Organic chemistryPDF电子书下载

INTRODUCTION 2

The Origins of Organic Chemistry 2

Berzelius，Wohler，and Vitalism 2

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 16

Electrostatic Potential Maps 19

1.6 Structural Formulas of Organic Molecules 19

1.7 Formal Charge 22

1.8 Resonance 24

1.9 The Shapes of Some Simple Molecules 29

Molecular Modeling 30

1.10 Molecular Dipole Moments 32

1.11 Curved Arrows and Chemical Reactions 33

1.12 Acids and Bases：The Arrhenius View 35

1.13 Acids and Bases：The Bronsted-Lowry View 36

1.14 What Happened to pKb？ 40

1.15 How Structure Affects Acid Strength 41

1.16 Acid-Base Equilibria 45

1.17 Lewis Acids and Lewis Bases 48

1.18 Summary 49

Problems 52

Descriptive Passage and Interpretive Problems 1：Amide Lewis Structures 57

CHAPTER 2 Alkanes and Cycloalkanes：Introduction to Hydrocarbons 58

2.1 Classes of Hydrocarbons 59

2.2 Electron Waves and Chemical Bonds 60

2.3 Bonding in H2：The Valence Bond Model 61

2.4 Bonding in H2：The Molecular Orbital Model 63

2.5 Introduction to Alkanes：Methane，Ethane，and Propane 64

Methane and the Biosphere 65

2.6 sp3 Hybridization and Bonding in Methane 66

2.7 Bonding in Ethane 68

2.8 Isomeric Alkanes：The Butanes 68

2.9 Higher n-Alkanes 68

2.10 The C5H12 Isomers 69

2.11 IUPAC Nomenclature of Unbranched Alkanes 71

What’s In a Name？ Organic Nomenclature 72

2.12 Applying the IUPAC Rules：The Names of the C6H14 Isomers 73

2.13 Alkyl Groups 74

2.14 IUPAC Names of Highly Branched Alkanes 76

2.15 Cycloalkane Nomenclature 77

2.16 Sources of Alkanes and Cycloalkanes 78

2.17 Physical Properties of Alkanes and Cycloalkanes 80

2.18 Chemical Properties：Combustion of Alkanes 82

2.19 Oxidation-Reduction in Organic Chemistry 85

Thermochemistty 86

2.20 sp2 Hybridization and Bonding in Ethylene 89

2.21 sp Hybridization and Bonding in Acetylene 91

2.22 Which Theory of Chemical Bonding Is Best？ 92

2.23 Summary 93

Problems 97

Descriptive Passage and Interpretive Problems 2：Some Biochemical Reactions of Alkanes 100

CHAPTER 3 Alkanes and Cycloalkanes：Conformations and cis-trans Stereoisomers 102

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：Cyclic Forms of Carbohydrates 137

CHAPTER 4 Alcohols and Alkyl Halides 138

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 SN1 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 SN2 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 Enthalpies to Heats of Reaction 169

4.19 Summary 173

Problems 176

Descriptive Passage and Interpretive Problems 4：More About PotentialEnergy Diagrams 180

CHAPTER 5 Structure and Preparation of Alkenes：Elimination Reactions 182

5.1 Alkene Nomenclature 183

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 224

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 276

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 SN2 Mechanism of Nucleophilic Substitution 323

8.4 Steric Effects and SN2 Reaction Rates 326

8.5 Nucleophiles and Nucleophilicity 328

8.6 The SN1 Mechanism of Nucleophilic Substitution 330

Enzyme-Catalyzed Nucleophilic Substitutions of Alkyl Halides 331

8.7 Carbocation Stability and SN1 Reaction Rates 331

8.8 Stereochemistry of SN1 Reactions 334

8.9 Carbocation Rearrangements in SN1 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 354

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 Acetylenem…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 382

10.1 The Allyl Group 383

10.2 Allylic Carbocations 384

10.3 SN1 Reactions of Allylic Halides 385

10.4 SN2 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 π Molecular Orbitals of Ethylene and 1，3-Butadiene 407

10.17 A π 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 420

11.1 Benzene 421

11.2 Kekule 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 π 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 Huckel’s Rule 448

11.21 Annulenes 450

11.22 Aromatic Ions 452

11.23 Heterocyclic Aromatic Compounds 455

11.24 Heterocyclic Aromatic Compounds and Huckel’s Rule 457

11.25 Summary 459

Problems 462

Descriptive Passage and Interpretive Problems 11：The Hammett Equation 466

CHAPTER 12 Reactions of Arenes：Electrophilic Aromatic Substitution 470

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 516

13.1 Principles of Molecular Spectroscopy：Electromagnetic Radiation 518

13.2 Principles of Molecular Spectroscopy：Quantized Energy States 519

13.3 Introduction to 1H NMR Spectroscopy 519

13.4 Nuclear Shielding and 1H Chemical Shifts 521

13.5 Effects of Molecular Structure on 1H Chemical Shifts 524

Ring Currents：Aromatic and Antiaromatic 529

13.6 Interpreting 1H NMR Spectra 530

13.7 Spin-Spin Splitting in 1H NMR Spectroscopy 532

13.8 Splitting Patterns：The Ethyl Group 534

13.9 Splitting Patterns：The Isopropyl Group 536

13.10 Splitting Patterns：Pairs of Doublets 536

13.11 Complex Splitting Patterns 538

13.12 1H NMR Spectra of Alcohols 539

Magnetic Resonance Imaging （MRI） 540

13.13 NMR and Conformations 540

13.14 13C NMR Spectroscopy 541

13.15 13C Chemical Shifts 543

13.16 13C NMR and Peak Intensities 545

13.17 13C— 1H Coupling 546

13.18 Using DEPT to Count Hydrogens Attached to 13C 546

13.19 2D NMR：COSY and HETCOR 547

13.20 Introduction to Infrared Spectroscopy 550

Spectra by the Thousands 551

13.21 Infrared Spectra 552

13.22 Characteristic Absorption Frequencies 554

13.23 Ultraviolet-Visible （UV-VIS） Spectroscopy 557

13.24 Mass Spectrometry 559

13.25 Molecular Formula as a Clue to Structure 563

Gas Chromatography，GC/MS，and MS/MS 564

13.26 Summary 566

Problems 569

Descriptive Passage and Interpretive Problems 13：Calculating Aromatic 13C Chemical Shifts 575

CHAPTER 14 Organometallic Compounds 578

14.1 Organometallic Nomenclature 580

14.2 Carbon-Metal Bonds in Organometallic Compounds 580

14.3 Preparation of Organolithium Compounds 581

14.4 Preparation of Organomagnesium Compounds：Grignard Reagents 583

14.5 Organolithium and Organomagnesium Compounds as Bronsted Bases 584

14.6 Synthesis of Alcohols Using Grignard Reagents 586

14.7 Synthesis of Alcohols Using Organolithium Reagents 588

14.8 Synthesis of Acetylenic Alcohols 588

14.9 Retrosynthetic Analysis 589

14.10 Preparation of Tertiary Alcohols from Esters and Grignard Reagents 592

14.11 Alkane Synthesis Using Organocopper Reagents 593

14.12 An Organozinc Reagent for Cyclopropane Synthesis 595

14.13 Carbenes and Carbenoids 596

14.14 Transition-Metal Organometallic Compounds 599

An Organometallic Compound That Occurs Naturally：Coenzyme B12 601

14.15 Homogeneous Catalytic Hydrogenation 602

14.16 Olefin Metathesis 605

14.17 Ziegler-Natta Catalysis of Alkene Polymerization 607

14.18 Summary 610

Problems 613

Descriptive Passage and Interpretive Problems 14：Oxymercuration 617

CHAPTER 15 Alcohols，Diols，and Thiols 620

15.1 Sources of Alcohols 621

15.2 Preparation of Alcohols by Reduction of Aldehydes and Ketones 622

15.3 Preparation of Alcohols by Reduction of Carboxylic Acids and Esters 628

15.4 Preparation of Alcohols from Epoxides 629

15.5 Preparation of Diols 630

15.6 Reactions of Alcohols：A Review and a Preview 632

15.7 Conversion of Alcohols to Ethers 632

15.8 Esterification 635

15.9 Esters of Inorganic Acids 637

15.10 Oxidation of Alcohols 638

15.11 Biological Oxidation of Alcohols 640

Economic and Environmental Factors in Organic Synthesis 641

15.12 Oxidative Cleavage of Vicinal Diols 643

15.13 Thiols 644

15.14 Spectroscopic Analysis of Alcohols and Thiols 647

15.15 Summary 648

Problems 652

Descriptive Passage and Interpretive Problems 15：The Pinacol Rearrangement 658

CHAPTER 16 Ethers，Epoxides，and Sulfides 662

16.1 Nomenclature of Ethers，Epoxides，and Sulfides 663

16.2 Structure and Bonding in Ethers and Epoxides 664

16.3 Physical Properties of Ethers 665

16.4 Crown Ethers 667

16.5 Preparation of Ethers 668

Polyether Antibiotics 669

16.6 The Williamson Ether Synthesis 670

16.7 Reactions of Ethers：A Review and a Preview 671

16.8 Acid-Catalyzed Cleavage of Ethers 672

16.9 Preparation of Epoxides：A Review and a Preview 674

16.10 Conversion of Vicinal Halohydrins to Epoxides 675

16.11 Reactions of Epoxides：A Review and a Preview 676

16.12 Nucleophilic Ring Opening of Epoxides 677

16.13 Acid-Catalyzed Ring Opening of Epoxides 679

16.14 Epoxides in Biological Processes 682

16.15 Preparation of Sulfides 682

16.16 Oxidation of Sulfides：Sulfoxides and Sulfones 683

16.17 Alkylation of Sulfides：Sulfonium Salts 684

16.18 Spectroscopic Analysis of Ethers，Epoxides，and Sulfides 685

16.19 Summary 688

Problems 692

Descriptive Passage and Interpretive Problems 16：Epoxide Rearrangements and the NIH Shift 697

CHAPTER 17 Aldehydes and Ketones：Nucleophilic Addition to the Carbonyl Group 700

17.1 Nomenclature 701

17.2 Structure and Bonding：The Carbonyl Group 704

17.3 Physical Properties 706

17.4 Sources of Aldehydes and Ketones 707

17.5 Reactions of Aldehydes and Ketones：A Review and a Preview 710

17.6 Principles of Nucleophilic Addition：Hydration of Aldehydes and Ketones 711

17.7 Cyanohydrin Formation 715

17.8 Acetal Formation 718

17.9 Acetals as Protecting Groups 721

17.10 Reaction with Primary Amines：Imines 722

Imines in Biological Chemistry 725

17.11 Reaction with Secondary Amines：Enamines 727

17.12 The Wittig Reaction 728

17.13 Planning an Alkene Synthesis via the Wittig Reaction 730

17.14 Stereoselective Addition to Carbonyl Groups 732

17.15 Oxidation of Aldehydes 733

17.16 Baeyer-Villiger Oxidation of Ketones 734

17.17 Spectroscopic Analysis of Aldehydes and Ketones 736

17.18 Summary 738

Problems 742

Descriptive Passage and Interpretive Problems 17：Alcohols，Aldehydes，and Carbohydrates 749

CHAPTER 18 Enols and Enolates 752

18.1 The α 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 α Halogenation of Aldehydes and Ketones 768

18.8 Mechanism of α 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 α，β-Unsaturated Aldehydes and Ketones 774

18.12 Conjugate Addition to α，β-Unsaturated Carbonyl Compounds 775

18.13 Addition of Carbanions to α，β-Unsaturated Ketones：The Michael Reaction 778

18.14 Conjugate Addition of Organocopper Reagents to a，β-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 790

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 α 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 825

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 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

β-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 880

21.1 Ester α Hydrogens and Their pKa’s 881

21.2 The Claisen Condensation 883

21.3 Intramolecular Claisen Condensation：The Dieckmann Cyclization 886

21.4 Mixed Claisen Condensations 886

21.5 Acylation of Ketones with Esters 887

21.6 Ketone Synthesis via β-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 908

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 23 Aryl Halides 964

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 1022

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 26 Lipids 1064

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 Anti inflammatory Drugs （NSAIDs） and COX-2 Inhibitors 1078

26.7 Terpenes：The Isoprene Rule 1079

26.8 Isopentenyl Diphosphate：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 1106

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 1162

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 1200

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