Organic Chemistry Organic Chemistry—online support Each chapter in this book is accompanied by a set of problems, which are available free of charge online To access them visit the Online Resource Centre at www.oxfordtextbooks.co.uk/orc/clayden2e/ and enter the following: Username: clayden2e Password: compound This page intentionally left blank ORGANIC CHEMISTRY SECOND EDITION Jonathan Clayden Nick Greeves Stuart Warren University of Manchester University of Liverpool University of Cambridge 1 Great Clarendon Street, Oxford OX2 6DP Oxford University Press is a department of the University of Oxford It furthers the University’s objective of excellence in research, scholarship, and education by publishing worldwide in Oxford New York Auckland Cape Town Dar es Salaam Hong Kong Karachi Kuala Lumpur Madrid Melbourne Mexico City Nairobi New Delhi Shanghai Taipei Toronto With offices in Argentina Austria Brazil Chile Czech Republic France Greece Guatemala Hungary Italy Japan Poland Portugal Singapore South Korea Switzerland Thailand Turkey Ukraine Vietnam Oxford is a registered trade mark of Oxford University Press in the UK and in certain other countries Published in the United States by Oxford University Press Inc., New York © Jonathan Clayden, Nick Greeves, and Stuart Warren 2012 The moral rights of the authors have been asserted Crown Copyright material reproduced with the permission of the Controller, HMSO (under the terms of the Click Use licence.) Database right Oxford University Press (maker) First published 2001 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, without the prior permission in writing of Oxford University Press, or as expressly permitted by law, or under terms agreed with the appropriate reprographics rights organization Enquiries concerning reproduction outside the scope of the above should be sent to the Rights Department, Oxford University Press, at the address above You must not circulate this book in any other binding or cover and you must impose this same condition on any acquirer British Library Cataloguing in Publication Data Data available Library of Congress Cataloging in Publication Data Library of Congress Control Number: 2011943531 Typeset by Techset Composition Ltd, Salisbury, UK Printed and bound in China by C&C Offset Printing Co Ltd ISBN 978-0-19-927029-3 10 Brief contents Abbreviations xv Preface to the second edition xvii Organic chemistry and this book xix What is organic chemistry? Organic structures 15 Determining organic structures Structure of molecules Organic reactions 43 80 107 Nucleophilic addition to the carbonyl group Delocalization and conjugation Acidity, basicity, and pKa 125 141 163 Using organometallic reagents to make C–C bonds 10 Nucleophilic substitution at the carbonyl group 182 197 11 Nucleophilic substitution at C=O with loss of carbonyl oxygen 12 Equilibria, rates, and mechanisms 13 1H 222 240 NMR: Proton nuclear magnetic resonance 269 14 Stereochemistry 302 15 Nucleophilic substitution at saturated carbon 16 Conformational analysis 17 Elimination reactions 328 360 382 18 Review of spectroscopic methods 19 Electrophilic addition to alkenes 407 427 20 Formation and reactions of enols and enolates 21 Electrophilic aromatic substitution 449 471 22 Conjugate addition and nucleophilic aromatic substitution 23 Chemoselectivity and protecting groups 24 Regioselectivity 498 528 562 25 Alkylation of enolates 584 26 Reactions of enolates with carbonyl compounds: the aldol and Claisen reactions 614 27 Sulfur, silicon, and phosphorus in organic chemistry 28 Retrosynthetic analysis 694 29 Aromatic heterocycles 1: reactions 723 30 Aromatic heterocycles 2: synthesis 757 31 Saturated heterocycles and stereoelectronics 32 Stereoselectivity in cyclic molecules 825 789 656 vi BRIEF CONTENTS 33 Diastereoselectivity 852 34 Pericyclic reactions 1: cycloadditions 877 35 Pericyclic reactions 2: sigmatropic and electrocyclic reactions 36 Participation, rearrangement, and fragmentation 37 Radical reactions 970 38 Synthesis and reactions of carbenes 39 Determining reaction mechanisms 40 Organometallic chemistry 41 Asymmetric synthesis 1069 1102 42 Organic chemistry of life 1134 43 Organic chemistry today 1169 Figure acknowledgements 1182 Periodic table of the elements 1184 Index 1187 1003 1029 931 909 Contents Abbreviations xv Preface to the second edition Organic chemistry and this book xvii xix Introduction 80 Electrons occupy atomic orbitals 83 Molecular orbitals—diatomic molecules 88 Bonds between different atoms 95 Organic chemistry and you Hybridization of atomic orbitals 99 Organic compounds Rotation and rigidity 105 Conclusion 106 11 Looking forward 106 Organic chemistry and this book 13 Further reading 106 Further reading 13 Organic reactions 107 Organic chemistry and the periodic table 80 What is organic chemistry? Organic chemistry and industry Structure of molecules Organic structures 15 Chemical reactions 107 Hydrocarbon frameworks and functional groups 16 Nucleophiles and electrophiles 111 Drawing molecules 17 Curly arrows represent reaction mechanisms 116 Hydrocarbon frameworks 22 Drawing your own mechanisms with curly arrows 120 Functional groups 27 Further reading 124 Carbon atoms carrying functional groups can be classified by oxidation level 32 Naming compounds 33 Nucleophilic addition to the carbonyl group 125 What chemists really call compounds? 36 How should you name compounds? 40 Molecular orbitals explain the reactivity of the carbonyl group 125 Further reading 42 Attack of cyanide on aldehydes and ketones 127 Determining organic structures 43 The angle of nucleophilic attack on aldehydes and ketones 129 Nucleophilic attack by ‘hydride’ on aldehydes and ketones 130 Addition of organometallic reagents to aldehydes and ketones 132 Addition of water to aldehydes and ketones 133 Introduction 43 Mass spectrometry 46 Mass spectrometry detects isotopes 48 Atomic composition can be determined by high-resolution mass spectrometry 50 Nuclear magnetic resonance Regions of the 13C NMR spectrum Different ways of describing chemical shift 52 56 57 Hemiacetals from reaction of alcohols with aldehydes and ketones 135 Ketones also form hemiacetals 137 Acid and base catalysis of hemiacetal and hydrate formation 137 Bisulfite addition compounds 138 Further reading 140 Delocalization and conjugation 141 Double bond equivalents help in the search for a structure 74 Introduction 141 Looking forward to Chapters 13 and 18 78 The structure of ethene (ethylene, CH2=CH2) 142 Further reading 78 Molecules with more than one C=C double bond 143 A guided tour of the simple molecules 13C NMR spectra of some 57 The 1H NMR spectrum 59 Infrared spectra 63 Mass spectra, NMR, and IR combined make quick identification possible 72 CONTENTS viii The conjugation of two π bonds 146 And to conclude 220 UV and visible spectra 148 Further reading 220 The allyl system 150 Delocalization over three atoms is a common structural feature 154 Nucleophilic substitution at C=O with loss of carbonyl oxygen 222 Aromaticity 156 Introduction 222 Further reading 162 Aldehydes can react with alcohols to form hemiacetals 223 Acidity, basicity, and pKa 163 Acetals are formed from aldehydes or ketones plus alcohols in the presence of acid 224 Organic compounds are more soluble in water as ions 163 Amines react with carbonyl compounds 229 Acids, bases, and pKa 165 Acidity 165 Imines are the nitrogen analogues of carbonyl compounds 230 The definition of pKa 168 Summary 238 171 Further reading 239 Equilibria, rates, and mechanisms 240 Constructing a pKa scale Nitrogen compounds as acids and bases 174 Substituents affect the pKa 175 Carbon acids 176 How far and how fast? 240 pKa in action—the development of the drug cimetidine 178 How to make the equilibrium favour the product you want 244 Lewis acids and bases 180 Further reading 181 Using organometallic reagents to make C–C bonds Introduction 10 11 12 182 182 Entropy is important in determining equilibrium constants 246 Equilibrium constants vary with temperature 248 Introducing kinetics: how to make reactions go faster and cleaner 250 Rate equations 257 Catalysis in carbonyl substitution reactions 262 183 Kinetic versus thermodynamic products 264 184 Summary of mechanisms from Chapters 6–12 266 Further reading 267 Organometallic compounds contain a carbon–metal bond Making organometallics Using organometallics to make organic molecules 189 Oxidation of alcohols 194 Looking forward 196 Further reading 196 13 1H NMR: Proton nuclear magnetic resonance 269 The differences between carbon and proton NMR 269 Integration tells us the number of hydrogen atoms in each peak 270 Nucleophilic substitution at the carbonyl group 197 The product of nucleophilic addition to a carbonyl group is not always a stable compound Regions of the proton NMR spectrum 272 197 Protons on saturated carbon atoms 272 Carboxylic acid derivatives 198 The alkene region and the benzene region 277 Why are the tetrahedral intermediates unstable? 200 Not all carboxylic acid derivatives are equally reactive 205 The aldehyde region: unsaturated carbon bonded to oxygen 281 Acid catalysts increase the reactivity of a carbonyl group 207 Protons on heteroatoms have more variable shifts than protons on carbon 282 Acid chlorides can be made from carboxylic acids using SOCl2 or PCl5 Coupling in the proton NMR spectrum 285 214 To conclude 301 Making other compounds by substitution reactions of acid derivatives Further reading 301 216 Making ketones from esters: the problem 216 Stereochemistry 302 Some compounds can exist as a pair of mirrorimage forms 302 Making ketones from esters: the solution 218 To summarize 220 14 CONTENTS Diastereoisomers are stereoisomers that are not enantiomers 15 16 17 ix 311 Anion-stabilizing groups allow another mechanism—E1cB Chiral compounds with no stereogenic centres 319 To conclude 404 Axes and centres of symmetry 320 Further reading 406 Review of spectroscopic methods 407 Separating enantiomers is called resolution 322 Further reading 327 18 399 There are three reasons for this chapter 407 Spectroscopy and carbonyl chemistry 408 Acid derivatives are best distinguished by infrared 411 Small rings introduce strain inside the ring and higher s character outside it 412 333 Simple calculations of C=O stretching frequencies in IR spectra 413 A closer look at the SN2 reaction 340 NMR spectra of alkynes and small rings 414 Contrasts between SN1 and SN2 342 The leaving group in SN1 and SN2 reactions 347 Proton NMR distinguishes axial and equatorial protons in cyclohexanes 415 415 Nucleophilic substitution at saturated carbon 328 Mechanisms for nucleophilic substitution 328 How can we decide which mechanism (SN1 or SN2) will apply to a given organic compound? 332 A closer look at the SN1 reaction The nucleophile in SN1 reactions 352 The nucleophile in the SN2 reaction 353 Interactions between different nuclei can give enormous coupling constants Nucleophiles and leaving groups compared 357 Identifying products spectroscopically 418 Tables 422 Looking forward: elimination and rearrangement reactions 358 Further reading 359 Conformational analysis Shifts in proton NMR are easier to calculate and more informative than those in carbon NMR 425 Further reading 426 Electrophilic addition to alkenes 427 360 19 Bond rotation allows chains of atoms to adopt a number of conformations 360 Alkenes react with bromine 427 Conformation and configuration 361 Oxidation of alkenes to form epoxides 429 Barriers to rotation 362 Conformations of ethane 363 Electrophilic addition to unsymmetrical alkenes is regioselective 433 Conformations of propane 365 Electrophilic addition to dienes 435 Conformations of butane 365 Unsymmetrical bromonium ions open regioselectively 436 Ring strain 366 A closer look at cyclohexane 370 Electrophilic additions to alkenes can be stereospecific 439 Adding two hydroxyl groups: dihydroxylation 442 Breaking a double bond completely: periodate cleavage and ozonolysis 443 Adding one hydroxyl group: how to add water across a double bond 444 To conclude .a synopsis of electrophilic addition reactions 447 Further reading 447 Formation and reactions of enols and enolates 449 Would you accept a mixture of compounds as a pure substance? 449 Tautomerism: formation of enols by proton transfer 450 Why don’t simple aldehydes and ketones exist as enols? 451 Substituted cyclohexanes 374 To conclude 381 Further reading 381 Elimination reactions 382 Substitution and elimination 382 How the nucleophile affects elimination versus substitution 384 E1 and E2 mechanisms 386 Substrate structure may allow E1 388 The role of the leaving group 390 E1 reactions can be stereoselective 391 E2 eliminations have anti-periplanar transition states 395 The regioselectivity of E2 eliminations 398 20 1224 INDEX pyrazine 9, 724 pKa of 748 pyrazole 725 pyrazoles, alkylation of 769 from 1,3-diketone and hydrazine 760, 768, 769 nitration of 769 retrosynthetic analysis of 768–9 pyrethrins 11, 664, 1016 pyrethrum flowers, chrysanthemic acid from 292 pyridazine 724 1H NMR spectrum 752 from 1,4-diketone and hydrazine 759–60, 767–8 from dihydropyridazolone 767–8 nucleophilic substitution of 748–9 pKa of 748 retrosynthetic analysis of 767 α-effect in 748 pyridine 37 1H NMR spectrum 282, 724 activated, electrophilic aromatic substitution of 729–30 as a polar organic solvent 337, 726 as a weak base 337 as nucleophilic catalyst of acylation 199–200 as nucleophilic catalyst of bromination 726, 731 comparison of structure with benzene 724 complex with chromium trioxide (Collins’ reagent) 194 conjugation in 282 electrophilic aromatic substitution of 726–7 Hantzsch synthesis 763–5, 783 HOMO of 729–30 nucleophilic substitution on 728 orbital structure of 724 pKa of 175, 630, 726, 792 reactivity of 725–6 retrosynthetic analysis of 763, 766 synthesis from 1,5-diketones 759, 765–6 synthesis, from acetaldehyde and ammonia 758 unreactivity towards Friedel–Crafts acylation 727 unreactivity towards nitration 727 use in Mannich reaction 624 pyridine N-oxide 730–1 2-methyl, reaction with acetic anhydride 731 reduction to pyridine 730 pyridinium chlorochromate see PCC pyridinium dichromate see PDC pyridinium tribromide 731 pyridones 728–9, 781 chlorination by reaction with POCl3, 729 from acetamide and 1,3-dicarbonyl 766–7 from hydroxypyridines 728 pyridoxal 235, 1151 pyridoxal phosphate 1157–8 pyridoxal transaminase 1159 pyridoxamine 235, 1151 pyrilium cation 733 pyrimidine 724 1H NMR spectrum 285–6 pKa of 748 pyrimidines, as bases in nucleic acids 1136 from amidine and 1,3-diketone 760, 770–1 retrosynthetic analysis of 770 role in biochemistry and medicine 754 pyrolysis, of formate group 968 pyrones, Diels–Alder reaction of 739 structure and regioisomers of 732 pyrophosphate (PP) 1166 pyrrole 725 1H NMR spectrum 283, 422, 725, 733 acylation by Vilsmeier reaction 733–4 asymmetric Friedel–Crafts reaction of 1128 Boc protection of 740 bond lengths in 733 bromination of 733 decarboxylation of 735 delocalization in 733 Diels–Alder reaction of 739 electrophilic aromatic substitution reactions of 733–5 formation of porphyrins from 753 HOMO of 733, 744 Knorr synthesis of 761–3 Mannich reaction of 734 nucleophilic substitution on 738–9 nucleophilicity at nitrogen 740 orbitals of 725 pKa of 732 polymerization with acid 733 retrosynthetic analysis of 758, 761–2 synthesis, from 1,4-dicarbonyl compounds 758–9 synthesis, strategies for substituted pyrroles 761–3 tert-butyl ester as blocking group with 761 pyrrolidine 233, 790–1 enamine formation with 592, 608 in Mannich reaction 622 N-Boc, asymmetric lithiation of 1113 rate of formation by ring-closing reaction 809–10 pyrrolidine alkaloids 1156–8 pyruvate 1153–4 pyruvic acid (2-oxopropanoic acid) 28, 229, 1134–5, 1153–4 conversion to alanine by reductive amination 235 reduction by NADH to form (S)-(+)-lactic acid 1150 Q quartet, in 1H NMR 291–2 quartz crystals, chiral 323 quaternary carbon, meaning of 27 queen bee substance, synthesis of 685 quinic acid 1155, 1175 quinine 2, 723, 755, 780 quinine-derived ligands, for Sharpless asymmetric dihydroxylation 749, 1123–6 quinoline 749, 755 as additive in catalytic hydrogenation 537–8 by reaction of aniline with α,β-unsaturated carbonyl compounds 781 from 1,3-dicarbonyl compounds and anilines 781–2 nitration of 749 N-oxide 750 oxidation with potassium permanganate 750 retrosynthetic analysis and synthesis of 781–2 role in biochemistry and medicine 755 Skraup synthesis 781–2 nucleophilic aromatic substitution of 784 8-quinolinol (oxine) 782 quinolone 781 reaction with POCl3 783–4 retrosynthetic analysis and synthesis of 782–3 synthesis, from enamine diester 783 quinolone antibiotics 782–3 quinone, as dienophile in Diels–Alder reaction 879 quintet, in 1H NMR 291–2 quinuclidine, pKa of 791 structure of 791 R R see gas constant R, as abbreviation for alkyl group 29 R,S nomenclature 308–9 racemic mixture 307–8 racemization, in SN1 343–4 of drugs in vivo 460 of stereogenic centres adjacent to carbonyl groups 459–60 radical abstraction 572–3, 972–3 radical addition, borane-oxygen method 998–9 C–C bonds by 992–9 concentration effects in 994–5 for formation of carbon–carbon bonds 993–4 frontier orbital effects in 995–6 of triplet carbenes to alkenes 1015 regioselectivity of 571–2, 574 tin method 993–6 to acrylonitrile 993–4 to alkenes 571–2, 971, 973, 992–7 radical anions and cations, in mass spectrometry 47 radical bromination, allylic 989–90 of alkanes 988–9 radical chain reaction 571–4, 984–1102 of alkene with HBr 984–5 summary of steps in 985–6 radical chlorination, regioselectivity of 986–8 radical copolymerization 997 radical initiator, AIBN as 991–2 borane-oxygen as 998–9 radical reactions 571–4, 970–1002 intramolecular 999–1002 regiocontrol in 571 radical substitution 972–3, 990–2 INDEX radical–radical reactions 980–4 by borane-oxygen method 998–9 radicals, by dissociation of hydrogen chloride 970 captodative 978 conjugate addition of 998–9 EPR for determination of structure 975–6 formation, by addition 973 by elimination 974 by homolysis of weak bonds 971–2, 974, 985 by hydrogen abstraction 972–3 by photochemical homolysis 971 summary 974 from dissolving metal reactions 542–3 hard/soft reactivity of 997–8 in acyloin reaction 983–4 in Birch reductions 542–3 in mass spectrometry 47 in McMurry reaction 982–3 ketyl, pinacol reaction of 981, 983–4 molecular orbitals (SOMO) of 976–9 persistent 974–5, 979 reduction of carbonyl group via 981 regiocontrol in reactions of 571 stability, factors affecting 977–9 summary of reactions 980, 998 trapping by vitamin E 975 unreactive 974–5, 979 writing mechanisms involving 972 radical-stabilizing groups, summary of 979 radio waves, in NMR 53 radioactive isotopes, use and disadvantages of 1037–8 see also isotopic labelling Raney nickel 537 for reduction of aromatic nitro groups 728 for reduction of sulfides and thioacetals 540, 663 for reduction of thiophene 737 ranitidine 512 raspberry ketone 536 raspberry ketone, 13C NMR spectrum 409 rate constant, k 257 rate-determining step (rate-limiting step) 257–8 change of 1049 experimental determination of 1041–8 in SN1 and SN2 reactions 330, 332 rate equation 257–62 experimental determination of 330 for SN1 332 for SN2 330 use in determining reaction mechanisms 1031–2 rate-limiting step see rate-determining step rate of bond rotation, relation to energy barriers 363 rate of reaction 250–66 effect of pH 262–3 effect of solvents 255 intramolecular vs intermolecular 938 nucleophilic substitution, effect of participation on 931–2 ring formation and relation to size 806–7 SN1 and SN2, factors affecting 331–2, 347–8 compared 345–6 rates, and spectroscopy 374 Re and Si, in assignment of prochiral faces and groups 856–7 reaction constant, ρ 1043–4 reaction coordinate, definition of 243 reaction intermediates 253 detection by spectroscopy 419–20 effect of solvent on 256 variation of concentration with time 264 reaction kinetics 250–66 reaction mechanism, detecting change of 1048 drawing curly arrows for 109, 120–4 establishing experimentally 1029–68 relationship to kinetics 258 reactivity, poor correlation with bond strength 207 quantified effects of structure (Hammett relationship) 1041–8 relation to 1H NMR chemical shifts 280, 281 reagent control, in asymmetric synthesis 1113–14 rearrangement, [1,5]-sigmatropic 919–22 [3,3]-sigmatropic 731 allylic, palladium catalysed 1097 Beckmann 958–60, 1145 benzilic acid 950 by alkyl group migration 940–4 by ring expansion to relieve ring strain 944–5 Claisen 909–12 Cope 913–17 Curtius 882, 1022 during Friedel–Crafts alkylation 945 Favorskii 950–3 guidelines for spotting 945 Ireland–Claisen 914 Lossen 1022 of carbenes 1020–1 of carbocations 940–5 of dienone to phenol 949–50 of diols 945–6 of epoxides 946 of nitrenes 1022 of β-halo amine 938 orbital description of 941–2 Payne 938–9 pinacol 945–9 semipinacol 947–9 sigmatropic 909–22 stereochemistry of 957–8 Wagner–Meerwein 942–4 Wolff 1021 working out mechanisms for 941, 943–5 rearrangement reactions 931, 937–59 recrystallization, for purification 1112 to improve ee 1112 red wine, resveratrole from 1164 RedAl, to reduce alkynes to E alkenes 682–3 reduced mass 64–5 reducing agents 530–43 bulky 603 chiral 1114–17 effect of size on diastereoselective reactions 826–8, 832, 834 1225 in nature (NADH or NADPH) 1140, 1149–50 summary (table) 534 reduction see also catalytic hydrogenation asymmetric, using CBS catalyst 1114–15 asymmetric, by hydrogenation 1115–17 in nature 1150 Birch, of aromatic rings or alkynes 542–3, 973 Bouveault–Blanc 981 by single electrons 542–3, 973, 981 chelation-controlled stereoselectivity of 863 chemoselective, of ketone in presence of ester 529 summary table of chemoselective reducing agents 534 Clemmensen 493–4 diastereoselective, of a cyclopentanone 834 of a four-membered ketone 833 of a spirocycle diketone 847 of bridged bicyclic compounds 840 of chiral carbonyl compounds 858–61 of Wieland–Miescher ketone 845 dissolving metal, of enones 602–3 Luche 506 of alkenes 534–7 see also hydrogenation of alkynes 537, 542–3 see also hydrogenation of amides 701, 702 of aromatic rings 537, 542 of aromatic nitro groups 495, 728, 769 of benzylic ketones to methylene groups 493–4 of carbonyl compounds, chemoselectivity in 530 of chiral ketone, chelation control in 864 Felkin–Anh model for 861 of conjugated double bonds 603 of diazonium salt to hydrazine 777 of imines by catalytic hydrogenation 538 of isoxazoles 751 of ketone with borohydride 119, 257–8 of nitrile to amine 716 of nitroalkene to nitroalkane 623, 624 of N–O bonds by zinc 902 of oximes 702 of pyridine N-oxides 730 of sulfones, by sodium amalgam, in Julia olefination 686 of thiophene with Raney Ni 737 of α,β-unsaturated ketones in presence of cerium chloride 506 reductive amination 234–7, 538, 701–2 asymmetric, in nature 1150–1 by catalytic hydrogenation 538 to form amine 701–2 using a nitrile 716 with benzylamine 717 reductive elimination, in palladium catalysed reactions 1074–87, 1093, 1096 in transition metal complexes 1074–5 reflux 245 Reformatsky reaction 631, 713 refractive index changes, detection by HPLC 1111 1226 INDEX regiocontrol see also regioselectivity in synthesis of aromatic compounds 566–8 strategies for 563–82 see also regioselectivity using tethers 568–9 regioselectivity 562–83 by kinetic or thermodynamic control 566 enones to control in enolate formation 601–5 from elimination reactions 569–70 of alkylation of acetoacetate dianion 601 of alkylation of ketone enolates 590, 592, 595–604, 613 of allylic substitution using palladium 1088–92 of aromatic sulfonation 565 of attack on cyclic sulfates 1125 of Baeyer–Villiger oxidation 953–8 of benzyne reactions 524, 568 of Birch reductions of aromatic compounds 542–3 of Claisen condensation of ketones 645 of conjugate addition to α,β-unsaturated carbonyl compounds 504–8, 581–2 of cycloaddition to form triazoles 775 of Diels–Alder reactions 889–91 of electrophilic addition to alkenes 433–5 of electrophilic aromatic substitution 479–80, 486–90, 565 of epoxide opening 438–9, 836–9, 1125 of formation of enamines and enols 592 of formation of enolates from ketones, summary 601 of halogenation of ketones 469 of halolactonization 568–9 of Heck reaction 1080–1 of hydration of alkenes and alkynes 444–7, 571 of hydroboration of alkenes 446–7 of intramolecular reactions 568–9, 653–4, 891 of nitrosation of ketones 464–5 of nucleophilic aromatic substitution 515–17 of nucleophilic attack on bromonium ions 436–7 of opening of cyclohexene epoxides 836–9 of photochemical [2+2] cycloadditions 898 of radical bromination of an alkene 986 of radical ractions compared with ionic reactions 571–4, 986 of reactions of indole 746 of reactions of pyrrole, thiophene, and furan 735 of reactions of silanes 672–7 of reactions of vinyl, aryl, and allyl silanes 676 of ring opening of aziridine 939 of SN1 reactions 336–7 of sulfonation of toluene 485–6 regiospecific, definition of 577 Reissert indole synthesis 779–80 relative configuration 313, 1104 relative stereochemistry 313, 1104 control of 825–76 relaxation, of protons, in 1H NMR 799 between axial substituents 374–8 between molecules 108–9 between orbitals in eclipsed conformation 364–5 resolution 322–7, 1106–7, 1111, 1133, 1173 resolving agent 325 resveratrole 6, 1164 retinal 1, 681 13C NMR spectrum 409 retro-aldol reaction 605–6 retro-Diels–Alder reaction 739–740, 884–5 retrosynthetic analysis (retrosynthesis) 694–722 chemoselectivity problems in 698–9 common starting materials for 711–12 definition of terms used in 697, 712 donor and acceptor synthons in 712 functional group interconversion (FGI) in 699–702 of 1,2-difunctional compounds 720 of 1,3-difunctional compounds 713, 717 of 1,4-difunctional compounds 721–2, 760, 770 of 1,5-difunctional compounds 719 of 2-amino alcohols 715 of 3-amino alcohols 715, 716–17 of 3-amino ketones 716 of 3-hydroxy ketones 713 of acetals 715 of alkenes 707, 720 of alkynes 706–7 of amides 695, 696, 701 of amines 698, 699–702 of aromatic heterocycles 757–88 of diols 720 of esters 695, 698, 707 of ethers 696–9, 704, 708, 717 of furan 758–9 of pyrrole 758 of sulfides 697–8 of α,β-unsaturated carbonyl compounds 713–14 of β-hydroxy ketones 713 umpolung reactivity in 719–21 using aldol reaction 712 using Claisen ester disconnection 717 using Friedel–Crafts acylation 720, 722, 782 using Mannich reaction 716–17 retrosynthetic arrows 694 reverse cycloaddition see also retroDiels–Alder [2+2], in olefin metathesis 1024 [3+2] 685, 906 [3+2], in decomposition of THF 795 reverse electron demand Diels–Alder reactions 887 reverse oxypalladation 1097 reverse pinacol rearrangement 949–50 reverse transcribtase inhibitor 1171 reversibility, of cyanohydrin formation 128 of Diels–Alder reaction 884–5 of reactions on heating 248–9 of sigmatropic rearrangements 918 ρ (rho), reaction constant 1043–4 rhodium, as catalyst, for asymmetric hydrogenation 1117–19 for carbene insertion 1019–20, 1023 for hydrogenation 535 for nitrile reduction 716 carbene complex of 1007 rhodopsin 681 ribofuranose 1143 ribonucleic acid see RNA ribonucleotide 1143 ribopyranose 1143 ribose 137, 315–16, 1134–7, 1142–3 ribosome 1139, 1180 ring-closing metathesis 1023–4 ring-closing reactions, activation energy of 806–7 classification of, by Baldwin’s rules 810 effect of ring size on reactions 806–7 in synthesis of saturated heterocycles 805–13 thermodynamic control of 808–10 Thorpe–Ingold effect in 808–10 ring closure, electrocyclic 922–3 ring contraction, in Favorskii rearrangement 952 ring current, effect on 1H NMR chemical shifts 277 ring expansion, by fragmentation 963–5 in α-caryophyllene alcohol synthesis 944–5 of cyclic ketone using diazomethane 949 ring flipping, of cis-decalin, 845 impossibility of in trans-decalins and steroids 378–9, 381 in substituted cyclohexanes 838 of six-membered rings 373–4, 376–81 ring formation, kinetic control of 806–10 rate and relation to size 806–7 thermodynamic control of 808–10 Thorpe–Ingold effect in 808–10 ring inversion see ring flipping ring opening, Baldwin’s rules for 810, 813–14 electrocyclic 922–4, 928–9 of aziridine 793, 929 of cyclic ethers 794 of epoxides, stereospecificity of 854 of small rings, by electrocyclic reactions 928–9 regioselective, of cyclohexene oxides of reactions 836–9 ring size, and 1H NMR 814–17 and geminal (2J) coupling 819–20 and neighbouring group participation 935 small, medium, and large, definition of 806 thermodynamic control of in acetal formation 808 ring strain 366–8 and leaving group ability 351–2 driving ring-opening reactions 793–4 driving rearrangement 944–5 effect on IR carbonyl stretching frequency 413 effect on orbital hybridization 413 effect on rate of ring formation 806–7 ring synthesis, by double alkylation of 1,3-dicarbonyl compounds 598 by intramolecular acyloin reaction of esters 984 INDEX by intramolecular alkylation 586–7 by intramolecular radical reactions 1000–1 by palladium catalysed cyclization 1091 five-membered, by [3+2]-dipolar cycloadditions 901–5 four-membered, by [2+2] cycloadditions 897–901 heterocycles, aromatic 757–788 saturated 805–14 seven membered, by [4+3] cycloadditions 893–4 ten-membered, using Stille coupling 1084 by alkene metathesis 1023–4 rings, bicyclic, stereoselectivity in 839–49 bond angles in (table) 367 bridged bicyclic, stereoselectivity in 839–41 cis and trans alkenes in 678–9 diastereoselectivity in, summary 851 effect on nucleophilicity of heteroatoms 791–2, 794 evidence for lack of planarity in 368, 370 five-membered, 1H NMR couplings in 817 conformation of 370, 834–5 stereoselective reactions of 835–6 formation by metathesis 1099–100 four-membered, 1H NMR coupling in 816–17 conformation of 369, 833 stereoselective reactions of 833 fused bicyclic, stereoselectivity in 841–6, 841–6, 848–50 in transition states and intermediates 847–51 saturated, rate of ring-closing reactions 806 six-membered, 1H NMR and axial/ equatorial substitution 797–9, 802, 818–19 conformational preference in 456, 457–74, 826–32, 837–9 diastereoselective attack on 826–9 equatorial vs axial attack on 825–32 germinal (2J) couplings in 819–20 how to draw 371–4 opening of epoxides fused to 836–9 reactions of 826–32, 837–9, 850–1 small, effect on pKa 794 fragmentation in 961 small, medium, and large, definitions of 368 spirocyclic, stereoselectivity in 846–7 temporary, for control of stereochemistry 847–51 three-membered, conformation of 369 NMR coupling in 815 ritonavir 10 Ritter reaction 353, 1173 determination of mechanism 1065–6 relationship to Beckmann fragmentation 959–60 RNA (ribonucleic acid) 1136, 1138–9 biological synthesis of 1139 stability compared with DNA 1138–9 Robinson, Robert 638 Robinson, tropinone synthesis of 1158 Robinson annelation 638–9 rogletimide 707–8, 719 ‘roofing’, in 1H NMR 298, 822 rose oxide ketone 790 rose, pigment from 1145 smell of rosoxacin, structure and synthesis of 783 rotation, of amide bond, rate constants 256 of bonds 360–1 energy barriers 362–3 in 1H NMR 274 rotation, of plane-polarized light (optical rotation) 309–10 ruminants, cellulose digestion in 1147 ruthenium, as catalyst 1099–100 for alkene metathesis 1023–7 for asymmetric reduction of carbonyl group 1115–17 for hydrogenation 535 in asymmetric hydrogenations of alkenes 1116–19 S s orbital 84–5 SAC see specific acid catalysis saccharides 1146–7 saccharin, synthesis of 485 para-toluenesulfonic acid as by-product 227 S-adenosyl methionine (SAM) 1136–7, 1157–8, 1160 salbutamol, protecting group strategy in synthesis of 552 salen (salicylethylenediamine) ligand 1122–3, 1179 salicylic acid, synthesis and 13C NMR spectrum 409, 481–2 salmefamol 530 SAM (S-adenosyl methionine) 1136–7, 1157–8, 1160 sandalwood oil, fragrance 942 sandaverine, synthesis of 793 santene 942 saponification 212 saturated carbons, protons attached to in 1H NMR 272–6 saturated fats 31, 211, 536 saturated fatty acids 1161 saturated, meaning of 29 Saytsev’s rule 399 SBC see specific base catalysis s-Bu see sec-butyl Schiff base 235 Schlosser’s base 1008, 1019 Schotten, Carl 203 Schotten–Baumann method 203 Schreiber, Stuart L 929–30 Schrock, Richard 1025, 1084 s-cis 879–80 scurvy, cause and treatment 1141 Seagal, Irving 1171 sea-hare (Dolabella), anticancer agent from 861 seaweed pheromone, [3,3]-sigmatropic rearrangement of 915 sec-butanol, inversion by SN2 343 1227 sec-butyl 26–7 second law of thermodynamics 246 second-order reaction 258–9, 329, 331–3 secondary carbon, meaning of 27 carbon, SN2 at 341–3, 347, 380–1 secondary metabolism 1134, 1156 selectivity see also chemoselectivity, regioselectivity, and stereoselectivity 528 selectride see L-selectride, K-selectride selenium dioxide, in allylic oxidation of alkenes 919 selenium, and sulfur compared 686 oxidation to selenoxides 685–6 selenoxides, by oxidation of selenides 685–6 elimination to form alkenes 686 in [2+3]-sigmatropic rearrangements 918–19 self-condensation, avoiding 585–613 in aldol reactions 616–18 semicarbazide 232 semicarbazone 232 semipinacol rearrangement 947–9 separation of enantiomers 322–7 septamycin, step in synthesis of 218 serine L-serine, as starting material in asymmetric synthesis 873–5, 1107 serine 554, 1104 serotonin 1, 755, 777 serricornin seven-membered ring synthesis, by [4+3] cycloaddition 893–4 sex hormone 379, 949, 1167 S-glycosides 1145–6 shape, of molecules 80–105 Sharpless, K Barry 1116 Sharpless asymmetric aminohydroxylations (AA) 1120 Sharpless asymmetric dihydroxylations (AD) 1120, 1123–6 Sharpless asymmetric epoxidation (AE) 1120–3, 1172 Sharpless ‘click’ synthesis of triazoles 775 shell, in electronic structure 86 shielding, in NMR 54, 270 shifts, chemical see chemical shifts sigmatropic 919 see also sigmatropic shifts shikimic acid 1154–6, 1163 13C NMR spectrum 409 in synthesis of oseltamivir (Tamiflu) 1175 pathway 1154–6 short-cuts (short-hand), allowable when drawing mechanisms 204, 217, 267 shower gel, ingredients of 6–8 Si and Re, in assignment of prochiral faces and groups 856–7 σ bond, as a nucleophile 113, 119 σ orbital 91–5 σ* orbital 91–5 σ, substituent constant 1042–3 σ-complex 1071 σ-conjugation 484 sigmatropic 910 [1,3]-sigmatropic hydrogen shifts 921, 919–22 [1,5]-sigmatropic hydrogen shifts 919–21 [1,7]-sigmatropic hydrogen shifts 921 1228 INDEX [2,3]-sigmatropic rearrangement 917–19 [3,3]-sigmatropic rearrangement 731, 909–17 in Fischer indole synthesis 776 in synthesis of citral 915 of silyl enol ethers and lithium enolates 914 sigmatropic reactions (rearrangements) 909–22 reversibility of 918 sigmatropic shifts 919–21 silanes 656, 668 alkynyl, for protection and activation 671–2 allyl, as nucleophiles 675–7 aryl, ipso substitution with electrophiles 672–3 reactivity of, compared to alkenes 675 regioselectivity of reactions of 672–7 vinyl and aryl and allyl, reactions with electrophiles, summary 676 vinyl, electrophilic substitution of 673–4 sildenafil see Viagra silica, SiO2 325 silicon, affinity for electronegative atoms 668–9 compared with carbon 668–74 in organic chemistry 669–77 nucleophilic substitution at 469, 669 β-cation stabilization by 672 silkworm, pheromone of 692 silver nitrate, in rearrangement of neopentyl iodide 940 silver oxide, as halogen-selective Lewis acid 934 silyl enol ethers, [3,3]-sigmatropic rearrangement of 914 1H NMR spectrum 280–1, 282 alkylation of 595 as specific enol equivalent 624, 466–7 for regioselective halogenation 469 formation, from lithium enolates 466 thermodynamic control in 599–600, 636 in aldol reactions 626 in conjugate additions 608–9 of esters 631 palladium catalysed oxidation ro enones 1097 reaction with PhSCl 470 stability, influence of substitution on 600 silyl ethers, as protecting group 549–50, 635, 670 for alcohols 670 cleavage by TBAF 669 from acyloin reaction of esters with TMSCl 984 removal of 550 silyl groups, as ‘super-protons’ 671–3 silyl halides, regioselective reaction with enolates 466–7 silyl ketene acetals 609 silyl triflates 670 silylating agents, in conjugate addition reactions 508 Simmons–Smith reaction 1009, 1017–18 single bonds, region in IR spectrum 65 single electron reductions 973 singlet carbene see carbene, singlet singlet, in 1H NMR 286 singly occupied molecular orbital see SOMO Singulair see montelukast sinigrin 1145 sirenin 1018 six-membered rings 456, 457–74 1H NMR of axial vs equatorial substitution 818–19 conformational preference in 826–32, 837–9 equatorial vs axial attack 825–32 fragmentation of in synthesis of nootkatone 968 geminal (2J) couplings in 819–20 how to draw 371–4 opening of epoxides fused to 836–9 rate of reaction 806–7 SN2 reactions on 379–81 stereochemical control in 826–32, 837–9 synthesis by [4+2] cycloadditions 878–93 vicinal (3J) coupling in 797–9, 802 16-electron complexes 1070 skeleton, of insects and crustaceans 1147 Skraup quinoline synthesis 781–2 skunk, smell of 4, 657 small rings, definition of 368, 806 effect on pKa 794 smell, and stereochemistry 1102–3 Smith, Kline and French 178 SmithKline Beecham 178 SN1 and SN2 see also substitution SN1 and SN2 mechanisms, choice between 333, 347 contrasts between 342–7 effect of leaving group 347–52, 357–8 effect of nucleophile 352–8 electronic effects 346–7 kinetic evidence for 329–33 reaction rate and structure (table) 342, 345–6, 347, 355–6 relative rates compared 345–6 solvent effects 344–6 stereochemical consequences 343–4 steric effects 342–3, 380–1 SN1 reaction, competition with E1 elimination 467–8 energy profile diagram 334 examples of 336, 558 of allyl systems 576 regioselectivity in 336–7 with aromatic electrophiles see nucleophilic aromatic substitution, SN1 mechanism with benzene as nucleophile 477 SN2 reaction 340–2, 557 at secondary centre 341–3, 347 at tertiary centre 343, 347, 705 effect of nucleophiles, (tables) 355–6 in opening of epoxide 438 inversion of stereochemistry in 439–41 loose see loose SN2 molecular orbitals and 356 on allylic compounds 574, 578–9 on six-membered rings 379–81 stereospecificity of 853 transition state of 340–1, 343 SN2’ reaction 574 compared with SN2 574–5 SNAr see nucleophilic aromatic substitution SEAr see electrophilic aromatic substitution soap 212, 1148 SOCl2 see thionyl chloride sodium, for reduction of carbonyl group 973, 981, 983–4 sodium acetylide, from deprotonation of acetylene 171, 187, 189 sodium amalgam, as reducing agent in Julia olefinition 686 sodium amide, as base 170–1, 187, 589 in formation of benzyne 523–5 sodium borohydride 131–2, 193, 251, 253 see also borohydride chemoselectivity of reactions with carbonyl compounds 132 comparison with lithium aluminium hydride 132 for reduction of aldehydes and ketones 130–2, 530–1 in demercuration 444–6 in radical chain reactions 994 mechanism of reduction with 131 reduction of lactones 617 of α,β-unsaturated carbonyl compounds 506, 536–7 of α,β-unsaturated nitro compounds 511 sodium bromide, insolubility in acetone 255 sodium chloride, bonding in 96–7 energy level diagram of 97 in Krapcho decarboxylation of esters 598 reaction with sulfonic acid 477 sodium cyanide see cyanide sodium cyanoborohydride 234 sodium enolates 589, 607 sodium ethoxide, as a base 644, 596 sodium hexamethyldisilazide (NaHMDS) 589 sodium hydride, as base in Claisen condensation 645, 654 sodium hypochlorite (bleach) 195, 1123 sodium in liquid ammonia, as reducing agent 542–3, 682 sodium iodide, solubility in acetone 255 sodium nitrite, in formation of diazonium compounds 521 in nitrosation of enols 464–5 sodium periodate 443, 661 sodium triacetoxyborohydride 234 sodium trichloroacetate, in dichlorocarbene synthesis 1009 sodium triphenylmethyl, as base 643 sodium vapour lamps 82 soft and hard nucleophiles 357, 658 radicals 998 Solanaceae alkaloids 1156 solanine, alkaloid 1156 solenoid 277 solubility, of acids and bases 163–4 solvation, of salts by water 255 solvent choice, for ionic salts 187, 345 for organometallics 187 in organic reactions 255 solvent effects, in SN1 and SN2 344–6 INDEX solvent isotope effect, use in determining reaction mechanisms 1055–6 solvent peak, in 13C NMR 55 solvent, as catalyst 256–7 as nucleophile 337–8, 345–6, 353 as reagent 255 see also solvolysis choice of, for ionic salts 187, 345 classes of (protic, aprotic, polar, non-polar) 163, 255–6 deuterated, for NMR 272, 284–5 dielectric constants (polarity) of (table) 256 effect on Diels–Alder reaction 888 effect on reaction rates and products 255–7 effect on SN1 vs SN2 substitution reaction 344–6 for organolithium and Grignard reagents 186, 255, 795 in limiting pKa 170–1 pyridine as 337, 726 solvolysis 337–8, 931–2 SOMO (singly occupied molecular orbital) 976–7, 995–7 Sonogashira coupling 1083, 1087–8 sp orbital 102 sp2 orbital 100–2 sp3 orbital 99–100 sparteine 1113–14 spearmint odour, (R)-(–)-carvone 1102–3 specific acid catalysis (SAC) 262, 1053 evidence for 1053–5 in acetal hydrolysis 1059 in dienone–phenol rearrangement 1054 in ester hydrolysis 1053 inverse solvent isotope effect in 1054–5 specific base catalysis (SBC) 262, 1053 evidence for 1055–6 in epoxide opening 1055 in hydrolysis of ester 1056 specific enol equivalents (table) 624–5 for aldehydes and ketones 591–5, 595, 632, 634 for control of acylation 648–52 for esters 631 from 1,3-dicarbonyl compounds 628 Wittig reagents as 627 specific rotation 310 spectrometry, mass see mass spectrometry spectroscopic methods, for identification of unknown compounds 72–8, 418–22 summary of 46, 408 spectroscopy 43 and rates 374 EPR (ESR) see EPR for detection of reactive intermediates 419–20 NMR see NMR, 1H NMR or 13C NMR sphingosine 683 spider toxin, synthesis of 236–7 spin, of electrons 84 spin-flipping, in carbenes 1014–15 spiro compounds 432, 653 chirality of 320 spiroacetals 803 spirocycles, stereoselectivity in 847 synthesis via pinacol rearrangement 946 spiroepoxides 432 spiroketals 803 square brackets, in nomenclature of sigmatropic rearrangements 910 in terminology of cycloadditions 894 stability, of cyclic and acyclic hemiacetals and acetals 223, 227, 247 of radicals, factors affecting 977–9 of tetrahedral intermediates 200–1, 218–20 stability, relative, of cis vs trans alkenes 241 stabilized ylids 689–90, 691–3 staggered conformation 363–4 stannanes, in Stille coupling 1084–7 star anise 1175 starting materials, choosing, for synthesis 711–12 stationary phase, chiral, for determination of enantiomeric excess 1111 in chromatography 325–7 Staudinger reaction 1176 stearic acid (octadecanoic acid) 212, 536, 1161 stereochemical memory 835 stereochemistry 302–27 absolute 313 control of 1102–33 as means of determining reaction mechanisms 1063–7 cis vs trans, and coupling constants 815 drawing 21 effect on fragmentation 962–4 elucidation using NOE 799–800 in rings, control of 825–51 in SN1 and SN2 reactions 343–4 indication of neighbouring group participation 932–4, 936–7 inversion of in Mitsunobu reaction 350–1 of [2,3]-sigmatropic rearrangements 917–18 of electrocyclic reactions 925–6, 929 of epoxide opening 352, 354 of ester formation 351 of sigmatropic shifts, summary 919–21 of sugars 1142–5 relative 313 control of 825–76 stereoelectronic effects 789–824 and conformation of saturated heterocycles 801–5 anomeric effect 801–3 explanation for Baldwin’s rules 810–14 in acyclic acetals 804 in esters 804–5 orbital requirements for 804 summary 801 stereogenic centre 306–7 how to draw 309 nitrogen as in aziridine 794 compound with more than one 313–17 stereoisomers 303, 306, 309, 311, 361 number of possible 316–18 of imines and oximes 231 of substituted cyclohexanes 376–8 stereoselective, definition of 396, 852 stereoselectivity, effect of chelation 862–5 Felkin–Anh control 864 in [2+2] cycloadditions 897, 900–1 1229 in reactions of vinyl silanes 673–4 in alkylation of enolates 603, 604–5, 867–8 in bicyclic molecules 839–49 bridged bicyclic compounds 839–41 fused bicyclic compounds 841–6, 848–50 spirocyclic bicyclic compounds 846–7 in cyclic molecules 825–51 in Diels–Alder reaction 881–9 in five-membered rings 834–6 in four-membered rings 833 in synthesis of alkenes, summary 693 of Alder ene reaction 895–6 of alkene dihydroxylation 905–6 of alkene hydrogenation 842, 845 of allylic substitution using palladium 1088–92 of carbonyl ene reaction 896 of catalytic hydrogenation 535 of Claisen rearrangement 910–11 of electrophilic addition to alkenes 439 of elimination reactions 678, 853–5 of epoxidations of alkenes 514, 866–7 cyclic alkenes 843–4, 850–1, 855 of rearrangement reactions 957–8 of the Heck reaction 1081–2 of the Julia olefination 686–7 of the Wittig reaction 690–3 with cyclic transition states and cyclic intermediates 847–51 stereospecific, definition of 396, 852 stereospecificity, in cross-coupling reactions 1082 in epoxidation of alkenes 430–1, 514, 854–5 in synthesis of alkenes 688–93 of electrophilic addition reactions 440–1, 853–4 of epoxide opening reactions 854 of iodolactonization reactions 853–4 of Peterson elimination 688–9 of singlet vs triplet carbene reaction with alkenes 1014–15 of SN2 reactions 853 steric hindrance 129 effect on reactivity of radicals 979 effect on regioselectivity of electrophilic aromatic substitution 483 in nucleophilic additions to carbonyl compounds 129 in SN1 and SN2 reactions 342–3, 380–1 steroids 639, 848–50, 1156, 1167 conformation of 379, 841 synthesis in nature 1167 stilbene, asymmetric dihydroxylation of 1124 epoxidation of 431 reaction with NBS and water 441 Stille coupling 1083–5 stomach, pH of 163 Stork, Gilbert 634 strain, in rings 366–8 s-trans 804–5, 879–80 conformation, of esters 804–5 Strecker reaction 236, 307–8, 324 Streptomyces fungi 1020 1230 INDEX stretching frequency, in IR 64 see also IR spectra structural variation, for determination of reaction mechanisms 1034, 1036, 1040–8 structure determination 43–78, 407–26 by 1H NMR 269–301 by degradation 1037 structure, of molecules 80–105 strychnine 25, 745 styrene, reaction with hydrogen bromide 433 substituent constant, σ 1042–3 substituent effects, in Hammett relationship 1041–8 substituents, axial and equatorial 371, 374–7 effect on radical stability 977 effect on ring-forming reactions 808–10 substitution see also SN1, SN2 and elimination, competition between 384–6 aromatic see nucleophilic or electrophilic aromatic substitution at saturated carbon and C=O compared 355–6 at the carbonyl group 197–221, 262–3 with loss of C=O 222–39 kinetic studies and mechanisms 257–63 compared with elimination 404–5 electrophilic, aromatic see electrophilic aromatic substitution in acyl chlorides 198–9, 202–3, 218 in anhydrides 198–9 intramolecular, in synthesis of saturated heterocycles 812 nucleophilic aromatic see nucleophilic aromatic substitution nucleophilic, at saturated carbon 328–59 see also SN1, SN2 effect of neighbouring group on rate of 931–2 intramolecular SN2, in synthesis of saturated heterocycles 805–10 mechanisms compared 328–9 stereospecificity of 853 radical 972–3 substitution, stereochemistry and 343–4 substrate control, in asymmetric synthesis 1107–13 succinic anhydride, Friedel–Crafts acylation with 494, 722 sucralose 1146 sucrose 3, 29, 32, 1146 Sudafed 314 suffixes, in names of compounds 35 sugars 1134–5, 1142–7 amino 1147 as examples of stable hemiacetals and acetals 229, 808 conformation of 801–2 in cell membranes 1147 protection of 808 stereoisomers of 315–16 sulfa drugs 753–4 sulfamethoxazole 753 sulfamethoxypyridazine 753 sulfanilamide 565 sulfapyridine 565, 723 sulfate, cyclic 1125 sulfenate ester 918 sulfene 403–4 sulfenyl chloride 658–9 sulfenylation, of silyl enol ethers 470 sulfides 656–9, 660 alkylation to give sulfonium salt 664 by sulfenylation of enol ethers 470 from thiols 336 in mustard gas 935 neighbouring group participation by 932, 934 oxidation of 685 retrosynthetic analysis of 697–8 synthesis of, by SN2 354–5, 380 sulfinate anion 659 sulfite 657, 1125 sulfonamide 657 sulfonates 390, 657 see also toluenesulfonate, methanesulfonate as leaving groups sulfonation, of aromatic rings 476–7, 485–6, 490, 565 regioselectivity of 565 sulfone 656, 657, 659–60 anion from 663, 664 allylic, conjugate addition of 664 as activating substituent in nucleophilic aromatic substitution 519 reaction with aldehydes 686 sulfonic acids 659, 476–7 see also toluenesulfonic acid, methanesulfonic acid by sulfonation of aromatic compounds 485–6 in regiocontrolled aromatic substitution 565 sulfonium salt 658–9, 664–5 in S-adenosyl methionine 1136 sulfonium ylids 665–7, 1018 sulfonyl chlorides see also toluenesulfonyl chloride, methanesulfonyl chloride sulforaphane 1145–6 sulfoxides 659, 660 activating substituents in nucleophilic aromatic substitution 519 alkylation of 661 allylic, in [2,3]-sigmatropic rearrangements 918 as oxidizing agent 545 chiral 660 elimination to form alkenes 684–5 oxidation 685 stabilization of anion by 661 sulfoxonium ylids 667–8 sulfur compounds, basicity and pKa 660, 663 smell of sulfur dioxide 658 sulfur heterocycles, saturated, reactions of 795 sulfur nucleophiles, in SN2 354–5, 380 sulfur trioxide, electrophilic aromatic substitution by 485–6 sulfur ylids see also sulfonium ylids, sulfoxonium ylids sulfur, bond strengths to 657 comparison with selenium 686 crystalline 657 electronegativity of 657 functional groups containing 659–60 in organic chemistry 656–68 oxidation states of 657 stabilization of adjacent anion 660, 795 versatility of 657 sulfuric acid, as dehydrating reagent 637 for hydrolysis of nitrile to carboxylic acid 586 in catalysis of E1 elimination of alcohols 389 in E1 elimination 383–4 pKa of 170 sulfuryl chloride 658, 659 sumatriptan, structure and synthesis 755, 777, 778 superacid 334–5, 485 supercritical carbon dioxide 1136 superglue superimposable mirror images, and chirality 303–4 super-protons, silyl groups as 671–3 suprafacial 892 in sigmatropic rearrangements 913 Suzuki, Akira 1084 Suzuki coupling 1083, 1085–7 Swern oxidation 545, 626, 667–8 mechanism of 668 swine flu 1174–5 symmetric stretch, in IR spectra 67, 70 symmetry, centre of 320–2 planes of 304–6, 312, 320–1 planes of, centres of, and axes of, summary 322 syn aldol product 868–71 syn diols, from alkenes and osmium tetroxide 905–6 syn/anti nomenclature 858 synclinal (gauche) conformation 365–6 syn-periplanar 365–6 Syntex 325 synthesis, asymmetric 1102–33 diversity orientated 1180 of natural products 872–5 planning see retrosynthetic analysis synthon 695–6, 712 donor and acceptor 712, 719–20 systematic nomenclature 34–41 T Taber, Douglass F 1020 Tamao oxidation see Fleming–Tamao oxidation 673 Tamiflu see oseltamivir tamoxifen, synthesis of 393 tandem reactions 603–5, 640 taranabant 1117 tartaric acid 31, 317–18, 1105 tautomerism 629 in NMR 449–50 in thioamide 772 keto-enol 450–1 INDEX of 1,3-dicarbonyl compounds 457–8 of carboxylic acids 451 of hydroxypyridines 728 of imidazole 451 of imines 456–7 of tetrazole 744 of triazoles 743 tautomers 629 Taxol (paclitaxel) 1169–70 geminal (2J) coupling in 820 synthesis via pinacol radical reaction 982 tazadolene 717 TBAF (tetra-n-butylammonium fluoride) 550, 669 TBDMS (tert-butyldimethylsilyl), as protecting group 549–50, 670 TBDPS (tert-butyldiphenylsilyl), as alcohol protecting group 670 t-Bu, t-butyl see tert-butyl TCP 480 temperature, convenience of –78 °C 253 effect on equilibrium constants 248–9 effect on rates of reaction 250–3, 257, 266 TEMPO (2,2′,6,6′-tetramethylpiperidine N-oxide) 975 ten-membered ring, conformational drawing of 637 formation, using Stille coupling 1084 terephthalic acid 210 termination, of radical reactions 572–3 termite, defence mechanism 501, 623, 624 pheromone of 685 termolecular reactions 260–1 terodilin 702 terpenes 1156, 1164–7 terpenoid 274 tert-butanol, 13C NMR spectrum 62 1H NMR spectrum 283 as solvent 1123 in E1 elimination reaction 383–4 reaction with HBr in synthesis of tert-butyl bromide 329 reaction with thiols in synthesis of sulfide 336 tert-butoxide, as base in E2 elimination 386 see also potassium tert-butoxide tert-butyl bromide, by reaction of tert-butanol with HBr 329 in E2 elimination reaction 382–3 tert-butyl cation, 1H and 13C NMR spectrum 940–1 tert-butyl ester, as blocking group in pyrrole synthesis 761 as protecting group 556 SN1 cleavage of 598 use of to avoid Claisen self-condensation 589 tert-butyl group 27 1H NMR spectrum 273–4 effect on conformation of cyclohexanes 377–8 tert-butyl hydroperoxide, use as oxidant 919, 1120–2 tert-butyl methyl ether, 1H NMR spectrum 61 tert-butylamine, 1H NMR spectrum 283 tert-butylcyclohexanol 311, 797 tert-butyldimethylsilyl see TBDMS tert-butyldiphenylsilyl see TBDPS tert-butyloxycarbonyl see Boc tert-butylthiol 4, 283 tertiary amine, as non-nucleophilic base 455 tertiary carbocations, stability 334–5 tertiary carbon, meaning of 27 Terylene (polyester) 210 TES (triethylsilyl), as alcohol protecting group 670 testosterone 25, 1167 tet nomenclature, in Baldwin’s rules 810 tethers, for regio and stereocontrol 568–9, 847–8 tetraalkylammonium chloride, as phase transfer catalyst 585 tetracarbonyl ferrate, iron acyl complex from 1076 tetradecanoic acid (myristic acid) 211 tetrahedral angle 18 tetrahedral intermediate 199–202 evidence for existence 201–2 formation of in rate-determining step 258 stability of 200–1, 218–20 tetrahedrane 420–1 tetrahydrofolic acid 754 tetrahydrofuran see THF tetrahydropyrans 479 see also THP anomeric effect in 802–3 synthesis by ring-closing reaction 805 tetrahydropyranyl see THP tetrakistriphenylphosphinepalladium(0) [Pd(PPh3)4] 12, 1072 tetralin, from naphthalene 161 tetralone, regioselective synthesis of 568 2,2′,6,6′-tetramethylpiperidine (TMP) 793 2,2′,6,6′-tetramethylpiperidine N-oxide (TEMPO) 975 tetramethylsilane (TMS), in 1H NMR 55–6, 270 tetra-n-butylammonium fluoride see TBAF tetra-n-propylammonium perruthenate see TPAP tetrazole, as carboxylic acid substitute in medicinal chemistry 744, 774 by [3+2] cycloaddition of azide and nitrile 774, 904 pKa of 744 retrosynthetic analysis of 774 structure and tautomerism 725, 744 use in one-step Julia olefination 687–8 tetrodotoxin, structure of 790 TFAE (2,2,2-trifluoro-1-(9-anthryl)ethanol) 1111–12 theobromine 1137 thermal cycloadditions see cycloadditions thermodynamic and kinetic control 264–6 in conjugate vs direct addition reactions 605–6 in electrophilic aromatic substitution 566 in reactions of sulfur ylids 666–7 thermodynamic control, in acetal formation 808, 835, 1143 in conjugate addition 504–5 in Diels–Alder reactions 884 in electrophilic addition 434–6 1231 in enamine formation 592 in enolate and enol ether formation 599–602, 636 in intramolecular aldol reaction 637 in reactions of sulfonium ylids 667 in ring-closing reactions 808–10 in synthesis of aromatic heterocycles 758 in synthesis of Z-alkenes 264–6 of enolate conjugate addition 605 thermodynamic enolate, formation of 636 thermodynamic silyl enol ethers, formation of 636 thermodynamic stability, vs kinetic stability 250 thermodynamics, second law of 246 thermodynamics, summary of principles 249 THF (tetrahydrofuran) 39, 794 decomposition by organometallics 253, 795 in lithium enolate complex 625–6 ring opening of 794 thiadiazole, 1,2,5- 752, 785 thiazoles 725, 751, 771–2 thienamycin 816–17 thiiranium see episulfonium thioacetals 657, 661–2 see also dithianes for removal of carbonyl groups 540 hydrolysis of 663 of glucose 1144 thioacetate, as nucleophile in SN2 355 thioamide 772 thioate anion 657, 658 thiocarbonyl compounds, stability of 662 thiocetic acid, 13C NMR spectrum see lipoic acid thioesters 355 compared with esters 1153 of coenzyme A 1152–3 thioether see sulfide 659 thiol 27, 657–8 in glutathione 1140 reaction with epoxide 121–3 sulfide from 336 thiolate anion 659 conjugate addition to nitroalkene 904 in nucleophilic aromatic substitution 517, 728 in Payne rearrangement 938–9 thiols as nucleophiles 354–5 from hydrogen sulfide and alkene 434–5 in conjugate addition 500–1, 506–8, 582 oxidation to dilsulfides 1140 thionyl chloride, in synthesis of acyl chlorides 214–15, 462, 658 thiophene 735–7 desulfurization 737 electrophilic aromatic substitution reactions 735, 737 from 1,4-dicarbonyl compounds 759 oxidation of 739 reaction with butyllithium 737 regioselectivity in reactions of 735 sulfone 739 sulfoxide 739 thiophenesaccharin, synthesis of 582 1232 INDEX thiophile 918 third-order kinetics 260 Thorpe–Ingold effect 808–10 THP (tetrahydropyran, -yl) 469, 550–1, 794 three-dimensional structures, drawing 21 three-membered rings see also cyclopropane, epoxide, aziridine etc conformation of 369 effect on 1H NMR 414, 815 fragmentation of 967 rate of formation 806–7 threonine 554 thromboxane antagonist 705 thromboxane 714, 1156, 1162 thujone 1156 thymidine 1138 thymine 1136 thymoxamine, synthesis of 521–2 Tiffeneau–Demjanov rearrangement 949, 956–7 timolol 752, 785–6 tin, decline in use of 1099 for reduction of aromatic nitro groups 495 tin hydrides, in radical carbon-carbon bond formation 993–4 tin tetrachloride, as Lewis acid 595 tin(II) chloride, for reduction of diazonium salt to hydrazine 777 TIPS (triisopropylsilyl), as alcohol protecting group 670 titanium alkoxide, in Sharpless asymmetric epoxidation 1120–2 titanium tetrachloride, as Lewis acid 595, 609, 626, 676 titanium tetraisopropoxide, as Lewis acid 1122 titanium, use in McMurry reaction 982–3 TMP (2,2,6,6-tetramethylpiperidine) 793 TMS see trimethylsilyl, trimethylsilane TNT (2,4,6-trinitrotoluene) 30, 176 tolmetin, synthesis of 734 toluene 37 bromination of 484–5 protonation of 485 sulfonation and chlorosulfonation of 485–6 toluenesulfinate, as leaving group 344, 349, 380, 390–1, 664, 948 toluenesulfonate esters (tosylates), synthesis from alcohols 349, 403 as alkylating agents 596 toluenesulfonic acid (PTSA, TsOH, tosic acid) 227, 389, 485, 627 toluenesulfonyl azide 1006–7 toluenesulfonyl chloride (tosyl chloride, TsCl) 344, 349, 658, 659 toluenesulfonyl hydrazine, -one see tosylhydrazine, -one topanol 354 50, 61–2 Toray process 986 torsion angle 364 tosic see toluenesulfonic tosyl see toluenesulfonyl tosylate see toluenesulfonate tosylhydrazine, in Eschenmoser fragmentation 965 tosylhydrazone 965, 1007–8 TPAP (tetra-n-propylammonium perruthenate) 545 tranquillizers 793 trans and cis coupling constants, and ring size 814–17 trans-alkenes see alkenes, trans transannular strain, in medium rings 807 trans-cycloheptene 679 trans-cyclooctene 679 trans-decalin 378–9, 381, 841 trans-diaxial opening, of epoxide 849 trans-enolate, in aldol reactions 868–71 transesterification 209–10 transfer hydrogenation 1115–17 trans-fused bicyclic rings 841–2, 848–50 trans-hexatriene, conformations of 145 transition metal catalysis, gold 1099 palladium 1069–99 ruthenium 1099–100 transition metal complexes, bonding and reactions in 1073–8 chiral 1115–17, 1117–26 stability and 18-electron rule 1070 transition metals, as oxidizing agents 194–5 in formation of carbenes 1007 valence electrons of, table 1070 transition state, cyclic, to control stereochemistry in reactions 850–1, 862–5, 869–70 definition of 251, 253 effect of solvent on 256 experimental investigation of 1041–8 Felkin–Anh 859–62 for amide C–N bond rotation 256 for CBS reductions 1115 for diastereoselective epoxidation 835–6, 850 for ring-opening of an epoxide 837 Hammond postulate and 989 how to draw 251 in Baeyer–Villiger oxidation 956 in catalysed reactions 254 in Grignard reagent formation 185 in reduction of a ketone with borohydride 251 mimic of by HIV protease inhibitors 1171 of [2,3]-sigmatropic rearrangements 917 of Alder ene reaction 896 of Claisen rearrangement 910–11 of Diels-Alder reaction 878, 885, 891 of SN2 reaction 340–1, 343 Zimmerman–Traxler 869–70, 1130 transmetallation 189, 218, 1083–8 trans-retinal, 13C NMR spectrum 409 trans-stilbene, asymmetric dihydroxylation of 1124 epoxidation of 431 travel sickness, drug for treatment of 791 trialkylborane 446 trialkylsilyl chloride, for protection of hydroxyl group 549–50 trianions, chemoselective reactions of 547 triazine, 1,3,5-, structure and conformation of 804 triazole, pKa of 743 reaction with epoxide 743 triazoles 725 1,2,3-, synthesis, from azide and alkyne 776 1,4-disubstituted, selective synthesis of 775 acid/base properties in 743 by [3+2] cycloaddition 775 in fungicides 11 tautomerism of 743 tributyltin hydride 991–4 trichloroacetaldehyde, hydration of 134–5 2,4,6-trichlorophenol 480 2,4,6-trichlorophenyl ester, for activation of carboxylic acids 558–9 trienes, cycloaddition of 894 electrocyclic ring closing of 922–3 triethylamine, pKa of 174, 791 triethylsilane, as reducing agent 668, 1175–6 triethylsilyl see TES 2,2,2-trifluoro-1-(9-anthryl)ethanol (TFAE) 1111–12 trifluoroacetic acid, 13C NMR spectrum 416–17 pKa of 176 trifluoromethylbenzene, nitration of 487 trifluoromethyl group 487, 519 trifluoroperacetic acid see peroxy trifluoroacetic acid trig nomenclature, in Baldwin’s rules 810 triglyceride 1148 triisopropylsilyl see TIPS trimethoprim 770–1 trimethylenemethane 1091–2 trimethyloxonium fluoroborate see Meerwein’s salt trimethylphosphite, as nucleophile for sulfur 918 trimethylsilyl (TMS), as protecting group 670 as ‘super-proton’ 671–3 trimethylsilyl chloride, as electrophile 466–7 for formation of silyl enol ethers 670 in conjugate addition reactions 508 in silyl enol ether formation 626 use in acyloin reaction 983–4 use in enolate trapping 632 trimethylsilyl triflate, as Lewis acid with allyl silanes 676 trimethylsilylacetylene 671–2 trimetozine, synthesis of 791 2,4,6-trinitrophenol (picric acid) 176 2,4,6-trinitrotoluene see TNT 176 triphenylmethyl see also trityl 337 anion 643 radical, and dimer 973–5, 979 triphenylphosphine, as nucleophile in SN2 358 for reduction of azides 354, 1176 for reduction of ozonide 443, 907 in Mitsunobu reaction 349–51 in synthesis of secondary allylic chlorides 577–8 in Wittig reaction 237 to cause CO insertion into transition metal ligands 1076 INDEX triphenylphosphine oxide, as by-product of the Witttig reaction 238 triple bonds, carbon–carbon see alkynes region in IR spectrum 65, 69 stability and acidity 188 triplet (codon) 1139 triplet carbene 1010 triplet, in 1H NMR 289–92 trisporol B 1086 tritium (3H, T), as radioactive label 1037 Triton B (benzyltrimethylammonium hydroxide) 612 trityl cation (triphenylmethyl cation) 337 trityl chloride (TrCl), reaction with primary alcohols 337 trivial names 33–4, 36–9 tropinone 1157–8 truffle, smell of 4, 657 tryptophan 16, 554, 755, 1154 as precursor to indole alkaloids 745 X-ray crystal structure 20 TsCl see toluenesulfonyl chloride TsDPEN, as chiral ligand 1115–17 TsOH see toluenesulfonic acid turpentine 1164 twist-boat conformation 370, 373–4, 378, 830, 839 tyrosine 554, 1154 alkaloids from 1159–61 in synthesis of L-dopa 954 U ulcer treatment drug, cimetidine 178–80 ultraviolet absorption, for detection in HPLC 1111 ultraviolet light, associated energy of 971 for radical initiation 572 ultraviolet–visible (UV-vis) spectroscopy 148–50 umpolung 720 Uncertainty Principle, Heisenberg’s 83 unimolecular reactions 259–60 universe, number of atoms in 250 unknown compounds, identification of 418–22 unsaturated carbonyl compounds see α,βunsaturated carbonyl compounds unsaturated fat 31, 536 unsaturated fatty acid 1148, 1161–3 unsaturated, meaning of 29 unstabilized ylids 689–91, 693 uracil 754, 1136 uric acid 750–1 UV see ultraviolet UV–visible spectra 148–50 V valerian root oil 948 valine 554, 1104 chiral auxiliary from 1108 Valium 326, 793 vanadyl acetoacetonate 850–1 vancomycin 308, 1142 vanillin 13C NMR spectrum 409 Vaska’s complex 1074 venlafaxine 715–16 vernolepin 508 Viagra 723, 768–70 vibrational spectroscopy 64 vicinal (3J) coupling see also coupling 295, 300 and ring size 814–17 in saturated heterocycles 796–9, 802, 814–17 in six-membered rings 797–9, 802 Villiger, V 953 Vilsmeier reaction 733–4, 746 vinegar 28 vinyl alcohol 456–7 vinyl cation, structure and reactions of 264 vinyl epoxides, synthesis and reactivity 1090 vinyl group, coupling constants in 299–300, 293–4, 295 vinyl halides, elimination to give alkynes 398 from 1,2 dibromoalkenes 398 vinyl silanes, molecular orbitals of 674 alkenes from 673–4 by reduction of alkynyl silanes 683 vinylogous 512 violet oil 707 vision, chemistry of 681 vitamins A, retrosynthetic analysis and synthesis of 708, 915 B12 38 B6 235 C (ascorbic acid) 6, 1141, 1146 1H NMR spectrum 275 acidity of 458–9 D, biosynthesis of 922, 927 D2 921, 927 E, as radical trap 975 vivalan, structure and synthesis 612 Vollhardt, K P C 548 von Liebig, Justus 950 W Wacker oxidation 1096 Wadsworth–Emmons reaction see Horner– Wadsworth–Emmons reaction Wagner–Meerwein rearrangement 942–4 water, addition to carbonyl group 133–5 as a solvent for organic compounds 163–4 as an acid and a base 167–8, 170 as nucleophile 113 as solvent in amide synthesis 177 as solvent in Diels–Alder reaction 888 concentration of, in water 169, 243 deuterated (heavy water, D2O), as NMR solvent 272, 284–5 ionization constant (Kw) 168 pKa of 169, 170 reaction with carboxylic acid derivatives (hydrolysis) 206 shape of molecule 82 solvation of salts by 255 Watson, James D 1137 1233 wavefunctions, of orbitals see orbital, wavefunctions of wavelength, absorption and colour (table) 64, 149 wave–particle duality 83 W-coupling, in 1H NMR 295–6, 301 weak base, acetate as 263 catalysis by 1057 pyridine as 199–200 wedged bonds 302 Weinreb, S M 219 Weinreb amides (N-methoxy-N-methyl amides) 219, 1112 Wieland–Miescher ketone 845 wiggly bonds 306, 680 wiggly line, meaning of 21 wild type enzymes 1180 Wilkinson, G 1084, 1117–18 Wilkinson’s catalyst 1074, 1117–18 Williamson ether synthesis 340 wine, chemical responsible for taste of corked 790 health benefits of 6, 1164 wing-shaped, conformation of cyclobutane 369 Wittig, Georg 237 Wittig reaction 237–8, 570, 689–93 examples of 628, 1121 in retrosynthetic analysis 720 stereoselectivity and mechanism 689–93 Wittig reagents, as specific enol equivalents 627 Wolff rearrangement, of α-carbonyl carbene 1021 Wolff–Kishner reduction 540 Woodward, Robert 892 Woodward–Hoffmann rules 892–3 and [1,5]-sigmatropic hydrogen shifts 920–1 and [2,3]-sigmatropic rearrangements 917–18 and [2+2] photochemical cycloadditoins 897 and [3,3]-sigmatropic rearrangements 912 and Alder ene reaction 895 and Diels–Alder reaction 892–3 and electrocyclic reactions 923–4 X X, as abbreviation for halogen 30 xanthine oxidase 751 xanthine, oxidation to uric acid 751 XantPhos 1093 X-ray crystallography 44–5 xylene, as solvent 358 xylose 316 Y yew tree 1170 ylid (ylide) 237 from carbene attack on lone pair 1023 phosphorus, in aldol reaction 627, 628 in Wittig reaction 237, 689–93 stabilized and unstabilized 689–93 sulfur, for formation of epoxides 665–7 1234 INDEX Z Z/E-alkenes, calculating energy difference between 265 Z-alkenes see alkenes Zantac see ranitidine zeolite 226 Ziegler–Natta polymerization 1076 zig-zag, drawing carbon chains as framework 18–19 Zimmerman–Traxler transition state, for aldol reaction 869–70, 1130 zinc carbenoid, in Simmons–Smith reaction 1009, 1017 zinc enolates, [4+3] cycloaddition reaction of 893–4 formation of 631 zinc, as reducing agent 494, 658–9, 899, 902 organometallic derivatives of 189 Zovirax see acyclovir zwitterion 167, 174 of glycine, 1H NMR spectrum 284–5 Clayden, Greeves, & Warren: Organic Chemistry 2e Errata Updated: July 2012 Page 364 Line 18 (half way down page) Correction Date Chemdraw figure: the bottom right diagram (of the figure half way 08/05/12 down the page) should show a staggered, not an eclipsed, structure (as per the staggered structure of ethane in the margin of the previous page) Replacement figure: Margin table Line of the 2nd blue box 5 3rd set of chemdaw diagrams (line 15) The heading of the 3rd column (“109.5o˗˗internal angle”) After 109.5o, this should be a minus sign, not an em dash The value ‘0.5 ppm’ should be ‘0.25 ppm’ 08/05/12 The cross reference should be to p.148 not p.138 ‘Product9’ at the head of the green column should be ‘Product’ Chemdraw figure: ‘X’ needs replacing with ‘N3’ (twice) 08/05/12 08/05/12 08/05/12 30 2nd set of chemdraw diagrams (line 14) Chemdraw figure: nitrazepam has NH not Nme Replacement figure: Chemdraw The wrong stereochemistry in the attachment to the quinuclidine ring 367 374 435 806 838 08/05/12 Replacement figure: © Oxford University Press, 2012 All rights reserved 08/05/12 23/05/12 Clayden, Greeves, & Warren: Organic Chemistry 2e Errata figure in the margin in quinine Replacement figure: 432 2nd set of chemdraw diagrams (line 11) Chemdraw figure: 'carconigenic' should be ‘carcinogenic’ on a diagram 23/05/12 Replacement figure: 723 Chemdraw The wrong stereochemistry in the attachment to the quinuclidine ring diagrams in quinine at bottom of page Replacement figure: 23/05/12 755 2nd chemdraw diagram at top of page (quinine) 23/05/12 The wrong stereochemistry in the attachment to the quinuclidine ring in quinine Replacement figure: © Oxford University Press, 2012 All rights reserved Clayden, Greeves, & Warren: Organic Chemistry 2e Errata 780 quinine diagram in margin The wrong stereochemistry in the attachment to the quinuclidine ring in quinine 23/05/12 Replacement figure: 913 Green box in margin 1082 Second chemdraw diagram The reference to Fleming's book should be: 'Ian Fleming (2009) Molecular Orbitals and Organic Chemical Reactions, Student Edition, Wiley-Blackwell’ The silver carbonate in the diagram should be Ag2CO3 and not AgCO3 Replacement figure: © Oxford University Press, 2012 All rights reserved 23/05/12 25/06/12 ... meaningless Chemistry continues across the old boundaries between organic chemistry and inorganic chemistry, organic chemistry and physical chemistry or materials, or organic chemistry and biochemistry... to the second edition xvii Organic chemistry and this book xix What is organic chemistry? Organic structures 15 Determining organic structures Structure of molecules Organic reactions 43 80 107... and to illuminate the way that organic chemistry underpins life itself 40 Organometallic chemistry 41 Asymmetric synthesis 42 Organic chemistry of life 43 Organic chemistry today ‘Connections’