CHAPTER 1: Structure Determines Properties

1.1 Atoms, Electrons, and Orbitals
1.2 Ionic Bonds
1.3 Covalent Bonds, Lewis Structures, and the Octet Rule
1.4 Double Bonds and Triple Bonds
1.5 Polar Covalent Bonds and Electronegativity
Electrostatic Potential Maps
1.6 Structural Formulas of Organic Molecules
1.7 Formal Charge
1.8 Resonance
1.9 The Shapes of Some Simple Molecules
Molecular Modeling
1.10 Molecular Dipole Moments
1.11 Curved Arrows and Chemical Reactions
1.12 Acids and Bases: The Arrhenius View
1.13 Acids and Bases: The Brønsted–Lowry View
1.14 What Happened to pK_b?
1.15 How Structure Affects Acid Strength
1.16 Acid–Base Equilibria
1.17 Lewis Acids and Lewis Bases
1.18 Summary
Problems
Descriptive Passage and Interpretive Problems 1: Amide Lewis Structures

CHAPTER 2: Alkanes and Cycloalkanes: Introduction to Hydrocarbons

2.1 Classes of Hydrocarbons
2.2 Electron Waves and Chemical Bonds
2.3 Bonding in H₂: The Valence Bond Model
2.4 Bonding in H₂: The Molecular Orbital Model
2.5 Introduction to Alkanes: Methane, Ethane, and Propane Methane and the Biosphere
2.6 sp³ Hybridization and Bonding in Methane
2.7 Bonding in Ethane
2.8 Isomeric Alkanes: The Butanes
2.9 Higher n-Alkanes
2.10 The C₅H₁₂ Isomers
2.11 IUPAC Nomenclature of Unbranched Alkanes
What's in a Name: Organic Nomenclature
2.12 Applying the IUPAC Rules: The Names of the C₆H₁₄ Isomers
2.13 Alkyl Groups
2.14 IUPAC Names of Highly Branched Alkanes
2.15 Cycloalkane Nomenclature
2.16 Sources of Alkanes and Cycloalkanes
2.17 Physical Properties of Alkanes and Cycloalkanes
2.18 Chemical Properties: Combustion of Alkanes
2.19 Oxidation–Reduction in Organic Chemistry Thermochemistry
2.20 sp 2 Hybridization and Bonding in Ethylene
2.21 sp Hybridization and Bonding in Acetylene
2.22 Which Theory of Chemical Bonding Is Best?
2.23 Summary
Problems
Descriptive Passage and Interpretive Problems 2: Some Biochemical Reactions of Alkanes

CHAPTER 3: Alkanes and Cycloalkanes: Conformations and cis–trans Stereoisomers

3.1 Conformational Analysis of Ethane 104
3.2 Conformational Analysis of Butane 107
Molecular Mechanics Applied to Alkanes and Cycloalkanes 109 3.3 Conformations of Higher Alkanes 110
3.4 The Shapes of Cycloalkanes: Planar or Nonplanar? 110
3.5 Small Rings: Cyclopropane and Cyclobutane 111
3.6 Cyclopentane 112
3.7 Conformations of Cyclohexane 112
3.8 Axial and Equatorial Bonds in Cyclohexane 113
3.9 Conformational Inversion (Ring Flipping) in Cyclohexane 115
3.10 Conformational Analysis of Monosubstituted Cyclohexanes 116
3.11 Disubstituted Cycloalkanes: cis-trans Stereoisomers 119
Enthalpy, Free Energy, and Equilibrium Constant 120
3.12 Conformational Analysis of Disubstituted Cyclohexanes 121
3.13 Medium and Large Rings 125
3.14 Polycyclic Ring Systems 125
3.15 Heterocyclic Compounds 128
3.16 Summary 129
Problems 132
Descriptive Passage and Interpretive Problems 3: Forms of carbohydrates 137

CHAPTER 4: Alcohols and Alkyl Halides

4.1 Functional Groups 139
4.2 IUPAC Nomenclature of Alkyl Halides 141
4.3 IUPAC Nomenclature of Alcohols 142
4.4 Classes of Alcohols and Alkyl Halides 142
4.5 Bonding in Alcohols and Alkyl Halides 143
4.6 Physical Properties of Alcohols and Alkyl Halides: Intermolecular Forces 144
4.7 Preparation of Alkyl Halides from Alcohols and Hydrogen Halides 148
4.8 Mechanism of the Reaction of Alcohols with Hydrogen Halides 149
4.9 Potential Energy Diagrams for Multistep Reactions: The SN 1 Mechanism 154
4.10 Structure, Bonding, and Stability of Carbocations 155
4.11 Effect of Alcohol Structure on Reaction Rate 158
4.12 Reaction of Methyl and Primary Alcohols with Hydrogen Halides: The SN 2 Mechanism 159
4.13 Other Methods for Converting Alcohols to Alkyl Halides 160
4.14 Halogenation of Alkanes 161
4.15 Chlorination of Methane 162
4.16 Structure and Stability of Free Radicals 162
4.17 Mechanism of Methane Chlorination 167
4.18 Halogenation of Higher Alkanes 168
From Bond Energies to Heats of Reaction 169
4.19 Summary 173
Problems 176
Descriptive Passage and Interpretive Problems 4: More About Potential Energy Diagrams 180

CHAPTER 5: Structure and Preparation of Alkenes: Elimination Reactions

5.1 Alkene Nomenclature
5.2 Structure and Bonding in Alkenes 185
Ethylene 186
5.3 Isomerism in Alkenes 187
5.4 Naming Stereoisomeric Alkenes by the E–Z Notational System 188
5.5 Physical Properties of Alkenes 189
5.6 Relative Stabilities of Alkenes 191
5.7 Cycloalkenes 195
5.8 Preparation of Alkenes: Elimination Reactions 196
5.9 Dehydration of Alcohols 197
5.10 Regioselectivity in Alcohol Dehydration: The Zaitsev Rule 198
5.11 Stereoselectivity in Alcohol Dehydration 199
5.12 The E1 and E2 Mechanisms of Alcohol Dehydration 200
5.13 Rearrangements in Alcohol Dehydration 202
5.14 Dehydrohalogenation of Alkyl Halides 205
5.15 The E2 Mechanism of Dehydrohalogenation of Alkyl Halides 207
5.16 Anti Elimination in E2 Reactions: Stereoelectronic Effects 209
5.17 Isotope Effects and the E2 Mechanism 210
5.18 The E1 Mechanism of Dehydrohalogenation of Alkyl Halides 211
5.19 Summary 213
Problems 217
Descriptive Passage and Interpretive Problems 5: A Mechanistic Preview of Addition Reactions 222

CHAPTER 6: Addition Reactions of Alkenes

6.1 Hydrogenation of Alkenes 225
6.2 Heats of Hydrogenation 226
6.3 Stereochemistry of Alkene Hydrogenation 229
6.4 Electrophilic Addition of Hydrogen Halides to Alkenes 229
6.5 Regioselectivity of Hydrogen Halide Addition: Markovnikov’s Rule 231
6.6 Mechanistic Basis for Markovnikov’s Rule 233
Rules, Laws, Theories, and the Scientific Method 235
6.7 Carbocation Rearrangements in Hydrogen Halide Addition to Alkenes 235
6.8 Free-Radical Addition of Hydrogen Bromide to Alkenes 236
6.9 Addition of Sulfuric Acid to Alkenes 239
6.10 Acid-Catalyzed Hydration of Alkenes 241
6.11 Thermodynamics of Addition–Elimination Equilibria 243
6.12 Hydroboration–Oxidation of Alkenes 246
6.13 Stereochemistry of Hydroboration–Oxidation 248
6.14 Mechanism of Hydroboration–Oxidation 248
6.15 Addition of Halogens to Alkenes 251
6.16 Stereochemistry of Halogen Addition 251
6.17 Mechanism of Halogen Addition to Alkenes: Halonium Ions 252
6.18 Conversion of Alkenes to Vicinal Halohydrins 254
6.19 Epoxidation of Alkenes 255
6.20 Ozonolysis of Alkenes 257
6.21 Introduction to Organic Chemical Synthesis 259
6.22 Reactions of Alkenes with Alkenes: Polymerization 260
Ethylene and Propene: The Most Important Industrial Organic Chemicals 265
6.23 Summary 266
Problems 269
Descriptive Passage and Interpretive Problems 6: Some Unusual Electrophilic Additions 274

CHAPTER 7: Stereochemistry

7.1 Molecular Chirality: Enantiomers 277
7.2 The Chirality Center 279
7.3 Symmetry in Achiral Structures 281
7.4 Optical Activity 282
7.5 Absolute and Relative Configuration 284
7.6 The Cahn–Ingold–Prelog R–S Notational System 285
7.7 Fischer Projections 288
7.8 Properties of Enantiomers 290
Chiral Drugs 291
7.9 Reactions That Create a Chirality Center 292
7.10 Chiral Molecules with Two Chirality Centers 295
7.11 Achiral Molecules with Two Chirality Centers 297
7.12 Molecules with Multiple Chirality Centers 299
Chirality of Disubstituted Cyclohexanes 300
7.13 Reactions That Produce Diastereomers 301
7.14 Resolution of Enantiomers 303
7.15 Stereoregular Polymers 305
7.16 Chirality Centers Other Than Carbon 306
7.17 Summary 307
Problems 310
Descriptive Passage and Interpretive Problems 7: Prochirality 316

CHAPTER 8: Nucleophilic Substitution 318

8.1 Functional Group Transformation by Nucleophilic Substitution 319
8.2 Relative Reactivity of Halide Leaving Groups 322
8.3 The SN 2 Mechanism of Nucleophilic Substitution 323
8.4 Steric Effects in SN 2 Reaction Rates 326
8.5 Nucleophiles and Nucleophilicity 328
8.6 The SN 1 Mechanism of Nucleophilic Substitution 330
Enzyme-Catalyzed Nucleophilic Substitutions of Alkyl Halides 331
8.7 Carbocation Stability and SN 1 Reaction Rates 331
8.8 Stereochemistry of SN 1 Reactions 334
8.9 Carbocation Rearrangements in SN 1 Reactions 335
8.10 Effect of Solvent on the Rate of Nucleophilic Substitution 337
8.11 Substitution and Elimination as Competing Reactions 339
8.12 Nucleophilic Substitution of Alkyl Sulfonates 342
8.13 Looking Back: Reactions of Alcohols with Hydrogen Halides 344
8.14 Summary 346
Problems 347
Descriptive Passage and Interpretive Problems 8: Nucleophilic Substitution 352

CHAPTER 9: Alkynes

9.1 Sources of Alkynes 355
9.2 Nomenclature 357
9.3 Physical Properties of Alkynes 357
9.4 Structure and Bonding in Alkynes: sp Hybridization 357
9.5 Acidity of Acetylene and Terminal Alkynes 360
9.6 Preparation of Alkynes by Alkyation of Acetylene and Terminal Alkynes 361
9.7 Preparation of Alkynes by Elimination Reactions 363
9.8 Reactions of Alkynes 364
9.9 Hydrogenation of Alkynes 365
9.10 Metal–Ammonia Reduction of Alkynes 367
9.11 Addition of Hydrogen Halides to Alkynes 368
9.12 Hydration of Alkynes 370
9.13 Addition of Halogens to Alkynes 371
Some Things That Can Be Made from Acetylene...But Aren't 372
9.14 Ozonolysis of Alkynes 372
9.15 Summary 373
Problems 376
Descriptive Passage and Interpretive Problems 9: Thinking Mechanistically About Alkynes 380

CHAPTER 10: Conjugation in Alkadienes and Allylic Systems

10.1 The Allyl Group 383
10.2 Allylic Carbocations 384
10.3 SN 1 Reactions of Allylic Halides 385
10.4 SN 2 Reactions of Allylic Halides 388
10.5 Allylic Free Radicals 389
10.6 Allylic Halogenation 390
10.7 Allylic Anions 393
10.8 Classes of Dienes 394
10.9 Relative Stabilities of Dienes 395
10.10 Bonding in Conjugated Dienes 396
10.11 Bonding in Allenes 398
10.12 Preparation of Dienes 399
10.13 Addition of Hydrogen Halides to Conjugated Dienes 400
10.14 Halogen Addition to Dienes 403
10.15 The Diels–Alder Reaction 403
Diene Polymers 404
10.16 The Pi Molecular Orbitals of Ethylene and 1,3-Butadiene 407
10.17 A Pi Molecular Orbital Analysis of the Diels–Alder Reaction 408
10.18 Summary 410
Problems 413
Descriptive Passage and Interpretive Problems 10: Intramolecular and Retro Diels-Alder Reactions 417

CHAPTER 11: Arenes and Aromaticity

11.1 Benzene 421
11.2 Kekulé and the Structure of Benzene 422
11.3 A Resonance Picture of Bonding in Benzene 424
11.4 The Stability of Benzene 424
11.5 An Orbital Hybridization View of Bonding in Benzene 426
11.6 The Pi Molecular Orbitals of Benzene 427
11.7 Substituted Derivatives of Benzene and Their Nomenclature 428
11.8 Polycyclic Aromatic Hydrocarbons 430
11.9 Physical Properties of Arenes 431
Carbon Clusters, Fullerenes, and Nanotubes 432
11.10 Reactions of Arenes: A Preview 432
11.11 The Birch Reduction 433
11.12 Free-Radical Halogenation of Alkylbenzenes 436
11.13 Oxidation of Alkylbenzenes 438
11.14 Sn1 Reactions of Benzylic Halides 440
11.15 Sn2 Reactions of Benzylic Halides 441
11.16 Preparation of Alkenylbenzenes 442
11.17 Addition Reactions of Alkenylbenzenes 443
11.18 Polymerization of Styrene 445
11.19 Cyclobutadiene and Cyclooctatetraene 446
11.20 Hückel’s Rule 448
11.21 Annulenes 450
11.22 Aromatic Ions 452
11.23 Heterocyclic Aromatic Compounds 455
11.24 Heterocyclic Aromatic Compounds and Hückel’s Rule 457
11.25 Summary 459
Problems 462
Descriptive Passage and Interpretive Problems 11: The Hammett Equation 46

CHAPTER 12: Reactions of Arenes: Electrophilic Aromatic Substitution

12.1 Representative Electrophilic Aromatic Substitution Reactions of Benzene 471
12.2 Mechanistic Principles of Electrophilic Aromatic Substitution 472
12.3 Nitration of Benzene 474
12.4 Sulfonation of Benzene 476
12.5 Halogenation of Benzene 477
12.6 Friedel–Crafts Alkylation of Benzene 478
12.7 Friedel–Crafts Acylation of Benzene 481
12.8 Synthesis of Alkylbenzenes by Acylation–Reduction 483
12.9 Rate and Regioselectivity in Electrophilic Aromatic Substitution 484
12.10 Rate and Regioselectivity in the Nitration of Toluene 485
12.11 Rate and Regioselectivity in the Nitration of (Trifluoromethyl)benzene 488
12.12 Substituent Effects in Electrophilic Aromatic Substitution: Activating Substituents 490
12.13 Substituent Effects in Electrophilic Aromatic Substitution: Strongly Deactivating Substituents 493
12.14 Substituent Effects in Electrophilic Aromatic Substitution: Halogens 496
12.15 Multiple Substituent Effects 498
12.16 Regioselective Synthesis of Disubstituted Aromatic Compounds 499
12.17 Substitution in Naphthalene 502
12.18 Substitution in Heterocyclic Aromatic Compounds 502
12.19 Summary 504
Problems 507
Descriptive Passage and Interpretive Problems 12: Nucleophilic Aromatic Substitution 512

CHAPTER 13: Spectroscopy

13.1 Principles of Molecular Spectroscopy: Electromagnetic Radiation
13.2 Principles of Molecular Spectroscopy: Quantized Energy States
13.3 Introduction to ¹H NMR Spectroscopy
13.4 Nuclear Shielding and ¹H Chemical Shifts
13.5 Effects of Molecular Structure on ¹H Chemical Shifts
Ring Currents: Aromatic and Antiaromatic
13.6 Interpreting ¹H NMR Spectra
13.7 Spin–Spin Splitting in ¹H NMR Spectroscopy
13.8 Splitting Patterns: The Ethyl Group
13.9 Splitting Patterns: The Isopropyl Group
13.10 Splitting Patterns: Pairs of Doublets
13.11 Complex Splitting Patterns
13.12 ¹H NMR Spectra of Alcohols
Magnetic Resonance Imaging (MRI)
13.13 NMR and Conformations
13.14 ¹³C NMR Spectroscopy
13.15 ¹³C Chemical Shifts
13.16 ¹³C NMR and Peak Intensities
13.17 ¹³C ¹H Coupling
13.18 Using DEPT to Count Hydrogens Attached to ¹³C
13.19 2D NMR: COSY and HETCOR
13.20 Introduction to Infrared Spectroscopy
Spectra by the Thousands
13.21 Infrared Spectra
13.22 Characteristic Absorption Frequencies
13.23 Ultraviolet-Visible (UV-VIS) Spectroscopy
13.24 Mass Spectrometry
13.25 Molecular Formula as a Clue to Structure
Gas Chromatography, GC/MS, and MS/MS
13.26 Summary
Problems
Descriptive Passage and Interpretive Problems 13: Calculating Aromatic ¹³C Chemical Shifts

CHAPTER 16: Ethers, Epoxides, and Sulfides

16.1 Nomenclature of Ethers, Epoxides, and Sulfides
16.2 Structure and Bonding in Ethers and Epoxides
16.3 Physical Properties of Ethers
16.4 Crown Ethers
16.5 Preparation of Ethers
Polyether Antibiotics
16.6 The Williamson Ether Synthesis
16.7 Reactions of Ethers: A Review and a Preview
16.8 Acid-Catalyzed Cleavage of Ethers
16.9 Preparation of Epoxides: A Review and a Preview
16.10 Conversion of Vicinal Halohydrins to Epoxides
16.11 Reactions of Epoxides: A Review and a Preview
16.12 Nucleophilic Ring Opening of Epoxides
16.13 Acid-Catalyzed Ring Opening of Epoxides
16.14 Epoxides in Biological Processes
16.15 Preparation of Sulfides
16.16 Oxidation of Sulfides: Sulfoxides and Sulfones
16.17 Alkylation of Sulfides: Sulfonium Salts
16.18 Spectroscopic Analysis of Ethers, Epoxides, and Sulfides
16.19 Summary
Problems
Descriptive Passage and Interpretive Problems 16: Epoxide Rearrangements and the NIH Shift

CHAPTER 17: Aldehydes and Ketones: Nucleophilic Addition to the Carbonyl Group

17.1 Nomenclature
17.2 Structure and Bonding: The Carbonyl Group
17.3 Physical Properties
17.4 Sources of Aldehydes and Ketones
17.5 Reactions of Aldehydes and Ketones: A Review and a Preview
17.6 Principles of Nucleophilic Addition: Hydration of Aldehydes and Ketones
17.7 Cyanohydrin Formation
17.8 Acetal Formation
17.9 Acetals as Protecting Groups
17.10 Reaction with Primary Amines: Imines
Imines in Biological Chemistry
17.11 Reaction with Secondary Amines: Enamines
17.12 The Wittig Reaction
17.13 Planning an Alkene Synthesis via the Wittig Reaction
17.14 Stereoselective Addition to Carbonyl Groups
17.15 Oxidation of Aldehydes
17.16 Baeyer–Villiger Oxidation of Ketones
17.17 Spectroscopic Analysis of Aldehydes and Ketones
17.18 Summary
Problems
Descriptvie Passage and Interpretive Problems 17: Alcohols, Aldehydes, and Carbohydrates

CHAPTER 18: Enols and Enolates

18.1 The -Hydrogen and Its pKa 753
18.2 The Aldol Condensation 757
18.3 Mixed Aldol Condensations 761
18.4 Alkylation of Enolate Ions 763
18.5 Enolization and Enol Content 764
18.6 Stabilized Enols 766
18.7 Halogenation of Aldehydes and Ketones 768
18.8 Mechanism of Halogenation of Aldehydes and Ketones 768
18.9 The Haloform Reaction 770
18.10 Some Chemical and Stereochemical Consequences of Enolization 772
The Haloform Reaction and the Biosynthesis of Trihalomethanes 773
18.11 Effects of Conjugation in ,-Unsaturated Aldehydes and Ketones 774
18.12 Conjugate Addition to ,-Unsaturated Carbonyl Compounds 775
18.13 Addition of Carbanions to ,-Unsaturated Ketones: The Michael Reaction 778
18.14 Conjugate Addition of Organocopper Reagents to ,-Unsaturated Carbonyl Compounds 778
18.15 Summary 779
Problems 782
Descriptive Passage and Interpretive Problems 18: Enolate Regiochemistry and Stereochemistry 787

CHAPTER 19: Carboxylic Acids

19.1 Carboxylic Acid Nomenclature 791
19.2 Structure and Bonding 793
19.3 Physical Properties 794
19.4 Acidity of Carboxylic Acids 794
19.5 Salts of Carboxylic Acids 797
19.6 Substituents and Acid Strength 799
19.7 Ionization of Substituted Benzoic Acids 801
19.8 Dicarboxylic Acids 802
19.9 Carbonic Acid 802
19.10 Sources of Carboxylic Acids 803
19.11 Synthesis of Carboxylic Acids by the Carboxylation of Grignard Reagents 806
19.12 Synthesis of Carboxylic Acids by the Preparation and Hydrolysis of Nitriles 806
19.13 Reactions of Carboxylic Acids: A Review and a Preview 807
19.14 Mechanism of Acid-Catalyzed Esterification 808
19.15 Intramolecular Ester Formation: Lactones 811
19.16 Alpha Halogenation of Carboxylic Acids: The Hell–Volhard–Zelinsky Reaction 813
19.17 Decarboxylation of Malonic Acid and Related Compounds 815
19.18 Spectroscopic Analysis of Carboxylic Acids 817
19.19 Summary 818
Problems 821
Descriptive Passage and Interpretive Problems 19: Lactonization Methods 825

CHAPTER 20: Carboxylic Acid Derivatives: Nucleophilic Acyl Substitution

20.1 Nomenclature of Carboxylic Acid Derivatives 830
20.2 Structure and Reactivity of Carboxylic Acid Derivatives 831
20.3 General Mechanism for Nucleophilic Acyl Substitution 834
20.4 Nucleophilic Acyl Substitution in Acyl Chlorides 836
20.5 Nucleophilic Acyl Substitution in Carboxylic Acid Anhydrides 839
20.6 Sources of Esters 842
20.7 Physical Properties of Esters 842
20.8 Reactions of Esters: A Review and a Preview 844
20.9 Acid-Catalyzed Ester Hydrolysis 844
20.10 Ester Hydrolysis in Base: Saponification 848
20.11 Reaction of Esters with Ammonia and Amines 851
20.12 Amides 852
20.13 Hydrolysis of Amides 857
20.14 Lactams 861
-Lactam Antibiotics 861
20.15 Preparation of Nitriles 862
20.16 Hydrolysis of Nitriles 863
20.17 Addition of Grignard Reagents to Nitriles 864
20.18 Spectroscopic Analysis of Carboxylic Acid Derivatives 866
20.19 Summary 867
Problems 870
Descriptive Passage and Interpretive Problems 20: Thioesters 876

CHAPTER 21: Ester Enolates

21.1 Ester Hydrogens and Their pK_a ’s
21.2 The Claisen Condensation 883
21.3 Intramolecular Claisen Condensation: The Dieckmann Reaction 886
21.4 Mixed Claisen Condensations 886
21.5 Acylation of Ketones with Esters 887
21.6 Ketone Synthesis via -Keto Esters 888
21.7 The Acetoacetic Ester Synthesis 889
21.8 The Malonic Ester Synthesis 892
21.9 Michael Additions of Stabilized Anions 894
21.10 Reactions of LDA-Generated Ester Enolates 895
21.11 Summary 897
Problems 899
Descriptive Passage and Interpretive Problems 21: The Enolate Chemistry of Dianions 903

CHAPTER 22: Amines

22.1 Amine Nomenclature 909
22.2 Structure and Bonding 911
22.3 Physical Properties 913
22.4 Basicity of Amines 914
Amines as Natural Products 919
22.5 Tetraalkylammonium Salts as Phase-Transfer Catalysts 921
22.6 Reactions That Lead to Amines: A Review and a Preview 922
22.7 Preparation of Amines by Alkylation of Ammonia 923
22.8 The Gabriel Synthesis of Primary Alkylamines 924
22.9 Preparation of Amines by Reduction 926
22.10 Reductive Amination 928
22.11 Reactions of Amines: A Review and a Preview 929
22.12 Reaction of Amines with Alkyl Halides 931
22.13 The Hofmann Elimination 931
22.14 Electrophilic Aromatic Substitution in Arylamines 932
22.15 Nitrosation of Alkylamines 935
22.16 Nitrosation of Arylamines 937
22.17 Synthetic Transformations of Aryl Diazonium Salts 938
22.18 Azo Coupling 942
From Dyes to Sulfa Drugs 943
22.19 Spectroscopic Analysis of Amines 944
22.20 Summary 947
Problems 953
Descriptive Passage and Interpretive Problems 22: Synthetic Applications of Enamines 960

CHAPTER : Aryl Halides

23.1 Bonding in Aryl Halides 965
23.2 Sources of Aryl Halides 966
23.3 Physical Properties of Aryl Halides 966
23.4 Reactions of Aryl Halides: A Review and a Preview 966
23.5 Nucleophilic Substitution in Nitro-Substituted Aryl Halides 968
23.6 The Addition–Elimination Mechanism of Nucleophilic Aromatic Substitution 971
23.7 Related Nucleophilic Aromatic Substitution Reactions 973
23.8 The Elimination–Addition Mechanism of Nucleophilic Aromatic Substitution: Benzyne 974
23.9 Diels–Alder Reactions of Benzyne 978
23.10 m-Benzyne and p-Benzyne 979
23.11 Summary 980
Problems 982
Descriptive Passage and Interpretive Problems 23: The Heck Reaction 986

CHAPTER 24: Phenols 990

24.1 Nomenclature 991
24.2 Structure and Bonding 992
24.3 Physical Properties 993
24.4 Acidity of Phenols 994
24.5 Substituent Effects on the Acidity of Phenols 995
24.6 Sources of Phenols 996
24.7 Naturally Occurring Phenols 998
24.8 Reactions of Phenols: Electrophilic Aromatic Substitution 999
24.9 Acylation of Phenols 1001
24.10 Carboxylation of Phenols: Aspirin and the Kolbe–Schmitt Reaction 1002
24.11 Preparation of Aryl Ethers 1004
Agent Orange and Dioxin 1005
24.12 Cleavage of Aryl Ethers by Hydrogen Halides 1006
24.13 Claisen Rearrangement of Allyl Aryl Ethers 1006
24.14 Oxidation of Phenols: Quinones 1007
24.15 Spectroscopic Analysis of Phenols 1009
24.16 Summary 1010
Problems 1013
Descriptive Passage and Interpretive Problems 24: Directed Metalation of Aryl Ethers 1018

CHAPTER 25: Carbohydrates

25.1 Classification of Carbohydrates 1023
25.2 Fischer Projections and D–L Notation 1024
25.3 The Aldotetroses 1025
25.4 Aldopentoses and Aldohexoses 1026
25.5 A Mnemonic for Carbohydrate Configurations 1028
25.6 Cyclic Forms of Carbohydrates: Furanose Forms 1029
25.7 Cyclic forms of Carbohydrates: Pyranose Forms 1032
25.8 Mutarotation and the Anomeric Effect 1035
25.9 Ketoses 1037
25.10 Deoxy Sugars 1038
25.11 Amino Sugars 1039
25.12 Branched-Chain Carbohydrates 1040
25.13 Glycosides 1040
25.14 Disaccharides 1042
25.15 Polysaccharides 1044
How Sweet It Is! 1045
25.16 Reactions of Carbohydrates 1047
25.17 Reduction of Monosaccharides 1047
25.18 Oxidation of Monosaccharides 1047
25.19 Cyanohydrin Formation and Chain Extension 1049
25.20 Epimerization, Isomerization, and Retro-Aldol Cleavage 1050
25.21 Acylation and Alkylation of Hydroxyl Groups 1052
25.22 Periodic Acid Oxidation 1053
25.23 Summary 1054
Problems 1057
Descriptive Passage and Interpretive Problems 25: Emil Fischer and the Structure of (+)-Glucose 1061

CHAPTER 26L Lipids

26.1 Acetyl Coenzyme A 1066
26.2 Fats, Oils, and Fatty Acids 1067
26.3 Fatty Acid Biosynthesis 1070
26.4 Phospholipids 1073
26.5 Waxes 1075
26.6 Prostaglandins 1076
Nonsteroidal Antiinflammatory Drugs (NSAIDS) and COX-2 Inhibitors 1078
26.7 Terpenes: The Isoprene Rule 1079
26.8 Isopentenyl Pyrophosphate: The Biological Isoprene Unit 1082
26.9 Carbon–Carbon Bond Formation in Terpene Biosynthesis 1082
26.10 The Pathway from Acetate to Isopentenyl Diphosphate 1086
26.11 Steroids: Cholesterol 1087
26.12 Vitamin D 1090
Good Cholesterol? Bad Cholesterol? What’s the Difference? 1091
26.13 Bile Acids 1092
26.14 Corticosteroids 1092
26.15 Sex Hormones 1093
26.16 Carotenoids 1093
Anabolic Steroids 1094
Crocuses Make Saffron from Carotenes 1095
26.17 Summary 1096
Problems 1098
Descriptive Passage and Interpretive Problems 26: Polyketides 1101

CHAPTER 27: Amino Acids, Peptides, and Proteins

27.1 Classification of Amino Acids 1108
27.2 Stereochemistry of Amino Acids 1113
27.3 Acid–Base Behavior of Amino Acids 1114
27.4 Synthesis of Amino Acids 1117
Electrophoresis 1117
27.5 Reactions of Amino Acids 1119
27.6 Some Biochemical Reactions of Amino Acids 1120
27.7 Peptides 1127
27.8 Introduction to Peptide Structure Determination 1130
27.9 Amino Acid Analysis 1130
27.10 Partial Hydrolysis of Peptides 1131
27.11 End Group Analysis 1132
27.12 Insulin 1133
27.13 The Edman Degradation and Automated Sequencing of Peptides 1134
Peptide Mapping and MALDI Mass Spectrometry 1136
27.14 The Strategy of Peptide Synthesis 1137
27.15 Amino Group Protection 1138
27.16 Carboxyl Group Protection 1140
27.17 Peptide Bond Formation 1141
27.18 Solid-Phase Peptide Synthesis: The Merrifield Method 1143
27.19 Secondary Structures of Peptides and Proteins 1145
27.20 Tertiary Structure of Polypeptides and Proteins 1148
27.21 Coenzymes 1152
Oh NO! It’s Inorganic! 1153
27.22 Protein Quaternary Structure: Hemoglobin 1153
27.23 Summary 1154
Problems 1156
Descriptive Passage and Interpretive Problems 27: Amino Acids in Enantioselective Synthesis 1159

CHAPTER 28: Nucleosides, Nucleotides, and Nucleic Acids

28.1 Pyrimidines and Purines 1163
28.2 Nucleosides 1166
28.3 Nucleotides 1167
28.4 Bioenergetics 1170
28.5 ATP and Bioenergetics 1170
28.6 Phosphodiesters, Oligonucleotides, and Polynucleotides 1172
28.7 Nucleic Acids 1173
28.8 Secondary Structure of DNA: The Double Helix 1174
“It Has Not Escaped Our Notice . . .” 1175
28.9 Tertiary Structure of DNA: Supercoils 1177
28.10 Replication of DNA 1178
28.11 Ribonucleic Acids 1180
28.12 Protein Biosynthesis 1183
RNA World 1184
28.13 AIDS 1184
28.14 DNA Sequencing 1185
28.15 The Human Genome Project 1187
28.16 DNA Profiling and the Polymerase Chain Reaction 1188
28.17 Summary 1191
Problems 1194
Descriptive Passage and Interpretive Problems 28: Oligonucleotide Synthesis 1195

CHAPTER 29: Synthetic Polymers

29.1 Some Background 1201
29.2 Polymer Nomenclature 1202
29.3 Classification of Polymers: Reaction Type 1203
29.4 Classification of Polymers: Chain-Growth and Step-Growth 1204
29.5 Classification of Polymers: Structure 1205
29.6 Classification of Polymers: Properties 1207
29.7 Addition Polymers: A Review and a Preview 1209
29.8 Chain Branching in Free-Radical Polymerization 1211
29.9 Anionic Polymerization: Living Polymers 1214
29.10 Cationic Polymerization 1216
29.11 Polyamides 1217
29.12 Polyesters 1218
29.13 Polycarbonates 1219
29.14 Polyurethanes 1220
29.15 Copolymers 1221
29.16 Summary 1223
Problems 1225
Descriptive Passage and Interpretive Problems 29: Chemical Modification of Polymers 1227