Organic chemistry structure, mechanism and synthesis by robert j ouellette and j david rawn

Organic Chemistry:

Structure, Mechanism, and Synthesis


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Organic Chemistry:

Structure, Mechanism, and Synthesis

Robert J. Ouellette
Professor Emeritus, Department
of Chemistry, The Ohio State University

And

J. David Rawn
Professor Emeritus,
Towson University

AMSTERDAM • BOSTON • HEIDELBERG • LONDON • NEW YORK • OXFORD
PARIS • SAN DIEGO • SAN FRANCISCO • SINGAPORE • SYDNEY • TOKYO


Elsevier
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Library of Congress Cataloging-in-Publication Data
Rawn, J. David, 1944Organic chemistry / J. David Rawn, Robert J. Ouellette. – First edition.
  pages cm
  Includes index.
  ISBN 978-0-12-800780-8
  1. Chemistry, Organic–Textbooks. I. Ouellette, Robert J., 1938- II. Title.
  QD251.3.R39 2014
 547–dc23
British Library Cataloguing in Publication Data
A catalogue record for this book is available from the British Library
For information on all Elsevier publications
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Printed and bound in China
14 15 16 17 18  10 9 8 7 6 5 4 3 2 1
ISBN: 978-0-12-800780-8

2013050560

To our families

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Contents
Acknowledgments
Preface

xxxiii
xxxv

Chapter 1 structure and bonding in organic compounds
Table of Contents
1.1 Brief review of atomic structure

Page
1

Atomic Structure
Atomic Orbitals
Valence Shell Electrons

1

1.2 Atomic properties

3

Atomic Radius

3

Electronegativity

3

1.3 ionic and covalent bonds

4

Ionic Bonds
Covalent Bonds
Structural Formulas
Multiple Covalent Bonds
Polar Covalent Bonds

4

1.4 strategies for writing Lewis structures
1.5 formal charge
1.6 molecular geometry

8

2
3

5
6
6
7
10
11

Bond Lengths
Drawing Structures

11

1.7 resonance structures

12

Nonequivalent Resonance Structures

13

1.8 valence shell electron Pair repulsion theory
1.9 dipole moments

15

Determining Charge Separation
Bond Polarity and Molecular Geometry

16

1.10 molecular orbital theory

18

Molecular Orbitals

18

1.11 The hydrogen molecule
1.12 bonding in carbon compounds

19

Orbital Hybridization

21

1.13 sp3 hybridization of carbon in methane
1.14 sp3 hybridization of carbon in ethane
1.15 sp2 hybridization of carbon in ethene
1.16 sp hybridization of carbon in ethYne
1.17 effect of hybridization on bond length and bond strength
1.18 hybridization of nitrogen
1.19 hybridization of oxygen

21

12

16
17

20

22
23
25
27
27
30
vii


Summary of Orbital Hybridization and Its Relation to VSEPR Theory

32

exercises

33

Chapter 2 Part I: Functional Groups and Their Properties
Table of Contents
2.1 INTRODUCTION TO FUNCTIONAL GROUPS: HYDROCARBONS AND HALOALKANES

Page
41

Hydrocarbons
Haloalkanes

41

2.2 FUNCTIONAL GROUPS THAT CONTAIN OXYGEN

43

Carbon–Oxygen Single Bonds in Alcohols and Ethers
Carbon–Oxygen Double Bonds in Aldehydes and Ketones
Carbon–Oxygen Bonds in Carboxylic Acids and Esters

43

2.3 FUNCTIONAL GROUPS THAT CONTAIN NITROGEN
2.4 FUNCTIONAL GROUPS THAT CONTAIN sulfur
2.5 STRUCTURAL FORMULAS
2.6 BOND-LINE STRUCTURES

45

Recognizing Structural Features in Complex Molecules

50

2.7 isomers

52

Nomenclature

54

Part II: Identification of Functional Groups by infrared
spectroscopy
2.8 SPECTROSCOPY
2.9 infrared sPECTROSCOPY

42

43
44
47
48
49

55
57

The Relation of Vibrational Frequencies and the Masses of Bonded Atoms

57

2.10 IDENTIFYING HYDROCARBONS
2.11 IDENTIFYING OXYGEN-CONTAINING COMPOUNDS

58

The Carbonyl Group
Alcohols and Ethers
Carboxylic Acids
Esters
Carboxylic Acid Anhydrides

61

2.12 IDENTIFYING nitroGEN-CONTAINING COMPOUNDS

64

Amines
Nitriles

65

2.13 BENDING DEFORMATIONS

66

Alkenes
Bending Modes in Aromatic Compounds

66

end-of-chapter exercises

69

61
62
63
63
64

66

66

Chapter 3 Introduction to organic reaction mechanisms
Table of Contents
3.1 acid-base reactions
viii

Page
75


Brønsted-Lowry Acids and Bases
Lewis Acids

75

3.2 CHEMICAL EQUILIBRIUM AND EQUILIBRIUM CONSTANTS

78

Le Chatelier’s Principle

79

3.3 pH AND pK VALUES

80

Ka and pKa
Kb and pKb
Applying pKa Values in Organic Acid-Base Reactions

80

76

81
82

3.4 EFFECT OF STRUCTURE ON ACIDITY

84

Effect of Periodic Trends on Acidity and Basicity
Effect of Resonance on Acidity and Basicity
Inductive Effects
Effect of Hybridization on Acidity

84

3.5 STANDARD FREE ENERGY CHANGES IN CHEMICAL REACTIONS

86

The Standard Free Energy Change and the Equilibrium Constant

86

3.6 ENTHALPY CHANGES IN CHEMICAL REACTIONS
3.7 BOND DISSOCIATION ENERGIES

88

Effect of Electronegativity on Bond Energies
Effect of Hybridization on Bond Energies
Effect of Multiple Bonds on Bond Energies

89

3.8 INTRODUCTION TO REACTION MECHANISMS

90

Concerted and Multistep Reactions
Types of Bond Cleavage

90

3.9 STRUCTURES AND STABILITIES OF CARBON RADICALS, CARBOCATIONS,

AND CARBANIONS

91

Carbocations
Carbon Radicals
Methyl Radical
Carbanions

91

3.10 FACTORS THAT INFLUENCE REACTION RATES

94

The Effect of Structure on Reactivity
The Effect of Reactant Concentration on Reaction Rates
The Effect of Temperature on Reaction Rates
The Effect of Catalysts on Reaction Rates

94

3.11 reaction rate theory

97

Reaction Coordinate Diagrams
Reaction Coordinate Diagrams and Reaction Mechanisms
Catalysis
Transition State Structure: The Hammond Postulate

97

3.12 STABILITY AND REACTIVITY
end-of-chapter exercises

84
85
85

89
90
90

90

93
93
93

95
95
96

98
100
101
102
103

ix


Chapter 4 Alkanes and Cycloalkanes: Structures and reactions
Table of Contents

Page

4.1 CLASSES OF HYDROCARBONS

111

4.2 alkanes

112

Classification of Carbon Atoms

113

4.3 NOMENCLATURE OF ALKANES

114

IUPAC Rules for Naming Alkanes
Names of Alkyl Groups

114

4.4 CONFORMATIONS OF ALKANES

119

Conformations of Ethane
Newman Projection Formulas
Barrier to Rotation in Ethane
Confirmations of Propane
Conformations of Butane
Conformations of Acyclic Compounds
Conformations and Biological Activity

119

4.5 cyclolakanes

126

Geometric Isomerism
Nomenclature of Cycloalkanes
Relative Stabilities of Cycloalkanes

126

4.6 CONFORMATIONS OF CYCLOALKANES

131

Cyclopropane
Cyclobutane
Cyclopentane

Cyclohexane
Drawing Cyclohexane Rings

131

4.7 CONFORMATIONAL MOBILITY OF CYCLOHEXANE

134

Chair-Chair Interconversion of Cyclohexane Rings
Boat Conformation of Cyclohexane
Twist Boat Conformation of Cyclohexane

134

4.8 MONOSUBSTITUTED CYCLOHEXANES
4.9 DiSUBSTITUTED CYCLOHEXANES

136

cis- and trans-1,4-Dimethylcyclohexanes
cis- and trans-1,2-Dimethylcyclohexanes
Compounds with Two Different Substituents

137

4.10 polycyclic molecules

141

cis- and trans-Decalin
The Steroid Ring System
Human Physiological Effects of steroids

141

4.11 PHYSICAL PROPERTIES OF ALKANEs

142

van der Waals Forces (London Forces)
Boiling Points of Alkanes
Solubility of Alkanes

142

x

116

120
120
121
122
124
125

128
129

131
132
132
133

134
135
137
139
140

141
142

143
144


Densities of Alkanes

144

4.12 STABILITIES OF ALKYL RADICALS

145

Bond Dissociation Energies of Alkanes

145

4.13 CHLORINATION OF AN ALKANE—A RADICAL REACTION

148

Regioselectivity of Alkane Halogenation

148

Reactivity and Statistical Factors

150

Enthalpy Changes for Halogenation Reactions

151

Activation Energy for Halogenation

152

Reactivity and Selectivity

153

EXERCISES

155

Chapter 5 Alkenes Structures and properties
Table of Contents

Page

5.1 ALKENES

163

5.2 STRUCTURE AND bonding OF ALKENES

164

Bond Length and Bond Energies
Classification of Alkenes

165

5.3 UNSATURATION NUMBER
5.4 GEOMETRIC ISOMERISM
5.5 E,Z NOMENCLATURE OF GEOMETRICAL ISOMERS

167

Sequence Rules

171

5.6 NOMENCLATURE OF ALKENES

173

Common Names of Alkenyl Groups
IUPAC Names of Alkenes

173

5.7 PHYSICAL PROPERTIES OF ALKENES

175

Density of Alkenes
Polarity of Alkenes
Boiling Points of Alkenes

175

5.8 stability of ALKENES
5.9 reduction OF ALKENES

177

Regioselectivity of Catalytic Hydrogenation
Homogenous Catalytic Hydrogenation

180

5.10 mechanism of catalytic hydrogenation

181

Stereochemistry of Hydrogenation

Stereoselectivity of Hydrogenation

181

5.11 HEATS OF HYDROGENATION OF ALKENES

183

Structural Effects on Heats of Hydrogenation

183

EXERCISES

185

166
168
170

173

175
176
178
180

181

Chapter 6 Alkenes: Addition reactions

Table of Contents

Page

6.1 CHARACTERISTICS OF ADDITION REACTIONS

195

Stereochemistry of Addition Reactions

196

xi


Carbocations in Addition Reactions

196

6.2 ADDITION OF HYDROGEN HALIDES TO ALKENES

197

Regiospecificity of Hydrogen Halide Addition
Markovnikov’s Rule
Synthesis of Alkyl Chlorides

197

6.3 THE MECHANISTIC BASIS OF MARKOVNIKOV’S RULE

199

Hammond Postulate and Electrophilic Addition

200

6.4 CARBOCATION REARRANGEMENT REACTIONS
6.5 HYDRATION OF ALKENES

201

Reversibility of Hydration

204

6.6 ADDITION OF HALOGENS

205

Stereochemistry of Halogen Addition
Mechanism of Halogen Addition
Formation of Halohydrins

206

6.7 ADDITION OF CARBENES

208

Formation of Dichlorocarbene
Stereospecificity of Carbene Addition Reaction
Carbenoid Species

208

6.8 EPOXIDATION OF ALKENES

210

Mechanism of Epoxidation

211

6.9 DIHYDROXYLATIN OF ALKENES

212

Dihydroxylation with Osmium Tetraoxide
Mechanism of Syn Dihydroxylation

213

6.10 OZONOLYSIS OF ALKENES

214

Mechanism of Ozonolysis
Reductive and Oxidative Workup

214

exercises

217

198
199

204

206
207

209
209

213

215

Chapter 7 alkynes
Table of Contents

Page

7.1 OCCURRENCE AND USES OF ALKYNES

223

7.2 STRUCTURE AND PROPERTIES OF ALKYNES

224

Classification of Alkynes
Hybridization, Bond Length, and Bond Energies in Alkynes
Physical Properties of Alkynes
Chemical Properties of Alkynes

224

7.3 IUPAC NAMES OF ALKYNES
7.4 ACIDITY OF TERMINAL ALKYNES
7.5 HYDROGENATION OF ALKYNES

227

Syn Addition of Hydrogen
Anti Addition of Hydrogen
Mechanism of Anti Addition

229

xii

224
225
226
228
228

229
230


7.6 ELECTROPHILIC ADDITION REACTIONS

231

Addition of Hydrogen Halides
Addition of Halogens
Hydration of Alkynes

231

7.7 SYNTHESIS OF ALKYNES

234

Elimination Reactions of Dihalides
Alkylation of Alkynes

234

exercises

236

232
233

235

Chapter 8 stereochemistry
Table of Contents
8.1 STEREOISOMERS

Page

8.2 MIRROR IMAGE OBJECTS, MIRROR IMAGE MOLECULES, AND CHIRALITY

241

Chiral Molecules

242

Mirror Image Isomers

243

Properties of Enantiomers

245

8.3 OPTICAL ACTIVITY

246

Plane-Polarized Light

246

Specific Rotation

246

Circularly Polarized Light and Optical Rotation

247

Optical Purity

248

8.4 FISCHER PROJECTION FORMULAS

250

8.5 ABSOLUTE CONFIGURATION

251

R,S Configurations: The Kahn-Ingold-Prelog System of Configurational Nomenclature

252

Priority Rules

252

8.6 MOLECULES WITH TWO (OR MORE) STEREOGENIC CENTERS

254

Nonequivalent Stereogenic Centers

255

Nomenclature of Diastereomers

256

Equivalent Stereogenic Centers

257

8.7 Cyclic Molecules with Stereogenic Centers

260

Cyclic Structures with One Stereogenic Center
Cyclic Structures with Two Stereogenic Centers: Disubstituted Cyclobutanes
Cyclic Structures with Two Stereogenic Centers: Dimethyl Cyclohexanes
Chirality and Our Senses of Taste and Smell

260

8.8 SEPARATION OF ENANTIOMERS

266

General Principles
Chiral Chromatography

266

8.9 CHEMICAL REACTIONS AT STEREOGENIC CENTERS

268

Reactions of Chiral Molecules That Do Not Occur at the Stereogenic Center
Preview: Stereochemistry of a Substitution Reaction at a Stereogenic Center
Stereochemistry of a Free Radical Reaction

268

241

261
261
265

267

268
269
xiii


8.10 REACTIONS THAT PRODUCE STEREOGENIC CENTERS

270

Stereochemistry of Markovnikov Addition to Alkenes
Stereochemistry of Alkene Bromination

270

8.11 REACTIONS THAT FORM DIASTEREOMERS
8.12 PROCHIRAL CENTERS
exercises

273

271
274
276

Chapter 9 Haloalkanes and alcohols Introduction to
Nucleophilic Substitution and Elimination Reactions
Table of Contents

Page

9.1 FUNCTIONALIZED HYDROCARBONS

287

Classification of Haloalkanes and Alcohols
Interconversion of Haloalkanes and Alcohols

287

9.2 NOMENCLATURE OF HALOALKANES

288

IUPAC Names of Haloalkanes

289

9.3 NOMENCLATURE OF alcohols
9.4 STRUCTURE AND PROPERTIES OF HALOALKANES
9.5 STRUCTURE AND PROPERTIES OF alcohols

290

Boiling Points of Alcohols
Solubility of Alcohols in Water
Alcohols as Solvents

294

9.6 ORGANOMETALLIC COMPOUNDS

295

Grignard Reagents
Organolithium Reagents

295

9.7 REACTIONS OF HALOALKANES
9.8 NUCLEOPHILIC SUBSTITUTION REACTIONS OF HALOALKANES
9.9 MECHANISMS OF NUCLEOPHILIC SUBSTITUTION REACTIONS
OF HALOALKANES

297

The SN2 Mechanism
Biological Methylation by an SN2 Mechanism
The SN1 Mechanism
Carbocation Rearrangements in SN1 Reactions

300

288

292
293
295
295

297
298
300

301
303
304

9.10 REACTIONS OF ALCOHOLS
9.11 ACID-BASE REACTIONS OF ALCOHOLS
9.12 SUBSTITUTION REACTIONS OF ALCOHOLS

306

Reaction Mechanisms
Structural Effects in SN2 and SN1 Mechanisms

308

307
308
309

9.13 ALTERNATE METHODS FOR THE SYNTHESIS OF ALKYL HALIDES
9.14 ELIMINATION REACTIONS

310

Dehydrohalogenation
Dehydration

310

9.15 REGIOSELECTIVITY IN DEHYDROHALOGENATION

312

xiv

310
311


9.16 MECHANISMS OF DEHYDROHALOGENATION REACTIONS

313

The E2 Mechanism
Stereoelectronic Effects in the E2 Reaction
Stereoselectivity in E2 Reactions
The E1 Mechanism

313

9.17 REGIOSELECTIVITY IN DEHYDRATION reactions

316

Regioselectivity in the Dehydration of Alcohols
Mechanism of Alcohol Dehydration Reactions
Rearrangements in Dehydration Reactions

316

exercises

320

313
315
315

316
317

Chapter 10 Nucleophilic Substitution and Elimination
Reactions
Table of Contents

Page

10.1 PROPERTIES OF NUCLEOPHILES

333

Trends in Nucleophilicity Within a Period
Effects of Solvent on Nucleophilicity
Trends in Nucleophilicity Within a Group
Effect of Charge on Nucleophilicity
Steric Effects on Nucleophilicity

333

10.2 BIOLOGICAL SN2 REACTIONS of SULFUR-CONTAINING NUCLEOPHILES
10.3 STEREOCHEMISTRY OF NUCLEOPHILIC SUBSTITUTION REACTIONS
Stereochemistry of the SN2 Mechanism
Stereochemistry of the SN1 Mechanism

10.4 SN1 VERSUS SN2 REACTIONS
The Effect of Substrate Structure on SN1 and SN2 Reaction
The Effect of the Nucleophile on SN1 and SN Reactions

336

334
334
335
335
337
337
338
339
339
341

The Effect of the Leaving Group on Nucleophilic Substitution Reactions
The Effect of the Solvent on Nucleophilic Substitution Reactions

341

10.5 MECHANISMS OF ELIMINATION REACTIONS

346

Stereoelectronic Effects in Elimination Reactions
Deuterium Isotope Effects in Elimination Reactions
Base Strength and Competing E2 and E1 Mechanisms
Steric Effect of the Base on the Regiochemistry of E2 Reactions

346

10.6 EFFECTS OF STRUCTURE ON COMPETING SUBSTITUTION AND ELIMINATION
REACTIONS

348

Competing Substitution and Elimination Reactions of Tertiary Haloalkanes
Competing Substitution and Elimination Reactions of Primary Haloalkanes
Competing Substitution and Elimination Reactions of Secondary Haloalkanes

348

exercises

352

344

347
347
347

349
350

xv

Chapter 11 conjugated alkenes and allylic systems
Table of Contents

Page

11.1 CLASSES OF DIENES

357

Isoprene and Neoprene

357

11.2 STABILITY OF CONJUGATED DIENES
11.3 MOLECULAR ORBITALS OF ETHENE AND 1,3-BUTADIENE

360

Molecular Orbitals of Ethene
Symmetry of Molecular Orbitals
Molecular Orbitals of 1,3-Butadiene

361

11.4 STRUCTURAL EFFECTS OF CONJUGATION IN 1,3-BUTADIENE

366

Effects on Bond Length
Effect of Conjugation On the Barrier to Rotation of 1,3-Butadiene

366

11.5 ALLYLIC SYSTEMS

367

Allylic Carbocations
Allylic Free Radicals
Free Radical Reactions at Allylic Centers
Free Radical Reactions at Allylic Centres Catalyzed by N-Bromosuccinimide
Mechanism of Reaction Catalyzed by NBS
Allylic Free Radicals and Vitamin E

367

11.6 HÜCKEL MOLECULAR ORBITALS OF ALLYL SYSTEMS

375

Allylic Oxidation and the Metabolism of Marijuana

378

11.7 ELECTROPHILIC ADDITION TO CONJUGATED DIENES

379

1,2- and 1,4-Electrophilic Addition Reactions
Kinetic Control of 1,2- and 1,4-Electrophilic Addition Reactions

Thermodynamic Control of 1,2- and 1,4-Electrophilic Addition Reactions

379

11.8 the diels-alder reaction
11.9 the electromagnetic spectrum
11.10 ultravioltet-visible spectroscopy of alkenes and conjugated
systems

382

Molecular Orbitals and Electronic Transitions
Conjugated Double Bonds and the Colors of Organic Compounds

386

exercises

390

361
362
363

366

369
370
371
371

373

380
380
384
386

387

Chapter 12 arenes and aromaticity
Table of Contents

Page

12.1 aromatic compounds

397

12.2 THE COVALENT STRUCTURE OF BENZENE

398

Resonance Theory and Benzene
Resonance Energy

399

12.3 THE HÜCKEL RULE

401

Nonaromatic and Antiaromatic Cyclic Polyenes
Aromatic Ions

401

xvi

400

402


12.4 MOLECULAR ORBITALS OF AROMATIC AND ANTIAROMATIC COMPOUNDS
12.5 HETEROCYCLIC AROMATIC COMPOUNDS
12.6 POLYCYCLIC AROMATIC COMPOUNDS

405

Carcinogenic Aromatic Compounds

410

exercises

412

407
409

Chapter 13 Electrophilic Aromatic Substitution
Table of Contents

Page

13.1 NOMENCLATURE OF BENZENE DERIVATIVES

417

13.2 mechanism of ELECTROPHILIC AROMATIC SUBSTITUTION

420

Mechanism of Electrophilic Aromatic Substitution

420

13.3 common electrophilic aromatic substitution reactions

422

Halogenation
Nitration
Sulfonation
Alkylation: The Friedel-Crafts Reaction
Friedel-Crafts Acylation

422

Limitations of the Fridel-Crafts Reaction

427

13.4 SUBSTITUENT effects ON the REACTIVITY OF BENZENE RINGS

429

Effects of Ring Substituents on Reaction Rate
Orientation Effects of Ring Substituents

429

13.5 INTERPRETATION OF THE EFFECT OF SUBSTITUENTS ON REACTION RATES

432

Inductive Effects of Substituents
Resonance Effects of Substituents

432

13.6 INTERPRETATION OF DIRECTING EFFECTS
13.7 FUNCTIONAL GROUP MODIFICATION

434

Alkyl Side Chain Oxidation
Conversion of an AcyI Group to an AlkyI Group
Reduction of a Nitro Group to an Amino Group
Converting an Amino Group to a Diazonium Ion: The Sandmeyer Reaction

437

13.8 SYNTHESIS OF SUBSTITUTED AROMATIC COMPOUNDS

440

Strategies for Aromatic Synthesis: Order of Group Substitution
Modifying Ring Substituents

441

exercises

444

422
423
424
425

430

433
437
438
439
439

442

Chapter 14 methods for structure determination
nuclear magnetic resonance and mass spectrometry
Table of Contents

Page

14.1 STRUCTURE DETERMINATION

453

14.2 NUCLEAR MAGENTIC RESONANCE SPECTROSCOPY

454

Detecting Nuclear Spin
The Role of Magnetic Field Strength in NMR

454
455
xvii


14.3 the chemical shift

456

The Delta Scale
The Operating Radio Frequency and the Chemical Shift

457

14.4 DETECTING SETS OF NONEQUIVALENT HYDROGEN ATOMS

458

Diastereotopic and Enantiotopic Hydrogen Atoms

459

14.5 EFFECTS OF STRUCTURE ON CHEMICAL SHIFT

461

Electronegativity Effects
Effect of π Electrons
Chemical Shifts of Hydrogen Atoms

461

14.6 RELATIVE PEAK AREAS AND PROTON COUNTING
14.7 SPIN-SPIN SPLITTING

463

Characteristics of Multiplets
Splitting Patterns of the Ethyl Group and the Isopropyl Group
Multiple Splitting: The Vinyl Group

466

14.8 EFFECT OF STRUCTURE ON COUPLING CONSTANTS

471

Effect of Dihedral Angle on Coupling Constants
Long-Range Coupling in Aromatic Compounds

471

14.9 EFFECT OF DYNAMIC PROCESSES

473

Conformational Changes
Hydroxyl Hydrogens

473

14.10 CARBON-13 NMR SPECTROSCOPY

475

Characteristics of C Spectra
Proton-Decoupled Spectra
Counting Carbon Atoms in 13C Spectra

475

14.11 INTRODUCTION TO MASS SPECTROMETRY

478

The Mass Spectrometer
The Production of Ions in a Mass Spectrometer
Mass Spectrometry of Hydrocarbons
Identifying Chlorine and Bromine-Containing Compounds in a Mass Spectrum
Mass Spectrometry of Alcohols
Identifying of Nitrogen-Containing Compounds in a Mass Spectrum

479

exercises

485

13

457

461
462
464
467
469

472

474

476
477

479
480
481
482
483

Chapter 15 alcohols: reactions and synthesis
Table of Contents
15.1 OVERVIEW OF ALCOHOL REACTIONS

Page

15.2 CONVERTING ALCOHOLS INTO ESTERS

492

Esters of Nitric, Sulfuric, and Phosphoric Acid
Esters of Carboxylic Acids
Phosphate and Pyrophosphate Esters

492

15.3 CONVERSION OF ALCOHOLS TO HALOALKANES

497

Reaction of Alcohols with Thionyl Chloride

498

xviii

491

494
495


Mechanism of the Reaction of Alcohols with Thionyl Chloride
Reaction of Alcohols with Phosphorus Tribromide

498

15.4 OXIDATION OF ALCOHOLS

500

Oxidizing Agents for Alcohols
Mechanism of Oxidation by Chromium(VI)
Toxicity of Alcohols

501

15.5 REACTIONS OF VICINAL DIOLS

504

The Pinacol Rearrangement
Oxidative Cleavage of Vicinal Diols

504

15.6 SYNTHESIS OF ALCOHOLS

507

Overview of Synthetic Methods
Reductive Synthetic Methods
Alkylation Synthetic Methods

507

15.7 SYNTHESIS OF ALCOHOLS FROM HALOALKANES
15.8 INDIRECT HYDRATION METHODS

508

Oxymercuration-Demercuration
Hydroboration-Oxidation

509

15.9 REDUCTION OF CARBONYL COMPOUNDS

514

Reduction by Metal Hydrides

Solvents for Lithium Aluminum Hydride and Sodium Borohydride
Regioselectivity of Hydride Reduction
Reduction of Other Carbonyl Compounds
Stereoselectivity of Metal Hydride Reduction

514

15.10 ALCOHOL SYNTHESIS USING GRIGNARD REAGENTS

518

Synthesis of Alcohols Using Grignard Reagents
Limitations of the Grignard Reaction
Alcohol Protecting Groups
Acetylenic Alcohols

519

15.11 thiols and thioethers

521

Physical Properties of Thiols
Reactions of Thiols
Synthesis of Thiols

521

exercises

524

499

502
502

505

507
508
509
511

515
515
517
517

519
520
520

521
522

Chapter 16 ethers and epoxides
Table of Contents
16.1 STRUCTURE OF ETHERS

Page

16.2 NOMENCLATURE OF ETHERS

536

Common Names
IUPAC Names
Cyclic Ethers

536

16.3 PHYSICAL PROPERTIES OF ETHERS

538

Dipole Moments and Boiling Points

538

535

536
537

xix


Solubility in Water
Ethers as Solvents

Polyethers

539

16.4 POLYETHER ANTIBIOTICS
16.5 SYNTHESIS OF ETHERS: ALKOXYMERCURATION-DEMERCURATION OF ALKENES
16.6 THE WILLIAMSON ETHER SYNTHESIS

541

Formation of Cyclic Ethers
Rates of Cyclization Reactions

543

16.7 REACTIONS OF ETHERS
16.8 ETHERS AS PROTECTING GROUPs
16.9 SYNTHESIS OF EPOXIDES
16.10 REACTIONS OF EPOXIDES

545

Ring Opening by Nucleophiles
Acid-Catalyzed Ring Opening
Regioselectivity of Ring Opening
Stereochemistry of Ring Opening
Biochemical Reactions of Epoxides

549

16.11 SULFIDES

556

Synthesis of Sulfides
Oxidation of Sulfides

556

16.12 SPECTROSCOPY OF ETHERS, thiols AND SULFIDES

557

Infrared Spectroscopy of Ethers
Proton NMR Spectroscopy
C-13 NMR Spectroscopy

557

exercises

561

539
539
542
543
544
547
548

549
550
550
552
554

557

558
559

Chapter 17 Organometallic chemistry of transition metal
elements and introduction to retrosynthesis
Table of Contents

Page

17.1 brief overview of transition metal complexes

567

Transition Metal Complexes

567

Geometry of Transition Metal Complexes

568

Formation of p Complexes

569

17.2 The gilman reagent

570

Overview of Gilman Reagents

570

Preparation of Gilman Reagents

570

Reactions of Gilman Reagents

571

Oxidative Addition and Reductive Elimination in the Gilman Reaction

572

17.3 overview of palladium catalyzed cross-coupling reactions

573

17.4 the suzuki coupling REACTION

574

Preparation of Aryl Boronic Acids
The Catalytic Cycle in the Suzuki Coupling Reaction

574

xx

576


17.5 the heck reaction

576

The Catalytic Steps in the Heck Reaction

577

17.6 the sonOgashira reaction

579

The Catalytic Cycles in the Sonogashira Reaction
The Palladium Cycle
The Copper Cycle

579

17.7 THE wilkinson catalyst: homogeneous catalytic hydrogenation

580

Relative Reactivities of Alkenes in Wilkinson Homogenous Hydrogenation

581

17.8 asymmetric hydrogenation with chiral ruthenium catalysts

582

Chiral Binaphthyl Compounds
Noyori Asymmetric Reduction of Ketones

582

17.9 The Grubbs reaction: A metathesis reaction for alkene synthesis

584

The Grubbs Metathesis Reaction
The Grubbs Catalyst
The Chauvin Mechanism for the Grubbs Reaction

584

17.10 introduction to retrosynthesis: thinking backwards

586

The Terminology of Retrosynthesis
Synthesis of Terpinolene: A Retrosynthetic Analysis

586

exercises

590

579
580

583

584
586

587

Chapter 18 aldehydes and ketones
Table of Contents
18.1 THE CARBONYL GROUP

Page

Carbonyl Compounds
Naturally Occurring Aldehydes and Ketones

596

18.2 NOMENCLATURE OF ALDEHYDES AND KETONES

597

Common Names of Aldehydes
IUPAC Names of Aldehydes
IUPAC Names of Ketones

597

18.3 PHYSICAL PROPERTIES OF ALDEHYDES AND KETONES

600

Boiling Points of Aldehydes and Ketones
Solubility of Aldehydes and Ketones in Water
Acetone and 2-Butanone as Solvents

601

18.4 OXIDATION-REDUCTION REACTIONS OF CARBONYL COMPOUNDS

603

Oxidation of Aldehydes
Reduction of Aldehydes and Ketones to Alcohols
Reduction of a Carbonyl Group to a Methylene Group
NAD-Dependent Oxidation of Ethanol

603

18.5 SYNTHESIS OF CARBONYL COMPOUNDS: A REVIEW

606

Oxidation of Alcohols
Friedel-Crafts Acylation
Ozonolysis of Alkenes
Oxidative Cleavage of Vicinal Diols

606

595
597

598
599

601
602

604
604
605

607
607
608

xxi

Hydration of Alkynes

608

18.6 SYNTHESIS OF CARBONYL COMPOUNDS: A PREVIEW

610

Reduction of Acid Chlorides
Reduction of Esters
Reactions of Acid Derivatives with Organometallic Reagents
Synthesis of Carbonyl Compounds From Nitriles

610

18.7 SPECTROSCOPY OF ALDEHYDES AND KETONES

614

Infrared Spectroscopy
Proton NMR Spectroscopy
C-13 NMR Spectroscopy

614

exercises

618

611
612
613

615
616

Chapter 19 aldehydes and ketones: Nucleophilic Addition
Reactions
Table of Contents
19.1 RELATIVE STABILITIES OF ALDEHYDES AND KETONES

Page

19.2 formation of cyanohydrins
19.3 HYDRATION OF CARBONYL COMPOUNDS

630

Steric Effects on Nucleophilic Addition Reactions
Inductive Effects on Addition Reactions

631

19.4 MECHANISMS OF ACID- AND BASE-CATALYZED CARBONYL ADDITION REACTIONS

633

Acid-Catalyzed Nucleophilic Addition Reactions

Base-Catalyzed Nucleophilic Addition Reactions

634

19.5 FORMATION OF ACETALS AND KETALS

635

Mechanism of Acetal and Ketal Formation

636

19.6 ACETALS AS PROTECTING GROUPS

638

Synthesis of Cyclic Acetals
Selective Acetal Synthesis
Protection of Alcohols by Acetal Formation

638

19.7 THIOACETALS AND THIOKETALS
19.8 ADDITION OF NITROGEN COMPOUNDS TO ALDEHYDES AND KETones

641

Stable Imine Derivatives

644

19.9 THE WITTIG REACTION

646

Preparation of Phosphorus Ylides

646

Mechanism of the Wittig Reaction

647

The Wittig Reaction in Organic Synthesis

648

exercises

649

629
630
632

634

639
640
643

Chapter 20 carboxylic acids
Table of Contents
20.1 CARBOXYLic acids AND ACYL GROUPS

Page

The Acyl Group and Carboxylic Acid Derivatives

660

xxii

659


20.2 NOMENCLATURE OF CARBOXYLIC ACIDS

661

Common Names
IUPAC Names of Carboxylic Acids
Names of Carboxylate Anions

661

20.3 PHYSICAL PROPERTIES of carboxylic acids

665

Boiling Points
Melting Points
Solubilities

665

20.4 ACIDITY OF CARBOXYLIC ACIDS

668

Resonance Stabilization of the Carboxylate Ion
Inductive Effect on Acidity
Acidity of Aromatic Carboxylic Acids

668

20.5 CARBOXYLATE ANIONS

671

Carboxylate Ions in Water
Carboxylate Ions in Basic Solution
Separation and Purification of Carboxylic Acids
Soaps and Detergents

671

20.6 SYNTHESIS OF CARBOXYLIC ACIDS

674

Oxidative Methods
Carboxylation of Grignard Reagents
Hydrolysis of Nitriles

674

20.7 REDUCTION OF CARBOXYLIC ACIDS

676

Reduction With Lithium Aluminum Hydride

676

Reduction with Diborane

677

20.8 DECARBOXYLATION REACTIONS

677

The Hunsdiecker Reaction
Biochemical Decarboxylation Reactions

678

20.9 REACTIONS OF CARBOXYLIC ACIDS AND THEIR DERIVATIVES: A PREVIEW

680

Nucleophilic Acyl Substitution

680

20.10 CONVERSION OF CARBOXYLIC ACIDS INTO ACYL HALIDES
20.11 CONVERSION OF CARBOXYLIC ACIDS INTO esters

681

Alkylation of Carboxylate Anions
Esterification With Diazomethane
Reaction of Acyl Chlorides With Alcohols
Fischer Esterification

682

20.12 MECHANISM OF ESTERIFICATION
20.13 brief synthetic Review

684

Functional Group Modification in Organic Synthesis

685

20.14 SPECTROSCOPY OF CARBOXYLIC ACIDS

686

Infrared Spectroscopy
Proton NMR Spectroscopy
Carbon-13 NMR Spectroscopy

686

exercises

691

663
664

666
667

668
670

671
671
672

674
675

679

682

682
683
684
685

687
687
xxiii


Chapter 21 carboxylic acid derivatives
Table of Contents
21.1 NOMENCLATURE OF CARBOXYLIC ACID DERIVATIVES

Page

The Acyl Group and Acid Derivatives

699

Names of Acid Halides

699

Names of Acid Anhydrides

699

Names of Esters

700

Names of Amides

700

Nitriles

701

Names of Nitriles

701

21.2 PHYSICAL PROPERTIES OF ACYL DERIVATIVES

702

Esters
Amides
Nitriles

703

21.3 BASICITY OF CARBOXYLIC ACID DERIVATIVES
21.4 MECHANISM OF NUCLEOPHILIC ACYL SUBSTITUTION

705

Acid-Catalyzed Acyl Substitution Reactions

Base-Catalyzed Acyl Substitution Reactions
Relative Reactivity of Acyl Derivatives
Predicting the Direction of a Nucleophilic Acyl Substitution Reaction

707

21.5 HYDROLYSIS OF ACYL DERIVATIVES

712

Hydrolysis of Acid Chlorides and Anhydrides
Hydrolysis of Esters
Hydrolysis of Amides
Hydrolysis of Nitriles

712

21.6 REACTION OF ACYL DERIVATIVES WITH ALCOHOLS

717

Acid Chlorides
Acid Anhydrides
Esters
Biochemical Hydrolysis of Penicillin

717

21.7 REACTION OF ACYL DERIVATIVES WITH AMINES

719

Acid Chlorides

719

Acid Anhydrides

720

Esters

720

21.8 REDUCTION OF ACYL DERIVATIVES

721

Reduction of Acid Chlorides
Reduction of Esters
Reduction of Amides
Reduction of Nitriles

721

21.9 REACTION OF ACYL DERIVATIVES WITH ORGANOMETALLIC REAGENTS

724

Acid Chlorides

Esters

724

xxiv

699

704
705
706
708
708
711

713
713
714

717
717
718

721
722
722

724