NfIC CHEMIST

Third Edition

NG?-\NfICCHEMIST - ?A(

Structure and Function

K. Peter C. Vollhardt

Neil E. Schore

0-7167-2721-8

, 1999 by W. H. Freeman and Company.

Preface: A User's Guide to "Organic Chemistry: Structure and Function" xxiii

About the Authors xxxiv

0 Structure and Bonding in Organic Molecules 1

© Alkanes 51Molecules Lacking Functional Groups

0 Reactions of Alkanes 93Bond-Dissociation Energies, Radical Halogenation, and Relative Reactivity

0 Cyclic Alkanes 129

© Stereoisomers 165

O Properties and Reactions of Haloalkanes 211Bimolecular Nucleophilic Substitution

0 Further Reactions of Haloalkanes 247

Unimolecular Substitution and Pathways of Elimination

0 Hydroxy Functional Group 283

Properties of the Alcohols and Strategy in Synthesis

Q Further Reactions of Alcohols and the Chemistryof Ethers 330

W Using Nuclear Magnetic Resonance Spectroscopy toDeduce Structure 384

Alkenes and Infrared Spectroscopy 438

Reactions of Alkenes 483

AlkynesThe Carbon-Carbon Triple Bond 543

Delocalized Pi Systems 583Investigation by Ultraviolet and Visible Spectroscopy

® Unusual Stability of the Cyclic Electron Sextet 637Benzene, Other Cyclic Polyenes, and Electrophilic Aromatic Substitution

Electrophilic Attack on Derivatives of Benzene 689Substituents Control Regioselectivity

Aldehydes and Ketones 728The Carbonyl Group

a) Enols and Enones 780

a,ß-Unsaturated Alcohols, Aldehydes, and Ketones

Carboxylic Acids 825

20 Carboxylic Acid Derivatives and Mass Spectrometry 878

Amines and Their Derivatives 936Functional Groups Containing Nitrogen

Chemistry of Benzene Substituents 982

Alkylbenzenes, Phenols, and Benzenamines

® Ester Enolates and Acyl Anion Equivalents 1037Syntheses of ß-Dicarbonyl and a-Hydroxycarbonyl Compounds

Carbohydrates 1068

Polyfunctional Compounds in Nature

Heterocycles 1116

Heteroatoms in Cyclic Organic Compounds

`' Amino Acids, Peptides, Proteins, and Nucleic Acids 1156Nitrogen-Containing Polymers in Nature

Answers to Exercises

Index

Preface: A User's Guide to "Organic Chemistry: Structure and Function" xxiii

About the Authors xxxiv

0 Structure and Bonding in Organic Molecules1-1 The Scope of Organic Chemistry: An Overview 2

Chemical Highlight 1-1 Saccharin: One of the Oldest

Synthetic Organic Compounds in Commercial Use 41-2 Coulomb Forces: A Simplified View of Bonding 6

1-3 Ionic and Covalent Bonds: The Octet Rule 7

1-4 Electron-Dot Model of Bonding: Lewis Structures 141-5 Resonance Forms 191-6 Atomic Orbitals: A Quantum Mechanical Description

of Electrons Around the Nucleus 22

1-7 Molecular Orbitals and Covalent Bonding 29

1-8 Hybrid Orbitals: Bonding in Complex Molecules 32

1-9 Structures and Formulas of Organic Molecules 37

Chapter Integration Problem 40

Important Concepts 43Problems 44

0 Alkanes: Molecules Lacking Functional Groups 512-1 Functional Groups: Centers of Reactivity 512-2 Straight-Chain and Branched Alkanes 55

2-3 Naming the Alkanes 562-4 Structural and Physical Properties of Alkanes 61

2-5 Rotation About Single Bonds: Conformations 642-6 Potential-Energy Diagrams 67

2-7 Rotation in Substituted Ethanes 69

2-8 Kinetics and Thermodynamics of Conformational

Isomerism and of Simple Reactions 72

2-9 Acids and Bases: A Review 78


Important Concepts 86

Problems 87

© Reactions of Alkanes: Bond-Dissociation Energies,Radical Halogenation, and Relative Reactivity 93

3-1 Strength of Alkane Bonds: Radicals 94

3-2 Structure of Alkyl Radicals: Hyperconjugation 97

3-3 Conversion of Petroleum: Pyrolysis 98

Chemical Highlight 3-1 The Function of a Catalyst 99

Chemical Highlight 3-2 Petroleum and Gasoline: Our

Main Energy Sources 101

3-4 Chlorination of Methane: The Radical Chain Mechanism 101

3-5 Other Radical Halogenations of Methane 106

3-6 Chlorination of Higher Alkanes: Relative Reactivity

and Selectivity 1093-7 Selectivity in Radical Halogenation with Fluorine

and Bromine 113

3-8 Synthetic Radical Halogenation 115

Chemical Highlight 3-3 Chlorination, Chloral, and DDT 1 16

3-9 Synthetic Chlorine Compounds and the Stratospheric

Ozone Layer 116

3-10 Combustion and the Relative Stabilities of Alkanes 119

Chemical Highlight 3-4 Enzymatic Oxidation of the Alkanes 120



Problems 124

0 Cyclic Alkanes 1294-1 Names and Physical Properties of Cycloalkanes 1304-2 Ring Strain and the Structure of Cycloalkanes 1324-3 Cyclohexane: A Strain-Free Cycloalkane 1364-4 Substituted Cyclohexanes 141

4-5 Larger Cycloalkanes 146

4-6 Polycyclic Alkanes 1464-7 Carbocyclic Products in Nature 148

Chemical Highlight 4-1 Cubane Derivatives Have

Potential as Explosives 149

Chemical Highlight 4-2 Controlling Fertility:

From "the Pill" to RU-486 153


I mportant Concepts 156

Problems 157

© Stereoisomers 165

5-1 Chiral Molecules 167Chemical Highlight 5-1 Chiral Substances in Nature 169

5-2 Optical Activity 171

5-3 Absolute Configuration: R-S Sequence Rules 174

Chemical Highlight 5-2 Absolute Configuration:

A Historical Note 175

5-4 Fischer Projections 179

5-5 Molecules Incorporating Several Stereocenters:

Diastereomers 183

Chemical Highlight 5-3 Stereoisomers of

Tartaric Acid 186

5-6 Meso Compounds 187

5-7 Stereochemistry in Chemical Reactions 190

Chemical Highlight 5-4 Chiral Drugs: Racemic

or Enantiomerically Pure? I95

5-8 Resolution: Separation of Enantiomers 196Chemical Highlight 5-5 Why Is Nature "Handed"? 196



Problems 202

O Properties and Reactions of Haloalkanes: Bimolecular _Nucleophilic Substitution 211

6-1 Naming the Haloalkanes 212

6-2 Physical Properties of Haloalkanes 213

6-3 Nucleophilic Substitution 214

Chemical Highlight 6-1 Halogenated Organic Compounds -

and the Environment 215

6-4 Reaction Mechanisms Involving Polar Functional Groups:

Using "Electron-Pushing" Arrows 218

6-5 A First Look at the Nucleophilic Substitution Mechanism:

Kinetics 220

6-6 Frontside or Backside Attack? Stereochemistry of

the SN2 Reaction 222

6-7 Consequences of Inversion in S N2 Reactions 224

6-8 S N2 Reactivity and Leaving-Group Ability 226

6-9 Effect of Nucleophilicity on the S N2 Reaction 228

6-10 Effect of the Alkyl Group on the SN2 Reaction 234

Chemical Highlight 6-2 The Dilemma of Bromomethane:

Highly Useful but Also Highly Toxic 236

Chapter Integration Problem 238Important Concepts 240Problems 240

O Further Reactions of Haloalkanes: UnimolecularSubstitution and Pathways of Elimination 247

7-1 Solvolysis of Tertiary and Secondary Haloalkanes 247

7-2 Unimolecular Nucleophilic Substitution 249

7-3 Stereochemical Consequences of S N 1 Reactions 252Chemical Highlight 7-1 Incomplete Racemization

in SN 1 Reactions 253

7-4 Effects of Solvent, Leaving Group, and Nucleophile on

Unimolecular Substitution 253

7-5 Effect of the Alkyl Group on the SN I Reaction:

Carbocation Stability 255

7-6 Unimolecular Elimination: El 258

7-7 Bimolecular Elimination: E2 261

7-8 Competition Between Substitution and Elimination 264

7-9 Summary of Reactivity of Haloalkanes 267


New Reactions 272


Problems 273

4 Hydroxy Functional Group: Properties of the Alcoholsand Strategy in Synthesis 283

8-1 Naming the Alcohols 284

8-2 Structural and Physical Properties of Alcohols 285

8-3 Alcohols as Acids and Bases 288

8-4 Industrial Sources of Alcohols: Carbon Monoxide and Ethene 292

8-5 Synthesis of Alcohols by Nucleophilic Substitution 292

8-6 Synthesis of Alcohols: Oxidation-Reduction Relation

Between Alcohols and Carbonyl Compounds 294

Chemical Highlight 8-1 Biological Oxidation and Reduction 296

8-7 Organometallic Reagents: Sources of Nucleophilic

Carbon for Alcohol Synthesis 301

Chemical Highlight 8-2 The Breath Analyzer Test 302

8-8 Organometallic Reagents in the Synthesis of Alcohols 305

8-9 Complex Alcohols: An Introduction to Synthetic Strategy 307


New Reactions 316

Reaction Summary Road Map: Preparation of Alcohols 319

Reaction Summary Road Map: Reactions of Alkyllithium

and Grignard Reagents 320


Problems 321

O Further Reactions of Alcohols and the Chemistryof Ethers 330

9-1 Reactions of Alcohols with Base: Preparation of Alkoxides 331

9-2 Reactions of Alcohols with Strong Acids: Alkyloxonium Ions

in Substitution and Elimination Reactions of Alcohols 333

9-3 Carbocation Rearrangements 335

9-4 Organic and Inorganic Esters from Alcohols 340

9-5 Names and Physical Properties of Ethers 3439-6 Williamson Ether Synthesis 347

Chemical Highlight 9-I Chemiluminescence

of 1,2-Dioxacyclobutanes 349

9-7 Synthesis of Ethers: Alcohols and Mineral Acid 3509-8 Reactions of Ethers 352

Chemical Highlight 9-2 Protecting Groups in Synthesis 354

9-9 Reactions of Oxacyclopropanes 354Chemical Highlight 9-3 Epoxy Resins as Adhesives 356

9-10 Sulfur Analogs of Alcohols and Ethers 3599-11 Physiological Properties and Uses of Alcohols and Ethers 362

Chemical Highlight 9-4 Garlic and Sulfur 366Chapter Integration Problem 367New Reactions 368Reaction Summary Road Map: Reactions of Alcohols 372


Problems 373

Using Nuclear Magnetic Resonance Spectroscopy toDeduce Structure 384

10-1 Physical and Chemical Tests 38410-2 Defining Spectroscopy 38510-3 Proton Nuclear Magnetic Resonance 388

Chemical Highlight 10-1 Recording an NMR Spectrum 39310-4 Using NMR Spectra to Analyze Molecular Structure:

The Proton Chemical Shift 394

10-5 Tests for Chemical Equivalence 399Chemical Highlight 10-2 Magnetic Resonance Imaging

in Medicine 401

10-6 Integration 402

10-7 Spin-Spin Splitting: The Effect of Nonequivalent

Neighboring Hydrogens 404

10-8 Spin-Spin Splitting: Some Complications 412

10-9 Carbon-13 Nuclear Magnetic Resonance 418

Chemical Highlight 10-3 Structural Characterization

of Medicinal Agents from Marine Sources 423

Chapter Integration Problem 425Important Concepts 427Problems 427

Alkenes and Infrared Spectroscopy 43811-1 Naming the Alkenes 439

11-2 Structure and Bonding in Ethene: The Pi Bond 442

11-3 Physical Properties of Alkenes 446

11-4 Nuclear Magnetic Resonance of Alkenes 447

Chemical Highlight 11-1 Prostaglandins 448

11-5 Infrared Spectroscopy 452

Chemical Highlight 11-2 The Garlic Story:

Infrared Spectroscopy in Food Chemistry 456

11-6 Degree of Unsaturation: Another Aid to Identifying

Molecular Structure 458

11-7 Relative Stability of Double Bonds: Heats of Hydrogenation 459

11-8 Preparation of Alkenes from Haloalkanes and Alkyl Sulfonates:

Bimolecular Elimination Revisited 462

11-9 Preparation of Alkenes by Dehydration of Alcohols 466

Chemical Highlight 11-3 Acid-Catalyzed Dehydration

of a-Terpineol 467


New Reactions 470


Reaction Summary Road Map: Preparation of Alkenes 472

Problems 473

® Reactions of Alkenes 483

12-1 Why Addition Reactions Proceed: Thermodynamic Feasibility 484

12-2 Catalytic Hydrogenation 484

Chemical Highlight 1 2-1 Optically Active Amino Acids

by Asymmetric Hydrogenation 488

12-3 Nucleophilic Character of the Pi Bond: Electrophilic Addition

of Hydrogen Halides 488

12-4 Alcohol Synthesis by Electrophilic Hydration:

Thermodynamic Control 491

12-5 Electrophilic Addition of Halogens to Alkenes 493

12-6 The Generality of Electrophilic Addition 496

12-7 Oxymercuration-Demercuration: A Special Electrophilic Addition 498

Chemical Highlight 1 2-2 Synthesis of a Juvenile

Hormone Analog 501

12-8 Hydroboration-Oxidation: A Stereospecific

Anti-Markovnikov Hydration 502

12-9 Oxacyclopropane Synthesis: Oxidation by

Peroxycarboxylic Acids 504

12-10 Vicinal Syn Dihydroxylation with Osmium Tetroxide 506

Chemical Highlight 1 2-3 Enantioselective Dihydroxylation

in the Synthesis of Antitumor Drugs 508

12-11 Oxidative Cleavage: Ozonolysis 50912-12 Radical Additions: Anti-Markovnikov Product Formation 51012-13 Dimerization, Oligomerization, and Polymerization of Alkenes 513

Chemical Highlight 12-4 Steroid Synthesis in Nature 51412-14 Synthesis of Polymers 515

Chemical Highlight 12-5 Polymers in the Cleanupof Oil Spills 517

12-15 Ethene: An Important Industrial Feedstock 519Chemical Highlight 12-6 Polymer-Supported Synthesis

of Chemical Libraries 52012-16 Alkenes in Nature: Insect Pheromones 521

Chapter Integration Problem 523New Reactions 526Reaction Summary Road Map: Reactions of Alkenes 530Important Concepts 532Problems 532

Alkynes: The Carbon-Carbon Triple Bond 54313-1 Naming the Alkynes 54413-2 Properties and Bonding in the Alkynes 54513-3 Spectroscopy of the Alkynes 54613-4 Stability of the Triple Bond 54913-5 Preparation of Alkynes by Double Elimination 55013-6 Preparation of Alkynes by Alkylation of Alkynyl Anions 55213-7 Reduction of Alkynes: The Relative Reactivity of

the Two Pi Bonds 55313-8 Electrophilic Addition Reactions of Alkynes 557

Chemical Highlight 13-1 Synthesis of a Sex Pheromone 55813-9 Anti-Markovnikov Additions to Triple Bonds 56013-10 Chemistry of Alkenyl Halides and Cuprate Reagents 56113-11 Ethyne as an Industrial Starting Material 56313-12 Naturally Occurring and Physiologically Active Alkynes 565

Chapter Integration Problem 567New Reactions 569Important Concepts 571Reaction Summary Road Map: Reactions of Alkynes 572Problems 573

Delocalized Pi Systems: Investigation byUltraviolet and Visible Spectroscopy 583

14-1 Overlap of Three Adjacent p Orbitals: Electron Delocalizationin the 2-Propenyl (Allyl) System 584

14-2 Radical Allylic Halogenation 58714-3 Nucleophilic Substitution of Allylic Halides: Kinetic

and Thermodynamic Control 588

14-4 Allylic Organometallic Reagents: Useful Three-Carbon

Nucleophiles 59114-5 Two Neighboring Double Bonds: Conjugated Dienes 59214-6 Electrophilic Attack on Conjugated Dienes 59614-7 Delocalization Among More Than Two Pi Bonds: Extended

Conjugation and Benzene 598Chemical Highlight 14-1 Use of Sorbic Acid in Making Wine 598

14-8 A Special Transformation of Conjugated Dienes:

Diels-Alder Cycloaddition 60014-9 Electrocyclic Reactions 607

Chemical Highlight 14-2 An Extraordinary Electrocyclic

Reaction of Anticancer Agents 612

14-10 Polymerization of Conjugated Dienes: Rubber 612

14-11 Electronic Spectra: Ultraviolet and Visible Spectroscopy 616

14-12 A Summary of Organic Reaction Mechanisms 621

Chapter Integration Problem 624New Reactions 627


Problems 629

Unusual Stability of the Cyclic Electron Sextet:Benzene, Other Cyclic Polyenes, and ElectrophilicAromatic Substitution 637

15-1 Naming the Benzenes 639

15-2 Structure and Resonance Energy of Benzene: A First Look

at Aromaticity 641

15-3 Pi Molecular Orbitals of Benzene 644

15-4 Spectral Characteristics of the Benzene Ring 646

15-5 Polycyclic Benzenoid Hydrocarbons 651

15-6 Fused Benzenoid Hydrocarbons: Naphthalene and

the Tricyclic Systems 651

Chemical Highlight 15-1 The Allotropes of Carbon:

Graphite, Diamond, and Fullerenes 654

15-7 Other Cyclic Polyenes: Hückel's Rule 656

15-8 Hückel's Rule and Charged Molecules 661

15-9 Synthesis of Benzene Derivatives: Electrophilic

Aromatic Substitution 663

15-10 Halogenation of Benzene: The Need for a Catalyst 665

15-11 Nitration and Sulfonation of Benzene 667

15-12 Friedel-Crafts Alkylation 670

15-13 Limitations of Friedel-Crafts Alkylations 672

15-14 Friedel-Crafts Alkanoylation (Acylation) 674


New Reactions 678

Reaction Summary Road Map: Reactions

of Benzene and Substituted Benzenes 680


Electrophilic Attack on Derivatives of Benzene:Substituents Control Regioselectivity 689

16-1 Activation or Deactivation by Substituents on a Benzene Ring 69016-2 Directing Inductive Effects of Alkyl Groups 69216-3 Directing Effects of Substituents in Conjugation

with the Benzene Ring 696Chemical Highlight 16-1 Explosive Nitroarenes:

TNT and Picric Acid 698

16-4 Electrophilic Attack on Disubstituted Benzenes 702

16-5 Synthetic Strategies Toward Substituted Benzenes 705

16-6 Reactivity of Polycyclic Benzenoid Hydrocarbons 709

16-7 Polycyclic Aromatic Hydrocarbons and Cancer 712


New Reactions 717


Problems 718

Aldehydes and Ketones: The Carbonyl Group 728

17-1 Naming the Aldehydes and Ketones 729

17-2 Structure of the Carbonyl Group 731

17-3 Spectroscopic Properties of Aldehydes and Ketones 733

17-4 Preparation of Aldehydes and Ketones 736

17-5 Reactivity of the Carbonyl Group: Mechanisms of Addition 738

17-6 Addition of Water to Form Hydrates 742

17-7 Addition of Alcohols to Form Hemiacetals and Acetals 743

17-8 Acetals as Protecting Groups 746

Chemical Highlight 1 7-1 Protecting Groups

in Vitamin C Synthesis 748

17-9 Nucleophilic Addition of Ammonia and Its Derivatives 749

Chemical Highlight 1 7-2 Imines in Biological

Transformations 750

17-10 Deoxygenation of the Carbonyl Group 753

17-11 Addition of Hydrogen Cyanide to Give Cyanohydrins 755

17-12 Addition of Phosphorus Ylides: The Wittig Reaction 756

Chemical Highlight 1 7-3 The Wittig Reaction in Synthesis 759

17-13 Oxidation by Peroxycarboxylic Acids:

The Baeyer-Villiger Oxidation 760

17-14 Oxidative Chemical Tests for Aldehydes 761


New Reactions 764Reaction Summary Road Map: Preparation

of Aldehydes and Ketones 768

Reaction Summary Road Map: Reactions

of Aldehydes and Ketones 770Important Concepts 772Problems 772

Enols and Enones: a,ß-Unsaturated Alcohols,Aldehydes, and Ketones 780

18-1 Acidity of Aldehydes and Ketones: Enolate Ions 78118-2 Keto-Enol Equilibria 782

18-3 Halogenation of Aldehydes and Ketones 785

Chemical Highlight 18-1 Haloform Reaction:_

A Test for Methyl Ketones 787

18-4 Alkylation of Aldehydes and Ketones 787

18-5 Attack by Enolates on the Carbonyl Function:

Aldol Condensation 790

Chemical Highlight 18-2 Aldol Condensations in Nature 790

18-6 Crossed Aldol Condensation 794

Chemical Highlight 18-3 Enzymes in Crossed Aldol

Condensations 795

18-7 Intramolecular Aldol Condensation 796

18-8 Other Preparations of a,ß-Unsaturated Aldehydes and Ketones 798

Chemical Highlight 18-4 Reactions of Unsaturated

Aldehydes in Nature: The Chemistry of Vision 799

18-9 Properties of a,ß-Unsaturated Aldehydes and Ketones 799

18-10 Conjugate Additions to a,ß-Unsaturated

Aldehydes and Ketones 802

18-11 1,2- and 1,4-Additions of Organometallic Reagents 804

18-12 Conjugate Additions of Enolate Ions: Michael Addition

and Robinson Annulation 805

Chemical Highlight 18-5 Prostaglandins: a,ß-Dialkylation

in Synthesis 806


New Reactions 810


Problems 815

Carboxylic Acids 825

19-1 Naming the Carboxylic Acids 826

19-2 Structural and Physical Properties of Carboxylic Acids 828

19-3 NMR and IR Spectroscopy of Carboxylic Acids 830

19-4 Acidic and Basic Character of Carboxylic Acids 832

19-5 Carboxylic Acid Synthesis in Industry 835

19-6 Methods for Introducing the Carboxy Functional Group 836

19-7 Substitution at the Carboxy Carbon:

The Addition-Elimination Mechanism 839

19-8 Carboxylic Acid Derivatives: Alkanoyl (Acyl)

Halides and Anhydrides 842

19-9 Carboxylic Acid Derivatives: Esters 844

19-10 Carboxylic Acid Derivatives: Amides 847

19-11 Reduction of Carboxylic Acids by Lithium Aluminum Hydride 849

19-12 Bromination Next to the Carboxy Group:

The Hell-Volhard-Zelinsky Reaction 850

19-13 Biological Activity of Carboxylic Acids 851

Chemical Highlight 19-1 Soaps from

Long-Chain Carboxylates 852

Chemical Highlight 19-2 Trans Fatty Acids and

Your Health 853

Chemical Highlight 19-3 Biodegradable Polyester Plastics 857


New Reactions 861

Reaction Summary Road Map: Preparation of Carboxylic Acids 865

Reaction Summary Road Map: Reactions of Carboxylic Acids 866


Problems 867

C) Carboxylic Acid Derivatives and Mass Spectrometry 87820-1 Relative Reactivities, Structures, and Spectra of Carboxylic

Acid Derivatives 879

Chemical Highlight 20-1 Spectroscopic Characterization of

the Lactone Ring in Manoalide 882

20-2 Chemistry of Alkanoyl Halides 883

20-3 Chemistry of Carboxylic Anhydrides 887

20-4 Chemistry of Esters 888

20-5 Esters in Nature: Waxes, Fats, Oils, and Lipids 893

20-6 Amides: The Least Reactive Carboxylic Acid Derivatives 896

Chemical Highlight 20-2 Penicillin: An Antibiotic

Containing a ß-Lactam Ring 898

20-7 Amidates and Their Halogenation: The Hofmann Rearrangement 900

Chemical Highlight 20-3 Methyl Isocyanate and

the Bhopal Tragedy 902

20-8 Alkanenitriles: A Special Class of Carboxylic Acid Derivatives 903

20-9 Measuring the Molecular Weight of Organic Compounds:

Mass Spectrometry 907

20-10 Fragmentation Patterns of Organic Molecules 911

Chemical Highlight 20-4 The Contribution of Mass

Spectrometry to the Characterization of Manoalide 917

20-11 High-Resolution Mass Spectrometry 918

Chapter Integration Problem 920New Reactions 921Important Concepts 926Problems 926

Amines and Their Derivatives: Functional GroupsContaining Nitrogen 936

21-1 Naming the Amines 937Chemical Highlight 21-1 Physiologically Active

Amines and Weight Control 938

21-2 Structural and Physical Properties of Amines 94021-3 Spectroscopy of the Amine Group 942

21-4 Acidity and Basicity of Amines 945Chemical Highlight 21-2 Separation of Amines from Other

Organic Compounds by Aqueous Extraction Techniques 946

21-5 Synthesis of Amines by Alkylation 950

21-6 Synthesis of Amines by Reductive Amination 95321-7 Synthesis of Amines from Carboxylic Amides 954

21-8 Quaternary Ammonium Salts: Hofmann Elimination 955

21-9 Mannich Reaction: Alkylation of Enols by Iminium Ions 957

21-10 Nitrosation of Amines: N-Nitrosamines and Diazonium Ions 959Chemical Highlight 21-3 Carcinogenicity of

N-Nitrosodialkanamines and Cured Meats 960

21-11 Diazomethane, Carbenes, and Cyclopropane Synthesis 961

21-12 Amines in Industry: Nylon 964


New Reactions 967


Reaction Summary Road Map: Preparation of Amines 971

Reaction Summary Road Map: Reactions of Amines 972

Problems 973

® Chemistry of Benzene Substituents: Alkylbenzenes,Phenols, and Benzenamines 982

22-1 Reactivity at the Phenylmethyl (Benzyl) Carbon:

Benzylic Resonance Stabilization 983

22-2 Benzylic Oxidations and Reductions 987

22-3 Names and Properties of Phenols 989

22-4 Preparation of Phenols: Nucleophilic Aromatic Substitution 992

Chemical Highlight 22-1 Toxicity of Chlorophenols 995

Chemical Highlight 22-2 Economics of Industrial Synthesis

of Phenol: The Cumene Hydroperoxide Process 1000

22-5 Alcohol Chemistry of Phenols 1001

22-6 Electrophilic Substitution of Phenols 1002

Chemical Highlight 22-3 Aspirin: A Phenyl

Alkanoate Drug 1003

22-7 Claisen and Cope Rearrangements 100622-8 Oxidation of Phenols: Cyclohexadienediones (Benzoquinones) 1008

Chemical Highlight 22-4 Chemical Warfare in

Nature: The Bombardier Beetle 1008

22-9 Oxidation-Reduction Processes in Nature 1011

22-10 Arenediazonium Salts 1016

22-11 Electrophilic Substitution with Arenediazonium Salts:

Diazo Coupling 1019


New Reactions 1022


Problems 1028

CD Ester Enolates and Acyl Anion Equivalents:Syntheses of ß-Dicarbonyl anda-Hydroxycarbonyl Compounds 1037

23-1 ß-Dicarbonyl Compounds: Claisen Condensations 1038Chemical Highlight 23-1 Claisen Condensations

in Biochemistry 1042

23-2 ß-Dicarbonyl Compounds as Synthetic Intermediates 1044

23-3 ß-Dicarbonyl Anion Chemistry: Michael Additions 1048

23-4 Alkanoyl (Acyl) Anion Equivalents: Preparation of

a-Hydroxyketones 1050

Chemical Highlight 23-2 2-Oxopropanoic (Pyruvic) Acid,

a Natural a-Ketoacid 1052

Chemical Highlight 23-3 Thiamine: A Natural,

Catalytically Active Thiazolium Ion 1055


New Reactions 1059Important Concepts 1060

Problems 1061

CI) Carbohydrates: Polyfunctional Compoundsin Nature 1068

24-1 Names and Structures of Carbohydrates 1069

24-2 Conformations and Cyclic Forms of Sugars 1073

24-3 Anomers of Simple Sugars: Mutarotation of Glucose 1077

24-4 Polyfunctional Chemistry of Sugars: Oxidation

to Carboxylic Acids 1079

24-5 Oxidative Cleavage of Sugars 1081

24-6 Reduction of Monosaccharides to Alditols 1082

24-7 Carbonyl Condensations with Amine Derivatives 1083

24-8 Ester and Ether Formation: Glycosides 1084

Chemical Highlight 24-1 ' sF-Labeled Glucose as

a Radiotracer: Imaging the Human Brain 108524-9 Step-by-Step Buildup and Degradation of Sugars 1087

Chemical Highlight 24-2 Sugar Biochemistry 108824-10 Relative Configurations of the Aldoses: An Exercise

in Structure Determination 109024-11 Complex Sugars in Nature: Disaccharides 1093

Chemical Highlight 24-3 Carbohydrate-DerivedSugar Substitutes 1095

24-12 Polysaccharides and Other Sugars in Nature 1097Chapter Integration Problem 1102New Reactions 1106


Heterocycles: Heteroatoms in Cyclic OrganicCompounds 1116

25-1 Naming the Heterocycles 1119

25-2 Nonaromatic Heterocycles 1120

Chemical Highlight 25-1 Azacyclopropene Antibiotics 1122

Chemical Highlight 25-2 Nicotine and Cancer 1123

25-3 Structure and Properties of Aromatic Heterocyclopentadienes 1124

25-4 Reactions of the Aromatic Heterocyclopentadienes 1127

25-5 Structure and Preparation of Pyridine: An Azabenzene 1130

25-6 Reactions of Pyridine 1133

Chemical Highlight 25-3 Pyridinium Salts in Nature:

Nicotinamide Adenine Dinucleotide 1135

25-7 Quinoline and Isoquinoline: The Benzopyridines 1136

25-8 Alkaloids: Physiologically Potent Nitrogen Heterocycles

in Nature 1137

Chemical Highlight 25-4 Azanaphthalenes in Nature 1138

Chemical Highlight 25-5 Nature Is Not Always Green:

Natural Pesticides 1140


New Reactions 1144


Problems 1147

ED Amino Acids, Peptides, Proteins, and Nucleic Acids:Nitrogen-Containing Polymers in Nature 1156

26-1 Structure and Properties of Amino Acids 1157

Chemical Highlight 26-1 Arginine and Nitric Oxide

in Biochemistry and Medicine 1161

26-2 Synthesis of Amino Acids: A Combination of Amine

and Carboxylic Acid Chemistry 1 163

26-3 Synthesis of Enantiomerically Pure Amino Acids 1 165

Chemical Highlight 26-2 Synthesis of Optically

Pure Amino Acids 1 167

26-4 Peptides and Proteins: Amino Acid Oligomers and Polymers 1 167

Chemical Highlight 26-3 Glutathione and the

Toxicity of Methyl Isocyanate 1 169

26-5 Determination of Primary Structure: Amino

Acid Sequencing 1 175

26-6 Synthesis of Polypeptides: A Challenge in the Application

of Protecting Groups 1180

26-7 Merrifield Solid-Phase Peptide Synthesis 1183

26-8 Polypeptides in Nature: Oxygen Transport by

the Proteins Myoglobin and Hemoglobin 1184

26-9 Biosynthesis of Proteins: Nucleic Acids 1186

Chemical Highlight 26-4 Synthetic Nucleic Acid Bases

and Nucleosides in Medicine 1 188

26-10 Protein Synthesis Through RNA 1191

26-11 DNA Sequencing and Synthesis: Cornerstones

of Gene Technoloogy 1194


New Reactions 1201


Problems 1204

Answers to Exercises A-1

Photograph Credits C-1

Index I-1

NfIC CHEMIST

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