CourseSmart - 9780471684961 - Organic Chemistry, 9th Edition

Organic Chemistry, 9th Edition

by Solomons, T. W. Graham, University of South Florida ; Fryhle, Craig B., Pacific Lutheran University

Publisher: John Wiley & Sons

Publishing Date: 2007/02/16

eText ISBN-10

0-470-26682-1

eText ISBN-13

978-0-470-26682-3

Print ISBN-10

0-471-68496-1

Print ISBN-13

978-0-471-68496-1

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Organic Chemistry, 9th Edition

by Solomons, T. W. Graham, University of South Florida ; Fryhle, Craig B., Pacific Lutheran University

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Preface, ix

About the Authors, xxxiii

1. THE BASICS: Bonding and Molecular Structure, 1

Molecular Graphic: Glycine, an organic molecule found in space, 1

1.1. Organic Chemistry and Life, 2

1.2. The Structural Theory of Organic Chemistry, 3

1.3. Isomers: The Importance of Structural Formulas, 4

1.4. Chemical Bonds: The Octet Rule, 5

1.5. Writing Lewis Structures, 7

1.6. Exceptions to the Octet Rule, 9

1.7. Formal Charge, 10

1.8. Resonance Theory, 13

1.9. Quantum Mechanics and Atomic Structure, 18

1.10. Atomic Orbitals and Electron Configuration, 20

1.11. Molecular Orbitals, 21

1.12. The Structure of Methane and Ethane: sp³ Hybridization, 24

THE CHEMISTRY OF …: Calculated Molecular Models: Electron Density Surfaces, 28

1.13. The Structure of Ethene (Ethylene): sp² Hybridization, 28

1.14. The Structure of Ethyne (Acetylene): sp Hybridization, 33

1.15. A Summary of Important Concepts that Come from Quantum Mechanics, 35

1.16. Molecular Geometry: The Valence Shell Electron Pair Repulsion Model, 36

1.17. Representation of Structural Formulas, 39

1.18. Applications of Basic Principles, 44

2. REPRESENTATIVE CARBON COMPOUNDS: Functional Groups, Intermolecular Forces, and Infrared (IR) Spectroscopy, 51

Structure and Function: Organic Chemistry, Nanotechnology, and Bioengineering / Molecular Graphic: A molecular template for bone growth, 51

2.1. Carbon–Carbon Covalent Bonds, 52

2.2. Hydrocarbons: Representative Alkanes, Alkenes, Alkynes, and Aromatic Compounds, 52

2.3. Polar Covalent Bonds, 55

THE CHEMISTRY OF …: Calculated Molecular Models: Maps of Electrostatic Potential, 56

2.4. Polar and Nonpolar Molecules, 56

2.5. Functional Groups, 59

2.6. Alkyl Halides or Haloalkanes, 60

2.7. Alcohols, 61

2.8. Ethers, 63

2.9. Amines, 63

2.10. Aldehydes and Ketones, 65

2.11. Carboxylic Acids, Esters, and Amides, 65

2.12. Nitriles, 67

2.13. Summary of Important Families of Organic Compounds, 68

2.14. Physical Properties and Molecular Structure, 68

2.15. Summary of Attractive Electric Forces, 75

THE CHEMISTRY OF …: Organic Templates Engineered to Mimic Bone Growth, 75

2.16. Infrared Spectroscopy: An Instrumental Method for Detecting Functional Groups, 76

2.17. Applications of Basic Principles, 84

3. AN INTRODUCTION TO ORGANIC REACTIONS AND THEIR MECHANISMS: Acids and Bases, 91

Shuttling the Protons / Molecular Graphic: Diamox, a drug that prevents altitude sickness, 91

3.1. Reactions and Their Mechanisms, 92

3.2. Acid–Base Reactions, 94

THE CHEMISTRY OF …: HOMOs and LUMOs in Reactions, 97

3.3. Heterolysis of Bonds to Carbon: Carbocations and Carbanions, 97

3.4. The Use of Curved Arrows in Illustrating Reactions, 98

3.5. The Strength of Acids and Bases: K_a and pK_a, 100

3.6. Predicting the Outcome of Acid–Base Reactions, 103

3.7. The Relationship between Structure and Acidity, 105

3.8. Energy Changes, 108

3.9. The Relationship between the Equilibrium Constant and the Standard Free-Energy Change, ΔGº, 110

3.10. The Acidity of Carboxylic Acids, 111

3.11. The Effect of the Solvent on Acidity, 115

3.12. Organic Compounds as Bases, 116

3.13. A Mechanism for an Organic Reaction, 117

THE CHEMISTRY OF …: Carbonic Anhydrase, 118

3.14. Acids and Bases in Nonaqueous Solutions, 119

3.15. Acid–Base Reactions and the Synthesis of Deuterium- and Tritium-Labeled Compounds, 120

3.16. Applications of Basic Principles, 121

4. NOMENCLATURE AND CONFORMATIONS OF ALKANES AND CYCLOALKANES, 129

To Be Flexible or Inflexible – Molecular Structure Makes the Difference / Molecular Graphic: A portion of the structure of diamond, an exceptionally rigid molecule, 129

4.1. Introduction to Alkanes and Cycloalkanes, 130

THE CHEMISTRY OF …: Petroleum Refining, 130

4.2. Shapes of Alkanes, 132

4.3. IUPAC Nomenclature of Alkanes, Alkyl Halides, and Alcohols, 134

4.4. Nomenclature of Cycloalkanes, 141

4.5. Nomenclature of Alkenes and Cycloalkenes, 143

4.6. Nomenclature of Alkynes, 145

4.7. Physical Properties of Alkanes and Cycloalkanes, 146

THE CHEMISTRY OF …: Pheromones: Communication by Means of Chemicals, 148

4.8. Sigma Bonds and Bond Rotation, 148

4.9. Conformational Analysis of Butane, 151

4.10. The Relative Stabilities of Cycloalkanes: Ring Strain, 153

4.11. The Origin of Ring Strain in Cyclopropane and Cyclobutane: Angle Strain and Torsional Strain, 155

4.12. Conformations of Cyclohexane, 156

THE CHEMISTRY OF …: Nanoscale Motors and Molecular Switches, 159

4.13. Substituted Cyclohexanes: Axial and Equatorial Hydrogen Atoms, 160

4.14. Disubstituted Cycloalkanes: Cis–Trans Isomerism, 163

4.15. Bicyclic and Polycyclic Alkanes, 166

THE CHEMISTRY OF …: Elemental Carbon, 167

4.16. Chemical Reactions of Alkanes, 168

4.17. Synthesis of Alkanes and Cycloalkanes, 168

4.18. Structural Information from Molecular Formulas and the Index of Hydrogen Deficiency, 169

4.19. ¹³C NMR Spectroscopy – A Practical Introduction, 171

4.20. Applications of Basic Principles, 175

5. STEREOCHEMISTRY: Chiral Molecules, 181

The Handedness of Life / Molecular Graphic: The mirror-image stereoisomers of alanine, a chiral amino acid, 181

5.1. The Biological Significance of Chirality, 182

5.2. Isomerism: Constitutional Isomers and Stereoisomers, 183

5.3. Enantiomers and Chiral Molecules, 184

5.4. More about the Biological Importance of Chirality, 187

5.5. Historical Origin of Stereochemistry, 188

5.6. Tests for Chirality: Planes of Symmetry, 189

5.7. Nomenclature of Enantiomers: The R,S-System, 190

5.8. Properties of Enantiomers: Optical Activity, 194

5.9. The Origin of Optical Activity, 198

5.10. The Synthesis of Chiral Molecules, 200

5.11. Chiral Drugs, 202

THE CHEMISTRY OF …: Selective Binding of Drug Enantiomers to Left- and Right-Handed Coiled DNA, 203

5.12. Molecules with More than One Chirality Center, 203

5.13. Fischer Projection Formulas, 207

5.14. Stereoisomerism of Cyclic Compounds, 209

5.15. Relating Configurations through Reactions in Which No Bonds to the Chirality Center Are Broken, 211

5.16. Separation of Enantiomers: Resolution, 213

5.17. Compounds with Chirality Centers Other than Carbon, 214

5.18. Chiral Molecules that Do Not Possess a Chirality Center, 215

6. IONIC REACTIONS: Nucleophilic Substitution and Elimination Reactions of Alkyl Halides, 221

Breaking Bacterial Cell Walls with Organic Chemistry / Molecular Graphic: Lysozyme, 221

6.1. Organic Halides, 222

6.2. Nucleophilic Substitution Reactions, 224

6.3. Nucleophiles, 224

6.4. Leaving Groups, 225

6.5. Kinetics of a Nucleophilic Substitution Reaction: An S_N2 Reaction, 226

6.6. A Mechanism for the S_N2 Reaction, 227

6.7. Transition State Theory: Free-Energy Diagrams, 228

6.8. The Stereochemistry of S_N2 Reactions, 231

THE CHEMISTRY OF …: Lysozyme, 234

6.9. The Reaction of tert-Butyl Chloride with Hydroxide Ion: An S_N1 Reaction, 235

6.10. A Mechanism for the S_N1 Reaction, 236

6.11. Carbocations, 237

6.12. The Stereochemistry of S_N1 Reactions, 239

6.13. Factors Affecting the Rates of S_N1 and S_N2 Reactions, 241

6.14. Organic Synthesis: Functional Group Transformations Using S_N2 Reactions, 250

THE CHEMISTRY OF …: Biological Methylation: A Biological Nucleophilic Substitution Reaction, 251

6.15. Elimination Reactions of Alkyl Halides, 253

6.16. The E2 Reaction, 255

6.17. The E1 Reaction, 256

6.18. Substitution versus Elimination, 257

6.19. Overall Summary, 260

7. ALKENES AND ALKYNES I: Properties and Synthesis. Elimination Reactions of Alkyl Halides, 269

Cell Membrane Fluidity / Molecular Graphic: cis-9-Octadecenoic acid, an unsaturated fatty acid incorporated into cell membrane phospholipids, 269

7.1. Introduction, 270

7.2. The (E)–(Z) System for Designating Alkene Diastereomers, 270

7.3. Relative Stabilities of Alkenes, 272

7.4. Cycloalkenes, 274

7.5. Synthesis of Alkenes via Elimination Reactions, 274

7.6. Dehydrohalogenation of Alkyl Halides, 275

7.7. Acid-Catalyzed Dehydration of Alcohols, 280

7.8. Carbocation Stability and the Occurrence of Molecular Rearrangements, 285

7.9. Synthesis of Alkynes by Elimination Reactions, 288

7.10. The Acidity of Terminal Alkynes, 290

7.11. Replacement of the Acetylenic Hydrogen Atom of Terminal Alkynes, 290

7.12. Alkylation of Alkynide Anions: Some General Principles of Structure and Reactivity Illustrated, 292

7.13. Hydrogenation of Alkenes, 292

THE CHEMISTRY OF …: Hydrogenation in the Food Industry, 293

7.14. Hydrogenation: The Function of the Catalyst, 294

THE CHEMISTRY OF …: Homogeneous Asymmetric Catalytic Hydrogenation: Examples Involving L-DOPA, (S)-Naproxen, and Aspartame, 295

7.15. Hydrogenation of Alkynes, 297

7.16. An Introduction to Organic Synthesis, 298

THE CHEMISTRY OF …: From the Inorganic to the Organic, 302

8. ALKENES AND ALKYNES II: Addition Reactions, 311

The Sea: A Treasury of Biologically Active Natural Products / Molecular Graphic: Dactylyne, a halogenated marine natural product, 311

8.1. Introduction: Addition to Alkenes, 312

8.2. Electrophilic Addition of Hydrogen Halides to Alkenes: Mechanism and Markovnikov’s Rule, 314

8.3. Stereochemistry of the Ionic Addition to an Alkene, 319

8.4. Addition of Sulfuric Acid to Alkenes, 320

8.5. Addition of Water to Alkenes: Acid-Catalyzed Hydration, 321

8.6. Alcohols from Alkenes through Oxymercuration–Demercuration: Markovnikov Addition, 323

8.7. Alcohols from Alkenes through Hydroboration–Oxidation: Anti-Markovnikov Syn Hydration, 326

8.8. Hydroboration: Synthesis of Alkylboranes, 326

8.9. Oxidation and Hydrolysis of Alkyboranes, 329

8.10. Summary of Alkene Hydration Methods, 331

8.11. Protonolysis of Alkyboranes, 331

8.12. Electrophilic Addition of Bromine and Chlorine to Alkenes, 332

8.13. Stereochemistry of the Addition of Halogens to Alkenes, 334

8.14. Halohydrin Formation, 337

8.15. Divalent Carbon Compounds: Carbenes, 338

8.16. Oxidations of Alkenes: Syn 1,2-Dihydroxylation, 340

THE CHEMISTRY OF …: Catalytic Asymmetric Dihydroxylation, 342

8.17. Oxidative Cleavage of Alkenes, 343

8.18. Electrophilic Addition of Bromine and Chlorine to Alkynes, 345

8.19. Addition of Hydrogen Halides to Alkynes, 346

8.20. Oxidative Cleavage of Alkynes, 347

8.21. Synthetic Strategies Revisited, 347

THE CHEMISTRY OF …: Cholesterol Biosynthesis: Elegant and Familiar Reactions in Nature, 350

9. NUCLEAR MAGNETIC RESONANCE AND MASS SPECTROMETRY: Tools for Structure Determination, 363

A Thermos of Liquid Helium / Molecular Graphic: 1-chloro-2-propanol, 363

9.1. Introduction, 364

9.2. Nuclear Magnetic Resonance (NMR) Spectroscopy, 364

9.3. Interpreting Proton NMR Spectra, 369

9.4. Nuclear Spin: The Origin of the Signal, 371

9.5. Detecting the Signal: Fourier Transform NMR Spectrometers, 373

9.6. Shielding and Deshielding of Protons, 374

9.7. The Chemical Shift, 376

9.8. Chemical Shift Equivalent and Nonequivalent Protons, 377

9.9. Signal Splitting: Spin–Spin Coupling, 379

9.10. Proton NMR Spectra and Rate Processes, 388

9.11. Carbon-13 NMR Spectroscopy, 390

9.12. Two-Dimensional (2D) NMR Techniques, 396

THE CHEMISTRY OF …: Magnetic Resonance Imaging in Medicine, 399

9.13. An Introduction to Mass Spectrometry, 399

9.14. Formation of Ions: Electron Impact Ionization, 400

9.15. Depicting the Molecular Ion, 400

9.16. Fragmentation, 401

9.17. Determination of Molecular Formulas and Molecular Weights, 407

9.18. Mass Spectrometer Instrument Designs, 412

9.19. GC/MS Analysis, 415

9.20. Mass Spectrometry of Biomolecules, 416

10. RADICAL REACTIONS, 427

Radicals in Biology, Medicine, and Industry / Molecular Graphic: Nitric oxide and Cialis^®, 427

10.1. Introduction, 428

10.2. Homolytic Bond Dissociation Energies, 429

10.3. The Reactions of Alkanes with Halogens, 433

10.4. Chlorination of Methane: Mechanism of Reaction, 435

10.5. Chlorination of Methane: Energy Changes, 437

10.6. Halogenation of Higher Alkanes, 443

10.7. The Geometry of Alkyl Radicals, 446

10.8. Reactions that Generate Tetrahedral Chirality Centers, 446

10.9. Radical Addition to Alkenes: The Anti-Markovnikov Addition of Hydrogen Bromide, 449

10.10. Radical Polymerization of Alkenes: Chain-Growth Polymers, 451

10.11. Other Important Radical Reactions, 455

THE CHEMISTRY OF …: Calicheamicin λ₁¹: A Radical Device for Slicing the Backbone of DNA, 456

THE CHEMISTRY OF …: Antioxidants, 458

THE CHEMISTRY OF …: Ozone Depletion and Chlorofluorocarbons (CFCs), 459

SPECIAL TOPIC A: CHAIN-GROWTH POLYMERS, 464

11. ALCOHOLS AND ETHERS, 469

Molecular Hosts / Molecular Graphic: Monensin sodium salt, an antibiotic that transports ions across cell membranes, 469

11.1. Structure and Nomenclature, 470

11.2. Physical Properties of Alcohols and Ethers, 472

11.3. Important Alcohols and Ethers, 474

11.4. Synthesis of Alcohols from Alkenes, 476

11.5. Reactions of Alcohols, 478

11.6. Alcohols as Acids, 479

11.7. Conversion of Alcohols into Alkyl Halides, 480

11.8. Alkyl Halides from the Reaction of Alcohols with Hydrogen Halides, 480

11.9. Alkyl Halides from the Reaction of Alcohols with PBr₃ or SOCl₂, 483

11.10. Tosylates, Mesylates, and Triflates: Leaving Group Derivatives of Alcohols, 484

THE CHEMISTRY OF …: Alkyl Phosphates, 487

11.11. Synthesis of Ethers, 487

11.12. Reactions of Ethers, 492

11.13. Epoxides, 493

THE CHEMISTRY OF …: The Sharpless Asymmetric Epoxidation, 494

11.14. Reactions of Epoxides, 496

THE CHEMISTRY OF …: Epoxides, Carcinogens, and Biological Oxidation, 498

11.15. Anti 1,2-Dihydroxylation of Alkenes via Epoxides, 500

THE CHEMISTRY OF …: Environmentally Friendly Alkene Oxidation Methods, 502

11.16. Crown Ethers: Nucleophilic Substitution Reactions in Relatively Nonpolar Aprotic Solvents by Phase-Transfer Catalysis, 503

11.17. Summary of Reactions of Alkenes, Alcohols, and Ethers, 506

12. ALCOHOLS FROM CARBONYL COMPOUNDS: Oxidation–Reduction and Organometallic Compounds, 513

The Two Aspects of the Coenzyme NADH / Molecular Graphic: Nicotinamide (niacin), 513

12.1. Introduction, 514

12.2. Oxidation–Reduction Reactions in Organic Chemistry, 515

12.3. Alcohols by Reduction of Carbonyl Compounds, 517

THE CHEMISTRY OF …: Alcohol Dehydrogenase, 519

THE CHEMISTRY OF …: Stereoselective Reductions of Carbonyl Groups, 520

12.4. Oxidation of Alcohols, 521

12.5. Organometallic Compounds, 526

12.6. Preparation of Organolithium and Organomagnesium Compounds, 526

12.7. Reactions of Organolithium and Organomagnesium Compounds, 528

12.8. Alcohols from Grignard Reagents, 531

12.9. Protecting Groups, 539

FIRST REVIEW PROBLEM SET, 546

13. CONJUGATED UNSATURATED SYSTEMS, 550

Molecules with the Nobel Prize in Their Synthetic Lineage / Molecular Graphic: Morphine, the synthesis of which involved the Diels-Alder reaction, 550

13.1. Introduction, 551

13.2. Allylic Substitution and the Allyl Radical, 551

THE CHEMISTRY OF …: Allylic Bromination, 554

13.3. The Stability of the Allyl Radical, 555

13.4. The Allyl Cation, 558

13.5. Summary of Rules for Resonance, 559

13.6. Alkadienes and Polyunsaturated Hydrocarbons, 563

13.7. 1,3-Butadiene: Electron Delocalization, 564

13.8. The Stability of Conjugated Dienes, 566

13.9. Ultraviolet–Visible Spectroscopy, 568

THE CHEMISTRY OF …: The Photochemistry of Vision, 573

13.10. Electrophilic Attack on Conjugated Dienes: 1,4 Addition, 576

13.11. The Diels–Alder Reaction: A 1,4-Cycloaddition Reaction of Dienes, 580

THE CHEMISTRY OF …: Asymmetric and Intramolecular Diels—Alder Reactions, 586

14. AROMATIC COMPOUNDS, 595

Green Chemistry / Molecular Graphic: Benzene, parent molecule in the family of aromatic compounds, 595

14.1. Aromatic Compounds: Why the Name?, 596

14.2. Nomenclature of Benzene Derivatives, 597

14.3. Reactions of Benzene, 599

14.4. The Kekulé Structure for Benzene, 600

14.5. The Stability of Benzene, 601

14.6. Modern Theories of the Structure of Benzene, 602

14.7. Hückel’s Rule: The 4n + 2π Electron Rule, 605

14.8. Other Aromatic Compounds, 613

THE CHEMISTRY OF …: Nanotubes, 616

14.9. Heterocylic Aromatic Compounds, 617

14.10. Aromatic Compounds in Biochemistry, 618

14.11. Spectroscopy of Aromatic Compounds, 620

THE CHEMISTRY OF …: Sunscreens (Catching the Sun’s Rays and What Happens to Them), 624

15. REACTIONS OF AROMATIC COMPOUNDS, 636

Biosynthesis of Thyroxine: Aromatic Substitution Involving Iodine / Molecular Graphic: Thyroxine, an aromatic iodine-containing hormone associated with regulation of metabolic rate, 636

15.1. Electrophilic Aromatic Substitution Reactions, 637

15.2. A General Mechanism for Electrophilic Aromatic Substitution: Arenium Ions, 637

15.3. Halogenation of Benzene, 640

15.4. Nitration of Benzene, 641

15.5. Sulfonation of Benzene, 642

15.6. Friedel–Crafts Alkylation, 643

15.7. Friedel–Crafts Acylation, 645

15.8. Limitations of Friedel–Crafts Reactions, 647

15.9. Synthetic Applications of Friedel–Crafts Acylations: The Clemmensen Reduction, 649

15.10. Effect of Substituents on Reactivity and Orientation, 650

15.11. Theory of Substituent Effects on Electrophilic Aromatic Substitution, 653

THE CHEMISTRY OF …: Iodine Incorporation in Thyroxine Biosynthesis, 662

15.12. Reactions of the Side Chain of Alkylbenzenes, 664

THE CHEMISTRY OF …: Industrial Styrene Synthesis, 665

15.13. Alkenylbenzenes, 668

15.14. Synthetic Applications, 670

15.15. Allylic and Benzylic Halides in Nucleophilic Substitution Reactions, 674

15.16. Reduction of Aromatic Compounds, 676

16. ALDEHYDES AND KETONES I: Nucleophilic Addition to the Carbonyl Group, 686

A Very Versatile Vitamin, Pyridoxine (Vitamin B₆) / Molecular Graphic: Pyridoxal phosphate (Vitamin B₆), 686

16.1. Introduction, 687

16.2. Nomenclature of Aldehydes and Ketones, 687

16.3. Physical Properties, 689

THE CHEMISTRY OF …: Aldehydes and Ketones in Perfumes, 690

16.4. Synthesis of Aldehydes, 690

16.5. Synthesis of Ketones, 694

16.6. Nucleophilic Addition to the Carbon–Oxygen Double Bond, 696

16.7. The Addition of Alcohols: Hemiacetals and Acetals, 699

16.8. The Addition of Primary and Secondary Amines, 706

THE CHEMISTRY OF …: Pyridoxal Phosphate, 708

16.9. The Addition of Hydrogen Cyanide, 710

16.10. The Addition of Ylides: The Wittig Reaction, 711

16.11. Oxydation of Aldehydes, 715

16.12. Chemical Analyses for Aldehydes and Ketones, 715

16.13. Spectroscopic Properties of Aldehydes and Ketones, 716

16.14. Summary of Aldehyde and Ketone Addition Reactions, 719

17. ALDEHYDES AND KETONES II: Enols and Enolates, 732

TIM (Triose Phosphate Isomerase) Recycles Carbon via an Enol / Molecular Graphic: Glyceraldehyde-3-phosphate, a key intermediate in metabolic energy production, 732

17.1. The Acidity of the α Hydrogens of Carbonyl Compounds: Enolate Anions, 733

17.2. Keto and Enol Tautomers, 735

17.3. Reactions via Enols and Enolate Anions, 736

17.4. The Aldol Reaction: The Addition of Enolate Anions to Aldehydes and Ketones, 742

THE CHEMISTRY OF …: A Retro-Aldol Reaction in Glycolysis—Dividing Assets to Double the ATP Yield, 745

17.5. Crossed Aldol Reactions, 747

17.6. Cyclizations via Aldol Condensations, 752

17.7. Lithium Enolates, 754

THE CHEMISTRY OF …: Silyl Enol Ethers, 758

17.8. α-Selenation: A Synthesis of α,β-Unsaturated Carbonyl Compounds, 759

17.9. Additions to α,β-Unsaturated Aldehydes and Ketones, 760

THE CHEMISTRY OF …: Calicheamicin λ₁¹ Activation for Cleavage of DNA, 763

17.10. Summary of Enolate Chemistry, 764

18. CARBOXYLIC ACIDS AND THEIR DERIVATIVES: Nucleophilic Addition–Elimination at the Acyl Carbon, 778

A Common Bond / Molecular Graphic: A portion of nylon 6,6, a polyamide, 778

18.1. Introduction, 779

18.2. Nomenclature and Physical Properties, 779

18.3. Preparation of Carboxylic Acids, 789

18.4. Nucleophilic Addition–Elimination at the Acyl Carbon, 791

18.5. Acyl Chlorides, 794

18.6. Carboxylic Acid Anhydrides, 795

18.7. Esters, 797

18.8. Amides, 802

THE CHEMISTRY OF …: Penicillins, 809

18.9. Derivatives of Carbonic Acid, 810

18.10. Decarboxylation of Carboxylic Acids, 812

THE CHEMISTRY OF …: Thiamine, 813

18.11. Chemical Tests for Acyl Compounds, 815

SPECIAL TOPIC B: STEP-GROWTH POLYMERS, 830

19. SYNTHESIS AND REACTIONS OF β-DICARBONYL COMPOUNDS: More Chemistry of Enolates, 840

Imposters / Molecular Graphic: 5-Fluorouracil, an enzyme inhibitor that has anticancer activity by masquerading as a natural substrate, 840

19.1. Introduction, 841

19.2. The Claisen Condensation: The Synthesis of β-Keto Esters, 842

19.3. The Acetoacetic Ester Synthesis: Synthesis of Methyl Ketones (Substituted Acetones), 847

19.4. The Malonic Ester Synthesis: Synthesis of Substituted Acetic Acids, 853

19.5. Further Reactions of Active Hydrogen Compounds, 857

19.6. Direct Alkylation of Esters and Nitriles, 858

19.7. Alkylation of 1,3-Dithianes, 858

19.8. The Knoevenagel Condensation, 860

19.9. Michael Additions, 860

19.10. The Mannich Reaction, 862

THE CHEMISTRY OF …: A Suicide Enzyme Substrate, 863

19.11. Synthesis of Enamines: Stork Enamine Reactions, 864

THE CHEMISTRY OF …: Antibody-Catalyzed Aldol Condensations, 866

19.12. Barbiturates, 867

SPECIAL TOPIC C: THIOLS, SULFUR YLIDES, AND DISULFIDES, 881

SPECIAL TOPIC D: THIOL ESTERS AND LIPID BIOSYNTHESIS, 886

20. AMINES, 899

Neurotoxins and Neurotransmitters / Molecular Graphic: Histrionicotoxin, a paralyzing neurotoxin from certain poison dart frogs, 899

20.1. Nomenclature, 900

20.2. Physical Properties and Structure of Amines, 902

20.3. Basicity of Amines: Amine Salts, 903

THE CHEMISTRY OF …: HPLC Resolution of Enantiomers, 910

THE CHEMISTRY OF …: Biologically Important Amines, 910

20.4. Preparation of Amines, 912

20.5. Reactions of Amines, 919

20.6. Reactions of Amines with Nitrous Acid, 921

THE CHEMISTRY OF …: N-Nitrosoamines, 922

20.7. Replacement Reactions of Arenediazonium Salts, 923

20.8. Coupling Reactions of Arenediazonium Salts, 926

20.9. Reactions of Amines with Sulfonyl Chlorides, 929

THE CHEMISTRY OF …: Chemotherapy and Sulfa Drugs, 930

20.10. Synthesis of Sulfa Drugs, 933

20.11. Analysis of Amines, 934

20.12. Eliminations Involving Ammonium Compounds, 935

SPECIAL TOPIC E: ALKALOIDS, 949

21. PHENOLS AND ARYL HALIDES: Nucleophilic Aromatic Substitution, 954

A Silver Chalice / Molecular Graphic: 4-tert-Butylcalix[4]arene, a chalice-shaped molecule, 954

21.1. Structure and Nomenclature of Phenols, 955

21.2. Naturally Occurring Phenols, 956

21.3. Physical Properties of Phenols, 957

21.4. Synthesis of Phenols, 957

THE CHEMISTRY OF …: Polyketide Anticancer Antibiotic Biosynthesis, 958

21.5. Reactions of Phenols as Acids, 961

21.6. Other Reactions of the O—H Group of Phenols, 963

21.7. Cleavage of Alkyl Aryl Ethers, 964

21.8. Reactions of the Benzene Ring of Phenols, 964

21.9. The Claisen Rearrangement, 967

21.10. Quinones, 968

21.11. Aryl Halides and Nucleophilic Aromatic Substitution, 969

THE CHEMISTRY OF …: The Bombardier Beetle’s Noxious Spray, 970

THE CHEMISTRY OF …: Bacterial Dehalogenation of a PCB Derivative, 972

21.12. Spectroscopic Analysis of Phenols and Aryl Halides, 977

SECOND REVIEW PROBLEM SET, 986

SPECIAL TOPIC F: ARYL HALIDES: THEIR USES, 992

SPECIAL TOPIC G: ELECTROCYCLIC AND CYCLOADDITION REACTIONS, 995

SPECIAL TOPIC H: TRANSITION METAL ORGANOMETALLIC COMPOUNDS, 1008

22. CARBOHYDRATES, 1020

Carbohydrate Recognition in Healing and Disease / Molecular Graphic: Sialyl Lewis^x, a carbohydrate that is important in the recognition and healing of traumatized tissue, 1020

22.1. Introduction, 1021

22.2. Monosaccharides, 1023

22.3. Mutarotation, 1028

22.4. Glycoside Formation, 1029

22.5. Other Reactions of Monosaccharides, 1032

22.6. Oxidation Reactions of Monosaccharides, 1035

22.7. Reduction of Monosaccharides: Alditols, 1040

22.8. Reactions of Monosaccharides with Phenylhydrazine: Osazones, 1041

22.9. Synthesis and Degradation of Monosaccharides, 1042

22.10. The D Family of Aldoses, 1044

22.11. Fischer’s Proof of the Configuration of D-(+)-Glucose, 1044

THE CHEMISTRY OF …: Stereoselective Synthesis of All the L-Aldohexoses, 1047

22.12. Disaccharides, 1049

THE CHEMISTRY OF …: Artificial Sweeteners (How Sweet It Is), 1052

22.13. Polysaccharides, 1053

THE CHEMISTRY OF …: Oligosaccharide Synthesis on a Solid Support—The Glycal Assembly Approach, 1057

22.14. Other Biologically Important Sugars, 1059

22.15. Sugars that Contain Nitrogen, 1059

22.16. Glycolipids and Glycoproteins of the Cell Surface: Cell Recognition and the Immune System, 1061

THE CHEMISTRY OF …: Vaccines Against Cancer, 1063

22.17. Carbohydrate Antibiotics, 1064

23. LIPIDS, 1073

Insulation for Nerves / Molecular Graphic: A sphingomyelin molecule, found in myelin sheath membranes, 1073

23.1. Introduction, 1074

23.2. Fatty Acids and Triacylglycerols, 1075

THE CHEMISTRY OF …: Olestra and Other Fat Substitutes, 1078

THE CHEMISTRY OF …: Self-Assembled Monolayers—Lipids in Materials Science and Bioengineering, 1082

23.3. Terpenes and Terpenoids, 1083

23.4. Steroids, 1087

23.5. Prostaglandins, 1095

23.6. Phospholipids and Cell Membranes, 1097

THE CHEMISTRY OF …: STEALTH^® Liposomes for Drug Delivery, 1099

23.7. Waxes, 1100

24. AMINO ACIDS AND PROTEINS, 1107

Catalytic Antibodies: Designer Catalysts / Molecular Graphic: A synthetic Diels-Alderase catalytic antibody with a bound hapten, 1107

24.1. Introduction, 1108

24.2. Amino Acids, 1109

24.3. Synthesis of α-Amino Acids, 1115

24.4. Polypeptides and Proteins, 1119

24.5. Primary Structure of Polypeptides and Proteins, 1122

24.6. Examples of Polypeptide and Protein Primary Structure, 1126

THE CHEMISTRY OF …: Sickle-Cell Anemia, 1128

24.7. Polypeptide and Protein Synthesis, 1129

24.8. Secondary, Tertiary, and Quaternary Structure of Proteins, 1135

24.9. Introduction to Enzymes, 1140

24.10. Lysozyme: Mode of Action of an Enzyme, 1141

24.11. Serine Proteases, 1145

24.12. Hemoglobin: A Conjugated Protein, 1148

THE CHEMISTRY OF …: Some Catalytic Antibodies, 1148

24.13. Purification and Analysis of Polypeptides and Proteins, 1150

24.14. Proteomics, 1152

25. NUCLEIC ACIDS AND PROTEIN SYNTHESIS, 1158

Tools for Finding Families / Molecular Graphic: A cytosine-guanine base pair, 1158

25.1. Introduction, 1159

25.2. Nucleotides and Nucleosides, 1160

25.3. Laboratory Synthesis of Nucleosides and Nucleotides, 1163

25.4. Deoxyribonucleic Acid: DNA, 1166

25.5. RNA and Protein Synthesis, 1173

25.6. Determining the Base Sequence of DNA: The Chain-Terminating (Dideoxynucleotide) Method, 1180

25.7. Laboratory Synthesis of Oligonucleotides, 1184

25.8. The Polymerase Chain Reaction, 1184

25.9. Sequencing of the Human Genome: An Instruction Book for the Molecules of Life, 1188

ANSWERS TO SELECTED PROBLEMS, A-1

GLOSSARY, G-1

PHOTO CREDITS, C-1

INDEX, I-1

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