TEXTBOOK OF PRACTICAL ORGANIC CHEMISTRY FIFTH EDITION B.S.FURNISS « A.J.HANNAFORD © P.W.G.SMITH * AR. TATCHELLVOGEL’s TEXTBOOK OF PRACTICAL ORGANIC CHEMISTRY FIFTH EDITION Revised by former and current members of The School of Chemistry, Thames Polytechnic, London Brian S. Furniss Antony J. Hannaford Peter W. G. Smith Austin R. Tatchell > my Longman man Scientific & = wae |Technical corset in the United States with John Wiley & Sons, Inc., New YorkLongman Scientific & Technical Longman Group UK Limited Longman House, Burnt Mill, Harlow Essex CM20 2JE, England and Associated Companies throughout the world Copublished in the United States with John Wiley & Sons, Inc., 605 Third Avenue, New York, NY 10158 © Longman Group UK Limited 1989 All rights reserved; no part of this publication may be reproduced, stored in a retrieval system, or transmitted in any form or by any means, electronic, mechanical, photocopying, recording, or otherwise, without either the prior written permission of the Publishers, or a licence permitting restricted copying in the United Kingdom issued by the Copyright Licensing Agency Ltd, 33-34 Alfred Place, London, WCIE 7DP. First published 1948 New Impression with minor corrections, October 1948 Second Edition 1951 New Impression with addition of Chapter XII on Semimicro Technique 1954 Third Edition 1956 New Impression with corrections and additions 1957 New Impressions 1959, 1961, 1962, 1964, 1965, 1967 Fourth Edition 1978 Reprinted, with minor corrections 1979, 1981, 1984, 1986, 1987, 1988 Fifth Edition 1989 British Library Cataloguing in Publication Data Vogel, Arthur Israel Vogel's textbook of practical organic chemistry ~ Sth ed 1. Organic chemistry. Laboratory techniques 1, Title I. Furniss, B. S. (Brian Stanley), 1941 — 5470028 ISBN 0-582-46236-3 Library of Congress Cataloging-in-Publication Data Vogel, Arthur Israel, Vogel's Textbook of practical organic chemistry — Sth ed. / rev. by Brian S. Furniss ... [et al.] pcm, Fourth ed. published in 1978 under title: Vogel's Textbook of practical organic chemistry, including qualitative organic analysis. Includes bibliographies and indexes. ISBN 0-470-21414-7 1. Chemistry, Organic—Laboratory manuals. 2. Chemistry, Analytic—Qualitative, I. Furniss, Brian S. (Brian Stanley), 1941— II, Vogel, Arthur Israel. Vogel's Textbook of practical organic chemistry, including qualitative organic analysis. III, Title. QD261.V63 1989 347—de19 88-36786 CIP Set in 10/11 pt. Lasercomp Times New Roman Filmset by Eta Services (Typesetters) Ltd, Beccles, Suffolk Printed in Great Britain by The Bath PressCONTENTS CHAPTER 1 ORGANIC SYNTHESIS 1.1. INTRODUCTION 1.2 STRUCTURE OF THE TARGET MOLECULE 1.3 REACTION MECHANISM AND THE METHODOLOGY OF SYNTHESIS 1.4 REACTION MECHANISM AND THE STRATEGY OF SYNTHESIS 1.5 CONCLUSION REFERENCES CHAPTER 2 EXPERIMENTAL TECHNIQUES 2.1 GENERAL INSTRUCTIONS FOR SAFE WORKING IN ORGANIC CHEMICAL LABORATORIES 2.2 PLANNING OF EXPERIMENTS AND RECORDING OF RESULTS 2.3 HAZARDS IN ORGANIC CHEMISTRY LABORATORIES 2.3.1 Introduction 34 2.3.2 Explosion and fire hazards 35 2.3.3 Reactive inorganic reagents 42 2.3.4 Hazards due to toxic chemicals 44 2.3.5 Electrical safety 51 2.3.6 Ultraviolet radiation 52 APPARATUS AND REACTION PROCEDURES 2.4 INTERCHANGEABLE GROUND GLASS JOINTS 2.5 TYPES OF GROUND GLASS JOINTS 2.6 CARE AND MAINTENANCE OF GROUND GLASS JOINTS 2.7 APPARATUS WITH INTERCHANGEABLE GROUND GLASS JOINTS SUITABLE FOR GENERAL USE IN PREPARATIVE ORGANIC CHEMISTRY 28 OTHER TYPES OF INTERCHANGEABLE JOINTS AND STOPCOCKS 2.9 THE USE OF CORKS AND RUBBER STOPPERS 2.10 CUTTING AND BENDING OF GLASS TUBING 10 7 23 26 26 cD) 52 55 57 63 64CONTENTS 21 2412 213 214 215 2.16 247 GENERAL LABORATORY APPARATUS COOLING OF REACTION MIXTURES HEATING OF REACTION MIXTURES MECHANICAL AGITATION TYPICAL GROUND GLASS JOINT ASSEMBLIES FOR STANDARD REACTION PROCEDURES PRECAUTIONS FOR UNATTENDED REACTIONS APPARATUS FOR SPECIAL REACTION TECHNIQUES 2.17.1 Catalytic hydrogenation 87 2.17.2 Reactions under pressure 97 2.17.3. Uncatalysed and catalysed vapour phase reactions 99 2.17.4 Ozonolysis 103 2.17.5 Organic photochemistry 106 2.17.6 Electrolytic (anodic) syntheses 115 2.17.7 Liquid ammonia techniques 116 2.17.8 Reactions involving air-sensitive compounds 120 ISOLATION AND PURIFICATION PROCESSES 218 219 2.20 221 222 223 224 2.25 2.26 227 2.28 2.28 2.30 2H 232 GENERAL CONSIDERATIONS FILTRATION TECHNIQUES RECRYSTALLISATION TECHNIQUES ‘SUBLIMATION TECHNIQUES — FREEZE DRYING ‘SOLVENT EXTRACTION DRYING OF LIQUIDS OR OF SOLUTIONS OF ORGANIC COMPOUNDS IN ORGANIC SOLVENTS DISTILLATION AT ATMOSPHERIC PRESSURE STEAM DISTILLATION FRACTIONAL DISTILLATION AT ATMOSPHERIC PRESSURE DISTILLATION UNDER DIMINISHED PRESSURE (‘VACUUM’ DISTILLATION) HIGH VACUUM DISTILLATION — MOLECULAR DISTILLATION VACUUM PUMPS MANOMETERS, VACUSTATS, VACUUM GAUGES AND MANOSTATS CHROMATOGRAPHY STORAGE OF SAMPLES DETERMINATION OF PHYSICAL CONSTANTS 2.33 234 235 236 237 MELTING POINT — MIXED MELTING POINTS DETERMINATION OF BOILING POINT DETERMINATION OF MOLECULAR WEIGHT DETERMINATION OF OPTICAL ROTATORY POWER DETERMINATION OF REFRACTIVE INDEX REFERENCES vi n B 86 87 131 131 135 153 156 165 169 in 173 181 186 191 193 197 234 236 236 2a 243 24 249CONTENTS CHAPTER 3 SPECTROSCOPIC METHODS AND THE 3 34 INTERPRETATION OF SPECTRA Introduction 254 The electromagnetic spectrum 255 INFRARED SPECTROSCOPY Instrumental features of infrared spectrophotometers 258 Determination of infrared spectra 259 Sample preparation 260 Features of an infrared spectrum 268 Interpretation of an infrared spectrum 271 Characteristic group frequencies 273 NUCLEAR MAGNETIC RESONANCE SPECTROSCOPY Features of the nuclear magnetic resonance spectrum 319 The chemical shift 324 Spin-spin splitting 338 Protons attached to heteroatoms 348 Simplification of 'H spectra 350 Interpretation of the p.m.r. spectrum 359 Further information from \3C-spectra 360 MASS SPECTROMETRY The mass spectrum 362 Appearance of the mass spectrum 372 Interpretation of the mass spectrum 373 Mass spectra of classes of organic compounds 373 ULTRAVIOLET—VISIBLE SPECTROSCOPY Instrumental features of ultraviolet—-visible spectrophotometers 384 Determination of ultraviolet-visible spectra 384 Laws of light absorption 385 Solvents for ultraviolet spectroscopy 386 Solution preparation 386 Optical cells and their care 387 Features of an ultraviolet—visible spectrum 388 REFERENCES CHAPTER 4 SOLVENTS AND REAGENTS 41 THE PURIFICATION OF COMMON ORGANIC SOLVENTS Saturated aliphatic hydrocarbons 397 Aromatic hydrocarbons 398 Halogenated hydrocarbons 399 Aliphatic alcohols 400 Ethers 404 Ketones 407 Esters 409 254 256 316 361 383 393 395 395 viiNitrogen-containing solvents 409 Sulphur-containing solvents 411 Phosphorus-containing solvents 412 4.2. THE PREPARATION AND PURIFICATION OF REAGENTS 413 REFERENCES 468 CHAPTER 5 ALIPHATIC COMPOUNDS 470 5.1. ALKANES 470 52 5.3 Vili Structure 470 Summary of preparative methods and of retrosynthetic strategies 471 Spectroscopic features 472 5.1.1 The catalytic hydrogenation and chemical reduction of alkenes 472 5.1.2. The hydrolysis of alkylmagnesium halides and the hydrogenolysis of alkyl halides and of alkyl methane- or toluene-p-sulphonates 474 5.1.3 The reduction of aldehydes and ketones 476 5.1.4 Coupling reactions (a) using organometallic compounds, and (5) at the anode 477 ‘ALKENES 484 Structure 484 Summary of preparative methods and of retrosynthetic strategies 485 Spectroscopic features 486 5.2.1 1,2-Elimination processes (f-elimination) 486 5.2.2. The partial hydrogenation of alkynes 493 5.2.3 Wittig and related reactions 495 5.2.4 Selected rearrangements of alkynes to allenes 504 ‘ALKYNES 507 ‘Structure 507 Summary of preparative methods and of retrosynthetic strategies 508 Spectroscopic features 508 5.3.1 The dehydrogenation of vic- and gem-dihalides 509 5.3.2. The oxidation of dihydrazones of 1,2-diketones 512 5.3.3 Alkylation of a terminal alkyne 513 5.3.4 Coupling reactions leading to diynes 515 ALIPHATIC ALCOHOLS 517 ‘Structure 517 ‘Summary of preparative methods and of retrosynthetic strategies 517 Spectroscopic features 519 5.4.1 The reduction of aldehydes, ketones and esters 519 5.4.2 The interaction of carbonyl-containing compounds with organometallic reagents 531 5.4.3. The hydroboration-oxidation of alkenes 542 5.4.4 The oxymercuration-demercuration of alkenes 545 5.4.5 The hydroxylation of alkenes 547 5.4.6 Methods for the protection of the hydroxyl group 55055 5.6 57 58 ALIPHATIC HALIDES 553 Structure 553 Summary of preparative methods and of retrosynthetic strategies 554 Spectroscopic features 554 5.5.1 Preparation of alkyl chlorides from alcohols 555 5.5.2 Preparation of alkyl bromides from alcohols 559 5.5.3 Preparation of alkyl iodides from alcohols 566 5.5.4 Displacement reactions involving a halogen atom 570 5.5.5 Displacement reactions involving a methanesulphonyloxy group 572 5.5.6 Displacement reactions involving the amino group 574 5.5.7 Addition of hydrogen halides or halogens to alkenes 574 5.5.8 The replacement of reactive allylic hydrogen atoms by bromine 577 ALIPHATIC ETHERS 579 Structure 579 Summary of preparative methods and of retrosynthetic strategies 580 Spectroscopic features 580 5.6.1 The formation of ethers from alcohols under acidic conditions 581 5.6.2 The interaction of an alcohol with a halogen compound under basic conditions 583 ALIPHATIC ALDEHYDES 585 Structure 585 Summary of preparative methods and of retrosynthetic strategies 585 Spectroscopic features 587 5.7.1 The controlled oxidation or dehydrogenation of primary alcohols 587 5.7.2 The oxidative cleavage of 1,2-diols 590 5.7.3. The ozonolysis of suitably substituted alkenes 592 5.7.4 The reduction of nitriles, carboxylic acids and carboxylic acid chlorides 594 5.7.5 Methods based upon alkyl halides 596 5.7.6 The hydrolysis and decarboxylation of «,B-epoxy esters (glycidic esters) 598 5.7.7 The oxidative hydrolysis of nitronate salts derived from primary nitroalkanes 599 5.7.8 Methods for the alkylation of the carbon chain 600 ALIPHATIC KETONES 604 Structure 604 Summary of preparative methods and of retrosynthetic strategies 605 Spectroscopic features 606 5.8.1 The oxidation of secondary alcohols 607 5.8.2 The hydration of alkynes 612 5.8.3 The thermal decarboxylation of acids over a metal oxide catalyst 612 5.8.4 The interaction of organometallic compounds with carboxylic acid chlorides and N,N-dimethylcarboxamides 616CONTENTS: 5.8.5 The hydrolysis and decarboxylation of B-keto esters and the hydrolysis of B-diketones 619 5.8.6 The acid-catalysed rearrangement of 1,2-diols 623 5.8.7 The oxidative hydrolysis of nitronate salts from secondary nitroalkanes 623 5.8.8 Methods for the protection of the carbonyl group in aldehydes and ketones 623 5.9 DICARBONYL COMPOUNDS 626 Structure 626 5.9.1 1,2-Dicarbonyl compounds 627 5.9.2 1,3-Dicarbonyl compounds 632 5.9.3 1,4-Dicarbonyl compounds 635 5.10 CARBOHYDRATES 637 Structure 637 5.10.1 Carbohydrate interconyersions 642 5.10.2 Carbohydrate interconversions 644 5.10.3 Carbohydrate interconversions 651 5.10.4 Carbohydrate interconversions 658 5.10.5 Carbohydrate interconversions 660 5.11 ALIPHATIC CARBOXYLIC ACIDS 664 Structure 664 Summary of preparative methods and of retrosynthetic strategies 664 Spectroscopic features 666 5.11.1 Oxidative methods 667 5.11.2. Hydrolysis of alkyl cyanides 671 5.11.3 Carboxylation of Grignard reagents 673 5.11.4 The Arndt—Eistert method 675 5.11.5 Electrolytic (anodic) coupling 677 5.11.6 Methods utilising diethyl malonate 680 5.11.7 The synthesis of optically active carboxylic acids 687 5.11.8 Methods for the protection of the carboxyl group 690 5.12 CARBOXYLIC ACID DERIVATIVES 691 Structure 691 Summary of retrosynthetic strategies 692 ‘Spectroscopic features 692 5.12.1 Acyl halides 692 5.12.2 Acid anhydrides 693 5.12.3 Esters 695 5.12.4 Acid amides 708 §.13 ALIPHATIC NITRILES 10 Summary of preparative methods and of retrosynthetic strategies 710 Spectroscopic features 711 5.13.1 Displacement with cyanide ion on an alkyl halide 711 5.13.2 Displacement with cyanide ion on an arylsulphonylhydrazone 712 5.13.3 Dehydration of amides and aldoximes 715514 5.15 5.16 517 518 5.19 5.13.4 Cyanoethylation procedures and the a-alkylation of nitriles 717 SUBSTITUTED CARBOXYLIC ACIDS AND THEIR DERIVATIVES 19 Structure 719 Spectroscopic features 720 5.14.1 Halogeno acids 720 5.14.2. Hydroxy acids and lactones 725 5.14.3 Keto acids and esters 735 5.14.4 Amino acids and peptides 746 NITROALKANES 763 Structure 763 Summary of preparative methods and of retrosynthetic strategies 764 Spectroscopic features 764 5.15.1 The displacement of a halogen by a nitrite ion in an alkyl halide 764 5.15.2 The oxidation of oximes and amines 765 5.15.3 C-Alkylation of nitroalkanes and other homologation procedures 768 ALIPHATIC AMINES 763 Structure 769 Summary of preparative methods and of retrosynthetic strategies 770 Spectroscopic features 771 5.16.1 The reduction of alkyl azides, alkyl cyanides and amides 771 5.16.2 The reduction of nitro compounds and oximes 774 5.16.3. The reductive alkylation of ammonia or amines 776 5.16.4 The alkylation of ammonia and its derivatives 779 5.16.5 Imine and enamine formation 782 5.16.6 Molecular rearrangements of the Hofmann type 783 5.16.7 Methods for the protection of the amino and imino groups 784 ALIPHATIC SULPHUR COMPOUNDS 786 Structure 786 Spectroscopic features 787 5.17.1 Thiols and thioacetals 787 5.17.2 Dialkyl sulphides (thioethers) and trialkylsulphonium salts 789 5.17.3 Sulphoxides and sulphones 791 5.17.4 O,S-Dialky| dithiocarbonates (xanthate esters) 792 UNSATURATED COMPOUNDS 7394 5.18.1 Unsaturated alcohols 794 5.18.2 Unsaturated carbonyl compounds 798 5.18.3 Unsaturated acids and esters 820 RESOLUTION OF RACEMATES 809 REFERENCES 816 xiCONTENTS CHAPTER 6 AROMATIC COMPOUNDS 824 6.1 62 63 64 65 xii AROMATIC HYDROCARBONS 824 Structure 824 Spectroscopic features 825 6.1.1 Alkylbenzenes 826 6.1.2 and triarylmethanes 833 6.1.3 Biphenyl systems 835 6.1.4 Condensed polycyclic systems 839 6.1.5 Some non-benzenoid systems 847 AROMATIC NITRO COMPOUNDS 850 Summary of preparative methods and of retrosynthetic strategies 850 Spectroscopic features 851 6.2.1 Direct nitration 851 6.2.2 The oxidation of amines 857 6.2.3 The replacement of a diazo group by a nitro group 858 AROMATIC HALOGEN COMPOUNDS 858 Structure 858 ‘Summary of preparative methods and of retrosynthetic strategies 858 Spectroscopic features 859 6.3.1 Direct halogenation 860 6.3.2 Chloromethylation 865 6.3.3 The replacement of a diazo group by a halogen 867 6.3.4 The replacement of a hydroxyl group by a halogen 867 6.3.5 Methods leading to polyvalent iodine compounds 868 AROMATIC SULPHONIC ACIDS AND THEIR DERIVATIVES 872 Structure 872 Summary of preparative methods and of retrosynthetic strategies 872 Spectroscopic features 873 6.4.1 Direct sulphonation 873 6.4.2, The preparation of arylsulphony! chlorides 877 6.4.3 The preparation of arylsulphonamides 879 6.4.4 The preparation of arylsulphonate esters 883 6.4.5 Reduction products from arylsuphonyl chlorides 887 AROMATIC AMINES 888 Structure 888 Summary of preparative methods and of restrosynthetic strategies 889 Spectroscopic features 890 6.5.1 The reduction of nitro compounds 892 6.5.2 Molecular rearrangements of the Hofmann type 897 6.5.3 The replacement of halogen by an amino group 900 6.5.4 The replacement of a phenolic hydroxyl group by an amino group 900 6.5.5 Alkylation and reductive alkylation procedures 901 6.5.6 Some methods for the protection of the amino and imino groups 9066.6 SUBSTITUTION PRODUCTS OF AROMATIC AMINES 906 6.6.1 Nuclear substitution products 906 6.6.2 Acylated amines and their substitution reactions 916 6.7 FORMATION OF DIAZONIUM SALTS AND THEIR USES 920 6.7.1 Reactions involving replacement of the diazo group 922 6.7.2 Coupling reactions 946 6.8 MISCELLANEOUS AROMATIC NITROGEN COMPOUNDS 953 6.8.1 Intermediate products in the reduction of nitro compounds 953 6.8.2 Arylhydrazines 959 6.8.3 Arylureas and related compounds 963 6.9 PHENOLS AND PHENYL ETHERS 968 Summary of preparative methods and of retrosynthetic strategies 968 Spectroscopic features 969 6.9.1 Methods for the introduction of a hydroxyl group into an aromatic ring 970 6.9.2 Substitution reactions of phenols 975 6.9.3 Formation of phenyl ethers 984 6.9.4 Some methods for the protection of the phenolic hydroxyl group 988 6.10 AROMATIC ALDEHYDES 989 Summary of preparative methods and of retrosynthetic strategies 989 Spectroscopic features 990 6.10.1 Aromatic formylation reactions 990 6.10.2 Reactions involving modification of aromatic ring substituents 999 6.11 AROMATIC KETONES AND QUINONES 1005 ‘Summary of preparative methods and of retrosynthetic strategies for aromatic ketones 1005 Spectroscopic features 1005 6.11.1 Friedel-Crafts-type acylation processes 1006 6.11.2 Synthesis of aromatic ketones from carboxylic acid derivatives 1008 6.11.3 Quinones 1019 6.12 SOME REACTIONS OF AROMATIC CARBONYL COMPOUNDS 1028 6.12.1 The Cannizzaro reaction 1028 6.12.2 The Claisen-Schmidt and related reactions 1032 6.12.3 The Perkin and Doebner reactions 1036 6.12.4 The synthesis of diphenylpolyenes 1041 6.12.5 The benzoin condensation 1043 6.12.6 Oxime formation 1047 6.12.7 Some reactions of alkyl aryl ketones 1050 6.12.8 Methods for the protection of the aromatic carbonyl group 1056 6.13 AROMATIC CARBOXYLIC ACIDS 1056 Summary of preparative methods and of retrosynthetic strategies 1056 Spectroscopic features 1057 xiii6.14 6.15 6.13.1 Oxidative methods 1057 6.13.2. The hydrolysis of nitriles 1062 6.13.3 Carboxylation of the aromatic ring system 1067 6.13.4 Nuclear nitration of aromatic carboxylic acids and esters 1071 6.13.5 Some methods for the protection of the carboxyl group 1072 AROMATIC CARBOXYLIC ACID DERIVATIVES 1073 Structure 1073 ‘Spectroscopic features 1073 6.14.1 Acid halides 1073 6.14.2 Acid anhydrides 1074 6.14.3 Esters 1076 6.14.4 Acid amides 1080 AROMATIC NITRILES 1081 Summary of preparative methods and of retrosynthetic strategies 1081 6.15.1 The Sandmeyer procedure 1081 6.15.2. The displacement of halogen by cyanide in an aryl halide 1082 6.15.3 The dehydration of amides and aldoximes 1082 REFERENCES 1085 CHAPTER 7 SELECTED ALICYCLIC COMPOUNDS 1087 7.1 INTRAMOLECULAR NUCLEOPHILIC DISPLACEMENT REACTIONS 1087 7.2 INTRAMOLECULAR ADDITION REACTIONS OF CARBANIONS TO A CARBONYL GROUP 1092 7.3, INSERTION REACTIONS 1106 7.4 RING EXPANSION AND RING CONTRACTION REACTIONS 1111 7.5 REDUCTION OF AROMATIC COMPOUNDS 1114 7.6 CYCLOADDITION REACTIONS 1117 REFERENCES 1126 CHAPTER 8 SELECTED HETEROCYCLIC COMPOUNDS 1127 8.1. THREE-MEMBERED HETEROCYCLES 1127 82 xiv 8.1.1 Intramolecular cyclisation of a 1,2-bifunctional compound 1128 8.1.2 Insertion of a methylene group into a carbon-heteroatom double bond 1131 8.1.3 Insertion of a heteroatom into a carbon-carbon double bond 1132 8.1.4 Heteroatom exchange 1137 FOUR-MEMBERED HETEROCYCLES 1138 8.2.1 Cyclisation reactions 1138 8.2.2 Cycloaddition reactions 1141CONTENTS: 83 FIVE-MEMBERED HETEROCYCLES 1144 8.3.1 Pyrroles, furans, thiophenes and pyrazolones from dicarbonyl compounds 1146 8.3.2 Hydantoins from urea, and thiazoles from thiourea or thioamides 1151 8.3.3. Oxazolones (and azlactones) from a-amino acids 1155 8.3.4 Indoles, benzofurans and benzothiophenes 1156 8.3.5 Benzimidazoles and benzotriazole from o-phenylene diamine 1162 ‘SIX-MEMBERED HETEROCYCLES 1164 8.4.1 Pyridines and pyrylium salts 1165 8.4.2 Pyrones and pyridones 1172 8.4.3 Barbituric acid and barbiturates 1174 8.4.4 Quinolines, isoquinolines and quinoxalines 1180 8.4.5 Coumarins and chromones 1190 REFERENCES 1194 CHAPTER 9 INVESTIGATION AND CHARACTERISATION OF a1 92 93 oa 95 96 ORGANIC COMPOUNDS 1196 PHYSICAL CONSTANTS 1197 THE STUDY OF SOLUBILITY BEHAVIOUR 1198 DETECTION OF ELEMENTS PRESENT 1204 SPECTROSCOPIC INFORMATION 1210 FUNCTIONAL GROUP IDENTIFICATION 1211 9.5.1 Acidic compounds 1211 9.5.2 Basic compounds 1215 9.5.3 Neutral compounds 1218 PREPARATION OF DERIVATIVES 1234 9.6.1 Saturated aliphatic hydrocarbons 1235 9.6.2 Unsaturated aliphatic hydrocarbons 1235 9.6.3 Aromatic hydrocarbons 1238 9.6.4 Alcohols and polyhydric alcohols 1241 9.6.5 Carbohydrates 1245 9.6.6 Phenols 1248 9.6.7 Enols 1251 9.6.8 Aliphatic halogen compounds 1251 9.6.9 Aromatic halogen compounds 1253 9.6.10 Aliphatic ethers 1254 9.6.11 Aromatic ethers 1255 9.6.12 Acetals 1257 9.6.13 Aldehydes and ketones 1257 9.6.14 Quinones 1261 9.6.15 Carboxylic acids 1261 9.6.16 Carboxylic acid chlorides and anhydrides 1265 9.6.17 Esters 1266 xvCONTENTS: 9.6.18 Primary amides 1270 9.6.19 Substituted amides 1271 9.6.20 Nitriles 1271 9.6.21 Primary and secondary amines 1273 9.6.22 Tertiary amines 1278 9.6.23 o-Amino acids 1279 9.6.24 Nitro compounds 1281 9.6.25 Thiols 1283 9.6.26 Sulphonic acids 1284 9.6.27 Sulphonamides 1286 9.7 SEPARATION OF MIXTURES OF ORGANIC COMPOUNDS 9.7.1 Introduction 1287 9.7.2 Preliminary examination of a mixture 1290 9.7.3 Separation of water-insoluble mixtures 1292 9.7.4 Separation of water-soluble mixtures 1295 CHAPTER 10 PHYSICAL CONSTANTS OF ORGANIC COMPOUNDS Tables of derivatives 1298 Index to tables 1298 APPENDICES THE LITERATURE OF ORGANIC CHEMISTRY . INFRARED CORRELATION TABLES NUCLEAR MAGNETIC RESONANCE CORRELATION TABLES }. MASS SPECTROMETRY CORRELATION TABLES . USEFUL SOLVENT CHARACTERISTICS: HAZARD SYMBOLS COMMON SYNTHONS AND THEIR REAGENT EQUIVALENTS |. SELECTION OF MANUFACTURERS AND SUPPLIERS OF LABORATORY APPARATUS, EQUIPMENT AND CHEMICALS NPP Pen Table of atomic weights 1454 Index 1455 Reference data 1511 Abbreviations 1513 1287 1298 1401 1412 1423 1435 1447 1451PREFACE TO FIFTH EDITION This is the second time that we have prepared a new edition of Vogel’s Textbook of Organic Chemistry and it is important to reaffirm the aims set out by the late Dr A. I. Vogel in the preface to the first edition. Thus in this new edition every endeavour is made to retain the comprehensive character of the book, and to ensure that it continues to be a one-volume reference text which is of value to practising organic chemists throughout their undergraduate, postgraduate and subsequent careers. During the preparation of the previous (fourth) edition considerable reorgan- isation and rewriting of the text was necessary. This arose from the many changes which had taken place in the practice and theory of organic chemistry during the preceding twenty years. Among these changes were the ready avail- ability of a much wider range of substrates and reagents; the development of a whole host of new synthetic reagents; a greater awareness of the hazards asso- ciated with handling of organic chemicals; the routine use of chromatographic and spectroscopic techniques; and the use of mechanistic concepts to rationalise and predict the outcome of organic reactions. That revision included a modified chapter on experimental techniques, which was arranged under the headings ‘Apparatus and reaction procedures’, ‘Isolation and purification processes’, and ‘Determination of physical constants’. New sections were introduced on safe working in organic laboratories, chromatography, and spectroscopic methods. The interpretation of spectroscopic data was discussed in the reorganised chapter entitled Qualitative Organic Analysis. The preparative chapters were reorganised on the basis of aliphatic compounds, aromatic compounds, alicyclic compounds, and heterocyclic compounds, and within these chapters a selection of new synthetic methods was introduced. Following the practice adopted in previous editions these new preparations were checked in the laboratories of the School of Chemistry, Thames Polytechnic. In this new (fifth) edition, in order to ensure that the book retains its rele- vance to current teaching of organic chemistry, we have adopted the same struc- ture of the book since we are of the opinion that it provides a bridge between the treatment of organic chemistry theory provided by current standard under- graduate textbooks, and the wider specialist fields of the research literature. Furthermore, in addition to the introduction of new reagents and techniques, the last decade has seen the development of a philosophy of organic synthesis (the strategy of synthesis) which was just beginning to emerge during the writing of the previous edition. It is our intention to reflect this development, since we consider that the teaching of organic chemistry must closely integrate mechanis- tic theory with the strategy and methodology of synthesis. xviiPREFACE TO THE FIFTH EDITION The book now commences with Chapter 1, Organic Synthesis, which reviews the important concepts which need to be borne in mind when considering the problem: ‘how may compound X be synthesised?’ The chapter discusses the structural and stereoisomeric features of molecules, the importance of control, selectivity and protection in organic reaction sequences, and the increasing im- portance of asymmetric synthesis. These topics are developed further in the sub- sequent text. The use of computers in organic synthesis is reviewed, and this topic leads to a short summary of the most significant contribution to the teach- ing of organic synthesis of the recent decade, namely the disconnection (or syn- thon) approach developed by Dr S. Warren and based upon the original concept of Professor E. J. Corey. This approach has been integrated with the theoretical discussions on preparative procedures which precede the preparative examples in the aliphatic and aromatic chapters. In particular the retrosynthetic analysis of target molecules has provided a framework around which the later alicyclic and heterocyclic chapters have been rewritten. By using this approach we hope that undergraduates and others, who become acquainted with this philosophy in lectures and tutorials, may find this text a useful further source of information. The first three sections of Chapter 2 deal with Codes of Practice and respons- ibility, and a summary of hazards which may be encountered in the organic chemistry laboratory. These are intended to acquaint the student with the essen- tial features of safe working practice, and to advise strongly on the importance of consulting with senior members of the laboratory or the appointed safety officer, and of consulting comprehensive specialist texts which should be readily accessible to laboratory users. In particular the advice of safety officers should be sought, since by virtue of their office they have available the latest informa- tion. Hazards associated with particular chemicals and procedures are noted in the text as far as information is available. The remainder of Chapter 2, Experi- mental Techniques, has been up-dated on the availability of new equipment and the applicability of new techniques. An important section on reactions involving air-sensitive compounds has been introduced. The chromatography section now includes the important preparative techniques of flash chromatography, dry column flash chromatography and the ‘Chromatotron’, together with a fuller discussion on high-performance liquid chromatography. Spectroscopic methods and the interpretation of spectra are now treated to- gether in Chapter 3. The most significant addition to this chapter is a more detailed coverage, with examples of spectra, of '*C-n.m.r. spectroscopy which is considered alongside 'H-n.m.r. spectroscopy. The inclusion of detailed spectro- scopic data in the preparative chapters has vastly increased the opportunities for practise by the reader in problems relating to elucidation of structure. Thus each functional group section in the aliphatic and aromatic chapters includes a summarising statement of the important spectroscopic features, and many of the preparations conclude with a description of key data. These spectroscopic data are only quoted if they provide information for the student from which a definit- ive structural assignment may be deduced. The information is quoted in several styles. If the spectrum (ir., n.m.r., ms., or u.v—visible) is simple and straight- forward the style is of the type ‘record and interpret (assign)’. If the spectrum has interesting interpretative features, the spectroscopic details are quoted and some guidance is provided to assist in the elucidation of structure. If, and this is par- xviiiPREFACE TO THE FIFTH EDITION ticularly appropriate with aromatic compounds, regioisomers may be com- pared, these features are noted. Chapter 4, Solvents and Reagents, has been extended to include important new reagents including alkyllithiums, boranes and new oxidants and reductants, which are used in subsequent chapters. Approximately 100 new experiments have been introduced into the prepara- tive chapters [Aliphatic (Ch. 5), Aromatic (Ch. 6), Alicyclic (Ch. 7), and Hetero- cyclic (Ch. 8)]. Of particular interest is the introduction of some illustrative asymmetric syntheses, important protection methods, the use of air- and moisture-sensitive reagents, the wider use of phase transfer reactions, silicon, phosphorus, boron, and titanium reagents, as well as examples of important named reactions. The procedures for these new reactions have been quoted directly from the literature but not checked in the laboratory. The examples have been selected on the basis of their interest, generality and importance. The style of presentation of these new experiments is sometimes somewhat briefer than that of those experiments retained from previous editions, but we believe that they provide a useful introduction for the advanced student to research methods. Many further examples of reagents and techniques have been noted in the theoretical discussions. They have been included since they provide possible project ideas for further investigation by advanced students. It is hoped that all these experiments will provide suitable material for the design of a full range of practical courses. Finally, as noted above, the theoretical discussions have been rewritten to provide an integrated and balanced coverage of mechanisms, metho- dology and strategy in synthesis. Chapter 9, Investigation and Characterisation of Organic Compounds, con- tains much of the chemical information and preparative methods from the chapter previously entitled Qualitative Analysis. The emphasis of this chapter is now on achieving an understanding of chemical behaviour in association with spectroscopic features, and correlating this information to provide a definitive structural elucidation. In this way we hope that the material fulfils the require- ments of a range of courses which deal in this topic. The tables of physical con- stants (Ch. 10) remain unchanged, and the appendices have been up-dated. . We wish to thank Professor B. R. Currell, Ph.D., C.Chem., F.R.S.C., and Dr J. R. Parsonage, C.Chem., F.R.S.C., former and current Heads of School of Chemistry at Thames Polytechnic, for their interest in this project and for grant- ing permission for the use of various facilities. We are indebted to Dr E. Vidgeon for recording the majority of the !°C-n.m.r. spectra, and to Mr V. Kyte and Mr J. Williams for providing information on the availability and usage of labora- tory equipment. The assistance of the company representatives of very many manufacturers of chemicals and of laboratory, spectroscopic and chromato- graphic equipment has been invaluable; general and specific help is noted in the acknowledgements. We are indebted to the referees who made valuable com- ments on the manuscript which undoubtedly helped to improve the final text. BSF. AJH. P.WGS ART. April 1988 xixPREFACE TO FIRST EDITION The present volume is an attempt to give to students of practical organic chemistry the benefit of some twenty years’ experience in research and teaching of the subject. The real foundations of the author’s knowledge of the subject were laid in 1925-1929 when, as a research student at the Imperial College under the late Professor J. F. Thorpe, F.R.S., he was introduced to the methods and experimental technique employed in a large and flourishing school of research in organic chemistry. Since that period the author and his students have been en- gaged inter alia in researches on Physical Properties and Chemical Constitution (published in the Journal of the Chemical Society) and this has involved the pre- paration of over a thousand pure compounds of very varied type. Many of the new procedures and much of the specialised technique developed and employed in these researches are incorporated in this book. Furthermore, new experiments for the elementary student have emanated from these researches; these have been tried out with large classes of undergraduate students over several sessions with gratifying success and have now been included in the present textbook. In compiling this book, the author has drawn freely from all sources of in- formation available to him — research notes, original memoirs in scientific journals, reference works on organic chemistry, the numerous textbooks on practical organic chemistry, and pamphlets of manufacturers of specialised apparatus. Whilst individual acknowledgement cannot obviously be made — in many cases the original source has been lost track of — it is a duty and a pleasure to place on record the debt the writer owes to all these sources. Mention must, however, be made of Organic Syntheses, to which the reader is referred for further details of many of the preparations described in the text. The book opens with a chapter on the theory underlying the technique of the chief operations of practical organic chemistry: it is considered that a proper understanding ‘of these operations cannot be achieved without a knowledge of the appropriate theoretical principles. Chapter II is devoted to a detailed discus- sion of experimental technique; the inclusion of this subject in one chapter leads to economy of space, particularly in the description of advanced preparations. It is not expected that the student will employ even the major proportion of the operations described, but a knowledge of their existence is thought desirable for the advanced student so that he may apply them when occasion demands. Chapters III and IV are confined to the preparation and properties of Aliphatic Compounds and Aromatic Compounds respectively. This division, although perhaps artificial, falls into line with the treatment in many of the exist- ing theoretical textbooks and also with the author’s own lecture courses. A short theoretical introduction precedes the detailed preparations of the various classes XXxiPREFACE TO THE FIRST EDITION of organic compounds: it is recommended that these be read concurrently with the student’s lecture course and, it is hoped, that with such reading the subject will become alive and possess real meaning. The partition of the chapters in this manner provides the opportunity of introducing the reactions and the methods of characterisation of the various classes of organic compounds; the foundations of qualitative organic analysis are thus laid gradually, but many teachers may prefer to postpone the study of this subject until a representative number of ele- mentary preparations has been carried out by the student. The division into sec- tions will facilitate the introduction of any scheme of instruction which the teacher considers desirable. Chapters V—X deal respectively with Heterocyclic and Alicyclic Compounds, Miscellaneous Reactions; Organic Reagents in Inorganic and Organic Chemistry; Dyestuffs, Indicators and Related Compounds; Some Physiologically-Active Compounds; and Synthetic Polymers. Many of these preparations are of course intended for advanced students, but a mere perusal of the experimental details of selected preparations by those whose time for experimental-work is limited may assist to impress them on the memory. Attention is particularly directed to the chapter on Organic Reagents in Inorganic and Organic Chemistry. It is always a good plan to set advanced students or adequately-trained laboratory assistants on the preparation of those compounds which are required in the laboratory for organic and inorganic analysis; the resulting cost is comparatively low (for o-phenanthroline, for example, it is less than one-tenth of the commercial price) and will serve to promote the use of these, otherwise relatively expensive, organic reagents in the laboratory. Chapter XI is devoted to Qualitative Organic Analysis. The subject is dicussed in moderate detail and this, coupled with the various Sections and Tables of Physical Constants of Organic Compounds and their Derivatives in Chapters III and IV, will provide a satisfactory course of study in this important branch of chemistry. No attempt that has been made to deal with Quantitative Organic Analysis in this volume. The textbook is intended to meet the requirements of the student of chemistry throughout the whole of his training. Considerable detail is given in those sec- tions of particular interest to the elementary student; in the author's opinion it is the duty of a writer of a practical textbook to lay a secure foundation of sound experimental technique for the beginner. The subject matter of the book is suffi- ciently comprehensive to permit the teacher to cover any reasonable course of instruction. It will be observed that the scale of the preparations varies consider- ably; the instructor can easily adapt the preparation to a smaller scale when such a step is necessary from considerations of cost and time or for other reasons. Quantities of liquid reagents are generally expressed as weights and volumes: the latter refer to a temperature of 20°. The book will be suitable for students pre- paring for the Pass and Honours (General and Special) B.Sc. of the Universities, the A.R.LC. and the F.R.I.C. (Organic Chemistry). It will also provide an intro- duction to research methods in organic chemistry and, it is hoped, may serve as an intermediate reference book for practising organic chemists. Attention is directed to the numerous references, particularly in Chapter II on Experimental Technique, to firms supplying specialised apparatus. The author has usually had first-hand experience with this apparatus and he feels that some readers may wish to know the present source of supply and also from whom to obtain additional information. It must be mentioned that most of the xxii