CONTENTS
vii
4.10 Buffers
152
4.11 Using pK a values
155
4.11.1
Predicting acid–base interactions
155
4.11.2
Isotopic labelling using basic reagents
157
4.11.3
Amphoteric compounds: amino acids
159
4.11.4
pK a and drug absorption
164
5
Reaction mechanisms
167
5.1
Ionic reactions
167
5.1.1
Bond polarity
170
5.1.2
Nucleophiles, electrophiles, and leaving groups
171
5.2
Radical reactions
171
5.3
Reaction kinetics and mechanism
173
5.4
Intermediates and transition states
173
5.5
Types of reaction
174
5.6
Arrows
175
6
Nucleophilic reactions: nucleophilic substitution
183
6.1
The S N 2 reaction: bimolecular nucleophilic substitution
183
6.1.1
The effect of substituents
184
6.1.2
Nucleophiles: nucleophilicity and basicity
185
6.1.3
Solvent effects
187
6.1.4
Leaving groups
188
6.1.5
S N 2 reactions in cyclic systems
190
6.2
The S N 1 reaction: unimolecular nucleophilic substitution
191
6.2.1
The effect of substituents
193
6.2.2
S N 1 reactions in cyclic systems
195
6.2.3
S N 1 or S N 2?
195
6.3
Nucleophilic substitution reactions
198
6.3.1
Halide as a nucleophile: alkyl halides
198
6.3.2
Oxygen and sulfur as nucleophiles: ethers, esters, thioethers,
epoxides
198
6.3.3
Nitrogen as a nucleophile: ammonium salts, amines
201
6.3.4
Carbon as a nucleophile: nitriles, Grignard reagents, acetylides
204
6.3.5
Hydride as nucleophile: lithium aluminium hydride and sodium
borohydride reductions
205
6.3.6
Formation of cyclic compounds
206
6.4
Competing reactions: eliminations and rearrangements
206
6.4.1
Elimination reactions
207
6.4.2
Carbocation rearrangement reactions
214
7
Nucleophilic reactions of carbonyl groups
221
7.1
Nucleophilic addition to carbonyl groups: aldehydes and ketones
221
7.1.1
Aldehydes are more reactive than ketones
222
7.1.2
Nucleophiles and leaving groups: reversible addition reactions
223
7.2
Oxygen as a nucleophile: hemiacetals, hemiketals, acetals and ketals
224
7.3
Water as a nucleophile: hydrates
234
7.4
Sulfur as a nucleophile: hemithioacetals, hemithioketals, thioacetals
and thioketals
235
vii
4.10 Buffers
152
4.11 Using pK a values
155
4.11.1
Predicting acid–base interactions
155
4.11.2
Isotopic labelling using basic reagents
157
4.11.3
Amphoteric compounds: amino acids
159
4.11.4
pK a and drug absorption
164
5
Reaction mechanisms
167
5.1
Ionic reactions
167
5.1.1
Bond polarity
170
5.1.2
Nucleophiles, electrophiles, and leaving groups
171
5.2
Radical reactions
171
5.3
Reaction kinetics and mechanism
173
5.4
Intermediates and transition states
173
5.5
Types of reaction
174
5.6
Arrows
175
6
Nucleophilic reactions: nucleophilic substitution
183
6.1
The S N 2 reaction: bimolecular nucleophilic substitution
183
6.1.1
The effect of substituents
184
6.1.2
Nucleophiles: nucleophilicity and basicity
185
6.1.3
Solvent effects
187
6.1.4
Leaving groups
188
6.1.5
S N 2 reactions in cyclic systems
190
6.2
The S N 1 reaction: unimolecular nucleophilic substitution
191
6.2.1
The effect of substituents
193
6.2.2
S N 1 reactions in cyclic systems
195
6.2.3
S N 1 or S N 2?
195
6.3
Nucleophilic substitution reactions
198
6.3.1
Halide as a nucleophile: alkyl halides
198
6.3.2
Oxygen and sulfur as nucleophiles: ethers, esters, thioethers,
epoxides
198
6.3.3
Nitrogen as a nucleophile: ammonium salts, amines
201
6.3.4
Carbon as a nucleophile: nitriles, Grignard reagents, acetylides
204
6.3.5
Hydride as nucleophile: lithium aluminium hydride and sodium
borohydride reductions
205
6.3.6
Formation of cyclic compounds
206
6.4
Competing reactions: eliminations and rearrangements
206
6.4.1
Elimination reactions
207
6.4.2
Carbocation rearrangement reactions
214
7
Nucleophilic reactions of carbonyl groups
221
7.1
Nucleophilic addition to carbonyl groups: aldehydes and ketones
221
7.1.1
Aldehydes are more reactive than ketones
222
7.1.2
Nucleophiles and leaving groups: reversible addition reactions
223
7.2
Oxygen as a nucleophile: hemiacetals, hemiketals, acetals and ketals
224
7.3
Water as a nucleophile: hydrates
234
7.4
Sulfur as a nucleophile: hemithioacetals, hemithioketals, thioacetals
and thioketals
235