Structure determination of organic compounds: tables of spectral data

Structure Determination of Organic Compounds

Ern¨o Pretsch · Philippe B¨uhlmann · Martin Badertscher

Structure Determination of Organic Compounds Tables of Spectral Data

Fourth, Revised and Enlarged Edition

123

Prof. Dr. Ern¨o Pretsch ETH Z¨urich Institute of Biogeochemistry and Pollutant Dynamics Universit¨atsstr. 16 8092 Z¨urich Switzerland [email protected]

Prof. Dr. Philippe B¨uhlmann University of Minnesota Dept. of Chemistry 209 Pleasant Street SE., Minneapolis, MN 55455 USA [email protected]

Dr. Martin Badertscher ETH Z¨urich Laboratory of Organic Chemistry Wolfgang-Pauli-Str. 10 8093 Z¨urich Switzerland [email protected]

ISBN 978-3-540-93809-5

e-ISBN 978-3-540-93810-1

DOI 10.1007/978-3-540-93810-1 Library of Congress Control Number: 2009920112 c Springer-Verlag Berlin Heidelberg 2009  This work is subject to copyright. All rights are reserved, whether the whole or part of the material is concerned, specifically the rights of translation, reprinting, reuse of illustrations, recitation, broadcasting, reproduction on microfilm or in any other way, and storage in data banks. Duplication of this publication or parts thereof is permitted only under the provisions of the German Copyright Law of September 9, 1965, in its current version, and permission for use must always be obtained from Springer. Violations are liable to prosecution under the German Copyright Law. The use of general descriptive names, registered names, trademarks, etc. in this publication does not imply, even in the absence of a specific statement, that such names are exempt from the relevant protective laws and regulations and therefore free for general use. Cover design: WMXDesign GmbH Printed on acid-free paper 9 8 7 6 5 4 3 2 1 springer.com

Preface

The ongoing success of the earlier versions of this book motivated us to prepare a new edition. While modern techniques of nuclear magnetic resonance spectroscopy and mass spectrometry have changed the ways of data acquisition and greatly extended the capabilities of these methods, the basic parameters, such as chemical shifts, coupling constants, and fragmentation pathways remain the same. However, since the amount and quality of available data has considerably increased over the years, we decided to prepare a significantly revised manuscript. It follows the same basic concepts, i.e., it provides a representative, albeit limited set of reference data for the interpretation of 13C NMR, 1H NMR, IR, mass, and UV/Vis spectra. We also added a new chapter with reference data for 19F and 31P NMR spectroscopy and, in the chapter on infrared spectroscopy, we newly refer to important Raman bands. Since operating systems of computers become outdated much faster than printed media, we decided against providing a compact disk with this new edition. The limited versions of the NMR spectra estimation programs can be downloaded from the home page of the developing company (www.upstream.ch/support/book_downloads.html). We thank numerous colleagues who helped us in many different ways to complete the manuscript. We are particularly indebted to Dr. Dorothée Wegmann for her expertise with which she eliminated many errors and inconsistencies of the earlier versions. Special thanks are due to Prof. Wolfgang Robien for providing us with reference data from his outstanding 13C NMR database, CSEARCH. Another highquality source of information was the Spectral Database System of the National Institute of Advanced Industrial Science and Technology (http://riodb01.ibase.aist. go.jp/sdbs/), Tsukuba, Ibaraki (Japan). In spite of great efforts and many checks to eliminate errors, it is likely that some mistakes or inconsistencies remain. We would like to encourage our readers to contact us with comments and suggestions under one of the following addresses: Prof. Ernö Pretsch, Institute of Biogeochemistry and Pollutant Dynamics, ETH Zürich, CH-8092 Zürich, Switzerland, e-mail: [email protected], Prof. Philippe Bühlmann, Department of Chemistry, University of Minnesota, 207 Pleasant St. SE, Minneapolis, MN 55455, USA, e-mail: [email protected], or Dr. Martin Badertscher, Laboratory of Organic Chemistry, ETH Zürich, CH-8093 Zürich, Switzerland, e-mail: [email protected]. Zürich and Minneapolis, November 2008



Contents

1 Introduction���������������������������������� 1 1.1 Scope and Organization�������������������������� 1 1.2 Abbreviations and Symbols������������������������ 3

2 Summary Tables������������������������������ 5 2.1 General Tables������������������������������ 5 2.1.1 Calculation of the Number of Double Bond Equivalents from the Molecular Formula�������������������� 5 2.1.2 Properties of Selected Nuclei����������������������� 6 2.2 13C NMR Spectroscopy������������������������� 7 2.3 1H NMR Spectroscopy������������������������� 10 2.4 IR Spectroscopy���������������������������� 13 2.5 Mass Spectrometry��������������������������� 18 2.5.1 Average Masses of Naturally Occurring Elements with Masses and Representative Relative Abundances of Isotopes���� 18 2.5.2 Ranges of Natural Isotope Abundances of Selected Elements  25 2.5.3 Isotope Patterns of Naturally Occurring Elements������ 26 2.5.4 Calculation of Isotope Distributions������������� 27 2.5.5 Isotopic Abundances of Various Combinations of Chlorine, Bromine, Sulfur, and Silicon���������������� 29 2.5.6 Isotope Patterns of Combinations of Cl and Br�������� 31 2.5.7 Indicators of the Presence of Heteroatoms���������� 32 2.5.8 Rules for Determining the Relative Molecular Weight (Mr)� 34 2.5.9 Homologous Mass Series as Indications of Structural Type� 35 2.5.10 Mass Correlation Table������������������� 37 2.5.11 References�������������������������� 45 2.6 UV/Vis Spectroscopy�������������������������� 46

3 Combination Tables���������������������������

3.1 Alkanes, Cycloalkanes������������������������� 3.2 Alkenes, Cycloalkenes������������������������� 3.3 Alkynes���������������������������������

49 49 50 51

VIII

Contents

3.4 3.5 3.6 3.7

4

Aromatic Hydrocarbons������������������������ Heteroaromatic Compounds���������������������� Halogen Compounds�������������������������� Oxygen Compounds�������������������������� 3.7.1 Alcohols and Phenols��������������������� 3.7.2 Ethers����������������������������� 3.8 Nitrogen Compounds�������������������������� 3.8.1 Amines����������������������������� 3.8.2 Nitro Compounds����������������������� 3.9 Thiols and Sulfides��������������������������� 3.10 Carbonyl Compounds������������������������� 3.10.1 Aldehydes�������������������������� 3.10.2 Ketones���������������������������� 3.10.3 Carboxylic Acids����������������������� 3.10.4 Esters and Lactones��������������������� 3.10.5 Amides and Lactams���������������������

52 53 54 56 56 57 59 59 60 61 62 62 63 64 65 67

13C

69

NMR Spectroscopy�������������������������

4.1 Alkanes��������������������������������� 4.1.1 Chemical Shifts������������������������ 4.1.2 Coupling Constants���������������������� 4.1.3 References��������������������������� 4.2 Alkenes��������������������������������� 4.2.1 Chemical Shifts ������������������������ 4.2.2 Coupling Constants���������������������� 4.2.3 References��������������������������� 4.3 Alkynes��������������������������������� 4.3.1 Chemical Shifts������������������������ 4.3.2 Coupling Constants���������������������� 4.3.3 References��������������������������� 4.4 Alicyclics�������������������������������� 4.4.1 Chemical Shifts ������������������������ 4.4.2 Coupling Constants���������������������� 4.5 Aromatic Hydrocarbons������������������������ 4.5.1 Chemical Shifts������������������������ 4.5.2 Coupling Constants���������������������� 4.5.3 References��������������������������� 4.6 Heteroaromatic Compounds���������������������� 4.6.1 Chemical Shifts������������������������

69 69 78 79 80 80 84 84 85 85 85 86 87 87 92 93 93 100 100 101 101



Contents 4.6.2 Coupling Constants���������������������� 4.7 Halogen Compounds�������������������������� 4.7.1 Fluoro Compounds���������������������� 4.7.2 Chloro Compounds���������������������� 4.7.3 Bromo Compounds���������������������� 4.7.4 Iodo Compounds����������������������� 4.7.5 References��������������������������� 4.8 Alcohols, Ethers, and Related Compounds��������������� 4.8.1 Alcohols���������������������������� 4.8.2 Ethers����������������������������� 4.9 Nitrogen Compounds�������������������������� 4.9.1 Amines����������������������������� 4.9.2 Nitro and Nitroso Compounds���������������� 4.9.3 Nitrosamines and Nitramines����������������� 4.9.4 Azo and Azoxy Compounds������������������ 4.9.5 Imines and Oximes���������������������� 4.9.6 Hydrazones and Carbodiimides���������������� 4.9.7 Nitriles and Isonitriles��������������������� 4.9.8 Isocyanates, Thiocyanates, and Isothiocyanates������� 4.10 Sulfur Compounds��������������������������� 4.10.1 Thiols����������������������������� 4.10.2 Sulfides���������������������������� 4.10.3 Disulfides and Sulfonium Salts��������������� 4.10.4 Sulfoxides and Sulfones������������������� 4.10.5 Sulfonic and Sulfinic Acids and Derivatives��������� 4.10.6 Sulfurous and Sulfuric Acid Derivatives����������� 4.10.7 Sulfur-Containing Carbonyl Derivatives����������� 4.11 Carbonyl Compounds������������������������� 4.11.1 Aldehydes�������������������������� 4.11.2 Ketones���������������������������� 4.11.3 Carboxylic Acids����������������������� 4.11.4 Esters and Lactones��������������������� 4.11.5 Amides and Lactams��������������������� 4.11.6 Miscellaneous Carbonyl Derivatives������������� 4.12 Miscellaneous Compounds���������������������� 4.12.1 Compounds with Group IV Elements������������ 4.12.2 Phosphorus Compounds������������������� 4.12.3 Miscellaneous Organometallic Compounds���������

IX 108 109 109 111 112 113 113 114 114 115 117 117 119 120 120 120 121 122 122 123 123 123 124 125 126 126 127 128 128 129 131 133 135 137 139 139 140 142

Contents

X

4.13 Natural Products���������������������������� 4.13.1 Amino Acids������������������������� 4.13.2 Carbohydrates������������������������ 4.13.3 Nucleotides and Nucleosides���������������� ­4.13.4 Steroids���������������������������� 4.14 Spectra of Solvents and Reference Compounds������������ 4.14.1 13C NMR Spectra of Common Deuterated Solvents ���� 4.14.2 13C NMR Spectra of Secondary Reference Compounds �� 4.14.3 13C NMR Spectrum of a Mixture of Common Nondeuterated Solvents������������������ 5

1H

144 144 148 150 152 153 153 155 156

NMR Spectroscopy�������������������������� 157

5.1 Alkanes��������������������������������� 5.1.1 Chemical Shifts������������������������ 5.1.2 Coupling Constants���������������������� 5.2 Alkenes��������������������������������� 5.2.1 Substituted Ethylenes��������������������� 5.2.2 Conjugated Dienes���������������������� 5.2.3 Allenes����������������������������� 5.3 Alkynes��������������������������������� 5.4 Alicyclics�������������������������������� 5.5 Aromatic Hydrocarbons������������������������ 5.6 Heteroaromatic Compounds���������������������� 5.6.1 Non-Condensed Heteroaromatic Rings������������ 5.6.2 Condensed Heteroaromatic Rings��������������� 5.7 Halogen Compounds�������������������������� 5.7.1 Fluoro Compounds���������������������� 5.7.2 Chloro Compounds���������������������� 5.7.3 Bromo Compounds���������������������� 5.7.4 Iodo Compounds����������������������� 5.8 Alcohols, Ethers, and Related Compounds��������������� 5.8.1 Alcohols���������������������������� 5.8.2 Ethers����������������������������� 5.9 Nitrogen Compounds�������������������������� 5.9.1 Amines����������������������������� 5.9.2 Nitro and Nitroso Compounds���������������� 5.9.3 Nitrites and Nitrates���������������������� 5.9.4 Nitrosamines, Azo and Azoxy Compounds���������� 5.9.5 Imines, Oximes, Hydrazones, and Azines�����������

157 157 162 164 164 170 171 172 173 177 184 184 191 196 196 197 198 199 200 200 202 205 205 207 208 208 209



Contents

5.10

5.11

5.12

5.13

5.14

5.9.6 Nitriles and Isonitriles��������������������� 5.9.7 Cyanates, Isocyanates, Thiocyanates, and Isothiocyanates�� Sulfur Compounds��������������������������� 5.10.1 Thiols����������������������������� 5.10.2 Sulfides���������������������������� 5.10.3 Disulfides and Sulfonium Salts��������������� 5.10.4 Sulfoxides and Sulfones������������������� 5.10.5 Sulfonic, Sulfurous, and Sulfuric Acids and Derivatives�� 5.10.6 Thiocarboxylate Derivatives����������������� Carbonyl Compounds������������������������� 5.11.1 Aldehydes�������������������������� 5.11.2 Ketones���������������������������� 5.11.3 Carboxylic Acids and Carboxylates������������� 5.11.4 Esters and Lactones��������������������� 5.11.5 Amides and Lactams��������������������� 5.11.6 Miscellaneous Carbonyl Derivatives������������� Miscellaneous Compounds���������������������� 5.12.1 Compounds with Group IV Elements������������ 5.12.2 Phosphorus Compounds������������������� 5.12.3 Miscellaneous Compounds����������������� 5.12.4 References�������������������������� Natural Products���������������������������� 5.13.1 Amino Acids������������������������� 5.13.2 Carbohydrates������������������������ 5.13.3 Nucleotides and Nucleosides���������������� Spectra of Solvents and Reference Compounds������������ 5.14.1 1H NMR Spectra of Common Deuterated Solvents����� 5.14.2 1H NMR Spectra of Secondary Reference Compounds��� 5.14.3 1H NMR Spectrum of a Mixture of Common Nondeuterated Solvents������������������

XI 210 211 212 212 213 214 214 215 215 216 216 217 218 219 220 224 226 226 227 230 231 232 232 235 237 239 239 241 242

6 Heteronuclear NMR Spectroscopy������������������ 243 6.1

19F

NMR Spectroscopy������������������������� 6.1.1 19F Chemical Shifts of Perfluoroalkanes����������� 6.1.2 Estimation of 19F Chemical Shifts of Substituted Fluoroethylenes����������������������� 6.1.3 Coupling Constants in Fluorinated Alkanes and Alkenes��� 6.1.4 19F Chemical Shifts of Allenes and Alkynes���������

243 243 247 248 249

XII

Contents 6.1.5

19F

Chemical Shifts and Coupling Constants of Fluorinated Alicyclics�������������������������������� 250 6.1.6 19F Chemical Shifts and Coupling Constants of Aromatics and Heteroaromatics������������������������� 251 19 6.1.7 F Chemical Shifts of Alcohols and Ethers��������� 254 6.1.8 19F Chemical Shifts of Fluorinated Amine, Imine, and Hydroxyl­amine Derivatives���������������� 255 19 6.1.9 F Chemical Shifts of Sulfur Compounds���������� 256 6.1.10 19F Chemical Shifts of Carbonyl and Thiocarbonyl Compounds������������������������ 257 6.1.11 19F Chemical Shifts of Fluorinated Boron, Phosphorus, and Silicon Compounds�������������������� 258 19 6.1.12 F Chemical Shifts of Natural Product Analogues����� 259 6.1.13 References�������������������������� 260 6.2 31P NMR Spectroscopy������������������������� 261 6.2.1 31P Chemical Shifts of Tricoordinated Phosphorus, PR1R2R3 261 6.2.2 31P Chemical Shifts of Tetracoordinated Phosphonium Compounds������������������������ 262 6.2.3 31P Chemical Shifts of Compounds with a P=C or P=N Bond 263 6.2.4 31P Chemical Shifts of Tetracoordinated P(=O) and P(=S) Compounds������������������������ 264 31 6.2.5 P Chemical Shifts of Penta- and Hexacoordinated Phosphorus Compounds������������������ 266 6.2.6 31P Chemical Shifts of Natural Phosphorus Compounds��� 267 7 IR Spectroscopy����������������������������� 269 7.1 Alkanes��������������������������������� 269 7.2 Alkenes��������������������������������� 272 7.2.1 Monoenes ��������������������������� 272 7.2.2 Allenes����������������������������� 275 7.3 Alkynes��������������������������������� 276 7.4 Alicyclics�������������������������������� 277 7.5 Aromatic Hydrocarbons������������������������ 279 7.6 Heteroaromatic Compounds���������������������� 282 7.7 Halogen Compounds�������������������������� 284 7.7.1 Fluoro Compounds���������������������� 284 7.7.2 Chloro Compounds���������������������� 285 7.7.3 Bromo Compounds���������������������� 286 7.7.4 Iodo Compounds����������������������� 286



Contents 7.8 Alcohols, Ethers, and Related Compounds��������������� 7.8.1 Alcohols and Phenols��������������������� 7.8.2 Ethers, Acetals, and Ketals������������������ 7.8.3 Epoxides���������������������������� 7.8.4 Peroxides and Hydroperoxides���������������� 7.9 Nitrogen Compounds�������������������������� 7.9.1 Amines and Related Compounds��������������� 7.9.2 Nitro and Nitroso Compounds���������������� 7.9.3 Imines and Oximes���������������������� 7.9.4 Azo, Azoxy, and Azothio Compounds������������ 7.9.5 Nitriles and Isonitriles��������������������� 7.9.6 Diazo Compounds����������������������� 7.9.7 Cyanates and Isocyanates������������������� 7.9.8 Thiocyanates and Isothiocyanates��������������� 7.10 Sulfur Compounds��������������������������� 7.10.1 Thiols and Sulfides���������������������� 7.10.2 Sulfoxides and Sulfones������������������� 7.10.3 Thiocarbonyl Derivatives������������������ 7.10.4 Thiocarbonic Acid Derivatives���������������� 7.11 Carbonyl Compounds������������������������� 7.11.1 Aldehydes�������������������������� 7.11.2 Ketones���������������������������� 7.11.3 Carboxylic Acids����������������������� 7.11.4 Esters and Lactones��������������������� 7.11.5 Amides and Lactams��������������������� 7.11.6 Acid Anhydrides����������������������� 7.11.7 Acid Halides������������������������� 7.11.8 Carbonic Acid Derivatives������������������ 7.12 Miscellaneous Compounds���������������������� 7.12.1 Silicon Compounds��������������������� 7.12.2 Phosphorus Compounds������������������� 7.12.3 Boron Compounds���������������������� 7.13 Amino Acids������������������������������ 7.14 Solvents, Suspension Media, and Interferences������������ 7.14.1 Infrared Spectra of Common Solvents������������ 7.14.2 Infrared Spectra of Suspension Media������������ 7.14.3 Interferences in Infrared Spectra���������������

XIII 287 287 288 290 291 292 292 294 296 298 299 300 301 302 304 304 305 307 307 310 310 311 314 316 319 322 323 324 327 327 328 331 332 333 333 334 335

XIV

Contents

8 Mass Spectrometry��������������������������� 337 8.1 Alkanes��������������������������������� 337 8.2 Alkenes��������������������������������� 339 8.3 Alkynes��������������������������������� 341 8.4 Alicyclics�������������������������������� 342 8.5 Aromatic Hydrocarbons������������������������ 345 8.6 Heteroaromatic Compounds���������������������� 347 8.7 Halogen Compounds�������������������������� 352 8.8 Alcohols, Ethers, and Related Compounds��������������� 8.8.1 Alcohols and Phenols��������������������� 8.8.2 Hydroperoxides������������������������ 8.8.3 Ethers����������������������������� 8.8.4 Aliphatic Epoxides����������������������

354 354 356 356 359

8.9 Nitrogen Compounds�������������������������� 8.9.1 Amines����������������������������� 8.9.2 Nitro Compounds����������������������� 8.9.3 Diazo Compounds and Azobenzenes������������� 8.9.4 Azides����������������������������� 8.9.5 Nitriles and Isonitriles��������������������� 8.9.6 Cyanates, Isocyanates, Thiocyanates, and Isothiocyanates�� 8.9.7 References���������������������������

362 362 364 364 365 366 367 369

8.8.5 Aliphatic Peroxides���������������������� 360 8.8.6 References��������������������������� 361

8.10 Sulfur Compounds��������������������������� 8.10.1 Thiols����������������������������� 8.10.2 Sulfides and Disulfides�������������������� 8.10.3 Sulfoxides and Sulfones������������������� 8.10.4 Sulfonic Acids and Their Esters and Amides��������

371 371 371 373 376

8.10.5 Thiocarboxylic Acid Esters����������������� 377 8.10.6 References�������������������������� 378

8.11 Carbonyl Compounds������������������������� 8.11.1 Aldehydes�������������������������� 8.11.2 Ketones���������������������������� 8.11.3 Carboxylic Acids����������������������� 8.11.4 Carboxylic Acid Anhydrides����������������� 8.11.5 Esters and Lactones��������������������� 8.11.6 Amides and Lactams���������������������

379 379 380 381 382 382 384



Contents

XV

8.11.7 Imides���������������������������� 386 8.11.8 References�������������������������� 387 8.12 Miscellaneous Compounds���������������������� 388 8.12.1 Trialkylsilyl Ethers���������������������� 8.12.2 Phosphorus Compounds������������������� 8.12.3 References�������������������������� 8.13 Mass Spectra of Common Solvents and Matrix Compounds����� 8.13.1 Electron Impact Ionization Mass Spectra of Common Solvents�������������������������� 8.13.2 Spectra of Common FAB MS Matrix and Calibration Compounds������������������������� 8.13.3 Spectra of Common MALDI MS Matrix Compounds���� 8.13.4 References��������������������������

388 388 389 390 390 393 398 400

9 UV/Vis Spectroscopy�������������������������� 401 9.1 Correlation between Wavelength of Absorbed Radiation and Observed Color��������������������������������� 401 9.2 Simple Chromophores������������������������� 401 9.3 Conjugated Alkenes��������������������������� 403 9.3.1 Dienes and Polyenes���������������������� 403 9.3.2 α,β-Unsaturated Carbonyl Compounds������������ 404 9.4 Aromatic Hydrocarbons������������������������ 406 9.4.1 Monosubstituted Benzenes������������������ 406 9.4.2 Polysubstituted Benzenes������������������� 407 9.4.3 Aromatic Carbonyl Compounds���������������� 408 9.5 Reference Spectra���������������������������� 409 9.5.1 Alkenes and Alkynes��������������������� 409 9.5.2 Aromatic Compounds��������������������� 410 9.5.3 Heteroaromatic Compounds������������������ 415 9.5.4 Miscellaneous Compounds������������������ 417 9.5.5 Nucleotides�������������������������� 419 9.6 Common Solvents��������������������������� 420 Subject Index��������������������������������� 421

1 Introduction

1.1 Scope and Organization The present data collection is intended to serve as an aid in the interpretation of molecular spectra for the elucidation and confirmation of the structure of organic compounds. It consists of reference data, spectra, and empirical correlations from 1H, 13C, 19F, and 31P nuclear magnetic resonance (NMR), infrared (IR), mass, and ultraviolet–visible (UV/Vis) spectroscopy. It is to be viewed as a supplement to textbooks and specific reference works dealing with these spectroscopic techniques. The use of this book to interpret spectra only requires the knowledge of basic principles of the techniques, but its content is structured in a way that it will serve as a reference book also to specialists. Chapters 2 and 3 contain Summary Tables and Combined Tables of the most relevant spectral characteristics of structural elements. While Chapter 2 is organized according to the different spectroscopic methods, Chapter 3 for each class of structural elements supplies spectroscopic information obtained with various techniques. These two chapters should assist users less familiar with spectra interpretation to identify the classes of structural elements present in samples of their interest. The four chapters with data from 13C NMR, 1H NMR, IR spectroscopy, and mass spectrometry are ordered in the same manner by compound types. These cover the various carbon skeletons (alkyl, alkenyl, alkynyl, alicyclic, aromatic, and heteroaromatic), the most important substituents (halogen, single-bonded oxygen, nitrogen, sulfur, and carbonyl), and some specific compound classes (miscellaneous compounds and natural products). Finally, a spectra collection of common solvents, auxiliary compounds (such as matrix materials and references), and commonly found impurities is provided with each method. Not only the strictly analogous order of the data but also the optical marks on the edge of the pages help fast crossreferencing between the various spectroscopic techniques. Because their data sets are less comprehensive, the chapters on 19F and 31P NMR and UV/Vis are organized somewhat differently. Although currently UV/Vis spectroscopy is only marginally relevant to structure elucidation, its importance might increase by the advent of high-throughput analyses. Also, the reference data presented in the UV/Vis chapter are useful in connection with optical sensors and the widely applied UV/Vis detectors in chromatography and electrophoresis. Since a great part of the tabulated data either comes from our own measurements or is based on a large body of literature data, comprehensive references to published sources are not included. Whenever possible, the data refer to conventional modes and conditions of measurement. For example, unless the solvent is indicated, the NMR chemical shifts were normally determined with deuterochloroform. Likewise, the IR spectra were measured using solvents of low polarity, such as chloroform or

2

1 Introduction

carbon disulfide. Mass spectral data were recorded with electron impact ionization at 70 eV. While retaining the basic structure of the previous editions, numerous reference entries have been updated and new entries have been added. Altogether, about 20% of the data is new. The chapter on 19F and 31P NMR is entirely new, and the section on IR spectroscopy now includes references to important Raman bands.



1.2 Abbreviations and Symbols

1.2 Abbreviations and Symbols al alk alken ar as ax comb d δ DFTMP DMSO eq ε frag γ gem hal ip J liq M+. m/z ~ ν oop sh st sy TFA THF TMS vic

aliphatic alkyl alkenyl aromatic asymmetric axial combination vibration doublet IR: deformation vibration NMR: chemical shift 1,1-difluoro-1-(trimethylsilyl)methylphosphonic acid dimethyl sulfoxide equatorial molar absorptivity fragment skeletal vibration geminal halogen in plane vibration coupling constant liquid molecular radical ion mass to charge ratio wavenumber out of plane vibration shoulder stretching vibration symmetric trifluoroacetic acid tetrahydrofuran tetramethylsilane vicinal

3

2 Summary Tables

2.1 General Tables 2.1.1 Calculation of the Number of Double Bond Equivalents from the Molecular Formula General Equation

double bond equivalents = 1 + ½ ∑ni (vi – 2) i

ni: number of atoms of element i in molecular formula vi: formal valence of element i Short Cut For compounds containing only C, H, O, N, S, and halogens, the following steps permit a quick and simple calculation of the number of double bond equivalents: 1. O and divalent S are deleted from the molecular formula 2. Halogens are replaced by hydrogen 3. Trivalent N is replaced by CH 4. The resulting hydrocarbon, CnHx, is compared with the saturated hydrocarbon, CnH2n+2. Each double bond equivalent reduces the number of hydrogen atoms by 2:

double bond equivalents = ½ (2 n + 2 – x)

6

2 Summary Tables

2.1.2 Properties of Selected Nuclei Isotope Natural Spin abundance quantum [%] number, I 1H 2H 3H

10B 11B

13C

14N 15N 17O 19F 31P 33S

117Sn 119Sn 195Pt

199Hg 207Pb

99.985 0.015 0.000 19.58 80.42 1.108 99.635 0.365 0.037 100.000 100.000 0.76 7.61 8.58 33.8 16.84 22.6

1/2 1 1/2 3 3/2 1/2 1 1/2 5/2 1/2 1/2 3/2 1/2 1/2 1/2 1/2 1/2

Frequency Relative Relative [MHz] at sensitivity sensitivity 2.35 Tesla of nucleus at natural abundance 100.0 15.4 106.7 10.7 32.1 25.1 7.3 10.1 13.6 94.1 40.5 7.6 35.6 37.3 21.5 17.8 20.9

1 9.6×10-3 1.2 2.0×10-2 1.6×10-1 1.6×10-2 1.0×10-3 1.0×10-3 2.9×10-2 8.3×10-1 6.6×10-2 2.3×10-3 4.5×10-2 5.2×10-2 9.9×10-3 5.7×10-3 9.2×10-3

1 1.5×10-6 0 3.9×10-3 1.3×10-1 1.8×10-4 1.0×10-3 3.8×10-6 1.1×10-5 8.3×10-1 6.6×10-2 1.7×10-5 3.4×10-3 4.4×10-3 3.4×10-3 9.5×10-4 2.1×10-4

Electric quadrupole moment [e × 10-24 cm2] 2.8×10-3 7.4×10-2 3.6×10-2 1.9×10-2 -2.6×10-2 -6.4×10-2

2.2 13C NMR Spectroscopy



2.2

13C

7

NMR Spectroscopy

Summary of the Regions of Chemical Shifts, δ (in ppm), for Carbon Atoms in Various Chemical Environments (carbon atoms are specified as follows: Q for CH3, T for CH2, D for CH, and S for C) 240 220 200 180 160 140 120 100 80 60 H3C C

40 20

H3C C X H3C C X

Q

H3C S

Q

C CH2 C

T

C CH2 S

T

C CH C C

D Q

H3C COX; X: C, O, N C C

D,S

CH3Cl

Q

C CH S C

D

H3C N

Q

C C C C C

S

C CH2COX; X: C, O, N

T

C CHCOX; X: C, O, N C

D

C CH2 N

T

C S C C C

S T

C CH2Cl C CH N C C COX; X: C,O,N C C C

D S

H3C O C N C C C C CH Cl C H3C NO2

0 ppm

Q S D Q 240 220 200 180 160 140 120 100 80 60

40 20

0 ppm

2 Summary Tables

8

240 220 200 180 160 140 120 100 80 60 C CH2 O

S D S T D

C C

D, S

O O

T, D, S S

C X; X: any substituent C X C X: any substituent C

D, S

C N X

C N

D

S

C H; X: any substituent

C N C

0 ppm

T

C Cl C C C C CH NO2 C C O C C C C NO2 C C C H C C H

N

40 20

D

C CH2 NO2

C

0 ppm

T

C CH O C

X

40 20

S D, S

X: any substituent

C

C N

O

D, S S S S

C COX; X: O, N, Cl C COOH

S S

C CSX; X: O, N

S S D

C CHO C C O C C C S C

S S 240 220 200 180 160 140 120 100 80 60

2.2 13C NMR Spectroscopy

13C

Chemical Shifts of Carbonyl Groups (δ in ppm)

R –H –CH3 –CH2CH3 –CH(CH3)2 –C(CH3)3 –n-C8H17 –CH2Cl –CHCl2 –CCl3 –cyclohexyl –CH=CH2 –C ––– CH –phenyl

R–CHO 197.0 200.5 202.7 204.6 205.6 202.6 193.3

R –H –CH3 –CH2CH3 –CH(CH3)2 –C(CH3)3 –n-C8H17 –CH2Cl –CHCl2 –CCl3 –cyclohexyl –CH=CH2 –C ––– CH –phenyl

R–CHO 161.6 171.3 173.3 177.4 178.8 174.4 167.8 165.1 162.5 175.3 166.5 153.4 166.8

176.9 204.7 194.4 176.8 192.0

R–COCH3 200.5 206.7 207.6 211.8 213.5 207.9 200.1 193.6 186.3 209.4 197.5 183.6 196.9

R–COOH 166.3 176.9 180.4 184.1 185.9 180.7 173.7 170.4 167.1 182.1 171.7 156.5 172.6

R–COO– 171.3 182.6 185.1

R–COCH3 167.6 173.4 177.2

R–COOH 158.5 167.4 170.3 172.8 173.9 169.4 162.1 157.6 154.1

R–COO–

162.8

168.0

180.9 176.3 168.3 177.3 168.3 169.7

188.6 183.1 175.9 171.8 167.6 185.4 174.5 177.6

170.4 174.7 178.0 180.3 173.8 167.7 165.5 176.3 165.6

9

10

2.3

2 Summary Tables 1H

NMR Spectroscopy

Summary of the Regions of Chemical Shifts, δ (in ppm), for Hydrogen Atoms in Various Chemical Environments 14 13 12 11 10 9

8

7

6

5

4

3

2

1

0 ppm

14 13 12 11 10 9

8

7

6

5

4

3

2

1

0 ppm



2.3 1H NMR Spectroscopy

11

14 13 12 11 10 9

8

7

6

5

4

3

2

1

0 ppm

14 13 12 11 10 9

8

7

6

5

4

3

2

1

0 ppm

2 Summary Tables

12

14 13 12 11 10 9

8

7

6

5

4

3

2

1

0 ppm

14 13 12 11 10 9

8

7

6

5

4

3

2

1

0 ppm

CH2 Cl

O S O H2C O H 2C

OH

H 2C

Cl S

O CH O O

Cl CH2 N

CH2 O

O C CH O C C O CH2 N N CO H O CH2Cl H; heteroaromatic CH O

H

N

O

H

O

heteroaromatic NH O O

H

C N

OH

CHO COOH



2.4 IR Spectroscopy

13

2.4 IR Spectroscopy Summary of the Most Important IR Absorption Bands ( ~ν in cm-1) 3500

3000

2500

2000

1500

1000

500 cm -1

3500

3000

2500

2000

1500

1000

500 cm -1

δ

δ δ

14

2 Summary Tables

Summary of IR Absorption Bands of Carbonyl Groups ( ~ν in cm-1) 1900

1850

1800

1750

1700

1650

1600 1550 cm-1

1900

1850

1800

1750

1700

1650

1600 1550 cm-1



2.4 IR Spectroscopy

15

1900

1850

1800

1750

1700

1650

1600 1550 cm-1

1900

1850

1800

1750

1700

1650

1600 1550 cm-1

16

2 Summary Tables 1900

1850

1800

1750

1700

1650

1600 1550 cm-1

1900

1850

1800

1750

1700

1650

1600 1550 cm-1



2.4 IR Spectroscopy

17

1900

1850

1800

1750

1700

1650

1600 1550 cm-1

1900

1850

1800

1750

1700

1650

1600 1550 cm-1

(in solution)

(solid)

18

2 Summary Tables

2.5 Mass Spectrometry 2.5.1 Average Masses of Naturally Occurring Elements with Masses and Representative Relative Abundances of Isotopes [1–3] Element Isotope H

1H 2H

He

3He 4He

Li

6Li 7Li

Be

9Be

B

10B 11B

C

Mass

1.00794a,b 1.007825 2.014102

6.941a 6.015123 7.016005 9.012182 9.012182 10.811a 10.012937 11.009305

12C 13C

N

14.0067a

15N

O

16O 17O 18O

(in water) 100c 0.0115

4.002602a (in air) 3.016029 0.000134 4.002603 100

12.0107a 12.000000 13.003355

14N

Abundance

14.003074 15.000109 15.9994a 15.994915 16.999132 17.999161

8.21d 100

100

24.8c 100

100 1.08

100 0.365

100 0.038 0.205

Element Isotope

Mass

Abundance

F

18.998403 18.998403

Ne

20.1797a 19.992440 20.993847 21.991385

(in air) 100c 0.38 10.22

Na

22.989769 22.989769

100

Mg

24.3050 23.985042 24.985837 25.982593

100 12.66 13.94

Al

26.981538 26.981538

100

Si

28.0855a 27.976927 28.976495 29.973770

100 5.080 3.353

P

30.973762 30.973762

100

S

32.065a 31.972071 32.971459 33.967867 35.967081

100c 0.79 4.47 0.01

19F

20Ne 21Ne 22Ne

23Na

24Mg 25Mg 26Mg

27Al

28Si 29Si 30Si

31P

32S 33S 34S 36S

100



2.5 Mass Spectrometry Element Isotope Cl

Mass

35Cl 37Cl

35.453 34.968853 36.965903

Ar

39.948a

36Ar 38Ar 40Ar

K

39K 40K 41K

Ca

40Ca 42Ca 43Ca 44Ca 46Ca 48Ca

49Ti 50Ti

V

50V 51V

32.0

100 0.0125 7.2167

40.078 39.962591 41.958618 42.958767 43.955482 45.953693 47.952534

100 0.667 0.139 2.152 0.004 0.193

47.867 45.952632 46.951763 47.947946 48.947870 49.944791

48Ti

50Cr

39.0983 38.963707 39.963998 40.961826

Ti

47Ti

100c

35.967545 37.962732 39.962383

44.955912 44.955912

46Ti

Element Isotope

(in air) 0.3379 0.0635 100

Sc

45Sc

Abundance

50.9415 49.947159 50.943960

100

11.19 10.09 100 7.34 7.03

0.251 100

Cr

52Cr 53Cr 54Cr

Mass

51.9961 49.946044 51.940508 52.940649 53.938880

Abundance 5.186 100 11.339 2.823

Mn

54.938045 54.938045

100

Fe

55.845 53.939611 55.934938 56.935394 57.933276

6.370 100 2.309 0.307

Co

58.933195 58.933195

100

Ni

58.6934 57.935343 59.930786 60.931056 61.928345 63.927966

100 38.5198 1.6744 5.3388 1.3596

63.546a 62.929598 64.927790

100 44.61

65.409 63.929142 65.926033 66.927127 67.924844 69.925319

100 57.96 8.49 39.41 1.31

55Mn

54Fe 56Fe 57Fe 58Fe

59Co

58Ni 60Ni 61Ni 62Ni 64Ni

Cu

63Cu 65Cu

Zn

64Zn 66Zn 67Zn 68Zn 70Zn

19

20

2 Summary Tables

Element Isotope Ga

69Ga 71Ga

Ge

70Ge 72Ge 73Ge 74Ge 76Ge

As

75As

Se

74Se 76Se 77Se 78Se 80Se 82Se

Br

79Br 81Br

Kr

78Kr 80Kr 82Kr 83Kr 84Kr 86Kr

Mass

69.723 68.925574 70.924701 72.64 69.924247 71.922076 72.923459 73.921178 75.921403 74.921597 74.921597

Abundance 100c

66.36

55.50 74.37 21.13 100 21.32

100

Element Isotope Rb

Mass

Abundance

85.4678 84.911790 86.909181

100 38.56

87.62a 83.913425 85.909260 86.908877 87.905612

0.68 11.94 8.48 100

Y

88.905848 88.905848

100

Zr

91.224 89.904704 90.905646 91.905041 93.906315 95.908273

100 21.81 33.33 33.78 5.44

Nb

92.906378 92.906378

100

95.94 91.906811 93.905088 94.905842 95.904680 96.906022 97.905408 99.907477

61.06 38.16 65.72 68.95 39.52 100 39.98

85Rb 87Rb

Sr

84Sr 86Sr 87Sr 88Sr

89Y

90Zr

78.96 73.922476 75.919214 76.919914 77.917309 79.916521 81.916699

1.79 18.89 15.38 47.91 100 17.60

79.904 78.918337 80.916291

100 97.28

Mo

83.798 77.920382 79.916379 81.913484 82.914136 83.911507 85.910611

(in air) 0.623c 4.011 20.343 20.180 100 30.321

95Mo

91Zr 92Zr 94Zr 96Zr

93Nb

92Mo 94Mo 96Mo 97Mo 98Mo 100Mo



2.5 Mass Spectrometry Element Isotope Ru

96Ru 98Ru 99Ru

100Ru 101Ru 102Ru 104Ru

Rh

103Rh

Pd

102Pd 104Pd 105Pd 106Pd 108Pd 110Pd

Ag

107Ag 109Ag

Cd

106Cd 108Cd 110Cd 111Cd

112Cd 113Cd 114Cd 116Cd

Mass

101.07 95.907598 97.905287 98.905939 99.904220 100.905582 101.904349 103.905433 102.905504 102.905504 106.42 101.905609 103.904036 104.905085 105.903486 107.903892 109.905153 107.8682 106.905097 108.904752 112.411 105.906459 107.904184 109.903002 110.904178 111.902758 112.904402 113.903359 115.904756

Abundance 17.56 5.93 40.44 39.94 54.07 100 59.02

100

3.73 40.76 81.71 100 96.82 42.88

100 92.90

4.35 3.10 43.47 44.55 83.99 42.53 100 26.07

Element Isotope In

113In 115In

Sn

112Sn 114Sn 115Sn 116Sn 117Sn 118Sn 119Sn

120Sn 122Sn 124Sn

Sb

121Sb 123Sb

Te

120Te 122Te 123Te 124Te 125Te 126Te 128Te 130Te

I

127I

Mass

21

Abundance

114.818 112.904058 114.903878

4.48 100

118.710 111.904818 113.902779 114.903342 115.901741 116.902952 117.901603 118.903309 119.902195 121.903439 123.905274

2.98 2.03 1.04 44.63 23.57 74.34 26.37 100 14.21 17.77

121.760 120.903816 122.904214

100 74.79

127.60 119.904020 121.903044 122.904270 123.902818 124.904431 125.903312 127.904463 129.906224

0.26 7.48 2.61 13.91 20.75 55.28 93.13 100

126.904473 126.904473

100

22

2 Summary Tables

Element Isotope Xe

124Xe 126Xe 128Xe 129Xe 130Xe 131Xe 132Xe 134Xe 136Xe

Cs

133Cs

Ba

130Ba 132Ba 134Ba 135Ba 136Ba 137Ba 138Ba

La

138La 139La

Ce

136Ce 138Ce 140Ce 142Ce

Pr

141Pr

Mass

131.293 123.905893 125.904274 127.903531 128.904779 129.903508 130.905082 131.904154 133.905395 135.907219 132.905452 132.905452 137.327 129.906321 131.905061 133.904508 134.905689 135.904576 136.905827 137.905247 138.90547 137.907112 138.906353

Abundance 0.354c

0.330 7.099 98.112 15.129 78.906 100 38.782 32.916

100

0.148 0.141 3.371 9.194 10.954 15.666 100

0.090 100

140.116 135.907172 137.905991 139.905439 141.909244

0.209 0.284 100 12.565

140.907653 140.907653

100

Element Isotope Nd

142Nd 143Nd 144Nd 145Nd 146Nd 148Nd 150Nd

Sm

144Sm 147Sm 148Sm 149Sm 150Sm 152Sm 154Sm

Eu

151Eu 153Eu

Gd

152Gd 154Gd 155Gd 156Gd 157Gd 158Gd 160Gd

Tb

159Tb

Mass

Abundance

144.242 141.907723 142.909815 143.910087 144.912574 145.913117 147.916893 149.920891

100 44.9 87.5 30.5 63.2 21.0 20.6

150.36 143.911999 146.914898 147.914823 148.917185 149.917276 151.919732 153.922209

11.48 56.04 42.02 51.66 27.59 100 85.05

151.964 150.919850 152.921230

91.61 100

157.25 151.919791 153.920866 154.922622 155.922123 156.923960 157.924104 159.927054

0.81 8.78 59.58 82.41 63.00 100 88.00

158.925347 158.925347

100



2.5 Mass Spectrometry Element Isotope Dy

156Dy 158Dy 160Dy 161Dy 162Dy 163Dy 164Dy

Mass

162.500 155.924283 157.924409 159.925198 160.926933 161.926798 162.928731 163.929175

Ho

164.930322 164.930322

Er

167.259 161.928778 163.929200 165.930293 166.932048 167.932370 169.935464

165Ho

162Er 164Er 166Er 167Er 168Er 170Er

Abundance 0.20 0.34 8.24 66.84 90.15 88.10 100 100

0.41 4.78 100 68.26 80.52 44.50

Tm

168.934213 168.934213

Yb

173.04 167.933897 169.934762 170.936326 171.936382 172.938211 173.938862 175.942572

0.41 9.55 44.86 68.58 50.68 100 40.09

174.967 174.940772 175.942686

100 2.66

169Tm

168Yb 170Yb 171Yb 172Yb 173Yb 174Yb 176Yb

Lu

175Lu 176Lu

100

Element Isotope Hf

174Hf 176Hf 177Hf 178Hf 179Hf 180Hf

Ta

180Ta 181Ta

W

180W 182W 183W 184W 186W

Re

185Re 187Re

Os

184Os 186Os 187Os 188Os 189Os 190Os 192Os

Ir

191Ir 193Ir

Mass

23

Abundance

178.49 173.940046 175.941409 176.943221 177.943699 178.944816 179.946550

0.46 14.99 53.02 77.77 38.83 100

180.94788 179.947465 180.947996

0.012 100

183.84 179.946704 181.948204 182.950223 183.950931 185.954364

0.39 86.49 46.70 100.0 92.79

186.207 184.952955 186.955753

59.74 100

190.23 183.952489 185.953838 186.955751 187.955838 188.958148 189.958447 191.961481

0.05 3.90 4.81 32.47 39.60 64.39 100

192.217 190.960594 192.962926

59.49 100.0

24

2 Summary Tables

Element Isotope Pt

190Pt 192Pt 194Pt 195Pt 196Pt 198Pt

Mass

195.084 189.959932 191.961038 193.962680 194.964791 195.964952 197.967893

Au

196.966569 196.966569

Hg

200.59 195.965833 197.966769 198.968280 199.968326 200.970302 201.970643 203.973494

197Au

196Hg 198Hg 199Hg 200Hg 201Hg 202Hg 204Hg

Abundance 0.041 2.311 97.443 100 74.610 21.172 100 0.50 33.39 56.50 77.36 44.14 100 23.01

Element Isotope Tl

Mass

Abundance

204.3833 202.972344 204.974428

41.88 100

207.2a 203.973044 205.974465 206.975897 207.976653

2.7 46.0 42.2 100

Bi

208.980399 208.980399

100

Th

232.038055 232.038055

100

U

238.02891 234.040952 235.043930 238.050788

0.0054e 0.7257 100

203Tl 205Tl

Pb

204Pb 206Pb 207Pb 208Pb

209Bi

232Th

234U 235U 238U

a Natural variations in the isotopic composition of terrestrial materials do not allow

to give a more precise value.

b The mole ratio of 2H in hydrogen from gas cylinders was reported to be as low as

0.000032.

c Commercially

available materials may have substantially different isotopic compositions if they were subjected to undisclosed or inadvertent isotopic fractionation. d Materials depleted in 6Li are commercial sources of laboratory shelf reagents and are known to have 6Li abundances in the range of 2.0007–7.672 atom percent, with natural materials at the higher end of this range. Average atomic masses vary between 6.939 and 6.996; if a more accurate value is required, it must be determined for the specific material. e Materials depleted in 235U are commercial sources of laboratory shelf reagents.



2.5 Mass Spectrometry

25

2.5.2 Ranges of Natural Isotope Abundances of Selected Elements [3] Element Isotope

Range [atom %]

H 1H 2H

99.9816–99.9974 0.0026–0.0184

He 3He 4He

4.6×10-8–0.0041 99.9959–100

Li 6Li 7Li B

10B 11B

C

12C 13C

N

14N 15N

O

16O 17O 18O

Ne 20Ne 21Ne 22Ne

7.225–7.714 92.275–92.786

18.929–20.386 79.614– 81.071 98.853–99.037 0.963–1.147 99.579–99.654 0.346–0.421 99.738–99.776 0.037–0.040 0.188–0.222 88.47–90.51 0.27–1.71 9.20– 9.96

Element Isotope Si 28Si 29Si 30Si S

32S

Range [atom %] 92.205–92.241 4.678–4.692 3.082–3.102

Element Isotope Sr 84Sr 86Sr 87Sr 88Sr

Range [atom %] 0.55–0.58 9.75–9.99 6.94–7.14 82.29–82.75

Ce

36S

94.454–95.281 0.730–0.793 3.976–4.734 0.013–0.019

Cl 35Cl 37Cl

142Ce

0.185–0.186 0.251–0.254 88.446–88.449 11.114–11.114

75.644–75.923 24.077–24.356

Ca 40Ca 42Ca 43Ca 44Ca 46Ca 48Ca

96.933–96.947 0.646–0.648 0.135–0.135 2.082–2.092 0.004–0.004 0.186–0.188

Nd 142Nd 143Nd 144Nd 145Nd 146Nd 148Nd 150Nd

26.80–27.30 12.12–12.32 23.79–23.97 8.23–8.35 17.06–17.35 5.66–5.78 5.53–5.69

33S 34S

V

50V 51V

Cu 63Cu 65Cu

0.2487–0.2502 99.7498–99.7513 68.983–69.338 30.662–31.017

136Ce 138Ce 140Ce

Pb

204Pb 206Pb 207Pb 208Pb

U

234U 235U 238U

1.04–1.65 20.84–27.48 17.62–23.65 51.28–56.21 0.0050–0.0059 0.7198–0.7207 99.2739–99.2752

26

2 Summary Tables

2.5.3 Isotope Patterns of Naturally Occurring Elements The mass of the most abundant isotope is given under the symbol of the element. The lightest isotope is shown at the left end of the x axis. H 1

He 4

Li 7

Be 9

B 11

C 12

N 14

O 16

F 19

Ne 20

Na 23

Mg 24

Al 27

Si 28

P 31

S 32

Cl 35

Ar 40

K 39

Ca 40

Sc 45

Ti 48

V 51

Cr 52

Mn 55

Fe 56

Co 59

Ni 58

Cu 63

Zn 64

Ga 69

Ge 74

As 75

Se 80

Br 79

Kr 84

Rb 85

Sr 88

Y 89

Zr 90

Nb 93

Mo 98

Ru 102

Rh 103

Pd 106

Ag 107

Cd 114

In 115

Sn 120

Sb 121

Te 130

I 127

Xe 132

Cs 133

Ba 138

La 139

Ce 140

Pr 141

Nd 142

Sm 152

Eu 153

Gd 158

Tb 159

Dy 164

Ho 165

Er 166

Tm 169

Yb 174

Lu 175

Hf 180

Ta 181

W 184

Re 187

Os 192

Ir 193

Pt 195

Au 197

Hg 202

Tl 205

Pb 208

Bi 209

Th 232

U 238



2.5 Mass Spectrometry

27

2.5.4 Calculation of Isotope Distributions The characteristic abundance patterns resulting from the combination of more than one polyisotopic element can be calculated from the relative abundances of the different isotopes. The following polynomial expression gives the isotope distribution of a polyisotopic molecule: {pi1 Α0 + pi2 Α(mi2 - mi1) + pi3 Α(mi3 - mi1) + …}ni ×

{pj1 Α0 + pj2 Α(mj2 - mj1) + pj3 Α(mj3 - mj1) + …}nj × {…

where pix is the relative abundance of the xth isotope of element i, mix is the mass of the xth isotope of the element i, and the exponent ni stands for the number of atoms of the element i in the molecule. The expansion of this polynomial expression after inserting the pix and mix values for all the isotopes 1, 2, 3, … of the elements i, j, … of a given molecule yields an expression that represents the isotope distribution: w0 Α0 + wr Αr + ws Αs + wt Αt + …

where the values of w0, wr, ws, wt, … are the relative abundances of M+·, [M + r]+·, [M + s]+·, [M + t]+·,… , respectively. The use of Α(mix - mi1) allows to determine the values of r, s, t,… simply by expanding the general polynomial. A numerical value for A, which has no intrinsic meaning, is never needed. For example, for CBr2Cl2, the above equation gives rise to the following expression: {p12 Α0 + p13 Α(m13C - m12C ) } × C

{p79

Br

{p35

Cl

0

C

Α + p81

Α0 + p37

Br

Cl

Α(m81Br - m79Br ) }2 ×

Α(m37Cl - m35Cl) }2

For sufficient resolution, (mix - mi1) and (mjx - mj1) differ from one another. This results in very complex isotope patterns even for very small molecules. Thus, owing to the occurrence of 12C, 13C, 79Br, 81Br, 35Cl, and 37Cl, there are 18 signals for CBr2Cl2. However, the limited resolution of many real life experiments can make many pairs of (mix - mi1) and (mjx - mj1) indistinguishable within experimental error, thereby reducing the number of separate peaks. For example, at unit resolution, one obtains (m13C - m12C) = 1 and (m81Br - m79Br) = (m37Cl - m35Cl) = 2. Consequently, the expression for CBr2Cl2 becomes:

28

2 Summary Tables

{p12 Α0 + p13 Α1 } × {p79

Α0 + p81 Α2 }2 × {p35 Α0 C Br Br Cl 2 2 0 p12 p79 p35 } Α + C Br Cl 2 { p13 p79 p235 } Α1 + C Br Cl p12 p79 p81 p235 + p12 p279 p35 p37 } Α2 + C Br Br Cl C Br Cl Cl 2 2 { p13 p79 p81 p35 + p13 p79 p35 p37 } Α3 + C Br Br Cl C Br Cl Cl C

{

{

+ p37

Cl

Α2 }2 =

{ p12 p281

p2 + 4 p12 p79 p81 p35 p37 + p12 p279 p237 } Α4 + Br 35Cl C Br Br Cl Cl C Br Cl 2 2 2 { p13 p81 p35 + 4 p13 p79 p81 p35 p37 + p13 p79 p237 } Α5 C Br Cl C Br Br Cl Cl C Br Cl 2 2 6 p12 p79 p81 p37 + p12 p81 p35 p37 } Α + C Br Br Cl C Br Cl Cl C

{

p p2 C Br 81Br 37Cl p12 p281 p237 } Α8 + C Br Cl { p13 p79

{

{ p13 p281 C

Br

p237 } Α9 Cl

+ p13 p281 C

Br

p35 p37 Cl

Cl

+

} Α7 +

This shows that at unit resolution, CBr2Cl2 gives rise to only 10 peaks (M+·, [M+1]+·, [M+2]+·, ... [M+9]+·) rather than 18 peaks, as they would be expected for very high resolution. Moreover, the contribution of isotopes of low abundance can often be neglected without sacrificing much precision. For example, the effect of 2H on isotope patterns is usually insignificant. Also, 13C is often negligible when focussing on peaks of the series [M+2n]+·, which then results in patterns that are characteristic for halogens, sulfur, and silicon. In large molecules, however, isotopes of low abundance cannot be neglected. For example, in the case of buckminster fullerene (C60), not only M+· (relative intensity, 100%) and [M+1]+· (64.80%), but also [M+2]+· (20.65%), [M+3]+· (4.31%), and even [M+4]+· (0.66%) are quite significant ions. With the above algorithm, typical isotope patterns can be readily calculated manually by applying the general equation and neglecting isotopes of low abundance. The outlined procedure can also be easily implemented and evaluated with generic computer software that allows simple calculations. Dedicated and user-friendly programs that already contain the necessary isotope abundances and masses are available. Incidentally, because the use of the above equation for systems with 1000 or more polyisotopic atoms results in excessive calculation times, more efficient but somewhat more complicated algorithms have been developed for implementation in dedicated programs [4]. Typical isotope patterns are given on the following pages.



2.5 Mass Spectrometry

29

2.5.5 Isotopic Abundances of Various Combinations of Chlorine, Bromine, Sulfur, and Silicon Elements

Mass Relative Ele abunments dance

Cl1

35 37

100 31.96

Br1

Cl2

70 72 74

100 63.92 10.21

Cl3

105 107 109 111

Cl4

Cl5

Cl6

Mass Relative Ele abunments dance 79 81

100 97.28

Br2

158 160 162

51.40 100 48.64

100 95.88 30.64 3.26

Br3

237 239 241 243

34.27 100 97.28 31.54

140 142 144 146 148

78.22 100 47.94 10.21 0.82

Br4

316 318 320 322 324

17.61 68.53 100 64.85 15.77

175 177 179 181 183 185

62.53 100 63.92 20.43 3.26 0.21

Br5

395 397 399 401 403 405

10.57 51.40 100 97.28 47.32 9.21

210 212 214 216 218 220 222

52.15 100 79.90 34.05 8.16 1.04 0.06

Br6

474 476 478 480 482 484 486

5.43 31.70 77.10 100 72.96 28.39 4.60

Mass Relative abun dance

S1

32 33 34

100 0.80 4.52

S2

64 65 66 68

100 1.60 9.05 0.20

S3

96 97 98 99 100

100 2.40 13.58 0.22 0.61

S4

128 129 130 131 132

100 3.20 18.12 0.43 1.23

S5

160 161 162 163 164 166

100 4.00 22.66 0.72 2.05 0.09

30 Elements

2 Summary Tables Mass Relative Ele abunments dance 100 5.08 3.35

Si2

Mass Relative Ele abunments dance

Si1

28 29 30

56 57 58 59 60

Cl1Br1

114 116 118

77.38 Cl1Br2 100 24.06

193 195 197 199

Cl1Br4

351 353 355 357 359 361

14.45 60.84 100 79.42 29.94 4.14

Cl2Br1

Cl3Br1

184 186 188 190 192

51.77 100 64.15 17.12 1.64

Cl1S1

67 68 69 70 71

100 0.80 36.48 0.26 1.44

100 10.15 6.95 0.34 0.11

Mass Relative abun dance 84 85 86 87 88

100 15.23 10.82 1.03 0.36

44.14 Cl1Br3 100 69.23 13.35

272 274 276 278 280

26.51 85.85 100 48.46 7.80

149 151 153 155

62.03 100 44.91 6.16

Cl2Br2

228 230 232 234 236

38.69 100 88.68 31.09 3.74

Cl3Br2

263 265 267 269 271 273

32.07 93.14 100 49.27 11.34 0.99

Cl4Br1

219 221 223 225 227 229

44.42 100 82.47 32.28 6.11 0.45

Cl1S2

99 100 101 102 103

100 1.60 41.01 0.58 3.10

Cl2S1

102 103 104 105 106 108

100 0.80 68.44 0.51 13.10 0.46

Si3



2.5 Mass Spectrometry Elements

Mass Relative Ele abunments dance

Cl1Si1

63 64 65 66 67

100 5.08 35.31 1.62 1.07

Mass Relative Ele abunments dance

Cl2Si1

98 99 100 101 102 103 104

100 5.08 67.27 3.25 12.35 0.52 0.34

31

Mass Relative abun dance

Cl3Si1

133 134 135 136 137 138 139

100 5.08 99.23 4.87 33.85 1.56 4.29

2.5.6 Isotope Patterns of Combinations of Cl and Br

The signals are separated by 2 mass units. The mass for the most abundant signal is shown under the symbol of the element. The combination of the lightest isotopes is given on the left side of the x axis. See Chapter 2.5.5 for exact abundances of many of these combinations. Signals separated by 2 units

Br 79

Br2 160

Br3 239

Br4 320

Br5 399

Cl 35

ClBr 116

ClBr2 195

ClBr3 276

ClBr4 355

ClBr5 436

Cl2 70

Cl2Br 151

Cl2Br2 230

Cl2Br3 311

Cl2Br4 390

Cl2Br5 471

Cl3 105

Cl3Br 186

Cl3Br2 267

Cl3Br3 346

Cl3Br4 427

Cl4 142

Cl4Br 221

Cl4Br2 302

Cl4Br3 381

Cl4Br4 462

Cl5 177

Cl5Br 256

Cl5Br2 337

Cl5Br3 418

Cl6 212

Cl9 319

Cl12 426

Br6 480

Br9 718

32

2 Summary Tables

2.5.7 Indicators of the Presence of Heteroatoms In low-resolution mass spectra, one often observes characteristic isotope patterns, specific masses of fragment ions, and characteristic mass differences (Δm) between the molecular ion (M+·) and fragment ions (frag+) or between fragment ions. High resolution mass spectra can be used to confirm the elemental composition provided that the resolution is sufficient to discriminate alternative compositions. Moreover, tandem mass spectrometry (also called MS/MS) may be used to identify characteristic losses of heteroatoms from parent or fragment ions: Indication of O:

Δm 17 from M+·, in N-free compounds Δm 18 from M+· Δm 18 from frag+, particularly in aliphatic compounds Δm 28, 29 from M+· for aromatic compounds Δm 28 from frag+ for aromatic compounds m/z 15, relatively abundant m/z 19 m/z 31, 45, 59, 73, … + (14)n m/z 32, 46, 60, 74, … + (14)n m/z 33, 47, 61, 75, … + (14)n for 2 × O, in absence of S m/z 69 for aromatic compounds meta-disubstituted by O

Indication of N:

M+· odd-numbered (indicates odd number of N in M+·) Large number of even-numbered fragment ions Δm 17 from M+· or frag+, in O-free compounds Δm 27 from M+· or frag+, for aromatic compounds or nitriles Δm 30, 46 for nitro compounds m/z 30, 44, 58, 72, … + (14)n for aliphatic compounds

Indication of S:

Isotope peak [M+2]+· ≥ 5% of M+· Δm 33, 34, 47, 48, 64, 65 from M+· Δm 34, 48, 64 from frag+ m/z 33, 34, 35 m/z 45 in O-free compounds m/z 47, 61, 75, 89, … + (14)n unless compound with 2 × O m/z 48, 64 for S-oxides

Indication of F:

Δm 19, 20, 50 from M+· Δm 20 from frag+ m/z 20 m/z 57 without m/z 55 in aromatics



2.5 Mass Spectrometry

33

Indication of Cl: Isotope peak [M+2]+· ≥ 33% of M+· Δm 35, 36 from M+· Δm 36 from frag+ m/z 35/37, 36/38, 49/51 Indication of Br: Isotope peak [M+2]+· ≥ 98% of M+· Δm 79, 80 from M+· Δm 80 from frag+ m/z 79/81, 80/82 Indication of I:

Isotope peak [M+1]+ of very low abundance at relatively high mass Δm 127 from M+· Δm 127, 128 from frag+ m/z 127, 128, 254

Indication of P: m/z 47 in compounds without S or 2 × O m/z 99 without isotope peak at m/z 100 in alkyl phosphates

34

2 Summary Tables

2.5.8 Rules for Determining the Relative Molecular Weight (Mr) The molecular ion (M+·) is defined as the ion that comprises the most abundant isotopes of the elements in the molecule. Interestingly, the lightest isotopes of most elements frequently occurring in organic compounds and their common salts (H, C, N, O, F, Si, P, S, Cl, As, Br, I, Na, Mg, Al, K, Ca, Rb, Cs) are also the most abundant ones. Notable exceptions are B, Li, Se, Sr, and Ba. M+· is always accompanied by isotope peaks. Their relative abundance depends on the number and kind of the elements present and their natural isotopic distribution. The abundance of [M+1]+· indicates the maximum number of carbon atoms (Cmax) according to the following relationship: Cmax = 100 × intensity([M + 1]+·) / {1.1 × intensity(M+·)}

[M + 2]+· and higher masses indicate the number and kind of elements that have a relatively abundant heavier isotope (such as S, Si, Cl, Br). Note that, in analogy to the calculation of Cmax, the ratio of the intensities of [M + 2]+· and M+· for a compound with n silicon, o sulfur, p chlorine, or q bromine atoms can be approximated with quite high accuracy from n × 3.35%, o × 4.52%, p × 31.96%, or q × 97.28%, respectively (see also Chapters 2.5.4 to 2.5.6). The mass of M+· is always an even number if the molecule contains only elements for which the atomic mass and valence are both even- (C, O, S, Si) or both odd-numbered (H, P, F, Cl, Br, I). In the presence of other elements (e.g., 14N) and isotope labels (e.g., 13C, 2H), M+· becomes an odd number if they are present in an odd number. The molecular ion can only form fragment ions of masses that differ from that of M+· by chemically logical values (Δm). In this context, chemically illogical differences are Δm = 3 (in the absence of Δm = 1) to Δm = 14, Δm = 21 (in the absence of Δm = 1) to Δm = 24, Δm = 37, 38, and all Δm less than the mass of an element of characteristic isotope pattern in cases where the same isotope pattern is not retained in the fragment ion. M+· must contain all elements (and the maximum number of each) that are shown to be present in the fragment ions. If ionization is performed by electron impact, M+· is the ion with the lowest appearance potential. If a pure sample flows into the ion source through a molecular leak, M+· exhibits the same effusion rate as can be determined from the fragment ions. The abundance of M+· is proportional to the sample pressure in the ion source. For polar compounds, [M + H]+ is often observed in mass spectra obtained not only with fast atom bombardment and atmospheric pressure chemical ionization but also with electron impact ionization. In this latter case, the abundance of [M + H]+ changes in proportion to the square of the sample pressure in the ion source. In the absence of a signal for M+·, the relative molecular weight must have a value that shows a logical and reasonable mass difference, Δm, to all the observed fragment ions.



2.5 Mass Spectrometry

35

2.5.9 Homologous Mass Series as Indications of Structural Type Certain sequences of intensity maxima in the lower mass range and the masses of unique signals are often characteristic of a particular compound type. The intensity distribution of such ion series is in general smooth. Therefore, abrupt changes (maxima and minima) are of structural significance. The ion or ion series most indicative of a particular compound type is set in italics. ­ Mass Elemental values, m/z composition 12 + 14n

CnH2n-2

13 + 14n

CnH2n-1

14 + 14n

CnH2n-3O CnH2n

15 + 14n

CnH2n-2O CnH2n+1

16 + 14n 17 + 14n 18 + 14n 19 + 14n

20 + 14n

CnH2n-1O CnH2nO CnH2n+2N CnH2nNO CnH2n+1O CnH2n-1O2 CnH2nO2 CnH2n+3O CnH2n+1O2 CnH2n+1O2 CnH2n+1S C8H8 + CnH2n CnH2n+2O2 CnH2n+2S

Compound types alkenes, monocycloalkanes, alkynes, dienes, cycloalkenes, polycyclic alicyclics, cyclic alcohols alkanes, alkenes, monocycloalkanes, alkynes, dienes, cycloalkenes, polycyclic alicyclics, alcohols, alkyl ethers, cyclic alcohols, cycloalkanones, aliphatic acids, esters, lactones, thiols, sulfides, glycols, glycol ethers, alkyl chlorides cycloalkanones alkanes, alkenes, monocycloalkanes, polycyclic alicyclics, alcohols, alkyl ethers, thiols, sulfides, alkyl chlorides cycloalkanones alkanes, alkenes, monocycloalkanes, alkynes, dienes, cycloalkenes, polycyclic alicyclics, alkanones, alkanals, glycols, glycol ethers, alkyl chlorides, acid chlorides alkanones, alkanals, cyclic alcohols, acid chlorides alkanones, alkanals alkyl amines, aliphatic amides aliphatic amides alcohols, alkyl ethers, aliphatic acids, esters, lactones, glycols, glycol ethers aliphatic acids, esters, lactones aliphatic acids, esters, lactones alcohols, alkyl ethers aliphatic acids, esters, lactones glycols, glycol ethers thiols, sulfides alkylbenzenes glycols, glycol ethers thiols, sulfides

36

2 Summary Tables

Mass values m/z 21 + 14n

22 + 14n 23 + 14n 24 + 14n 25 + 14n

Elemental composition

C7H7 + CnH2n C7H5O CnH2nCl CnH2nCOCl C6H6N + CnH2n CnH2n–6 CnH2n–5 CnH2n–4 CnH2n–3

39, 52±1, CnHn±1 64±1, 76±2, 91±1

Compound types alkylbenzenes aryl ketones alkyl chlorides acid chlorides alkylanilines polycyclic alicyclics polycyclic alicyclics polycyclic alicyclics alkynes, dienes, cycloalkenes, polycyclic alicyclics alkylbenzenes, aromatic hydrocarbons, phenols, aryl ethers, aryl ketones



2.5 Mass Spectrometry

37

2.5.10 Mass Correlation Table Note: As long as it makes sense chemically, CH2, CH4, CH3O, and O2 in the formulae of the second column may be replaced by N, O, P, and S, respectively. Mass Ion

Product ion (and neutral particle lost)

Substructure or compound type

1

[M+1]+, [M-1]–

particularly in FAB spectra, in which M±1 occurs even for moderately basic and acidic compounds, but intensive M+· without M±1 is unusual in FAB spectra in the presence of Li+ (with isotope signal for 6Li) in FAB spectra of organic Li+ salts

7

Li+·

12 13 14

C+·

15 16

[M+7]+ [M-7]–

CH+ CH2+·, N+, N2++, CO++ CH3+ [M-15]+· O+·, NH2+, O2++

[M-16]+·

17

OH+, NH3+· [M-17]+·

18

H2O+·, NH4+

19 20

H3O+, F+ HF+·, Ar++, CH2CN++ C2H2O++ CO2++

21 22

[M-18]+· [M-19]+ [M-20]+·

(CH3) nonspecific; abundant: methyl, N-ethylamines (CH4) methyl (rare) (O) nitro compounds, sulfones, epoxides, N-oxides (NH2) primary amines (OH) acids (especially aromatic acids), hydroxylamines, N-oxides, nitro compounds, sulfoxides, tertiary alcohols (NH3) primary amines (H2O) nonspecific; abundant: alcohols, some acids, aldehydes, ketones, lactones, cyclic ethers O indicator (F) fluoro compounds F indicator (HF) fluoro compounds F indicator

38

2 Summary Tables

Mass Ion

23

Na+

24 25 26

+·

27 28

29 30

31

32

C2 C2H+ C2H2+·, CN+

Product ion (and neutral particle lost)

Substructure or compound type

[M+23]+

in FAB spectra in the presence of Na+; sometimes strong even if Na+ is only an impurity in FAB spectra of organic Na+ salts

[M-23]– [M-25]+ (C2H) [M-26]+· (C2H2) (CN) + [M-27] (C2H3)

terminal acetylenyl aromatics nitriles + C2H3 , terminal vinyl, some ethyl esters and HCN+· N-ethylamides, ethyl phosphates + · [M-27] (HCN) aromatic N, nitriles C2H4+·, CO+·, [M-28]+· (C2H4) nonspecific; abundant: cyclo­hexenes, N2+·, HCNH+ ethyl esters, propyl ketones, propylsubstituted aromatics (CO) aromatic O, quinones, lactones, lactams, unsaturated cyclic ketones, allyl aldehydes (N2) diazo compounds; air (inten­sity 3.7 times larger than for O2+·, m/z 32) + + + C2H5 , CHO [M-29] (C2H5) nonspecific; abundant: ethyl (CHO) phenols, furans, aldehydes + + · · CH2O , [M-30] (C2H6) ethylalkanes, polymethyl compounds CH2NH2+, (CH2O) cyclic ethers, lactones, primary NO+, C2H6+·, alcohols BF+·, N2H2+· (NO) nitro and nitroso compounds N indicator CH3O+, [M-31]+ (CH3O) methyl esters, methyl ethers, primary CH3NH2+·, alcohols O indicator CF+, N2H3+ (CH3NH2) N-methylamines (N2H3) hydrazides O2+·, [M-32]+· (O2) cyclic peroxides; air (intensity 3.7 CH3OH+·, times smaller than for N2+·, m/z 28) + + · · N2H4 , S (CH3OH) methyl esters, methyl ethers (S) sulfides (with 34S isotope signal) O indicator



2.5 Mass Spectrometry Mass Ion

33

CH3OH2+, SH+, CH2F+

34

SH2+·

35

SH3+, Cl+

36

HCl+·, C3+

37

C3H+ 37Cl+

38 39

C3H2+· C3H3+ K+

40 41

42

43

Product ion (and neutral particle lost) [M-33]+

39

Substructure or compound type

(SH)

nonspecific (with isotope signal for 34S) S indicator (CH3 + H2O) nonspecific O indicator (CH2F) fluoromethyl + · [M-34] (SH2) nonspecific (with 34S isotope signal) S indicator (OH + OH) nitro compounds [M-35]+ (Cl) chloro compounds (with 37Cl isotope signal) (OH + H2O) nitro compounds 2 × O indicator + · [M-36] (HCl) chloro compounds (H2O + H2O) 2 × O indicator chloro compounds (with isotope signal for 35Cl) [M-39]+ (C3H3) [M+39]+

[M-39]– C3H4+·, Ar+·, [M-40]+· CH2CN+ (CH2CN) C3H5+, [M-41]+ (C3H5) CH3CN+· (CH3CN) C3H6+·, C2H2O+·, CON+, C2H4N+

[M-42]+· (C3H6)

C3H7+, C2H3O+, CONH+·

[M-43]+ (C3H7)





(C2H2O)

(CH3CO)

aromatics in FAB spectra often strong even if K+ is only an impurity (with isotope signal for 41K) in FAB spectra of organic K+ salts cyanomethyl alicyclics (especially polyalicyclics), alkenes 2-methyl-N-aromatics, N‑methylanilines nonspecific; abundant: propyl esters, butyl ketones, butylaromatics, methylcyclohexenes acetates (especially enol acetates), acetamides, cyclohexenones, a,b‑unsaturated ketones nonspecific; abundant: propyl, alicyclics, cycloalkanones, cycloalkylamines, cycloalkanols, butylaromatics methyl ketones, acetates, aromatic methyl ethers

40

2 Summary Tables

Mass Ion

44

45

46

47

48 49

50 51

Product ion (and neutral particle lost)

CO2+·, [M-44]+· (C3H8) + C2H6N , (C2H6N) C2H4O+·, (C2H4O) CS+·, C3H8+·, CH4Si+· (CO2)

Substructure or compound type

propylalkanes N,N-dimethylamines, N-ethylamines cycloalkanols, cyclic ethers, ethylene ketals, aliphatic aldehydes (McLafferty rearrangement) anhydrides, lactones, carboxylic acids + + C2H5O , [M-45] (C2H5O) ethyl esters, ethyl ethers, lactones, C2H7N+·, ethyl sulfonates, ethyl sulfones CHS+ (with (CHO2) carboxylic acids isotope signal (C2H7N) N,N-dimethylamines, N-ethylamines for 34S) O indicator S indicator C2H5OH+·, [M-46]+· (C2H6O) ethyl esters, ethyl ethers, ethyl NO2+ sulfonates (H2O + C2H4) primary alcohols (H2O + CO) carboxylic acids (NO2) nitro compounds CH3S+, CCl+, [M-47]+ (CH3S) methyl sulfides (with isotope signal C2H5OH2+, for 34S) + CH(OH)2 , 2 × O indicator PO+ S indicator P indicator CH3SH+·, [M-48]+· (CH4S) methyl sulfides SO+·, CHCl+· (SO) sulfoxides, sulfones, sulfonates (with isotope signal for 34S) + + CH2Cl , [M-49] (CH2Cl) chloromethyl (with 37Cl isotope + CH3SH2 signal) (with iso­tope sig­nal for 34S) C4H2+·, [M-50]+· (CF2) trifluoromethylaromatics, perfluoro+ · CH3Cl , alicyclics CF2+· C4H3+, CHF2+



2.5 Mass Spectrometry Mass Ion

52 53 54 55 56

57 58

C4H4+· C4H5+ C4H6+·, C2H4CN+ C4H7+, C3H3O+ C4H8+·, C3H4O+· C4H9+, C3H5O+, C3H2F+ C3H8N+, C3H6O+·

59

C3H7O+, C2H5NO+·

60

C2H4O2+·, CH2NO2+, C2H6NO+ , C2H4S+· C2H5O2+, C2H5S+

61

62

63 64

41

Product ion (and neutral particle lost)

Substructure or compound type

[M-54]+· (C4H6) (C2H4CN) [M-55]+ (C4H7)

cyclohexenes cyanoethyl nonspecific; abundant: alicyclics, butyl esters, N-butylamides butyl esters, N-butylamides, pentyl ketones, cyclohexenes, tetralins, pentylaromatics methylcyclohexenones, b-tetralones nonspecific ethyl ketones

[M-56]+· (C4H8) (C3H4O) [M-57]+ (C4H9) (C3H5O) [M-58]+· (C4H10) (C3H6O) [M-59]+ (C3H7O) (C2H3O2) (C3H9N) [M-60]+· (C3H8O) (C2H4O2) (CH3OH + CO) (C2H4S) [M-61]+ (C2H5O2)

(C2H5S)

C2H6O2+·, C2H3Cl+· C2H6S+·

[M-62]+· (C2H6O2)

C5H3+, C2H4Cl+, COCl+ C5H4+·, SO2+·, S2+·

[M-63]+ (C2H4Cl) (CO + Cl)



[M-64]+·

(C2H6S)

(SO2) (S2)

alkanes a-methylalkanals, methyl ketones, isopropylidene glycols N indicator O indicator propyl esters, propyl ethers methyl esters amines, amides O indicator propyl esters, propyl ethers acetates methyl esters O indicator glycols, ethylene ketals 2 × O indicator ethyl sulfides (with 34S isotope signal) S indicator methoxymethyl ethers, ethylene glycols, ethylene ketals ethyl sulfides (with 34S isotope signal) chloroethyl carboxylic acid chlorides (with 37Cl isotope signal) sulfones, sulfonates disulfides (with 34S isotope signal)

42

2 Summary Tables

Mass Ion

65 66 67 68 69

70 71 72 73 74 75

C5H5+, H2PO2+ C5H6+· S2H2+·

C5H7+, C4H3O+ C5H8+·, C4H4O+·, C3H6CN+ C5H9+, C4H5O+, C3HO2+ CF3+ C5H10+· C4H6O+· C4H8N+ C5H11+ C4H7O+ C4H8O+·

C4H10N+ C6+· C4H9O+ C3H5O2+ C3H9Si+ C4H10O+· C3H6O2+· C3H7O2+ C3H7S+

76 77

C2H7SiO+ C6H4+· C6H5+ C3H6Cl+

Product ion (and neutral particle lost)

Substructure or compound type

[M-65]+ [M-66]+·

disulfides

(S2H) (SO2H) (C5H6)

[M-67]+ (C4H3O)

cyclopentenes disulfides (with 34S isotope signal) furyl ketones

[M-68]+· (C5H8) (C4H4O)

cyclohexenes, tetralins cyclohexenones, b-tetralones

[M-69]+

alicyclics, alkenes



(C5H9) (CF3)

trifluoromethyl alkanes, alkenes, alicyclics cycloalkanones pyrrolidines alkanes, larger alkyl groups alkanones, alkanals, tetrahydrofurans alkanones, alkanals O indicator aliphatic amines N indicator perhalogenated benzenes alcohols, ethers, esters O indicator carboxylic acids, esters, lactones trimethylsilyl compounds ethers methyl esters of carboxylic acids, a-methyl carboxylic acids methyl acetals, glycols 2 × O indicator sulfides, thiols (with 34S isotope signal) S indicator trimethylsilyloxyl compounds aromatics aromatics chloro compounds (with 37Cl isotope signal)



2.5 Mass Spectrometry

Mass Ion 78 79 80

81 82

83 84 85

86 87 88 89 90 91

C6H6+· C5H4N+ C3H7Cl+· C6H7+ C5H5N+· Br+ C6H8+· C5H4O+· HBr+· C5H6N+ C6H9+ C5H5O+ 81Br+ C6H10+· C5H6O+·

C5H8N+ C4H6N2+· CCl2+· C6H11+ C5H7O+ C5H10N+ C6H13+ C5H9O+ CClF2+ C5H10O+· C5H12N+ C5H11O+ C4H7O2+ C4H8O2+· C4H9O2+ C4H9S+ C7H6+· C7H7+ C4H8Cl+

Compound type

43

aromatics pyridines chloro compounds (with 37Cl isotope signal) aromatics with H-containing substituents pyridines, pyrroles bromo compounds (with 81Br isotope signal) cyclohexenes, polycyclic alicyclics cyclopentenones bromo compounds (with 81Br isotope signal) pyrroles, pyridines cyclohexanes, cyclohexenyls, dienes furans, pyrans bromo compounds (with 79Br isotope signal) cyclohexanes cyclopentenones, dihydropyrans tetrahydropyridines pyrazoles, imidazoles chloro compounds (with isotope signals at m/z 84 and 86) alkenes, alicyclics, monosubstituted alkanes cycloalkanones piperidines, N-methylpyrrolidines alkanes alkanones, alkanals, tetrahydropyrans, fatty acid derivatives chlorofluoroalkanes (with 37Cl isotope signal) alkanones, alkanals aliphatic amines N indicator alcohols, ethers, esters O indicator esters, carboxylic acids ethyl esters of carboxylic acids, a-methyl-methyl esters, a-C2-carboxylic acids diols, glycol ethers 2 × O indicator 34 sulfides (with S isotope signal) disubstituted aromatics aromatics alkyl chlorides (with 37Cl isotope signal)

44

2 Summary Tables

Mass Ion 92 93 94 95 96 97 98 99

104 105 106 111 115 119

120 121

C7H8+· C6H6N+ C6H5O+ C6H7N+·

CH2Br+ C6H6O+· C5H4NO+ C5H3O2+ C7H12+· C7H13+ C6H9O+ C5H5S+ C6H12N+ C7H15+ C6H11O+ C5H7O2+ H4PO4+ C8H8+· C7H4O+·

C8H9+ C7H5O+ C6H5N2+ C7H8N+ C5H3OS+ C9H7+ C6H11O2+ C5H7O3+ C9H11+ C8H7O+ C2F5+ C7H5NO+· C7H4O2+·

C8H10N+ C8H9O+ and C7H5O2+

Compound type

alkylbenzenes alkylpyridines phenols, phenol derivatives anilines bromo compounds (with 81Br isotope signal) phenol esters, phenol ethers pyrryl ketones, pyridone derivatives furyl ketones alicyclics alicyclics, alkenes cycloalkanones alkylthiophenes (with 34S isotope signal) N-alkylpiperidines alkanes alkanones ethylene ketals alkyl phosphates tetralin derivatives, phenylethyl derivatives disubstituted a-ketobenzenes alkylaromatics benzoyl derivatives diazophenyl derivatives alkylanilines thiophenoyl derivatives (with 34S isotope signal) aromatics esters diesters alkylaromatics tolyl ketones perfluoroethyl derivatives phenyl carbamates g-benzopyrones, salicylic acid derivatives pyridines, anilines hydroxybenzene derivatives



2.5 Mass Spectrometry Mass Ion 127

128

130 131 135 141 142 149 152 165 167 205 223

C10H7+ C6H7O3+ C6H6NCl+· I+ C10H8+· C6H5OCl+· HI+· C9H8N+ C9H6O+· C10H11+ C5H7S2+ C3F5+ C4H8Br+ C11H9+ C10H8N+ C8H5O3+ C12H8+· C13H9+ C8H7O4+ C12H13O3+ C12H15O4+

45

Compound type

naphthalenes unsaturated diesters chlorinated N-aromatics (with 37Cl isotope signal) iodo compounds naphthalenes chlorinated hydroxybenzene derivatives (with 37Cl isotope signal) iodo compounds quinolines, indoles naphthoquinones tetralins thioethylene ketals (with 34S isotope signal) perfluoroalkyl derivatives alkyl bromides (with 81Br isotope signal at m/z 137) naphthalenes quinolines phthalates diphenyl aromatics diphenylmethane derivatives (fluorenyl cation) phthalates phthalates phthalates

2.5.11 References [1] M.E. Wieser, Atomic weights of the elements 2005, J. Phys. Chem. Ref. Data 2007, 36, 485. [2] G. Audi, A.H. Wapstra, The AME2003 atomic mass evaluation, (II). Tables, graphs and references, Nucl. Phys. A 2003, 729, 337. [3] J.K. Böhlke, J.R. de Laeter, P. De Bièvre, H. Hidaka, H.S. Peiser, K.J.R. Rosman, P.P.D. Taylor, Isotopic compositions of the elements, 2001, J. Phys. Chem. Ref. Data 2005, 34, 57. [4] H. Kubinyi, Calculation of isotope distributions in mass spectrometry. A trivial solution for a non-trivial problem, Anal. Chim. Acta 1991, 247, 107.

46

2 Summary Tables

2.6 UV/Vis Spectroscopy UV/Vis Absorption Bands of Various Compound Types (Α: alkyl or H; R: alkyl; sh: shoulder) Compound Type Transition (log ε) π→π

(3–4)

n→σ

(3.6)

n→σ

(2.4)

π→π

(3.7–4)

n→σ

(2.5)

n→σ π→π n→π π→π n→π n→σ

200

300

400

500

600

700 nm

200

300

400

500

600

700 nm

(3.5)

(3–4) (1–2) (2) (0.9–1.4) (3.5)

n→σ n→σ n→σ n→σ n→σ n→σ

(3.2) (2.2 sh) (3–3.6) (2–3 sh) (3–4) (2.6)

n→σ

(2.5)

n→π

(1.7)

n→π

(1.7)

n→π

(1.8)

π→π n→π

(≈4) (1–2)

π→π

(3.9–4.4)

π→π

(4.2–4.8)

π→π

(4.3–5.2)



2.6 UV/Vis Spectroscopy

Compound Type Transition (log ε) R Cl

O

R NO

400

500

600

700 nm

n→π* (1.7) n=0–4

R I

300

200

47

(4 – 5)

a

n→σ* (2.6) (2.0) (1.3)

n=0–4

(2.4–4.1)

a n→π* (conjugated systems) n→π* π→π* (conjugated systems) π→π* n→σ* σ→σ*

a longest

wavelength absorption maximum 300 200

400

500

600

700 nm

3 Combination Tables

3.1 Alkanes, Cycloalkanes

13C

1H

IR

MS

Assignment CH3 CH2 CH C

Range 5–35 ppm 5–45 ppm 25–60 ppm 30–60 ppm

CH3 CH2 CH

0.8–1.2 ppm 1.1–1.8 ppm 1.1–1.8 ppm

CH st CH3 δ as CH2 δ CH3 δ sy CH2 γ

Fragments

UV

Lower shift values in three-membered rings

3000–2840 cm-1 Higher frequency in three-membered rings ≈1460 cm-1 ≈1460 cm-1 ≈1380 cm-1 Doublet for geminal methyl groups 770–720 cm-1 In C–(CH2)n–C with n ≥ 4 at ca. 720 cm-1

Molecular ion m/z 14n + 2

Rearrangements

Comments CH3, CH2, CH, and C can be differentiated by multipulse experiments (DEPT, APT), off-resonance decoupling, 2D CH correlation spectra, or based on relaxation times Lower shift values in three-membered rings

m/z 14n m/z 14n - 2

Weak in n-alkanes Very weak in isoalkanes n-Alkanes: local maxima at 14n + 1, intensity variations: smooth, minimum at [M-15]+ Isoalkanes: local maxima at 14n + 1, intensity distribution: irregular (relative maxima due to fragmentation at branching points with charge retention at the most highly substituted C) n-Alkanes: unspecific Isoalkanes: elimination of alkenes Monocycloalkanes: elimination of alkanes No absorption above 200 nm

50

3 Combination Tables

3.2 Alkenes, Cycloalkenes

13C

Assignment C=C C–(C=C)

Range 100–150 ppm 10–60 ppm

Comments Considerable differences between Z and E: C

X

C

H

1H

H–(C=C) CH3–(C=C) CH2–(C=C)

4.5–6.5 ppm ≈1.7 ppm ≈2.0 ppm

H



X

Coupling constants, |Jgem| 0–3 Hz Jcis 5–12 Hz Jtrans 12–18 Hz Coupling constants, 3JCH3–CH=C ≈ 7 Hz 3JCH –CH=C ≈ 7 Hz 2 H In rings, |J| smaller: n = 2, 3J ≈ 0.5 Hz H n = 3, 3J ≈ 1.5 Hz H n = 4, 3J ≈ 4.0 Hz C n

Long-range coupling, 4JHC–C=CH 0–2 Hz

IR

H–C(=C) st 3100–3000 cm-1 C=C st 1690–1635 cm-1 Of variable intensity H–C(=C) δ oop 1000–675 cm-1 CH2–(C=C) δ 1440 cm-1

MS Molecular ion Fragments

m/z 14n m/z 14n - 2 m/z 14n - 1 m/z 14n - 3

Rearrangements

Alkenes: moderate intensity Monocycloalkenes: medium intensity Local maxima for alkenes Local maxima for monocyclic alkenes Usually, double bonds cannot be localized n-Alkenes: unspecific except for: +.

R

R H

X

R

- X C H =CH 2

R

R

+. H

R

Cyclohexenes: retro-Diels–Alder reaction: +

UV

C=C π   π*

< 210 nm (log ε 3–4) (C=C)2 π   π* 215–280 nm (log ε 3.5–4.5)



.

+ +

.

Isolated double bonds; for highly substituted double bonds often absorption tail



3.3 Alkynes

51

3.3 Alkynes

13C

1H

IR MS

UV

Assignment C ––– C

Range 65–85 ppm

C–(C ––– C) H–(C ––– C)

1.5–3.0 ppm

CH3–(C ––– C) CH2–(C ––– C) CH–(C ––– C) H–C(––– C) st C ––– C st Molecular ion Fragments Rearrangements C ––– C π   π*

0–30 ppm

≈1.8 ppm ≈2.2 ppm ≈2.6 ppm

Comments Coupling constant 2JHC ––– 13C ≈50 Hz; often leading to unexpected signs of signals in DEPT spectra and unexpected signals in 2D heteronuclear correlation spectra Coupling constants, |4JCH–C ––– CH| ≈3 Hz |5JCH–C ––– C–CH| ≈3 Hz

3340–3250 cm-1 Sharp, intensive 2260–2100 cm-1 Sometimes very week

< 210 nm (log ε 3.7–4.0)

Weak, in the case of 1-alkynes up to C7 often absent [M-1]+ often significant Extensive rearrangements, not very characteristic Isolated double bonds; for highly substituted double bonds often absorption tail

52

3 Combination Tables

3.4 Aromatic Hydrocarbons

13C 1H

IR

MS

Assignment ar C ar CH al C–C ar

Range 120–150 ppm 110–130 ppm 10–60 ppm

CH3–C ar CH2–C ar CH–C ar ar C–H st comb ar C–C st

≈2.3 ppm ≈2.6 ppm ≈2.9 ppm 3080–3030 cm-1 2000–1650 cm-1 ≈1600 cm-1 ≈1500 cm-1 ≈1450 cm-1 960–650 cm-1

H–C ar

ar C–H δ oop

6.5–7.5 ppm

Comments Same ranges for polycyclic aromatic hydrocarbons In polycyclic aromatic hydrocarbons up to ≈9 ppm Coupling constants, 3Jortho ≈7 Hz 4J meta ≈2 Hz 5J para <1 Hz Often line broadening due to long-range coupling with aromatic protons Often multiple bands, weak Very weak Of variable intensity, sometimes not all bands observable Strong, frequently multiple bands

Molecular ion Strong, often base peak Fragments m/z 39, 50–53, Often doubly charged fragment ions 63–65, 75–78, [M-26]+·, [M-39]+ Benzylic cleavage

CH 1-3

Other typical fragments





m/z 91 (90, 92) m/z 127 +.



m/z 152 m/z 165



+

Rearrangements

+. R R

R H

X

- X C H =CH 2

R R

R

+. H



UV

Assignment

3.5 Heteroaromatics

53

Range Comments ≈200–210 nm In benzene and alkylbenzenes (log ε ≈4) ≈260 nm (log ε ≈2.4)

3.5 Heteroaromatic Compounds

13C 1H

IR

MS

UV

Assignment ar C–X ar C–C H–C ar

H–N ar

ar C–H st ar N–H st ar C–C st ar C–H δ oop

Range 120–160 ppm 100–150 ppm 6–9 ppm

7–14 ppm

3100–3000 cm-1 3500–2800 cm-1 ≈1600 cm-1 ≈1500 cm-1 ≈1450 cm-1 1000–650 cm-1

Molecular ion Fragments m/z 39, 50–53, 63–65, 75–78, [M-26]+·, [M-39]+ m/z 45 [CHS]+ Benzyl-analogous cleavage Rearrangements

Comments Coupling constants in 6-membered rings similar to those in aromatic hydrocarbons; smaller in 5-membered rings Strongly solvent dependent, generally broad Often multiple bands, weak

Often split, sometimes not all bands observable Often strong, frequently multiple bands Strong, often base peak

Often doubly charged fragment ions S-Heteroaromatics Loss of HCN (Δm 27, N-heteroaromatics) Loss of CO (Δm 28, O-heteroaromatics) Loss of CS (Δm 44, S-heteroaromatics) cf. UV/Vis Reference Spectra, Chapter 8.5.3

54

3 Combination Tables

3.6 Halogen Compounds

13C

1H

Assignment al C–F (C)=C–F C=(C–F) ar C–F ar C–(C–F)

Range 70–100 ppm 125–175 ppm 65–115 ppm 140–165 ppm 105–135 ppm

al C–Cl (C)=C–Cl C=(C–Cl) ar C–Cl ar C–(C–Cl) al C–Br (C)=C–Br C=(C–Br) ar C–Br ar C–(C–Br) al C–I (C)=C–I C=(C–I) ar C–I ar C–(C–I)

30–60 ppm 100–150 ppm 100–155 ppm 120–150 ppm 125–135 ppm 10–45 ppm 90–140 ppm 90–140 ppm 110–140 ppm 125–135 ppm -20 to +30 ppm 60–110 ppm 120–150 ppm 85–115 ppm 125–145 ppm

CH2–F

CH2–Cl CH2–Br CH2–I

≈3.5 ppm ≈3.4 ppm ≈3.1 ppm

Coupling, with 19F (isotope abundance, 100%; I = 1/2): |2JHF| 40–80 Hz |3JHF| 0–50 Hz |4JCF| 0–5 Hz

H–CX=C

5.5–8.0 ppm

Similar shifts for all halogens

H–phenyl–hal

7.0–7.6 ppm

Shielding by F in ortho and para positions; small effects for Cl and Br; deshielding by I in ortho, and shielding in meta position

H–C=CF H–C=CCl H–C=CBr H–C=CI

IR

≈4.3 ppm

Comments CF3: ≈115 ppm Coupling, with 19F (isotope abundance, 100%; I = 1/2): |1JCF| 100–300 Hz |2JCF| 10–40 Hz |3JCF| 5–10 Hz |4JCF| 0–5 Hz

C–F st C–Cl st C–Br st C–I st

4.0–6.0 ppm 4.5–6.5 ppm 5.0–7.0 ppm 5.5–7.5 ppm

1400–1000 cm-1 850–600 cm-1 700–500 cm-1 650–450 cm-1

Strong Strong Strong Strong



MS

3.6 Halogen Compounds

Assignment Range Molecular ion

Fragments

m/z 69, 50–53

Comments Often weak for saturated aliphatic halogen compounds, often absent from spectra of aliphatic polyhalogenated compounds Characteristic isotope pattern for Cl and Br CF3 Upon fragmentation of the C–hal bond, the positive charge preferably remains on the alkyl side, and on the halogen side upon fragmentation of the neighboring bond: R

Rearrangements

UV

hal n   π*

[M-20]+· [M-50]+· or [frag-50]+ [M-36]+· ≤280 nm (log ε ≈2.5)

55

C

hal

>

R

C

hal

HF elimination CF2 elimination HCl elimination For C–I; for C–Br and C–Cl in general only absorption tail, for C–F no absorption

56

3 Combination Tables

3.7 Oxygen Compounds 3.7.1 Alcohols and Phenols Assignment

Range 50–80 ppm al C–(C–OH) 10–60 ppm al C–(C–C–OH) 10–60 ppm

Comments Shift with respect to C–H ≈50 ppm Hardly any shift with respect to C–(C–CH3) Shift with respect to C–(C–C–CH3) ≈-5 ppm

HO–C al HO–C ar CH2–(OH) CH–(OH) ar CH–(C–OH)

Often broad; position and shape strongly depend on experimental conditions

13C al C–OH

ar C–OH ar C–(C–OH)

1H

IR

O–H st C–O(H) st

MS Molecular ion Fragments

140–155 ppm 100–130 ppm 0.5–6 ppm 4–12 ppm 3.5–4.0 ppm 3.8–4.2 ppm 6.5–7.0 ppm

3650–3200 cm-1 1260–970 cm-1

Shift with respect to C–H ≈+25 ppm Shift with respect to C–(C–H): ortho ≈-13 ppm, meta ≈+1 ppm, para ≈-8 ppm

Shift with respect to CH–(C–H): ortho ≈-0.6 ppm, meta ≈-0.1 ppm, para ≈-0.5 ppm Position and shape depend on the degree of association. Often different bands for Hbonded and free OH Strong

Aliphatic: weak, often missing in the case of primary and highly branched alcohols; in this case, peaks at highest mass are often due to [M-18]+· or [M-15]+ Aromatic: strong Aliphatic: Primary: m/z 31 > m/z 45 ≈ m/z 59 m/z 31, 45, 59, … Secondary, tertiary: local maxima due to [M-33]+ α-cleavage: R . R

Rearrangements

Aromatic: [M-28]+· (CO) [M-29]+ (CHO) Aliphatic: [M-18]+· [M-46]+· Unsaturated

C H

+.

OH

-R

R

C H

+.

OH

CO and CHO elimination also from fragments. H2O elimination ([M-18]+·) only with alkyl substituent in ortho position Elimination of H2O from M+· followed by alkene elimination; elimination of H2O from products of α-cleavage Vinylcarbinols: spectra similar to those of ketones Allyl alcohols: specific aldehyde elimination: R 1

+.

OH

+.

- R 2C H O R2

R1



MS

Assignment

3.7 Oxygen Compounds Range Aromatic:

57

Comments Ortho effect with appropriate substituents: O Y

H Z

+.

O Y

+.

+

H Z

with Y–Z as –CO–OR, C–hal, –O–R, and similar

UV Aliphatic Aromatic

≈200–210 nm (log ε ≈3.8) ≈270 nm (log ε ≈2.4)

No absorption above 200 nm In alkaline solution, shift to longer wavelength and increase in intensity due to deprotonation

3.7.2 Ethers Assignment

Range 50–90 ppm al C–(C–O) 10–60 ppm al C–(C–C–O) 10–60 ppm O–C–O 85–110 ppm (C)=C–O 115–165 ppm C=(C–O) 70–120 ppm ar C–O 140–155 ppm ar C–(C–O) 100–130 ppm

Comments Oxiranes: outside the normal range Hardly any shift with respect to C–(C–CH3) Shift with respect to C–(C–C–CH3) ≈-5 ppm

CH3–O CH2–O O–CH2–O CH–O CH(O)3 H–C(O)=C H–C=C–O ar CH–C–O

Singlet

13C al C–O

1H

IR

3.3–4.0 ppm 3.4–4.2 ppm 4.5–6.0 ppm 3.5–4.3 ppm ≈ 5–6 ppm 5.7–7.5 ppm 3.5–5.0 ppm 6.6–7.6 ppm

H–C(–O) st

2880–2815 cm-1

H–CH(O)2 st

2880–2750 cm-1

C–O–C st

1310–1000 cm-1

Shift with respect to (C)=C–C ≈+15 ppm Shift with respect to C=(C–C) ≈-30 ppm Shift with respect to ar C–H ≈+25 ppm Shift with respect to ar C–(C–H): ortho ≈-15 ppm meta ≈+1 ppm para ≈-8 ppm

Shift with respect to H–C(H)=C ≈+1.2 ppm Shift with respect to H–C(=C–H) ≈-1 ppm For CH3–O and CH2–O; similar range for corresponding amines Two bands Strong, sometimes two bands

58

MS

3 Combination Tables

Assignment Molecular ion Fragments

Range

Comments Aliphatic: weak, tendency to protonate Aromatic: strong Aliphatic: Base peak of aliphatic ethers generally due to m/z 31, 45, 59, … fragmentation of the bond next to the ether . -R + +. [M-33]+ bond: R C O R C O R or due to heterolytic cleavage of the C–O bond (especially for polyethers): 1

R1

Alkyl aryl ethers Diaryl ethers

1

2

O

R2

+ . - R 1 –O

2

.

R Preferential loss of the alkyl chain Preferential loss of CO (Δm 28) from M+· and/or [M-H]+ as well as: ar ar O Elimination of water or alcohol 2

+

2

1

Rearrangements

Aliphatic: [M-18]+· [M-46]+· Aromatic

Ethyl and higher alkyl ethers: alkene elimination to the phenol: +.

H O

UV

Aliphatic Aromatic



R

+. - R C H =C H 2

OH

No absorption above 200 nm Shift to higher wavelength and increase in intensity due to the ether group



3.8 Nitrogen Compounds

59

3.8 Nitrogen Compounds 3.8.1 Amines

13C

Assignment Range al C–N 25–70 ppm al C–(C–N) 10–60 ppm al C–(C–C–N) 10–60 ppm (C)=C–N C=(C–N) ar C–N ar C–(C–N)

1H

IR

120–170 ppm 75–125 ppm 130–150 ppm 100–130 ppm

HN–C al HN–C ar HN+–C al or ar CH3–N CH2–N CH–N CH–N+ ar CH–C–N

0.5–4.0 ppm 2.5–5.0 ppm 6.0–9.0 ppm 2.3–3.1 ppm 2.5–3.5 ppm 3.0–3.7 ppm 3.2–4.0 ppm 6.0–7.5 ppm

ar CH–C–N+

7.5–8.0 ppm

N–H st

3500–3200 cm-1

N+–H st

3000–2000 cm-1

N–H δ N+–H

δ

H–C(–N) st

1650–1550 cm-1 1600–1460 2850–2750

cm-1 cm-1

Comments Shift with respect to C–H ≈+20 ppm Shift with respect to C–(C–CH3) ≈+2 ppm Shift with respect to C–(C–C–CH3) ≈-2 ppm Shift with respect to (C)=C–C ≈+20 ppm Shift with respect to C=(C–C) ≈-25 ppm Shift with respect to C–H ≈+20 ppm Shift with respect to C–(C–H): ortho ≈-15 ppm meta ≈+1 ppm para ≈-10 ppm Often broad Singlet

Shift with respect to CH–(C–H): ortho ≈-0.8 ppm meta ≈-0.2 ppm para ≈-0.7 ppm Shift with respect to CH–(C–H): ortho ≈+0.7 ppm meta ≈+0.4 ppm para ≈+0.3 ppm

Position and shape depend on the degree of association. Often different bands for H-bonded and free NH. For NH2, always at least two bands Broad, similar to COOH but more structured Weak or absent Often weak

For CH3–N and CH2–N in amines; similar range for corresponding ethers

60

MS

3 Combination Tables

Assignment Molecular ion

Fragments

Range

Comments Odd nominal mass number for odd number of N atoms Aliphatic: weak, tendency to protonate, [M+H]+ is often important Aromatic: strong, no tendency to protonate Aliphatic: Base peak of aliphatic amines generally due m/z 30, 44, 58, … to fragmentation of the bond next to the amine bond: R1

N

CH 2

R3

+.

- R3

.

R1

CH 2

NH

CH 2

R R Elimination of alkenes following amine R cleavage: + + 2

2

Rearrangements

+

N

1

N

CH 2

R1

R No absorption above 200 nm In acidic solutions, shift to lower wavelength and decrease in intensity 2

UV Aliphatic Aromatic 3.8.2 Nitro Compounds

13C

Assignment Range al C–NO2 55–110 ppm al C–(C–NO2) 10–50 ppm al C–(C–CNO2) 10–60 ppm ar C–NO2 130–150 ppm ar C–(C–NO2) 120–140 ppm

1H

al CH–NO2 ar CH–C–NO2

IR

NO2 st as NO2 st sy Molecular ion

1660–1490 cm-1 1390–1260 cm-1

Fragments Rearrangements Aliphatic Aromatic

[M-16]+·, [M-46]+ m/z 30, [M-17]+, [M-30]+, [M-47]+· ≈275 nm (log ε <2) ≈350 nm (log ε ≈2)

MS

UV

4.2–4.6 ppm 7.5–8.5 ppm

Comments Shift with respect to C–H ≈+50 ppm Shift with respect to C–(C–C) ≈-6 ppm Shift with respect to C–(C–C–C) ≈-2 ppm Shift with respect to C–H ≈+20 ppm Shift with respect to C–(C–H): ortho ≈-5 ppm, meta ≈+1 ppm, para ≈+6 ppm Shift with respect to CH–(C–H): ortho ≈+1 ppm, meta ≈+0.3 ppm, para ≈+0.4 ppm Strong to very strong Strong to very strong Odd nominal mass number for odd number of N atoms Aliphatic: weak or absent Aromatic: strong



3.9 Thiols and Sulfides

61

3.9 Thiols and Sulfides

13C 1H

Assignment al C–S ar C–S HS–C al HS–C ar al CH–S ar CH–S

IR S–H st MS Molecular ion Fragments Rearrangements

UV

Aliphatic

Range 5–60 ppm 120–140 ppm 1.0–2.0 ppm 2.0–4.0 ppm 2.0–3.2 ppm 7.0–7.5 ppm

2600–2540 cm-1

Comments No significant shift with respect to C–C Vicinal coupling constant, J, 5–9 Hz

Frequently weak

peak at [M+2]+· ≈4.5% Aliphatic: intensity higher than for corresponding alcohols and ethers m/z 47, 61, 75, … Sulfide cleavage: m/z 34, 35, 48 [M-33]+ [M-34]+·

34S-isotope



R1

S

CH 2

R2

+.

- R2

.

R1

+ S

Alkene elimination after sulfide cleavage

<225 nm (log ε 3–4) 220–250 nm (log ε 2–3)

CH 2

62

3 Combination Tables

3.10 Carbonyl Compounds 3.10.1 Aldehydes

13C

1H

IR

Assignment Range CHO 190–205 ppm al C–(CHO) 30–70 ppm al C–(C–CHO) 5–50 ppm (C)=C–(CHO) 110–160 ppm C=(C–CHO) 110–160 ppm ar C–(CHO) 120–150 ppm H–(C=O) 9.0–10.5 ppm al CH–(CHO) 2.0–2.5 ppm (CH)=CH(CHO) 5.5–7.0 ppm CH=(CH–CHO) 5.5–7.0 ppm ar CH–(C–CHO) 7.2–8.0 ppm

comb C=O

MS Molecular ion

Comments Coupling constant 1JCH 172 Hz Coupling constant |2JCH| 20–50 Hz Shift with respect to C–(C–CH3) ≈-10 ppm

3J 3J

0–3 Hz HH ≈8 Hz HH

Shift with respect to CH–(C–H): ortho ≈+0.6 ppm meta ≈+0.2 ppm para ≈+0.3 ppm

2900–2700 cm-1 Two weak bands 1765–1645 cm-1 Aliphatic: ≈1730 cm-1 Conjugated: ≈1690 cm-1

Fragments

[M-1]+

Rearrangements

[M-29]+ m/z 44 [M-44]+·

Aliphatic: moderate Aromatic: strong For aliphatic aldehydes, only significant up to C7 Aliphatic aldehydes R

H

+. O

+. - RCH =CH 2

H

UV

n   π*



270–310 nm (log ε ≈1) Saturated aldehydes ≥207 nm (log ε ≈4) α,β-Unsaturated aldehydes ≥250 nm (log ε >3) Aromatic aldehydes

OH H



3.10 Carbonyl Compounds

63

3.10.2 Ketones

13C

1H

IR

Assignment C=O al C–(C=O) al C–(C–C=O) (C)=C–(C=O) C=(C–C=O) ar C–(C=O) al CH–(C=O)

Range 195–220 ppm 25–70 ppm 5–50 ppm 105–160 ppm 105–160 ppm 120–150 ppm

Comments Shift with respect to C–(C–CH3) ≈-6 ppm

2.0–3.6 ppm

CH=CH–(C=O) ar CH–(C–C=O)

al CH–C(=O)–C al 2.0–2.6 ppm al CH–C(=O)–C ar 2.5–3.6 ppm

5.5–7.0 ppm 7.2–8.0 ppm

1775–1650 cm-1

C=O st

MS Molecular ion

Shift with respect to CH–(C–H): ortho ≈+0.6 ppm meta ≈+0.1 ppm para ≈+0.2 ppm Aliphatic: ≈1715 cm-1 Cyclic: ring size ≥6: ≈1715 cm-1 ring size <6: ≥1750 cm-1 Conjugated: ≈1690–1665 cm-1 Aliphatic: moderate Aromatic: strong Ketone cleavages:

Fragments

+.

O R1

Rearrangements

R1

UV

π   π* n   π*

R 1 CO + , R 1 + , R 2 CO + , R 2 +

Aliphatic ketones

m/z 44 [M-44]+·



R2

H

+. O

- R 1 CH=CH 2 R2

<200 nm (log ε 3–4) 250–300 nm (log ε 1–2) ≥215 nm (log ε ≈4) ≥245 nm (log ε >3)

+. OH

+. O

R2

Saturated ketones Saturated ketones α,β-Unsaturated ketones Aromatic ketones

R2

64

3 Combination Tables

3.10.3 Carboxylic Acids Assignment

13C COOH

1H

al C–(COOH) al C–(C–COOH) (C)=C–(COOH) C=(C–COOH) ar C–(COOH) COOH

Range 170–185 ppm 25–70 ppm 5–50 ppm 105–160 ppm 105–160 ppm 120–150 ppm

10.0–13.0 ppm

al CH–(COOH) CH=CH–(COOH) ar CH–(C–COOH)

IR

COO–H st C=O st

COO–H δ oop

MS Molecular ion Fragments Rearrangements

2.0–2.6 ppm 5.2–7.5 ppm 7.2–8.0 ppm

Comments For COO–, shift with respect to COOH: 0 to +8 ppm Shift with respect to C–(C–CH3) ≈-6 ppm

Position and shape strongly depend on experimental conditions Shift with respect to CH–(C–H): ortho ≈+0.8 ppm, meta ≈+0.2 ppm, para ≈+0.3 ppm

3550–2500 cm-1 Broad

1800–1650 cm-1 Aliphatic: ≈1715 cm-1 Conjugated: ≈1695 cm-1 For COO–, two bands: 1580 and 1420 cm-1 -1 ≈920 cm For dimers

[M-17]+ [M-45]+ m/z 60, 61 [M-18]+·

Aliphatic: moderate, strong for long chains, tendency to protonate Aromatic: strong Strong for aromatic acids Aliphatic acids Aromatic acids Ortho effect with aromatic acids: +.

O OH

UV

n   π*



X

R

- ROH

C X

<220 nm (log ε 1–2) Saturated acids ≥193 nm (log ε ≈4) α,β-Unsaturated acids ≥230 nm (log ε >3) Aromatic acids

O

+.

for X : CH 2 , O, N, S, etc.



3.10 Carbonyl Compounds

65

3.10.4 Esters and Lactones Assignment

Range 165–180 ppm al C–(COOR) 20–70 ppm al C–(OCOR) 50–100 ppm (C)=C–(COOR) 105–160 ppm C=(C–COOR) 105–160 ppm (C)=C–(OCOR) 100–150 ppm C=(C–OCOR) 80–130 ppm ar C–(COOR) 120–150 ppm ar C–(OCOR) 130–160 ppm ar C=(C–OCOR) 105–130 ppm

13C COOR

1H

IR

al CH–COOR

2.0–2.5 ppm

al CH–OCOR

3.5–5.3 ppm

CH=CH–COOR

5.5–8.0 ppm

CH=CH–OCOR

6.0–8.0 ppm

ar CH–C–COOR

7.0–8.0 ppm

ar CH–C–OCOR

6.8–7.5 ppm

C=O st

C–O st

Comments Shift with respect to COOH -5 to -10 ppm Shift with respect to C–(OH) +2 to +10 ppm

CH3COOR ≈2.0 ppm CH2COOR ≈2.3 ppm CHCOOR ≈2.5 ppm CH3OCOR ≈3.5–3.9 ppm CH2COOR ≈4.0–4.5 ppm CHCOOR ≈4.8–5.3 ppm Shift with respect to CH=CH–H: gem ≈+0.8 ppm, cis ≈+1.1 ppm trans ≈+0.5 ppm Shift with respect to CH=CH–H: gem ≈+2.1 ppm, cis ≈-0.4 ppm trans ≈-0.6 ppm Shift with respect to CH–(C–H): ortho ≈+0.7 ppm, meta ≈+0.1 ppm, para ≈+0.2 ppm Shift with respect to CH–(C–H): ortho ≈-0.2 ppm, meta ≈0 ppm, para ≈-0.1 ppm

1745–1730 cm-1 Strong; range for aliphatic esters Higher wavenumbers for hal–C–COOR, COO–C=C, COO–C ar, and for small ring lactones Lower wavenumbers for C=C–COOR and ar C–COOR 1330–1050 cm-1 Mostly two bands, at least one of them strong For COO–, two bands: 1580 and 1420 cm-1

66

MS

3 Combination Tables

Assignment Molecular ion

Range

Fragments

[M - RO]+ [M - ROCO]+

Rearrangements R1

Comments Aliphatic esters: weak, tendency to protonate Aliphatic lactones: medium to weak, tendency to protonate Aromatic esters and lactones: strong

Esters Esters Lactones: loss of α-substituents (attached to ether carbon), decarbonylation, for aromatic lactones also double decarbonylation Alkene elimination from the alcohol moiety: H

+.

O



+.

O R 1 CH=CH 2

R2

+ R 2 COOH

Elimination of the alcohol side chain with double H transfer (for alcohols with Cn>2): R1

COOR 2

+

+.

OH

R1

OH Alcohol elimination from ortho-substituted aromatic esters:

+.

O

- ROH

OR

UV

n   π*

[M-18]+·

X

H

X

Lactones

<220 nm (log ε 1–2) ≥193 nm (log ε ≈4) ≥230 nm (log ε >3)

C

O

Aliphatic esters α,β-Unsaturated esters Aromatic esters

+.

for X : CH 2 , O, N, S, etc.



3.10 Carbonyl Compounds

67

3.10.5 Amides and Lactams Assignment

Range 165–180 ppm al C–(CONR2) 20–70 ppm al C–(C–CONR2) 5–50 ppm al C–(NCOR) 25–80 ppm C=C–(CONR2) 105–160 ppm ar C–(CONR2) 120–150 ppm ar C–(NCOR) 110–150 ppm

13C CONR2

1H

CONH

5–10 ppm

al CH–CONR2 al CH–NCOR

2.0–2.5 ppm 2.7–4.8 ppm

CH=CH–CONR2

5.2–7.5 ppm

C=CH–NCOR CH=C–NCOR

6.0–8.0 ppm 4.5–6.0 ppm

ar CH–C(CONR2) 7.5–8.5 ppm ar CH–C(NCOR)

IR

N–H st

C=O st (amide I) N–H δ and N–C=O st sy (amide II)

6.8–7.5 ppm

Comments Shift with respect to C–(C–CH3) ≈-6 ppm Shift with respect to C–(NH) ≈-1 to -2 ppm

Frequently broad to very broad; splitting due to H–N–C–H coupling often recognizable only in the CH signal CH3NCOR ≈2.7–3.0 ppm CH2NCOR ≈3.1–3.5 ppm CHNCOR ≈3.8–4.8 ppm Shift with respect to CH=CH–(H): gem ≈+1.4 ppm, cis ≈+1.0 ppm trans ≈+0.5 ppm Shift with respect to CH=CH–(H): gem ≈+2.1 ppm, cis ≈-0.6 ppm trans ≈-0.7 ppm Shift with respect to CH–C–(H): ortho ≈+0.6 ppm, meta ≈+0.1 ppm, para ≈+0.2 ppm Shift with respect to CH–C–(H): ortho ≈0 ppm, meta ≈0 ppm, para ≈-0.2 ppm

3500–3100 cm-1 Position and shape depend on the extent of association, often different bands for H-bonded and free NH, always at least two bands for NH2 1700–1650 cm-1 Strong; range for amides as well as for δand larger lactams, higher wavenumbers for β- and γ-lactams 1630–1510 cm-1 Often strong, missing in the case of tertiary amides and lactams

68

MS

3 Combination Tables

Assignment Molecular ion

Range

Fragments

Rearrangements

UV

n   π*

[M-18]+·

<220 nm (log ε 1–2)

Comments Aliphatic amides: moderate, tendency to protonate Aromatic amides: strong

Amides: cleavage on both sides of the carbonyl group followed by loss of CO; large number of fragments of even mass Lactams: loss of α-substituent, loss of CO Amides: elimination of the amine moiety, elimination of alkene from the amine or acid moiety in analogy to esters Lactams

Aliphatic amides and lactams

4

13C

NMR Spectroscopy C

4.1 Alkanes

C

C

C

C

4.1.1 Chemical Shifts 13C

Chemical Shifts (δ in ppm) 7.3

-2.3

CH4

15.9

CH3

15.4

CH3

22.8

24.1 25.0

13.0

32.0 11.8

34.8 14.2

22.3 30.1

24.8 31.3

N

Hal

27.7

O N

32.2

14.2

23.1

29.5

23.1

32.4 14.1

32.1 29.5

14.1

S

22.8

C

X

P Si Natural Products Solvents

70 13C

C

Chemical Shifts of Methyl Groups (δ in ppm) Substituent R

C

C

C

C

N

Hal O N S C

4 13C NMR

X

P Si Natural Products Solvents

C

–H –CH3 –CH2CH3 –CH(CH3)2 –C(CH3)3 –(CH2)6CH3 –CH2–phenyl –CH2F –CH2Cl –CH2Br –CH2I –CHCl2 –CHBr2 –CCl3 –CBr3 –CH2OH –CH2OCH3 –CH2OCH2CH3 –CH2OCH=CH2 –CH2O–phenyl –CH2OCOCH3 –CH2NH2 –CH2NHCH3 –CH2N(CH3)2 –CH2NO2 –CH2SH –CH2S(O)2CH3 –CH2S(O)2OH –CH2CHO –CH2COCH3 –CH2COOH –cyclopentyl –cyclohexyl –CH=CH2 –C ––– CH –phenyl –1-naphthyl –2-naphthyl

δCH3–R -2.3 7.3 15.4 24.1 31.3 14.1 15.7 15.8 18.7 19.1 20.4 31.6 31.8 46.3 49.4 18.2 14.7 15.4 14.6 14.9 14.4 19.0 14.3 12.8 12.3 19.7 6.7 8.0 5.2 7.0 9.6 20.5 23.1 18.7 3.7 21.4 19.1 21.5

Substituent R

C

X O

N

–2-pyridyl –3-pyridyl –4-pyridyl –2-furyl –2-thienyl –2-pyrrolyl –2-indolyl –3-indolyl –4-indolyl –5-indolyl –6-indolyl –7-indolyl –F –Cl –Br –I –OH –OCH3 –OCH2CH3 –OCH(CH3)2 –OC(CH3)3 –OCH2CH=CH2 –O–cyclohexyl –OCH=CH2 –O–phenyl –OCOCH3 –OCO–cyclohexyl –OCOCH=CH2 –OCO–phenyl –OCOOCH3 –OS(O)2–4-tolyl –OS(O)2OCH3 –OP(OCH3)2 –NH2 –NH3+ –NHCH3 –NH–cyclohexyl –NH–phenyl

δCH3–R 24.2 18.0 20.6 13.7 14.7 11.8 13.4 9.8 21.6 21.5 21.7 16.6 71.6 25.6 9.6 -24.0 50.2 60.9 57.6 54.9 49.4 57.4 55.1 52.5 54.8 51.5 51.2 51.5 51.8 54.9 56.3 59.1 48.8 28.3 26.5 38.2 33.5 30.2



4.1 Alkanes Substituent R

N

–N(CH3)2 –N-pyrrolidinyl –N-piperidinyl –N(CH3)phenyl –N-pyrrolyl –N-imidazolyl –N-pyrazolyl –N-indolyl –NHCOCH3 –N(CH3)CHO –N(CH3)COCH3

S

O || C

–N(CH3)P[N(CH3)2]2 –NO2 –C ––– N –NC –NCS –SH –SCH3 –S–n-C8H17 –S–phenyl –SSCH3 –S(O)CH3 –S(O)2CH3 –S(O)2CH2CH3 –S(O)2Cl –S(O)2OH –S(O)2ONa –CHO –COCH3 –COCH2CH3 –COCCl3

δCH3–R 47.5 42.7 47.7 39.9 35.9 32.2 38.4 32.1 26.1 31.5, 36.5 35.0, 38.0 33.9 61.2 1.7 26.8 29.1 6.5 19.3 15.5 15.6 22.0 40.1 42.6 39.3 52.6 39.6 41.1 31.2 30.7 27.5 21.1

Substituent R

O || C

M

–COCH=CH2 –CO–cyclohexyl –CO–phenyl –COOH –COO– –COOCH3 –COOCOCH3 –CONH2 –CON(CH3)2 –COSH –COSCH3 –COCOCH3 –COCl –COBr –COSi(CH3)3 –Li –B(CH3)2 –B–(CH3)3 Li+ –Si(CH3)2CH=CH2 –SiCl3 –Ge(CH3)3 –Sn(CH3)3 –Pb(CH3)3 –P(CH3)(n-C4H9) –P+(CH3)3 I– –As(CH3)2 –As+(CH3)3 I– –In(CH3)2

71

δCH3–R 25.7 27.6 25.7 21.7 24.4 20.6 21.8 22.3 21.5 32.6 30.2 23.2 33.6 39.1 35.7 -16.6 14.8 6.2 -2.0 9.8 -3.6 -9.3 -4.2 14.4 10.7 11.2 8.4 -6.3

C C

C

C

C

N

Hal O N S C

X

P Si Natural Products Solvents

72 13C

Chemical Shifts of Monosubstituted Alkanes (δ in ppm) Substituent

C C

C

C

C

C

X O

N

Hal

N

O N S C

4 13C NMR

S X

P Si Natural Products Solvents

O || C

–H –CH=CH2 –C ––– CH –phenyl –F –Cl –Br –I –OH –OCH3 –OCH2CH3 –OCH(CH3)2 –OC(CH3)3 –O–phenyl –OCOCH3 –OCO–phenyl –OS(O)2–4-tolyl –NH2 –NHCH3 –N(CH3)2 –NHCOCH3 –NO2 –C ––– N –NC –SH –SCH3 –SSCH3 –S(O)CH3 –S(O)2CH3 –S(O)2Cl –S(O)2OH –CHO –COCH3 –CO–phenyl –COOH –COOCH3 –CONH2 –COCl

Methyl –CH3 -2.3 18.7 3.7 21.4 71.6 25.6 9.6 -24.0 50.2 60.9 57.6 54.9 49.4 54.8 51.5 51.8 56.3 28.3 38.2 47.6 26.1 61.2 1.7 26.8 6.5 19.3 22.0 40.1 42.6 52.6 39.6 31.3 30.7 25.7 21.7 20.6 22.3 33.6

Ethyl –CH2 –CH3 7.3 27.4 12.3 29.1 80.1 39.9 27.6 -1.6 57.8 67.7 66.0

7.3 13.4 13.8 15.8 15.8 18.9 19.4 20.6 18.2 14.7 15.4

–CH2

56.8 63.2 60.4 60.8 66.9 36.9 45.9 53.6 34.4 70.8 10.8 36.4 19.1

16.4 14.9 14.4 14.4 14.7 19.0 14.3 12.8 14.6 12.3 10.6 15.3 19.7

31.8

14.7

48.2 60.2 46.7 36.7 35.2 31.7 28.5 27.2 29.0 41.0

6.7 9.1 8.0 5.2 7.0 8.3 9.6 9.2 9.7 9.3

15.4 36.2 20.6 38.3 85.2 46.8 35.6 9.1 64.2 74.5 72.5

1-Propyl –CH2 –CH3 15.9 22.4 22.2 24.8 23.6 26.3 26.4 27.0 25.9 23.2 23.2

15.4 13.6 13.4 13.8 9.2 11.6 13.0 15.3 10.3 10.5 10.7

69.4 66.2 66.4 72.2 44.6 54.0 61.8 40.7 77.4 19.3 43.4 26.4

22.8 22.4 22.2 22.3 27.4 23.2 20.6 22.5 21.2 19.0 22.9 27.6

10.6 10.5 10.5 10.0 11.5 12.5 11.9 11.1 10.8 13.3 11.0 12.6

56.3 67.1 53.7 45.7 45.2 40.4 36.2 35.6

16.3 18.4 18.8 15.7 17.5 17.7 18.7 18.9

13.0 12.1 13.7 13.3 13.5 13.8 13.7 13.8

48.9

18.8

13.0



4.1 Alkanes

13C

C X O

N

S

O || C

73

Chemical Shifts of Monosubstituted Alkanes (δ in ppm, contd.)

–H –CH=CH2 –C ––– CH –phenyl –F –Cl –Br –I –OH –OCH3 –OCH2CH3 –OCH(CH3)2 –OC(CH3)3 –O–phenyl –OCOCH3 –OCO–phenyl –NH2 –NHCH3 –N(CH3)2 –NHCOCH3 –NO2 –C ––– N –NC –SH –SCH2CH3 –S(O)2CH3 –S(O)2Cl –S(O)2OH –CHO –COCH3 –CO–phenyl –COOH –COOCH3 –CONH2 –COCl

2-Propyl –CH –CH3 15.9 15.4 32.3 22.1 20.3 22.8 34.3 24.0 87.3 22.6 53.7 27.3 44.8 28.5 20.9 31.2 64.0 25.3 72.6 21.4 68.5 63.5 69.3 67.5 68.2 43.0 50.5 55.5 40.5 78.8 19.8 45.5 29.9 34.4 53.5 67.6 52.9 41.1 41.6 35.2 34.1 34.1 34.9 46.5

23.0 25.2 22.0 21.9 21.9 26.5 22.5 18.7 22.3 20.8 19.9 23.4 27.4 23.4 15.2 17.1 16.8 15.5 18.2 19.1 18.8 19.1 19.5 19.0

tert-Butyl –C –CH3 25.0 24.1 33.8 29.4 27.4 31.1 34.6 31.4 93.5 28.3 66.7 34.6 62.1 36.4 43.0 40.4 68.9 31.2 72.7 27.0 72.6 27.7 73.0 28.5 76.3 33.8 79.9 80.7 47.2 50.4 53.6 49.9 85.2 28.1 54.0 41.1

28.1 28.2 32.9 28.2 25.4 28.6 26.9 28.5 30.7 35.0

57.6 74.2 55.9 42.4 44.3 43.5 38.7 38.7 38.6 49.4

22.7 24.5 25.0 23.4 26.5 27.9 27.1 27.3 27.6 27.1

C C

C

C

C

N

Hal O N S C

X

P Si Natural Products Solvents

4 13C NMR

74 13C

Chemical Shifts of 1-Substituted n-Octanes (δ in ppm) Substituent

C C

C

C

C

C X O

N

N

Hal O

S

N

O || C

S C

X

P Si Natural Products Solvents

Si

–H –CH=CH2 –phenyl –F –Cl –Br –I –OH –O–n-C8H17 –O–phenyl –OCO–n-propyl –OCO–phenyl –ONO –NH2 –N(CH3)2 –N+(CH3)3 Cl– –NO2 –C ––– N –SH –SCH3 –S(O)–n-C8H17 –CHO –COCH3 –CO–phenyl –COOH –COOCH3 –CONH2 –COCl –Si(OCH3)3

* Assignment uncertain

1 2 3 4 5 6 7 8 –CH2 –CH2 –CH2 –CH2 –CH2 –CH2 –CH2 –CH3 14.1 34.5 36.2 84.2 45.1 33.8 6.9 63.1 71.1 68.0 64.4 65.1 68.3 42.4 60.1 66.6 75.8 17.2 24.7 34.5 52.6 44.0 43.7 38.6 34.2 34.2 35.5 47.2 9.2

22.8 ~29.6 31.7 30.6 32.8 33.0 33.7 32.9 30.0 26.2 28.8 28.8 29.2 34.1 29.5* 26.2 26.2 25.5 34.2 29.0 ≈29.1 22.2 24.1 24.4 24.8 25.1 25.4 25.1 22.7

32.1 29.5 29.5 ~29.6 ~29.6 ~29.6 ~29.6 ~29.6 ~29.6 25.3 29.3 29.3 27.0 29.0 29.2 28.3 28.8 29.2 30.6 28.6 29.1 25.9 29.5 29.4 26.3 29.6 29.4 29.3 29.4 29.4 26.1 29.3 29.3 26.1 29.3 29.3 26.0 29.3 29.3 27.0 29.6 29.4 ≈27.9* ≈27.7* 29.7* 23.2 29.1* 29.0* 27.9 ≈29.6 ≈29.6 ≈29.9 ≈29.9 ≈29.9 28.5 29.2 29.1 29.4 29.4 29.4 ≈29.1 ≈29.1 ≈29.1 ≈29.3 ≈29.3 ≈29.3 ≈29.5 ≈29.5 ≈29.5 29.5 29.5 29.5 ≈29.3 ≈29.3 ≈29.3 29.3 29.3 29.3 29.1 29.1 29.1 28.5 29.1 29.1 33.2 29.3 29.3

32.1 32.2 32.1 31.9 31.9 31.8 31.8 31.9 32.0 31.9 31.9 31.9 31.9 31.9 32.0 31.6 31.4 31.8 31.9 31.9 31.8 31.9 32.0 31.9 31.9 31.9 31.6 31.8 32.0

22.8 23.0 22.8 22.7 22.8 22.7 22.6 22.8 22.8 22.7 22.8 22.7 22.7 22.7 22.8 22.5 22.6 22.7 22.7 22.8 22.7 22.7 22.8 22.7 22.7 22.8 22.3 22.7 22.7

14.1 13.9 14.1 14.1 14.1 14.1 14.1 14.1 14.1 14.1 14.1 14.1 14.0 14.1 14.4 14.0 14.0 14.0 14.1 14.1 14.1 14.1 14.1 14.0 14.1 14.1 14.0 14.1 14.1



4.1 Alkanes

75

Estimation of 13C Chemical Shifts of Aliphatic Compounds (δ in ppm) The chemical shifts of sp3-hybridized carbon atoms can be estimated with the help of an additivity rule using the shift value of methane (-2.3 ppm) and increments (Z) C for substituents in α, β, γ, and δ position (see next pages). Some substituents occupy two positions. Thus, the quaternary carbon atom c in the example given below is in δ position relative to the carbon atom a since the sp3-hybridized oxygen of the C C β-COO group occupies the γ position. This simple linear model needs corrections in case of strong branching of the observed C atom and/or its neighbors (steric corrections, S). Substituents for which such corrections are necessary are those with C C varying branching, i.e., a varying number of directly bonded H atoms. They are marked with an asterisk (*) in the Table of Increments (next page). Further correction terms are needed if γ substituents are in a sterically fixed position (conformational corrections, K). The chemical shifts estimated with this additivity rule, in general, differ by less than ca. 4 ppm from the experimental values. Larger discrepancies may be expected for highly branched systems (particularly for quaternary carbon atoms). For carbon atoms bearing several halogen, oxygen, and/or other strongly deshielding substituents, additional correction terms are needed [1]. Without such corrections, deviations can be so large as to render the rule useless. N Example: Estimation of chemical shifts for N-(tert-butoxycarbonyl)alanine

c O

c

OH

N a H

a

Hal

b

O

d

O

O

base value 1 α-C 1 α-COOH 1 α-NH 1 β-COO 1 δ-C 1 S(tert,2) estimated exp

-2.3 9.1 20.1 28.3 2.0 0.3 -3.7 53.8 49.0

b

base value 3 α-C 1 α-OCO 1 γ-NH 1 δ-C 3 S(quat,1) estimated exp

-2.3 27.3 56.5 -5.1 0.3 -4.5 72.2 78.1

d

base value 1 α-C 1 β-COOH 1 β-NH 1 γ-COO 1 S(prim,3) estimated exp

-2.3 9.1 2.0 11.3 -2.8 -1.1 16.2 17.3

base value 1 α-C 2 β-C 1 β-OCO 1 δ-NH 1 S(prim,4) estimated exp

-2.3 9.1 18.8 6.5 0.0 -3.4 28.7 28.1

N S C

X

P Si Natural Products Solvents

76

4 13C NMR

Estimation of 13C Chemical Shifts of Aliphatic Compounds (δ in ppm) δ = -2.3 + ∑ Zi + ∑ Sj + ∑ Kk i

C

Substituent

C

C

C

C

C X O

N

Hal

N

O

S

N S C

X

P Si Natural Products Solvents

O || C

–H –C* –C*=C –C ––– C– –phenyl –F –Cl –Br –I –O–* –OCO– –ONO –N* –N+,* –NH3+ –NO2 –C ––– N –NC –S*– –SCO– –S*(O)– –S*(O)2– –S(O)2Cl –SCN –CHO –CO– –COOH –COO– –COO– –CO–N –COCl –C=NOH syn –C=NOH anti –CS–N –Sn

j

k

Increment Zi for substituents in position α β γ 0.0 0.0 0.0 9.1 9.4 -2.5 19.5 6.9 -2.1 4.4 5.6 -3.4 22.1 9.3 -2.6 70.1 7.8 -6.8 31.0 10.0 -5.1 18.9 11.0 -3.8 –7.2 10.9 -1.5 49.0 10.1 -6.2 56.5 6.5 -6.0 54.3 6.1 -6.5 28.3 11.3 -5.1 30.7 5.4 -7.2 26.0 7.5 -4.6 61.6 3.1 -4.6 3.1 2.4 -3.3 31.5 7.6 -3.0 10.6 11.4 -3.6 17.0 6.5 -3.1 31.1 7.0 -3.5 30.3 7.0 -3.7 54.5 3.4 -3.0 23.0 9.7 -3.0 29.9 -0.6 -2.7 22.5 3.0 -3.0 20.1 2.0 -2.8 24.5 3.5 -2.5 22.6 2.0 -2.8 22.0 2.6 -3.2 33.1 2.3 -3.6 11.7 0.6 -1.8 16.1 4.3 -1.5 33.1 7.7 -2.5 -5.2 4.0 -0.3

δ 0.0 0.3 0.4 -0.6 0.3 0.0 -0.5 -0.7 -0.9 0.3 0.0 -0.5 0.0 -1.4 0.0 -1.0 -0.5 0.0 -0.4 0.0 0.5 0.3 0.0 0.0 0.0 0.0 0.0 0.0 0.0 -0.4 0.0 0.0 0.0 0.6 0.0



4.1 Alkanes

77

Steric Corrections, Sj Observed 13C center primary (CH3) secondary (CH2) tertiary (CH) quaternary (C)

a To

S for number of substituents at the α atoma 1 2 3 4 0.0 0.0 -1.1 -3.4 0.0 0.0 -2.5 -6.0 0.0 -3.7 -8.5 -10.0 -1.5 -8.0 -10.0 -12.5

be applied to each of the neighboring atoms that has an unspecified number of nonhydrogen substituents (marked with an asterisk (*) in the Table of Increments, Zi).

C C

C

C

C

Conformational Corrections, Kk, for γ Substituents Conformation synperiplanar (eclipsed)

synclinal (gauche)

anticlinal

CX C

-4.0 X

C

C

antiperiplanar (anti) not fixed

K

X

-1.0

N

Hal O

0.0

N

2.0 X

0.0

S C

X

One can also use the chemical shifts of a reference compound as the base value if its structure is closely related to that assumed for the unknown. The increments cor- P Si responding to the structural elements missing in the reference compound are then added to the base value, while those of structural elements present in the reference Natural but absent in the unknown are subtracted (see example on next page).

Products Solvents

4 13C NMR

78

Example: Estimation of the chemical shifts for the carbon atoms a and b in N-(tertbutoxycarbonyl)alanine using the chemical shifts of valine as base values (a', b'):

C

Target:

C

C

C

N

Hal

c O

N a H

a

b'

OH

base value (a') 1 β-COO 1 δ-C 1 S(tert,2) - 2 β-C - 1 S(tert,3) estimated exp

O

61.9 2.0 0.3 -3.7 -18.8 8.5 50.2 49.0

OH

H2 N a' O

b

base value (b') 1 γ-COO 1 S(prim,3) - 2 α-C - 1 S(tert,3) estimated exp

30.3 -2.8 -1.1 -18.2 8.5 16.6 17.3

4.1.2 Coupling Constants 13C-1H

Coupling Constants

Coupling through one bond (1JCH in Hz)

O

The 13C-1H coupling constant of 125 Hz in methane increases in the presence of electronegative substituents and can be estimated by using the following additivity rule: JCHZ Z Z = 125.0 + ∑ Zi 1 2 3 i

N S C

b

O

d

C

Reference:

X

P Si Natural Products Solvents

Substituent –H –CH3 –C(CH3)3 –CH2Cl –CH2Br –CH2I –CHCl2 –CCl3 –C ––– C –phenyl –F –Cl

Increment Zi 0.0 1.0 -3.0 3.0 3.0 7.0 6.0 9.0 7.0 1.0 24.0 27.0

Substituent –Br –I –OH –O–phenyl –NH2 –NHCH3 –N(CH3)2 –C ––– N –S(O)CH3 –CHO –COCH3 –COOH

Example: Estimation of 13C-1H coupling constant of CHCl3: J = 125.0 + 3 × 27.0 = 206.0 Hz (exp: 209.0 Hz).

Increment Zi 27.0 26.0 18.0 18.0 8.0 7.0 6.0 11.0 13.0 2.0 -1.0 5.5



4.1 Alkanes

79

Coupling through more than one bond (|JCH| in Hz)

The coupling constants can be estimated from the corresponding 1H-1H coupling constants [2]: JCH ≈ 0.62 JHH

Typical values: 2J 1– 6 CH 3J 0–10 CH

13C-1H

Examples: 1H–CH –13CH 4.5 2 3 1H–CH –CH –13CH 5.8 2 2 3

C C

C

The coupling constants for coupling across three bonds depend on the dihedral angle in the same way as the vicinal 1H-1H coupling constants (see ChapC ter 5.1.2): 13 13 13 C C C H

≈ 6

H

≈ 0

C

≈9 H

13C-13C

H 3 C CH 3

H3 C a

O

N

Coupling Constants (|JCC| in Hz) 1J

34.6

b

1J

a

ab 34.6

b a

c

O CH3 2Jab b

2.4

H3 C a

CH3 2Jab 16.1 b

d

H

a

O

OH

b

N

CH3

CH3

2J 4.6 ac 3J 4.6 ad 2J <1 bd

Hal

2J 0.5 ab 2J 4.9 ac

N

O

c

The 13C-13C coupling constants for coupling over three bonds depend on the dihedral angle in the same way as the vicinal 1H-1H (see Chapter 5.1.2) and 13C-1H coupling constants. Maximum values of ca. 4–6 Hz are observed for dihedral angles C of 0o and 180o and minimal values around 0 Hz at 90o. 4.1.3 References

S X

P Si

[1] A. Fürst, E. Pretsch, W. Robien, A comprehensive parameter set for the predic- Natural tion of the 13C NMR chemical shifts of sp3-hybridized carbon atoms in organic Products compounds, Anal. Chim. Acta 1990, 233, 213. [2] J.L. Marshall, Carbon-Carbon and Carbon-Proton NMR couplings, Verlag Chemie International, Deerfield Beach, FL, 1983. Solvents

80

4 13C NMR

4.2 Alkenes 4.2.1 Chemical Shifts

C

13C

C

C

C

C

N

Hal O

The 13C chemical shifts of the carbons of C=C double bonds typically range from ca. 80–160 ppm; a wider range of 40–210 ppm is observed with O and N substituents. In unsaturated acyclic hydrocarbons, they can be predicted with high accuracy (see below). To estimate the 13C chemical shifts in all other substituted alkenes, one can use the substituent effects listed for chemical shifts in vinyl groups. However, since no configuration-dependent parameters are available, the values thus estimated are less accurate than those for unsaturated acyclic hydrocarbons. The 13C chemical shifts of sp3-hybridized carbon atoms in the vicinity of double bonds can be estimated using the additivity rule given in Chapter 4.1.1. The conformational correction factors, K, for γ substituents of cis- vs. trans-disubstituted alkenes differ by 6 ppm because the relative position of these substituents is fixed by the double bond.

Estimation of the 13C Chemical Shifts of sp2-Hybridized Carbon Atoms in Unsaturated Acyclic Hydrocarbons (δ in ppm) C–C–C'=C–C–C–C γ' β' α' α β γ



N

Base value: 123.3

Increments for C substituents:

S C

Chemical Shifts (δ in ppm)

X

P Si Natural Products Solvents

at C atom under consideration (C) α 10.6 β 4.9 γ -1.5

at neighboring C atom (C') α' -7.9 β' -1.8 γ' 1.5

Steric corrections: • • • •

for each pair of cis-α,α'-substituents for a pair of geminal α,α-substituents for a pair of geminal α',α'-substituents if one or more β-substituents are present

-1.1 -4.8 2.5 2.3



4.2 Alkenes

81

Example: Estimation of chemical shifts of cis-4-methyl-2-pentene

C a

a

base value 1 α-C 1 α'-C 2 β'-C cis-α,α' estimated exp

b

123.3 10.6 -7.9 -3.6 -1.1 121.3 121.8

Effect of Substituents on the ppm) 1



R

C

X

13C

base value 1 α-C 2 β-C 1 α'-C cis-α,α' 1 β-substituent estimated exp

123.3 10.6 9.8 -7.9 -1.1 2.3 137.0 138.8

C

C

C

C

Chemical Shifts of Vinyl Compounds (δ in

2

CH CH2

Substituent R Z1 –H 0.0 –CH3 12.9 –CH2CH3 17.2 –CH2CH2CH3 15.7 –CH(CH3)2 22.7 –(CH2)3– 14.6 –C(CH3)3 26.0 –CH2Cl 10.2 –CH2Br 10.9 –CH2I 14.2 –CH2OH 14.2 –CH2OCH2CH3 12.3 –CH=CH2 13.6 –C ––– CH -6.0 –phenyl 12.5 –F 24.9 –Cl 2.8 –Br -8.6 –I -38.1

* Estimated values

b

Z2 0.0 -7.4 -9.8 -8.8 -12.0 -8.9 -14.8 -6.0 -4.5 -4.0 -8.4 -8.8 -7.0 5.9 -11.0 -34.3 -6.1 -0.9 7.0

δCi = 123.3 + Zi

O N

S O || C Si

Substituent R Z1 –OH 25.7 –OCH3 29.4 –OCH2CH3 28.8 –O(CH2)3CH3 28.1 –OCOCH3 18.4 –N(CH3)2 28.0* –N+(CH3)3 19.8 –N-pyrrolidonyl 6.5 –NO2 22.3 –C ––– N -15.1 –NC -3.9 –SCH2CH3 9.0 –S(O)2CH=CH2 14.3 –CHO 15.3 –COCH3 13.8 –COOH 5.0 –COOCH2CH3 6.3 –COCl 8.1 –Si(CH3)3 16.9 –SiCl3 8.7

N

Hal Z2 O -35.3 -38.9 -37.1 N -40.4 -26.7 -32.0* S -10.6 -29.2 -0.9 C X 14.2 -2.7 -12.8 P Si 7.9 14.5 4.7 Natural 9.8 Products 7.0 14.0 6.7 Solvents 16.1

4 13C NMR

82

The values listed on the preceding page can also be used to estimate the 13C chemical shifts of sp2-hybridized carbon atoms in alkenes with more than one substituent (note that the cis/trans configuration is not taken into account):

C C

δCi = 123.3 + ∑ Zi

C

C

C

Example: Estimation of chemical shifts of 1-bromo-1-propene a

a

base value Z1(Br) Z2(CH3)

Hal O

C

NC a C

b N(CH3 )2

C

N(CH3 )2 Ha C

(CH3 )2 N

S

13C

X

P Si Natural Products Solvents

107.3 108.9 (cis) 104.7 (trans)

base value Z2(Br) Z1(CH3) estimated exp

123.3 -0.9 12.9 135.3 129.4 (cis) 132.7 (trans)

The following examples show some larger deviations between measured and estimated (in parentheses) chemical shifts. This is usually to be expected when several substituents are present that strongly interact with the π electrons of the double bond:

NC

N

b

123.3 -8.6 -7.4

estimated exp

N

b

Br CH CH CH3

b NO2

C

H

Ha C

a 39.1 (29.1) b 171.0 (207.7)

H H a C H

a 151.0 (150.4) b 111.4 (113.6)

b N(CH3 )2

C

N(CH3 )2 b OCH3

C

OCH3

a 69.2 (59.3) b 163.0 (179.3) a 54.7 (45.5) b 167.9 (182.1)

Chemical Shifts of cis- and trans-1,2-Disubstituted Alkenes (δ in ppm) Substituent R –CH3 –CH2CH3 –Cl –Br –I –C ––– N –OCH3 –COOH –COOCH3

R

R

R

H

H

H

H

R

123.3 131.2 118.1 116.4 96.5 120.8 130.3 130.4 130.1

124.5 131.3 119.9 109.4 79.4 120.2 135.2 134.2 133.5

13C

4.2 Alkenes

83

Chemical Shifts of Enols (δ in ppm)

The carbon atom bonded to the enolic OH group is strongly deshielded so that its shift is close to that of a carbonyl carbon. The other carbon atom of the double bond is strongly shielded. Enol: O a

b

Ketone:

H

a 22.5 b 190.5 c 99.0

O

c

a c

HO d

13C

b e

O

O b

a

a 28.3 b 32.8 c 46.2 d 191.1 e 103.3

a 28.5 b 201.1 c 56.6

O c

a b

c

O d

e

O

C C

C

C

C

a 28.3 b 31.0 c 54.2 d 203.6 e 57.3

Chemical Shifts of Allenes (δ in ppm) R1 R2

R1 –H –CH3 –CH3 –CH3 –CH2CH3 –C(CH3)3 –CH=CH2 –C ––– CH –phenyl –F –Cl –Br –I –OCH3 –N(CH3)2 –C ––– N –SCH3 –COOH

R2 –H –H –CH3 –H –H –C(CH3)3 –H –H –H –H –H –H –H –H –H –H –H –H

a

b

c

C C C

R3 –H –H –H –CH3 –H –H –H –H –H –H –H –H –H –H –H –H –H –H

N

R3

Hal

H

a 74.8 84.4 93.4 85.4 91.7 119.6 93.9 74.8 94.4 129.8 88.8 72.7 35.3 123.1 113.1 67.4 90.0 88.1

b 213.5 210.4 207.3 207.1 208.9 207.0 211.4 217.7 210.0 200.2 207.9 207.6 208.0 202.0 204.2 218.7 206.1 217.7

c 74.8 74.1 72.1 85.4 75.3 75.8 75.1 77.3 78.8 93.9 84.5 83.8 78.3 90.3 85.5 80.7 81.3 80.0

O N S C

X

P Si Natural Products Solvents

4 13C NMR

84

4.2.2 Coupling Constants 13C-1H

C C

Coupling through one bond

C

C

Coupling Constants (|JCH| in Hz)

C

CH2

1J

CH2

CH



156.4

CH2

C

1J

CH2

CH



167.8

Coupling through two bonds H

H 13

2J

C

H

CH



H

H

-2.4

13

H

Additivity rule for the estimation of

2J

Cl

CH

2J

C

CH



6.9

H

of alkenes: see [2].

Coupling through three bonds

The trans-1H–C=C–13C coupling constant of alkenes is always larger than the corresponding cis coupling constant so that an assignment is possible if both isomers are available: see [3].

N

Hal O

Ha C Hb

N S C

Ha C Hb

13

c

CH3

C H 13

X

P Si

3J 7.6 ac 3J 12.6 bc

c

COOH

C CH3

13C-13C

Ha C Hb a

3J 7.6 ac 3J 14.1 bc

C

c

CH3

C Cl 13

H H3 C

13

3J ac 3J bc

4.1 8.1

c

COOH

C 13

CH3 b

Ha C Hb

3J ab 3J ac

7.7 7.4

13

c

COOH

C H 13

H3 C C H a

3J 7.6 ac 3J 14.1 bc

c

COOH

C 13

CH3 b

3J 6.9 ab 3J 13.2 ac

Coupling Constants (|JCC| in Hz)

CH2

CH2

1J

CC

67.6

CH2

C

1J

CC

98.7

CH2

a

CH2

b

b a

c

CH

CH3 d

c

1J ab 1J bc

1J ab 1J bc

68.8 53.7

70.0 41.9

2J ac 3J ad

<1 9.0

4.2.3 References

Natural Products [1] R.H.A.M. Janssen, R.J.J.Ch. Lousberg, M.J.A. de Bie, An additivity relation Solvents

for carbon-13 chemical shifts in substituted allenes, Recl. Trav. Chim. Pays-Bas 1981, 100, 85. [2] U. Vögeli, D. Herz, W. von Philipsborn, Geminal C,H spin coupling in substituted alkenes, Org. Magn. Reson. 1980, 13, 200. [3] U. Vögeli, W. von Philipsborn, Vicinal C,H spin coupling in substituted alkenes. Org. Magn. Reson. 1975, 7, 617.



4.3 Alkynes

85

4.3 Alkynes 4.3.1 Chemical Shifts 13C

C

Chemical Shifts of Alkynes (δ in ppm) a

b

R C C H

a 71.9 80.4 85.5 84.0 83.0 89.2 92.6 88.7 83.0 82.8 68.8 84.6 90.9 72.6 81.8 81.9 74.0 74.8

Substituent R –H –CH3 –CH2CH3 –CH2CH2CH3 –CH2CH2CH2CH3 –CH(CH3)2 –C(CH3)3 –cyclohexyl –CH2OH –CH=CH2 –C ––– C–CH3 –phenyl –OCH2CH3 –SCH2CH3 –CHO –COCH3 –COOH –COOCH3

C

O S O || C

b 71.9 68.3 67.1 68.7 66.0 67.6 66.8 68.3 73.8 80.0 64.7 78.3 26.5 81.4 83.1 78.1 78.6 75.6

Additivity rule for estimating the chemical shifts of sp-hybridized carbon atoms in alkynes: see [1]. 4.3.2 Coupling Constants 13C-1H a

b

Coupling Constants (|JCH| in Hz) [2] c

H C a

H a

H3 C

C

b

c

C

d e

C b

C

1J 249.0 ab 2J 49.3 ac

H

50.1 -10.4

3J ad 3J be

3.4 4.7

CH3 2Jab -10.3

3J ac

4.3

CH3 c

C

(in substituted acetylenes: 40–60)

2J ac 2J ce

C

C

C

C

N

Hal O N S C

X

P Si Natural Products Solvents

86

C C

C

C

C

4 13C NMR

With acetylenes, the results of multipulse experiments (such as DEPT, INEPT, SEFT, or APT) to determine the number of protons attached to the carbon atoms must be interpreted with care. As a consequence of the unusually large 13C-1H coupling constants through one and two bonds, the sign of the signals may be opposite to the expected one. For the same reasons, unexpected signals may occur in twodimensional heteronuclear correlation spectra (HSQC, HMBC). 13C-13C

H C

Coupling Constants (|1JCC| in Hz)

C

H

1J

CC

171.5

H

a

b

c

C

C

C

C

H

1J ab 1J bc

190.3 153.4

4.3.3 References

N

Hal O N S C

X

P Si Natural Products Solvents

[1] W. Höbold, R. Radeglia, D. Klose, Inkrementen-Berechnung von 13C-chemischen Verschiebungen in n-Alkinen, J. Prakt. Chem. 1976, 318, 519. [2] K. Hayamizu, O. Yamamoto, 13C,1H Spin coupling constants of dimethylacetylene, Org. Magn. Reson. 1980, 13, 460.



4.4 Alicyclics

87

4.4 Alicyclics 4.4.1 Chemical Shifts

C

Saturated Monocyclic Alicyclics (δ in ppm) -2.8

13C

27.1

22.9

28.8

25.6

26.8

(CH 2 )n

X O N O || C

δ 26.0 25.1 26.3 23.8 26.2 25.2 27.0 28.0 29.3 29.4 29.7

C

C

C

C

Chemical Shifts of Monosubstituted Cyclopropanes (δ in ppm) R

C

n 9 10 11 12 13 14 15 20 30 40 72

Substituent R –H –CH3 –CH2CH3 –CH2CH2CH2CH3 –C(CH3)3 –CH2Cl –CH2OH –CH=CH2 –phenyl –Cl –Br –I –OH –NH2 –NO2 –C ––– N –CHO –COCH3 –CO–phenyl –COOH –COOCH3

a -2.8 4.9 12.8 10.9 22.7 13.6 12.7 14.7 15.3 27.3 14.2 -20.1 45.7 24.0 54.3 -4.5 22.7 20.1 17.1 12.7 12.2

a

N

b

b -2.8 5.6 4.1 4.4 0.3 5.5 2.2 6.6 9.2 8.9 9.1 10.4 6.8 7.4 11.7 6.2 7.4 9.6 11.5 8.9 7.7

other

Hal O

CH3 19.4 CH2 27.8, CH3 13.6 1-CH2 34.7, 2-CH2 32.0 C 29.3, CH3 28.2 CH2 50.3 CH2 66.5 CH 142.4, CH2 111.5 C 143.9, CH 125.3–128.2

N S C

X

P Si CN 121.5 CO 202.1 CO 207.3, CH3 29.1 CO 181.6 CO 174.7, CH3 51.1

Natural Products Solvents

88 13C

4 13C NMR Chemical Shifts of Monosubstituted Cyclopentanes (δ in ppm)

C

R

C

C

C

C

C

X O

N

Hal O

S O

N

||

C

S C

N

X

P Si Natural Products Solvents

Substituent R –H –CH3 –CH2CH3 –CH(CH3)2 –C(CH3)3 –CH2OH –F –Cl –Br –I –OH –OCH3 –OCOCH3 –NH2 –NO2 –C ––– N –SH –CO–phenyl –COOH –COOCH3

a 26.0 34.8 42.3 47.4 50.3 41.2 95.5 62.0 53.5 28.7 73.7 82.2 77.7 53.4 87.0 27.0 38.3 46.4 43.0 43.7

b 26.0 34.8 32.6 30.0 26.5 28.3 32.8 37.2 37.9 40.7 35.4 31.4 33.8 36.4 32.6 30.5 37.7 30.0 29.2 30.0

a

b

c 26.0 25.4 25.4 24.7 25.1 24.5 22.5 23.1 23.3 24.9 23.4 23.1 24.9 24.0 24.8 24.2 24.6 26.3 25.1 25.8

c

other CH3 21.4 CH2 29.2, CH3 13.2 CH 33.9, CH3 21.7 C 32.5, CH3 27.6 CH2 67.0 1J 2 3 CF 173.5, JCF 22.1, JCF <1.5 Hz

CH3 56.0 CO 170.8, CH3 21.7 CN 123.4 CO 183.8 CO 177.0, CH3 51.4



4.4 Alicyclics

89

13C Chemical Shifts of Equatorially and Axially Monosubstituted Cyclohexanes

(δ in ppm)

c

b

d

C

X O N

S O || C

Substituent R –H –CH3 –CH2CH3 –CH2CH2CH3 –CH(CH3)2 –CH2CH2CH2CH3 –C(CH3)3 –cyclohexyl –CH=CH2 –C ––– CH –phenyl –F –Cl –Br –I –OH –OCH3 –OCOCH3 –OCO–phenyl –OSi(CH3)3 –NH2 –NHCH3 –N(CH3)2 –NH3+Cl– –N=C=N–cyclohexyl –NO2 –N3 –C ––– N –NC –NCS –SH –CHO –COCH3 –COOH –COO– –COOCH3 –COCl

a 27.1 33.2 40.1 40.0 44.6 38.4 48.8 44.3 42.1 28.7 45.1 91.0 59.8 52.4 31.2 70.4 79.2 72.3 72.8 70.5 51.1 58.7 64.3 51.8 55.7 84.6 59.5 28.0 51.9 55.3 38.3 50.1 51.5 43.7 47.2 43.4 55.4

b 27.1 36.0 33.4 33.6 30.0 34.1 28.1 30.8 32.3 32.1 34.9 32.8 37.4 38.3 40.1 35.8 32.2 32.2 31.5 36.0 37.6 32.7 29.2 32.2 35.0 31.4 31.5 29.6 33.7 33.9 38.1 26.0 29.0 29.6 30.9 29.6 29.7

a

c

R

c 27.1 27.1 26.9 26.6 26.8 27.1 27.7 27.4 26.0 25.2 27.4 23.6 26.1 27.3 28.3 25.1 24.5 24.4 24.1 24.7 25.8 25.7 26.5 24.8 24.8 24.7 24.5 24.6 24.4 24.5 26.6 25.2 26.6 26.2 26.9 26.0 25.5

d 27.1 27.0 27.2 26.9 27.3 27.3 27.1 27.4 27.1 24.4 26.7 25.3 25.4 25.6 25.4 26.3 26.4 26.1 24.7 25.0 26.3 26.8 26.9 25.2 25.5 25.5 24.5 25.1 25.2 24.8 25.3 26.1 26.3 26.6 26.9 26.4 25.9

b

R

d

C

a

a b c d 27.1 27.1 27.1 27.1 28.4 32.4 20.6 26.9 35.5 30.0 21.4 27.1

C

C

C

C

41.1 30.2 21.6 27.1

37.0 28.0 35.2 88.1 60.1 55.4 38.3 65.5 74.9

30.0 30.0 30.1 30.1 33.9 34.9 36.0 33.2 30.0

21.2 21.2 21.9 19.8 20.4 21.5 22.8 20.5 21.1

27.1 25.7 27.7 25.0 26.0 26.4 26.1 27.1 26.6

N

Hal O

69.0 29.3 20.3 24.7 66.1 33.1 19.8 25.0 47.4 33.8 20.0 27.1

N S

56.8 26.4 50.3 52.8 35.9 46.4

29.0 27.4 30.5 31.3 33.1 24.7

20.1 21.9 20.1 20.4 19.4 22.7

25.2 25.0 25.2 24.8 25.7 27.1

39.1 27.7 24.1 26.7

C

X

P Si Natural Products Solvents

4 13C NMR

90

Estimation of 13C Chemical Shifts of Alicyclic Compounds (δ in ppm)

C C

C

C

C

The 13C chemical shift of the parent compound (e.g., 22.9 for cyclobutane, 26.0 for cyclopentane, and 27.1 ppm for cyclohexane) and the same increments as for alkanes (see Chapter 4.1) can be used to estimate the chemical shifts of sp3-hybridized carbon atoms of alicyclic compounds. Appropriate use of the conformational correction terms, K, is especially important with axial and equatorial substituents in cyclohexanes. The additivity rule is, however, not suitable for estimating chemical shifts of substituted cyclopropanes. 13C

Chemical Shifts of Unsaturated Alicyclics (δ in ppm) 108.7

137.2 31.4

2.3 124.9 134.3 152.6 123.4

N

Hal O N

29.8

S C

X

P Si Natural Products Solvents

cis

130.4 26.0 27.0

130.2 25.7 26.4 29.5

130.8 32.8 23.3

127.4 25.4 23.0

128.2

28.7

126.1 124.6 22.3

26.0

134.1 129.8 28.8

123.3

128.5 28.5

132.8 34.3 34.4 trans

41.6

124.5

28.8 130.9 27.1

132.7 132.7

cis, cis

131.5



4.4 Alicyclics

13C

91

Chemical Shifts of Condensed Alicyclics (δ in ppm)

20.2

27.6 16.7

21.5

5.8

23.9

9.4

10.3

22.9

28.1 H

33.3 24.6

H

31.8 H 45.4 26.5

29.4 H H

43.3 34.3

H

26.8

24.1

42.6

24.8

36.8 29.7 24.5

H

24.5 38.7 38.7

36.5

32.4 H 27.1

47.3

31.7 22.1

C

C

C

C

H

H

H

48.8

29.9 22.6

23.8

26.4

38.5

39.9

28.0 H

C

H

44.0 34.6 27.1

H

N

Hal

37.6 22.0

O

27.5 32.7 33.2

29.8

42.0 135.8

37.9 28.5

29.7

32.2

N 23.2

9.9 75.2

50.4

143.2

47.3

S

15.0

C 24.6 26.7 24.4 28.4

28.8

X

P Si Natural Products Solvents

4 13C NMR

92

124.2

C C

C

C

C

125.9

143.9 32.8 25.3

143.5 123.6 39.1 124.5 126.1

133.8

136.8 125.5 29.5 129.0 23.6

132.1 120.9 144.7

4.4.2 Coupling Constants 13C-1H

Coupling Constants

Coupling through one bond (|1JCH| in Hz) 160

N

134

125

3.0

3.7

Coupling through two bonds (|2JCH| in Hz)

Hal O

2.6

3.5

Coupling through three bonds (|3JCH| in Hz)

N

H 2.1 13

S C

128

X

P Si Natural Products Solvents

13C-13C

C

H 8.1

Coupling Constants (|1JCC| in Hz)

12.4

a

b

c

CH3

1J ab 1J bc

13.4 44.0

32.7



4.5 Aromatic Hydrocarbons

93

4.5 Aromatic Hydrocarbons 4.5.1 Chemical Shifts 13C

C

Chemical Shifts of Aromatic Hydrocarbons (δ in ppm) [1] 133.7 128.5

122.4 131.9

124.2

129.0

128.0

125.5

126.3 126.3 128.3 130.1 126.6

32.8 25.3

136.8 125.5 29.5

124.6 130.9 127.0 124.6

143.9

125.9

126.0

124.5 126.1

123.6

143.5

39.1

120.9

132.1

144.7

23.6

128.7

122.7

129.7 140.0 124.3 127.9

128.4

127.4

C

C

C

C

119.7

140.1 137.4 137.4

123.9

N

119.7

Hal O

126.5 126.5

124.8 36.8 143.2

N

134.7

S

29.2 128.0

145.9 119.5 128.2

132.1

135.2

133.8

137.3

30.3

125.3

141.6

37.7 128.0 139.7

131.8 126.2 128.1

127.5 127.5

137.3 123.9 127.5

C

X

P Si

143.2 Natural

Products Solvents

94

4 13C NMR

Effect of Substituents on (δ in ppm) 3

C

4

C

C

C

C

N

Hal O N S C

2

X

P Si Natural Products Solvents

C

Substituent R –CH3 –CH2CH3 –CH2CH2CH3 –CH(CH3)2 –CH2CH2CH2CH3 –C(CH3)3 –cyclopropyl –cyclopentyl –cyclohexyl –1-adamantyl –CH2F –CF3 –CH2Cl –CHCl2 –CCl3 –CH2Br –CH2I –CH2OH –CH2OCH3 –CH2NH2 –CH2NHCH3 –CH2N(CH3)2 –CH2NO2 –CH2CN –CH2SH –CH2SCH3 –CH2S(O)CH3 –CH2S(O)2CH3 –CH2CHO –CH2COCH3 –CH2COOH –CH2Li –CH=CH2 –C(CH3)=CH2 –C ––– CH –phenyl –2-pyridyl –4-pyridyl

13C

1

Chemical Shifts of Monosubstituted Benzenes

δC = 128.5 + Zi

R

i

Z1 9.2 11.7 10.3 20.2 10.9 18.6 15.1 17.8 16.3 22.2 8.5 2.5 9.3 11.9 16.3 9.5 10.5 12.4 8.7 14.9 12.6 7.8 2.2 1.6 12.5 9.8 0.8 -0.1 7.4 5.8 6.5 32.2 8.9 12.6 -6.2 8.1 11.2 9.6

Z2 0.7 -0.6 -0.2 -2.2 -0.2 -3.3 -3.3 -1.5 -1.8 -2.9 -0.7 -3.2 0.3 -2.4 -1.7 0.7 0.0 -1.2 -0.9 -1.4 -0.3 0.5 2.2 0.5 -0.6 0.4 1.5 2.1 1.3 0.8 1.4 -22.0 -2.3 -3.1 3.6 -1.1 -1.4 -1.6

Z3 -0.1 -0.1 0.1 -0.3 -0.2 -0.4 -0.6 -0.4 -0.3 -0.5 0.4 0.3 0.2 0.1 -0.1 0.3 0.0 0.2 -0.1 -0.2 -0.3 -0.3 2.2 -0.8 0.0 -0.1 0.4 0.6 0.5 0.1 0.4 -0.4 -0.1 -0.4 -0.4 0.5 0.5 0.5

Z4 -3.0 -2.8 -2.7 -2.8 -2.8 -3.1 -3.6 -2.9 -2.8 -3.1 0.5 3.3 0.0 1.2 1.8 0.2 -0.9 -1.1 -0.9 -2.0 -1.8 -1.5 1.2 -0.7 -1.6 -1.6 -0.2 0.6 -1.1 -1.6 -1.2 -24.3 -0.8 -1.2 -0.3 -1.1 -1.4 0.5



4.5 Aromatic Hydrocarbons

X O

N

S

Substituent R –F –Cl –Br –I –OH –ONa –OCH3 –OCH=CH2 –O–phenyl –OCOCH3 –OSi(CH3)3 –OPO(O–phenyl)2 –OCN –NH2 –NHCH3 –N(CH3)2 –NH–phenyl –N(phenyl)2 –NH3+ –NH2+CH(CH3)2 –N+(CH3)3 –N(O)(CH3)2 –NHCOCH3 –NHOH –NHNH2 –N=CH–phenyl –N=NCH3 –NO –NO2 –C ––– N –NC –NCO –NCS –N+ –– N –SH –SCH3 –SC(CH3)3 –S(CH3)2+ –SCH=CH2 –S–phenyl –S–S–phenyl –S(O)CH3 –S(O)2CH3 –S(O)2OH –S(O)2OCH3

Z1 33.6 5.3 -5.4 -31.2 28.8 39.6 33.5 28.2 27.6 22.4 26.8 21.9 25.0 18.2 15.0 16.0 14.7 13.1 0.1 5.5 19.5 26.2 9.7 21.5 22.8 24.7 22.2 37.4 19.9 -16.0 -1.8 5.1 3.0 -12.7 4.0 10.0 4.5 -1.0 5.8 7.3 7.5 17.6 12.3 15.0 6.4

Z2 -13.0 0.4 3.3 8.9 -12.8 -8.2 -14.4 -11.5 -11.2 -7.1 -8.4 -8.4 -12.7 -13.4 -16.2 -15.4 -10.6 -7.0 -5.8 -4.1 -7.3 -8.4 -8.1 -13.1 -16.5 -6.5 -6.2 -7.6 -4.9 3.5 -2.2 -3.7 -2.7 6.0 0.7 -1.9 9.0 3.1 2.0 2.5 -1.3 -5.0 -1.4 -2.2 -0.6

Z3 1.6 1.4 2.2 1.6 1.4 1.9 1.0 0.7 -0.3 0.4 0.9 1.2 2.6 0.8 0.8 0.9 0.9 0.9 2.2 1.1 2.5 0.8 0.2 -2.2 0.5 1.3 0.5 0.8 0.9 0.7 1.4 1.1 1.3 5.7 0.3 0.2 -0.3 2.2 0.2 0.6 0.8 1.1 0.8 1.3 1.5

Z4 -4.4 -1.9 -1.0 -1.1 -7.4 -13.6 -7.7 -5.8 -6.9 -3.2 -7.1 -3.0 -1.0 -10.0 -11.6 -10.5 -10.5 -5.6 2.2 0.7 2.4 0.6 -4.4 -5.3 -9.6 -1.5 -3.0 7.1 6.1 4.3 0.9 -2.8 -1.0 16.0 -3.2 -3.6 0.0 6.3 -1.8 -1.5 -1.1 2.4 5.1 3.8 5.9

95

C C

C

C

C

N

Hal O N S C

X

P Si Natural Products Solvents

96

S

C C

C

C

C

N

Hal

O || C

P

O N

M

S C

X

P Si Natural Products Solvents

4 13C NMR Substituent R –S(O)2F –S(O)2Cl –S(O)2NH2 –SCN –CHO –COCH3 –COCF3 –COC ––– CH –CO–phenyl –COOH –COONa –COOCH3 –CONH2 –CON(CH3)2 –COCl –COSH –CH=NCH3 –CS–phenyl –P(CH3)2 –P(phenyl)2 –P+(phenyl)2CH3 –PO(CH3)2 –PO(phenyl)2 –PO(OH)2 –PO(OCH2CH3)2 –PS(CH3)2 –PS(OCH2CH3)2 –Li –MgBr –SiH3 –SiH2CH3 –Si(CH3)3 –Si(phenyl)3 –SiCl3 –Ge(CH3)3 –Sn(CH3)3 –Pb(CH3)3 –AsH2 –As(phenyl)2 –As(O)(OH)2 –SeCH=CH2 –SeCN –Sb(phenyl)2 –Hg–phenyl –HgCl

Z1 4.6 15.6 10.8 -3.7 8.2 8.9 -5.6 7.4 9.3 2.1 9.7 2.0 5.0 6.0 4.7 6.2 8.8 18.7 13.6 8.9 -9.7 2.5 5.8 -1.9 1.6 6.7 6.1 -43.2 -35.8 -0.5 4.8 11.6 5.8 3.0 13.7 13.2 20.1 1.7 11.1 3.8 0.7 -5.3 9.8 41.6 22.5

Z2 0.0 -1.7 -3.0 2.5 1.2 0.1 1.8 1.0 1.6 1.6 4.6 1.2 -1.2 -1.5 2.7 -0.6 0.5 1.0 1.6 5.2 5.2 1.1 3.9 3.6 3.6 2.0 2.8 -12.7 -11.4 7.3 6.3 4.9 7.9 4.6 4.5 7.2 8.0 7.9 5.0 1.6 4.7 5.1 7.7 9.3 8.0

Z3 1.5 1.2 0.3 2.2 0.5 -0.1 0.7 0.0 -0.3 -0.1 2.2 -0.1 0.1 -0.2 0.3 0.2 0.1 -0.6 -0.6 0.0 2.0 0.1 -0.1 1.5 -0.2 0.2 -0.4 2.4 2.7 -0.4 -0.5 -0.7 -0.6 0.1 -0.5 -0.4 -0.1 0.8 0.1 0.8 0.4 2.9 0.3 -0.9 -0.6

Z4 7.5 6.8 3.2 2.2 5.8 4.4 6.7 5.9 3.7 5.2 4.6 4.3 3.4 1.0 6.6 5.4 2.3 2.4 -1.0 0.1 6.7 3.0 3.0 5.6 3.4 2.9 3.4 3.1 4.0 1.3 1.0 0.4 1.1 4.2 -0.2 -0.4 -1.0 0.0 -0.1 4.5 -1.4 2.1 0.0 -1.6 -0.9



4.5 Aromatic Hydrocarbons

97

Estimation of 13C Chemical Shifts of Multiply Substituted Benzenes and Naphthalenes (δ in ppm) The 13C chemical shifts of multiply substituted benzenes and naphthalenes (see next pages) can be estimated using the substituent effects in the corresponding monosubstituted hydrocarbons. Example: Estimation of the chemical shifts for 3,5-dimethylnitrobenzene CH3 4

3

2

1

C C

C

C

C

NO2

CH3

C-1

C-3

base value Z1(NO2) 2 Z3(CH3) estimated exp

128.5 19.9 -0.2 148.2 148.5

C-2

base value Z1(CH3) Z3(CH3) Z3(NO2) estimated exp

128.5 9.2 -0.1 0.9 138.5 139.6

C-4

base value Z2(NO2) Z2(CH3) Z4(CH3) estimated exp

128.5 -4.9 0.7 -3.0 121.3 121.7

base value 2 Z2(CH3) Z4(NO2) estimated exp

128.5 1.4 6.1 136.0 136.2

N

Hal O N S

Larger discrepancies between estimated and experimental values are to be expected C if the substituents are ortho to each other or if strongly electron-donating and electron-accepting groups occur simultaneously.

X

P Si

Natural Products Solvents

98

4 13C NMR

Effect of Substituents in Position 1 on 13C Chemical Shifts of Monosubstituted Naphthalenes (δ in ppm)

C C

8

C

C

7 6

C

5

C N

Hal

X

O

O

N

N

S C

X

P Si Natural Products Solvents

O || C

R 9 10

for R: H

1 2 3

δC1 = 128.0

δC2 = 125.9 δC9 = 133.6

4

Substituent R C-1 C-2 C-3 C-4 C-5 C-6 C-7 –CH3 6.0 0.5 0.6 -1.8 0.3 -0.7 -0.5 –C(CH3)3 17.9 -2.8 -0.9 -0.6 1.6 -1.4 -1.4 –CH2Br 4.0 1.1 -0.9 1.3 0.5 -0.1 0.3 –CH2OH 8.2 -0.9 -0.6 0.1 0.5 -0.3 0.1 –CF3 -1.9 -1.3 -1.8 5.0 1.0 0.8 2.0 –F 31.5 -16.1 0.1 -3.8 0.1 1.4 0.7 –Cl 3.9 0.2 -0.2 -0.9 0.2 3.1 0.8 –Br -5.4 3.6 -0.2 -0.5 -0.1 0.4 1.0 –I -28.4 12.3 1.7 1.7 1.4 1.6 2.6 –OH 23.5 -17.2 -0.1 -7.3 -0.4 0.5 0.3 –OCH3 27.3 -22.3 -0.2 -7.9 -0.7 0.3 -0.9 –OCOCH3 18.6 -7.9 -0.6 -2.1 0.0 0.4 0.4 –NH2 14.0 -16.5 0.3 -9.3 0.3 -0.3 -1.3 –N(CH3)2 23.7 -11.2 0.6 -4.6 1.0 0.4 -0.3 –NH3+ -3.8 -4.6 -0.9 3.4 1.4 2.1 2.8 –NHCOCH3 5.7 -4.4 -0.5 -3.0 0.0 -0.1 -0.3 –NO2 18.5 -2.1 -2.0 6.5 0.5 1.3 3.4 –C ––– N -19.2 5.1 -2.4 3.8 -0.7 0.2 1.2 –CHO 2.9 10.8 -1.4 6.7 0.2 0.6 2.7 –COCH3 6.9 2.9 -1.7 4.9 0.3 0.4 2.0 –COOH -1.5 3.6 -2.4 4.3 -0.6 -0.9 0.6 –COOCH3 -0.9 4.5 -1.2 5.4 0.7 0.5 1.9 –CON(CH3)2 6.8 -2.1 -0.8 0.9 0.4 0.4 1.0 –COCl 1.2 10.6 -0.5 9.3 1.9 2.1 4.5 –Si(CH3)3 9.8 5.1 -0.4 1.7 1.2 -0.8 -0.7

C-8 -4.1 -1.2 -4.6 -4.5 -3.4 -7.1 -3.6 -1.3 4.4 -6.6 -6.1 -6.9 -7.3 -3.2 -9.0 -5.3 -5.1 -4.5 -3.5 -2.0 -3.2 -1.8 0.1 -2.1 0.1

C-9 -1.1 -1.6 -2.8 -2.6 1.0 -9.3 -2.8 -2.0 1.3 -9.3 -8.1 -6.9 -10.2 -3.9 -7.4 -5.9 -8.7 -2.8 -3.6 -3.5 -3.2 -1.9 -4.1 -2.1 3.8

C-10 -0.2 2.2 0.1 0.0 -3.9 2.1 1.0 0.6 1.3 1.0 0.8 0.9 0.6 2.1 1.2 0.1 0.6 -2.2 -0.3 0.2 -0.8 0.5 -0.2 1.0 0.2



4.5 Aromatic Hydrocarbons

99

Effect of Substituents in Position 2 on 13C Chemical Shifts of Monosubstituted Naphthalenes (δ in ppm)

C 8 6 5

C

X O N

O || C

1

9

7

2 3

10

Substituent R –CH3 –C(CH3)3 –CH2Br –CH2OH –CF3 –F –Cl –Br –I –OH –OCH3 –OCOCH3 –NH2 –N(CH3)2 –NH3+ –NHCOCH3 –NO2 –C ––– N –CHO –COCH3 –COOH –COOCH3 –COCl –Si(CH3)3

for R: H

R

* Assignment uncertain

C-2 9.3 22.5 9.0 12.3 1.9 34.9 5.7 -6.2 -34.1 27.3 31.8 22.5 16.7 23.6 -0.3 9.6 20.0 -16.7 7.9 8.3 2.4 1.8 9.1 11.9

δC2 = 125.9 δC9 = 133.6

4

C-1 -1.3 -3.3 -1.7 -2.7 -2.0 -17.0 -1.4 1.8 9.2 -18.6 -22.2 -9.5 -20.6 -21.1 -5.9 -11.0 -3.4 5.8 6.2 1.9 2.7 3.0 2.5 5.8

δC1 = 128.0

C-3 2.0 -3.0 1.9 -4.4 -4.2 -9.6 0.8 3.1 9.0 -8.3 -7.1 -4.8 -8.9 -8.8 -6.5 -5.7 -6.7 0.1 -3.6 -2.2 -0.6 -0.5 -0.7 3.9

C-4 -0.8 -0.4 -0.4 -0.1 1.1* 2.4 1.5 1.5 2.3 1.8 1.5 1.3 -0.2 1.2 3.2 0.6 1.7 1.0 0.8 0.2 0.2 0.2 0.2* -1.0

C-5 -0.5 0.0 -0.5 -0.4* 0.1* 0.0 -0.2 -0.3 0.5 -0.3 -0.3 -0.4 -1.6 0.0 0.2 -0.4* 0.1 -0.2 -0.3 -0.4 -0.3 -0.1 -0.4 0.1

C-6 -1.1 -0.7 0.7 -0.2* 2.4* -0.7 0.2 0.2 1.3 -2.4 -2.2 -0.3 -4.8 -3.4 2.3 -0.9 4.0 3.0 2.9 2.3 2.4 2.4 2.2* 0.3

C-7 -0.2 -0.2 0.3 0.1* 1.5 1.1 1.1 0.8 1.5 0.5 0.5 0.6 -0.9 0.7 2.0 1.6* 2.2 1.6 0.9 0.7 0.9 0.9 0.8 -0.2

C-8 -0.6 -0.6 0.6 -0.2* 1.1 -0.6 -1.1 -1.1 -0.6 -1.7 -1.2 -0.4 -3.5 -1.1 0.2 -1.6 2.1 0.2 1.8 1.4 1.3 1.4 1.2 0.1

C

C

C

C

C-9 -0.1 0.4 -0.6 -0.3 -1.1 0.7 0.7 -2.0 2.1 0.9 1.0 0.1 -0.1 2.4 0.1 0.2 -1.1 -1.6 2.4 1.8 -1.3 -1.0

C-10 -2.0 -1.3 -0.7 -0.8 N 1.3 -3.0 -1.9 Hal 0.7 -0.8 O -4.7 -4.3 -2.2 N -7.0 -5.9 -0.3 S -3.0 2.4 0.7 C X -1.4 -1.3 1.5 P Si 1.9 -1.4 Natural -0.5 0.2

Products Solvents

4 13C NMR

100

4.5.2 Coupling Constants 13C-1H

C C

C

C

C

Coupling Constants (|J| in Hz)

C

O

1J ab 2J ac 3J ad

57.0 2.5 10.0

a

CH3 b

c d

e

1J ab 2J ac 3J ad 4J ae

44.2 3.1 3.8 0.9

4.5.3 References [1] P.E. Hansen, 13C NMR of polycyclic aromatic hydrocarbons. A review, Org. Magn. Reson. 1979, 12, 109.

N S C

d

Coupling Constants (|J| in Hz)

b c

Hal

Hb

Hd

a

In benzene: In derivatives: 159.0 1.0 1–4 7.6 7–10 -1.3

1J13 CH 2J13 a CH 3J13 b CH 4J13 c CHd

Hc

13C-13C

N



Ha 13

X

P Si Natural Products Solvents



4.6 Heteroaromatics

101

4.6 Heteroaromatic Compounds 4.6.1 Chemical Shifts 13C

C

Chemical Shifts of Monocyclic Heteroaromatics (δ in ppm)

O

150.6

N O

150.0

N

O

N N N H

HN

134.6

135.9 N

+

109.9 143.0

125.4 138.1

N H

136.2

100.5 158.9

147.9

N H

133.3

N

147.4

120.1

N H

N H

N H

148.4 + N H

122.3 122.3

104.7 133.3

N

N

157.0

N

N

123.4 147.8

S

130.4

N

N H

Te

N N

+ N I–

121.4 156.4

128.6 146.0

CH3 49.8

N N

135.6 + N

128.0 139.6

Cl– OH

(in DMSO) N

144.9 N

166.5 N N

128.8 131.0

N H

N

C

C

C

147.3 135.8

N

Hal O

N

N

103.4 138.5

125.7 N

S C

127.2 139.4

X

P Si Natural Products

O

N N

C

137.6 126.2

143.3

N –

N

146.0

S

N N

109.0 126.8 N – 135.0 145.1

129.0 142.5

N

S

N

Se

143.2 118.6

N

152.7

(in ethanol) N 126.5 151.4 158.0

126.4 124.9

S

147.4

N

HN +

N H

123.7 149.8

N

107.7 118.0

160.9 N

Solvents

102

4 13C NMR

Effect of Substituents in Position 2 on 13C Chemical Shifts of Monosubstituted Pyridines (δ in ppm)

C

5

C

C

C

C

6

4

N

Substituent R –CH3 –CH2CH3 –CH=CH2 –phenyl –F –Cl –Br –I –OH* –OCH3 –O–phenyl –OCOCH3 –NH2 –NHCH3 –N(CH3)2 –NHCOCH3 –NO2 –C ––– N –SH –SCH3 –S(O)CH3 –S(O)2CH3 –CHO –COCH3 –COOH –COOCH3 –CONH2 –Si(CH3)3 –Sn(CH3)3 –Pb(CH3)3

for R: H

3 2

X

N

Hal O

N

N S C

O

S

X

P Si Natural Products Solvents

O || C

M

* Keto form (2-pyridone)

δC3,5 = 123.7 δC4 = 135.9

R

C

δC2,6 = 149.8

C-2 8.6 13.7 5.9 7.7 13.9 1.8 -7.5 -31.6 15.5 14.3 13.9 7.6 8.4 10.9 9.6 1.4 6.9 -15.8 30.4 10.2 16.2 8.5 3.0 3.8 -3.7 -1.7 -0.3 18.6 23.3 33.4

C-3 -0.5 -1.7 -1.3 -1.6 -14.0 0.8 4.6 11.3 -3.6 -12.7 -12.2 -7.3 -15.1 -16.2 -17.9 -9.8 -5.7 4.8 10.7 -4.6 -4.4 -2.6 -2.0 -2.1 0.0 1.5 -1.2 5.0 7.6 9.2

C-4 0.3 0.4 1.1 0.8 5.4 2.8 2.6 1.7 -1.1 2.6 3.5 3.4 1.8 1.5 1.2 2.6 3.9 1.1 2.1 0.0 2.2 2.4 1.2 0.9 2.5 1.1 1.4 -2.0 -2.7 -2.6

C-5 -3.0 -2.8 -2.5 -3.2 -2.5 -1.4 -1.1 -0.8 -17.0 -7.1 -5.3 -1.8 -9.7 -11.3 -12.3 -3.9 5.4 3.2 -10.6 -2.2 0.9 3.7 4.2 3.4 4.2 3.3 2.8 -1.1 -1.7 -2.3

C-6 -0.7 -0.6 -0.3 0.2 -2.0 0.0 0.5 1.0 -8.2 -2.9 -2.0 -1.6 -1.6 -1.3 -1.9 -2.1 -0.8 1.4 -12.1 -0.5 -0.2 0.3 0.4 -0.8 -1.7 0.0 -1.5 0.3 0.6 1.1



4.6 Heteroaromatics

103

Effect of Substituents in Position 3 on 13C Chemical Shifts of Monosubstituted Pyridines (δ in ppm) 5 6

4

N

Substituent R –CH3 –CH2CH3 –phenyl –F –Cl –Br –I –OH –OCH3 –OCOCH3 –NH2 –NHCH3 –N(CH3)2 –C ––– N –SH –SCH3 –CHO –COCH3 –COOH –COOCH3 –CONH2 –Si(CH3)3 –Ge(CH3)3 –Sn(CH3)3 –Sn(n-C4H9)3 –Pb(n-C4H9)3

C X

O N S

O || C

M

3 2

for R: H

R

C

δC2,6 = 149.8

δC3,5 = 123.7 δC4 = 135.9

C-2 1.3 -0.4 -1.4 -11.5 -0.3 2.1 7.1 -10.7 -12.5 -6.5 -11.9 -13.6 -14.0 3.6 -12.8 -13.6 2.4 3.5 -6.4 -0.6 2.7 2.7 3.9 5.9 6.6 7.1

C-3 8.9 15.4 12.8 36.1 8.1 -2.7 -28.5 31.3 31.5 23.4 21.4 23.1 23.3 -13.8 26.1 24.6 7.8 8.5 13.0 1.0 5.9 9.1 12.8 13.0 12.6 21.7

C-4 0.0 -0.8 -1.8 -13.2 -0.4 2.7 8.9 -12.4 -15.9 -7.0 -14.4 -18.2 -17.1 4.2 -11.3 -11.7 -0.2 -0.7 11.1 -0.5 1.1 3.0 4.2 7.1 7.7 8.5

C-5 -0.9 -0.5 -0.3 0.8 0.6 1.1 2.3 1.2 0.1 -0.1 0.8 0.6 0.1 0.5 7.3 10.6 0.5 -0.2 4.3 -1.8 1.2 -2.3 -0.4 0.1 0.0 0.9

C-6 -2.3 -2.7 -1.3 -3.9 -1.4 -0.9 0.3 -8.6 -8.4 -3.2 -10.8 -11.9 -11.6 4.2 -2.8 -3.0 5.4 0.0 -6.0 1.8 -1.5 -1.2 -0.1 -0.3 -0.4 -1.8

C

C

C

C

N

Hal O N S C

X

P Si Natural Products Solvents

104

4 13C NMR

Effect of Substituents in Position 4 on 13C Chemical Shifts of Monosubstituted Pyridines (δ in ppm)

C C

C

C

for R: H

R 5 6

4

N

3

δC3,5 = 123.7 δC4 = 135.9

2

C Substituent R –CH3 –CH2CH3 –CH(CH3)2 –C(CH3)3 –CH=CH2 –phenyl –F –Br –I –OH* –OCH3 –OCOCH3 –NH2 –NHCH3 –N(CH3)2 –C ––– N –SH –SCH3 –CHO –COCH3 –COOCH3 –CONH2 –Si(CH3)3 –Ge(CH3)3 –Sn(CH3)3 –Pb(CH3)3

C

X

N

Hal O

O N

N

S

S C

δC2,6 = 149.8

X

P Si Natural Products Solvents

O || C M

* Keto form (4-pyridone)

C-2 0.5 -0.1 0.4 0.9 0.3 0.4 2.7 3.0 0.2 -9.8 0.9 1.7 0.7 0.5 0.6 2.1 -16.9 0.1 1.7 1.6 1.0 0.4 -2.8 -1.1 -1.1 -0.5

C-3 0.7 -0.5 -1.9 -2.6 -3.0 -2.2 -11.9 3.3 9.1 -6.2 -13.9 -6.7 -13.8 -15.9 -16.3 2.1 5.9 -3.3 -0.7 -2.7 -0.8 -0.9 2.4 4.4 7.3 9.1

C-4 10.6 16.8 21.2 23.9 8.4 12.2 32.8 -3.2 -30.8 45.4 29.0 23.9 19.3 19.8 19.2 -15.9 54.3 14.6 5.3 6.6 1.4 6.2 11.9 16.8 16.2 24.6



4.6 Heteroaromatics

105

Estimation of 13C Chemical Shifts of Multiply Substituted Pyridines (δ in ppm) The 13C chemical shifts in multiply substituted pyridines can be estimated using the substituent effects in the monosubstituted parent compound. Example: Estimation of the chemical shifts for 2-amino-5-methylpyridine H3 C

C-2

base value 2-NH2 5-CH3 estimated exp

C-4

135.9 1.8 0.0

base value 2-NH2 5-CH3

149.8 -1.6 1.3

estimated exp

137.7 138.6

C

C

C

C

4 5 6

N

3 2

NH2

C-3

155.9 156.9

base value 2-NH2 5-CH3 estimated exp

C-6

149.8 8.4 -2.3

C

C-5

base value 2-NH2 5-CH3 estimated exp

123.7 -15.1 -0.9 107.7 108.4

base value 2-NH2 5-CH3 estimated exp

123.7 -9.7 8.9 122.9 122.5

N

Hal O N S

149.5 147.6

C

X

Larger discrepancies between estimated and experimental values are to be expected P Si if the substituents are ortho to each other and if strongly electron-donating and -accepting groups occur simultaneously. Also, tautomerization and zwitterion formation have large effects on 13C chemical shifts. Natural

Products Solvents

106 13C

Chemical Shifts of Condensed Heteroaromatics (δ in ppm)

C C

C

C

123.2 124.6

C 125.4 124.4

N

Hal

123.0 130.6

O N

120.0 131.1

S C

X

P Si

4 13C NMR

127.2

121.6

111.8 120.5

110.8 124.3

127.9 106.9 145.0

O

155.5 140.1 N

152.6

O

124.4

122.9 122.9

150.0 122.2 147.1 N

109.9

119.6 121.7

O

120.1 125.8

162.7

120.5

111.0 115.4

115.4 120.4

127.6 102.1 N H

137.9 N N H

111.2

117.2

125.1

123.5

144.4 N

133.4 99.5 114.1

113.0

115.6 142.1

139.9 155.4 N

155.7

S

135.7

N

110.0

139.9

124.1 128.6

123.4 126.8

126.4

S

N H

156.1

N

125.6

122.6

139.8 124.0

122.8 133.4

N

O

119.6

127.5 126.9

137.9

119.3

145.5 N

129.0

N N

108.8

133.1

Solvents 110.5

141.5

O

114.7

124.3 124.4

135.5

118.4 155.3

N

Natural Products

124.1

123.8

129.0

148.9

134.5 144.5 S

121.6

121.6

N

161.5 155.2 N S N

CH3 33.7

120.7 100.5

N

122.1

N H

125.5

144.8 152.0

128.4

N N

154.9

N N H

147.9



4.6 Heteroaromatics

128.0 127.6 135.7 126.3 120.8 129.2 150.0 N

129.2 148.1

125.2 127.4 155.9 N 127.9 134.1 160.7

135.7 126.9 126.4 120.4 128.0 124.7 130.2 142.9 132.2 146.1 127.2 N N 132.1 127.5 152.4 128.6

142.8 129.6 N 129.4

N

122.6 127.0

O

156.2 142.7 O N H

111.6

114.5

120.0 123.0

112.8 131.8

142.2 O

120.6

116.2

123.6

O

122.6

N H

139.6

126.7 126.7 152.0 N 144.8 133.1

149.1 144.0 N N

120.0

118.4 125.4

110.8

128.3 125.5

130.3

130.9

130.2

134.9

S

138.5 116.8 S N H

145.7

119.9 S O

151.9 * Assignment uncertain

C

C

C

C

N

126.6 135.8 129.5 N

C

N

129.5 151.0

N

128.6 150.1 124.2

107

121.9

124.6 127.0

122.9

N

Hal O

126.7

121.3 125.6

N

113.8

127.4*

124.2 126.5*

117.5

S C

X

P Si Natural Products Solvents

4 13C NMR

108

4.6.2 Coupling Constants 13C-1H

C C

C

C

C

Coupling Constants (|1J| in Hz)

a

O b a

1J CaHa b 1JC H b b

a

N H a

N

1J C H 1J a a CbHb

186 177

1J b 1 CaHa JCbHb c 1 JCcHc

161 163 178

N

a

175 202

1J CaHa b 1JC H b b

N H a

N

N H

N

1J

CaHa

169 183 194

b

N

b

a

N H N

N N H

a

1J C H 1J a a CbHb

206 189

1J

CaHa

209

CaCb

64.2

N

Hal O

C

13C-13C a

O

N

a

S

N

X

P Si Natural Products Solvents

b

Coupling Constants (|1J| in Hz) 1J

CaCb

b 1JC C 1J a b c CbCc

a

69.1 N H

53.7 54.3

b

1J

CaCb

a

65.6 S

b

1J



4.7 Halogen Compounds

109

4.7 Halogen Compounds The additivity rules for estimating the 13C chemical shifts of various skeletons can be applied to those haloalkanes that do not have more than one halogen atom at C a given carbon atom. In all other cases, the simple linear models fail but correction terms for non-additivity are available for halomethanes and derivatives (see C C [1, 2]).

C

4.7.1 Fluoro Compounds

C

19F

(natural abundance 100%) has a spin quantum number I of 1/2. The signals of carbon atoms up to a distance of about four bonds are split by coupling to 19F. 13C

Chemical Shifts and 19F-13C Coupling Constants (δ in ppm, |J| in Hz)

CH3 F 71.6 1J

2J

1J

CF 161.9

21.1 16.4

2J

CF

F

83.7 1J 160.1 CF

14.1

31.9

4J

2J

F

0 2JCF 18.3 29.3 30.6 3J

F3 C

25.3 84.2 1 CF 6.2 JCF 164.8

78.9

173.5 O 2J 22 CF

28.3 F

108.1

OH

167.2 O 2J 28 CF

S

CF 24.8

CF3

88.5 1J

F

147.7 CF 267.2

CF 283.2

115.0

F3 C

O

F

N

1J 271 CF 2J 48.1 CF

1J

Hal

93.5

2J

116.2

CF 239

F2 HC

CF 259.2

87.8 1J 162.1 CF

CF ≈

F

1J

CF 274.3

23.0

N

CF4 118.5

CF 22.4

85.2 1J 163.3 CF

1J

OH

1J

CF 234.8

23.6

9.2 3J 6.7 CF

CF 177

FH2 C

CHF3 116.4

CF 19.5



22.7 29.3

1J

CH2 F2 109.0

OH

C

X

P Si Natural Products

163.0 Solvents CF 43.6

O 2J

4 13C NMR

110 F

C C

C

C

C

F

91.0; 1J

CF 245.1 115.5; 2JCF 21.0 130.1; 3JCF 7.8 124.1; 4JCF 3.2

CHF2 114.8; 1JCF 238.6

CF3 124.5; 1JCF 272.2

F

131.8; 5JCF ≈ 0

N

134.4; 2J 125.5; 3J

CF 22.2

CF

122.7; 2JCF 17.7

145.9; 4J

CF 3.7

N

159.8; 1JCF 255.1 121.2; 4JCF 4.2 138.3; 2JCF 22.5 147.8; 3JCF 14.9

Hal

109.7; 2JCF 37.6 N

F

163.7; 1JCF 236.3

Estimation of 13C Chemical Shifts of Linear Perfluoroalkanes (δ in ppm)

N

δ = 124.8 + ∑ Zi

S C

168.7; 1JCF 261.8 111.8; 2JCF 16.1 152.5; 3JCF 6.4

141.3; 3JCF 7.5

F

124.5; 3JCF 4.3

129.0; 5JCF 3

131.0; 2JCF 36.6 125.3; 3JCF 3.7 128.8; 4JCF 1

5.6

130.7

O

137.0; 2JCF 16.5 127.8; 3JCF 6.1 128.9; 4JCF 1

CF 170.6 32.8; 2JCF 19.0 23.6; 3JCF 7.6 25.3; 4JCF 1.5

128.6

N

CH2 F 84.9; 1JCF 166.0

163.3; 1J

X

P Si Natural Products Solvents

Increments Zi for the CF2 or CF3 substituent in position: α β γ -8.6 1.8 0.5 Example: Estimation of the chemical shifts in perfluorobutane F3 C

CF3

base value 1 α-CF2 1 β-CF2 1 γ-CF3 estimated exp

124.8 -8.6 1.8 0.5 118.5 118.5

CF2

CF2

CF3

CF2

base value 1 α-CF3 1 α-CF2 1 β-CF3 estimated exp

124.8 -8.6 -8.6 1.8 109.4 109.3



4.7 Halogen Compounds

111

4.7.2 Chloro Compounds 13C

Chemical Shifts of Chloro Compounds (δ in ppm)

25.6

54.0

CH3 Cl

18.9

Cl

39.9 31.6

11.6

117.2

27.3

69.3

113.3

Cl

Cl

Cl

117.6

Cl

Cl

Cl

125.1

Cl

173.7

144.8 126.8

Cl

130.3

128.4

148.4

119.9

Cl

N

Cl

Cl

Hal

135.5 N

129.9

Cl

88.9

Cl3 C

170.4

133.8 128.9

126.6

124.3

C

Cl3 C CCl3

OH

O

CCl3 97.7

C

O

Cl2 HC

26.1

C

105.3

118.1

63.7

59.8 37.4

25.4

Cl

C

121.3

OH

O

Cl

66.7

Cl Cl

Cl

Cl Cl

ClH2 C

96.2

127.1

Cl

40.7

46.3

Cl

Cl

126.1

34.6

53.7

46.8

Cl

96.1

CCl4

Cl

Cl

51.7

Cl

Cl

77.2

CHCl3

CH2 Cl2

26.3

C

122.3 131.8 149.5 149.8

O

CH2 Cl 46.2

137.8 128.8

128.5 138.7 N

128.7

124.5 151.6 Cl

N

OH

167.0

CHCl2 71.9

140.4 126.1

129.7

128.6

S C

X

P Si Natural Products Solvents

4 13C NMR

112

4.7.3 Bromo Compounds 13C

C C

C

C

C

Chemical Shifts of Bromo Compounds (δ in ppm)

9.6

21.4

CH3 Br

19.4

26.4

Br

27.6 31.8

12.1

13.0

Br

40.1

28.5

49.4

Br

31.5

Br

122.4

N

Hal

127.2

114.7

Br Br

Br

Br

O

Br

112.4

Br

Br

Br

N

Br

X

P Si Natural Products Solvents

95.0

52.4 38.3

25.6

27.3

CBr3 36.5

147.0 126.5

130.1

128.1

Br

Br

N

25.9

93.7

152.8

53.4

Br3 C

116.4 OH

O

172.0

Br

31.3

Br2 HC

124.8 148.9

138.6 N

121.0 151.9

169.7

CHBr2 41.2

141.9 126.5

128.8

Br

Br

OH

O

138.0 129.2

128.7

CBr3

109.4

CH2 Br 33.4

130.7

132.7 127.0

Br

62.1

Br

BrH2 C

123.1 131.8

127.5

Br

Br Br

Br

97.0

Br

S C

Br

36.4

44.8

35.6

Br

CBr4

Br

Br

32.4

-28.7

CHBr3

CH2 Br2

129.8

122.6 150.3

138.5 N

128.6

128.3 142.3 Br



4.7 Halogen Compounds

113

4.7.4 Iodo Compounds Chemical Shifts of Iodo Compounds (δ in ppm)

13C

-24.0

-54.0

20.6 -1.6

I

15.3

I

I

31.2 40.1

25.4 I

N

28.3

105.1 132.8 150.0

4.7.5 References

I

126.0 150.1

79.4

I

144.8 N

I

95.2 156.9

122.9 150.8

145.2 126.3

128.7

137.6 N

C

C

C

CHI2 -0.6

139.2 128.7

127.8

C

I

I

CH2 I 5.8

130.1

I

43.0

96.5

97.3 137.4

127.4

40.4

I

I

I

85.2 I

CI4

20.9

9.1

130.3

-292.5

CHI3

31.2

27.0

I

3.0

-139.9

CH2 I2

CH3 I

C

129.0

128.2

N

Hal O N

135.0 118.2 I

S C

X

[1] G.R. Somayajulu, J.R. Kennedy, T.M. Vickrey, B.J. Zwolinski, Carbon-13 chemical shifts for 70 halomethanes, J. Magn. Reson. 1979, 33, 559. P Si [2] A. Fürst, W. Robien, E. Pretsch, A comprehensive parameter set for the prediction of the 13C NMR chemical shifts of sp3-hybridized carbon atoms in organic Natural compounds, Anal. Chim. Acta 1990, 233, 213. [3] D.W. Ovenall, J.J. Chang, Carbon-13 NMR of fluorinated compounds using Products wide-band fluorine decoupling, J. Magn. Reson. 1977, 25, 361.

Solvents

4 13C NMR

114

4.8 Alcohols, Ethers, and Related Compounds 4.8.1 Alcohols

C C

Chemical Shifts of Alcohols (δ in ppm)

13C

C

50.2

18.2

CH3 OH

C

57.8

C 15.2 36.0

31.2

OH

14.2 31.9 32.9 23.0 25.8

Hal O

63.4

62.1

14.3

68.2 (72.7)

OH

S C

HO

OH

64.5

OH

HO

OH

48.3

X

P Si Natural Products Solvents

66.0

HO

91.2

63.4

OH

125.1 F3 C

OH

61.4

|1JCF| |2JCF|

278 35

75.5

Cl3 C

75.9

OH OH

in parentheses: in D2O 76.1

66.1

72.9

OH

OH OH

HO OH

HO

OH

91.2

65.8

OH

74.3

74.5 OH

83.3

OH

OH

63.4

99.1

39.4 30.5

18.7 (23.0) 67.7 (71.6)

OH

OH

HO

64.3

OH

19.2 10.1 72.2 OH

23.5

N 73.7

73.3

67.2

HO

32.7

63.2

60.2

OH

26.2

OH

OH

36.4

HO

OH

64.0

64.2

15.3 29.4

23.2 39.2

25.3

OH

23.8 33.6

OH

14.3 28.2

OH

OH

HO

10.3

68.9

20.3 62.9

N

25.9

OH

OH

114.9 137.5

OH

OH

73.8 83.0

50.0



4.8 Alcohols, Ethers, and Related Compounds OH

65.1

70.4 35.8 25.1

26.3 13C

OH

OH

157.3 115.7

140.9 127.3

127.4

128.7

121.1

115

103.6

HO

129.9

131.6

OH

157.7 108.5

Chemical Shifts of Enols (δ in ppm) OH

88.0

190.5

149.0 32.8

28.3

46.2 191.1

22.5

22.5

O

56.6

H3 C

60.9

C

28.5

28.3

O

57.3

N

Hal 57.6

H3 C

CH3

O

73.4 O

52.5

H3 C

C

Chemical Shifts of Ethers (δ in ppm)

59.1 H3 C

C

201.1

4.8.2 Ethers 13C

C

54.2 203.6

O

O

O

190.5

99.0

28.3

103.3

O

31.0

46.2 191.1

HO

H

O

C

20.5

32.9 15.0

67.7 O

H3 C

14.7 H3 C

84.4

O

79.2 32.2

26.4

24.5

O

72.7 H3 C

73.1 116.4 O

134.4

O

54.9

10.5

H3 C

23.2 58.4

O

72.3

H3 C

O

55.1 CH3

74.5

27.0

49.4

57.4

152.7 O

59.1

O

14.2

O

72.6

O

26.5

159.9 114.1 129.5

120.8

156.1

O

121.6

C

X

P Si Natural Products

54.8 O

S

CH3

90.9

74.6

CH3

N

21.4

117.3 128.2

Solvents

4 13C NMR

116

C

C

C

O

O

39.5

O

C

O

109.9

O

24.9

99.9

48.1

O CH3

H3 C

O CH3

O CH3

H3 C

O CH3

P Si Natural Products Solvents

19.4

O

64.8 22.6

95.0

141.1 101.1

121.8

108.8 147.8 O

64.5

O

51.1

O

O

27.5

X

O

144.1 99.4

94.8

S

68.5 27.0

S

75.3 126.3

24.9

69.5 27.7

Chemical Shifts of Acetals, Ketals, and Ortho Esters (δ in ppm) 53.7

N

C

O

68.6 28.5

O

68.4 26.5

O

68.1 46.7

N H

Hal O

O

O

13C

N

72.6

22.9

67.6

145.6 98.4

O

O

C

Chemical Shifts of Cyclic Ethers (δ in ppm)

O

13C

67.5

O O

121.0

50.4

H3 C O

O CH3

H3 C O

O CH3

O CH3

93.7

O

O O

H3 C

115.0

119.7 O

O

O

O

O CH3

14.8 58.3

100.7

112.9

O

59.5 15.2



4.9 Nitrogen Compounds

117

4.9 Nitrogen Compounds 4.9.1 Amines 13C

C

Chemical Shifts of Amines and Ammonium Salts (δ in ppm)

The protonation of amines causes a shielding of the carbon atoms in the vicinity of C the nitrogen. This shielding amounts to -2 ppm for an α carbon atom, -3 to -4 for a β carbon, and -0.5 to -1.0 ppm for a γ carbon. The most frequent exceptions occur in branched systems: Tertiary and quaternary carbon atoms in the α-position are C generally deshielded by protonation of the nitrogen (Δδ = +0.5 to +9 ppm) [1]. In the following, shifts induced by protonation (δamine hydrochloride - δamine, measured in D2O) are given in parentheses. 38.2 (-2.0)

28.3 (-1.8)

47.6 (-1.2)

H3 C NH2

H3 C

H3 C

15.7 44.5 (-3.2) (-0.6)

19.0 (-5.0)

NH2

27.4 (-5.4)

NH2

11.5 44.6 (-0.4) (-1.8) 26.5 (-4.9)

43.0 (+2.2)

64.2 (-5.4) HO

44.6 (-1.9)

N+ I-

N

24.0 (-2.6)

NH

52.4 (-1.4)

H N

21.3 12.0

45.7

N

Hal

HO

56.8

10.9

51.3 NH

N

N+ I-

60.4

S C

NH2

HO

60.3 (-3.5) HO

X

P Si

47.2 (+5.7)

(in D2O)

60.5

16.0

N

32.9 (-4.7)

22.8

HO NH2

55.4 9.5

O

12.0 (-0.5)

NH2

12.9 51.4 (-1.7) (+1.3)

NH

36.9 (-0.2)

(CH3 )4 N+ I–

N CH3

NH

C

56.5

H3 C

H3 C

C

57.4 (-1.0) N

Natural Products OH

Solvents

4 13C NMR

118 14.3 (-2.6)

C C

CH3

45.9 35.2 (-0.4) (-1.8)

C

C

23.2 (-2.9)

H N

C

12.8 (-2.1)

20.6 (-2.0)

CH3

53.6 44.6 (+0.5) (-1.3)

H3 C

N

Hal O

N H

51.2 (-3.0; -2.7*)

CH3

X

P Si

Natural Products 46.3

HN

Solvents

143.4 127.1 128.3

126.5

CH3

40.9 (-0.8)

55.5 (+3.8)

N

N

57.2

149.9 112.3 129.3

116.9

HN

143.2 117.9 129.4

118.0

CH3

38.7 (+0.2)

NH2

113.6 139.9

H3 C

58.7 (+0.6) 32.7 (-2.7) 25.7 (-0.3) 26.8 (-0.7) CH3 30.2

N

44.8

CH3

CH3 33.5 (-1.5)

CH3

53.6 (+8.9)

46.1 (-1.0; -2.3*) -0.2*) * doubly protonated form

NH2

NH2

N

CH3

28.5 (-2.7)

25.4 (-0.8)

CH3

CH3

H N

50.4 (+6.6)

CH3 (-2.6;

HN

118.5

18.7 (-1.3)

H3 C

NH2

146.7 115.1 129.3

CH3

CH3

36.6 (-1.3; -0.5*) * doubly protonated form

S

28.2 (-1.2) 33.9 (-2.5)

50.5 (+1.9)

CH3 N

H N

CH3

11.9 61.8 45.2 (-0.8) (-1.6) (-1.2)

51.1 (+0.7) 37.6 (-5.4) 25.8 (-1.0) 26.3 (-1.1)

N

C

H N

22.5 (-3.1)

12.5 54.0 36.1 (-0.9) (-2.1) (-2.0)

CH3 N

H N

N

CH3 41.1 (-0.7)

64.3 (+2.4) 29.2 (-1.6) 26.5 (-0.9) 26.9 (-1.2) H3 C

N

CH3 39.9

151.0 113.1 129.4

117.0

N

141.6 121.5 129.4

122.9



4.9 Nitrogen Compounds

13C

Chemical Shifts of Cyclic Amines (δ in ppm) H N

N

18.2

H N

N

47.1

48.6

N

124.3

19.3

42.7

H N

56.7

24.4

45.9

H N

54.2 125.0

25.9 H N

46.7 68.1

O

46.4

H N

28.5

25.7

51.7 26.2

119

N

45.3

57.7

17.5 N

47.9 27.8

47.7

26.4 H N

47.9

57.2 26.4

C C

C

C

C

49.2

31.3

N H

27.2

N

Hal O

4.9.2 Nitro and Nitroso Compounds 13C

Chemical Shifts of Nitro and Nitroso Compounds (δ in ppm)

61.2

12.3

CH3 NO2

13.3

29.6

19.8 75.6

70.8

NO2

NO2

87.0 32.6 24.8

NO2

NO2

10.1

85.0

28.6

NO2

18.7

84.6 31.4 24.7

25.5

21.2 10.8 77.4

20.8

NO2

82.9

NO2

C NO2

85.2

NO2

NO

134.6

135.5

148.4 123.6 129.4

S

78.8 26.9

28.2 19.6

NO2

N

X

P Si Natural Products

165.9 120.8 Solvents 129.3

4 13C NMR

120

4.9.3 Nitrosamines and Nitramines

C

C

C

Chemical Shifts of Nitrosamines (δ in ppm)

13C

C

C

32.1

H3 C

N

O

N

N

H3 C

N

41.5

H3 C–NH–NO2

19.1

N

23.7

54.2

11.8

40.0 H3 C

NO2

H3 C N

H3 C

NO2

45.4

O N

N

51.1

N NO2

4.9.4 Azo and Azoxy Compounds

Hal

13C

Chemical Shifts of Azo and Azoxy Compounds (δ in ppm) ­ 152.7

130.9

O

129.0

N

N

N

122.8

144.0

129.5 128.7

125.5

N+

122.3

N

128.7 131.5

O–

148.3

4.9.5 Imines and Oximes

S C

N

O

Chemical Shifts of Nitramines (δ in ppm)

32.5

N

45.2

20.3 22.5

14.5 47.0

39.9

13C

11.3

11.5 38.4

O

13C

X

P Si Natural Products Solvents

Chemical Shifts of Imines and Oximes (δ in ppm)

22.6

H3 C

154.2

N H

29.7

56.6

128.8 128.8 131.4

H N

29.3 163.4 17.8

N

50.6

120.9 129.2

136.3 160.4 152.1

23.6

125.9

128.1 129.7

169.2 128.5

N

41.3 128.1

139.8 136.4

127.7 129.7

128.3 127.2 17.3 119.4 128.9 130.4 123.2 N 139.5 165.3 151.7



4.9 Nitrogen Compounds

11.2

OH

H3 C

13.6

OH

H

19.6

N

N

H 147.8

H3 C 148.2 15.0

15.0 H3 C

N

OH N

32.3 26.3

21.7 H3 C 155.4

24.6

H 151.9

H3 C

27.5 26.1

N

20.2

N

12.4

OH

H

OH

31.5

13.9

155.9 OH

OH

159.4

27.1

121

152.3

154.3

N

N

H3 C

21.4

136.5 126.0 128.5

OH

134.0 128.0 128.0

C C

C

C

C

129.0

129.1

4.9.6 Hydrazones and Carbodiimides 13C

Chemical Shifts of Hydrazones and Carbodiimides (δ in ppm)

159.6

30.6 40.9

25.1

N

37.2 NH2

164.6

29.3

N HN

N

18.0

13.7

22.6 N

47.1

112.8 128.9 119.0

14.2

N C N

N

47.0

N HN

46.5

119.0

35.0 24.8

139.9 N C N

N S

112.8 128.9

140.7

24.8 49.0

O

N

16.2

143.2

140.2

Hal

40.5

20.1 167.2

N 167.2 19.7 N 33.1

N

55.7

25.5

C

X

P Si Natural Products Solvents

4 13C NMR

122

4.9.7 Nitriles and Isonitriles

C

Chemical Shifts of Nitriles (δ in ppm)

13C

C

CH3 CN

C

C

10.6

1.7 117.4

C

13.2

10.8 CN

CN

118.0

NC

14.6

CN 122.4

118.2

CH3

20.7

CN

CN 118.7

28.3 30.1 24.6

CN

CN

112.5 132.0 129.2

25.8

132.8

Chemical Shifts and 13C–14N Couplings of Isonitriles (δ in ppm, |J| in Hz) 13C

Hal O

Because of the symmetrical electron distribution around the nitrogen atom, the 13C‑ 14N coupling can be observed in the 13C NMR spectra of isonitriles, leading to triplets with intensities of 1:1:1 (spin quantum number of 14N: I = 1, natural abundance, 99.6%). 2J

7.5 1J 5.8 26.8 158.2

N

CH3 NC

S C

8.6

119.2

CN

19.8

13.3 19.3* * assignment uncertain 110.5 NC

123.7

19.9

CN

CN

131.2

107.8

N

CN

28.1

117.2

137.5

19.0* 119.9

125.1

28.5

21.9 119.8

16.8 27.4

120.8

3J

1J

≈0 15.3

3J

5.3 156.8

≈0 120.6

NC

36.4 6.5

P Si Natural Products Solvents

5.0 165.7

NC 165.7; 1J 5.2

126.7; 1J 13.2 126.3; 2J ≈ 0

NC

119.4 11.7

2J

X

1J

129.9; 3J ≈ 0 129.4; 4J ≈ 0

2J

4.9.8 Isocyanates, Thiocyanates, and Isothiocyanates 13C

26.3

Chemical Shifts (δ in ppm) 121.5

CH3 NCO

15.4 28.7

111.8

SCN

13.6

34.2

20.4 130.4

125 (broad) NCO

110.7

133.6 124.8 129.6

NCO

124.7

43.3

SCN– NH4 +

NCO 124.9

124.2

29.3 128.7 CH3 NCS

125.8

13.3

32.3

20.0

45.0

131 (broad)

NCS



4.10 Sulfur Compounds

123

4.10 Sulfur Compounds 4.10.1 Thiols

C

Chemical Shifts (δ in ppm)

13C

6.5

19.7

CH3 SH

12.0

21.0 14.0

19.1

35.7

35.0

SH

31.4 34.1

22.6

12.6

38.3 37.7

38.5 38.5 26.8

24.6

25.9

C

C

SH

27.3

SH

N

SH

141.0 127.9 128.5

130.6 129.2 128.8

126.8

C

38.8

64.2 HO

C

31.8 SH

28.1

24.6

28.8

SH

SH

SH

SH

HS

28.1 24.7

29.9

33.9

14.0 30.6 28.7

SH

SH

SH

26.4

22.2

SH

41.1

23.7

27.4

27.6

SH

Hal O

125.3

N

4.10.2 Sulfides 13C

H3 C

S

Chemical Shifts (δ in ppm) 19.3

S

25.5

CH3

S

S

14.8

34.1 22.0 S

30.4

23.2

S

S

43.1

30.9

33.4

S

15.5

H3 C

S

28.0 S

23.2

33.2

45.6

31.4 13.7

54.8 S

23.6

34.3 13.7

14.4 S

Natural

31.4 13.7 Products 59.2

S

H3 C

H3 C

X

P Si

34.1 22.0 S

C

S

CH3

Solvents

4 13C NMR

124

141.8

25.4 132.3 14.2

C C

C

C

S

S

C

110.5

138.5 126.6 128.7

S

18.7

S

S C

S

39.1

S

S

26.0

38.1

29.1

S

27.9 26.4

S

34.4 S

S

S

26.6

O

69.7

31.7 31.2

S

29.3 28.2

26.9 69.2

S

18.6

S

28.0

128.8

N

135.8 131.0 129.1

127.0

S

N

O

72.6 81.4

Chemical Shifts of Cyclic Sulfides (δ in ppm)

S

Hal

106.9

S

CH3 15.6

124.9

13C

S

27.0 68.5

O

S

31.9 S

S

33.9 S

29.8

X

P Si Natural Products Solvents

4.10.3 Disulfides and Sulfonium Salts 13C

H3 C

Chemical Shifts of Disulfides (δ in ppm)

S

22.0 S

CH3

S

32.8 S

14.5

S

136.0 S

127.2

127.4 129.3

13C

4.10 Sulfur Compounds Chemical Shifts of Sulfonium Salts (δ in ppm)

I–

CH3 S+

134.0

22.4

27.5 H3 C

125

I– CH3

S+

CH3 S+

26.9 13.6

39.8

21.8

22.7

130.1 131.0 7.1

I–

37.8 20.5

126.9

S+

22.1 BF4 –

C C

C

C

C

4.10.4 Sulfoxides and Sulfones 13C

Chemical Shifts of Sulfoxides and Sulfones (δ in ppm) O

H3 C

S

CH3

S

42.6

S

54.3

40.1

O O S H3 C CH3

O

O

O

25.4

O O S H3 C

25.3

6.7

48.2

39.3

49.0 19.3

CH3 43.9

146.1 123.5 129.6

130.9

O O S H3 C

O O 16.3 S H3 C

40.3

S

56.3 13.0

37.1

N

Hal O

15.2

N

53.5

S O O S H3 C

34.2

22.7 57.6

O

S

O

O

51.1

22.7

S

O

24.3

O

52.6 25.1

S

O 127.6

141.6

129.3 133.2

C

X

P Si Natural Products Solvents

4 13C NMR

126

4.10.5 Sulfonic and Sulfinic Acids and Derivatives Chemical Shifts of Sulfonic and Sulfinic Acids and Derivatives (δ in ppm) 13C

C C

C

C

C

39.6

8.0

CH3 SO3 H

46.7

52.6

9.1

CH3 SO2 Cl

60.2

18.8

SO3 H

13.7

12.1

67.1

SO2 Cl

17.1

13.7 51.8 15.5

S

N

S

S

42.7

Hal

23.3

O

18.2

59.8 25.1

S

48.7

CH3 56.5

135.2 128.0 129.4

132.3

24.5

SO2 Cl

O

S

O

S

26.2

35.3

48.4 22.9

S

O

23.5

O

74.6

SO2 NH2

144.1 126.8 129.7

134.0

SO2 Cl

74.2

SO2 Cl

SO2

143.5 126.3 129.8

N

O S

25.5

O SO3 H

O

S

O

SO3 H

55.9

67.6

O O

25.0

SO3 H

52.9

53.7

18.4

SO2 Cl

16.8

SO3 H

139.3 125.5 128.8

135.3

131.7

S 4.10.6 Sulfurous and Sulfuric Acid Derivatives

C

X

P Si

Chemical Shifts of Sulfurous and Sulfuric Acid Derivatives (δ in ppm) 13C

Natural Products

O

Solvents

S

O H3 C

O

58.3 O

O S

O

O

O

O

15.4 59.1 CH3

O

S

O

O

67.6 O O

O S

O

S

26.0

69.6 14.5

O

57.1



4.10 Sulfur Compounds

127

4.10.7 Sulfur-Containing Carbonyl Derivatives 13C

Chemical Shifts (δ in ppm)

The 13C chemical shifts of thiocarbonyl groups are higher by about 30 ppm than those of the corresponding carbonyl groups:

C C

C

Carbonyl groups of thiocarboxylic acids and their esters are deshielded by about 20 ppm with respect to the corresponding oxygen compounds. C

C

δC=S ≈ 1.5 × δC=O - 57.5

252.7

S

278.4

H3 C

CH3

41.8

232.8 H3 C

42.1 S

202.1

H3 C

39.2

S

20.6

49.6

140.1 128.1 128.8

12.3

132.1

12.3

226.2 S 20.2 H3 C

S

183.8 S

CH3

H2 N

S

H3 C

32.7

196.5

41.3 –

S

Na

+

S

N

49.6

45.2

(in D2O)

NH2

13.6

S

44.3 N

CH3

N

Hal

CH3

42.3

O

40.7 118.2

N

132.8

S C

194.0 S 43.2

S

S

22.2

32.1

199.4

NH2

S

28.4 S

30.1

H3 C

N

O

H3 C

33.3 206.7

NH2

205.6

CH3

S

194.1

SH

32.6

53.7

234.1

SH

O

194.5 H3 C

33.0

S

S

H3 C

CH3

N

N

CH3

CH3

43.2

X

P Si Natural Products Solvents

128

4 13C NMR

4.11 Carbonyl Compounds 4.11.1 Aldehydes

C C

C

C

Additivity Rule for Estimating the 13C Chemical Shifts of Aldehyde Carbon Atoms (δ in ppm) δC=O = 193.0 + ∑ Zi

C

–Cβ–Cα–CHO Substituent i

Zα

–C –CH=CH2 –CH=CH–CH3 –phenyl

Zβ

6.5 -0.8 0.2 -1.2

2.6 0.0 0.0 0.0

N

Hal O

Chemical Shifts of Aldehydes (δ in ppm)

197.0

H2 C O

N S C

13C

15.5

X

P Si

204.6 CHO

41.1

194.4 CHO

Natural 137.8 138.6 Products Solvents

31.3 200.5

H3 C CHO

36.7 201.3

13.8 24.3 22.4 43.6

CHO

176.8 CHO

83.1 81.8

202.7

5.2

CHO

205.6

23.4

CHO

42.4

CHO 204.7

50.1 26.1 25.2

25.2

15.7

201.6

13.3 45.7

CHO

95.3 176.9

Cl3 C CHO

CHO 192.0

136.7 129.7 129.0

134.3



4.11 Carbonyl Compounds

129

4.11.2 Ketones Additivity Rule for Estimating the 13C Chemical Shifts of Ketone Carbon Atoms (δ in ppm) δC=O = 193.0 + ∑ Zi O ǁ –Cβ–Cα–C –Cα–Cβ– Substituent i

Zα

–C –CH=CH2 –CH=CH–CH3 –phenyl

13C

207.6

O

6.5 -0.8 0.2 -1.2

H3 C

206.8

O

H3 C

31.9 14.0

218.0

O

28.6

209.4

O

H3 C

51.5

24.5

197.5

25.7

29.0

213.5 H3 C

H3 C

45.6

7.0

O

O

H3 C

25.7 137.4

O

O

215.1

8.0

183.6

O

128.6

O N

O

17.8

S

38.0 207.9

81.9

C O

21.1

H3 C

78.1

29.9

195.2 128.4 132.9

18.2 41.6

27.5

35.5

32.4

O

C

Hal

H3 C

45.2 13.5

H3 C

137.1

211.8

17.5

210.7

26.5

128.0

C

N

44.3

196.9 26.6 26.3

206.6 29.3

O

C

2.6 0.0 0.0 0.0

H3 C

35.2

27.5

43.5 23.8

29.4

27.6

H3 C

CH3

30.7

O

C

Zβ

Chemical Shifts of Ketones (δ in ppm)

206.7

C

O

137.8

130.1

10.3

128.2 132.2

X

P Si Natural Products Solvents

4 13C NMR

130 13C

Chemical Shifts of Halogenated Aliphatic Ketones (δ in ppm)

203.5

C

H3 C

84.9

C

C

25.1

C

C

200.1 27.2

H3 C

Hal O

O

N

Cl

203.5 Br

X

Natural Products

O

Solvents O

Cl

23.1

Br

84.9

Br

F

F F

21.1

Cl

F

Cl Cl

Cl Cl

114.4

F

175.5

96.5

O

H3 C

187.5

O

F F

O

O

Cl

F F

90.2

Cl

Cl Cl

115.6

O

H3 C

23.1

Br

Br Br

Chemical Shifts of Cyclic Ketones and Quinones (δ in ppm) O

208.9

155.1 158.3

P Si

Cl

70.2

172.9

115.6

O

H3 C

186.3

H3 C

25.1

109.8

O

22.1

187.0 136.4

O

219.1 38.2 23.4

9.9

O

F

H3 C

47.8

S C

13C

F

23.4

O

35.5

27.0

187.5

O

H3 C

193.6 49.4

199.0

F

O

H3 C

N

197.4

O

O

34.0

29.1

24.6 O

209.8 134.2

38.2 22.9

165.3

O O

O

209.7 41.5 26.6

180.4 130.8 139.7

30.6 O

199.0 129.9

25.8

214.9 43.9 24.5

150.6

185.8 127.3 156.7 37.9 26.7

131.8 O 126.2 184.7

133.7

138.5

O



4.11 Carbonyl Compounds

13C

Chemical Shifts of Diketones (δ in ppm)

197.7

201.1

O CH3

H3 C

23.2

131

O

H3 C

O

H3 C

CH3

56.6

28.5

O

206.9

O

Enol form: see Chapter 4.8.1

37.0

29.6

CH3 O

4.11.3 Carboxylic Acids

C C

C

C

C

Additivity Rule for Estimating the 13C Chemical Shifts of Carboxyl Carbon Atoms (δ in ppm) δC=O = 166.0 + ∑ Zi –Cγ–Cβ–Cα–COOH Substituent i

Zα

–C –CH=CH2 –phenyl

13C

12.0 5.0 6.0

3.0 0.5 1.0

N

Zγ

Hal

-1.0 -1.5 -2.0

O N

Chemical Shifts of Carboxylic Acids (δ in ppm) 166.3

H COOH

18.8

Zβ

184.1

COOH

34.1

172.0

COOH

133.2 128.1

20.8 178.1

H3 C COOH

180.6

14.2 27.7 22.7 34.8

COOH

156.5

COOH

78.6 74.0

181.5

8.9 27.6

COOH

185.9

27.0

COOH

38.7

182.1

COOH

43.7 29.6 26.2

26.6

18.4 13.6

36.2

30.6 29.6

180.7

179.4

47.9

COOH

172.6

COOH

130.6 130.1 128.4

133.7

S

COOH

C

X

P Si Natural Products Solvents

4 13C NMR

132

Chemical Shifts of Halogenated Carboxylic Acids (δ in ppm)

13C

C C

115.0 163.0 F3 C

COOH

63.7 170.4

88.9 167.1

Cl3 C COOH

Cl2 HC COOH

C

C

C

13C

Chemical Shifts of Dicarboxylic Acids (δ in ppm)

160.1

COOH COOH

N

13C

Hal O

40.9

169.2

COOH

28.9

COOH

173.9

COOH COOH

H

COO–

24.4 182.6 20.8* 177.6*

181.8

P Si Natural Products Solvents

134.2

166.6

COOH

HOOC

COOH

H3 C

11.1 185.1 10.6* 181.3*

COO–

COO–

COO– Na+

36.1

188.6

COO–

174.5

COO–

126.7 134.3

20.5

138.2 133.1 130.7

133.1

184.8

COO– Na+

COO– 185.4

47.2 30.9 26.9

26.9

(in DMSO)

COO– 177.6

20.2

14.2 40.5 31.5 28.4* (in DMSO) * in CDCl3/DMSO

* in CDCl3

X

COOH

Measured in water unless indicated otherwise. 171.3

S

130.4

166.1

Chemical Shifts of Carboxylate Anions (δ in ppm)

N

C

40.7 173.7

ClH2 C COOH

45.0 175.9

ClH2 C COO–

65.6 171.8

Cl2 HC COO–

96.2 167.6

Cl3 C COO–



4.11 Carbonyl Compounds

133

4.11.4 Esters and Lactones Additivity Rule for Estimating the 13C Chemical Shifts of Ester Carbon Atoms (δ in ppm) δC=O = 166.0 + ∑ Zi –Cγ–Cβ–Cα–COO–Cα' – Substituent i

Zα

–C –CH=CH2 –phenyl

13C

12.0 5.0 6.0

Zγ

3.0

Zα'

-1.0

C

C

C

C

-5.0 -9.0 -8.0

1.0

Chemical Shifts of Acetic Acid Esters (δ in ppm)

171.3 O H3 C

51.5 O

20.6 168.0 O H3 C

CH3

170.7 O H3 C

60.4 O

20.9

14.4

170.3 O H3 C

H3 C

97.5

21.0

O

67.5

O

21.3

169.2 O 72.3

141.4 O

20.6

13C

Zβ

C

32.2

170.2 O H3 C

O

21.9 22.3 169.2 O

26.1 24.4

79.9

H3 C

O

H

49.1 O

177.4 O 19.1 34.1

CH3

H3 C

20.6 51.5

O

171.3 O

CH3

51.5 O

CH3

173.3 O 9.2 27.2

173.4 O 15.1 28.5 23.9 34.9

51.5 O

51.6 O

CH3

CH3

O

125.3 121.4

N

128.9

S

Chemical Shifts of Methyl Esters (δ in ppm)

161.6 O

Hal

28.1

150.9

20.8

N

C 172.2 O 18.9 13.8 35.6

51.9 O

178.8 O 27.3

38.7

CH3

X

P Si Natural Products

51.5 Solvents O

CH3

4 13C NMR

134

167.8 O Cl

C C

C

C

C

165.1 O

53.0 O

40.7

Cl

CH3

153.4 O 74.8

75.6

26.0 26.4

175.3 O 29.6

167.6

O

O CH3 53.1

O

O CH3

Hal

O

O

41.2

O O

CH3 52.1 CH3

133.5 H3 C

13C

X

O

58.7

69.3

CH3

O

128.4 132.8

CH3

166.8 O 129.7

51.8

CH3

O

130.5

173.1 O

CH3 52.3

29.1

O O

CH3

CH3 51.3 CH3

O

O

CH3 52.2

O

O

152.3

CH3 53.6

74.6

O

O

CH3

Chemical Shifts of Lactones (δ in ppm)

Natural Products 171.2 O Solvents

51.2

51.5 O

128.8

89.6

O

168.6 O

P Si

Cl

O

O

S

O

CH3

165.3 O O

N

C

O

165.8 O 130.1

O

166.5 O 55.7 130.4

43.3

158.4

N

Cl Cl

64.1

Cl

O

CH3

O

CH3

162.5 O

54.2

O

22.3

178.1 O 39.1

177.1 O 27.8

O

68.8 22.3 163.8 O O 29.2 19.1 66.6

24.0

O

174.4 O 34.2

153.6 100.2 (in acetone) 161.6 O

146.2 121.4

152.1

O

106.0

O

67.9

87.6 180.5

OH

176.0 O 117.0 142.9

O

69.2

34.6 23.0

29.3 29.0



4.11 Carbonyl Compounds

135

4.11.5 Amides and Lactams Additivity Rule for Estimating the 13C Chemical Shifts of Amide Carbon Atoms (δ in ppm) δC=O = 166.0 + ∑ Zi –Cγ–Cβ–Cα–CO–N

Substituent i –C –CH=CH2 –phenyl

13C

Zα

Zβ

7.7 3.3 4.7

/

Cα' –Cβ'

\

Cα' –Cβ' Zγ

4.5

Zα'

-0.7

-1.5

H

H

33.0 N H

14.6

≈ 90%

Hal

N H

CH3

H

162.6 O NH

H

CH3 28.2

N

H

36.9

≈ 10%

H

16.8

H3 C

171.7 O NH2

22.3 * in water: 177.0

H3 C

22.7

26.1

N H

CH3

N

CH3

162.6 O NH

CH3

36.5

≈ 10%

164.9 O

O

31.5

36.7 N

41.9

S 12.8 C

14.9

Primary and Secondary Acetamides: 173.4* O

C

N

166.5 O

24.8

≈ 90% 161.8 O

C

-4.5

163.3 O NH2

C

-0.3

Formamides:

H

C

Zβ'

Chemical Shifts of Amides (δ in ppm)

167.6 O

C

22.8

P Si Natural Products

171.0 O H3 C

X

34.4 N H

14.6

Solvents

4 13C NMR

136

169.8 O H3 C

C

22.5

C

C

C

C

40.7 N H

168.3 O H3 C

22.9

168.6 O

11.1

H3 C

22.5

168.1 O

128.6 N H

N H

22.6

H3 C

95.5

N H

22.7

H3 C

22.3

47.5

N H

23.6

138.2 169.5 O

25.4 24.7

32.6

49.9

169.0 O

40.5

H3 C

124.1

N H

24.1

28.6

120.4

128.7

Tertiary Amides: 170.0 O H3 C

21.5

N

Hal O

CH3 35.0

N

S

172.2 O 18.9

13C

X

P Si

N

40.0 N

42.9

170.1 O 13.1

H3 C

21.5

14.2

N

50.6

143.2 169.1 O 23.2 H3 C 143.2

13.2

14.4

N

47.4

11.4

21.0 11.2 22.2

126.7 127.6

129.1

127.6 129.1

Chemical Shifts of Lactams (δ in ppm)

179.4 O HN

175.5 O 30.3

42.4 20.8

HN

125.1

21.4

40.1

Natural Products 171.9 O Solvents

H3 C

CH3 38.0

14.0 35.1 42.0

N

C

169.6 O

105.1

HN

127.6

49.5 147.6 164.7 O

30.5 20.1

171.9 O

HN

37.9

22.5

HN

42.0

22.3

31.5 20.9

165.0 O HN 123.2 139.7 136.1

106.6

169.4 O 34.4 N

49.9

23.3

32.3 21.6

179.4 O 120.8 142.0

HN

42.5

36.8 23.4

29.9 30.7



4.11 Carbonyl Compounds

137

4.11.6 Miscellaneous Carbonyl Derivatives 13C

Chemical Shifts of Carboxylic Acid Halides (δ in ppm)

161.0 O

170.4 O

H3 C

H3 C

Cl

I

47.3

176.3O 29.7

25.5 25.9

Cl

131.4

H3 C

Br

39.1

C

156.1 O

Cl

55.4

128.8 135.1

168.0 O 131.2

C

C

C

C

Cl

133.2

Chemical Shifts of Carboxylic Acid Anhydrides (δ in ppm)

158.5

O

166.6 O

O

H

O

13.4 37.2

35.2

CF 48 Hz 150.1 O O

O

113.5 1J CF 285 Hz

O

172.5

O O

172.8 O 18.3

O

2J

F3 C

O

22.1

O

154.0 O CF3

Cl3 C

87.9

O

137.4

165.9

O O

170.9 O 8.5

O

H3 C

H

169.6 O 18.2

28.2

Cl

33.6

165.6 O 137.3

41.0

13C

H3 C

F

174.7 O 9.3

165.7 O

CH3

O

O

CCl3

30.1 16.7

27.4

40.2

O

128.9 134.5

O

168.5

O O

O

Hal

O

173.9 O 26.5

O

N

O

O

N

O

S

162.4 O 130.5

O

C

O

128.9

X

P Si Natural Products

131.1 O 125.3 163.1 136.1 Solvents O O

4 13C NMR

138 13C

Chemical Shifts of Carboxylic Acid Imides (δ in ppm)

171.6 O

C

H3 C

C

C

173.0 O

O N H

24.1

CH3

H3 C

C

135.5

CH3 31.3

O

P Si Natural Products Solvents

O

H3 C

O

CH3

O

O 155.9 O O

O

14.4

68.1

H2 N

NH2

N

N H

N H

45.0

48.0

O

O–

N

H3 C

12.3

14.7

12.3

S

S

N

38.5

N

CH3

S– Na+

49.6 (in D2O)

194.0 S 43.2

N

43.2

N

140.3

N

22.3

O

226.2 S 20.2

165.4 O 38.5

34.0

35.6

N

168.2

O

206.7 S 49.6

60.7 O

15.5 (in DMSO) 156.9 O

162.0 O

–

O 148.7 O O

21.7

O

158.7 O

S

13.6 30.9

157.8 O 27.4

163.5 O

31.4

O

O

H3 C

O

155.9 O 19.1 67.3

131.7 O 153.4

(in D2O)

H2 N

S C

155.4 O 63.8

O– NH4 +

H2 N

192.8

O C O

162.0 O

X

23.2

124.2

156.5 O 54.9

N

C

N CH3

Chemical Shifts of Carbonic Acid Derivatives (δ in ppm)

65.0

S

131.5 O 122.4 167.5

O

C O

Hal

24.0

O

133.7

N CH3

N CH3

23.6

181.3

N

O

170.8

134.3

NH O

13C

CH3

177.6

27.9

NH

O

173.0

O

183.6

30.3

N

26.0

O

C

O

O

N C N

24.7

49.0

N



4.12 Miscellaneous Compounds

139

4.12 Miscellaneous Compounds 4.12.1 Compounds with Group IV Elements 13C

C

Chemical Shifts of Silicon Compounds (δ in ppm) CH3

CH3

0.0

H3 C Si CH3

Cl Si CH3

CH3

CH3

7.4

O

4.7

Cl Cl Si

3.1

Cl

169.0

O

5.0 O

16.2 16.6

138.7

26.6

21.6

Si

Cl

6.7

Cl Si CH3

CH3

Si

Cl

3.3

Si

9.8

Cl Si CH3 Cl

-2.0

Si

C

N

Hal

Si

58.3

-7.1 O

C

135.7

18.3

O

C

136.3

129.6

H3 C Si O

C

134.3

136.4 129.6

O

127.9

N

13C

Chemical Shifts and Coupling Constants of Germanium and Lead Compounds (δ in ppm, |J| in Hz) CH3

CH3

H3 C Ge CH3 -3.6

H3 C Sn CH3 -9.3

CH3

1J

CH3 3J 2J

52 38

4J 1J

128.3

137.9

19

C 3J 2J

478

Sn

135.4 129.1

11

531

Ge

136.2

H3 C Pb CH3 -4.2

CH3 4J

80 67

Pb

137.2

128.6 129.1 Couplings with 119Sn (8.58%, I = 1/2)

S

CH3

150.1

137.6

129.5 128.5 Couplings with 207Pb (22.6%, I = 1/2)

X

P Si Natural Products Solvents

140

4 13C NMR

4.12.2 Phosphorus Compounds 31P

(natural abundance, 100%) has a spin quantum number I of 1/2. Couplings to protons through up to 3–4 bonds are usually observed.

C C

C

C

Phosphines and Phosphonium Compounds (δ in ppm, |J31P13C| in Hz) 1 11 1J 12 J 16 24.5 32.6 14.4 3J

C

13.9 4J 0

28.3 2J 14

3J

12 1J 11 24.8 28.6

CH3

P

14.0 4J 0

CH3

27.9 2J 15

1J

12 126.0 P

PH2

130.8 2J 20

2J

1J

15 11.3

3J 4J

N

Hal

CH3

1J

H3 C

P

P

H3 C

CH3

39.3 1J 8

55 10.7 P+

CH3 CH3

I–

1J

O

2J

5 6.3

N

1J

49 12.3

I

15 1J 48 24.1 18.7

Solvents

23.7 2J 4

10 3J 12 134.0 130.7 2J

P Si Natural Products

13.3 4J 0

–

X

Br–

86 2J 10 3J 12 118.3 133.7 130.6 4J 2 135.1

3J

P+

S C

10 2J 14 27.0 28.9

0 26.0

20 3J 7 4 133.6 128.4 J 0 1J 12 128.5 137.2

P+

P+

Br– I

22.7 1J 50 24.6 3J 5 10 3J 13 134.3 131.0 2J

4J

3 135.6

117.3 1J 90

119.1 145.5 1J 80 2J 0

23.8 2J 15

P+

–

Cl–

P+

4J

3 135.9

117.4 1J 89

13.8 4J 0



4.12 Miscellaneous Compounds

141

Phosphine Oxides and Sulfides (δ in ppm, |J31P13C| in Hz) 3J

13 24.4

4J

0 13.6

3J

2J

5 24.0 P

3J

1J

13.6 4J 0

24.8 2J 4

54 16 54 23.9 34.6 CH3 20.8

1J

66 27.8 O

4J

1J

P

16 24.0

0 13.6

2J

4 24.6

S

P

1J

51 30.9 S

CH3

132.3; 4J

131.5; 4J

3 128.8; 3J 12 132.3; 2J 10 135.6; 1J 104

P

P O

3 128.5; 3J 13 132.3; 2J 10 133.1; 1J 85

11 1J 20 24.7 33.6 14.0 4J 0

24.8 2J 16

5J

3J

0 13.7 ­

3J

11 1J 44 23.4 42.9

2J

P O

O

12 53.4

CH3

13.7 4J 0

CH3

25.1 2J 14

O

P

O

5J

N

O

H3 C

O

16.5 3J 6

N

33.9 2J 19

0 3J 7 129.5 124.1

C

C

P O

O

N

Hal O

CH3

48.8 2J 12

N

O P

151.5 2J 4

C

O

O

O P

6.6 2 19.0 J 7 1J 143

16.3 2J 6

5 62.1 O P O

128.5 1J 187

X

P Si

2J

7 61.4

O

S

O

0 124.1

2J

P

C

4J

5 33.4

19.1 61.9 4J 0 2J 11

N

H3 C

PCl2

C

S

Phosphinic and Phosphorous Acid Derivatives (δ in ppm, |J31P13C| in Hz) 3J

C

O 2J 10

Natural Products

131.7 128.5 Solvents 3J 15 132.4 4J 3

4 13C NMR

142

Phosphoric Acid Derivatives (δ in ppm, |J31P13C| in Hz) 4J

C C

C

0 18.9 13.6 5J 0

3J

7 32.6

125.5; 5J 0

O

O

67.2 2J 6 O

O

C

125.1; 5J 0

P O

C

129.8; 4J 0 120.5; 3J 4 150.4; 2J 8

O P O

H3 C O P O

O

129.7; 4J 0 120.1; 3J 5 150.4; 2J 8

O

O

Phosphoranes and Phosphorus Ylides (δ in ppm, |J31P13C| in Hz)

N O

P O O O

Hal O

24.1 3J 6

N

3J

11 128.5

1J

1J 90 56 19.7 CH3 -1.5

H3 C P

9 132.9

130.6 4J 3

CH2

CH3

(in benzene)

68.5 2J 13

2J

1J

P

111 2J 4 3.2 11.0

CH

CH3

133.3 1J 83

4.12.3 Miscellaneous Organometallic Compounds

S C

O

Lithium Compounds (δ in ppm)

X

-15.3

H3 C

Li

183.4

33.5 9.7 18.9 33.9

Li

132.5

P Si Natural Magnesium Compounds (δ in ppm) Products Solvents

-14.6

H3 C MgI

17.0

141.0 102.0

15.0

MgBr

Li

85.3 115.8 130.9

Li

131.6

MgBr

93.2 117.6 131.7

133.0



4.12 Miscellaneous Compounds

143

Boron Compounds (δ in ppm, |J| in Hz) CH3

14.8

H3 C B

–

H3 C B

CH3

H3 C

11.8

6.2

CH3 Li

+

15.3

CH3

B–

109.9

85.7

Na+

121.4; 4J 51.3

H3 C O

64.9

O

CH3

B

B O

CH3

O

10.3

163.3; 1J

24.9

C

C

125.2; 3J 3 C 135.5; 2J 1

C

0

50

C

B–

O

H3 C O

Na+

Couplings with 11B (80.4%, I = 3/2)

N

Arsenic, Antimony, and Bismuth Compounds (δ in ppm)

134.8

H3 C 11.2 As CH3 H3 C

120.2

CH3 8.4 H3 C As+ CH3 I–

As

CH3

131.3 132.8

Hal O

+

N

–

Cl

S 133.7 128.6

136.8 129.4

128.4

As

139.6

Sb

129.1

138.1 131.0

139.3

5.9

3.5

H3 C Hg

165.5

C N

Couplings with 199Hg (16.8%, I = 1/2)

2J

C

X

P Si

131.1

Mercury Compounds (δ in ppm, |J| in Hz)

H3 C Hg Cl

128.3

Bi

3J

85 104 137.4 128.3 Hg

170.3; 1J 1275

Natural Products

128.0 Solvents 4J 20

4 13C NMR

144

4.13 Natural Products 4.13.1 Amino Acids

C C

13C

Chemical Shifts (δ in ppm; solvent: water)

C

41.5 +

C

H3 N

C

42.8

OH

O

+

171.2

H3 N

H3 N

OH

O

175.7

+

H3 N

+

Hal

O

17.9 30.0

N

174.0

+

+

H3 N

O

172.7

X

P Si

+

30.3 +

H3 N

O

174.0

15.3 37.1 +

H3 N

+

172.8

(pH 0.28)

17.5 51.9 O–

177.0

H3 N

19.2 61.9 O–

175.4

21.8 25.1 40.7 22.9 54.4 O–

H3 N

O

15.9 37.1 +

H3 N

176.3

12.4 25.6

60.9 O– O

175.0

(pH 6.04)

182.7

O

H2 N

39.3 41.6

O–

O

182.7

(pH 12.56)

H2 N

21.7 52.7 O–

185.7

O

(pH 12.52) 17.9

(pH 7.00)

25.9

O

179.4

(pH 5.64)

12.1

58.7 OH

O

O

(pH 0.37)

Natural Products Solvents

22.1 25.1 40.1 22.7 52.8 OH

H3 N

17.8

(pH 1.34)

S

O–

(pH 4.96)

18.5 59.6 OH

34.8

O

(pH 0.43)

O

C

H3 N

16.5 50.1 OH

38.8

O–

H2 N

(pH 12.01)

(pH 5.03)

(pH 0.49)

N

46.0

(pH 4.53)

36.6 32.2

173.6

O

(pH 0.45) +

O–

32.9 H2 N

20.3 63.2 O– O

184.1

(pH 12.60) 22.5 25.6 45.5 23.7 55.9 – O

185.4

H2 N

O

(pH 13.00) 16.7 39.8 H2 N

12.3 25.2

62.3 O– O

184.1

(pH 12.84)



4.13 Natural Products 60.4

+

H3 N

OH

61.2

56.0 OH O

+

171.3

H3 N

+

H3 N

66.9

+

171.7

(pH 1.36) 25.1 +

H3 N

(pH 5.87)

SH

55.9 O

25.5 OH

+

171.9

H3 N

173.1

(pH 5.14)

H3 N

62.1 O– O

H2 N

30.6

53.2 OH

+

172.9

H3 N

C

C

C

C

SH

60.7 O– O

182.1

N

Hal O

14.9 S

29.8

34.0

54.9 O– O

(pH 1.55)

C

177.3

(pH 11.02)

S

29.5

O

20.3

14.8

S

+

H2 N

32.0

56.7 O–

14.8

176.1

(pH 9.27)

SH

O

(pH 1.75)

29.9

68.6

173.6

O

57.8 O– O

HO

61.5 O–

H3 N

H2 N

OH

(pH 9.28)

20.6

HO

59.8 OH O

173.2

(pH 6.05)

20.2

66.3

62.9

57.5 O– O

(pH 1.12) HO

OH

145

174.8

(pH 5.83)

H2 N

N

30.4 55.8 O– O

181.3

S

(pH 9.80)

C O

37.4 +

H3 N Cl–

O NH3

HO

+ –

–

Cl

NH3 +

O

S

S

S

S

51.2 OH O

X

168.9

(in DMSO)

44.1 +

H3 N

Natural Products

55.8 O– O

P Si

180.7

(in D2O)

Solvents

4 13C NMR

146

130.0 130.2 128.5 136.0 37.2 56.9 O–

C C

C

C

C

+

H3 N

O

174.7

O

35.0 +

+

116.8 OH 131.7 155.8 127.8 36.4 57.1 O–

H3 N

O

OH

172.0

50.6 O (pH 0.41) O

N

Hal

26.1 +

O N

172.6 53.4 O (pH 0.32)

+

S

H3 N

28.1 +

C

OH

X

P Si

Solvents

OH

172.8 53.7 O (pH 0.46)

H3 N

O

28.2 +

182.4 34.7 O

28.7

40.3 24.0 O–

175.3 55.5 O (pH 5.02)

H2 N

27.6 22.6 OH

173.2

54.0 O (pH 0.50)

40.5 31.2 H2 N

181.3 O– O–

H2 N

183.4

55.3 O (pH 12.73) O

33.0

–

175.8 56.0 O (pH 6.95) H3 N

44.5

OH

H3 N

+

173.8

O

O–

184.0 35.3 O–

H2 N

183.9 57.2 O (pH 12.51) H2 N

33.3

41.9 29.4 O–

H2 N

184.6 57.2 O (pH 13.53)

NH3 +

NH3 +

30.5 +

24.0

H3 N

40.5

Natural Products

40.2

O–

175.5

53.5 O (pH 6.73)

172.4 30.7

H3 N

178.7 OH

H3 N

OH

H3 N

(in D2O/DCl)

37.8 +

+

O

O

174.4 OH

H3 N

174.9

118.6 OH 133.5 157.7 128.2 37.3 56.7 OH

NH2

27.7 22.6 O–

175.8

55.9 O (pH 6.03)

41.8

35.7 H2 N

33.0 23.6 O–

184.6

57.3 O (pH 13.85)

+

4.13 Natural Products H2 N HN

157.8

28.0 +

+

NH2

24.9

28.8 H2 N

172.8

53.9 O (pH 1.33)

H2 +

O

HO

38.5 71.1 61.0 O– 54.0 175.1 N

118.9

73.9 57.7

NH3 +

N

42.1 25.6

32.7

175.4

O–

183.9

H2 N

56.6 O (pH 11.52)

O

117.7

H

C

C

C

C

O

(pH 9.80)

N

Hal O

O

NH3 +

C

24.8 30.0 62.4 O– 47.2 175.8 N

41.9 64.5 O– 179.2 N H2 +

O

157.8

–

(pH 7.26)

HO

N

25.0 O

NH2

HN

41.6

24.8 30.0 62.3 O– 47.2 175.4 N

(pH 1.27)

H2 +

HN

157.9

55.4 O (pH 7.87)

24.4 29.4 61.0 OH 47.4 173.3 N H2 +

NH2

HN

41.5

OH

H3 N

H2 N

147

N

N

118.2

NH2

53.6 OH 55.7 O– 56.1 O– S 172.1 174.8 176.9 135.0 N 137.2 N 137.1 N 26.2 29.0 30.1 H H H O O O 127.7 133.1 133.5 C X (pH 1.74) (pH 7.82) (pH 9.21) NH3 +

121.8 120.5

56.0 O 128.9 28.2 174.7 124.5 OH

N H

114.2 127.6

114.2 138.6 (in D2O/DCl)

NH3 +

120.3 119.3

P Si

56.1 O 127.7 27.2 174.8 Natural 122.9 Products O–

N

112.7 H 137.3 (80 oC)

108.7 125.8

Solvents

4 13C NMR

148

4.13.2 Carbohydrates 13C

C C

Ribose

C

C

Chemical Shifts of Monosaccharides (δ in ppm)

HO

68.1 63.8 O

70.1

C

HO

94.3

OH OH 70.8 OH

62.1

83.8 70.8

HO

N

Hal

HO

70.4

HO

S C

X

P Si Natural Products Solvents

97.1

71.7

OH

OH OH 69.2 O

CH3 56.7

63.3

OH 71.0

61.9

84.6 69.8

OH

O

101.7 76.0

OH

O O CH3 55.5

71.1

OH

HO

HO

O OH 103.1 CH3 57.0

OH 71.9

HO HO

100.4

OH OH 94.7

83.3 71.2

OH

68.6 63.9 O

68.6

69.7

HO

67.4 60.8 O

O N

O

HO

68.2 63.8 O

62.9

83.0 70.9 HO

O CH3 55.3

O

108.0 74.3

OH

Glucose 70.6

HO HO

70.6

HO HO

OH 61.6

72.3

70.6

O

73.8

92.9

OH 72.5 OH

OH 61.6

72.5

70.6

O

74.1

OH 72.2 O

HO HO

100.0 CH3 55.9

HO HO

OH 61.7

76.8

O

76.7

OH OH 96.7

75.1

OH 61.8

76.8

O

76.8

O OH 104.0 CH3 58.1

74.1



4.13 Natural Products OAc 61.1

70.0

68.1

AcO AcO

69.4

O

70.0

89.2

OAc 69.4 OAc

AcO AcO

149

OAc 61.7

72.8

O

72.8

OAc

OAc 91.8

70.5

Fructose HO

HO O

71.3

70.9

OH

65.9 OH OH

traces in water and in DMSO

HO

61.9

82.2 77.0

105.5 O

63.8

OH

OH

OH

HO

82.9 4% in water, 20% in DMSO 13C-1H

99.1 OH

64.1 70.0

O

OH

OH

C C

C

C

C

64.7

70.5 68.4 75% in water, 25% in DMSO HO

HO

HO

63.2

81.6 75.4

HO

N

102.6 O

OH OH

63.6

Hal

OH

O

76.4 21% in water, 55% in DMSO

N

Coupling Constants through One Bond (1JCH in Hz) O

1 13 C H JCH 169–171

OR

S

O 13

C OR

H 1JCH 158–162

C

X

P Si Natural Products Solvents

4 13C NMR

150

4.13.3 Nucleotides and Nucleosides 13C

C C

C

C

C

Chemical Shifts of Nucleotides (δ in ppm)

.

NH2

93.4b, 95.8a 143.5b, 144.0a

N

N H

160.8

159.9a, 157.8b O

O

H3 C

107.7b, 110.9a 137.6b, 139.8a

N

N H

O

O

144.5

N

N

140.3

153.9a, 151.5b O

N H

N

N

145.8

149.8

(in D2O)

S

152.3 O

N N H

N

N

N H

153.4

N

151.7 (in DMSO)

119.6 O 150.1

N H

119.1 NH2 156.4

NH

115.9 NH2 . HCl 151.4

NH

(in DMSO)

(in D2O)

168.3a, 164.9b

N H

165.1

101.0 142.9

149.7

(a in D2O, b in DMSO)

Hal

C

N

146.9

(a in D2O, b in DMSO) 11.7b, 12.1a

O

NH2 HCl

168.1a, 167.5b

108.4 O

168.8 NH

137.9 NH2

N

162.2 160.0

N N H

(in D2O)

155.7 NH

N

.

NH2 HCl

150.5 153.8

(in DMSO)

Nucleosides (δ in ppm)

X

P Si

93.9b,

141.5b,

166.9a, 165.5b

96.9a

N

142.4a

HO Natural Products 60.6b, 61.7a

84.1b, 84.6a

Solvents

O

NH2

73.9b, 70.2a

N O

158.2a, 155.4b O

91.2a, 89.2b

74.8a, 69.4b OH OH

(a in D2O, b in DMSO)

101.7b, 140.6b, 60.8b,

166.9a, 163.0b

103.1a

NH

142.6a

N

HO

61.6a

84.8b, 85.0a

69.8b, 70.3a

152.4a, 150.7b

O

O

90.2a, 87.7b

74.5a, 73.5b OH OH

(a in D2O, b in DMSO)



4.13 Natural Products O

12.3

H3 C

HO

61.6 85.0

152.6

N O

O

NH

109.3b, 112.2a 136.0b, 138.3a O

70.4b, 71.3a

74.2

39.4a, 39.5b

120.1b, 119.6a NH2 155.5a, 156.9b

62.4b,

86.6b,

HO

62.0a

86.3a

N

71.4b, 71.1a

N

N

149.0a,

O

88.9a,

152.1a, 153.2b

149.8b

88.8b

74.3a, 74.3b

117.7 O 136.7 HO

62.5 86.3

62.6a

88.7b, 88.3a

O

71.8b, 72.1a

N N

C

C

C

157.8 NH

N

N

152.3 87.5

154.7 NH2

N

Hal

74.8

N

N

149.0a,

153.0a, 154.7b

151.9b

85.5a, 83.8b

40.0a, 39.7b OH

(a in D2O, b in DMSO)

O

(in DMSO)

117.7b, 119.7a NH2 156.1a, 157.9b

HO

C

OH OH

(a in D2O, b in DMSO)

62.8b,

N

O

71.4

OH OH

136.4b, 141.1a

85.9a, 83.7b

(a in D2O, b in DMSO)

(in D2O)

N

C

O

OH

OH OH

140.7b, 141.4a

152.4a, 150.4b

N

HO

61.3b, 62.0a 87.2b, 87.3a

89.9

70.2

167.2a, 163.6b

H3 C

NH

112.3 138.2

O

12.1b, 12.3a

167.2

151

117.4 O 138.5 HO

62.5 88.0

O

72.0

N

N

159.7

S

NH

N

N

152.0 84.8

39.6 OH

(in D2O)

154.6 NH2

C

X

P Si Natural Products Solvents

152

4 13C NMR

­4.13.4 Steroids 13C

C C

C

C

C

21.2 26.8

Chemical Shifts (δ in ppm) 18.3 40.7 40.7 24.1 20.7 37.6 43.6 54.5 40.3 26.9

33.8

N

Hal

22.7

S C

27.3

P Si Natural Products Solvents

26.9

36.1 20.4 27.4

11.0 36.8 42.9 17.0 21.0 35.8 54.3 50.8 38.7

170.1

35.8 23.5 31.9

12.6 40.7 43.0 12.5 21.3 39.2 55.3 57.1 47.6 29.2

X

H

O 197.7 123.9 32.5

O N

27.2

36.7

H

29.2

25.4 38.0

22.0 26.6

17.3 40.3 40.6 12.0 20.7 37.6 54.5 54.9 46.9 28.9

OH 81.0 30.4

32.6

36.1

H

28.9

13.0 36.0 43.7 17.0 21.2 35.7 54.7 56.2 169.3

38.3

O 197.4 124.0 32.3 19.1 36.3 56.8 36.7

35.7 20.3 32.3

33.9 23.0 30.7

12.0 40.0 42.4 19.4 21.2 37.5 50.5 56.9

25.3 38.8

O

197.8

63.3 24.4 38.8

18.8 35.4 56.5 36.4

28.7 24.4 28.3 24.1 31.6 36.5 32.3 24.3 40.0 39.6 71.3 141.2 28.5 28.0 32.0 HO 23.1 23.8 22.5 22.8 42.4 121.3

36.0 24.6 32.6



4.14 Spectra of Solvents and References

153

4.14 Spectra of Solvents and Reference Compounds 4.14.1 13C NMR Spectra of Common Deuterated Solvents (125 MHz, δ in ppm) Acetone-d6 206.0

29.8 31

200

180

Acetonitrile-d3

160

140

120

100

80

30 60

40

Benzene-d6

160

140

120

C

C

C

20

0

1.3 2

180

C

29

118.3

200

C

100

80

60

N

1

40

20

0

Hal

128.0 129 200

180

Bromoform-d

128 160

O

127 140

120

100

80

60

40

20

N

0

S

10.3 11 200

180

Chloroform-d

160

140

120

180

80

60

40

20

0

77.0

78 200

100

C

10

160

140

120

77

80

60

P Si Natural Products

76 100

X

40

20

0

Solvents

4 13C NMR

154

Cyclohexane-d12

C C

26.4

C

C

C

27 200

180

160

Dimethyl sulfoxide-d6

140

120

100

80

26 60

40

0

20

0

20

0

20

0

39.5 40 200

180

Methanol-d1

160

140

120

100

39

80

60

40

49.9

N

Hal

51 200

180

Methanol-d4

O

160

140

120

50

100

49 80

60

40 49.0

N

50 200

S C

20

180

Pyridine-d5

149.9

X

P Si Natural Products

160

151 200

150 180

140

135.5

120

160

48 80

60

40

123.5

149

Tetrahydrofuran-d8

100

49

136.0 135.0 140

120

100

80

124.0 123.0 60

40

67.4

Solvents

68 200

180

160

140

120

67 100

26 80

60

20

0

25.3 25 40

20

0



4.14 Spectra of Solvents and References

4.14.2

13C

155

NMR Spectra of Secondary Reference Compounds

Chemical shifts in 13C NMR spectra are usually reported relative to the peak position of tetramethylsilane (TMS), which is added as an internal reference. If TMS is C not sufficiently soluble in the sample, the use of a capillary with TMS as external reference is recommended. In this case, owing to the difference in volume susceptibilities, the local magnetic fields in the solvent and reference are different. C C Therefore, the position of the reference must be corrected. For a D2O solution in a cylindrical sample with TMS in a capillary, the correction amounts to +0.68 and -0.34 ppm for superconducting and electromagnets, respectively. These values must C C be subtracted from the 13C chemical shifts relative to the external TMS signal if its position is set to 0.00 ppm. Alternatively, secondary references with (CH3)3SiCH2 groups may be used. The following spectra of two secondary reference compounds in D2O were measured at 125 MHz with a superconducting magnet and TMS as external reference. Chemical shifts are reported in ppm relative to TMS upon correction for the difference in the volume susceptibilities of D2O. As a result, the peak for the external TMS appears at 0.68 ppm. 3-(Trimethylsilyl)-1-propanesulfonic acid sodium salt (sodium 4,4-dimethyl-4silapentane-1-sulfonate; DSS) H3C

H3C

200

CH3 Si

180

0.68 TMS (external reference)

SO3Na

160

55.1 140

120

100

80

60

40

2,2,3,3-D4-3-(Trimethylsilyl)-propionic acid sodium salt H3C D D H3C Si COONa H3C D D

186.3

200

180

19.8

-1.9

15.8

20

160

186 33 140

120

32 100

31

13 80

12 60

31.9 40

Hal O

0

N

-2.0

0.68 TMS (external reference) 187

N

S

12.7 20

0

C

X

P Si Natural Products Solvents

156

4 13C NMR

4.14.3 13C NMR Spectrum of a Mixture of Common Nondeuterated Solvents

C C

C

C

C

The broad-band-decoupled 13C NMR spectrum (125 MHz, δ in ppm relative to TMS) of a CDCl3 sample with 20 common solvents (0.05–0.4 vol%) shown below serves as a guide to identify possible solvent impurities. Chemical shifts of signals marked with an asterisk (*) may change up to a few ppm if the sample contains solutes having functional groups that can form hydrogen bonds. DMF: dimethyl formamide; THF: tetrahydrofuran; EGDME: ethylene glycol dimethyl ether.

206.8* acetone 210 205 pyridine 136.0 toluene 137.9

N

Hal

180 175 170

129.1 toluene 128.4, 128.3 toluene, benzene 125.3 toluene 123.8 pyridine 116.3* acetonitrile

165 160 155 150 CDCl3 77.1* CHCl3 77.3* 96.2* CCl4

140 135 130 125 120 115 110 105 100

O

95

90

85

67.1 dioxane 60.4 ethyl acetate 71.9 EGDME 65.9 diethyl ether 59.1* ethanol THF 68.0 58.4 EGDME

N

75

S C

200 195 190 185

DMF 162.5

ethyl acetate 171.1

192.6 CS2

149.9* pyridine

70

65

60

dimethyl sulfoxide 41.1

X

DMF 36.4 50

P Si Natural Products Solvents

25

45

40

20

15

(top part of signal not drawn) 75

53.4 CH2Cl2 methanol 50.7*

55

50

30

25

27.0 cyclohexane 30.9 acetone hexane 31.6 25.6 THF

35

15.3 diethyl ether 22.7 hexane 14.2 ethyl acetate 21.4 toluene 21.0 ethyl acetate 14.1 hexane 18.5 ethanol 10

DMF 31.3

80

145 140

1.8 acetonitrile

TMS

5

0

5

1H

NMR Spectroscopy C

5.1 Alkanes

C

C

C

C

5.1.1 Chemical Shifts 1H

Chemical Shifts and Coupling Constants (δ in ppm, J in Hz)

CH4 0.23 2J

gem

CH3 0.86

-12.4

CH3 0.91 3Jvic 7.4 CH3 a 0.91 3Jab 7.3 2J -12.4 CH2 b 1.31 3 bb' CH2 1.33 Jbc 5.7 3J 8.5 CH3 CH2

CH3

CH3 CH3 0.89 CH 1.74 H3 C

CH3

3J

CH3 0.90

vic

6.8

H3 C

CH3 CH3

CH3 0.88

bc'

N

Hal O

CH2 1.27 CH2 1.27

N

CH2 CH3

In long-chain alkanes, the methyl groups at δ ca. 0.8 ppm typically show distorted triplets due to secondorder effects:

S C

X

P Si Natural Products Solvents

158 1H

Chemical Shifts of Monosubstituted Alkanes (δ in ppm) Substituent

C C

C

C

C

C

X O

N

Hal

N

O N

S

S C

5 1H NMR

X

P Si Natural Products Solvents

O || C

–H –CH=CH2 – C ––– CH –phenyl –F –Cl –Br –I –OH –O–alkyl –OCH=CH2 –O–phenyl –OCOCH3 –OCO–phenyl –OS(O)2–4-tolyl –NH2 –NHCH3 –N(CH3)2 –NHCOCH3 –NO2 –C––– N –NC –SH –S–alkyl –SS–alkyl –S(O)CH3 –S(O)2CH3 –CHO –COCH3 –CO–phenyl –COOH –COOCH3 –CONH2 –COCl

Methyl –CH3 0.23 1.71 1.80 2.35 4.27 3.06 2.69 2.16 3.48 3.24 3.16 3.73 3.67 3.88 3.70 2.47 2.30 2.22 2.79 4.29 1.98 2.85 2.00 2.09 2.30 2.50 2.84 2.20 2.17 2.55 2.10 2.01 2.02 2.66

–CH2 0.86 2.00 2.16 2.63 4.55 3.47 3.37 3.16 3.71 3.37 3.66 3.98 4.12 4.37 4.07 2.66

Ethyl –CH3 0.86 1.00 1.15 1.21 1.35 1.33 1.66 1.88 1.24 1.15 1.21 1.38 1.26 1.38 1.30 1.11

2.32 3.26 4.37 2.35 3.39 2.44 2.49 2.67

1.06 1.14 1.58 1.31 1.28 1.31 1.25 1.35

2.94 2.46 2.44 2.92 2.36 2.32 2.23 2.93

2.80 1.13 1.06 1.18 1.16 1.15 1.13 1.24

–CH2 0.91 2.02 2.10 2.59 4.30 3.47 3.35 3.16 3.59 3.27

1-Propyl –CH2 –CH3 1.33 1.43 1.50 1.65 1.68 1.81 1.89 1.88 1.59 1.55

0.91 0.91 0.97 0.95 0.97 1.06 1.06 1.03 0.94 0.93

3.86 4.02 4.25 3.94 2.65

1.70 1.65 1.76 1.60 1.46

1.05 0.95 1.07 0.95 0.91

3.18 4.28 2.34

1.55 2.01 1.70

0.96 1.03 1.08

2.50 2.43 2.63

1.63 1.59 1.71

0.99 0.98 1.03

2.37 2.40 2.86 2.31 2.22 2.19 2.87

1.64 1.60 1.72 1.68 1.65 1.68 1.74

0.97 0.93 1.02 1.00 0.98 0.99 1.00

 5.1 Alkanes 1H

159

Chemical Shifts of Monosubstituted Alkanes (δ in ppm, contd.) Substituent

C X O

N

S O || C

–H –CH=CH2 –C ––– C– –phenyl –F –Cl –Br –I –OH –O–alkyl –OCH=CH2 –O–phenyl –OCOCH3 –OCO–phenyl –OS(O)2–4-tolyl –NH2 –NHCOCH3 –NO2 –C ––– N –NC –SH –S–alkyl –SS–alkyl –S(O)2CH3 –CHO –COCH3 –CO–phenyl –COOH –COOCH3 –CONH2 –COCl

2-Propyl –CH –CH3 1.33 0.91 2.59 2.89 4.84 4.14 4.21 4.24 4.02 3.55 4.06 4.51 4.99 5.22 4.70 3.07 4.01 4.44 2.67 3.87 3.16 2.93

1.15 1.25 1.34 1.55 1.73 1.89 1.21 1.08 1.23 1.31 1.23 1.37 1.25 1.03 1.13 1.53 1.35 1.45 1.34 1.25

3.13 2.39 2.58 3.58 2.56 2.56 2.44 2.97

1.41 1.13 1.11 1.22 1.21 1.17 1.18 1.31

n-Butyl –CH2 –CH2 1.31 1.31 ≈1.5 ≈1.2 1.52 1.41 1.60 1.34 1.65 1.68 1.41 1.84 1.46 1.80 1.42 1.56 1.39 1.54 1.38 1.61 1.39 1.76 1.47 1.60 1.39

–CH3 0.91 0.90 0.92 0.93 0.95 0.92 0.93 0.93 0.94 0.92 0.94 0.97 0.94

1.62 1.43 1.49 2.07 1.63

1.36 1.35 1.35 1.50 1.50

0.88 0.92 0.92 1.07 0.96

2.52 1.59 2.49 1.56 2.69 1.64

1.43 1.42 1.42

0.92 0.92 0.93

2.42 1.59

1.35

0.93

1.41 1.39 1.33 1.37 1.40

0.96 0.93 0.92 0.93 0.93

–CH2 0.91 2.06 2.18 2.61 4.34 3.42 3.42 3.20 3.64 3.40 3.68 3.94 4.06 4.03 2.69 3.21 4.47 2.34

2.95 2.35 2.31 2.22 2.88

1.72 1.62 1.61 1.60 1.67

tert-Butyl –CH3 0.89 1.02 1.24 1.32 1.34 1.60 1.76 1.95 1.26 1.24

C C

C

C

C

1.45 1.58 1.15 1.28 1.59 1.37 1.44 1.43 1.39 1.32 1.44 1.08 1.13 1.23 1.20 1.22

N

Hal O N S C

X

P Si Natural Products Solvents

160

5 1H NMR

Estimation of 1H Chemical Shifts of Substituted Alkanes (δ in ppm)

CH3



C

CH2

δCH3R1 = 0.86 + Zα

δCH2 = 1.37 + ∑ Zα + ∑ Zβ

C

C

δCH3CR1R2R3 = 0.86 + ∑ Zβ

C

C

Substituent (R1, R2, R3)

i

C X N

Hal O

N

N S C

O

X

P Si Natural Products Solvents

S

O || C

–C –C=C –C ––– C– –phenyl –F –Cl –Br –I –OH –O–C –OC=C –O–phenyl –O–CO– –N –N+ –N–CO– –NO2 –C ––– N –NCS –S– –S–CO– –S(O)– –S(O)2– –SCN –CHO –CO– –COOH –COO– –CO–N –COCl

CH

i

i

j

δCH = 1.50 + ∑ Zα + ∑ Zβ

j

i

i

i

Zα

CH3

0.00 0.85 0.94 1.51 3.41 2.20 1.83 1.30 2.53 2.38 2.64 2.87 2.81 1.61 2.44 1.88 3.43 1.12 2.51 1.14 1.41 1.64 1.98 1.75 1.34 1.23 1.22 1.15 1.16 1.94

Zβ

0.05 0.20 0.32 0.38 0.41 0.63 0.83 1.02 0.25 0.25 0.36 0.47 0.44 0.14 0.39 0.34 0.65 0.45 0.54 0.45 0.37 0.36 0.42 0.66 0.21 0.20 0.23 0.28 0.28 0.22

Zα

CH2

0.00 0.63 0.70 1.22 2.76 2.05 1.97 1.80 2.20 2.04 2.63 2.61 2.83 1.32 1.91 1.63 3.08 1.08 2.20 1.23 1.54 1.24 2.08 1.62 1.07 1.12 0.90 0.92 0.85 1.51

Zβ

-0.06 0.00 0.13 0.29 0.16 0.24 0.46 0.53 0.15 0.13 0.33 0.38 0.24 0.22 0.40 0.22 0.58 0.33 0.36 0.26 0.63 0.30 0.52 0.29 0.24 0.23 0.35 0.24 0.25

Zα

CH

0.17 0.68 1.04 1.28 1.83 1.98 2.44 2.46 1.73 1.85 2.00 2.20 2.47 1.13 1.78 2.10 2.31 1.00 1.94 1.06 1.31 1.25 1.50 1.64 0.86 0.87 0.83 0.94

Zβ

-0.01 0.03 0.38 0.27 0.31 0.41 0.15 0.08 0.32 0.30 0.50 0.59 0.23 0.56 0.62 0.60 0.31 0.19 0.40 0.22 0.32 0.63 0.30

j

j

 5.1 Alkanes 1H

161

Chemical Shifts of Aromatically Substituted Alkanes (δ in ppm) 2.63 1.21

2.35

CH3

CH2

2.46

CH3

CH3

CH

CH3

CH3 2.65

1.32

2.89 1.25

C

CH3

3.10 1.38

CH2 CH3

CH3

CH3

C

CH3

C

C

2.81 1.32

C

C

CH2 CH3

CH3 1.94 CH3 2.17

O

N

CH3 2.05

N CH3 2.42

N H

N H CH3 2.34

N

CH3 3.50

O

N H

N

H

N

Hal O

CH3 3.83

N

O

S

H

CH3 2.41

CH3 2.55

N CH3 3.58

N S

S CH3 2.32

N

N

CH3 2.44

O

CH3 2.21 S

N

H3 C 2.18 N

N N

CH3 2.16

H3 C 2.27 N

H3 C 2.05

N

N H

N

S

CH3 2.35

N

N H

CH3 2.74

H3 C 2.33 N

C

X

P Si Natural Products

CH3 2.31

CH3 2.40 N H

Solvents

162

5 1H NMR

5.1.2 Coupling Constants Geminal Coupling Constants (2J in Hz)

C

H C

2J

HCH

-8 to -18

C

C



C

C

Electronegative substituents cause a decrease in |J|gem while a double or triple bond next to the CH2 group causes an increase. The latter effect is strongest if one of the C–H bonds is parallel to the π orbitals:

H

H H

Influence of Substituents on the Geminal Coupling Constant

N

O

CH3

-14.3

-12.4 -10.8 -7.5 -10.8

Compound



CH3COCH3 CH3COOH CH3CN CH2(CN)2 CH2 CN

Jgem

-14.9 -14.5 -16.9 -20.3 -18.5

Vicinal Coupling Constants (3J in Hz)

S C

Jgem

CH4 CH3Cl CH2Cl2 CH3OH

Hal

N

Compound

H

X

P Si Natural Products Solvents

H

conformation ­­­not fixed: 3JHCCH ≈ 7 fixed: 3JHCCH ≈ 0–18

Influence of Substituents on the Vicinal Coupling Constant Compound

CH3CHF2 CH3CHCl2 CH3CH2F CH3CH2Cl

Jvic

4.5 6.1 6.9 7.2

Compound

CH3CH2OH (CH3CH2)3O+ BF4– (CH3CH2)3N (CH3CH2)4N+ I–

Jvic 6.9 7.2 7.1 7.3

Compound

CH3CH2CN (CH3CH2)2S (CH3CH2)4Si CH3CH2Li

Jvic 7.6 7.4 8.0 8.4

 5.1 Alkanes

163

Vicinal coupling constants strongly depend on the dihedral angle, φ (Karplus equation): 3J 3J

= J0 cos2 φ - 0.3 0o ≤ φ ≤ 90o 180 2 = J cos φ - 0.3 90o ≤ φ ≤ 180o

C

The same relationship between torsional angle and vicinal coupling con- C C stant holds for substituted alkanes if appropriate values are used for J0 and J180. These limiting values depend on the electronegativity and orientation of substituents, the hybridization of carbon atoms, bond lengths, and bond C C angles. J / Hz 15 10

N

5

Hal

0 0

30

60

90

120

150

180

φ / degrees

Long-Range Coupling Constants (|J| in Hz)

O N

Coupling constants through more than three bonds (long-range coupling) in alkanes S are generally much smaller than 1 Hz and, thus, not visible in routine 1D NMR spectra. They are, however, much larger than 1 Hz for fixed conformations (e.g., in condensed alicyclic systems, see Chapter 5.4) and in unsaturated compounds (see C X Chapter 5.2). They are also significant when electronegative substituents are present between the coupling partners, as e.g.:

P Si

RO RO

CH3 CH3

4J

HH

0.7

Natural Products Solvents

5 1H NMR

164

5.2 Alkenes 5.2.1 Substituted Ethylenes

C

1H

C

C

C

C

Chemical Shifts and Coupling Constants (δ in ppm, J in Hz)

H

H

H

H

b

H3 C Hc

2J gem 3J cis 3J trans

Ha 5.55 d

CH3 1.58

2.5 11.6 19.1

4J ab 3J ac 3J ad 5J bd

-1.7 15.1 6.5 1.6

4.88 H b

H a 5.73

4.97 H c

CH3 1.72

Hb H3 C c

d

H a 5.37 CH3 1.54 d

3J ab 3J ac 3J ad 2J bc 4J bd 4J cd

10.0 16.8 6.4 2.1 -1.3 -1.8

3J ab 4J ac 3J ad 5J cd

10.9 -1.8 6.8 1.2

N

Hal O N

H a 5.78

4.94 H c

CH2 CH3

d

e

2.00 1.00

3J 10.3 ab 3J ac 17.2 3J 6.2 ad 2J 2.0 bc

4J bd 4J cd

-1.3 -1.7

Geminal and Vicinal Couplings of Alkenes (J in Hz)

S C

4.87 H b

X

P Si Natural Products Solvents

The values of the coupling constants strongly depend on the electronegativity of the substituents (see Table on pp 166, 167). They decrease with increasing electronegativity and number of electronegative substituents. The same trend holds for the signed values of geminal coupling constants but not for the absolute values because Jgem can be positive or negative. Although the total ranges of cis and trans vicinal coupling constants overlap, Jtrans > Jcis always holds for given substituents. Typical ranges:

Jgem -4 to 4 Jcis 4 to 12 Jtrans 14 to 19

 5.2 Alkenes

165

Coupling Over More than Three Bonds in Alkenes (Long-Range Coupling, J in Hz) Allylic Coupling

C

φ



Hb

C

Ha

Hc

cisoid: 4Jab -3.0 to +2.0 transoid: 4Jac -3.5 to +2.5

In acyclic systems, the coupling constants range from ca. -0.8 to -1.8 Hz and, usually, |J|cisoid is larger than |J|transoid. The magnitudes of the coupling constants depend on the conformation. Largest absolute values are observed if the C–H bond of the substituents overlaps with the π electrons of the double bond (φ = 0 or 180o): 4J

φ 0o 90o 180o 270o

4J

ab

-3.0 +1.8 -3.0 0.0

C

C

C

ac

-3.5 +2.2 -3.5 0.8

N

Hal

Homoallylic Coupling Hb

C

O

Ha

cisoid: |5Jab| 0–3 transoid: |5Jac| 0–3



N

Hc

The values of homoallylic coupling constants between methyl groups and of allylic ones are comparable: 5J 4 H C–C=C–CH ≈ JH–C=C–CH 3

3

3

In acyclic systems, |Jcisoid| < |Jtransoid| usually holds. Large homoallylic coupling constants are occasionally observed in cyclic systems with fixed conformation between the protons: a H

R

X

X

b H

R

5J

ab

X: CH, N R: any substituent

5–11

R Ha

X

R Hb

X: O, NH R: any substituent

4J

ab

0–7

S C

X

P Si Natural Products Solvents

166

5 1H NMR

1H

Chemical Shifts and Coupling Constants of Monosubstituted Ethylenes (δ in ppm, J in Hz)

C C

C

C

C

Substituent R

C

N

Hal O

X

N

O

S C

X

P Si Natural Products Solvents

N

–H –CH3 –CH2CH=CH2 –CH2–phenyl –cyclopropyl –cyclohexyl –CF3 –CH=C=CH2 –C ––– C–CH3 –phenyl –2-naphthyl –2-nitrophenyl –3-nitrophenyl –4-nitrophenyl –2-pyridyl –4-pyridyl –F –Cl –Br –I –OH –OCH3 –OCH=CH2 –O–phenyl –OCHO –OCOCH3 –OCOCH=CH2 –OCO–phenyl –OP(O)(O–ethyl)2 –NH2 –N+(CH3)3Br– –NHCOCH3 –NO2 –C ––– N –NC –NCO

Ha

5.28 5.73 5.71 5.89 5.32 5.79 5.90 6.31 5.62 6.72 6.87 7.19 6.74 6.77 6.84 6.61 6.17 6.26 6.44 6.53 6.45 6.44 6.49 6.64 7.33 7.28 7.39 7.52 6.58 ≈6.05 6.50 ≈7.33 7.12 5.69 5.90 6.12

Hb

Ha

Hc

R

Hb

5.28 4.88 4.92 5.00 4.84 4.88 5.56 4.99 5.24 5.20 5.32 5.45 5.42 5.48 5.45 5.42 4.03 5.39 5.97 6.23 3.82 3.88 4.21 4.40 4.66 4.56 4.62 4.67 4.59 ≈3.99 5.54 ≈4.68 5.87 6.11 5.35 4.77

Hc

5.28 4.97 4.95 5.01 5.04 4.95 5.85 5.19 5.39 5.72 5.86 5.68 5.86 5.90 6.22 5.91 4.37 5.48 5.84 6.57 4.18 4.03 4.52 4.74 4.96 4.88 4.96 5.04 4.91 ≈4.04 5.76 ≈4.53 6.55 6.24 5.58 5.01

Jab

Jac

Jbc

11.6 10.0 10.3 10.0 10.4 10.5 11.1 10.1 11.1 11.1

19.1 16.8 16.9 17.0 17.1 17.6 17.5 17.2 17.0 17.9

2.5 2.1 2.2 1.9 1.8 1.9 0.2 1.6 2.3 1.0

10.7 10.9 10.9 11.3 10.8 4.7 7.5 7.1 7.8 6.4 7.0 6.4 6.1 6.4 6.3 6.4 6.3 6.0

17.4 17.5 17.4 18.5 17.6 12.8 14.5 14.9 15.9 14.2 14.1 14.0 13.7 13.9 14.1 14.2 13.8 13.8

1.1 0.4 0.8 1.4 0.7 -3.2 -1.4 -1.9 -1.5 -1.0 -2.0 -1.8 -1.6 -1.7 -1.6 -1.6 -1.7 -2.1

8.2 15.1

-4.3

7.0 11.8 8.6 7.6

14.6 17.9 15.6 15.2

1.4 0.9 -0.5 -0.1

Other CH3 1.72 CH2 2.72 CH2 3.19

CH3 3.16 CHO 8.07 CH3 2.13

 5.2 Alkenes Substituent R

S

O || C

P

M

–SCH3 –S–phenyl –S(O)CH3 –S(O)2CH3 –S(O)2CH=CH2 –S(O)2OH –S(O)2OCH3 –S(O)2NH2 –S(O)2NH–phenyl –SF5 –SCN –CHO –COCH3 –COCH=CH2 –CO–phenyl –COOH –COOCH3 –CONH2 –CON(CH3)2 –COF –COCl –P(CH3)2 –P(CH=CH2)2 –P(phenyl)2 –PCl2 –P(O)(phenyl)2 –PSCl2 –P(S)(CH3)2 –P(S)(phenyl)2 –Li –MgBr –Si(CH3)3 –Sn(CH=CH2)3 –Pb(CH=CH2)3 –HgBr

Ha

6.43 6.53 6.77 6.76 6.67 6.73 6.57 6.93 6.56 6.63 6.19 6.37 6.30 6.67 7.20 6.15 6.12 6.48 6.64 6.14 6.35 6.23 6.16 7.38 7.48 6.72 6.42 6.60 6.82 7.29 6.66 6.11 6.39 6.70 6.45

Hb

5.18 5.32 5.92 6.14 6.17 6.13 6.22 5.98 5.86 5.64 5.70 6.52 5.91 5.82 5.81 5.95 5.83 5.71 5.55 6.25 6.16 5.51 5.64 6.31 6.68 6.21 5.90 6.14 6.17 6.65 6.15 5.88 6.21 6.19 5.92

Hc

4.95 5.32 6.08 6.43 6.41 6.41 6.43 6.17 6.18 5.96 5.66 6.35 6.21 6.28 6.52 6.53 6.41 6.17 6.12 6.60 6.63 5.39 5.59 7.07 6.64 6.25 6.13 6.26 6.34 5.91 5.51 5.63 5.75 5.46 5.52

Jab

Jac

Jbc

10.3 9.6 9.8 10.0 10.0 10.2 10.1 10.0 10.1 9.8

16.4 16.7 16.7 16.5 16.4 16.8 16.9 16.3 16.7 16.6

-0.3 -0.2 -0.6 -0.5 -0.6 -1.2 -0.6 0 -0.3 0.4

10.0 10.7 11.0 9.9 10.5 10.6 7.9 9.8 10.7 10.6 11.8 11.8 12.5 11.7 12.9 11.0 11.8 11.7 19.3 17.7 14.6 13.4 12.2 11.9

17.4 18.7 17.9 17.7 17.2 17.4 17.3 17.0 17.3 17.4 18.3 18.4 18.2 18.6 18.9 17.5 17.9 17.9 23.9 23.3 20.2 20.7 19.8 18.7

1.0 1.3 1.4 2.3 1.8 1.5 5.0 3.4 0.8 0.2 2.0 2.0 0 0.4 1.8 0.3 1.8 1.6 7.1 7.6 3.8 3.1 2.1 3.1

167

Other

CH3 2.25 CH3 2.61 CH3 2.96 CH3 3.85 NH2 6.7 NH 9.07

C C

C

C

C

CHO 9.59 CH3 2.29 COOH 12.8 CH3 3.77 NH2 7.55

N

Hal O

CH3 0.95

N S C CH3 0.06

X

P Si Natural Products Solvents

168

5 1H NMR

Estimation of 1H Chemical Shifts of Substituted Ethylenes (δ in ppm) R cis

C

R trans

C

C

C

C

Substituent R

N

Hal O N

C

X X

P Si Natural Products Solvents

R gem

δ C=CH = 5.25 + Zgem + Zcis + Ztrans

C

S

H

O N

–H –alkyl –alkyl ring1 –CH2–aromatic –CH2X, X: F, Cl, Br –CHF2 –CF3 –CH2O– –CH2N –CH2CN –CH2S– –CH2CO– –C=C –C=C conjugated2 –C ––– C– –aromatic –aromatic, fixed3 –aromatic, o-substituted –F –Cl –Br –I –OC (sp3) –OC= (sp2) –OCO– –OP(O)(OCH2CH3)2 –NR2; R: H, C (sp3) –NR–; R: C= (sp2 ) –NCO–R –N=N–phenyl –NO2 –C ––– N

Zgem 0.00 0.45 0.69 1.05 0.70 0.66 0.66 0.64 0.58 0.69 0.71 0.69 1.00 1.24 0.47 1.38 1.60 1.65 1.54 1.08 1.07 1.14 1.22 1.21 2.11 1.33 0.80 1.17 2.08 2.39 1.87 0.27

Zcis

0.00 -0.22 -0.25 -0.29 0.11 0.32 0.61 -0.01 -0.10 -0.08 -0.13 -0.08 -0.09 0.02 0.38 0.36 – 0.19 -0.40 0.18 0.45 0.81 -1.07 -0.60 -0.35 -0.34 -1.26 -0.53 -0.57 1.11 1.30 0.75

Ztrans

0.00 -0.28 -0.28 -0.32 -0.04 0.21 0.32 -0.02 -0.08 -0.06 -0.22 -0.06 -0.23 -0.05 0.12 -0.07 -0.05 0.09 -1.02 0.13 0.55 0.88 -1.21 -1.00 -0.64 -0.66 -1.21 -0.99 -0.72 0.67 0.62 0.55

 5.2 Alkenes Substituent R

S

O || C

Zgem

–S– –S(O)– –S(O)2– –SCO– –SCN –SF –CHO –CO– –CO– conjugated2 –COOH –COOH conjugated2 –COOR –COOR conjugated2 –CON –COCl –P(O)(OCH2CH3)2

1.11 1.27 1.55 1.41 0.94 1.68 1.02 1.10 1.06 0.97 0.80 0.80 0.78 1.37 1.11 0.66

Zcis

-0.29 0.67 1.16 0.06 0.45 0.61 0.95 1.12 0.91 1.41 0.98 1.18 1.01 0.98 1.46 0.88

169

Ztrans

-0.13 0.41 0.93 0.02 0.41 0.49 1.17 0.87 0.74 0.71 0.32 0.55 0.46 0.46 1.01 0.67

C

1) The increment "alkyl ring" is to be used if the substituent and the double bond are part of a cyclic structure. 2) The increment "conjugated" is to be used if either the double bond or the substituent is conjugated to other substituents. 3) The increment "aromatic, fixed" is to be used if the double bond conjugated to an aromatic ring is part of a fused ring (such as in 1,2-dihydronaphthalene).

C

C

C

C

N

Hal O N

Influence of cis- and trans-Substituents on the 1H Chemical Shift of Methyl Groups at the Double Bond in Isobutenes (δ in ppm­) 1.70 H3 C

1.68 H3 C

H

1.62 H3 C

1.75 H3 C

H 5.78

1.65 H3 C

H 6.79

1.91 H3 C

H 5.63

1.75 H3 C

Br

1.65 H3 C

OCOCH3

2.11 H3 C

CHO

1.86 H3 C

H 5.97

1.84 H3 C

H 5.62

1.97 H3 C

H 6.01

2.06 H3 C

COCH3

2.12 H3 C

COOCH3

2.12 H3 C

COCl

H3 C

H 5.13

1.80 H3 C

S

H 5.17

H 4.63

C

1.88 H3 C

X

P Si Natural Products Solvents

5 1H NMR

170

Chemical Shifts and Coupling Constants of Enols (δ in ppm, J in Hz) ≈16 ≈16 1H

C C

O

C

C

8.40 H a

H

3J 9.7 ab 3 J ≈8 bc

O H c ≈9.3

Hb

O

7.90 Ha

5.04

C

H

3J

O

ab

CH3 2.11 Hb

5.60

5.2.2 Conjugated Dienes 1H

5.06

N

Hal O

6.27 Ha

Hf

H b

He Hc

Hd

5.16 4.86

6.21 5.61 Ha

H

N

Hf

b

P Si Natural Products Solvents

5.03

5.98

6.59

H

1.71

Hd

4.98

X

e

CH3

Hc

S C

Chemical Shifts and Coupling Constants (δ in ppm, J in Hz)

1.72

CH3 f

Ha

b

He

Hc

5.11

Hd

5.92

5.45

3J ab 3J ac 3J ad 4J ae 4J af

10.2 17.1 10.4 -0.9 -0.8

2J bc 5J be 5J bf 5J cf

1.8 1.3 0.6 0.7

3J ab 3J ac 3J ad 5J ae 4J af

10.2 16.9 10.3 0.4 -0.8

2J bc 4J bd 6J be 5J bf 4J cd

1.9 -0.8 -0.7 0.7 -0.8

6J ce 5J cf 4J de 3J df 3J ef

-0.7 0.7 -1.6 15.1 6.6

3J ab 3J ac 3J ad 4J ae 5J af

10.2 16.9 10.9 -1.1 0.2

2J bc 4J bd 5J be 6J bf 4J cd

2.1 -0.8 -0.7 0.7 -0.8

5J ce 6J cf 3J de 4J df 3J ef

0.7 -0.6 10.8 -1.8 7.0

5.1

 5.2 Alkenes

171

5.2.3 Allenes 1H

Chemical Shi­fts and Coupling Constants (δ in ppm, J in Hz) 4.67

H

C C C Hc

Ha Hb

Hb

2J -9 ab 4J -6 ac

C C C H3 C c

CH3 a Hd

5J 3.2 ab 6J 0 ac 3J 6.8 ad 4J -6.4 bd

C C

C

C

C

1H

Chemical Shifts and Coupling Constants of Monosubstituted Allenes (δ in ppm, J in Hz) Hb C C C H

Substituent R –H –CH3 –CH2CH3 –CH2Cl –CH=CH2 –Cl –Br –I –phenyl –OCH3 –COCH3 –C ––– N –Si(CH3)3 –SiCl3 –SnCl3

Ha

4.67 4.94 5.03 5.4.3 5.96 5.76 5.85 5.63 5.91 6.77 5.77 4.97 4.92 5.35 4.98

Hb

4.67 4.50 4.55 4.92 4.92 5.17 4.83 4.48 4.92 5.48 5.25 5.04 4.31 4.92 4.11

a =CH , H (d) 5.19, 4J -0.8, 6J 2 cis ad bd 6J  -1.8, 3J 10.1, 2J 1.6 be ce de

Jab

-9.0 -6.7 -6.8 -6.6 -6.6 -6.1 -6.1 -6.3

Ha R

N

Other CH3 (c) 1.59, 3Jac 7.2, 5Jbc 3.4 CH2 (c) 1.95, 3Jac 6.2, 5Jbc 3.5 CH2 (c) 4.11, 3Jac 7.7, 5Jbc 2.2 CH (c) 6.31, 3Jac 10.4, 5Jbc 1.1a

Hal O N S

-5.9 -6.4 -5.9 -7.2

-1.5, 3Jcd 17.2; CH2, Htrans (e) 4.99, 4Jae -0.9,

C

X

P Si Natural Products Solvents

5 1H NMR

172

5.3 Alkynes 1H

C

Chemical Shifts of Substituted Alkynes (δ in ppm) R

C

C

C

C

C

X

N

Hal O

O N

N S C

Substituent R

–H –CH3 –CH2CH3 –C(CH3)3 –CF3 –CH=CH2 –C ––– CH –phenyl –1-naphthyl –F –Cl –Br –I –OCH2CH3 –OCH=CH2 –O–phenyl –N(CH2CH3)2 –N(phenyl)2 –C ––– N

1H,1H

X

P Si Natural Products Solvents

a

H

Ha

1.91 1.91 1.97 2.07 2.95 3.07 2.16 3.07 3.43 1.74 2.05 2.32 2.34 1.48 2.04 2.07 2.30 2.86 2.63

C C Ha

S O  || C Si P

Substituent R

Ha

–SCH2CH3 –SCH=CH2 –S–phenyl –S(O)2–n-butyl –COCH3 –CO–phenyl –COOH –COOCH2CH3 –CONH2 –Si(CH3)3 –Si(phenyl)3 –P(CH2CH3)2 –P(phenyl)2 –P(O)(CH2CH3)2 –P(O)(phenyl)2

2.79 3.26 3.28 3.95 3.65 3.48 3.17 2.90 3.05 2.34 2.47 2.85 3.22 3.33 3.48

Coupling Constants of Substituted Alkynes (J in Hz) b

4J

CH3

a

b

H3 C

b

a

H

c

H H3 C d

2.9

|5Jab| 2.7

CH3

H

ab

4J ab 5J ac 6J ad 3J bc 4J bd 3J cd

2.0 1.0 0.6 10.5 1.6 6.5

a H

a H 3C

a

H

b c CH 2 CH 3 b CH 2 CH 3 b

c d

4J ab 5J ac 3J bc

2.6 0 7.4

|5Jab| 2.5 5J 0.3 ab 6J -0.1 ac 7J 0.2 ad

 5.4 Alicyclics

173

5.4 Alicyclics 1H

Chemical Shifts and Coupling Constants of Saturated Alicyclic Hydrocarbons (δ in ppm, J in Hz) 0.20 2Jgem -4.3 In derivatives: 3J 9.0 2J cis gem -3 to -9 3J 3J 6 to 12 5.6 trans cis 3J trans 2 to 9 Throughout: Jcis > Jtrans 1.51 In derivatives: 2J gem -8 to -18 3J 5 to 10 cis 3J trans 5 to 10

c

7.01

b a

d

0.92 c

e a

5.66

b 2.27

e d

H

2.08

a

d

6.53

5.67 b 5.79 c

b 2J gem -13.7 3J 1.0 a ab 4 J -0.3 2.57 ac

d

4J -2.3 bd 5J be,cis 2.1 5J be,trans 3.0 3J 5.8 cd

d

c

e

9.7 1.0 1.1 5.1

6.43 b

a

a

d

6.28

5.69

3J ab 3J bc

b

1.99 1.60 c

b

a

5.79 c

e

1.75

d

3J ad,cis 1.8 3J ad,trans 4.6 3J 2.8 bc

3J 1.3 ab 4J -1.5 ac 3J 5.0 bc

2.80

4J -0.2 bc 4J -0.4 bd 4J 2.0 be 2J 0.1 cd

5.1 0.5 1.4 1.3 2.0

3J ab 4J ac 5J ad 3J bc

5.95

c

2J gem,a -12.8 3J ab,cis 9.3 3J ab,trans 5.7 2J gem,b -16.1 3J 2.3 bc

3J ab 5 b 6.23 Jac 5J ad 4J c ae H 5.89 3Jaf a

1.44 In derivatives: 2J gem -11 to -14 3J ax,ax 8 to 13 3J eq,ax 2 to 6 At -100 °C 3J eq,eq 2 to 5 Hax 1.12 Generally: Heq 1.60 Jeq,ax ≈ Jeq,eq +1

In derivatives: 3J 1.5 to 2.0 ab 3J 0.5 to 1.5 bc

1.79

f

1.94 In derivatives: 2J gem -10 to -17 3J 4 to 12 cis 3J 2 to 10 trans 4J ≈ 0 cis 4J trans ≈ -1

2.12 1.50

3J ab 3J bc

≈10 1.5

≈10 3.7

C C

C

C

C

N

Hal O N

4J bd 1.1 5J be 2.0 3J cd 1.9

S C

X

P Si Natural Products Solvents

5 1H NMR

174 a g

C C

f

C

6.50 6.09

c

d 5.26

e, e'

2.22

C

C

b

a'

a

5.79

b'

b d

5.59

2.14 1.47 c

3J 11.2 ab 4J 0.8 ac 3J 5.5 bc 3J 8.9 cd 5J = 4J cf df

N

H

Hal

2.19

H 1.47 H 1.16

O

S C

X

P Si Natural Products

= 5Jdg = 0

5.56 d

1.5

2.11

3J ≈10 ab 3J 3.7 bc

1.5

7.90 1.76 1.87

6.02 H

H

2.87

H 1.63 H 0.98

H

H 1.50 H 1.23

2.48

7.12

2.00

H 1.12

H

7.38 8.31

7.52

6.25 H

1.50 1.50

N

e

1.34 H

H

b

c

3J 11.3 ab 3J 4.1 aa' 4J -0.6 ab' 5J 0.5 bb'

1.18

H

a

5J -0.6 cg 3J 6.7 de 2J -13.0 ee'

H

H

3.58

4.60

H 6.75

6.63

In condensed alicyclics, couplings over four bonds are often observed. Such longrange couplings are particularly large if the arrangement of the bonds between the two protons is W-shaped (cf. Jac vs. Jad and Jbd below left and Jac vs. Jbc below right). Owing to the rigid arrangement, vicinal coupling constants (3J) may assume unusually small values when the torsional angles are close to 90° (Jce below right).

a

H

b

H

Solvents Hc

4J ≈7 ac 4J ≈0 ad 4J ≈0 bd Hd

a

b

H 1.73

1.55 H 1.82 H 1.47

1.82 Hd

2.67 H

H 2.06 H 1.84

H H

e 1.50 Hc 2.59

O

4J ac 4J bc 3J ce 3J de

2.3 -0.1 0.1 4.7

 5.4 Alicyclics

175

1H

Chemical Shifts and Coupling Constants of Monosubstituted Cyclopropanes (δ in ppm, J in Hz) c

C

H R

e Hb

H

Ha

Hd

Substituent R

C X O N O || C

M

–H –CH3 –CH2OH –CH=CH2 –phenyl –F –Cl –Br –I –OH –NH2 –NH3+ –NO2 –C ––– N –CHO –COCH3 –CO–cyclopropyl –CO–phenyl –COOH –COOCH3 –CONH2 –COF –COCl –Li –MgBr –B(cyclopropyl)2 –Si(cyclopropyl)3 –P+(phenyl)3 –Hg–cyclopropyl

Ha Hb;d Hc;e

0.20 1.00 1.14 1.35 1.83 4.32 2.55 2.83 2.31 3.35 2.23 1.06 4.21 1.29 1.79 1.83 1.70 2.65 1.59 1.61 1.39 1.66 2.11 -2.53 -2.04 -0.25 -0.67 3.28 0.00

0.20 0.35 0.40 0.64 0.89 0.69 0.87 0.96 1.04 0.40 0.32 0.52 1.13 0.96 0.99 0.77 0.56 1.01 0.91 0.86 0.70 1.11 1.18 0.43 0.25 0.61 0.49 1.82 0.75

0.20 0.15 0.30 0.34 0.65 0.27 0.74 0.81 0.76 0.48 0.20 0.34 1.60 1.04 1.03 0.93 1.02 1.23 1.05 0.98 0.95 1.20 1.28 -0.12 -0.13 0.66 0.36 0.63 0.47

3J

ab

9.0

3J

ac

2J

bc

5.6 -4.3

3J

bd

9.0

8.2 9.5 5.9 7.0 7.1 7.5 6.2 6.6

4.9 6.3 2.4 3.6 3.8 4.4 2.9 3.6

-4.5 -4.5 -6.7 -6.0 -6.1 -5.9 -5.4 -4.3

7.0 8.4 8.0 7.9 7.9

3.4 5.1 4.6 4.6 4.6

-5.5 10.1 -4.7 9.2 -4.5 8.8 -3.5 9.2 -3.5 9.1

8.0 8.0

4.6 -4.0 4.6 -3.4

8.0 7.9 10.3 11.0 8.9 9.7 9.6

4.6 4.4 9.1 8.5 5.8 6.9

9.3 9.5 10.8 10.3 10.2 9.9 10.3 9.7

9.3 8.8

-4.5 10.1 -4.5 9.2 -1.6 7.7 -1.7 7.8 -3.3 8.2 -3.4 8.4

6.9 -3.7

8.5

3J

be

5.6

6.2 5.2 7.7 7.1 7.0 6.6 6.8 6.2

3J

ce

9.0

9.0 8.9 12.0 10.6 10.5 10.0 10.9 9.9

C

C

C

C

N

Hal

8.3 11.3 7.1 9.5 7.0 9.6 7.0 9.5 7.0 9.5 7.1 6.9

N

9.7 9.6

7.5 9.3 7.6 10.0 3.2 6.5 3.5 6.6 5.9 8.4 5.1 8.1 4.8

O

7.9

S C

X

P Si Natural Products Solvents

176

5 1H NMR

1H

Chemical Shifts and Coupling Constants of Equatorially and Axially Substituted Cyclohexanes (δ in ppm, J in Hz)

C R'

C

C

C

C

C

O

N

Hal

N S

O N

4

H

H

3

1

2

–D* –C* –C ––– C* –phenyl* –F* –Cl* –Br* –I* –OH** –OCOCH3* –NH2** –NHCOCH3** –NO2* –C ––– N** –SH* –COOCH3*

1.12 1.27 2.25 2.46 4.49 3.88 4.09 4.18 3.52­ 4.74 2.55 3.67 4.38 2.31 2.79 2.30

Ax. substituent R H1,eq

–D* 1.60 –C* 1.93 –C ––– C* 2.87 –phenyl* 3.16 –F* 4.94 –Cl* 4.59 –Br* 4.80 –I* 4.96 –OH** 4.03 –OCOCH3* 5.31 –NH2** 3.15 –NHCOCH3** 4.11 –NO2** 4.43 –C ––– N** 2.96 –SH** 3.43 * R': –H; ** R': –tert-butyl

C

S X

P Si Natural Products Solvents

X

O N S

H

R

H

R

R'

4

H

H

Eq. substituent R H1,ax

X

C

H

H

H

1

3

2

H

H

H

H2,ax

H2,eq

H3,ax

H3,eq

H4,ax

H4,eq

1.42 1.58 1.75 1.97 1.22 1.72 1.03 1.07 2.23 1.53 1.34 1.44

2.15 2.22 2.33 2.45 2.01 1.85 1.89 2.01 1.85 2.16 2.01 1.90

1.28 1.33 1.35 1.36 1.05 1.35 1.03 1.11 1.38 0.98 1.31 1.27

1.86 1.84 1.80 1.67 1.78 1.41 1.76 1.78 1.85 1.86 1.75 1.75

1.12 1.18 1.22 1.30 0.97 1.25 0.96 1.01 1.28 1.03 1.22 1.24

1.65 1.68 1.72 1.80

H2,ax

H2,eq

H3,ax

H3,eq

H4,ax

H4,eq

1.63 1.77 1.79 1.72 1.35

1.75 1.75 1.60 1.62 1.54

1.28 1.26 1.24 1.26 0.99

1.58 1.75 1.78 1.73

1.27 1.03

1.53 1.66

0.96 1.04

1.50

1.70

1.20

1.12 0.81 1.36

1.12 1.37 1.48 1.43 1.76 1.81 1.53 1.49 1.49 1.54 1.51 1.6 1.54 1.5

1.60 1.57 1.98

1.60 1.40 1.78 2.42 2.03 2.00 2.08 2.06 1.83 2.51 1.65 1.85 2.6 2.00 1.9

1.12 1.15 1.20

1.12 1.39

1.60 1.60 1.73

1.60 1.34

1.12 1.06 1.17

1.12 1.06

1.60 1.58 1.67

1.55 1.67 1.61 1.64

1.60 1.58

 5.5 Aromatic Hydrocarbons

177

5.5 Aromatic Hydrocarbons 1H

Chemical Shifts and Coupling Constants (δ in ppm, J in Hz) 7.34 In derivatives: 3J ortho 6.5–8.5 4J meta 1.0–3.0 5J para 0.0–1.0 8.01 a

b c

e

d

8.43 7.67 b

8.70 a

f

e

7.84

h

g

a

f

c e

7.48

d

In derivatives: 3J 8.5–9.5 7.47 4Jab 0.8–1.5 ac 5J 0.6–0.9 ad 5J ≈0.8 ae 3J 6.5–8.0 bc 4J ≈0.4 de

In derivatives: 8–9 6Jaf ≈-0.1 C 1–2 5Jag ≈0.2 4 ≈1 Jah ≈-0.5 5–7 7Jbf ≈0.3 C ≈0.9 6Jbg ≈0.1

3J ab 4J ac 5J ad 3J bc 5J ae

8.00

C C

7.39

8.67

3J ab 4J ac 5J ad 3J bc 4J bd 3J cd

8.4 1.2 c 7.61 0.7 d 7.90 7.2 1.3 7.75 8.1 In derivatives: 3J ≈9 ef

8.08 8.19

b

C

7.56 7.54

7.66 8.01

8.84 8.13 9.17

8.05

7.68

8.37 7.80

N 7.65 7.85

Hal O

7.62

N

8.90

7.47 8.20

S C

X

P Si Weak long-range couplings between aromatic protons and aliphatic substituents are usually not resolved but lead to a characteristic broadening of the corresponding lines.

4J -0.7 ab 5J 0.3 ac b 6Jad -0.6 c

CH3 a

d

CH3 a 5Jab ≈0.8 O b

Natural Products Solvents

178

5 1H NMR

Effect of Substituents on 1H Chemical Shifts of Monosubstituted Benzenes (in ppm) 3

C

4

C

C

C

C

C

N

Hal

X

O N

O

S C

2

X

P Si Natural Products Solvents

N

Substituent R

1

R

–CH3 –CH2CH3 –CH(CH3)2 –C(CH3)3 –CF3 –CCl3 –CH2OH –CH=CH2 –CH=CH–phenyl (trans) –C ––– CH –C ––– C–phenyl –phenyl –2-pyridyl –F –Cl –Br –I –OH –OCH3 –OCH2CH=CH2 –O–phenyl –OCOCH3 –OCO–phenyl –OS(O)2CH3 –NH2 –NHCH3 –N(CH3)2 –N(phenyl)2 –N+(CH3)3 I– –NHCHO (trans to O) –NHCHO (cis to O) –N(CH3)CHO –NHCOCH3 –NHCSNH2

δH = 7.34 + Zi i

Z2

-0.17 -0.14 -0.13 0.05 0.19 0.55 -0.07 0.08 0.16 0.16 0.20 0.22 0.73 -0.31 -0.01 0.15 0.36 -0.51 -0.44 -0.45 -0.33 -0.26 -0.12 -0.05 -0.67 -0.73 -0.60 -0.26 0.72 -0.25 -0.20 -0.16 0.15 0.14

Z3

-0.09 -0.05 -0.08 -0.04 -0.07 -0.07 -0.07 -0.02 0.00 -0.01 -0.04 0.06 0.09 -0.03 -0.06 -0.12 -0.24 -0.10 -0.05 -0.13 -0.02 0.03 0.10 0.07 -0.20 -0.16 -0.10 -0.10 0.40 0.03 0.21 0.07 -0.02 0.07

Z4

-0.17 -0.18 -0.18 -0.18 0.00 -0.09 -0.07 -0.09 -0.15 -0.01 -0.07 -0.04 0.02 -0.21 -0.12 -0.06 -0.02 -0.41 -0.40 -0.43 -0.25 -0.12 -0.06 -0.01 -0.59 -0.64 -0.62 -0.34 0.34 -0.13 -0.01 -0.05 -0.23 -0.14

 5.5 Aromatic Hydrocarbons Substituent R

S

O || C

M

–NHNH2 –N=N–phenyl –NO –NO2 –C ––– N –NCS –SH –SCH3 –S–phenyl –S–S–phenyl –S(O)–CH=CH2 –S(O)–phenyl –S(O)2CH3 –S(O)2OCH3 –S(O)2Cl –S(O)2NH2 –CHO –COCH3 –COCH2CH3 –CO–phenyl –CO–(2-pyridyl) –COOH –COOCH3 –COOCH(CH3)2 –COO–phenyl –CONH2 –COF –COCl –COBr –CH=N–phenyl –Li –MgBr –Mg–phenyl –Si(CH3)3 –Si(phenyl)2Cl –SiCl3 –P(phenyl)2 –P(O)(OCH3)2 –Pb+(phenyl) Cl– –Zn–phenyl –Hg–phenyl

Z2

-0.60 0.67 0.55 0.93 0.32 -0.11 -0.08 -0.08 -0.06 0.13 0.28 0.29 0.70 0.60 0.68 0.51 0.54 0.62 0.61 0.56 0.86 0.79 0.70 0.73 0.87 0.48 0.71 0.77 0.70 0.64 0.77 0.40 -0.49 0.19 0.32 0.52 0.0 0.46 0.30 -0.36 0.06

Z3

-0.08 0.20 0.29 0.26 0.14 0.04 -0.16 -0.10 -0.20 -0.05 0.15 0.09 0.37 0.26 0.27 0.28 0.19 0.12 0.11 0.12 0.11 0.14 0.09 0.11 0.18 0.11 0.21 0.15 0.15 0.24 0.26 -0.19 0.18 0.00 0.07 0.20 0.0 0.14 0.49 0.02 0.10

179

Z4

-0.55 0.20 0.35 0.39 0.28 -0.02 -0.22 -0.24 -0.26 -0.10 0.15 0.13 0.41 0.28 0.37 0.24 0.29 0.22 0.21 0.23 0.20 0.28 0.21 0.20 0.30 0.19 0.38 0.35 0.32 0.24 -0.29 -0.26 0.25 0.00 0.12 0.20 0.0 0.22 0.61 0.05 -0.10

C C

C

C

C

N

Hal O N S C

X

P Si Natural Products Solvents

180 1H-1H

5 1H NMR Coupling Constants in Selected Monosubstituted Benzenes (|J| in Hz) 3

C

4

C

C

C

C

5

C X O

N

Hal O

N S

N

O || C

S C

2

X

P Si Natural Products Solvents

M

Substituent R –CH3 –CH=CH2 –C ––– CH –phenyl –F –Cl –Br –I –OH –OCH3 –O–phenyl –OCOCH3 –NH2 –NHCOCH3 –NO2 –C ––– N –SH –S(O)2OCH3 –CHO –COCH3 –COOH -COOCH3 –CONH2 –COCl –Li –MgBr –P(phenyl)2 –PO(OCH3)2 –Zn–phenyl –Hg–phenyl

J23

7.7 7.8 7.8 7.8 8.4 8.1 8.0 7.9 8.2 8.3 8.3 8.2 8.0 8.2 8.4 7.8 7.9 8.0 7.7 8.0 7.9 7.9 7.9 8.0 6.7 6.9 7.6 7.7 6.6 7.5

1

R

6

J24

1.3 1.1 1.3 1.2 1.1 1.1 1.1 1.1 1.1 1.0 1.1 1.1 1.1 1.2 1.2 1.3 1.2 1.2 1.3 1.3 1.3 1.4 1.2 1.2 1.5 1.5 1.2 1.4 2.1 1.4

J25

0.6 0.6 0.6 0.6 0.4 0.5 0.5 0.5 0.5 0.4 0.5 0.5 0.5 0.5 0.5 0.7 0.6 0.6 0.6 0.6 0.6 0.6 0.6 0.6 0.8 0.7 0.6 0.6 0.7 0.6

J26

2.0 1.9 1.7 2.0 2.7 2.3 2.2 1.9 2.7 2.7 2.6 2.5 2.5 2.4 2.4 1.8 2.1 2.0 1.8 1.8 1.9 1.8 2.0 2.0 0.7 0.7 1.7 1.6 0.8 1.1

J34

7.5 7.4 7.6 7.5 7.5 7.5 7.4 7.5 7.4 7.4 7.4 7.5 7.4 7.4 7.5 7.7 7.5 7.6 7.5 7.5 7.4 7.5 7.5 7.5 7.4 7.4 7.4 7.6 7.4 7.5

J35

1.5 1.5 1.3 1.4 1.8 1.7 1.8 1.8 1.7 1.8 1.7 1.7 1.6 1.5 1.5 1.3 1.5 1.4 1.3 1.3 1.4 1.3 1.3 1.4 1.3 1.4 1.4 1.4 1.5 1.5

 5.5 Aromatic Hydrocarbons

181

1H

Chemical Shifts and Coupling Constants of Condensed AromaticAlicyclic Hydrocarbons (δ in ppm, J in Hz)

6.99

7.08

2.91

7.40 2.04 7.26 7.19

7.84

3.87 7.55

a

d

c

3.39 b

7.47

a

6.55 6.88

3.91

7.38 7.28

3J ab 4J ac 5J ad 3J bc

7.31

5.5 2.0 0.7 1.9

6.93

7.11 c 7.31 7.46

0.51

2.85

2.87 7.19

1.60

C

C

C

C

7.23 7.22

4J ab 5J ac 6J ad 3J bc 4J bd 3J cd

1.5 0 0.5 6.7 1.2 8.1

7.15

a

b c

d

7.79

-4.03 7.04

7.01

C

7.75 7.29

3.34 b

d

0.73

1.54

1.08 2.62

7.90 7.58

0.72

H

4J ab 5J ac 6J ad 3J bc 4J bd 3J cd

0 0 0 7 0.6 8

N

Hal O N

1.45

S

2.23; 2.91 6.86

C

X

P Si Natural Products Solvents

5 1H NMR

182

Effect of Substituents in Position 1 on the 1H Chemical Shifts of Monosubstituted Naphthalenes (in ppm)

C C

C

C

C

7

O

S C

X O

N

N X

P Si Natural Products Solvents

2

O || C

δH , δH , δH , δH = 7.84 1 4 5 8 δH , δH , δH , δH = 7.48 2

3

6

7

3 5

N

for R: H

R

6

C

Hal

8

4

Substituent R –CH3 –CH2CH3 –CH2C ––– CH –CH2Cl –CF3 –CH2OH –CH2NH2 –C ––– CH –phenyl –F –Cl –Br –I –OH –OCH3 –O–phenyl –OCOCH3 –NH2 –N(CH3)2 –NHCOCH3 –NO2 –C ––– N –NCO –NCS –CHO –COCH3 –COOH –COOCH3 –COCl

H-2 -0.20 -0.15 0.09 -0.10 0.51 -0.07 -0.14 0.22 -0.11 -0.35 0.06 0.29 0.20 -0.75 -0.84 -0.53 -0.31 -0.76 -0.46 0.24 0.71 0.42 -0.25 -0.13 0.46 0.40 0.72 0.65 1.03

H-3 -0.14 -0.08 -0.23 -0.18 -0.01 -0.10 -0.13 -0.14 -0.04 -0.10 -0.14 -0.25 -0.46 -0.22 -0.25 -0.10 -0.05 -0.22 -0.13 0.01 0.02 0.04 -0.13 -0.13 0.07 -0.02 0.14 -0.08 0.06

H-4 -0.17 -0.15 -0.23 -0.11 0.01 -0.09 -0.14 -0.08 -0.06 -0.23 -0.12 -0.04 0.13 -0.42 -0.55 -0.22 -0.27 -0.55 -0.36 -0.12 0.24 0.23 -0.18 -0.14 0.20 0.09 0.34 0.08 0.22

H-5 -0.03 0.00 -0.17 -0.07 0.06 -0.01 -0.05 -0.08 0.05 0.00 -0.02 -0.01 -0.22 -0.05 -0.18 0.03 -0.14 -0.07 -0.06 0.08 0.08 0.07 -0.03 -0.04 0.05 0.01 0.20 -0.05 0.02

H-6 -0.03 -0.02 -0.13 -0.05 0.07 -0.02 -0.07 -0.04 -0.13 0.05 0.02 0.04 -0.09 -0.03 -0.12 0.04 -0.23 -0.05 -0.03 0.04 0.04 0.14 0.05 0.03 0.06 0.02 0.13 -0.02 0.07

H-7 0.00 0.01 -0.03 0.02 0.13 0.01 -0.03 0.05 -0.07 0.03 0.09 0.11 -0.02 -0.01 -0.13 0.00 -0.09 -0.08 -0.06 0.08 0.16 0.21 0.01 0.08 0.17 0.09 0.20 0.09 0.17

H-8 0.12 0.21 0.52 0.22 0.35 0.18 0.10 0.51 -0.02 0.27 0.42 0.39 0.18 0.32 0.33 0.37 -0.01 -0.09 0.38 0.27 0.69 0.38 0.21 0.21 1.39 0.90 1.09 1.09 0.88

 5.5 Aromatic Hydrocarbons

183

Effect of Substituents in Position 2 on the 1H Chemical Shifts of Monosubstituted Naphthalenes (in ppm)

7

8

1

R

6

3 5

C

X O N S O || C a

for R: H

δH , δH , δH , δH = 7.84 1 4 5 8 δH , δH , δH , δH = 7.48 2

3

6

7

C C

C

C

C

4

Substituent R –CH3 –CH2CH3 –CH(CH3)2 –CF3 –CH2OH –CH=CH2 –C ––– CH –phenyl –Cl –Br –OH –OCH3 –O–phenyl –OCOCH3 –NH2 –N(CH3)2 –NHCOCH3 –NO2 –C ––– N –SH –CHO –COCH3 –CO–phenyl –COOH –COOCH3 –COCl b

H-1 -0.24 -0.22 -0.24 0.28 -0.13 -0.11 0.19 0.20 -0.04 0.14 -0.72 -0.76 -0.53 -0.30 -0.93 -1.07 0.33 0.90 0.40 -0.14 0.44 0.58 0.42 0.83 0.66 0.85

interchangeable; interchangeable

H-3 -0.18 -0.14 -0.15 0.14 -0.08 0.14 0.04 0.25 -0.08 0.05 -0.39 -0.33 -0.22 -0.27 -0.62 -0.49 -0.02 0.70 0.13 -0.19 0.45 0.51 0.46 0.57 0.50 0.58

H-4 -0.11 -0.08 -0.12 0.06 -0.07 -0.06 -0.05 0.06 -0.10 -0.16 -0.10 -0.14 -0.01 -0.04 -0.23 -0.30 -0.10 0.05 0.08 -0.17 0.05 0.01 0.09 0.20 -0.08 0.22

H-5 -0.06 -0.05 -0.10 -0.10 -0.05 -0.06 -0.03 0.01 -0.05a -0.12 -0.09 -0.10 -0.02 -0.04 -0.19 -0.29 -0.11 0.05 0.06 -0.11 0.03 0.01 0.06 0.19 -0.07 0.32

H-6 -0.09 -0.08 -0.12 0.09 -0.04 -0.06 0.02 0.02 -0.03b -0.02 -0.16 -0.14 -0.08 -0.04 -0.27 -0.39 -0.09 0.19 0.19 -0.09 0.14 0.08 0.13 0.20 -0.01 0.17

H-7 -0.05 -0.06 -0.10 0.06 -0.03 -0.04 0.02 -0.02 -0.01b 0.00 -0.06 -0.06 -0.04 -0.02 -0.15 -0.24 -0.06 0.15 0.13 -0.06 0.08 0.03 0.06 0.16 -0.05 0.21

H-8 -0.10 -0.08 -0.10 -0.10 -0.08 -0.06 -0.03 0.05 -0.12a -0.06 -0.18 -0.14 -0.15 -0.08 -0.27 -0.33 -0.09 0.14 0.06 -0.19 0.12 0.01 0.06 0.31 0.00 0.20

N

Hal O N S C

X

P Si Natural Products Solvents

5 1H NMR

184

5.6 Heteroaromatic Compounds 5.6.1 Non-Condensed Heteroaromatic Rings

C C

1H

Chemical Shifts and Coupling Constants (δ in ppm, |J| in Hz)

C

C

C

c

6.38

b

d

a

O

c

7.23

b

d

Se

N

7.42

a

7.88

3J 1.8 ab 4J 0.9 ac 4J 1.5 ad 3J 3.4 bc

6.23 3Jab 2.6 4 a 6.71 Jac 1.3 4J 2.1 N ad 3J 2.6 H e 8.1, ae broad 3Jbc 3.5 4J 2.6 be

c

b

d

3J 5.4 ab 4J 1.5 ac 4J 2.3 ad 3J 3.7 bc

7.15

b

N c

a

7.90 O

7.68

c d

3J 0.8 ab 4J 0.5 ac 4J 0.0 bc

7.09

b

a

S

b

N c

7.74 N

7.31

3J 4.8 ab 4J 1.0 ac 4J 2.8 ad 3J 3.5 bc

3J 1–2 ab 4J 1.0 a 7.13 ac 4J 1.0 bc

7.13

H 13.4

Hal O

c

b

S

8.54

b

c

X

N

S

7.98

a

8.88 S

N

C

N

7.41

3J ab 4 a 8.72 Jac 3J bc

7.26

8.31

3J 3.2 ab 4J 1.9 ac 4J 0.0 bc

b

c

N

4.7 0.4 1.7

6.38

a

O

8.49

7.74

3J 1.7 ab 4J 0.3 ac 3J 1.8 bc

c

N

8.19 N

O

7.75

N

N

N

N H ≈12

b

6.10

a

N H 13.7

7.74

N

3J 2.1 ab 4J 0.0 ac 3J 2.1 bc

N O

8.33

P Si Natural Products Solvents

N N

8.27

N H 13.5

N

S

N

8.58

9.18

HN c

+

7.58 a 7.58

b

N d H 13.5 Cl–

4J 1.4 ac 3J + 4J ad bd 3J 2.4 cd

= 4.4

 5.6 Heteroaromatics Solvent: CDCl3 a 8.59 b 7.25 c 7.62

c d

b

e

a

N

7.32 c

d

b

e

a

N

7.40 8.19

O

(in acetone)

c

d

N

DMSO 8.58 7.38 7.75

3J 6.5 ab 4J 1.1 ac 5J 0.6 ad 4J 1.9 ae 3J 7.7 bc 4J 2.1 bd

3J 4.9 b 7.56 4 ab J 2.0 a 9.22 5 ac Jad 3.5 3J 8.4 bc

N

c

N d

9.27 N

7.38 a 8.78

b

3J 5.0 ab 4J 2.5 ac 4J 0 ad 5J 1.5 bd

3J 6.0 ab 4J 1.9 ac 5J 0.9 ad 4J 0.4 ae 3J 7.6 bc 4J 1.6 bd

9.88 c

c d e

N

N N

b

+

a

N H

Solvent: ­CDCl3* DMSO** a 9.00 8.98 b 7.97 8.14 c 8.43 8.67

* p-toluylsulfonate ** HSO3–

9.48 8.84

b a

8.54 d

N

3J 2.7 ab 4J 0.0 ac 5J 2.2 bc

7.22 c

N O

c

d

8.98 N

N

8.63

c

d

N N O

N N

3J 5.3 b 7.83 4 ab J 1.0 a 8.26 5 ac Jad 1.0 3J 8.0 bc 4J 2.5 bd 3J 6.5 cd

7.34 a 8.43

b

O

N

3J 6.0 ab 4J 1.6 ac 5J 0.8 ad 4J 1.0 ae 3J 7.9 bc 4J 1.4 bd

C C

C

C

C

9.23

N

8.24 N

N

185

8.11 a 8.44

b

3J 6.8 ab 4J 1.6 ac 4J 2.0 ad 3J 4.9 bc 5J 1.0 bd 4J 0 cd 3J 4.1 ab 5J 0.8 ac 4J 0.6 ad 4J 0.4 bc

Hal O N S C

X

P Si Natural Products Solvents

186

5 1H NMR

Effect of Substituents on the 1H Chemical Shifts of Monosubstituted Furans (in ppm)

C C

C

C

C

5

4 O

C N

Hal

X O N

O N

S

S

O || C

X

P Si

M

Natural Products Solvents

δH-3 = 6.38 + Zi3 δH-4 = 6.38 + Zi4 δH-5 = 7.42 + Zi5

Substituent

C

δH-2 = 7.42 + Zi2

3 2

a

–CH3 –CH2CH3 –CH2OH –CH2SH –CH2SCH3 –CH=CHCOCH3 (trans) –Br –I –OCH3 –NO2 –C ––– N –SCH3 –SCN –CHO –COCH3 –COCO–2-furyl –COOH –COOCH3 –COCl –P(–x-furyl)2 –P(O)(–x-furyl)2 –P(S)(–x-furyl)2 –P+(CH3)(2-furyl)2 I– –HgCl –Hg–x-furyl

x = 2, b x = 3

H3 H4 H5 in position 2 or 5 Z23 Z24 Z25 Z54 Z53 Z52

-0.45 -0.42 -0.12 -0.22 -0.21 0.29 -0.23 0.04 -1.26 1.13 0.48 0.05 0.32 0.92 0.81 1.26 0.97 0.81 1.14 0.25a 0.76a 0.77a 1.53

-0.15 -0.12 -0.07 -0.09 -0.09 0.11 -0.17 -0.21 -0.14 0.47 -0.02 0.01 -0.02 0.25 0.16 0.27 0.19 0.14 0.32 -0.12a 0.15a 0.12a 0.49

-0.17 -0.14 -0.05 -0.09 -0.08 0.08 -0.17 -0.05 -0.57 0.47 -0.04 0.13 0.06 0.31 0.18 0.37 0.24 0.18 0.46 0.03a 0.30a 0.27a 0.77

0.18a

0.24a

0.47a

H2 H4 H5 in position 3 or 4 Z32 Z34 Z35 Z45 Z43 Z42

-0.25

-0.17

-0.12

-0.07

0.00

-0.06

-0.17 -0.50

-0.04 -0.36

-0.26 -0.41

0.41 -0.22 0.15 0.92 0.42

0.14 -0.13 0.11 0.47 0.28

-0.06 -0.19 -0.01 0.19 -0.16

0.70 0.60

0.40 0.37

0.03 0.01

-0.16b -0.10b -0.09b 0.14b 0.19b 0.31b 0.10b 0.18b 0.30b -0.09 0.02 0.25 -0.10b 0.10b -0.10b

 5.6 Heteroaromatics

187

Effect of Substituents on the 1H Chemical Shifts of Monosubstituted Pyrroles (in ppm)

5

4 N H1

δH-1 ≈ 8, broad, solvent-dependent

3 2

δH-2 = 6.71 + Zi2 δH-3 = 6.23 + Zi3 δH-4 = 6.23 + Zi4 δH-5 = 6.71 + Zi5

Substituent in position 1 –CH3 –CH2CH3 –CH2CH2CN –CH2–phenyl –phenyl –N(CH3)2 –COCH3 –CO–phenyl –Si(CH(CH3)2)3

Substituent

C N S O || C

–CH3 –NO2 –C ––– N –SCH3 –SCN –CHO –COCH3 –COOCH3

H3 Z12 Z15

-0.13 -0.16 -0.05 -0.12 0.36 0.11 0.56 0.57 0.08

H3 H4 H5 in position 2 or 5 Z23 Z24 Z25 Z54 Z53 Z52

5.72 7.11 6.88 6.23 6.53 7.01 6.93 6.84

5.89 6.29 6.28 6.10 6.15 6.34 6.26 6.18

6.36 7.05 7.13 6.72 6.90 7.18 7.06 6.91

C C

C

C

C

H4 Z13 Z14

-0.11 -0.12 -0.07 -0.04 0.11 -0.19 0.12 0.18 0.08

N

Hal O N

H2 H4 H5 in position 3 or 4 Z32 Z34 Z35 Z45 Z43 Z42

-0.33 1.06 0.83 0.18 0.48 0.78 0.70 0.79

-0.16 0.24 0.23 0.05 0.10 0.11 0.03 0.13

-0.26 0.43 0.51 0.10 0.28 0.47 0.35 0.29

S C

X

P Si Natural Products Solvents

188

5 1H NMR

Effect of Substituents on the 1H Chemical Shifts of Monosubstituted Thiophenes (in ppm)

C C

C

C

C

5

4

C

Hal O

X

N

S C

–CH3 –C ––– C –phenyl –2-thienyl –2-pyridyl –F –Cl –Br –I –OH* –OCH3 –NH2 –NO2 –C ––– N –SH –SCH3 –S(O)2CH3 –S(O)2Cl –SCN –CHO –COCH3 –CO–phenyl –COOH –COOCH3 –CONHNH2 –COCl * Keto form

O

N

X

P Si Natural Products Solvents

δH-3 = 7.09 + Zi3 δH-4 = 7.09 + Zi4 δH-5 = 7.31 + Zi5

Substituent

N

S

δH-2 = 7.31 + Zi2

3 2

S

O || C

H3 H4 H5 in position 2 or 5 Z23 Z24 Z25 Z54 Z53 Z52

-0.34 0.02

-0.20 -0.29

-0.24 -0.23

0.08 0.48 -0.78 -0.30 -0.05 0.11 -0.85 -0.93 -1.08 0.69 0.34 -0.13 -0.16 0.90 0.60 0.17 0.69 0.60 0.55 0.67 0.70 0.63 0.75

-0.09 0.01 -0.54 -0.35 -0.23 -0.34 0.44 -0.41 -0.58 -0.16 -0.13 -0.33 -0.31 0.07 -0.07 -0.18 0.13 0.03 0.06 -0.05 0.00 0.04 -0.07

-0.11 0.06 -0.86 -0.39 -0.10 -0.01 -3.21 -0.82 -0.96 0.19 0.17 -0.18 -0.16 0.68 0.34 0.17 0.47 0.32 0.40 0.29 0.22 0.41 0.33

H2 H4 H5 in position 3 or 4 Z32 Z34 Z35 Z45 Z43 Z42

-0.45

-0.22

-0.15

0.11

0.28

0.05

-0.80 -0.25 -0.23 -0.05

-0.40 -0.17 -0.21 -0.13

-0.31 -0.09 -0.21 -0.30

-1.10 -1.36 0.84 0.52 -0.33 -0.44 0.85

-0.36 -0.66 0.47 0.07 -0.33 -0.23 0.35

-0.17 -0.36 -0.08 0.04 -0.21 -0.14 0.35

0.14 0.81 0.74

-0.08 0.44 0.45

-0.06 0.06 0.01

0.93 0.67

0.48 0.34 -7.09 0.37

0.03 -0.16 -7.31 -0.08

-7.31

0.94

 5.6 Heteroaromatics

189

Effect of Substituents on the 1H Chemical Shifts of Monosubstituted Pyridines (in ppm) δH-2 = 8.59 + Zi2 C 4 δH-3 = 7.25 + Zi3 δH-4 = 7.62 + Zi4 5 3 δH-5 = 7.25 + Zi5 6 2 C C N δH-6 = 8.59 + Zi 6

C

X O N

S O || C

Substituent in position 2 or 6 –CH3 –CH2CH3 –CH2–phenyl –CH2OH –CH=CH2 –phenyl –2-pyridyl –F –Cl –Br –I –OH* –OCH3 –NH2 –NHCH2CH3 –N(CH3)2 –NHNH2 –NHCOCH3 –NHN=CH–2-pyridyl –NO2 –C ––– N –SH –CHO –COCH3 –CO–phenyl –COOH –COOCH3 –CONH2 –CH=N–NH–2-pyridyl –Si(CH3)3

* Keto form (2-pyridone)

H3 Z23 Z65

-0.11 -0.09 0.03 0.14 -0.07 0.42 1.27 -0.30 0.09 0.26 0.49 -0.63 -0.51 -0.76 -0.87 -0.77 -0.55 1.00 0.21 0.93 0.52 0.34 0.73 0.80 0.81 0.87 0.91 0.98 0.76 0.15

H4 Z24 Z63

-0.08 0.01 -0.06 0.03 -0.14 0.02 0.04 0.16 0.02 -0.06 -0.29 -0.13 -0.10 -0.24 -0.22 -0.23 -0.17 0.09 -0.01 0.44 0.26 -0.20 0.26 0.22 0.27 0.41 0.24 0.24 0.05 -0.22

H5 Z25 Z63

-0.15 -0.15 0.04 -0.08 -0.23 -0.09 -0.11 -0.05 0.00 0.03 0.04 -0.93 -0.41 -0.63 -0.69 -0.73 -0.58 -0.19 -0.42 0.45 0.35 -0.42 0.31 0.24 0.25 0.44 0.27 0.22 -0.06 -0.24

H6 Z26 Z62

-0.11 0.03 -0.04 -0.14 -0.12 0.07 0.00 -0.36 -0.10 -0.23 -0.23 -1.17 -0.43 -0.54 -0.52 -0.44 -0.48 -0.32 -0.36 0.00 0.15 -0.91 0.21 0.10 0.13 0.17 0.17 -0.01 -0.03 0.09

C

C

N

Hal O N S C

X

P Si Natural Products Solvents

190

C

Substituent

C

C

C

C

C

X O N

N

Hal

S

O

O || C

N S C

5 1H NMR

X

P Si Natural Products Solvents

–CH3 –CH2CH3 –CH2–phenyl –phenyl –CH=CH2 –F –Cl –Br –OH –OCH3 –OCOCH3 –NH2 –N(CH3)2 –NHCOCH3 –C ––– N –S–phenyl –S(O)2OH –CHO –COCH3 –CO–phenyl –COOH –COOCH3 –COO–phenyl –CONH2 –CSNH2 –CH=NOH –Si(CH3)

H2 Z32 Z56

-0.15 -0.13 -0.08 0.25

H4 H5 H6 in position 3 or 5 Z34 Z35 Z36 Z54 Z53 Z52 -0.16 -0.14 -0.18 0.20

-0.07 -0.06 -0.04 0.08

-0.17 -0.17 -0.14 -0.03

-0.05 0.09 0.09 -0.31 -0.27 -0.15 -0.51

-0.21 0.00 0.18 -0.29 -0.37 -0.15 -0.65

0.04 0.05 -0.04 0.06 -0.04 0.08 -0.20

-0.13 -0.05 -0.07 -0.50 -0.40 -0.13 -0.60

0.37 0.32

0.50 0.38

0.06 0.25

-0.16 0.26

0.70 0.52 0.58

1.14 0.58 0.61

0.81 0.30 0.20

0.70 0.28 0.20

0.54 0.64

0.57 0.67

0.20 0.16

0.24 0.19

0.49 0.68 0.39 0.08

0.50 0.67 0.43 0.00

0.15 0.24 0.19 -0.21

0.15 0.26 0.15 -0.11

H2

H3

-0.13 -0.12 0.00

-0.13 -0.14 -0.15

-0.12 -0.07 0.00 0.09

-0.08 -0.03 0.05 0.35

-0.16

-0.42

-0.15 -0.38 -0.19 0.24 0.05

-0.74 -0.77 0.16 0.32 -0.16

0.31 0.21 0.23 0.20 0.19 0.24

0.49 0.50 0.35 0.45 0.61 0.75

0.35 0.06 -0.08

0.68 0.32 0.01

in position 4 Z42 Z43 Z46 Z45

 5.6 Heteroaromatics

191

5.6.2 Condensed Heteroaromatic Rings 1H

Chemical Shifts and Coupling Constants (δ in ppm, |J| in Hz)

7.55 7.20 7.25

d e

c

b

6.69 a

O

f

7.54

7.47

7.82 7.36 d 7.33

e

c

b

7.33 a

S

f

7.42

7.88

3J 2.5 ab 5J 0.9 bf 3J 7.9 cd 4J 1.2 ce 5J 0.8 cf 3J 7.3 de 4J 0.9 df 3J 8.4 ef (all other coupling constants negligible)

3J 5.5 ab 5J 0.8 bf 3J 8.0 cd 4J 1.1 ce 5J 0.9 cf 3J 7.2 de 4J 1.0 df 3J 8.0 ef (all other coupling constants negligible)

7.64

3J 3.1 ab 3J 2.5 ag 7.12 d 5J 0.7 a 7.05 bf 4J 2.0 7.18 e N bg 3J 7.8 f H g 7.81 cd 7.27 4J 1.2 ce 5J 0.9 cf (chemical shifts in CDCl3, 5J 0.8 cg coupling constants in 3J 7.1 acetone) de 4J 1.3 df 3J 8.1 ef (all other coupling constants negligible) c

b

6.52

7.79 7.41 7.34

c d

b

e

N

a

O

8.10

7.58 (chemical shifts in CDCl3, coupling constants in acetone)

5J 0.2 ab 6J -0.1 ac 6J 0.4 ad 5J 0.0 ae 3J 8.2 bc 4J 1.0 bd 5J 0.7 be 3J 7.4 cd 4J 1.2 ce 3J 8.3 de

C C

C

C

C

N

Hal O N S C

7.70 7.26 7.26

c d

b

e

N N H

a

7.70 12.5* * in DMSO

8.08

3J 8.2 bc 4J 1.4 bd 5J 0.7 be 3J 7.1 cd (all other coupling constants negligible)

7.94 7.51 7.46

c d

b

e

N S

a

8.97

8.14 (chemical shifts in CDCl3, coupling constants in acetone)

5J 0.1 ab 6J -0.2 ac 6J 0.4 ad 5J 0.1 ae 3J 8.2 bc 4J 1.1 bd 5J 0.6 be 3J 7.2 cd 4J 1.1 ce 3J 8.2 de

X

P Si Natural Products Solvents

5 1H NMR

192

7.78 7.13

C

7.36

C

C

C

C

c d

a

N N H f­ 13.1

e­

7.58

(in DMSO)

7.95 7.39

b c

N N N H ≈16

d

7.42

a

b

3J 9.1 ab 4J 1.1 ac 5J 0.9 ad 3J 6.4 bc

N O

c

N

d

3J 8.9 ab 4J 1.2 ac 5J 0.9 ad 3J 6.7 bc

7.97

3J 8.3 ab 4J 1.0 ac 5J 0.9 ad 3J 7.0 bc

7.53

a

b

N S

c

N

d

(chemical shifts in CDCl3, coupling constants in acetone)

N

Hal O

8.61 7.61 b 7.66 c

a

3J 8.4 ab 4J 1.0 ac 5J 0.8 ad 3J 7.0 bc 4J 1.0 bd 3J 7.9 cd

N N S

d

8.08

N S C

a

7.83

5J 0.8 ae 3J 7.8 bc 4J 1.2 bd 5J 1.0 be 3J 7.0 cd 4J 1.2 ce 3J 7.9 de (all other coupling constants negligible)

8.10

b

7.25

X

P Si Natural Products Solvents

6.50 6.31

e f

d

g

7.76

c

N

6.28 b

a

6.64

7.14

3J 2.7 ab 4J 1.2 ac 5J 0.5 ad 3J 3.9 bc 6J 0.5 bf 5J 1.0 cg 3J 9.0 de 4J 1.0 df 5J 1.2 dg 3J 6.4 ef 4J 1.0 eg 3J 6.8 fg (all other coupling constants negligible)

9.21 b

N

8.99

c

N

N

a

8.70

N H d 13.5

(in DMSO)

7.68 6.97 6.55

d e

c

f

8.05

N

3J 1.2 ab 4J 0.7 N af 3J 9.0 b 7.67 cd 4J 1.3 ce a 7.60 5J 1.3 cf 3J 6.6 de 4J 1.3 df 3J 6.8 ef (all other coupling constants negligible)

 5.6 Heteroaromatics

6.58 d 7.41

c

e

b

N f­

7.88

6.52 6.71

b c

5J 1.0 ac 5J 0.5 bf 3J 9.2 cd 4J 1.1 ce 5J 1.1 cf 3J 6.4 de 4J 0.9 df 3J 7.1 ef (all other coupling constants negligible)

7.27

7.34

a

d

N a­

7.97

O O

5.77

3J 7.9 ab 4J 1.5 ac 5J 0.4 ad 3J 7.9 bc

7.44 6.58 6.97 6.62

d e

c

f

b

N

N

8.39

7.19 7.12

b c

a

d

193

3J 2.2 ab 6J 0.5 ad 5J 0.9 bf a 7.80 3J 8.9 cd 4J 1.2 ce 5J 1.0 cf 3J 6.8 de 4J 1.0 df 3J 6.9 ef (all other coupling constants negligible)

S

C C

C

C

C

3J 7.8 ab 4J 1.3 ac 5J 1.1 ad 3J 7.1 bc

6.42

S

N 7.46 7.70 7.23 d 7.47 e

c

f

7.22

7.82 7.55 7.72

e f

d

g

8.15

b

O

8.12 c

N

3J 9.6 ab 3J 7.7 a 6.36 4 cd Jce 1.6 3J 7.4 de O 4J 1.1 df 3J 8.4 ef (all other coupling constants negligible)

3J 4.2 ab 4J 1.8 ac b 7.39 3J 8.2 bc a 8.92 5J 0.8 cg 3J 8.2 de 4J 1.4 df 5J 0.7 dg 3J 6.9 ef 4J 1.2 eg 3J 8.5 fg (all other coupling constants negligible)

8.21 7.42 7.68

d e

c

f

O b a

O

6.34 7.88

7.47

3J 6.0 ab 3J 8.0 cd 4J 1.8 ce 5J 0.5 cf 3J 7.0 de 4J 1.1 df 3J 8.4 ef

Hal O N S

7.72 7.60 7.51

e f

d

g

7.86

7.55 c

a

b

N

9.22

8.50

5J ac 5J ad 3J bc 5J cg 3J de 4J df 5J dg 3J ef 4J eg 3J fg

1.0 C X 0.9 5.8 0.9 P Si 8.3 1.2 0.8 Natural 6.9 Products 1.2 8.3 Solvents

(all other coupling constants negligible)

5 1H NMR

194

7.90 7.68

C

7.79

C

C

C

C

e f

d

g

8.77

8.01 7.86 d 7.95

e

c

f

8.44

3J 6.1 ab 4J 1.0 ac b 7.32 3J 8.5 bc 5J 0.9 a 8.55 cg N 3J 8.2 de 4J 1.2 df O 5J 0.3 dg 3J 7.2 (all other couef pling constants 4Jeg 1.4 3J 8.6 negligible) fg c

8.18 b

N

a

9.29

N

N

Hal O

8.13 7.79

d e

N

c

f

d

S N

C

P Si Natural Products Solvents

N N

N

a

b a

8.85

c

8.97

b

7.58

3J 5.9 ab 5J 0.8 bf 3J 7.8 cd 4J 1.5 ce 5J 0.8 cf 3J 6.9 de 4J 1.3 df 3J 8.6 ef 3J 8.4 cd 4J 1.4 ce 5J 0.7 cf 3J 6.9 de

3J 8.0 ab 4J 1.8 ac 5J 0.6 ad 3J 4.1 bc

8.40

X

N

8.73

e

f

N

a

7.72 8.26

7.62* 7.60*

e f

d

g

7.79

7.68 c

a

c b

9.14 7.67

3J 8.4 ab 4J 1.6 ac 5J 0.9 ad 3J 4.2 bc 5J 0.9 df 3J 5.6 ef (all other coupling constants negligible)

b

N

8.14

4J ab 3J bc

1.7 7.0

O

8.78

* assignment uncertain

7.93 9.41 7.93* 7.67*

d e

c

b

N f

N

a

9.35

8.06 * assignment uncertain 7.93 9.44 7.85

c

d e

N f

7.93 8.76

e

N

d

f

a

N a

N

N a

8.21

4J 0.0 ab 5J 0.5 bf 3J 8.0 cd 4J 1.3 ce 5J 0.9 cf 3J 7.0 de 4J 1.3 df 3J 8.6 ef 5J 0.4 ac 3J 8.2 cd 4J 1.2 ce 5J 0.6 cf 3J 6.8 de

b

9.28 8.28

9.66 d

7.72

7.77

N

3J 8.2 ab 4J 1.9 c 9.10 5 ac Jad 0.9 b 7.52 3J 4.1 bc 3J 6.0 de 5J 0.9 df (all other coupling constants negligible)

c b

9.13 7.50

3J 8.2 ab 4J 2.0 ac 3J 4.3 bc

 5.6 Heteroaromatics 7.96 d

c b

O

a

7.35

7.46

7.57

8.16 d

c b

S

a

7.45

7.45

7.85

7.77 d

S O

O

O

c b

O

a

7.61

7.51

7.80

8.32 d

c b

a

7.46

7.36

7.70

3J 8.5 ab 4J 0.9 ac 5J 0.6 ad 3J 7.3 bc 4J 1.3 bd 3J 7.6 cd

3J 8.0 ab 4J 1.1 ac 5J 0.7 ad 3J 7.2 bc 4J 1.2 bd 3J 8.1 cd

3J 7.7 ab 4J 1.1 ac 5J 0.6 ad 3J 7.5 bc 4J 1.0 bd 3J 7.8 cd

3J 8.4 ab 4J 1.1 ac 5J 0.5 ad 3J 7.1 bc 4J 1.8 bd 3J 8.0 cd

8.08 e

c

N H a

d 7.24

b

8.03

7.42

7.42

7.79 d

S O

c b

a

7.58

7.48

7.97

8.59 7.86 e

N

O

N H a

d

c b

a

7.43

7.71

8.22

8.27 e

b

11.70

d 7.27

c 7.74 7.57

195

5J 0.7 ae 3J 8.1 bc 4J 1.0 bd 5J 0.7 be 3J 7.2 cd 4J 1.2 ce 3J 7.9 de

3J 7.7 ab 4J 1.1 ac 5J 0.7 ad 3J 7.5 bc 4J 1.1 bd 3J 7.6 cd

3J 8.9 ab 4J 1.1 ac 5J 0.8 ad 5J 0.9 ae 3J 6.7 bc 4J 1.5 bd 3J 8.4 cd 4J -0.5 de 5J ae 3J bc 4J bd 5J be 3J cd 4J ce 3J de

0.4 8.6 1.0 0.4 7.0 1.4 8.2

C C

C

C

C

N

Hal O N S C

X

P Si Natural Products Solvents

196

5 1H NMR

5.7 Halogen Compounds 5.7.1 Fluoro Compounds

C C

C

C

C

19F (natural abundance 100%) has a spin quantum number I of 1/2. The signals 1H atoms are split by coupling to 19F up to a distance of about four bonds. 1H

Chemical Shifts and Coupling Constants (δ in ppm, |J| in Hz)

4.27

2J­ HF

CH3 F

1.24 b

N

Hal

1.34

1.56 b

a

F

F 5.94

4.37 Hb

F

2J­ HF

CH2 F2

46.4 25.2 6.9

H

c

4.03

F Ha

6.17

2J­ 64.9 aF 3J­ 9.9 bF H 3J­ 21.0 cF F e Hb 3J­ 5.9 ab H 3J­ 2.4 ac Ha Hd 2J -6.7 bc 4.32 0.69 3J­ 10.8 bd 3 (in benzene/CFCl3) J­be 7.7 3J 12.0 ce

2J­ aF 3J­ bF 3J­ cF

c

X

P Si Natural Products Solvents

F a

e

d

b c

7.13

7.03 7.31

3J­ 8.9 aF 4J­ 5.7 bF 5J­ 0.2 cF

1.65

6.25

CHF3 2J­HF 79.2

50.2

2J­ aF 3J­ bF 3J­ ab

87.4 20.1 52.4

0.27

S C

5.45

46.4

2 F J­aF 3J­ a bF 4.36 3J­ab

O N

of

1.28

1.68

57.3 20.9 4.5

0.97

3J­ 12.8 ab 3J­ 4.7 ac 2J -3.2 bc

H

H

F H 2.15

H

H

1.12 H 1.86 H 1.42

3J­ 8.4 ab 4J­ 1.1 ac 5J 0.4 ad 4J­ 2.7 ae 3J­ 7.5 bc 4J 1.8 bd

1.58

a

e

b c

7.34

F

3J­ HF

1.63 H

H

15.3

F H

H 4.94

2.03 H 1.28 H 1.75 H 1.43

CF3 d

4.30

1.45

4.49

H

F

7.53 7.27

4J­ -0.8 aF 5J­ 0.8 bF 6J­ -0.7 cF

3J­ 7.9 ab 4J­ 1.2 ac 5J 0.6 ad 4J­ 2.0 ae 3J­ 7.6 bc 4J 1.3 bd

 5.7 Halogen Compounds CH3

Couplings with CH3: 4J 2.5 F 5 o Jm 0.0 6J­ 1.5 p

Ha

CF3

8.11

7.51 7.53

5J­ 2.2 aF

7.84

F a

7.61

b

7.13

7.38

197

3J­ 10.7 aF 4J­ 5.4 bF

5.7.2 Chloro Compounds 1H

Chemical Shifts and Coupling Constants (δ in ppm, J in Hz)

3.06

5.33

CH3 Cl

2.07 Cl

5.89

3J­

Cl

4.14

3J­

1.55

6.1

H e Hb

H

Hd

0.87

6.4

Cl a b c

1.06

6.8

5.48

Cl

3J­ ab 3J­ ac Cl 2Jbc 3J­ bd 3 Ha J­be 3 2.96 Jce

c

7.22­

3J­

7.33 7.28

7.0 3.6 -6.0 10.3 7.1 10.6

3J­ 8.1 ab 4J­ 1.1 ac 5J 0.5 ad 4J­ 2.3 ae 3J­ 7.5 bc 4J 1.7 bd

3.47

1.81

Cl

1.60

0.74

d

Cl

1.33

CHCl3

3.67

Cl

e

7.26

CH2 Cl2

Cl

H

Ha

c

1.33 H

C

C

C

1.68

1.41

3.42

Cl

N

Hal

Hb

5.39

1.68

3.47

C

Cl 3J­ 7.2

0.92

Cl

C

6.26

3J­ 14.5 ab 3J­ 7.5 ac 2J -1.4 bc

3.88 H

Cl

H 2.22

H

H

1.18 H 1.84 H 1.58

a

d

b c

7.25­

H

O

Cl

N 1.77 H

S

Cl

H 4.59 H C 2.00 H 1.26 H 1.55 H 1.76 H

X

P Si

CCl3 e

1.75

2.05

7.89 7.27

3J­ 8.1 ab 4J­ 1.1 ac 5J 0.5 ad 4J­ 2.4 ae 3J­ 7.5 bc 4J 1.4 bd

Natural Products Solvents

5 1H NMR

198

8.21 7.48

C

7.43

C

C

C

C

f

a

e

b

d

7.74

c

7.49

7.28

7.65

1H

2.47

N

4.94

O

5.86

3.63

7.40

1.73

N S

3J­ ab 3J­ ac Br 2Jbc 3J­ bd 3 Ha J­be 3 2.83 Jce

c

H e Hb

H

Hd

0.96

Natural Products

Br a

e

d

b c

7.28­

1.04 5.84

1.76

0.81

7.49 7.22

7.1 3.8 -6.1 10.2 7.0 10.5

3J­ 8.0 ab 4J­ 1.1 ac 5J 0.5 ad 4J­ 2.2 ae 3J­ 7.4 bc 4J 1.8 bd

3.36

1.89

Br

4.20

1.65

CHBr3

Br

Br

Br

Solvents

Cl

7.79* 7.74 *; **: assignments interchangeable

6.82

CH2 Br2

Br 3 J­ 6.4

Br

Hal

P Si

7.47** 7.45**

7.72* 7.65

Chemical Shifts and Coupling Constants (δ in ppm, J in Hz)

2.68

X

4J­ 1.0 df 5J­ 0.2 dg 3J 6.8 ef 4J­ 0.6 eg 3J­ 7.8 fg

5.7.3 Bromo Compounds

CH3 Br

C

3J­ 7.7 ab 4J­ 1.1 ac 3J 7.8 bc 5J­ 0.7 cg 3J­ 8.1 de

Cl

g

Hb

Br

H

Ha

c

5.97

1.72

3.36

1.35 H

H

H

6.44

4.09 H

Br H 2.33

7.51 7.44

7.73

1.78

7.70

7.21

3.42

Br

2.32 H

1.79 H

H

Br

Br H

H 4.81

2.08 H 1.24 H 1.60 H 1.81

Br

7.71

1.84

1.46

3J­ 14.9 ab 3J­ 7.1 ac 2J -1.9 bc

1.22 H 1.80 H 1.75

8.19

0.93

Br

Br

7.48 7.46

7.78

7.98

7.72

7.68

Br

7.53

 5.7 Halogen Compounds

199

5.7.4 Iodo Compounds 1H

Chemical Shifts and Coupling Constants (δ in ppm, J in Hz)

2.16

3.90

2.96

I

5.24

I

3J­

7.0

1.95

0.76

3J­ 7.5 ab 3J­ 4.4 ac 2J -5.9 I bc 3J­ 9.9 bd 3 Ha J­be 6.6 3 2.31 Jce 10.0

c

H e Hb

H

Hd

1.04

I a

d

7.32

b

7.70 7.10

3J­ 8.0 ab 4J­ 1.1 ac 5J 0.5 ad 4J­ 2.2 ae 3J­ 7.4 bc 4J 1.8 bd

3.16

6.57

I

1.89

e

1.04

Hb

I

H

Ha

c

6.23

1.80

1.36 H

6.53

I

7.46 7.39

7.62

3.20

I

C

C

C

C

2.06 H

I

N

Hal

H

I H 2.45

H

1.80

1.42

3J­ 15.9 ab 3J­ 7.8 ac 2J -1.5 bc

1.30 H 1.67 H 1.97

8.02­

0.93

4.18

H

I

3.15

1.86

I

I

4.24

1.86

CHI3

3.64

I

c

4.91

CH 2 I2

CH 3 I

C

1.73 H

1.72 H

I H

O

H 4.96

2.06 H 1.26 H 1.62 H 1.53

N S

I

7.68 7.97

7.02

C

X

P Si Natural Products Solvents

200

5 1H NMR

5.8 Alcohols, Ethers, and Related Compounds 5.8.1 Alcohols

C

1H

Chemical Shifts and Coupling Constants (δ in ppm, J in Hz)

C

C

Aliphatic and alicyclic alcohols: Phenols:

C

C

Hydrogen bonds strongly deshield hydroxyl protons. The position of the signal may depend heavily on the experimental conditions including the concentration of the sample. If a compound contains several kinds of hydroxyl protons (–OH, –COOH, H2O), in general only one signal at an average position is seen because of rapid exchange. In dimethyl sulfoxide (DMSO) as solvent, this exchange in most cases is so slow that isolated signals are obtained. In this case, the chemical shifts of hydroxyl protons are characteristic. However, if the sample contains strong acids or amine bases, the exchange rate increases and, also in DMSO, a single signal at an average position is observed. Frequently, intermediate exchange rates lead to very broad signals extending over several ppm and, therefore, sometimes not discernible in routine spectra. As a consequence of fast intermolecular exchange of the hydroxyl protons, their coupling with the protons on the adjacent carbon atoms is usually not observed. However, in very pure (acid-free) solutions or in DMSO, the exchange is sufficiently slow so that the H–O–C–H couplings become visible. Their dependence on the conformation is analogous to that shown by the H–C–C–H couplings (Chapter 5.1.2). In case of fast rotation: 3JHOCH ≈ 5 Hz. In cyclohexanols, the vicinal coupling constants for axial hydroxyl protons (3.0–4.2 Hz) are lower than those of equatorial ones (4.2–5.7 Hz).­

N

Hal O N S C

b

a

δOH = 0.5–3.0 (in DMSO: 4–6) ppm δOH = 4.0–8.0 (in DMSO: 8–12) ppm

CH3 OH

X

P Si Natural Products Solvents

CDCl3 a 1.13 b 3.49

DMSO D2O 4.05 3.17 3.34 3J 5.2 ab­

a

c b

CDCl3 a 1.51 b 3.71 c 1.24

OH

DMSO D2O 4.31 3.44 3.65 1.06 1.17 3J 4.8 ab­ 3J 6.9 bc­

a

c d

CDCl3 a 1.51 b 3.59 c 1.59 d 0.94

b

OH

DMSO 4.31 3.34 1.42 0.84

D2O 3.61 1.57 0.89

 5.8 Alcohols, Ethers, and Related Compounds a

c b

CDCl3 a 1.36 b 4.04 c 1.22

e

OH

d

DMSO D2O 4.30 3.78 4.02 1.04 1.17 3J 6.2 ab

CDCl3 a 1.50 b 3.64 c 1.56 d 1.39 e 0.94

b

OH

DMSO 4.30 3.38 1.40 1.30 0.87

5.2

a

b

a

c

D2O

OH

CDCl3 DMSO D2O a 1.37 4.19 b 1.28 1.11 1.24

3.61 1.51 1.35 0.91

5.6

0.34 c

H OH

e Hb

H

Ha

Hd

3.35

0.59

6.2 2.9 -5.4 10.3 6.8 10.9

f

1.63 H

e

H Hf

Hd

OH a

h 1.88 2.46 dH OH a H

1.41 H e gH

Hb

b

f

e

c d

CDCl3 a 4.69 b 6.83 c 7.24 d 6.93

4.23

Hc

2.24

H 3.52

3J­ 7.0 bc 3J­ 8.1 bd 4J 0 be 4J­ -1.1 bf 2J­ -11.0 cd 3J 7.9 ce

1.26 DMSO OH H 4.33 2.01 0.85 H H 4.09 1.78 H 0.97 1.22 1.44 1.61 1.35 OH 1.25 1.61 H 1.44 H H 4.03 1.83 0.86 H H1.54 H 0.99 1.49

DMSO 9.29 6.75 7.15 6.76

H

3J­ 8.0 bc 4J­ 1.1 bd 5J 0.5 be 4J­ 2.2 bf 3J­ 7.4 cd 4J 1.8 ce

C

C

(in DMSO)

1.05

CDCl3 a a 1.28 OH b 4.32 H b c 1.56 Hc d 1.76 e 1.76 f 1.56

C

3

(in DMSO) 3J­ ab 3J­ ac 2J bc 3J­ bd 3J­ be 3J ce

C

6.4

2

(in DMSO)

C

C OH

CH OH

CH2 OH

201

NO2

in DMSO

N

Hal O

Derivatives in DMSO: δOH 4.0–4.5 JCH,OH 4.2–5.7 Derivatives in DMSO: δOH 3.8–4.2

JCH,OH 3.0–4.2

OH 11.1

6.96 8.14

3J­ 2.3 cf 4J­ 5.2 cg 3J 10.4 de 3J­ 9.7 df 4J­ -0.9 dg 4J 0 dh 3J -11.0 ef

OH 10.57

7.16 7.58

NO2

7.00

8.10

in CDCl3

N S C

X

P Si Natural Products Solvents

5 1H NMR

202

Chemical Shifts and Coupling Constants of Enols (δ in ppm, J in Hz)

1H

C

≈16 O

C

C

C

C

H

15.5

≈16 3J­ ab 3J­ bc

O

Ha

Hc

9.7 ≈8

8.40 H b ≈9.3 5.04

O

H

Ha

O

N

H

O

O

2.04

O

6.16

1.06

O

2.00

O

(in CDCl3, partly enolized)

5.8.2 Ethers 1H

N

Chemical Shifts and Coupling Constants (δ in ppm, J in Hz) 3.24

S C

H

HO

2.18

H

2.04

O

12.45

Hal O

CH3

CH3

2.14

O

5.52 (in CDCl3, partly enol­ ized; for the keto form, see Chapter 5.11.2)

O

CH3

2.27

H

H3 C

2.11

16.2

H3 C

2.14

O

5.1

CH3

7.90 H b 5.60

16.6 H

3J­ ab

O

2J

O

X

3.65

P Si Natural Products Solvents

1.13

O

O

b

3J

a

O

3.48

gem -10.6

vic 6.1

O

alk

1.20

3J

3.34

vic 7.0

3.40 1.38 O

1.59

1.19

3.21 O

1.54 0.92

CDCl3 DMSO D2O a 3.40 3.24 3.37 b 3.55 3.43 3.60

3.34 0.93 O

3.16 a

6.44 Hb

3.88 Hc

O Hd

4.03

4J­ 0.3 ab 3J­ 7.0 bc 3J 14.1 bd 2J­ -2.0 cd

 5.8 Alcohols, Ethers, and Related Compounds

203

Chemical Shifts and Coupling Constants of Cyclic Ethers (δ in ppm, J in Hz) 1H

O

2.78 H

2.54

a b

O

3.07 H c

In derivatives: 2J­ 5–6 gem 3J­ 4.5 cis 3J­ trans 3.1 Throughout: Jcis > Jtrans O

d

3J­ ab 3J­ bc 3J bd 2J­ cd

a

CH3 1.47 H

3.34

b

CDCl3 DMSO a 3.74 3.60 b 1.85 1.76

O

b

O

3.67 2.87

N H 1.92

6.31 d

O

4.95 c

3.96 e 1.85 d

a

4.31

b 2.58

O c

a

b

6.34 4.64

1.98 O

6.38

CDCl3 a 3.65 b 1.57 c 1.64

a

c

O

O d

c

7.56

a

b

7.77 6.43

3J­ ab,cis 8.3 3J­ ab,trans 10.7 3J 2.5 bc 4J­ 2.6 bd 3J 2.6 cd 3J­ 6.2 ab 4J 2.0 ac 3J 3.8 bc 4J­ 0.6 bd

3J­ 5.0 ab 4J 2.4 ac 5J 1.2 ad 3J­ 6.3 bc 4J 1.5 bd 3J­ 9.4 cd

O

d c

e

d

a b

O

c

4.63

5.89

a

b

6.17 4.63

2.66

d

O

c

a

b

O

a

4.73

b 2.72 2J­ a,gem -5.8 2J­ b,gem -11.0 3J 8.7 cis 3J­ 6.6 trans |4Jac| <0.3

5.2 4.2 3.3 4.2

CDCl3 DMSO D2O 3.71 3.57 3.75

O

c

C

O

7.89 6.34

C

C

C

C

DMSO 3.53 1.47 1.58 O S

N 3.88 2.57

Hal O

3J­ 1.6 ab 4J­ -2.5 ac 4J ad,cis 7.1 4J­ ad,trans 4.6 3J 6.3 bc 3J­ 7.0 ab 4J 1.7 ac 4J 1.5 ae 3J­ 3.4 bc

3J­ 6.0 ab 5J 0.3 ac 4J 2.7 ad 4J­ 1.1 bc

N S C

X

P Si Natural Products Solvents

5 1H NMR

204

Chemical Shifts and Coupling Constants of Aromatic Ethers (δ in ppm, J in Hz) 1H

C C

C

C

C

a

O

3.75 b

f

e

c d

6.90 7.29

6.94

7.23* 7.21*

O

5.09

Hal O N

d

c

7.01 7.32

7.09

O

O

4.67

O

O O

3.20

5.00

6.81

O O

6.81

O

1.22 3.60

4.90

O

b

O

O

a

3.88

O

5.90

1.28

3.31 O 4.57 O

2J­ 1.5 gem

O 4.96 O 3.33

O 1.23 3.61

O 5.16 O

O

O

O

O

3.29

4.70 O 1.68

2J­ a,gem -7.5 3J ab,cis 7.3 3J­ ab,trans 6.0

O

Natural Products Solvents

b

8.3 1.1 0.5 2.6 7.4 1.7

Chemical Shifts and Coupling Constants of Acetals, Ket­als, and Ortho Esters (δ in ppm, J in Hz)

S

P Si

a

3J­ ab 4J­ ac 5J ad 4J­ ae 3J­ bc 4J bd

1.31

1H

4.44

X

1.38

e

O

4.51

O

O

* assignment uncertain

N

C

3.98

5J­ ≈0.8 ab 3J­ 8.3 bc 4J­ 1.0 bd 5J 0.4 be 4J­ 2.7 bf 3J­ 7.4 cd 4J 1.8 ce

1.62 0.91

3.80

3.32 O 4.29 O

1.22 O

O

O

O

3.58

 5.9 Nitrogen Compounds

205

5.9 Nitrogen Compounds 5.9.1 Amines

C

Amine and Ammonium Protons (δ in ppm, |J| in Hz)

Chemical shifts of amine protons lie around 0.5–6 ppm depending on solvent, con- C centration, and hydrogen bonding. Those of ammonium protons are found between ca. 7 and 12 ppm. Neighboring H bond acceptors lead to deshielding in all cases. Amines: δNH2, δNH Ammonium: δNH3+, δNH2+, δNH+

in CDCl3 <1–2 3–4 7–11 8–12

aliphatic aromatic aliphatic aromatic

in DMSO 2–4 4–7 7–11 8–12­­

C

C C

Coupl­ing of amine protons with vicinal H atoms is usually not seen in aliphatic amines because of their rapid intermolecular exchange. However, for =C–NH–CH moieties (enamines, aromatic amines, amides, etc.), the exchange rate is slower and N splitting (or line broadening at intermediate rates) is often observed. The H–C–N–H coupling depends on the conformation in a similar way as the H–C–C–H coupling Hal (see Chapter 5.1.2). For N–CH3 and N–CH2 groups: 3JHCNH ≈ 5–6 Hz. In acidic media (e.g., in trifluoroacetic acid as solvent), the exchange of the ammonium protons is slowed down to such an extent that the vicinal coupling H–N+– O C–H generally becomes observable. In other media, signals are usually broad owing to intermediate exchange rates. The signals o­f amine and especially of ammonium protons are often broadN ened additionally because the 14N–1H coupling is only partly eliminated by the quadrupole relaxation of 14N (spin quantum number, I = 1; natural abundance, 99.6%; 1JNH ≈ 60 Hz). This line broadening has no effect on the vicinal H–C–N–H S coupling so that sharp multiplets can be observed for neighboring H atoms even when the NH proton exhibits a broad signal. In ammonium compounds of high symmetry, the quadrupole relaxation is slow and the coupling with 14N leads to C X triplets of equal intensity for all three lines.

P Si NH4 +

1J­ 52.8 NH

N+ a

3.36

b

Br–

1.79

c

1.06

2J­ 0.5 aN 3J­ 1.6 bN 4J 0.0 cN

Natural Products Solvents

5 1H NMR

206 1 ­H

Chemical Shifts and Coupling Constants of Amines and Ammonium Salts (δ in ppm, J in Hz) 2.47

C C

C

C

1.10

CH3 NH2

C

2.74

≈2.3

1.11

(CH3 )2 NH

gem

-11.7

1.14–1.69 0.99 H 1.10 0.92

0.80 H N

2.62 0.91

N

N

Hal O N

NH2

3.07

N

0.88 1.05 H 1.10

c

H 0.20

X

P Si Natural Products Solvents

e Hb

H

H d 0.32

NH2 1.59 Ha 2.22

(neat)

1.72*

H H

I

1.68

–

N

2.63

N

3.40 N+

Br–

(in D2O)

2.79

S C

+

(CH3 )4 N+ AcO–

1.03 1.15

1.02 1.45

1.27 3.27

3.46 (in CDCl3)

1.41

1.29 2.38

3.21 (in D2O) (CH3 )4 N+ I–

NH2

1.35 2.69

1.03 2.52

(CH3 )3 N

1.11

1.43

2.66

2.22 2J

0.92

NH2

N

2.64

3J­ 6.6 ab 3J­ 3.6 ac 2J -4.3 bc 3J­ 9.7 bd 3J­ 6.2 be 3J 9.9 ce

1.37

1.55* H 1.64* H

H

H

2.23

1.87

H

NH2

H 3.40

H H

H H 1.76 H

1.27

1.30

H

0.96

1.64

2.55

H

0.84

N

2.59

2.23 * assignment uncertain

1.03

H 3.31

1.02

N

2.91

NH2

H 1.28* H 1.82 1.55 * assignment uncertain

1.0 1.04 H

1.03

H

NH2

1.89

1.30

NH2

3.15

H

0.86

H

1.65 H H 1.53 H

0.96

1.54

 5.9 Nitrogen Compounds NH2 3.61 e

a

d

b

c

6.67 7.14

3J­ 8.0 ab 4J­ 1.1 ac 5J 0.5 ad 4J­ 2.5 ae 3J­ 7.4 bc 4J 1.6 bd

6.75 δNH in DMSO: 4.94 2

3.66

2.83

e

a 6.61

HN

d

b 7.18

c

6.70 δNH in DMSO: 5.52

3.70

4.62 HN

N+ (CH3 )3 Cl–

3J­ 8.2 ab 4J­ 1.1 ac 5J 0.4 ad 4J­ 2.5 ae 3J­ 7.3 bc 4J 1.7 bd

N

2.94 a 6.74

e d

c

b 7.24

6.72

2.94

207

3J­ 8.4 ab 4J­ 1.0 ac 5J 0.4 ad 4J­ 2.8 ae 3J­ 7.3 bc 4J 1.8 bd

3.10

N

6.53

8.08 7.59 (in DMSO)

NO2

a

(neat)

1.61

2.23 N

2.33

1.41

1.59

N

H 2.08 N

2J­ ≈1 gem 3J­ ab,cis 6.3 3J ab,trans 3.8

H 2.18 N

H 2.01 N

2.33

CH3 NO2

1.53

NO2

1.53

1.53

4.44

N

2.26

H 2.59 N

N

O

O

2.86 3.67

1.58 4.43 1.07

O

2.79

2.75 1.59

3.63

Hal

N

2.32 3.62

NO2

2.07

1.50 4.47

Jvic 7.4

N H 1.72

NO2

2.01 1.03 1.59

S

2.37 2.88

C

X

P Si

Chemical Shifts and Coupling Constants (δ in ppm, J in Hz)

4.34

C

δNH in DMSO: 7.32

5.9.2 Nitro and Nitroso Compounds 1H

C

NO2

Chemical Shifts and Coupling Constants of Cyclic Amines (δ in ppm, J in Hz)

b

C

8.09

1H

H 0.9 N

C

6.59

8.09

7.64

C

NO2

4.28

NO2

Natural Products Solvents

5 1H NMR

208

4.91 2.26, 2.12

C C

1.67 H

C

C

Hb

Ha

Hc

NO2

6.55

H H

1.28 H 1.85 H 1.85

C 7.12

H

H

1.88, 1.70

5.87

4.38

1.38

NO2

3J­ 7.0 ab 3J­ 14.6 ac 2J­ 1.4 bc

e

a

d

b

c

NO2

8.27 7.60

7.73

4.43

H

2.23

H

3J­ 8.4 ab 4J­ 1.2 ac 5J 0.4 ad 4J­ 2.4 ae 3J­ 7.5 bc 4J 1.5 bd

NO2

NO2

H H

H

2.60

1.62

NO e

a

d

b

c

H

7.84 7.57

7.63

3J­ 7.9 ab 4J­ 1.3 ac 5J 0.6 ad 4J­ 2.0 ae 3J­ 7.4 bc 4J 1.4 bd

5.9.3 Nitrites and Nitrates

N

1H

Hal O

O NO

1.39

1.37

S

1.41

4.78

4.52

N

C

Chemical Shifts (δ in ppm) 0.96

O

1.72

1.06 O NO2

4.71

1.59 NO

O NO

4.39

1.78

5.19

1.37

O NO2

O NO2

5.9.4 Nitrosamines, Azo and Azoxy Compounds

X

P Si Natural Products

1H

Chemical Shifts (δ in ppm)

Owing to hindered rotation around the N–NO bond, corresponding protons in cis and trans positions have different chemical shifts in the neighborhood of the N=O group. In general: δcis < δtrans for α-CH3, α-CH2, and β-CH3 δcis > δtrans for α-CH

Solvents

N

3.76

N

O

2.96

N

1.52 4.26

N

O

1.15 4.89

0.97

1.75

N N

O

1.75

0.93

1.39 4.07 3.53 1.39

 5.9 Nitrogen Compounds 3.7 N

3.4

N

N

N

7.92

N

N

209

7.50 7.45

4.16 N+

N

O–

1.48 N+

3.16

7.54

N

7.51

8.30 +

N

1.28

O–

8.17

N

7.48

C C

C

C

C

7.39

O–

5.9.5 Imines, Oximes, Hydrazones, and Azines 1H

Chemical Shifts (δ in ppm)

7.46 7.89

3.4 7.46

CH N

8.40

7.20 7.38 7.22

CH N

8.43

In aldoximes and ketoximes, the chemical shift difference between syn and anti protons at the α-CH group, Δδ = δsyn - δanti, depends on the dihedral angle, φH–C–C=N: H

φ

φ

9.9

N

N

H

OH

N

1.83 7.52

2.22

6.9

OH

N

2.50 1.74–1.55

2.60

S 10.18

OH

1.89 1.90

8.9

N

N

9.3

H

6.92 1.86

O

1 0 -0.3

9.9

OH

Hal

Δδ = δsyn - δanti

0o 60o 115o

N

N

OH

N

2.23

OH

2.25

1.66

1.64

(in DMSO)

7.0

N

OH

2.30

C

X

P Si Natural Products Solvents

5 1H NMR

210

2.14 7.57 CH3 CH

C C

H N

N

C

7.79

5.78

NO2

H H

NO2 NO2 9.12

H

5.74 2.03

N H

7.89

N

Hal

H

1.83

8.06* 7.14 8.18 H N

N

NO2

8.66 CH

N

N

CH

5.9.6 Nitriles and Isonitriles Chemical Shifts and Coupling Constants of Nitriles (δ in ppm, J in Hz) 1H

O

1.98

N

1.31

CH3 CN

X

1.37

1.70

CN

2.35

3J

S C

N

NO2 9.10

* in DMSO: 11.33

7.44

N

N

7.81

7.44 7.83

2.00

NO2

2.33

CH

7.3–7.5

6.62

H N

N

7.69

H N

N

11.04 7.94 8.29

H

1.99

11.12 7.96 8.32

H

7.56

1.03

NO2 9.10

C

C

11.02 7.93 8.28

vic

CN

P Si

1.08 2.34

7.6 6.11

5.69

Hc

CN

Hb

6.24

Natural Products

c

H 1.04 e Hb

Solvents H

Hd 0.96

CN Ha

1.29

3J­ 8.4 ab 3J­ 5.1 ac 2J -4.7 bc 3J­ 9.2 bd 3J­ 7.1 be 3J 9.5 ce

Ha

CN

1.35

0.96 1.63

CN

2.67

1.50 2.34

CN 3J­ 11.8 ab 3J­ 17.9 ac 2J­ 0.9 bc

e d

a b

c

H

H

7.48

7.62 1.50

1.22 H 2.39 H

CN

2.08 H H 1.76 H 1.52 1.20

1.70

7.66

H

H

1.70

3J­ 7.8 ab 4J­ 1.3 ac 5J 0.7 ad 4J­ 1.8 ae 3J­ 7.7 bc 4J 1.3 bd

CN H

H

CN

2.96

H

2.00

H 1.70 H 1.54

1.20

 5.9 Nitrogen Compounds

211

Chemical Shifts and Coupling Constants of Isonitriles (δ in ppm, |J| in Hz) 1H

Because of the symmetrical electron distribution around the N atom, the quadrupole C relaxation of the nitrogen nucleus is so slow that the 14N-1H coupling becomes observable and leads to triplets with relative intensities of 1:1:1 (spin quantum number C C of 14N: I = 1; natural abundance, 99.6%): b

a

14

CH2 CH2

2.85 a

CH3 NC |2JaN|

1.45 a

NC

1.28 b

2.3

NC

a

3.89

NC 3 | JaN| 2.1

|2JaN| |3JbN|

1.8–2.8 1.5–3.5

C

1.45

|2JaN| 2.0 |3JbN| 2.4 |3Jab| 7.3

b

a

|2JaN| 1.8 3 3.87 |3JbN| 2.6 | Jab| 7.0 NC

5.35 H b

H a 5.90 |2J­aN| 2.3

5.58 H c

NC

|3J­bN| 6.1 |3JcN| 3.1

3J­ 8.6 ab 3J­ 15.6 ac 2J -0.5 bc

N

Hal

5.9.7 Cyanates, Isocyanates, Thiocyanates, and Isothiocyanates 1H

O

Chemical Shifts and Coupling Constants (δ in ppm, J in Hz)­

1.45

OCN

4.54 1.29

NCO

CH3 NCO

0.94

3.72

2.60

CH3 SCN

3.37

CH3 NCS

1.20

3.02

1.58

1.42

1.53 2.98 1.40 3.64

3.37

0.99

4.77

Hb

NCO

3.29

SCN

1.63

NCO

Hc

5.01

6.12

Ha NCO

3.26

N

NCO

3J­ 7.6 ab 3J­ 15.2 ac 2J -0.1 bc

S C

X

P Si

SCN

Natural Products

3.48

NCS NCS

C

7.15 Solvents

NCS

3.98

7.24

7.30

5 1H NMR

212

5.10 Sulfur Compounds 5.10.1 Thiols

C

1H

C

C

C

C

Chemical Shifts and Coupling Constants (δ in ppm, J in Hz)

Typical ranges of SH chemical shifts: alk–SH

1–2

SH

2–4

The exchange with other SH, OH, NH, or COOH protons is generally so slow that the chemical shift is characteristic and the vicinal coupling with SH protons becomes visible (5–9 Hz in aliphatic systems with fast rotation). 2.00 1.26

N

CH3 SH

Hal O

1.59

1.43

1.32* SH

1.63

SH

0.99 2.50

1.43

2.52

1.31

X

SH

1.82

P Si Natural Products Solvents

H H H 1.75 H

1.22

3.16

1.51** H

5.7

SH 1.62 H

H

H 3.19

2.04* 1.59* *; **: assignments uncertain

H

H

1.61

1.56

b SH a 3J ab

1.79** H

SH

2.79

H

1.34

1.33

* in DMSO: 2.17

S C

1.39

2.44

(in benzene) 0.92

N

1.31

Jvic 7.4

SH 1.51

2.01

1.34

SH

H

H H

H

H

1.5

3.43

H

1.9

SH 3.40 e d

a c

7.04

b

7.18 7.10

3J­ 7.9 ab 4J­ 1.2 ac 5J 0.6 ad 4J­ 2.1 ae 3J­ 7.5 bc 4J 1.5 bd

 5.10 Sulfur-Compounds 5.10.2

213

Sulfides

Chemical Shifts and Coupling Constants (δ in ppm, J in Hz)

1H

2.12

2.10

S

S

2.09 2.49 S

S

7.02

S

1.26

S e

a

d

b

c

7.20 7.06

7.20

2.93

S

H a 6.43

1.26 C

C

C

C

3J­ 10.3 ab

H b 5.18 3J­ac 16.4

S

2.47 7.18 7.16

1.25

2.25

S

0.92

2.55

1.60

1.42

1.42

1.56

0.99

2.48

2.51

C

2J

H c 4.95

bc -0.3

3J­ 7.8 ab 4J­ 1.2 ac 5J 0.6 ad 4J­ 2.0 ae 3J­ 7.4 bc 4J 1.5 bd

N

Hal O

1H

Chemical Shifts and Coupling Constants of Cyclic Sulfides (δ in ppm, J in Hz) S

2.36

S

S S

2J­ 0 gem 3J 7.2 cis 3J trans 5.7

3.67 5.81

2.85

6.06

S

c

b

a

3.21

2.94

S

d

5.48

a b

c

S

2.08

2.83

3.08 2.62

3.79 S

2J­ a,gem -8.7 2J­ b,gem -11.7 3J ab,cis 8.9 3J­ ab,trans 6.3 4J ac,cis 1.2 4J­ ac,trans -0.2 3J­ 9.2 ab 3J­ 2.5 bc 4J 2.2 bd 3J­ 6.1 cd

S

2.84

S

N

3.81

2.82

S

1.94

S

S

3.11

C S

≈1.7

5.97 5.55

S

2.57

≈1.7

2.57 3.88

O

P Si Natural Products

S S

X

4.28 S

(in DMSO)

Solvents

5 1H NMR

214 5.10.3 1H

C C

C

C

C

Disulfides and Sulfonium Salts

Chemical Shifts and Coupling Constants (δ in ppm, J in Hz)

S

2.30

S

Hal O

e

a

d

b

5.10.4

N

C

X

Solvents

7.47

1.00 2.66

3J­ 7.5 ab 4J­ 1.4 ac 5J 0.5 ad 4J­ 2.0 ae 3J­ 7.2 bc 4J 1.6 bd

1.31

S

S

2.7 1.9

S

S

1.01

7.29

2.94

S

1.57

3.75

1.84

(CH3 )3 S+ I–

S+ I–

(in DMSO)

Sulfoxides and Sulfones

Chemical Shifts and Coupling Constants (δ in ppm, J in Hz) O

O

S

S

2.62 (in DMSO) neat: 2.50 O

P Si Natural Products

S

S

7.24

1H

S

c

1.70

S

2.69

S

S

N

1.32

alk

O

S

S

2.61

H 6.08 H

H

6.77 O

O

2.84

S

5.92

O

1.47

2.80 2.94

O H 6.43 H

2.96 H 6.14 6.76

O

S

O

O

S

S

2.42 1.92

O

S

3.15

O

2.88

O

O

3.13

1.41 S

S

2.43 2.05

2.85 O

2.64

O

S

1.44 O

O

3.74

O

O S

3.06 7.94

6.08 7.65

7.61

 5.10 Sulfur-Compounds 5.10.5 1H

Sulfonic, Sulfurous, and Sulfuric Acids and Derivatives

Chemical Shifts and Coupling Constants (δ in ppm, J in Hz)

1.42 3.17 CH3 CH2

SO2

11.1

3.02

OH

CH3

Apparently lower δOH values in DMSO due to fast exchange with H2O 3.70

3.91

SO2

2.78

CH3

O CH3

OH 11–12

OCH3

Cl

NH2 7.37

SO2

SO2

SO2

SO2

7.62

O

O O

S

S

7.94 7.60

3.97 4.03

O O

O

S

O

O 3.94

5.10.6

8.02 7.61

7.71

3.64

O

1H

215

1.26

O

O

O

S

2.86 SO2

5.07

C

C

C

2.63

7.86 7.4–7.7

7.58 (in DMSO)

O O

S

4.49 O O

1.43

O

3.25

N

Hal

2.64 S

O

O

N

O

4.68

S

Thiocarboxylate Derivatives

Chemical Shifts and Coupling Constants (δ in ppm, J in Hz) O

O

2.41 H3 C

SH 5.09

a

S

4.29

c

b

6.47

7.84

S O

2.30 H3 C

C

SO2

O 4.34 O

CH3

NHCH3

7.85 7.58

2J­ -10.3 gem 3J­ 6.7 vic 3J'­ 6.9 vic

CH3

N

C

9.56 HN SCH3 2.27

3.38

1.79

2.98 1.72 1.65

3J­ 5.9 ab 4J­ 2.0 ac 3J­ 2.8 bc

C

S

7.1

O

7.7

6.4

6.9

X

P Si Natural Products Solvents

216

5 1H NMR

5.11 Carbonyl Compounds 5.11.1 Aldehydes

C

1H

C

Chemical Shifts and Coupling Constants (δ in ppm, J in Hz)­

C

C

alk

C

alken

CHO

Hal

C

a

3J

b

ab

9.57

N S

6.52

P Si Natural Products

9.48

Hd

6.37 Hb

6.35

O H a 9.59

O

H 10.03

7.88

Solvents 7.63

7.53

1.67 0.97

1.35

3J­ 4.7 ab 4J­ <1 ac 4J <1 ad

H 10.24

O

2.64

7.77 7.33

7.45

7.43

3J­ 10.0 bc 4J­ 17.4 bd 2J 1.0 cd

7.23

Hc

7.4

O

7.4 H 9.95

7.53

3J

2.42

9.74

CHO b

9.76

a CHO b

2.42 ab 1.9

9.67

CHO a

H 6.69 b

3J­ 7.8 ab 3J ­ 16.0 bc

H 11.54

O

8.99

7.76 7.32

a

2.42 3J 2.0 ab

0.93 1.59

CHO

ab 1.1

Hc

X

9.79

a CHO b

2.46 3J 1.4 ab

3.0

1.08

a CHO b 2.39 3J

0–3 ≈8

1.13

H3 C CHO

|2Jgem| 42.4

1.13

O

vic

2.20 9.79

O

(in TMS)

N

vic

meta-, para-substituted: 9.5–10.2

R

9.60

3J

ortho-substituted: 10–10.5

CHO

CH2

3J

9–10 9–10

CHO

8.71

8.07

7.69 7.56

 5.11 Carbonyl Compounds

217

5.11.2 Ketones 1H

Chemical Shifts and Coupling Constants (δ in ppm, J in Hz)­ O

O

2.17

2.14

O

2.44

1.13 2.29

Hc

Hb

Ha

6.30 O

7.96 7.46

7.95 2.60

7.56

O

7.95

5.91

3J­ 10.7 ab 3J 18.7 ac 2J 1.3 bc

7.45

O

H

1.96 1.44

0.97

H

O H

2.40 H H 2.08 H 2.31

1.46

Ha

6.67 7.95

7.42

3.03

7.77 7.37 7.59

7.48

C

3J­ 11.0 ab 3J­ 17.9 ac H b 2Jbc 1.4

O

1.77

N

2.93 1.00

Hal O N

O

S

O

2.17 1.98

8.01

O

3.15

C

6.78

O

2.70

C

O

7.90

2J­ aa,gem -17.5 3J­ ab,cis 10.0 3J­ ab,trans 6.3 4J­ 4.2 ac,cis 4J­ -3.0 ac,trans 2J bb,gem -11.1

C

5.82

7.57

a b

2.58

7.46

O

1.65

Hc

7.55

3.54

c

6.28

O

H

1.22

1.11

2.14

H

O

1.22

O

0.93

2.98

7.55

O

1.60

2.13 2.40

6.21

O

2.14

O

1.06

C

7.46* 7.33*

1.71

2.33 1.88

C

X

P Si Natural Products

O

2.63

2.12 Solvents

7.21 2.93 * assignment uncertain

5 1H NMR

218 1H

Chemical Shifts of Diketones (δ in ppm)­ O

C C

C

C

C

O

2.34

O

O

3.62 2.17 For the enol form, see Chapter 5.8.1

3.0

O

7.96

O

O

7.87

3.24 O

Long-Range Coupling in Ketones (|J| in Hz)­ For fixed conformations, the coupling over the C=O group is often detectable for W-arrangement of the coupling path. O R

R a

N

Hal O

C

|4J

b

Br

W-arrangement

Chemical Shifts (δ in ppm)­ b

a

N

H COOH

S

CDCl3 DMSO D2O a 8.05 8.13 8.26 b 10.85 12.50

X

Solvents

|4Jab| 1.0

Hb

5.11.3 Carboxylic Acids and Carboxylates

a

Natural Products

0–0.5

No W-arrangement

1H

P Si

ab|

Ha O

1.68 1.00

2.31

1.06

COONa

2.18 (in D2O)

H3 C COOH

2.56

2.43

11.88

COOH

12.2

6.53

COOH COOH

(in DMSO)

H

5.95

11.96

2.35

COOH

1.23

8.12

OH H

6.15

11.49

COOH

COOH 12.09

O

H

COOH

CDCl3 DMSO a 1.16 1.00 b 2.39 2.21 c 10.35 11.90

0.93 1.62 1.39

c

b

CDCl3 DMSO a 2.10 1.91 b 11.51 11.91

11.51 1.21

COOH

a

b

12.8

7.62

7.45

 5.11 Carbonyl Compounds

219

5.11.4 Esters and Lactones 1H

Chemical Shifts and Coupling Constants of Carboxylic Acid Esters C (δ in ppm, J in Hz)­ 7.33 O Hb O 3.76 4J­ -0.7 3J 6.4 C C bc ab 4 Hc CH3 | J­ab| 0.8 5J­ 1.6 3J 13.9 Ha O Ha O bd b 4.66 5 ac J­ad 0.8 2Jcd -1.7 8.07 8.07 H d

O

O

3.67 O

2.01 O

O

2.02

2.13

1.23 7.28

O

O

4.99

Ha

4.56 Hb

O

1.26

2.29

4.88 1.15

O

2.32

O

0.92 1.61 1.33 2.31

O

1.65

3.67

3.66 O

1.20

O

d

a

c b

O

7.37

3J­ 8.2 ab 4J­ 1.1 ac 5J 0.5 ad 4J­ 2.5 ae 3J­ 7.5 bc 4J 1.7 bd

O

F

O N S C

4.41 O

Hal

3.67 O

2.56

F F

N

1.45

O

1.17

3.66 O

7.22

7.08

O

0.98 2.22

O

O

e

O

Hc

1.65

O

1.60 0.94

3J­ 6.3 ab 3J 14.1 ac 2J -1.6 bc

C

4.02 0.95 O

2.05

4.06 1.39 O

2.04

O

4.12 O

2.04

C

4.96

X

P Si Natural

1.40 Products

Solvents

5 1H NMR

220 6.41 H

C

O

5.83

C

C

C

H

3.77

H

C

O

1.38

O

O

N

Hal

O

3.56

O

Ha

4.09

S X

P Si Natural Products Solvents

2.49

8.21 7.52

≈1.6

6.05

7.44 7.28

7.64 O O

4.91

2.50

a

O

7.10

7.48 d

b

c

6.31

7.33

6.25

5.11.5 Amides and Lactams Amide Protons (δ in ppm, J in Hz) O R

O NH2

5–7 R: alk or ar

R

O N H

6–8.5 R: alk or ar

alk

3.92

7.22

O

O

O

4.44

O

7.55

2J­ -12.7 cd 3J­ 7.9 ce 3J­ 6.3 cf 2J­ -8.8 ef

O

3.31 ≈1.6

O

5.22

2J­ -17.5 ab 3J­ 9.5 ac 3J­ 6.9 ad 4J­ 0.3 ae 4J­ -0.5 af

Hc

O O

1.37

7.46

4.32 Hf H d 2.26

O N

O

Hb

He

4.29

6.13

7.99 7.37

7.52

8.04 7.43

1.30

H

O

4.36

O

4.21 O

5.81

6.12

O

O

H

H

8.05 7.41

C

6.37

O

R

N H

7.5–10 R: alk or ar

Higher values in DMSO or with H bond acceptors in the neighborhood.

6.18 7.59 3J­ 9.4 ab 4J­ 1.5 ac 5J­ 1.3 ad 3J­ 6.3 bc 4J­ 2.4 bd 3J­ 5.0 cd

 5.11 Carbonyl Compounds

221

The signals of the NH protons are often broad because the 14N–1H coupling is only partly eliminated by the quadrupole relaxation of 14N (spin quantum number, I = 1; 1JNH ≈ 60). In primary amides, the hindered rotation around the CO–N bond is another reason for line broadening. At slow rotation, the chemical shifts of the two C primary amide protons differ by about 0.4–1 ppm. Therefore, at intermediate rotation rates, line widths of up to 1 ppm may be observed. Due to the slow intermolecular exchange of amide protons, their coupling to C C neighboring hydrogen atoms is usually detectable. The splitting of the C–H signal is clearly observed even in those cases where the signal of the NH proton is broad C C and featureless. The H–N–C–H coupling depends on the conformation in a similar way as the H–C–C–H coupling (see Chapter 5.1.2). For N–CH3 and N–CH2 groups: 3J HNCH ≈ 7 Hz. Tertiary Alkylamides The rotation around the CO–N bond is usually so slow that, for identical substituents, two separate signals are observed for cis and trans positions. With different Nsubstituents, two separate pairs of signals are observed for the two conformers. In general, the following relationships hold: for NCH3, NCH2CH3, and NCH(CH3)2 δcis to O ≤ δtrans to O for NCH(CH3)2 and NC(CH3)3 δtrans to O ≤ δcis to O for NCH2 δcis to O ≈ δtrans to O

N

Hal

Formamides (δ in ppm, J in Hz)

O

In the more stable conformer of monosubstituted formamides, the substituent occupies the cis position relative to the carbonyl oxygen. In the more stable conformer of asymmetrically disubstituted formamides, the larger substituent occupies the trans position relative to the carbonyl oxygen.

N

O Ha

O

O N Hc

Hb

CDCl3 DMSO a 8.23 7.98 b 5.80 7.14 c 5.48 7.41

Ha

N Hc

b

≈ 90% in CDCl3

CDCl3 DMSO a 8.19 8.01 b 2.86 2.59 c 5.55 7.90

Ha

2.88

O

NH c b

≈ 10% in CDCl3

CDCl3 DMSO a 8.06 7.81 b 2.94 2.72 c 5.86 7.90

Ha

8.02

N c

2.97

4J­ ≈0.3 ab 4J­ ≈0.7 ac

b

S C

X

P Si Natural Products Solvents

5 1H NMR

222 O H

C C

H

N

8.00 3.30

8.13

O

3.32 N

H

1.17

H

6.6

O

C H

N

1.20

H

4.12

4.78

N

1.10

2.83

1.19

≈ 30%

NH

8.69

1.14

N

8.34

H

3.32

O

2.71

≈ 70%

O

8.06 3.34

7.15 7.33

O

7.09 7.37

7.21 ≈ 35% 3J HCNH 10.6

H

8.40

3J

N H

7.55

7.14

≈ 65% HCNH ≈0

Amides of Aliphatic Carboxylic Acids (δ in ppm, J in Hz)

N

Hal

In monosubstituted acetamides, the substituent of the only observable conformer is cis to the carbonyl oxygen. In disubstituted acetamides, the more stable conformer has the larger substituent cis to the carbonyl oxygen.

O

O

S X

P Si Natural Products

CDCl3 DMSO a 2.03 1.76 b 5.42 7.30 c 5.42 6.70

6.7 O

Solvents 1.98

1.14 3J­ ab

≈2.0

7.05

N

a

Hb

O

3.18 0.96 N H

1.55

1.49 0.92

bc

4.8

N Hb

≈2.0

8.1

a 4.01

1.13 3J­ ab

8.4

O

O

≈2.0

c 3J

CDCl3 DMSO a 1.98 1.78 b 5.53 7.70 c 2.80 2.50

5.9

3.21 1.35 N H

Hc

O

a

N Hb

Hd

CDCl3 DMSO a 1.17 0.97 b 2.26 2.04 c 5.38 7.16 d 6.14 6.62

3.26

O

O N

b

Hb

1.98

O

a

Hc

N

a

N

C

H

1.21

C

C

O

6.6

N H

7.3

1.28

2.08

N

3.01 2.94

 5.11 Carbonyl Compounds O

2.70 N

4.11

O

H

N H H

O

1.03

3.67 H H 2.01

5.56 1.85

H H 1.66 H

1.04

1.51 O

2.08

3.40 N

3.54

3.42 1.96

NH 1.11 H

e

1.57*

N H

2.18

1.54*

1.64* * assignment uncertain

d

c b

a

0.84

C

C

C

C

H H 1.78 H

1.07

O

C

1.86

5.42

0.87

H

3.46 N

2.05

2.83 ≈ 60%

1.15

1.99

O

4.52

N

3.92

≈ 40%

1.03

O

223

1.01 3J­ 8.2 ab 4J­ 1.2 ac 5J 0.5 ad 4J­ 2.4 ae 3J­ 7.4 bc 4J 1.5 bd

7.11

7.32

7.49

N

Hal O

Lactams (δ in ppm, J in Hz) O

2.75

2.82

N

6.06

HN

3J

3.29

O

2.37 1.81

1.82

3.35

HN

NH O 3J

O

2.37

N

3.39 2.03

6.33

8.00

HNCH2 2.2

6.35

HN

3.21

O

3.31

1.65 1.75

1.69

2.36

3.36

N

S

1.81

1.79

C

X

P Si

O

2.98 2.46

N

O

HN

HNCH2 0.8

O N

2.30

2.85

3.40 2.14

3.20

2.94

O

2.52 Natural

1.65 1.70

1.66 Products

Solvents

5 1H NMR

224

5.11.6 Miscellaneous Carbonyl Derivatives Carboxylic Acid Halides (δ in ppm, J in Hz)

C

O

C

C

C

C

Cl

2.66

H

O

Hb

F

6.16

H

O

O O

3.01

X

O

1.22 Cl

2.93

3.03

O

3J­ 10.6 ab 3J­ 17.4 Cl 2 ac Jbc 0.2

Cl

e

a

d

b

c

8.11 7.49

7.69

O

7.05

O

O

Br

3J­ 8.0 ab 4J­ 1.2 ac 5J 0.6 ad 4J­ 2.0 ae 3J­ 7.5 bc 4J 1.4 bd

1.70

O

O

8.13 7.49 7.64

O

O

O

2.33

O

7.93

O

8.04

O O

O

O

O

O

(in DMSO)

Carboxylic Acid Imides (δ in ppm, J in Hz)

Natural Products 2.77 Solvents

O

1.00 2.43

O

P Si

I

6.35

1.69

N

C

Ha

O

1.24

Carboxylic Acid Anhydrides (δ in ppm)

2.22

S

O

Hc

6.14

Hal

3.00

6.63

O

H

N

Br

2.82

6.60

6.25

O

O

O

O NH O

8.9

2.70

N O

O

O

3.56 1.17

6.73

NH O

8.5

6.72

N O

3.58 1.19

 5.11 Carbonyl Compounds O

O

2.61

O

7.85

N

N

2.06

7.85

O

O

3.81

3.48

2.48

7.72

O

7.82

3.18

N

NH

11.4

2.36

225

O

O

(in DMSO) O

2.57

O

2.97

N Cl

N C N

N Br

O

3.56 1.22

C C

C

C

C

O

(in DMSO) Carbonic Acid Derivatives (δ in ppm, J in Hz) O

3.79 O

O

1.31

4.54

O

4.19 O

4.86

1.50

H

H3 C

O

N

O

O

O

O

O

4.03 H

O

H

Hal

4.56 O

2.78 N H

4.11 O

1.24

4.8

N H

3J

HNCH

NH2 5.45

3.28

O N

S

S S S

4.7

N

5.92 (in DMSO)

3.97

N H 5.69

N H

N H

3J

HNCH 4.8

3.27

N

1.26

S 3.26 1.98

N H

2.92 C

N

O N

S

3.02 N H 6.50

O

N H

2.78

O N H

O

2.54

(in DMSO)

2.97 0.98

O

3.39 N H

(in D2O)

1.16

X

P Si Natural Products Solvents

5 1H NMR

226

5.12 Miscellaneous Compounds 5.12.1 Compounds with Group IV Elements

C

Silicon Compounds (δ in ppm, J in Hz)­

C

C

C

C

Coupling with silicon: ­­­The isotope 29Si (natural abundance, 4.7 %) has a spin quantum number I of 1/2. Doublets with the corresponding intensity ("Si satellites") are usually observed. Typical coupling constants: 1JHSi -150 to -380 Hz 2J 5 to 10 Hz HCSi H

0.19

H

N

Hal

H3 C Si CH3 0.00 2J

O

C

P Si

Hb Hc

Natural 5.63 Products Solvents

H

0.42

Cl

0.79

Cl Si CH3 CH3

Cl

H 1J

Ha

CH3 Si CH 3 CH3 0.06

CH3

OH

CH3

OH

3J­ 14.6 ab 3J 20.2 ac 2J 3.8 bc

H CH3

2.63 HSi -209.4 7.37

1.14

7.31 7.56

Cl Si CH3 Cl

1.25

6.11

H

H Si N Si H 4.35

1J HSi -189 2J HCSi 7.6 3J HSiCH 3.6

CH3

5.88

1J HSi -190 2J HCSi 7.5 3J HSiCH 3.8

CH3

H3 C Si CH3

X

CH3 0.33

Si H 4.45

CH3

Cl

S

7.3

HCSi 5.5

N

CH3

1J HSi -202.5 2J HCSi 7.7 3J HSiCH 4.3

7.3 7.53

CH3

H3 C Si H 4.00

H

H

CH3

0.08

H3 C Si H 3.83

1J HSi -202.5 3J HSiCH 4.7

HSi -202.5

CH3

0.14

H3 C Si H 3.58

H Si H 3.20 1J

H

Si H 5.47

3.85 O

O

Si H 4.29 O

1J

HSi

-199.1

pH-dependent shift of the methyl H atoms relative to DSS.

H3 C Si CF2 P O Between pH 4.3 and 8.2 [1]:

 0.224 - δ  pH = 6.246 - log   δ - 0.193 

 5.12 Miscellaneous Compounds

227

The silanol hydrogen is exchangeable with D2O. Slow intermolecular exchange is observed in DMSO as solvent so that the vicinal coupling in H–Si–O–H is detectable (3JHSiOH ≈ 2–7 Hz). CH3

H Si OH 4.42 CH3

5.45 H Si OH 5.78 3J HSiOH 2.0 (in DMSO)

3J

HSiOH 1.8 (in DMSO)

C C

C

C

C

Germanium, Tin, and Lead Compounds (δ in ppm, J in Hz)­ CH3

CH3

H3 C Ge CH3 0.13

H3 C Sn

CH3

CH3

H3 C Pb CH3 0.71

CH3 0.07

2J 117 HC Sn 2J 119 HC Sn

N

CH3

CH3

51.9 (7.6 %) 54.3 (8.6 %)

Hal O

5.12.2 Phosphorus Compounds 31P

(natural abundance, 100%) has a spin quantum number I of 1/2. Couplings to protons through up to 5 bonds are usually observed.

N

Phosphines and Phosphonium Compounds (δ in ppm, J in Hz)­ 0.98 2.63

PH3 1.79

1J

HP

H3 C

PH2

1J HP 186.4 2J HCP 4.1 3J HCPH 8.2

184.9

1.06

H3 C P

H3 C

H 3.13

H3 C

2J

2.52 1.28 P

a

1.20

b

0.96

2J aP 3J bP 3J ab

13.7 0.5 7.6

a

+

P

b

I–

0.97 C

P

CH3

HCP

2.1

H3 C

1J HP 191.6 2J HCP 3.6 3J HCPH 7.7

S X

P Si Natural Products

2J aP 3J bP 3J ab

12.8 18.0 7.6

Solvents

228

5 1H NMR

5.64

6.16

Hc

P

Hb

C C

C

C

C

2J­ 11.7 aP 3J 30.2 bP 3J 13.6 cP 3J­ 11.8 ab 3J 18.4 ac 2J 2.0 bc

Ha

5.59

CH=CH2 CH=CH2

≈7.3 ≈7.3 a

b

c

P

≈7.3

7.33 7.46

1.68 1.00

7.30

3J aP 4J bP 5J cP

7.5 1.4 0.7

P

+

P

Cl– a

N

Hal O

7.51 b

a

P

N

C

3J aP 4J bP 5J ab

1.65

a

7.95

O

CH3

2.02

11.9 16.3 7.8

7.49 b

6.72

P

O

6.21

H

Ha

P

b

O

Hc

6.25 3J­ 13.2 aP

P Si Natural Products 1.32

7.47 7.73

X

Solvents

7.83

Phosphine Oxides and Sulfides (δ in ppm, J in Hz)­

1.10

S

7.64 b

c

3J 13.1 aP 4J 3.7 bP 5J 2.1 cP

H a 7.85 P

H

O

3J­ 12.9 ab 3J 18.9 ac 2J 1.8 bc

7.3–7.6

1.62

c

2J­ 25.9 aP 3J 41.8 bP 3J 22.3 cP

1J­ 481.7 aP 4J 0 bP 5J 0 cP

7.3–7.6 7.71 P

O

 5.12 Miscellaneous Compounds 1.85

7.06 CH3 H P S CH3

2J

6.82 H

b

HCP 13.0

1.31

Ha P

b

a

2J aP 3J bP 3J ab

6.60

1.81

P

CH3

1J HP 14.3 2J HCP 4.4

6.17

1.17

1.74 CH3 H3 C P S

6.14

H

S

Ha

b

Hc

b

2J­ 25.9 aP

CH3

2J

CH3 d 3J 45.3 bP P S 3JcP 25.4

c

P

a

P

S

C C

C

C

C

7.44 7.72

b

H a 7.86

S

dP 13.5 3J­ 11.8 ab 3J 17­.9 ac 2J 1.8 bc

7.50 1.67

c

7.50

1.78

6.26

11.3 18.1 7.5

229

S

H

Hc

6.34

2J­ 24.9 aP 3J 47.0 bP 3J 25.5 cP

3J­ 11.7 ab 3J 17.9 ac 2J 1.6 bc

1J­ 466.2 aP 4J 4.8 bP 5J 1.1 cP

N

3J­ 13.3 aP 4J 3.1 bP 5J 2.1 cP

Hal

Phosphinic and Phosphonic Acid Derivatives (δ in ppm, J in Hz) 1.52

12.0

H3 C P

4.15

OH

OH

P

O

CH3

2J­ 14.4 HP

7.3–7.6

O

1.37

7.76 12.79 O

6.81 H a P O

H 6.11

1.43

OCH3 b

H3 C P O a

2J­ aP 3J bP

OCH3

17.3 11.0

3.65 1.72 OCH3 c a

b

P

O

OCH3

1.06 2J­ -18.0 aP 3J 19.5 bP 3J 10.0 cP 3J 7.5 ab

S

O

1J­ 570.4 HP

1J­ 691.7 aP 3J 7.1 bP

3.66

N

b O

7.40 7.72 b

a

7.48 c

3.76

OCH3 d P O

3J­ aP 4J bP 5J cP 3J dP

OCH3

13.3 4.1 1.2 11.1

C

X

P Si Natural Products Solvents

5 1H NMR

230

Phosphonous and Phosphorous Acid Derivatives (δ in ppm, J in Hz) O

C C

O

P

CH3 a

C

C

C

H3 C

O

H3 C

1.10

O

P

b

2J aP 3J bP 4J cP

1.20 4.20 c

a

O

CH3

P

3.49

O

3J

aP

9.7 9.5 6.0

N

b 3JaP 4J bP 3J ab

a

3.85

O

10.8

N

c

2.96

b

CH3 a 1.18

1.25

O

P

1.01

8.0 0.6 7.1

N

P

2J aP 3J bP 4J cP 3J bc

8.7 8.0 ≈1.0 7.5

N

a

2.48 3J 9.1 aP

N

Phosphoric Acid Derivatives (δ in ppm, J in Hz) 1.35 4.11 b

3.78

OCH3

N

3J

b

O

CH3 O P O

Hal

1.28 4.06

a

O P

OCH3

O

O

HP 11.0

3J aP 4J bP 3J ab

a

O

8.0 0.9 7.1

O P O

3J

aP

10.0

3J

ab

7

S 4JbP 0.7

Phosphorus Ylids (δ in ppm, J in Hz)

O N S C

P

Pc b

P Si

H a 1.72 2J ab 2J ac

X

P

Pc b

CH3 a 1.82 3J ab 3J ac

12.7 -1.2

5.12.3 Miscellaneous Compounds

Natural Products Organometallic Compounds (δ in ppm, J in Hz) Solvents

Li

CH3

-1.32 (in benzene) -1.74 (in ether)

6.65

7.29

Hc

Li

Hb

5.91

Ha

3J ab 3J ac 2J bc

19.3 23.9 7.1­­­

15.9 3.6

 5.12 Miscellaneous Compounds 6.15 Hb Hc

5.51

6.66

3J ab 3J ac 2J bc

Ha

MgBr

17.7 23.3 7.6­­­

5.92

7.15 7.74 7.08

MgBr

3J ab 3J ac 2J bc

Ha

Hc

HgBr

5.52

(in THF)

11.9 18.7 3.1­­­

7.40 7.44

1.06 1.35 Hg

6.45

Hb

231

7.24

Hg

1.82 0.91

C C

C

C

C

Boron Compounds (δ in ppm, J in Hz) 1.50

BH3

2.26

. CH SCH 3

1J 11 104 H B (11B: 80.4%,

0.86

1.23

0.34

-0.49 4.01

Hm H t B B H H H

H

3

2J mt 1J 11 m B 1J 11 t B

I = 3/2)

1.30

B

1.23 1.23 0.57 (in DMSO)

OH

7.33

OH

O

B

3.73

B

H3 C

3J

7.5 46.2 133.0

HH

H

B

H

3.0

CH3 CH3

N

Hal 7.75 7.55 Br

8.2

O

OH B OH

(in DMSO)

N S

Na+

1.55 0.91 O

1.10

H3 C

B

–

O

6.80

7.20 6.94

(in DMSO) 5.12.4 References [1] M.D. Reily, L.C. Robosky, M.L. Manning, A. Butler, J.D. Baker, R.T. Winters, DFTMP, an NMR reagent for assessing the near-neutral pH of biological samples, J. Am. Chem. Soc. 2006, 128, 12360.

C

X

P Si Natural Products Solvents

5 1H NMR

232

5.13 Natural Products 5.13.1 Amino Acids

C C

Chemical Shifts and Coupling Constants (δ in ppm, J in Hz)­

C

C

C

7.47 4.28 b +

a

3.58

OH

H3 N

+

O

5.7 (in TFA)

7.33

N

Hal

+

c

a

H3 N

O

1.00

2.60

OH

4.32 O

3J­ ab 3J­ bc 3J­ cd

5.7 4.2 6.9

+

H3 N

1.04

c,d

7.38

O–

+

e

a

OH

+

1.10 f

4.28 O

O

3J­ ab 3J­ bc 3J­ bd 3J­ eg 3J­ ef

(in D2O)

5.5 ≈6.7 ≈6.7 6.1 5.7

X +

P Si Natural Products Solvents

c,d

4.51 4.56

OH

H3 N b a

7.70

4.65

O

3J­ ≈6 ab 3J­ 4.0* bc 3J 4.0* bd 2J -13.5 cd

(in TFA) * average value

HO

d

2.28 +

+

a

7.35

3J­ ab 3J­ bc 3J cd 3J­ ce

a

7.63

4.44

3J­ ab 3J­ bc 3J cd

O

5.5 4.5 6.5

(in TFA)

1.10 1.55 1.70

OH

4.41 O

5.5 3.6 7.0 6.1

3J 8.4 cf 2J­ -13.6 ef 3J­ 7.0 eg 3J­ 7.0 fg

(in TFA)

HO

4.82

H3 N b

e,f

c

H3 N b

d

OH

O

g

1.21

1.67 c

3.79

O–

(in D2O)

(in TFA)

HO

H3 N

O

OH

H3 N b

S C

1.11 ≈2 g

≈2

2.26

3.61

4.49

1.49

(in TFA)

(in TFA)

N

H3 N

(in D2O)

d

b

+

O

3J­ ab

1.25

O–

H3 N

1.86

7.41

+

H3 N

1.33 4.26 3.60

O

(in D2O)

O–

 5.13 Natural Products 1.84 e

HS +

c,d

7.58

3.12 3.18

HS –

Cl + H3 N 4.35

OH

4.68

a

2.27

3.36 3.41

H3 N b

O

+

O

3.37 3.64 +

a

7.33

4.67

+

H 3N

3.86

O

≈7.45

7.43

7.33 3.13 3.29

OH

+

4.68 O

H3 N

3J­ 8.5 bc 3J­ 4.5 bd 2J -14.5 cd

3.99

7.27 3.34 3.60

O–

+

+

H3 N b a

7.73

4.76

3J­ ab 3J­ bc

O

5.1 4.7 (in TFA)

C C

C

C

C

O

2.55 2.63 +

c,d

OH

7.4

e

OH

H3 N b a

7.71

4.60

3.01

O

3J­ 5.5 2J­ -15.5 ab cd 3J­ 5.6* 3J 6.2* bc ce 3J­ 5.6* 3J­ 6.2* bd de

(in TFA) * average value

3.38 2.26 2.35 +

c,d

H3 N b a

7.60

Hal

OH

4.64 O

O

3J­ 8.5 bc 3J­ 4.5 bd 2J -15.0 cd

N

(in TFA)

NH3 + g

OH

N

H3 N b

6.97 O

OH

O

c,d

a

(in D2O)

O OH

O–

7.03

h

c

2.64

(in D2O)

7.38

(in TFA)

3.55

S

(in TFA) * average value

c,d

H3 N b

OH

3J­ 5.5 2J­ -15.7 ab cd 3J­ 7.7 3J 6.5* bc ce 3J­ 4.4 3J­ 6.5* bd de

(in TFA) * average value

≈7.45

a

2.09– 2.23

2.96

e

H3 N b

7.73

2.14

f

S

2.50 2.65 c,d

OH

(in D2O)

3J­ 5.3 2J­ -15.5 ab cd 3J­ 5.0* 3J 9.1* bc ce 3J­ 5.0* 3J­ 9.1* bd de

7.3

233

f

2.00

e

≈1.8 OH

4.52 O

3J­ 5.8 2J­ -15.0 ab cd 3J­ 5.6* 3J 6.0* bc ce 3J­ 5.6* 3J­ 6.0* bd de

(in TFA) * average value

2.98

1.73 1.43

1.68 H2 N

S

NH3 +

3.44

OH O

(in D2O)

C

X

P Si Natural Products Solvents

5 1H NMR

234

6.19 + H2 N 6.50

C C

C

C

C

d HN

Hal O N S

g e f

2.25 c 2.34 d +

a

7.60

3.43 ≈2.00 ≈2.08 OH

H3 N b

4.46 O

+

3J­ ab 3J bc 3J bd 2J­ ≈ cd 3J­ eg 3J fg 3J gh

5.5 5.3* 5.3* -15.0 6.5* 6.5* 5.3

H2 N

b c

2.42 2.14

OH

a

H2 +

4.33

3J­ 8.5 ab 3J 6.5 ac 2J -13.5 bc 3J­ 7.5 bd 3J 5.5 be 4J -0.4 bf 4J 0.0 bg

3J­ 5.5 cd 3J 7.5 ce 2J -13.0 de 3J­ 5.5 df 3J 7.5 dg 3J 7.5 ef 3J 5.5 eg 2J -11.0 fg

(in D2O, pH 2.0)

3.21 1.63

1.63 H2 N

3.27

OH O

(in D2O)

1.63 d 1.60 e 3.04 f 2.95 g N

b c

3J­ 8.4 ab 3J 6.2 ac 2J -13.5 bc 3J­ 7.6 bd 3J 5.4 be 4J -0.4 bf 4J 0.0 bg

1.96 1.68

O–

a

H2 +

O

NH2 HN

(in TFA) * average value

2.06 d 2.04 e 3.46 f 3.39 g N

N

C

NH2 6.19

3.74

O

3J­ 5.6 cd 3J 7.8 ce 2J -13.0 de 3J­ 5.7 df 3J 7.9 dg 3J 7.9 ef 3J 5.7 eg 2J -11.0 fg

(in D2O, pH 7.0)

1.05 d 1.07 e 2.08 f 2.36 g N H

3J­ 8.6 ab 3J 6.6 ac 2J -12.0 bc 3J­ 8.1 bd 3J 5.9 be 4J -0.6 bf 4J 0.0 bg

b c

1.04 1.45

O–

a

2.81

O

3J­ 6.7 cd 3J 8.5 ce 2J -11.0 de 3J­ 5.5 df 3J 8.1 dg 3J 7.7 ef 3J 5.7 eg 2J -10.5 fg

(in D2O, pH 13.0)

X

P Si Natural Products Solvents

HO

3.9* e 3.9* f 8.00 8.60

≈5 d

b c

2.95 2.56

N a + g H2 O h

≈5

(in TFA) * average value

OH

3J­ 8.2 ab 3J 10.4 ac 2J bc -15.0 3J­ <2 bd 3J 4.2 cd

HO 4.35 2.17

3.37 3.49

2.44

N H2 +

O– O

4.67 (in D2O)

 5.13 Natural Products 7.05

a

NH3 +

3.79 c 3.57 d

b

OH 3J­ 4.0 bc 3J 8.0 bd 2J -15.5 cd

O

7.25

N H

≈8

4.71

7.05 6.96

(in TFA) c

N d

8.73

7.82

7.66

NH3 + a

b

3.87

N H

4.91 3Jab 6.4 OH 4 Jcd 1.4

3.53

NH3 +

3.04 3.33 7.58

O–

N H 11.1

7.36 (in DMSO)

8.69

7.42

(in TFA)

C

C

C

C

4.06

NH3 +

O– N H

O

C

O

7.26

N

235

3.36 3.38

O

(in D2O)

N 5.13.2 Carbohydrates Chemical Shifts and Coupling Constants (δ in ppm, J in Hz)

Hal O

≈3.7 H ≈3.7 3.52

3.61 H 3.93 3.23 HO HO

H

HO

HO HO

OH

H

g

H

f

H H

He



c H

HO

HO HO

H

≈3.7 (in D2O)

3.43 4.58 (in D2O)

OH Hb OH

d OH a

a b c d e f g h

N

HO

OH H ≈3.7 OH

OH H 3.32 H

h

H

D2O DMSO 4.55 4.07 3.72 3.54 3.14 4.51 3.64 3.37 4.46 3.27 2.93 4.31

H 5.20

S C

X

P Si Natural Products Solvents

5 1H NMR

236 ­

g

H

C

h

C

C

C

C

OH l j,k

HO HO f

OH a

Hi

He

OH

d Hb

(in DMSO ca. 80%)

g

OH l

H

j,k

h

HO HO

N

c

H O

f

He

Hal

Hi

c

H O Hb OH

d OH a

(in DMSO ca. 20%)

O N

C

X

P Si Natural Products Solvents

D2O* DMSO D2O DMSO 3J­ 3.6 3J­ 4.5 a 6.20 ab bc 3J 9.5 3J 6.8 b 5.09 4.91 cd ce 3J 9.5 3J 4.8 c 3.41 3.10 ef eg 3J­ 9.5 3J­ 5.5 d 4.84 gh gi 3J 2.8 3J 5.7 e 3.61 3.42 jl ij 3J 5.7 3J 6.2 f 4.64 kl ik 2J -12.8 g 3.29 3.04 jk h 4.77 i 3.72 3.57 j 3.72 3.57 (* relative to internal k 3.63 3.42 acetone at δ = 2.12) l 4.37

D2Oa DMSOb a 4.48 a H OH f b 3.68 3.39 j OH H c 3.53 3.25 h H O b,c d 3.76 3.55 OH H e 4.23 e HO f 3.86 3.58 HO g H d i g 4.38 h 3.96 3.62 i 4.32 j 4.00 3.77 a 25% β-D k 3.68 3.41 b 75% β-D l 5.14 k

S

D2O DMSO D2O* DMSO 3J­ 7.8 3J­ a 6.58 6.5 bc ab 3J 9.5 3J 4.5–6 b 4.51 4.27 ce cd 3J 9.5 3J 4.5–6 c 3.13 2.89 eg ef d 4.84 3J­ 9.5 3J­ 4.5–6 gi gh e 3.37 3.10 3J 2.8 3J 5.5 ij jl f 4.84 3J 5.7 3J 6.0 ik kl g 3.30 3.10 2J -12.8 jk h 4.84 i 3.35 3.04 j 3.60 3.42 (* relative to internal k 3.75 3.66 acetone at δ = 2.12) l 4.48

3.52, 3.40

HO

HO

O

H

3.69

OH H

DMSO

l

OH H

OH

OH

3.72 3.77 (in DMSO, 20% α-D)

3.53

f,g

eH

3J­ 7.4c ab 3J 5.4c ac 2J -11.3d bc 3J­ 6.8c de 3J 10.1d df 3J 5.8c fg 3J 4.0d fh 3J 3.8c hi 3J 1.9d hj 3J 1.6d c at 25 oC hk 2J -12.1d d at 70 oC jk

3.48, 3.37 O

OH OH a,b

H OH H OH

3.40, 3.23

3.79 d c 3.80 (in DMSO, 55% β-D)

2J­ -11.0 ab 3J 7.1 cd 3J 5.9 de 3J­ 2.3 ef 3J 3.6 eg 2J -11.3 fg

 5.13 Natural Products

237

5.13.3 Nucleotides and Nucleosides Chemical Shifts and Coupling Constants (δ in ppm, J in Hz) NH2 a

N

b

N H

O

D2O DMSO a 5.97 5.57 b 7.50 7.31 Jab 7

O

5.47 7.41

b

N Hc

O

C

C

C

C

10.82 (in DMSO) O

1.75

O NH 11.0

7.28

N H

8.98

O

10.6

NH2 d N

c

N

NH2 7.24

5.75 7.87 5.09 HO 3.83

3.95

a b

O

N c d

OH OH

N H

N

NH2

N

Hal

O

5.79

3.95

5.06* 5.36* (in DMSO) * interchangeable

O N

NH 11.3

7.71 2J­ ab 3J cd

7.4 3.8

3.55 3.60

5.04 HO 3.77

S

O

1.78

N

3.56 3.66

N

D2O DMSO CDCl3 TFA a 8.62 8.12 8.11 8.88 b 12.8 c 8.57 8.10 8.14 9.31 d 7.09

N

N Hb

N

(in TFA)

(in DMSO)

a

3J 7.5 ab 3J 5.7 bc

NH 11.02

a

C

O

4.26

OH

N

O

6.18

2.08

5.25

(in DMSO)

C

X

P Si Natural Products Solvents

238

5 1H NMR NH2 7.41

8.17

C C

C

C

C

3.70 5.48 HO 3.58

N

N

N

N

8.13

8.38

3.62 3.53

5.25 HO

O

3.99

NH2 7.31

5.91

4.17

4.41

OH OH

OH

5.24 5.51

5.31

(in DMSO)

N

N

O

3.88

4.64

N N

6.34

2.73 2.26

(in DMSO)

O

O

N

7.97

Hal

3.63 5.10 HO 3.55

O

3.90

4.11

N

NH 10.75 N

O

5.72

4.43 OH OH

5.20 5.45 (in DMSO)

S C

N N

X

P Si Natural Products Solvents

8.34

7.95

NH2

6.52

NH 10.7

N

N

3.55

4.99 HO 3.83

N

O

4.36

OH

6.14

2.53 2.22

5.31 (in DMSO)

NH2

6.50

 5.14 Spectra of Solvents and References

239

5.14 Spectra of Solvents and Reference Compounds 5.14.1

1H

NMR Spectra of Common Deuterated Solvents

500 MHz; ≈1 000 data points per 1 ppm; δ in ppm relative to TMS­

C C

C

C

C

N

Hal O N S C

X

P Si Natural Products Solvents

240

C C

C

C

C

N

Hal O N S C

X

P Si Natural Products Solvents

5 1H NMR

 5.14 Spectra of Solvents and References

241

C

5.14.2

1H

NMR Spectra of Secondary Reference Compounds

Chemical shifts in 1H NMR spectra are usually reported relative to the peak position of tetramethylsilane (TMS) added to the sample as an internal reference. If TMS is not sufficiently soluble, a capillary with TMS may be used as external reference. In this case, owing to the different volume susceptibilities, the local magnetic fields in the sample and reference differ, and the peak position of the reference must be corrected. For a D2O solution in a cylindrical sample and neat TMS in a capillary, the correction amounts to +0.68 and -0.34 ppm for superconducting and electromagnets, respectively. These values must be subtracted from the chemical shifts relative to the external TMS signal if its position is set to 0.00 ppm. Alternatively, secondary references with (CH3)3SiCH2 groups may be used. The following spectra of two such secondary reference compounds in D2O were measured at 500 MHz with TMS as external reference. Chemical shifts are reported in ppm relative to TMS upon correction for the difference in the volume susceptibilities of D2O and TMS. As a result, the peak for the external TMS appears at 0.68 ppm.

C

C

C

C

N

Hal O N S C

X

P Si Natural Products Solvents

242

5 1H NMR

5.14.3 1H NMR Spectrum of a Mixture of Common Nondeuterated Solvents

C C

C

C

C

N

Hal O N S C

X

P Si Natural Products Solvents

The following 1H NMR spectrum (500 MHz, δ in ppm relative to TMS) of CDCl3 containing 18 common solvents (0.05–0.4 vol%) is shown as a guide for the identification of possible impurities. Where the signals of several solvents overlap, insets show signals for the individual compounds from separate spectra. Peaks in these insets are labeled with the corresponding chemical shifts from their main spectrum but their values may differ by up to 0.03 ppm. Signals that are particularly prone to vary in their position are marked with *. THF: tetrahydrofuran; EGDME: ethylene glycol dimethyl ether.

6 Heteronuclear NMR Spectroscopy

6.1

19F

NMR Spectroscopy

6.1.1 19F Chemical Shifts of Perfluoroalkanes (δ in ppm relative to CFCl3) -63

-83

-89

CF4

F3 C

F3 C CF3

-83 CF2 -131

F3 C

-82

F 3C CF 2

F3 C

-130

F2 C -123 CF2 F3 C

F 2C CF 3

-81

-85

CF2 -126 F2 C -122 CF2 F2 C CF3

CF2 -129 F2 C -125 CF2 -124 F2 C CF2 F3 C

F3 C

-75

F3 C -189 CF CF3 F3 C

-73

F3 C -187 CF CF3 F2 C -116 CF3 -83

-65

F3 C F3 C

-55

CF3 CF3

F3 C F3 C F3 C

CF2 -127

F3 C

-70

F3 C -179 CF CF3 F3 C CF CF3

CF3 CF3 CF3

-80

CF2 -117 F3 C CF -184 CF2 F3 C

-71

-60

F3 C F3 C

F3 C

CF3

CF2

-97

CF3 CF3 CF3

244

6 Heteronuclear NMR

19F Chemical

Shifts of CF3 Groups (δ in ppm)

Substituent

C

–H –CH3 –CH2CH3 –n-C7H15 –CH2OH –CH2NH2 –CH2COOH –CH2CH2–1-pyridinium –C(CF3)3 –CF3 –CF2CF3 –perfluorocyclohexyl –CCl3 –CH=CH2 –C ––– CH –phenyl –C6F5 –4-nitrophenyl –4-aminophenyl –C6(CF3)5 –1-naphthyl –2-naphthyl –2-pyridyl –3-pyridyl –4-pyridyl

δ

-78 -62 -70 -67 -78 -72 -64 -75 -65 -89 -83 -70 -82 -67 -56 -64 -55 -64 -62 -53 -75 -73 -68 -62 -65

Substituent

X O

N S

O  || C P

–F –Cl –Br –I –OH –O–cyclohexyl –O–CF3 –O–phenyl –O–CO–CO–O–CF3 –NH2 –C––– N –NC –SH –S–CF3 –SS–CF3 –SO3H –S(O)2–phenyl –COCF3 –CO–phenyl –COOH –COO– –COOCH2CH3 –COF –P(O)(OCH2CH3)2 –P(CF3)2 –P+(phenyl)3

δ

-63 -29 -18 -5 -55 -58 -58 -58 -31 -49 -53 -51 -32 -39 -47 -79 -79 -85 -58 -77 -74 -74 -76 -73 -51 -58

6.1 19F NMR

19F Chemical

Shifts of CHF2 Groups (δ in ppm)

Substituent

–H –CH3 –CH2CH3 –CH2CH2CH3 –CH2–phenyl –CF3 –CF2CF3 –cyclohexyl 19F Chemical

δ

-144 -110 -120 -117 -115 -141 -138 -126

Substituent

δ

–CCl3 –phenyl –O–CH3 –O–CF3 –C––– N –S–phenyl –COOH –P(CF3)2

-122 -111 -88 -86 -120 -121 -127 -126

Shifts of CH2F Groups (δ in ppm)

Substituent

–H –CH3 –CH2CH3 –CH2CH2CH3 –CH2CH2CH2CH3 –CH2OH –CH2–phenyl –CF3 –CF2CF3 19F Chemical

245

δ

-268 -212 -212 -219 -219 -226 -216 -241 -243

Substituent

δ

–CCl3 –CH=CH2 –C ––– CH –phenyl –C––– N –CO–phenyl –COOH –COO–

-198 -216 -218 -206 -251 -226 -229 -218

Shifts of CF2R2, CHFR2, and CFR3 Groups (δ in ppm)

Substituent –CH3 –CH2CH3 –CF3 –phenyl –Cl

CF2R2 -85 -92 -132 -89 -7

CHFR2 -165 -183 -77 -167 -81

CFR3 -131 -156 -189 -127 0

6 Heteronuclear NMR

246

19F Chemical

Shifts of Monosubstituted Perfluoroalkanes (δ in ppm) [1]

CF3 -81.7 F2 C -125.9 CF2 -123.0 F2 C -121.7 CF2 -121.7 F2 C -121.7 CF2 -122.6 F2 C -116.8 COOH CF3 -80.5 F2 C -126.3 CF2 -122.8 F2 C -121.8 CF2 -121.6 F2 C -121.6 CF2 -121.7 F2 C -121.6 CF2 -123.6 F2 C -115.2

I

CF3 -81.8 F2 C -126.9 CF2 F2 C CF2 F2 C CF2 -118.0 F2 C -64.0 Br

CF3 -81.8 F2 C -127.0 CF2 F2 C CF2 F2 C CF2 -120.9 F2 C -68.7 Cl

F3 C -85.2 F3 C -85.2 CF3 -86.0 -190.7 -121.1 CF CF3 -76.9 CF F2 C -131.0 2 -75.6 F2 C -119.5 CF2 -127.4 F3 C CF -189.8 CF2 -125.3 CF2 -117.3 F2 C -126.6 F2 C -125.9 F2 C -124.2 CF2 -126.4 CF2 -125.0 CF2 -124.8 F2 C -126.3 -125.1 F2 C -117.9 F2 C -117.8 CF2 SO2 R SO2 R F2 C -117.8 SO2 R

-110.3 CF3 -83.0 F2 C CF3 -64.1 F3 C CF3 -66.5 F3 C C -105.5 C F2 C CF3 -64.1 CF2 -108.6 CF2 -120.0 F2 C -121.5 F2 C -117.1 CF2 -124.2 SO2 R F2 C -117.6 SO2 R

Halogen Bonding (δ in ppm) [2] X

X –F –Br –I

a

-81.1 -65.1 -60.0

CF3 -81.8 F2 C -126.8 CF2 F2 C CF2 F2 C CF2 -113.7 F2 C -59.0 I

in cyclohexane b

-121.7 -118.1 -114.6

c

-122.5 -122.6 -122.5

d

b F 2 C

C a F2

-126.1 -123.2 -123.3

dF 2 C

C c F2

a

-80.9 -67.7 -71.6

CF3 -74.1 F3 C CF -184.9 -179.8 CF CF3 -75.0 F2 C -113.3 CF2 -122.7 F2 C -116.2 SO2 R

-74.1

R: NHCH2 C6 H5

C F2

F2 C

C F2

F2 C

X

in pyridine b

-122.1 -117.9 -115.2

c

-122.8 -122.2 -122.0

d

-126.2 -122.8 -122.8

6.1 19F NMR



247

6.1.2 Estimation of 19F Chemical Shifts of Substituted Fluoroethylenes (δ in ppm relative to CFCl3) [3] Rcis

Rtrans

F

Rgem

δC=CF = -133.9 + Zcis + Ztrans + Zgem + Scis/trans + Scis/gem + Strans/gem Substituent R

Zcis

–H –CH3 –CF3 –CH=CH2 –CF=CF2 –phenyl –F –Cl –Br –I –OC2H5 –COF –SCH3

Substituent

–H –H –H –H –H –CF3 –CF3 –CF3 –CF3 –CH3 –CH3 –CH3 –OCH2CH3 –phenyl –phenyl

-7.4 -6.0 -25.3 – -23.8 -15.7 0.0 -16.5 -17.7 -21.3 -77.5 -46.5 -25.1 Substituent

–H –CF3 –CH3 –OCH2CH3 –phenyl –H –CF3 –CH3 –phenyl –H –CF3 –phenyl –H –H –CF3

Scis/trans

-26.6 -21.3 – -47.0 -4.8 -7.5 -5.9 17.0 -15.6 – – – -5.1 – -23.2

Ztrans

-31.3 -43.0 -40.7 – -38.9 -35.1 0.0 -29.4 -40.0 -46.3 – -56.8 -43.7

Scis/gem

– – 11.4 – – -10.6 -5.3 – – -12.2 -13.8 -19.5 – – –

Zgem

49.9 9.5 54.3 47.7 44.7 38.7 0.0 – – 17.4 84.2 54.1 16.6

Strans/gem 2.8 – – – 5.2 12.5 -4.7 – -23.4 – -8.9 -19.5 – 20.1 –

6 Heteronuclear NMR

248

6.1.3 Coupling Constants in Fluorinated Alkanes and Alkenes (JFF in Hz) |4J

FF|

F3 C

8.9

CF2 F2 C

|3JFF| <1 |3J

Cl

|4J

FF| 1.8

FF|

F3 C

8.5

CF2 F2 C

|5JFF| 13

|4JFF| 13 R: NHCH2 C6 H5

F3 C CF2

|3JFF| 10.3 |3JFF| 8.7 |4JFF| 9.8 |4J

FF|

5.8

|4JFF| 21.0

F2 C CF2 FC CF

F3 C CF2 F3 C CF CF2 F2 C CF2 F2 C SO2 R

|3JFF| 140

F3 C F3 C

CF2 F2 C CF2 FC CF

F2 C

|3JFF| 13.3

CF2

|5JFF| 6.8

|3JFF| 6.0

F3 C

CF3

|4JFF| 13.6

|3JFF| 0.3

|5JFF| 2.4

|4JFF| 12.2

|5JFF| 7.2

|4JFF| 26.1

|3JFF| 1.6

CF2 F2 C CF2 FC CF F3 C

F3 C

|3JFF| 0.8

|3JFF| 2.2, 1.1

COOH

|5JFF| 6.8 F3 C CF3 F3 C C CF2 F2 C CF2 F2 C SO2 R

|3JFF| 1.1

CF3

|4JFF| 8.2

F2 C CF2

|4JFF| 7.6

|5JFF| 1.5

|5JFF| 2.5 |4JFF| 9.5 |4J

FC FC |3JFF| 2.3 FF| 3.4 FC CF2 |3JFF| 7.6 FC CF2 |4JFF| 8.2 CF3 CF3

|3JFF| 12.5

|5JFF| 3.0

CF3

F2 C

6 CF2 | JFF| 4.6

FC FC CF2 CF3

6.1 19F NMR

3J 3J

F

FF

-132

FF

+19.1

F

F

2J

FF

F

+36.4

F

F

2J

FF

F 3J

|3JFF| 21 F3 C

|2JFF| 12

3J

F

+87

FF

-119

+33 3J

N3

2J

FF +124

|3JFF| 127

F3 C

FF

+73.3

F

F

F

F

3J

FF

-114

|5JFF| 11.3

|5JFF| 1.3

Cl

FF

F

F

F

249

F

F3 C

CF3

Cl

CF3 F

6.1.4 19F Chemical Shifts of Allenes and Alkynes (δ in ppm relative to CFCl3, |JFF| in Hz) -176 F

-107 F

H C C C

-273 F

H C C C

H

H

H

-261 F

F

|3J

FF| 2.1

F

H

-203 F

|4JFF| 4.3

CF3

6 Heteronuclear NMR

250

6.1.5 19F Chemical Shifts and Coupling Constants of Fluorinated Alicyclics (δ in ppm relative to CFCl3, |JFF| in Hz) -160

-218 F

CF2

|2JFF| 160

|2J

FF|

-165

F

F2 C

CF2

F2 C

220

-160

F

-133

CF2 F2 C CF2 CF2

CF2

-174

F

-135

-151 F2 C

-171

F

F

-133 F2 C

CF2

F2 C

CF2

CF2 CF2

-120 CF2

F2 C

CF2

F2 C

CF2

CF2

F2 C

|2JFF| 284

CF2

F -186 F -166

-122 -140 -142 F

F

F

F

F

F

-124

F

F

F

-70

F F

CF3

-132

F

F

F F

|2JFF| 284 |4JFF| 25

13.5

F

F

|3J

FF|

13.5

F

F

F

F

F

F

|4JFF| 20

F

F

F

F

F

CF3

|4JFF| 3

F

F -224

F

F F

F

F -121 F

F F

|3JFF| 13

CF3

|2JFF| 291

|4JFF| 2 F

F F

F

F

F

F

F

F

F

FF|

F

F

-120 |2JFF| 286

|3J

F -130

-189

F

F

|4JFF| 6

F

F

F F

F

F

|3J

F FF|

F

0

CF2

CF3

CF2

6.1 19F NMR



251

6.1.6 19F Chemical Shifts and Coupling Constants of Aromatics and Heteroaromatics (δ in ppm relative to CFCl3) Estimation of 19F Chemical Shifts of Substituted Fluorobenzenes [4] 3

2

4

F 5

Substituent

C X

O N

S

O || C

δF = -113.9 + ∑ Zi

6

–CH3 –CF3 –CH=CH2 –C ––– CH –F –Cl –Br –I –OH –OCH3 –OCOCH3 –NH2 –NHCOOCH3 –NHCONH2 –N3 –NO2 – C ––– N –NCO –SH –SCH3 –S(O)2F –S(O)2–CF3 –S(O)2OCH2CH3 –CHO –COCH3 –COOH -COOCH3 –CONH2 –COF –COCl –B(OH)2 –Si(CH3)3

Z2,6

-3.9 0.4 -4.4 – -23.2 -0.3 7.6 19.9 -23.5 -18.9 – -22.9 – – -11.4 -5.6 6.9 -9.2 10.0 6.5 7.5 9.5 – -7.4 2.5 2.3 3.3 0.5 -14.8 3.4 6.8 13.8

Z3,5

-0.4 3.1 0.7 – 2.0 3.5 3.5 3.6 0.0 -0.8 – -1.3 0.1 0.9 2.8 3.8 4.1 2.3 0.9 1.2 5.8 5.5 3.7 2.1 1.8 1.1 3.8 -0.8 3.0 3.5 0.8 0.3

Z4

-3.6 5.8 -0.6 3.3 -6.6 -0.7 0.1 1.4 -13.3 -9.0 -3.7 -17.4 -7.1 -8.1 -0.3 9.6 10.1 -2.2 -3.5 -4.5 13.8 -14.3 9.1 10.3 7.6 6.5 7.1 3.4 6.2 12.9 2.1 1.6

6 Heteronuclear NMR

252

F

-163

F

F

-64

CF3

F F

-147

F F

-55

CF3

-160

F

F

F -141

F

Estimation of 19F Chemical Shifts of Substituted Pyridines, Pyrimidines, Pyrazines, and Triazines (δ in ppm) [5]

δF = Y + ∑ Zi To estimate the 19F chemical shifts of substituted 6-ring heteroaromatics, the same increments, Zi, can be used as for substituted fluorobenzenes (see preceding page). However, different base values, Y (as given below), apply depending on the number and position of nitrogens and the position of the fluorine substituent in question: F

F

Y:

F

N

F N

N

-47.8

-3.0

F

-18.3

N

N

-45.7

N

N

-3.5

F N

N

Y:

F

N

-67.7

N

-52.1

F

N

F

N N

-18.7

F

N

-41.8

N

N N

-74.6

6.1 19F NMR



253

Coupling Constants in Aromatics and Heteroaromatics (JFF in Hz)

3J

FF

4J

-20.8

FF

5J

+6.5

F

F

+17.6

FF

F

F

F

F

4J

FF

FF

-0.1

+8.6 CH3 F

F

F

5J

3J

F

3J

F 4J

FF

FF

+13.7

F

+6.7 NO2 F

5J

+5.4 F

F

F

FF

F F

F 4J

3J

3J 3J

FF

FF

3J

FF 0.0

+5.1

3J

FF

FF

FF

-20.5

-20.8

-2.4

-19.9

-0.4

-20.3

FF -18.1

FF

-21.2

FF

FF

+26.0

N

N

+26.3 FF

+3.9

+6.7

5J FF

FF

3J

4J

FF

5J

5J

F

-2.3

FF

FF -15.0

N

F

F

4J

4J

F

-7.3

F

4J

NH 2

F

F FF

FF

+5.1

FF

FF -19.4

4J 4J

4J

-20.9

5J

F 4J

FF +8.6

-20.3

F

F 4J

FF

F 4JFF -3.0

F

F

3J

F

F

F F

3J

FF

+17.9

6 Heteronuclear NMR

254

6.1.7 19F Chemical Shifts of Alcohols and Ethers (δ in ppm relative to CFCl3) OH

OH

OH

F3 C

CF3

-55

F3 C

-78

F3 C -85 CF2 -133 F2 C -88 O F2 C -92 CF3 -91

-88

F3 C -84 CF2 -129 F2 C -129 CF2 -87 O CF2 -56 O CF2 -57 O CF2 O CF2 F2 C CF2 F3 C

F3 C -84 CF2 -129 F2 C -129 CF2 -87 O CF2 -54 O CF2 F2 C CF2 F3 C

F2 C F2 C

O

-91 O

CF2 CF2

F2 C CF2 CF2 F2 C O O CF2 F2 C O CF F2 C O 2 F2 C F2 C

O

F2 C O

-89

O

CF2 CF2

O CF2

CF2 F2 C O O CF2 F2 C F2 C CF2

-83

HO F3 C

CF3

-93 -57

F3 C

O F3 C CF -149 CF2 -86 O CF2 -92 F3 C -91

F3 C -82 CF2 -130 F2 C -84 O F2 C -83 CF2 -129 F2 C -83 n O F2 C -88 CF3 -87

F3 C

OH CF3

F3 C -85 CF2 -133 F2 C -86 O -83 F3 C CF -148 CF2 -84 O CF2 -92 F3 C -91 F3 C -84 CF2 -131 F2 C -84 O -80 F3 C CF -144 CF2 -82 O n CF2 -91 F3 C -89

F3 C CF2

F2 C O F3 C CF CF2 O n CF CF3 O F -130

+26

CF2 F2 C O F3 C CF CF2 O n CF CF3 O OH -132

6.1 19F NMR



255

6.1.8 19F Chemical Shifts of Fluorinated Amine, Imine, and Hydroxyl­ amine Derivatives (δ in ppm relative to CFCl3) F +147 N

F

F

-92 F

F3 C

N

N

F3 C

CF3 -57

F

F3 C

F3 C -82

H

F2 C -117 N F F +17

N

N

F2 HC

F3 C

C F2

N

CF3

F2 C

N

CF2 -95

CF2 -134 C F2 -136

F2 C

F -16

F3 C

-59

F2 C

CF3 F3 C N N F2 C CF2 -93

N H

F2 -104 CF3 N C F3 C C N -66 F2 OH

N O

CF2 -88

F2 -105 CF3 N C F3 C C N -69 F2 O

F2 C

N

-94 N

CF2

F2 C CF2 -123 F2 C CF2 -129

CF2

CF3 F3 C

-62 N

H

-98

F2 C

F -46

OH

O

F2 C

F3 C Ph3 P O

Pt

-71 CF3

H N

C -81 F2

O– N

CF3 -84

CF3 -84 F2 C -90 N CF2 -86 F2 C

CF3 -54

CF2 -95

CF2 -121

CF2 -120 F C -86 2 N CF2 F2 C CF 2 F2 C CF 2 F3 C CF 2 CF3

-57

CF3 -55

CF3 -53 F2 C

F2 C

N H H

N CF 2 F2 C CF 2 F2 C CF 3 F3 C

-129 F2 C

-63 CF3

-84 F2 C

CHF2

-53 CF3 -93 N

F3 C

F3 C -82

F2 C -106 N F F2 C CF -91 2 F3 C CHF2 -96

F2 C

H

CF2 -121

CF3 -56 CF3

N

CF3 -58

F3 C -82

CF2 -128

H

-75

F3 C

F +19

-84

O

-99

F2 C

N

C -83 F2

O

F3 C -82

CF3 -68 PPh3 O

-62

F3 C N -109 N CF3 F2 C CF2

CF2 -125 F2 C -96 N O F2 C CF -129 2 F2 C CF 2 F3 C -89 CF3

-82

6 Heteronuclear NMR

256

6.1.9 19F Chemical Shifts of Sulfur Compounds (δ in ppm relative to CFCl3) F -352

H S

S CF3

+93

-167 F

F

S

+34 F

F

F S

F

F

S F

-48

CF3

+52

-70

-70

F2 C

-78

S

-92 S

CF2 CF2

SF3 +7 SF3

+72 F

F

S F

F

+12

CF3 F F +19 S F F CF3

CF3

-26

S

F3 C

-58

S

F2 C

-88 F2 C

F

F

F

F

F

S

F

-65

F3 C

CF2 -133

+57

F

F -14

O

S

F2 C CF2 -87

CF 3

-57

F3 C

F2 C

S

CF3

-32

-39

CF 3

+50

F

F

S F

OH

S

O

-71 -65

F3 C

CF3

-64

CF3

O

O F3 C

F

CF3 S CF3

O– O–

S

F +65 O

6.1 19F NMR



257

6.1.10 19F Chemical Shifts of Carbonyl and Thiocarbonyl Compounds (δ in ppm relative to CFCl3) O R

Substituent R

δ

–H –CH3 –C(CH3)3 –CH2F –CF3 –CF(CF3)3 –CH=CH2

+41 +49 +22 +26 +15 +31 +24

O

F

Substituent R

–phenyl –F –NH–CH2CH2CH3 –O–cyclohexyl –O–phenyl –S–phenyl

O

O

H

O

F3 C

F3 C

-81

N

O

-77

O F -187

O F3 C

H

O CF3

-77

S F

N

S F +41

-75 F3 C

F +53

δ

+17 -23 -16 -8 -17 +47

258

6 Heteronuclear NMR

6.1.11 19F Chemical Shifts of Fluorinated Boron, Phosphorus, and Silicon Compounds (δ in ppm relative to CFCl3, JFP in Hz) -151 F F

F

F

F

B

F

–

-120 F F

F

B

–

F

–

F OH

CF3

–

F3 C

FF F

F F F

FF F

P F

F -34 1J

F3 C

CF3

F -164

F

H3 C

FP -1441

CF3

P

F -219

CH3

1J

F F

F

F P F

F3 C

– F -71 F 1J -706 FP

O

P F -65 CH3

Si

F

FP -830

O H3 C

-63

B

F -168

F

CF3

F -132 F

B

F F

F3 C

H3 C

O

H3 C

F

H3 C

F -164

H3 C

Si

P O

F -87

CH3 F -160

6.1 19F NMR



259

6.1.12 19F Chemical Shifts of Natural Product Analogues (δ in ppm relative to CFCl3, JFF in Hz) H3 N+

COO–

H3 N+

COO–

F

-116 H3 N+

H3 N+

OH

F -113

COO–

F -125

H3 N+

F -137 COO–

F -122 N

N

H

H OH HO HO

COO–

OH O OH F -146

OH

F O

HO HO

3J

F

OH -139

-150

F

-151

≈ 19.5

AcO

AcO AcO

-171

NH O

-150

O OAc AcO

O

F

H

F -119

N H

FF

F

O

AcO

-171 F

-205

3J

AcO AcO

F

O OAc

O

HO HO

F -235

FF ≈ 12.4

H AcO AcO

O

HO HO

-222

OH

NH2 F

N N H

O

F -138

260

6 Heteronuclear NMR

6.1.13 References [1] G. Arsenault, B. Chittim, J. Gu, A. McAlees, R. McCrindle, V. Robertson, Separation and fluorine nuclear magnetic resonance spectroscopic (19F NMR) analysis of individual branched isomers present in technical perfluorooctanesulfonic acid (PFOS), Chemosphere 2008, 73, S53. [2] P. Metrangolo, W. Panzeri, F. Recupero, G. Resnati, Perfluorocarbon–hydrocarbon self-assembly, Part 16. 19F NMR study of the halogen bonding between halo-perfluorocarbons and heteroatom containing hydrocarbons, J. Fluorine Chem. 2002, 114, 27. [3] R.E. Jetton, J.R. Nanney, C.A.L. Mahaffy, The prediction of the 19F NMR signal positions of fluoroalkenes using statistical methods, J. Fluorine Chem. 1995, 72, 121. [4] C.A.L. Mahaffy, J.R. Nanney, The prediction of the 19F NMR spectra of fluoroarenes using statistical substituent chemical shift values, J. Fluorine Chem. 1994, 67, 67. [5] J.R. Nanney, C.A.L. Mahaffy, The use of the 19F NMR spectra of fluoropyridines and related compounds to verify the 'statistical' substituent chemical shift values of fluoroarenes, J. Fluorine Chem. 1994, 68, 181.

6.2 31P NMR



6.2

31P

261

NMR Spectroscopy

6.2.1 31P Chemical Shifts of Tricoordinated Phosphorus, PR1R2R3 (δ in ppm relative to H3PO4) Substituent R1

H2 H C

X

O N S

–H –CH3 –CH2CH3 –phenyl –CH3 –CH2CH3 –phenyl –OCH3 –CH3 –CH2CH3 –CH2CH2CH3 –CH(CH3)2 –C(CH3)3 –phenyl –phenyl –phenyl –CH3 –CH3 –CH3 –CH3 –CH3 –CH3 –CH3 –F –Cl –Br –I –OCH3 –OCH3 –OCH3 –OCH2CH3 –N(CH3)2 –N(CH3)2 –N(CH3)2 –N(CH3)2 –SCH3

R2

–H –H –H –H –CH3 –CH2CH3 –phenyl –OCH3 –CH3 –CH2CH3 –CH2CH2CH3 –CH(CH3)2 –C(CH3)3 –CH3 –phenyl –phenyl –CH3 –CH3 –CH3 –F –Cl –Br –I –F –Cl –Br –I –CH3 –OCH3 –OCH3 –OCH2CH3 –CH3 –phenyl –N(CH3)2 –N(CH3)2 –SCH3

R3

–H –H –H –H –H –H –H –H –CH3 –CH2CH3 –CH2CH2CH3 –CH(CH3)2 –C(CH3)3 –CH3 –CH3 –phenyl –F –Cl –Br –F –Cl –Br –I –F –Cl –Br –I –CH3 –CH3 –OCH3 –OCH2CH3 –CH3 –phenyl –CH3 –N(CH3)2 –SCH3

δ

-235 -164 -127 -124 -99 -55 -41 171 -63 -20 -33 20 62 -48 -28 -6 185 92 88 244 192 184 131 97 220 227 178 91 183 140 138 39 65 86 123 125

262

6 Heteronuclear NMR

6.2.2 31P Chemical Shifts of Tetracoordinated Phosphonium Compounds (δ in ppm relative to H3PO4) 31P Chemical PR+4

Shifts of Symmetrically Substituted Phosphonium Compounds,

Substituent R –CH3 –CH2CH3 –n-propyl

31P Chemical

Substituent R

δ 25 41 31

–n-butyl –phenyl –OCH3

δ 34 23 5

Shifts of Triphenylphosphonium Compounds, P(phenyl)3R+

Substituent R

–CH3 –CH2CH3 –CH2Cl –CH2OH –CH2COCH3 –CH2COOCH2CH3

Substituent R –CH=CH2 –CH=C=CH2 –C ––– C–phenyl –NH2 –N(CH3)2 –OCH2CH3

δ 23 26 24 18 26 21

27

N

P 68 N

P

H N P 21 N H

δ 19 19 5 36 48 62

6.2 31P NMR



263

6.2.3 31P Chemical Shifts of Compounds with a P=C or P=N Bond (δ in ppm relative to H3PO4) 290 P

-2

P

P

389

92

Si

P

20

P

15

N

P

N

Si

P

7

P

15 O

18

P

O O

-20

P P

25

3

P

N P

n-C12H27

7

P

P

N

NO2

32

N P

n-C12H27

N

3

P

264

6 Heteronuclear NMR

6.2.4 31P Chemical Shifts of Tetracoordinated P(=O) and P(=S) Compounds (δ in ppm relative to H3PO4) 31P Chemical

Shifts of Tetracoordinated P(=O) Compounds

O R1

Substituent R1

C X

N O

2 O

–CH3 –CH3 –CH2CH3 –phenyl –CH3 –CH3 –CH3 –CH2CH3 –phenyl –CH3 –CH3 –CH3 –CH2CH3 –F –Cl –Br –N(CH3)2 –H –CH3 –CH3 –CH3 –phenyl –phenyl –CH3 –Cl –F –H –CH3 –CH3 –CCl3 –phenyl –phenyl –Cl

R2

–CH3 –CH3 –CH2CH3 –phenyl –CH3 –CH3 –CH3 –CH2CH3 –phenyl –F –Cl –Br –Cl –F –Cl –Br –N(CH3)2 –H –H –CH3 –CH3 –phenyl –phenyl –Cl –Cl –F –OCH3 –OH –OCH3 –OCH2CH3 –OH –OCH3 –OCH2CH3

R3

–H –CH3 –CH2CH3 –phenyl –F –Cl –Br –Cl –Cl –F –Cl –Br –Cl –F –Cl –Br –N(CH3)2 –OCH3 –OH –OH –OCH3 –OH –OCH3 –OCH2CH3 –OCH3 –OCH2CH3 –OCH3 –OH –OCH3 –OCH2CH3 –OH –OCH3 –OCH2CH3

P R2

R3

δ

63 41 48 27 66 65 51 77 43 27 44 9 55 -36 2 -103 24 19 35 31 52 29 32 40 6 -21 11 31 32 7 18 21 3

6.2 31P NMR

Substituent R1

3 O

S 31P Chemical

–OH –OCH3 –OCH2CH3 –OCH(CH3)2 –O–phenyl –O–phenyl –O–phenyl –S–n-butyl –S–n-butyl

R2

–OH –OCH3 –OCH2CH3 –OCH(CH3)2 –OH –O–phenyl –O–phenyl –S–n-butyl –S–n-butyl

R3

–OH –OCH3 –OCH2CH3 –OCH(CH3)2 –OH –OH –O–phenyl –OH – S–n-butyl

Shifts of Tetracoordinated P(=S) Compounds

C X

N  O S

–CH3 –CH2CH3 –phenyl –CH3 –phenyl –CH3 –CH2CH3 –CH3 –CH2CH3 –F –Cl –Br –Br –N(CH2CH3)2 –CH3 –OCH2CH3 –CH3 –S–n-butyl –S–n-propyl

R2

–CH3 –CH2CH3 –phenyl –CH3 –phenyl –CH3 –F –Cl –Cl –F –Cl –Br –I –N(CH2CH3)2 –OCH3 –OCH2CH3 –S–n-propyl –S–n-butyl –S–n-propyl

R3

0 0 -1

-13 -4 -11 -18 37 62

S R1

Substituent R1

δ

–CH3 –CH2CH3 –phenyl –Cl –Cl –Br –F –Cl –Cl –F –Cl –Br –I –N(CH2CH3)2 –OCH3 –OCH2CH3 –S–n-propyl –OCH3 –S–n-propyl

P R2

R3

δ

59 53 43 87 80 63 111 81 95 32 29 -112 -315 78 100 68 78 111 93

265

266

6 Heteronuclear NMR

6.2.5 31P Chemical Shifts of Penta- and Hexacoordinated Phosphorus Compounds (δ in ppm relative to H3PO4)

F

F P

F

F

-80

O

O

O

-88

P

O

O

Cl

-145

Cl P

O

O P -71 O O

-67

O

O P

O

Cl

-74

Br

O

O

–

Br

P

Br

P -89

P

Br

Br

Cl

P -81 Cl Cl

F

P

Cl

Cl

O

-85

O

– Cl

F

Cl

F

Cl -299

F P

– F

F F -144

–

O

P

N3 P

O

-152

– N3

N3 N3 -143

6.2 31P NMR



267

6.2.6 31P Chemical Shifts of Natural Phosphorus Compounds (δ in ppm relative to H3PO4) HO

O

HO

HO HO P O

+ –

HN

+

H3 N

–

O H C C O–

O–

+

H3 N

CH2 O –

-1.1

O

O H C C O–

+

H3 N

O P 4.0 CH3 – – O O

4.6

NH2 O

O

HO

O 3.2 P O – O– O

O

O

O

H3 C CH3 + N CH3

3.7 P

O O P O

H3 C

N

O H C C O–

O H C C O–

+

H3 N

CH2 CH2

N

CH2

N

+

H3 N

– O O -4.5 P N O –

O 4.0 O P O O–

O H C C O–

–

O–

P

NH

O

O -5.5

–

–

CH2

H

O HO

OH

H

O P NH

-3.0

N O

H

C NH

O

O

OH O O

4.0

P O– O–

3.7

P O– O O–

CH2

HC O

O P – O O

–

–

–

NH 3

O

-4.3

P O– O O– OH

CH3

O

N CH3 O HN P -2.5 – O– O

HO

O

O O

-3.9

P O– O–

O

-1.5

O

HO HO HO

P

H H

4.5 O– O– H O OH OH

H

6 Heteronuclear NMR

268

NH2 N

O

H

O–

H

OH

N

N

N

O 4.0 – O P O

NH2

N

-5.6 O –

H H

N

O -9.7

O P O P O O–

H

O–

(pH 7.8, 5 mM MgCl2)

H

N

H

O

OH

N

H H

H

NH2 N O –

-7.3

-21.8

O

O

-11.0

N

O P O P O P O O–

O–

H

O–

H

N

O

OH

H H

N

(pH 7.8, H 5 mM MgCl2)

NH2 N N O O –

H P

O 1.6

H

O

O

NH2 N

N

N

N HO

H H

H

H

H

O

–

O

O

O

P

H O O

H

-20.4

HN O

N N N HO

NH2

OH N

HO –

O O

O

N

O

P O P O O–

-10.8 and -11.3

H H

O

OH

H H

H

N N

N N

7 IR Spectroscopy C

7.1 Alkanes

C

C

C

C

%T CH3 δ sy CH 3 δ as CH 2 δ 1600 1200

C–H st 3600

2800

2000

CH2 δ

800

400

Typical Ranges (v~ in cm-1) Assignment C–H st

Range

3000–2840

Comments

N

Hal

Intensity variable, often multiplet

O

Beyond normal range: 2850–2815 CH3–O, methyl ethers 2880–2830

2880–2835, 2780–2750 ≈2820 3050–3000 2900–2800, 2780–2750 2820–2780 3100–3050, 3035–2995 2930–2915, 2900–2850 3080–2900

N

CH2–O, ethers

O–CH2–O, methylenedioxy

S

O–CH–O, acetals: weak O,

N

CH=O, aldehydes: Fermi resonance CH3–N, CH2–N; amines

cyclohexanes: weak, comb at ≈2700 CH–hal st

C

X

P Si Natural Products Solvents

270

Assignment CH3 δ as

C C

C

C

7 IR

CH2 δ

C

Range 1470–1430

Beyond normal range: 1440–1400 1475–1450

≈1425 1395–1365 ≈1385, ≈1370 ≈1385, ≈1365

Medium, coincides with CH3 δ as

CH2–C=C CH2–C ––– C CH2–C=O, CH2– C ––– N, CH2–X (X: hal, NO2, S, P) Medium. Doublet in compounds with geminal methyl groups: CH(CH3)2, of equal intensity (γ: 1175–1140, d)

C(CH3)2, 1385 weaker than 1365 (γ: 1220– 1190, often d) ≈1390, ≈1365 C(CH3)3, of equal intensity, sometimes triplet (γ: 1250–1200, d) N(CH3)2, no doublet Solid-state spectra: sometimes doublet also in the absence of geminal methyl groups Beyond normal range:

N

Hal O

1325–1310 1330–1290

N

1310–1280

S

CH3–C=O, methyl ketones, acetals, CH3–C=C

Beyond normal range: ≈1440

CH3 δ sy

Comments Medium, coincides with CH2 δ

CH3 γ

1275–1260

S–CH3, sulfides P–CH3

Si–CH3, strong, sharp

X

1175–1140

Intensity variable, of no practical significance. Strong band in compounds with geminal methyl groups: CH(CH3)2, doublet

P Si

1250–1200

C(CH3)3, doublet, often not resolved

C

Natural Products Solvents

1250–800

SO2–CH3

1220–1190

C(CH3)2, generally doublet

Beyond normal range: ≈765 ≈855, ≈800 ≈840, ≈765

SiCH3

Si(CH3)2 Si(CH3)3

 7.1 Alkanes Assignment CH2 γ

Range

770–720

Comments

Medium, sometimes doublet C–(CH2)n–C

Beyond normal range: C–D st

271

for n > 4 at ≈720; for n < 4 at higher wavenumbers; in cyclohexanes at ≈890, weaker

1060–800

Cycloalkanes, numerous bands, unreliable

2200–2080

In general, substitution of L by isotope L': ~ ν X–L' = ~ ν X–L

C C

C

C

C

1 / m x +1 / m L' 1 / m x +1 / m L

N

Hal O N S C

X

P Si Natural Products Solvents

272

7 IR

7.2 Alkenes 7.2.1 Monoenes

C C

C

C

C

%T overtone =CH 2

3600

2800

C=C–H δ oop

C=C st

C–H st 2000

1600

1200

800

400

Typical Ranges (v~ in cm–1)

N

Hal

Assignment

Range

Comments

=CH2 st

3095–3075

Medium, often multiple bands

=CH st

O

Medium, often multiple bands CH st in aromatic hydrocarbons and three-membered rings fall into the same range In cyclic compounds: ≈3075 ≈3060

N

≈3045

S C

3040–3010

≈3020

X

P Si Natural Products Solvents

=CH δ ip

=CH δ oop

1420–1290

Of no practical significance

1005–675

A number of bands

In the same range: ar CH δ oop, C–O–C γ, and C–N–C γ in saturated heterocyclics, OH δ oop in carboxylic acids, NH γ, NO st, SO st, CH2 γ, CF  st, CCl st

 7.2 Alkenes Assignment

Range

Subranges: C=C CH=CH2

C=CH2 H H H

H

H

C=C st

Comments C=C–C=O

1005–985 920–900 (overtone at 1850–1800) 900–880 (overtone at 1850–1780)

C=C–OR

≈980 ≈960 ≈810

≈960 ≈815

≈940 ≈810

≈795

990–960

≈975

≈960

725–675

≈820

840–800

≈820

1690–1635 Subranges: 1650–1635 1660–1640 1690–1665 1665–1635 1690–1660

273

C=C–O–C=O ≈950 ≈870

C

C

C

C

≈950

Of variable intensity, weak for highly symmetric compounds, strong for N–C=C and O–C=C

N

Hal O

CH=CH2 C=CH2

H H H

N

Weak

S

H

H

Weak, often absent Weak, often absent

1690–1650 Beyond normal range: down to ≈1590

C

C=C–X with X: O, N, S; of higher intensity; in vinyl ethers often doublet due to rotational isomers

C

X

P Si Natural Products Solvents

7 IR

274

At lower frequency if conjugated with:

C C

C

C

C

C=C

≈1650 ≈1600

≈1630

C ––– C

≈1600

≈1640

C ––– N

≈1620

C=O

≈1630

O

≈1640

Examples (v~ in cm-1)

N

Hal

Cl Cl

O N

neat: 1610

O

987 810

S C

X

P Si

1647 889 669

1682 972 963

1670 968

1650 709

1667 825

1575 826 761

1595 848 714

CCl4: 1634 1608 964 943

O

1663

O

1663

Natural Products Solvents

1645 994 912

N

1640

Cl

Cl

1655 1592 958 793

O

O

N

1660

1628

N

1662

Cl Cl

Cl

1587 929 835 780 1670 1652 937 925

O

1673

O

N

1650

 7.2 Alkenes 1830 1621 987 818

1652 1612 1607 (2270) CHO CO OCH 3

1618 (1704) 1637 (1735)

1636 O

1618 (1684)

275 1800 1621 941 899

CN

COO H

1645 1612 1635 1615 (1730) (1706)

C C

C

C

C

7.2.2 Allenes Typical Ranges (v~ in cm–1) Assignment

(C=C)=C–H st C=C=C st as

Range

3050–2950 1950–1930

C=C=C st sy

1075–1060

(C=C)=CH2 δ oop

≈850

N

Comments Strong, doublet in X–C=C=CH2 if X other than alkyl Ring strain increases frequency: C CH 2 ≈2020

Hal O

Weak, absent with highly symmetric substitution. In Raman, strong Strong; overtone at ≈1700 (weak)

N S C

X

P Si Natural Products Solvents

276

7 IR

7.3 Alkynes C

%T

C

C

C

C

C–H st 3600

overtone C–H δ

C C st

2800

2000

C–H δ 1600

1200

800

400

Typical Ranges (v~ in cm–1)

N

Assignment ––– C–H st

Range

C––– C st

2260–2100

O

Subranges:

N

≈2220

≈2120 ≈2240

S

≈2240

X

P Si Natural Products Solvents

Strong, sharp; in the same region also OH st, NH st Weak, sharp. In Raman, strong

Beyond normal range: R–C ––– C–H; at the lower end of the cited range

Hal

C

3340–3250

Comments

––– C–H δ

R–C ––– C–R; usually 2 bands (Fermi resonance), often missing if symmetrical, strong in Raman C–C ––– C–H C–C ––– C–C

C–C ––– C–CN C–C ––– C–COOH

≈2240, C–C ––– C–COOCH3 ≈2140 In the same range: C ––– Z st, X=Y=Z st, Si–H st 700–600

Strong, broad; overtone at 1370–1220 (broad, weak)

 7.4 Alicyclics

277

7.4 Alicyclics Cyclic Alkanes

C

%T CH 2 δ CH st 3600

2800

2000

1600

1200

800

C

C

C

C

400

Cyclic Alkenes %T

N

Hal

C=C st 3600

2800

2000

1600

1200

800

400

O

The other vibrations are similar to those in noncyclic alkenes and cyclic alkanes.

N

Typical Ranges (v~ in cm-1) Assignment C–H st

Range

Comments

H–C–H δ

1470–1430

Weak

C=C st

1780–1610

Varies with ring size and substitution

3090–2860

S

Strong

Twisting and wagging CH2 as well as C–C st do not significantly differ from the corresponding vibrations in noncyclic compounds and are of limited diagnostic value.

C

X

P Si Natural Products Solvents

278

7 IR

Examples (v~ in cm-1)

C C

C

C

C

N

Hal O N S C

X

P Si Natural Products Solvents

3090 3019 2933 1434

2974 2896 1450

2951 2871 1455

2920 2860 1447

2933 2865 1462

2941 1471 1451

≈1640

≈1780

≈1570

≈1640

≈1680

≈1690

≈1610

≈1660

≈1660

≈1670

≈1690

≈1570

≈1650

≈1675

≈1650

≈1665

≈1670

≈1615

O

≈1650

 7.5 Aromatic Hydrocarbons

279

7.5 Aromatic Hydrocarbons C

%T C–H st

3600

2800

overtones and comb

C–H δ oop C=C δ

skeletal vibrations 2000

1600

1200

800

400

C

C

C

C

Typical Ranges (v~ in cm-1) Assignment ar C–H st

Range

ar C–C

1625–1575

3080–3030

Comments

Often numerous bands; in the same range also CH st of alkenes and small rings

Medium, often doublet; generally weak in benzene derivatives having a center of symmetry in the ring

N

Hal O

In the same range: C=C st, C=N st, C=O st, N=O st, C–C in heterocyclics, NH δ 1525–1450

N

Medium, often doublet: Weak in: O

S O

In the same range: C=O st, N=O st, C–C in heterocyclics, B–N st, CH3 δ, CH2 δ, NH δ comb

2000–1650

ar C–H δ ip

1250–950

Very weak; useful for determining substitution patterns in 6-membered aromatic rings In the same range: C=O st, B–H…B st, N+–H st, H2O δ

C

X

P Si

Natural Numerous bands of variable intensity; of no Products practical significance. May be very strong in Raman and, thereby, indicative of substitution type Solvents

280

7 IR

Assignment

Range

ar C–H δ oop 900–650

C C

C

C

C

Comments

One or more strong bands; useful for determining substitution patterns in 6-membered aromatic rings. In Raman, generally weak In the same range: =C–H δ oop, C–O–C γ and C–N–C γ in saturated heterocyclics, OH δ oop in carboxylic acids, NH δ, N–O st, S–O st, CH2 γ, C–F δ, C–Cl st

Determination of Substitution Patterns in 6-Membered Aromatic Rings: Position and Shape of Bands Related to the Number of Adjacent H Atoms (v~ in cm-1) Not to be used for ring systems with strongly conjugated substituents such as C=O, NO2, C––– N. Comb, overtones

N

≈900 770–730 710–690

Hal O

2000

1600

N S C

2000

1600

2000

1600

Natural Products Solvents

m-di900–860 865–810 810–750 725–680 1,2,4-tri-

770–735

2000

1600

1,2,3,4-tetra-

2000

1600

1600

p-di860–780

2000

1600

860–780

2000

vic-tri800–770 780–760 720–685

900–860 860–800 730–690

X

P Si

Substitution type; Comb, overtones Substitution type; CH δ oop, ar C–C γ CH δ oop, ar C–C γ monoo-di-

1,3,5-tri900–840 850–800 730–675

2000

1600

 7.5 Aromatic Hydrocarbons Comb, overtones

2000

1600

Substitution type; Comb, overtones Substitution type; CH δ oop, ar C–C γ CH δ oop, ar C–C γ 1,2,3,5-tetra-

1,2,4,5-tetra-

900–840

900–840

penta-

2000

1600

900–840

2000

281

1600

hexa-

C C

C

C

C

–

2000

1600

Examples (v~ in cm-1)

Cl

3080 3040 1968 1818

3021 1945 1862 1808 1739

3080

3040 1915 1845 1775

3086

N

Hal OH OH

O

1927 1887 1764

N S C

X

P Si Natural Products Solvents

282

7 IR

7.6 Heteroaromatic Compounds Pyridines

C C

%T

C

C

C–H st

overtones and comb

C 3600

2800

C–H δ oop C=C δ C=N δ

skeletal vibrations 2000

1600

1200

800

400

Furans %T

overtones C–H st

N

Hal O

2800

2000

1600

C–H δ C–O–C st

1200

800

400

Pyrroles

N

%T

S C

3600

skeletal vibrations

overtones N–H st

X

P Si Natural Products Solvents

3600

2800

skeletal vibrations 2000

1600

1200

C–H δ

800

400

 7.6 Heteroaromatics

283

Typical Ranges (v~ in cm-1) Assignment N–H st

Range

Overtones

2100–1800

Medium, narrow; shifted by formation of hydrogen bonds Weak, characteristic

Ring skeleton

1610–1360

Strong, sharp bands

C–H δ

1000–700

Strong, broad; difficult to identify

C–H st

3100–3000

Medium, sharp

CO–C st

1190–990

Medium or strong; of variable intensity

3450–3200

Comments

C C

C

C

C

Pyridines:

The frequencies of pyridines are very similar to those observed in benzenes. The nitrogen atom behaves like a substituted carbon atom in benzenes. 5-Ring Heteroaromatics

N

Hal O

N H

NH st free

3500–3400

NH st H-bonded

3400–2800

S

CH st

≈3100

≈3100

≈3100

Ring skeleton: intensity variable, generally multiplets

1610–1560 1510–1475

1590–1560 1540–1500

1535–1515 1455–1410

CH δ oop: generally strong

990–725

770–710

935–700

O N S C

X

P Si Natural Products Solvents

284

7 IR

7.7 Halogen Compounds 7.7.1 Fluoro Compounds

C C

C

C

C

%T

C–F st 3600

2800

2000

1600

1200

800

400

Typical Ranges (v~ in cm-1) Assignment C–F st

N

1400–1000 Subranges:

Hal

1100–1000 1150–1000 1350–1100

O

1350–1150

N

≈1745 1250–1100

S C

Range

X

P Si Natural Products Solvents

CF2 CF3

Comments

Strong, often more than one band (rotational isomers), often not resolved. In Raman, weak to medium al CF2 (FC–H st: 3080–2990) al CF2 al CF3 C=CF

C=CF2 st ar CF

In the same range: strong bands for C–O st, NO2 st sym, C=S st, S=O st 780–680 780–680

Medium or weak, assignment uncertain (C–F δ?)

S–F st

815–755

Strong

P–F st

1110–760

Si–F st

980–820

B–F st

1500–800

 7.7 Halogen Compounds

285

7.7.2 Chloro Compounds %T

C

C–Cl st 3600

2800

2000

1600

1200

800

C–Cl δ

C

C

400

C

C

Typical Ranges (v~ in cm-1) Assignment

Range

C–Cl δ

400–280

Other

1100–1020

P–Cl st

<600

Si–Cl st

<625

B–Cl st

1100–650

C–Cl st

830– <600

Comments

Strong, often broad (rotational isomers), absent in chloroaromatics Of medium strength and width Strong, narrow or of medium width; chloroaromatics

N

Hal O

In disubstituted halobenzenes, characteristic skeletal vibrations:

R

X

X Cl Br I

ortho 1055–1035 1045–1030

meta 1080–1075 1075–1065

N

para 1095–1090 1075–1070 1060–1055

S C

X

P Si Natural Products Solvents

286

7 IR

7.7.3 Bromo Compounds %T

C C

C

C

C

C–Br st 3600

2800

2000

1600

1200

800

400

Typical Ranges (v~ in cm-1) Assignment

Range

C–Br δ

350–250

Other

1080–1000

C–Br st

N

700–500

Hal

Comments

Strong, of medium width; absent in bromoaromatics Of medium strength and width Strong, narrow or of medium width; bromoaromatics

7.7.4 Iodo Compounds

O

%T

N C–I st

S C

3600

X

P Si Natural Products Solvents

2800

2000

1600

1200

Typical Ranges (v~ in cm-1) Assignment

Range

Comments

C–I δ

300–50

Of medium strength and width

C–I st

650–450

Strong, two or more bands

800

400

 7.8 Alcohols, Ethers, and Related Compounds

287

7.8 Alcohols, Ethers, and Related Compounds 7.8.1 Alcohols and Phenols

C

Alcohols %T C–O–H δ

O–H st

C

C

C

C

C–O st 3600

2800

2000

1600

1200

800

400

Phenols %T

N O–H st 3600

C–O–H δ 2800

2000

1600

Hal

C–O st 1200

800

O

400

N

Typical Ranges (v~ in cm-1) Assignment O–H st

Range

3650–3200

Comments

Subranges: 3650–3590

Free OH; sharp

3550–3450

H-bonded OH; broad

3500–3200

Polymer OH; broad, often numerous bands

Beyond normal range: 3200–2500 O–H δ ip

S

Of variable intensity. In Raman, generally weak

Enols, chelates; often very broad

In the same range: NH st, ––– CH st (≈3300, sharp), H2O 1450–1200 Medium, of no practical significance

C

X

P Si Natural Products Solvents

288

7 IR

Assignment C–O st

C C

Range

1260–970

Strong, often doublet

Subranges: 1075–1000

C

C

Comments

1125–1000

C

CH2–OH CH–OH

1210–1100

C–OH

1275–1150

ar C–OH

In the same range: C–F st, C–N st, N–O st, P–O st, C=S st, S=O st, P=O st, Si–O st, Si–H δ <700 Medium, of no practical significance

O–H δ oop

Examples (v~ in cm-1) OH

N

Hal

OH

O N

3335 1350

OH

3215 1368 1220

OH OH

OH

3450 1370 1260 1195

OH

3290 1430 1020 3460 1315 1237 1210

7.8.2 Ethers, Acetals, and Ketals

S C

3250 1430 1075 1050

%T

X

P Si Natural Products Solvents

C–O–C st sy C–O–C st as 3600

2800

2000

1600

1200

800

400

In acetals and ketals, the C–O stretching vibrations are split into 3, sometimes even 4 to 5 bands. Acetals have an additional band due to a special C–H δ vibration. The C–H st vibration frequency is especially low for OCH3 st (2850–2815) and OCH2 st (2880–2835).

 7.8 Alcohols, Ethers, and Related Compounds

289

Typical Ranges (v~ in cm-1) Assignment

C–O–C st as

Range

1310–1000

Comments

Strong, sometimes split

Subranges for noncyclic ethers: 1150–1085 CH2–O–CH2 1170–1115 CH–O–CH, often split 1225–1180 C=C–O–al C 1275–1200 ar C–O–al C

C C

C

C

C

Subranges for cyclic ethers: 1280 sy 870 as ≈1030 sy ≈980 as

O O

≈1070 sy ≈915 as

O

N

≈1235

O

≈1100 as ≈815 sy ≈950

O

O O

O

≈800 C–O–C st sy

1055–870

ketals, acetals: 4 to 5 bands O

1075–1020

S

O O O O

in acetals: C–H st, ≈2820, weak

Strong, sometimes multiple bands

Subranges for noncyclic ethers: 1125–1080

N

O

≈925 1024, 1086 as ≈880 sy

Hal

C=C–O–al C, medium ar C–O–al C, medium

In the same range: strong bands for C–O st, C–F st, C–N st, N–O st, P–O st, C=S st, S=O st, P=O st, Si–O st, Si–H δ

C

X

P Si Natural Products Solvents

7 IR

290

Examples (v~ in cm-1)

C

C

C

1136 935 917

O

C O

O

1188 1138 1111 1046

O

C

O

O

1225 1218 1211 1003 1172 1132 1077 1057 1038

1250 1040

O

7.8.3 Epoxides %T C–H st

N

ring st as

ring δ ring st sy

1200

800

Hal 3600

O

2000

1600

400

Typical Ranges (v~ in cm-1)

N

Assignment

Range

ring st as

1280–1230

Frequency higher than normally found in alkanes Variable intensity

ring st sy

950–815

Variable intensity

ring δ

880–750

Variable intensity

C–H st

S C

2800

X

P Si Natural Products Solvents

Comments

3050–2990

Examples (v~ in cm-1) O

1280 870

O

1230 sy 885 as 845 δ

O

1260 sy 890 as 780 δ

 7.8 Alcohols, Ethers, and Related Compounds

291

7.8.4 Peroxides and Hydroperoxides %T

C O–O st C–O–O st

3600

2800

2000

1600

1200

800

400

C

C

C

C

Typical Ranges (v~ in cm-1) Assignment O–O–H st

Range

Comments

3450–3200

Of variable intensity

Subranges: Free OOH; H-bonded: ≈30 cm-1 higher than in corresponding alcohols In the same range: OH st, NH st, ––– CH st, H2O ≈3450 C–O–O st

O–O st Also:

Strong, ≈20 cm-1 lower than in corresponding alcohols In the same range: strong bands for C–O st, C–F st, C–N st, N–O st, P–O st, C=S st, S=O st, P=O st, Si–O st, Si–H δ 1000–800 Medium or weak, often doublet, assignment uncertain 1760–1745 C=O st in peracids 1200–1000

1820–1770

O

1017 880

Hal O N

C=O st in diacylperoxides (two bands)

S

Examples (v~ in cm-1) O

N

O

O

1070 1060 943

O O O

1100 852

C

X

P Si Natural Products Solvents

292

7 IR

7.9 Nitrogen Compounds 7.9.1 Amines and Related Compounds

C C

Primary Amines

C

C

%T

C–H st Fermi resonance (Ar-NH 2 ) NH2 st

C

3600

2800

2000

NH 2 δ

1600

C–N st

1200

NH2 δ

800

400

Secondary Amines %T

N

Hal

3600

2800

2000

1600

N–H δ

1200

800

400

1200

800

400

Ammonium %T

S C

C–N st

N–H st

O N

N–H δ

C–H st

+

+

X

P Si Natural Products Solvents

N –H δ

N –H st and comb 3600

2800

2000

1600

 7.9 Nitrogen Compounds

293

Typical Ranges (v~ in cm-1) Assignment

Range

NH st

3450–3300

NH2 st

NH3+ st NH2+ st NH+ st

NH2 δ NH δ

Comments

C Of variable intensity, generally 2 sharp bands, ~ Δν  = 65–75 At lower wavenumbers (<3200) and broader if C C H-bonded. Free and H-bonded forms often simultaneously observed In primary aromatic amines, additional combinaC C tion band at ≈3200 In the same range: OH st, ––– CH st 3500–3300

Of variable intensity, only one band At lower wavenumbers (<3200) and broader if H-bonded. Free and H-bonded forms often simultaneously observed In the same range: OH st, ––– CH st, H2O 3000–2000 Medium, broad, highly structured 3000–2700 Major maximum, comb: ≈2000 3000–2000 Medium, broad, highly structured 3000–2700 Major maximum 3000–2000 Medium, broad, highly structured 2700–2250 Major maximum In the same range: OH st, NH st, CH st, SH st, PH st, SiH st, BH st, X=Y=Z st, X––– Y st 1650–1590 1650–1550

Medium or weak Weak

NH3+ δ

1600–1460

NH2+ δ

1600–1460

NH+ δ

1600–1460

C–N st

1400–1000

Medium, often more than one band; weak in aliphatic amines Medium, often more than one band; weak in aliphatic amines Medium, often more than one band; weak in aliphatic amines Medium, of no practical significance

NH2 δ

850–700

Medium or weak; 2 bands in primary amines

NH δ

850–700

Medium or weak

P–N–C st

1110–930 770–680

N

Hal O N S C

X

P Si Natural Products Solvents

294

7 IR

Examples (v~ in cm-1) CH 3 NH 2

C C

C

C

C

H N

N H

3470 3360 1622

3357 3278 3200 sh 1605

NH 2

H 2N

3487 3405

NH 2

3279

NH2

NH

3356 3274 3175 1650 3416 3386 1322 1266

7.9.2 Nitro and Nitroso Compounds Nitro Compounds %T

N

Hal

C–N st

O

3600

N

2000

1600

1200

ring δ

800

400

Nitroso Compounds %T

S C

2800

NO2 st as NO 2 st sy

C–N st C–N st N=O st N=O st

X

P Si Natural Products Solvents

3600

2800

2000

1600

1200

800

400

 7.9 Nitrogen Compounds

295

Typical Ranges (v~ in cm-1) Assignment NO2 st as

NO2 st sy

Ring δ N=O st

C–N st N–N st

Range

Comments

Subranges: 1660–1625 1570–1540 1560–1490 1630–1530

O–NO2, nitrates; missing in Raman C–NO2, aliphatic nitro compounds C–NO2, aromatic nitro compounds N–NO2, nitramines

1660–1490

1390–1260 Subranges: 1285–1270 1390–1340 1360–1310

Very strong, of medium width. In Raman, of weak to medium intensity

C C

C

C

C

Strong, of medium width

O–NO2, nitrates C–NO2, aliphatic nitro compounds C–NO2, aromatic nitro compounds; often 2 bands 1315–1260 N–NO2, nitramines In nitrates also: ≈870 N–O st, strong ≈760 NO2 γ ≈700 NO2 δ 760–705 Strong; modified deformation of aromatic ring 1680–1450 Very strong, in monomers 1420–1250 Very strong, in dimers Subranges: 1680–1650 O–NO (nitrites) trans; 1625–1610: cis 1585–1540 C–NO, aliphatic C-nitroso compounds C–NO, aromatic C-nitroso compounds 1510–1490 N–NO, N-nitroso compounds ≈1450 In nitrites also: 3300–3200, comb ≈2500, 2300–2250 ≈800 N–O st trans; cis: very weak ≈600 O–NO δ trans; cis: ≈650 ≈850 C–NO, aliphatic C-nitroso compounds; coupled with other vibrations ≈1100 C–NO, aromatic C-nitroso compounds ≈1040 N-Nitroso compounds

N

Hal O N S C

X

P Si Natural Products Solvents

7 IR

296

Examples (v~ in cm-1) CH 3 NO

C C

1564 842

NO

1506 1110 810

NO

O

C

C

1497 1112 858

NO 2

C

1524 1359 851

NO2

1527 1351 853 720

NO2 NO2

1506 1351 1261 873 748

7.9.3 Imines and Oximes Imines

N

%T

Hal O

C=N st 3600

N

2000

1600

1200

800

400

Oximes

S C

2800

%T

X

P Si Natural Products Solvents

O–H δ

O–H st O–H st free H-bonded

3600

2800

NO st

C=N st 2000

1600

1200

800

400

 7.9 Nitrogen Compounds

297

Typical Ranges (v~ in cm-1) Assignment C=N st

Range

1690–1520 Subranges: ≈1670 ≈1645 ≈1630 ≈1655 ≈1645 ≈1635 ≈1555 ≈1645 ≈1625 1685–1580 1670–1600 1690–1645 1680–1635 2050–2000

OH st

OH δ N–O st

1580–1520 1685–1650 1650–1615 1690–1645 1640–1605 1640–1580 3600–2700 Subranges: ≈3600 3300–3100 ≥ ≈2700 1475–1315 1050–400

Comments

Generally strong. In Raman, generally strong R–CH=N–R' R–CH=N–R' R–CH=N–R' R

R" O

N

R, R': al R or R': conjugated R, R': conjugated R, R', R'': al R: conjugated R, R': conjugated

R'

R H2N

N

R

Additional band at 1540–1515 in:

CH=N–N=CH RO RO

NH

R RH N

N

C

C

N R

Additional bands: NH st: ≈3300, C–O st: ≈1325, ≈1100

Additional bands: NH2+ st: ≈3000 RO NH2+ δ: 1590–1540 C=C=N; ketimines, very strong, sometimes doublet Quinone oximes: C=O st 1680–1620 Aliphatic oximes Aromatic oximes O–C=N S–C=N S–S–C=N Strong RO

C

R, R': al R, R': conjugated

NH

R'

C

Additional band: ≈1655 C=O st

N

R

C

Hal O

+ NH2

Free H-bonded, broad Quinone oximes, more than one band Of no practical significance Of no practical significance

N S C

X

P Si Natural Products Solvents

7 IR

298

Examples (v~ in cm-1) NH

C

1667

N

C

C

C

C

N

OH

1603 N

1675

1672 (solid) 1662 (gas)

OH

1637

N

N

OH

1684

7.9.4 Azo, Azoxy, and Azothio Compounds %T N=N st

N

3600

Hal

C

N=N st

Range

1580–1400

N

1480–1450 1335–1315

S

≈1450 ≈1060

X

P Si Natural Products Solvents

2000

1600

1200

800

400

Typical Ranges (v~ in cm-1) Assignment

O

2800

Comments

Very weak, missing in compounds of high symmetry. In Raman, generally strong O st as (mainly N=N st) st sy (mainly N–O st) N N st as (mainly N=N st) st sy (mainly N–S st)

S N N O

1410–1175 Subranges: 1290–1175 1425–1385, 1345–1320 1300–1250 ≈1410, ≈1395

N N

Dimers of C-nitroso compounds

O

Aliphatic trans Aliphatic cis Aromatic trans Aromatic cis

 7.9 Nitrogen Compounds

299

7.9.5 Nitriles and Isonitriles Nitriles

C

%T C N st

3600

2800

2000

1600

1200

800

C

C

C

C

400

Isonitriles %T

+

N

–

–N C st 3600

2800

2000

1600

1200

800

400

Hal O

Typical Ranges (v~ in cm-1) Assignment C––– N st

Range

2260–2240 Medium to strong, sharp; for O–CH2–C ––– N, N–CH2–C ––– N: of low intensity or absent. In Raman, of medium to high intensity Beyond normal range: 2240–2215 C=C–C ––– N 2240–2215 2240–2230 ≈2275 2225–2175

–N+––– C–

2210–2185 2200–2070 2150–2110

N

Comments

C N

XC–C ––– N, X: Cl, Br, I –CF2–C ––– N N C N

>N–C=C–C ––– N C ––– N– Strong

+ – N C N

S C

X

P Si Natural Products Solvents

300

7 IR

Examples (v~ in cm-1)

C C

CN

C

C

C

NC

CN

NC

CN

NC

CN

2222 2273

CN NC

CN

2235

CN

CN

NC CN

2257 2222

NaCN, KCN 2080–2070

CN

2235

AgCN

2252 2252

2245

OH

2220

2178

NH2–CN

2268

7.9.6 Diazo Compounds Typical Ranges (v~ in cm-1)

N

Hal O

C=N+=N–

N S C

Assignment –N+––– N st

X

P Si Natural Products Solvents

Range

Comments

2180–2010

O

2310–2130 Medium, frequency depends on anion In the same range: C ––– C st, X=Y=Z st as, NH+ st, PH st, POH st, SiH st, BH st 2050–2010 Very strong Subranges: 2050–2035 R–CH=N+=N–, R: al or ar 2035–2010 R2–C=N+=N–, R: al or ar Beyond normal range: 2100–2050 R–CO–C=N+=N– C=O st ≈1645 (R: al) C=O st ≈1615 (R: ar) C=N+=N– st sy: ≈1350, strong + – N N

C=O st 1655–1560

 7.9 Nitrogen Compounds

301

7.9.7 Cyanates and Isocyanates Cyanates

C

%T

C–O st

C N st 3600

2800

2000

1600

1200

800

C

C

C

C

400

Isocyanates %T –N=C=O st sy

N 3600

–N=C=O st as 2800

2000

1600

1200

800

400

Hal O

Typical Ranges (v~ in cm-1) Assignment OC––– N st C–O st N=C=O st as N=C=O st sy

Range

N

Comments

2260–2130 Medium to strong 2220–2130 (OC ––– N)– st as 1335–1290 (OC ––– N)– st sy 1200–1080 Strong 2280–2230 Strong, sharp. In Raman, weak or absent ≈2300 –CF2–NCO 1450–1380 Weak Beyond normal range: 2220–2130 (N=C=O)–

S C

X

P Si Natural Products Solvents

302

7 IR

Examples (v~ in cm-1)

C

CH3–OCN

2248

OCN

2248 2282

2265

NCO

2280

C

C

CH3–NCO

C

C

N CO

O CN

NCO

N CO

2256 (1629 C=C)

O

2267

NCO

2235 2261 2282 2270 2246

7.9.8 Thiocyanates and Isothiocyanates Thiocyanates %T

N

Hal O

3600

N

2800

2000

1600

1200

800

400

Isothiocyanates

S C

C–S st

C N st

%T

X

C–N st –N=C=S st sy

P Si Natural Products Solvents

–N=C=S st as 3600

2800

2000

1600

1200

800

400

 7.9 Nitrogen Compounds

303

Typical Ranges (v~ in cm-1) Assignment SC––– N st C–S st N=C=S st as N=C=S st sy

C–N st

Range

Comments

2170–2130 Medium, sharp 2090–2020 (SC ––– N)– 750-550 Often doublet 2200–2050 Very strong, generally doublet, Fermi resonance 950–650 ≈950 aliphatic –N=C=S 700–650 aromatic –N=C=S Beyond normal range: 2090–2020 (N=C=S)– 1090–1075

C C

C

C

C

Examples (v~ in cm-1) CH3–SCN

2157

CH3–NCS

neat: in CCl4: 2206 2221 2114 2106 2077

NCS

SCN

2158

SCN

2170

N

2105

N CS

N CS

2062

NCS

2173 2097 2068

Hal O

neat: 2090 in CCl4: 2065 in CHCl3: 2112

N S C

X

P Si Natural Products Solvents

7 IR

304

7.10 Sulfur Compounds 7.10.1 Thiols and Sulfides

C C

C

C

C

%T

3600

2800

C–S st

CH 2 and CH 3 δ

S–H st

2000

1600

1200

800

400

Typical Ranges (v~ in cm-1) Assignment

Range

S–S st Also:

≈500 ≈2880 ≈2860 ≈1430 1330–1290 ≈1425 815–755 ≈630 725–550

S–H st S–H δ C–S st

N

Hal O N S C

X

Solvents

Often weak, narrow. In Raman, strong Weak, of no practical significance Weak, broad, of no practical significance. In Raman, strong Weak, of no practical significance (S–)CH3 st as (S–)CH2 st as (S–)CH3 δ as (S–)CH3 δ sy (S–)CH2 δ S–F st, strong S–N st in S–N=O S–C in S– C ––– N, often doublet

Examples (v~ in cm-1) SH

P Si Natural Products

2600–2540 915–800 710–570

Comments

S

S

2950 698 668 641

HS

SH

S

S

SH

2525

566

S

S

2585

662

 7.10 Sulfur Compounds

305

7.10.2 Sulfoxides and Sulfones Sulfoxides

C

%T

S=O st 3600

2800

2000

1600

1200

800

C

C

C

C

400

Sulfones %T

N SO 2 st as SO 2 st sy S–O st 3600

2800

2000

1600

1200

800

400

Hal O

Typical Ranges (v~ in cm-1) Assignment S=O st

Range

1225–980 Subranges: 1060–1015 ≈1100 ≈1135 1225–1195 ≈1135 ≈1030, ≈980 ≈1100, ≈1050

N

Comments

Strong, sometimes multiple bands. In Raman, weak to medium R–SO–R R–SO–OH R–SO–OR RO–SO–OR R–SO–Cl R–SO2– R=SO

S–O st 870–810 OH st free ≈3700, H-bonded ≈2900, ≈2500 S–O st 740–720, 710–690

N=SO: ≈1250, ≈1135

S C

X

P Si Natural Products Solvents

7 IR

306

Assignment S

C C

C

C

C

O st as O st sy

N

Hal O

S–O st

N S C

X

P Si Natural Products Solvents

Range

1420–1300 1200–1000 Subranges: 1370–1290, 1170–1110 1375–1350, 1185–1165 ≈1340, ≈1150 1415–1390, 1200–1185 1365–1315, 1180–1150

Comments

Very strong; in Raman, often missing Very strong; in Raman, strong R–SO2–R R–SO2–OR R–SO2–SR RO–SO2–OR R–SO2–N

1410–1375, 1205–1170 1355–1340, 1165–1150

R–SO2–hal

1250–1140, 1070–1030 1315–1220, 1140–1050 870–690

R–SO3–

R–SO2–OH

N–H st: 3330–3250; N–H δ: ≈1570; S–N st: 910–900 O–H st, H-bonded: ≈2900, ≈2400 hydrated: 2800–1650, broad

RO–SO3– Of variable intensity, weak in sulfites

 7.10 Sulfur Compounds

307

7.10.3 Thiocarbonyl Derivatives %T

C

S–H st C=S st 3600

2800

2000

1600

1200

800

400

C

C

C

C

Typical Ranges (v~ in cm-1) Assignment C=S st

Range

1275–1030 Subranges: 1075–1030 1210–1080 ≈1215 1125–1075 1100–1065 1140–1090 750–580

Also:

Comments

Strong, narrow. In Raman, strong Thioketones Thioesters Dithiocarboxylic acids SH st: ≈2550 SH δ: ≈860 Thiocarboxylic acid perfluorinated: fluoride 1130–1105 Thiocarboxylic acid perchlorinated: chloride 1100–1075 Thioamides and C–N st: 1535–1520 thiolactams NH δ: 1380–1300 P=S st

N

Hal O N S

7.10.4 Thiocarbonic Acid Derivatives

C

Trithiocarbonates %T

P Si

S–H st

Natural Products

C=S st 3600

2800

X

2000

1600

1200

800

400

Solvents

308

7 IR

Xanthates %T

C

S–H st

C

C

C

C

COC st as C=S st COC st sy 3600

2800

2000

1600

1200

800

400

800

400

800

400

Thiocarbonates %T

C=S st

N

Hal O

3600

2800

2000

1600

1200

Thioureas %T

N C=S st

S C

3600

X

P Si Natural Products Solvents

2800

2000

1600

1200

Typical Ranges (v~ in cm-1) Assignment S–H st

C=S st

COC st as COC st sy

Range

2560–2510 2600–2500 1100–1020 1070–1000 1250–1180 1400–1100 1260–1140 1150–1090

Comments

Weak, narrow Weak, narrow Very strong Strong Strong Strong Strong Strong to medium

trithiocarbonates xanthates trithiocarbonates xanthates thiocarbonates thioureas xanthates xanthates

 7.10 Sulfur Compounds

309

Examples (v~ in cm-1) O S

O

O S

S

O N

S

O

S H 2N

in CCl4: 1718 1677 1640

NH 2

O S

S

S S

S

solid: 1400

O

in CCl4: 1653

S

O

S

neat: 1076

in CCl4: 1662 in CS2: 2562 2522

S HS

in CCl4: 1719

S

S

S HS

S O

O

S N

N

solid: 1212

solid: 1130

O

S O

O

S N

N

in CCl4: 1757 solid: 1058 in CCl4: 1083 1079

C C

C

C

C

gas: 2593 2548 neat: 2470 solid: 1234

solid: 1131

N

Hal O N S C

X

P Si Natural Products Solvents

310

7 IR

7.11 Carbonyl Compounds 7.11.1 Aldehydes

C C

C

C

C

%T =C–H δ

C–H comb

3600

2800

C=O st 2000 1600

1200

800

400

Typical Ranges (v~ in cm-1) Assignment C–H comb

N

Hal O

C=O st

N S C

X

P Si Natural Products Solvents

C–H δ

Range

Comments

2900–2800 Weak, Fermi resonance with C–H δ at ≈1390 2780–2680 (for extreme position of C–H δ only one band) Subranges: 2830–2810, Aliphatic 2720–2690 2830–2810, Aromatic, with o-substitution often higher 2750–2720 In the same range: cyclohexanes at ≈2700, weak 1765–1645 Strong; in Raman, weak to medium Subranges: 1740–1720 Aliphatic 1765–1730 α-Halogenated aliphatic 1710–1685 Aromatic 1695–1660 α,β-Unsaturated aromatic 1670–1645 With intramolecular H bonds 1390 Weak, of no practical significance

 7.11 Carbonyl Compounds

311

Examples (v~ in cm-1) CH3–CHO

CCl3–CHO

CH O

O

1748

1725

H

H

H

1687

CH O OH

O

CHO

O

1760

Cl

CH O

1670

1696 N

NO 2

1742 1700

in CCl4: 1717 in CHCl3: 1710

C C

C

C

C

7.11.2 Ketones %T

N

Hal O

C=O st 3600

2800

2000

1600

1200

800

400

N

Typical Ranges (v~ in cm-1) Assignment C=O st

Range

1775–1650

Subranges: ≈1715

Comments

Aliphatic, branching at α position causes shift to lower wavenumbers: O

≈1775–1705

S

Strong; in Raman, weak to medium

C

X

O

P Si ≈1695 ≈1685 Cyclic, ~ ν decreases with increasing ring size Natural [contd.] Products Solvents

312

7 IR

Assignment

Range

O

C

O

≈1775

C

C

C

C

≈1715 Conjugated:

≈1675

≈1695 ≈1665 ≈1670

N

≈1690

Hal

≈1675

O

α,β-Unsaturated, often 2 bands (rotational isomers) C=C st O

al

α,β,γ,δ-Diunsaturated; α,β;α',β'-diunsaturated O

C C

Aryl ketones O

ar

Diaryl ketones, with N or O in p-position: down to ≈1600 Shifted toward higher wavenumbers depending on dihedral angle φ between C=O and C-hal; largest effect for φ = 0°, no effect for φ = 90° Maximal shifts: α-chloro α,α-dichloro

≈25 ≈45 α,α'-dichloro ≈45

S X

α-Diketones:

P Si Natural Products Solvents

≈1705

≈1665 α-Halogenated ketones:

N

≈1750 O

O

1650–1600

C

Comments

≈1720

≈1775, ≈1760 ≈1760, ≈1730 ≈1675 ≈1680

β-Diketones:

≈1675 ≈1720 ≈1650

Aliphatic

α-bromo α-iodo α,α-difluoro perfluoro

≈20 ≈0 ≈60 ≈90

Aliphatic 5-ring Aliphatic 6-ring Aliphatic enolized, C=C st: ≈1650 Aromatic

o-Quinones, with peri-OH: ≈1675, ≈1630 Keto form, sometimes doublet Enol form

 7.11 Carbonyl Compounds Assignment

Range

Comments

≈1615

γ-Diketones:

≈1675

C=C=O st as

313

2155–2130

Enol with intramolecular H bonds, C=C st: ≈1600, strong As monoketones p-Quinones; with peri-OH: ≈1675, ≈1630 C=C st: ≈1600 Very strong

C C

C

C

C

Examples (v~ in cm-1) O

O

1691

O

1697

O

s-trans O

1672 1660

O

O

1678 (2222)

1676

1664

O

O

C4H9 O

O

OH

N

1752 1726 (rotamers)

O Cl 3 C O

O

CCl 3 O

1648 O

1780 1751

O

1700 1655

O

1755 1725 1635 1590

N

O

1639

N

1710

1724 (keto form) 1608 (enol form)

O

H2N O

O

Hal

1702 O 2N

O

N

1692 O

1701

H9C4

s-cis

O

O

Cl

s-trans 1690 s-cis 1707

O

Cl

O

1722

1735

O

S C

X

P Si Natural Products

1630 1607 Solvents

314

7 IR

O

C

O

C

C

C

C

OH

O

1669

1669

1675

O

O

O O

O

1623 OH

O

1678

1662 O

O

7.11.3 Carboxylic Acids Carboxylic Acids %T

N

O–H st (free) O–H st (H-bonded)

Hal O

3600

C=O st 2000 1600

O–H δ oop

1200

800

400

Carboxylate Anions

N

%T

S C

2800

O–H δ ip

–

–

X

P Si Natural Products Solvents

3600

2800

– COO st as COO st sy 2000 1600 1200

COO δ 800

400

 7.11 Carbonyl Compounds

315

Typical Ranges (v~ in cm-1) Assignment COO–H st

C=O st

OC–OH st, C–OH δ OC–OH δ oop

Range

Comments

3550–2500 Intensity variable Subranges: 3550–3500 Free, sharp, only in highly diluted solutions 3300–2500 H-bonded, broad, often more than one band In the same range: OH st, NH st, CH st, SiH st, SH st, PH st 1800–1650 Strong; in Raman, weak to medium 1800–1740 Free (also in dicarboxylic acids) 1740–1650 H-bonded (dimer, also in dicarboxylic acids) Subranges for H-bonded C=O: 1725–1700 al–COOH 1715–1690 C=C–COOH 1700–1680 ar–COOH 1740–1720 hal–C–COOH 1670–1650 Intramolecular H bond 1440–1210 Of no practical significance 960–880

(COO)– st as

1610–1550

(COO)– st sy

1450–1400

(COO)– δ

≈775 ≈925 ≈680 ≈600

Medium, generally broad (only in dimers); in the same range: =CH δ, ar CH δ, NH δ Very strong; in α-halogen carboxylates near the higher value, with more than one α-hal beyond the normal range; in polypeptides at ≈1575 Strong, of no practical significance, in polypeptides at ≈1470 Formates, weak Acetates Benzoates CF3COO–

H

OH

neat: 1727 in CCl4: 1756 1724

C

C

C

C

N

Hal O N S C

Examples (v~ in cm-1) O

C

O OH

neat: 1759 1718 in CCl4: 1768 1717

O OH

in CCl4: 1704 solid: 1686

X

P Si Natural Products Solvents

7 IR

316 O

H

C

OH H

C

C

C

C

OH

NH 3 +

O

solid: 1605

O–

O

HO

OH

solid: 1650

OH

solid: 1690 in CCl4: 1730 in CHCl3: 1706

O

N

Hal

O OH

O

OH

N H3+ O

OH

O

HO

OH

neat: 1725

OH OH

O OH O

O

HO

OH

O

solid: 1724

OH

solid: 1690

O

solid: 1667 in CCl4: 1696 in CHCl3: 1661

in CCl4: 1788 1725

OH

O

O

O

neat: 1730

OH

O

solid: 1740 solid: 1735 1703

O

Cl

solid: 1690 O

OH

O

OH

in CCl4: 1750 O

solid: 1693 in CCl4: 1696

7.11.4 Esters and Lactones

S C

O

HO

O

O

N

neat: 1700 in CCl4: 1694

X

%T

P Si Natural Products Solvents

3600

2800

C=O st 2000 1600

O–C–C st as CO–O st as 1200 800

400

 7.11 Carbonyl Compounds

317

Typical Ranges (v~ in cm-1) Assignment C=O st

Conjugated esters:

Diesters: Keto esters:

Lactones:

Range

1790–1650 Subranges: 1750–1735 1730–1710 1730–1715 1690–1670 1790–1740 ≈1760 ≈1760 ≈1735 1755–1725 ≈1750 (ketone) ≈1735 (ester) ≈1650 ≈1740, ≈1715 O

O

O

O

O

O

≈1840

Comments

Aliphatic esters α,β-Unsaturated esters Aromatic esters With intramolecular H bonds α-Halogenated esters Vinyl esters, C=C st: 1690–1650, strong Phenol esters Phenol esters of aromatic acids As the corresponding monoesters α-Keto esters, generally one band β-Keto esters, keto form β-Keto esters, enol form, C=C st: ≈1630, strong γ-Keto esters, pseudoesters: ≈1770 O

O

≈1770

≈1750 (additional band at ≈1780 if α position is not substituted) ≈1760

C

Strong. In Raman, weak to medium

O

O

≈1720

O

O

O

O

O

O

C

C

C

C

N ≈1800

Hal O

≈1735

N

≈1730 (often doublet)

S

C–O st

1330–1050

C–O st as:

Subranges: ≈1185 Formates, propionates, higher aliphatic esters P Si ≈1240 Acetates ≈1210 Vinyl esters, phenol esters ≈1180 γ-Lactones, δ-lactones Natural ≈1165 Methyl esters of aliphatic carboxylic acids Products In the same range: Strong bands for C–F st, C–N st, N–O st, P–O st, C=S st, S=O st, P=O st, Si–O st, Solvents Si–H δ

2 bands: st as, very strong, at higher wavenumbers; st sy, strong, at lower wavenumbers

C

X

7 IR

318

Examples (v~ in cm-1) O

C C

H

O O

C

C

1730

O

C

Br

O

O

O

S

O

O

1734

O

O

O

1774 1754

X

O

1737

O 2N O O O O

1746

1725

O

O

1760 1742

O

O

O

O

1727

O

1727

O

Solvents

O

O

OH O

Natural Products

O

1752 (1675)

O

O O

1724

O

O O

P Si

O

1725

Si

O

1740

O

N

C

O

1787

O

O O

O

O

F3C

1758 (1690)

O

ester: 1704 ketone: 1690 enol: 1645

O

Hal

O

1730 (1658) (1638)

O

O

1743

O

Br

O

N

O

1726

O

1743

O

1747

O

O

O

O

O O

O O

1684

1766

O N

O O

1715

1743

 7.11 Carbonyl Compounds

319

7.11.5 Amides and Lactams Primary Amides

C

%T C–N st NH 2 δ

NH 2 st 3600

2800

2000

C=O st 1600

1200

800

C

C

C

C

400

Secondary Amides %T

NH st 3600

N

NH δ C=O st 2800

2000

1600

1200

800

400

Hal O

Tertiary Amides %T

N

3600

2800

2000

C=O st

1600

S 1200

800

400

Typical Ranges (v~ in cm-1) Assignment N–H st

Range

3500–3100 Subranges: 3500–3400 3350–3100 ≈3350, ≈3180 ≈3200, ≈3100 ≈3200

Comments

Medium, in primary amides two bands, in proteins multiplet Free H-bonded In primary amides generally two bands In lactams generally two bands Monohydrazides

C

X

P Si Natural Products Solvents

320

7 IR

Assignment

C C

C

C

C

C=O st (amide I)

N

Hal O N

C–N st (?)

S C

NH δ and N–C=O st sy (amide II)

NH δ ip

X

P Si Natural Products Solvents

NH δ oop

Range

Comments

≈3100 Dihydrazides ≈3250 Imides In the same range: OH st, ––– CH st (≈3300, sharp), H2O 1740–1630 Generally strong. In Raman, weak to medium Subranges: ≈1690 NH2C=O free amides, H-bonded: ≈1650 ≈1685 NHC=O free amides, H-bonded: ≈1660 ≈1650 NC=O free amides, H-bonded: ≈1650 ≈1745 4-Ring lactams ≈1700 5-Ring lactams ≈1650 6-, 7-Ring lactams ≈1670 Monohydrazides ≈1600 Dihydrazides 1740–1670 Imides ≈1750, 1700 5-Ring imides, 2 bands 1655–1630 Polypeptides ≈1690 Isocyanurates; with aromatic substitution: ≈1770 ≈1720, Trifluoroacetamides 1755 sh 1630–1510 Generally strong, absent in lactams Subranges: ≈1610 NH2C=O free, H-bonded: ≈1630 ≈1530 NHC=O free, H-bonded: ≈1540 1560–1510 Polypeptides ≈1555 Trifluoroacetamides ≈1400 NH2C=O ≈1250 NHC=O ≈1330 Lactams ≈1150 NH2C=O ≈1465 Lactams 750–600 NH2C=O ≈700 NHC=O ≈800 Lactams

 7.11 Carbonyl Compounds

321

Examples (v~ in cm-1) O H

N

H

neat: 1672 in CHCl3: 1709

N

solid: 1631 in CHCl3: 1679

H O

H

H

O H

N

H

O N

in CCl4: 1690

N

in CS2: 1675 1650

H O

O

H

solid: 1677

O

NH 2

solid:1656 in CHCl3: 1678 neat: 1700 1625 1540

O

N H O

O NH 2

O

O N H

solid: 1734 1505 solid: 1760 1690 in CCl4: 1721 1705

O N O

O N O O N O O

solid: 1718 1670 in CCl4: 1729 1686 solid: 1790 1735

neat: 1672

solid: 1658 in CHCl3: 1691 in CCl4: 1705

N

H

N

H

O

O N

O N Br O

O NH O

solid: 1628 1595 solid: 1736 1706 1689 in CHCl3: 1783 1733 solid: 1774 1749 1724 in CHCl3: 1778 1735

neat: 1670 in CHCl3: 1673

O H

N

O

in CCl4: 1647

N

O

C C

C

C

C

in CCl4: 1667

N

N O N

O NH O O NH O

O N O

solid: 1631 1584

Hal

solid: 1771 1698 in CCl4: 1753 1727

O

in CCl4: 1742 1730 1718

S

in CHCl3: 1772 1712

N

C

X

P Si Natural Products Solvents

7 IR

322

7.11.6 Acid Anhydrides %T

C C

C

C

C

C–O–C st C=O st sy C=O st as 3600

2800

2000

1600

1200

400

800

Typical Ranges (v~ in cm-1) Assignment C=O st sy C=O st as

N

Hal C–O–C st

O N

Comments

1870–1770 1800–1720 Subranges: ≈1820, ≈1760 ≈1850, ≈1775 ≈1800, ≈1760 1300–900 ≈1040 ≈920

Strong. In Raman, weak to medium Strong. In Raman, weak to medium Linear anhydrides, higher band stronger 5-Ring, lower band stronger 6-Ring, lower band stronger Strong, several bands Linear anhydrides Cyclic anhydrides

Examples (v~ in cm-1)

S

O

C

Range

X

1825 1748

O O

O

1810 1740 1045 1040

O O

P Si Natural Products Solvents

O

O O

1780 1725

O

O O

1790 1727 1035 1015 995

O

O

1803 1743

O

O O O

1865 1782 920

 7.11 Carbonyl Compounds O

O

1859 1789

O O O O O

O O

1840 1810 1760 912

O

O

1845 1780

O O O

1802 1761

O O

O O

323 1850 1800 900

1802 1761

C C

C

C

C

7.11.7 Acid Halides %T C–hal st

N

C–C= st C=O st 3600

2800

2000

1600

Typical Ranges (v~ in cm-1) Assignment C=O st

Range

1820–1750 1900–1870

C–CO st

1000–800

C–hal st

1200–500

Comments

1200

800

400

Hal O N

Chlorides, strong; in Raman, weak to medium. S Of narrow or medium width, for bromides and iodides at lower wavenumber Fluorides, strong, of narrow or medium width, additional band at ≈1725 in aromatic acid C X chlorides and bromides 1000–900 aliphatic, assignment uncertain 900–800 aromatic, assignment uncertain P Si 1200–800 F 750–550 Cl Natural 700–500 Br Products 600–500 I

Solvents

324

7 IR

7.11.8 Carbonic Acid Derivatives Carbonic Acid Esters

C

%T

C

C

C

C

C–O st as C=O st 3600

2800

2000

1600

1200

800

400

Carbamates %T N–CO–O st sy N–H δ N–CO–O st as C=O st

N–H st

N

Hal O

3600

2800

2000

1200

800

400

800

400

Ureas %T

N

C–N–H δ

N–H st

NH 2 δ

S C

1600

C=O st

X

P Si Natural Products Solvents

3600

2800

2000

1600

1200

Typical Ranges (v~ in cm-1) Assignment

Range

C–O st as

1750–1680 1690–1620 1260–1150

C=O st

1820–1740

Comments

Strong. In Raman, weak to medium Carbonic acid esters Strong. In Raman, weak to medium Carbamates Strong. In Raman, weak to medium Ureas Strong Carbonic acid esters

 7.11 Carbonyl Compounds Assignment

Range

N–H δ NH2 δ N–CO–O st as N–CO–O st sy C–N–H δ

3500–3200 1650–1500 1650–1600 1270–1210 1050–850 1600–1500

N–H st

Comments

3500–3250

Medium, two bands for NH2, one for NH Medium, two bands for NH2 Medium Medium Medium Weak Weak

325

Carbamates Ureas Carbamates Ureas Carbamates Carbamates Ureas

C C

C

C

C

Examples (v~ in cm-1) O H 2N

O

O H2N

O

O

NH2 O

O O O S

O

O S

S

O H2N

O

in CHCl3: 1725

NH2

O

N

solid: 1690

O O

1679 1627

O

O

in CCl4: 1786

in CCl4: 1718 1677 1640 solid:

O

H

in CCl4: 1719

in CCl4: 1727

O

O

O S

S

S S

S

O N H

NH2

O N

in CCl4: 1758 in CHCl3: 1751

O O

in CCl4: 1822 1748 in CCl4: 1653

neat: 1076 solid: 1645 1567 1418

in CHCl3: 1684

O

O

O N

S

O S

O

S S

S

Hal O

in CCl4: 1662

N

in CCl4: 1757

S

solid: 1058 C in CCl4: 1083 1079

X

P Si

O N

in CCl4: 1748

N

NH 2

solid: 1656 1610 Natural 1511 Products

Solvents

7 IR

326

solid: 1622 1580 1530 in CHCl3: 1663 1548

O

C C

N H

N H

O

O

C

C

C

N H

solid: 1667 NH2 1634

O N

NH O NH

N

Hal

N

S

O

HS

N

O

S H 2N

S C

N

X

P Si Natural Products Solvents

NH 2

solid: 1712 1676 neat: 1600 in CS2: 2562 2522 solid: 1400

O N

N

O HN

NH

O HN

N O NH

HN

NH

S O

O S

N

N

solid: 1645 1560 1497 in CHCl3: 1675

in CCl4: 1735 1718

solid: 1748 1706 solid: 1767 1681 1621 solid: 1212

solid: 1130

solid: 1650

O N

N

H

H

O HN

NH

solid: 1776 1697

O O HN

NH O

S HS

O

S O

O

S N

N

solid: 1767 1695 gas: 2593 2548 neat: 2470 solid: 1234

solid: 1131

 7.12 Miscellaneous Compounds

327

7.12 Miscellaneous Compounds C

7.12.1 Silicon Compounds %T Si–H st

3600

2800

2000

Si–H δ 1600

1200

800

C

C

C

C

400

Typical Ranges (v~ in cm-1) Assignment Si–H st

Si–H δ (Si–)CH3 δ as (Si–)CH3 δ sy (Si–)CH3 γ

Si–O st

Si–C st Si–N st

Range

2250–2090 Subranges: 2160–2090 ≈2250 2220–2120 1010–700 ≈1410 1275–1260 860–760 ≈765 ≈855, ≈800 ≈840, ≈765 1110–1000, 900– <600 1110–1000, 850–800 1090–1030, < 650 900–800 3700–3200 ≈1030 850–650 1250–830 Subranges: 950–830 ≈3400

Comments

Medium. In Raman, medium to strong R3Si–H; also for R as H; for SiH3: 2 bands hal–Si–H (Si–O)Si–H Strong, broad, generally 2 bands Weak Very strong, sharp, typical for SiCH3, not split for Si(CH3)2

N

Hal O N

SiCH3 Si(CH3)2 Si(CH3)3 Si–O–C Si–O–Si Si–OH Si–OH st Si–OH δ

Si–N–Si Si2NH st

S C

X

P Si Natural Products Solvents

328

7 IR

Assignment

C C

C

C

C

Si–F st

Si–Cl st

Range

950–830 1250–1100 ≈3570, ≈3390 ≈1540 980–820 Subranges: 920–820 945–870 980–860 < 625

Comments N–Si–N Si–NH2 SiN–H2 st Si–NH2 δ

Si–F SiF2, 2 bands SiF3, 2 bands

7.12.2 Phosphorus Compounds Phosphorus Compounds

N

Hal

%T P–H st

O

P=O st 3600

N

2000

1600

1200

800

400

Phosphines

S C

2800

%T

X

P Si Natural Products Solvents

P–H st 3600

2800

2000

–CH3 and P–H δ P–C st –CH 2 CH3 1600

1200

800

400

 7.12 Miscellaneous Compounds

329

Typical Ranges (v~ in cm-1) Assignment

Range

PO–H st POH comb

2700–2650 2300–2250 1740–1600 1260–855 Subranges: 1050–970, 830–740 1260–1160 995–915 875–855 1100–940 980–900 1300–960 Subranges: 1190–1150 1265–1200 1280–1240 1300–1260 1220–1150 1250–990 1125–970, 1000–960 1205–1090 1200–1090, 1090–995 ≈1250 1230–1210, 1030–1020 1140–1050, 1010–970 1250–1210 1285–1120, 1120–1050 1220–1170 1245–1150, 1110–1050

P–H st

P–O st

P=O st

2440–2275

Comments

Weak to medium, generally one band, in R3PH+ very broad. In Raman, weak to medium Weak, very broad Weak, very broad Additional band in O=P–OH (dimer?)

C C

C

C

C

P–O–C al st; strong for upper band, often weak for lower band P–O–C ar st P(V) P(III) P–OH st, broad, for P(OH)2 often two bands P–O–P st Strong. In Raman, weak to medium R3P=O, also for R: H R2(R'O)P=O, also for R: H R(R'O)2P=O, also for R: H (RO)3P=O R(HO)2P=O R(HO)PO2–, more than one band RPO32–

N

Hal O N

R2(HO)P=O R2PO2– RO(HO)2P=O RO(HO)PO2– ROPO32– (RO)2(HO)P=O (RO)2PO2– R(RO)(HO)P=O R(RO)PO2–

S C

X

P Si Natural Products Solvents

330

7 IR

Assignment

C C

C

C

C

N

Hal O N P=N P–OH δ P–C st

S C

X

P Si Natural Products Solvents

P–H δ P–N–C st P=N–al st P=N–ar st P=N–C=O st P=N–PR2 st P=S st P–S st (P–)CH3 δ sy P–F st

Range

Comments

1240–1205

O O R P P R O R R

1310–1260

O O RO P P OR O RO OR

≈1195

O O HO P P OH O R OR

≈1275

O O RO P P OR O R2N NR 2

1265–1250

O O R P P R O RO OR

≈1300, ≈1240

O O RO P P NR 2 O RO NR 2

≈1250

O O RO P P OR O HO OH

≈1235

O O R2N P P NR 2 O R 2N NR 2

1265–1240 1365–1260 1330–1280 1365–1260 1500–1170 ≈1280 800–700 1090–910 1110–930, 770–680 1500–1230 1390–1300 1370–1310 1295–1170 750–580 <600 1310–1280 905–760

R2(X)P=O, X: F, Cl, Br R(X)2P=O, X: F, Cl, Br (RO)2(X)P=O, X: F, Cl, Br RO(X)2P=O, X: F, Cl, Br Weak, of no practical significance Intensity varies widely, of no practical significance Strong, for (RO)2HP=O very strong

Intensity varies widely

 7.12 Miscellaneous Compounds Assignment PF2 P–Cl st

Range

331

Comments

1110–800 <600

More than one band

C

7.12.3 Boron Compounds %T

B–H st 3600

2800

B–O st 2000

1600

1200

C

C

C

C

B–C st 800

400

N Typical Ranges (v~ in cm-1) Assignment B–H st

Range

BO–H st B–N st B–C st

2640–2200 2200–1540 1380–1310 ≈1500 3300–3200 1550–1330 1240–620

B–F st B–Cl st

1500–800 1100–650

B–O st

Comments

Hal O

Strong, in Raman weak to medium B–H...B, more than one band Very strong Haloboroxines Very broad Very strong Strong, 2 bands if substitution highly asymmetric

N S C

X

P Si Natural Products Solvents

332

7 IR

7.13 Amino Acids C

%T

C

C

C

C

+ NH 3

st and comb 3600

2800

+

NH 3 δ sy C=O st 2000 1600

+

NH 3 δ rocking 1200

800

400

Typical Ranges (v~ in cm-1) Assignment N–H st O–H st

N

Hal NH3+ δ as NH3+ δ sy COO– st as

O N S C

X

P Si Natural Products Solvents

Range

Comments

3400–2000

Generally strong, broad, very structured

Subranges: 3100–2000 3350–2000 3400–3200 1660–1590 1550–1480 1760–1595 Subranges: ≈1595 1755–1700 ≈1595

Zwitterions, distinct side band at 2200–2000 Hydrochlorides Na+ salts Weak, for hydrochlorides near the lower limit Medium Strong Zwitterions Hydrochlorides; in α-amino acids: 1760–1730 Na+ salts

 7.14 Solvents, Suspension Media, Interferences

333

7.14 Solvents, Suspension Media, and Interferences 7.14.1 Infrared Spectra of Common Solvents

C

The low transmission in regions where the solvent absorbs may lead to artifacts. For the interpretation of spectra, these regions should be disregarded. In the following, they are indicated by bars. C Chloroform: 0.2 mm cell % Transmission

100 80 60 40 20 0 4000 3500 3000 2500 2000 1800 1600 1400 1200 1000

Chloroform: 1 mm cell % Transmission

100 80 60 40 20 0 4000 3500 3000 2500 2000 1800 1600 1400 1200 1000

Carbon tetrachloride: 0.2 mm cell % Transmission

100 80 60 40 20 0 4000 3500 3000 2500 2000 1800 1600 1400 1200 1000

Carbon tetrachloride: 1 mm cell % Transmission

100 80 60 40 20 0 4000 3500 3000 2500 2000 1800 1600 1400 1200 1000

C

C

800

C

600

N

Hal 800

O

600

N S 800

600

C

X

P Si Natural Products 800

600

Solvents

334

7 IR

Carbon disulfide: 0.2 mm cell

C

C

% Transmission

100 80 60 40 20 0 4000 3500 3000 2500 2000 1800 1600 1400 1200 1000

C

C

Carbon disulfide: 1 mm cell

100 80 60 40 20 0 4000 3500 3000 2500 2000 1800 1600 1400 1200 1000

% Transmission

C

600

800

600

7.14.2 Infrared Spectra of Suspension Media

N

As it is difficult to prepare pellets and thin mineral oil films of reproducible thickness, the bands of these suspension matrixes are always found superimposed on the sample spectra.

O

Mineral oil (nujol): 10 µm thickness

N

% Transmission

Hal

100 80 60 40 20 0 4000 3500 3000 2500 2000 1800 1600 1400 1200 1000

X

P Si Natural Products Solvents

800

600

800

600

Potassium bromide: pellet 100 80 60 40 20 0 4000 3500 3000 2500 2000 1800 1600 1400 1200 1000

% Transmission

S C

800

 7.14 Solvents, Suspension Media, Interferences

335

7.14.3 Interferences in Infrared Spectra Traces of water in carbon tetrachloride or chloroform may give rise to two bands in the vicinity of 3700 and 3600 cm-1 as well as one around 1600 cm-1. At higher con- C centrations, a broad band at 3450 cm-1 is found. Water in the vapor phase exhibits many sharp bands between 2000 and 1280 cm-1. If present in high concentration, they may temporarily block the detector and appear as shoulders when occurring at C C a steep side of a strong signal. Dissolved carbon dioxide shows an absorption band at 2325 cm-1. In solutions that contain amines and traces of water, CO2 can form carbonates, which lead to the C C appearance of unexpected bands of protonated N-containing groups. In improperly balanced double beam instruments, gaseous CO2 can give rise to two signals at approximately 2360 and 2335 cm-1 as well as a signal at 667 cm-1. Chloroform, saturated with water: 0.2 mm cell % Transmission

100 80 60 40 20 0 4000 3500 3000 2500 2000 1800 1600 1400 1200 1000

N 800

600

Water vapor with carbon dioxide % Transmission

100 80 60 40 20 0 4000 3500 3000 2500 2000 1800 1600 1400 1200 1000

Hal O N

800

600

S

Commercially available polymers often contain phthalates as plasticizers, which can be found in apparently pure samples and give rise to a band at 1725 cm-1. The presence of such phthalates can be confirmed by MS (m/z 149). In the course of C X chemical reactions, phthalates may be transformed into phthalic anhydride, which shows a band at 1755 cm-1. Other frequently encountered contaminants are silicones, which generally ex- P Si hibit a band at 1625 cm-1, together with a broad signal in the region from 1100 to 1000 cm-1. Natural

Products Solvents

8 Mass Spectrometry C

8.1 Alkanes [1]

C

C

C

C

Unbranched Alkanes [2,3] Fragmentation: Larger alkyl fragments (with Cn > 4) are chiefly formed by direct cleavage. They dehydrogenate and undergo substantial H and skeleton rearrangements. Smaller alkyl fragments (C2 to C4) are mainly formed by secondary decomposition of higher alkyl fragments. Eliminations of groups from within the chain (and recombination of its ends) also occur. Ion series: Consecutive peaks corresponding to CnH2n+1 (m/z 29, 43, 57, 71, …), accompanied by CnH2n-1 (m/z 27, 41, 55, 69, …) and CnH2n (m/z 28, 42, 56, 70, …) of lower intensity. Intensities: Maximum intensity at m/z 43 or 57; with increasing masses, intensity of local maxima smoothly decreasing to a minimum at [M-15]+. Molecular ion: Medium intensity. Branched Alkanes [2,3] Fragmentation: In most cases, apparently simple bond cleavages, preferably at branched C atoms. The positive charge remains mainly on the branched C atom. Mechanistically, many H and skeleton rearrangements take place. This is reflected by the fact that no specific localization of heavy isotopes is possible. R1 H

+. C

CHR 2

R1 – R3H

R3

+. CH

CH 2 R 2

+

.

– R3

R1

CH

N

Hal O N S

CH 2 R 2

Ion series: Consecutive peaks corresponding to CnH2n+1 (m/z 29, 43, 57, 71, …), C X accompanied by CnH2n-1 (m/z 27, 41, 55, 69, …) and CnH2n (m/z 28, 42, 56, 70, …) of lower intensity. Intensities: Local intensity maxima at those masses that result from cleavage at P Si branched C atoms if the charge is localized there. Both CnH2n+1 and (often more characteristically) CnH2n show this tendency. Natural Molecular ion: Intensity decreasing with increasing degree of branching. No M+· is Products observed in highly branched systems.

Solvents

338

8 Mass Spectrometry

References

C C

C

C

C

N

Hal O N S C

X

P Si Natural Products Solvents

[1] J.T. Bursey, M.M. Bursey, D.G. Kingston, Intramolecular hydrogen transfer in mass spectra. 1. Rearrangements in aliphatic hydrocarbons and aromatic compounds, Chem. Rev. 1973, 73, 191. [2] K. Levsen, H. Heimbach, G.J. Shaw, G.W.A. Milne, Isomerization of hydrocarbon ions. VIII. The electron impact induced decomposition of n‑dodecane, Org. Mass Spectrom. 1977, 12, 663. [3] A. Lavanchy, R. Houriet, T. Gäumann, The mass spectrometric fragmentation of n-alkanes, Org. Mass Spectrom. 1979, 14, 79.



8.2 Alkenes

339

8.2 Alkenes [1–4] Unbranched Alkenes

C

Fragmentation: Dominant loss of alkyl residues and neutral alkenes. The position of highly substituted double bonds can be localized because in this case alkene eliminations are specific McLafferty-type reactions. Otherwise, double bonds can C be localized in derivatives, such as epoxides and glycols, or by means of low energy ionization techniques. Branching effects are less characteristic than in isoalkanes. Alicyclic compounds exhibit very similar spectra. C Ion series: Consecutive peaks corresponding to CnH2n-1 (m/z 41, 55, 69, 83, …), accompanied by alkyl and alkene ions, CnH2n+1 (m/z 43, 57, 71, 85, …) and CnH2n (m/z 42, 56, 70, 84, …), mostly of lower intensity. Intensities: Dominant maxima in the lower mass range, peaking around C4. Local even-mass maxima due to alkene eliminations if the double bond is highly substituted. Molecular ion: Significant, but not necessarily strong. Branched Alkenes Fragmentation: Highly substituted double bonds are less easily displaced than the unsubstituted ones and give rise to specific alkene eliminations of the McLafferty type, resulting in significant local maxima corresponding to CnH2n (see scheme). The latter may allow to localize the double bond. With unsubstituted double bonds, no reliable localization is possible and only moderately useful branching effects can be observed. The branching position is more easily determined after reduction to an alkane (in situ in GC/MS with H2 as carrier gas and heated Pt wool as catalyst). R2

R1

H

R3

+.

R2

R1

+. +

R3

C C

N

Hal O N

Ion series: Maxima of the alkene type (CnH2n-1; m/z 41, 55, 69, 83, …), accompanied S by weaker alkyl fragments, CnH2n+1 (m/z 43, 57, 71, 85, …), in the low mass range and more significant alkene ions, CnH2n (m/z 42, 56, 70, 84, …). Intensities: Intensive peaks in the lower mass range. Diagnostically important local C X maxima of even mass, frequently also in the higher mass range. Molecular ion: Usually significant. Polyenes and Polyynes

P Si

Fragmentation: The spectra of aliphatic compounds with several triple and/or double Natural bonds are similar to those of aromatic hydrocarbons. A characteristic difference in Products the case of polyenes and polyynes is the presence of a signal at m/z 27, which is absent from spectra of purely aromatic compounds. Ion series: Very similar to those of aromatic hydrocarbons, but fragments with Solvents higher hydrogen contents than in aromatics (m/z 54, 55; 66, 67; 79, 80) are usually found in polyenes and polyynes.

340

8 Mass Spectrometry

Intensities: Very similar distribution of peak intensities as for aromatic hydrocarbons. Molecular ion: Usually strong, as in aromatic hydrocarbons.

C

References

C

C

C

C

N

Hal O N S C

X

P Si Natural Products Solvents

[1] A.G. Loudon, A. Maccoll, The mass spectrometry of the double bond. In: The Chemistry of Alkenes, Vol. 2; J. Zabicky, Ed.; Interscience: London, 1970; p 327. [2] J.T. Bursey, M.M. Bursey, D.G. Kingston, Intramolecular hydrogen transfer in mass spectra. 1. Rearrangements in aliphatic hydrocarbons and aromatic compounds, Chem. Rev. 1973, 73, 191. [3] N.J. Jensen, M.L. Gross, Localization of double bonds. Mass Spectrom. Rev. 1987, 6, 497. [4] C. Dass, Ion–molecule reactions of [ketene]+· as a diagnostic probe for distinguishing isomeric alkenes, alkynes, and dienes: A study of the C4H8 and C5H8 isomeric hydrocarbons, Org. Mass Spectrom. 1993, 28, 940.



8.3 Alkynes

341

8.3 Alkynes [1] C

Aliphatic Alkynes

Fragmentation: Tendency to lose a non-acetylenic H· from M+·. Extensive rearrangements (including consecutive McLafferty rearrangements to the triple C bond) result in uncharacteristic degradation:

C

C

C

H

CH 3

+.

H C

– C 3H 6

+.

+. C

H CH 2

– C3H6

m/z 54 (base peak for 5-decyne)

In nonbranched alkynes with Cn > 8, the rearrangement products at m/z 82 and 96 are dominant. Consecutive loss of methyl radical occurs. In general, no reliable localization of the triple bond is possible except in derivatives (as in ethylene glycol adducts [1], see scheme). R

1

C HO CH 2 CH 2 OH C

R2

O

R1

O

O

CH 2 R 2

O

O

R2

O

O

CH 2 R 1

O

+ R

1

+

+ R2

+

O

+

CH 2 R 2

O O O

+ CH 2 R 1

N

Hal

Ion series: Prominent peaks for CnH2n-3 (m/z 25, 39, 53, 67, 81, …), accompanied by CnH2n-1 (m/z 41, 55, 69, 83, …) and alkyl ions CnH2n+1 (m/z 43, 57, 71, 85, …). Occasionally, even-mass maxima for CnH2n-2 (m/z 26, 40, 54, 68, 82, …). Intensities: Intensive peaks mainly in the lower mass range. Molecular ion: Weak or missing in spectra of smaller molecules, significant in those of larger ones. Generally, [M-1]+ is present. In terminal acetylenes, it is normally more abundant than M+·.

O N S

References [1] C. Lifshitz, A. Mandelbaum, Mass spectrometry of acetylenes. In: The C Chemistry of the Carbon-Carbon Triple Bond, Part 1; S. Patai, Ed.; Wiley: Chichester, 1978; p 157.

X

P Si

Natural Products Solvents

342

8 Mass Spectrometry

8.4 Alicyclics [1] Cyclopropanes [2,3]

C C

C

C

Fragmentation: Generally, spectra of cyclopropanes and alkenes are very similar because at 70 eV ionization, the ring readily isomerizes to the corresponding alkene radical cations. kJ/m ol

+.

C

+.

C 3H 5 + + H 205

≈167 42

.

0

Reaction coordinate

Preferred primary fragmentation by bond cleavage at branched C atoms. Loss of alkyl residues and of neutral alkenes dominates. The ring of monosubstituted cyclopropanes is opened exclusively at the 1,2- and not at the 2,3-bond. The primarily formed double bond is predominantly (for R: OCH3) or exclusively (for R: H, alk, COOCH3) found in the β,γ-position (even for COOCH3, where the α,βunsaturation is thermodynamically more stable).

N

Hal

3

+.

1

R

– C3H6

H

H H

. H

H

R +

+.

b g

R a

Molecular ions of cyclopropyl cyanide, allyl cyanide, methacrylonitrile, and pyrrole rearrange to one common radical cation, most likely that of pyrrole [4]. Ion series: Consecutive maxima corresponding to CnH2n-1 (m/z 41, 55, 69, 83, …), accompanied by alkyl and alkenyl ions of the type CnH2n+1 (m/z 43, 57, 71, 85, …) and CnH2n (m/z 42, 56, 70, 84, …), mostly of lower intensity. Intensities: Dominant peaks in the low mass range, peaking around C4. Local evenmass maxima due to alkene eliminations if the resulting double bond is highly substituted. Molecular ion: Significant, but not necessarily strong.

O N S C

2

X

P Si Natural Products Solvents

Saturated Monocyclic Alicyclics [5] Fragmentation: Preferred primary fragmentation by bond cleavage at branched C atoms, followed by loss of alkyl residues and alkenes. Ion series: Consecutive maxima corresponding to CnH2n-1 (m/z 41, 55, 69, 83, …), accompanied by CnH2n+1 (m/z 43, 57, 71, 85, …) and CnH2n (m/z 42, 56, 70, 84, …) of lower intensities. In general, the maxima are so similar to those of alkenes that no clear distinction is possible. Intensities: Overall distribution of peaks maximizing in the lower mass range, around C4 or C5. Local maxima can result from branching effects. Molecular ion: Significant, mostly of medium intensity.



8.4 Alicyclics

343

Polycyclic Alicyclics Fragmentation: Most important primary cleavage at highly branched carbon atoms, followed by H rearrangements and complex fragmentations. C Ion series: With increasing number of rings, the position of unsaturated hydrocarbon fragments in the upper m/z range shifts from CnH2n-1 (m/z 41, 55, 69, 83, …) to CnH2n-3 (m/z 39, 53, 67, 81, …) and to CnH2n-5 (m/z 51, 65, 79, 93, …). Typically, C C maxima in the lower m/z range have a lower degree of unsaturation than those in the upper m/z range. Intensities: Major maxima evenly distributed, somewhat more intensive in the high C C mass or M+· range. Molecular ion: Strong. Cyclohexenes Fragmentation: Loss of larger ring substituents as well as retro-Diels–Alder reaction, yielding fragments of even-mass maxima with one or two double-bond equivalents, CnH2n (m/z 42, 56, 70, 84, …) and CnH2n-2 (m/z 40, 54, 68, 82, …), unless the retro-Diels–Alder product corresponds to ethylene. Somewhat unexpectedly, the base peak of cyclohexene is at [M-15]+. The retro-Diels–Alder reaction often accounts for prominent fragments of cyclohexenes and 1,4-cyclohexadienes: R2 R1

R3

+.

+ R1

R2 R3

+.

N

Hal O

However, double-bond migration may or may not occur beforehand. Also, other fragmentation pathways may dominate. Therefore, a reliable localization of the double bond in cyclohexene derivatives of unknown structure is not necessarily N possible. For example, the base peak of 1,2-dimethylcyclohexene is at m/z 68 rather than at the expected m/z 82. Ion series: Unsaturated hydrocarbon fragments in the upper m/z range are shifted, S relative to cyclohexane fragments, by two mass units to CnH2n-3 (m/z 39, 53, 67, 81, …). Typically, maxima in the lower m/z range correspond to a lower degree of unsaturation than those in the upper m/z range. C X Intensities: Intensive peaks evenly distributed over whole mass range. Molecular ion: Medium intensity (ca. 40% in cyclohexene). References

P Si

[1] J.T. Bursey, M.M. Bursey, D.G. Kingston, Intramolecular hydrogen transfer in Natural mass spectra. 1. Rearrangements in aliphatic hydrocarbons and aromatic com- Products pounds, Chem. Rev. 1973, 73, 191. [2] H. Schwarz, The chemistry of ionized cyclopropanes in the gas phase. In: The Chemistry of the Cyclopropyl Group, Part 1; Z. Rappoport, Ed.; Wiley: Chich- Solvents ester, 1987; p 173.

344

C C

C

C

C

N

Hal O N S C

X

P Si Natural Products Solvents

8 Mass Spectrometry

[3] J.R. Collins, G.A. Gallup, Energy surfaces in the cyclopropane radical ion and the photoelectron spectrum of cyclopropane, J. Am. Chem. Soc. 1982, 104, 1530. [4] G.D. Willet, T. Baer, Thermochemistry and dissociation dynamics of stateselected C4H4X ions. 3. C4H5N+, J. Am. Chem. Soc. 1980, 102, 6774. [5] E.F.H. Brittain, C.H.J. Wells, H.M. Paisley, Mass spectra of cyclobutanes and cyclohexanes of molecular formula C10H16, J. Chem. Soc. B 1968, 304.



8.5 Aromatic Hydrocarbons

345

8.5 Aromatic Hydrocarbons [1–4] Aromatic Hydrocarbons

C

Fragmentation: Weak tendency of fragmentation. Elimination of H· and successive H2 eliminations, yielding [M-1]+, [M-3]+, and [M-5]+ of decreasing intensities. In condensed aromatics, [M-2]+· can be a dominating fragment. Further typical frag- C mentation reactions are the eliminations of acetylene (Δm 26) and C3H3 (Δm 39). Some CH3 elimination frequently occurs in pure aromatic compounds. In the case of diphenyl compounds, biphenylene (m/z 152) and, if a CH2 group is available, C fluorene (m/z 165) ions are typically observed. +. C H

m/z 165

Ion series: CnHn and CnHn±1 (m/z 39, 51–53, 63–65, 75–77, …), for polycyclic aromatics gradually changing to more highly unsaturated ions. Doubly charged ions occur frequently, in particular as the size of the π-electron system increases. Intensities: Weak fragments. The intensity pattern of doubly charged ions does not follow that of the corresponding singly charged ions. Molecular ion: Strong.

N

Hal

Alkylsubstituted Aromatic Hydrocarbons

O

Fragmentation: Dominant loss of alkyl residues by benzylic cleavage, followed by elimination of alkenes. +.

.

– R1

CH 2

C

+

m /z 152

CH 2 R 1 R2

C

+ R2

R3

R3 +

+ CH 2

R2 –

N

R2 +

R3

R3

H

R2 3 R

S

+

C

X

At low resolution, methylbenzyl and β-phenylethyl have the same mass as benzoyl (m/z 105). In contrast to benzoyl, dehydrogenation products (m/z 104, 103) as well as protonated benzene (m/z 79) are also present if m/z 105 is a hydrocarbon rest. P Si Ion series: Aromatic hydrocarbon fragments, CnHn and CnHn±1 (m/z 39, 51–53, 63–65, 75–77, …), in the lower mass range. Intensities: Intensive peaks mainly in the higher mass range. Maxima by benzylic Natural Products cleavage. Molecular ion: Strong or medium.

Solvents

346

8 Mass Spectrometry

References

C C

C

C

C

N

Hal O N S C

X

P Si Natural Products Solvents

[1] J.T. Bursey, M.M. Bursey, D.G. Kingston, Intramolecular hydrogen transfer in mass spectra. 1. Rearrangements in aliphatic hydrocarbons and aromatic compounds, Chem. Rev. 1973, 73, 191. [2] W. Schönfeld, Fragmentation diagrams for elucidation of decomposition reactions of organic compounds. 1. Aromatic hydrocarbons (in German), Org. Mass Spectrom. 1975, 10, 321. [3] C. Lifshitz, Tropylium ion formation from toluene: Solution of an old problem in organic mass spectrometry. Acc. Chem. Res. 1994, 27, 138. [4] M.V. Buchanan, B. Olerich, Differentiation of polycyclic aromatic hydrocarbons using electron-capture negative chemical ionization, Org. Mass Spectrom. 1984, 19, 486.



8.6 Heteroaromatics

347

8.6 Heteroaromatic Compounds [1,2] General Characteristics

C

Fragmentation: Mostly fragments of aromatic character with specific eliminations including heteroatoms, e.g., elimination of HCN, CO, CHO, CS, and CHS from M+·, and of HCN, CO, and CS from fragments. In the case of alkyl-substituted C heteroaromatics, occurrence of benzylic-type cleavage and McLafferty rearrangements of substituents with Cn > 1 as well as specific rearrangements including heteroatoms, especially in N aromatics. C Ion series: Aromatic fragments, CnHn and CnHn±1 (m/z 39, 51–53, 63–65, …), in the lower mass range if the necessary number of C atoms is present (no such fragments, e.g., in pyrazine). Ions including heteroatoms like HCN+· (m/z 27), CH3CNH+ (m/z 42), and CS+· (m/z 44). Intensities: Intensive peaks mainly in the higher mass range. Molecular ion: Generally strong. [M-1]+ is often relevant in alkyl-substituted heteroaromatics. Furans [3] Fragmentation: Oxygen can be lost from M+· together with the neighboring C as CHO (Δm 29). In 2- or 6-methylfurans, CH3CO+ (m/z 43) can be seen (base peak in 2,5-dimethylfuran). As in aromatic methyl ethers, [M-43]+ is a product of a two-step reaction: (M+· - CH3· - CO). Furans substituted with an alkyl group (Cn > 1): benzylictype cleavage (to pyrylium ion, C5H5O+, m/z 81), followed by loss of CO. Ion series: Mainly aromatic hydrocarbon fragments, CnHn and CnHn±1 (m/z 39, 51–53, 63–65, …). Intensities: Intensive peaks mainly in the higher mass range. The fragments are usually more important than in purely aromatic hydrocarbons. Molecular ion: Strong. No pronounced tendency to protonate. Usually, [M-1]+ is very strong in methylfurans.

C

N

Hal O N S

Thiophenes [4] Fragmentation: Sulfur can be lost from M+· together with the neighboring C as CHS (Δm 45) or CS (Δm 44). Typical for thiophenes substituted with an alkyl group (Cn > 1) is benzylic-type cleavage followed by loss of CS (Δm 44). Protonated thiophene (m/z 85) is a characteristic product of monoalkylated thiophenes. Ion series: Aromatic hydrocarbon fragments, CnHn and CnHn±1 (m/z 39, 51–53, 63–65, …). Besides the isotope peak at [M+2]+·, the signals at m/z 44 and 45 (CS+· and CHS+) are indicators of sulfur. Intensities: Dominant peaks for M+· and products of benzylic-type cleavage. Molecular ion: Strong. Characteristic S isotope signal ([M+2]+· corresponds to 4.5% of M+·). No pronounced tendency of protonation. Usually, [M-1]+ is very strong in methylthiophenes.

C

C

X

P Si Natural Products Solvents

348

8 Mass Spectrometry

Pyrroles [5]

C C

C

C

C

Fragmentation: HCN elimination (Δm 27) from M+· and from fragments. In methylpyrroles, [M-1]+ is dominant. Benzylic-type cleavage in C- and N-alkyl­ pyrroles with or without (nonspecific) H rearrangements. Ion series: Aromatic hydrocarbon fragments, CnHn and CnHn±1 (m/z 39, 51–53, 63–65, …). Intensities: Dominant peaks for M+· and products of benzylic-type cleavage. Molecular ion: Strong (odd mass for odd number of N in the molecule). No tendency to protonate. In methyl-substituted pyrroles, [M-1]+ is dominant. Pyridines Fragmentation: HCN elimination (Δm 27) from fragments and the ion H2CN+ (m/z 28) are characteristic. Additional reactions in 2- or 6-methylpyridines are CH3CN elimination (Δm 41) and the formation of CH3CNH+ (m/z 42). Benzylic cleavage is dominant for 3-alkyl-, strong for 4-alkyl-, and weak for 2-alkylpyridines. Typical rearrangements with participation of the N atom in 2- and 6-alkylpyridine derivatives. Intramolecular N-alkylation in 2-alkyl derivatives:

N

Hal O

N+

N +. R

R

.

–R

N+

N+

.

–R

N+

m/z 106

N

. R

. N+

m/z 120

m/z 134

McLafferty rearrangements are important in 2- and 4-alkylpyridines: R1

S C

–R

N +.

N +. H

X

P Si

–

R1

R2

.

R2

CH 2 N+

H

Ion series: Aromatic hydrocarbon fragments, CnHn, CnHn±1 and CnHn±1N (m/z 39–41, 51–54, 63–67, 75–80, …). Intensities: Dominant peaks for M+· or, if possible, for products of benzylic-type cleavage. Molecular ion: Strong, except when benzylic-type cleavage is possible. Odd mass for an odd number of N in the molecule. No tendency to protonate. [M-1]+ is usually present and is strong in alkyl-substituted pyridines.

Natural Products N-Oxides of Pyridines and Quinolines

Fragmentation: The [M - O]+· radical ion, of variable intensity, is probably due

Solvents to thermal decomposition. The fragments [M - CO]+· and, if an alkyl group is

present on the neighboring C atom, [M - OH]+ are relevant for quinoline N-oxides. Rearrangements with ring formation including the N–O moiety if alkyl or aryl groups



8.6 Heteroaromatics

349

are present in the neighboring positions. Ion series: As for the corresponding heteroaromatics, aromatic hydrocarbon fragments, CnHn, CnHn±1 and CnHn±1N (m/z 39–41, 51–54, 63–67, 75–80, …), are C observed. Intensities: Dominant peaks for M+· and products of benzylic-type cleavage. Molecular ion: Strong, except when [M - O]+· dominates due to experimental conditions or when benzylic-type cleavage is possible. Odd mass for odd number of C C N atoms in the molecule. No tendency to protonate. Pyridazines and Pyrimidines Fragmentation: Loss of N2 or CH2N· (Δm 28) from pyridazines. Also, loss of N2H· (especially important in methylpyridazines) to give [M-29]+. In pyridazine N-oxides, consecutive loss of NO· and HCN. Consecutive losses of two HCN (2 × Δm 27) molecules from pyrimidines. From 2-, 4-, and 6-methylpyrimidines, CH3CN (Δm 41) is eliminated and the ion CH3CNH+ (m/z 42) occurs. Ion series: Aromatic hydrocarbon fragments (CnHn, CnHn±1) and, for pyrimidines, CnHn±1N, at low masses (m/z 39, 51–53). Intensities: Dominant peak for M+·. Molecular ion: Strong. No tendency to protonate. For pyrimidines, [M-1]+ is usually observable. Pyrazines Fragmentation: Consecutive losses of two HCN (2 × Δm 27) molecules. For methylpyrazines, elimination of CH3CN (Δm 41) and formation of CH3CNH+ (m/z 42). Ion series: No aromatic character of the spectra. Intensities: Dominant peak for M+·. Molecular ion: Strong. No tendency to protonate. Usually, [M-1]+ is observable; it can be stronger than M+· in alkyl-substituted (Cn > 1) pyrazines. Indoles

C

C

N

Hal O N S

Fragmentation: Analogous to pyrrole; HCN elimination (Δm 27) from M+· and C X from fragments. From M+· also CH2N· (Δm 28) elimination (in one or two steps). In methyl-substituted indoles, [M-1]+ is dominant. In N-methylindoles, [M-15]+ is significant. Benzylic-type cleavage in C- and N-alkylindoles with or without (nonP Si specific) H rearrangements. Ion series: Aromatic ion series. Intensities: Dominant maxima in the higher mass range. Natural Molecular ion: Strong. No tendency to protonate. In methyl-substituted indoles, Products strong signal for [M-1]+.

Solvents

350

8 Mass Spectrometry

Quinolines and Isoquinolines

C C

C

C

C

Fragmentation: Similar to pyridine: HCN elimination (Δm 27) from M+·, [M-1]+, and fragments. In methylquinolines and methylisoquinolines also CH3CN elimination (Δm 41). In alkyl-substituted (Cn > 1) quinolines, benzylic cleavage dominates except when neighboring effects of N play a role. For 2- and 8-alkylquinolines as well as 1- and 3-alkylisoquinolines, see rearrangements in pyridines. Ion series: Aromatic hydrocarbon fragments, CnHn, CnHn±1, and CnHn±1N (m/z 39–41, 51–54, 63–67, 75–80, …). Intensities: Dominant peak for M+· or, if possible, for products of benzylic-type cleavage. Molecular ion: Strong, except when benzylic-type cleavage is possible. Odd mass for odd number of N atoms in the molecule. No tendency to protonate. [M-1]+ is usually present and is strong in alkyl-substituted quinolines. Rearrangements in 8-alkylquinolines: +. N

+. N

N

. –R

Hal

+ N

O

R

. –R

m/z 156

+ N

– CH 2 =CHR

m/z 170

. CH 2

+ N

H

H H R

m/z 143

Cinnoline, Phthalazine, Quinazoline, Quinoxaline

N S C

R

+. N

X

P Si

Fragmentation: Same as for the corresponding monocyclic heteroaromatics pyridazine, pyrimidine, and pyrazine. Characteristic for pyridazine, cinnoline, and phthalazine is the elimination of N2 (Δm 28) and N2H· (Δm 29) from their alkyl derivatives. Phthalazine loses HCN (Δm 27) twice. Ion series: Aromatic hydrocarbon fragments, (CnHn, CnHn±1) and CnHn±1N (m/z 39–41, 51–54, 63–67, 75–80, …). Intensities: Dominant maximum for M+· or, if possible, for products of benzylictype cleavage. Molecular ion: Strong, except when benzylic-type cleavage is possible. Odd mass for odd number of N atoms in the molecule. No tendency to protonate. [M-1]+ is usually present and is strong in alkyl-substituted compounds.

Natural Products References Solvents

[1] Q.N. Porter, Mass Spectrometry of Heterocyclic Compounds, 2nd ed.; Wiley: New York, 1985. [2] D.G.I. Kingston, B.W. Hobrock, M.M. Bursey, J.T. Bursey, Intramolecular hydrogen transfer in mass spectra. III. Rearrangements involving the loss of small neutral molecules, Chem. Rev. 1975, 75, 693.



8.6 Heteroaromatics

351

[3] R. Spilker, H.-F. Grützmacher, Isomerization and fragmentation of methylfuran ions and pyran ions in the gas phase, Org. Mass Spectrom. 1986, 21, 459. [4] W. Riepe, M. Zander, Mass-spectrometric fragmentation behavior of thiophene C benzologs. Org. Mass Spectrom. 1979, 14, 455. [5] H. Budzikiewicz, C. Djerassi, A.H. Jackson, G.W. Kenner, D.J. Newmann, J.M. Wilson, Mass spectra of monocyclic derivatives of pyrrole, J. Chem. Soc. 1964, 1949. C C

C

C

N

Hal O N S C

X

P Si Natural Products Solvents

352

8 Mass Spectrometry

8.7 Halogen Compounds [1–3] Saturated Aliphatic Halides

C C

C

C

C

Fragmentation: Loss of halogen radical (I > Br > Cl > F) followed by elimination of alkenes. Loss of alkyl radical followed by elimination of acid HX. Loss of acid HX to give an alkene radical cation. – HX

–X R CH 2 X

.

R

+ . – CH 2 –R

Alkene +

.

. X

– RCH 2

.

CH 2

.

+

Hal

W eak but characteristic halogen indicators

CH 2 =X +

W eak but characteristic halogen indicators

N S C

Ion series: The dominant hydrocarbon fragments are mainly alkenyl fragments (CnH2n-1) for F and Cl, mixed alkyl (CnH2n+1) and alkenyl fragments (CnH2n-1) for Br, and mainly alkyl fragments (CnH2n+1) for I. Intensities: Intensive peaks mainly in the lower mass range. Characteristic maxima for Cl and Br at C4H8X+ (m/z 91, 93 and 135, 137, respectively), which has a cyclic structure: . R

O

X

P Si

W ith successive alkene elimination; im portant for Br and I Relevant for F and Cl com pounds of intermediate chain length and for a-branching

R+

X+

N

Important for F and Cl

+ X

–R

.

+ X

m /z 91, 93 for X : Cl m /z 135, 137 for X: Br

Alkyl substituents on the chain reduce the intensity of this fragment. If it is strong, [M - X]+ is weak. In the case of iodoalkanes, some I+ and HI+· at m/z 127, 128 is usually detectable. Molecular ion: Strong for the smallest alkanes, with increasing intensity in the sequence F, Cl, Br, I. Decreases rapidly with increasing mass and with increasing branching. It is negligible for F and Cl if the n-alkyl chains are longer than pentyl, and for Br and I if they are longer than heptyl and nonyl, respectively. Low tendency to protonate. Characteristic isotope patterns for Cl and Br. Iodine can be detected because of its high mass; the 13C signals of M+· and its fragments are conspicuously weak. Polyhaloalkanes Fragmentation: Preferred fragmentation of the C–C bond if several halogen atoms

Natural are bonded to one of these carbon atoms. CF3 (m/z 69) is often the base peak in Products terminally perfluorated alkanes, and so is CHCl2 (m/z 83, 85, 87) in terminally Solvents

dichlorinated compounds. Often, X2 is eliminated besides the usual fragmentation of X· and HX. Interchange of halogens may occur. For example, m/z 85 (CF2Cl) is a dominant signal (ca. 60%) for CF3CFCl2. Ion series: Most fragments are halogenated alkyl and alkenyl groups, easily detectable on the basis of the isotope signals in the cases of Cl and Br.



8.7 Halogen Compounds

353

Intensities: Intensive peaks mainly in the lower mass range. Molecular ion: Weak, decreasing with increasing number of halogen atoms. Absent from the spectra of many polyhalogenated compounds.

C

Aromatic Halides Fragmentation: Consecutive losses of halogen radicals and/or acid HX. In perhalo- C genated aromatics, decomposition down to Cx+, with x from 1 to 6 (m/z 12, 24, 36, 48, 60, 72). If alkyl-substituted (Cn > 1), the base peak is mostly the result of benzylic cleavage. In an otherwise aromatic environment, m/z 57 is a F indicator (C3H2F+). C Elimination of CF2 (Δm 50) from CF3 groups attached to the aromatic ring (from M+· or fragments). Ion series: Aromatic fragments, CnHn, CnHn-1, and CnHn-2 (m/z 39, 51–53, 63–65, 75–77, …). In the higher mass range: Cn(H,X)n. Intensities: Dominant peaks in the M+· region. Molecular ion: Usually very strong. Characteristic isotope signals for Cl and Br.

C C

References [1] A.G. Loudon, Mass spectrometry and the carbon-halogen bond. In: The Chemistry of the Carbon-Halogen Bond, Part 1; S. Patai, Ed.; Wiley: London, 1973; p 223. [2] D.G.I. Kingston, B.W. Hobrock, M.M. Bursey, J.T. Bursey, Intramolecular hydrogen transfer in mass spectra. III. Rearrangements involving the loss of small neutral molecules, Chem. Rev. 1975, 75, 693. [3] J.M. Miller, T.R.B. Jones, The mass spectra of azides and halides. In: Suppl. D: The Chemistry of Halides, Pseudo-Halides, and Azides, Part 1; S. Patai, Z. Rappoport, Eds.; Wiley: Chichester, 1983; p 75.

N

Hal O N S C

X

P Si Natural Products Solvents

354

8 Mass Spectrometry

8.8 Alcohols, Ethers, and Related Compounds [1,2] 8.8.1 Alcohols and Phenols

C

Aliphatic Alcohols [3]

C

C

C

C

Fragmentation: Elimination of water from M+· and from fragments. Strong for primary alcohols. If an aliphatic H atom can be transferred in a 6-ring process, it is involved in the water elimination in 90% of the investigated cases. If a CH2CH2 group is attached to the O-bearing C atom, water elimination is often followed by loss of ethylene. Water elimination is dominant for long-chain alcohols, rendering their spectra similar to those of alkenes. +. H HO

R1

.

R2 – H 2O

R1

R1

+

.

R2 – CH 2 CH 2

R1

R2

+.

Cleavage of bonds next to the OH-bearing C atom to form oxonium ions, then elimination of water and of alkenes. The α-cleavage is often dominant. Usually, its importance increases with increasing branching at the α-carbon atom. The larger substituent is lost most readily.

N

Hal O N S C

+ H2O

R2

X

P Si

R

R1

2

C

R3

+. OH

– R3

.

R1 C R2

+ OH

m/z 31 for primary alcohols (R 1 , R 2 : H ) m/z 30 + R 1 (45, 59, 73, ...) for secondary alcohols (R 2 : H) m/z 29 + R 1 + R 2 (59, 73, 87, ...) for tertiary alcohols

Consecutive H2O and alkene eliminations in longer-chain primary alcohols lead to [M-46]+·, [M-74]+·, [M-102]+·, …. In particular, branched alcohols frequently show a typical series of fragments at [M-15]+, [M-18]+·, and [M-33]+. Ion series: Dominant alkene ions corresponding to CnH2n-1 (m/z 41, 55, 69, …), CnH2n (m/z 42, 56, 70, …), accompanied by weaker fragments, CnH2n+1O (m/z 31, 45, 59, …), with one or more local maxima in the latter series (m/z 31 dominates in primary alcohols). Intensities: Intensive peaks in the lower mass range, local maxima among alkenetype fragment ions of the type CnH2n+1O+. Molecular ion: Mostly weak, often missing, especially in tertiary and long-chain alcohols. Indirect determination of M+· is often possible from the fragments at [M-15]+, [M-18]+· and [M-33]+. [M+1]+ is often significant. In primary and secondary alcohols also [M-1]+ can usually be seen. Sometimes, [M-2]+· is formed because of oxidation to carbonyl compounds during sample introduction.

Natural Alicyclic Alcohols Products Fragmentation: Elimination of water from M+·, followed by loss of alkyl or alkenyl Solvents

residues. Ring cleavage at the O-bearing C atom, followed by loss of alkyl residues after H rearrangement (see scheme). Ion series: Alkene hydrocarbon fragments CnH2n-1 (m/z 41, 55, 69, …), CnH2n-3 (m/z 39, 53, 67, 81, …), and unsaturated O fragments, CnH2n-1O (m/z 43, 57, 71, …), as well as acetaldehyde and its homologues (m/z 44, 58, 72, …).



8.8 Alcohols, Ethers, and Related Compounds +. OH

H

(CH 2 ) n

–

CH 3 (CH 2 ) n

+. OH

+ OH

+ OH

.

– C n+ 3 H 2n+ 6 (CH 2 ) n

m/z 57

355

CH 2

.

C

m /z 44

Intensities: Local maxima evenly distributed over the whole mass range. C Molecular ion: Usually weak but in contrast to aliphatic alcohols practically never + + missing. [M+1] typically contains a significant amount of [M+H] .

C

Unsaturated Aliphatic Alcohols [3] Allyl alcohols: The spectra are similar to those of the corresponding carbonyl compounds, which are (partly) formed by double H rearrangement of M+·. γ,δ-Unsaturated alcohols: Aldehyde elimination through a McLafferty-type rearrangement.

C

+.

OH

R2

H

O

R +.

O R1

– R 1 CHO

C

+. R +.

R2

Vicinal Glycols Fragmentation: Cleavage of bonds next to the OH-bearing C atom (α-cleavage) dominates. Preferable fragmentation of the C–C bond between the two oxygens, the charge remaining predominantly on the larger fragment. Water elimination from these fragments, but scarcely from M+·. Ion series: Saturated and unsaturated aliphatic ions (m/z 43, 57, 71, … and 41, 55, 69, …) and intensive peaks from O-containing saturated rests (m/z 45, 59, 73, …). Intensities: Dominant peaks for the products of α-cleavages and their dehydrated derivatives. Molecular ion: Weak.

N

Hal O N S

Phenols Fragmentation: Decarbonylation (Δm 28) and loss of CHO· (Δm 29) followed by elimination of acetylene. An important fragment of alkyl derivatives is [M-1]+, as is [M-15]+ if at least two alkyl carbons are present (dimethyl or ethyl). Elimination of CO from the primary fragments. [M-18]+· mainly with ortho-alkylphenols. In derivatives with a longer alkyl chain, benzylic cleavage and alkene elimination (McLafferty rearrangement) are the dominant primary fragmentation processes. The fragments then lose CO (Δm 28). Ion series: Aromatic hydrocarbon fragments, CnHn and CnHn±1 (m/z 39, 51–53, 63–65, 75–77, …). The presence of some m/z 55 (C3H3O) is common. A peak at m/z 69 (O––– CCH=C=O) is characteristic of 1,3-dihydroxy substitution. Intensities: Dominant peaks in the higher mass range. Molecular ion: Dominant, no tendency to form [M+H]+; [M-1]+ is weak.

C

X

P Si Natural Products Solvents

356

8 Mass Spectrometry

Benzyl Alcohols Fragmentation: Loss of H· and consecutive elimination of CO (Δm 28) to give a protonated benzene molecule, which further loses H2.

C

.

C

C

–H

.

– CO

OH + . M + (80% )

C

C

H

+

– H2

m/z 79 (100% )

C6H5+ m/z 77 (65% )

Elimination of OH· (Δm 17) to yield the tropylium cation is the second important fragmentation path: – OH

. .

+

.

OH

+ + [M -17] + , C 7 H 7 + , m/z 91 (25% )

M + (80% )

Ion series: Aromatic fragments corresponding to CnHn and CnHn±1 (m/z 39, 51–53, 63–65, 75–77, …). Intensities: Dominant peaks for the products described under Fragmentation. For benzyl alcohol decreasing in the sequence of [M-29]+, M+·, [M-1]+, [M-31]+, [M-17]+. Molecular ion: Strong.

N

Hal O

8.8.2 Hydroperoxides Aliphatic Hydroperoxides [4]

N S C

OH

[M -1] + (65% )

C6 H 7+

X

P Si

Fragmentation: Most pronounced is the loss of the hydroperoxy radical HO2· (Δm 33), especially when a tertiary alkyl cation is formed. Important, in decreasing order, is loss of H2O2 (Δm 34), H2O (Δm 18), HO· (Δm 17), and O (Δm 16). Ion series: Mainly saturated and unsaturated alkyl fragments, CnH2n+1 (m/z 43, 57, 71, …) and CnH2n-1 (m/z 41, 55, 69, …). The oxygen-indicating fragment at m/z 31 and its homologues are always present. Intensities: Intensive peaks mainly in the lower mass range. Molecular ion: Weak. 8.8.3 Ethers Aliphatic Ethers [5,6]

Natural Fragmentation: Homolysis of the C–C bond next to the O atom to yield oxygenProducts containing fragments. Preferably, the bond at the highest substituted C atom breaks Solvents

and the larger alkyl group is lost. R1

O +.

R2 R3

.

– R3

R1

+ O CH R 2 R1 O CH R 2 + C n H 2n+ 1 O + , m/z 31, 45, 59, ...



8.8 Alcohols, Ethers, and Related Compounds

357

This homolysis is followed by the elimination of alkenes, aldehydes, or, less importantly, of water. H

R1

O CH R 2 +

R1

O CH R 2 +

C

+ H O=CH R 2 [30 + R 2 ] +

– R 1 CH =CH 2

– R 2 CH =O

C

R 1 CH 2 CH 2 + m/z 29, 43, 57, ...

C

As a competing process, especially with increasing molecular weight, heterolysis at the O atom takes place to yield strong alkyl ion signals. The larger as well as the C branched alkyl rests are fragmented preferably. The base peak often arises from heterolysis of the C–O bond. +. O

R1

R2

– R 1 CH 2 CH 2 O

.

R3

C

R2 H 2C + R 3 m/z 29, 43, 57, ...

In contrast to the H2O elimination from alcohols, the H transfer involved in the elimination of RCH2CH2OH from ethers is nonspecific. H

+. O

R1

R2 R

3

.

R1

H

+ O

R2 R

– R 1 CH 2 CH 2 O H

3

+.

N

R 3 CH=R 2 m/z 28, 42, 56, ...

Ion series: Alkyl fragments, CnH2n+1 (m/z 29, 43, 57, …), with maxima due to cleavage of the C–O bond. Alkene ion series, CnH2n (m/z 28, 42, 56, …), due to elimination of alcohol. Oxygen-containing fragments, CnH2n+1O (m/z 31, 45, 59, …), with maxima due to cleavage of the C–C bond next to the oxygen. Intensities: Intensive peaks mainly in the lower mass range. Molecular ion: Significant or weak. Decreasing with increasing chain length and branching.

Hal O N

Unsaturated Ethers [7] Fragmentation of vinylic and acetylenic alkyl ethers: Dominant homolysis of the alkyl C–C bond next to the O atom on the saturated side, leading to C3H5O+ (m/z 57) for vinylic and C3H3O+ (m/z 55) for acetylenic ethers of primary aliphatic alcohols. C For alkyl (Cn > 5) vinyl ethers, ethanol elimination after triple H transfer. [M-15]+ in vinyl ethers predominantly by elimination of the vinyl CH2 after H rearrangement. H

alk

. CH 3

O +.

O +

alk

.

– CH 3

alk H3C

O +.

S X

P Si

alk O + [84 + alk] +

Natural Products

Fragmentation of allylic ethers: Heterolysis of both C–O bonds, leading to strong Solvents C3H5+ (m/z 41) and alkyl (m/z 29, 43, 57, …) cations. Formation of ionized allyl alcohol (C3H6O+·, m/z 58) by nonspecific H transfer from the alkyl rest. In allylic

358

C C

C

C

C

N

Hal O

and propargylic ethers, no cleavage of the C–C bond next to the O atom of the alkenyl group occurs. Hence, loss of vinyl or acetylenyl cannot be observed. Ion series: CnH2nO (m/z 44, 58, 72, …) for alkenyl alkyl ethers and CnH2n-2O (m/z 42, 56, 70, …) for dialkenyl ethers. Unsaturated aliphatic (CnH2n-1; m/z 41, 55, 69, …) as well as saturated aliphatic and unsaturated oxygen-containing fragments (CnH2n+1 and CnH2n-1O; m/z 43, 57, 71, …). Intensities: Intensive peaks mainly in the lower mass range. Molecular ion: Weak to medium, very weak for acetylenic ethers. Alkyl Cycloalkyl Ethers Fragmentation of methyl ethers of cycloalkanols with  >  3 C atoms: After primary cleavage of the ring C–C bond next to the O atom, the prominent fragments formed are CH3OCH=CH2+· (m/z 58) and, for alicyclics with > 4 C atoms, CH3O=CHCH=CH2+ (m/z 71, rearrangement in analogy to that observed for cycloalkanols). Loss of methanol to give hydrocarbon fragments, CnH2n-2 (m/z 54, 68, 82, …). Fragmentation of ethyl and higher alkyl ethers of cycloalkanols with > 3 C atoms: Alkene elimination to yield the protonated cycloalkanol (m/z 72, 86, 100, …) and heterolytic cleavage of the C–O bond to give dominating cycloalkyl ions (m/z 69, 83, …). Ion series: Besides the fragments already mentioned, mainly unsaturated hydrocarbon fragments (CnH2n-1, m/z 27, 41, 55, 69, …). Intensities: The above mentioned fragments dominate the spectrum. Molecular ion: Weak or intermediate. Cyclic Ethers

N

Fragmentation: Primary ring cleavage at C–C bonds next to the O atom, followed by loss of CH2O (Δm 30), H2O (Δm 18), or alkyl (Δm 15, 29, …). Elimination of H· to give [M-1]+ , followed by CO elimination (Δm 28) to [M-29]+. When α-substituted, dominant loss of substituents, followed by water elimination. Formation of acyl cation if two α-substituents are present.

S C

8 Mass Spectrometry

X

P Si

(CH 2 ) n

(CH 2 ) n

O +.

O +.

R

. –R

(CH 2 ) n O +

R – RCH O

+. (CH 2 ) n

(CH 2 ) n R1 O R2 . +

.

– R2

(CH 2 ) n O +

R

– 1

(CH 2 ) n

R1 C O+

Natural Products Ion series: Mainly ions of the alkene type. Weak saturated, oxygen-containing fragSolvents

ments (m/z 31, 45, …). Intensities: Intensive peaks evenly distributed over the whole mass range. Molecular ion: Often significant but sometimes weak, especially when α-substituted. Intensity of [M-1]+ usually comparable to that of M+· if no α substituent is present.



8.8 Alcohols, Ethers, and Related Compounds

359

Methoxybenzenes Fragmentation: Loss of methyl radical, followed by decarbonylation to [M-43]+; elimination of formaldehyde (Δm 30) from M+· or from primary fragments. C Ion series: Aromatic fragments corresponding to CnHn and CnHn±1 (m/z 39, 51–53, 63–65, 75–77, …). Intensities: Intensive peaks in the M+· region. C C Molecular ion: Strong.

C

Alkyl Aryl Ethers [8] Fragmentation: Commonly dominating alkene elimination to give the corresponding phenol ion (nonspecific hydrogen migration), followed by decarbonylation. In the case of aryl methyl ethers, loss of CH2O from M+· or from primary fragments as well as CH3· elimination followed by decarbonylation. Ion series: Mostly aromatic fragments, CnHn and CnHn±1 (m/z 39, 51–53, 63–65, 75–77, …). Intensities: Usually maximum at the mass of the corresponding phenol. Otherwise, intensive peaks mainly concentrated in the high and medium mass range. Molecular ion: Strong. Aromatic Ethers Fragmentation: Loss of H· (Δm 1), CO (Δm 28), and CHO· (Δm 29) from M+·. Cleavage at the C–O bond and decarbonylation of the resulting product, followed by dehydrogenation. Ion series: Aromatic fragments corresponding to CnHn and CnHn±1 (m/z 39, 51–53, 63–65, 75–77, …). Intensities: Intensive peaks mainly in the M+· region. Molecular ion: Strong.

C

N

Hal O N S

8.8.4 Aliphatic Epoxides [9]

Fragmentation: The most important primary fragmentation is the cleavage of C–C C X bonds next to the O atom (α-cleavage), resulting in complex degradation due to the related multiple choice and extensive secondary rearrangements. The products allow mass-spectrometric localization of double bonds after epoxidation. Due to ring opening prior to fragmentation, β-cleavage is as relevant as the P Si . + + α‑cleavage. +. O R O – CH R R O

2

.

m/z 57

γ-Cleavage is the most important fragmentation mechanism, especially in termi. nal epoxides: . +. –R O

R

+O

R

+

O

m/z 71

Natural Products Solvents

360

8 Mass Spectrometry

Mainly in terminal epoxides, rearrangement with alkene elimination, formally leading to alkene-OH+· (CnH2nO, m/z 44, 58, 72, …) and alkene+· (CnH2n, m/z 28, 42, 56, …): R . R

C C

C

C

C

+. H OCH 2 CH =CH 2

H +. O

+. O

+.

R-CH =CH 2

+ CH 2 =CHO H

H

RCH 2 CH =CH 2

+.

Mainly in nonterminal epoxides, transannular cleavage with H transfer and elimination of an alkenyl radical, leading to CnH2n+1O fragments (m/z 45, 59, 73, …): +. O

.

H

O R1

R2

R2

+

R

1

– alkenyl

.

+ R 2 -CH =OH

Ion series: Mixed, not characteristic. Intensities: Intensive peaks mainly in the lower mass range. Molecular ion: Usually weak.

N

Hal O N

Fragmentation: Alkene elimination to give hydroperoxide radical cations and hydroperoxide elimination to yield alkene radical cations (dominating if larger alkyl groups are present). Alkene elimination can be followed by loss of OH·, resulting in products that formally correspond to those obtained by O–O cleavage, which probably is not a one-step process: R1

S C

8.8.5 Aliphatic Peroxides [4]

O

H

O +.

P Si Natural Products Solvents

R1 H

R2 +. H O O

X

– CH 2 =CHR 2

R1

R2

– R 1 OO H

O +. OH

– OH

+ R 1 -CH =OH

.

[30 + R 1 ] +

R2

+.

Elimination of O· or O2 may occur in cyclic peroxides. tert-Butyl peroxides predominantly eliminate tert-butyl-OO· to give [M-89]+. Ion series: Saturated or unsaturated alkyl groups (CnH2n+1, m/z 29, 43, 57, …; CnH2n-1, m/z 27, 41, 55, …) and alkenyl ions (CnH2n, m/z 28, 42, 56, …) dominate. The fragment at m/z 31 and sometimes its homologues indicate the presence of oxygen. Intensities: Intensive peaks mainly in the lower mass range. Molecular ion: Weak to moderate.



8.8 Alcohols, Ethers, and Related Compounds

361

8.8.6 References [1] D.G.I. Kingston, J.T. Bursey, M.M. Bursey, Intramolecular hydrogen transfer in mass spectra. II. The McLafferty rearrangement and related reactions, Chem. C Rev. 1974, 74, 215. [2] D.G.I. Kingston, B.W. Hobrock, M.M.Bursey, J.T. Bursey, Intramolecular hydrogen transfer in mass spectra. III. Rearrangements involving the loss of small C C neutral molecules, Chem. Rev. 1975, 75, 693. [3] R.G. Cooks, The mass spectra of hydroxyl compounds. In: The Chemistry of the Hydroxyl Group, Part 2; S. Patai, Ed.; Interscience: London, 1971; p 1045. C C [4] H. Schwarz, H.-M. Schiebel, Mass spectrometry of organic peroxides. In: The Chemistry of Peroxides; S. Patai, Ed.; Wiley: Chichester, 1983; p 105. [5] C.C. van de Sande, The mass spectra of ethers and sulphides. In: The Chemistry of Ethers, Crown Ethers, Hydroxyl Groups and Their Sulphur Analogues, Suppl. E, Part 1; S. Patai, Ed.; Wiley: Chichester, 1980; p 299. [6] S.L. Bernasek, R.G. Cooks, The β-cleavage reaction in ethers, Org. Mass Spectrom. 1970, 3, 127. [7] J.P. Morizur, C. Djerassi, Mass spectrometric fragmentation of unsaturated ethers, Org. Mass Spectrom. 1971, 5, 895. [8] G. Sozzi, H.E. Audier, P. Morgues, A. Millet, Alkyl phenyl ether radical cations N in the gas phase: A reaction model, Org. Mass Spectrom. 1987, 22, 746. [9] Q.N. Porter, Mass Spectrometry of Heterocyclic Compounds, 2nd ed.; Wiley: New York, 1985. Hal

O N S C

X

P Si Natural Products Solvents

362

8 Mass Spectrometry

8.9 Nitrogen Compounds [1,2] 8.9.1 Amines

C

Saturated Aliphatic Amines [3]

C

C

C

C

Fragmentation: Dominating loss of alkyl residues by cleavage of the C–C bond next to the N atom ("N-cleavage"). Larger substituents are eliminated preferably. When a γ-H is available, subsequent elimination of alkenes by McLafferty-type reactions: 3 . 1 R

R

N 2 +. R

– R3

H

R1

– R 1 -CH=CH 2

N 2 + R

N 2 + R

Otherwise, unspecific H transfer onto the N atom: R3

R1

N

Hal O N S C

X

P Si

N + . R2

– R 1 -CH=CH 2

R1

N 2 + R

H

N H + R2

NH3, RNH2, and RR'NH eliminations from primary, secondary, and tertiary amines, respectively, are negligible except from some multifunctional compounds (e.g., diamines and phenyl-phenoxy-substituted amines). Ion series: Even-mass fragments of the type CnH2n+2N (m/z 30, 44, 58, 72, 86, …). Intensities: Mainly peaks in the low mass range. Dominating base peak from “N-cleavage” at [28 + m(R1) + m(R2) + m(R4) + m(R5)]+ for R1R2R3CNR4R5 (e.g., m/z 30 for RCH2NH2, m/z 44 for RCH2NHCH3, m/z 58 for RCH2N(CH3)2, and m/z 86 for RCH2N(CH2CH3)2). Local maximum at m/z 86 (C5H12N+) for n-alk–NH2 (protonated piperidine, 6-membered ring). Molecular ion: Usually weak or absent, especially if the α-C atom is substituted. Decreasing intensity with increasing molecular weight. Tendency to protonate to [M+H]+. Odd mass for odd number of N atoms in the molecule. Cycloalkylamines Fragmentation: The most important primary reaction is the ring cleavage next to the N atom, followed by H rearrangement and loss of an alkyl residue. Some elimination of amine, R1R2NH. R +. NH

Natural Products Solvents

.

– R3

R +. N

H

.

(CH 2 ) n R

+. NH

(CH 2 ) n R H

(CH 2 ) n

.

– C n+ 1 H 2n+ 3

+. NH

. (CH 2 ) n

– (CH 2 ) n+ 2

+ NH

R

.

R + NH

[55 + R] + –R

.

+ NH m /z 56



8.9 Nitrogen Compounds

363

Ion series: Even-mass fragments of the type CnH2nN (m/z 42, 56, 70, 84, …). Intensities: Intensive local maxima evenly distributed over the whole mass range. Molecular ion: Usually significant. Odd mass for odd number of N atoms in the molecule. Cyclic Amines

C C

C

Fragmentation: Dominating primary reaction is the cleavage of C–C bonds next to N, resulting in the loss of substituents next to N or in primary ring cleavage. Primary ring cleavage is followed by H rearrangement and loss of alkenes or alkyl groups. C The most important primary fragmentation for substituted cyclic amines is the loss of substituents at C atoms next to N. Piperidine: –H

+. N H m/z 85 (43% )

. .

– CH 3

+ N H

.

+ N m/z 84 (100% )

.

CH 3 H – C3H 6

+ N CH 2

+. H 2 C N CH 3

m/z 70 (14% )

m/z 43 (34% )

+ N H

+ H 3 C N CH 2 H m/z 44 (43% )

– C2H 4

– C 2H 4

+ N H –H

.

.

+ N H

+ H 2 N CH 2

N

Hal

m/z 30 (52% )

O

Ion series: Even-mass fragments of the type CnH2nN (m/z 42, 56, 70, 84, …) and CnH2n+2N (m/z 30, 44, 58, …) as well as odd-mass fragments of the type CnH2n+1N (m/z 43, 57, 71, 85, …). Intensities: Intensive local maxima evenly distributed over the whole mass range if no substituent is bonded to the C atom next to N. Otherwise, dominating maxima by loss of such substituents. Molecular ion: Significant or strong if no substituent is bonded to the C atom next to N; otherwise, weak. Tendency to form [M-H]+. Odd mass for odd number of N atoms in the molecule. Piperazines

C

N S C

X

Fragmentation: As for cyclic amines, enhanced primary ring cleavage at C–C bonds P Si next to the N atom. Ion series: Even-mass fragments of the type CnH2nN (m/z 42, 56, 70, 84, …) and CnH2n+2N (m/z 30, 44, 58, …) as well as odd-mass series of the type CnH2n+1N Natural (m/z 43, 57, 71, 85, …). Products Intensities: Intensive local maxima evenly distributed over the whole mass range if no substituent is bonded to the C atom next to N. Otherwise, dominating maxima by loss of such substituents. Solvents Molecular ion: Significant or strong if no substituent is bonded to the C atom next to N; otherwise, weak. Tendency to form [M-H]+. Odd mass for odd number of N atoms in the molecule.

364

8 Mass Spectrometry

Aromatic Amines

C C

C

C

C

Fragmentation: Dominating cleavage of alkyl bond at N-bearing C atom (“N-cleavage”) followed by alkene elimination if aliphatic substituents with C n ≥ 2 are present. Otherwise, loss of H· from primary and secondary anilines and benzylic amines. Loss of HCN from M+· or from fragments. A local maximum at m/z 42 is typical of an aromatically bonded dimethylamino group. Ion series: Aromatic hydrocarbon fragments (CnHn and CnHn±1; m/z 39, 51–53, 63–65, 75–77, …). Intensities: Dominating maxima by “N-cleavage” and following alkene loss if aliphatic substituents with Cn > 1 are present. Molecular ion: Abundant if no aliphatic substituents with more than one C atom are present, otherwise, medium or weak. No tendency to protonate. In primary and secondary aromatic and benzylic amines, [M-H]+ is important. Odd mass for odd number of N atoms in the molecule. 8.9.2 Nitro Compounds Aliphatic Nitro Compounds

N

Hal O N

Aromatic Nitro Compounds

S C

Fragmentation: Loss of NO· (Δm 30), NO2· (Δm 46), and HNO2 (Δm 47) as well as the formation of some m/z 30 as N indicator. Spectra with only few characteristic features. Ion series: Mixed alkyl and alkenyl fragments, CnH2n+1 (m/z 43, 57, 71, …) and CnH2n-1 (m/z 41, 55, 69, …). Intensities: Dominant peaks in the lower mass range. Molecular ion: Weak or missing. Odd mass for odd number of N atoms in the molecule.

X

P Si

Fragmentation: Loss of O (Δm 16), NO· (Δm 30, followed by elimination of CO, Δm 28), and NO2· (Δm 46) from M+· or from a major primary cleavage product. Extensive rearrangement of the functional group to a nitroso ester. Ion series: Aromatic fragments corresponding to CnHn and CnHn±1 (m/z 39, 51–53, 63–65, 75–77, …). Intensities: Intensive peaks mainly in the upper mass range. Molecular ion: Strong. Odd mass for odd number of N atoms in the molecule.

Natural Products 8.9.3 Diazo Compounds and Azobenzenes Solvents

Diazo Compounds [4,5] Diazonium: Because of the low volatility of diazo compounds, their electron impact mass spectra show thermal decomposition products. These are formed by loss of N2



8.9 Nitrogen Compounds

365

(e.g., a diazonium chloride gives rise to the corresponding aromatic chloro compound). From a phenyl diazonium ortho-carboxylate zwitterion, biphenylene is formed as dimerization product. Diazomethane and derivatives: M+· is strong except when catalytic decomposition occurs on metal surfaces of the inlet system. Loss of N2 is a dominant reaction of diazomethane and diazoketones.

C C

C

Fragmentation: Cleavage at the azo group followed by loss of N2, giving rise to the C dominant base peak. Ion series: Aromatic fragments (CnHn, CnHn±1; m/z 39, 51–53, 63–65, 75–77, …). Intensities: Dominant M+· and azo cleavage products. Molecular ion: Strong. Odd mass for odd number of N atoms in the molecule.

C

Azobenzenes

8.9.4 Azides Aliphatic Azides [6] Fragmentation: [M-42]+ (N3· elimination) or [M-28]+· (N2 elimination) dominant in most cases. The spectra are similar to those of the corresponding aliphatic compounds. Ion series: Aliphatic hydrocarbon series. Intensities: Dominant peaks in the lower mass range, as in aliphatic compounds. Molecular ion: Absent or weak. Odd mass for odd number of N atoms in the molecule.

N

Hal O N

Aromatic Azides [7] Fragmentation: In most cases, [M-28]+· (N2 elimination) is the base peak. The next step is the elimination of HCN (Δm 27) or acetylene (Δm 26), or, if there is a substituent X on the ring, of X· or HX. +.

X

N3

– N2

X

–X H4 m/z 90 – C2N2 C 4H 2 N + m/z 64

+.

.

H4 – HX

m/z 89 – C2H2

– H CN C 5H 3 + m/z 63

N

– HCN or C 2 H 2 m /z 37–39

.

[90 + X ] +

– H CN C5 H 3X +

.

[63 + X ] +

– H CN

C 4H N + m/z 63

N C6 H 4N X +

+.

H3

+ N

X

N

C5H2+ m/z 62

S

+.

– HX

.

C

X

P Si Natural Products Solvents

366

Ion series: Aromatic hydrocarbon fragments (CnHn and CnHn±1; m/z 39, 51–53, 63–65, 75–77, …). Intensities: Dominant peaks in the higher mass range; [M-28]+· (N2 elimination) and [M-55]+· (N2 and HCN elimination) are the most intensive peaks. Molecular ion: Weak. Odd mass for odd number of N atoms in the molecule.

C C

C

C

C

N

Hal O

8.9.5 Nitriles and Isonitriles Aliphatic Nitriles (R–CN) [4] Fragmentation: Elimination of alkyl radicals to give (CH2)nCN+ (m/z 40, 54, 68, …). McLafferty rearrangement yielding CR2=C=NH+· (m/z 41 for R: H). In most cases, C–CN cleavage and HCN elimination are not significant reactions. Complex rearrangements in unsaturated nitriles if other functional groups are present. Ion series: Saturated and unsaturated alkyl ions mainly in the lower mass range (CnH2n+1 and CnH2n-1; m/z 29, 43, 57, … and 27, 41, 55, …). Rearrangement products corresponding to CnH2n-1N contribute, to a significant extent, to the ion series m/z 41, 55, 69, …. For alkyl chains with Cn > 5, dominating (CH2)nCN+ (i.e., CnH2n‑2N, m/z 82, 96, 110, …, probably with a cyclic structure). Intensities: Intensive peaks due to the above mentioned ions. Molecular ion: Weak or missing. Both [M+H]+ and [M-H]+ are usually more intensive than M+·. In some aliphatic nitriles, [M+2H]+· is as intensive as M+·. Odd mass for odd number of N atoms in the molecule. Aromatic Nitriles (R–CN)

N S C

8 Mass Spectrometry

X

P Si Natural Products Solvents

Fragmentation: Consecutive elimination of HCN and acetylene. Ion series: Aromatic fragments corresponding to CnHn and CnHn±1 (m/z 39, 51–53, 63–65, 75–77, …). Intensities: Intensive peaks in the M+· region. Molecular ion: Dominant intensity, often base peak. In contrast to aliphatic and benzylic nitriles, [M-1]+ is usually not important. Odd mass for odd number of N atoms in the molecule. Aliphatic Isonitriles (R–NC) Fragmentation: In general, the spectra are similar to those of the corresponding nitriles. The most important difference lies in the loss of CN· (Δm 26) and the higher probability of losing HCN (Δm 27). Further important fragmentations are the elimination of alkyl radicals to give (CH2)nCN+ ions and the McLafferty rearrangement to yield CR2=N=CH+· (m/z 41 for R: H). Ion series: Saturated and unsaturated alkyl ions mainly in the lower mass range (CnH2n+1, m/z 29, 43, 57, … and CnH2n-1, m/z 27, 41, 55, …). Rearrangement products corresponding to CnH2n-1N contribute, to a significant extent, to the ion series of m/z 41, 55, 69, …. Intensities: Intensive peaks in the lower mass range.



8.9 Nitrogen Compounds

367

Molecular ion: Weak, decreasing with increasing chain length and degree of branching. Both [M+H]+ and [M-H]+ can be stronger than M+·. Odd mass for odd number of N atoms in the molecule.

C

Aromatic Isonitriles (R–NC) [4]

Fragmentation: Dominant loss of HCN ([M-27]+·). In methylphenyl and benzyl C isocyanides also formation of isocyanotropylium ion, [M-1]+, followed by loss of HCN to [M-28]+. C Ion series: Aromatic (CnHn and CnHn±1; m/z 39, 51–53, 63–65, 75–77, …). Intensities: Intensive peaks in the higher mass range. Molecular ion: Dominant; base peak for phenyl isocyanide. Odd mass for odd number of N atoms in the molecule.

C C

8.9.6 Cyanates, Isocyanates, Thiocyanates, and Isothiocyanates Aliphatic Cyanates (R–OCN) [8] Fragmentation: Spectra often very similar to those of the corresponding isocyanates (see below). Cleavage of the C–C bond next to O, with the charge remaining on CH2OCN (m/z 56) for short-chain cyanates and preferably on the alkyl substituent if it has a Cn > 2 chain (m/z 29, 43, 57, …). Cleavage of the C–O bond with H rearrangement to give HCNO+· (m/z 43) or alkene+· (m/z 42, 56, 70, …). For cyanates with Cn > 5 substituents, alkene elimination yields m/z 99. Ion series: Saturated and unsaturated alkyl cations (CnH2n+1, m/z 29, 43, 57, … and CnH2n-1, m/z 27, 41, 55, …). Alkene radical cations (CnH2n, m/z 42, 56, 70, …) together with isobaric ions of the composition CnH2nNCO. Intensities: Intensive peaks mainly in the lower mass range. Molecular ion: Usually weak or absent. [M-H]+ is often more intensive. Odd mass for odd number of N atoms in the molecule. Aromatic Cyanates (R–OCN) [8]

N

Hal O N S

Fragmentation: Loss of OCN· (Δm 42) or, to a lesser extent, of CO (Δm 28), with C X subsequent HCN elimination (Δm 27). Ion series: Aromatic fragments corresponding to CnHn and CnHn±1 (m/z 39, 51–53, 63–65, 75–77, …). P Si Intensities: Intensive peaks in the higher mass range. Molecular ion: Strong. Odd mass for odd number of N atoms in the molecule. Aliphatic Isocyanates (R–NCO) [8]

Natural Products

Fragmentation: Spectra often very similar to those of the corresponding cyanates. Solvents Cleavage of the C–C bond next to N, the charge remaining on the CH2NCO (m/z 56) for short-chain isocyanates and preferably on the alkyl substituent for compounds with a Cn > 2 chain (m/z 29, 43, 57, …). Cleavage of the C–N bond with H

368

8 Mass Spectrometry

rearrangement to give HNCO+· (m/z 43) or alkene+· (m/z 42, 56, 70, …) ions. For isocyanates with Cn > 5 alkyl chains, alkene elimination, yielding m/z 99.

C

+

CH 2 –N =C=O m /z 56

C

C

C

C

– R

. R–CH 2 –N=C=O

R

– CH 2 N CO

+

R N +

.

O

H

.

+.

– R=CH 2

H–N =C=O m/z 43

– HN CO

R=CH 2

+.

+.

m/z 99

– R-CH =CH 2 N +.

OH

Ion series: Saturated and unsaturated alkyl cations (CnH2n+1, m/z 29, 43, 57, … and CnH2n-1, m/z 27, 41, 55, …). Alkene radical cations (CnH2n, m/z 42, 56, 70, …) together with isobaric ions of the composition CnH2nOCN. Intensities: Intensive peaks mainly in the lower mass range. Molecular ion: Usually weak or absent. [M-H]+ is often more intensive. Odd mass for odd number of N atoms in the molecule.

N

Aromatic Isocyanates (R–NCO) [8]

Hal O N

Aliphatic Thiocyanates (R–SCN) [8]

S C

Fragmentation: Consecutive elimination of CO (Δm 28) and HCN (Δm 27). In contrast to aromatic cyanates, practically no elimination of NCO· (Δm 42). Ion series: Aromatic fragments corresponding to CnHn and CnHn±1 (m/z 39, 51–53, 63–65, 75–77, …). Intensities: Intensive peaks in the higher mass range. Molecular ion: Dominating; base peak for phenyl isocyanate. Odd mass for odd number of N atoms in the molecule.

X

P Si Natural Products

Fragmentation: Elimination of HCN (Δm 27) followed by loss of an alkyl group. The cleavage of the C–C bond next to SCN is unimportant except in short-chain thiocyanates. Ion series: Saturated and unsaturated alkyl cations (CnH2n+1, m/z 29, 43, 57, … and CnH2n-1, m/z 27, 41, 55, …). Intensities: Intensive peaks in the lower mass range. Molecular ion: Weak. Decreasing with increasing chain length and degree of branching; absent from the spectrum of hexyl thiocyanate. Odd mass for odd number of N atoms in the molecule. Both [M+H]+ and [M-H]+ are detectable. Characteristic 34S isotope peak at [M+2]+· and [frag+2] for S-containing fragments (4.5% per S atom).

Solvents Aromatic Thiocyanates (R–SCN) [8]

Fragmentation: The most important fragmentation is the elimination of SCN· (Δm 58). Further elimination reactions are loss of CN· (Δm 26), HCN (Δm 27),



8.9 Nitrogen Compounds

369

and CS (Δm 44). Ion series: Aromatic fragments corresponding to CnHn and CnHn±1 (m/z 39, 51–53, 63–65, 75–77, …). Weak signal at m/z 45 (CHS+) indicates sulfur. C Intensities: Intensive peaks in the higher mass range. Molecular ion: Dominant; base peak in phenyl thiocyanate. Odd mass for odd number of N atoms in the molecule. Characteristic 34S isotope peak at [M+2]+· and [frag+2] for S-containing fragments (4.5% per S atom). C C Aliphatic Isothiocyanates (R–NCS) [8] Fragmentation: Cleavage of the C–C bond next to NCS, leading to m/z 72 (CH2NCS) or to its homologues if the α-C atom is substituted. Loss of the alkyl residue with concomitant double hydrogen rearrangement to yield H2NCS+ (m/z 60). With a Cn > 4 alkyl chain, loss of SH· (Δm 33). With Cn > 5 alkyl chains, loss of alkene leading to m/z 115, probably according to the mechanism shown for aliphatic isocyanates. Ion series: Mainly saturated and unsaturated alkyl cations (CnH2n+1, m/z 29, 43, 57, … and CnH2n-1, m/z 27, 41, 55, …). Signal for CH2NCS+ (m/z 72) or its homologues (m/z 86, 100, 114, …) if the α-C atom is substituted. Intensities: Intensive peaks mainly in the lower mass range. Molecular ion: Medium to weak, decreasing with increasing chain length and degree of branching. More intensive than in the corresponding thiocyanates; 1% for hexadecyl isothiocyanate. Both [M+H]+ and [M-H]+ are relevant. Odd mass for odd number of N atoms in the molecule. Characteristic 34S isotope peak at [M+2]+· and [frag+2] for S-containing fragments (4.5% per S atom). Aromatic Isothiocyanates (Ar-NCS) [8]

C

C

N

Hal O

N Fragmentation: Dominant loss of NCS· (Δm 58). In contrast to aromatic thiocyanates, the loss of HCN (Δm 27) or CS (Δm 44) leads to very weak fragments only. Ion series: Aromatic fragments corresponding to CnHn and CnHn±1 (m/z 39, 51–53, 63–65, 75–77, …). Weak signal at m/z 45 (CHS+) indicates sulfur. S Intensities: Intensive peaks in the higher mass range. Molecular ion: Dominant; base peak in phenyl isothiocyanate. Odd mass for odd number of N atoms in the molecule. Characteristic 34S isotope peak at [M+2]+· and C X [frag+2] for S-containing fragments (4.5% per S atom). 8.9.7 References

P Si

[1] H. Schwarz, K. Levsen, The chemistry of ionized amino, nitroso and nitro com- Natural pounds in the gas phase. In: Suppl. F, The Chemistry of the Amino, Nitroso and Products Nitro Compounds and Their Derivatives, Part 1; S. Patai, Ed.; Wiley: Chichester, 1982; p 85. [2] D.G.I. Kingston, B.W. Hobrock, M.M. Bursey, J.T. Bursey, Intramolecular Solvents hydrogen transfer in mass spectra. III. Rearrangements involving the loss of small neutral molecules, Chem. Rev. 1975, 75, 693.

370

C C

C

C

C

N

Hal O N S C

X

P Si Natural Products Solvents

8 Mass Spectrometry

[3] R.D. Bowen, The chemistry of CnH2n+2N+ ions. Mass Spectrom. Rev. 1991, 10, 225. [4] K.-P. Zeller, Mass spectra of cyano, isocyano and diazo compounds. In: Suppl. C, The Chemistry of Triple-Bonded Functional Groups, Part 1; S. Patai, Z. Rappoport, Eds.; Wiley: Chichester, 1983; p 57. [5] C.W. Thomas, L.L. Levsen, Electron-impact spectra of 2-diazoacetophenones, Org. Mass Spectrom. 1978, 13, 39. [6] J.M. Miller, T.R.B. Jones, The mass spectra of azides and halides. In: Suppl. D, The Chemistry of Halides, Pseudo-Halides and Azides, Part 1; S. Patai, Z. Rappoport, Eds.; Wiley: Chichester, 1983; p 75. [7] R.A. Abramovitch, E.P. Kyba, E.F. Scriven, Mass spectrometry of aryl azides, J. Org. Chem. 1971, 36, 3796. [8] K.A. Jensen, G. Schroll, Mass spectra of cyanates, isocyanates, and related compounds. In: The Chemistry of Cyanates and Their Thio Derivatives, Part 1; S. Patai, Ed.; Wiley: Chichester, 1977, p 273.



8.10 Sulfur Compounds

371

8.10 Sulfur Compounds [1] 8.10.1 Thiols

C

Aliphatic Thiols [2]

Fragmentation: Elimination of H2S (Δm 34; or SH, Δm 33, from secondary thiols) C C followed by loss of alkenes; consecutive losses of ethylene from unbranched thiols. Cleavage of the α,β-C–C bond (next to the SH group) leads to CH2SH+ (m/z 47). Note that this fragment also occurs in secondary and tertiary thiols. The S atom is C C poorer than N, but better than O, at stabilizing such a fragment. Cleavage at the next C–C bonds leads to signals at m/z 61, 75, and 89. In secondary and tertiary thiols, prominent fragments are formed by loss of the largest α-alkyl group. Ion series: Dominant alkenyl fragments (CnH2n-1, m/z 41, 55, 69, …) and smaller aliphatic fragments (CnH2n+1, m/z 43, 57, 71, …). Sulfur-containing aliphatic fragments: CnH2n+1S (m/z 47, 61, 75, 89, …). Often significant sulfur-indicating fragments: HS+, H2S+·, H3S+, and CHS+ (m/z 33, 34, 35, and 45). Intensities: More intensive peaks in the lower mass range, mostly of the alkene type. Characteristic local maxima from S-containing fragments, CnH2n+1S (m/z 47, 61, 75, 89, …). In n-alkyl thiols, the intensity of the signal at m/z 61 is roughly half N that of m/z 47; the signal at m/z 89 is more intensive than that at m/z 75, presumably because it is stabilized by cyclization. Molecular ion: Relatively strong except for higher tertiary thiols. Characteristic Hal 34S isotope peak at [M+2]+· and [frag+2] for S-containing fragments (4.5% per S atom). Aromatic Thiols [2]

O

N Fragmentation: CS elimination from M+· and [M-1]+, yielding [M-44]+· and + + + · · [M‑45] . HS elimination from M to give [M-33] . Ion series: HCS+ (m/z 45) is characteristic besides the aromatic fragments, CnHn and CnHn±1 (m/z 39, 51–53, 63–65, 75–77, …). S Intensities: Intensive peaks in the higher mass range. Molecular ion: Usually dominating; base peak in thiophenol. [M-1]+ is usually strong. Characteristic 34S isotope peak at [M+2]+· and [frag+2] for S-containing C X fragments (4.5% per S atom). 8.10.2 Sulfides and Disulfides Aliphatic Sulfides [1]

P Si Natural Products

Fragmentation: Loss of alkyl radicals by cleavage of the C–C bond next to S (the largest group being lost preferably) and of the C–S bond, followed by alkene and Solvents H2S elimination. Alkene elimination from M+· to form the corresponding thiol ions. + · · In contrast to thiols and cyclic sulfides, no H2S or HS elimination from M .

372

8 Mass Spectrometry +. alk–SH

C C

C

R + C R R

alk

C

C

– alk-S

+. S

R

+.

.

alk

R

S

– R

C R R

– R

.

–

. CR

alk

+ S

.

+ alk–S=CR 2 3

– alkene

+ H S=CR 2

alk–S +

– alkene

H

+ S

m/z 61

In general, the H rearrangements are nonspecific. The transfer of secondary H predominates over that of primary H. Ion series: Sulfur-containing aliphatic fragments, CnH2n+1S (m/z 47, 61, 75, 89, …). The hydrocarbon fragments may dominate in long-chain sulfides. Intensities: Intensive peaks in the lower mass range. Characteristic local maxima from S-containing fragments, CnH2n+1S (m/z 47, 61, 75, 89, …). Molecular ion: Usually strong. Characteristic 34S isotope peak at [M+2]+· and [frag+2] for S-containing fragments (4.5% per S atom). Alkyl Vinyl Sulfides

N

Hal O N

Fragmentation: Loss of alkyl radicals (Δm 15, 29, 43, …). Elimination of thioethanol (Δm 62) after triple H rearrangement. Dominant m/z 60 (CH3CH=S+·) accompanied by m/z 61 (CH3CH2S+). Ion series: Sulfur-containing unsaturated aliphatic fragments, CnH2n-1S (m/z 45, 59, 73, …). Unsaturated hydrocarbon ions, CnH2n (m/z 42, 56, 70, …) and CnH2n-2 (m/z 40, 54, 68, …) Intensities: Intensive peaks evenly distributed over the whole mass range. Molecular ion: Of medium intensity. Characteristic 34S isotope peak at [M+2]+· and [frag+2] for S-containing fragments (4.5% per S atom). Cyclic Sulfides

S C

– alkene

X

P Si Natural Products Solvents

Fragmentation: Primary cleavage of the C–C bond next to S, followed by rearrangements and elimination of CH3· (base peak for tetrahydrothiapyrane) and C2H5·. In tetrahydrothiophene, [M-1]+ is also significant. HS·, H2S, and C2H4 elimination from M+·. Ion series: Sulfur-containing aliphatic fragments with one degree of unsaturation, CnH2n-1S (m/z 45, 59, 73, 87, 101, …), m/z 87 being of special dominance. Intensities: Overall distribution of peaks maximizing in the low mass range due to S-containing fragments, CnH2n-1S (m/z 45, 59, 73, 87, …). Molecular ion: Very strong. Characteristic 34S isotope peak at [M+2]+· and [frag+2] for S-containing fragments (4.5% per S atom). Aromatic Sulfides [2]

Fragmentation: Loss of CS (Δm 44) and of HS· (Δm 33) from M+·. Ion series: HCS+ (m/z 45) is characteristic besides the aromatic fragments, CnHn and CnHn±1 (m/z 39, 51–53, 63–65, 75–77, …).



8.10 Sulfur Compounds

373

Intensities: Intensive peaks mainly in the higher mass range. Molecular ion: Strong. Characteristic 34S isotope peak at [M+2]+· (4.5% relative to M+· per S atom) and [frag+2] for S-containing fragments.

C

Disulfides Fragmentation: Loss of RSS·, leading to alkyl cations and alkene elimination to C give RSSH+·. Cleavage of the S–S bond with or without H rearrangements, leading to RS+, [RS - H]+·, and [RS - 2H]+. Loss of one or two S with or without H atoms is a common process in cyclic, unsaturated, and aromatic disulfides. C Ion series: In saturated aliphatic disulfides, H2S2 and its alkyl homologues are characteristic (m/z 66, 80, 94, …). Intensities: Variable. Molecular ion: Usually strong. Characteristic 34S isotope peak at [M+2]+· and [frag+2] for S-containing fragments (4.5% per S atom).

C C

8.10.3 Sulfoxides and Sulfones

N

Aliphatic Sulfoxides [4,5] Fragmentation: Most fragments are produced after rearrangement with non-specific H transfer to the O atom and subsequent OH· elimination to yield [M-17]+ or alkene elimination to [M-alkene]+·, followed by OH·, SOH· (giving alk+ ions), or alk· elimination (yielding CH2=S–OH+, m/z 63). R1

R1

O S

OH S +

+.

H R2

.

OH

R1

SH +

– CH 2 =CHR 2 R2 + R-CH 2 m/z 29, 43, 57

R –

1

. SO H

– OH

.

OH

R2

+.

– OH

S

– R

.

.

Hal O

. R1

R1

S +

S

N

R2 +

+ CH 2 =S-O H m/z 63

S C

X

Ion series: Characteristic ion at m/z 63 (CH2=S–OH+) as well as alkyl and alkenyl fragments, CnH2n+1 (29, 43, 57, 71, …) and CnH2n-1 (27, 41, 55, 69, …). P Si Intensities: Intensive peaks evenly distributed over the whole mass range. Molecular ion: Of medium intensity. Characteristic 34S isotope peak at [M+2]+· and Natural [frag+2] for S-containing fragments (4.5% per S atom). Products

Solvents

374

8 Mass Spectrometry

Alkyl Aryl and Diaryl Sulfoxides [4,5]

C C

C

C

C

Fragmentation: Most fragments of methyl aryl sulfoxides are produced, after rearrangement to CH3S–O–ar+·, by elimination of CH2S (yielding [M-46]+·, a phenol), of CO (to [M-28]+·), and of CH3· (to [M-15]+). The latter ion loses CO to give the thiapyranyl cation (m/z 97 if ar is phenyl). S

O

+.

– CH 2 S

.

OH

m /z 112

N

Hal O

C

S

[M -16] +

P Si

+.

S+

+.

S

– SO

.

O

– PhS

[M -29] +

S

.

– CS

. +

+. [M -48] +

+

– PhO

.

+.

S

X

– CO

m /z 97

+.

O

–O

S

[M -15] + m/z 125

3

The skeletal rearrangement is not relevant for the fragmentation of higher alkyl aryl sulfoxides. Here, direct cleavage of the C–S bonds and McLafferty rearrangements dominate. For diaryl sulfoxides, elimination of SO (to give [M-48]+·) as well as of O, OH·, and CHO· (yielding [M-16]+·, [M-17]+, and [M-29]+, respectively). After rearrangement to sulfenates, cleavage of the S–O bond to produce ar–S+ and ar–O+ ions, which further lose CS and CO, respectively, to give C5H5+ (m/z 65).

– CH O

N

. CH

S +.

– CO [M -28] +

–

O

O

– CO

C 5H 5 + m/z 65

.

Ion series: Besides the ions described under Fragmentation, mainly fragments of the aromatic type, i.e., CnHn and CnHn±1 (m/z 39, 51–53, 63–65, 75–77, …), as well as O- and S-containing ions. Intensities: Intensive peaks mainly in the high mass range. Molecular ion: Very strong. Characteristic 34S isotope peak at [M+2]+· and [frag+2] for S-containing fragments (4.5% per S atom). Aliphatic Sulfones [4,5]

Natural Products Fragmentation: Fragmentation of the S–C bond with the charge remaining on either Solvents

side. Single and double H rearrangements to give RS(O)OH+· and RS(OH)2+. The probability of the double H rearrangement increases with increasing chain length. If one of the substituents is unsaturated, rearrangement to RS(O)O–alkene followed by cleavage of the S–O bond yields the ion RSO+.



8.10 Sulfur Compounds

375

Ion series: Dominating aliphatic fragments, CnH2n+1 (m/z 29, 43, 57, …) and CnH2n-1 (m/z 27, 41, 55, …). Usually, one significant fragment corresponding to alk–S(O)OH+· (from the series of m/z 80, 94, 108, …) or alk–S(OH)2+ (from the C series of m/z 81, 95, 109, …) can be observed. Intensities: Intensive peaks mainly of aliphatic fragments in the lower mass range. Molecular ion: Weak. Characteristic 34S isotope peak at [M+2]+· and [frag+2] for S-containing fragments (4.5% per S atom). C C C 4H 9

S

O

+.

O

OH m/z 122

– CH 2 =CH Et

+ OH S OH

.

C 4H 9

– C4H7

C 4H 9

O

OH S+

O

S

C 4H 9 C4 H 9 m/z 178

m/z 123 (70% )

– C 4 H 9 SO 2

C4H9+ m/z 57 (100% )

.

– OH

.

C H +.

.

+ O C 4H 9 S m/z 161

– C2H5

– C 4H 9

C4H9

.

C 4 H 9 SO 2 m/z 121

.

+

C

C

+ O S

O

m/z 149

Cyclic Sulfones [4] Fragmentation: Dominant elimination of SO2 (Δm 64, followed by loss of CH3·), HSO2· (Δm 65, followed by loss of C2H4), or CH2SO2 (Δm 78). Weak signal at [M-17]+ due to OH· elimination. Ion series: Mainly unsaturated hydrocarbon fragments, CnH2n-1 (m/z 27, 41, 55, …). Intensities: Intensive peaks in the lower mass range. Molecular ion: Moderate. Characteristic 34S isotope peak at [M+2]+· and [frag+2] for S-containing fragments (4.5% per S atom).

N

Hal O N S

Alkyl Aryl Sulfones [4] Fragmentation: Isomerization of M+· to ar–OS(=O)alk and formation of the phenoxy ion or the phenol radical cation with H rearrangement. The migration of the aryl group depends on the type of substituents. It is facilitated by electron donators and hindered by acceptors. Mainly in substituted or unsaturated alkyl derivatives also isomerization to ar–S(=O)O–alk(ene) and formation of ar–S=O+ (m/z 125 if ar is phenyl). Single and double H rearrangements to give ar–S(=O)OH+· and ar–S(OH)2+. The probability of the double H rearrangement increases with increasing chain length. In some derivatives, SO2 elimination from M+· dominates. Substituents X of the alkyl group may migrate to the aryl group to yield X–ar–S=O+ ions. Ion series: Aromatic hydrocarbon fragments, CnHn and CnHn±1 (m/z 39, 51–53, 63–65, 75–77, ...), as well as S- and O-containing aromatic fragments at higher masses. Intensities: Intensive peaks mainly in the higher mass range. Molecular ion: Strong. Characteristic 34S isotope peak at [M+2]+· and [frag+2] for S-containing fragments (4.5% per S atom).

C

X

P Si Natural Products Solvents

376

8 Mass Spectrometry

Diaryl Sulfones [4,5]

C C

C

C

C

Fragmentation: Predominant aromatic fragments of the type ar–O+ and ar–SO+ (m/z 125 if ar is phenyl), formed after migration of one of the aryl groups. The ar–SO2+ ion is unimportant; ar+ is intensive. Small signals due to SO2, SO2H·, and SO2H2 eliminations (Δm 64, 65, and 66, respectively). With alkyl substituents in ortho position, [M - OH]+ and [M - H2O]+· are formed, upon which SO elimination follows. Ion series: Aromatic fragments, CnHn and CnHn±1 (m/z 39, 51–53, 63–65, 75– 77, …) and the S- and O-containing aromatic fragments at higher masses. Usually, ar–SO+ (m/z 125 if ar is phenyl) is very strong. Intensities: Intensive peaks mainly in the higher mass range. Molecular ion: Strong. Characteristic 34S isotope peak at [M+2]+· and [frag+2] for S-containing fragments (4.5% per S atom). 8.10.4 Sulfonic Acids and Their Esters and Amides Aromatic Sulfonic Acids [6]

N

Hal O N S C

Fragmentation: The most prominent fragment, [M - HSO3]+ (Δm 81), is formed in a two-step process. In the first step, OH· elimination leads to a weak fragment ion [M - OH]+ (Δm 17). If an alkyl group is present in ortho position, [M - H2SO3]+· (Δm 82) is formed instead of [M-81]+. Other important fragments are [M - SO2]+· (Δm 64), [M - HSO2]+ (Δm 65), and [M - SO3]+· (Δm 80). Ion series: Aromatic hydrocarbon fragments, CnHn and CnHn±1 (m/z 39, 51–53, 63–65, 75–77, ...), and O-containing aromatic fragments at higher masses. Intensities: Intensive peaks mainly in the higher mass range. Molecular ion: Very strong. Characteristic 34S isotope peak at [M+2]+· and [frag+2] for S-containing fragments (4.5% per S atom). Alkylsulfonic Acid Esters [6]

X

P Si Natural Products Solvents

Fragmentation: Loss of alkyl by fragmentation of the C–O bond with concomitant double H rearrangement to form the protonated sulfonic acid ion (m/z 97 for methanesulfonates), which then loses water. Loss of the alkoxyl residue (fragmentation of the S–O bond). Formation of an alkene ion from the alkyl ester group by a McLafferty-type rearrangement. In aryl esters, the phenoxy ion and the phenol radical cations dominate the spectrum. Ion series: Besides RSO3H2+ and RSO2+ (m/z 97 and 79 for methanesulfonates), for aliphatic esters mainly alkene fragments. In aryl esters, aromatic fragments, CnHn and CnHn±1 (m/z 39, 51–53, 63–65, 75–77, …), as well as O-containing aromatic fragments at higher masses. Intensities: Intensive peaks in the lower mass range. Molecular ion: Small or negligible signal for alkyl esters; intensive for aryl esters. Characteristic 34S isotope peak at [M+2]+· and [frag+2] for S-containing fragments (4.5% per S atom).



8.10 Sulfur Compounds

377

Arylsulfonic Acid Esters [6] Fragmentation: Dominating fragments resulting from cleavage of the S–O bond (leading to the ar–SO2+ ion), which loses SO2 (m/z 155 and 91 for p‑toluenesul- C fonates). In arylsulfonates with longer chains, double H rearrangement to give the protonated acid (m/z 173 for p-toluenesulfonates). Ion series: Aromatic hydrocarbon fragments, CnHn and CnHn±1 (m/z 39, 51–53, C C 63–65, 75–77, …). Intensities: Intensive peaks mainly in the higher mass range. Molecular ion: Medium or weak. Characteristic 34S isotope peak at [M+2]+· and C C [frag+2] for S-containing fragments (4.5% per S atom). Aromatic Sulfonamides [6] Fragmentation: In N-alkylamides, the C–C bond next to N is split preferably. In N-arylsulfonamides, besides [M - SO2]+· and [M - HSO2]+, the ions ar–SO2+ and ar'–NH+ are formed. . +.

+

O

S NH2

O

O

– NH 2

O

. +

SO 2

– SO 2

– SO NH

+.

S NH 2

– SO 2 +. NH 2

– SO 2

C5H6+

– HCN

OH

N

– CO

Hal

.

O

C 6 H 5 + (100% )

N

Ion series: Typical for the tosyl group are ions at m/z 155, 91, and 65. Molecular ion: In arylsulfonamides, M+· is dominant. Characteristic 34S isotope peak at [M+2]+· and [frag+2] for S-containing fragments (4.5% per S atom). 8.10.5 Thiocarboxylic Acid Esters [7] In contrast to esters, the major fragmentation process is elimination of the alkyl radical from the thiol site. Ethylene sulfide is eliminated from thioesters with longer alkyl chains. Aromatic dithiocarboxylic acid esters usually fragment in two steps to R the aryl cation. +. +. O

R

O

alk

S

– alk

.

– S

R

S

– SR

. R

O + [M –60] +

R

.

+ C m/z 121

. S

C

X

P Si Natural Products

SR

S

R

O +

S

+.

S

– CS

C6H5+

Solvents

378

8 Mass Spectrometry

8.10.6 References

C C

C

C

C

N

Hal O N S C

X

P Si Natural Products Solvents

[1] C.C. van de Sande, The mass spectra of ethers and sulphides. In: Suppl. E, The Chemistry of Ethers, Crown Ethers, Hydroxyl Groups and Their Sulphur Analogues, Part 1; S. Patai, Ed.; Wiley: Chichester, 1980; p 299. [2] C. Lifshitz, Z.V. Zaretskii, The mass spectra of thiols. In: The Chemistry of the Thiol Group, Part 1; S. Patai, Ed.; Wiley: London, 1974; p 325. [3] Q.N. Porter, Mass Spectrometry of Heterocyclic Compounds, 2nd ed.; Wiley: New York, 1985. [4] K. Pihlaja, Mass spectra of sulfoxides and sulfones. In: The Chemistry of Sulphones and Sulphoxides; S. Patai, Z. Rappoport, C.G. Stirling, Eds.; Wiley: Chichester, 1988; p 125. [5] R.A. Khmel'nitskii, Y.A. Efremov, Rearrangements in sulphoxides and sulphones induced by electron impact, Russ. Chem. Rev. 1977, 46, 46. [6] S. Fornarini, Mass spectrometry of sulfonic acids and their derivatives; In: The Chemistry of Sulphonic Acids, Esters, and their Derivatives; S. Patai, Z. Rappoport, Eds.; Wiley: Chichester, 1991; p. 73. [7] K.B. Tomer, C. Djerassi, Mass spectrometry in structural and stereochemical problems—CCXXV: Sulfur migration in the [M–C2H4]+· ion of S-ethyl thiobenzoate, Org. Mass Spectrom. 1973, 7, 771.



8.11 Carbonyl Compounds

379

8.11 Carbonyl Compounds [1–4] 8.11.1 Aldehydes

C

Aliphatic Aldehydes [5]

Fragmentation: Cleavage of the bond next to CO. The fragmentation of the hydro- C C carbon chain is similar to that in corresponding alkanes. McLafferty rearrangement with localization of the charge on either side, giving rise to CnH2n+· (m/z 28, 42, 56, …) and, often less important, to CnH2nO+· ions (m/z 44, 58, 72, …). At least one C C product (often both) is significant. Elimination of water from the molecular ion to give [M-18]+·, occasionally very pronounced. Ion series: Dominating fragments of the series of CnH2n+1 and CnH2n‑1O (in both cases: m/z 29, 43, 57, …). Weaker signals of the series CnH2n-1 (m/z 41, 55, 69, …) and rearrangement products, CnH2n (m/z 28, 42, 56, …). Intensities: Intensive peaks concentrated in the lower mass range. Local even-mass maxima from McLafferty-type reactions ([M-44]+· when the aldehyde is not substituted in α-position). Molecular ion: Only strong for molecules of low molecular weight; very weak for Cn > 9. [M-1]+ may be more relevant than M+·. N Unsaturated Aliphatic Aldehydes Fragmentation: Cleavage of the bond next to CO, leading to [M-1]+ (more significant than in saturated aldehydes), [M-29]+, and m/z 29. No McLafferty rearrangement occurs if the γ-hydrogen atom is attached to a double-bonded carbon or if there is a double bond in α,β-position. Ion series: Fragments of the series of CnH2n-1 and CnH2n-3O (in both cases, m/z 41, 55, 69, …). Molecular ion: Stronger than in saturated aldehydes. Usually, [M-1]+ is relevant. Aromatic Aldehydes

Hal O N S

Fragmentation: Characteristic H· loss to yield the corresponding benzoyl ion, [M‑1]+, followed by decarbonylation to a phenyl ion, [M-1-28]+, of lower intensity. C X To a small extent also decarbonylation of the molecular ion, leading to [M-28]+·. Weak signal at m/z 29 (CHO+). Ion series: Aromatic fragments corresponding to CnHn and CnHn±1 (m/z 39, 51–53, P Si 63–65, 75–77, …). Intensities: Intensive peaks predominantly in the molecular ion region. Natural Molecular ion: Usually prominent. [M-1]+ is strong. Products

Solvents

380

8 Mass Spectrometry

8.11.2 Ketones Aliphatic Ketones

C C

C

C

C

N

Hal

Unsaturated Ketones Fragmentation: Cleavage of the bond next to CO, more favorably on the saturated side, is the most important primary fragmentation. The acyl ion then loses CO. The McLafferty rearrangement occurs neither when the unsaturated substituents are in α,β-position nor when the only available γ-hydrogen atom is attached to a doublebonded carbon. Molecular ion: Relatively abundant.

O N S C

Fragmentation: Cleavage of the bond next to CO is the most important primary fragmentation. The charge can remain on either side. The acyl ions then lose CO. McLafferty rearrangement giving rise to CnH2nO+· ions (m/z 58, 72, 86, …). Consecutive rearrangements occur if both alkyl chains contain a γ-H atom. Ketoenol tautomerism of the first rearrangement product is not a prerequisite for the second rearrangement to occur. Oxygen is sometimes indicated by weak signals at [M-18]+· and m/z 31, 45, 59. Fragmentation of the hydrocarbon chain similar to that in the corresponding alkanes. Ion series: Dominating fragments of the series CnH2n+1 and CnH2n-1O (in both cases m/z 29, 43, 57, …, but often distinguishable by the intensity of the 13C isotope signal), with maxima due to cleavage at the CO group to give acyl ions and their decarbonylation products. Weaker signals in the series CnH2n-1 (m/z 41, 55, 69, …). Even-mass maxima, CnH2nO (m/z 58, 72, 86, …), due to alkene elimination (McLafferty rearrangement). Usually, m/z 43 (CH3CO+) is strong if an unsubstituted α-CH2 group is present. Intensities: Intensive peaks mainly in the lower mass range. Molecular ion: Relatively abundant, weak in long-chain and branched ketones.

Cyclic Ketones

X

Fragmentation: Major primary fragmentation by bond cleavage next to carbonyl, followed by loss of alkyl residue. R1

P Si

O +. H

R1 .

R2

O+

R2

.

– CH 2 CH 2 CH 2 R

2

R1

O+ m /z 55 (for R 1 : H)

Natural Prominent McLafferty-type elimination of larger alkyl groups in position 2 or 6 as alkenes. This rearrangement is very favorable; even aromatically bonded H atoms Products can rearrange. For cyclohexanones, a consecutive retro-Diels–Alder reaction can Solvents

occur:

+. H O

R – CH 2 =CHR

+. OH

+. OH

– CH 2 =CH 2 m /z 98

m/z 70



8.11 Carbonyl Compounds

381

Oxygen is sometimes indicated by a weak signal at [M-18]+·. Ion series: Alkene fragments of the type of CnH2n-1 or CnH2n-3O (for both: m/z 41, 55, 69, …) with maxima due to alkyl loss after ring opening next to the carbonyl group and H transfer. Prominent even-mass maxima by elimination of substituents C at position 2 or 6 as alkenes via sterically favored McLafferty rearrangements. Intensities: Overall more intensive peaks in the lower mass range or even distribution of major peaks over the whole mass range. Local maxima from major fragmentation C C pathway. Molecular ion: Abundant. Aromatic Ketones Fragmentation: Dominant α-cleavage to give the benzoyl ion, followed by decarbonylation to a phenyl ion of lower intensity. α-Cleavage in acetophenone also produces the acetyl cation (m/z 43). Even-mass maxima due to alkene elimination via McLafferty rearrangement. CO elimination from diaryl ketones through skeletal rearrangements. Ion series: Aromatic fragments corresponding to CnHn and CnHn±1 (m/z 39, 51–53, 63–65, 75–77, …). Intensities: Intensive peaks predominantly in the molecular ion region. Molecular ion: Strong. 8.11.3 Carboxylic Acids Aliphatic Carboxylic Acids

C

C

N

Hal O

Fragmentation: Cleavage of the C–CO bond leading to m/z 45 and to [M‑45]+. Loss N of OH· leading to [M-17]+; may be followed by decarbonylation. Cleavage of the + γ-bond (relative to CO) leads to CH2CH2COOH (m/z 73) if there is no branching on the α- and β-C atoms. Loss of H· (not the carboxylic one) gives [M-1]+. Water elimination to give [M-18]+· if the alkyl group consists of at least 4 C atoms; may S be followed by decarbonylation. McLafferty rearrangement to m/z 60 (acetic acid) if there is no α-substituent. Ion series: Saturated and unsaturated alkyl ions mainly in the lower mass range C X (CnH2n+1 and CnH2n-1, m/z 29, 43, 57, … and 27, 41, 55, …). With long-chain aliphatic acids, CnH2n-1O2 series (m/z 59, 73, 87, …), exhibiting maxima for n = 3, 7, 11, 15, … (m/z 73, 129, 185, 241, …). Even-mass maxima, CnH2nO2 (m/z 60, 74, P Si 88, …), due to McLafferty rearrangements. Intensities: Intensive peaks due to the above mentioned ions. Molecular ion: Generally detectable. Easily protonated to [M+H]+. Natural

Products

Aromatic Carboxylic Acids

Fragmentation: Pronounced loss of OH·, leading to [M-17]+ and followed by Solvents decarbonylation (Δm 28) to a phenyl ion of lower intensity. Water elimination to

382

8 Mass Spectrometry

[M-18]+· if a H-bearing ortho-substituent is present. Some acids decarboxylate (Δm 44). Loss of CO (Δm 28) from M+·. +.

O

C

– H 2O

OH

C

C

C

C

X

C

H

O

+. X: CH 2 , m /z 118 X: N H, m /z 119 X: O , m/z 120

X

Ion series: Aromatic hydrocarbon fragments, CnHn and CnHn±1 (m/z 39, 51–53, 63–65, 75–77, …). Intensities: Intensive peaks predominantly in the molecular ion region. Molecular ion: Strong. 8.11.4 Carboxylic Acid Anhydrides Fragmentation: In the case of linear anhydrides, abundant acyl ions due to cleavage next to carbonyl group. For cyclic anhydrides, maxima due to decarboxylation (Δm 44), followed by decarbonylation. Molecular ion: Weak or absent (especially in linear aliphatic anhydrides), easily protonated to [M+H]+. Relatively strong for phthalic anhydrides.

N

Hal O

Esters of Aliphatic Carboxylic Acids

N S C

8.11.5 Esters and Lactones

X

Fragmentation: Dominant fragmentation of the bonds next to the carbonyl C, leading to alk-CO+ (m/z 43, 57, 71, …; decreasing intensity with increasing length of the alkyl chain) and followed by decarbonylation, as well as fragmentation to COOR+ (m/z 59, 73, 87, …) and to alk+ (m/z 15, 29, 43, …). Alcohol elimination to give CnH2n-2O (m/z 42, 56, 70, …), followed by decarbonylation (Δm 28) or ketene elimination (Δm 42). Alkene elimination from the acid side via McLafferty rearrangements, leading to CnH2nO2 (m/z 60, 74, 88, …). The larger alkyl group participates in the rearrangement if several γ-H atoms are available. In the following example, the alternative process leading to [M-C2H4]+· is negligible: H

P Si

+.

O O CH 3

– C 5 H 10

+. OH

.

O CH 3 [M –70] +

.

– CH 3

+ O O CH 3

Natural Nonspecific H rearrangements on the alcohol side (from M+· or the McLafferty Products product) lead to CnH2nO2 and to the corresponding alkene, CnH2n (m/z 28, 42, Solvents

56, …). In methyl esters of long chain acids, the ions [(CH2)2+4nCOOCH3]+ (m/z 87, 143, 199, …) correspond to maxima. For esters of higher alcohols (Cn   ≥  3), double H rearrangement to the protonated acid, CnH2n+1CO2H2+ (m/z 61, 75, 89,  …). α-Substituted esters may lose the substituent and then CO (Δm 28) via alkoxyl rearrangement. Analogously, β-substituted esters may eliminate ketene (Δm 42).



8.11 Carbonyl Compounds

383

Besides usual ester reactions, specific rearrangements can be observed in formates. H O

+.

R2

O

.

– CO , – R 2

H

R1

+ O

H R1

(m/z 31 for R 1 : H )

C

Ion series: CnH2n+1 (m/z 29, 43, 57, …) for the alkyl groups at the ester oxygen (except for methyl esters). CnH2n-1 (m/z 27, 41, 55, …). CnH2n-1O2 (m/z 59, 73, C 87, ...), exhibiting maxima for n = 4, 8, 12, … (m/z 87, 143, 199, …) in the case of methyl esters of long-chain acids. Even-mass maxima for CnH2nO2 (m/z 60, 74, 88, …) due to alkene elimination via McLafferty rearrangements on both sides of C the carboxyl group. CnH2n (m/z 28, 42, 56, …) as H rearrangement product from the alcohol side. Intensities: Intensive peaks due to the above mentioned ions in the lower mass range. Molecular ion: Often of low abundance. Easily protonated to [M+H]+.

C C

Esters of Unsaturated Carboxylic Acids α,β-Unsaturated esters: Loss of alk–O· followed by CO elimination is the dominant fragmentation path. Also, loss of the δ-substituent yields a 6-membered oxonium ring: +. O CH 3

O

–R

O CH 3

.

O +

R

N

Hal

m/z 113

Significant difference between Z and E isomers of long-chain α,β-unsaturated O esters: Single H rearrangement occurs with Z esters, and double H rearrangements (leading to protonated acids) have been found for E esters. β,γ-Unsaturated esters: Only slight qualitative, but significant quantitative differN ences have been observed as compared to α,β-unsaturated esters (e.g., less intensive signals for M+· of β,γ- than of α,β-unsaturated esters). γ,δ-Unsaturated esters: Loss of the alcohol chain as a radical, R·, followed by S ketene elimination. Aliphatic enol esters and aryl esters: Formation of alk–CO+ (m/z 43, 57, 71, …). Elimination of a ketene to give the enol or phenol radical cation. The rearrangement occurs prodominantly, but not exclusively, through a 4-membered transition state: C X O

R

H

+.

O

Esters of Aromatic Acids

+.

– RCH=C=O H

O

.

[M –42] + for R: H

P Si Natural Products

Fragmentation: Dominant loss of RO· to form the benzoyl ion, followed by decarbonylation (Δm 28) and further loss of acetylene (Δm 26). Ethyl esters also Solvents eliminate C2H4 (Δm 28) to give the acid radical cation, which then loses OH· to yield the benzoyl ion. In higher alkyl esters, besides the acid, the protonated

384

C C

C

C

C

8 Mass Spectrometry

acid is formed (double H rearrangement). In ortho-substituted aryl esters with an α-hydrogen atom on the substituent, an alcohol is eliminated from M+·. In the case of alkyl phthalates (other than dimethyl phthalate), alkenyl elimination from one ester group to give the protonated ester acid, followed by alkene elimination from the other ester group, and subsequent water elimination to the protonated anhydride ion, which forms the base peak at m/z 149. Ion series: Aromatic hydrocarbon fragments, CnHn and CnHn±1 (m/z 39, 51–53, 63–65, 75–77, …). Intensities: Prominent maximum at the mass of the related benzoyl ion and its decarbonylation product. Molecular ion: Usually strong. Lactones

N

Hal O N

8.11.6 Amides and Lactams

S C

Fragmentation: The most prominent reaction is the loss of substituents (or H·) at the O-bearing C atom, followed by decarbonylation (Δm 28), decarboxylation (Δm 44, mainly in smaller molecules), and ketene elimination (Δm 42). Decarboxylation of M+· is rarely significant. Competing reactions are several kinds of primary ring cleavages. Aromatic lactones show maxima due to two consecutive decarbonylations. Ion series: No specific ion series. The acetyl ion (m/z 43) is often an important fragment. Intensities: Maxima at the mass resulting from loss of substituents at the C atom next to oxygen. Otherwise, intensive peaks evenly distributed over the whole mass range. Molecular ion: Usually of low intensity and easily protonated to [M+H]+ in aliphatic lactones; abundant in the case of aromatic lactones.

Amides of Aliphatic Carboxylic Acids

X

P Si Natural Products Solvents

Fragmentation: Alkene elimination on the acid side via McLafferty reaction to yield the corresponding acetamide radical cation. Loss of alkenes on the amine side to give the ion of the desalkyl amide, often via double H rearrangement to the protonated desalkyl amide ion. Bond cleavage on both sides of the carbonyl group. Cleavage of the C–C bond attached to N, and the β,γ-C–C bond (relative to N): +.

O

R

N H

–R

O

.

H

– CH 2 C=O

+ N

∆m 42

H + N H

m/z 44

Cleavage of the bonds to the β-C (see scheme) and to the γ-C on the acid side. R

O

NH2

+.

–R

. O +

NH 2

Ion series: Even-mass fragments corresponding to CnH2nNO (m/z 44, 58, 72, …)



8.11 Carbonyl Compounds

385

produced by cleavage of the bond next to CO on the acid side. Odd-mass fragments (in secondary and tertiary amides), CnH2n-1O (m/z 43, 57, 71, …), produced by cleavage of the bond next to CO on the amine side. Intensities: Overall peak distribution maximizing in the low mass range. Local maxima from McLafferty and from γ-cleavage products. Molecular ion: Significant. Strong tendency to protonate to [M+H]+.

C C

C

Fragmentation: Maxima due to amide bond cleavage yielding the benzoyl ion, C followed by decarbonylation (Δm 28). Ion series: Aromatic fragments corresponding to CnHn and CnHn±1 (m/z 39, 51–53, 63–65, 75–77, …). Intensities: Intensive peaks predominantly in the molecular ion region. Molecular ion: Abundant. [M-H]+ is significant in N,N-disubstituted anilides, weaker in monosubstituted derivatives, and absent from the spectrum of benzamide. It is formed exclusively by loss of ortho-hydrogens of the aromatic ring.

C

Amides of Aromatic Carboxylic Acids

Anilides Formanilides: Loss of CO (Δm 28) to give the aniline radical cation and consecutive HCN elimination (Δm 27). Acetanilides: Ketene elimination gives the aniline radical cation (often base peak), which can eliminate HCN (Δm 27), and formation of the acetyl cation (m/z 43). Trichloroacetanilides: Dominant loss of CCl3· (Δm 117). Pivalanilides: Besides reactions analogous to those of acetanilides (Δm 84, formation of the aniline radical cation), also formation of the tert-butylbenzene radical cation through elimination of HNCO (Δm 43). Lactams

N

Hal O N

Fragmentation: Cleavage of the C–C bond at the N-bearing C atom. Cleavage of S the CO–N bond, followed by loss of CO (Δm 28) or by further cleavage of the C–C bond next to N, giving an iminium ion. In 2-pyrrolidone and 2-piperidone, the signal at m/z 30 ([CH2=NH2]+) is strong. The base peak of 2-pyridone is formed by C X CO elimination (Δm 28). 2-Pyrrolidone: . CH CH 2

H N+ H

O

+.

.

N H

N

O

. – CH O

– HN CO

.

+ CH 2 =N H 2 m /z 30

C 3 H 6 + m /z 42 –H

.

C 3 H 5 + m/z 41

P Si

2

N+ H

.C N H

C O+

H N C O +.

O +

– C2H 5 O

+.

m/z 56

.

CH 2 =N=C=O +

Natural Products Solvents

386

8 Mass Spectrometry

2-Piperidone: +.

C C

.

H2C H

C

C

N+ H

+ CH 2 =NH 2 m/z 30

N H

O

– C 2H 4

C

.N

C

– CH 2 NH

m/z 55

O

m/z 71

C O+

+ C N H

O

N H

.

– C 2H 5

+.

+.

O+ H m/z 99

+ C O

N H

m/z 99

m/z 99 H

CH 2

O

.

– CHO

O

.

+ N H

m/z 70

Molecular ion: Often observable; more abundant than for the corresponding lactones.

N

8.11.7 Imides

Hal

Saturated acyclic imides: Consecutive CO (Δm 28) and alkoxy elimination:

O

N

– CO

+.

O

O

– CH 3 O

.

+ C N

m /z 56

N

Ketene elimination:

N

O

H

+.

N

S C

+.

O

X

P Si Natural Products Solvents

– CH 2 CO

O

O

+.

H

– CH 3

.

+ OH C N m/z 58

N

If the N-substituent chain is sufficiently long, cleavage of the C–C bonds next to N, with or without H rearrangement. Dibenzoylamine: Loss of CO to N-phenylbenzamide: +.

H N

O O

+.

– CO

H N

O

– C6 H 5N H

.

C

+O

m/z 105



8.11 Carbonyl Compounds

387

Cyclic imides: The spectra of saturated cyclic imides are almost identical to those of the corresponding diketones. Loss of HNCO (Δm 43) from succinimide, followed by CO elimination (Δm 28). Aroyl migration and loss of CO2 from aromatic cyclic imides. O

N R O

+.

O

O

+.

– CO 2

[M –44] +

.

C C

C

C

C

NR

8.11.8 References [1] J.H. Bowie, Mass spectrometry of carbonyl compounds. In: The Chemistry of the Carbonyl Group, Vol. 2; J. Zabicky, Ed.; Interscience: London, 1970; p 277. [2] S.W. Tam, Mass spectra of acid derivatives. In: Suppl. B, The Chemistry of Acid Derivatives, Part 1; S. Patai, Ed.; Wiley: Chichester, 1979; p 121. [3] D.G.I. Kingston, J.T. Bursey, M.M. Bursey, Intramolecular hydrogen transfer in mass spectra. II. The McLafferty rearrangement and related reactions, Chem. Rev. 1974, 74, 215. [4] D.G.I. Kingston, B.W. Hobrock, M.M.Bursey, J.T. Bursey, Intramolecular hydrogen transfer in mass spectra. III. Rearrangements involving the loss of small neutral molecules, Chem. Rev. 1975, 75, 693. [5] A.G. Harrison, High-resolution mass spectra of aliphatic aldehydes, Org. Mass Spectrom. 1970, 3, 549.

N

Hal O N S C

X

P Si Natural Products Solvents

388

8 Mass Spectrometry

8.12 Miscellaneous Compounds 8.12.1 Trialkylsilyl Ethers [1,2]

C C

C

C

C

Fragmentation: Loss of alkyl attached to Si (preferential loss of larger groups). Cleavage of the C–C bond adjacent to O, followed by alkene elimination. Loss of alkoxyl, followed by alkene eliminations. Elimination of trialkylsilanol. The R2Si–OR' cation has the tendency to attack, in an electrophilic manner and even over long distances, free electron pairs and π-electron centers, causing the expulsion of neutral fragments from the interior of the molecule via a rearrangement: Br (CH 2 ) 10

+. O Si

.

– C(CH 3 ) 3 ∆m 57

– (CH 2 ) 10 O ∆m 156

Br Si +

Ion series: [CnH2n+3OSi]+ (m/z 75, 89, 103, 117, …). [CnH2n+3Si]+ (m/z 45, 59, 73, 87, …). Occasionally, maxima at even mass due to elimination of trialkylsilanol. Molecular ion: M+· often of low abundance or absent, easily protonated to [M+H]+. Typical isotope patterns owing to 28Si, 29Si, and 30Si (see Chapter 2.5.5).

N

8.12.2 Phosphorus Compounds

Hal

Fragmentation: Maxima due to alkenyl loss from M+· via double H rearrangement, followed by successive alkene eliminations down to protonated phosphoric acid (m/z 99). Ion series: PO+ (m/z 47), H2PO2+ (m/z 65), H2PO3+ (m/z 81), often as nonspecific P indicators. Molecular ion: M+· observable.

O N S C

Alkyl Phosphates [3]

Aliphatic Phosphines

X

P Si

Ion series: Maxima of the ion series of [CnH2n+3P]+ (m/z 48, 62, 76, 90, …) due to alkene eliminations. Molecular ion: M+· observable. Aromatic Phosphines and Phosphine Oxides Fragmentation: Maxima due to loss of an aryl group, followed by H2 elimination to

Natural yield the 9-phosphafluorenyl ion (m/z 183). Products Molecular ion: M+· abundant, easily losing H· to give [M-1]+. Solvents

+ P m/z 183



8.12 Miscellaneous Compounds

389

8.12.3 References [1] D.G.I. Kingston, B.W. Hobrock, M.M. Bursey, J.T. Bursey, Intramolecular hydrogen transfer in mass spectra. III. Rearrangements involving the loss of C small neutral molecules, Chem. Rev. 1975, 75, 693. [2] H. Schwarz, Positive and negative ion chemistry of silicon-containing molecules in the gas phase. In: The Chemistry of Organic Silicon Compounds, Part 1; S. C C Patai, Z. Rappoport, Eds.; Wiley: Chichester, 1989; p 445. [3] D.G.I. Kingston, J.T. Bursey, M.M. Bursey, Intramolecular hydrogen transfer in mass spectra. II. The McLafferty rearrangement and related reactions, Chem. C C Rev. 1974, 74, 215.

N

Hal O N S C

X

P Si Natural Products Solvents

8 Mass Spectrometry

390

8.13 Mass Spectra of Common Solvents and Matrix Compounds

C

8.13.1 Electron Impact Ionization Mass Spectra of Common Solvents

C

C

C

C

The label {50} indicates that the intensity scale ends at 50% relative intensity and is subdivided in 10% steps. In these cases, the height of the base peak has to be doubled to bring it to 100%. All spectra represent positive ions only. Water {50}

Methanol

18

Acetonitrile 31

41

15

Ethanol {50} 31

N

Hal

15

15

29

Tetrahydrofuran {50}

X

P Si Natural Products Solvents

28 15

Furan

42

39

43

15

62

Pentane

27

14

68

29

N,N-Dimethylformamide 18

72

60

27

31

29

S

43 15

Ethylene glycol {50} 60

15

Acetone {50}

45

45

43

N

C

Dimethyl ether

Acetic acid

O

14 26

57 72

44

73

15 28 58



8.14 Spectra of Solvents and References Methyl acetate {50}

Diethyl ether

74

59

63

12

26

56

84

27

69

27

39

71

Tetramethylsilane {50}

15

29

53

15

Diisopropyl ether {50}

41

84

61 70

N

35

Hal

1,4-Dioxane {50} 28

88

43

15

O

88

58

N S

29

91

C

60

90

15 27

39 51 65

Butyl acetate {50} 43

87 69

C

57

56

45

27

C

66

45

88

59

C

1,2-Dimethoxyethane {50} Toluene

73 43

C

Methylene chloride

43

86

42 56

28

69 84

57

43

64

84

18

Ethyl acetate {50}

15

15 29

14

79

15

Hexane

44 38

Benzene-d6 {50}

1-Hexene

41

29

74

52

52

C

32

Pyridine

Cyclohexane

15

59

15

78

15 26

76

45

Benzene {50}

39

Carbon disulfide {50}

31

43 15 28

391

102

15

28

P Si Natural Products

56

61 73

74

X

87 101

Solvents

8 Mass Spectrometry

392

Chloroform

83

C C

C

C

C

35

Chloroform-d

47 118

Trichloroethylene

12

25 35 47

35

95

130

119

82

35

82

94

Dibutyl phthalate [25] (frequent impurity due to its use as polymer plasticizer)

O

149

N

29 41 57 65 76 93 105 121

S C

82

47

166

129 35 47 59

119

Carbon tetrachloride

Tetrachloroethylene

Hal

47

60

N

84

168 182

203 223

278

Dioctyl phthalate (frequent impurity due to its use as polymer plasticizer) 149

X

P Si Natural Products Solvents

28 43

57

71

83 104 113 132 93

167

279

Heptacosafluorotributylamine (calibration reagent) 69

131 114 100 150 181 119 50 93

219

264 314

502 414 376 464 538 426

576

614



8.14 Spectra of Solvents and References

393

8.13.2 Spectra of Common FAB MS Matrix and Calibration Compounds Fast atom bombardment (FAB) mass spectra (MS) usually exhibit signals for the protonated or deprotonated molecular ions, [M±H]±, and protonated clusters, C [Mn+Xm±H]± (n, m = 0, 1, 2, …), of the sample and matrix molecules, X. Even traces of metal salts in the sample give rise to clusters of the type [Mn+Xm+metal cation]+. Na+ (23 u) and K+ (39 u) adducts are often found. The nature of the clusters is C C often revealed by the regular intervals at which their peaks occur in the spectra.

C

Calibration Compounds in Positive Ionization FAB Mass Spectra

C

Ultramark 1621 (erroneously also referred to as perfluoroalkyl phosphazine) 1390

20 0 1300 20

1400

654

0 100

1470

1570 1622

1500

1600

700 800 900 51 228 69 95 113 166 31 213 249

50 0

0

100

200

1700

1800

1078

978

866 878

766

1722

RO N OR RO P P OR R: CH2(CF2)nH n = 2, 4, 6, ... N N P RO OR 1922

1000 322 300

1190

1100

1200

442

542

400

500

1900

1290

1300

N

Hal O

600

Polyethylene glycol 600 (often used as internal reference for high resolution m/z determinations) 1.0

503 547

0.5

0.0 500 100

550 45

50

5.0

0

(Cs+,

2.5 0.0 500 100 50

0

0

50

132.9;

540.9

635

600

73

0

CsI

591

89

650 133

100

I–,

576.8

150

679

767

700 750 0.8 219 177 200

250

811 800

283 300

855 850

327

900 415

371 350

950

400

459 450

616.7

652.5 708.7 668.9 744.6 800.8 836.6 876.5

100

150

200

750 225.0

800

250

300

850

900

C

]+)

500

928.7 950

1000

392.7 448.9 277.1 317.0 356.8 409.0 484.8 350

400

450

S

1000

126.9) in glycerol (formation of [glycerolm-Hn+Csp+Iq

550 600 650 700 93.1 132.9 57.0 185.1 45.0 75.0 50

723

N

500

X

P Si Natural Products Solvents

8 Mass Spectrometry

394

Matrix Compounds in Positive Ionization FAB Mass Spectra 3-Nitrobenzyl alcohol (Mr 153.1)

C

2.0 1.0

C

C

C

C

0.0 500 100 50

0

596 613 550

600

77 39 51

89 107

50

100

0

766

650 700 136 154 150

750

800

850

5

289 307

200

250

300

900

350

950

1000

460

400

450

500

950

1000

Glycerol (Mr 92.1) 3.0 1.5 0.0 500 100 50

N

Hal O

0

0

Natural Products Solvents

100

650

150

700 185

200

829

750

800 277

10 250

921

850

900

369 300

350

461 400

450

500

541 600 650 700 750 800 850 91 217 181 325 73 109 45 57 165 199 239 279 307 131 23

50

P Si

600 93

737

1-Thioglycerol (Mr 108.2. Note m/z 23, Na+; 131, [M+Na]+; 239, [2M+Na]+. Similarly, small K+ impurities give signals at m/z 39, 147, 255)

0.0 500 100

X

75

50

3.0

S

645

550 45 57

6.0

N

C

0

553

550

0

50

100

150

200

250

300

350

900

950

1000

400

450

500

1,4,7,10,13,16-Hexaoxacyclooctadecane (18-crown-6, Mr 264.3. Also used as an additive; binds metal ions and reduces [M+metal ion]+ in favor of [M+H]+, which can be important for samples with exchangeable H+, such as for peptides [1]) 2.0

527

1.0 0.0 500 100 50

0

0

789 550 45 31 59 50

600 87

650 133

73 100

150

700 750 800 219 265 177 221 200

250

300

850

900

950

1000

350

400

450

500



8.14 Spectra of Solvents and References

395

2-Nitrophenyl octyl ether (Mr 251.3) 5.0 2.5

503 0.0 500 550 600 650 43 100 57 140 29 71 120 50 94 0 0 50 100 150

C

735 700

750

800

252 10 221 235

850

900

333 364

950

1000

471 486

200

250

300

350

400

450

500

650 700 150

750

800

850

900

950

1000

C

C

C

C

Triethanolamine (Mr 149.2) 1.0 0.5

597

0.0 500 100 50

0

550 30

0

45 56 74 50

600 118

132

100

194

150

4

200

267 281

250

307

448

300

400

Hal

Sulfolane (Mr 120.2) [2] 10

5

0 500 100 50

0

27 0

550 41 55 50

600

105

87

100

650 121 151 150

10

5

25

0

0

O

601 700 166

750 241 225

200

800

850

900

950

286 250

300

1000

350

400

450

500

690

608

550 600 650 700 750 80 43 80 55 93 29 120 148 176 69 204 50

100

150

200

250

N

481

Hexadecylpyridinium bromide (Mr 384.4; for [hexadecylpyridinium]+ m/z 304.3) in 2-nitrobenzyl alcohol

0 500 50

N

500

800 850 304

900

300

400

950

1000

500

S C

X

P Si Natural Products Solvents

8 Mass Spectrometry

396

Calibration Compounds in Negative Ionization FAB Mass Spectra Ultramark 1621 (erroneously also referred to as perfluoroalkyl phosphazine)

C C

C

C

1306

80 40

C

0 1300 80 40

124

0

1600

860 894 800

19

1606

1500

760

211

163

100

RO N OR RO P P OR R: CH2(CF2)nH n = 2, 4, 6, ... N N 1706 ROPOR

1700 1006

960

900 243

1000

200

1106

1806 1800

1100

1906 1900 1206 1294

1200

298

398

492 498

300

400

500

1300 592 600

Polyethylene glycol 600 (often used as internal reference for high resolution m/z determinations)

N

100

Hal O

501 545

50

KI

0

(K+,

100

S

50

39.1;

I–,

P Si Natural Products Solvents

633

0 500 100 50

0

100

550

150

50

721 700

193 200

624.5

600

650 126.9

59.0 91.0 0

677

765

809

750 237

800 281

250

853

897

850 325

300

900

369 350

941 950

400

100

150

754.5 700

750

790.4 800 292.8

198.9 226.9 256.9 200

250

319.0 300

450

]-)

920.4 850

350

1000

457

413

126.9) in glycerol (formation of [glycerolm-Hn+Kp+Iq 588.6

50

X

589

0 500 550 600 650 100 61 105 43 85 149 50 0

N

C

692 700

50

1506

1400

0 100 0

1406

500

956.2

900

950 1000 458.6 392.8 422.8 400

450

500



8.14 Spectra of Solvents and References

397

Matrix Compounds in Negative Ionization FAB Mass Spectra 3-Nitrobenzyl alcohol (Mr 153.1)

C

100 50

612

0 500 100

550

0

600

650 700 153 199 122 138 168

46

50

0

765

50

100

150

200

750

250

800

306

850

900

950

1000

459

352

300

350

400

450

500

650 700 750 800 50 183 275 30 10

850

900

950

1000

150

350

C

C

C

C

Glycerol (Mr 92.1) 50 25

551

0 500 100

550

50

0

643 600 91

59 71 0

50

100

735

200

250

300

367

N

459 400

450

500

2-Nitrophenyl octyl ether (Mr 251.3)

Hal O

100

50 502 518 0 500 550 100 46 25 50 0

0

50

600

650 138 122 153 93 108 100

150

700

200

750 800 251 266 235 297 250

300

850

900

950

N

1000

470 350

400

450

S

500

2-Nitrobenzyl alcohol solution of hexadecylpyridinium bromide (Mr 384.4; C enhances detectability and reduces metal ion adducts of sample [3])

P Si

100 50

845

0 500 100 50

0

X

25 0

550 79

600

650

700

750

800

850

900

950 462

1000

50

100

150

200

250

300

350

400

450

500

Natural Products Solvents

398

8 Mass Spectrometry

8.13.3 Spectra of Common MALDI MS Matrix Compounds

C C

C

C

C

Matrix-assisted laser desorption ionization (MALDI) mass spectra (MS) usually show signals for protonated or deprotonated molecular ions, [M±H]±, and protonated clusters, [Mn+Xm±H]± (n, m = 0, 1, 2, …), of the sample and matrix molecules, X. In positive ionization mass spectra, clusters of the type [Mn+Xm+metal cation]+ occur even if there are only traces of metal salts in the sample. Sodium (23 u) and potassium (39 u) ion adducts are often encountered. The nature of the clusters is revealed by the regular intervals at which their signals occur in the spectra [4]. Matrix Compounds in Positive Ionization MALDI Mass Spectra 3-Aminoquinoline (Mr 144.2) 145

NH2 N

289

N

0

Hal

50 100 150 200 250 300 350 400 450 500 550 600 650 700 750 800

α-Cyano-4-hydroxycinnamic acid (Mr 189.2; m/z 212, [M+Na]+) 102

O 0

CN

HO

379

50 100 150 200 250 300 350 400 450 500 550 600 650 700 750 800

2,5-Dihydroxybenzoic acid (Mr 154.1; m/z 177, [M+Na]+; m/z 193, [M+K]+)

S C

COOH

190 212

N

433

23 39

X

P Si Natural Products Solvents

0

137

HO

155

COOH OH

177 288 193 273

50 100 150 200 250 300 350 400 450 500 550 600 650 700 750 800

2,6-Dihydroxyacetophenone (Mr 152.1; m/z 175, [M+Na]+; m/z 191, [M+K]+; m/z 365, [2M+Na+K-H]+ ?) 153 23 39

0

175 191

HO

365

O OH

50 100 150 200 250 300 350 400 450 500 550 600 650 700 750 800



8.14 Spectra of Solvents and References

399

Dithranol (Mr 226.2) 227

OH OH OH

OH O

OH

211 195 177 0

50 100 150 200 250 300 350 400 450 500 550 600 650 700 750 800

Ferulic acid (4-hydroxy-4-methoxycinnamic acid; Mr 194.2) 177

O

195

C

C

C

C

COOH

HO

371 389 0

C

50 100 150 200 250 300 350 400 450 500 550 600 650 700 750 800

Sinapinic acid (3,5-dimethoxy-4-hydroxycinnamic acid; Mr 224.2; m/z 471, [2M+Na]+ ) 208 225 242

23 0

288

39

O

414

316

471

HO

640

N

COOH

Hal

O

O

50 100 150 200 250 300 350 400 450 500 550 600 650 700 750 800

N

Matrix Compounds in Negative Ionization MALDI Mass Spectra 3-Aminoquinoline (Mr 144.2) 143

0

153

295

N

437

50 100 150 200 250 300 350 400 450 500 550 600 650 700 750 800

α-Cyano-4-hydroxycinnamic acid (Mr 189.2; m/z 399, [2M+Na-2H]-) 188

COOH

HO

144 0

S

NH2

285

CN

290 333 377 399

50 100 150 200 250 300 350 400 450 500 550 600 650 700 750 800

C

X

P Si Natural Products Solvents

400

8 Mass Spectrometry

2,5-Dihydroxybenzoic acid (Mr 154.1) 153

C C

C

C

C

99 0

308

110

COOH OH

416

50 100 150 200 250 300 350 400 450 500 550 600 650 700 750 800

Dithranol (Mr 226.2)

225

OH OH OH

240

193 0

330

HO

387

OH O

465

OH

688

50 100 150 200 250 300 350 400 450 500 550 600 650 700 750 800

Ferulic acid (4-hydroxy-4-methoxycinnamic acid; Mr 194.2)

N

387

193

582 0

50 100 150 200 250 300 350 400 450 500 550 600 650 700 750 800

Sinapinic acid (3,5-dimethoxy-4-hydroxycinnamic acid; Mr 224.2) 223

N

188

S C

COOH

HO

Hal O

O

0

X

P Si Natural Products Solvents

447

O

HO

COOH

O

50 100 150 200 250 300 350 400 450 500 550 600 650 700 750 800

8.13.4 References [1] R. Orlando, Analysis of peptides contaminated with alkali-metal salts by fast atom bombardment mass spectrometry using crown ethers, Anal. Chem. 1992, 64, 332. [2] P.K. Singh, L. Field, B.J. Sweetman, Organic disulfides and related substances, J. Org. Chem. 1988, 53, 2608. [3] Z.-H. Huang, B.-J. Shyong, D.A. Gage, K.R. Noon, J. Allison, N Alkylnicotinium halides: A class of cationic matrix additives for enhancing the sensitivity in negative ion fast-atom bombardment mass spectrometry of polyanionic analytes, J. Am. Soc. Mass Spectrom. 1994, 5, 935. [4] A.E. Ashcroft, Ionization Methods in Organic Mass Spectrometry, The Royal Society of Chemistry: Cambridge, 1997.

9 UV/Vis Spectroscopy

9.1 Correlation between Wavelength of Absorbed Radiation and Observed Color Absorbed light Wavelength [nm] 400 425 450 490 510 530 550 590 640 730

Corresponding color violet indigo blue blue blue-green green yellow-green yellow orange red purple

Observed (transmitted) color yellow-green yellow orange red purple violet indigo blue blue blue-green green

9.2 Simple Chromophores Chromophore Compound

C–H C–C C=C

C=C=C

CH4 CH3–CH3 CH2=CH2 (CH3)2C=C(CH3)2 CH2=C=CH2

C ––– C

HC ––– CH n-C5H11–C ––– C–CH3

C–Cl C–Br

CH3Cl n-C3H7Br

Transition

σ  σ  π  π 

 σ*  σ*  π*  π*

n   σ* n   σ*

λmax [nm] εmax 122 135 162 196 170 227 173 178 196 222 173 208

strong strong 15000 11500 4000 630 6000 10000 2000 160 200 300

Solvent

gas gas heptane heptane gas hexane hexane hexane

402

9 UV/Vis

Chromophore Compound C–I C–O C–N C=N

CH3I CH3OH CH3OCH3 (C2H5)2NH (CH3)3N NH

n  n  n  n  n 

 σ*  σ*  σ*  σ*  σ*

(CH3)2C=NOH (CH3)2C=NONa CH3–N=N–CH3 (CH3)3C–NO (CH3)3C–NO2 n-C4H9–O–NO

C ––– N X=Y=Z

C2H5–O–NO2 CH3C ––– N C2H5–N=C=S C2H5–N=C=N–C2H5

C–S

CH3SH C2H5–S–C2H5 C2H5–S–S–C2H5

C=S

(CH3)2C=S

n  n  n  n  n  n 

 σ*  σ*  σ*  σ*  σ*  σ*

(CH3)2C=O CH3COOH CH3COONa CH3COOC2H5 CH3CONH2 O

C=C=O

H N

O

(C2H5)2C=C=O

259 177 184 193 199

n  π  n  n  n  n  n 

 σ*  π*  π*  π*  π*  π*  π*

400 200 2500 2500 4000

Solvent hexane hexane gas hexane hexane

15 water

193 2000 ethanol 265 200 ethanol 340 16 ethanol 300 100 ether 665 20 276 27 ethanol 218 1050 ethanol 313–384 20–40 ethanol 260 15 ethanol <190 250 1200 hexane 230 4000 270 25 195 1800 gas 235 180 194 4500 gas 225 1800 194 5500 hexane 250 380 460 weak 495

S

C=O

λmax [nm] εmax

265

NH 2 . HCl

H2N

N=N N=O

Transition

weak ethanol

166 189 279 200 210 210 220

16000 900 15 50 150 50 63

191

15200 CH3CN

227 375

360 20

gas hexane hexane gas water gas water



9.3 Conjugated Alkenes

403

9.3 Conjugated Alkenes 9.3.1 Dienes and Polyenes The π   π* transition of conjugated double bonds is above ≈200 nm with typical intensities of the order of log ε ≈ 4. Its position can be estimated with the Woodward– Fieser rule. For cross-conjugated systems, the value for the chromophore absorbing at the longest wavelength has to be calculated. Woodward–Fieser rule for estimating the position of the π   π * transition (λmax in nm) Parent system

Increments

acyclic

217

heteroannular

214

homoannular

253

for each additional conjugated double bond for each exocyclic double bond for each substituent

Solvent correction

C C

C-substituent Cl Br O–alkyl OCOCH3 N(alkyl)2 S–alkyl

+30 +5 +5 +5 +5 +6 0 +60 +30 ≈0

404

9 UV/Vis

Example: Estimation of the absorption maximum for

O O

base value (homoannular) 1 additional conjugated double bond 1 exocyclic double bond 3 C-substituents 1 OCOCH3 estimated experimental

253 30 5 15 0 303 306

9.3.2 α,β-Unsaturated Carbonyl Compounds The π   π* transition of α,β-unsaturated carbonyl compounds is above ≈200 nm with typical intensities of the order of log ε ≈ 4. Its position can be estimated with the extended Woodward rule. For cross-conjugated systems, the value for the chromophore absorbing at the longest wavelength must be calculated. Extended Woodward rule for estimating the position of the π   π * transition (λmax in nm) γ

α O

δ

Parent system

O X O

O

β

X

X: alkyl X: H X: OH X: O–alkyl

215 207 193 193 215 202



9.3 Conjugated Alkenes

Increments

for each additional conjugated double bond for each exocyclic double bond

+30 +5

C C

for each homoannular diene system For each substituent on double bond system

α 10 15 25 35 35 6

C-substituent Cl Br OH O–alkyl O–COCH3 S–alkyl N(alkyl)2

Solvent corrections

+39

Increment β γ 12 18 12 30 30 30 17 6 6 85 95

Solvent water hexane cyclohexane chloroform methanol ethanol diethyl ether dioxane

δ and beyond 18 50 31 6

Correction term -8 11 11 1 0 0 7 5

Example: Estimation of the absorption maximum in ethanol for

O

base value 2 additional conjugated double bonds exocyclic double bond homoannular diene system 1 β-C-substituent 3 additional C-substituents solvent correction estimated experimental

405

215 60 5 39 12 54 0 385 388

406

9 UV/Vis

9.4 Aromatic Hydrocarbons 9.4.1 Monosubstituted Benzenes Typical Ranges for Monosubstituted Benzenes (λmax in nm) Transition π  π  π  n 

 π* (allowed)  π* (forbidden)  π* (substituent delocalized by aryl; K band)  π* (substituent with lone pair; R band)

λmax

180–230 250–290 220–250 275–350

ε

2000–10000 100–2000 10000–30000 10–100

Specific Examples of Monosubstituted Benzenes (λmax in nm) π   π* (allowed) Substituent R (solvent) λmax ε

–H (cyclohexane) –CH3 (hexane) –CH=CH2 (ethanol) –C ––– CH (hexane) –Cl (ethanol) –OH (water) –O– (water) –NH2 (water) –NH3+ (water) –NO2 (Hexan) –C ––– N (water) –CHO (hexane) –COCH3 (ethanol) –COOH (water)

198 208 210 211 235 230 203 208 213

202

π   π* (forbidden) λmax ε

8000 255 7900 262 282 278 7500 257 6200 270 9400 287 8600 280 7500 254 9800 270 8100 271 280 278 8000 270

π   π* (K band) λmax ε

230 230 450 244 12000 650 236 12500 170 1450 2600 1430 160 800 251 9000 1000 1400 1100 800

224 242 243 230

n   π* (R band) λmax ε

322

150

13000 14000 ≈330 13000 319 10000

≈60 50



9.4 Aromatic Hydrocarbons

407

9.4.2 Polysubstituted Benzenes Estimation of the position of the allowed π   π * transition in multiply substituted benzenes (λmax in nm, log ε ≈4) Base value: 203.5 Substituent –CH3 –Cl –Br –OH –O– –OCH3 –NH2 –NHCOCH3 –NO2 –C ––– N –CHO –COCH3 –COOH

Increment [nm] 3.0 6.0 6.5 7.0 31.5 13.5 26.5 38.5 65.0 20.5 46.0 42.0 25.5

408

9 UV/Vis

9.4.3 Aromatic Carbonyl Compounds Scott rules for estimating the position of the K band (solvent: ethanol; λmax in nm, ε = 10000–30000) Parent systems O

O H

250

O

230

OR

230

O alk

Increments

OH

246 Substituent –alkyl –cycloalkyl –Cl –Br –OH –O–alkyl –O– –NH2 –N(CH3)2 –NHCOCH3

ortho 3 3 0 2 7 7 11 13 20 20

meta 3 3 0 2 7 7 20 13 20 20

Example: Estimation of the absorption maximum (K band) for O

O

base value ortho-cycloalkyl para-O–alkyl estimated experimental

246 3 25 274 276

para 10 10 15 25 25 78 58 85 45



9.5 Reference Spectra

409

9.5 Reference Spectra 9.5.1 Alkenes and Alkynes log ε

log ε

5

5

4

4

3

3

2

2

1

1

0 200

300

400

λ / nm

log ε

0 200 log ε

5

4

3

3

2

2

1

1 300

400

λ / nm

log ε

λ / nm

HO

OH

0 200

300

400

λ / nm

log ε

5

O

4

H

3

5 3 2

1

1 300

400

λ / nm

O

4

2 0 200

400

5

4

0 200

300

0 200

300

400

λ / nm

410

9 UV/Vis

log ε

log ε

5

O

4

OH

3

5

2

1

1 300

400

λ / nm

O

3

2 0 200

O

4

0 200

–

300

400

λ / nm

300

400

λ / nm

300

400

λ / nm

300

400

λ / nm

9.5.2 Aromatic Compounds log ε

log ε

5

5

4

4

3

3

2

2

1

1

0 200

300

400

λ / nm

log ε

0 200 log ε

5

5

4

4

3

3

2

2

1

1

0 200

300

400

λ / nm

log ε

0 200 log ε

5

5

4

4

3

3

2

2

1

1

0 200

300

400

λ / nm

0 200



9.5 Reference Spectra log ε

log ε

5

5

Cl

4

3

2

2

1

1 300

400

λ / nm

log ε

0 200

5

OH

4

3

2

2

1

1 300

400

λ / nm

log ε

λ / nm

0 200

300

400

λ / nm

log ε

5

5

O

4

3

2

2

1

1 300

400

O

4

3

λ / nm

log ε

0 200

300

400

λ / nm

log ε

5

5

NH2

4

3

2

2

1

1 300

400

NH3 +

4

3

0 200

400

O–

4

3

0 200

300

log ε

5

0 200

I

4

3

0 200

411

λ / nm

0 200

300

400

λ / nm

412

9 UV/Vis

log ε

log ε

5

5

N

4 3

3

2

2

1

1

0 200

300

log ε

400

λ / nm

3

2

2

1

1 300

400

λ / nm

log ε

0 200

300

5

CN

4

λ / nm

400

3

2

2

1

1 300

400

SH

4

3

λ / nm

log ε

0 200

300

λ / nm

400

log ε

5

5

S

4

3

2

2

1

1 300

400

S

4

3

0 200

NO

log ε

5

0 200

λ / nm

400

4

3

0 200

300

5

N

4

0 200 log ε

N

5

H N

4

λ / nm

0 200

300

400

λ / nm



9.5 Reference Spectra log ε

log ε

5

SO3

4

5

–

3

2

2

1

1 300

400

λ / nm

log ε

0 200

400

3

2

2

1

1 300

400

λ / nm

O

4

3

λ / nm

log ε

0 200

300

400

λ / nm

log ε

5

5

O

4

OH

3

2 1 400

log ε

λ / nm O

5

O

0 200

5 4

3

3

2

2

1

1 400

λ / nm

300

400

λ / nm

log ε

4

300

O–

3

1 300

O

4

2

0 200

300

5

O

4

0 200

H

log ε

5

0 200

O

4

3

0 200

413

0 200

O

O

300

400

λ / nm

414

9 UV/Vis

log ε

log ε

5

5

4

4

3

3

2

2

1

1

0 200

300

400

λ / nm

log ε

0 200

4

3

3

2

2

1

1 300

400

λ / nm

log ε

0 200

300

400

λ / nm

300

400

λ / nm

300

400

λ / nm

log ε

5

5

4

4

3

3

2

2

1

1 300

400

λ / nm

log ε

0 200 log ε

5

5

4

4

3

3

2

2

1

1

0 200

λ / nm

5

4

0 200

400

log ε

5

0 200

300

300

400

λ / nm

0 200



9.5 Reference Spectra log ε

log ε

5

5

4

4

3

3

2

2

1

1

0 200

300

400

λ / nm

log ε

0 200

400

λ / nm

300

400

λ / nm

300

400

λ / nm

5

4

4

3

3

2

2

1

1 300

400

λ / nm

log ε

0 200 log ε

5

5

4

4

3

3

2

2

1

1

0 200

300

log ε

5

0 200

415

300

400

λ / nm

0 200

9.5.3 Heteroaromatic Compounds log ε

log ε

5

5

4

4

O

3 2

2

1

1

0 200

300

400

N H

3

λ / nm

0 200

300

400

λ / nm

416

9 UV/Vis

log ε

log ε

5

5

4

4

S

3 2

2

1

1

0 200

300

λ / nm

400

log ε

0 200

N

3 1

1 400

N

3 2

300

N

4

N

2

λ / nm

log ε

0 200

300

λ / nm

400

log ε

5 4 3

N

5

N

3 2

1

1 300

400

N

4

2

λ / nm

log ε

0 200

N N

300

400

λ / nm

log ε

5

5

4

O

3

4 2

1

1 300

400

λ / nm

N H

3

2 0 200

λ / nm

400

5

4

0 200

300

log ε

5

0 200

N

3

0 200

300

400

λ / nm



9.5 Reference Spectra log ε

log ε

5

5

4

4

S

3

2

1

1 300

λ / nm

400

log ε

0 200

300

λ / nm

400

log ε

5

5

4

N

3

3 2

1

1 300

λ / nm

400

N

4

2 0 200

N

3

2 0 200

417

0 200

300

λ / nm

400

9.5.4 Miscellaneous Compounds log ε

log ε

5

5

CHCl3

4 3

3

2

2

1

1

0 200

300

400

λ / nm

log ε

0 200

300

λ / nm

400

log ε

5

Br

4

5 3

2

2

1

1 300

400

λ / nm

I

4

3

0 200

CHBr3

4

0 200

300

400

λ / nm

418

9 UV/Vis

log ε

log ε

5

5

N

4

4

3

3

2

2

1

1

0 200

300

400

λ / nm

log ε

0 200

CH 3 NO2

4

5 3

2

2

1

1 300

400

λ / nm

log ε

λ / nm

400

0 200

300

λ / nm

400

log ε

5

SH

4

5 3

2

2

1

1 300

400

λ / nm

log ε

S

4

3

0 200

300

400

λ / nm

log ε

5

S

4

S

5 3

2

2

1

1 300

400

λ / nm

S

4

3

0 200

O

KSCN

4

3

0 200

300

N

log ε

5

0 200

O

0 200

NH2

300

400

λ / nm



9.5 Reference Spectra log ε

log ε

5

5

O

4

2

1

1 λ / nm

400

log ε

0 200

O 300

400

OH O OH OH

λ / nm

log ε

5

O

5

3

NH

3

2

O

4

1 0 200

HO

3

2

300

O

4

OH

3

0 200

419

300

O

4

O N H

NH2

2 1 λ / nm

400

0 200

300

400

λ / nm

9.5.5 Nucleotides log ε

log ε

5 4

N H

2 1 300

400

NH

3

O

N H

2 1

λ / nm

log ε

0 200

300

400

O

λ / nm

log ε

5 4

N

3

N H

2

NH2 N N

1 0 200

O

4

N

3

0 200

5

NH2

5

O

4

N

3

N H

2

NH N

NH2

1 300

400

λ / nm

0 200

300

400

λ / nm

420

9 UV/Vis

9.6 Common Solvents The end absorption, λend, of several common solvents is given here as the wavelength at which the solvents absorb 80% of the irradiated light (λend in nm; cell length, 1 cm; reference, water). Solvent

acetone acetonitrile benzene carbon disulfide carbon tetrachloride chloroform cyclohexane dichloromethane diethyl ether 1,4-dioxane ethanol

λend 335 190 285 380 265 245 210 230 210 215 205

Solvent

ethyl acetate heptane hexane methanol pentane 2-propanol pyridine tetrahydrofuran toluene 2,2,4-trimethylpentane xylene

λend 205 195 195 205 200 205 305 230 285 210 290