Organlc

Chemlstry
FrFTH EDrrloN
Marc Loudon
Purdue University

ROBERTS AND COMPANY PUBLISHERS

Greenwood Village, Colorado

Contents
Preface
Reviewers and Consultants
About the Author
1

CHEMIGAT BONDING AND CHEMIGAT STRUGTURE

1.1

1.2

1.3

lntroduction

xxxl
xxxvi
xxxix
1
1

A. What Is Organic Chemistry?

B. Emergence of Organic Chemistry
C. Why Study Organic Chemistry?

Classical Theories of Chemical Bonding

A. Electrons in Atoms
B. The Ionic Bond

C. The Covalent Bond

D. The Polar Covalent Bond

Structures of Covalent Gompounds

A. Methods for Determining Molecular Geometry
B. Prediction of Molecular Geometry

1
1

13
13

I4

1.4

Resonance Structures

20

1.5

Wave Nature of the Electron

22

Electronic structure of the Hydrogen Atom

23

1.6

A. Orbitals, Quantum Numbers, and Energy

B. Spatial Characteristics of Orbitals
C. Summary: Atomic Orbitals of Hydrogen

23
25
28

1.7

Electronic Structures of More Complex Atoms

29

1.8

Another took at the Covalent Bond: Molecular Orbitals

32

A. Molecular Orbital Theory

B. Molecular Orbital Theory and the Lewis Structure of H,

32
36

1.9

Hybrid Orbitals

37

A. Bonding in Methane
B. Bonding in Ammonia

40

37

vii

viii

coNrENrs

Key ldeas in Chapter

Additional Problems

ALKANES

43

46

2.1 Hydrocarbons
2.2 Unbranched Alkanes
2.3 conformations of Alkanes

46

A. Conformation of Ethane
B. Conformations of Butane

50

Gonstitutional lsomers and Nomenclature

57

A. Isomers
B. Organic Nomenclature

57
58
59

2.4

C. Substitutive Nomenclature of Alkanes

D. Highly Condensed Structures
E. Classification of Carbon Substitution

2.5 Cycloalkanes and skeletal structures

2.6 Physical Properties of Alkanes

50
53

64
66

67

70
70

C. Other Physical Properties

74

A. Functional Groups and Compound Classes

B. "R" Notation

Key ldeas in Chapter 2

Additional Problems

ACIDS AND BASES. THE CURVED.ARROW NOTATION

3.1

48

A. Boiling Points
B. Melting Points

2.7 Gombustion
2.8 occurrence and use of Alkanes
2.9 Functional Groups, Gompound Classes, and the "R" Notation

42

Lewis Acid-Base Association Reactions

A. Electron-Deficient Compounds
B. Reactions of Electron-Deficient Compounds with Lewis Bases
C. The Curved-Arrow Notation for Lewis Acid-Base Association and
Dissociation Reactions

73

76

78
81
81

82

83
83

87
87
87
88
89

CONTENTS iX

3.2 Electron-pair oisplacement Reactions

90

B. The Curved-Arrow Notation for Electron-Pair Displacement Reactions

91

3.3 Review of the Curued-Arrow Notation

A. Use of the Curved-Arrow Notation to Represent Reactions
B. Use of the Curved-Arrow Notation to Derive Resonance Structures

3.4 Bronsted-Lowry

Acids and Bases

A. Definition of Brgnsted Acids and Bases

B. Nucleophiles, Electrophiles, and Leaving Groups
C. Strengths of Brpnsted Acids
D. Strengths of Brgnsted Bases
E. Equilibria in Acid-Base Reactions

3.5 Free Energy and Chemical Equilibrium

3.6 Relationship of Structure to Acidity
A. The Element Effect
B. The Charge Effect
C. The Polar Effect

Key ldeas in Chapter 3

Additional Problems

90

A. Donation of Electrons to Atoms That Are Not Electron-Deficient

INTRODUGTION TO AIKENES.
STRUCTURE AND REACTIVITY

4"1 Structure and Bonding in Rfkenes

94
94
94

95
96
98
101

103

104

106
108
108

110

lll

116
117

122
122

A. Carbon Hybridization in Alkenes

B. The n- (Pi) Bond

r23
r25

C. Double-Bond Stereoisomers

128

4.2 Nomenclature

of Alkenes

A. IUPAC Substitutive Nomenclature

B. Nomenclature of Double-Bond Stereoisomers: The E,Z Svstem

4.3 Unsaturation Humber

4.4 Phy$ical Propefties of Alkenes
4.5 Relative $tabilities of Allcene lsomers
A. Heats of Formation
B. Relative Stabilities of Alkene Isomers

4.5 Additisn Reactions of Alkenes

4"7 Addition of Hydrcgen Halides to nlilrenas
A. Regioselectivity of Hydrogen Halide Addition
B. Carbocation Intermediates in Hydrogen Halide Addition

131
131

t34
139

140
141

I4I
r44

147
147
148

r49

CONTENTS

C. Structure and Stability of Carbocations

D. Carbocation Rearrangement in Hydrogen Halide Addition

4.8

158
160

r62
r64

D. Hammond's Postulate

166

catalysis

168

A. Catalytic Hydrogenation of Alkenes

B. Hydration of Alkenes
C. Enzyme Catalysis

r69
172

172
174

Key ldeas in Chapter 4

Additional Problems

r54

157

Reaction Rates
A. The Transition State
B. The Energy Barrier
C. Multistep Reactions and the Rate-Limiting Step

4.9

151

178

ADDITION REACTIONS OF ALKENES

5.1

An Overuiew of Electrophilic Addition Reactions

5.2

Reactions of Alkenes

with Halogens

178
181

A. Addition of Chlorine and Bromine

B. Halohydrins

181
183

5.3

writing organic Reactions

186

5.4

Gonverion of Alkenes into Alcohols

187

A. Oxymercuration-Reduction of Alkenes
B. Hydroboration-Oxidation of Alkenes
C. Comparison of Methods for the Synthesis of Alcohols from Alkenes

r87
190

194

5.5

Ozonolysis of Alkenes

196

5.6

Free-Radical Addition of Hydrogen Bromide to Rlkenes

200

A. The Peroxide Effect

B. Free Radicals and the "Fishhook" Notation

200

C. Free-Radical Chain Reactions

D. Explanation of the Peroxide Effect
E. Bond Dissociation Energies

202

5.7 Polymeni: Free-Radical Polymerization

5.8 Alkenes in the Ghemical lndustry
Key ldeas in Chapter 5
Additional Problems

20r
207

zrl
of Alkenes

214
216
219
220

CONTENTS

PRINCIPLES OF STEREOCHEMISTRY

226

6.1 Enantiomelri, Chirality, and Symmetry

226

A. Enantiomers and Chirality

B. Asymmetric Carbon and Stereocenters
C. Chirality and Symmetry

226
229
229

6.2 Nomenclature of Enantiomers: The R,S System

6.3 Physical Properties of Enantiomers: Optical Activity
A. Polarized Light
B. Optical Activity
C. Optical Activities of Enantiomers

6.4 Racemates
5.5 Stereochemical Correlation
6.6 Diastereomers
6.7 Meso Compounds
6.8 Enantiomeric Resolution
6.9 Ghiral Molecules without Asymmetric
6.10
6,17
6.12

231

234
235
235

238

239
241

242
246
249

Atoms

Conformational Stereoisomers
A. Stereoisomers Interconvefied by Internal Rotations
B. Asymmetric Nitrogen: Amine Inversion

xl

251

253
253
255

Drawing Structures That Contain

Three-Dimensional lnformation

257

The Postulation of Tetrahedral Carbon

2s9

Key ldeas in Chapter 6

Additional Problems

263
253

cYcHc coMPouNDs.

STEREOCHEMISTRY OF REACTIONS

7.1 Relative Stabilities of the Monocyclic Alkanes

7.2 Conformations of Gyclohexane

268
268
269

A. The Chair Conformation

B. Interconversion of Chair Conformations

273

C. Boat and Twist-Boat Conformations

274

269

xtl

CONTENTS

7.3

Monosubstituted Gyclohexalres. Gonformational Rnalysis

7.4

Disu

7,5

bstituted Gyclohexanes

281

A. Cis-Trans Isomerism in Disubstituted Cyclohexanes

B. Conformational Analysis
C. Use of Planar Structures for Cyclic Compounds

281

D. Stereochemical Consequences of the Chair Interconversion

285

Gyclopentar, Gyclobutane, and Gyclopropane

288

283

284

A. Cyclopentane
B. Cyclobutane and Cyclopropane

7.6

288

289

Bicyclic and Polycyclic Gompounds

290
290
292
294
296

A. Classification and Nomenclature

B. Cis and Trans Ring Fusion
C. Trans-Cycloalkenes and Bredt's Rule
D. Steroids

7.7

Relative Reactivities of Stereoisomers

298
298

A. Relative Reactivities of Enantiomers

B. Relative Reactivities of Diastereomers

7.8

Reactions That Form Stereoisomers

A. Reactions of Achiral Compounds That Give Enantiomeric

300

301
Products

B. Reactions That Give Diastereomeric Products

7.9

Stereochemistry of Ghemical Reactions

A. Stereochemistry of Addition Reactions
B. Stereochemistry of Substitution Reactions
C. Stereochemistry of Bromine Addition
D. Stereochemistry of Hydroboration-Oxidation
E. Stereochemistry of Other Addition Reactions

Key ldeas in Chapter 7

Additional Problems

277

INTRODUCTION TO ATKYL HAIIDES, ALCOHOLS,

ETHERS, THIOLS, AND SUTFIDES

8.1 Nomenclature
A. Nomenclature of Alkyl Halides
B. Nomenclature of Alcohols and Thiols
C. Nomenclature of Ethers and Sulfides

8.2 Structures
8.3 Effect of Molecular

Polarity and
Hydrogen Bonding on Physical Properties

A. Boiling Points of Ethers and Alkyl Halides

301

304

305
30s
306
308

312
313

314
316

323
324
324

326
330

332
333
333

CONTENTS

8,4

B. Boiling Points of Alcohols

335

C. Hydrogen Bonding

336

Solvents in Organic Chemistry

A. Classification of Solvents
B. Solubility

8,5
8,6

XI II

339
339

340

Application$ of Solubility and Solvation principle$

346

A. Cell Membranes and Drug Solubility

B. Cation-Binding Molecules

351

Acidity of Alcohols and Thiols

3S5

A. Formation of Alkoxides and Mercaptides

B. Polar Effects on Alcohol Acidity
C. Role of the Solvent in Alcohol Acidity

8.7 Bssicity of Alcohols and Ethers

8.8 Grignard and Organolithium Reagents
A. Formation of Grignard and Organolithium Reagents
B. Protonolysis of Grignard and Organolithium Reagents

346

356
358
358

359
361
361

362

8.9 Industrial Prepsration

and Use of
Alkyl Halides, Alcohols, and Ethers

364

A. Free-Radical Halogenation of Alkanes

B. Uses of Halogen-Containing Compounds
C. Production and Use of Alcohols and Ethers

365
368

D. Safety Hazards of Ethers

3tl

Key ldeas in Chapter I

l\dditional Problems

372
373

THE CHEMISTRY OF ALKYL HALIDES

9.1

An Overview of ruucleophilic Substitution

and p-Elimination Reactions

377
377

A. Nucleophilic Substitution Reactions

377

B. B-Elimination Reactions
C. Competition between Nucleophilic Substitution and B-Elimination Reactions

380

9.2 Equilibria in tUucleophilic

9.3 Reaction Rates

9.4

364

Substitution Reactaons

378

381

382

A. Definition of Reaction Rate

B. The Rate Law

382

C. Relationship of the Rate Constant to the Standard Free Energy of Activation

384

The S*2 Reaction

A. Rate Law and Mechanism of the S*2 Reaction

383

385
386

XIV

CONTENTS

B. Comparison of the Rates of S*2 Reactions and Bronsted Acid-Base Reactions

C. Stereochemistry of the S*2 Reaction
D. Effect of Alkyl Halide Structure on the S0.2 Reaction
E. Nucleophilicity in the S*2 Reaction
F. Leaving-Group Effects in the S*2 Reaction
G. Summary of the S*2 Reaction

9.5

C. Leaving-Group Effects on the E2 Reaction

D. Deuterium Isotope Effects in the E2 Reaction
E. Stereochemistry of the E2 Reaction
F. Regioselectivity of the E2 Reaction
G. Competition between theE2 and S,o2 Reactions: A Closer Look
H. Summary of the E2 Reaction

10

390

392
398

399

400

The E2 Reaction
A. Rate Law and Mechanism of theE2 Reaction
B. Why theE2 Reaction Is Concerted

9.5

388
388

The S*1 and El Reactions

400
400
402
402
404
406
407

4tl

412

A. Rate Law and Mechanism of S*1 and El Reactions

B. Rate-Limiting and Product-Determining Steps
C. Reactivity and Product Distributions in S*1-E1 Reactions

412

D. Stereochemistry of the S"l Reaction

E. Summary of the S*l and El Reactions

418
420

9.7

Summary of Substitution and Elimination

Reactions of Alkyl Halides

429

9.8

Carbenes and Carbenoids

424

A. a-Elimination Reactions
B. The Simmons-Smith Reaction

424
426

Key ldeas in Chapter 9

Additional Problems

428
429

THE CHEMISTRY OF AICOHOIS AND THIOTS

10.1

Dehydration of Alcohols

4t4
4t6

436
435

1O.2 Reactions of Alcohols with Hydrogen Halides

440

10.3 Sulfonate and Inorganic

443

Ester Derivatives of Alcohols

A. Sulfonate Ester Derivatives of Alcohols

B. Alkylating Agents
C. Ester Derivatives of Strong Inorganic Acids
D. Reactions of Alcohols with Thionyl Chloride and Phosphorus Tribromide

1O.4 Conversion of Alcohols intoAlkyl Halides: Summary

443
447
448
449

450

CONTENTS

10.5 Oxidation and Reduction in Organic Ghemistry

A. Half-Reactions and Oxidation Numbers
B. Oxidizing and Reducing Agents

10.6 Oxidation of Alcohols

A. Oxidation to Aldehydes and Ketones
B. Oxidation to Carboxylic Acids

452
452
156

459
459

46r

1O"7 Biological Oxidation of Ethanol

462

10.8 Chemlcal

465

and Stereochemical Grcup Relationships

A. Chemical Equivalence and Nonequivalence

B. Stereochemistry of the Alcohol Dehydrogenase Reaction

10.9 Oxidation

of Thiols

465
469

471

1O.1O $ynthesis of Alcohols

474

10.11 Desigil of Organic Synthesis

474

Key ldeas in Chapter 10

Additional Problems

11

XV

THE CHEMISTRY OF ETHERS, EPOXIDES,

GLYGOLS, AND SULFIDES

11.'l

Synthesis of Ethers and Sulfides

A. Williamson Ether Synthesis
B. Alkoxymercuration-Reduction of Alkenes
C. Ethers from Alcohol Dehydration and Alkene Addition

11,2 Synthesis of Epoxides

A. Oxidation of Alkenes with Peroxycarboxylic Acids
B. Cyclization of Halohydrins

11.3 Gleavage of Ethers

11.4 Nucleophilic Substitutioil Reactisns of Epoxides
A. Ring-Opening Reactions under Basic Conditions
B. Ring-Opening Reactions under Acidic Conditions
C. Reaction of Epoxides with Organometallic Reagents

11.5

Preparation and Oxldative Cleavage of Glycols

A. Preparation of Glycols
B. Oxidative Cleavage of Glycols

11.5 oxonium

and sulfonium salts

A. Reactions of Oxonium and Sulfonium Salts

B. S-Adenosylmethionine: Nature's Methylating Agent

476
477

482
482
482
484
485

488
488

49r

492
495
495
497

500

503
503

s06

508
508
509

xvl

CONTENTS

11.7 tntramolecular Reactlons

and the Proximity Effect

5r0

C. Stereochemical Consequences of Neighboring-Group Participation

5r6

11.8 Oxidation of Ethers and Sulfides

11.9 The Three Fundamental Operations of Organic Synthesis
11.10 Synthesis of Enantiomerically pure Compounds:

12

5r0

A. Neighboring-Group Participation
B. The Proximity Effect and Effective Molarity

513

518
520

Asymmetric Epoxidation

5e2

Key ldeas in chapter 11

Additional Problems

5?7

ITUTRODUCTION TO SPECTROSCOPY. INFRARED

SPECTROSCOPY AND MASS SPECTROMETRY

12,1 Introduction to Spectroscopy

s?8

s36
536

A. Electromagnetic Radiation
B. Absorption Spectroscopy

536
538

12.2 lnfrared Spectroscopy

540

A. The Inf-rared Spectrum

B. Physical Basis of IR Spectroscopy

12.3 lnfrared Absorption and Chemical Structure

A. Factors That Determine IR Absorption Position
B. Factors That Determine IR Absorption Intensity

12.4 Functional-Group Infrared Absorptions

A. IR Spectra
B. IR Spectra
C. IR Spectra
D. IR Spectra

of
of
of
of

Alkanes

540
54?

544
545

548

552

Alkyl Halides

5s2
552

Alkenes

553

Alcohols and Ethers

556

12.5 Obtaining an Infrared Spectrum

12.6 lntroduction to Mass Spectrometry

557

558

A. Electron-Impact Mass Spectra

B. Isotopic Peaks

558

C. Fragmentation
D. The Molecular Ion. Chemical-Ionization Mass Spectra
E. The Mass Spectrometer

563

Key ldeas in Chapter 12

Additional Problems

560
566
569

571
571

CONTENTS

13

NUCLEAR MAGNETIC RESONANCE SPECTROSCOPY

13.1

An Overview of Proton NMR Spectroscopy

13.2 physlcal
13.3

13.4

Basls of NMR spectroscopy

The NMR Spectrum: Ghemlcal Shift and htegral

578
581

s83

C. Relationship of Chemical Shift to Structure

D. The Number of Absorptions in an NMR Spectrum
E. Counting Protons with the Integral
F. Using the Chemical Shift and Integral to Determine Unknown Structures

586
589
592

585

The NMR Spectrum: spin-spln splltting

593

59S

A. The n * 1 Splitting Rule

B. Why Splitting Occurs

596
599

C. Solving Unknown Structures with NMR Spectra Involving Splitting

601

Use of Deuterlum in Proton NMR

13.7 Characterlstic Functlonal-Group NMR Absorptions

A. NMR SPectra
B. NMR Spectra
C. NMR Spectra
D. NMR SPectra

of Alkenes
of Alkanes and Cycloalkanes
of Alkyl Halides and Ethers
of Alcohols

NMR Spectroscopy of Dynamic Systems

13.9 Carbon NMR

13.10 Solving Structure

603
603
607

611
6',12

612
614
616
616

619
629

Problems with Spectroscopy

6e9

13.11 The NMR Spectrometer

639

13.12 Other Uses of NMR

634

Key ldeas in ChaPter 13

Additional Problems

14

578

583

A. Multiplicative Splitting
B. Breakdown of the n * I Rule

13.8

A. Chemical Shift
B. Chemical Shift Scales

13.5 Complex NMR Specffa

13.6

XVI

THE CHEMISTRV OF ATKYNES

14.1 Nomenclature

t{.e

of AlkYnes

$tructure and Bonding in Alltynes

635
63S

644
644
646

XViii

CONTENTS

14.3

Physical Properties of Rlkynes

649

A. Boiling Points and Solubilities

B. IR Spectroscopy of Alkynes
C. NMR Spectroscopy of Alkynes

14.4
14.5

649
649

6s0

Introduction to Addition Reactions of the Triple Bond

5s2

Conversion of Alkynes into Aldehydes and Ketones

654

A. Hydration of Alkynes
B. Hydroboration-Oxidation of Alkynes

14.6

654
657

Reduction of Alkynes

659

A. Catalytic Hydrogenation of Alkynes

B. Reduction of Alkynes with Sodium in Liquid Ammonia

14.7

Acidity of l-Alkynes

662

A. Acetylenic Anions
B. Acetylenic Anions

662
665

as

Nucleophiles

14.9

Organic Synthesis Using Alkynes

666

14.9

Pheromones

668

Occurrence and Use of Alkynes

574

Key ldeas in Chapter 14

Additional Problems

57

14.10

15

659
660

671

DIENES, RESONANCE, AND AROMATICITY

15.1 Structure and Stability of Dienes

677
680

682

15.2 Ultraviolet-Visible Spectroscopy

684

A. The UV-Vis Spectrum

B. Physical Basis of UV-Vis Spectroscopy
C. UV-Vis Spectroscopy of Conjugated Alkenes

684
686
687

The Diels-Alder Reaction

690

A. Reaction of conjugated Dienes with Alkenes

B. Effect of Diene Conformation on the Diels-Alder Reaction
C. Stereochemistry of the Diels-Alder Reaction

15.4 Addition of Hydrogen Halides to conjugated

Dienes

A. 1,2- and 1,4-Additions

B. Allylic Carbocations. The Connection between Resonance and Stabilitv
C. Kinetic and Thermodynamic Control

676
677

A. Stability of Conjugated Dienes. Molecular Orbitals

B. Structure of Conjugated Dienes
C. Structure and Stability of Cumulared Dienes

15.3

690
694
696

700
700
702
705

CONTENTS XIX

15,5

Diene Polymers

708

15.6

Resonance

749
7t0

A. Drawing Resonance Structures

B. Relative Importance of Resonance Structures

7Ir

714

C. Use of Resonance Structures

15.7 Introduction to Aromatic Compound$

A. Benzene, aPuzzling 'Alkene"
B. Structure of Benzene
C. Stability of Benzene
D. Aromaticity and the Hiickel an | 2 Rule
E. Antiaromatic Compounds

718

721

72r
728

730

Key ldeas in Chapter 15

Additional Problems

16

716
l17

731

THE CHEMISTRY OF BENZENE AND ITS DERIVATIVES 74O

16.1 Nomenclature of Benzene Derivatives

744

16.2

Physical troperties of Benzene Derivatives

743

16.3

Spectroscopy of Benzene Derivatives

743
143
744

A. IR SPectroscoPy
B. NMR Spectroscopy
c. r3C NMR spectroscopy

748
748

D. UV Spectroscopy

16.4 Electrophilic Aromatic Substitution

Reactions of Benzene

A. Halogenation of Benzene
B. Electrophilic Aromatic Substitution
C. Nitration of Benzene

753
754
755
756

D. Sulfonation of Benzene
E. Friedel-Crafts Alkylation of Benzene
F. Friedel-Crafts Acylation of Benzene

16.5 Electrophilicaromatic Substitution

759

Reactions

of Substituted Benzenes

A. Directing Effects of Substituents

B. Activating and Deactivating Effects of Substituents
C. Use of Electrophilic Aromatic Substitution in Organic Synthesis

16.6 Hydrogenation of Benzene Derivatives

15.7 source and lndustrial

Use of Aromatic ttydrocarbons

rey ldeas in ChaPter t6

Additional Problems

750
75r

762
762

768
772

776
777
780
780

XX

CO NTE NTS

17

ALTYLIG AND BENZYLIG REAGTIVITY

17.1 Reactions tnvolvlng Allylic and Benzyllc Carbocations

17.2 Reactions lnvolvlng Allyllc and Benzylic Radicals
17.3 Reactions tnvolvlng Allylic and Benzyllc Anions
A. Allylic Grignard Reagents
B. E2 Eliminations Involving Allylic or Benzylic Hydrogens

17.4 Allyllc and Benzylic Sn2 Reactions

17.s Allyllc and Benzylic Oxidation

793
798
799
801

803
803
805

Terpenes

807

A. The Isoprene Rule

B. Biosynthesis of Terpenes

807

810

Key ldeas in chapter 17

Additional Problems

18

789

802

A. Oxidation of Allylic and Benzylic Alcohols

B. Benzylic Oxidation of Alkylbenzenes

17.6

788

813
814

THE CHEM|STRY OF ARYL HAL|DES, VtNyLtc HALIDES,

AND PHENOLS. TRANSITION.METAL

CATALYSIS

822

18.1 Lack of Reactivity

under

SNz

of vinylic and Aryl Halides

Gonditlons

18.2 Elimination Reactions of vinylic Halides

18.3 Lack of Reactivlty of Vinylic and
Aryl Halldes under SNI Gonditions

8?3
825

826

18.4 NucleophilicAromatic substitution

Reactions of Aryl Halides

18,5 Introduction to Transition-Metal

828

Catalyzed Reactions

A. Transition Metals and Their Complexes

B. Oxidation State
C. The d'Notation
D. Electron Counting: The 16- and lS-Electron Rules
E. Fundamental Reactions of Transition-Metal Complexes

18-6

Examples ofTransition-Metal-Catalyzed Reactions

A. The Heck Reaction
B. The Suzuki Coupling

831
832
835

836
836
839

845
845
848

CONTENTS XXi
C. Alkene Metathesis
D. Other Examples of Transition-Metal-Catalyzed Reactions

18.7 Acidity of Phenols

A. Resonance and Polar Effects on the Acidity of Phenols
B. Formation and Use of Phenoxides

858
858
861

18.8 Oxidation of Phenols to Quinones

862

18.9

867

Electrophillc eromatic Substitution Reactions of Phenols

18.10 Reactivity of the Aryl-oxygen Bond

A. Lack of Reactivity of the Aryl-Oxygen Bond in S*l and S*2 Reactions
B. Substitution at the Aryl-Oxygen Bond: The Stille Reaction

18.11 hdustrial Preparation and Use of Phenol

Key ldeas in Chapter 18
Additional Problems

19

852
857

THE GHEMISTRY OF ALDEHYDES AND KETONES.

CARBONYT.ADDITION REACTIONS

19.1 Nomenclature of Aldehydes and Ketones

A. Common Nomenclature
B. Substitutive Nomenclature

19.2

Physical Properties of Aldehydes and Ketones

19.3 Spectroscopy

of Aldehydes and Ketones

A. IR Spectroscopy

B. Proton NMR Spectroscopy

C. Carbon NMR Spectroscopy

870
870

872

874
875

876

888
890
890

892

894
895
895
897
898

D. UV Spectroscopy

899

E. Mass Spectrometry

901

19.4 Synthesis of Aldehydes and Ketones

903

19.5 htroduction to Aldehyde and Ketone Reactions

19.6 Basicity of Aldehydes and Ketones
19.7 Reversible Rddition Reactions of Aldehydes and Ketones

903

19.8

904
997
907

A. Mechanisms of Carbonyl-Addition Reactions

B. Equilibria in Carbonyl-Addition Reactions

910

C. Rates of Carbonyl-Addition Reactions

913

Reduction of Aldehydes and Ketones to Alcohols

914

xxii

coNrENrs

1g.g
19.10

Reactions of Aldehydes and Ketones with

Grignard and Related Reagents

918

Acetals and Their Use as Protecting Groups

921

A. Preparation and Hydrolysis of Acetals

B. Protecting Groups

19.11

Reactions of Aldehydes and Ketones with Amines

921
925

926

A. Reaction with Primary Amines and Other Monosubstituted

Derivatives of Ammonia

926

B. Reaction with Secondary Amines

20

929

19,12

Reduction of carbonyl Groups to Methylene Groups

931

19.13

The Wittig Alkene Synthesis

933

19,14

Oxidation of Aldehydes to Carboxylic Acids

936

19.15

Manufacture and use of Aldehydes and Ketones

938

Key ldeas in Chapter

Additional Problems

93e
940

19

THE CHEMISTRY OF CARBOXYLIC ACIDS

20.1

Nomenclature of Carboxylic Rcids

A. Common Nomenclature
B. Substitutive Nomenclature

948
948
948
951

20.2

Structure and Physical Properties of Carboxylic Rcids

953

20.3

Spectroscopy of Carboxylic Rcids

955

A. IR Spectroscopy
B. NMR Spectroscopy

2A,4

Acid-Base Properties of Garboxylic Rcids

A. Acidity of Carboxylic and Sulfonic Acids
B. Basicity of Carboxylic Acids

955
955

957
957

960

20.5

Fatty Acids, Soaps, and Detergents

960

20,6

Synthesis of Carboxylic Rcids

963

20.7

lntroduction to carboxylic Rcid Reactions

964

Gonversion of carboxylic Rcids into Esters

965

20.9

A. Acid-Cataly zed Esterifi cation

B. Esterification by Alkylation

965
968

CONTENTS

20.9

Gonversion of Carboxylic Acids into Acid

Chlorides and Anhydrides

XXI

9IO
970

A. Synthesis of Acid Chlorides

B. Synthesis of Anhydrides

972

20.10 Reduction of Garboxylic Acids to Primary Alcohols

974

2O.11 Decarboxylation of Garboxylic Acids

976

Key ldeas in Chapter 20

Additional Problems

21

II

978
979

THE CHEMISTRY OF GARBOXYTIC AGID DERIVATIVES 986

21.1 Nomenclature and Glassification

of Carboxylic Acid Derivatives

986
986
988
988
989
989

A. Esters and Lactones

B. Acid Halides
C. Anhydrides
D. Nitriles
E. Amides, Lactams, and Imides
F. Nomenclature of Substituent Groups
G. Carbonic Acid Derivatives

99r
99r

21.2 Structures of Carboxylic Acid Derivatives

992

21.3

994

Physical Propefties of Carboxylic Acid Derivatives

A. Esters
B. Anhvdrides and Acid Chlorides
C. Nitriles

994
994

D. Amides

99s

21.4 Spectroscopy of Carboxylic Rcid Derivatives

995

996
996

A. IR Spectroscopy
B. NMR Spectroscopy

997

21.5 Basicity of Garboxylic Acid Derivatives

1000

21.6 Introduction to the Reactions of carboxylic Acid Derivatives

1003

21,7 llydrolysis of Carboxylic Acid Derivatives

1004

A. Hydrolysis of Esters
B. Hydrolysis of Amides
C. Hydrolysis of Nitriles
D. Hydrolysis of Acid Chlorides and Anhydrides
E. Mechanisms and Reactivity in Nucleophilic Acyl Substitution Reactions

1004
I
r

008
009

1011
101

XX|V

CoNTENTS

21.8

Reactions of Carboxylic ncid

Derivatives with Nucleophiles

1016

A. Reactions of Acid Chlorides with Nucleophiles

B. Reactions of Anhydrides with Nucleophiles
C. Reactions of Esters with Nucleophiles

21.9 Reduction of Garboxylic Acid Derivatives

A. Reduction of Esters to Primary Alcohols
B. Reduction of Amides to Amines

1016
1019

1022
t022

s ftt*:ti:t :i xt#nffiT?:*il'ffT*
'/

10

ffifiit?ll

A. Reaction of""ff:[3fr]['il:#?$,3"'iva*ves
Esters with Grignard Reagents
B. Reaction of Acid Chlorides with Lithium Dialkylcuprates

21.11 Synthesis of Carboxylic Acid Derivatives

21

12

Hi':11

lfilll'ffi

"'**iTlox'r

THE CHEMISTRY OF ENOTATE IONS, ENOLS,

AND a,B-UNSATURATED CARBONYL GOMPOUNDS
Compounds

A. Formation of Enolate Anions

B. Introduction to Reactions of Enolate Ions

22.2 Enolization of Carbonyl Compounds

22.3 orHalogenation of Carbonyl Compounds
A. Acid-Catalyzed a-Halogenation
B. Halogenation of Aldehydes and Ketones in Base: The Haloform Reaction
C. a-Bromination of Carboxylic Acids
D. Reactions of a-Halo Carbonyl Compounds

22.4 Aldol Addition

and Aldol Gondensation

A. Base-Catalyzed Aldol Reactions

B. Acid-Catalyzed Aldol Condensation
C. Special Types of Aldol Reactions
D. Synthesis with the Aldol Condensation

025
028

'1o29
r029
103

1032

ffi1,iff::,.;':[il;T"

22.1 Acidity of Garbonyl

023

1034

A. Nylon and Polyesters

B. Waxes, Fats, and Phospholipids

22

t02l

E. Relative Reactivities of Carbonyl Compounds

21

020

031

l 036

037
1 038
1

1047
1048
r

048

105

1053
1057
l 057
1

059

1060

r062

1063
063
1066
I

r067
I

070

CONTENTS XXV

22.5 Gondensation Reactions |nvolving Ester Enolate lons

1072

A. Claisen Condensation
B. Dieckmann Condensation

1012
r07 6

C. Crossed Claisen Condensation

D. Synthesis with the Claisen Condensation

22.6 Biosynthesis of Fatty Acids

22,7 Alkylation of Ester Enolate lons

r07 6
1

1081

1084

A. Malonic Ester Synthesis

B. Direct Alkylation of Enolate Ions Derived from Monoesters
C. Acetoacetic Ester Synthesis

22.8 Conjugate-Addition

084
086
I 089
I

Reactions

1492

A. Conjugate Addition to a,B-Unsaturated Carbonyl Compounds

B. Conjugate Addition Reactions versus Carbonyl-Group Reactions
C. Conjugate Addition of Enolate Ions

r092

22.9 Reduction of n,F-Unsaturated Carbonyl Gompounds

22.10 Reactions of c,F-Unsaturated Garbonyl
Compounds with Organometallic Reagents

22.11 Organic Synthesis with Conjugate-Addition Reactions

Key ldeas in Chapter 22
Additional Problems

THE CHEMISTRY OF AMINES

23.1 Nomenclature of Amines

A. Common Nomenclature
B. Substitutive Nomenclature

095

t091
1

100

101

A. Addition of Organolithium Reagents to the Carbonyl Group

B. Conjugate Addition of Lithium Dialkylcuprate Reagents

23

078

1101

I 102
1

103

105
1146

1116
1117

IttT

tln

23.2 Structure of Amines

1119

23.3
23.4

Physical Properties of Amines

1124

Spectroscopy of Amines

1127

A. IR Spectroscopy
B. NMR Spectroscopy

23.5

Basicity and Acidity of Amines

A. Basicity of Amines
B. Substituent Effects on Amine Basicity
C. Separations Using Amine Basicity
D. Acidity of Amines
E. Summary of Aciditv and Basicity

ttzl
ttzl
1122
tt22
tt23
1

t27

128

rr29

XXVI

CoNTENTS

23.6 Quaternary Ammonium and Phosphonium Salts

23.7 Alltylation and Acylation Reactions of Rmines

1129
1131

A. Direct Alkvlation of Amines

B. Reductive Amination
C. Acylation of Amines

23.8

Hofmann Elimination of Quaternary Ammonium

1131

Hydroxides

23.9 Aromatic Substitution Reactions of Aniline Derivatives

23.10 Diazotization; Reactions of Diazonium lons
A. Formation and Substitution Reactions of Diazonium Salts
B. Aromatic Substitution with Diazonium Ions
C. Reactions of Secondary and Tertiary Amines with Nitrous Acid

23.11 Synthesis of Amines

A. Gabriel Synthesis of Primary Amines
B. Reduction of Nitro Compounds
C. Amination of Aryl Halides and Aryl Triflates

23.12

133

135

1136
1

138

1139
1

139

Ir42
II44
1145
tr45
t146
tr47

D. Curtius and Hofmann Rearrangements

E. Synthesis of Amines: Summary

I 150

Use and Occurrence of Amines

1155

A. Industrial Use of Amines and Ammonia

B. Naturally Occurring Amines

Key ldeas in Chapter 23

Additional Problems

24

CARBOHYDRATES

24,1 Glassification and Properties of Carbohydrates

24.2 FischerProiections
24.3 Structures of the Monosaccharides
A. Stereochemistry and Confi guration
B. Cyclic Structures of the Monosaccharides

lt54
1

155

I 155

1157

1158

1156
1167
1168

1173
tt73
1178

24.4 Mutarotation of Garbohydrates

1183

24.5 Base-Catalyzed lsomerization of Aldoses and Ketoses

24.6 Glycosides
24.7 Ether and Ester Derivatives of Garbohydrates
24.8 Oxidation and Reduction Reactions of Carbohydrates

1186

A. Oxidation to Aldonic Acids

1188
1191
1193

tt94

CONTENTS XXVI I
B. Oxidation to Aldaric Acids
C. Periodate Oxidation
D. Reduction to Alditols

195

196

rr97

24.9 Kiliani-Fischer Synthesis

r 198

24.10 Proof of Glucose Stereochemistry

1199

A. Which Diastereomer? The Fischer Proof

B. Which Enantiomer? The Absolute Configuration of n-(+)-Glucose

24.11 Disaccharides and Polysaf,charides

1199

r203

1205

A. Disaccharides
B. Polysaccharides

1205

r209

Key ldeas in Chapter 24

Additional Problems

25

1212
1213

THE CHEMISTRY OF THE AROMATIC HETEROGYCTES 1220

25.1 Nomenclature

and Structure of the Aromatic Heterocycles

1220
r220

A. Nomenclature
B. Structure and Aromaticity

r22l

25.2 Sasicity and Acidity of the Nitrogen Heterocycles

1224

A. Basicity of the Nitrogen Heterocycles

B. Acidity of Pyrrole and Indole

25.3

1224

r226

The Chemistry of Furan, Pyrrolq and Thiophene

1226
t226

A. Electrophilic Aromatic Substitution

B. Addition Reactions of Furan

r229
r230

C. Side-Chain Reactions

25.4

The chemistry of eyridine

1231
I23T

A. Electrophilic Aromatic Substitution

B. Nucleophilic Aromatic Substitution
C. N-Alkylpyridinium Salts and Their Reactions
D. Side-Chain Reactions of Pyridine Derivatives
E. Pyridinium Ions in Biology: Pyridoxal Phosphate

25.5

t234
1238

r239
r240

tuucleosides, Nucleotides, and Nucleic Acids

1245
t245

A. Nucleosides and Nucleotides

B. The Structures of DNA and RNA
C. DNA Modification and Chemical Carcinogenesis

25.6 Other Biologically lmportant Heterocyclic

Key ldeas in Chapter 25
Additional Problem$

t248
t253

Compounds

r 255

1?57
1

258

xxviii
26

coNrENrs

AMINO ACIDS, PEPTIDES, AND PROTEINS

26.1 Nomenclature

of Amino Acids and Peptides

1255
1266

A. Nomenclature of Amino Acids

B. Nomenclature of Peptides

r266
t267

26.2 Stereochemistry of the rAffiiro Acids

1270

26.3

1271
r27 |

Acid-Base Properties of Amino Acids and Peptides

A. Zwitterionic Structures of Amino Acids and Peptides
B. Isoelectric Points of Amino Acids and Peptides
C. Separations of Amino Acids and Peptides Using Acid-Base Properties

26.4 Synthesis and Enantiomeric Resolution of a-Ami]ro Acids

t273
r271

1279

A. Alkylation of Ammonia
B. Alkylation of Aminomalonate Derivatives

1279

C. Strecker Synthesis
D. Enantiomeric Resolution of a-Amino Acids

26.5 Acylation and Esterification

Reactions of Amino Acids

26.6 Solid-PhasePeptideSynthesis
26.7 Hydrolysis of Peptides

1279

1282
r 283
129?^

A. Complete Hydrolysis and Amino Acid Analysis

B. Enzyme-C ataly zed Peptide Hydrolysis

r292

26.8 Primary Structure of Peptides and Proteins

1296

A. Peptide Sequencing by Mass Spectrometry

B. Peptide Sequencing by the Edman Degradation

I 303

1295

r299

C. Protein Sequencing
D. Posttranslational Modification of Proteins

26.9

Higher-Order Structures of Proteins

I 305
1

A. Secondary Structure
B. Tertiary and Quaternary Structure

26.10 Enzymes: Biological Catalysts

Key ldeas in Chapter 26
Additional Problems

PERICYCLIC REACTIONS

27.1

Molecular Orbitals of Gonjugated rrElectron Systems

A. Molecular Orbitals of Conjugated Alkenes

305

308
I 308
1310

131 5

A. The Catalytic Action of Enzymes

B. Enzymes as Drug Targets: Enzyme Inhibition

27

280

128 I

1315
1318

323
1324

1333
1

336
I

336

coNrENrs xxix
B. Molecular Orbitals of Conjugated Ions and Radicals

340
1343
I

C. Excited States

27.2 Electrocyclic

Reactions

1343

A. Ground-State (Thermal) Electrocyclic Reactions

B. Excited-State (Photochemical) Electrocyclic Reactions

1343

C. Selection Rules and Microscopic Reversibility

t317

27.3 Cycloaddition Reactions

27.4 Thermal Sigmatropic Reaction$
A. Classiflcation and Stereochemistry
B. Thermal [3,3] Sigmatropic Reactions
C. Summary: Selection Rules for Thermal Sigmatropic Reactions

27.5 Fluxional Molecules

27.6 Biological Pericyclic

r346

1349
1

3S3
1353
I

360

t362

1364

Reactions:
The Formation of Vitamin D

1365

Key ldeas in Chapter 27

Additional Prohlems

1367
1 368

APPENDIGES

A-1

Appendix l.

Substitutive Nomenclature of Organic Gompounds

A-1

Appendix ll.

lnfrared Absorptions of Organic Compounds

A-2

Appendix lll.

Proton NMR Chemical Shifts in Organic Compounds

A'5

A. Protons within Functional Groups

B. Protons Adjacent to Functional Groups

A-5
A-5

t3C NMR

A-7

APPENDIX IV.

Chemical Shifts in Organic Gompounds

A. Chemical Shifts of Carbons within Functional Groups

B. Chemical Shifts of Carbons Adjacent to Functional Groups

ITPPENDIX V.

A-l
A-1

Summary of Synthetic Method$

A-g

A. Synthesis of Alkanes and Aromatic Hydrocarbons

A-8
A-9
A-9
A-9
A-9

B. Synthesis of Alkenes
C. Synthesis of Alkynes

D. Synthesis of Alkyl, Aryl, and Vinylic Halides

E. Synthesis of Grignard Reagents and Related Organometallic Compounds
F. Synthesis of Alcohols and Phenols
G. Synthesis of Glycols
H. Synthesis of Ethers, Acetals, and Sulfides
I. Synthesis of Epoxides
J. Synthesis of Disulfides

A-10
A-10
A- 10

A-10
A-10

xxx

loNrENrs
K. Synthesis of Aldehydes

A-11
A-11
A-11
A-11
A-T2
A-T2

L. Synthesis of Ketones
M. Synthesis
N. Synthesis
O. Synthesis
P. Synthesis
Q. Synthesis
R. Synthesis
S. Synthesis
T. Synthesis
U. Synthesis

APPENDIXVI.
APPENDIXVII.

of Sulfoxides and Sulfones

of Carboxylic and Sulfonic Acids
of Esters
of Anhydrides
of Acid Chlorides
of Amides
of Nitriles
of Amines
of Nimo Compounds

A-t2
A-12

A-t2
A.T2
A-13

Reactions Used to Form Garbon-Carbon Bonds

Typlcal Aclditles and Baslcltles of OGanlc Functlonal
A. Acidities of Groups That Ionize to Give Anionic Conjugate Bases
B. Basicities of Groups That Protonate to Give Cationic Conjugate Acids

Credits
Index

A-13

Groups

A-14
A-14
A-15

c-1
l-1