Organic chemistry

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Organic Chemistry


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Organic
Chemistry
Structure and
Function
PETER VOLLHARDT
University of California at Berkeley

NEIL SCHORE
University of California at Davis

W. H. Freeman and Company
New York

SIXTH
EDITION

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Publisher: Clancy Marshall
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Printing and Binding: World Color (USA) Corp
Library of Congress Cataloging-in-Publication Data
Vollhardt, K. Peter C.
Organic chemistry : structure and function / K. Peter C. Vollhardt, Neil E. Schore.—6th ed.
p. cm.
ISBN-13: 978-1-4292-0494-1
ISBN-10: 1-4292-0494-X
1. Chemistry, Organic—Textbooks. I. Schore, Neil Eric, 1948– II. Title.
QD251.3.V65 2009
547—dc22
2009040318
© 1999, 2003, 2007, and 2011 W. H. Freeman and Company
All rights reserved

Printed in the United States of America
First printing
W. H. Freeman and Company
41 Madison Avenue
New York, NY 10010
Houndmills, Basingstoke RG21 6XS, England
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B R I E F

C O N T E N T S

PREFACE: A User’s Guide to Organic Chemistry:
Structure and Function

xxiii

1

STRUCTURE AND BONDING IN ORGANIC MOLECULES

2

STRUCTURE AND REACTIVITY

49

3

REACTIONS OF ALKANES

95

4

CYCLOALKANES

131

5

STEREOISOMERS

169

6

PROPERTIES AND REACTIONS OF HALOALKANES

215

7

FURTHER REACTIONS OF HALOALKANES

251

8

HYDROXY FUNCTIONAL GROUP: Alcohols

287

9

FURTHER REACTIONS OF ALCOHOLS AND
THE CHEMISTRY OF ETHERS

333

USING NUCLEAR MAGNETIC RESONANCE
SPECTROSCOPY TO DEDUCE STRUCTURE

387

ALKENES; INFRARED SPECTROSCOPY AND
MASS SPECTROMETRY

445

10
11

INTERLUDE: Solving Problems in Organic Chemistry

1

499

12

REACTIONS OF ALKENES

507

13

ALKYNES

567

14

DELOCALIZED PI SYSTEMS

609

INTERLUDE: A Summary of Organic Reaction Mechanisms

15

BENZENE AND AROMATICITY

668
673
v

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vi

Brief Contents

16

ELECTROPHILIC ATTACK ON DERIVATIVES
OF BENZENE

731

17

ALDEHYDES AND KETONES

775

18

ENOLS, ENOLATES, AND THE ALDOL CONDENSATION

827

19

CARBOXYLIC ACIDS

871

20

CARBOXYLIC ACID DERIVATIVES

925

21

AMINES AND THEIR DERIVATIVES

971

22

CHEMISTRY OF BENZENE SUBSTITUENTS

1019

23

ESTER ENOLATES AND THE CLAISEN CONDENSATION

1081

24

CARBOHYDRATES: Polyfunctional Compounds
in Nature

1117

HETEROCYCLES: Heteroatoms in Cyclic Organic
Compounds

1165

AMINO ACIDS, PEPTIDES, PROTEINS, AND NUCLEIC
ACIDS: Nitrogen-Containing Polymers in Nature

1211

25
26

MCAT® Questions
Answers to Exercises
Photograph Credits
Index

MCAT-1
A-1
C-1
I-1


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C O N T E N T S

PREFACE: A User’s Guide to Organic Chemistry:
Structure and Function

1

STRUCTURE AND BONDING IN ORGANIC MOLECULES

1-1
The Scope of Organic Chemistry: An Overview
Chemical Highlight 1-1 Urea: From Urine to Wöhler’s

Synthesis to Industrial Fertilizer
1-2
Coulomb Forces: A Simplified View of Bonding
1-3
Ionic and Covalent Bonds: The Octet Rule
1-4
Electron-Dot Model of Bonding: Lewis Structures
1-5
Resonance Forms
1-6
Atomic Orbitals: A Quantum Mechanical Description
of Electrons Around the Nucleus
1-7
Molecular Orbitals and Covalent Bonding
1-8
Hybrid Orbitals: Bonding in Complex Molecules
1-9
Structures and Formulas of Organic Molecules
Chapter Integration Problems

Important Concepts
Problems

2

STRUCTURE AND REACTIVITY

xxiii

1
2
4
5
7
13
18
23
28
31
37
40
43
44

49

2-1

Kinetics and Thermodynamics of Simple
Chemical Processes

2-2
Acids and Bases; Electrophiles and Nucleophiles;
Using Curved “Electron-Pushing” Arrows
Chemical Highlight 2-1 Stomach Acid and Food Digestion
2-3
Functional Groups: Centers of Reactivity
2-4
Straight-Chain and Branched Alkanes
2-5
Naming the Alkanes
2-6
Structural and Physical Properties of Alkanes
Chemical Highlight 2-2 “Sexual Swindle” by Means of
Chemical Mimicry
2-7
Rotation about Single Bonds: Conformations

50
56
59
67
70
71
76
79
79
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viii

Contents

2-8

3

Rotation in Substituted Ethanes
Chapter Integration Problems
Important Concepts
Problems

82
86
88
89

REACTIONS OF ALKANES

95

3-1
Strength of Alkane Bonds: Radicals
3-2
Structure of Alkyl Radicals: Hyperconjugation
3-3
Conversion of Petroleum: Pyrolysis
Chemical Highlight 3-1 Sustainability and the Needs of the

96
99
100

21st Century: “Green” Chemistry
3-4
Chlorination of Methane: The Radical Chain Mechanism
3-5
Other Radical Halogenations of Methane
3-6
Chlorination of Higher Alkanes: Relative
Reactivity and Selectivity
3-7
Selectivity in Radical Halogenation with
Fluorine and Bromine
3-8
Synthetic Radical Halogenation
Chemical Highlight 3-2 Chlorination, Chloral, and DDT
3-9
Synthetic Chlorine Compounds and the Stratospheric
Ozone Layer
3-10 Combustion and the Relative Stabilities of Alkanes
Chapter Integration Problems
Important Concepts
Problems

103
104
109

4

CYCLOALKANES

111
115
116
118
119
122
124
126
127

131

4-1
Names and Physical Properties of Cycloalkanes
4-2
Ring Strain and the Structure of Cycloalkanes
4-3
Cyclohexane: A Strain-Free Cycloalkane
4-4
Substituted Cyclohexanes
4-5
Larger Cycloalkanes
4-6
Polycyclic Alkanes
Chemical Highlight 4-1 Cyclohexane, Adamantane, and Diamandoids:

132
135
140
144
149
149

Diamond “Molecules”
4-7
Carbocyclic Products in Nature
Chemical Highlight 4-2 Cholesterol: How Is It Bad and
How Bad Is It?
Chemical Highlight 4-3 Controlling Fertility: From “the Pill”
to RU-486
Chapter Integration Problems
Important Concepts
Problems

151
152
155
156
158
161
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Contents

5

STEREOISOMERS

169

5-1
Chiral Molecules
Chemical Highlight 5-1 Chiral Substances in Nature
5-2
Optical Activity
5-3
Absolute Configuration: R – S Sequence Rules
5-4
Fischer Projections
Chemical Highlight 5-2 Absolute Configuration:

171
173
174
177
182

A Historical Note
5-5
Molecules Incorporating Several Stereocenters:
Diastereomers
Chemical Highlight 5-3 Stereoisomers of Tartaric Acid
5-6
Meso Compounds

5-7
Stereochemistry in Chemical Reactions
Chemical Highlight 5-4 Chiral Drugs: Racemic or
Enantiomerically Pure?
Chemical Highlight 5-5 Why Is Nature “Handed”?
5-8
Resolution: Separation of Enantiomers
Chapter Integration Problems
Important Concepts
Problems

183

6

PROPERTIES AND REACTIONS OF
HALOALKANES

187
190
191
193
196
199
202
205
207
208

215

6-1
Physical Properties of Haloalkanes
Chemical Highlight 6-1 Halogenated Steroids as Anti-

215

Inflammatory and Anti-Asthmatic Agents
6-2
Nucleophilic Substitution
6-3
Reaction Mechanisms Involving Polar Functional Groups:
Using “Electron-Pushing” Arrows
6-4
A Closer Look at the Nucleophilic Substitution
Mechanism: Kinetics
6-5
Frontside or Backside Attack? Stereochemistry of
the SN2 Reaction
6-6
Consequences of Inversion in SN2 Reactions
6-7
Structure and SN2 Reactivity: The Leaving Group
6-8
Structure and SN2 Reactivity: The Nucleophile
6-9
Structure and SN2 Reactivity: The Substrate
Chemical Highlight 6-2 The Dilemma of Bromomethane:
Highly Useful but Also Highly Toxic
Chapter Integration Problems

Important Concepts
Problems

217
218
221
223
226
228
231
233
240
241
244
245
246

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Contents

7

FURTHER REACTIONS OF HALOALKANES

7-1

7-2
7-3
7-4

Solvolysis of Tertiary and Secondary Haloalkanes
Unimolecular Nucleophilic Substitution
Stereochemical Consequences of SN1 Reactions
Effects of Solvent, Leaving Group, and Nucleophile
on Unimolecular Substitution
7-5
Effect of the Alkyl Group on the SN1 Reaction:
Carbocation Stability
Chemical Highlight 7-1 Unusually Stereoselective SN1 Displacement
in Anticancer Drug Synthesis
7-6
Unimolecular Elimination: E1
7-7
Bimolecular Elimination: E2
7-8
Competition Between Substitution and Elimination:
Structure Determines Function
7-9
Summary of Reactivity of Haloalkanes
Chapter Integration Problems
New Reactions
Important Concepts
Problems

8
8-1

8-2
8-3
8-4

HYDROXY FUNCTIONAL GROUP: Alcohols

Naming the Alcohols
Structural and Physical Properties of Alcohols
Alcohols as Acids and Bases
Industrial Sources of Alcohols: Carbon Monoxide and
Ethene
8-5
Synthesis of Alcohols by Nucleophilic Substitution
8-6
Synthesis of Alcohols: Oxidation - Reduction Relation
Between Alcohols and Carbonyl Compounds
Chemical Highlight 8-1 Biological Oxidation and
Reduction
Chemical Highlight 8-2 The Breath Analyzer Test
8-7
Organometallic Reagents: Sources of Nucleophilic
Carbon for Alcohol Synthesis
8-8
Organometallic Reagents in the Synthesis of Alcohols
8-9
Complex Alcohols: An Introduction to Synthetic
Strategy
Chemical Highlight 8-3 Transition Metal-Catalyzed
Cross-Coupling Reactions
Chapter Integration Problems

New Reactions
Important Concepts
Problems

251
251
252
256
258
260
263
264
267
270
273
275
277
277
278

287
288
289
292
295
295
297
298
302
304

307
309
310
319
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Contents

9

FURTHER REACTIONS OF ALCOHOLS AND
THE CHEMISTRY OF ETHERS

9-1
9-2

Reactions of Alcohols with Base: Preparation of Alkoxides
Reactions of Alcohols with Strong Acids: Alkyloxonium
Ions in Substitution and Elimination Reactions of Alcohols
9-3
Carbocation Rearrangements
9-4
Esters from Alcohols and Haloalkane Synthesis
9-5
Names and Physical Properties of Ethers
9-6

Williamson Ether Synthesis
Chemical Highlight 9-1 Chemiluminescence of
1,2-Dioxacyclobutanes
9-7
Synthesis of Ethers: Alcohols and Mineral Acids
9-8
Reactions of Ethers
Chemical Highlight 9-2 Protecting Groups in Synthesis
9-9
Reactions of Oxacyclopropanes
Chemical Highlight 9-3 Hydrolytic Kinetic Resolution of
Oxacyclopropanes
9-10 Sulfur Analogs of Alcohols and Ethers
9-11 Physiological Properties and Uses of Alcohols
and Ethers
Chemical Highlight 9-4 Garlic and Sulfur
Chapter Integration Problems
New Reactions
Important Concepts
Problems

10

USING NUCLEAR MAGNETIC RESONANCE
SPECTROSCOPY TO DEDUCE STRUCTURE

10-1 Physical and Chemical Tests
10-2 Defining Spectroscopy
10-3 Hydrogen Nuclear Magnetic Resonance
Chemical Highlight 10-1 Recording an NMR Spectrum

10-4 Using NMR Spectra to Analyze Molecular Structure:

The Proton Chemical Shift
10-5 Tests for Chemical Equivalence
Chemical Highlight 10-2 Magnetic Resonance Imaging

in Medicine
10-6 Integration
10-7 Spin – Spin Splitting: The Effect of Nonequivalent
Neighboring Hydrogens
10-8 Spin – Spin Splitting: Some Complications
Chemical Highlight 10-3 The Nonequivalence of Diastereotopic
Hydrogens

333
334
335
338
344
347
350
351
355
357
359
360
362
365
367
371

372
374
376
377

387
388
388
390
393
395
400
404
405
407
414
418

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Contents

10-9 Carbon-13 Nuclear Magnetic Resonance
Chemical Highlight 10-4 Correlated NMR Spectra: COSY and

422

HETCOR

428

Chemical Highlight 10-5 Structural Characterization of Natural Products:

Antioxidants from Grape Seeds
Chapter Integration Problems
Important Concepts
Problems

11

ALKENES; INFRARED SPECTROSCOPY AND
MASS SPECTROMETRY

430
432
435
436

445

11-1 Naming the Alkenes
11-2 Structure and Bonding in Ethene: The Pi Bond
11-3 Physical Properties of Alkenes
11-4 Nuclear Magnetic Resonance of Alkenes
Chemical Highlight 11-1 Prostaglandins
11-5 Catalytic Hydrogenation of Alkenes: Relative Stability of

446
449
452
453
459

Double Bonds
11-6 Preparation of Alkenes from Haloalkanes and Alkyl
Sulfonates: Bimolecular Elimination Revisited
11-7 Preparation of Alkenes by Dehydration of Alcohols
11-8 Infrared Spectroscopy
11-9 Measuring the Molecular Mass of Organic Compounds:
Mass Spectrometry
Chemical Highlight 11-2 Security in the 21st Century:
Applications of IR and MS
Chemical Highlight 11-3 Detecting Performance-Enhancing
Drugs Using Mass Spectrometry
11-10 Fragmentation Patterns of Organic Molecules
11-11 Degree of Unsaturation: Another Aid to Identifying
Molecular Structure
Chapter Integration Problems
New Reactions
Important Concepts
Problems
INTERLUDE: Solving Problems in Organic Chemistry

459

12

12-1
12-2
12-3

REACTIONS OF ALKENES
Why Addition Reactions Proceed: Thermodynamic
Feasibility
Catalytic Hydrogenation
Nucleophilic Character of the Pi Bond: Electrophilic
Addition of Hydrogen Halides

462
466
468
473
475
476
478
482
484
486
487
488
499

507
507
509
512

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Contents

12-4

Alcohol Synthesis by Electrophilic Hydration:
Thermodynamic Control
12-5 Electrophilic Addition of Halogens to Alkenes
12-6 The Generality of Electrophilic Addition
12-7 Oxymercuration – Demercuration: A Special Electrophilic
Addition
Chemical Highlight 12-1 Juvenile Hormone Analogs in the
Battle against Insect-Borne Diseases
12-8 Hydroboration – Oxidation: A Stereospecific
Anti-Markovnikov Hydration
12-9 Diazomethane, Carbenes, and Cyclopropane Synthesis
12-10 Oxacyclopropane (Epoxide) Synthesis: Epoxidation by
Peroxycarboxylic Acids
12-11 Vicinal Syn Dihydroxylation with Osmium Tetroxide
Chemical Highlight 12-2 Synthesis of Antitumor Drugs: Sharpless
Enantioselective Oxacyclopropanation and Dihydroxylation
12-12 Oxidative Cleavage: Ozonolysis
12-13 Radical Additions: Anti-Markovnikov Product Formation
12-14 Dimerization, Oligomerization, and Polymerization of
Alkenes
12-15 Synthesis of Polymers
Chemical Highlight 12-3 Polymers in the Clean-up of Oil Spills
12-16 Ethene: An Important Industrial Feedstock
12-17 Alkenes in Nature: Insect Pheromones

Chemical Highlight 12-4 Metal-Catalyzed Alkene Metathesis for
Constructing Medium and Large Rings
Chapter Integration Problems
New Reactions
Important Concepts
Problems

13
13-1
13-2
13-3
13-4
13-5
13-6

ALKYNES

Naming the Alkynes
Properties and Bonding in the Alkynes
Spectroscopy of the Alkynes
Preparation of Alkynes by Double Elimination
Preparation of Alkynes from Alkynyl Anions
Reduction of Alkynes: The Relative Reactivity of the
Two Pi Bonds
13-7 Electrophilic Addition Reactions of Alkynes
13-8 Anti-Markovnikov Additions to Triple Bonds
13-9 Chemistry of Alkenyl Halides
Chemical Highlight 13-1 Metal-Catalyzed Stille, Suzuki, and
Sonogashira Coupling Reactions

516
518
521
525
526
528
531
532
535
536
538
540
542
543
545
547
548
548
550
553
555
556

567
568
568
571
576
577
579

582
585
587
588

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Contents

13-10 Ethyne as an Industrial Starting Material
13-11 Naturally Occurring and Physiologically Active Alkynes

14

Chapter Integration Problems
New Reactions
Important Concepts
Problems

590
592
594
595
599
599

DELOCALIZED PI SYSTEMS

609

14-1

Overlap of Three Adjacent p Orbitals: Electron
Delocalization in the 2-Propenyl (Allyl) System
14-2 Radical Allylic Halogenation
14-3 Nucleophilic Substitution of Allylic Halides: SN1 and SN2
14-4 Allylic Organometallic Reagents: Useful Three-Carbon
Nucleophiles
14-5 Two Neighboring Double Bonds: Conjugated Dienes
14-6 Electrophilic Attack on Conjugated Dienes: Kinetic and
Thermodynamic Control
Chemical Highlight 14-1 “Face-to-Face” Interaction of
Two Double Bonds
14-7 Delocalization Among More than Two Pi Bonds:
Extended Conjugation and Benzene
14-8 A Special Transformation of Conjugated Dienes:
Diels-Alder Cycloaddition
Chemical Highlight 14-2 Conducting Polyenes: Novel
Functional Materials
Chemical Highlight 14-3 The Diels-Alder Reaction is “Green”
14-9 Electrocyclic Reactions
Chemical Highlight 14-4 An Electrocyclization Cascade
in Nature: Immunosuppressants from Streptomyces Cultures
14-10 Polymerization of Conjugated Dienes: Rubber
14-11 Electronic Spectra: Ultraviolet and Visible Spectroscopy
Chemical Highlight 14-5 The Contributions of IR, MS, and UV to

the Characterization of Viniferone
Chapter Integration Problems
New Reactions
Important Concepts
Problems
INTERLUDE: A Summary of Organic Reaction Mechanisms

15
15-1
15-2

610
612
614
616
617
621
622
626
628
630
637
640
644
647
650
655
656
659
660

661
668

BENZENE AND AROMATICITY

673

Naming the Benzenes
Structure and Resonance Energy of Benzene: A First
Look at Aromaticity

674
677


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Contents

15-3 Pi Molecular Orbitals of Benzene
15-4 Spectral Characteristics of the Benzene Ring
15-5 Polycyclic Aromatic Hydrocarbons
Chemical Highlight 15-1 The Allotropes of Carbon: Graphite,

679
682
687

Diamond, and Fullerenes
15-6 Other Cyclic Polyenes: Hückel’s Rule
Chemical Highlight 15-2 Juxtaposing Aromatic and Antiaromatic

Rings in Fused Hydrocarbons
15-7 Hückel’s Rule and Charged Molecules
15-8 Synthesis of Benzene Derivatives: Electrophilic Aromatic
Substitution
15-9 Halogenation of Benzene: The Need for a Catalyst
15-10 Nitration and Sulfonation of Benzene
15-11 Friedel-Crafts Alkylation
15-12 Limitations of Friedel-Crafts Alkylations
15-13 Friedel-Crafts Acylation (Alkanoylation)
Chapter Integration Problems
New Reactions
Important Concepts
Problems

688
693

16

ELECTROPHILIC ATTACK ON DERIVATIVES OF BENZENE

694
699
701
704
705
708
712
714
717

720
722
722

731

16-1

Activation or Deactivation by Substituents on a
Benzene Ring
16-2 Directing Inductive Effects of Alkyl Groups
16-3 Directing Effects of Substituents in Conjugation with the
Benzene Ring
Chemical Highlight 16-1 Explosive Nitroarenes: TNT and
Picric Acid
16-4 Electrophilic Attack on Disubstituted Benzenes
16-5 Synthetic Strategies Toward Substituted Benzenes
16-6 Reactivity of Polycyclic Benzenoid Hydrocarbons
16-7 Polycyclic Aromatic Hydrocarbons and Cancer
Chapter Integration Problems
New Reactions
Important Concepts
Problems

17
17-1
17-2
17-3
17-4

732
734
738
741
745
749
754
758
760
764
765
766

ALDEHYDES AND KETONES

775

Naming the Aldehydes and Ketones
Structure of the Carbonyl Group
Spectroscopic Properties of Aldehydes and Ketones
Preparation of Aldehydes and Ketones

776
778
779
785

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Contents

17-5 Reactivity of the Carbonyl Group: Mechanisms of Addition
17-6 Addition of Water to Form Hydrates
17-7 Addition of Alcohols to Form Hemiacetals and Acetals
17-8 Acetals as Protecting Groups
17-9 Nucleophilic Addition of Ammonia and Its Derivatives
Chemical Highlight 17-1 Imines in Biology
17-10 Deoxygenation of the Carbonyl Group
17-11 Addition of Hydrogen Cyanide to Give Cyanohydrins
17-12 Addition of Phosphorus Ylides: The Wittig Reaction
17-13 Oxidation by Peroxycarboxylic Acids: The Baeyer-

787
789
791
793
797
799
802
804
804

Villiger Oxidation
17-14 Oxidative Chemical Tests for Aldehydes
Chapter Integration Problems
New Reactions

Important Concepts
Problems

808
809
810
812
815
815

18
18-1
18-2
18-3
18-4
18-5

ENOLS, ENOLATES, AND THE ALDOL CONDENSATION

Acidity of Aldehydes and Ketones: Enolate Ions
Keto – Enol Equilibria
Halogenation of Aldehydes and Ketones
Alkylation of Aldehydes and Ketones
Attack by Enolates on the Carbonyl Function: Aldol
Condensation
18-6 Crossed Aldol Condensation
Chemical Highlight 18-1 Enzyme-Catalyzed Stereoselective
Aldol Condensations in Nature
Chemical Highlight 18-2 Enzymes in Synthesis: Stereoselective
Crossed Aldol Condensations

18-7 Intramolecular Aldol Condensation
Chemical Highlight 18-3 Reactions of Unsaturated Aldehydes
in Nature: The Chemistry of Vision
18-8 Properties of a,b-Unsaturated Aldehydes and Ketones
18-9 Conjugate Additions to a,b-Unsaturated Aldehydes and
Ketones
18-10 1,2- and 1,4-Additions of Organometallic Reagents
18-11 Conjugate Additions of Enolate Ions: Michael Addition
and Robinson Annulation
Chemical Highlight 18-4 Alexander Borodin: Composer,
Chemist, and Pioneering Teacher
Chapter Integration Problems
New Reactions
Important Concepts
Problems

827
828
829
832
834
837
840
841
842
843
844
846
848
850

852
853
856
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19

CARBOXYLIC ACIDS

19-1
19-2
19-3

Naming the Carboxylic Acids
Structural and Physical Properties of Carboxylic Acids
Spectroscopy and Mass Spectrometry of Carboxylic
Acids
19-4 Acidic and Basic Character of Carboxylic Acids
19-5 Carboxylic Acid Synthesis in Industry
19-6 Methods for Introducing the Carboxy Functional Group
19-7 Substitution at the Carboxy Carbon: The Addition –
Elimination Mechanism
19-8 Carboxylic Acid Derivatives: Acyl Halides and
Anhydrides

19-9 Carboxylic Acid Derivatives: Esters
19-10 Carboxylic Acid Derivatives: Amides
19-11 Reduction of Carboxylic Acids by Lithium Aluminum
Hydride
19-12 Bromination Next to the Carboxy Group: The HellVolhard-Zelinsky Reaction
19-13 Biological Activity of Carboxylic Acids
Chemical Highlight 19-1 Soaps from Long-Chain Carboxylates
Chemical Highlight 19-2 Trans Fatty Acids and Your Health
Chemical Highlight 19-3 Plastics, Fibers, and Energy from
Biomass-Derived Hydroxyesters
Chapter Integration Problems
New Reactions
Important Concepts
Problems

20

CARBOXYLIC ACID DERIVATIVES

871
872
874
875
879
882
883
886
889
892
896

897
898
899
900
903
905
907
910
913
913

925

20-1

Relative Reactivities, Structures, and Spectra of
Carboxylic Acid Derivatives
20-2 Chemistry of Acyl Halides
20-3 Chemistry of Carboxylic Anhydrides
20-4 Chemistry of Esters
20-5 Esters in Nature: Waxes, Fats, Oils, and Lipids
Chemical Highlight 20-1 Greener Alternatives to Petroleum:
Fuels from Vegetable Oil
20-6 Amides: The Least Reactive Carboxylic Acid Derivatives
Chemical Highlight 20-2 Battling the Bugs: Antibiotic Wars
20-7 Amidates and Their Halogenation: The Hofmann
Rearrangement
Chemical Highlight 20-3 Methyl Isocyanate, Carbamate-Based
Insecticides, and Safety in the Chemical Industry

926
930
934
936
942
944
944
946
950
953

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Contents

20-8

21

Alkanenitriles: A Special Class of Carboxylic Acid
Derivatives
Chapter Integration Problems
New Reactions
Important Concepts
Problems

953
957
960
963
964

AMINES AND THEIR DERIVATIVES

971

21-1 Naming the Amines
21-2 Structural and Physical Properties of Amines
Chemical Highlight 21-1 Physiologically Active Amines and

972
973

Weight Control

974
977
981

21-3 Spectroscopy of the Amine Group
21-4 Acidity and Basicity of Amines
Chemical Highlight 21-2 Separation of Amines from Other

Organic Compounds by Aqueous Extraction Techniques

984

21-5 Synthesis of Amines by Alkylation
986
21-6 Synthesis of Amines by Reductive Amination
989
21-7 Synthesis of Amines from Carboxylic Amides
992
21-8 Reactions of Quaternary Ammonium Salts: Hofmann Elimination 992
21-9 Mannich Reaction: Alkylation of Enols by Iminium Ions
994
21-10 Nitrosation of Amines
996
Chemical Highlight 21-3 N-Nitrosodialkanamines and Cancer
998
Chemical Highlight 21-4 Amines in Industry: Nylon
1000

Chapter Integration Problems
New Reactions
Important Concepts
Problems

22

CHEMISTRY OF BENZENE SUBSTITUENTS

1003
1006
1011
1011

1019

22-1

Reactivity at the Phenylmethyl (Benzyl) Carbon:
Benzylic Resonance Stabilization
22-2 Benzylic Oxidations and Reductions
22-3 Names and Properties of Phenols
Chemical Highlight 22-1 Two Phenols in the News:
Bisphenol A and Resveratrol
22-4 Preparation of Phenols: Nucleophilic Aromatic
Substitution
22-5 Alcohol Chemistry of Phenols
Chemical Highlight 22-2 Aspirin: A Phenyl Alkanoate Drug
22-6 Electrophilic Substitution of Phenols
22-7 An Electrocyclic Reaction of the Benzene Ring:
The Claisen Rearrangement

1020
1024
1026
1030
1030
1041
1043
1044
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Contents

22-8 Oxidation of Phenols: Benzoquinones
Chemical Highlight 22-3 Chemical Warfare in Nature:

1051

The Bombardier Beetle
22-9 Oxidation-Reduction Processes in Nature
22-10 Arenediazonium Salts
22-11 Electrophilic Substitution with Arenediazonium Salts:
Diazo Coupling
Chemical Highlight 22-4 William Perkin and the Origins of
Industrial and Medicinal Chemistry
Chapter Integration Problems
New Reactions
Important Concepts
Problems

1053
1053
1058

23

ESTER ENOLATES AND THE CLAISEN CONDENSATION

1061
1062

1064
1066
1071
1071

1081

23-1 b-Dicarbonyl Compounds: Claisen Condensations
Chemical Highlight 23-1 Claisen Condensations in

1082

Biochemistry
23-2 b-Dicarbonyl Compounds as Synthetic Intermediates
23-3 b-Dicarbonyl Anion Chemistry: Michael Additions
23-4 Acyl Anion Equivalents: Preparation of
a-Hydroxyketones
Chemical Highlight 23-2 Thiamine: A Natural, Metabolically
Active Thiazolium Salt
Chapter Integration Problems
New Reactions
Important Concepts
Problems

1086
1090
1095

24
24-1

24-2
24-3
24-4

CARBOHYDRATES: Polyfunctional Compounds
in Nature

Names and Structures of Carbohydrates
Conformations and Cyclic Forms of Sugars
Anomers of Simple Sugars: Mutarotation of Glucose
Polyfunctional Chemistry of Sugars: Oxidation to
Carboxylic Acids
24-5 Oxidative Cleavage of Sugars
24-6 Reduction of Monosaccharides to Alditols
24-7 Carbonyl Condensations with Amine Derivatives
24-8 Ester and Ether Formation: Glycosides
Chemical Highlight 24-1 Protecting Groups in Vitamin C
Synthesis
24-9 Step-by-Step Buildup and Degradation of Sugars
Chemical Highlight 24-2 Sugar Biochemistry

1098
1100
1104
1107
1109
1109

1117
1117

1122
1127
1128
1130
1131
1132
1133
1135
1136
1138

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24-10 Relative Configurations of the Aldoses: An Exercise in

Structure Determination
24-11 Complex Sugars in Nature: Disaccharides
Chemical Highlight 24-3 Carbohydrate-Derived Sugar

Substitutes
24-12 Polysaccharides and Other Sugars in Nature
Chemical Highlight 24-4 Sialic Acid, “Bird Flu”, and Rational
Drug Design
Chapter Integration Problem

New Reactions
Important Concepts
Problems

25

HETEROCYCLES: Heteroatoms in Cyclic Organic
Compounds

1139
1142
1144
1146
1152
1153
1156
1158
1159

1165

25-1 Naming the Heterocycles
25-2 Nonaromatic Heterocycles
Chemical Highlight 25-1 Smoking, Nicotine, Cancer, and

1167
1168

Medicinal Chemistry
25-3 Structure and Properties of Aromatic

Heterocyclopentadienes
25-4 Reactions of the Aromatic Heterocyclopentadienes
25-5 Structure and Preparation of Pyridine: An Azabenzene
25-6 Reactions of Pyridine
Chemical Highlight 25-2 Pyridinium Salts in Nature:
Nicotinamide Adenine Dinucleotide, Dihydropyridines,
and Organocatalysis
25-7 Quinoline and Isoquinoline: The Benzopyridines
Chemical Highlight 25-3 Folic Acid, Vitamin D, Cholesterol,
and the Color of Your Skin
25-8 Alkaloids: Physiologically Potent Nitrogen Heterocycles
in Nature
Chemical Highlight 25-4 Nature Is Not Always Green:
Natural Pesticides
Chapter Integration Problems
New Reactions
Important Concepts
Problems

1170

26

AMINO ACIDS, PEPTIDES, PROTEINS, AND NUCLEIC
ACIDS: Nitrogen-Containing Polymers in Nature

1172
1175
1179
1184

1186
1188
1188
1191
1192
1195
1198
1200
1200

1211

26-1 Structure and Properties of Amino Acids
Chemical Highlight 26-1 Arginine and Nitric Oxide in

1212

Biochemistry and Medicine

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Contents

26-2

Synthesis of Amino Acids: A Combination of Amine and
Carboxylic Acid Chemistry

26-3 Synthesis of Enantiomerically Pure Amino Acids
Chemical Highlight 26-2 Enantioselective Synthesis of
Optically Pure Amino Acids: Phase-Transfer Catalysis
26-4 Peptides and Proteins: Amino Acid Oligomers and
Polymers
26-5 Determination of Primary Structure: Amino Acid
Sequencing
26-6 Synthesis of Polypeptides: A Challenge in the Application
of Protecting Groups
26-7 Merrifield Solid-Phase Peptide Synthesis
26-8 Polypeptides in Nature: Oxygen Transport by the Proteins
Myoglobin and Hemoglobin
26-9 Biosynthesis of Proteins: Nucleic Acids
Chemical Highlight 26-3 Synthetic Nucleic Acid Bases and
Nucleosides in Medicine
26-10 Protein Synthesis Through RNA
26-11 DNA Sequencing and Synthesis: Cornerstones of Gene
Technology
Chemical Highlight 26-4 DNA Fingerprinting
Chapter Integration Problems
New Reactions
Important Concepts
Problems
MCAT® Questions
Answers to Exercises
Photograph Credits
Index

1217
1220

1222
1222
1230
1234
1238
1239
1241
1243
1246
1248
1256
1260
1262
1264
1264
MCAT-1
A-1
C-1
I-1

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P R E F A C E

A User’s Guide to ORGANIC CHEMISTRY: Structure and Function

I

n this edition of Organic Chemistry: Structure and Function, we maintain our goal of
helping students organize all the information presented in the course and fit it into a
logical framework for understanding contemporary organic chemistry. This framework
emphasizes that the structure of an organic molecule determines how that molecule functions in a chemical reaction. In the sixth edition, we have strengthened the themes of
understanding reactivity, mechanisms, and synthetic analysis to apply chemical concepts
to realistic situations. We have incorporated new applications of organic chemistry in the
life sciences, industrial practices, green chemistry, and environmental monitoring and
clean-up. This edition includes more than 100 new or substantially revised problems,
including new problems on synthesis and green chemistry, and new “challenging” problems. Organic Chemistry: Structure and Function is offered in an online version to give
students cost-effective access to all content from the text plus all student media resources.
For more information, please visit our Web site at .

CONNECTING STRUCTURE AND FUNCTION
This textbook emphasizes that the structure of an organic molecule
determines how that molecule functions in a chemical reaction. By
understanding the connection between structure and function, we
can learn to solve practical problems in organic chemistry.
Chapters 1 through 5 lay the foundation for making this connection.
In particular, Chapter 1 shows how electronegativity is the basis for
polar bond formation, setting the stage for an understanding of polar
reactivity. Chapter 2 makes an early connection between acidity and
electrophilicity, as well as their respective counterparts, basicitynucleophilicity. Chapter 3 relates the structure of radicals to their
relative stability and reactivity. Chapter 4 illustrates how ring size
affects the properties of cyclic systems, and Chapter 5 provides an

early introduction to stereochemistry. The structures of haloalkanes
and how they determine haloalkane behavior in nucleophilic substitution and elimination reactions are the main topics of Chapters 6 and
7. Subsequent chapters present material on functional-group compounds according to the same scheme introduced for haloalkanes:
nomenclature, structure, spectroscopy, preparations, reactions, and
biological and other applications. The emphasis on structure and function allows us to discuss the mechanisms of all new important reactions concurrently, rather than scattered throughout the text. We
believe this unified presentation of mechanisms benefits students by
teaching them how to approach understanding reactions rather than
memorizing them.

N
O
O

O

O

most of the energy
ized society. We
s lack functional
does combustion
that alkanes are
undergo several
cesses, of which
nvolve acid-base
adical reactions.
dical reactions in
significant roles
isease processes),
he Earth’s ozone

synthetic fabrics
e breaking of a bond, or bond dissociation. We examine
iscuss the conditions under which it occurs. The majority
enation, a radical reaction in which a hydrogen atom in
The importance of halogenation lies in the fact that it
up, turning the alkane into a haloalkane, which is suitable
ach of these processes, we shall discuss the mechanism
the reaction occurs. We shall see that different alkanes,
same alkane molecule, may react at different rates, and
Ä
C
A carbon radical

er of mechanisms are needed to describe the very large
mistry. Mechanisms enable us to understand how and why
are likely to form in them. In this chapter we apply mechcts of halogen-containing chemicals on the stratospheric
rief discussion of alkane combustion and show how that
thermodynamic information about organic molecules.

NASA’s X-43A hypersonic
research aircraft being dropped
from under the wing of a B-52B
Stratofortress on June 2, 2001.
Most supersonic aircraft
produce exhaust gases
containing molecules such as
nitric oxide (NO), whose radical
reactions are destructive to the
Earth’s stratospheric ozone (O3)
layer. In the 1970s the United

States abandoned plans to build
a fleet of supersonic aircraft
(SSTs, or supersonic transports)
for just this reason. In contrast,
the X-43A is hydrogen fueled,
posing no risk to stratospheric
ozone, and may represent the
first step toward the development of environmentally
acceptable high-speed flight. In
2008, Boeing flew successfully
the first manned hydrogen-fuelcell-powered aircraft, another
aviation milestone.

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