Organic chemistry Fifth EditionPDF电子书下载

INTRODUCTION 1

The Origins of Organic Chemistry 1

Berzelius，Wohler，and Vitalism 1

The Structural Theory 3

Electronic Theories of Structure and Reactivity 3

The Influence of Organic Chemistry 4

Computers and Organic Chemistry 4

Challenges and Opportunities 5

Where Did the Carbon Come From？ 6

CHAPTER 1 STRUCTURE DETERMINES PROPERTIES 7

1.1 Atoms，Electrons，and Orbitals 7

1.2 Ionic Bonds 10

1.3 Covalent Bonds and the Octet Rule 12

1.4 Double Bonds and Triple Bonds 14

1.5 Polar Covalent Bonds and Electronegativity 14

Electrostatic Potential Maps 16

1.6 Formal Charge 17

1.7 Structural Formulas of Organic Molecules 21

1.8 Constitutional Isomers 23

1.9 Resonance 24

Learning By Modeling 28

1.10 The Shapes of Some Simple Molecules 29

1.11 Molecular Dipole Moments 31

1.12 Acids and Bases：The Arrhenius View 32

1.13 Acids and Bases：The Bronsted-Lowry View 33

Curved Arrows 34

1.14 What Happened to pKb？ 37

1.15 How Structure Affects Acid Strength 38

1.16 Acid-Base Equilibria 43

1.17 Lewis Acids and Lewis Bases 45

1.18 SUMMARY 47

Problems 50

CHAPTER 2 HYDROCARBON FRAMEWORKS.ALKANES 57

2.1 Classes of Hydrocarbons 57

2.2 Electron Waves and Chemical Bonds 58

2.3 Bonding in H2：The Valence Bond Model 60

2.4 Bonding in H2：The Molecular Orbital Model 61

2.5 Introduction to Alkanes：Methane，Ethane，and Propane 63

2.6 sp3 Hybridization and Bonding in Methane 63

Methane and the Biosphere 66

2.7 Bonding in Ethane 67

2.8 Isomeric Alkanes：The Butanes 67

2.9 Higher n-Alkanes 68

2.10 The C5H12 Isomers 69

2.11 IUPAC Nomenclature of Unbranched Alkanes 70

2.12 Applying the IUPAC Rules：The Names of the C6H14 Isomers 71

2.13 Alkyl Groups 73

2.14 IUPAC Names of Highly Branched Alkanes 75

2.15 Cycloalkane Nomenclature 77

A Brief History of Systematic Organic Nomenclature 78

2.16 Sources of Alkanes and Cycloalkanes 79

2.17 Physical Properties of Alkanes and Cycloalkanes 80

2.18 Chemical Properties.Combustion of Alkanes 83

Thermochemistry 86

2.19 Oxidation-Reduction in Organic Chemistry 87

2.20 sp2 Hybridization and Bonding in Ethylene 89

2.21 sp Hybridization and Bonding in Acetylene 92

2.22 Which Theory of Chemical Bonding Is Best？ 93

2.23 SUMMARY 95

Problems 99

CHAPTER 3 CONFORMATIONS OF ALKANES AND CYCLOALKANES 104

3.1 Conformational Analysis of Ethane 105

3.2 Conformational Analysis of Butane 109

3.3 Conformations of Higher Alkanes 110

Molecular Mechanics Applied to Alkanes and Cycloalkanes 111

3.4 The Shapes of Cycloalkanes：Planar or Nonplanar？ 112

3.5 Small Rings：Cyclopropane and Cyclobutane 114

3.6 Cyclopentane 115

3.7 Conformations of Cyclohexane 116

3.8 Axial and Equatorial Bonds in Cyclohexane 117

3.9 Conformational Inversion （Ring Flipping） in Cyclohexane 119

3.10 Conformational Analysis of Monosubstituted Cyclohexanes 120

Enthalpy，Free Energy，and Equilibrium Constant 122

3.11 Disubstituted Cycloalkanes：Stereoisomers 124

3.12 Conformational Analysis of Disubstituted Cyclohexanes 125

3.13 Medium and Large Rings 129

3.14 Polycyclic Ring Systems 129

3.15 Heterocyclic Compounds 131

3.16 SUMMARY 132

Problems 136

CHAPTER 4 ALCOHOLS AND ALKYL HALIDES 142

4.1 Functional Groups 143

4.2 IUPAC Nomenclature of Alkyl Halides 144

4.3 IUPAC Nomenclature of Alcohols 145

4.4 Classes of Alcohols and Alkyl Halides 146

4.5 Bonding in Alcohols and Alkyl Halides 146

4.6 Physical Properties of Alcohols and Alkyl Halides：Intermolecular Forces 147

4.7 Preparation of Alkyl Halides from Alcohols and Hydrogen Halides 151

4.8 Mechanism of the Reaction of Alcohols with Hydrogen Halides 153

4.9 Potential Energy Diagrams for Multistep Reactions： 159

The SN1 Mechanism 159

4.10 Structure，Bonding，and Stability of Carbocations 160

4.11 Effect of Alcohol Structure on Reaction Rate 162

4.12 Reaction of Primary Alcohols with Hydrogen Halides：The SN2 Mechanism 163

4.13 Other Methods for Converting Alcohols to Alkyl Halides 165

4.14 Halogenation of Alkanes 166

4.15 Chlorination of Methane 166

4.16 Structure and Stability of Free Radicals 167

4.17 Mechanism of Methane Chlorination 172

4.18 Halogenation of Higher Alkanes 173

From Bond Energies to Heats of Reaction 174

4.19 SUMMARY 178

Problems 182

CHAPTER 5 STRUCTURE AND PREPARATION OF ALKENES：ELIMINATION REACTIONS 187

5.1 Alkene Nomenclature 187

Ethylene 189

5.2 Structure and Bonding in Alkenes 190

5.3 Isomerism in Alkenes 192

5.4 Naming Stereoisomeric Alkenes by the E-Z Notational System 193

5.5 Physical Properties of Alkenes 196

5.6 Relative Stabilities of Alkenes 197

5.7 Cycloalkenes 200

5.8 Preparation of Alkenes：Elimination Reactions 202

5.9 Dehydration of Alcohols 202

5.10 Regioselectivity in Alcohol Dehydration：The Zaitsev Rule 204

5.11 Stereoselectivity in Alcohol Dehydration 205

5.12 The E1 and E2 Mechanisms of Alcohol Dehydration 206

5.13 Rearrangements in Alcohol Dehydration 208

5.14 Dehydrohalogenation of Alkyl Halides 211

5.15 The E2 Mechanism of Dehydrohalogenation of Alkyl Halides 214

5.16 Anti Elimination in E2 Reactions：Stereoelectronic Effects 216

5.17 The E1 Mechanism of Dehydrohaloge nation of Alkyl Halides 217

5.18 SUMMARY 220

Problems 223

CHAPTER 6 REACTIONS OF ALKENES：ADDITION REACTIONS 230

6.1 Hydrogenation of Alkenes 230

6.2 Heats of Hydrogenation 231

6.3 Stereochemistry of Alkene Hydrogenation 234

6.4 Electrophilic Addition of Hydrogen Halides to Alkenes 235

6.5 Regioselectivity of Hydrogen Halide Addition：Markovnikov’s Rule 236

6.6 Mechanistic Basis for Markovnikov’s Rule 238

Rules，Laws，Theories，and the Scientific Method 239

6.7 Carbocation Rearrangements in Hydrogen Halide Addition to Alkenes 241

6.8 Free-Radical Addition of Hydrogen Bromide to Alkenes 242

6.9 Addition of Sulfuric Acid to Alkenes 245

6.10 Acid-Catalyzed Hydration of Alkenes 247

6.11 Hydroboration-Oxidation of Alkenes 250

6.12 Stereochemistry of Hydroboration-Oxidation 252

6.13 Mechanism of Hydroboration-Oxidation 252

6.14 Addition of Halogens to Alkenes 254

6.15 Stereochemistry of Halogen Addition 256

6.16 Mechanism of Halogen Addition to Alkenes：Halonium Ions 256

6.17 Conversion of Alkenes to Vicinal Halohydrins 259

6.18 Epoxidation of Alkenes 260

6.19 Ozonolysis of Alkenes 262

6.20 Introduction to Organic Chemical Synthesis 265

6.21 Reactions of Alkenes with Alkenes：Polymerization 266

Ethylene and Propene：The Most Important Industrial Organic Chemicals 269

6.22 SUMMARY 271

Problems 274

CHAPTER 7 STEREOCHEMISTRY 281

7.1 Molecular Chirality：Enantiomers 281

7.2 The Chirality Center 282

7.3 Symmetry in Achiral Structures 286

7.4 Optical Activity 287

7.5 Absolute and Relative Configuration 289

7.6 The Cahn-Ingold-Prelog R-5 Notational System 290

7.7 Fischer Projections 293

7.8 Properties of Enantiomers 295

Chiral Drugs 296

7.9 Reactions That Create a Chirality Center 297

7.10 Chiral Molecules with Two Chirality Centers 300

7.11 Achiral Molecules with Two Chirality Centers 303

Chirality of Disubstituted Cyclohexanes 305

7.12 Molecules with Multiple Chirality Centers 306

7.13 Reactions That Produce Diastereomers 307

7.14 Resolution of Enantiomers 310

7.15 Stereoregular Polymers 312

7.16 Chirality Centers Other Than Carbon 314

7.17 SUMMARY 315

Problems 318

CHAPTER 8 NUCLEOPHILIC SUBSTITUTION 326

8.1 Functional Group Transformation by Nucleophilic Substitution 326

8.2 Relative Reactivity of Halide Leaving Groups 330

8.3 The SN2 Mechanism of Nucleophilic Substitution 330

8.4 Stereochemistry of SN2 Reactions 331

8.5 How SN2 Reactions Occur 333

8.6 Steric Effects in SN2 Reactions 334

8.7 Nucleophiles and Nucleophilicity 336

An Enzyme-Catalyzed Nucleophilic Substitution of an Alkyl Halide 339

8.8 The SN1 Mechanism of Nucleophilic Substitution 339

8.9 Carbocation Stability and SN1 Reaction Rates 341

8.10 Stereochemistry of SN1 Reactions 342

8.11 Carbocation Rearrangements in SN1 Reactions 344

8.12 Effect of Solvent on the Rate of Nucleophilic Substitution 345

8.13 Substitution and Elimination as Competing Reactions 348

8.14 Sulfonate Esters as Substrates in Nucleophilic Substitution 350

8.15 Looking Back：Reactions of Alcohols with Hydrogen Halides 354

8.16 SUMMARY 355

Problems 357

CHAPTER 9 ALKYN ES 363

9.1 Sources of Alkynes 363

9.2 Nomenclature 364

9.3 Physical Properties of Alkynes 365

9.4 Structure and Bonding in Alkynes：sp Hybridization 365

Natural and “Designed” Enediyne Antibiotics 368

9.5 Acidity of Acetylene and Terminal Alkynes 368

9.6 Preparation of Alkynes by Alkylation of Acetylene and Terminal Alkynes 370

9.7 Preparation of Alkynes by Elimination Reactions 372

9.8 Reactions of Alkynes 374

9.9 Hydrogenation of Alkynes 374

9.10 Metal-Ammonia Reduction of Alkynes 376

9.11 Addition of Hydrogen Halides to Alkynes 377

9.12 Hydration of Alkynes 379

9.13 Addition of Halogens to Alkynes 381

9.14 Ozonolysis of Alkynes 381

9.15 SUMMARY 382

Problems 384

CHAPTER 10 CONJUGATION IN ALKADIENES AND ALLYLIC SYSTEMS 390

10.1 The Allyl Group 390

10.2 Allylic Carbocations 391

10.3 Allylic Free Radicals 395

10.4 Allylic Halogenation 396

10.5 Classes of Dienes 398

10.6 Relative Stabilities of Dienes 399

10.7 Bonding in Conjugated Dienes 400

10.8 Bonding in Allenes 402

10.9 Preparation of Dienes 404

10.10 Addition of Hydrogen Halides to Conjugated Dienes 405

10.11 Halogen Addition to Dienes 407

Diene Polymers 408

10.12 The Diels-Alder Reaction 409

10.13 The π Molecular Orbitals of Ethylene and 1，3-Butadiene 412

10.14 A π Molecular Orbital Analysis of the Diels-Alder Reaction 414

10.15 SUMMARY 415

Problems 418

CHAPTER 11 ARENES AND AROMATICITY 423

11.1 Benzene 424

11.2 Kekule and the Structure of Benzene 424

Benzene，Dreams，and Creative Thinking 426

11.3 A Resonance Picture of Bonding in Benzene 427

11.4 The Stability of Benzene 428

11.5 An Orbital Hybridization View of Bonding in Benzene 430

11.6 The π Molecular Orbitals of Benzene 430

11.7 Substituted Derivatives of Benzene and Their Nomenclature 432

11.8 Polycyclic Aromatic Hydrocarbons 434

Carbon Clusters，Fullerenes，and Nanotubes 436

11.9 Physical Properties of Arenes 438

11.10 Reactions of Arenes：A Preview 438

11.11 The Birch Reduction 438

11.12 Free-Radical Halogenation of Alkylbenzenes 439

11.13 Oxidation of Alkylbenzenes 443

11.14 Nucleophilic Substitution in Benzylic Halides 444

11.15 Preparation of Alkenylbenzenes 446

11.16 Addition Reactions of Alkenylbenzenes 447

11.17 Polymerization of Styrene 449

11.18 Cyclobutadiene and Cyclooctatetraene 449

11.19 Huckel’s Rule 451

11.20 Annulenes 454

11.21 Aromatic Ions 456

11.22 Heterocyclic Aromatic Compounds 460

11.23 Heterocyclic Aromatic Compounds and Huckel’s Rule 462

11.24 SUMMARY 463

Problems 467

CHAPTER 12 REACTIONS OF ARENES：ELECTROPHILIC AROMATIC SUBSTITUTION 473

12.1 Representative Electrophilic Aromatic Substitution Reactions of Benzene 474

12.2 Mechanistic Principles of Electrophilic Aromatic Substitution 474

12.3 Nitration of Benzene 477

12.4 Sulfonation of Benzene 478

12.5 Halogenation of Benzene 480

12.6 Friedel-Crafts Alkylation of Benzene 481

12.7 Friedel-Crafts Acylation of Benzene 484

12.8 Synthesis of Alkylbenzenes by Acylation-Reduction 486

12.9 Rate and Regioselectivity in Electrophilic Aromatic Substitution 488

12.10 Rate and Regioselectivity in the Nitration of Toluene 489

12.11 Rate and Regioselectivity in the Nitration of （TrifIuoromethyl）benzene 492

12.12 Substituent Effects in Electrophilic Aromatic Substitution：Activating Substituents 494

12.13 Substituent Effects in Electrophilic Aromatic Substitution：Strongly Deactivating Substituents 498

12.14 Substituent Effects in Electrophilic Aromatic Substitution：Halogens 500

12.15 Multiple Substituent Effects 502

12.16 Regioselective Synthesis of Disubstituted Aromatic Compounds 504

12.17 Substitution in Naphthalene 506

12.18 Substitution in Hetereocyclic Aromatic Compounds 507

12.19 SUMMARY 508

Problems 512

CHAPTER 13 SPECTROSCOPY 519

13.1 Principles of Molecular Spectroscopy：Electromagnetic Radiation 520

13.2 Principles of Molecular Spectroscopy：Quantized Energy States 521

13.3 Introduction to 1H NMR Spectroscopy 522

13.4 Nuclear Shielding and 1H Chemical Shifts 525

13.5 Effects of Molecular Structure on 1H Chemical Shifts 526

Ring Currents：Aromatic and Antiaromatic 530

13.6 Interpreting 1H NMR Spectra 532

13.7 Spin-Spin Splitting in 1H NMR Spectroscopy 535

13.8 Splitting Patterns：The Ethyl Group 538

13.9 Splitting Patterns：The Isopropyl Group 540

13.10 Splitting Patterns：Pairs of Doublets 541

13.11 Complex Splitting Patterns 543

13.12 1H NMR Spectra of Alcohols 544

13.13 NMR and Conformations 545

Magnetic Resonance Imaging 546

13.14 13C NMR Spectroscopy 547

13.15 13C Chemical Shifts 549

13.16 13C NMR and Peak Intensities 551

13.17 13C—1H Coupling 552

13.18 Using DEPT to Count Hydrogens Attached to 13C 553

Spectra by the Thousands 555

13.19 2D NMR：COSY and HETCOR 556

13.20 Infrared Spectroscopy 559

13.21 Ultraviolet-Visible （UV-VIS） Spectroscopy 565

13.22 Mass Spectrometry 567

Gas Chromatography，GC/MS，and MS/MS 572

13.23 Molecular Formula as a Clue to Structure 573

13.24 SUMMARY 575

Problems 578

CHAPTER 14 ORGANOMETALLIC COMPOUNDS 587

14.1 Organometallic Nomenclature 588

14.2 Carbon-Metal Bonds in Organometallic Compounds 588

14.3 Preparation of Organolithium Compounds 589

14.4 Preparation of Organomagnesium Compounds：Grignard Reagents 591

14.5 Organolithium and Organomagnesium Compounds as Bronsted Bases 592

14.6 Synthesis of Alcohols Using Grignard Reagents 594

14.7 Synthesis of Alcohols Using Organolithium Reagents 597

14.8 Synthesis of Acetylenic Alcohols 597

14.9 Retrosynthetic Analysis 598

14.10 Preparation of Tertiary Alcohols from Esters and Grignard Reagents 601

14.11 Alkane Synthesis Using Organocopper Reagents 602

14.12 An Organozinc Reagent for Cyclopropane Synthesis 604

14.13 Carbenes and Carbenoids 606

14.14 Transition Metal Organometallic Compounds 608

14.15 Ziegler-Natta Catalysis of Alkene Polymerization 610

An Organometallic Compound That Occurs Naturally：Coenzyme B12 611

14.16 SUMMARY 614

Problems 617

CHAPTER 15 ALCOHOLS，DIOLS，AND THIOLS 623

15.1 Sources of Alcohols 623

15.2 Preparation of Alcohols by Reduction of Aldehydes and Ketones 627

15.3 Preparation of Alcohols by Reduction of Carboxylic Acids and Esters 632

15.4 Preparation of Alcohols from Epoxides 632

15.5 Preparation of Diols 633

15.6 Reactions of Alcohols：A Review and a Preview 635

15.7 Conversion of Alcohols to Ethers 635

15.8 Esterification 638

15.9 Esters of Inorganic Acids 640

15.10 Oxidation of Alcohols 641

Economic and Environmental Factors in Organic Synthesis 644

15.11 Biological Oxidation of Alcohols 645

15.12 Oxidative Cleavage of Vicinal Diols 647

15.13 Thiols 648

15.14 Spectroscopic Analysis of Alcohols and Thiols 651

15.15 SUMMARY 653

Problems 657

CHAPTER 16 ETHERS，EPOXIDES，AND SULFIDES 665

16.1 Nomenclature of Ethers，Epoxides，and Sulfides 665

16.2 Structure and Bonding in Ethers and Epoxides 667

16.3 Physical Properties of Ethers 668

16.4 Crown Ethers 668

Polyether Antibiotics 670

16.5 Preparation of Ethers 671

16.6 The Williamson Ether Synthesis 672

16.7 Reactions of Ethers：A Review and a Preview 673

16.8 Acid-Catalyzed Cleavage of Ethers 674

16.9 Preparation of Epoxides：A Review and a Preview 676

16.10 Conversion of Vicinal Halohydrins to Epoxides 676

16.11 Reactions of Epoxides：A Review and a Preview 678

16.12 Nucleophilic Ring-Opening of Epoxides 679

16.13 Acid-Catalyzed Ring-Opening of Epoxides 681

16.14 Epoxides in Biological Processes 684

16.15 Preparation of Sulfides 685

16.16 Oxidation of Sulfides：Sulfoxides and Sulfones 685

16.17 Alkylation of Sulfides：Sulfonium Salts 686

16.18 Spectroscopic Analysis of Ethers，Epoxides，and Sulfides 688

16.19 SUMMARY 691

Problems 695

CHAPTER 17 ALDEHYDES AND KETONES：NUCLEOPHILIC ADDITION TO THE CARBONYL GROUP 703

17.1 Nomenclature 703

17.2 Structure and Bonding：The Carbonyl Group 706

17.3 Physical Properties 708

17.4 Sources of Aldehydes and Ketones 709

17.5 Reactions of Aldehydes and Ketones：A Review and a Preview 712

17.6 Principles of Nucleophilic Addition：Hydration of Aldehydes and Ketones 712

17.7 Cyanohydrin Formation 717

17.8 Acetal Formation 720

17.9 Acetals as Protecting Groups 723

17.10 Reaction with Primary Amines：Imines 724

17.11 Reaction with Secondary Amines：Enamines 727

Imines in Biological Chemistry 728

17.12 The Wittig Reaction 730

17.13 Planning an Alkene Synthesis via the Wittig Reaction 732

17.14 Stereoselective Addition to Carbonyl Groups 734

17.15 Oxidation of Aldehydes 736

17.16 Baeyer-Villiger Oxidation of Ketones 736

17.17 Spectroscopic Analysis of Aldehydes and Ketones 738

17.18 SUMMARY 741

Problems 745

CHAPTER 18 ENOLS AND ENOLATES 755

18.1 The α-Carbon Atom and Its Hydrogens 756

18.2 α Halogenation of Aldehydes and Ketones 757

18.3 Mechanism of α Halogenation of Aldehydes and Ketones 757

18.4 Enolization and Enol Content 759

18.5 Stabilized Enols 761

18.6 Base-Catalyzed Enolization.Enolate Anions 763

18.7 The Haloform Reaction 765

The Haloform Reaction and the Biosynthesis of Trihalomethanes 767

18.8 Some Chemical and Stereochemical Consequences of Enolization 768

18.9 The Aldol Condensation 769

18.10 Mixed Aldol Condensations 774

18.11 Effects of Conjugation in α，β-Unsaturated Aldehydes and Ketones 775

18.12 Conjugate Addition to α，β-Unsaturated Carbonyl Compounds 777

18.13 Addition of Carbanions to α，β-Unsaturated Ketones： 779

The Michael Reaction 779

18.14 Conjugate Addition of Organocopper Reagents to α，β-Unsaturated Carbonyl Compounds 780

18.15 Alkylation of Enolate Anions 781

18.16 SUMMARY 781

Problems 784

CHAPTER 19 CARBOXYLIC ACIDS 791

19.1 Carboxylic Acid Nomenclature 792

19.2 Structure and Bonding 793

19.3 Physical Properties 794

19.4 Acidity of Carboxylic Acids 795

19.5 Salts of Carboxylic Acids 797

Quantitative Relationships Involving Carboxylic Acids 798

19.6 Substituents and Acid Strength 801

19.7 Ionization of Substituted Benzoic Acids 803

19.8 Dicarboxylic Acids 804

19.9 Carbonic Acid 804

19.10 Sources of Carboxylic Acids 806

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 808

19.13 Reactions of Carboxylic Acids：A Review and a Preview 809

19.14 Mechanism of Acid-Catalyzed Esterification 810

19.15 Intramolecular Ester Formation：Lactones 814

19.16 α Halogenation of Carboxylic Acids：The Hell-Volhard-Zelinsky Reaction 815

19.17 Decarboxylation of Malonic Acid and Related Compounds 816

19.18 Spectroscopic Analysis of Carboxylic Acids 819

19.19 SUMMARY 821

Problems 824

CHAPTER 20 CARBOXYLIC ACID DERIVATIVES：NUCLEOPHILIC ACYL SUBSTITUTION 830

20.1 Nomenclature of Carboxylic Acid Derivatives 831

20.2 Structure and Reactivity of Carboxylic Acid Derivatives 833

20.3 General Mechanism for Nucleophilic Acyl Substitution 836

20.4 Nucleophilic Substitution in Acyl Chlorides 838

20.5 Preparation of Carboxylic Acid Anhydrides 841

20.6 Reactions of Carboxylic Acid Anhydrides 842

20.7 Sources of Esters 845

20.8 Physical Properties of Esters 846

20.9 Reactions of Esters：A Review and a Preview 846

20.10 Acid-Catalyzed Ester Hydrolysis 848

20.11 Ester Hydrolysis in Base：Saponification 852

20.12 Reaction of Esters with Ammonia and Amines 857

20.13 Thioesters 858

20.14 Preparation of Amides 859

20.15 Lactams 861

20.16 Imides 862

20.17 Hydrolysis of Amides 862

20.18 Preparation of Nitriles 867

Condensation Polymers：Polyamides and Polyesters 868

20.19 Hydrolysis of Nitriles 870

20.20 Addition of Grignard Reagents to Nitriles 871

20.21 Spectroscopic Analysis of Carboxylic Acid Derivatives 872

20.22 SUMMARY 874

Problems 877

CHAPTER 21 ESTER ENOLATES 886

21.1 The Claisen Condensation 887

21.2 Intramolecular Claisen Condensation：The Dieckmann Reaction 890

21.3 Mixed Claisen Condensations 891

21.4 Acylation of Ketones with Esters 892

21.5 Ketone Synthesis via β-Keto Esters 893

21.6 The Acetoacetic Ester Synthesis 894

21.7 The Malonic Ester Synthesis 897

21.8 Barbiturates 900

21.9 Michael Additions of Stabilized Anions 901

21.10 α Deprotonation of Carbonyl Compounds by Lithium Dialkylamides 902

21.11 SUMMARY 905

Problems 908

CHAPTER 22 AMINES 913

22.1 Amine Nomenclature 913

22.2 Structure and Bonding 916

22.3 Physical Properties 918

22.4 Basicity of Amines 919

22.5 Tetraalkylammonium Salts as Phase-Transfer Catalysts 923

Amines as Natural Products 924

22.6 Reactions That Lead to Amines：A Review and a Preview 926

22.7 Preparation of Amines by Alkylation of Ammonia 928

22.8 The Gabriel Synthesis of Primary Alkylamines 929

22.9 Preparation of Amines by Reduction 931

22.10 Reductive Amination 934

22.11 Reactions of Amines：A Review and a Preview 935

22.12 Reaction of Amines with Alkyl Halides 937

22.13 The Hofmann Elimination 938

22.14 Electrophilic Aromatic Substitution in Arylamines 939

22.15 Nitrosation of Alkylamines 943

22.16 Nitrosation of Arylamines 945

22.17 Synthetic Transformations of Aryl Diazonium Salts 946

22.18 Azo Coupling 950

From Dyes to Sulfa Drugs 951

22.19 Spectroscopic Analysis of Amines 951

22.20 SUMMARY 955

Problems 962

CHAPTER 23 ARYL HALIDES 971

23.1 Bonding in Aryl Halides 971

23.2 Sources of Aryl Halides 972

23.3 Physical Properties of Aryl Halides 972

23.4 Reactions of Aryl Halides：A Review and a Preview 973

23.5 Nucleophilic Substitution in Nitro-Substituted Aryl Halides 975

23.6 The Addition-Elimination Mechanism of Nucleophilic Aromatic Substitution 977

23.7 Related Nucleophilic Aromatic Substitution Reactions 980

23.8 The Elimination-Addition Mechanism of Nucleophilic Aromatic Substitution：Benzyne 981

23.9 Diels-Alder Reactions of Benzyne 985

23.10 SUMMARY 986

Problems 988

CHAPTER 24 PHENOLS 993

24.1 Nomenclature 993

24.2 Structure and Bonding 994

24.3 Physical Properties 995

24.4 Acidity of Phenols 996

24.5 Substituent Effects on the Acidity of Phenols 998

24.6 Sources of Phenols 999

24.7 Naturally Occurring Phenols 1001

24.8 Reactions of Phenols：Electrophilic Aromatic Substitution 1002

24.9 Acylation of Phenols 1004

24.10 Carboxylation of Phenols：Aspirin and the Kolbe-Schmitt Reaction 1006

24.11 Preparation of Aryl Ethers 1008

Agent Orange and Dioxin 1009

24.12 Cleavage of Aryl Ethers by Hydrogen Halides 1010

24.13 Claisen Rearrangement of Allyl Aryl Ethers 1011

24.14 Oxidation of Phenols：Quinones 1012

24.15 Spectroscopic Analysis of Phenols 1014

24.16 SUMMARY 1016

Problems 1019

CHAPTER 25 CARBOHYDRATES 1026

25.1 Classification of Carbohydrates 1026

25.2 Fischer Projections and D-L Notation 1027

25.3 The Aldotetroses 1029

25.4 Aldopentoses and Aldohexoses 1030

25.5 A Mnemonic for Carbohydrate Configurations 1032

25.6 Cyclic Forms of Carbohydrates：Furanose Forms 1032

25.7 Cyclic Forms of Carbohydrates：Pyranose Forms 1036

25.8 Mutarotation 1040

25.9 Ketoses 1041

25.10 Deoxy Sugars 1042

25.11 Amino Sugars 1042

25.12 Branched-Chain Carbohydrates 1043

25.13 Glycosides 1043

25.14 Disaccharides 1046

25.15 Polysaccharides 1048

25.16 Cell-Surface Glycoproteins 1050

How Sweet It Is！ 1051

25.17 Carbohydrate Structure Determination 1052

25.18 Reduction of Carbohydrates 1052

25.19 Oxidation of Carbohydrates 1053

25.20 Cyanohydrin Formation and Chain Extension 1055

25.21 Epimerization，Isomerization，and Retro-Aldol Cleavage 1056

25.22 Acylation and Alkylation of Hydroxyl Groups in Carbohydrates 1058

25.23 Periodic Acid Oxidation of Carbohydrates 1059

25.24 SUMMARY 1061

Problems 1065

CHAPTER 26 LIPIDS 1069

26.1 Acetyl Coenzyme A 1070

26.2 Fats，Oils，and Fatty Acids 1071

26.3 Fatty Acid Biosynthesis 1075

26.4 Phospholipids 1077

26.5 Waxes 1079

26.6 Prostaglandins 1080

Nonsteroidal Antiinflammatory Drugs （NSAIDs） and COX-2 Inhibitors 1083

26.7 Terpenes：The Isoprene Rule 1084

26.8 Isopentenyl Pyrophosphate：The Biological Isoprene Unit 1087

26.9 Carbon-Carbon Bond Formation in Terpene Biosynthesis 1087

26.10 The Pathway from Acetate to Isopentenyl Pyrophosphate 1091

26.11 Steroids：Cholesterol 1093

Good Cholesterol？ Bad Cholesterol？ What’s the Difference？ 1096

26.12 Vitamin D 1096

26.13 Bile Acids 1097

26.14 Corticosteroids 1098

26.15 Sex Hormones 1098

Anabolic Steroids 1099

26.16 Carotenoids 1100

26.17 SUMMARY 1101

Problems 1103

CHAPTER 27 AMINO ACIDS，PEPTIDES，AND PROTEINS 1109

27.1 Classification of Amino Acids 1110

27.2 Stereochemistry of Amino Acids 1115

27.3 Acid-Base Behavior of Amino Acids 1117

Electrophoresis 1120

27.4 Synthesis of Amino Acids 1121

27.5 Reactions of Amino Acids 1123

27.6 Some Biochemical Reactions of Amino Acids 1123

27.7 Peptides 1126

27.8 Introduction to Peptide Structure Determination 1129

27.9 Amino Acid Analysis 1130

27.10 Partial Hydrolysis of Peptides 1130

27.11 End Group Analysis 1131

27.12 Insulin 1131

27.13 The Edman Degradation and Automated Sequencing of Peptides 1133

27.14 The Strategy of Peptide Synthesis 1135

27.15 Amino Group Protection 1137

27.16 Carboxyl Group Protection 1138

27.17 Peptide Bond Formation 1139

27.18 Solid-Phase Peptide Synthesis：The Merrifield Method 1141

27.19 Secondary Structures of Peptides and Proteins 1143

27.20 Tertiary Structure of Peptides and Proteins 1145

27.21 Coenzymes 1147

27.22 Protein Quaternary Structure：Hemoglobin 1148

Oh NO！ It’s Inorganic！ 1149

27.23 SUMMARY 1150

Problems 1152

CHAPTER 28 NUCLEOSIDES，NUCLEOTIDES，AND NUCLEIC ACIDS 1155

28.1 Pyrimidines and Purines 1155

28.2 Nucleosides 1158

28.3 Nucleotides 1160

28.4 Bioenergetics 1162

28.5 ATP and Bioenergetics 1162

28.6 Phosphodiesters，Oligonucleotides，and Polynucleotides 1164

28.7 Nucleic Acids 1165

28.8 Secondary Structure of DNA：The Double Helix 1166

“It Has Not Escaped Our Notice…” 1167

28.9 Tertiary Structure of DNA：Supercoils 1170

28.10 Replication of DNA 1172

28.11 Ribonucleic Acids 1172

RNA World 1177

28.12 Protein Biosynthesis 1178

28.13 AIDS 1179

28.14 DNA Sequencing 1180

28.15 The Human Genome Project 1182

28.16 DNA Profiling and the Polymerase Chain Reaction 1183

28.17 SUMMARY 1186

Problems 1189