Francis Carey,
University of Virginia, Charlottesville
ISBN: 0072828374 Copyright year: 2006
Detailed Table of Contents
INTRODUCTION
The Origins of Organic Chemistry 2
Berzelius, Wöhler, and Vitalism 3
The Structural Theory 4
Electronic Theories of Structure and Reactivity 4
The Influence of Organic Chemistry 5
Computers and Organic Chemistry 5
Challenges and Opportunities 5
Where Did the Carbon Come From? 7
CHAPTER 1
STRUCTURE DETERMINES PROPERTIES 8
1.1 Atoms, Electrons, and Orbitals 9
1.2 Ionic Bonds 12
1.3 Covalent Bonds, Lewis Structures, and the Octet Rule 14
1.4 Double Bonds and Triple Bonds 16
1.5 Polar Covalent Bonds and Electronegativity 17 Electrostatic Potential Maps 19
1.6 Structural Formulas of Organic Molecules 20
1.7 Formal Charge 23
1.8 Resonance 25 Learning By Modeling 30
1.9 The Shapes of Some Simple Molecules 31
1.10 Molecular Dipole Moments 33
1.11 Curved Arrows and Chemical Reactions 34
1.12 Acids and Bases: The Arrhenius View 36
1.13 Acids and Bases: The Brønsted–Lowry View 37
1.14 What Happened to pKb? 41
1.15 How Structure Affects Acid Strength 42
1.16 Acid–Base Equilibria 46
1.17 Lewis Acids and Lewis Bases 49
1.18 SUMMARY 50 PROBLEMS 53 LEARNING BY MODELING 59
CHAPTER 2
HYDROCARBON FRAMEWORKS: ALKANES 62
2.1 Classes of Hydrocarbons 63
2.2 Electron Waves and Chemical Bonds 64
2.3 Bonding in H2 : The Valence Bond Model 65
2.4 Bonding in H2 : The Molecular Orbital Model 67
2.5 Introduction to Alkanes: Methane, Ethane, and Propane 68
2.6 sp 3 Hybridization and Bonding in Methane 69 Methane and the Biosphere 70
2.7 Bonding in Ethane 72
2.8 Isomeric Alkanes: The Butanes 73
2.9 Higher n-Alkanes 73
2.10 The C5 H12 Isomers 74
2.11 IUPAC Nomenclature of Unbranched Alkanes 76 A Brief History of Systematic Organic Nomenclature 77
2.12 Applying the IUPAC Rules: The Names of the C6 H14 Isomers 77
2.13 Alkyl Groups 79
2.14 IUPAC Names of Highly Branched Alkanes 81
2.15 Cycloalkane Nomenclature 83
2.16 Sources of Alkanes and Cycloalkanes 84
2.17 Physical Properties of Alkanes and Cycloalkanes 85
2.18 Chemical Properties: Combustion of Alkanes 88
2.19 Oxidation–Reduction in Organic Chemistry 90 Thermochemistry 91
2.20 sp 2 Hybridization and Bonding in Ethylene 93
2.21 sp Hybridization and Bonding in Acetylene 95
2.22 Which Theory of Chemical Bonding Is Best? 97
2.23 SUMMARY 98 PROBLEMS 102 LEARNING BY MODELING 106
CHAPTER 3
CONFORMATIONS OF ALKANES AND CYCLOALKANES 108
3.1 Conformational Analysis of Ethane 110
3.2 Conformational Analysis of Butane 113
3.3 Conformations of Higher Alkanes 115
3.4 The Shapes of Cycloalkanes: Planar or Nonplanar? 115 Molecular Mechanics Applied to Alkanes and Cycloalkanes 116
3.5 Small Rings: Cyclopropane and Cyclobutane 118
3.6 Cyclopentane 119
3.7 Conformations of Cyclohexane 119
3.8 Axial and Equatorial Bonds in Cyclohexane 120
3.9 Conformational Inversion (Ring Flipping) in Cyclohexane 122
3.10 Conformational Analysis of Monosubstituted Cyclohexanes 123
3.11 Disubstituted Cycloalkanes: Stereoisomers 126 Enthalpy, Free Energy, and Equilibrium Constant 127
3.12 Conformational Analysis of Disubstituted Cyclohexanes 129
3.13 Medium and Large Rings 132
3.14 Polycyclic Ring Systems 132
3.15 Heterocyclic Compounds 136
3.16 SUMMARY 137 PROBLEMS 140 LEARNING BY MODELING 145
CHAPTER 4
ALCOHOLS AND ALKYL HALIDES 148
4.1 Functional Groups 150
4.2 IUPAC Nomenclature of Alkyl Halides 151
4.3 IUPAC Nomenclature of Alcohols 152
4.4 Classes of Alcohols and Alkyl Halides 153
4.5 Bonding in Alcohols and Alkyl Halides 153
4.6 Physical Properties of Alcohols and Alkyl Halides: Intermolecular Forces 154
4.7 Preparation of Alkyl Halides from Alcohols and Hydrogen Halides 158
4.8 Mechanism of the Reaction of Alcohols with Hydrogen Halides 160
4.9 Potential Energy Diagrams for Multistep Reactions: The SN 1 Mechanism 165
4.10 Structure, Bonding, and Stability of Carbocations 167
4.11 Effect of Alcohol Structure on Reaction Rate 169
4.12 Reaction of Methyl and Primary Alcohols with Hydrogen Halides: The SN 2 Mechanism 171
4.13 Other Methods for Converting Alcohols to Alkyl Halides 172
4.14 Halogenation of Alkanes 173
4.15 Chlorination of Methane 173
4.16 Structure and Stability of Free Radicals 174
4.17 Mechanism of Methane Chlorination 179 From Bond Energies to Heats of Reaction 181
4.18 Halogenation of Higher Alkanes 182
4.19 SUMMARY 185 PROBLEMS 189 LEARNING BY MODELING 194
CHAPTER 5
STRUCTURE AND PREPARATION OF ALKENES: ELIMINATION REACTIONS 196
5.1 Alkene Nomenclature 198 Ethylene 200
5.2 Structure and Bonding in Alkenes 200
5.3 Isomerism in Alkenes 202
5.4 Naming Stereoisomeric Alkenes by the E–Z Notational System 203
5.5 Physical Properties of Alkenes 204
5.6 Relative Stabilities of Alkenes 206
5.7 Cycloalkenes 210
5.8 Preparation of Alkenes: Elimination Reactions 211
5.9 Dehydration of Alcohols 212
5.10 Regioselectivity in Alcohol Dehydration: The Zaitsev Rule 213
5.11 Stereoselectivity in Alcohol Dehydration 215
5.12 The E1 and E2 Mechanisms of Alcohol Dehydration 215
5.13 Rearrangements in Alcohol Dehydration 217
5.14 Dehydrohalogenation of Alkyl Halides 220
5.15 The E2 Mechanism of Dehydrohalogenation of Alkyl Halides 222
5.16 Anti Elimination in E2 Reactions: Stereoelectronic Effects 225
5.17 Isotope Effects and the E2 Mechanism 226
5.18 The E1 Mechanism of Dehydrohalogenation of Alkyl Halides 227
5.19 SUMMARY 230 PROBLEMS 233 LEARNING BY MODELING 239
CHAPTER 6
REACTIONS OF ALKENES: ADDITION REACTIONS 242
6.1 Hydrogenation of Alkenes 243
6.2 Heats of Hydrogenation 244
6.3 Stereochemistry of Alkene Hydrogenation 247
6.4 Electrophilic Addition of Hydrogen Halides to Alkenes 248
6.5 Regioselectivity of Hydrogen Halide Addition: Markovnikov’s Rule 250
6.6 Mechanistic Basis for Markovnikov’s Rule 251 Rules, Laws, Theories, and the Scientific Method 254
6.7 Carbocation Rearrangements in Hydrogen Halide Addition to Alkenes 254
6.8 Free-Radical Addition of Hydrogen Bromide to Alkenes 255
6.9 Addition of Sulfuric Acid to Alkenes 258
6.10 Acid-Catalyzed Hydration of Alkenes 260
6.11 Thermodynamics of Addition–Elimination Equilibria 262
6.12 Hydroboration–Oxidation of Alkenes 265
6.13 Stereochemistry of Hydroboration–Oxidation 267
6.14 Mechanism of Hydroboration–Oxidation 267
6.15 Addition of Halogens to Alkenes 270
6.16 Stereochemistry of Halogen Addition 270
6.17 Mechanism of Halogen Addition to Alkenes: Halonium Ions 271
6.18 Conversion of Alkenes to Vicinal Halohydrins 273
6.19 Epoxidation of Alkenes 274
6.20 Ozonolysis of Alkenes 276
6.21 Introduction to Organic Chemical Synthesis 278
6.22 Reactions of Alkenes with Alkenes: Polymerization 280 Ethylene and Propene: The Most Important Industrial Organic Chemicals 284
6.23 SUMMARY 285 PROBLEMS 288 LEARNING BY MODELING 293
CHAPTER 7
STEREOCHEMISTRY 296
7.1 Molecular Chirality: Enantiomers 298
7.2 The Chirality Center 300
7.3 Symmetry in Achiral Structures 302
7.4 Optical Activity 303
7.5 Absolute and Relative Configuration 305
7.6 The Cahn–Ingold–Prelog R–S Notational System 306
7.7 Fischer Projections 308
7.8 Properties of Enantiomers 310 Chiral Drugs 311
7.9 Reactions That Create a Chirality Center 313
7.10 Chiral Molecules with Two Chirality Centers 316
7.11 Achiral Molecules with Two Chirality Centers 318
7.12 Molecules with Multiple Chirality Centers 320 Chirality of Disubstituted Cyclohexanes 321
7.13 Reactions That Produce Diastereomers 322
7.14 Resolution of Enantiomers 324
7.15 Stereoregular Polymers 327
7.16 Chirality Centers Other Than Carbon 328
7.17 SUMMARY 329 PROBLEMS 332 LEARNING BY MODELING 339
CHAPTER 8
NUCLEOPHILIC SUBSTITUTION 342
8.1 Functional Group Transformation by Nucleophilic Substitution 344
8.2 Relative Reactivity of Halide Leaving Groups 347
8.3 The SN 2 Mechanism of Nucleophilic Substitution 347
8.4 Steric Effects in SN 2 Reactions 351
8.5 Nucleophiles and Nucleophilicity 353
8.6 The SN 1 Mechanism of Nucleophilic Substitution 355 Enzyme-Catalyzed Nucleophilic Substitutions of Alkyl Halides 356
8.7 Carbocation Stability and SN 1 Reaction Rates 358
8.8 Stereochemistry of SN 1 Reactions 359
8.9 Carbocation Rearrangements in SN 1 Reactions 360
8.10 Effect of Solvent on the Rate of Nucleophilic Substitution 362
8.11 Substitution and Elimination as Competing Reactions 365
8.12 Sulfonate Esters as Substrates in Nucleophilic Substitution 367
8.13 Looking Back: Reactions of Alcohols with Hydrogen Halides 370
8.14 SUMMARY 371 PROBLEMS 373 LEARNING BY MODELING 378
CHAPTER 9
ALKYNES 380
9.1 Sources of Alkynes 381
9.2 Nomenclature 382
9.3 Physical Properties of Alkynes 383
9.4 Structure and Bonding in Alkynes: sp Hybridization 384
9.5 Acidity of Acetylene and Terminal Alkynes 386 Natural and “Designed” Enediyne Antibiotics 387
9.6 Preparation of Alkynes by Alkyation of Acetylene and Terminal Alkynes 389
9.7 Preparation of Alkynes by Elimination Reactions 391
9.8 Reactions of Alkynes 393
9.9 Hydrogenation of Alkynes 393
9.10 Metal–Ammonia Reduction of Alkynes 394
9.11 Addition of Hydrogen Halides to Alkynes 396
9.12 Hydration of Alkynes 398
9.13 Addition of Halogens to Alkynes 400
9.14 Ozonolysis of Alkynes 400
9.15 SUMMARY 401 PROBLEMS 404 LEARNING BY MODELING 408
CHAPTER 10
CONJUGATION IN ALKADIENES AND ALLYLIC SYSTEMS 410
10.1 The Allyl Group 412
10.2 Allylic Carbocations 412
10.3 SN 1 Reactions of Allylic Halides 414
10.4 Allylic Free Radicals 417
10.5 Allylic Halogenation 418
10.6 Classes of Dienes 420
10.7 Relative Stabilities of Dienes 421
10.8 Bonding in Conjugated Dienes 422
10.9 Bonding in Allenes 424
10.10 Preparation of Dienes 425
10.11 Addition of Hydrogen Halides to Conjugated Dienes 426
10.12 Halogen Addition to Dienes 429 Diene Polymers 430
10.13 The Diels–Alder Reaction 430
10.14 The Molecular Orbitals of Ethylene and 1,3-Butadiene 434
10.15 A Molecular Orbital Analysis of the Diels–Alder Reaction 435
10.16 SUMMARY 437 PROBLEMS 439 LEARNING BY MODELING 443
CHAPTER 11
ARENES AND AROMATICITY 446
11.1 Benzene 448
11.2 Kekulé and the Structure of Benzene 448
11.3 A Resonance Picture of Bonding in Benzene 450 Benzene, Dreams, and Creative Thinking 451
11.4 The Stability of Benzene 451
11.5 An Orbital Hybridization View of Bonding in Benzene 453
11.6 The Pi Molecular Orbitals of Benzene 454
11.7 Substituted Derivatives of Benzene and Their Nomenclature 455
11.8 Polycyclic Aromatic Hydrocarbons 457 Carbon Clusters, Fullerenes, and Nanotubes 459
11.9 Physical Properties of Arenes 460
11.10 Reactions of Arenes: A Preview 461
11.11 The Birch Reduction 461
11.12 Free-Radical Halogenation of Alkylbenzenes 463
11.13 Oxidation of Alkylbenzenes 465
11.14 Nucleophilic Substitution in Benzylic Halides 467
11.15 Preparation of Alkenylbenzenes 469
11.16 Addition Reactions of Alkenylbenzenes 470
11.17 Polymerization of Styrene 471
11.18 Cyclobutadiene and Cyclooctatetraene 472
11.19 Hückel’s Rule 475
11.20 Annulenes 477
11.21 Aromatic Ions 479
11.22 Heterocyclic Aromatic Compounds 483
11.23 Heterocyclic Aromatic Compounds and Hückel’s Rule 484
11.24 SUMMARY 486 PROBLEMS 490 LEARNING BY MODELING 494
CHAPTER 12
REACTIONS OF ARENES: ELECTROPHILIC AROMATIC SUBSTITUTION 496
12.1 Representative Electrophilic Aromatic Substitution Reactions of Benzene 498
12.2 Mechanistic Principles of Electrophilic Aromatic Substitution 498
12.3 Nitration of Benzene 501
12.4 Sulfonation of Benzene 502
12.5 Halogenation of Benzene 504
12.6 Friedel–Crafts Alkylation of Benzene 505
12.7 Friedel–Crafts Acylation of Benzene 507
12.8 Synthesis of Alkylbenzenes by Acylation–Reduction 509
12.9 Rate and Regioselectivity in Electrophilic Aromatic Substitution 511
12.10 Rate and Regioselectivity in the Nitration of Toluene 512
12.11 Rate and Regioselectivity in the Nitration of (Trifluoromethyl)benzene 515
12.12 Substituent Effects in Electrophilic Aromatic Substitution: Activating Substituents 517
12.13 Substituent Effects in Electrophilic Aromatic Substitution: Strongly Deactivating Substituents 520
12.14 Substituent Effects in Electrophilic Aromatic Substitution: Halogens 523
12.15 Multiple Substituent Effects 524
12.16 Regioselective Synthesis of Disubstituted Aromatic Compounds 526
12.17 Substitution in Naphthalene 529
12.18 Substitution in Heterocyclic Aromatic Compounds 529
12.19 SUMMARY 531 PROBLEMS 534 LEARNING BY MODELING 540
CHAPTER 13
SPECTROSCOPY 542
13.1 Principles of Molecular Spectroscopy: Electromagnetic Radiation 544
13.2 Principles of Molecular Spectroscopy: Quantized Energy States 545
13.3 Introduction to 1 H NMR Spectroscopy 545
13.4 Nuclear Shielding and 1 H Chemical Shifts 549
13.5 Effects of Molecular Structure on 1 H Chemical Shifts 550 Ring Currents—Aromatic and Antiaromatic 556
13.6 Interpreting 1 H NMR Spectra 557
13.7 Spin–Spin Splitting in 1 H NMR Spectroscopy 559
13.8 Splitting Patterns: The Ethyl Group 562
13.9 Splitting Patterns: The Isopropyl Group 563
13.10 Splitting Patterns: Pairs of Doublets 564
13.11 Complex Splitting Patterns 566
13.12 1 H NMR Spectra of Alcohols 567 Magnetic Resonance Imaging (MRI) 568
13.13 NMR and Conformations 568
13.14 13 C NMR Spectroscopy 569
13.15 13 C Chemical Shifts 571
13.16 13 C NMR and Peak Intensities 573
13.17 13 C 1 H Coupling 574
13.18 Using DEPT to Count Hydrogens Attached to 13 C 575
13.19 2D NMR: COSY and HETCOR 575
13.20 Infrared Spectroscopy 578 Spectra by the Thousands 579
13.21 Ultraviolet-Visible (UV-VIS) Spectroscopy 584
13.22 Mass Spectrometry 586
13.23 Molecular Formula as a Clue to Structure 590 Gas Chromatography, GC/MS, and MS/MS 591
13.24 SUMMARY 593 PROBLEMS 596 LEARNING BY MODELING 602
CHAPTER 14
ORGANOMETALLIC COMPOUNDS 604
14.1 Organometallic Nomenclature 606
14.2 Carbon–Metal Bonds in Organometallic Compounds 606
14.3 Preparation of Organolithium Compounds 608
14.4 Preparation of Organomagnesium Compounds: Grignard Reagents 609
14.5 Organolithium and Organomagnesium Compounds as Brønsted Bases 610
14.6 Synthesis of Alcohols Using Grignard Reagents 612
14.7 Synthesis of Alcohols Using Organolithium Reagents 614
14.8 Synthesis of Acetylenic Alcohols 615
14.9 Retrosynthetic Analysis 616
14.10 Preparation of Tertiary Alcohols from Esters and Grignard Reagents 619
14.11 Alkane Synthesis Using Organocopper Reagents 620
14.12 An Organozinc Reagent for Cyclopropane Synthesis 622
14.13 Carbenes and Carbenoids 624
14.14 Transition-Metal Organometallic Compounds 626 An Organometallic Compound That Occurs Naturally: Coenzyme B12 628
14.15 Homogeneous Catalytic Hydrogenation 629
14.16 Olefin Metathesis 632
14.17 Ziegler–Natta Catalysis of Alkene Polymerization 635
14.18 SUMMARY 638 PROBLEMS 641 LEARNING BY MODELING 646
CHAPTER 15
ALCOHOLS, DIOLS, AND THIOLS 648
15.1 Sources of Alcohols 650
15.2 Preparation of Alcohols by Reduction of Aldehydes and Ketones 651
15.3 Preparation of Alcohols by Reduction of Carboxylic Acids and Esters 657
15.4 Preparation of Alcohols from Epoxides 658
15.5 Preparation of Diols 659
15.6 Reactions of Alcohols: A Review and a Preview 661
15.7 Conversion of Alcohols to Ethers 661
15.8 Esterification 664
15.9 Esters of Inorganic Acids 666
15.10 Oxidation of Alcohols 667 Economic and Environmental Factors in Organic Synthesis 670
15.11 Biological Oxidation of Alcohols 671
15.12 Oxidative Cleavage of Vicinal Diols 673
15.13 Thiols 674
15.14 Spectroscopic Analysis of Alcohols and Thiols 676
15.15 SUMMARY 678 PROBLEMS 682 LEARNING BY MODELING 688
CHAPTER 16
ETHERS, EPOXIDES, AND SULFIDES 690
16.1 Nomenclature of Ethers, Epoxides, and Sulfides 691
16.2 Structure and Bonding in Ethers and Epoxides 693
16.3 Physical Properties of Ethers 693
16.4 Crown Ethers 695 Polyether Antibiotics 697
16.5 Preparation of Ethers 698
16.6 The Williamson Ether Synthesis 698
16.7 Reactions of Ethers: A Review and a Preview 700
16.8 Acid-Catalyzed Cleavage of Ethers 701
16.9 Preparation of Epoxides: A Review and a Preview 702
16.10 Conversion of Vicinal Halohydrins to Epoxides 703
16.11 Reactions of Epoxides: A Review and a Preview 705
16.12 Nucleophilic Ring Opening of Epoxides 706
16.13 Acid-Catalyzed Ring Opening of Epoxides 708
16.14 Epoxides in Biological Processes 711
16.15 Preparation of Sulfides 711
16.16 Oxidation of Sulfides: Sulfoxides and Sulfones 712
16.17 Alkylation of Sulfides: Sulfonium Salts 713
16.18 Spectroscopic Analysis of Ethers, Epoxides, and Sulfides 714
16.19 SUMMARY 717 PROBLEMS 721 LEARNING BY MODELING 726
CHAPTER 17
ALDEHYDES AND KETONES: NUCLEOPHILIC ADDITION TO THE CARBONYL GROUP 728
17.1 Nomenclature 729
17.2 Structure and Bonding: The Carbonyl Group 732
17.3 Physical Properties 734
17.4 Sources of Aldehydes and Ketones 735
17.5 Reactions of Aldehydes and Ketones: A Review and a Preview 738
17.6 Principles of Nucleophilic Addition: Hydration of Aldehydes and Ketones 739
17.7 Cyanohydrin Formation 743
17.8 Acetal Formation 747
17.9 Acetals as Protecting Groups 750
17.10 Reaction with Primary Amines: Imines 751 Imines in Biological Chemistry 754
17.11 Reaction with Secondary Amines: Enamines 756
17.12 The Wittig Reaction 757
17.13 Planning an Alkene Synthesis via the Wittig Reaction 759
17.14 Stereoselective Addition to Carbonyl Groups 761
17.15 Oxidation of Aldehydes 763
17.16 Baeyer–Villiger Oxidation of Ketones 763
17.17 Spectroscopic Analysis of Aldehydes and Ketones 766
17.18 SUMMARY 768 PROBLEMS 772 LEARNING BY MODELING 780
CHAPTER 18
ENOLS AND ENOLATES 782
18.1 The -Hydrogen and Its pKa 784
18.2 The Aldol Condensation 787
18.3 Mixed Aldol Condensations 792
18.4 Alkylation of Enolate Ions 793
18.5 Enolization and Enol Content 794
18.6 Stabilized Enols 797
18.7 Halogenation of Aldehydes and Ketones 799
18.8 Mechanism of Halogenation of Aldehydes and Ketones 800
18.9 The Haloform Reaction 801
18.10 Some Chemical and Stereochemical Consequences of Enolization 804 The Haloform Reaction and the Biosynthesis of Trihalomethanes 805
18.11 Effects of Conjugation in ,-Unsaturated Aldehydes and Ketones 806
18.12 Conjugate Addition to ,-Unsaturated Carbonyl Compounds 807
18.13 Addition of Carbanions to ,-Unsaturated Ketones: The Michael Reaction 810
18.14 Conjugate Addition of Organocopper Reagents to ,-Unsaturated Carbonyl Compounds 810
18.15 SUMMARY 811 PROBLEMS 814 LEARNING BY MODELING 820
CHAPTER 19
CARBOXYLIC ACIDS 822
19.1 Carboxylic Acid Nomenclature 824
19.2 Structure and Bonding 825
19.3 Physical Properties 826
19.4 Acidity of Carboxylic Acids 827
19.5 Salts of Carboxylic Acids 829
19.6 Substituents and Acid Strength 832
19.7 Ionization of Substituted Benzoic Acids 834
19.8 Dicarboxylic Acids 835
19.9 Carbonic Acid 835
19.10 Sources of Carboxylic Acids 836
19.11 Synthesis of Carboxylic Acids by the Carboxylation of Grignard Reagents 838
19.12 Synthesis of Carboxylic Acids by the Preparation and Hydrolysis of Nitriles 839
19.13 Reactions of Carboxylic Acids: A Review and a Preview 841
19.14 Mechanism of Acid-Catalyzed Esterification 842
19.15 Intramolecular Ester Formation: Lactones 845
19.16 Alpha Halogenation of Carboxylic Acids: The Hell–Volhard–Zelinsky Reaction 847
19.17 Decarboxylation of Malonic Acid and Related Compounds 848
19.18 Spectroscopic Analysis of Carboxylic Acids 851
19.19 SUMMARY 852 PROBLEMS 855 LEARNING BY MODELING 860
20.1 Nomenclature of Carboxylic Acid Derivatives 864
20.2 Structure and Reactivity of Carboxylic Acid Derivatives 866
20.3 General Mechanism for Nucleophilic Acyl Substitution 869
20.4 Nucleophilic Acyl Substitution in Acyl Chlorides 870
20.5 Nucleophilic Acyl Substitution in Carboxylic Acid Anhydrides 873
20.6 Sources of Esters 876
20.7 Physical Properties of Esters 877
20.8 Reactions of Esters: A Review and a Preview 879
20.9 Acid-Catalyzed Ester Hydrolysis 879
20.10 Ester Hydrolysis in Base: Saponification 883
20.11 Reaction of Esters with Ammonia and Amines 887
20.12 Thioesters 887
20.13 Amides 889
20.14 Lactams 893
20.15 Hydrolysis of Amides 894 Condensation Polymers: Polyamides and Polyesters 898
20.16 Preparation of Nitriles 898
20.17 Hydrolysis of Nitriles 900
20.18 Addition of Grignard Reagents to Nitriles 901
20.19 Spectroscopic Analysis of Carboxylic Acid Derivatives 903
20.20 SUMMARY 904 PROBLEMS 908 LEARNING BY MODELING 914
CHAPTER 21
ESTER ENOLATES 916
21.1 Ester Hydrogens and Their pKa ’s 917
21.2 The Claisen Condensation 919
21.3 Intramolecular Claisen Condensation: The Dieckmann Reaction 922
21.4 Mixed Claisen Condensations 923
21.5 Acylation of Ketones with Esters 924
21.6 Ketone Synthesis via -Keto Esters 925
21.7 The Acetoacetic Ester Synthesis 926
21.8 The Malonic Ester Synthesis 929
21.9 Michael Additions of Stabilized Anions 932
21.10 Reactions of LDA-Generated Ester Enolates 933
21.11 SUMMARY 934 PROBLEMS 937 LEARNING BY MODELING 941
CHAPTER 22
AMINES 942
22.1 Amine Nomenclature 944
22.2 Structure and Bonding 946
22.3 Physical Properties 948
22.4 Basicity of Amines 948 Amines as Natural Products 954
22.5 Tetraalkylammonium Salts as Phase-Transfer Catalysts 956
22.6 Reactions That Lead to Amines: A Review and a Preview 957
22.7 Preparation of Amines by Alkylation of Ammonia 959
22.8 The Gabriel Synthesis of Primary Alkylamines 960
22.9 Preparation of Amines by Reduction 961
22.10 Reductive Amination 964
22.11 Reactions of Amines: A Review and a Preview 965
22.12 Reaction of Amines with Alkyl Halides 967
22.13 The Hofmann Elimination 967
22.14 Electrophilic Aromatic Substitution in Arylamines 969
22.15 Nitrosation of Alkylamines 972
22.16 Nitrosation of Arylamines 974
22.17 Synthetic Transformations of Aryl Diazonium Salts 975
22.18 Azo Coupling 979 From Dyes to Sulfa Drugs 980
22.19 Spectroscopic Analysis of Amines 981
22.20 SUMMARY 984 PROBLEMS 991 LEARNING BY MODELING 999
CHAPTER 23
ARYL HALIDES 1002
23.1 Bonding in Aryl Halides 1003
23.2 Sources of Aryl Halides 1004
23.3 Physical Properties of Aryl Halides 1004
23.4 Reactions of Aryl Halides: A Review and a Preview 1006
23.5 Nucleophilic Substitution in Nitro-Substituted Aryl Halides 1007
23.6 The Addition–Elimination Mechanism of Nucleophilic Aromatic Substitution 1009
23.7 Related Nucleophilic Aromatic Substitution Reactions 1012
23.8 The Elimination–Addition Mechanism of Nucleophilic Aromatic Substitution: Benzyne 1013
23.9 Diels–Alder Reactions of Benzyne 1018
23.10 m-Benzyne and p-Benzyne 1018
23.11 SUMMARY 1020 PROBLEMS 1021 LEARNING BY MODELING 1026
CHAPTER 24
PHENOLS 1028
24.1 Nomenclature 1029
24.2 Structure and Bonding 1030
24.3 Physical Properties 1031
24.4 Acidity of Phenols 1033
24.5 Substituent Effects on the Acidity of Phenols 1034
24.6 Sources of Phenols 1035
24.7 Naturally Occurring Phenols 1037
24.8 Reactions of Phenols: Electrophilic Aromatic Substitution 1038
24.9 Acylation of Phenols 1041
24.10 Carboxylation of Phenols: Aspirin and the Kolbe–Schmitt Reaction 1042
24.11 Preparation of Aryl Ethers 1044 Agent Orange and Dioxin 1046
24.12 Cleavage of Aryl Ethers by Hydrogen Halides 1046
24.13 Claisen Rearrangement of Allyl Aryl Ethers 1047
24.14 Oxidation of Phenols: Quinones 1048
24.15 Spectroscopic Analysis of Phenols 1050
24.16 SUMMARY 1051 PROBLEMS 1054 LEARNING BY MODELING 1059
CHAPTER 25
CARBOHYDRATES 1062
25.1 Classification of Carbohydrates 1064
25.2 Fischer Projections and D–L Notation 1064
25.3 The Aldotetroses 1066
25.4 Aldopentoses and Aldohexoses 1067
25.5 A Mnemonic for Carbohydrate Configurations 1069
25.6 Cyclic Forms of Carbohydrates: Furanose Forms 1069
25.7 Cyclic forms of Carbohydrates: Pyranose Forms 1073
25.8 Mutarotation 1076
25.9 Ketoses 1077
25.10 Deoxy Sugars 1078
25.11 Amino Sugars 1079
25.12 Branched-Chain Carbohydrates 1080
25.13 Glycosides 1080
25.14 Disaccharides 1083
25.15 Polysaccharides 1084 How Sweet It Is! 1085
25.16 Carbohydrate Structure Determination 1087
25.17 Reduction of Carbohydrates 1087
25.18 Oxidation of Carbohydrates 1088
25.19 Cyanohydrin Formation and Chain Extension 1091
25.20 Epimerization, Isomerization, and Retro-Aldol Cleavage 1092
25.21 Acylation and Alkylation of Hydroxyl Groups in Carbohydrates 1094
25.22 Periodic Acid Oxidation of Carbohydrates 1095
25.23 SUMMARY 1096 PROBLEMS 1100 LEARNING BY MODELING 1103
CHAPTER 26
LIPIDS 1106
26.1 Acetyl Coenzyme A 1108
26.2 Fats, Oils, and Fatty Acids 1109
26.3 Fatty Acid Biosynthesis 1113
26.4 Phospholipids 1115
26.5 Waxes 1117
26.6 Prostaglandins 1118 Nonsteroidal Antiinflammatory Drugs (NSAIDS) and COX-2 Inhibitors 1121
26.7 Terpenes: The Isoprene Rule 1122
26.8 Isopentenyl Pyrophosphate: The Biological Isoprene Unit 1125
26.9 Carbon–Carbon Bond Formation in Terpene Biosynthesis 1125
26.10 The Pathway from Acetate to Isopentenyl Pyrophosphate 1129
26.11 Steroids: Cholesterol 1131 Good Cholesterol? Bad Cholesterol? What’s the Difference? 1134
26.12 Vitamin D 1134
26.13 Bile Acids 1135
26.14 Corticosteroids 1136
26.15 Sex Hormones 1136
26.16 Carotenoids 1137 Anabolic Steroids 1138 Crocuses Make Saffron from Carotenes 1139
26.17 SUMMARY 1140 PROBLEMS 1142 LEARNING BY MODELING 1146
CHAPTER 27
AMINO ACIDS, PEPTIDES, AND PROTEINS 1148
27.1 Classification of Amino Acids 1150
27.2 Stereochemistry of Amino Acids 1156
27.3 Acid–Base Behavior of Amino Acids 1158
27.4 Synthesis of Amino Acids 1160 Electrophoresis 1161
27.5 Reactions of Amino Acids 1163
27.6 Some Biochemical Reactions of Amino Acids 1164
27.7 Peptides 1170
27.8 Introduction to Peptide Structure Determination 1174
27.9 Amino Acid Analysis 1174
27.10 Partial Hydrolysis of Peptides 1175
27.11 End Group Analysis 1175
27.12 Insulin 1177
27.13 The Edman Degradation and Automated Sequencing of Peptides 1178
27.14 The Strategy of Peptide Synthesis 1180
27.15 Amino Group Protection 1181
27.16 Carboxyl Group Protection 1184
27.17 Peptide Bond Formation 1184
27.18 Solid-Phase Peptide Synthesis: The Merrifield Method 1186
27.19 Secondary Structures of Peptides and Proteins 1189
27.20 Tertiary Structure of Polypeptides and Proteins 1191
27.21 Coenzymes 1194
27.22 Protein Quaternary Structure: Hemoglobin 1196 Oh NO! It’s Inorganic! 1197
27.23 SUMMARY 1198 PROBLEMS 1200 LEARNING BY MODELING 1202
CHAPTER 28
NUCLEOSIDES, NUCLEOTIDES, AND NUCLEIC ACIDS 1204
28.1 Pyrimidines and Purines 1206
28.2 Nucleosides 1209
28.3 Nucleotides 1211
28.4 Bioenergetics 1212
28.5 ATP and Bioenergetics 1213
28.6 Phosphodiesters, Oligonucleotides, and Polynucleotides 1214
28.7 Nucleic Acids 1216
28.8 Secondary Structure of DNA: The Double Helix 1217 “It Has Not Escaped Our Notice . . .” 1218
28.9 Tertiary Structure of DNA: Supercoils 1220
28.10 Replication of DNA 1222
28.11 Ribonucleic Acids 1222
28.12 Protein Biosynthesis 1227 RNA World 1228
28.13 AIDS 1228
28.14 DNA Sequencing 1229
28.15 The Human Genome Project 1232
28.16 DNA Profiling and the Polymerase Chain Reaction 1232
28.17 SUMMARY 1235 PROBLEMS 1238 LEARNING BY MODELING 1240
CHAPTER 29
SYNTHETIC POLYMERS 1242
29.1 Some Background 1243
29.2 Polymer Nomenclature 1244
29.3 Classification of Polymers: Reaction Type 1245
29.4 Classification of Polymers: Chain-Growth and Step-Growth 1247
29.5 Classification of Polymers: Structure 1248
29.6 Classification of Polymers: Properties 1251
29.7 Addition Polymers: A Review and a Preview 1252
29.8 Chain Branching in Free-Radical Polymerization 1254
29.9 Anionic Polymerization: Living Polymers 1257
29.10 Cationic Polymerization 1259
29.11 Polyamides 1260
29.12 Polyesters 1262
29.13 Polycarbonates 1263
29.14 Polyurethanes 1263
29.15 Copolymers 1264
29.16 SUMMARY 1266 PROBLEMS 1269 LEARNING BY MODELING 1271
APPENDIX 1
PHYSICAL PROPERTIES A-1
APPENDIX 2
ANSWERS TO IN-TEXT PROBLEMS A-8
GLOSSARY G-1
CREDITS C-1
INDEX I-1
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