Chapter1 Introduction 001
1.1 The Development of Organic Chemistry 001
1.2 The Structural Theory of Organic Chemistry 001
1.2.1 Atomic orbitals 002
1.2.2 Ionic bonding 002
1.2.3 Covalent bonding 003
1.2.4 Hybridization 003
1.2.5 Polar covalent bond, electronegativity and dipole moment 007
1.3 Acid-Base Theory in Organic Chemistry 008
1.3.1 Brnsted-Lowry acids and bases 008
1.3.2 Lewis acids and bases 009
1.4 Function Groups and Classify of Organic
Chemical Compounds 010
Extending reading: Linus Pauling 012
Problems 016

Chapter2 Alkanes 017
2.1 Introduction 017
2.2 Nomenclature of Alkanes 018
2.2.1 Nomenclature of unbranched alkyl groups 020
2.2.2 Nomenclature of branched-chain alkanes 020
2.2.3 Nomenclature of branched alkyl groups 022
2.2.4 Classification of hydrogen atoms 023
2.3 Structure and Conformations of Alkanes 023
2.3.1 Structure of methane 023
2.3.2 Structure of ethane 024
2.3.3 Free rotation, conformations, torsional strain of the carbon-carbon single bond 025
2.3.4 Propane and the butane 027
2.3.5 Conformations of n-butane: van der Waals repulsion 028
2.4 Physical Properties of Alkanes 029
2.4.1 Boiling point 029
2.4.2 Melting point 030
2.4.3 Solubility in water 031
2.5 Chemical Properties of Alkanes 032
2.5.1 Combustion of alkanes 032
2.5.2 Pyrolysis of alkanes: Cracking 034
2.5.3 Halogenation of alkanes 035
2.6 Occurrence and Uses of Alkanes 044
2.6.1 Sources of alkanes: petroleum 044
2.6.2 Petroleum refining 045
2.6.3 Cracking 045
Extending reading: Jacobus Henricus van’t Hoff 045
Problems 047

Chapter3 Alkenes 049
3.1 Structure of Alkenes 049
3.2 Nomenclature and Geometric Isomerism of Alkenes 050
3.2.1 Nomenclature of alkenes 050
3.2.2 Geometric isomerism of alkenes and its nomenclature 051
3.3 Physical Properties of Alkenes 052
3.4 Preparation and Uses of Alkenes 053
3.4.1 Dehydration 053
3.4.2 Dehydrohalogenation 054
3.4.3 Cracking 055
3.4.4 Use of alkenes 055
3.5 Chemical Properties of Alkenes 055
3.5.1 Catalytic hydrogenation reaction 055
3.5.2 Electrophilic addition to alkenes 056
3.5.3 HBr free radical addition 060
3.5.4 Addition of diboranes 061
3.5.5 Reactions of alkenes with oxygen electrophiles 062
3.5.6 The reaction of α-H 066
3.6 Polymer and Plastics 067
Extending reading: Synthesis of Palytoxin 069
Problems 070

Chapter4 Dienes and Conjugation 072
4.1 Nomenclature of Dienes 072
4.2 Structure and Stability of Conjugated Dienes 073
4.2.1 Conjugative effect 073
4.2.2 Molecular orbital (MO) of 1,3-butadiene 074
4.3 Chemical Properties of Conjugative Dienes 075
4.3.1 Electrophile addition 075
4.3.2 Diels-Alder reaction 076
4.4 Rubber 078
Extending reading 1: Otto Paul Hermann Diels 080
Extending reading 2: Kurt Alder 080
Problems 081

Chapter5 Cycloalkanes 083
5.1 Nomenclature of Cycloalkanes 083
5.1.1 Nomenclature of monocycloalkanes 083
5.1.2 Nomenclature of polycycloalkanes 084
5.2 Stabilities of Cycloalkanes 086
5.3 Structures and Conformation of Cycloalkanes 087
5.3.1 Structures and conformation of cyclopropane and cyclobutane 087
5.3.2 Structures and conformation of cyclopentane 089
5.3.3 Structures and conformation of cyclohexane 089
5.3.4 Conformations of higher cycloalkanes 091
5.3.5 Substituted cyclohexanes: axial and equatorial hydrogen atoms 092
5.4 Chemical Properties of Cycloalkanes 096
Extending reading: Derek Harold Richard Barton 097
Problems 098

Chapter6 Alkynes 101
6.1 Structure of Alkynes 101
6.2 Nomenclature of Alkynes 102
6.3 Physical Properties of Alkynes 103
6.4 Preparation and Uses of Alkynes 103
6.4.1 Preparation of ethyne (HC≡CH) 103
6.4.2 By elimination reaction 103
6.5 Chemical Properties of Alkynes 104
6.5.1 Acidity of terminal alkynes 104
6.5.2 Addition by electrophilic reagents 106
6.5.3 Hydroboration/oxidation of alkynes 108
6.5.4 Reduction of alkynes 108
6.5.5 Oxidation of alkynes 109
6.5.6 Alkynes anions as nucleophiles 110
Extending reading: Discovery of Acetylene 110
Problems 111

Chapter7 Stereochemistry 113
7.1 Enantiomerism and Chirality 113
7.2 Plane Polarized Light, Optical Activity and Specific Rotation 116
7.3 Fischer Projection 117
7.4 Configuration Representation Method, Configuration Labeling and Isomer Naming 118
7.4.1 R/S absolute configuration representation 119
7.4.2 D/L Relative configuration representation 119
7.5 Diastereomers 120
7.6 Resolution of Racemates 121
Extending reading: The Critical Role of Stereochemistry in Organic Chemistry — Insights from the Thalidomide Tragedy 122
Problems 123

Chapter8 Alkyl Halides 125
8.1 Classification and Nomenclature of Halogenated Hydrocarbons 125
8.2 Structure of Halides 126
8.3 Physical Properties of Halides 126
8.4 Chemical Properties of Halogenated Hydrocarbons 127
8.4.1 Nucleophilic substitution reaction 127
8.4.2 Elimination reactions of alkyl halides 132
8.4.3 Organometallic compounds and their reactions 133
8.5 Reaction Mechanism and Influencing Factors of Nucleophilic Substitution Reaction 135
8.5.1 The mechanism for SN2 reaction 135
8.5.2 The mechanism for SN1 reaction 137
8.5.3 Factors affecting the rates of SN1 and SN2 reactions 140
8.6 Mechanisms of Dehydrohalogenation 147
8.6.1 Bimolecular elimination reaction: E2 reaction 147
8.6.2 Unimolecular elimination reaction: E1 reaction 148
8.7 Substitution versus Elimination 149
8.7.1 SN2 versus E2 150
8.7.2 Tertiary halides: SN1 versus E1 151
8.8 Halogenated Alkenes 152
8.8.1 Vinyl halogenated alkenes 152
8.8.2 Allyl halide alkenes 153
8.9 Commonly Halogenated Hydrocarbons 154
Extending reading: Paul Walden 155
Problems 156

Chapter9 Benzene and Aromatic Chemistry 158
9.1 Structure of Benzene and Aromaticity 159
9.1.1 Kekulé and the structure of benzene 159
9.1.2 A resonance of bonding in benzene 159
9.1.3 The stability of benzene 161
9.1.4 The molecular orbitals of benzene 162
9.2 Nomenclature of Benzene Derivatives 163
9.3 Physical Properties of Benzene Derivatives 164
9.4 Chemical Properties of Benzene Derivatives 165
9.4.1 Reduction 165
9.4.2 Oxidation of alkyl side-chains 165
9.4.3 Free-radical halogenation of alkylbenzenes 166
9.5 Electrophilic Aromatic Substitution Reactions of Substituted Benzenes 167
9.5.1 Ortho, para-directing groups 173
9.5.2 Meta-directing groups 178
9.6 Polycyclic Aromatic Compounds 181
9.6.1 Non-fused polycyclic aromatic hydrocarbons 181
9.6.2 Fused polycyclic aromatic hydrocarbons 181
9.7 Non-Benzene Aromatic Hydrocarbons 185
9.7.1 Hückel rule 185
9.7.2 Cyclobutadiene and cyclooctatetraene 187
9.7.3 Annulene 187
9.7.4 Cyclopentadiene and cycloheptatriene 188
Extending reading: Discovery of Benzene and the Theory of Molecular Structure of Benzene 188
Problems 189

Chapter10 Alcohols, Phenols and Ethers 192
10.1 Structure of Alcohols, Phenols and Ethers 192
10.1.1 Structure of alcohols 192
10.1.2 Structure of phenols 192
10.1.3 Structure of ethers 193
10.2 Nomenclature of Alcohols, Phenols and Ethers 193
10.2.1 Nomenclature of alcohols 193
10.2.2 Nomenclature of phenols 194
10.2.3 Nomenclature of ethers 195
10.3 Physical Properties of Alcohols, Phenols and Ethers 195
10.3.1 Physical properties of alcohols 195
10.3.2 Physical properties of phenols 196
10.3.3 Physical properties of ethers 197
10.4 Preparation and Uses of Alcohols 197
10.4.1 Synthesis of alcohols by hydration of alkenes 197
10.4.2 Synthesis of alcohols by addition to carbonyl groups 199
10.4.3 Synthesis of alcohols by reduction of carbonyl-containing compounds 200
10.5 Chemical Properties of Alcohols 201
10.5.1 Acidity of alcohols 201
10.5.2 Conversion to alkyl halides 202
10.5.3 Dehydration of alcohols 203
10.5.4 Esterification of alcohols 204
10.5.5 Oxidation of alcohols 206
10.6 Preparation and Uses of Phenols 207
10.6.1 Laboratory synthesis 207
10.6.2 Industrial synthesis 207
10.7 Chemical Properties of Phenols 208
10.7.1 Acidity of phenols 208
10.7.2 Other reaction of the OH group of phenols 209
10.7.3 Reaction of the benzene ring of phenols 211
10.8 Preparation of Ethers 213
10.9 Chemical Properties of Ethers 214
10.9.1 The formation of oxonium salts 214
10.9.2 Acid-catalyzed cleavage of ethers 214
10.9.3 Autoxidation of ethers 215
10.10 Thiols, Sulfides and Disulfides 215
Extending reading: Victor Grignard 217
Problems 218

Chapter11 Nuclear Magnetic Resonance Spectroscopy 219
11.1 Principles of Nuclear Magnetic Resonance 219
11.1.1 Discovery of nuclear magnetic resonance 219
11.1.2 Spin phenomenon of atomic nucleus 219
11.1.3 The reasons of nuclear magnetic resonance 219
11.2 Chemical Shift 221
11.2.1 Definition of chemical shift 221
11.2.2 Shielding effect 221
11.2.3 Practical representation of chemical shift 222
11.2.4 Factors affecting chemical shift 223
11.3 Chemical Shifts of Characteristic Protons in 1H-NMR 225
11.4 Integration Curves and Peak Areas 228
11.5 Spin Coupling 228
11.5.1 The causes of spin coupling 228
11.5.2 Coupling constant (J) 230
11.5.3 The law of coupling and splitting 230
11.5.4 Spectrum analysis 231
11.6 NMR Instrument 233
11.7 Carbon Spectrum (13C-NMR) 234
Extended reading: Paul Lauterbur 235
Problems 237

Chapter12 Infrared Spectroscopy 241
12.1 Theoretical Background 241
12.1.1 Introduction 241
12.1.2 Generation conditions of infrared absorption spectra 242
12.1.3 Molecular vibration 243
12.1.4 Vibrational forms of molecules 244
12.2 The Infrared Spectrometer 245
12.3 Characteristic Absorption of Functional Groups 247
12.3.1 The functional group and fingerprint regions 247
12.3.2 Characteristic infrared absorption bands 248
12.3.3 The intensity of absorption bands 249
12.3.4 The infrared spectra of alkane, haloalkane, alkene, benzene and alcohol 249
12.4 Identifying Infrared Spectra 251
Extended reading: Kirchhoff and Bunsen on Spectroscopy 253
Problems 254

Chapter13 Aldehydes and Ketones 259
13.1 Structure and Nomenclature of Aldehydes and Ketones 259
13.1.1 Structure and bonding of carbonyl group 259
13.1.2 Nomenclature of aldehydes and ketones 260
13.1.3 Physical properties 261
13.2 Preparation of Aldehydes and Ketones 261
13.2.1 Oxidation of alcohols (dehydrogenation) 261
13.2.2 Oxidation of alkenes (ozonolysis) 263
13.2.3 Hydrolysis of gem-dihalides 263
13.2.4 Hydration of alkynes 263
13.2.5 Friedel-Crafts acylation 263
13.2.6 Hydroformylation of the linear α-olefins 264
13.2.7 Oxidation of side chain of arenes 264
13.3 Reactions of Aldehydes and Ketones 265
13.3.1 Nucleophilic addition 265
13.3.2 The activity of α-hydrogen in aldehydes and ketones 270
13.3.3 Oxidation reactions 275
13.3.4 Reduction 276
13.4 α,β-Unsaturated Carbonyl Compounds 277
Extended reading: Organic Chemist Huang Minglong 278
Problems 279

Chapter14 Carboxylic Acids and Acid Derivatives 281
14.1 Nomenclature of Carboxylic Acids and Their Derivatives 281
14.1.1 Nomencalture of carboxylic acids 281
14.1.2 Nomenclature of carboxylic acid derivatives 284
14.2 Structure and Physical Properties of Carboxylic Acids and Their Derivatives 287
14.2.1 Structure of carboxylic acids and their derivatives 287
14.2.2 Physical properties of carboxylic acids and their derivatives 290
14.3 Preparation of Carboxylic Acids 291
14.3.1 Oxidation reaction 291
14.3.2 Hydrolysis of carboxylic acid derivatives 293
14.3.3 Reaction of organometallic compounds with carbon dioxide 293
14.3.4 Other methods 294
14.4 Acidity of Carboxylic Acids 295
14.5 Formation of Acid Halides and Anhydrides 298
14.5.1 Formation of acid halides 298
14.5.2 Formation of acid anhydrides 299
14.6 Hydrolysis of Carboxylic Acid Derivatives 301
14.6.1 Hydrolysis reaction 301
14.6.2 Hydrolysis reaction mechanism 302
14.7 Alcoholysis of Carboxylic Acid Derivatives 304
14.7.1 Acylation 304
14.7.2 Transesterification 306
14.7.3 Esterification reaction mechanism 306
14.8 Aminolysis of Carboxylic Acid Derivatives 308
14.8.1 Reaction of carboxylic acid derivatives with amines 308
14.8.2 Nucleophilic substitution reaction mechanism of amines 310
14.9 Reaction of Carboxylic Acid Derivatives with Metal Reagents 310
14.9.1 Reaction with metal magnesium reagents 310
14.9.2 Reaction with metal lithium reagents 311
14.9.3 Reaction with metal copper-lithium reagents 311
14.9.4 Reaction with metal cadmium reagents 312
14.10 Reductions of Carboxylic Acids and Their Derivatives 312
14.10.1 Reduction of carboxylic acids 312
14.10.2 Reduction of acid halides 313
14.10.3 Reduction of esters 314
14.10.4 Reduction of amides 314
14.10.5 Reduction of nitriles 315
14.11 Other Reactions of Carboxylic Acids and Their Derivatives 316
14.11.1 Decarboxylation reaction 316
14.11.2 α-Substituted carboxylic acids and their derivatives 318
14.11.3 Elimination reaction of esters 319
14.11.4 Hoffmann degradation reaction of amides 320
14.12 Lactones 320
14.13 Lipids and Waxes 322
14.14 Carbonic Acid Derivatives 323
14.15 Surfactants and Soaps 324
Extended reading 1: August Wilhelm von Hofmann 326
Extended reading 2: Aspirin (acetylsalicylic acid) 327
Problems 327

Chapter15 Difunctional Compounds 333
15.1 Introduction 333
15.2 Hydroxy Aldehydes and Ketones 334
15.2.1 Properties 334
15.2.2 Preparation 334
15.2.3 Reactions 335
15.3 Hydroxy Acids 335
15.3.1 Properties 335
15.3.2 Preparation 335
15.3.3 Dehydration of hydroxy acid 336
15.4 Dicarboxylic Acids 337
15.4.1 Property and reactions 337
15.4.2 Acidity of dicarboxylic acids 338
15.5 Dicarbonyl Compounds 338
15.5.1 Acidity of β-dicarbonyl compounds and stability of enol anion 338
15.5.2 Diethyl malonate 339
15.5.3 Ethyl acetoacetate 340
15.5.4 Michael addition reaction 341
15.6 Summary 342
Extended reading: Possible Substitutes for White Pollution—Lactic Acid Polymer 344
Problems 344

Chapter16 Amines and Other Nitrogen-Containing Compounds 348
16.1 Amines 348
16.1.1 Nomenclature 348
16.1.2 Structure and physical properties 350
16.1.3 Preparation 351
16.1.4 Chemical properties 354
16.1.5 Reactions of diazonium ions 361
16.2 Nitro Compounds 363
16.3 Nitriles 365
16.3.1 Nomenclature 365
16.3.2 Physical properties 365
16.3.3 Preparation 365
16.3.4 Reactions of nitriles 365
Extended reading: The Development of Nitroglycerin 366
Problems 368

Chapter17 Heterocyclic Compounds 370
17.1 Heterocyclic System 370
17.2 Classification and Nomenclature of Heterocycles 371
17.3 Structure and Aromaticity of Heterocycles 372
17.4 Five-Membered Unsaturated Heterocycles 373
17.4.1 Furan 373
17.4.2 Thiophene 375
17.4.3 Pyrrole 375
17.4.4 Indole 376
17.5 Six-Membered Unsaturated Heterocycles 378
17.6 Quinoline and Isoquinoline 380
17.6.1 Quinoline 380
17.6.2 Isoquinoline 381
Extended reading: Tu Youyou and Artemisinin 382
Problems 383

Chapter18 Carbohydrates and Nucleic Acids 386
18.1 Stereochemistry of Sugars 386
18.1.1 The D and L notation 386
18.1.2 Configurations of aldoses 387
18.1.3 Configurations of ketoses 389
18.2 Structure of Glucose 389
18.3 Reactions of Monosaccharides 392
18.3.1 Reduction 392
18.3.2 Oxidation 393
18.3.3 Osazone formation 394
18.3.4 Ester formation 395
18.3.5 Chain elongation 395
18.3.6 Chain shortening 396
18.4 Disaccharides 396
18.5 Polysaccharides 399
Extended reading: Hermann Emil Fischer 401
Problems 403

Chapter19 Amino Acids, Peptides, Proteins and Nucleic Acids 405
19.1 Amino Acids 405
19.1.1 Nomenclature of amino acids 405
19.1.2 Physical properties of amino acids 407
19.1.3 The acidity and alkalinity of amino acids 407
19.1.4 Amino acid reaction 410
19.1.5 Amino acid synthesis 412
19.2 Peptides and Proteins 413
19.2.1 Peptide nomenclature 414
19.2.2 Synthesis of peptides and proteins 414
19.2.3 Determination of polypeptide structure 419
19.2.4 Protein hierarchy 424
19.3 Enzyme 427
19.4 Nucleic Acid 428
Extended reading: Human Genome Project 431
Problems 432

Chapter20 Organometallic Compounds 434
20.1 Preparation of Organometallic Compounds 434
20.1.1 Preparation of organolithium compounds 434
20.1.2 Preparation of organomagnesium compounds 435
20.1.3 Preparation of organocopper compounds 435
20.1.4 Preparation of organozinc compounds 436
20.2 Main Reactions of Organometallic Compounds 436
20.2.1 Organometallic compounds as Brnsted bases 436
20.2.2 Organometallic compounds as nucleophilic reagents 437
Extended reading: Karl Ziegler 440
Problems 440

Chapter21 Orbitals and Organic Chemistry: Pericyclic Reactions 443
21.1 Introduction 443
21.1.1 Evolution of the theory of concerted reactions 443
21.1.2 A review of π molecular orbitals 444
21.1.3 Interactions between molecular orbitals 445
21.2 Electrocyclic Reaction 445
21.3 Cycloaddition Reaction 447
21.3.1 Photochemical dimerization of alkenes 447
21.3.2 Diels-Alder reaction 448
21.4 Sigmatropic Rearrangements 448
Extended reading: Robert Burns Woodward 449
Problems 450
Reference 452