STRUCTURE ELUCIDATION BY NMR IN ORGANIC CHEMISTRY A Practical Guide

Eberhard Breitmaier

University of Bonn, Germany

Translated by Julia Wade

•••

JOHN WILEY & SONS Chichester • New York • Brisbane • Toronto • Singapore

CONTENTS

Preface

Symbols and Abbreviations

1 Short Introduction to Basic Principles and Methods

1.1 Chemical shift 1.2 Spin-spin coupling 1.3 Coupling constants 1.4 Signal multiplicity (multiplets) 1.5 Spectra of first and higher order 1.6 Chemical and magnetic equivalence 1.7 Continuous wave (CW) and Fourier transform (FT) NMR

spectra 1.8 Spin decoupling 1.9 Nuclear Overhauser effect 1.10 Relaxation, relaxation times

2 Recognition of Structural Fragments by NMR

Introduction to tactics and strategies of structure elucidation by one- and two-dimensional NMR

2.1 Functional groups 2.1.1 'H chemical shifts 2.1.2 Deuterium exchange 2.1.3 13C chemical shifts 2.1.4 15N chemical shifts

2.2 Skeletal structure (atom Connectivities) 2.2.1 HH multiplicities 2.2.2 CH multiplicities 2.2.3 HH coupling constants 2.2.4 CH coupling constants 2.2.5 NH coupling constants 2.2.6 HH COSY (geminal, vicinal, w-relationships of protons 2.2.7 CC INADEQUATE (CC bonds) 2.2.8 CH COSY (CH bonds) 2.2.9 CH COLOC (geminal and vicinal CH relationships)

CONTENTS

2.3 Relative configuration and conformation 42 2.3.1 HH coupling constants 42 2.3.2 CH coupling constants 46 2.3.3 NH coupling constants 48 2.3.4 13C chemical shifts 49 2.3.5 NOE difference spectra 52 2.3.6 Htf NOESY 54

2.4 Absolute configuration 54 2.4.1 Diastereotopism 54 2.4.2 Chiral shift reagents (ee determination) 56

2.5 Intramolecular and intermolecular interactions 58 2.5.1 Anisotropie effects 58 2.5.2 Ring current of aromatic Compounds 59 2.5.3 Intra- and intermolecular hydrogen bonding 60 2.5.4 Protonation effects 61

2.6 Molecular dynamics (fluxionality) 62 2.6.1 Temperature-dependent NMR spectra 62 2.6.2 13C spin-lattice relaxation times 64

2.7 Summary 68

Problems 1-50 71

1-10 Application of one-dimensional' H NMR spectra 71 11-12 Temperature dependent 'H and 13C NMR spectra 83 13-18 Application of one-dimensional 13C NMR spectra 85 19-20 CC INADEQUATE diagrams 91 21-23 One-dimensional 'H and 13C NMR spectra 93 24-25 One-dimensional 'H, 13C and 15N NMR spectra 96 26-38 Combined application of one- and two-dimensional

'H and 13C NMR experiments 100 39-50 Identification and structural elucidation of natural

products by one- and two-dimensional 'H and 13C NMR 127

Solutions to problems 1-50 171

1 Dimethyl ds-cyclopropane-l,2-dicarboxylate 171 2 Ethyl acrylate 171 3 ds-l-Methoxy-but-l-en-3-yne 172 4 £rans-3-(N-Methylpyrrol-2-yl)propenal 172 5 l,9-Bis(pyrrol-2-yl)pyrromethane 173 6 3-Acetylpyridine 174 7 6,4'-Dimethoxyisoflavone 175 8 Catechol (3,5,7,3',4'-pentahydroxyflavane) 176 9 Methyloxirane and monordene 178

CONTENTS Vll

10 2-Methyl-6-(N,N-dimethylamino)-trans-4-nitro-frans-5-phenylcyclohexene 179

11 (E)-3-(N,N-Dimethylamino)acrolein 180 12 eis- 1,2-Dimethylcyclohexane 181 13 5-Ethynyl-2-methylpyridine 183 14 5-Hydroxy-3-methyl-lH-pyrazole 183 15 o-Hydroxyacetophenone 184 16 Potassium l-acetonyl-2,4,6-trinitrophenylcyclohexadienate 185 17 trans-3-[4-(AT,N-Dimethylamino)phenyl]-2-ethylpropenal 186 18 iV-Butylsalicylaldimine 187 19 Benzo[/?]furan 187 20 3-Hydroxypropyl 2-ethylcyclohexa-l,3-diene-5-carboxylate 188 21 2-(Ar,AT-Diethylamino)ethyl 4-aminobenzoate hydrochloride

(procaine hydrochloride) 189 22 2-Ethoxycarbonyl-4-(3-hydroxypropyl)-l-methylpyrrole 190 23 2-p-Tolylsulphonyl-5-propylpyridine 192 24 Triazolo[l,5-a]pyrimidine 194 25 6-n-Butyltetrazolo[l,5-a]pyrimidine and

2-azido-5-n-butylpyrimidine 194 26 Hex-3-yn-l-ol 196 27 6-Methoxytetralin-l-one 198 28 Hydroxyphthalide 199 29 Nona-2-trans-6-ds-dienal 201 30 trans-1 -Cyclopropyl-2-methyl-buta-1,3-diene

(trans-isopren-1 -yl-cyclopropane) 202 31 Dicyclopentadiene 204 32 ci's-6-Hydroxy-l-methyl-4-isopropylcyclohexene (carveol) 204 33 Menthane-3-carboxylic aeid (l,3-cis-3,4-trans-) 205 34 meso-<x,a,a,a-Tetrakis{2-[(p-menth-3-ylcarbonyl)amino]phenyl}porphyrin 207 35 trans-2-(2-Pyridyl)methylcyclohexanol 207 36 2-Hydroxy-3,4,3',4'-tetramethoxydeoxybenzoin 209 37 3',4',7,8-Tetramethoxyisoflavone 211 38 3',4',6,7-Tetramethoxy-3-phenylcoumarin 213 39 AflatoxinBx 215 40 Asperuloside 217 41 9/?-Hydroxycostic aeid 220 42 14-(Umbelliferon-7-0-yl)driman-3a,8a-diol 224 43 3,4,5-Trimethyl-5,6-dihydronaphtho[2,3-b]furan 228 44 6^-Acetoxy-4,4a,5,6,7,8,8a,9-octahydro-3,4aiS,5iS-trimethyl-9-

oxonaphtho[2,3-b]furan-4ß-yl-2-methylpropanoic aeid ester (Sendarwin) 230

45 8a-Acetoxydehydrocostus lactone 23^ 46 Panaxatriol 237 47 4,5-Dimethoxycanthin-6-one

(4,5-dimethoxy-6H-indolo[3,2,l-rfe] [l,5]naphthyridin-6-one) 241 48 Cocaine hydrochloride 244 49 Viridifioric aeid 7-retronecine ester (heliospathulin) 247 50 frans-N-Methyl-4-methoxyproline 250

V111 CONTENTS

5 References 253

Formula index of Solutions to problems 255

Subject index 261