Organic chemistry

Cover......Page 1
Title Page......Page 4
Copyright......Page 5
Contents......Page 10
List of Important Features......Page 20
Preface......Page 25
Acknowledgments......Page 33
CHAPTER 1 Structure Determines Properties......Page 37
1.1 Atoms, Electrons, and Orbitals......Page 38
1.2 Ionic Bonds......Page 41
1.3 Covalent Bonds, Lewis Structures, and the Octet Rule......Page 43
1.4 Double Bonds and Triple Bonds......Page 45
1.5 Polar Covalent Bonds, Electronegativity, and Bond Dipoles......Page 46
1.6 Formal Charge......Page 48
1.7 Structural Formulas of Organic Molecules......Page 51
1.8 Resonance......Page 54
1.9 Writing Organic Structures......Page 58
Molecular Modeling......Page 61
1.11 Molecular Dipole Moments......Page 63
1.12 Curved Arrows and Chemical Reactions......Page 64
1.13 Acids and Bases: The Arrhenius View......Page 67
1.14 Acids and Bases: The Brønsted-Lowry View......Page 68
1.15 What Happened to pK[sub(b)]?......Page 72
1.16 How Structure Affects Acid Strength......Page 73
1.17 Acid-Base Equilibria......Page 77
1.18 Lewis Acids and Lewis Bases......Page 80
1.19 Summary......Page 81
Problems......Page 84
Descriptive Passage and Interpretive Problems 1: Amide Lewis Structures......Page 90
CHAPTER 2 Alkanes and Cycloalkanes: Introduction to Hydrocarbons......Page 91
2.1 Classes of Hydrocarbons......Page 92
2.2 Electron Waves and Chemical Bonds......Page 93
2.3 Bonding in H[sub(2)]: The Valence Bond Model......Page 94
2.4 Bonding in H[sub(2)]: The Molecular Orbital Model......Page 95
2.5 Introduction to Alkanes: Methane, Ethane, and Propane......Page 97
2.6 sp[sup(3)] Hybridization and Bonding in Methane......Page 98
2.8 Isomeric Alkanes: The Butanes......Page 100
2.9 Higher n-Alkanes......Page 101
2.10 The C[sub(5)]H[sub(12)] Isomers......Page 102
2.11 IUPAC Nomenclature of Unbranched Alkanes......Page 104
What’s in a Name? Organic Nomenclature......Page 105
2.12 Applying the IUPAC Rules: The Names of the C[sub(6)]H[sub(14)] Isomers......Page 106
2.13 Alkyl Groups......Page 107
2.14 IUPAC Names of Highly Branched Alkanes......Page 109
2.15 Cycloalkane Nomenclature......Page 110
2.16 Sources of Alkanes and Cycloalkanes......Page 111
2.17 Physical Properties of Alkanes and Cycloalkanes......Page 113
2.18 Chemical Properties: Combustion of Alkanes......Page 115
Thermochemistry......Page 117
2.19 Oxidation-Reduction in Organic Chemistry......Page 118
2.20 sp[sup(2)] Hybridization and Bonding in Ethylene......Page 120
2.21 sp Hybridization and Bonding in Acetylene......Page 122
2.22 Bonding in Water and Ammonia: Hybridization of Oxygen and Nitrogen......Page 124
2.23 Which Theory of Chemical Bonding Is Best?......Page 125
2.24 Summary......Page 126
Problems......Page 130
Descriptive Passage and Interpretive Problems 2: Some Biochemical Reactions of Alkanes......Page 134
CHAPTER 3 Alkanes and Cycloalkanes: Conformations and cis-trans Stereoisomers......Page 135
3.1 Conformational Analysis of Ethane......Page 137
3.2 Conformational Analysis of Butane......Page 140
Molecular Mechanics Applied to Alkanes and Cycloalkanes......Page 142
3.4 The Shapes of Cycloalkanes: Planar or Nonplanar?......Page 143
3.5 Small Rings: Cyclopropane and Cyclobutane......Page 144
3.6 Cyclopentane......Page 145
3.7 Conformations of Cyclohexane......Page 146
3.8 Axial and Equatorial Bonds in Cyclohexane......Page 147
3.9 Conformational Inversion in Cyclohexane......Page 149
3.10 Conformational Analysis of Monosubstituted Cyclohexanes......Page 150
Enthalpy, Free Energy, and Equilibrium Constant......Page 153
3.11 Disubstituted Cyclohexanes: cis-trans Stereoisomers......Page 154
3.12 Conformational Analysis of Disubstituted Cyclohexanes......Page 155
3.14 Polycyclic Ring Systems......Page 159
3.15 Heterocyclic Compounds......Page 162
3.16 Summary......Page 163
Problems......Page 166
Descriptive Passage and Interpretive Problems 3: Cyclic Forms of Carbohydrates......Page 171
CHAPTER 4 Alcohols and Alkyl Halides......Page 172
4.1 Functional Groups......Page 173
4.2 IUPAC Nomenclature of Alkyl Halides......Page 175
4.4 Classes of Alcohols and Alkyl Halides......Page 176
4.5 Bonding in Alcohols and Alkyl Halides......Page 177
4.6 Physical Properties of Alcohols and Alkyl Halides: Intermolecular Forces......Page 178
4.7 Preparation of Alkyl Halides from Alcohols and Hydrogen Halides......Page 182
4.8 Mechanism of the Reaction of Alcohols with Hydrogen Halides: Hammond’s Postulate......Page 183
Mechanism 4.1 Formation of tert-Butyl Chloride from tert-Butyl Alcohol and Hydrogen Chloride......Page 184
4.9 Potential Energy Diagrams for Multistep Reactions: The S[sub(N)]1 Mechanism......Page 188
4.10 Structure, Bonding, and Stability of Carbocations......Page 189
4.11 Effect of Alcohol Structure on Reaction Rate......Page 192
4.12 Reaction of Methyl Primary Alcohols with Hydrogen Halides: The S[sub(N)]2 Mechanism......Page 193
Mechanism 4.2 Formation of 1-Bromoheptane from 1-Heptanol and Hydrogen Bromide......Page 194
4.14 Other Methods for Converting Alcohols to Alkyl Halides......Page 195
Mechanism 4.3 Conversion of an Alcohol to an Alkyl Chloride with Thionyl Chloride......Page 196
4.16 Chlorination of Methane......Page 197
4.17 Structure and Stability of Free Radicals......Page 198
From Bond Energies to Heats of Reaction......Page 202
Mechanism 4.4 Free-Radical Chlorination of Methane......Page 203
4.19 Halogenation of Higher Alkanes......Page 205
4.20 Summary......Page 209
Problems......Page 212
Descriptive Passage and Interpretive Problems 4: More About Potential Energy Diagrams......Page 217
CHAPTER 5 Structure and Preparation of Alkenes: Elimination Reactions......Page 219
5.1 Alkene Nomenclature......Page 220
5.2 Structure and Bonding in Alkenes......Page 222
Ethylene......Page 223
5.3 Isomerism in Alkenes......Page 224
5.4 Naming Stereoisomeric Alkenes by the E-Z Notational System......Page 225
5.5 Physical Properties of Alkenes......Page 227
5.6 Relative Stabilities of Alkenes......Page 229
5.7 Cycloalkenes......Page 232
5.8 Preparation of Alkenes: Elimination Reactions......Page 233
5.9 Dehydration of Alcohols......Page 234
5.10 Regioselectivity in Alcohol Dehydration: The Zaitsev Rule......Page 235
5.12 The E1 and E2 Mechanisms of Alcohol Dehydration......Page 237
Mechanism 5.1 The E1 Mechanism for Acid-Catalyzed Dehydration of tert-Butyl Alcohol......Page 238
5.13 Rearrangements in Alcohol Dehydration......Page 239
Mechanism 5.2 Carbocation Rearrangement in Dehydration of 3,3-Dimethyl-2-butanol......Page 240
Mechanism 5.3 Hydride Shift in Dehydration of 1-Butanol......Page 242
5.14 Dehydrohalogenation of Alkyl Halides......Page 243
5.15 The E2 Mechanism of Dehydrohalogenation of Alkyl Halides......Page 245
Mechanism 5.4 E2 Elimination of an Alkyl Halide......Page 246
5.16 Anti Elimination in E2 Reactions: Stereoelectronic Effects......Page 247
5.17 Isotope Effects and the E2 Mechanism......Page 248
5.18 The E1 Mechanism of Dehydrohalogenation of Alkyl Halides......Page 249
Mechanism 5.5 The E1 Mechanism for Dehydrohalogenation of 2-Bromo-2-methylbutane in Ethanol......Page 250
5.19 Summary......Page 251
Problems......Page 255
Descriptive Passage and Interpretive Problems 5: A Mechanistic Preview of Addition Reactions......Page 259
CHAPTER 6 Addition Reactions of Alkenes......Page 261
6.1 Hydrogenation of Alkenes......Page 262
6.2 Heats of Hydrogenation......Page 263
Mechanism 6.1 Hydrogenation of Alkenes......Page 264
6.3 Stereochemistry of Alkene Hydrogenation......Page 265
6.4 Electrophilic Addition of Hydrogen Halides to Alkenes......Page 267
Mechanism 6.2 Electrophilic Addition of a Hydrogen Halide to an Alkene......Page 268
6.6 Mechanistic Basis for Markovnikov’s Rule......Page 270
6.7 Carbocation Rearrangements in Hydrogen Halide Addition to Alkenes......Page 272
6.8 Addition of Sulfuric Acid to Alkenes......Page 274
6.9 Acid-Catalyzed Hydration of Alkenes......Page 275
Mechanism 6.3 Acid-Catalyzed Hydration of 2-Methylpropene......Page 276
6.10 Thermodynamics of Addition-Elimination Equilibria......Page 277
6.11 Hydroboration-Oxidation of Alkenes......Page 280
6.13 Mechanism of Hydroboration-Oxidation......Page 282
Mechanism 6.4 Hydroboration of 1-Methylcyclopentene......Page 283
Mechanism 6.5 Oxidation of an Organoborane......Page 284
6.15 Stereochemistry of Halogen Addition......Page 285
6.16 Mechanism of Halogen Addition to Alkenes: Halonium Ions......Page 286
Mechanism 6.6 Electrophilic Addition of Bromine to Ethylene......Page 287
6.17 Conversion of Alkenes to Vicinal Halohydrins......Page 288
6.18 Free-Radical Addition of Hydrogen Bromide to Alkenes......Page 289
Mechanism 6.8 Free-Radical Addition of Hydrogen Bromide to 1-Butene......Page 291
6.19 Epoxidation of Alkenes......Page 292
6.20 Ozonolysis of Alkenes......Page 294
6.21 Reactions of Alkenes with Alkenes: Polymerization......Page 296
Mechanism 6.10 Acid-Catalyzed Dimerization of 2-Methylpropene......Page 297
Ethylene and Propene: The Most Important Industrial Organic Chemicals......Page 298
Mechanism 6.11 Free-Radical Polymerization of Ethylene......Page 299
6.22 Summary......Page 301
Problems......Page 304
Descriptive Passage and Interpretive Problems 6: Oxymercuration......Page 310
CHAPTER 7 Stereochemistry......Page 313
7.1 Molecular Chirality: Enantiomers......Page 314
7.2 The Chirality Center......Page 316
7.3 Symmetry in Achiral Structures......Page 318
7.4 Optical Activity......Page 319
7.5 Absolute and Relative Configuration......Page 321
7.6 The Cahn-Ingold-Prelog R-S Notational System......Page 323
7.7 Fischer Projections......Page 325
7.8 Properties of Enantiomers......Page 327
7.9 Chirality Axis......Page 328
Chiral Drugs......Page 329
7.10 Reactions That Create a Chirality Center......Page 331
7.11 Chiral Molecules with Two Chirality Centers......Page 334
7.12 Achiral Molecules with Two Chirality Centers......Page 336
7.13 Molecules with Multiple Chirality Centers......Page 338
Chirality of Disubstituted Cyclohexanes......Page 339
7.14 Reactions That Produce Diastereomers......Page 340
7.15 Resolution of Enantiomers......Page 342
7.16 Stereoregular Polymers......Page 344
7.17 Chirality Centers Other Than Carbon......Page 345
7.18 Summary......Page 346
Problems......Page 349
Descriptive Passage and Interpretive Problems 7: Prochirality......Page 355
CHAPTER 8 Nucleophilic Substitution......Page 357
8.1 Functional Group Transformation by Nucleophilic Substitution......Page 358
8.2 Relative Reactivity of Halide Leaving Groups......Page 361
Mechanism 8.1 The S[sub(N)]2 Mechanism of Nucleophilic Substitution......Page 362
8.4 Steric Effects in S[sub(N)]2 Reaction Rates......Page 365
8.5 Nucleophiles and Nucleophilicity......Page 367
8.6 The S[sub(N)]1 Mechanism of Nucleophilic Substitution......Page 369
Enzyme-Catalyzed Nucleophilic Substitutions of Alkyl Halides......Page 370
Mechanism 8.2 The S[sub(N)]1 Mechanism of Nucleophilic Substitution......Page 371
8.7 Carbocation Stability and S[sub(N)]1 Reaction Rates......Page 372
8.8 Stereochemistry of S[sub(N)]1 Reactions......Page 373
8.9 Carbocation Rearrangements in S[sub(N)]1 Reactions......Page 374
Mechanism 8.3 Carbocation Rearrangement in the S[sub(N)]1 Hydrolysis of 2-Bromo-3-methylbutane......Page 375
8.11 Substitution and Elimination as Competing Reactions......Page 379
8.12 Nucleophilic Substitution and Elimination of Alkyl Sulfonates......Page 382
8.13 Summary......Page 385
Problems......Page 386
Descriptive Passage and Interpretive Problems 8: Nucleophilic Substitution......Page 391
CHAPTER 9 Alkynes......Page 394
9.1 Sources of Alkynes......Page 395
9.4 Structure and Bonding in Alkynes: sp Hybridization......Page 397
9.5 Acidity of Acetylene and Terminal Alkynes......Page 400
9.6 Preparation of Alkynes by Alkyation of Acetylene and Terminal Alkynes......Page 402
9.7 Preparation of Alkynes by Elimination Reactions......Page 403
9.9 Hydrogenation of Alkynes......Page 405
9.10 Metal-Ammonia Reduction of Alkynes......Page 407
Mechanism 9.1 Sodium–Ammonia Reduction of an Alkyne......Page 408
9.12 Hydration of Alkynes......Page 410
Mechanism 9.2 Conversion of an Enol to a Ketone......Page 411
9.13 Addition of Halogens to Alkynes......Page 412
9.14 Ozonolysis of Alkynes......Page 413
9.15 Summary......Page 414
Problems......Page 417
Descriptive Passage and Interpretive Problems 9: Thinking Mechanistically About Alkynes......Page 421
CHAPTER 10 Conjugation in Alkadienes and Allylic Systems......Page 423
10.1 The Allyl Group......Page 424
10.2 Allylic Carbocations......Page 425
10.3 S[sub(N)]1 Reactions of Allylic Halides......Page 427
Mechanism 10.1 Hydrolysis of an Allylic Halide......Page 428
10.4 S[sub(N)]2 Reactions of Allylic Halides......Page 429
10.5 Allylic Free Radicals......Page 430
10.6 Allylic Halogenation......Page 431
Mechanism 10.2 Allylic Chlorination of Propene......Page 432
10.7 Allylic Anions......Page 434
10.8 Classes of Dienes......Page 435
10.9 Relative Stabilities of Dienes......Page 436
10.10 Bonding in Conjugated Dienes......Page 437
10.11 Bonding in Allenes......Page 439
10.12 Preparation of Dienes......Page 440
Diene Polymers......Page 441
10.13 Addition of Hydrogen Halides to Conjugated Dienes......Page 442
Mechanism 10.3 Addition of Hydrogen Chloride to 1,3 Cyclopentadiene......Page 443
10.14 Halogen Addition to Dienes......Page 444
10.15 The Diels-Alder Reaction......Page 445
10.16 The π Molecular Orbitals of Ethylene and 1,3-Butadiene......Page 450
Mechanism 10.4 Orbital Interaction in the Diels–Alder Reaction......Page 452
10.18 Summary......Page 453
Problems......Page 456
Descriptive Passage and Interpretive Problems 10: Intramolecular and Retro Diels–Alder Reactions......Page 460
CHAPTER 11 Arenes and Aromaticity......Page 463
11.1 Benzene......Page 464
11.2 The Structure of Benzene......Page 465
11.3 The Stability of Benzene......Page 467
11.4 An Orbital Hybridization View of Bonding in Benzene......Page 468
11.5 The α Molecular Orbitals of Benzene......Page 469
11.6 Substituted Derivatives of Benzene and Their Nomenclature......Page 470
11.7 Polycyclic Aromatic Hydrocarbons......Page 473
11.8 Physical Properties of Arenes......Page 474
11.9 Reactions of Arenes: A Preview......Page 475
11.11 Free-Radical Halogenation of Alkylbenzenes......Page 477
Mechanism 11.1 The Birch Reduction......Page 478
11.12 Oxidation of Alkylbenzenes......Page 481
11.13 S[sub(N)]1 Reactions of Benzylic Halides......Page 483
11.14 S[sub(N)]2 Reactions of Benzylic Halides......Page 484
11.15 Preparation of Alkenylbenzenes......Page 485
11.16 Addition Reactions of Alkenylbenzenes......Page 486
Mechanism 11.2 Free-Radical Polymerization of Styrene......Page 488
11.18 Cyclobutadiene and Cyclooctatetraene......Page 489
11.19 Hückel’s Rule......Page 491
11.20 Annulenes......Page 493
11.21 Aromatic Ions......Page 495
11.22 Heterocyclic Aromatic Compounds......Page 498
11.23 Heterocyclic Aromatic Compounds and Hückel’s Rule......Page 500
11.24 Summary......Page 502
Problems......Page 505
Descriptive Passage and Interpretive Problems 11: The Hammett Equation......Page 509
CHAPTER 12 Reactions of Arenes: Electrophilic and Nucleophilic Aromatic Substitution......Page 513
12.1 Representative Electrophilic Aromatic Substitution Reactions of Benzene......Page 514
12.2 Mechanistic Principles of Electrophilic Aromatic Substitution......Page 515
12.3 Nitration of Benzene......Page 517
Mechanism 12.1 Nitration of Benzene......Page 518
12.5 Halogenation of Benzene......Page 519
Mechanism 12.2 Sulfonation of Benzene......Page 520
Mechanism 12.3 Bromination of Benzene......Page 521
12.6 Friedel-Crafts Alkylation of Benzene......Page 523
Mechanism 12.4 Friedel–Crafts Alkylation......Page 524
12.7 Friedel-Crafts Acylation of Benzene......Page 525
Mechanism 12.5 Friedel–Crafts Acylation......Page 526
12.8 Synthesis of Alkylbenzenes by Acylation-Reduction......Page 527
12.9 Rate and Regioselectivity in Electrophilic Aromatic Substitution......Page 529
12.10 Rate and Regioselectivity in the Nitration of Toluene......Page 530
12.11 Rate and Regioselectivity in the Nitration of (Trifluoromethyl) Benzene......Page 532
12.12 Substituent Effects in Electrophilic Aromatic Substitution: Activating Substituents......Page 534
12.13 Substituent Effects in Electrophilic Aromatic Substitution: Strongly Deactivating Substituents......Page 538
12.14 Substituent Effects in Electrophilic Aromatic Substitution: Halogens......Page 541
12.15 Multiple Substituent Effects......Page 542
12.16 Regioselective Synthesis of Disubstituted Aromatic Compounds......Page 545
12.17 Substitution in Naphthalene......Page 547
12.18 Substitution in Heterocyclic Aromatic Compounds......Page 548
12.19 Nucleophilic Aromatic Substitution......Page 549
12.20 Nucleophilic Substitution in Nitro-Substituted Aryl Halides......Page 550
12.21 The Addition-Elimination Mechanism of Nucleophilic Aromatic Substitution......Page 551
Mechanism 12.6 Nucleophilic Aromatic Substitution in p-Fluoronitrobenzene by the Addition-Elimination Mechanism......Page 553
12.22 Related Nucleophilic Aromatic Substitutions......Page 555
12.23 Summary......Page 556
Problems......Page 560
Descriptive Passage and Interpretive Problems 12: Benzyne......Page 569
CHAPTER 13 Spectroscopy......Page 573
13.1 Principles of Molecular Spectroscopy: Electromagnetic Radiation......Page 574
13.3 Introduction to [sup(1)]H NMR Spectroscopy......Page 576
13.4 Nuclear Shielding and [sup(1)]H Chemical Shifts......Page 578
13.5 Effects of Molecular Structure on [sup(1)]H Chemical Shifts......Page 581
Ring Currents—Aromatic and Antiaromatic......Page 586
13.6 Interpreting [sup(1)]H NMR Spectra......Page 587
13.7 Spin-Spin Splitting in [sup(1)]H NMR Spectroscopy......Page 590
13.8 Splitting Patterns: The Ethyl Group......Page 592
13.10 Splitting Patterns: Pairs of Doublets......Page 594
13.11 Complex Splitting Patterns......Page 596
13.12 [sup(1)]H NMR Spectra of Alcohols......Page 598
13.13 NMR and Conformations......Page 599
13.14 [sup(13)]C NMR Spectroscopy......Page 600
13.15 [sup(13)]C Chemical Shifts......Page 602
13.16 [sup(13)]C NMR and Peak Intensities......Page 604
13.18 Using DEPT to Count Hydrogens Attached to [sup(13)]C......Page 605
13.19 2D NMR: COSY and HETCOR......Page 607
13.20 Introduction to Infrared Spectroscopy......Page 609
Spectra by the Thousands......Page 610
13.21 Infrared Spectra......Page 611
13.22 Characteristic Absorption Frequencies......Page 613
13.23 Ultraviolet-Visible (UV-VIS) Spectroscopy......Page 617
13.24 Mass Spectrometry......Page 619
13.25 Molecular Formula as a Clue to Structure......Page 624
13.26 Summary......Page 625
Problems......Page 628
Descriptive Passage and Interpretive Problems 13: Calculating Aromatic [sup(13)]C Chemical Shifts......Page 638
CHAPTER 14 Organometallic Compounds......Page 641
14.1 Organometallic Nomenclature......Page 642
14.2 Carbon-Metal Bonds in Organometallic Compounds......Page 643
14.3 Preparation of Organolithium Compounds......Page 644
14.4 Preparation of Organomagnesium Compounds: Grignard Reagents......Page 645
14.5 Organolithium and Organomagnesium Compounds as Brønsted Bases......Page 647
14.6 Synthesis of Alcohols Using Grignard Reagents......Page 649
14.8 Synthesis of Acetylenic Alcohols......Page 651
14.9 Retrosynthetic Analysis......Page 652
14.10 Alkane Synthesis Using Organocopper Reagents......Page 655
Mechanism 14.1 Formation of a Lithium Diaklycuprate (Gilman Reagent)......Page 656
14.11 An Organozinc Reagent for Cyclopropane Synthesis......Page 657
14.12 Carbenes and Carbenoids......Page 658
Mechanism 14.2 Similarities Between the Mechanisms of Reaction of an Alkene with Iodomethylzinc Iodide and a Peroxy Acid......Page 659
14.13 Transition-Metal Organometallic Compounds......Page 660
An Organometallic That Occurs Naturally: Coenzyme B[sub(12)]......Page 662
14.14 Homogeneous Catalytic Hydrogenation......Page 663
Mechanism 14.3 Homogeneous Hydrogenation of Propene in the Presence of Wilkinson’s Catalyst......Page 664
14.15 Olefin Metathesis......Page 666
Mechanism 14.4 Olefin Cross-Metathesis......Page 667
14.16 Ziegler-Natta Catalysis of Alkene Polymerization......Page 669
Mechanism 14.5 Polymerization of Ethylene in the Presence of a Ziegler-Natta Catalyst......Page 670
14.17 Summary......Page 671
Problems......Page 674
Descriptive Passage and Interpretive Problems 14: The Heck Reaction......Page 678
CHAPTER 15 Alcohols, Diols, and Thiols......Page 681
15.1 Sources of Alcohols......Page 682
15.2 Preparation of Alcohols by Reduction of Aldehydes and Ketones......Page 683
Mechanism 15.1 Sodium Borohydride Reduction of an Aldehyde or Ketone......Page 688
15.4 Preparation of Alcohols from Epoxides......Page 689
15.5 Preparation of Diols......Page 691
15.7 Conversion of Alcohols to Ethers......Page 693
Mechanism 15.2 Acid-Catalyzed Formation of Dietyl Ether from Ethyl Alcohol......Page 695
15.9 Oxidation of Alcohols......Page 698
Mechanism 15.3 Chromic Acid Oxidation of 2-Propanol......Page 700
Mechanism 15.4 Dimethyl Sulfoxide Oxidation of an Alcohol......Page 701
Economic and Environmental Factors in Organic Synthesis......Page 702
Mechanism 15.5 Oxidation of Ethanol by NAD[sup(+)]......Page 704
15.12 Thiols......Page 705
15.13 Spectroscopic Analysis of Alcohols and Thiols......Page 709
15.14 Summary......Page 710
Problems......Page 714
Descriptive Passage and Interpretive Problems 15: The Pinacol Rearrangement......Page 719
CHAPTER 16 Ethers, Epoxides, and Sulfides......Page 721
16.1 Nomenclature of Ethers, Epoxides, and Sulfides......Page 722
16.2 Structure and Bonding in Ethers and Epoxides......Page 723
16.3 Physical Properties of Ethers......Page 724
16.4 Crown Ethers......Page 725
16.5 Preparation of Ethers......Page 727
Polyether Antibiotics......Page 728
16.6 The Williamson Ether Synthesis......Page 729
16.7 Reactions of Ethers: A Review and a Preview......Page 730
16.8 Acid-Catalyzed Cleavage of Ethers......Page 731
Mechanism 16.1 Cleavage of Ethers by Hydrogen Halides......Page 732
16.9 Preparation of Epoxides: A Review and a Preview......Page 733
16.10 Conversion of Vicinal Halohydrins to Epoxides......Page 734
16.11 Reactions of Epoxides: A Review and a Preview......Page 735
16.12 Nucleophilic Ring Opening of Epoxides......Page 736
16.13 Acid-Catalyzed Ring Opening of Epoxides......Page 738
Mechanism 16.3 Acid-Catalyzed Ring Opening of Ethylene Oxide......Page 739
16.15 Preparation of Sulfides......Page 741
16.16 Oxidation of Sulfides: Sulfoxides and Sulfones......Page 742
16.17 Alkylation of Sulfides: Sulfonium Salts......Page 743
16.18 Spectroscopic Analysis of Ethers, Epoxides, and Sulfides......Page 744
16.19 Summary......Page 746
Problems......Page 750
Descriptive Passage and Interpretive Problems 16: Epoxide Rearrangements and the NIH Shift......Page 756
CHAPTER 17 Aldehydes and Ketones: Nucleophilic Addition to the Carbonyl Group......Page 759
17.1 Nomenclature......Page 760
17.2 Structure and Bonding: The Carbonyl Group......Page 763
17.4 Sources of Aldehydes and Ketones......Page 765
17.5 Reactions of Aldehydes and Ketones: A Review and a Preview......Page 769
17.6 Principles of Nucleophilic Addition: Hydration of Aldehydes and Ketones......Page 770
Mechanism 17.1 Hydration of an Aldehyde or Ketone in Basic Solution......Page 773
Mechanism 17.2 Hydration of an Aldehyde or Ketone in Acid Solution......Page 774
Mechanism 17.3 Cyanohydrin Formation......Page 775
17.8 Acetal Formation......Page 777
Mechanism 17.4 Acetal Formation from Benzaldehyde and Ethanol......Page 778
17.9 Acetals as Protecting Groups......Page 780
17.10 Reaction with Primary Amines: Imines......Page 781
Mechanism 17.5 Imine Formation from Benzaldehyde and Methylamine......Page 782
Imines in Biological Chemistry......Page 784
17.11 Reaction with Secondary Amines: Enamines......Page 786
17.12 The Wittig Reaction......Page 787
Mechanism 17.7 The Witting Reaction......Page 789
17.13 Planning an Alkene Synthesis via the Wittig Reaction......Page 790
17.14 Stereoselective Addition to Carbonyl Groups......Page 792
17.15 Oxidation of Aldehydes......Page 793
17.16 Spectroscopic Analysis of Aldehydes and Ketones......Page 794
17.17 Summary......Page 796
Problems......Page 799
Descriptive Passage and Interpretive Problems 17: The Baeyer-Villiger Oxidation......Page 807
CHAPTER 18 Carboxylic Acids......Page 811
18.1 Carboxylic Acid Nomenclature......Page 812
18.2 Structure and Bonding......Page 814
18.4 Acidity of Carboxylic Acids......Page 815
18.5 Substituents and Acid Strength......Page 818
18.6 Ionization of Substituted Benzoic Acids......Page 820
18.7 Salts of Carboxylic Acids......Page 821
18.8 Dicarboxylic Acids......Page 823
18.9 Carbonic Acid......Page 824
18.10 Sources of Carboxylic Acids......Page 825
18.11 Synthesis of Carboxylic Acids by the Carboxylation of Grignard Reagents......Page 827
18.12 Synthesis of Carboxylic Acids by the Preparation and Hydrolysis of Nitriles......Page 828
18.14 Mechanism of Acid-Catalyzed Esterification......Page 829
Mechanism 18.1 Acid-Catalyzed Esterification of Benzoic Acid with Methanol......Page 831
18.15 Intramolecular Ester Formation: Lactones......Page 833
18.16 Decarboxylation of Malonic Acid and Related Compounds......Page 834
18.17 Spectroscopic Properties of Carboxylic Acids......Page 837
18.18 Summary......Page 838
Problems......Page 840
Descriptive Passage and Interpretive Problems 18: Lactonization Methods......Page 844
CHAPTER 19 Carboxylic Acid Derivatives: Nucleophilic Acyl Substitution......Page 847
19.1 Nomenclature of Carboxylic Acid Derivatives......Page 849
19.2 Structure and Reactivity of Carboxylic Acid Derivatives......Page 850
19.3 General Mechanism for Nucleophilic Acyl Substitution......Page 853
19.4 Nucleophilic Acyl Substitution in Acyl Chlorides......Page 855
Mechanism 19.1 Acid-Catalyzed Hydrolysis of an Acyl Chloride via a Tetrahedral Intermediate......Page 857
19.5 Nucleophilic Acyl Substitution in Acid Anhydrides......Page 858
Mechanism 19.2 Nucleophilic Acyl Substitution in an Anhydride......Page 859
19.6 Sources of Esters......Page 860
19.8 Reactions of Esters: A Preview......Page 862
19.9 Acid-Catalyzed Ester Hydrolysis......Page 864
Mechanism 19.3 Acid-Catalyzed Ester Hydrolysis......Page 865
19.10 Ester Hydrolysis in Base: Saponification......Page 867
Mechanism 19.4 Ester Hydrolysis in Basic Solution......Page 869
19.11 Reaction of Esters with Ammonia and Amines......Page 870
19.12 Reaction of Esters with Grignard Reagents: Synthesis of Tertiary Alcohols......Page 871
Mechanism 19.5 Reaction of an Ester with a Grignard Reagent......Page 872
19.13 Reaction of Esters with Lithium Aluminum Hydride......Page 873
19.14 Amides......Page 874
19.15 Hydrolysis of Amides......Page 878
Mechanism 19.6 Amide Hydrolysis in Acid Solution......Page 879
Mechanism 19.7 Amide Hydrolysis in Basic Solution......Page 881
β-Lactam Antibiotics......Page 882
19.17 Preparation of Nitriles......Page 883
19.18 Hydrolysis of Nitriles......Page 884
19.19 Addition of Grignard Reagents to Nitriles......Page 885
Mechanism 19.8 Nitrile Hydrolysis in Basic Solution......Page 886
19.20 Spectroscopic Analysis of Carboxylic Acid Derivatives......Page 887
19.21 Summary......Page 888
Problems......Page 891
Descriptive Passage and Interpretive Problems 20: Thioesters......Page 898
CHAPTER 20 Enols and Enolates......Page 901
20.1 Aldehyde, Ketone, and Ester Enolates......Page 902
20.2 Enolate Regiochemistry......Page 907
20.3 The Aldol Condensation......Page 908
Mechanism 20.1 Aldol Addition of Butanal......Page 909
Mechanism 20.2 Dehydration in a Base-Catalyzed Aldol Condensation......Page 911
20.4 Mixed Aldol Condensations......Page 913
Chalcones: From the Mulberry Tree to Cancer Chemotherapy......Page 915
20.5 The Claisen Condensation......Page 917
Mechanism 20.3 The Claisen Condensation of Ethyl Acetate......Page 918
20.6 Intramolecular Claisen Condensation: The Dieckmann Cyclization......Page 919
20.7 Mixed Claisen Condensations......Page 920
20.8 Acylation of Ketones with Esters......Page 921
20.9 Alkylation of Enolates......Page 922
20.10 The Acetoacetic Ester Synthesis......Page 924
20.11 The Malonic Ester Synthesis......Page 926
20.12 Alkyation of Chiral Enolates......Page 928
20.13 Enolization and Enol Content......Page 930
Mechanism 20.5 Acid-Catalyzed Enolization of an Aldehyde or Ketone in Aqueous Solution......Page 934
20.14 α Halogenation of Aldehydes and Ketones......Page 935
Mechanism 20.6 Acid-Catalyzed Bromination of Acetone......Page 936
Mechanism 20.7 Cleavage of a Tribromomethyl Ketone......Page 938
The Haloform Reaction and the Biosynthesis of Trihalomethanes......Page 939
20.16 Some Chemical and Stereochemical Consequences of Enolization......Page 941
20.17 Effects of Conjugation in α,β-Unsaturated Aldehydes and Ketones......Page 942
20.18 Conjugate Addition to α,β-Unsaturated Carbonyl Compounds......Page 943
20.19 Addition of Carbanions to α,β-Unsaturated Ketones: The Michael Reaction......Page 945
20.20 Conjugate Addition of Organocopper Reagents to α,β-Unsaturated Carbonyl Compounds......Page 947
20.21 Summary......Page 948
Problems......Page 952
Descriptive Passage and Interpretive Problems 20: The Enolate Chemistry of Dianions......Page 961
CHAPTER 21 Amines......Page 965
21.1 Amine Nomenclature......Page 966
21.2 Structure and Bonding......Page 968
21.3 Physical Properties......Page 970
21.4 Basicity of Amines......Page 971
Amines as Natural Products......Page 976
21.5 Tetraalkylammonium Salts as Phase-Transfer Catalysts......Page 977
21.6 Reactions That Lead to Amines: A Review and a Preview......Page 978
21.7 Preparation of Amines by Alkylation of Ammonia......Page 980
21.8 The Gabriel Synthesis of Primary Alkylamines......Page 981
21.9 Preparation of Amines by Reduction......Page 982
Mechanism 21.1 Lithium Aluminum Hydride Reduction of an Amide......Page 985
21.10 Reductive Amination......Page 986
21.11 Reactions of Amines: A Review and a Preview......Page 987
21.13 The Hofmann Elimination......Page 989
21.14 Electrophilic Aromatic Substitution in Arylamines......Page 991
21.15 Nitrosation of Alkylamines......Page 993
Mechanism 21.2 Reactions of an Alkyl Diazonium Ion......Page 995
21.17 Synthetic Transformations of Aryl Diazonium Salts......Page 996
21.18 Azo Coupling......Page 1000
From Dyes to Sulfa Drugs......Page 1001
21.19 Spectroscopic Analysis of Amines......Page 1002
21.20 Summary......Page 1005
Problems......Page 1011
Descriptive Passage and Interpretive Problems 21: Synthetic Applications of Enamines......Page 1019
CHAPTER 22 Phenols......Page 1023
22.1 Nomenclature......Page 1024
22.2 Structure and Bonding......Page 1025
22.3 Physical Properties......Page 1026
22.4 Acidity of Phenols......Page 1027
22.5 Substituent Effects on the Acidity of Phenols......Page 1028
22.6 Sources of Phenols......Page 1030
22.7 Naturally Occurring Phenols......Page 1031
22.8 Reactions of Phenols: Electrophilic Aromatic Substitution......Page 1032
22.9 Acylation of Phenols......Page 1034
22.10 Carboxylation of Phenols: Aspirin and the Kolbe-Schmitt Reaction......Page 1036
22.11 Preparation of Aryl Ethers......Page 1037
James Bond, Oxidative Stress, and Antioxidant Phenols......Page 1039
22.12 Cleavage of Aryl Ethers by Hydrogen Halides......Page 1041
22.13 Claisen Rearrangement of Allyl Aryl Ethers......Page 1042
22.14 Oxidation of Phenols: Quinones......Page 1043
22.15 Spectroscopic Analysis of Phenols......Page 1044
22.16 Summary......Page 1046
Problems......Page 1048
Descriptive Passage and Interpretive Problems 22: Directed Metalation of Aryl Ethers......Page 1054
CHAPTER 23 Carbohydrates......Page 1057
23.1 Classification of Carbohydrates......Page 1058
23.2 Fischer Projections and D,L Notation......Page 1059
23.3 The Aldotetroses......Page 1060
23.4 Aldopentoses and Aldohexoses......Page 1061
23.5 A Mnemonic for Carbohydrate Configurations......Page 1063
23.6 Cyclic Forms of Carbohydrates: Furanose Forms......Page 1064
23.7 Cyclic forms of Carbohydrates: Pyranose Forms......Page 1067
23.8 Mutarotation......Page 1070
Mechanism 23.1 Acid-Catalyzed Mutarotation of D-Glucopyranose......Page 1072
23.9 Carbohydrate Conformation: The Anomeric Effect......Page 1073
23.10 Ketoses......Page 1074
23.11 Deoxy Sugars......Page 1075
23.12 Amino Sugars......Page 1076
23.13 Branched-Chain Carbohydrates......Page 1077
23.14 Glycosides: The Fischer Glycosidation......Page 1078
Mechanism 23.2 Preparation of Methyl D-Glucopyranisides by Fischer Glycosidation......Page 1079
23.15 Disaccharides......Page 1081
23.16 Polysaccharides......Page 1083
How Sweet It Is!......Page 1084
23.18 Reduction of Monosaccharides......Page 1085
23.19 Oxidation of Monosaccharides......Page 1086
23.20 Periodic Acid Oxidation......Page 1088
23.21 Cyanohydrin Formation and Chain Extension......Page 1089
23.22 Epimerization, Isomerization, and Retro-Aldol Cleavage......Page 1090
23.23 Acylation and Alkylation of Carbohydrate Hydroxyl Groups......Page 1091
23.24 Glycosides: Synthesis of Oliosaccharides......Page 1093
Mechanism 23.3 Silver-Assisted Glycosidation......Page 1095
23.25 Glycobiology......Page 1097
23.26 Summary......Page 1099
Problems......Page 1102
Descriptive Passage and Interpretive Problems 23: Emil Fischer and the Structure of (+)-Glucose......Page 1107
CHAPTER 24 Lipids......Page 1109
24.1 Acetyl Coenzyme A......Page 1110
24.2 Fats, Oils, and Fatty Acids......Page 1112
24.3 Fatty Acid Biosynthesis......Page 1115
Mechanism 24.1 Biosynthesis of a Butanoyl Group from Acetyl and Malonyl Building Blocks......Page 1117
24.5 Waxes......Page 1120
24.6 Prostaglandins......Page 1121
Nonsteroidal Anti-Inflammatory Drugs (NSAIDS) and COX-2 Inhibitors......Page 1123
24.7 Terpenes: The Isoprene Rule......Page 1125
24.9 Carbon-Carbon Bond Formation in Terpene Biosynthesis......Page 1128
24.10 The Pathway from Acetate to Isopentenyl Diphosphate......Page 1131
24.11 Steroids: Cholesterol......Page 1133
Mechanism 24.2 Biosynthesis of Cholesterol from Squalene......Page 1135
24.12 Vitamin D......Page 1136
Good Cholesterol? Bad Cholesterol? What’s the Difference?......Page 1137
24.15 Sex Hormones......Page 1138
24.16 Carotenoids......Page 1139
Crocuses Make Saffron from Carotenes......Page 1140
24.17 Summary......Page 1141
Problems......Page 1143
Descriptive Passage and Interpretive Problems 24: Polyketides......Page 1147
CHAPTER 25 Amino Acids, Peptides, and Proteins......Page 1151
25.1 Classification of Amino Acids......Page 1153
25.2 Stereochemistry of Amino Acids......Page 1158
25.3 Acid-Base Behavior of Amino Acids......Page 1159
Electrophoresis......Page 1162
25.4 Synthesis of Amino Acids......Page 1163
25.6 Some Biochemical Reactions of Amino Acids......Page 1165
Mechanism 25.1 Pyridoxal 5\'-Phosphate-Mediated Decarboxylation of an α-Amino Acid......Page 1166
Mechanism 25.2 Transamination: Biosynthesis of L-Alanaine from L-Glutamic Acid and Pyruvic Acid......Page 1170
25.7 Peptides......Page 1172
25.9 Amino Acid Analysis......Page 1175
25.11 End Group Analysis......Page 1176
25.12 Insulin......Page 1178
25.13 The Edman Degradation and Automated Sequencing of Peptides......Page 1179
Mechanism 25.3 The Edman Degradation......Page 1180
Peptide Mapping and MALDI Mass Spectrometry......Page 1181
25.14 The Strategy of Peptide Synthesis......Page 1182
25.15 Amino Group Protection......Page 1183
25.17 Peptide Bond Formation......Page 1186
Mechanism 25.4 Amide Bond Formation Between a Carboxylic Acid and Amine Using N,N\'-Dicyclohexylcarboiimide......Page 1187
25.18 Solid-Phase Peptide Synthesis: The Merrifield Method......Page 1188
25.19 Secondary Structures of Polypeptides and Proteins......Page 1190
25.20 Tertiary Structure of Peptides and Proteins......Page 1194
Mechanism 25.5 Carboxypeptidase-Catalyzed Hydrolysis......Page 1197
25.21 Coenzymes......Page 1198
25.22 Protein Quaternary Structure: Hemoglobin......Page 1199
25.23 G-Coupled Protein Receptors......Page 1200
25.24 Summary......Page 1201
Problems......Page 1203
Descriptive Passage and Interpretive Problems 25: Amino Acids in Enatioselective Synthesis......Page 1206
CHAPTER 26 Nucleosides, Nucleotides, and Nucleic Acids......Page 1209
26.1 Pyrimidines and Purines......Page 1210
26.2 Nucleosides......Page 1213
26.3 Nucleotides......Page 1215
26.5 ATP and Bioenergetics......Page 1217
26.6 Phosphodiesters, Oligonucleotides, and Polynucleotides......Page 1219
26.7 Nucleic Acids......Page 1220
26.8 Secondary Structure of DNA: The Double Helix......Page 1221
“It has not escaped our notice . . . ”......Page 1223
26.9 Tertiary Structure of DNA: Supercoils......Page 1225
26.10 Replication of DNA......Page 1226
26.11 Ribonucleic Acids......Page 1228
26.12 Protein Biosynthesis......Page 1231
26.13 AIDS......Page 1232
26.14 DNA Sequencing......Page 1233
26.15 The Human Genome Project......Page 1235
26.16 DNA Profiling and the Polymerase Chain Reaction......Page 1236
26.17 Recombinant DNA Technology......Page 1239
26.18 Summary......Page 1240
Problems......Page 1243
Descriptive Passage and Interpretive Problems 26: Oligonucleotide Synthesis......Page 1245
CHAPTER 27 Synthetic Polymers......Page 1251
27.1 Some Background......Page 1252
27.2 Polymer Nomenclature......Page 1253
27.3 Classification of Polymers: Reaction Type......Page 1254
27.4 Classification of Polymers: Chain Growth and Step Growth......Page 1255
27.5 Classification of Polymers: Structure......Page 1256
27.6 Classification of Polymers: Properties......Page 1258
27.7 Addition Polymers: A Review and a Preview......Page 1260
27.8 Chain Branching in Free-Radical Polymerization......Page 1262
Mechanism 27.1 Branching in Polyethylene Caused by Intramolecular Hydrogen Transfer......Page 1263
Mechanism 27.2 Branching in Polyethylene Caused by Intermolecular Hydrogen Transfer......Page 1264
Mechanism 27.3 Anionic Polymerization of Styrene......Page 1265
27.10 Cationic Polymerization......Page 1267
Mechanism 27.4 Cationic Polymerization of 2-Methylpropene......Page 1268
27.12 Polyesters......Page 1269
27.14 Polyurethanes......Page 1271
27.15 Copolymers......Page 1272
Conducting Polymers......Page 1274
27.16 Summary......Page 1276
Problems......Page 1278
Descriptive Passage and Interpretive Problems 27: Chemical Modification of Polymers......Page 1280
Glossary......Page 1284
Credits......Page 1306
Index......Page 1308