Chemistry of the Carbonyl Group: A Step–by–Step Approach to Understanding Organic Reaction Mechanisms

TEACHES AND ENABLES STUDENTS TO BUILD CONFIDENCE IN DRAWING AND MANIPULATING CURLY ARROWS, A FUNDAMENTAL SKILL FOR ALL ORGANIC CHEMISTS

This book is an interactive approach to learning about chemistry of the carbonyl group inviting students to work through its pages with pencil and paper in hand. It educates with the belief that the most effective way to learn is by practice and interaction. With this in mind, the reader is asked to predict what would happen under a specific set of reaction conditions. The book is divided into frames: each frame poses a question and invites the reader to predict what will happen. Subsequent frames give the solution but then pose more questions to develop a theme further.

Chemistry of the Carbonyl Group: A Step–by–Step Approach to Understanding Organic Reaction Mechanisms provides a solid grounding in the fundamental reactions of carbonyls. Presented in full colour to enhance the understanding of mechanisms within chemistry, the chapters of this step–by–step guide cover: nucleophilic addition to the carbonyl group; nucleophilic substitution; nucleophilic substitution at the carbonyl group with complete removal of carbonyl oxygen; carbanions and enolisation; and building organic molecules from carbonyl compounds.

A must–have book for undergraduate chemists to emphasise understanding in carbonyl group chemistry Goes through all the stages of basic carbonyl chemistry, detailing even the simplest mechanisms A step–by–step learning guide to synthetic chemistry for the first year of a chemistry degree, with all the information needed for independent learning Provides a solid grounding in the fundamental reactions of carbonyls which will inform the understanding of many other organic chemistry reactions

Chemistry of the Carbonyl Group: A Step–by–Step Approach to Understanding Organic Reaction Mechanisms is packed with all the information on synthetic chemistry that every first–year student will need in order to learn independently.

PREFACE xi

ACKNOWLEDGEMENTS xiii

SOME HELP THAT YOU MAY NEED xv

WHAT DO YOU NEED TO KNOW BEFORE YOU START? xvii

INTRODUCTION xix

1 Nucleophilic Addition to the Carbonyl Group 1

Nucleophilic addition: what it is and how it happens 3

Alcohols as nucleophiles: acetal formation 6

Some carbon carbon bond–forming reactions with carbon nucleophiles: cyanide ion, acetylide ion and Grignard reagents 10

Hydride ion and its derivatives LiAlH4 and NaBH4. Reduction of aldehydes and ketones 17

Meerwein Ponndorf reduction and Oppenauer oxidation, with a branch program on how to draw transition states 19

Two general revision problems 25

2 Nucleophilic Substitution 29

Substitution: how it happens 31

LiAlH4 reduction of esters 33

Reaction of Grignard reagents with esters 34

Alkaline hydrolysis of esters 38

Acid hydrolysis of amides 39

Summary of acid and base catalysis 41

Reaction between carboxylic acids and thionyl chloride 41

Synthesis of esters and anhydrides from carboxylic acids 43

Review questions 45

3 Nucleophilic Subsitution at the Carbonyl Group with Complete Removal of Carbonyl Oxygen 49

Imine formation from aldehydes and ketones 51

Oxime formation and the structure of oximes 53

Hydrazone and semicarbazone formation 54

Reduction of C=O to CH2 56

Conversion of C=O to CCl2 60

DDT synthesis 64

Chloromethylation of aromatic compounds 65

Review questions 66

4 Carbanions and Enolisation 69

Carbanions 71

Tautomerism 72

Equilibration and racemisation of ketones by enolisation 73

Halogenation of ketones 78

Formation of bromo–acid derivatives 83

Organo–zinc derivatives and their use in synthesis 85

Review questions 87

5 Building Organic Molecules from Carbonyl Compounds 89

Using enols as nucleophiles to attack other carbonyl groups 92

The aldol reaction 92

The Claisen ester condensation 93

Acid catalysed condensation of acetone 94

Self–condensation reactions 96

Elaboration of a skeleton in synthesis 97

Cross–condensations with molecules which cannot enolise 98

Mannich reaction 103

Perkin reaction 105

Stable enols from –dicarbonyl compounds 108

Knoevenagel reaction 110

Alkylation of –dicarbonyl compounds 113

Michael reaction 116

Decarboxylation 125

Base cleavage of –dicarbonyl compounds 131

Cyclisation reactions: the Dieckmann condensation 134

Cyclisation of diketones 136

The dimedone synthesis 137

Ring opening by base cleavage of –dicarbonyl compounds 141

Revision questions 142

Examples of syntheses: two steroid syntheses 145

Stork s cedrene synthesis 150

INDEX 155

TIMOTHY K. DICKENS, FRSC, is Official Fellow, College Lecturer and Director of Studies in Chemistry at Peterhouse, Cambridge. Dr Dickens graduated from the University of Kent in 1982, and, after two years′ research at Oxford, he joined Glaxo where he spent 24 years in both scientific and technology senior roles. In 2008, he joined the University of Cambridge, where his research has focused on Ring Currents in conjugated systems.

STUART WARREN, PHD, is the author of the textbooks Organic Chemistry, Organic Synthesis: The Disconnection Approach and Organic Synthesis. He retired from Churchill College, Department of Chemistry, University of Cambridge in 2006, having fostered some of the most successful organic chemistry academics in the UK.