Chemistry of the Carbonyl Group

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 β-dicarbonyl compounds 108

Knoevenagel reaction 110

Alkylation of β-dicarbonyl compounds 113

Michael reaction 116

Decarboxylation 125

Base cleavage of β-dicarbonyl compounds 131

Cyclisation reactions: the Dieckmann condensation 134

Cyclisation of diketones 136

The dimedone synthesis 137

Ring opening by base cleavage of β-dicarbonyl compounds 141

Revision questions 142

Examples of syntheses: two steroid syntheses 145

Stork’s cedrene synthesis 150

Index 155