Writing Organic Reaction Mechanisms:

A Practical Guide

by

Michael Edenborough

Taylor &Francis ' Pttblishevs since 1798

Contents

Contents v Preface xi

Part I: Basic Principles

1 Introduction 1 1.1 The Aim of this Book 1 1.2 What is Organic Chemistry? 2 1.3 Organic Synthesis 3 1.4 The Need for Mechanisms 3 1.5 Examples 4 1.6 How to use this Book 7

2 Electron Counting 9 2.1 Introduction 9 2.2 Atoms 9 2.3 Uncharged Molecules 14 2.4 Molecules with Whole Charges 17

3 Covalent Bonding and Polarization 27 3.1 Introduction 27 3.2 Partially Charged Species 27 3.3 Bond Fission 31 3.4 Isolated Multiple Bonds 33 3.5 Conjugated Multiple Bonds 37

4 Shape of Molecules 41 4.1 Introduction 41 4.2 Types of Bonding 41 4.3 Tetrahedral Geometry 44 4.4 Trigonal Planar Geometry 49 4.5 Linear Geometry 54 4.6 Further Examples 56

5 Stabilization of Charged Species 63 5.1 Introduction 63

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5.2 Inductive Effects 64 5.2.1 Charged Hydrocarbon Species 64 5.2.2 Charged Non-Hydrocarbon Species 68

5.3 Mesomeric Effects 69 5.3.1 Charged Hydrocarbon Species 69 5.3.2 Charged Non-Hydrocarbon Species 71

5.4 Degree of S Orbital Character 75 5.5 D Orbital Involvement 76 5.6 Aromatic Character 77 5.7 Hydrogen Bonding 80 5.8 Steric Effects 82

6 Thermodynamic and Kinetic Effects 85 6.1 Introduction 85 6.2 Thermodynamic Considerations 87 6.3 Kinetic Considerations 91 6.4 Catalysis 96

6.4.1 General Considerations 96 6.4.2 Acid/Base Catalysis 97

7 Acid/Base Characteristics 99 7.1 Introduction 99 7.2 Definitions of Acids and Bases 99

7.2.1 Arrhenius 100 7.2.2 Brönsted-Lowry 100 7.2.3 Lewis 106 7.2.4 Cady-Elsey 107

7.3 Electrophilic and Nucleophilic Properties 108 7.4 External Effects 112

Part II: Mechanisms

8 Introduction 117

9 Nucleophilic Substitution Reactions 119 9.1 Introduction 119 9.2 Substitution at a Saturated Carbon 120

9.2.1 Introduction 120 9.2.2 Unimolecular Substitution 121 9.2.3 Bimolecular Substitution 126 9.2.4 Intramolecular Substitution 131 9.2.5 Formation and Cleavage of Three Membered Rings 134

9.3 Substitution at an Unsaturated Carbon 136 9.3.1 SNI and SN2 Mechanisms 136

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9.3.2 Tetrahedral Mechanism 138 9.3.3 Ester Hydrolysis 139

9.4 Trigonal Bipyramidal Substitution 142

10 Electrophilic Substitution Reactions 145 10.1 Introduction 145 10.2 Aromatic Substitution 146

10.2.1 Arenium Ion Mechanism 146 10.2.2 Orientation and Reactivity 150 10.2.3 OrthojPara Ratio 153 10.2.4 Multiple Substitutions 154

10.3 Aliphatic Substitution 156

11 Radical Substitution Reactions 161 11.1 Introduction 161 11.2 Photochlorination of Methane 161 11.3 Reactivity and Structure 165 11.4 Neighbouring Group Assistance 168 11.5 Further Examples of Radical Reactions 170

12 Addition Reactions to Carbon/Carbon Multiple Bonds 177 12.1 Introduction 177 12.2 Cyclic Addition 179

12.2.1 Heterogeneous Catalytic Hydrogenation 179 12.2.2 Other Syn-Additions 180 12.2.3 Pericyclic Reactions 182

12.3 Electrophilic Addition 185 12.3.1 The Addition of a Symmetrical Molecule 185 12.3.2 The Rate of Addition 192 12.3.3 Orientation of Addition 193 12.3.4 Some other Electrophilic Additions 196

12.4 Radical Addition 199 12.5 Nucleophilic Addition 200 12.6 Conjugated Addition 201

13 Addition Reactions to Carbon/Oxygen Double Bonds 205 13.1 Introduction 205 13.2 Structure and Reactivity 205 13.3 Hydration 208 13.4 Other Addition Reactions 211 13.5 Addition of Carbon Anions 213

13.5.1 Cyanide, Acetylene and Alkyl Anions 213 13.5.2 Carbonyl Stabilized Anions 216

13.6 Stereochemical Consequences 223 13.7 Conj ugated Addition 224

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14 Elimination Reactions 227 14.1 Introduction 227 14.2 Bimolecular 1,2-Elimination Reactions 228

14.2.1 Anti- Elimination 228 14.2.2 Syrt-Elimination 236

14.3 Unimolecular 1,2-Elimination Reactions 237 14.4 1,1-Elimination Reactions 242 14.5 Pyrolytic Elimination Reactions 243

15 Sequential AdditionIElimination Reactions 249 15.1 Introduction 249 15.2 Addition/Elimination Reactions 249 15.3 Elimination/Addition Reactions 255

16 Rearrangement and Fragmentation Reactions 259 16.1 Introduction 259 16.2 Carbon/Carbon Rearrangements 259 16.3 Carbon/Nitrogen Rearrangements 266 16.4 Carbon/Oxygen Rearrangements 269 16.5 Fragmentation Reactions 270

17 Redox Reactions 273 17.1 Introduction 273 17.2 Reduction Reactions 274

17.2.1 Electron Donors 274 17.2.2 Hydride Ion Donors 278

17.3 Oxidation Reactions 280 17.4 Disproportionation Reactions 284

Part III: Appendices

18 Glossary 289

19 Abbreviations 353 19.1 Atomic, Group and Molecular Abbreviation 353 19.2 Mechanistic Abbreviations 355 19.3 Reaction Type Abbreviations 356

20 Molecular Notations 359 20.1 Non-Structural Notations 359

20.1.1 Empirical Formulae 359 20.1.2 Molecular Formulae 359

20.2 Two Dimensional Structural Notations 360 20.2.1 Dot and Cross 360 20.2.2 Line Notation 361

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20.2.3 Expanded Line Notation 362 20.2.4 Stick Notation 362 20.2.5 Two Dimensional Skeletal Notation 363

20.3 Three Dimensional Structural Notations 365 20.3.1 Haworth Notation 365 20.3.2 Three Dimensional Skeletal Notation 366 20.3.3 Stereo Projection 366 20.3.4 Sawhorse Projection 367 20.3.5 Newmann Projection 368 20.3.6 Fischer Projection 368

21 Stereochemical Terminology 369 21.1 Introduction 369 21.2 Structural Isomerism 370

21.2.1 Skeletal Isomerism 371 21.2.2 Positional Isomerism 372 21.2.3 Functional Isomerism 374 21.2.4 Tautomeric Isomerism 375 21.2.5 Meta Isomerism 375

21.3 Stereoisomerism 376 21.3.1 Optical Isomerism 378 21.3.2 Geometrical Isomerism 383 21.3.3 Conformers 386

22 Oxidation Numbers 391 22.1 Introduction 391 22.2 Oxidation Numbers in Ionic Species 391 22.3 Oxidation Numbers in Covalent Species 393

23 Skeletal Index 397 23.1 Hydrocarbon Compounds 397 23.2 Oxygen Containing Compounds 402 23.3 Nitrogen Containing Compounds 408 23.4 Nitrogen and Oxygen Containing Compounds 413 23.5 Sulfur Containing Compounds 417 23.6 Phosphorus Containing Compounds 419