Heterocyclic Chemistry

Transcription

1 Heterocyclic Chemistry Third Edition Thomas L. Gilchrist University of Liverpool 1 Longman

2 Contents Preface to the third edition Preface to the second edition Preface to the first edition Acknowledgements xii xiii xv xvii 1 Introduction: uses of heterocyclic Compounds Aromatic heterocycles The common structural types Six-atom, six-7r-electron heterocycles Five-atom, six-7r-electron heterocycles Benzo-fused ring Systems Other fused heterocycles Some criteria of aromaticity in heterocycles Bond lengths Ring current effects and chemical shifts in 'H NMR spectra Molecular orbitals and delocalization energy Resonance energies Dewar resonance energies and other calculated resonance energies General conclusions Aromatic character and other types of unsaturated heterocycles Monocyclic Systems that conform to the Hückel rule Other unsaturated heterocycles Reactivity of heteroaromatic Compounds Tautomerism of heteroaromatic Compounds 32 Summary 35 Problems 35

3 vi Contents Nonaromatic heterocycles Introduction Bond angle strain Angle strain and bonding in small-ring heterocycles Some consequences otbond angle strain in small rings Angle strain in larger rings Torsional energy barriers Single bonds Double bonds and partial double bonds Influence of bond lengths and van der Waals radii: conformational preferences of flexible heterocycles Saturated six-membered heterocycles Four- and five-membered heterocycles Other types of interaction in saturated heterocycles Through-bond' orbital interactions: the anomeric effect Attractive 'through-space' interactions 56 Summary 57 Problems 58 Ring synthesis Introduction Cyclization reactions Reaction types Displacement at saturated carbon Intramolecular nucleophilic addition to carbonyl groups Intramolecular addition of nucleophiles to other double bonds Cyclization on to triple bonds Radical cyclization Carbene and nitrene cyclization Electrocyclic reactions Cycloaddition reactions Reaction types ,3-Dipolar cycloaddition Hetero-Diels-Alder reactions [2 + 2] Cycloaddition Cheletropic reactions Ene reactions 120 Summary 121 Problems 121

4 Contents vii Six-memberec 1 ring Compounds with one heteroatom 5.1 Introduction 5.2 Pyridines Introduction Ring synthesis General features of the chemistry of pyridines Basicity Alkylation, acylation and complexation on nitrogen Electrophilic Substitution at carbon Nucleophilic Substitution Didehydropyridines (pyridynes) Radical Substitution Palladium-catalysed coupling reactions and Heck reactions Reduction of pyridines and pyridinium salts: dihydropyridines Photochemical isomerization Pyridine iv-oxides, 7V-imides and N-ylides Hydroxy- and aminopyridines Alkyl- and alkenylpyridines Pyridinecarboxylic acids Quinolines and isoquinolines Introduction Synthesis of quinolines Synthesis of isoquinolines General features of the chemistry of quinolines and isoquinolines Electrophilic Substitution Nucleophilic Substitution Nucleophilic addition Oxidative cleavage JV-Oxides and JV-imides Properties of substituents Cyanine dyes Other fused pyridines Quinolizines Acridines Phenanthridines Indolizines Ring Systems containing oxygen Pyrylium salts 2i/-Pyran-2-ones 4iJ-Pyran-4-ones Benzo-fused Systems

5 viii Contents Summary 186 Problems 187 Five-membered ring Compounds with one heteroatom Introduction Pyrroles Introduction Ring synthesis Acidity and metallation reactions Substitution at nitrogen Substitution at carbon Addition and cycloaddition reactions Properties of substituted pyrroles Porphyrins and related pyrrolic natural products Furans Introduction Ring synthesis Reactions with electrophiles Radical Substitution and nucleophilic Substitution Cycloaddition reactions Ring-cleavage reactions Some properties of substituted furans Thiophenes Introduction Ring synthesis Electrophilic Substitution Nucleophilic and radical Substitution Addition and cycloaddition reactions Reductive desulfurization Photochemical isomerization Properties of some substituted thiophenes Indoles and related Compounds Introduction Ring synthesis Reaction with electrophiles Radical Substitution and coupling reactions Oxidation and reduction Properties of some substituted indoles Other benzo[a]-fused heterocycles Benzofurans Benzo[ft]thiophenes Carbazoles Benzo[c]-fused heterocycles 249

6 Contents ix Introduction Synthesis Chemical properties Phthalocyanines Summary Problems Six-membered ring Compounds with two or more heteroatoms 7.1 Introduction 7.2 General aspects of the chemistry of diazines, triazines and tetrazines 7.3 Pyrimidines and purines Introduction Synthesis of pyrimidines Synthesis of purines Reactions of pyrimidines Reactions of purines Pyrimidines and purines in nucleic acids 7.4 Other diazines, triazines and tetrazines Introduction Methods of ring synthesis Chemical properties 7.5 Some fused ring Systems Introduction Ring synthesis Chemical properties 7.6 Oxazines and thiazines Introduction ,3-Oxazines Phenothiazines Summary Problems Five-membered ring Compounds with two or more heteroatoms 8.1 Introduction 8.2 Imidazoles Introduction Ring synthesis Reactions 8.3 Pyrazoles, triazoles and tetrazoles Introduction Ring synthesis Substitution reactions

7 x Contents Ring cleavage Azoles as orf/io-directing groups for metallation Benzodiazoles and benzotriazoles Oxazoles and thiazoles and their benzo derivatives Introduction Ring synthesis Chemical properties Isoxazoles, isothiazoles and their benzo derivatives Introduction Ring synthesis Chemical properties Oxadiazoles, thiadiazoles and related Systems Introduction Ring synthesis Chemical properties Betaines and mesoionic Compounds AT-Oxides and AT-imides Mesoionic Compounds 341 Summary Problems Three- and four-membered ring Compounds 9.1 Introduction 9.2 Aziridines Introduction Ring synthesis Functionalization at nitrogen Ring-opening reactions Fragmentation reactions 9.3 Oxiranes Introduction Ring synthesis Reactions 9.4 Thiiranes 9.5 2/f-Azirines 9.6 Diaziridines and 3//-diazirines 9.7 Oxaziridines 9.8 Azetidines and azetidinones 9.9 Other four-membered heterocycles Oxetanes Thietanes Some unsaturated four-membered rings Summary Problems

8 Contents xi 10 Seven-membered ring Compounds Introduction Azepines Oxepins and thiepins Diazepines and benzodiazepines 379 Summary 381 Problems Nomenclature Introduction Trivial names of common ring Systems Systematic (Hantzsch-Widman) nomenclature for monocyclic Compounds The naming of fused ring Systems Replacement nomenclature 392 Summary 392 Problems 393 Answers and references to selected problems 394 Index 400