COMPENOIUM OF ORGANIC SYNTHETIC METHODS
294
SECTION 1 1 4
4 8 % (R=H) 9% (R=Me) Chem Corn (1966) 752
CH2=CH( CH2) 3CH=CHCH20Ph
PdCl2( Ph3P)z
CH2=CH( CH2)3CH=CHCH20AC
_____+
HOAc
Chem Corn (1970) 1392
70%
BU20
TsOAc
MeCN
*
BuOAc
JACS (1968)
90 3878
BF3.EtzO Me0
AcpO
50%
93% AcO
J O C (1965) 2 1734 Chem Rev (1954) 54 615
SECTION 115
ESTERS FROM HALIDES AND SULFONATES HOAc
BUOBu-t
S e c t i o n 115
PrBr
BuBr
PhBr
1 Mg
TsOH
BuOAC
Tetr L e t t ( 1 9 7 0 ) 4269
0000000000000000000000000000000000
-
Et20
PrC=CHCH2COOEt
he
1 Mg E t 2 0
2 CdC12
1 Li
Me
2 CuBr
Me
@
2
EtOH
PrCHCH2CH2COOEt 1
Me
66
1764
~60%
Org Synth ( 1 9 6 1 )
41 6 0
53% JOC ( 1 9 6 8 )
2
1675
PhCH2COOEt
b
51 % Chem Corn ( 1 9 6 9 ) 515
3 N2CHCOOEt
1 Li
Pt02
PhCH2COOEt
t
Et20
H2
BuFHCH2COOBu-s
--t
2 MeCH=CHCOOBu-s
THF
-
JACS ( 1 9 4 4 )
3 BrCH2COOEt
PhBr
94%
E s t e r s f r o m H a l i d e s and S u l f o n a t e s
2 MeCOCH2CH2COOEt CgH6 3 soc12 4 185-195"
1 Mg
295
Et2O
dH
MeS03H
3 BrCH2COOEt t-BuOK t-BuOH
*
73% Me @cH*cooEt JACS (1969)
91 4304
COMPENDIUM OF ORGANIC SYNTHETIC METHODS
296
Ye
Ye
EtCHCOOEt NaH
BuBr
*
diglyme
SECTION 115
38%
BuCCOOEt I
Et
J O C (1964)
29
2990
F u r t h e r examples o f t h e a l k y l a t i o n o f e s t e r s w i t h h a l i d e s a r e i n c l u d e d i n s e c t i o n 113 ( E s t e r s f r o m E s t e r s )
CH3COOEt
PhBr
EtI
NaNH2
Cti2 ( C O O E t ) 2
---_-------+
NH3
42%
PhCH2COOEt JACS (1959)
t
E t C H ( COOEt)2
1627
NaCN Me2SO
*
EtCH2COOEt
T e t r Lett (1967) 215
MeCOCH2COOEt C10H21Br
EtONa
EtOH
C1 OH21CHCOOEt MedO
EtONa EtOH
J O C (1962)
C1 OH21CH2COOEt
27
84%
622
COOEt
1 Mg
Et2O
68-73% Org S y n t h (1943) C o l l Vol 2 282
ocl- 0
COOEt
2 C(OEt)4
Ber (1905)
2 561
SECTION 1 1 5
PhBr
ESTERS FROM H A L I D E S AND SULFONATES
1 Mg
Et20
2 ClCOOEt
N i (C0)4 C7H15*
t-BuOH
N i (C0)4
RBr
t-BuOK
MeONa
*
MeOH
PhCOOEt
36
Ber (1903)
*
C7H1 ~ C O O B U - t JACS (1969) (1963)
NaOAc
75% 3087
91
1233 2779
66%
88% ( R = P h ) 95% (R= PhCH=CH)
RCOOMe JACS (1969)
CH2C1
297
91 1233
HOAc @fH2OAC NO2 O r g S y n t h (1955) C o l l Vol 3 650 Ber (1956) 1732
CH20Ms H
NHCOPh O o
e
NHCOPh
NaOAc
DMF*
""OMe NHCOPh
NHCOPh
Ber (1970)
JACS (1951) (1949)
103 37
73 5487
2 3214
298
COMPENDIUM COOMe
'
AgOAc
OF ORGANIC SYNTHETIC METHODS
'0 COOMe
HOAc
O M O B r
OAc
0
T e t r a h e d r o n (1968) Ber (1964) 97 443
Meo MeqNOAc
Me2CO
J A C S (1955)
(1967)
JCS
Bu I
MeC002H
1 4 0 - 1 60"
HOAc
xylene
2 5421
76%
*
Me@ 6 r
SECTION 115
C
77 4042
2758
(1969) 1605
79%
phcoQMe J A C S (1966)
4521
BuOAc
78% J O C (1969)
34 3974
SECTION 116 S e c t i o n 116
299
ESTERS FROM HYDRIDES (RH) E s t e r s f r o m H y d r i d e s (RH)
P
T h i s s e c t i o n c o n t a i n s examples o f t h e r e a c t i o n RH 3 RCOOR' or R ' C O O R ( R = a l k y l , a l l y l , v i n y l , a r y l e t c . ) and A r H -+A r - X - C O O R ( X = a l k y l c h a i n )
Me CH2=CH(CH2)2COOEt
Me
PhH
CH( CH2)2COOEt
AlC13
81 %
18 1499 T e t r a h e d r o n (1967)
JOC (1953)
C1 CH2CH2COOEt A1 C13
+
3 2481
PhCH2CHzCOOEt
68%
Dokl (1945) 257 (Chem Abs 2 4638)
PhH
PhCHxCH2
PhCH=CH2
C1 COOPh A1 C13
*
Electrolysis MeONa
CO (70 kg/cm2)
MeOH
1 PdC12 2 CO
PhCooPh
JOC (1957)
*
64%
22 325
PhCH=CHCOOMe
Bull Chem SOC Jap (1965) J A C S (1965) 3525
+
Et3N MeOH
38
2122
41 %
PhCH=CHCOOMe J O C (1969)
@
co ( O E t ) 2
CH2L i
2
738
@
CH2COOEt
JACS (1953)
75 3843
44%
300
0 0
0
COMPENDIUM OF ORGANIC SYNTHETIC METHODS C1 C O O E t
hV
-
SECTION 116
COOEt
15% Bull Chem SOC J a p (1966)
Pb (OAc l4
hV
2 2463
24%
HOAc Nature (1966)
a
D i isopropyl peroxydicarbonate
209
395
OCOOPr- i
JCS (1965) 1932
PhC002Bu-t PhCOO Proc Chem SOC (1962) 6 3 JACS (1958) 756
-
MeCO02Bu t
c u p r ic
3 , 3 , 5 - t r i m e t h y l hexanoate
*
Hg(0Ac)Z
HOAc
G””
JACS (1962)
65%
84 4969
774
QoAc
Annalen (1953)
581 59
S E C T I O N 116
ESTERS FROM HYDRIDES (RH)
Se02
EtCHzCHCH3
301
Ac20 T e t r a h e d r o n (1964) 20 1017 Org React (1949) 2 Bl
Pd (OAc )
EtCHCHzCH2 I
OAc
88
JACS (1966)
Electrolysis
C5H11 CHzCH=CH2
HOAc
Et4NTs
*
2054
C5H11eHCH=CH2 OAc T e t r L e t t (1968) 6207
PhCH3
D i - t - b u t y l peroxide
RCOOCH2Ph
(PhC00)2C~ RCOOH
(R=Ph, Me)
Proc Chem Soc (1962) 63
90% J O C (1966)
CH3
Pb(OAc)4
HOAc
*
+ 90
QCH2OAc
JACS (1968)
Diisopropyl peroxydicarbonate ph
CuC12
MeCN
2 2033
?-
1082
@zPh
J O C (1969)
OCOOPr
34
3302
86%
302
SECTION 117
COMPENDIUM OF ORGANIC SYNTHETIC METHODS
Me Benzoyl p e r o x i d e
*
PhCOO B u l l Chem SOC J a p (1969) 42 2733 Rec T r a v Chim (1927)
a Sa
S e c t i o n 117
Ph2CO
E s t e r s f r o m Ketones
0000000000000000000
---+
Ph2CO
N2H4
PhCOMe
EtCHCOPr I Me
Ph2CHCOMe
Ni(CO)q
Ph2CN2
EtOH
EtOH
Br2
c12
---+
*
Pb(OAc)4
*
I Me
Ph2CHOAc
b
CgHg
Br
93 1840
CH2C12
JCS
EtCCOPr
74%
Ph2CHCOOEt
Ber (1960)
Ph2CzNNH2
PhgSnH MeCOCl
-
CO
C
(1970)
1033
PhFHOAc
rie
MeONa Et20
100%
JACS (1966)
1833 4970
Pr I
EtCCOOMe
44%
I
Me
64
JACS (1942) 300 Org R e a c t (1960)
Ph2CCOMe L1
EtONa
EtOH
43%
261
Ph2CHCH2COOEt Org R e a c t (1960)
11 261
SECTION 1 1 7
ESTERS FROM KETONES
303
* m COOMe
MeOH
KOCl
OMe
OMe JACS (1944)
1 i-PrCH20NO
HC1
2 NaOH Me2SO4
H20*
66
208
rnCOOMe
Compt Rend (1942)
Et2CO
H202
(CF$O)20
Na2HP04
i-PrCH2COMe
*
CH2C12
214
113
EtCOOEt
78% JACS (1955)
HOOCCH=CHC020H CH2C12
PhC002H
80%
+
2287
i-PrCH20Ac T e t r a h e d r o n (1962)
g 31
CHC13
72%
67%
JACS (1949) 14 Org React (1957) 9 73 F o r use o f rn-chloroperbenzoic a c i d see JACS (1967) 89 4530 and J O C (1964) c 2 9 1 4
62% J O C (1962)
2 24
COMPENDIUM OF ORGANIC SYNTHETIC METHODS
304
:OH (CF3)zCOH CH2C12
C5H11 COMe
C5lii 1OAc
*
PhN02
SECTION 118
81%
Tetr Lett ( 1 9 7 0 ) 2 7 4 1
Esters may also be prepared by conversion of ketones into carboxylic acids followed by esterification. See section 27 (Carboxylic Acids from Ketones)
Section 118
PhCH2CN
Esters from Nitriles 00000000000000000000
C7H150H TsOH
PhCH2COOC7H15
t
J O C (1958) (1960)
PhCH2CN
PhCH2CN
CH2zCHCN
EtOH H20 H2SO4
PhCH2COOEt
b
70%
23 1225 25 560
83-87%
Org Synth ( 1 9 4 1 ) C o l l V o l 1 2 7 0
HOCH2CH20H
____t
PhCH2COOCH2CH20H
JCS ( 1 9 6 3 ) 2 4 1 7
Ph3P=CHCOOEt C6H6
*
CH2=CHCOOEt
Tetr Lett ( 1 9 6 7 ) 2 4 0 7
Esters may also be prepared by hydrolysis of nitriles to carboxylic acids followed by esterification. See section 28 (Carboxylic Acids from Nitriles)
SECTION 119 S e c t i o n 119
ESTERS FROM OLEFINS
305
E s t e r s from O l e f i n s 0000000000000000000
1 B2Hg
THF
CH2COOEt
2 BrCH2COOEt
THF
75%
potassium di-t-butylphenoxide J A C S (1969) (1968)
BuCH=CH2
1 B2Hg
THF
2 N2CHCOOEt
1 B2Hg
*
THF
t-
91 6855
2146 818 1911
Bu( CH2)3COOEt J A C S (1968)
b
2 Me2SCHCOOEt
90 6891
C5H11 (CH2)3COOEt J A C S (1967)
83%
45% 6804
CH3COO-C) d i - t - b u t y l peroxide
CtjH13(CH2)3C00
59%
J C S (1965) 1918
Ni(C0)4 HOAC
EtOH 72%
H20 J C S (1963) 410
12%
COMPENDIUM OF O R G A N I C SYNTHETIC METHODS
306
0
CH=CH2
CO
SECTION 119
(Ph3P)2PdC12
MeOH Angew (1968) ( I n t e r n a t Ed
HCOOH
HClO4
80
352
7 329)
Hcooo
69%
JACS (1953) 75 6212 Org Synth (1965) 5 7 4
(I M e ooAc Me
JACS (1967)
5199
50%
Can J Chem (1965)
43 319
E s t e r s may a l s o be p r e p a r e d by c o n v e r s i o n o f o l e f i n s i n t o c a r b o x y l i c a c i d s o r a l c o h o l s f o l l o w e d by e s t e r i f i c a t i o n . See s e c t i o n 29 ( C a r b o x y l i c A c i d s f r o m O l e f i n s ) and s e c t i o n 44 ( A l c o h o l s f r o m O l e f i n s )
SECTION 120
ESTERS FROM MISCELLANEOUS COMPOUNDS
S e c t i o n 120
307
E s t e r s f r o m M i s c e l l a n e o u s Compounds
000000000000000000000OOOOOD000~~00~~0~0
OMe
OMe J C S (1936) 192 JACS (1962) 4951
PhCH=CHCOOCH2Ph
H2
(Ph-jP)-jRhCl
*
PhCH2CH2COOCH2Ph Compt Rend (1966)
Ph3SnH
Me$=CHCOOEt
hV MeOH
65%
263
Me2CHCH2COOEt
251
40%
T e t r L e t t (1967) 4805
TJCOOK PhCH=CHCOOMe
NCOOK
Pyr
HOAc
*
PhCH2CH2COOMe JOC (1965)
30
96% 3985
!COOK
NCOOK
PhCH=CHOAc
dioxane
HOAc
*
PhCH2CH20Ac J O C (1965)
OAc
@hHCooMe Me0
tiiAcPd
H2SO4
*
@
Me0
30
50%
3985
CH2CooMe
Ber (1941) 748 315 Org React (1953) 1 2 6 3
308
ClCHZCOOPr-i
COMPENDIUM OF ORGANIC S Y N T H E T I C METHODS
Mg
1 PhNH2 PhCH=CHCHO
2 NaOH
i-PrOH
NaCN MeOH
SECTION 1 2 0
MeCOOPr-i
63%
Proc Chem SOC (1963) 219
?Me
*
PhCHzCHzC=NPh
---t PhCH2CH2COOMe
Chem Comm (1967) 1290 Chem Ind (1967) 5 8 3
Compendium of Organic Synthetic Methods, Volume 1 Edited by Ian T. Harrison, Shuyen Harrison Copyright 0 1971 by John Wiley & Sons, Inc.
Chapter 9
PREPARATION
OF
ETHERS AND EPOXIDES
Section 121
Ethers and Epoxides from Acetylenes
00000000000000000000000000000000000
No examples
Section 122 YOOMe CH2CHCH2COOH I Me
Ethers from Carboxylic Acids
~
~
~
~
~
~
O
0O0 0O0 0 O 000 O 0 0~0 0O0 0 O
Electrolysis MeO(CH2)2COOH
*
MeONa MeOH
YOoMe CH2yHCH2(CH2 )20Me Me
J C S (1956) 1620
Advances i n O r g Chem (1960) _1. 1
El ec trol ys is
MeONa MeOH
J O C (1962) 27 4689 (1960) 25 136 JACS (1960) 82 2645
309
31 0
COMPENDIUM OF ORGANIC SYNTHETIC METHODS
i t 2 e r - s f r o m A l c o h o l s and Phenols
S e c t i o n 123
0
0
0
0
0
0
0
0
~
0
0
0
0
0
~
0
0
0
0
0
~
~
~
~
~
SECTION 123
~
~
~
~
. . . . . . . . . . . . . . . . . . . page ......................
Ethers from alcohols E t h e r s f r o m phenols C y c l i c e t h e r s f r o m a l c o h o l s and d i o l s
.............
310-312 312-315 315-316
F o r t h e p r e p a r a t i o n o f a l l y l , t - b u t y l , methoxymethyl, t e t r a h y d r o p y r a n y l and t r i p h e n y l m e t h y l e t h e r s see s e c t i o n 45A ( P r o t e c t i o n o f A l c o h o l s and Phenols)
-
iooEt Ag20 E t I
MeCHOH
YOOEt MeCHOEt JACS (1932) 54 3732 JCS (1959) 2594
CH20H HO@H
Me1 Ag20
CH20Me
DMF *
Me0QMe NHAc
NHAc
Angew (1955) 67 32 JCS (1969) 2372 Can J Chem (1963) 5 1801
Me1
BaO
DMSO
*
a. k0
Gp; Oph
59%
JCS (1967) 2681
HO
2 BNaH U I DMF
BuO
Carbohydrate Res (1966) 2 167 Can J Chem (1966) fi 1 5 9 2
97%
SECTION 1 2 3
0
ETHERS FROM ALCOHOLS AND PHENOLS Me1
Et
NaH 91 %
CH20H
Me2COH
31 1
MeOCH2CHzOMe *
O C H Z O M e
fi 1591
Can J Chem (1966)
1 RMgBr
HMPA
2 EtBr
MezCOEt
c
Et
1 K
*
EtO
Dl
J O C (1961)
NaNHz
C 266
Compt Rend (1968)
toluene
2 EtI
HO
40%
26
~ 4 1 % 3
3
41 %
Et20 J O C (1958)
O ,Hfz PhCH
23
1700
yHOC18H37
O ‘ CHz J O C (1959) (1966)
99%
2
409
31 498
Ph MeOH I
CHZPh
1178
HzSO4
I
CH2Ph
T e t r a h e d r o n (1961) J bled Chem (1965)
16 85
8
57
312
HC(OMe)3
HC104
52%
Me0
HO
S
S t e r o i d s (1966)
C8H1 7 0 H
SECTION 123
COMPENDIUM OF ORGANIC SYNTHETIC METHODS
CHzN2
HBF4
Et2O
*
495
CgH17OMe T e t r a h e d r o n (1959) 5 36 Annalen (1963) 662 38 (1964) 55
84%
677
+DlNaBH4
HO
HCOO
J O C (1961)
(1962)
PhOH
PhOH
1 NaNH2
NH3
2 C5H11Br
PhCH2C1 1 5 0 - 1 90"
*
PhOC5H11 JACS (1935)
Et3N
*
Me0
2 1685 27 2127
57
45% 510
PhOCH2Ph
46% JOC
(1961)
26
5180
ETHERS FROM ALCOHOLS AND PHENOLS
S E C T I O N 123
@'i2
BuBr
K2C03
31 3
Me2CO
75-80%
Org Synth (1955) Coll Vol 3 140 418 Tetr Lett (1964) 1431 JACS (1950) 3 3396
Me I
PhOH
PhOH
PhOH
BuCHOTs
Me2S04
PrBr
KOH
DMF
+
NaOH
NaOH
H20
*
H20 w
Me I PhOCHBu
JACS (1969) 91 1376
PhOMe
72-75% Org Synth (1941) Coll Vol 1 58
63%
PhOPr JACS (1947)
&
CH2N2
69
2451
Et20 MeOHt
Me
Me OMe
OH
JACS (1950) (1962)
CH2N2 Ph.
38%
HBF4
3 3396 2972
CH2C12
*
Ph
@OMe
Tetrahedron (1959) 36 Annalen (1963) 662 38
41 %
S E C T I O N 123
COMPENDIUM OF ORGANIC S Y N T H E T I C METHODS
314
OH
MeOH
TsOH
100'
70% J O C (1960)
OH
EtOH
832
i o n exch r e s i n ( a c i d )
HOCH2
HOCH2
37%
@OEt
J O C (1962)
2662
moH t -
Me2SOCH2
7 7%
~
T e t r L e t t (1964) 857
t -
PhOH
M e 3 0 BF4
PhOFle
---+
Me*
i- P r C H Z
OMe OH
0
Ph+ N M e 3 O- E t
Mcd2 OMe
J P r a k t Chem (1937)
M
e i-PrCH2
N
p
147 257
1:
73%
53%
A 0
JACS (1953)
75 3632
A c t a Chem Scand (1956)
2
1006
85%
SECTION 123
ETHERS FROM ALCOHOLS A N D PHENOLS
Me
Me
31 5 87% (R=Me) 90% (RzCH2Ph)
Ber (1962) 95 2997 377 Angew (1963) ( I n t e r n a t Ed 2 218)
75
PhOH
HC( OCH2Ph ) 2NMe2
t
PhOCH2Ph Angew (1963) ( I n t e r n a t Ed
PhNH @OH
dioxane
@ocH=cH2
H2
64%
75 296
1. 211)
Nib
PhNH
PhNH Zh Obshch Khim (1964) (Chem Abs 62 2727)
34
3424
81 % JCS (1965) 4953 Chem Rev (1946)
PhOH
Di-p-tolyliodonium
NaOH H20
38
405
bromide
*
"'@Me
86%
JCS (1963) 4578
37% Tetr L e t t (1963) 2091 S y n t h e s i s (1970) 209
COMPENDIUM OF O R G A N I C SYNTHETIC METHODS
31 6
pentane
86 3905
JXCS (1964)
Ho;HJ ' (
CH OH
a:,,
Me2S0.
SECTION 124
1528
66%
CH2/ 0
J O C (1963)
S e c t i o n 124
28
1388
E t h e r s and Epoxides f r o m Aldehydes
aoooooooaoDooooooooooooooooooD0006
. . . . . . . . . . . . . . . . . . .page ....................
E t h e r s f r o m aldehydes Epoxides f r o m aldehydes
Pr2NCH2CH0
--+
PrzNCH$H(OMe)z
PhMgBr
xyl ene
PrZNCH2tHOMe
--*
i-PrCH2CH0
PrCH(OEt)2
--+
LiA1H4 Et2O
i-PrCH2CH(OEt)2
AlC13
+
--+
PhCH(0Et)Z
Et3SiH
73 4893
PrCH20Et
49%
JACS (1962) 2371 J O C (1958) 2 1088
(i-Bu)ZAlH
C6H6
PhCHO
65%
Ph
JACS (1951)
PrCHO
316-317 317-318
ZnC12
*
i-PrCH2CH20Et
I z v (1959) 2255 (Chem Abs 54 10837)
PhCti20Et
Compt Rend (1962)
254 1814
83%
S E C T I O N 124 Hp
i-PrCHO
Pt02
HC1
*
MeOH
PhCHO
31 7
ETHERS AND E P O X I D E S FROM ALDEHYDES
JCS (1963) 5598
(3200 p s i )
H2
i-PrCHpOMe
CO
t
c02co8
43%
PhCH20CHzPh JACS (1950)
12. 4375
0:: @c::@ 0
(MezN)$
50-55%
~
Org S y n t h (1966) 5 31 JACS (1963) 2 1884
BCHo
0
t-
Ph2SCHR THF
NO2
NO2 JACS (1964)
t
PhCHO
@fJCHR
-
Me3SO I
NaH
/ \
*
PhCHCH2
56%
JACS (1965)
-
@
c1
CHo
Me2SO
87 1353
0
P h f O M e BF4 NMe2
a 918
0
Me2SO
t
72% ( R = P h ) 40% (R=Bu)
NaH
74%
c1 JACS (1970)
92 6594
31 8
COMPENDIUM OF O R G A N I C SYNTHETIC METHODS
SECTION 128
35% Chem C o r n (1969) 1047
Some o f t h e methods l i s t e d i n s e c t i o n 132 ( E t h e r s and Epoxides f r o m Ketones) may a l s o be a p p l i e d t o t h e p r e p a r a t i o n o f e t h e r s and epoxides from aldehydes
Section 125
E t h e r s and Epoxides f r o m A l k y l s , Methylenes and A r y l s
OOOOOOOOOOOoOOOOOoOOooo~o~oooooooooooo~ooooooouoooooo
No examples o f t h e p r e p a r a t i o n o f e t h e r s and epoxides b y r e p l a c e m e n t o f a l k y l , m e t h y l e n e and a r y l groups o c c u r i n t h e l i t e r a t u r e . F o r t h e c o n v e r s i o n RH 3 ROR' ( R = a l k y l , a r y l e t c . ) see s e c t i o n 131 ( E t h e r s from Hydrides)
S e c t i o n 126
E t h e r s and Epoxides f r o m Amides
00000000000000000000000000000000
No examples
S e c t i o n 127
PhNH2
---+
S e c t i o n 128
OAc
E t h e r s f r o m Amines
000000000000000000
+
-
PhN2 C1
MeOH
PhOMe
JACS (1955) 77 1745 (1958) 80 6 0 7 2 Org React (1944) 2. 2 6 2
93%
Ethers from Esters
00000000000000000T
OCHqPh 48%
CHO
cHo
JCS (1948) 376 Ber (1943) 76 466
SECTION 1 2 8
ETHERS FROM ESTERS
31 9
PhCOO Me1
NaOH
DMF
H20
81% J O C (1964)
HCOOBu
PhCH&r L
NaH
MeOCHzCH20Me
2 2805
BuOCH2Ph
t
43%
T e t r L e t t (1965) 1713
-
LCOOBu t NaBH4
BF3.Et.20
diglyme
+
J O C (1962)
16””
76%
27
2127
C8H17 LiAlH4 AcO
BF3.Et20
EtpO
EtO
p78’ J O C (1961)
AcO
38%
HClO4Pt02HOAc H2
2 4553
EtO
J O C (1964) 29 228 Chem Ind (1964) 975
1685
2 4%
COMPENDIUM OF O R G A N I C SYNTHETIC METHODS
320 S e c t i o n 129
SECTION 130
E t h e r s and Epoxides f r o m E t h e r s and Epoxides
0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 ~ 0 ~ ~ ~ ~ ~ ~ ~ ~ ~ ~ ~ ~ ~ ~ ~ ~ 0 0 0 0 0 0
J O C (1964) 29 2031 T e t r a h e d r o n (1967)
23 3193
Chem C o r n (1966) 4 5 4
Et20
MeOS02F
EtOMe
c---
Chem Comm (1968) 1533
Helv (1949)
S e c t i o n 130
PrBr
Mg
2
275
E t h e r s and Epoxides f r o m H a l i d e s and S u l f o n a t e s OOOOOeOOOOOOoOOOOOOOoooonooonoooooooooooooooooo
MeCH(0Et)Z
PhPr-i
F
PrCHOEt
73%
I
Me
Rec Trav C h i m (1962) J A C S (1951) 2 4893
81 238
SECTION 1 3 0
BuBr
ETHERS AND EPOXIDES FROM HALIDES AND SULFONATES
---+
C1 CH~OBU
BuLi
____t
70%
BuCH20Bu Ber (1964)
CH2Br
Cyclohexanol
Me JOC (1958)
t-BuOK
‘1 gH370TS
t-BuOH
*
97 636
NaNH2
Me
44%
23 1700
99%
C18H370BU-t JACS (1964)
PhBr
RBr
t-BuOK
t-BuOH
1 Mg
3072
PhOBu-t
w
Me2S0
321
42-46% Org Synth (1965) 45 89 JOC (1968) 33 259-
Et20
2 PhC002Bu-t
t
ROBu-t
7 4 % (R=C8H17)
65% (R=Ph) 4230 Org Synth (1963) 43 55 JACS (1959)
Br
OPh PhOH
Cup0
67%
JCS (1965) 4953 Chem Rev (1946)
38
405
322
COMPENDIUM
OF ORGANIC SYNTHETIC METHODS
SECTION 131
OEt
Br
EtONa
CuI
100% JCS
C
(1969) 312
-
F u r t h e r examples o f t h e p r e p a r a t i o n o f e t h e r s by t h e r e a c t i o n ROH + RHal ROR a r e i n c l u d e d i n s e c t i o n 123 ( E t h e r s f r o m A l c o h o l s and Phenols)
S e c t i o n 131
E t h e r s f r o m H y d r i d e s (RHL 0000000000000000000000000
T h i s s e c t i o n l i s t s e x a m l e s o f t h e r e a c t i o n RH -+ ROR
f\ I
I
Electrolysis
Et4NTs
MeOH
OoMe . v I
21 %
I
Tetr Lett (1968) 6207
Electrolysis
MeONa 24%
MeOH Bull Chem SOC J a p (1964) T e t r Lett (1968) 2415
N-Methoxyphenanthridinium Me0
perchlorate
hv
+
Me0 @OM,
JACS (1970)
92 5814
37
1597
SECTION 132 S e c t i o n 132
ETHERS AND E P O X I D E S FROM KETONES
323
E t h e r s and Epoxides f r o m Ketones 000000000D00000000D0DODDOODOOOOO
. . . . . . . . . . . . . . . . . . . page .....................
E t h e r s f r o m ketones Epoxides f r o m ketones
1 MeMaI
MeCO
2 BuBr HMPA
I
Et
Bu~CO
Me2C0
H2
Pt02
HC1
t
MeOH
--+
40%
Me2COBu I
Et
Compt Rend (1968)
5266 1178
Bu2CHOMe
54% JCS (1963) 5598 Chem Corn (1967) 422
Me2C(OBu)2
H2
Rh-Al203
t
Me2CHOBu
J O C (1961)
t-Bu
323-324 324-325
<47%
a 1026
Do 0:;; - - ~
t-Bu
LEitA2 l0H 4
t-Bu
<92%
84
J A C S (1962) 2371 J O C (1958) 23 1088
< 50%
Compt Rend (1962)
254
1814
324
Ph2CO
COMPENDIUM OF ORGANIC SYNTHETIC METHODS
--+
hJ
Ph2CN2
MeOH
SECTION 132
Ph2CHOMe Annalen (1958)
614 19
Some o f t h e methods l i s t e d i n s e c t i o n 124 ( E t h e r s and Epoxides f r o m Aldehydes) may a l s o be a p p l i e d t o t h e p r e p a r a t i o n o f e t h e r s f r o m ketones
-
0
LiCHCl2
PhCOBu-t
BuLi
/ \
PhC-CHC1 I
Bu-t
0
I\
Phy-CHBu Bu-t
T e t r L e t t (1969) 2181
t -
77% t-Bu
t-au JACS (1965)
o
t
-
Me3SO I
1353
NaH
72%
h
Ph
Me2S0
Ph
J A C S (1965) 87 1353
(1970)
-
6594
t
Me2CHSOCMez Na I1
NTs
63%
Me2SO JACS (1970)
C6Hl3COMe
CH2Br2
Li
THF
*
92 5753
0
I\
C6H13F-cH2 Me Chem Corn (1969) 1047
52%
325
ETHERS AND EPOXIDES FROM OLEFINS
SECTION 1 3 4
OH
50% T e t r L e t t (1969) 305 Org React (1954) 5 364
0 2&
HBr
a[
H O 0A c + O I
21 NaBH4 KOH MeOH
Br
75 1704
J A C S (1953)
S e c t i o n 133
E t h e r s and Epoxides f r o m N i t r i l e s
a
~
~
~
o
o
~
o
o
o
~
o
~
o
o
o
~
~
~
20%
o,*ss
____)
~
~
~
~
~
o
~
No examples
S e c t i o n 134
E t h e r s and Epoxides f r o m O l e f i n s
aoaoooo~oooeaooo0ooooooooooooooo
......., ,.. .,....,....
Ethers from o l e f i n s Epoxides f r o m o l e f i n s
FOOMe CH=C( CH2)2CH=C(CH2)2CH=CMe2 I
Me
I
Me
I
1 HS(OAc)2 MeOH 2 KOH 3 NaBH4
, , , ,
. . . . . page 325-326 . . , , , . . . 326-328
YOOMe
CH=C(CH2),CH=C(CH2)2CH2FMe2 I
Me
I
Me
J bled C h e m (1969) 1 2 1 9 1 J A C S (1969) 91 5 6 4 a
OMe
74%
~
o
o
~
326
COMPENDIUM OF O R G A N I C SYNTHETIC METHODS
SECTION 134
OMe
60%
JACS (1967) 5199 Acc o f Chem Res (1969)
2 33
Review: E p o x i d a t i o n and H y d r o x y l a t i o n o f E t h y l e n i c Compounds w i t h Organic P e r a c i d s Org React (1953) l 3 7 8
HOCH2CH2FH(CH2)2CH=CMe2 Me
C1 oH2, CH=CH2
MeC002H
0
NaOAc
*
CH2C12
/\
HOCH2CH2yH(CH2)2CHCMe2
87%
Me
Helv (1965) 48 182 JACS (1960) 4328 Org Synth (1963) C o l l Vol 4 860
CF3COO2H Na2C03
CH2C12
*
*
0 C6H13CHCH2 T e t r a h e d r o n (1962)
CgH17CH=CH(CH2)7COOH
90%
c1 OH21CHCH2 JACS (1955) 77 89
HOOCCH=CHCOOzH CH2C12 CgH13CH=CH2
0
I\
PhC002H Me2CO
17 31
0 I\ C~HI~CHCH(CH~)~COOH Org React (1953)
80%
62-67%
378
F o r use o f m-chloroperbenzoic a c i d see J O C (1970) 35 251 and T e t r L e t t (1965) 849 F o r p r e p a r a t i o n and use o f m o n o p e r p h t h a l i c a c i d see Org React (1953) 7 378 and JACS (1960) 6373 F o r p r e p a r a t i o n o f v a r i o u s a l i p h a t i c and a r o m a t i c p e r a c i d s see J O C (1962) 27 1336
SECTION 1 3 4
P r C I{=C HMe
ETHERS AND EPOXIDES
H202
PhNCO
FROM O L E F I N S
327
0
CHC13
/\
+
PrCHCHMe Tetr Lett (1970) 2029
MeCH=CH2
OsO4
NaC103
HOAC
H20
1 I2
HgO
2 MeONa
0
I\
MeC HC H 2
Chem Corn (1968) 1610
H20 MeOH
*
01017
Tetrahedron (1964)
0
39%
Ag20
MeOCH2CH20Me
---* JOC
&-
(1967)
43
32
3888
502
C8H1 7
AcO
Aco@-*co&
Br OAc
JACS (1959)
2 2826
27%
COMPENDIUM
3 28
OF
1 NBA
O R G A N I C SYNTHETIC METHODS
HC104
d i o x a n e H20 2 KOAc E t O H
HO
SECTION 135
HO
JCS (1956) 4 4 1 7 JACS (1959) 81 2195
S e c t i o n 135
cF3-(@N02
NO2
E t h e r s and Epoxides f r o m M i s c e l l a n e o u s Compounds
O00000000000000000000000000000000000000000000000
MeONa MeOH
91 %
NO2
JCS (1951) 2013
Compendium of Organic Synthetic Methods, Volume 1 Edited by Ian T. Harrison, Shuyen Harrison Copyright 0 1971 by John Wiley & Sons, Inc.
PREPARATION OF HALIDES AND SULFONATES
Chapter 10
S e c t i o n 136
RCXH
HBr
Halides from Acetylenes
0 D 0 0 D 0 D 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0
!COOK
RCH=CHBr
NCOOK
HOAc
dioxane
J O C (1965) 2 3985 JACS (1936) 1806
S e c t i o n 137
H a l i d e s f r o m C a r b o x y l i c Ac!d:
FOOMe (CH2)8COOH
Electrolysis
00000000000000000000000000
MeONa
*
1 NH3 AgN03
i-Pr(CH2)3CHCH2COOH
2 Br2
I
Me
0
F ( CH2)gCOOH
MeOH
RCH2CH2Br
H20
CCl4
YOOMe (CH2)i 7 F JACS (1956) 78 2255 Advances i n Org Chem (1960) 1 1
*
i- P r ( CH2)3CHCH2Br I
JCS (1953) 132
Chem Rev (1956)
RCOOH
Br2
HgO
CCl4
b
RBr
Me
56
219
46% (R=Cl1 H23)
329
<83% (R=Ph) J O C (1965) 30 415
55%
COMPENDIUM
330
OF O R G A N I C SYNTHETIC METHODS
Ber (1968)
S E C T I O N 137
101 2010
-50%
I2
benzoyl p e r o x i d e
C17t135COOH
*
C17H351 J Amer O i l Chem SOC (1969)
5 615
70%
JCS (1965) 2438
RCOOH
12 cc14
Pb(OAc)4
hv
*
100% (R'C5H11)
RI
JCS (1965) 2438 JOC (1963) Zs 65
61% (R=Ph)
JOC (1963) 28 65 Annalen (1970) 735 47
SECTION 138
Pb(0Ac)q
BuCOOH
LiCl
C6H6
*
BuCl J O C (1965)
1 Hg(OAc)2
SOCl2
RCOCl
RhCl (Ph3P)3
34
RC1
96% 3265
1904
86% (R=PhCH2)
CH2C12
61% (R=Ph)
J A C S (1968) (1966)
S e c t i o n 138
30
N-methyl p y r r o l i d o n e
J O C (1969)
RCOOH
331
HALIDES AND SULFONATES FROM ALCOHOLS AND PHENOLS
90 99 94 88 3452
H a l i d e s and S u l f o n a t e s f r o m A l c o h o l s and Phenols
0000000000000000000000000000000000000000000000~0
. . . . . . . . . . . page 331-337 . . . . . . . . . . . . . . . . . 337
H a l i d e s f r o m a l c o h o l s and phenols Sulfonates from alcohols
c1 2H250H
HBr
H2SO4
------+
KI
HO(CH2)60H
I
I
I
c1 ZH25Br
91 %
Org Synth (1941) C o l l Vol 1 29 J C S (1953) 132
polyphosphoric acid f
I ( C H )61 ~
83-85%
Org Synth (1963) C o l l Vol 4 323
Et3COH
HC1
--+
Et3CC1
J O C (1966)
2
1090
94 %
332
COMPENDIUM OF ORGANIC SYNTHETIC METHODS
EtyHOtI Me
HC1
MeCN
130"
EtyHO:=NH*HCl Me Me
HC1
A c O&Me
-
CC13CN
SECTION 1 3 8
EtFHC1 Me JACS (1955) 77 2341
56%
CH2C.1
CHC13
+
A c OQ
M e OAc T e t r L e t t (1970) 2517
OAc
O
85-90%
CH2C1 91% OMe
PhCH2CH20H
OMe JCS (1942) 684 (1943) 99 (1950) 3650 T e t r L e t t (1970) 2931 (1971) 87 1 SOC12
Pyr
2 SOBrp
Pyr*HBr
b
PhCHzCH2Br
9 1%
Chem Ind (1954) 931 JOC (1961) 2 3645
Org S y n t h (1943) C o l l Vol 2 322
CH2'7CH2CH2CSCCH20H Me
PBr3
LiBr
collidine
Et20
*
CH2=yCH2CH2CXCH2Br Me
Chem Corn (1969) 611 JCS (1950) 3650
85%
87%
SECTION 1 3 8
Et2CHOH
H A L I D E S AND SULFONATES FROM ALCOHOLS AND PHENOLS PBr3 or PBr5
*
Et20
Et2CHBr
26 3645 (1959) 24 143 J L i p i d Res (1966)
333
22-47%
J O C (1961)
453
J C S (1936) 1605 (1970) 1124
BuOH
(Ph0)3P
Me1
77%
C7H151
2 I 2 CH2C12
JOC (1967) (1968)
Bu I
32 4160 2 300
90%
JCS (1953) 2224 (1954) 2281
59% I
0
xo
JACS (1964)
MeCH=C=CHCH20H
PhgP.Bt-2
Pyr
*
2093
MeCH=C=CHCH$r J C S (1967) 2260 JACS (1969) 91 7405 JOC (1965) 3 3469
)
334
c1
PhCH20H
-
(
'
COMPENDIUM OF ORGANIC SYNTHETIC METHODS OH
Ph3P.Br2 200" *
Ph3PeBrCN
c1
PhCHZBr
v NBS Ph3P
90%
JACS (1964)
964
Annalen (1959)
626
CH2Br J O C (1969)
PrCHOH I Me
ph3P.F~
PryHF Me
SECTION 138
26
92%
34
212
Chem Pharm B u l l (1968)
16 1009
52% 1784
(R=Ph or C8H17)
94%
(R=Ph or CgH17)
97%
Can J Chem (1968) 5 86 Chem Comm (1968) 1358 Chem Ind (1966) 900
C5H110H
CBrq R3P EtZO
*
C5H1 l B r
Can J Chem (1968)
46
86
S E C T I O N 138
H A L I D E S AND SULFONATES FROM ALCOHOLS AND PHENOLS CC14
(MezN)3P
t
335
70% Chem Corn (1968) 1350
COCl2
ROH
Ph3P
ROCOCl
RC1
65% ( R = E t ) 6 7 % (R=Ph) Annalen (1966) 698 106
&-a1-xa CgH1 7
COCl2
HO
c1 coo
EtCHOH I
Me
1 COC12
2 T1F2
EtfHOCOF Me
PYr
JOC (1967)
2
67% (X=Cl) 49% ( X = I ) 2633
EttHF Me JACS (1955)
64% 3099
0
35% T e t r L e t t (1962) 1065
fGoMe t
Ph
M e z N = C4H C l C 1 C2H2C1
OH
P h\OC < i O M e
Chem Comm (1967) 1152
~ 7 0 %
COMPENDIUM OF ORGANIC SYNTHETIC METHODS
336
.
SECTION 1 3 8
c1
EtCHOH I
Me
ClzC=GNEtz
Me
1 Ph2NCN c 1 OH21 OH
2 HF 3 KF2
t-8uOK
*
JACS (1960)
69%
82 909
c 1 OH21 F
250-300"
68%
Can J Chem (1965)
Naphthyl isothiocyanate
I'
CgH137HOH Me
Et?HCl
t-BuOK
*
43 3173
CgH13CHC1
47%
I
2 PhZCHC1
Me JCS (1953) 3572
MeOH
12 B2H6
Me1
Br I
EtyHOH Me
C~HI~CHCH~CH~COB~ * CgH13FHCH2CHpCOOyHEt Et20 Br Me JACS (1956)
( Me0)2CHCH2CH2C=CHCH20H I
Me
70%
Chem I n d (1964) 1582 (1965) 223
1 MeLi
HMPA
2 TsCl
LiCl
EtpO
+
175-180'
EtCHBr I Me
40%
78 4967
(MeO) pCHCH$H$=CHCH2Cl Me
T e t r L e t t (1969) 1393
SECTION 138
HALIDES AN0 SULFONATES FROM ALCOHOLS AND PHENOLS
TsCl
NaI
Pyr
Me2CO
JACS (1969)
91 4771
-
337
w39%
F u r t h e r examples o f t h e p r e p a r a t i o n o f h a l i d e s f r o m s u l f o n a t e s a r e i n c l u d e d i n s e c t i o n 145 ( H a l i d e s and S u l f o n a t e s f r o m H a l i d e s and S u l f o n a t e s )
OH
MsCl
NaOH H20
*
Me0
Me0
JCS (1955) 5 2 2
80%
OH
MsCl
Et3N
CHZC12
@;r.
J O C (1970)
PhCHDH I
Me
1
Me-(=&SOCl
+ 2 m-Chloroperbenzoic a c i d
2 3195
PhfHOTs Me T e t r L e t t (1969) 2705
53%
COMPENDIUM OF ORGANIC SYNTHETIC METHODS
338 S e c t i o n 139
PhCHD
H a l i d e s f r o m Aldehyde:
-
000000000000000000000
1 BuMaBr 2 HCOOEt
PhyHBr Bu
Zh Obshch Khim (1955) (Chem Abs 50 3 3 5 6 )
D i - t - b u t y l peroxide
*
i- P r C H O
SECTION 141
2194
Halides from A l k y l s OOOoOOOooOOOOODOOOO
cl@ c1
Pr- i
S2C12
S02C12
Fe
45%
c1
c1
c1 JACS (1947)
Me
I
Me
69 3146
H a l i d e s f r o m Amides
0000000000000000000
BuCH(CH2) 3CH(CH2)3NHCOP h I
For
c1
c1
S e c t i o n 141
56%
45%
JACS (1965)
The c o n v e r s i o n R R ' RHal ( R , R ' = a l k y l o r a r y l ) i s i n c l u d e d h e r e . t h e r e a c t i o n RH -+ RHal see s e c t i o n 146 ( H a l i d e s f r o m H y d r i d e s )
c1
505
i-PrC1
CCl4
S e c t i o n 140
25
PBr3
BuCH(CH2 )3CH( CH2)3Br I
Me
I
Me
Z P h y s i o l Chem (1942) 273 225 Org S y n t h (1941) C o l l Vol 1 428
SECTION 1 4 2
H A L I D E S FROM AMINES
Me
339
Me JACS (1962)
C
*
NCOPh
Section 142
769
C1 ( C H 2 ) s C l
55%
Ber (1963) 96 1387 Org S y n t h (1941) C o l l Vol 1 428
H a l i d e s from Amines 0000000000o
ooooooob
71% JACS (1956) 78 6037 Chem Ind (1961) 179 Org Synth (1944) C o l l Vol 2 295 Org React (1949) 2 193
NH2 1 N a N 0 2
IHC1
H 2 0*
@lJ'epF6 t
-
ar;l;
OMe 2 HPFs J O C (1961) (1963)
PhNH2
CuX2
NO MeCN
PhX
oilb
QF
OMe
2 5149 28
568
73% ( X = C l ) 65% ( X = B r ) Rec T r a v Chim (1966) JACS (1947) 69 1221
85 857
60%
COMPENDIUM OF ORGANIC S Y N T H E T I C METHODS
340
SECTION 1 4 2
+ @NH2
HC1
k;O2
CHO
CHO
CHO &75% ( X = C l ) ~ 6 5 %( X = B r ) Org Synth (1944) C o l l Vol 2 130
1 NaN02
H2S04
2 HgCl2
KC1
3 KC1
A
H20
c
J A C S (1936)
2194
N97% Ph
Ph
PhNH2
NaN02
HC1
H20
w
Org Prep and Procedures (1969)
+
-
P h N 2 C1
KI
H20
___f
PhI
1. 221
74-76%
Org Synth (1944) C o l l Vol 2 351 Chem Ind (1962) 1760
aNH2 ~~H6C5HlloNow
Me
Me
JOC
(1968)
QCHzBr CH=CH2
40%
33
1636
Org React (1953) 1. 198 Ber (1910) 43 3209
50%
HALIDES FROM AMINES
SECTION 142
CH2NEt2
MeCOCl
34 1
Et20
56%
NMe 2 Ber (1960)
BuNH2
Bu~N
1 p-Chlorobenzenediazonium h e x a f l uorophosphate 2 H B r EtzO
C1 COOPh CH2C12
+
b
93
1310 1305
BuBr T e t r L e t t (1961) 758
BuCl
(Not i s o l a t e d ) JCS (1967) 2015
PrZNPh
HBr
156"
PrBr
JOC
(1963)
S 3144
72% 0 " "
NH2NH
071 JCS
C
(1967) 252
H a l i d e s may a l s o be p r e p a r e d f r o m amines v i a amide i n t e r m e d i a t e s . s e c t i o n 141 ( H a l i d e s f r o m Amides)
See
342
COMPENDIUM OF ORGANIC SYNTHETIC METHODS
S e c t i o n 143
SECTION 143
Halides from Esters
P
F o r t h e c o n v e r s i o n o f s u l f o n i c a c i d e s t e r s t o h a l i d e s see s e c t i o n 145 ( H a l i d e s and S u l f o n a t e s f r o m H a l i d e s and S u l f o n a t e s )
Br2
PhCH2COOBu
p4
QO'PC~
Arch Pharm (1953) JCS 1 (1967) 1067
286
+
BUCl
AlCl3
Ber (1963)
2
c1 JCS (1957) 2071 Zesz Nauk Pol Slask (1964) (Chem Abs 63 11338) J A C S (1940) 62 1432
Pyre HC1
R'COOR
LiI
DMF
RI
PhMgI
Me
Me
BUCl
190-210"
73%
1387
EtpO
AcO
COOBU
80%
108
3
' 0
PhCOOBu
BuBr
Monatsh (1952)
83 1398
97%
2
193
66%
(Not i s o l a t e d )
JCS (1965) 6655
Bu20 J A C S (1942)
64 1450
54%
SECTION 144
343
HALIDES FROM ETHERS
Section 144
Halides from Ethers 0000000000000000000
KI
EtyH (CH2) 1oOMe Me
polyphosphoric acid
+
EtyH(CH2 11 01 Me
JACS (1965)
u97%
2 5452
81 % Helv (1946)
OMe
PhCOCl
29 1204
ZnC12 CHC13
84% J P r a k t Chem (1938) JCS (1954) 2819
Pr20
PhCH20Me
MeCOI
PrI
Cl2CHOMe
JACS (1933)
ZnCl2
t
PhCH2C1
55
378
151 61
45%
88% Ber (1959)
92
83
344
Et20
ROBu
COMPENDIUM OF ORGANIC SYNTHETIC METHODS SOC12
SnC14
BBrj
+
EtCl
B e r (1936)
698
1036
77% ( R = B u ) 76% (R=Ph)
BuBr JACS (1942)
64 1128
T e t r a h e d r o n (1968)
( C 5 H 1 1 ) ‘20
PhgPaBrp
PhCN
(1964)
5037
Chem Ind (1969)
IC1
LiBHq
2 2289
CgH1 lBr JACS
(n-Bu)20
SECTION 1 4 4
200
s-BuI Chem I n d (1965) 223
(1964) 1582
T e t r L e t t (1967) 4131
EtpO
Pyr.BHpI
CgHg
h
EtI J A C S (1968)
90 6260
SECTION 145 S e c t i o n 145
H a l i d e s and S u l f o n a t e s from H a l i d e s and S u l f o n a t e s
0 0 D 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 ~ ~ 0 ~ 0 0 ~ 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 ~ 0 ~ ~ ~ 0 0 0
................ and s u l f o n a t e s . and s u l f o n a t e s . and s u l f o n a t e s , and s u l f o n a t e s . . . . . . .. .. .. . ., ., .. ., .. ..
Homologation o f h a l i d e s A l i p h a t i c f l u o r i d e s from o t h e r halides A l i p h a t i c c h l o r i d e s from o t h e r halides A l i p h a t i c bromides f r o m o t h e r h a l i d e s Aliphatic iodides from o t h e r halides A1 i p h a t i c s u l f o n a t e s f r o m h a l i d e s , A r o m a t i c h a l o g e n exchange
1 Mg
Ph(CH2)4C1
Me+Cl
Et20
2 TsO(CH2)3Cl
CH2=CH2
c
A l C13
*
Et
C10H211
-
1 PhCH2SLi
THF
2 Me1 N a I
DMF
CH2N2
Cu
I
KF
.. ...
68
1491 1101
25%
JACS (1945)
67 1152
ClOHZlCH2I Tetr Lett (1968) 5787
+
CHZ-CH2CHZCl \ /
CH2
99 2855
HOCH2CH20H +
c1 1H23F JACS (1957)
KF
.
.. . .
, , , I
page 345 . 345-346 , 346-347 , 347 347-348 , . 348 348-349
Me2YCH2CH2Cl
Ber (1966)
c1 1H23C1
.
,
24%
JACS (1928) (1946)
CH2=CHCH2CH2Cl
____f.
. . , . .
Ph (CH2)7C1
Et
CHz=CHCH2Cl
CgH13Br
345
HALIDES AND SULFONATES FROM HALIDES AND SULFONATES
HOCH2CH20H
+
C6H1gF
48%
2 2311
40-45% Org Synth (1963) C o l l Vol 4 525
COMPENDIUM OF ORGANIC SYNTHETIC METHODS
346
1 L i THF Fc103
C12H25Br
pet ether
*
c12H25F Ber (1969)
@-CH2Br
HgF2
KF
102 1944
50% Me
diethylene glycol
BqNF
JACS (1948) 2 2310 Org React (1944) 2. 49
C6H13F Chem Ind (1958) 157 Can J Chem (1956) 34 757 JACS (1955) 489F
t
CH20Ts
39%
CHC13
Me
CgH130Ts
C1 F2CCOOAg
HCXCH2CH20Ts
LiCl
90%
MeCN
69%
P
C a r b o h y d r a t e Res (1967)
CgH17Br
SECTION 145
CgH17Cl
S
292
89% T e t r L e t t (1970) 3447
EtOCH2CH20H
*
HCECCH2CH2Cl JCS (1950) 3650
90%
SECTION 1 4 5
H A L I D E S AND SULFONATES FROM H A L I D E S AND SULFONATES
Pyr.HX
BuOTs
200'
BuX
34 7
89% ( X = C l ) 66% ( X = B r )
Monatsh (1952) 8 3 1398 J O C (1961) 5 2 m 3
HOCH2CXCH2C1
NaBr
1 Mg
PrI
2 Br2
Et20
MeOH
PrBr
Me
tie
KI PhCOO
HOCH2CXCH2Br JACS (1955)
11 165
JACS (1919)
41 287
J O C (1961) (1962) (1970)
26
O
J O C (1969)
30-40%
52%
7 2
3645 624 2803
M
e
34
3519
DMF PhCOO6
62%
82%
COMPENDIUM OF ORGANIC SYNTHETIC METHODS
348
13%
P
2 HgBr2
3 I2
91 5774 61 1585
JACS (1969)
Pyr
NaI
HCECCH~CH~OTS
(1939)
Me2CO
SECTION 1 4 5
64%
HCZCCH2CH2I JCS (1950) 3650
AgOTs
MeCN
C7H151
PhBr
PhI
PhBr
b
1 Li
EtzO
hv
ccl4
--+
PhCl
PhMgBr
Ph3PC12
81 4113
JACS (1959) J O C (1962)
PhF
2 ~ ~ 1 0 3
-
C7H150Ts
EtzO
*
2365
Ber (1969)
102 1944
JOC (1970)
2 528
1 Mg
2 Brp
Et20
76%
PhCl J O C (1967)
Phi
42%
PhBr JACS (1919)
2 3710
41 287
30-40%
SECTION 146
PhBr
1 Mg
Et20
HALIDES FROM HYDRIDES (RH)
349
PhI
90%
JACS (1919) 41 287 (1945) 67 1479 J O C (1938) 5 55
2 I2
PhBr
1 Mg
Et20
2 ICN
PhI
Annales de Chimie (1915)
5
64%
28
51 % JACS (1950)
&CuY
S e c t i o n 146
from
FCH2CH2X BF3 o r BBrg
*
Y =c1 c1 Br I
Br
84% 100% 100% 30%
JCS (1964) 1097 1108 Proc Chem SOC (1962) 113
Hydriclls,~~H~
..... ... .. . .... ....... .. ....
H a l o a l k y l a t i o n o f a r o m a t i c compounds H a l o g e n a t i o n o f a r o m a t i c compounds , , A l l y l i c and b e n z y l i c h a l o g e n a t i o n H a l o g e n a t i o n o f s a t u r a t e d a l i p h a t i c compounds
PhH
2767
X=Br
Pyr
Hai;!Es
72
PhCH2CH2X
I
I
I
.
50-94%
(X=Cl, Br o r I ) J O C (1964)
29
page 349-350
. . . . . 350-351 . . . . . 352 . , . . . 352-353 ,
2317
350
-m
COMPENDIUM OF ORGANIC SYNTHETIC METHODS
SECTION 146
CH2C1
Para formaldehyde H3PO4 HOAc
HC1
74-77%
Org Synth (1955) C o l l Vol 3 195 Org React (1942) 1 6 3
XeF2
PhH
HF
CCl4
b
68%
PhF
JACS (1969) 91 1563 JOC (1970) 35 723 4020 F o r a r o m a t i c f l u o r i n a t i o n w i t h CF3OF see JACS (1970) 92 7494
C12
CHC13
61 %
Me
Me Me
Me JACS (1936)
1
For a r o m a t i c c h l o r i n a t i o n w i t h T i C l q and CF3C002H see T e t r L e t t (1970) 2611 9,
9,
t,
I'
t r i c h l o r o c y a n u r i c a c i d see JOC (1970)
35 719
351
HALIDES FROM HYDRIDES (RH)
SECTION 146
PhCOCBr3 A1 Cl3 Zh Org Khim (1969) 5 387 (Chem Abs 70 105613)
Br2 I2 Fe
Me
Me
Org Synth (1955) C o l l Vol 3 138
For aromatic bromination with Tl(OAc)3 and Br2 sEe " NBS and II CBr4 see " CuBr2 " I,
,I
I1
,I
I,
,I
,I
I,
41
'I
,I
I
I'
T e t r Lett (1969) 1623 J O C (1965) 30 304 JACS (1958)-g 4327 JACS (1932) 2025 JACS (1964) 427
54
a
1,3-dibromo-5,5-dimethylhydantoin see An A r g e n t i n a (1950) (Chem Abs 5 2873)
38
181 188
22% I
Org React (1954)
-
JACS (1950)
12 HNO3
PhH
Me0
258
86-87%
PhI
I2 CFgCOOAg
8
72 2767
Org Synth (1932) C o l l Vol 1 323
*
Meo@l Me0
85-91% Org Synth (1963) C o l l Vol 4 547
c
For aromatic iodination with I2 and oleum see JCS (1970) 1480 II II II 'I 12 " KI03 'I JACS (1943) 65 1273 I1 ,I I' 12 I' Ag2S04 " JCS (1952) 150 I! 'I I 2 'I electrolysis see Tetr Lett (1968) 1831 " A113 " CuC12 see JOC (1970) 35 3436 I " (CF3C00)3T1 and KI see T e t r L e t t (1969) 2427 ,I
t,
,I I,
$,
I,
I,
II
352
COMPENDIUM OF ORGANIC SYNTHETIC METHODS
PrCHzCH=CHMe
NBS dibenzoyl peroxide
PrCHCH=CHMe I Br
t
cc14
SECTION 146 58-64%
Org Synth (1963) C o l l Vol 4 108
NBS dibenzoyl peroxide
CH2Br
CH3 C6H6
71 -79%
Org Synth (1963) C o l l Vol 4 9 2 1
Org Synth (1963) C o l l Vol 4 984
For reviews of allylic and benzylic halogenation see and
Chem Rev (1948) 43 271 Angew (1959) _71 349
The following reagents may also be used for allyliclbenzylic halogenation: N-Chloro-N-cyclohexylbenzenesulfonamide Annalen (1967) 703 34 SO2C12 JACS (1939) 61 2142 and JCS (1951) 1851 PCl5 J O C (1969) 34 3655 PhIC12 J O C (1964) 29 3692 1,2-Dibromotetrachloroethane Chem Ind (1963) 1954 BrCC13 JACS (1960) 82 391 CBr4 JACS (1932) 54 2025 Ph2C=NBr J O C (1967) 2 223 CC13S02Br JOC (1965) 30 38 1,3-Dibromo-5,5-dimethyl hydantoin Helv (1958) 41 70 t-BUOI
0
JACS (1968)
OF
JACS (1970)
90 808
92 7494
SECTION 148
353
HALIDES FROM NITRILES
For c h l o r i n a t i o n o f s a t u r a t e d compounds w i t h S02C12 see JCS (1951) 1851 I, I, ,I I, ,I " CC13S02C1 " JACS (1960) 82 5246 4, ,I ,I 0 I, " NCS " JOC (1953) 649
0
NBS d i b e n z o y l p e r o x i d e
*
cc14
(3"'
JOC (1953) 18 649 JCS (1952) 2240
F o r b r o m i n a t i o n o f s a t u r a t e d compounds w i t h B r 2 see ,I
I1
6,
,I
II
,I
EtCH2Me
t-BuOC1
I,
HgI2
hV
CCl4
S e c t i o n 147
Me
S e c t i o n 148 No examples
,,
*
I,
'I
4,
'I
Rec Trav Chim (1964) 67 CC13S02Br see JOC (1965) 2 38 PhzC=NBr see JOC (1967) 32 223
35%
EtCHMe I
JACS (1968)
I
2 808
H a l i d e s f r o m Ketones
00000000000000000000
Me
-
Yh Me
Halides from N i t r i l e s 000000000000000000000
pc15_
@CHCl
Et20 Me T e t r L e t t (1965) 525
Yh 64%
354 S e c t i o n 149
COMPENDIUM OF ORGANIC SYNTHETIC METHODS
SECTION 149
Halides from Olefins
00000000000000000000
The c o n v e r s i o n o f o l e f i n s i n t o s a t u r a t e d h a l i d e s i s c o n s i d e r e d i n t h i s s e c t i o n . F o r a l l y l i c h a l o g e n a t i o n see s e c t i o n 146 (Hal i d e s f r o m H y d r i d e s )
CgH73CH=CH2
CH3C1
d i - t - b u t y l peroxide
*
130'
C6H13(CH2)3Cl
23%
Chem Corn (1966) 258
60%
97% Helv (1955) 38 1587 J O C (1966) c 1 0 9 0 JACS (1957) 2 456
CgH13CH=CH2
1 B2Hg
THF
b
2 N-Chloropiperidine
C6H13CH2CH2Cl +
c1 JOC (1965)
BuCH=CH2
1 B2Hg
THF
2 Br2
1 B2Hg THF
2 Hg(OAc)2 3 B r 2 CC14
2 4313
93%
BuCH2CH2Br
3 MeONa
C7H1C F,H=CH~
CgH13fHMe
JACS (1970)
92 6660
C7Hi 5CH2CH2Br JACS (1970) 92 3221 Chem Comm (1970) 372
7212
69%
SECTION 149
PrCH=CHZ
HALIDES FROM OLEFINS HBr
ascaridole
HBr
HOAc
HBr
ACO(CH~)~CH=CH~ C6H6
HBr
MeCOCH2CH=CH2
pentane
355
b
PrCHZCHzBr
*
PrCHMe
81 %
> 84%
I
Br JACS (1934) 56 1642 Org React (1963) 3 150
dibenzoyl peroxide
h3
pentane
*
MeCOCH2CH2CH2Br T e t r a h e d r o n (1969)
PhC=CH2 I Me
1 B2H6
THF NaOH MeOH
63%
Me JACS (1968)
KI
g 5149
PhfHCH2 I
f
2 12
82%
ACO(CH~)~CH~CH~B~ J O C (1946) 11 281 JACS (1946) 68 1101
90 5038
H3PO4 88-90%
Org Synth (1963) C o l l Vol 4 543
I
I
CHzCH=CHz
CH2CHMe
@I@@HI
CHzCH=CH2
CgH6
@@Qj 83%
CH2CHMe
f
JCS (1957) 463
356
COMPENDIUM
S e c t i o n 150
PhN02
SECTION 150
H a l i d e s from M i s c e l l a n e o u s Compounds
D 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 00 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0
!COOK NCOOK dioxane
PhCH=CHBr
OF O R G A N I C SYNTHETIC METHODS
SOCl2
HOAc
*
190-200'
PhCl
b
&$
HC1
hr/
22%
PhCH2CH2Br
JOC (1965)
30
Monatsh (1915)
3985
36
100%
723
@J$j
CHC13
.go%
T e t r L e t t (1969) 4603
PhNO
NH2OH CuC12 HC1
PhCHzCH2S02Cl
H20
b
PhCl
200-220°
PhCH2CH2C1
Zh Obshch K h i m (1953) (Chem Abs 3 2568)
SOC12 c1
15-20%
JCS (1949) 5181
180° Monatsh (1915) 36 719 J O C (1970) 35 1895
59%
23
204
Compendium of Organic Synthetic Methods, Volume 1 Edited by Ian T. Harrison, Shuyen Harrison Copyright 0 1971 by John Wiley & Sons, Inc.
Chapter 11
PREPARATION OF
HYDRIDES
T h i s c h a p t e r l i s t s h y d r o g e n o l y s i s and r e l a t e d r e a c t i o n s by which f u n c t i o n a l groups a r e r e p l a c e d by hydrogen, e.g. RCH2X + RCH2-H o r R-H
S e c t i o n 151
Hydrides from Acetylenes 000000000000000000000000
No examples o f t h e r e a c t i o n R C X R ---t RH o c c u r i n t h e l i t e r a t u r e . F o r t h e h y d r o g e n a t i o n o f a c e t y l e n e s see s e c t i o n 61 ( A l k y l s and Methylenes from Acetylenes)
S e c t i o n 152
Hydrides from Carboxylic Acids 000000000000000000000000000000
T h i s s e c t i o n l i s t s examples o f t h e d e c a r b o x y l a t i o n of a c i d s , RCOOH -+ RH ( R = a l k y l , a r y l , v i n y l e t c ) . F o r t h e c o n v e r s i o n RCOOH -+ RCH3 see s e c t i o n 62 ( A l k y l s f r o m C a r b o x y l i c A c i d s )
Ph 64%
357
3 58
COMPENDIUM OF ORGANIC SYNTHETIC METHODS
@IcooH -
C002Bu-t
2 t-BuOOH
Di isopropyl-
benzene
SECTION 152 29%
t
150" JACS (1964) 3157 (1961) 3998 J Med Chem (1969) 12 192
JCS (1930) 1603 JACS (1950) 2 4359
CH=CHCOOH
@
Cu quinoline
c
OAc
CH=CH2
@
37%
OAc
JACS (1950) 72 1200 Org Synth (1963) C o l l Vol 4 857 Chem Comm (1967) 96
Copper t e t r a m i ne sulfate
Ph(CiC)3COOH
c
Me2CO
O':OOH
Ph( CEC)3H
Ber (1964)
Cu quinoline
____t
97
79%
2586
pJMe
83-89%
Org Synth (1963) C o l l Vol 4 628
COOH cuso4 qui no1 i ne OMe JACS (1951)
73 1414
OMe
H Y D R I D E S FROM ALCOHOLS AND PHENOLS
SECTION 153 S e c t i o n 153
359
H y d r i d e s f r o m A l c o h o l s and Phenols
-
0000000000000000000DDDDOODODDOO000~0
T h i s s e c t i o n l i s t s examples o f t h e h y d r o g e n o l y s i s o f a l c o h o l s and phenols, ROH -+ RH and RR'CHOY + RH ( R = a l k y l o r a r y l , R'=H o r a r y l ) . F o r t h e c o n v e r s i o n ROH RR ( R ' - a l k y l o r a r y l ) see s e c t i o n 63 ( A l k y l s and A r y l s from Alcohols)
. . . . . . . . . . . . . . . page .....................
Hydrides from alcohols Hydrides f r o m phenols
Ye
I
I
H2 (965 atmos)
i-PrCCH20H 1
Co-Al203
300'
Me
I
Me I i-PrCMe
*
(1951) (1933)
H2
Pt
CF3COOH
+
Me3CH
C5H11 F,HOH
1 P4
HOCH$H(CHCH2)5 (CHOH)$HMe
YH
bH
HI
JOC ( 1 9 6 4 )
H20 b
I
2 LiAlH4
HOCHzCHCH( CH2)g I Me
20%
I
Me
JACS ( 1 9 4 8 )
Me3COH
2 3793
73 5 5 3 55 1 2 9 3
2 2325
C5H11fH2 MeCH( CH2)13FHMe MeFHCH2(CH2)g Me
JACS ( 1 9 6 2 ) 84 2 1 7 0 JCS ( 1 9 5 9 ) 1 0 4 4 Tetrahedron (1970)
OH
Ph
H2
Pd-C
EtOH
*
u'"
JCS C ( 1 9 6 7 ) 1 3 6
26
Chem Ind ( 1 9 6 3 ) 1 3 5 4 Org React (1953) 263
PhyHMe OH
Na
NH3
359-362 362-363
PhCH2Me JCS ( 1 9 4 5 ) 8 0 9
(1949) 2531
I.
2199
13%
360
COMPENDIUM OF ORGANIC SYNTHETIC METHODS
Q CH20H
OH
Na
LiA1H4
NH3
SECTION 153
85% Ber (1956) 89 1549 JCS (1957) 1969 (1945) 809
AlCl3
EteO
Q h JOC (1964)
LiAlH4
9 121
AlCl3
OH T e t r L e t t (1967) 2447 F o r r e d u c t i o n o f b e n z y l i c a l c o h o l s see JCS (1957) 3755
T e t r L e t t (1969) 1837 34 3667
J O C (1969)
PhCH20
86%
-
P h C H Z o d4:A: :
JACS (1970) (1955)
p h c H z o ~79%
92 553
1820
F u r t h e r examples o f t h e r e d u c t i o n o f s u l f o n a t e s a r e i n c l u d e d i n s e c t i o n 160 ( H y d r i d e s f r o m H a l i d e s and S u l f o n a t e s )
SECTION 153
HYDRIDES FROM ALCOHOLS AND PHENOLS
JOC (1968)
361
2 1196
F o r f u r t h e r examples o f t h e r e a c t i o n ROH -+ RHal and RHal -+ RH see s e c t i o n 138 ( H a l i d e s and S u l f o n a t e s f r o m A l c o h o l s and Phenols) and s e c t i o n 160 ( H y d r i d e s f r o m H a l i d e s and S u l f o n a t e s )
0
-uEt
- J4 Ult
Et
1 MsCl
Pyr
2 PhCH2SNa EtOH
PhCH2S
COOEt
COOEt Helv (1959) 42 2431
J A C S (1953) (1963)
CH20CSNMe2
CH20H O
b
O
O
PhyHCH20H Me
P-
Me2NCSC1 NaH DMF
___t
f
Ni
COOEt
77%
2 384
173
hv MeOH
O
b
Chem Comm (1968) 3 2 3 Carbohydrate Res (1967)
H2 (100-200 atmos) 250"
c17H35CH20H
0
EtOH
Ni
*
c1 7H36 J A C S (1933)
55
JACS (1957)
2 1696
1293
PhCH2 I
Me
O Of-
5
115
~ 2 5 %
362
COMPENDIUM OF ORGANIC SYNTHETIC METHODS
t?eyh PhC-CHOH
t-BuOK
t-BuOH
SECTION 153
Me I PhFH
b
Et
Et J A C S (1969)
91 1009
A l c o h o l s (ROH) may a l s o be c o n v e r t e d i n t o h y d r i d e s (RH) v i a e s t e r o r e t h e r i n t e r m e d i a t e s . See s e c t i o n 158 ( H y d r i d e s f r o m E s t e r s ) and s e c t i o n 159 (Hydrides from Ethers) OH 93% T e t r Lett (1969) 1 5 7 7
18% @Ph
JOC (1961)
a 2528
dH Zn
Me
550'
Me
JACS (1951)
Me0
73 3439
JCS (1955) 522
Me0
F u r t h e r examples o f t h e r e d u c t i o n o f s u l f o n a t e s a r e i n c l u d e d i n s e c t i o n 160 ( H y d r i d e s f r o m H a l i d e s and S u l f o n a t e s )
24%
SECTION 154 OH Ph
HYDRIDES FROM ALDEHYDES
?H
Et3N Ccl4
1 (Et0)ZPO 2 Na
363
* @'Ph
NH3
JOC (1958) 2 131 J Med Chem (1965) JCS (1955) 522
48%
8
409
2,4-Dini trofl uorobenzene
NaH
Section 154
JOC (1964)
:I@
R= N-N
N-N
DMF
I
9-or
Ph
Hydrides from Aldehydes ooooooooaoooooooaoooooo
29 3124
40%
-@
Ph
JACS (1966)
70-76%
4271
-
This section lists examples o f the decarbonylation o f aldehydes, RMe see section 6 4 (Alkyls RCHO 3 RH. For the conversion RCHO from Aldehydes)
CHo
Pd( OH)z-BaS04
76%
155-1 95"
JOC (1959)
24 1369
364
COMPENDIUM OF ORGANIC SYNTHETIC METHODS
SECTION 154
CHO 80%
25 2215
J O C (1960)
Ni
PhfHCHO
EtOH
PhFH2
____t
Me
Me
RhCl (Ph3P)3
RCHO
RH
J A C S (1957)
R=C,jH13,
PhCH=C I
Et
or
2 1696
"
J A C S (1968) 90 99 T e t r L e t t (1970) 823
(1968) 1899
PhCHZCHCHO
-
D i t-bu t y l peroxide
I
*
PhCHzYH2
Me
69%
Me J O C (1964) 29 1663 J A C S (1941) 63 226
n hd E t O H 90% Proc C h e m SOC (1963) 114
BuFHCHO Et
h J PhCH2SSCHzPh 140-1 45'
*
68%
BuCH2 I
Et T e tr L e t t (1962) 43
SECTION 155
HYDRIDES FROM ALKYLS
365 C-CH
CXCHO
NaOH MeOH
H20
JCS
S e c t i o n 155
C
(1969) 2173
P d r i d e s from Alkyls
0000000000000000 0 0 6
T h i s s e c t i o n l i s t s examples o f t h e c o n v e r s i o n R R ' aryl etc.)
PhzCHCHPhz
t-BuCHZPr-i
Hz
Cu-Cr o x i d e
A1C13
Me
CgH6
-
2
1668
JACS ( 1 9 3 5 )
57
2415
t-BuH
C6H6
60%
Et
Me
H2S04+
S03H
76 4 9 5 2 59 1 4 1 7
3 H20
Me Me
90%
JACS ( 1 9 3 2 )
JACS ( 1 9 5 4 ) (1937)
Me&Me
RH ( R , R ' = a l k y l ,
PhzCHZ
methylcyclohexane
HF
Et
*
h
88% Me
Me
Me
Org React ( 1 9 4 2 )
1. 3 7 0
COMPENDIUM OF ORGANIC SYNTHETIC METHODS
366
SECTION 156
The c o n v e r s i o n A r - A l k y l --f ArH may a l s o be a c h i e v e d v i a i n t e r m e d i a t e c a r b o x y l i c a c i d s ArCOOH. See s e c t i o n 20 ( C a r b o x y l i c A c i d s f r o m A l k y l s and A r y l s ) and s e c t i o n 152 ( H y d r i d e s f r o m C a r b o x y l i c A c i d s ) S e c t i o n 156
H y d r i d e s f r o m Amides oobooooooooooooooooO
T h i s s e c t i o n l i s t s examples o f t h e c o n v e r s i o n s RCONH2 -+ RH and RNHCOR' -+ RH. F o r t h e c o n v e r s i o n s RCONR':, + RR" and RNHCOR'+ ( R " = a l k y l or a r y l ) see s e c t i o n 66 ( A l k y l s ahd A r y l s f r o m Amides)
RR"
H3P04
190-2100
JACS ( 1 9 5 1 )
Ph2CHCONH2
BuLi
THF
hexane
NaNH2 NH3
Et20
*
86%
Ph2CH2 JACS (1969)
PhCECCONH2
73 4 3 6
91
7774
PhCXH
90%
JCS ( 1 9 6 3 ) 4 4 0 2
PhNHAc
---+
PhyAc NO
Et2O
250
PhH JACS ( 1 9 6 4 )
3180
Amides may a l s o be c o n v e r t e d i n t o h y d r i d e s v i a i n t e r m e d i a t e amines o r c a r b o x y l i c a c i d s . See s e c t i o n 157 ( H y d r i d e s f r o m Amines) and s e c t i o n 152 ( H y d r i d e s f r o m Carboxyl i c A c i d s )
SECTION 157 S e c t i o n 157
HYDRIDES FROM AMINES
367
H y d r i d e s f r o m Amines
--
ooooooo~oaoooooooooo
T h i s s e c t i o n l i s t s examples o f t h e c o n v e r s i o n s RNH2 -+ RH, RCH2NH2 ----t RH and R'NR3' XR'H. F o r t h e c o n v e r s i o n RNH2 -+ R R ' ( R ' = a l k y l o r a r y l ) see s e c t i o n 67 ( A l k y l s and A r y l s f r o m Amines) Review: Replacement o f t h e Aromatic P r i m a r y Amino Group by Hydrogen Org React (1944) 2 262
t
-
r75% J O C (1963)
t
MeD
2 568
-
80%
H3po2_ Me0 @
Me0@JN2
JACS (1952)
2
3074
Org S y n t h (1963) C o l l Vol 4 947
(1955) C o l l Vol 3 295 F o r r e d u c t i o n o f d i a z o n i u m s a l t w i t h NaBH4 see JACS (1961) 1251 4,
HCtIO d e r i v a t i v e s see Angew (1958) 70 211 ,I I, 4, I, " " H3PO2, tiCHO, Etm, Zn o r N2H4 see Org React (1944) 2 262 For s e l e c t i v e d i a z o t i z a t i o n o f ArNH2 i n t h e presence o f r l i p h N H 2 see JACS (1949) 2 2137 I,
I,
I,
'I
"
OH
T e t r L e t t (1969) 1577
Aromatic amines (RNH2) may a l s o be c o n v e r t e d i n t o h y d r i d e s (RH) v i a N - a c e t y l d e r i v a t i v e s . See s e c t i o n 156 ( H y d r i d e s f r o m Amides)
CgH17NH2
TsCl
Pyr
CgH17NHTs
NH20S03H NaOH EtOH
H20
JACS (1964)
* 5
C8H18 1152
25-30%
COMPENDIUM OF ORGANIC SYNTHETIC METHODS
368 HNF2
BuNH2
BuH
-----.e
Me
KIO4
I
PhCNHNH2
KOH
JACS (1963) (1964)
*
61 %
86 2233
ye
H20
I
97
SECTION 158
68%
PhtH
Et
Et
JACS (1963)
Ni
PhCH2CH2NH2
+
Me&Me
EtOH
PhCH2Me JACS (1957)
- Na-H9_
CH2NMe3 I
Me
t
PhMe
H20
2 1696
Me&Me Me
Me
Me
Me
S e c t i o n 158
1108
JACS (1951) 73 4122 0 r g React (1953) 263
Hydrides from Esters 00000000000000000000
T h i s s e c t i o n l i s t s examples o f t h e h y d r o g e n o l y s i s o f e s t e r s , R'COOR --+ RH F o r t h e c o n v e r s i o n R ' C O O R --+ R ' R " or RR" ( R " = a l k y l ) see s e c t i o n 68 ( A l k y l s and A r y l s f r o m E s t e r s ) . The r e d u c t i o n o f e s t e r s o f s u l f o n i c a c i d s ( e . g . ROTS + RH) i s i n c l u d e d i n s e c t i o n 160 ( H y d r i d e s f r o m H a l i d e s and Sul f o n a t e s 1
;1 e PhFOAc
COOH
H2
Pd-C
EtOAc f
Me PhiH COOH JCS C (1967) 136 Org React (1953) I 2 6 3
99%
SECTION 159
&
369
HYDRIDES FROM ETHERS
C8H17
AcO
LiEtNHz*
94% JCS (1957) 1969
J O C (1968)
S e c t i o n 159
33 435
Hydrides from Ethers
00000000000000000000
This s e c t i o n l i s t s exayples o f the hydrogenolysis o f ethers, ROR' F o r t h e c o n v e r s i o n ROR --P RR" ( R " = a l k y l o r a r y l ) see s e c t i o n 69 ( A l k y l s and A r y l s f r o m E t h e r s )
PhCH20Et
(i-Bu)zAlH
PhMe
Izv (1959) 2255 (Chem Abs 54 10837)
J C S (1957) 1969
PhCH=CHCHzOPh
LiAlH4
NiC12
THF
*
PhCH=CHMe JACS (1957)
79 5463
-+RH
92%
370
COMPENDIUM
H2
PhCH20Bu
Ni
OF
SECTION 160
ORGANIC SYNTHETIC METHODS
Org React (1953) 7 263 Chem Ind (1963) 1354
PhMe
w93%
F u r t h e r examples o f t h e h y d r o g e n o l y s i s o f a l l y 1 and benzyl e t h e r s a r e i n c l u d e d i n s e c t i o n 39 ( A l c o h o l s and Phenols f r o m E t h e r s and Epoxides) and s e c t i o n 45A ( P r o t e c t i o n o f A l c o h o l s and Phenols)
S e c t i o n 160
H y d r i d e s f r o m H a l i d e s and S u l f o n a t e s
1
...... ........ . .. .. . . ..... .. .........
..
page C a t a l y t i c r e d u c t i o n of h a l i d e s and s u l f o n a t e s D e s u l f u r i z a t i o n o f t h i o e t h e r s d e r i v e d f r o m ha1 i d e s and s u l f o n a t e s D i s s o l v i n g metal r e d u c t i o n o f h a l i d e s Reduction o f halides v i a Grignard type intermediates M e t a l h y d r i d e r e d u c t i o n o f h a l i d e s and s u l f o n a t e s M i s c e l l a n e o u s methods I
H2 HO&OMe
Pd
MeOH
I
. .. .... ... .... I
I
370-371 371 372-373 373 373-374 374-375
Et3N
81 %
HO&Me JOC (1969)
2
3519
37% CH2 I
PrF
Me
H2
Pd-C
190"
Br
JAGS (1950)
Helv (1946)
PrH
72 561 29 378
J Phys Chem (1956)
360
60 1454
100%
SECTION 160
HYORIOES FROM H A L I D E S AN0 SULFONATES
371
c1 N2H4
Pd-C
EtOH
88%
C h e m Ind (1959) 1348
H2
Ni
KOH
90%
_____t
MeOH
Ber (1958)
-0 H2
Ni
91 1376
EtOH
90% NHAc
JCS (1949) 5178 Aust J C h e m (1963)
16 647
AcO
Ni
--t
C5H1 ( N H 2 loH )2CS
.
c
o
p
55%
UI
I
CHzSC=NH
Me
I
NHZ
Helv (1946) J A C S (1969)
(1950)
EtSK
t-BuOH
29 1199 91 7342
561
&[ &I Ni
EtOH*
C H ~ S E ~
J A C S (1953)
Me
75 384
COMPENDIUM OF ORGANIC SYNTHETIC METHODS
372
c1
Ni-A1
NaOH
SECTION 160
H20 COOH
COOH
J O C (1944)
9
1
100% or Zn-Cu
Zn HOAc
C16H33I
Li
c1
&lc
EtOH
Bull SOC Chim Fr (1967) 2018
C16H34
85% Org Synth (1943) C o l l Vol 2 320
*m
94%
t-BuOH THF
(Aliphatic halides are also reduced)
c1
T e t r L e t t (1962) 449 (1968) 1575 J O C (1964) 2 160
3::* $ Na
t-BuOH THF
JACS (1968)
Ft
i-Pr(CH2)3:Cl
Li
N H ~
i-Pr(CH2’3:H
80%
90 3594
Et I
Me
Rec Trav Chim (1964) JACS (1951) 73 3329 Chem Corn (1969) 138
367
HYDRIDES FROM HALIDES AND SULFONATES
SECTION 160
I4g
i-PrOH
-0
decalin
373
33% ( X = F ) 83% ( X = C l )
Proc Chem SOC (1963) 219
Ma
PhX
i-PrOH
decalin
*
PhH
89% (X=C1 o r B r ) 95% (X=I)
Proc Chem SOC (1963) 219
1 Mg
PrCHBr
Bu~O
2 H2SO4
I
Me
*
PrFH2
H20
Me
NaBH4
CgH17C1
NaBH4
PrDTs
50-53% Org Synth (1943) C o l l Vol 2 478
Me2SO
Me2SO
t
C8H18
PrH
J O C (1969) 2 3923 T e t r Lett (1969) 3495
J O C (1969)
2 3923
. 4C8H17Br HlAi L, ,
C8H18
Cgti13FHCH2Br Br
PhBr
LiAlH4
THF
PhH
JACS (1948) 3664 3738 Org React (1951) 5 469
J O C (1969)
3 3918
42%
90%
~ 7 0 %
95%
COMPENDIUM OF ORGANIC SYNTHETIC METHODS
374
SECTION 160
1 LiAlH4 Et20
2 H2 Pt HOA:
Tetrahedron (1964) 2 2903 Helv (1949) 2 1371 JACS (1970) 92 553
-
fN
fN
Bu3SnH
(CH2)3CH2Br
(CH2)3Me
Ph3SnH
c1
c1
150'
BuBr
Cr2+
NH~CH~CHZNH~
Me2SO H20
@
Cr(C104)2 DMF
Br
H20
b
BuH
JOC (1969)
34
JOC (1960) (1969) (1959)
25 2203 2 2014 2 294
75%
100%
JACS (1966) 4094 Angew (1968) 80 271 (Internat Ed 1 2 4 7 )
NHzCHzCH2NH2
100%
(Vinyl halides are also reduced) Tetrahedron (1968)
Br
60%
2014 Synthesis (1970) 499
PhCH20Na Cu20
24
3503
95%
SECTION 162
375
H Y D R I D E S FROM KETONES
Br
Ac20
Cup0
Pyr
64%
JCS (1964) 1112
Proc Chem SOC (1962) 113
hU
PhCl
@'OM'
i-PrOH
PhH
;i;ctrolysis
T e t r L e t t (1969) 1267
Et4NBrt
@POMe
72%
94%
( A r o m a t i c ha1 i d e s may a l s o be s e l e c t i v e l y reduced i n t h e Dresence o f a l i D h a t i c h a l i d e s ) JOC (1970) 35 1232 Ber (1968) 4179
Br
S e c t i o n 161
Hydrides from Hydrides
0000000000000000000000
c---'-l-?
T h i s s e c t i o n l i s t s examDles o f hydrocarbon e D i m e r i z a t i o n . Manv r e l a t e d r e a c t i o n s a r e i n c l u d e d i n s e c t i o n 65 ( A l k y l s ' a n d A r y l s f r o m A l k y l s and Aryl s )
tic"'
cyclohexane hJ HgBr2
____)
H
H
JACS
S e c t i o n 162
(1970)
92
1094
H y d r i d e s f r o m Ketones
000000000000000000000
T h i s s e c t i o n l i s t s examples o f t h e c o n v e r s i o n R2CO + RH. F o r t h e c o n v e r s i o n R2CO -+ R2CH2 o r R2CHR' see s e c t i o n 72 ( A l k y l s , Methylenes and A r y l s f r o m Ketones)
Compt Rend (1910) 150 661 Org React (1957) 2-i-
70%
376
COMPENDIUM OF ORGANIC SYNTHETIC METHODS
S E C T I O N 163
B u l l Acad S c i URSS (1941) 167 (Chem Abs 37 3749)
COMe
JACS (1946)
NaNH2
PhCXCOPh
NH3
THF -t
2 2176
PtiCECH
25%
B u l l Chem SOC J a p (1962)
S e c t i o n 163
2 1488
Hydrides from N i t r i l e s OOOOOOOOoOOOoOoOOOOOoo
T h i s s e c t i o n l i s t s examples o f t h e c o n v e r s i o n RCN --t RH. F o r t h e c o n v e r s i o n RCN --+ RMe see s e c t i o n 73 ( A l k y l s from N i t r i l e s )
PhO( CH2) 3tHPh CN
Na
RCN
NH3
Na
EtOH
t o 1 uene
89%
PhO (CH2) 3CH2Ph JACS (1934) 56 I614 3 525 Gazz (1963) 9 (Chem Abs 59 8825)
RH
35% (R=C12H25) 90% (RzPhCH2) JACS (1969)
Ph2CCN MeZNCHkHz I
CH2NMe2
EtMgBr Et20
* xy’ene
91 2059
Ph2CH I MezNCHCHZ I
CH2NMe2
JACS (1952) 74 5793 Chem Comm (1970) 350
SECTION 165
CN
H Y D R I D E S FROM MISCELLANEOUS COMPOUNDS
Electrolysis
377
LiCl
60-80%
EtNH2 T e t r L e t t (1968) 1975
Mirphosphoric acid
*
Me
CN
S e c t i o n 164
Me
JACS (1953)
75 3600
Hydrides from O l e f i n s
000000000000000000000
T h i s s e c t i o n l i s t s examples o f t h e c o n v e r s i o n R2C=CR2 --+ R2CH2. F o r t h e h y d r o g e n a t i o n , d i m e r i z a t i o n and a l k y l a t i o n o f o l e f i n s see s e c t i o n 74 ( A l k y l s , Methylenes and A r y l s f r o m O l e f i n s )
NIi2NHNa
Ph2CzCH2
S e c t i o n 165
Et20
*
PhzCH2
Angew (1962) 2 650 ( I n t e r n a t Ed 1 4 5 6 )
97%
H y d r i d e s f r o m M i s c e l l a n e o u s Compounds
00000000000000~00000DODODDOODODOODOOD
T h i s s e c t i o n l i s t s examples o f t h e replacement o f m i s c e l l a n e o u s f u n c t i o n a l groups by hydrogen (RX -+RH) H2 (100 atmos) C6H13SH
300'
MoS2
*
C6H14
C o l l Czech (1966)
JACS (1956)
31 2202
2 6414
90%
88%
COMPENDIUM OF ORGANIC SYNTHETIC METHODS
378
Ni
Ph-X-Ph
EtOH
PhH
68% (X=S)
75% ( X = S O )
6 5 % (X=S02) JACS (1943)
F o r use o f N i 2 8 see JOC (1965)
C1oH21-X-C10H21
Li
Ni
SECTION 1 6 5
MeNH2
c 1 OH22
30
1013 1316
or S o p )
(X=S J A C S (1960)
2 2872
EtOH
95%
Ph Helv (1946) J A C S (1953) (1963)
371
75 384
85
173
9 1% Et
Et Org React (1942)
1. 370
Compendium of Organic Synthetic Methods, Volume 1 Edited by Ian T. Harrison, Shuyen Harrison Copyright 0 1971 by John Wiley & Sons, Inc.
Chapter 12
S e c t i o n 166
EtCXEt
PREPARATION OF KETONES
Ketones f r o m A c e t y l e n e s
P
1 NaBH4 BF3eEt20 2 H202
diglyme
*
H20
EtCH2COEt
62%
JACS (1961) 8 3 3834 (1967) 5086 Org React (1963) 1
13
BF3.Et.20
COOEt CH2COMe
HgO
CC13COOH MeOH*
0 0 JCS (1952) 4086 Helv (1945) 2 1355 (1943)
/\fO::CH
W
Ion exch resin-HgSOn MeOH
2 680
f\fo:OMe
80%
H20 JCS (1954) 3257
CgH13CXH
HgO BF3.Et20 HOCH2CH20H
+
CgH13/C\Me
Lo
379
--- +
75%
C6H13COMe
Chem C o r n (1967) 200 JACS (1934) 56 1130 80 (1936)
380
EtCSCEt
COMPENDIUM OF O R G A N I C SYNTHETIC METHODS 1 ClS02CNO
CH2C12
*
2 H20
SECTION 167
EtCOCH2Et
67%
T e t r L e t t (1970) 27
Br @J''='~Z DMF
Me0
",Xi3
Me0 H e l v (1964)
H20* Me0
2 194
BCoM 73%
l f i O COAc HBr2
NBA
NaOAc
Zn
NaOAc
v
___3
HOAC
HOAC H20
H20
AcO
S e c t i o n 167
,fiOble
JACS (1958)
67%
6118
Ketones f r o m C a r b o x y l i c A c i d s , A c i d H a l i d e s and A n h y d r i d e s
0 0 0 0 0 0 0 D 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 ~ 0 ~ 0 ~ ~ ~ ~ 0 0 0 0 0 0 0 ~ 0 0 0 0 00 0 00 0 0 0 0
Ketones f r o m c a r b o x y l i c a c i d s by Kolbe c o u p l i n g page 380 Ketones f r o m c a r b o x y l i c a c i d s and d e r i v a t i v e s by r e a c t i o n w i t h o r g a n o m e t a l l i c compounds 380-382 M i s c e l l a n e o u s methods 382-385 Ketones f r o m d i c a r b o x y l i c a c i d s 385-386 Me I
C17H34COOH
PhCH2COOH
Me
HOOCCH2CHCH2hHCH2COFle* electrolysis
-
MeLi
Et20
Me Me C17H34tH2LHCH2CHCH2COMe 1 A c t a Chem Scand (1956) lo 478 Advances i n Org Chem (1960) I_ 1
PhCH2COMe
Acta Chem Scand (1952) Org R e a c t (1970) 18 1
2
782
76%
SECTION 167
381
KETONES FROM CARBOXYLIC A C I D S , A C I D HALIDES AND ANHYDRIDES PhLi
EtzO
^___c
JACS (1969) (1970)
EtMgBr
Et20
Et COO Na
k
Et2Co
91 456 92 2590
Ber (1909) 42 4500 JACS (1933) 2 1258 JCS (1950) 2012
Review: The S y n t h e s i s of Ketones f r o m A c i d H a l i d e s and O r g a n o m e t a l l i c Compounds o f Magnesium, Z i n c and Cadmium Org React (1954)
C17H35COC1
-
P h C H 2 C H 2Mg B r Cd C12 Et20
*
CgHg
For use o f a r y l cadmium r e a g e n t s see
YOOEt
i-PrCH2MgBr
(CH2)8COC1
C5H11C O C l
EtpO k
Bu2CuLi
S
28
C17H35COCHpCH2Ph
65%
Org React (1954) S 28 JACS (1950) 2 5333 JACS (1945) 67 740
tOOEt
(CH2)8COCH2Pr-i O r g React (1954) S 28 J O C (1961) 6 1768 T e t r L e t t (1970) 2523
79%
C5H11 COBU T e t r L e t t (1970) 4647
382
COMPENDIUM OF ORGANIC SYNTHETIC METHODS t-BuMgC1 -CdC12
(P hCO ) 20
---+
C5H11 COOH
F
CgH11 C O N 3
MqSiCH2Ph
PhCOCl
Et2O
BuLi
HMPA
t
PhCOBu-t JOC (1941) (1948) Ber (1964)
SECTION 167
40%
a 462
13 592 91 1649
EtMgBr
C5H11 C O E t Et2O Annalen (1962) 655 90
N
64%
PhCOCH2Ph Tetr Lett (1970) 1137
PhCOCl
PrCOCl
PhCOCl
Tenside (1967) 4 167 (Chem Abs 61 116507)
CH2N2 -----*PhCOCHN2
p-Tolylcopper
P~COCH~QM~
Chem Comm (1969) 515 R
CioH21COCl
Mg!C ( COOEt ) 2 CgH6
EtOH
JCS (1950) 322 Org S y n t h (1963) Coll Vol 4 285 F o r use o f m a l o n i c t e t r a h y d r o p y r a n y l e s t e r s see JCS (1952) 3945 I, I, II I1 I, " JACS (1952) 2 831 t-butyl I1 ,I I1 I1 I, I' JCS (1950) 325 benzyl and JACS (1963) fi 1409
78%
~31%
KETONES FROM CARBOXYLIC ACIDS, A C I D HALIDES AND ANHYDRIDES
SECTION 167
PhCOCl
PhCOCl
Et2CHCOOEt PhjCNa
*
PhCOCEt2 I COOEt
Et20
Naphthalene
H2SO4 Or
HOAc
*
H2° J A C S (1941)
*&
AlCl3
PhCOCHEt2
383
44%
63 3163
PhNOz
J C S (1949) S99 Chem Rev (1955)
55
229
For f u r t h e r examples of t h e a c y l a t i o n o f a r o m a t i c compounds see s e c t i o n 176 (Ketones from H y d r i d e s )
PhCOOH
C-0 O HI~/ T- -C- O O H Fe
*
250"
PhCOC8H17
JOC (1963)
879 Org S y n t h (1963) C o l l Vol 4 854
JACS (1950)
( PrC0)20
(Me3Si)z
AlC13 +
28
72 3294
PrCOMe
Compt Rend (1965)
PhCOCl
PhCOCl
Et3SiH
RhCl3( PBuzPh)3
c
1 MeCH=PPh3 C6H6
2 H20
c
261 1329
70%
64%
75%
PhZCO
Chem Comm (1970) 1703
< 85%
PhCOCH2Me Tetr Lett (1960) (4) 7 Annalen (1964) 674 11 Ber (1962)
95
1513
COMPENDIUM OF ORGANIC SYNTHETIC METHODS
384
t -
1 BuqP B r
PrCOOAg
MeOH
*
2 300”
SECTION 1 6 7
39%
PrCOBu J O C (1963)
1133
- /y\”cOOMe Zn N a I
1 CH2N2
COCH2er
2 HBr Et20
AcO
HOAc ,yCOMe
75%
T e t r L e t t (1969) 51 JACS (1943) 65 1516
CH2COC1
do CH2COMe
1 CH2=C(OMe)2 2 HC1
H20
-
HOAc
JACS (1956)
78 6086
A u i t J Chem (1955) 8 506 F o r p r e p a r a t i o n o f c y c l i c k e t o n e s f r o m d i c a r b o x y l i c a c i d s see JACS (1948) 22 34
P y r i d i n e N-oxide
(Me2CHCO) 20
*
PhCl
Me2CO T e t r L e t t (1965) 233
a
C
O
O
H
KMnO4 KOH
H20
PiaBiOg H3PO4
H20
J O C (1964) 29 2914 JCS (1953) z Z 9 3580
SECTION 167
KETONES FROM CARBOXYLIC A C I D S , A C I D HALIDES AND ANHYDRIDES
385
C8H17
@N3
H2s04*fi[
1 t-Butyl hypochlorite
CHC13
NaHC03
2 NaOH H20
2 EtONa 3 H2SD4 J O C (1965)
Et20 EtOH ti20
65%
2 3775 ~ 8 0 %
C7H15 Compt Rend (1955) 240 317 Helv (1945) 1 6 5 7
Helv (1947) 2 2158 Org Synth (1941) C o l l Vol 1 192
KF
250-280"
52-72%
or BaO 320-330' JOC
Bu2C(COOH)2
1 Pb(0Ac)q 2 KOH MeOH
Pyr HpO
CgHg
h
(1962)
27
1034
BupCO T e t r L e t t (1966) 6145 29 2914
JOC (1964)
70%
COMPENDIUM O F ORGANIC SYNTHETIC METHODS
386
1 ClCOOEt
Et3N
*
Me2CO
CON^
2 NaN3
S e c t i o n 168
!??!+
Pho C o N 3 J O C (1962) (1964)
SECTION 168
P
h
e
H20 1647 9 2914
O 45%
Ketones f r o m A l c o h o l s and Phenols
00000000000000000000000000000000~
C o n v e r s i o n o f a l c o h o l s i n t o ketones w i t h l o n g e r c a r b o n c h a i n s , , , , O x i d a t i o n o f 2 r y a l c o h o l s t o ketones O x i d a t i o n o f a l l y l i c and b e n z y l i c a l c o h o l s t o ketones Ketones f r o m 3 r y a l c o h o l s and 1 , 2 - d i o l s , Ketones f r o m p h e n o l s
.
. . . . ..... ................
. . . .
... ... .. .. ..
. page ... .. .. .. ...
386 386-393 393-394 394-396 396
GLt
CHZ=CMe
Me2CCH=CHz
TsOH MeOH
*
I
Me2C=CHCH2CHzCOMe
OH
Helv (1967)
Me
Me I
HOCHCH-CH2
i-PrOH
--+
I
MeCOCH2COOCHCH=CH2
MeCOCH2COOEt
*
MeCOfHCOOEt
i- P r
BF3
AcO
CrO3
HOAc
Ph2O
MeCH=CHCH2CH2COMe 220° trans T e t r L e t t (1969) 3253
76%
MeCOfH2
i-Pr
60-67%
OH
2091
--+
41%
Org S y n t h (1955) C o l l Vol 3 405
H20
69%
AcO JCS (1949) 615 i i 9 4 o j 10 F o r use o f Cr03-Mn(N03)2 see JOC (1967) 1098
2
SECTION 168
KETONES
FROM ALCOHOLS AND PHENOLS
CrO3 Me0
Et20
(CH2)3COCH=CH2
H20
( 2 phases)
387
63%
Me0 JCS C (19661 1972 Chem-Pharm Bull (1964) J O C (1971) 36 387
@
12 1184
C8H17
HO
Na2Cr207,
96% 0
HOAc
Br B r
PhCHCECH I
OH
CrO3
H2SO4
Me2CO H20
(Jones ' r e a g e n t )
Eri
Org Synth (1963) C o l l Vol 4 195 Annalen (1967) 707 203 t
PhCOCXH
77%
JCS (1946) 39 (1970) 2631 J O C (1960) 25 1434
79% Ber (1961)
94 729
OH
Tetr L e t t (1968) 3363 F o r use o f CrO3 i n Pyr-HZO see T e t r a h e d r o n (1962) g 1351 F o r i n s i t u p r e p a r a t i o n o f Cr03-Pyr see J O C (1970) 2 4000
0
t - B u t y l chromate CCl4 Biochem J (1962) 84 195 Helv (1957) 40 4 8 F
COMPENDIUM OF ORGANIC S Y N T H E T I C METHODS
388
CH20Ac
CH20Ac
tHNHAc CHOH
CIiNHAc
KMn04
@
HOAC
* @
H2SO4
H20
I
NO2
G
O
H
NO2
OH
Ru02
NaIO4
CCl4
H20
86%
Ber (1960) (1961)
Go
93
387 169
96%
JACS (1958)
Ru04 cc’4 *
S E C T I O N 168
80 6682
79% Tetr Lett (1967) 4729 (1970) 4233 T e t r a h e d r o n (1963) 19 1959
JCS C (1969) 968 JOC (1968) 33 175 2814 (1958)
BuCHMe I
OH
Li
NH~CHZCH~NH~ b
3 899
BuCOMe
JOC (1962)
45%
3 2662
SECTION 1 6 8
KETONES FROM ALCOHOLS AND PHENOLS
02
Pt
02
OH
h3
Ph2CO
1 COC12
2 Me2SO 3 Et3N
0
EtOAc
-
PrCHMe OH
389
50% JACS (1955) 190 T e t r a h e d r o n (1968) 24 6583 Angew (1957) 69 600Advances i n Carbohydrate Chem (1962) 169
11
PrCOMe Ber (1963)
5
509
Go
Et20
*
20%
JCS (1964) 1855
-DCC
CF3COOH
Pyr
Me2SO
92%
CgHg
JACS (1965) 87 5670 Chem Rev (1967) 67 247 Can J Chem (1966) 2517
fi
JACS (1967)
5505
&
390
SECTION 168
COMPENDIUM OF ORGANIC SYNTHETIC METHODS
Ac20
&o
MeZSO
30%
t
0 JACS (1967) 2416 C a r b o h y d r a t e Res (1966)
2
251
0
PH
80%
Org React (1951)
&'
HO
t-BuOLi
a 207
EtCOMe &0b
68%
JCS
C
(1969) 804
T e t r L e t t (1964) 3481
NBA MezCO
Ph(CH2)3CHMe I OH
I1
1,
41
II
I,
II
I,
*
Ph(CHz)$OMe
59%
Chem Comm (1965) 5 JACS (1954) 76 3682 Chem Rev (1963) 63 21
F o r o x i d a t i o n w i t h NBS
It
H20
"
" "
see JCS (1959) 2594 and J O C (1957) 22 1678
N-broniocaprolactam see J O C (1960) NCS " Helv (1953) T r i b r o m o i s o c y a n u r i c a c i d see
2 263
a 1763
Bull Chem SOC J a p (1958) 'I
1 - c h l o r o b e n z o t r i a z o l e see JCS
c (1969)
1474
31 450
KETONES FROM ALCOHOLS AND PHENOLS
SECTION 168
391
Me C HC H 2 C H2 COO R
HO
44%
HO"' JACS (1945)
Br2
MeCH2CMe2 OH
PhCHMe I
H20
MeCHCMe2 I I Br Br
t - B u t y l hypochl ori t e +
IN03
C5H11 YHMe
JACS (1933)
Pyr
CHC13
55 1136
83%
C5H11 COMe
>
JCS
MeFHCH2CHz:HMe
55%
Helv (1953) 36 1763 JACS (1955) ? 7 - 172
OH
OH
MeCOCHMe2
PhCOMe
Pyr cc14
OH
67 312
Pb(OAc)4
Pyr
b
65%
C
(1970) 676
MeCOCHzCH2COMe
OH
89%
T e t r L e t t (1964) 3071 JACS (1960) 82 4956
.
AgzC03-cel i t e
C6H6
lb Compt Rend (1968) C 267 900 JACS (1955) I_z 490--
99%
392
COMPENDIUM OF ORGANIC SYNTHETIC METHODS
OH
Ago
HOAc
SECTION 168
H3P04
55% T e t r L e t t (1967) 4193 (1968) 5685
LToH ;A;e;tic
pic01i n a t e
Ph
Ph T e t r L e t t (1967) 415 Can J Chem (1969) 47 1649
EtCHMe I
OH
PdC12
Cu(N03)~
OH t-Bu
EtCOMe
t
02
32
J O C (1967)
-
4-Phenyl-1 , 2 , 4 - t r i a z o l i n e 3,5-dione
C6Hg
t-Bu
2816
oo
Chem Comm
75%
(1966) 744
!COOEt PhFHMe
NCOOEt CgHg
t
PhCOMe
JOC
OH
Me2CHOH
(1967)
32
727
B u l l Chem SOC J a p (1968)
XeO3
H20
Me2CO JXCS (1964)
2078
91491
SECTION 168
KETONES FROM ALCOHOLS AND PHENOLS
393
100%
HO Proc Chem SOC (1964) 110 Chem Corn (1966) 121
-
~ ; = C H ; ; C H C H = C H C H OM I eH
Mn02
oi=CHi;CHCH=CHCOMe
Pet e t h e r (Applicable t o a l l y l i c and b e n z y l i c a l c o h o l s o n l y ) J C S (1952) 1094 JACS (1955) 4330 J O C (1959) 24 1051
HO
@
- o #
( A p p l i c a b l e t o a l l y l i c and b e n z y l i c a l c o h o l s o n l y ) B u l l SOC Chim Fr (1969) 335
Chloranil
PhCHCH=CH2 1
CCl4
*
PhCOCHzCH2
66%
( A p p l i c a b l e t o a l l y l i c and b e n z y l i c a l c o h o l s o n l y ) JCS (1956) 3070
OH
OH
CHEt
HO
DDQ
dioxane
HO
OMe
OMe ( A p p l i c a b l e t o a l l y l i c and b e n z y l i c a l c o h o l s o n l y ) Acta Chem Scand (1961) 1 5 218 Tetr Lett (1960) ( 9 ) 14Chem Pharm B u l l (1970) 18 2343 Chem Rev (1967) 67 153
&-
394
HO
COMPENDIUM OF O R G A N I C SYNTHETIC METHODS
A l ( O B u -C6H6 Me2CO t)3
SECTION 168
&o
> 65%
23-26'
(Method f o r s e l e c t i v e o x i d a t i o n o f a l l y l i c a l c o h o l s ) Helv (1961)
fl 179
N2O4 CHC13 PhYHC8H17 OH
92%
( A p p l i c a b l e t o benzyl i c a l c o h o l s o n l y ) J C S (1957) 5087
02
PhFHMe
PhCOCgH17
_.___)
h 3 Me2SO
PhCOMe
b
OH
(Applicable t o benzylic alcohols only)
Bull Chem SOC Jap (1965)
Pr-i
B r 2 AgOAc
53%
2 1225
CCl4 38% JACS (1965)
CrO3
HOAc
m O H -
87 1807
Po Helv (1942) 2 1364
Ph
155'
Ph
Rec T r a v C h i m (1948)
JACS (1957) Helv (1948)
79 2
147 1077
67 489
82%
SECTION 168 OHoH I I PhC-CHMe I Me
MezC-CMez
AHAH
HO
Ac20 PY r
KETONES FROM ALCOHOLS AND PHENOLS
YHTAc
Zn
--+
PhF-CHMe Me
H2SO4
H20
PhCHCOMe I Me J O C (1970)
170'
Me3CCOMe
#@-;;:;
395
~ 6 7 %
35
660
65-72% Org Synth (1941) C o l l Vol 1 462 JACS (1960) 4965
JACS (1960)
82 4965
Helv (1959)
42
1620
&o Helv (1938) JACS (1962)
Me2C-CMe2 I
I
OHOH
Nickel peroxide
-t
21 546
84 2241 61 %
Me2CO Chem Pharm B u l l (1964)
12 403
396
HO
COMPENDIUM OF O R G A N I C SYNTHETIC METHODS
&-
Me2C-CMe2
K2S2O8 AgN03
H20
JACS (1954)
OHOH
OH
H2 (2,500 p s i )
Helv (1941) 24 828 JACS (1956) 78 3087 Org React (1944) 1. 341
Me2CO
b
I 1
Pd
N-ethyl morphol ine EtOH
*
SECTION 169
76 6345
100%
@Do 40%
JACS (1946)
68
2172
96%
S e c t i o n 169
Ketones f r o m Aldehydes
0 0 0 0 0 0 0 0 0 0 D 0 0 0 D D 0 0 0 0 0 0
T e t r Lett (1964) 3323
C6Hl3CHO
1 Ph3P=CHMe THF f
2 I2
CgH13CH2COMe T e t r Lett (1970) 447
SECTION 169 SMe t -1 MeCPO(OEt)2 Li
C5H11 CHO
397
KETONES FROM ALDEHYDES
SMe
C5H11 CH=CMe
t
THF
HgC12 MeCN
*
H20
2
J O C (1970)
PhCHO
PhCHO
PhCHO
EtCHO
CH2(CN)2 g l y c i n e EtOH
--+
t
H20
PhCH=C(CN)z
1 BuLi
PhCkO]
Cyclohexyl amine
Me2NH. HC1 KC N
30
226
- 0phcG Na H
Me I
Acid
PhC-N
Can J Chem (1970)
EtYHCN NMe2
1 EtBr
KNH2 NH3
PhCOMe
4s 570
< 75%
EtCOEt
t
H20
99%
87%
PhCOBu
J O C (1965)
Me@
-
* PhCOMe
2 NaOH H20 Tetr L e t t (1963) 955
*
50%
777
1 CH2N2 Et20
Et20 cyclohexane
2 H20
‘0
C5H11CH2COMe
Bull Soc Chim F r (1961) 1653
JACS (1960) J O C (1961)
EtN02 MeNH2.HCl HO
NazC03 E t O H
*
MeO@CH=;; HO
82 1960
a 4740
Fe FeCl 3 ~ M e 0 . @ $ C H 2 C O M e EtOH H20
16
no
J O C (1951) 221 Chem Comm (1967) 1258
398
COMPENDIUM OF ORGANIC SYNTHETIC METHODS
-
0
CN
Br PhkCHO I Me
Br2
Ph:HCHO Me
I \
1 ZnBr2
I
2 MeMgBr
PhC-CHCN
-+
Me
SECTION 1 6 9
Et20
*
PhCHCOMe I
50-70%
Me
T e t r L e t t (1970) 2947
BuMgBr
PhCHO
ICOOEt
PhCHOMgBr I
Bu
NCOOEt
50%
PhCOBu
B u l l Chem SOC J a p (1968) JCS (1966) 313
C
41 1491
PCHO Me
B r LHCOOEt
0 L
EtONa
O JACS (1963) 5 955 Org React (1949) 5 413 Chem Rev (1955) 55 283
CH2N2
Et20
62%
Org React (1954)
0 CHO
MeCHN2
C6H]$H=CH2 CgH13CHO
peroxide
E t 2 0*
S
364
QCOEt
100% JACS (1950)
72 2737
diacetyl
*
75%
C6H13COC8H17
14
J O C (1949) 248 Aust J Chem (1967)
20 2033
SECTION 169
PhCHO
Me3CCHO
PhfHCHO
Me
KETONES FROM ALDEHYDES
HOAc
KOH
MeOH
H20
-
electro7ysis
~ 1 ~ 1 3
*
PhCOMe
18%
T e t r L e t t (1968) 1781
Me2CHCOMe
1 NH2CONHNH2 2 H2SO4
399
69B
Ber (1936)
65%
P hCH2COMe
b
H20
Zh Obshch Khim (1948) (Chem Abs 43 4632)
- ifioAcl Ac20
Br2
AcO
ocHo oHND 02
57%
2617
MeOH
L e t t (1968) 3271 3267 Comm (1969) 314 (1955) 1212 1216 (1952) 74 3627
1,4-diazabicyclo[2.2.2.]-
octane 2 , 2 ' - b i p y r i d y l Cu(OAc)2 DMF
HOAc
r o s e bengal
hy
Tetr Chem F o r o x i d a t i o n o f enamines w i t h Na2Ct-207 see JACS I1 I1 I, ,I 'I 03 'I JACS
02
CHC13
2 03 3 Zn
JACS (1950)
Morpholine.
2000
P
NaOAc
0
100%
2244
jfi
T e t r L e t t (1969) 985 Chem I n d (1970) 1144 Ber (1967) 259
90%
COMPENDIUM OF ORGANIC SYNTHETIC METHODS
400 S e c t i o n 170
SECTION 170
Ketones f r o m A l k y l s and Methylenes
0000000000000000000000000000000000
T h i s s e c t i o n l i s t s examples o f t h e o x i d a t i o n o f methylenes (RCH R ' -+ R C O R ' ) , t h e r e p l a c e m e n t o f a l k y l groups by k e t o n i c groups and t i e d e g r a d a t i o n o f a l k y l groups t o ketones (R2CHR' + R2CO). F o r t h e a c y l a t i o n o f hydrocarbons (RH + RCOR') see s e c t i o n 176 (Ketones f r o m Hydrides )
0
C12
NO
HC1
h u CCl4
ONOH oo ---*
Ber (1965)
0
71%
98 3493
18
J O C (1953) 115 Compt Rend (1965)
0 - oo
3501
260 4514
ht! PhN02
Chem Corn (1970)
C15H31 COOMe
CrO3
HOAc
CH2C12
*
1390
M~(CH~),,CO(CH~)~J-~COOM~
n-7 t o 11
Chem Ind (1966) 2168 JACS (1952) 3910
fi
CrOg'Pyr
Ph
CH2C12
go Ph
JOC (1969)
71 %
34 3587
SECTION 170
KETONES FROM ALKYLS AND METHYLENES
CrO3
HOAc
401
< 20%
Me
Me
63 758 (1949) 71 2226 JOC (1970) 35 192 JACS (1941)
F o r o x i d a t i o n w i t h Na2CrO4 i n HOAc see
0
t - B u t y l chromate HOAc
Ac20
+ Qo
CCl4
22%
Ph
Ph
J C S (1951) 516
@
Helv (1952)
35 284
C8H17
THFH NBS CaC03 20
AcO
hv?o&
81 %
Chem Corn (1969) 1220
Se02
EtOH Helv (1940) 3 524 1477 Org React (1949) 5 331
Me
1 NOCl
Et20
2 Pyr
Me2CO
3 H2SO4
H20
Me
Zh Org Khim (1965) 1 8 6 5 (Chem Abs 63 6873) JCS (1951) 516
30%
COMPENDIUM OF ORGANIC SYNTHETIC METHODS
402
JACS (1967)
Air
SECTION 170
4809
(Phg)3RhCl
Me0
40%
Me0 T e t r L e t t (1968) 2917 (1967) 3665
2 FeS04 H20*
& Ber (1943)
PhCH2Me
Argentic picolinate
*
Me2SO
PhCH2Me
MgO
(NH4)2S208
PhCOMe T e t r L e t t (1967) 415
wn04 MeCO
768 1130
HNO~ b
H20
AW03
@
MeCO
CoMe
J O C (1961)
H20
*
If? 4151
PhCOMe
Org Prep and P r o c e d u r e s (1970)
DDQ MeOH HO
82%
<73%
2 207
78%
HO Chem Ind (1970) 158
403
KETONES FROM AMIDES
SECTION 171
n 76% T e t r L e t t (1966) 4493
I
Bu-t
MeCOCl
AlCl3
t-Bu
72%
t-Bu J A C S (1942)
Helv (1960)
Section 171
5
1473
Ketones from Amides
0000000000000000000
EtLi
PrFHCONMe2
Et20
Pr$HCOEt Me
J O C (1959)
Ni
200'
2
JACS (1939)
Ber
PhCHMe HCO~H
64 2421
80% 701
61 232 (1959) 92 2555
PhCOMe C o m p t Rend (1947) 225 457
404
‘4-
COMPENDIUM OF ORGANIC SYNTHETIC METHODS
Br2
Me 0 Me0
base
M
4
Me0
CONH2
JACS (1968) 2 2448 Org React (1946) 3 267
K2S20fj
(Me2CH)zNAc
PhCH2N e 0
SECTION 172
K2HP04
H20
Me2CO
t
JOC (1964)
29
3632
Amides may a l s o be c o n v e r t e d i n t o ketones v i a i n t e r m e d i a t e amines. See s e c t i o n 96 (Amines from Amides) and s e c t i o n 172 (Ketones f r o m Amines)
S e c t i o n 172
Ketones f r o m Amdnes
~ 0 0 0 0 0 0 0 0 0 0 0 0 0 00 0 5
NH2
1 NaN02
NaOAc
HC1
2 EtCH=NOH CuSO4 Na2S03 H20 3 HC1 H20
c1
NH2
EtO
H20
JCS (1954) 1297
H20*E t O
NaW04 H202
30%
c,
NaOAc
oNoH Etooo --*
an
Ber (1960)
NMe2
NaW04
Ph
* Q
H202
MeOH H20
Ph
93 132
54%
Ph
Ph
JACS (1968)
2 4892
S E C T I O N 172
oo
KETONES FROM AMINES
405
(R=H or Me)
(1960) 3559 JCS C (1966) 995 JCS
Ph2CO hU C6Hg
(Me$H)2NH
Me2C=NCHMe2
+
HC1
Me2CO
-95%
H20
JACS (1965)
-
EtqHNHR
Me
KMn04
CaS04
t-BuOH
H20
EtCOMe
91% (R=H) 96% ( R - E t f H ) Me
J O C (1967)
HO
2996
2 3129
!bo @pNH 1 NCS
2 EtONa
NH2
EtOH
__c
MeOH
Tetrahedron (1969) 2 4551 Ber (1955) 883 JACS (1968) 90 3245
-0"
t-Butyl hypochlorite NaHC03
Et20
JACS (1954)
0
H2S04
MeOH THF
73%
2 5554
NH2 A r g e n t i c p i c o l i n a t e
H20
31 %
41 % J C S (1965) 4962
66%
COMPENDIUM OF ORGANIC SYNTHETIC METHODS
406
1 2,4-Dinitrobenzaldehyde
Me2CHNH2
2 HC1
n
(CH2)11
CHNH2
LJ Ve
C6H13CHNH2
Pyr +
H20
JCS
(1954) 209
c
(or 3 , 5 - d i n i t r o m e s i t y l g l y o x a l )
2,4-Dini t r o c h l o r o b e n z e n e -+
46%
Me2CO
1 3,5-Di- t - b u t y l - 1 ,Z-benzoqui none
2 (C00H)z
(CH2)11
&
Me2N
H20
CO
JACS (1969)
1429
Me C6H13bHNH
Cro3 H2S04
0"' n02
H202
SECTION 173
JOC ( 1 9 6 2 )
86-97%
C6H13COMe 21 %
H20
21 4 5 2
1 (CF-JCO)~O
2 NaOH H20 0 M 0 eI 2 i JTetrahedron aA C S1 (1968) 90 ( 1 9 656227 ) *2 3 4 6 8 1
Aust J Chem (1955)
8 506
57%
SECTION 173
KETONES FROM ESTERS
i-PrCH2COOEt
Na H
i-PrCH2COFHCOOEt
--f
407
(i-PrCH2)2CO
--+
i-6r 52%
MezCHCOOEt
C7H] 5COOEt
1 Ph3CNa
Et20
*
2 PhCOCl
JACS (1946)
Me2yCOOEt COPh
t-BuLi
THF
hexane
H2SO4
HOAc
CgH13
Me2CHCOPh
-----+
H20 JACS (1941)
C7H15COyHCOOEt
2647
LiOH
63
3163 3156
(C7H15)zCO
H20
Dokl (1964) 155 1352 (Chem Abs 61 1750)
F o r t h e p r e p a r a t i o n o f ketones by a l k y l a t i o n o f O - k e t o e s t e r s w i t h h a l i d e s f o l l o w e d by h y d r o l y s i s see s e c t i o n 175 (Ketones f r o m H a l i d e s and S u l f o n a t e s )
-
1 Me1
t -
C5H11C O O E t
MeSOCH2
Me2SO
NaH Me2SO
C5H11COCH2Me 62%
C5H11COCH2SOMe C5H11COMe
J O C (1966) 2 2 3 5 5 JACS (1965) 1345
-
C17H35COOMe
t
MeS02CH2 Na Me2SO THF
C17H35COCH2S02Me
A1 -Hg H20
J O C (1968)
f'r
v
"OEt
- t
[LiCHzSONAr] L i
THF
THF
C17HyjCOMe
100%
67%
2 61
ncoMe 84%
v
JACS (1968)
90 5548
408
COMPENDIUM OEt
-
OF
1 CHz=hNMe2
PhCHzCOOEt
2 HC1
ORGANIC SYNTHETIC METHODS
PhCH2COMe Chem Pharm B u l l (1969)
H20
1 Ph3P=CH2 E t 2 0
PhCOOEt
Br2
Me2CHOAc
H20
Ber (1962)
pH 4.6
95
41% 1513
Me2CO
t
3555
JACS (1967)
CrO3
HzSO4
83-87%
____3
MezCO
4
C
H
O
\O Org Synth (1962)
(COOEt) 2 P~CHZCH~C,
Me
54%
2 2314
PhCOMe
t
2 NaOH MeOH
SECTION 174
N2H4
* PhCH2CH2y(CON3)2
2 NaN02 HOAc
Me
42
1 ROH
2 Acid
79
PhCH2CH2COMe
28%
O r g React (1946) 3 337 JOC (1962) 1647
S e c t i o n 174
Ketones f r o m E t h e r s and Epoxides OOOOOOOOoOoOOOOOOeOOoooooooooooo
. . . . . . . . . . . . . . . . . . . . page .....................
Ketones f r o m e t h e r s Ketones from e p o x i d e s
(Me2CHJz0
t - B u t y l perbenzoate BuOH CuCl
*
MezC(OBu)2
Acid
408-410 410-411
Me2CO
Angew (1961) 73 65 T e t r a h e d r o n (1961)
13 2 4 1
SECTION 1 7 4
409
KETONES FROM ETHERS AND EPOXIDES
Chem Comm (1965) 259
v
V
87% J P r a k t Chem (1938)
151 61
25% J O C (1962)
Me2CHOCH2Ph
Br2
H20
Me2CO 45%
+
27 2392
PhCHO 55% JACS (1967)
E t y HOMe Me
Electrolysis MeOH
MeONa
*
Etf(OMe)2
--+
~228'
3550
EtCOMe
Me JACS (1969)
Me2CHOCPh3
89
Me2CO JACS (1930) (1924)
91 2803
52 753
fi 2580
@'OM'
oo
COMPENDIUM OF ORGANIC SYNTHETIC METHODS
41 D
Li
EtNH2.
-
SECTION 174
40%
JACS (1955) 6042 JCS (1942) 689 Org S y n t h (1963) Coll Vol 4 903
Some o f t h e methods l i s t e d i n s e c t i o n 54 (Aldehydes f r o m E t h e r s and E p o x i d e s ) may a l s o be a p p l i e d t o t h e p r e p a r a t i o n o f ketones f r o m e t h e r s
Me
Me HC1
i-Pr
Et20
H20
*
79%
i-Pr JACS (1962)
284
a
JCS (1957) 4596 4765 Helv (1953) 398
75% Helv (1948) 51 1077 Chem Rev (1959) 2 737
0
/ \
PrCHCHPr
PrI
Me2SO
PrCH2COPr
100% Chem Corn (1968) 227
SECTION 175
KETONES FROM HALIDES AND SULFONATES
41 1
80%
90 4193
JACS (1968) (1965)
0
Co2(C0)8
/ \
MeCHCHMe
MeOH
MeCH2COMe
27
J O C (1962)
-
0
I\
PhC-CH2 I
Me
S e c t i o n 175
H202
KOH
MeOH
H20
PhCOMe
87 1405
77% 2706
85-90%
JACS (1957)
503
Ketones f r o m H a l i d e s and S u l f o n a t e s
~ ~ ~ ~ O O O O O O O O O O O O O O O O O O O O O O Q0 0 O 0O ~ ~ O
Ketones b y a l k y l a t i o n and h y d r o l y s i s o f D - k e t o e s t e r s , a c y l m a l o n a t e s and d i k e t o n e s Ketones f r o m o r g a n o m e t a l l i c r e a g e n t s , , , M i s c e l l a n e o u s methods , , , , ,
.
-
MeCOCH2COOEt EtONa
BuBr
EtOH
FRr c l z a v a g e :f 8-ke;oesters I,
-
BuBr
I,
I1
I,
-
THF
MeCOyHCOOEt Bu
*
BuCH2COCH2COOMe I
I I
i
NaOH H20
Org Synth w!,th CaI2 se: JOC L iI Org by p y r o l y s i s see J O C
t
CH2COCHCOOMe 2Na
page 411-412
. . . . . . . . . . . 412-415 . .... . . . . . . . . . . 415-417
1 NaH
2 BuLi 3 PhCH2C1
MeCOCH2Bu
(1941) C o l l Vol 1 248 351 (1966) 2 3267 S y n t h (1965) 45 7 (1957) 22 1 1 8 r
BufHCOCH2COOMe CH2Ph
I
Hydrolysis
BuCH2COMe
~ 4 0 %
BuFHCOMe CH2Ph JACS (1970)
92
6702
Hydrolysis
41 2
COMPENDIUM OF ORGANIC SYNTHETIC METHODS
SECTION 175
\TsOH
HOAc
CgH17CH2COC7H15 JACS (1952) 3 831 46% JCS (1952) 3945 (1950) 325 Bui
BuBr
BuBr
MeCOCH2COMe K2CO3
+
EtOH
EtpO
2 PhCN
0-
Bu
30
60%
3321
71%
BuCO(CH2)3Me 340-350" I z v (1964) 747 (Chem Abs 61 3057)
PhCOBu
c
JOC (1965)
Pt-C
1 Mg E t 2 0
1 Mg
BuCH2COMe
JACS (1957)
F u r t h e r examples of t h e r e a c t i o n RMgX + R ' C N s e c t i o n 178 (Ketones f r o m N i t r i l e s )
--+
2 881
RCOR' a r e i n c l u d e d i n
moMe moMe Br
COMe
f4;c,t.Br
Et20
3 MeCOCl CgHg
BuBr
1 Mg
2 Ac20
Et2O
BuCOMe
JCS (1955) 3986 Org React (1954)
8
JACS (1945) 67 1 5 4 JOC (1948) 13 592
28
79%
SECTION 175
41 3
KETONES FROM HALIDES AND SULFONATES
F u r t h e r examples o f t h e p r e p a r a t i o n o f ketones by r e a c t i o n o f o r g a n o m e t a l l i c d e r i v a t i v e s o f L i , Mg, Cd and Zn w i t h c a r b o x y l i c a c i d s , a c i d h a l i d e s and a n h y d r i d e s a r e i n c l u d e d i n s e c t i o n 167 (Ketones f r o m C a r b o x y l i c Acids, A c i d H a l i d e s and A n h y d r i d e s )
1 Li
i-PrC1
PhEr
Et20
(i -PrCH2CH2)pCO
2 Reflux 3 cop
1 Li
Et20
2 cop
JACS (1953)
Ph2CO
1 Li
Et2D
2 EtCONMep
1 EtLi
JACS (1933)
70%
1258 2806
(1955)
-
i-PrCH2CHZbr
75 1771
75%
i-PrCH2CH2COEt
Et20
P
2 Me2NCOOEt
J O C (1959)
24
701
($oMo 75%
T e t r L e t t (1970) 5219
BuBr
1 Li
2 CNCMe2 I
CH~BU-t
BuX
1 Mg
2 PrCHO
Li Bub=NCMe2 CH~BU-t
1 EtBr
2 (COOH)2
JACS (1970)
-
87%
BuCOEt
92 6675
iCOOEt
BuCHOMgX
Pr I
NCOOEt
66%
BuCOPr B u l l Chem SOC J a p (1968)
41 1491
COMPENDIUM
414
1 Mg Et2O
i-PrBr
2
P
MeCH=CHCOMe
OF
ORGANIC SYNTHETIC METHODS
MeyHCH2COMe i-Pr
SECTION 175
3 2721
J A C S (1951)
For promotion o f 1:4 addition o f Grignard reagents by CuX2 see JACS (1941) 63 2308 and J A C S (1965) f i 82 and J O C (1966) c 3 1 2 8
Br
0
1 Mg Et20
48%
2 2-Chlorocyclohexanone
2 843
JOC (1959)
-
12 737
(1947)
1 Li Et2O
PhBr
PhCH2COPh
2 CuBr 3 N2CHCOPh
0
35% C h e m Comm (1969) 515
Me I CHZCHCOMe
3
MeLi
4 (COOH)2
BuBr
1
Mg
EtpO
*
82%
91 5887
J A C S (1969)
BuCOCH~CH~P~
71 %
@CH2CH2Ph Me I 3 (COOH)2
PhCl
--+
H20
PhMgCl --* PhHgCl
92
JACS (1970)
CO RhC13 MeCN JACS (1968)
*
90
1084
Ph2CO 5546
<4ax
SECTION 175
BuBr
KETONES FROM HALIDES AND SULFONATES
Br 1 L i
2 Ph3P
THF
*
CgHg
BuzCO J A C S (1969)
2 3037
Et2O
2 9-Borabi c y c l o[ 3.3.11nonane
Me
PhCH2Br
1 c02(co)8
BuHgBr
--+
41 5
L i [PhCOFe(C0)4]
C6Hg +
95%
Me
PhCH2COPh
67%
J O C (1970) 2 4183 Tr a ns New York Acad S c i (1965)
1 Mg C6H13Br
t
-
CgH1 3COPr-i
fi
2 Ph3PCMe2 C1 I
PhCH2Br
9-
1, ~
2 Zn
BuBr
--+
HOAc
k
724
45%
T e t r L e t t (1969) 23
@CH=CMe
2 Zn
2
THF
COOEt
,
< 42%
C
HOAc
BuC(COOH)2 it
DMF
*
H2D
H H20
PhCH2CH2COMe
C DMA. 0 ~ ~ ~ ~ (PhCH2CH2)zCO A u s t J C h e m (1967)
Pb ( OAC ) 4 ----+
PYr
85%
2 2441
BuCOEt
C6Hg T e t r L e t t (1966) 6145
40%
41 6
BuBr
COMPENDIUM OF ORGANIC SYNTHETIC METHODS
--+
PrLI
BuOCHCH-CHMe
Me2NCH2CHzNMez
I
Me
*
BuYHCHZCOMe
SECTION 1 7 5
-30%
Me
T e t r Lett (1969) 821
2 BuLi i - P r I 3 HgC12
84%
( i- P r ) 2 C O
70%
Angew (1965) 77 1134 ( I n t e r n a t Ed 5 1075) T e t r L e t t (1969) 173 J O C (1968) 2 298 S y n t h e s i s (1969) 17
1 Na2Cr207
2 H2SO4
i-PrCOMe
oo
H20
H20
*
Ber (1956)
MgO
Me2SO
+-
Me3NO
CHC13
*
C6H13C0Me
JCS (1964) 520 JOC ( ' i g s g j 2 1792 (1960) 2 670 Chem Rev (1967) 67 247
oo Ber (1961)
1 Mg
Et20
2 02
Et20
1732
C6H13fHMe
91 %
OOH
NaOH
94 1360
CsH13COMe
77
JACS (1955) 6032 Ber (1960) 93 2151
32%
50%
SECTION 176
KETONES FROM HYDRIDES (RH)
41 7
T e t r L e t t (1970) 2679
t
-
PPh3 Br
NaNH2
.
u
p
C6H6
Ber (1963)
(1961)
h
3
96 1899 94 1987
oo 68%
J O C (1968)
Ph2CBr2
S e c t i o n 176
1 Morpholine 2 HC1
H20
,-
Ph2CO
2 300
B u l l SOC C h i m F r (1965) 3544 Org S y n t h (1941) C o l l Vol 1 95 JACS (1966) 3515
63%
Ketones f r o m H y d r i d e s (RH)
-
~ ~ O ~ O O ~ O O O O O O O O O O O O O O O ~ O O O
T h i s s e c t i o n l i s t s examples o f t h e r e p l a c e m e n t o f hydrogen b y k e t o n i c groups e.g. RH -+RCOMe ( R = a l k y l , a r y l , v i n y l e t c . ) . For the o x f d a t i o n of methylenes R2CH2 R2C0, and t h e d e g r a d a t i o n o f a l k y l s R2CHR + R2C0, see s e c t i o n 170 (Ketones f r o m A l k y l s and M e t h y l e n e s )
(I v
MeCOCOMe
*
dibenzoyl peroxide
nCoMe v JACS (1968)
90 3588
41 8
COMPENDIUM OF O R G A N I C SYNTHETIC METHODS
MeCOCl
MezCHCH3
AlCl3
*
MeCOOH
BuCH=CH2
SECTION 176
MeZCHCHzCOMe Ber (1936)
(CF3CO)zO +
2244
22%
BuCH=CHCOMe JCS (1953) 3628
Review: The F r i e d e l - C r a f t s A c y l a t i o n R e a c t i o n and i t s A p p l i c a t i o n t o P o l y c y c l i c Aromatic Hydrocarbons Chem Rev (1955) 229 COMe MeCOCl
AlC13
57-60%
CgH6
Ac2O
Br
AlCl3
Org S y n t h (1963) Coll Vol 4 8 (1955) C o l l Vol 3 23
CS2*
Br
69-79%
@'OM"
Org S y n t h (1941) C o l l Vol 1 109
RCOOH
(CF3CO)zO
* Me0
Me0
t
PhH
78% (R=Me) 56% (R-Ph)
@OR JCS (1951) 718
-
RCO SbF6
81 -93% ( R = E t ) 86-93% (R=Ph)
PhCOR JACS (1962)
3 2733
SECTION 177
KETONES FROM KETONES Me I C17H35COOC=CHz A l C7 3
*
Me
Me
41 9
@Jcocl
JOC (1970) S 2351
7H35
83%
COPh
70%
JOC (1952) 1281 JCS (1932) 642
S e c t i o n 177
Ketones f r o m Ketones
aooooooooooooooooooo
D i r e c t a l k y l a t i o n and a r y l a t i o n o f ketones w i t h h a l i d e s , o l e f i n s and a l c o h o l s A l k y l a t i o n and a r y l a t i o n o f ketones b y i n d i r e c t methods Homologation and r i n g e x p a n s i o n o f ketones T r a n s p o s i t i o n o f c a r b o n y l groups D e g r a d a t i o n and r i n g c o n t r a c t i o n o f ketones
. .. .. page 419-421 . . 421-426 . . . . . . . . . 427-429 . . . . . . . . . . . . . . . . 429-431 . . . . . . . . . . 432-433 I
I
A l l r e a c t i o n s o f enones f o r m i n g s a t u r a t e d ketones (e.g. RCH=CHCOR *
RCH2-CHCOR) a r e 1 i s t e d i n s e c t i o n i t o n e s f r o m M i s c e l l a n e o u s Compounds) RI
t-BuCOCH2Me
1 NaH THF
2 BuI
t- BuCo:HMe Bu
57% Bull SOC Chim F r (1968) 4990 T e t r a h e d r o n (1968) 24 6583
40%
JACS (1958)
5220
Om
COMPENDIUM OF ORGANIC SYNTHETIC METHODS
420
0 &Me1
1 t-BuOK
t-BuOH
SECTION 177
J C S (1956) 4490
(1960) 67
;I;:;&
MeI,
0
44% Me
J A C S (1960)
(1962)
Et I
MeCOCH3
MepCONa Et20
PhCH2Br
*
CgHg
2847 3402
MeCOC(CH2Ph)3 B u l l SOC Chim F r (1961) 836 (1956) 1392
45% U
91 1264 (1953) 75 369 Org Synth (1955) C o l l Vol 3 44
J A C S (1969)
MeCOCH2Et
NaNH2
PhBr
NH3
*
MeCOCHEt
65%
Ph J A C S (1959)
PhCOCH2Et
1 PhgCNa 2 EtBr
Et20
+
1169
PhCOyHEt
62%
Et J A C S (1957)
(1959)
79 881 81 1745
SECTION 177
i-PrCOCHMe2
KETONES FROM KETONES 1 BuMgBr
HMPA
*
2 Me2S04 o r Me1
421
i-PrCOCMe2 I
Me Compt Rend (1966)
2 263 488
Chem Corn (1969) 1498
PhCOCH3
d i - t - b u t y l peroxide
PhCOCH2C8H17
10%
JCS (1965) 1918
PhCH20H
PhCOCH3
PhCH20Li
70%
PhCOCH2CH2Ph
x y l ene
oro-gM
JACS (1956)
HCOOEt
MeONa
grH Me1
K2C03
___L
Qo Me
C6H6
Me
Me2CO
0 .
0
CO( OMe)2
___c
MeONa
Me@ M :”!eI
Meo
;;!-I
Me JCS (1954) 1373 JACS (1947) 69 1 3 6 1 (1957)
Me0 Me 0
78 4950
Me
0
32%
2 6313
2 HC1 H20 M ~ O HMe0 Me@:
_____t
0
HOAc T e t r a h e d r o n (1957) 1 4 9
83%
0"';
422
6'
0'
SECTION 177
COMPENDIUM OF ORGANIC SYNTHETIC METHODS
1 NaH CgHg.
EtONa
OO z:E:
C O O E t 2 Me1 3 TsOH
Me
HOAc
J A C S (1958) 04072 O r g Synth (1943) C o l l Vol 2 531 F o r t h e p r e p a r a t i o n o f O - k e t o e s t e r s f r o m ketones v i a enamines see J A C S (1963) 207
d l
41 %
CHZPh
DMF
21 MeMgC03 PhCHZBr
72%
J A C S (1959)
0
2598
0
0 COCOOEt 1 Me1
RO
K2CO3
* RO
Me2CO
2 EtONa EtOH J A C S (1958) 80 1967 5220
-]fi
COCOOEt 1 t-BuOK
(COOEt)Z
NaH
53%
P
CgHg
t
-
2 P h 2 I C1
Me0
3 MeONa J M e d C h e m (1967)
5
106
MeMgI RO
Me
no -
Me
-
Me1 E t 2 0 THF J C S (1964) 1161 J O C (1961) 26 2426 Tetr L e t t (1969) 2269
45%
PhMgBr
c1
EtpO
xyl ene
49% Me0
:
h
JOC (1947)
11
737 (1959) 2 843 J C S (1957) 4089
SECTION 177
KETONES FROM KETONES
i-PrCOCHMeZ
--+
423
i-Pr2CuLi
i-PrCOCMe2 Br
i-PrCOCMez i- P r
Tetr Lett (1971) 177
PhCOCH3
--+
PhCOCH2Br
Et3B
t-BuOK
THF
*
PhCOCH2Et
JACS (1968) (1969)
2
1 MeLi
90 6218 91 4304
6852
Et20
MeOCHZCHzOMe 2 Me1
2
J O C (1965)
2502
T e t r Lett (1971) 105
0' ON 9
J O C (1969)
L;;lidine*
1 BuI
2 1962
toluene
44%
2 H2SO4 H20 JACS (1963)
207
Advances i n Org Chem (1963) For p r e p a r a t i o n o f enamines f r o m u n r e a c t i v e ketones see JCS (1965) 5142 and J O C (1967) 32 213
41
COMPENDIUM
424
1 HCHO
2 Me1
Me2NHoHC1 KpCO3
OF ORGANIC SYNTHETIC METHODS
0' Z+
- Tricycle-,
CH NMe3 I
pentyl borane
JACS (1968)
HCHO - - - - - - - - + PhCHCOMe Me2NH*HC1 hHzNMe2aHCl
PhCHpCOMe
EtOH
JACS (1953)
-PhCHO
EtOH
NaOH
&Hph
85%
90 4166
H 2 (60-100 a t m o s ) Ni
SECTION 1 7 7
PhCHCOMe
+
1
56%
Me
7s 1128
ti o:d-C
_I_t
91 %
Hp0
Org Prep and P r o c e d u r e s (1970)
2 37
(yJ dCHo HCOOEt C6H6
&Me
MeONa +
70%
J O C (1965)
0
1 HCOOEt MeONa &cHoCOPh C6H6
2 PhCOCl
2 2502
Hp
PtOZ+
Et3N Pyr
dM
i- P r O H S y n t h e s i s (1970) 476 Org React (1954) 8 119
60-78%
KETONES FROM KETONES
SECTION 1 7 7
1 HCOOEt 2 BUSH
MeONa TSOH
6
0
C6Hg
Ni
425
6
EtOH,
CHSBu
0 Me
79%
Chem Ind (1960) 1534
@I -ogl
Et-jN HCHob PhSH EtOH 0
0
Ni
-80%
Me2CO
CH2SPh
Me
JCS (1962) 1091
Goea:e CHOH
CHSBu
0
TsOHr
0
- - ~
1 Me1
t-BuOK
M~ 2 KOH
JOC (1962)
2 1615
0:.
CHOPr-i 1 HCOOEt Me 2 i - P r I
MeONa K2CO3
0;:
1620 T e t r a h e d r o n (1968) 4 3095
Me
1 Me1
t-BuOK
2 HC1
H20
JACS (1947)
*
Me
69
74%
2
z
1361
n 1 HCOOEt MeONa 2 PhNHMe 2 NaOH EtOCH2CH20H T e t r a h e d r o n (1969) JOC (1970) 35 468
-60%
25 4011
426
COMPENDIUM
1 HCOOEt
OF ORGANIC SYNTHETIC METHODS
&:;
MeONa E t p O 2 KNH2 NH3
1 BuBr
Et20
2 NaOH
H20
JACS (1965)
1 MeMgI
Me
2 Dehydration
1 LiBH4
BF3-Et20
2 Na2Cr207
H2SO4
JACS (1961)
1 POC13-DMF
SECTION 1 7 7
-
81 82
Et20
H20
83
0:
2951
Wolff-
OHc‘fy1
Kishner reduction
0
T e t r L e t t (1964) 2161
AcO
&
OCH2CH=CH2
TsOH
0
95 351 63 11647)
Gazz (1965)
(Chem Abs
40%
B u l l Soc Chim F r (1964) 321
SECTION 177
KETONES FROM KETONES
l C1 Ph3PCHMe +OMe
t-BuOK
-
glyme
t
427
0'""' 0''' HC1
MeOH
45%
T e t r L e t t (1964) 3323
2 50" J O C (1970)
CCOOBU-t
Cl CHCOOBu-t
kH2
35 7 7 7
350-360"
66%
t-BuoK
JACS (1963) 955 Org R e a c t (1949) 5 413 Chem Rev (1955) 55 283
J O C (1966)
CH2N2)
KOH
EtOH
H20
24
-0
p-Tolyl sul fonylmethyl n i trosamide
(+
31
33-36%
Org Synth (1963) C o l l Vol 4 225 O r g React (1954) S 364 JACS (1966) 3515
COMPENDIUM OF ORGANIC SYNTHETIC METHODS
4 2%
OM:
i-PrCHN2
PhCHN2
A l C13
*
0: i-Pr
MeOH+
T e t r L e t t (1962) 775
0
76%
Ph
Org React (1954)
0'
1 brH2COOEt
Zn -----------_--__
2 Hydrolysis
1 HCN
SECTION 177
364
CH2CooH E l e c t r o l y s i s Et3N
JOC (1968)
DIlF
2 2704
piperidine
MeCOCl 3 LiAlH4 Et20
2 Ac20
H20 JOC (1964) 29 2914 JACS (1952) 74 2278 JCS C (1970) 1454
Org S y n t h (1963) Coll Vol 4 221
22%
0’dH2 :;i2 dH2N -0”
SECTION 1 7 7
429
KETONES FROM KETONES
HN02
bkf0
__c
Me2SO
JACS (1965)
4 NaOH
EtCOCH2Me
HClO4 H20
87
1353
J O C (1967)
32
J O C (1960) (1969)
2 1252
EtCH2COMe
3
26%
926
-63%
806
prsal -‘01 --+Blca[ PrSH
0
CHCl3
HBr
CHCl3
J O C (1963)
2 2626
11%
>OUi a/D l -*c:cJl 6 OMe
0
PY r
OMe
3 03
JCS
(1970) 2 4 4
/fi
430
COMPENDIUM OF ORGANIC SYNTHETIC METHODS
SECTION 177
PhCHO
__t
Chem Comm (1967) 898 Compt Rend (1967) C 265 929
/no
If?) - inNoH InNoH 0
RONO
.---+ N2H4
t-BuOK
KOH
NaHSO?
EtOH
”20
Chem Comm (1968) 1350
51 yrO- 1-f ONO H 0
OTs
HOAc
2 TsCl
Pyr Bull SOC Chim F r (1965) 6 7
PhCOCH2Me
1 RONO
2 NaBH4
3 Ac20
PhFHtMe
OAc
C r ( OAc ) 2
THF
H20
PhCH2COMe
J A C S (1970)
92
5276
OAc 1 Br2
AcO
2 NaOH 3 Ac~O
JCS (1956) 4330 4344
50%
SECTION 1 7 7
KETONES FROM KETONES
JOC (1968)
431
33
1733
JCS C (1970) 1454
0
21 HCOOEt T s S C H ~ CNa H~CH~STS
cgl0
3 HgC12
Pd-C
Ac:Ql [Ca
JOC (1969)
1 NH2NHTs
Me0
2 Na
EtOH c
HOCH2CH20H
3 KHS04
PrCOCH2Pr
hV
t-BuOH
PrCOMe
1 0
34 4188
1 P h C 0 0 2 H CHC1-j
2 KHSO4 Me0 Chem Pharm B u l l (1961)
T e t r L e t t (1968) 5385 Chem Corn (1969) 204
9
267
NH3
432
COMPENDIUM OF ORGANIC S Y N T H E T I C METHODS
.
0 2 t-BuOK t-BuOH THF
HO
/fiH
SECTION 1 7 7
6B 0a-s7e0 '
___)
ijp7
87%
Chem Ind ( 1 9 6 6 ) 25
*
monogl yme CONH2
1 NaBH4 HO
COMe JACS ( 1 9 6 8 )
90 2448
0
/A- ,&- 1 6slh CH2Me Ac20
cc14 AcO
JACS ( 1 9 4 2 )
64 1 2 7 6
Helv ( 1 9 4 4 )
2 549
1 6 CH2Me I
HC104
1 0 3
2 H2
JCS ( 1 9 6 2 ) 1 5 7 2
Pd-Bas04
- lb
35%
SECTION 1 7 8
ifi
KETONES FROM N I T R I L E S
]fi 45 CH=CHPh
y 3
CH=CHPh
I
F%CHO,
I
1 Al(OPr-i)3
i-PrOH 2 HOAc
(yJy$o;;;;*
0
433
__c
I-lelv (1949)
32
Ac20
1795
o m
77%
B u l l Soc C h i m Fr (1958) 1573
Bull SOC C h i m Fr (1958) 1573
J O C (1968)
S e c t i o n 178
PhCN
2157
85-90%
Ketones f r o m N i t r i l e s
0000000000000000~000D
1 MeCH2Li 2 BUI
33
HMPA
*
PhCOCHMe I
BU
70% C o m p t Rend (1967) 265 245 Bull SOC C h i m F r (1968) 4990
434
COMPENDIUM OF ORGANIC SYNTHETIC METHODS Me
SECTION 1 7 8
Me
CHCH2CN
i-PrCH2Li
CHCH2COCH2Pr-i
Et20
76%
heptane
JACS (1970)
MeMgI
92 336
Et2O
52-59%
Org Synth (1955) C o l l Vol 3 26
Bu3P=CHPh
BuCN
c1 1H23CN
Et3A1
Et20
C6H6
BU COCH2 P h
JACS (1967)
C11H23COEt Ber (1964)
a
C
N
2
73%
7009
89%
2 2661
NaOH
G
N c1
47%
Me2SO
Tetr Lett (1967) 437
Annalen (1933) (1934)
504
94
513 4 3
KETONES FROM OLEFINS
SECTION 179 S e c t i o n 179
435
Ketones f r o m O l e f i n s
0000000000000000000D
Conversion o f o l e f i n s i n t o ketones w i t h l o n g e r c a r b o n c h a i n s C o n v e r s i o n o f o l e f i n s i n t o ketones o f t h e same c h a i n l e n g t h O z o n o l y s i s and o t h e r d e g r a d a t i o n s o f o l e f i n s t o ketones Ketones f r o m d i e n e s
page 435-436 436-439 440-442 442
., . ...,. .....................,.
EtCHzCH2
1 B2H6 THF 2 BrCH2COMe
p o t a s s i u m 2,6-
t
di-t-butylphenoxide
Q
Et(CH2)3COMe
JACS (1969)
1 BpH6 THF
91 6852
84% 2147
CH2COMe
67%
2 N2CHCOMe 3 NaOH
H20
J A C S (1968)
90
5936
0 - ocHcH2c I
1 B2Hg THF
98%
2 MeCH=CHCOMe air
i-PrOH
1 B2Hg
THF
J A C S (1970)
92 714
COCH~BU
2 BuCXBr 2 NaOH H202
79% H20
J A C S (1967)
----+ (C H CH CH CgH1QCH'CH~ B2Hg l3
2)3B
5086
1 NaCN d i g l y m e 2 (CF$O)20 3 NaOH H202 H20
(CfjH13CH2CH2)2CO w95%
Chem Comm (1970) 1529
436
I" 1 Oicyclohexylborane
2 CO
H20
THF
72%
H20
1 B2Hg THF
2 co 3 NaOH H202
Q CsH13CH=CH2
MeCOCl
AlCl3
cyclohexane
(EtCH2CH2) $0
H20
J A C S (1967)
85%
4528 4530 5285
OoMe Ber (1936)
MeCH2COMe di-t-butyl
EtCH2CH2,-0
diglyme
3 NaOH H202
EtCH=CHz
SECTION 179
COMPENOIUFI OF ORGANIC SYNTHETIC METHODS
t
peroxide
MeCHO
49%
1820
-30%
C6H13CH2CH2yHCOMe Me J C S (1965) 1918
30%
*
dibenzoyl peroxide
A u s t J C h e m (1967) J O C (1964) 3 245 (1949) 248
14
20 2033
78% -Me
2 Na2Cr207 H$O4
H20
\/-Me J A C S (1961) 2951 J O C (1962) 27 2938 Org React (1963) 13 1
SECTION 179
437
KETONES FROM O L E F I N S
Chem Ind (1965) 1929
JACS (1970) 92 5276 Zh Org Khim (1966) 2 2178 (Chem Abs 66 75730)-
COMe
-
Br
COMe
COMe
2 Zn
NaOAc
Helv (1944)
2 821
438
C O M P E N D I W O F ORGANIC S Y N T H E T I C METHODS
SECTION 1 7 9
1 CroL CHC13
2 Zn
HO*"
J A C S (1956)
JOC (1968)
0
0 1
78
2
3749 3970
91 % JACS (1964)
1 T l (NO3)3
2 H2SO4
MeOH
H20
*
fi 4506
PhCH2COMe T e t r Lett (1970) 5275
81 I
68% JOC (1969) 2 3949 Synthesis (1970) 225
41 %
JOC (1967) 32 2669 (1962)
666
S E C T I O N 179
KETONES FROM OLEFINS
439
,k
I
CH:
Tetr Lett (1964) 3481
F u r t h e r examples o f t h e e p o x i d a t i o n o f o l e f i n s and t h e c o n v e r s i o n o f epoxides i n t o ketones a r e i n c l u d e d i n s e c t i o n 134 ( E t h e r s and Epoxides f r o m O l e f i n s ) and s e c t i o n 174 (Ketones f r o m E t h e r s and Epoxides)
fi 5 3
O r g Synth (1961)
NBS
-
Br
Q C H M e
Q
h
M
OH
e
E i-PrMgBr t 2 0 C6Hg
JOC (1970)
a
35
o
M
69-81 %
e
40%
2670
NgBr
6HCH2Br
NgcH=cH*
+ Br2 Et20
bh
I
KOH H20
EtOH
Ph
NJcofMe
71% I
Ph
JCS (1963) 3967
COMPENDIUM OF ORGANIC SYNTHETIC METHODS
440
'
@ hP &
1 03
HOAc
2 H2
Pd-CaC03 *
SECTION 179
@O r: Ph Ber (1954)
g
993
Ozonides may a l s o be reduced by t h e f o l l o w i n g r e a g e n t s :
Ph3P
JACS (1943) 65 752 JACS (1941) 63 3540 JACS (1948) 70 4069 Ber (1963) 5 1 5 6 4 Bull SOC Chim F r (1964) 729 Angew (1956) 68 473
P (OMe) 3-MeOH
J O C (1960)
Zn-HOAc Ni HCOOH Tetracyanoethylene
Na I - HOAc
KMn04
NaI04
K2CO3
H20
dioxane
PhC=CHPh I BU
os04
~a104
dioxane
*
H20
1031
J O C (1968) 1656 Ber (1955) 795 Ber (1954) S;. 993
PhNHNH2
CH2
25 2
J O C (1966)
+
PhCOBu 71%
2
3028
PhCHO JACS (1966) 88 476 (1957) 2 6313 JCS 2. (1966) 655
Pb ( OAC ) 4
JCS
o
q
C
(1966) 655
Bull SOC C h i m Fr (1964) 729 JCS (1962) 4745
KETONES FROM OLEFINS
SECTION 1 7 9 Me ~-BuCH~C=CH~
K2Ct-207
HpSO4
Hp0
*
44 1
JACS ( 1 9 5 0 )
1 CrO3
72 3701
zlp
4p
MeCHCH2CHzCH=CMez
56%
t-BuCHpCOMe
MeCHCH2CHzCOOMe
HOAc
2 CH2N2
MeCHCHzCH=CPhz
/1 NBS
/
J A C S (1970)
N- N i t r 0 s o p ip e r id ine
Ph C = C I i z I
hu
*
PhC=NOH I
Me
Me
C
H
PhCH=CMe2
Z
2 NH2NHNa
2059
--+
91 %
JACS (1965)
O
92
PhCOMe
87 4 6 4 2
0 ; O
JCS ( 1 9 5 1 ) 2999 3009
Et20
*
MezC=NNH2
---+
2 AcpO
Me2CO
53% Angew ( 1 9 6 2 ) 650 ( I n t e r n a t Ed 1 . 4 5 6 )
HOAc
COMPENDIUM OF ORGANIC SYNTHETIC METHODS
442
PhzC=CHEt
NaN3
H2SO4
PhCOCH2Et
b
64% JACS (1950)
Me I i-PrCBH2 I 1 Me
S e c t i o n 180
2 5777
THF
2 CO (70 atmos) 3 H202 NaOAc H20
CH=CH2
SECTION 180
60% Chem Comm (1968) 594
Ketones f r o m M i s c e l l a n e o u s Compounds
~
~
~
O
~
~
~
O
O
O
O
.. . . . .. . .. .. . .. . .. .. .. page 442-443 . . 443-445 . . . . . 445-446 . . . . . . . . . . . . . 446-447
O 0 0O0 0 O0 O 0 0O0 0O0 0 0 0 0 0 0 0 0 0
, , , , , , R e d u c t i v e a1 k y l a t i o n o f enones R e d u c t i o n o f enones t o ketones R e d u c t i o n o f hydroxy and a c e t o x y ketones t o ketones R e d u c t i o n o f h a l o ketones t o ketones Ketones f r o m m i s c e l l a n e o u s compounds
.............
448-449
< 83% Me
JACS (1965) 81 275 T e t r a h e d r o n (1964) 2 357 JOC (1967) 32 2851 Bull SOC Chim Fr (1969) 4356 4348
BuMgBr
Cu(OAc)2
71 I Bu JACS (1965) 82 J O C (1966) 5 3128 JCS (1943) 501
SECTION 180
MeCH=CHCOMe
KETONES FROM MISCELLANEOUS COMPOUNDS MeMgBr-Bu3PCuI
Me2CHCH2COMe
t
Et20
443
99%
JOC (1966) 31 3128
PhCU
Et20
Me
Me Tetr Lett (1970) 1579
H2
Pd-C
J O C (1958) 2 1853 Chem Ind (1966) 1796 F o r r e d u c t i o n o f enones w i t h HZ and Rh see J O C (1968) 33 3695
PhCH=CHCOMe
H2
Ni
CH2C12
PhCH2CH2COMe
t
93-96%
Bull SOC Chim Fr (1954) 522
Me2C=CHCOMe
Ni
H20
Me2CHCH2COMe
95% Bull Chem SOC J a p (1967)
CaH17
(Ph3P)3RhC1
0 @eOH
*
Me0 Me0
40% Ber (1968) 101 1154
40
1548
444
COMPENDIUM OF ORGANIC SYNTHETIC METHODS
H2
a 1 *m
(Ph3P)3RhC1
SECTION 180
NaI
* 0
0
JACS (1966)
1 Li
NH3
2 MeOH 3 CrO3
t-BUCH=CHCOBU-t
Na
HMPA
Et20
trans
H2SO4 Me2CO
THF
*
4537
63%
J O C (1970) 35 753 JACS (1965) 275
t-BuCH2CH2COBu-t JACS (1970) 92 2783 B u l l SOC Chim Fr (1968) 595
1 Na U
MezC=CHCOMe
t r i r n e s i t y l borane
MeOCH2CH20Me 2 MeOH
CrC12
NH3
*
0
3
JACS (1970)
H20
b
92 696
Me2CHCH2COMe Angew (1968) ( I n t e r n a t Ed
PhCH=CHCOPh
D i e t h y l 1,4-dihydro-2,6-
-
t
dime t hy 1 p y r id ine 3 ,5-d ic a r boxy 1a t e 156"
0
80 271 L 247)
PhCH2CH2COPh
JCS (1960) 3257
85-95%
445
KETONES FROM MISCELLANEOUS COMPOUNDS
S E C T I O N 180
40%
A
c
O
MeZC=CHCOMe
W
JCS
Ph3SnH
Compt Rend (1965)
NCH2Ph
PhCHzNH2
Me
(1967) 2032
MeZCHCHzCOMe
Q -------+Q 0
C
Me
t-BuOK+
260 581
o N = c H p h
HOAc_
Me JACS (1967)
g o Me
2794
40-70%
Zn HOAc
___t
AcO JCS C (1970) 244 JACS (1955) 77 4367
Ca
NH3
Et20
*
mo JOC (1969) 34 4188 JCS (1956) n 4 4
80%
COMPENDIUM OF ORGANIC SYNTHETIC METHODS
446
Na-Hg
SECTION 1 8 0
MeOH
95% B u l l Chem SOC J a p (1969)
42
2068
75-78% Org S y n t h (1963) C o l l Vol 4 218 JACS (1964) 3068
YH
EtCOCEt2
HI
HOAc
H20
*
EtCOCHEt2
JACS (1964) 3068 J O C (1938) 3 456
80%
80% JACS (1964)
5
3068
100% T e t r Lett (1971) 137
Me COOEt
ciC H ~ C O ~ H
COOEt COOEt
Zn
KI
HOAC
MeCOCH
COOEt
88% JACS (1961) 83 3114 Helv (1944) 27 821 T e t r L e t t (1968) 1575
KETONES FROM MISCELLANEOUS COMPOUNDS
SECTION 180 CrS04
PhCOCH2C1
DMF
H20
*
PhCOMe
JACS (1963) 2768 (1945) 67 1728 Angew (1968) 0271 ( I n t e r n a t Ed 1 2 4 7 )
447
79%
C8H17
B h &H2 ,
Pd
0
MeOH
KOAC, Me2CO
0 JCS (1964) 5535
Bu2SnHp
PhCOCH2C1
Et20
c
95%
PhCOMe JOC (1963)
4r
PhNMe2
Chirnia (1967) JCS
i-PrCH2COCHPr-i BI r
I
Br
70-76%
o r 2,6-dimethylphenol
0
PhCOCHMe
2165
1 Ph3P 2 EtOH
C6H6
c
C
i-PrCH2COCH2Pr-i JCS (1962) 2337 T e t r L e t t (1962) 471
-Ph2PH
CCl4
g 464
(1969) 301
100%
PhCOCH2Me JOC (1969)
34
2687
448
O o H
COMPENDIUM OF ORGANIC SYNTHETIC METHODS
---*
O O B U
SECTION 180
*Q
PrLi
MezNCH2CHzNMez
SU
T e t r L e t t (1969) 821
1 NH20H.HC1
Pyr
2 p-Acetarnidobenzenes u l f o n y l c h l o r i d e Pyr 3 H2SO4 H20
Ac 0
J O C (1956) 2 520 Org React (1960) 11 1
YAc
Me2CCHBu I
OH
154O
Zn
Me 2 C = C HCH2Ctl2$' HMe
68%
MeZCHCOBu Chem Corn (1968) 1639 J O C (1970) 5 660
Polyphosphori c a c i d
-
*
OH
D r H M e NO2
KMn04
M~~CHCH~CHZCH~COM~
80%
Bull SOC Chim Fr (1963) 1799 JACS (1965) 7 2 7 7 2
KOH
____t
77%
[)COMe
MgS04 H2° J O C (19bL)
3 3699
PROTECTION OF KETONES
SECTION 180A No2
1 EtONa
ph
2 HC1
449
EtOH
78%
E t O H*
H2O
0
:
h
11
J O C (1952) 581 Chem Rev (1955) 55 137
P R
ti I 04
I
I
__c
S e c t i o n 180A
R = CHOH
11
Helv (1938) 546 (1940) 23 170 (1941) 24 945 O r g React (1944) 2 341
P r o t e c t i o n o f Ketones
. ....,.,.... . ... . .. .. . ... . . ... . .. I
I
.,.,.. .,.,.. .,.,.. , . . . . . , . . . . . .. .. ,. . ... . ....,. . ,. . . . ,,,.. .... . I
I
I
. . . . . . . . . .
. . . . . . . . . . .
I
. . . . . . . . . . I
I
CHO
Me
~ ~ ~ ~ O O O O O O O O O O O ~ O O O O O
Ketals Hemithioketals Thioketals Thiazolidines Enol e t h e r s Thioenol ethers Enamines Oximes . Semicarbazones Hydrazones Cyanohydrins Miscellaneous
or
I
. .. .. .. ,, . . .. .. .. .. .. I
. . . .. , , ., .. .. ., ., ., .. ,
, , , ,
... . , . . . . . ..... ..... .. .. .. .. .. ..... . , . . . , . . . . . . . . . . , . . .... I
I
...
. . . . . . . . . . I
, ,
.
. . . . .
. . . . . . . ,
, , ,
.
page 449-451 , 451 , 451-453 . 453 453 454 454 454 455 455-456 , 456 , . 456
.. .. , . , . .. .. .. .. ,, .,
...
. . . . . .
K e t a l s a r e s t a b l e t o t h e f o l l o w i n g r e a g e n t s : NaOH, NaH, Na-NH3, RMgX, NaBH4, L i A l H 4 , Hz-Pd, CrO3 and SOC12-Pyr
PhCO
PrOH
MezC(0Me)p
TsOH
c
' v_ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ / Me Acid
PhC( O P r ) 2 I Me
H20
J O C (1960)
25
5 2 1 525
450
COMPENDIUM
MeOH
OF ORGANIC SYNTHETIC METHODS
HC(OMe)3
SECTION 180A
TsOH
t
+------------------A c i d H20 JACS (1968)
90 2448 656 9 7
Annalen (1962)
no MeOH
i o n exch r e s i n ( a c i d )
~.--------------------------
Acid
t
H20 JOC (1959)
2 1731
The f o l l o w i n g c a t a l y s t s may a l s o be used f o r t h e p r e p a r a t i o n o f k e t a l s : (Ph3P)3RhCl
Se02
. .Ber
....
101 1154 (1954) 2 6113
(1968)
.JACS
"
H3PO4 H20
MeCEt
JCS (1962) 4722 JACS (1964) 8 2183
TsOH
____t
O
+-----------
H
Acid
H20 JACS
&
(1954) (1953)
2 1359 75 1716
0
M e g HOAc
0
CH2C12,
S t e r o i d s (1963) 1 4 5
SECTION 180A
PROTECTION OF KETONES
0 0
1 ClCHzCH20H
*
2 Et3N
+.-------------
Acid
HO(CH2)nSH . I
H20
0
HO
K
CgHll
1 0
(Stable to base and LiAl H4)
Me2CO or CdC03 or HC1 HOCH2CH2OH
HgCl2
V
H2SO4 H20 THF
n
s o
ZnCl2 Na2S04
JACS (1951)
--*
n=2 or 3
75
d ioxane
Ni
1280
JACS (1953) 3704 (1954) 76 1945 see JAcS (1958) 4723
HOCH2CH2SH
*
33
(PhCH2)2C:;lCH2)n
+
TsOH Me2CO
CllO
J O C (1968)
TSOH C6H6
For cleavage w i t h Ni
RyC5H11 0
dn
0
(PhCH2)ZCO
451
73 4961
R y C 5 H 11 00 U
JACS (1968)
90 3245
COMPENDIUM OF ORGANIC SYNTHETIC METHODS
452
SECTION 180A
T h i o k e t a l s a r e s t a b l e t o t h e f o l l o w i n g r e a g e n t s : NaOH, L i A l H 4 , RMgX, C r 0 3 - P y r
P-
HSCH2CHzSH
I
HgC12 H20
BF3.Et20 -b
CdC03
Me2CO
JACS (1959) 81 4556 Can J Chem (1955) 33 716
CI s s
0
J Med Chem (1970)
- .
-
13 191
Monoperphthalic a c i d
0
THF 1 EtONa 2 02
EtCOMe
(PrS13B -+ .
MeOH
EtC(SPr)2 I
Et20
T e t r L e t t (1967) 165
(Neutral conditions)
Me
Can J Chem (1969) (1965)
47 859 43 307
SECTION 180A
(RCOOCH2)2CO
PROTECTION OF KETONES EtSH
*
HgC12
.
ZnClz Me2CO
453
(RCOOCH2) 2C ( S E t ) p
H20
33
Can J Chem ( 1 9 5 5 )
716
1 HSCH2CH2NH2 TsOH CgHg 2 Acetylation
0
Ni
Me2CO JOC ( 1 9 6 2 )
MezC(OMe)2 MeOH
0
HC1
TsOH
DMF
MeOH
*
H20
EtOH
0 Me
HC1
MeOH
a '
Me0 \
2
3925
TsOH
dioxane H20
Me
JACS ( 1 9 5 9 )
A c i d H20
1112
( S t a b l e t o base, RMgX and L i A l H 4 ) JOC (1961)
HC(OEt)3
2
81 4566
A n n a l e n ( 1 9 6 2 ) 656 97 Gazz ( 1 9 6 2 ) 9 2 3 0 9 (Chem Abs 2 7 2 5 7 2 )
COMPENDIUM OF O R G A N I C SYNTHETIC METHODS
454
Acid
LiA1H4
( S t a b l e t o LiA1H4)
JACS (1951)
EtOH
Pyrrolidine 0
HOAc
NaOAc MeOH
*
SECTION 180A
(Stable t o acid)
73 1528
CNJ3 ( S t a b l e t o RMgX and L i A l H 4 )
C o l l Czech (1961) 26 1646 JACS (1956) 78 430(1952) 3627
NH2OH.HCl
PhtO
*Ni
Et
PhCHzy0
NaOH
---+
NaOH EtOH
PhC=NOH
t
H20
EtOH
PhCH2CzNOH I
Me
Me Cr(oAc)z
I
Et
THF
JCS C (1966) 531
Ac20
H20
PhCHzC=NOAc I
Me
92
JACS (1970)
5276
Oximes may a l s o be cleaved by t h e f o l l o w i n g r e a g e n t s :
JOC (1966) 31 3446 NaHS03 MeCOCH2CH2COOH-HCl JACS (1959) g 4629 Zn-HOAc Tic13 (NH4)2Ce(N03)6 Fe(C0)5-BF3.Et20
J Indian Chem SOC (1969)
46 44
T e t r L e t t (1971) 195
Can J Chem (1969) J O C (1967)
2 2938
41 145
For p r e p a r a t i o n o f oximes o f u n r e a c t i v e and a c i d o r base s e n s i t i v e ketones ( u s i n g Me2SO-NHzOH.HCl) see Chem Ind (1969) 240
PROTECTION OF KETONES
SECTION 180A
-
NH20Me HC1
455
NH2CONHNH2.HCl
Pyr
*
EtOH
MeON ( S t a b l e t o a c i d and base)
0
HOAc
H20
JOC (1962) For cleavage o f methoximes w i t h 03 see JOC (1969)
NH2CONHN
27
34
914 2961
Semicarbazones a r e s t a b l e t o NaBH4 and Oppenauer o x i d a t i o n
(COOH)2
H20 Helv (1932)
Semicarbazones may a l s o be c l e a v e d by t h e H2S04 H20 HC1 -H20 MeCOCOOH
-
1220
f o l l o w i n g reagents: JCS (1946) 27 JACS (1950)
2 1751
JCS (1953) 3864 JACS (1955) 1221
MeCOCH2COMe-HCl Annalen (1962) 656 119 Ac20-Pyr JOC (1956) 2 795 (NHq)2Ce(N03)6 Can J Chem (1969) 47 145 MeC002H Ber (1961) 2 712 NaN02- HOAc R e c Trav Chirn (1946) 65 796 JACS (1955) 77 4781
PhCO I
NH2NMe2
Me I e I
EtOH
(1961)
PhC=NNMe2
H20
t!le
83
4249
( S t a b l e t o base, 82H6, L i A l H 4 and CrO3) Chem Comm (1969) 445
For cleavage o f d i m e t h y l hydrazones w i t h 03 see JOC (1969) I, II $1 I1 p e r a c i d see Ber (1961) Et2CO
PhNHNH2 --------+ MeCOCH2COMe HOAc
EtzCzNNHPh
0
Annalen (1962)
656
119
34
2961
g 712
456
COMPENDIUM OF O R G A N I C SYNTHETIC METHODS
SECTION 180A
Phenylhydrazones may a l s o be c l e a v e d b y t h e f o l l o w i n g r e a g e n t s : MnOZ J O C (1967) 2 2252 MeC002H J O C (1967)
2
2865
2,4-Dinitrophenylhydrazones a r e s t a b l e t o CrO3 and B2H6 C6H13f0 Me
Me
o-""?
2 , 4 - D i n i t r o p h e n y l h y d r a z i ne
I
- - - - - - - - - - - - - - - - - - - -CgH13C=NN -----*
+KHC03
HOCHzCH20H H20
NO2
A u s t J Chem (1968)
271
2,4-Dinitrophenylhydrazones may a l s o be c l e a v e d by t h e f o l l o w i n g r e a g e n t s :
g
MeCOCH2CH2COOH-HCl
JACS (1959)
SnC12-HC1 -Me2CO
N a t u r e (1954)
4629
173 266
C r C l 2-HC1
JCS (1962) 4729
03
Chem Corn (1968) 433 J O C (1951) 16 556
CUCO~.CU(OH)~-HCOOH N a t u r e (1954)
173 541
OH 1 Me2dCN 2 Ac20
0
KOH
MeOH
Et3N
Pyr
* AcO
CN
( S t a b l e t o a c i d s , p e r a c i d s , CrO3
oo-
Gazz (1961) 1 1 2 5 0 (Chem Abs 56 10211) S t e r o i d s (1967) lo 411 JACS (1953) 650
15
PhMgBr
RuC13
NaOCl
H20
Chen Conun (1970) 1420
and B r 2 )
Compendium of Organic Synthetic Methods, Volume 1 Edited by Ian T. Harrison, Shuyen Harrison Copyright 0 1971 by John Wiley & Sons, Inc.
PREPARATION OF
Chapter 13
NITRILES
S e c t i o n 181
BuCGCH
N i t r i l e s from Acetylenes
a o o o o o ~ o ~ ~ ~ ~ o o o o ~ o o o D o o o o
1 (i-Bu)pAlH
*
BUCHZCHCN
Et2O
2 MeLi
87%
3 (CN)2
1 Mg
CgHl g C X H
MeCECH
2 ClCN
COC12
NO
S e c t i o n 182
CN ((!H2)3COOH
EtMgBr
hv
*
BuCH~CH~CN
--+
JACS (1968)
CgH1gCXCN
--+
90 7139
CgH1gCH2CHzCN
Annales de C h i m i e (1926)
MeCN
JACS (1963)
2
5
3506
N i t r i l e s from Carboxylic Acids
000000000000000D00000000000000
Electrolysis
MeONa
MeOH
*
CN ( t H 2 )gCN
-41%
2 . N a t u r f o r s c h (1947) 2b 185 Advances i n Org Chem (1960) 1. 1
457
458
COMPENDIUM OF ORGANIC SYNTHETIC METHODS PhCHzCN
i-PrCOOH
H2SO4
SECTION 1 8 2
i-PrCN
40%
JCS (1956) 1686
COOH
-
I s o p h t h a 1on it r i1 e 259-294'
c1
c1
J O C (1958)
Pb(CNS)2
PhCH=CHCOOZnl/2
A
b
93%
@ NCJ
23
1350
27-36%
PhCH=CHCN JACS (1916)
38
2120
26%
JCS (1961) 3185
1 ClS02NCO
t-BuCOOH
2 DMF
@
COOH
NO2
pentane
b
p-to1 uenesul fonamide
200-205"
t-BuCN
68 %
Ber (1967) 100 2719 T e t r L e t t (1968) 1631
PCl
85-90%
Org S y n t h (1955) C o l l Vol 3 646 JCS (1946) 763
SECTION 183
NITRILES FROM ALCOHOLS
COOH
459
COCN
CN
JACS (1967)
COOH
CN I (TH2)8 CN
(fH2)8 COOH
(t-Bu)2CHCOOH
2338
46-49%
Org Synth (1955) C o l l Vol 3 768 (1963) C o l l Vol 4
-
1 soc12
SOCl2 * (~-Bu)~CHCONH~ 2 NaNH2 NH3 C6H6 JACS (1960)
62
(~-Bu)~CHCN
61%
2498
Further examples of the preparation o f nitriles from aniides are included in section 186 (Nitriles from Amides) C14H2gCH2COOH
1 SOC12
+
2 PhH AlCl3
C14H2gCH2COPh
i-PrCH2CH20NO HC1
* C14H2gCCOPh 11
1t5c1
NOH
NaOH
JACS (1953) 2 2347 J O C (1961) 26 3507
Section 183
Ph3COH
FN
C14H29CN
Nitriles from Alcohols 0000000000000000000000
CH2COOH ZnCl2
*
Ph3CCH2CN
Annalen (1963)
661 157
86%
460
COMPENDIUM OF O R G A N I C SYNTHETIC METHODS
CCl4
CgH13tHOH Me
Ph3P
CgH13tHC1 Me
-
NaCN Me2S0
JOC
TsCl
Pyr+
Me \
C6H13yHCN Me
2 855
0'- 0'
Me o L H c H 2 0 H
(1967)
SECTION 184
Me
Me
CHCHzOTs NaCN
CHCH2CN
Me \
Me2SO Me JACS ( 1 9 7 0 )
92
86%
336
F u r t h e r examples o f t h e p r e p a r a t i o n o f n i t r i l e s f r o m h a l i d e s and s u l f o n a t e s a r e i n c l u d e d i n s e c t i o n 190 ( N i t r i l e s f r o m H a l i d e s and S u l f o n a t e s ) NH3
PhCHzOH
MeONa
S e c t i o n 184
PhCHO
02
CuC12 MeOH
PhCN Rec T r a v Chim (1963)
30%
00000000000000000000000
KCN
H20
PhyHCN OTs
PhH A1C13
(Et0)ZOPCHzCN MeOCHZCHzOMe
NaH
+
PhCHZCHCN
66%
57%
PhCHCN bh
J O C (1954)
PhCHO
82 757
N i t r i l e s f r o m Aldehydes
TsCl
*
---*
JACS (1961)
19 1699
PhCHZCHZCN 1733
S E C T I O N 184
rooEt
FOOEt PrCHO
461
N I T R I L E S FROM ALDEHYDES
CH2CN
H2
Pd +
HOAc
PrCH2CHCN
1 Base
-------
2
A
.j
PrCH2CH2CN
Org Synth (1955) C o l l Vol 3 385 JACS (1959) 81 5397
PhCOOCHCN
&I-@@-
Arch Pharm (1957)
PhCHO
KC N
SOCl2
- - - * PhCHCN
bH
C H C ~ ~
Zn
PhCHCN
h1
HOAc
9218
J SOC Chem Ind (1935)
r $ S
NaOAc
o C H 2 C C O O H
1 AcNHCH~COOH
NaOAc
w
Ac20
2 NaOH H 2 0 3 HC1
Ac20_
Ac20
PhCH2iCOOH NOH
PhCH2CN
43-60%
H20 JACS (1942) 64 885 Org Re a c t (1946) 2 198
H20 NH3
nickel peroxide
50%
-b
c1
CH2CN
JACS (1940) 62 1512 JCS (1946) 958 Org Re a c t (1942) A 2 1 0
4 NH20H'HCI NaDH
II
NOH
23 NaOH NH2OH-HC1 EtONa
PhCHO
54 98T
H
oCHo 0
~ 5 6 %
PhCHZCN
Et20
c1 Chem Comm (1966) 1 7
462
COMPENDIUM OF ORGANIC SYNTHETIC METHODS
SECTION 1 8 4
59% Chem Ind (1965) 988
NH3 C6H13cm
PhCHO
MeONa
CuC12
02
MeOH
1 NH3 MeONa 2 I2
*
C6H13CN
6 3% Rec T r a v Chim (1963)
MeOH
+
82 757
PhCN
50% B u l l Chem SOC J a p (1966)
39
854
77% JACS (1961)
83 2 2 0 3
44%
74
JACS (1952) 1168 Org R e a c t (1946) 2 307
SECTION 184
NITRILES FROM ALDEHYDES CF3COONHCOCF3
PhCH=CHCHO
PYr
c
C6H6
463
PhCH=CHCN
88%
JACS (1959) ? 6340l -
aCHo Ni;;H.HCl
Me0
67%
Me0
Chem Ind (1961) 1873
JCS (1965) 1564
CHo
WH20H-HCl H20
Me0
NaOH
EtOH
70-76%
b
Me0
OMe
OMe OMe Org Synth (1943) C o l l Vol 2 622
The f o l l o w i n g r e a g e n t s may a l s o be used f o r d e h y d r a t i o n o f oximes t o n itri les: Can J Chem (1967) 45 1014 HC1-EtOH MsC1-Pyr-collidine
T e t r L e t t (1965) 2497
Ph NCO- Et3N
JOC
(1961)
26
782
Bull Chem SOC J a p (1962)
PhN=CC12
2 1104
(Ph0)2POH-CC14-Et3N J O C (1969) 2 2805 p - c h l o r o p h e n y l c h l o r o t h i o n o f o r m a t e Chem c o r n (1970) 1014
BuCHO
NH2NMe2
BuCH=NNMe2
CgH6
1 Me1
*
2 MeONa MeOH o r H202 H20
JOC (1962)
(1966)
PhCH2CHO
Ph2NNH2
PhCH2CHzNNPh2
02
hv
BuCN
42-47%
27 4372 2 4100
PhCH2CN
T e t r L e t t (1970) 2085
41 %
464
PhCHO
SECTION
COMPENDIUM OF ORGANIC SYNTHETIC METHODS
1
F NH2N kN
186
N
I
TSOH
2 190-200"
C6H6 +
PhCN 2 Chem (1964)
5
69% 304
Some o f t h e methods l i s t e d i n s e c t i o n 192 ( N i t r i l e s f r o m Ketones) may a l s o be used f o r t h e p r e p a r a t i o n o f n i t r i l e s f r o m aldehydes
S e c t i o n 185
N i t r i l e s from A l k y l s OOOCCOCOOOOOOOOOOCCO
T h i s s e c t i o n l i s t s examples o f t h e r e p l a c e m e n t o f a l k y l groups by n i t r i l e s . F o r t h e r e p l a c e m e n t o f hydrogen by n i t r i l e , RH -+ RCN, see s e c t i o n 191 ( N i tri 1 es f r o m H y d r i d e s )
PhEt
02
NH3
3890
S e c t i o n 186
Cr2O3
*
PhCN T e t r a h e d r o n (1968)
24
6277
N i t r i l e s f r o m Amides
ooooooocooooocooooo
RhCl (PPh3)3
25% (R=Et) 71% (R-H)
c1
c1
T e t r L e t t (1970) 1963
PhCH2CONH2
--+
PhCH2CONHBr
Ph3P
PhCH2CN
C6H6
JCS (1960) 2976
60%
SECTION 187 Ph3P
PhCONH2
465
NITRILES FROM A M I N E S CCl4
THF
*
PhCN
82%
T e t r L e t t (1970) 4383
fONH2
c1
CN
DCH3 5 c1
c1
c1
JACS (1949)
2 2650
The f o l l o w i n g r e a g e n t s may a l s o be used f o r t h e c o n v e r s i o n o f amides i n t o n it r i l e s : Org Synth (1963) C o l l Vol 4 436 SOCl2 SOC12-DMF
Chem Ind (1964) 752
TsCl -Pyr
JACS (1955)
COCl2-Pyr
JCS (1954) 3730
PhS03H (235')
JCS (1946) 763
77 1701
Org Synth (1963) C o l l Vol 4 144 p205 POC13-NaHS03 J O C (1957) 22 1142 ~ 1 ~ 1 3 JACS (1940) 62 1432
Et3SiH-ZnC12 Compt Rend (1962) 254 2357 Catechyl phosphorus t r i c h l o r i d e Ber (1963) 96 1387 C o l l Czech (1963)
DCC-Pyr
J O C (1961)
NaBHq-Pyr
Chem Pharm B u l l (1969) JOG (1967) 32 846
BuLi
S e c t i o n 187
NH2 @Me
8 2047
Me2NCHF2
J O C (1967)
(1966)
26
3356 98
2 3640 31 3873
N i t r i l e s f r o m Amines
00000000000000000000
0': aCN 70 NaN02 HC1
'l
Me
64-70%
CgH6
Org Synth (1932) C o l l Vol 1 514 Rec Trav Chim (1961) 1075
COMPENDIUM OF ORGANIC SYNTHETIC METHODS
466
BF4
NaCN
~
Me$O Ph
Ph
SECTION
187
gCN < 50%
Ph Org Prep and P r o c e d u r e s (1969) 1 2 2 1
c16‘ = &.
C8H17
&--+
“’NHCHO
$Lo
T e t r Lett (1966) 5087
JOC (1958) 2 1221
Nickel peroxide
*
C7H15CH2NH2
PhCH2Nti2
BuCH~NH~
PrCH2NH2
CgH6
Chem Pharm Bull (1963)
Pb(OAc)4
C6Hg
Ago
H20
1 C12
NaHC03
2 CsF
MeCN
*
PhCN
BuCN
*
11 296
T e t r a h e d r o n (1967) 3 721
T e t r L e t t (1968) 5685
H20
96%
C7H15CN
PrCN JOC (1968) 2 1008
59%
87%
SECTION 189
NITRILES FROM ETHERS IF5
C5H11 CHZNH2
CH2C12
Pyr
*
36%
C5H11C N JOC (1961)
S e c t i o n 188
467
26
2531
N i t r i l e s from Esters
ocooocoooooooooooo6
The r e a c t i o n ROTS -.+ RCN i s i n c l u d e d i n s e c t i o n 190 ( N i t r i l e s f r o m Hal i d e s and S u l f o n a t e s ) MeONO MeONa DMF
*
EtCHZCOOMe
EtCN
18%
J P r a k t Chem (1969)
C5H11ON0
PhCH=CHCHZCH(COOEt)2
PhCH=CHCHZCCOOH
NaOEt
Ac20
311 370
PhCHZCHCHzCN
{OH JCS (1950) 926
S e c t i o n 189
OMe
N i t r i l e s from Ethers
~
~
~
~
~
O
~
O 0 0D 0 0~
H20*
O
D
O
~
€‘~E;trolysis
30%
QCN
NO2
NO2
@OM‘
O
NaCN h 3 t-BuOH
Me0
C
JACS (1966)
88
2884
Et4NCNb
45% Me0 JACS (1969) 4181
SECTION 190
COMPENDIUM OF ORGANIC SYNTHETIC METHODS
468
KCN
ArOMe
S e c t i o n 190
MeCN
Ber (1933)
668
1623
N i t r i l e s f r o m H a l i d e s and S u l f o n a t e s 000000000000000000000000000000000000
1 NaNH2 NH3 c1
30%
2 PrCH2CN
OMe
OMe
COOEt I
EtI
CH2CN
---+
EtONa
-
FooEt Et2CCN
NaOH H20 A
EtBr
CH$N
J bled Chem (1971)
NaNH2 NH3
*
YOOH
Et2CCN
14 72
A
Et2CHCN
/
81 5397 (1938) 60 1 3 1 Org React (1957) 9 107 J A C S (1959)
EtCH2CN J A C S (1945)
67 2 1 5 2 101 3113
Ber (1968) Org React (1957)
9
58% 107
F u r t h e r examples o f t h e a l k y l a t i o n o f n i t r i l e s w i t h h a l i d e s a r e i n c l u d e d i n s e c t i o n 193 ( N i t r i l e s f r o m N i t r i l e s )
PhBr
----+
ClCH2CN p o t a s s i u m 2,6di-t-butylphenoxide
t
THF
J A C S (1969)
PhCH2CN
91 6854
< 75%
SECTION 190
NITRILES FROM HALIDES AND SULFONATES
469
JCS (1950) 926
CH2C1
NaCN NaI
CH2CN
Me2CO
*
Me0
-75%
Me0 Org S y n t h (1963) C o l l Vol 4 576
BUBr
NaCN Me2SO
CH20Ts
BuCN
NaCN Me2SO
J O C (1960)
25 257
92%
877
CH2CN
*
92%
CH2CN
CH~OTS
T e t r L e t t (1964) 2273 J A C S (1970) 92 336 J O C (1958) c 7 9 7 t
BuBr
-
NaCN PhCH2NMe3 CN
*
BuCN
H20
PhCH2Br
I o n exch r e s i n (CN f o r m )
69% Chem Pharm Bull (1962)
*
PhCH2CN
C6H6 JOC (1963)
lo
427
72%
28 698
COMPENDIUM OF ORGANIC SYNTHETIC METHODS
470
C7H15CXCH=CHCH2Br
RBr
1 Mg
Et2O
CuCN NaI x y l ene
*
C7H15CXCH=CHCH2CN JACS (1953) Ber (1954)
RCN
2‘ ClCN o r (CN)2
SECTION 190
31 %
75 3430 712
63% (R=PhCH$H2) 80% (R=Ph) Annales de Chimie (1915) 4 28 Compt Rend (1911) 152 388-
PhCH=
78%
PhCH= iCN JACS (1969) 91 1233 J O C (1969) 34 3626
m-
CN
Br
CuCN Pyr
Br
Org Synth (1955) C o l l Vol 3 631 212 JACS (1966) 88 3318 J O C (1952) 298
1 CuCN DMF 2 FeC13
Ac
82-90%
HC1
H20
OCN J O C (1961)
88%
2522
The f o l l o w i n g s o l v e n t s may a l s o be used i n t h e above N - M e t h y l p y r r o l i d o n e J O C (1961) 26 HMPA J O C (1969) Me2SO Proc Chem SOC
reaction: 2525
3 3626
PhCHpBr
1 Ph3P
2 NaNH2 NH3
PhCH=PPh3
NO
(1962) 113
24%
PhCN
Chem Comm (1969) 166 Annalen (1969) 721 34 B u l l Chem SOC J F ( 1 9 6 7 )
40 2983
SECTION 191 Section 191
NITRILES FROM HYDRIDES (RH)
471
Nitriles from Hydrides (RH)
a o o o o o ~ o o o o ~ o a o o o o o o ~ ~ ~ ~ ~ ~ ~
-
This section lists examples of the replacement o f hydrogen by CN, RH --+RCN. For the replacement o f alkyl groups by CN, RR RCN see section 185(Nitriles from Alkyls)
P
i-PrCH I Me
MeCH=CHZ
C5H11 C X H
Me
ClCW benzoyl peroxide
*
i -PrCCN
Me
JACS (1969) 91 3028 Ber (1963) 2 670
Pd(CN)2
DMF
c
1 EtMgBr Et20 * 2 ClCN
MeCH=CHCN
20%
4105
C5H11 CECCN
67%
Bull SOC Chim F r (1915)
OTs
Me0
JACS (1966)
PhiHCN AlC13 Me0
@IiCN
~ 6 0 %
J O C (1954) 19 1699 (1949) 839
JACS (1921) 43 898 JCS (1954) 6 E Chem Met Eng (1921) (Chem Abs 2 1703)
228
2 638
COMPENDIUM OF ORGANIC SYNTHETIC METHODS
472
1 (CF3COO)3T1
2 KCN H20 3 hv
Et
CF3COOH *
80%
Et JACS
@Q
(1970)
92
3520
1 ClS02NCO
81%
v
2 DMF
OMe
SECTION 191
OMe
Ber (1967)
100 2719
80% oc18H37
mcN JCS (1954) 678
1 CC13CN AlCl3 * 2 KOH
65%
Ber (1933)
““‘0.
668 339
KCN 02 hl,
OMe
PhC3
@
t-BuOH H20
53%
OMe JACS
(1966)
2884
NaCN electrolysis MeDH
t
PhCEC
Chem Comm (1970) 711 JACS (1969) 91 4181
35%
SECTION 192
Nitriles from K e t o n e s
S e c t i o n 192
0 0 0 0 0 0 0 0 0 0 0 ~ 0 0 0 0 0 0 0 0 ~
-
fOOEt CH2CN
EtCO I Me
HOAC
473
N I T R I L E S FROM KETONES
alanine CgH6
PhCH2MgCl
EtC=kN I Me
Et20
PhCH2 1
EtC-CHCN 11 Me COOEt
J
PhCH2 E t t CH2CN
Org Synth (1963) Coll Vol 4 93 JCS C (1969) 121
iOOH 1 CH2CN
NH40Ac
2 165-175'
t
76-91 %
COOEt I
EtCO II Me Me
CH2CN HOAc HOAc
H2 EE tt O O HH
Pd-C
NH40Ac
Org Synth (1963) Coll Vol 4 234
fOOEt b
EtCHCHCN I
Me
A
J A C S (1959)
EtCHCH2CN
he 5397
(Et0)20PCH2CN + N a O E t DMF 84%
Me 0
JOC (1965)
30
505
JOC (1968) 33 3402
64%
CONPENOIUM OF ORGANIC SYNTHETIC METHODS
474
-
-
CN
HOAc
1 KCN
H2
MsO
i-PrCH$H20NO C14H2gCH2COPh
HC1
*
H20 d i o x a n e
C
CN
Pd-C
EtOAc
2 POC13 Pyr
JCS
SECTION 193
HOAc
35%
(1968) 2283
TsCl
C14H29iCoPh NOH
NaOH H20
J A C S (1953) J O C (1961)
C14H29CN ,63%
75 2347
26 3507
Some o f t h e methods l i s t e d i n s e c t i o n 184 ( N i t r i l e s f r o m Aldehydes) may a l s o be a p p l i e d t o t h e p r e p a r a t i o n o f n i t r i l e s f r o m ketones
S e c t i o n 193
Review:
BuCH~CN
PhCH2CN
N i t r i l e s from N i t r i l e s
000000000000000000000
The A l k y l a t i o n o f E s t e r s and N i t r i l e s
BuBr
t o 1 uene
fir2
-
NaNH2
PhCHCN I
Br
Org React (1957)
Bu3CCN
107
80% J A C S (1948)
PhH AlC13
9
70 3091
Ph2CHCN
J O C (1949)
74%
3 839
NITRILES FROM OLEFINS
SECTION 194
PhCH2CN
NaOH
Me2SO
H20
1 NaNH2
PhCH2CN
PhCH2CN
MeBr
PhFHCN Me
NH3
*
2 C y c l o h e x y l bromide
1 BuLi 2 c02
475
79% J O C (1969)
34
226
PhCHCN
65-77%
Org Synth (1955) C o l l Vol 3 219 JCS (1946) 25 J O C (1958) 23 1346
PhCHCN 'OH
1 NaNH2 NH3
-
3' p ? d r e c a r b o x )
< 70%
PhTHCN
'B
J O C (1966)
2 3873
For f u r t h e r examples o f t h e a l k y l a t i o n o f n i t r i l e s w i t h h a l i d e s see s e c t i o n 190 ( N i t r i l e s f r o m H a l i d e s and S u l f o n a t e s )
S e c t i o n 194
EtCH=CH2
N i t r i l e s from Olefins 000000000000000000000
B2H6 ----+ (EtCHzCH2)38
Cl2CHCN p o t a s s i u m 2 , 6 - d i t-butylphenoxide
THF
JACS (1970)
EtCH=CH2 ----+ B2H6 (EtCHzCH2)38
THF
JACS (1969)
-85%
92 5790
ClCH2CN potassium 2,6-dit - b u t y l phenoxide
* (EtCH2CH2)2CHCN
*
2 6854
Et(CH2)3CN
476
BuCH-CHz
B2H6
THF
COMPENDIUM OF ORGANIC SYNTHETIC METHODS
(BuCH~CH~)~B
1 N2CHCN
2 KOH
H20
Bu(CH2)3CN
JACS (1968)
*
95%
90 6891
CH3CN d i b e n z o y l p e r o x i d e
CgH1 3CH=CH2
SECTION 195
Cf,H13(CH2)$N
17%
JCS (1965) 1918 1932
0
83% Chem Comrn (1969) 112
COOMe I
HCN (28 atmos)
(CH2)3CH=CHz
C02(CO)8 t
YOOMe (CHzl3:HMe
-1 9%
CN JACS (1954)
PhCH=CH2
-
-CNNO .
TsCl
PhiCH2N3 NOH
Et3N
JACS (1965)
S e c t i o n 195
MeCH=CHCN
76 5364
PhCN
87
4642
N i t r i l e s f r o m M i s c e l l a n e o u s Compounds 0000000000000000000000000000000000000
BugSnH
MeOH
MeCHzCH2CN Tetr L e t t (1967) 4805 (1969) 489
90%
SECTION 1 9 5
N I T R I L E S FROM MISCELLANEOUS COMPOUNDS
Pd-C
H2
EtOAc
L1
Zn
HOAc
92%
HOAc JCS
Ms 0
PhCHCN
C
(1968) 2283
PhCH2CN J SOC Chem Ind (1935)
PhCOOCHCN
2 98T
CH2CN H2
Pd-Bas04
EtDH
c
51% Arch Pharm (1957)
C7H15CH2N02
477
1 Base
2 B r 2 CCl4
Ph-jP
C7H15yHN02 Br
290 218
C7H15CN
50%
‘gH6
JCS (1960) 2976
PhCXCONH2
PhCH2COCOOH
NaOCl
H20
NH20H-HCl
PhCH2CN
H20 +
Rec Trav Chim (1920) (1927)
39
46
704 268
PhCH2CN Can J Chem (1961) J C S (1950) 926
90%
2 1340
478
COMPENDIUM
@
OF O R G A N I C S Y N T H E T I C METHODS
CgH1 7
(y$
270"
_.c
iN
NC
T e t r Lett ( 1 9 6 6 ) 5 0 8 7
SO3Na
CN
NH2
JCS (1954) 6 7 8
S E C T I O N 195
<70%
Compendium of Organic Synthetic Methods, Volume 1 Edited by Ian T. Harrison, Shuyen Harrison Copyright 0 1971 by John Wiley & Sons, Inc.
PREPARATION OF OLEFINS
Chapter 14
S e c t i o n 196
BuCZH
O l e f i n s from Acetylenes
0000000000D000000000000
1 Dicyclohexylborane
+
2 BuLi
(C5H11 )$o
Ye
2 NaOH 12 THF
( i-Bu)2A1H
THF
30-35%
Me
THF b
BuCH=CHCHPr-i
H20
cis JACS (1967)
BuCXH
B U C H ~ C H = C ( C ~1 H )2~
Tetr Lett (1966) 4315
1 (i-PrCH)zBH BuCXH
-
BuCHzCHLi2
BuCH$H[Al ( B u - i ) 2 ] 2
1 MeONa
2 HCHO
75%
89 3652
BuCH$H=CHz
T e t r L e t t (1966) 6021
MeC(CH2)3CXEt /\
Lo
BuCXEt
OF ORGANIC SYNTHETIC METHODS
COMPENDIUM
480
H2
Ni(0Ac)Z
NaBH4
EtOH
E lectralysis LiCl
Me,C,(CH2)3CH=CHEt
Lo
80%
cis T e t r a h e d r o n (1969)
trans
5149
58%
BuCH=CHEt
w
MeNH2
*
SECTION 196
J O C (1968)
33 2727
Na
NH3
trans JACS (1952) (1963)
NaNH2 NH3
Na
Et20
If?. 3643 622
75%
PrCH=CH( CH2)4CECH trans JCS (1955) 3558
PhCZCPh
1 Li
2 MeOH
THF
PhCH=CHPh cis
J O C (1970)
5 1702
SECTION 196
481
OLEFINS FRO14 ACETYLENES
CrS04
'XPh
DMF
@J.;;HPh
H20
*
a C O O H
trans
JACS (1964)
1 NaBH4
EtCXEt
B F 3 - E t 2 0 diglyme
2 HOAc
4358
EtCH=CHEt
b
68%
cis JACS (1959)
1512
OH CH=CH2
OH
CXH
85%
( ~ - B u ) ~ A ~CgH6 H
48% J O C (1959) (1963) Ber (1956)
1 (i-Bu)zAlH
24 627
2
90%
EtCH=CHEt cis
EtCXEt
88%
EtCH-CHEt
2 100-130"
trans JACS (1967)
E t CEC Et
1254 444
LiA1H4
11 7-138'
diglyrne
5085 5086
97%
EtCH=CHEt trans T e t r a h e d r o n (1967)
-
Zn HI C ~ O H ~ ~ C E C ( C H ~ ) ~ C+ O O H C1 o H ~ ~ C H = F ( C H ~ ) ~ C O O H HOAc
I
23 4509
C~OH~~CH=CH(CH~)~COOH
Compt Rend (1916)
162 944
482
MeCZCMe
COMPENDIUM OF ORGANIC SYNTHETIC METHODS
1 B2Cl4
2 HC1
S e c t i o n 197
MeCH=CHMe
H20
JACS (1967)
SECTION 197
89 4217
O l e f i n s f r o m C a r b o x y l i c Acids, A c i d H a l i d e s and Anhydrides
~ ~ ~ ~ ~ ~ O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O
The d e c a r b o x y l a t i o n o f a @ - and @ ’ / - u n s a t u r a t e d a c i d s , RCH=CHCOOH -+ RCH=CH2 and RCH=CHCH2COOH ---t RCHzCH=CHz, i s i n c l u d e d i n s e c t i o n 152 ( H y d r i d e s f r o m Carboxyl i c A c i d s )
!OOMe (CH2)4COOH
CH2=CH( CH2)8COOH electrolysis
+
YOOMe (CH2)1 2CH=CHz
MeOH
JCS (1953) 2393
(1954) 448 4219
F o r f u r t h e r examples o f t h e Kolbe e l e c t r o l y s i s see s e c t i o n 62 ( A l k y l s f r o m Carboxyl i c A c i d s )
BuCH~CH~COOH
Cu( OAc)? * H20
Pb( 0Ac)q
Pyr
*
BuCHZCH~
T e t r a h e d r o n (1968) JCS
t6H
Pb(OAc)4
__3
0 -co
I2
@ 0
C
(1969) 1047
24
py’-
72% 2215
60%
-co
0-co T e t r L e t t (1968) 2471
PhCHzCH2COCl
PdC12
200’
o r RhCl (PPh3)3
b
toluene
PhCHzCH2 JACS (1968)
90 9 4
53-71 % 99
SECTION 1 9 7
?'OH Bu2CCH2Pr
FROM CARBOXYLIC ACIDS, A C I D H A L I D E S
OLEFINS
CuCN
Bu2C=CHPr
220-240"
JACS (1950)
Se02
C13H27CH2CH2COOH
A
EtjN
Pyr
73%
72 2792
C ~ ~ H ~ ~ C H S C H ~ J Chem SOC J a p (1938)
Electrolysis COOH
483
AND ANHYDRIDES
59
262 271
*
35%
H20 T e t r L e t t (1968) 5117 5 1 2 3
76% JACS (1968) Helv (1958)
COOEt
*o COOEt
Pb02
0:1:
90 113 fi 1 1 9 1
170-1 90'
Helv (1958) JACS (1952)
t-BuOOH,
30-37% 1191
74 4370
0: -0 C002Bu- t C002Bu-t
A
o r hu
Chem Corn (1969) 98
484
COMPENDIUM OF ORGANIC SYNTHETIC METHODS
S e c t i o n 198
BuOH
--*
SECTION 198
O l e f i n s from A l c o h o l s
~ 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 ~ ~ ~ 0
BuOCH~CH-CH~
PrLi
pentane
*
BuCHzCH2
-73%
T e t r L e t t (1969) 821
OH
Q' CHCH3
c1
KHS04
80-82%
QCHzCH2 C1 Org Synth (1955) C o l l Vol 3 204
(1943) C o l l Vol 2 606 (1941) C o l l Vol 1 430
79-84% O r g Synth (1943) C o l l Vol 2 151
J A C S (1915)
37
1748
83%
JACS (1961) 5003 Chem Pharm Bull (1961) JCS (1967) 1115
9
854
SECTION 198
485
OLEFINS FROM ALCOHOLS
SOC12
(t-BU)pCCH3
bH
0,;
Pyr
JACS ( 1 9 6 0 )
Q.
160'
Me2SO
-70%
(~-Bu)~C=CH~ 2498
88%
29
J O C (1964)
123
@?, p - ,qI7% oMS
C8H17
QH
C8H17
C8H17
S t e r o i d s ( 1 9 6 4 ) 5 55 J O C ( 1 9 6 4 ) 29 7 4 2
H
26
(1961)
2883
F u r t h e r examples of t h e p r e p a r a t i o n o f o l e f i n s f r o m s u l f o n a t e s a r e i n c l u d e d i n s e c t i o n 205 ( O l e f i n s f r o m H a l i d e s and S u l f o n a t e s ) t
/O
-
1 Et3NS02NCOOMe
CH2hHCMe2 I
2 NaH
THF
*
ooH OH
MeOSOCl
__3
Pyr
EtpO
0
/ \ CHz-CHC=CH2
55%
I
Me J A C S ( 1 9 7 0 ) 92 5 2 2 4 J O C ( 1 9 7 0 ) 35 2 5 9 4
o o s o 2 M e 21 5-275"
.
($
J A C S (1954)
76 1 2 1 3
COMPENDIUM OF ORGANIC SYNTHETIC METHODS
486
0
SECTION 198
CH20H
JOC (1961)
2 4193 60 431
Chem Rev (1960)
Ac20 (600")
C16H33CHZCH2
b
(vapor phase)
68%
Chem Ind (1965) 681
80% JACS (1952)
74 3636
F o r examples o f t h e p r e p a r a t i o n o f o l e f i n s f r o m e s t e r s , b y p y r o l y s i s and by o t h e r methods, see s e c t i o n 203 ( D l e f i n s f r o m E s t e r s )
MeCOCH2COO D i ketene ___f
NaOAc
0"':
69%
A r k i v Kemi (1961)
CgH13CH2CH20H
1 BrCH2COC1
2 Bu3P
Pyr b
t
401
-
i7no
C ~ H ~ ~ C H ~ C H ~ O C O CBHr ~--+C6H1 PBU~ J O C (1964) 3 1003 JACS (1961) 3336
3CH=CH2 -72%
OLEFINS FROM ALCOHOLS
SECTION 198
1 NaH
Et20
3 Me1
8
Biphenyl
OCSMe
255"
J O C (1967) 32 2933 (1968) 33 2214 Can J Chem (1970) 48 970 Org React (1962) 1
12
( y 2 0 H
.
1 cs2
base 2 ClCHsCOOEt L
NaH
CsHl3CH2CH20H
0
s
CH20iSCH2COOEt
H20
MeZNCSC1
k!
diglyme
100"
Ind Eng Chem Prod Res Dev (1970)
DMF CgH13CH2CH20CNMe2
TsNCO
pH 4-5 ___c
180-200°
J O C (1969)
Me OH
487
230
C6H1 3CH-CH2
2 3604
OCONHTs 1 5 0 - 1 70' C h e m Corn (1970) 606
A u s t J C h e m (1954) 7 298 J A C S (1953) 2118-
7s
9
86%
4aa
COMPENDIUM OF ORGANIC SYNTHETIC METHODS
BuLi
SECTION 198
Et20
< 60%
JCS (1958) 843
PrCH-CHPr
b H dH
HBr
ZnBr2
____+.
PrCH-CHPr BI r 1 Br
H2°
Zn-Cu
EtOH
PrCH=CHPr
J A C S (1937) 2 403 JCS (1951) 1079
Chem C o r n (1968) 1593 T e t r L e t t (1965) 3655 JACS (1965) 8 7 934 (1963) 2677 HOtH2
HOCH HC ( O E t ) 3
1h2 CH
E t O C,OCH2 H I 'OCH
PhCOOH
HOAc C a r b o h y d r a t e Res (1965) 7 161 A u s t J Chem (1965) 21 ZOi3
Hc(0Me)2NMe2+j71NMe2
5
o/
A-0
+O
trans
T e t r L e t t (1970) 5223
F o r the p r e p a r a t i o n o f o l e f i n s from d i o l s v i a b i s s u l f o n a t e s see s e c t i o n 205 ( O l e f i n s f r o m H a l i d e s and S u l f o n a t e s )
SECTION 199
OLEFINS FROM ALDEHYDES
S e c t i o n 199
489
O l e f i n s f r o m Aldehydes
oooDDoooDoooooDoDoDooo
Examples o f t h e d e c a r b o n y l a t i o n o f a @ - u n s a t u r a t e d aldehydes, RCH=CHCHO RCH=CHz, a r e i n c l u d e d i n s e c t i o n 154 ( H y d r i d e s f r o m Aldehydes) PhCH2COOH Ac20
PhCH=CHCHO
PbO
*
PhCH=CHCH=CHPh
+
23-25%
Org Synth (1943) C o l l Vol 2 229
PhCH2CHO
O
C
H
KOH
O
EtOH
91 %
PhCHzCHCH2Ph J O C (1966)
31
396
- 0- 0 (Et0)3P
160'
CH=CH
I z v (1960) 1030 (Chem Abs 3 24627)
EtCH2CHO
MeQcHo
BY2
EtCH-FHOMe A r Br
CH3MgI
EtMgBr
MeQcHcH3
Et20
-
Zn EtyH-FHOMe EtCH=CHEt Br E t ProH JACS (1932) 54 751
TH
Me JACS (1946)
Reviews:
The W i t t i g R e a c t i o n
20%
KHS04
Me
Me
-
68 1085
Org React (1965) Quart Rev (1963)
270 406
New R e a c t i o n s o f A1 k y l idenephosphoranes and t h e i r P r e p a r a t i v e Uses 850 Angew (1965) ( I n t e r n a t Ed 4 830)
490
1 Ph3P=CH2
PhCHO
PhCHO
SECTION 199
COMPENDIUM OF ORGANIC SYNTHETIC METHODS
Et20
Ph3P.CHBu-t
PhCH=CHZ
L
2 65'
67% Ber (1954) S;. 1318
Et20
PhCH=CHBU-t
h
84%
J A C S (1965)
2 4156
t
Ph3PCH20
2Br Ph3PCH2 t
PhCHO
EtOLi
*
EtOH
pPhCH-CH hcH=cHJQ Org React (1965)
ii,)i
PhCHO
14 270
t
Ph3PCH2Pr F
CHO
PhCH=CHCHO
84%
MeOH
MeCN
+
41 % Ber (1970)
PhCH2Br- (Me2N)3P DMF
MeONa
Ph2PO(CH2Ph)
P
103 2 0 7 7
89%
PhCH-CHCH-CHPh A n n a l e n (1965)
t-BuOK
CgHg
L
682
PhCH=CHPh Ber (1959)
58
70%
92 2499
SECTION 199
PhCHO
0
-
t
PhCHO
/ \
Ph3PCH2Et B r
CH2-CH2
150"
*
PhCH=CHEt
74%
Angew (1968) ( I n t e r n a t Ed
P
1 LiCHPO(NMe2)z 2 Crystallization
-
?H PhCH-CHPO(NMe2)2 diastereomer A
/NaBH4
PhCOCHPO( NMe2) he
Ph3P=CHPr
PrCHCHPr
2 65'
535 536)
-
JACS (1966)
A
PhCH=CHMe cis trans
a
5653 5652 (1968) 90 6816 J O C (1969) 2 3053
1 PhLi
72%
PrCH=CHPr trans
Angew (1966) 2 115 ( I n t e r n a t Ed S 126) JACS (1970) 92 226
t -
Li 1 Me&PS(OMe)2
2
A
diastereomer B
PrCHO
491
OLEFINS FROM ALDEHYDES
-0 CH=CMe2
THF
JACS (1966)
68%
S 5654
Li 1 L i C H 2 S O h G Me 2 Toluene r e f l u x
THF +
C11 H23CH=CH2 JACS (1966) (1968)
56% 5656
90 5548
F u r t h e r examples o f t h e W i t t i g R e a c t i o n and a l i s t o f bases which may be used f o r t h e g e n e r a t i o n o f W i t t i g r e a g e n t s a r e i n c l u d e d i n s e c t i o n 207 ( O l e f i n s f r o m Ketones)
COMPENDIUM OF ORGANIC SYNTHETIC METHODS
492
CgH1 3CHO
1 Ph3P-CHMe
THF
2 BuLi
CgH13CH-C=PPh3 I 1 O L i Me
Me I
+ CgH13CH=CMe2
JACS (1970)
3 L i I
PhCHO
I2
MegSiCHzPh HMPA
SECTION 1 9 9
92
< 50%
226
T e t r L e t t (1970) 447
BuLi
b
> 50%
PhCH=CHPh T e t r Lett (1970) 1137
65%
c1 1 H23CH0 T e t r a h e d r o n (1970) 26 1281 J O r g a n o m e t a l l i c Chem (1968)
12 263
OLEFINS FROM ALKYLS, METHYLENES AND ARYLS
SECTION 200
C5H11 CHLi2
PhCHO
THF
*
493
PhCH=CHC5H11
45-50%
T e t r L e t t (1966) 4315
PhCH=CHCHO
LiCH2NC
THF
PhCH=CHCH=CHz Angew (1968) ( I n t e r n a t Ed
b
80 8 4 2 7 805)
0 .0" .0'' CHo 1 HCN
CHCN
H N CHCH2 BuONO
LiAlH4
o C H = C H 2
2 soc12
83% T e t r L e t t (1969) 4001
MeCHZCHO
--+
MeCH2CH(OEt)z
TsOH
MeCH=CHOEt
(i-Bu)zAlHq
J O C (1966)
2
MeCH=CHZ
44%
329
Some o f t h e methods i n c l u d e d i n s e c t i o n 207 ( O l e f i n s f r o m Ketones) may a l s o be a p p l i e d t o t h e p r e p a r a t i o n o f o l e f i n s f r o m aldehydes
S e c t i o n 200
PhCH2CH2Ph
O l e f i n s f r o m A l k y l s , Methylenes and A r y l s 00000000000000000000000000000000000000000
RhCl (PPh3)3 260"
37%
PhCHZCHPh T e t r L e t t (1970) 1825
494
COMPENDIUM OF ORGANIC S Y N T H E T I C METHODS
8
Rec Trav Chim (1964)
S E C T I O N 200
67
@ .
40%
J O C (1965)
3 2479
J O C (1967)
32
PhCOO
Helv (1958)
510
& 41 70
SECTION 201
OLEFINS FROM A M I D E S
495
69%
Bu-t
Li
NH~CH~CH~NH~
t-Bu
44%
t-Bu J O C (1966) 2 965 A u s t J Chem (1964)
;;x;ro1ysis
@Pr-i
55
Licl <81% J A C S (1964)
S e c t i o n 201
t-BuCHzCMe2
AHAc
86
5272
O l e f i n s f r o m Amides 000000000000000000
-
510’
( v a p o r phase)
+
t-BuCH=CMez
t-BuCHzC=CH2 I
Me
J O C (1958) 2 996 J A C S (1959) 1 6 5 1 (1958)
80 4588
OAc
OAc
Sulfosalicylic acid AcNH-”
T e t r L e t t (1965) 2369
496
Ac 0
COMPENDIUM OF ORGANIC SYNTHETIC METHODS
SECTION 202
COOMe
p2°5
C6H6 B u l l SOC Chim F r (1966) 2404
S e c t i o n 202
O l e f i n s f r o m Amines
nooooaoooooaooooooo
Review: The Hofmann E l i m i n a t i o n R e a c t i o n and Amine Oxide P y r o l y s i s Org R eact (1960) 11 317
JACS (1952) 2 3643 JCS (1955) 4016
Me I
C6H6
AcO
$HZ ‘1 Ag20
H20
_____L
2 KOH HOCH2CH20H JACS (1948)
70 887
58%
The f o l l o w i n g bases may a l s o be used i n p l a c e o f Ag20 i n t h e Hofmann d e g r a d a t i o n o f amines: Org Re a c t (1960) 11 317 Ag2S04-Ba(OH)2, NaOH, TlOH, i o n exchange r e s i n Ag2C03 J C S (1935) 1685
SECTION 202
497
OLEFINS FROM AMINES
Me2S04 BuCH~CH~NH~ H20
-
t
NaOH
* BuCH2CH2NMe3 (SO4)1/2
H2SO4
H20
------+
r e f 1ux Org React ( 1 9 6 0 )
BuCH=CHz
60%
11 317
66-68% Annalen (1958)
0 c H 2 N M e 2
tl-l(l;
+ "0.
0 C H 2 ? M e 2
0-
'609
612
102
0""" mas%
Org Synth (1963) C o l l Vol 4 612
Me PhdHCHCH3 tNMe2
Me2SO
THF
25"
or H20 132-138"
*
Me Phd=CHMe
f
Me PhdHCH=CH2
JACS (1962)
I
-0
NH2
1734
Sul f o s a l i c y 1i c a c i d
> 70% T e t r L e t t (1965) 2369
-
1 TsCl DMF BLJCH~CH~NH~ 2 NaH TsCl
-
KI BuCH~CH~NTS~
DMF
BuCH=CH~
JACS (1969)
91 2384
31 %
COMPENDIUM
498
PhCH2CH2NH2
p
OF ORGANIC SYNTHETIC METHODS
PhCHpCH2Nlco@) PhCH=CH2 so2 T e t r Lett (1967) 3027 JACS (1969) 91 2384
CgH170NO CHC13
HOAc
*
-
CH-CH2
S e c t i o n 203
< 65%
Me2C=CH2 JACS (1969)
NH
SECTION 203
27%
91 1790
BuONO
T e t r Lett (1969) 4001
Olefins from Esters
a
~
o
0
~ 0 000 0~0 0 ~ 0 0 0~
0
F o r t h e p r e p a r a t i o n o f o l e f i n s f r o m s u l f o n i c e s t e r s see s e c t i o n 205 ( O l e f i n s f r o m H a l i d e s and S u l f o n a t e s )
H C X ( CH2)7CH$OOEt
PhMgBr Et2D
HCSC(CH2)7CH2CPh2
220-230"
HCEC(CH2)7CH=CPh*
OH JCS (1957) 1622
92%
96%
JACS (1945)
67 2239
SECTION 203
OLEFINS FROM ESTERS Me
PhCOOMe
L i dHPO( NMe2) 2
THF
b
Me PhCOtHPO(NMe2)2
NaBH4
MeOH
PhCH=CHMe trans
JACS (1966)
Review:
Pyrolytic Cis Eliminations
530"
vapor phase
Me PhFHbHPO(NMe2)z
88
Chem Rev (1960)
JACS (1959)
CH20Ac
499
5653
60 431
3 1968
OCH2 JACS (1959)
647 651
< 80% JACS (1969) 91 3324 J O C (1965) 2 689
COMPENDIUM
500
OF O R G A N I C SYNTHETIC METHODS
SECTION 203
71% PhCOO JCS (1965) 4379
E s t e r s o f t h e f o l l o w i n g a c i d s have a l s o been used f o r t h e p r e p a r a t i o n o f o l e f i n s by liquid-phase p y r o l y s i s : JACS (1948) 2 2690 S t e a r ic JCS (1957) 1998
2 3944
d-Camphoric
JACS (1952)
2,4,6-Triethyl benzoic 2-Naphthoic
JACS (1953)
3,5-Dini trobenzoic
Chem Ind (1954) 1426
Ethyl carbonic
JACS (1952)
2 5454
2-Naphthyl c a r b o n i c Phenylcarbamic
JACS (1954)
6108
JACS (1954)
6011
?a
5692
Anthraquinone-2-carboxyl i c Helv (1944) 27 713 821 JACS (1953) 75 2118 Can J Chem (1953) 2 688
F u r t h e r examples o f t h e p r e p a r a t i o n o f o l e f i n s by p y r o l y s i s o f e s t e r s a r e i n c l u d e d i n s e c t i o n 198 ( O l e f i n s f r o m A l c o h o l s )
PhCH2fHPh
Et@Et
NaNH2
NH3
EtpO
PhCH=CHPh
Et JACS (1953)
75 6011
SECTION 204 S e c t i o n 204
OLEFINS FROM ETHERS AND E P O X I D E S
501
O l e f i n s f r o m E t h e r s and Epoxides
~ ~ ~ ~ O O O O O O O O O O O O O O O O ~ ~ ~ O O O ~ ~ ~ O D O
. . . . . . . . . . . . . . . . . . . . page .....................
O l e f i n s from ethers O l e f i n s from epoxides
501-502 502-504
-0
QoMe H3P04
82%
triethylene glycol
Ber (1967)
100 1764
24%
T e t r Lett (1964) 759
0'"'
N
JCS (1958) 843
?Me CgH13CHCH3
i-PrLi
pentane
c
CgH13CH=CH2 J A C S (1951)
OMe
73 5708
1263
Tetrachlorobenzyne
T e t r Lett (1968) 4455
60%
COMPENDIUM OF ORGANIC SYNTHETIC METHODS
502
E~CH~CH~OBU
N2CHCOOE t 140-1 50'
C r ( C104)2 DMF
SECTION 204
EtCH=CHZ Rec T r a v C h i m (1955)
NH2CHzCHzNHz
H20
-0
2 3503
MgBr2
80%
THF Chem Comm (1970) 1 4 4
Chem Corn (1970) 1450
0
I\
BuC-CHMe I
Me
HBr
LiBr
Me2CO
*
yr
OH I BuC-CHMe I
Zn HOAc
BuC-CHMe
Me Zn
NaI
NaOAc
6%
92%
T e t r a h e d r o n (1968)
Mg-Hg
74 1 4 3
HOAc
JCS (1959) 112 (1955) 1370
I
Me
SECTION 204
Me0
15' 1 3
OLEFINS FROM ETHERS AND E P O X I D E S
NaI
0
NaOAc HOAc
0
c1
503
1 SnC12
Pyr
2 POC13
Pyr
19 1265
Aust J Chem (1966) J C S (1959) 1 1 2
0
/ \
1 BuLi -HPO( NMe2)2
cis
2 CaC03
MeCHCHMe
0
/\
PhCHCH2
THF
MeCH=CHMe
t
s i l i c a gel
Ph3B
JOC (1969)
EtpO
70"
A Ph3P
L
',.,H
2NaOH
1
2 3053
PhCHZCH2
180"
1 (NH2)2CS
20%
trans
t o 1 uene
Ph3P
Ber (1955) fi 1654 Chem Ind (1959) 330
OH
1 s02c12
"SH
2 PhCOCl 3 SOZC12 4 PhNH2
2 A
OCOPh Pyr)
m-Chloroperbenzoic acid OCOPh
1 Base
"SONHPh
trans 25%
trans
J A C S (1968)
90
5553
SECTION 205
COMPENDIUM OF ORGANIC SYNTHETIC METHODS
504
0 P hC/H\CHPh
Potassium m e t h y l
cis
+
xanthate
7 7
PhCH-CHPh
(Me0)3P
PhCHSCHPh trans
JACS (1965)
PhOCH2CHCH2
KSCN
H20
\:
PhOCH2CHCH2
(EtO)$’
81 934
PhOCH2CH.CH2
JOC (1961)
2 3467
64%
Carbohydrate Res (1967)
S e c t i o n 205 Olefins Olefins Olefins Olefins Olefins Olefins Olefins
5
282
O l e f i n s f r o m H a l i d e s and S u l f o n a t e s
..
.. .. .. .. .. .. .. .. .. . ............ ...... ..... . . . . . .. .. . .. .. ... ...
00000000000000000000000000000000000
. . . ... ... ..
from W i t t i g reagents page 504-505 from organometallic reagents . 505-507 507 from halides v i a s u l f o x i d e s 507 from halides v i a t h i o l s . b y e l i m i n a t i o n o f HX f r o m h a l i d e s and s u l f o n a t e s 507-510 from 1,l-dihalides 510 f r o m 1 , 2 - d i h a l i d e s and 1 , 2 - d i s u l f o n a t e s , , 510-512 I
I
I
R I
I
I
-
?
The r e d u c t i o n o f v i n y l h a l i d e s , R C CX RzC=CH, i s i n c l u d e d i n s e c t i o n 160 ( H y d r i d e s f r o m H a l i d e s and s u f f a n a t e s )
PrCH2Br
1 Ph3P
2 NaNH2 THF
PrCH=PPh3
02
< 66%
PrCH=CHPr
2 1899 2848 (1966) (1961) 1987 Annalen (1969) 34 B e r (1963)
99 94
721
SECTION 205
OLEFINS FROM HALIDES AN0 SULFONATES 1 Ph3P
Ph(CH2)2CH2Br
-
+
NaNH2
Ph(CH2)2CH2PPh3 I 0 4
505
Ph(CH2)2CH=CH(CH2)2Ph < 33% 102 2259
8 8 8 ------+
2 ~a104
NH3 Ber (1969)
t
CH2Cl
-
CH2PPh3 C1
Ph3P
DMF
:;tl
.____t
CH2C1
EtOLi
CH2PPh3 C1 t
CH2=CHCH2Br
CH=CH2
Ph3P
C6H6
-
-
+
CH2=CHCH2PPh3 B r
CH=CH2
Org React (1965)
1 PhLi
Et20
2 PhCHO
2
270
CH2=CHCH=CHPh
53%
Ber (1954) 1318 Annalen (1965) 682 58
F u r t h e r examples o f t h e W i t t i g r e a c t i o n a r e i n c l u d e d i n s e c t i o n 199 ( O l e f i n s f r o m Aldehydes) and s e c t i o n 207 ( O l e f i n s f r o m Ketones) ?H CHCH3
Ph
PhBr
Ph
1 Mg
Et20
2 CH3COOEt
?H Ph2CCH3
A
A
@cH=cH2 Ph JACS (1946) 68 1109
Ph2CzCH2
Org Synth (1932) C o l l Vol 1 226
36%
506
COMPENDIUM OF ORGANIC SYNTHETIC METHODS
OOI
Me ( c H ~ = L) 2 c u L i O
*
QBr
SECTION 205
C=CH2 Me
45
J I n d i a n Chem SOC (1968)
[Me<
RBr
>
Nif r
l2
DMF
+
RCHzC=CH2
1026
90% (R= Me)
he
70% ( R = CH2zCH) 92% (R= PhCH2CHzCH2) JACS (1967)
OBr 1 Mg
Et2O
2755
70%
CH2CH=CH2
2 BrCH$H=CHZ
JACS (1946) 68 1101 J O C (1970) 3$ 2 2
F u r t h e r examples o f t h e c o u p l i n g o f h a l i d e s a r e i n c l u d e d i n s e c t i o n 70 ( A l k y l s and A r y l s f r o m H a l i d e s and S u l f o n a t e s )
BuCl
1 Mg
Et20
2 BrCH2yHBr
BuFHCH2Br OMe
Zn
BuCH=CHz J O C (1952)
OMe
BuBr
- YHhe y1 1 Li
Et20
2 MeCHCOMe c1
BuC-CHMe
NaOH
H20
0
807
-
/\
1 NaI
I
EtCOOH 2 SnC12 Pyr 3 p0c13 Pyr
BuC-CHMe
Me
I ‘Zn
NaI
NaOAc
NaOAc
JCS (1959) 112
BuC=CHMe I
Me
HOAC.
cis
trans
’ trans
SECTION 205 PrCHzBr
OLEFINS FROM HALIDES AND SULFONATES
--+
Br
CF2Br2
PrCH2MgBr
-
Et20
PrCH=CHCHzPr Ber (1962)
72%
1958
C5H1 1CH2Li
-
0 '
Et20
60%
260 4535
Compt Rend (1965)
HC<:>Et --+
95
OCH2
1 Mg 2 CHBr3
CgH11CH2Br
507
C5H11 CH=CHCH2C5H11
33%
trans T e t r L e t t (1964) 2547
NaH-CH3SOMe C15H31CHZX
*
C15H31 CH2CH2SOMe
X=Br o r OTs
C5H11 CH2Br
Me2SO
reflux
C15H31 CH=CH2
Chem Comm (1965) 29
---, C5H11 CH2SH
1 HCHO
HC1
I
* C5H11 CH2S02CH2Cl
2 m-Chloroperbenzoic a c i d
$H
C5H11 CHzCH2
MeCHCH2CH2COOMe
Collidine ___c
86
a1
JACS (1964)
TsO,"'
(85%
JOC (1961)
26
4383
2883
< 53%
5 oa
COMPENDIUM
@ c1
OF
ORGANIC SYNTHETIC METHODS
P y r or CaC03,
80%
DMF J O C (1963)
BuCH2CH2Br
HMPA
SECTION 205
180-210"
a 1976 6 1%
BuCH.CH2 Chem Corn (1971) 113
C3H7yHCH2Et Br
C5H11CHzCH2Br
Ph3CCH2CH2Cl
-
1,5-Diazabicyclo[5.4.O]undec-5-ene Me2SO
LiF
EtONa
C3H7CH=CHEt
91 %
Angew (1967) 79 53 ( I n t e r n a t Ed 2 76) Ber (1966) 99 2012
Li2CO3
Me2SO
*
-
HMPA
C5H11 CH-CH2
-51%
Bull SOC C h i m F r (1967) 2455 (1968) 283 J O C (1970) 35 76 1023
90%
Ph3CCH=CH2 JCS
(1967) 1115
J O C (1967) 32 510 (1965) 30 2054 T e t r L e t t (1967) 2273
SECTION 205
509
OLEFINS FROM HALIDES AND SULFONATES
t-BuOK
.
Me2SO
65%
4
S t e r o i d s (1964) 55 J O C (1964) 29 742
&
EtgCONa
52%
____)
Et3COH
JOC (1970) 35 196 Chem Corn (1968) 305
94%
_____c
(Method
f o r u n r e a c t i v e ha1 i d e s )
Annalen (1962) 652 96
The f o l l o w i n g b a s e s / s o l v e n t s may a l s o be used f o r t h e e l i m i n a t i o n o f HX f r o m h a l i d e s and s u l f o n a t e s : L i t h i u m d i c y c l o h e x y l a m i d e JOC (1967) 32 510 Na NH2- HMPA
Potassium t - a m y l a t e Me2SO (MeO)-jP-xylene C17H35COOAg-CgHg Ag20-CgH6
Bull SOC Chim F r (1966) 1293
Helv (1967)
2111
JACS (1959) 5428 T e t r L e t t (1968) 4191 tlelv (1958) 5 70 Ber (1942)
758 660
Helv (1951) 2 1176
5 10
COMPENDIUM OF ORGANIC SYNTHETIC METHODS
AcO(CHz)3FCHzPr Me
190-200"
SECTION 205
AcO(CH2)3C=CHPr
80%
he JOC
(1948)
13 239
GC1 6 + 6 ( v a p o r p h a s e )* -4000
JCS (1952) 453 Chem Rev (1960)
PhzCXZ
cu o r NaI o r Fe(C0)5
EtCH-CHEt
i1 k1
KOH
PrOH
*
60 431
PhzC=CPhz X = B r o r C1 Org S y n t h (1963) C o l l Vol 4 914 JCS (1959) 678 JACS (1961) 83 1623
EtCHzCEt
tl
Na L
NH3
EtCHGCHEt JACS (1951)
73 3329
C8H1 7
0
Org Synth (1963) C o l l Vol 4 195 JOC (1970) 2 1733 JCS (1961) 4547
SECTION 205
OLEFINS FROM HALIDES
AND SULFONATES
51 1
The f o l l o w i n g r e a g e n t s may a l s o be used f o r t h e c o n v e r s i o n o f 1 , 2 - d i h a l i d e s to olefins: NaI, K I
30 1658 (1959) 4 1 4 3 76 Annalen (1967) J O C (1965)
705
CrX2 (X=Cl, OAc e t c . ) JACS (1968) 90 1582 (1967) 89 6547 (1964) 4603 J O C (1959) 2 1621 1629 T e t r a h e d r o n (1968) ;14 3503 Bu3SnH
J O C (1963) 28 2165 Acc Chem Res (1968) 1 2 9 9
Na-NH3
JACS (1952)
2 4590
Sodium d i h y d r o n a p h t h y l i d e Chem Comm (1969) 78 Phenanthrene d i s o d i u m Angew (1964)
16 432
PhSNa, EtSNa
Rev Chim ( B u c h a r e s t ) (1962) 1 1 3 7 9 (Chem Abs 61 4208) J O C (1959) 4 1 4 3
Na2Se
J O C (1966) 3,-l
(NH2)2CS
Chem Ind (1966) 1418
KSCN
Chem Ind (1966) 1418
Potassium c y c l o h e x y l p h o s p h i d e Ber (1961)
94
4292
2664
2 3181
(Et0)3P
J O C (1970)
Na H-Me2SO
Chem Ind (1965) 345
LiAlH4
Can J Chem (1964)
PhLi
Annalen (1967)
PrMgBr
Bull SOC Chim F r (1946) 604
42 1294 705 76
73%
JCS (1950) 598 JACS (1952) 74 4894
SECTION 206
COMPENDIUM OF ORGANIC SYNTHETIC METHODS
51 2
TsO
/04H20CH2P w
Zn
NaI
82%
Bull SOC Chim Fr (1967) 4111
OTs
tH CH
KSeCN DMF ____c
45%
t:x
Carbohydrate Res (1967)
5
282
17%
S e c t i o n 206
O l e f i n s f r o m H y d r i d e s (RH)
~
~
O
~
~
~
~
~
~
~
~
O
O
~
~
~
O
O
O
~
O
O
O
O
T h i s s e c t i o n l i s t s examples o f t h e replacement o f hydrogen by o l e f i n i c groups. F o r t h e d e h y d r o g e n a t i o n o f a l k y l groups, e.g. RCH CH2R RCH=CHR, see s e c t i o n 200 ( O l e f i n s f r o m A l k y l s , Methylenes and A r y l s f
Me2CHCHMe2
HCXH
.
Me2CHCMe2
d i - t - b u t y l peroxide
CH=CH2 JOC
(1965)
2 3814
~
~
SECTION 207
OLEFINS FROM KETONES
51 3
Me
Me
Me
Me JACS (1948)
S e c t i o n 207
22%
2 1772
O l e f i n s f r o m Ketones
000000000000000000d
. page .... ..,
Conversion o f ketones i n t o o l e f i n s w i t h l o n g e r c a r b o n c h a i n s . Conversion o f ketones i n t o o l e f i n s o f t h e same c h a i n l e n g t h Conversion o f ketones i n t o o l e f i n s w i t h s h o r t e r carbon c h a i n s
Reviews:
Org React (1965) Quart Rev (1963)
The W i t t i g R e a c t i o n
513-516 516-519 520
2 270
406
New R e a c t i o n s o f A l k y l idenephosphoranes and t h e i r P r e p a r a t i v e Uses Angew (1965) (Internat Ed
t
-
OCH2
Ph3PCH3 B r
0
77 850 4 830)
86%
Org React (1965) 14 270 Ber (1954) 87 1 3 1 r
90% Bull SOC Chim F r (1967) 1936
PhCO I Me
PhCHpBr- (Me2N)3P MeONa
DMF
c
PhC-CHPh
35%
I
Me Annalen (1965)
682 58
COMPENDIUM OF ORGANIC SYNTHETIC METHODS
51 4
Ph2CO
Ph2P ( 0 ) C H2Me
t - Bu OK
*
t o 1 uene
SECTION 207
Ph$=CHMe Ber (1959)
51 %
92
2499
Me I
Ph2CO
1 LiCHPO(NMe2)2 THF 2 S i l i c a gel
CgHg
b
PhzC=CHMe
reflux
JACS (1966) J O C (1969)
87%
88
5652 5653
2 3053
Li
Me Ph2CO
LitHPS(0Me)z
-
THF
JACS (1966) (1968)
88 5656 90 5548
JACS (1966)
5654
Ph$=CHMe
93%
The f o l l o w i n g r e a g e n t s / s o l v e n t s may a l s o be used f o r t h e g e n e r a t i o n o f W i t t i g reagents: NaH-MezSO, NaNHz-NH3, P h L i , BuLi, EtOLi-EtOH, EtONa-EtOH Org React (1965) 14 270 Na Chem Abs (1940) 2 392
-
98
t B u0 K- Me 2SO
Ber (1965)
PhLi-t-BuOK-t-BuOH
Angew (1964) ( I n t e r n a t Ed
Ethylene oxide
Angew (1968) ( I n t e r n a t Ed
D i a z a b i c y c l o [ 3 4.OInon-5-ene I
Ber (1966)
604
76 683 3 636) 2 535
L 536)
2 2012
E l e c t r o l y s i s (non b a s i c ) JACS (1968) 90 2728 T e t r L e t t (1969) 3523
F u r t h e r examples o f t h e W i t t i g r e a c t i o n a r e i n c l u d e d i n s e c t i o n 199 ( O l e f i n s f r o m Aldehydes)
SECTION 207
OLEFINS FROM KETONES 1 Me3SiCHzMgCl
2 NaH THF
Et2O
51 5
> 50% T e t r L e t t (1970) 1137 J O C (1968) 33 780
30-35% T e t r L e t t (1966) 4 3 1 5
30%
Ph2CO
Li PhCHNC THF
PhzC=CHPh
Angew (1968) 3 8 4 2 ( I n t e r n a t Ed 1 . 8 0 5 )
J O C (1948) 1_5 239 J A C S (1949) 819
74%
75%
COMPENDIUM OF ORGANIC SYNTHETIC METHODS
516
CH~COOBU-t
LiCH2COOBu-t
SECTION 2 0 7
200-230" ___)
Et20
NH3 Bull SOC C h i m Fr (1960) 1196
Ph2CO
(i-Pr0)3P
Ph2C=CPh2
JOC (1964)
low y i e l d
2 2567
C h e m Comm (1970) 1226 1225
MeCOCH2Me
---c
MeCOCHMe I (-1
EtMgBr
OH Me;-CHMe
Et2O
i t 61
0
NaOH
/\
MeC-CHMe
--+
H2°
Et
J
N a I NaOAc EtCOOH HOAc
trans MeC=CHMe I
Et 4
1 SnC12
Pyr
2 POc13
Pyr
*
65%
Me:
?H
- CHMe
Et
!
JCS (1959) 112
-
1 LiAlH4
Et2O
TsOH 2 Br2
RO
K2C03
C h e m P h a r m Bull (1969) JCS (1955) 1370
17 1585
51 7
O L E F I N S FROM KETONES
SECTION 207
"01 0 1 N2H4
0
c y c l ohexene
0
X=F, C1, B r or I
J O C (1964)
% Et3N
9 958
1j-qL+/y-$E+
EtOH
RO
54-71 %
THF J C S (1962) 470
1 TsNHNH2
b C O C H 3
*
2 NaH or NaNH2
Go
1 TsNHNH2
P
2 MeLi
THF
6
I>CH=CH2 Annalen (1966)
-1 00%
691 41
Synthesis (1970) 595 J A C S (1967) 5734
79%
51 8
COMPENDIUM OF ORGANIC SYNTHETIC METHODS
SECTION 207
1 TsNHNH~
2 MeLi
-1 00%
Et20 CgHg JACS (1968)
90 4762
T e t r a h e d r o n (1963)
c1
@JCocH3
@JCHzCH2
HPO(OEt)2_ NaNH2
19 1127
c1
Angew (1963)
( I n t e r n a t Ed
60% 138
2 98)
C8H17
0
P
2 (Et0)2POC1
(Et0)20PO T e t r L e t t (1969) 2145 Chem Comm (1969) 1 1 2
&-Real C8H17
0
R=Ac or Me
B2H6
___3
2 Ac20
Gazz (1962) 92 309 (Chem Abs 57 12572)
81 %
0' --+o"k0 -0
SECTION 207
OLEFINS FROM KETONES
%
(i-Bu)2A1H
OEt
51 9
(32%
isooc t a n e
JOC (1966)
EtCH2COMe
Pyrrolidine
2
329
-
AlH3 o r LiAlH4-AlC13
EtCH=CMe
Et20
I
EtCH=CHMe
T e t r a h e d r o n (1968) 2 4489 Proc Chem SOC (1963) 19
c);"
Pyrrolidi: ---------
0'2
21 HOAc 62116
-0
THF
< 98%
diglyme T e t r L e t t (1964) 2039
Me
Me
Me
PrCOCH3
-0
Mn02
550" (1 s e c )
*
Meot$h nNp Ye
Me
:-Nitroper-
O-
benzoic acid
Me
T e t r L e t t (1964) 3853 Compt Rend (1967) C 264 710
62%
PrCH=CH2 Chem C o r n (1969) 461
520
COMPENDIUM
OF ORGANIC SYNTHETIC METHODS
31
JOC (1966)
H202
SECTION 209
1393
H20
K2CO3
t-BuOH
Chem Comm (1968) 558
AcO
<65%
Some o f t h e methods l i s t e d i n s e c t i o n 199 ( O l e f i n s f r o m Aldehydes) may a l s o be a p p l i e d t o t h e p r e p a r a t i o n o f o l e f i n s f r o m ketones
S e c t i o n 208
Ph2CH
AN
O l e f i n s from N i t r i l e s
~ ~ ~ ~ O ~ ~ ~ O O O O O ~ O O O O O O O
KNH2
* Ph2yCHPh CN
Me
S e c t i o n 209
-
ye
1 KNH2 NH3 2 PhyHCl
NH3
J A C S (1956) (1960)
71 %
78 82 1786
O l e f i n s from O l e f i n s
a o o o o o o o o ~ ~ ~ o o ~ o o ~ ~ ~
... .... .... . . .. ...,,, ........... . ....
Homologation and a l k y l a t i o n o f o l e f i n s O l e f i n metathesis , M i g r a t i o n o f d o u b l e bonds C i s - t r a n s i n t e r c o n v e r s i o n and e q u i l i b r a t i o n I
BuCHzCH2
Ye
Ph2C=CPh
1 B2H6 +
2 PhHgCClZBr
I
I
I
I
I
I
.
page 520-521
. . . . , 521 . . . . 521-524 . . . . . 524-526 ,
I
BuCH~CH~CH=CHCH~BU JACS (1966)
88
1834
SECTION 209
PhCH$H=CH2
O L E F I N S FROM O L E F I N S
Na H- Me2SO
PhCH2CHCH2SOMe I
Me
A
521
PhCH$=CH2 1
Me
J O C (1964)
MeCH=CHEt
WCl6
EtAlC12
EtOH
MeCH=CHMe
t
29 2699
EtCH=CHEt
T e t r L e t t (1967) 3327 JACS (1968) 90 4133
37% JACS (1970)
CH2CH3
1 NaBH4
BF3
92
528
CH=CH2 62%
diglyme 2 C8H17CH=CH2 JACS (1967) (1960)
567 561
82 2074
522
COMPENDIUM
Ac0 @lOAC
OF
ORGANIC S Y N T H E T I C METHODS
SECTION 2 0 9
1 Nitration
AcO
HOAc
JACS (1956) 2 6269 J O C (1948) 13 424
HC1_
OH3 OcH2
o c H 3
Et3COKb Et3COH
Chem Comm (1968) 305 2111 Helv (1967)
T e t r L e t t (1968) 2 2 5 3
CH2Me
hU xyl ene
O C H M e+
@2Me
35% JACS (1967)
89 5199
0
-62%
SECTION 209
OLEFINS FROM OLEFINS
CH2CH=CH2
RhCl (PPh3)3
-
C6H6
L
523
O
60% P c H = c H M e
L
O
T e t r L e t t (1968) 3797
ooMe OoMe RhCl (PPh3)3
CHC13
*
T e t r L e t t (1968) 3797
EtCH2CHzCH=CH2
RhC13.3H20
-
EtOH
EtCHzCH=CHCH3 + JACS (1964) Helv (1967)
0
1 RhC13.3H20
86 1776 2445
-0
EtOH
2 KCN
PrCH2CH2CH2CH=CH2
EtCH=CHCH2CH3
JACS (1964)
Fe3(CO)i2 pet ether
-
hv
PrCH2CHzCH=CHCH3
a 2516 + PrCH2CH=CHCH2CH3 -+
PrCH=CHCH2CH2CH3
Proc Chem SOC (1964) 408
Review:
The I s o m e r i z a t i o n o f O l e f i n s . P a r t I . Base C a t a l y z e d I s o m e r i z a t i o n o f O l e f i n s
Synthesis (1969) 97
80%
'
524
COMPENDIUM OF ORGANIC SYNTHETIC METHODS
fOOH (CH2)7CH2CH=CH2
L i NHCH2CHZNH2
*
SECTION 209
YOoH (CH2)7CH=CHMe T e t r a h e d r o n (1964) JOC (1958) 2 1136
20
2911
The f o l l o w i n g bases may a l s o be used f o r t h e m i g r a t i o n o f d o u b l e bonds: LiNHEt
JACS (1964)
n
H
5281
Ber (1966) 99 1737 J O C (1968) 2 2 2 1 JACS (1961) 3731
t-BuOK-MezSO Na-alumina
JACS (1965) 4107 JCS C (1967) 2149 (1966) 260
Na-PhCHpNa
T e t r L e t t (1964) 467
2-Naphthalenesulfonic acid
w
CH
P (CH2)7
11
u : si JACS (1952)
MeCH=C,
,CH=CrHMe CH=CH OH
cis
cis
I2
hV
EtOH
Ye
MeCH=C,
74 3643
Ve
CH=CH
'CH=~HM~ trans AH JACS (1954) 2 5719
UH-CH' trans
JCS
C (1966)
260
SECTION 209
O L E F I N S FROM O L E F I N S
Ph2S2
hd
cis
trans
Me\
CH=CH
/
Me
Helv (1968) 2 548 JACS (1967) 89 2758 JCS (1966) 260
PhCOMe h!J
Me
CgHg
b
<
\
CH=CH
cis
trans
-c”b
HOAc
Hg ( OAc ) 2
”‘OH
JCS
/
CH=CH cis
Me
Me
J
y c i s
\
\
(1966) 260
JCS
CH2=CH
525
Ferrocene
+
h$
C
(1967) 2514
CH2=CH \ CH=CH
*
trans
\
Me
JACS (1965)
Et
\
CH=CH trans \Et
C12 SbC15 -Et$H-CHEt CHC13
KOH
---+
c1 A1
ProH
EtCHZCEt b1
Na
87 1626
Et
\
-C
NH3
JACS (1951)
Et
CH=CH cis
2 3329
/
526 'gHl1
COMPENDIUM /Me 'CH=CH cis
1 INCO
OF ORGANIC
2 MeOH
*
3 180' 4 Base 5 H2SO4 6 Base
SYNTHETIC METHODS
C5H11CHCHMe \/ NH
BuONO
SECTION 210
C5H11 'CH=CH t r a n s \ Me
T e t r L e t t (1969) 4001
cis
J C S (1954) 4219 (1953) 2393 (1951) 1079
trans
F u r t h e r examples o f t h e c o n v e r s i o n o f d i o l s and d i h a l i d e s i n t o o l e f i n s a r e i n c l u d e d i n s e c t i o n 198 ( O l e f i n s f r o m A l c o h o l s ) and s e c t i o n 205 ( O l e f i n s f r o m Hal i d e s and S u l f o n a t e s )
S e c t i o n 210
O l e f i n s f r o m M i s c e l l a n e o u s Compounds
aoooOoooo~ao~ooooooooooooooeoooooooo
The r e d u c t i o n o f v i n y l h a l i d e s , R2C=CR I
4
R$=CHR
i s included i n section
c1 160 ( H y d r i d e s f r o m H a l i d e s and S u l f o n a t e s )
The h y d r o g e n o l y s i s o f u n s a t u r a t e d ketones, e.g.
R2C-F-FO -+ RzCH-F=;H
R i R R i s i n c l u d e d i n s e c t i o n 72 ( A l k y l s , Methylenes and A r y l s f r o m Ketones)
41 %
SECTION 2 1 0
O L E F I N S FROM MISCELLANEOUS COMPOUNDS
C15H-31 CH2CH2SOMe
(MezCH)2S02
PhfS
Ni
Me2SO
reflux
C15H31 CH=CH2
Me2S0
xylene
85%
C h e m Comm (1965) 29 J O C (1964) 2 2699
t-BuOK
527
100%
MeCH=CH2 C h e m I n d (1963) 1243 JOC (1967) 2 102
18%
PhC=CPh
___t
he he
Me
66
J A C S (1944)
1136
95%
2 1767 2 3467
J O C (1958) (1961)
Chem P h a r m B u l l (1960)
PhCH2CH2SD2Cl
Et3N
CH2N2
Et20
*
PhCH2tH-FHz
80" +
PhCH2CH=CH2
so2 Angew (1965)
(Internat Ed
BuCHCH2Br I
OMe
Zn P r O H
g 621
96%
77 4 1 4 70)
BuCH=CH2
78% J A C S (1932)
54 7 5 1
COMPENOIUM OF ORGANIC SYNTHETIC METHODS
5 28
%"17
Ac0
-
d P OH
Zn
".Br
SECTION 210
EtOH
AcO
JCS (1955) 1370
72%
bMe
CH2COOH
Carbohydrate Res (1967)
4
465
Cu quinoline
60% Bull Soc Chim Fr (1960) 1196
a 1 I
BuCOFCOOEt Me
NaI
HMPA
1 NaBH4 MeOH
2 Hydrolysis
70% J O C (1968)
B'I
* BufH-CCOOH OH
he
1 MsCl
Na2C03
* BuCH=CBu
-
2 Collidine
diastereomer A diastereomer B
2 4540
I
Me
trans cis
T e t r L e t t (1968) 4569
SECTION 210
AcO
OLEFINS FROM MISCELLANEOUS COMPOUNDS
@
19O-195Ob
hV CgHg
91 %
AcO
0 -co
C5H11 CH2CH2CH2COCOOH
C o l l Czech (1960)
C5H11 CH-CH2 JACS (1968)
PhCH=CHCH+Et2 OH
-
529
25
2341
88%
90 1840
PhCH2CH=CH2
A
JCS (1965) 7242
Me
Me
,-
1 Mg
THF
-.go% Tetr Lett (1963) 1457