Preview Marchs Advanced Organic Chemistry Reactions, Mechanisms, and Structure, 8th Edition by Michael B. Smith (2020)

MARCH’S
ADVANCED
ORGANIC
CHEMISTRY
R E AC T I O N S , M E C H A N I S M S , A N D S T R U C T U R E

E I G HTH EDITION

8

MI C H A E L B . S M I T H


MARCH’S ADVANCED
ORGANIC CHEMISTRY



MARCH’S ADVANCED
ORGANIC CHEMISTRY
REACTIONS, MECHANISMS,
AND STRUCTURE
EIGHTH EDITION

Michael B. Smith
Professor Emeritus
University of Connecticut
Department of Chemistry
69 Eldredge Road
Willington, CT
USA

This edition first published 2020
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Library of Congress Cataloging-in-Publication Data
Names: Smith, Michael, 1946 October 17- author. | March, Jerry, 1929–1997.
Title: March’s advanced organic chemistry : reactions, mechanisms, and structure.
Other titles: Advanced organic chemistry
Description: Eighth edition / Michael B Smith (University of Connecticut, Department of Chemistry). | Hoboken, NJ : John
Wiley & Sons, Inc., 2020. | Includes index.
Identifiers: LCCN 2019023265 (print) | LCCN 2019023266 (ebook) | ISBN 9781119371809 (cloth) | ISBN
9781119371786 (adobe pdf) | ISBN 9781119371793 (epub)
Subjects: LCSH: Chemistry, Organic.
Classification: LCC QD251.2 .M37 2020 (print) | LCC QD251.2 (ebook) | DDC 547—dc23
LC record available at />LC ebook record available at />Cover image: Background © atakan/iStock.com, All other images courtesy of Michael B. Smith
Cover design by Wiley
Set in 10/12pt TimesLTStd by Aptara Inc., New Delhi, India
10 9 8 7 6 5 4 3 2 1


CONTENTS

NEW REACTION SECTIONS CORRELATION: 7TH EDITION → 8TH
EDITION

xv

PREFACE

xxi

COMMON ABBREVIATIONS

xxv

BIOGRAPHICAL STATEMENT

xxxi

NEW FEATURES OF THE 8TH EDITION
PART I
1.

INTRODUCTION

1

Localized Chemical Bonding

3

1.A.
1.B.
1.C.
1.D.

1.E.
1.F.
1.G.
1.H.
1.I.
1.J.
1.K.
1.L.
2.

xxxiii

Covalent Bonding
Multiple Valence
Hybridization
Multiple Bonds
Photoelectron Spectroscopy
Electronic Structures of Molecules
Electronegativity
Dipole Moment
Inductive and Field Effects
Bond Distances
Bond Angles
Bond Energies

3
7
7
9
12

15
17
19
20
23
27
29

Delocalized Chemical Bonding

33

2.A. Molecular Orbitals
2.B. Bond Energies and Distances in Compounds Containing
Delocalized Bonds
2.C. Molecules that have Delocalized Bonds
2.D. Cross Conjugation
2.E. The Rules of Resonance
2.F. The Resonance Effect
2.G. Steric Inhibition of Resonance and the Influences of Strain
2.H. pπ–dπ Bonding: Ylids

34
37
39
44
46
48
48
52

v


vi

3.

CONTENTS

2.I.

Aromaticity
2.I.i.
Six-Membered Rings
2.I.ii.
Five-, Seven-, and Eight-Membered Rings
2.I.iii.
Other Systems Containing Aromatic Sextets
2.J. Alternant and Nonalternant Hydrocarbons
2.K. Aromatic Systems with Electron Numbers Other Than Six
2.K.i.
Systems of Two Electrons
2.K.ii.
Systems of Four Electrons: Antiaromaticity
2.K.iii. Systems of Eight Electrons
2.K.iv.
Systems of Ten Electrons
2.K.v.
Systems of More than Ten Electrons: 4n + 2 Electrons
2.K.vi.

Systems of More Than Ten Electrons: 4n Electrons
2.L. Other Aromatic Compounds
2.M. Hyperconjugation
2.N. Tautomerism
2.N.i.
Keto–Enol Tautomerism
2.N.ii.
Other Proton-Shift Tautomerism

54
58
62
67
68
70
72
73
76
77
80
85
89
92
96
97
100

Bonding Weaker Than Covalent

105

3.A.
3.B.
3.C.

105
113
114
114
117
122
125
127
131

3.D.
3.E.
4.

Hydrogen Bonding
π–π Interactions
Addition Compounds
3.C.i.
Electron Donor–Acceptor (EDA) Complexes
3.C.ii.
Crown Ether Complexes and Cryptates
3.C.iii.
Inclusion Compounds
3.C.iv.
Cyclodextrins

Catenanes and Rotaxanes
Cucurbit[n]Uril-Based Gyroscane

Stereochemistry and Conformation

133

4.A. Optical Activity and Chirality
4.B. Dependence of Rotation on Conditions of Measurement
4.C. What Kinds of Molecules Display Optical Activity?
4.D. The Fischer Projection
4.E. Absolute Configuration
4.E.i.
The Cahn-Ingold-Prelog System
4.E.ii.
Methods Of Determining Configuration
4.F. The Cause of Optical Activity
4.G. Molecules with More Than One Stereogenic Center
4.H. Asymmetric Synthesis
4.I. Methods of Resolution
4.J. Optical Purity
4.K. Cis–Trans Isomerism
4.K.i.
Cis–Trans Isomerism Resulting from Double Bonds
4.K.ii.
Cis–Trans Isomerism of Monocyclic Compounds
4.K.iii. Cis–Trans Isomerism of Fused and Bridged Ring Systems

133
135

136
147
148
150
152
156
157
161
166
173
175
175
179
180


CONTENTS

4.L.
4.M.
4.N.
4.O.

5.

Out–In Isomerism
Enantiotopic and Diastereotopic Atoms, Groups, and Faces
Stereospecific and Stereoselective Syntheses
Conformational Analysis
4.O.i.

Conformation in Open-Chain Systems
4.O.ii.
Conformation in Six-Membered Rings
4.O.iii. Conformation in Six-Membered Rings Containing
Heteroatoms
4.O.iv.
Conformation in Other Rings
4.P. Molecular Mechanics
4.Q. Strain
4.Q.i.
Strain in Small Rings
4.Q.ii.
Strain in Other Rings
4.Q.iii. Unsaturated Rings
4.Q.iv.
Strain Due to Unavoidable Crowding

181
183
186
187
188
194

Carbocations, Carbanions, Free Radicals, Carbenes, and Nitrenes

223

5.A.

224
224
224
234
237
237
244
249
250
250
261
265
266
266
269
274
276

5.B.

5.C.

5.D.

5.E.
6.

vii

Carbocations

5.A.i.
Nomenclature
5.A.ii.
Stability and Structure of Carbocations
5.A.iii. The Generation And Fate Of Carbocations
Carbanions
5.B.i.
Stability and Structure
5.B.ii.
The Structure Of Organometallic Compounds
5.B.iii.
The Generation And Fate Of Carbanions
Free Radicals
5.C.i.
Stability and Structure
5.C.ii.
The Generation and Fate of Free Radicals
5.C.iii.
Radical Ions
Carbenes
5.D.i.
Stability and Structure
5.D.ii.
The Generation and Fate of Carbenes
5.D.iii. N-Heterocyclic Carbenes (NHCs)
Nitrenes

199
202
204

206
207
213
215
218

Mechanisms and Methods of Determining Them

279

6.A.
6.B.
6.C.
6.D.
6.E.
6.F.
6.G.
6.H.
6.I.

279
280
283
284
288
290
291
291
292

Types of Mechanism
Types of Reaction
Thermodynamic Requirements for Reaction
Kinetic Requirements for Reaction
The Baldwin Rules for Ring Closure
Kinetic and Thermodynamic Control
The Hammond Postulate
Microscopic Reversibility
Marcus Theory


viii

CONTENTS

6.J.

7.

8.

9.

Methods of Determining Mechanisms
6.J.i.
Identification of Products
6.J.ii.
Determination of the Presence of an Intermediate
6.J.iii.
The Study of Catalysis

6.J.iv.
Isotopic Labeling
6.J.v.
Stereochemical Evidence
6.J.vi.
Kinetic Evidence
6.J.vii.
Isotope Effects
6.K. Catalyst Development

293
293
294
295
296
296
297
304
308

Irradiation Processes and Techniques that Influence Reactions in
Organic Chemistry

313

7.A.

Photochemistry
7.A.i.
Excited States and the Ground State

7.A.ii.
Singlet and Triplet States: “Forbidden” Transitions
7.A.iii. Types of Excitation
7.A.iv.
Nomenclature and Properties of Excited States
7.A.v.
Photolytic Cleavage
7.A.vi.
The Fate of the Excited Molecule: Physical Processes
7.A.vii. The Fate of the Excited Molecule: Chemical Processes
7.A.viii. The Determination of Photochemical Mechanisms
7.B. Sonochemistry
7.C. Microwave Chemistry
7.D. Flow Chemistry
7.E. Mechanochemistry

314
314
316
317
318
319
320
325
330
331
334
336
338

Acids and Bases

339

8.A.

Brønsted Theory
8.A.i.
Brønsted Acids
8.A.ii.
Brønsted Bases
8.B. The Mechanism of Proton Transfer Reactions
8.C. Measurements of Solvent Acidity
8.D. Acid and Base Catalysis
8.E. Lewis Acids and Bases
8.E.i.
Hard–Soft Acids–Bases
8.F. The Effects of Structure on the Strengths of Acids and Bases
8.G. The Effects of the Medium on Acid and Base Strength

339
340
347
350
352
355
357
359
361
370

Effects of Structure and Medium on Reactivity

375

9.A.
9.B.
9.C.
9.D.
9.E.
9.F.

375
377
380
390
390
391

Resonance and Field Effects
Steric Effects
Quantitative Treatments of the Effect of Structure on Reactivity
Effect of Medium on Reactivity and Rate
High Pressure
Water and Other Nonorganic Solvents


CONTENTS

9.G.

9.H.
PART II

ix

Ionic Liquid Solvents
Solventless Reactions

393
395

INTRODUCTION

397

10. Aliphatic Substitution, Nucleophilic and Organometallic
10.A. Mechanisms
10.A.i.
The SN 2 Mechanism
10.A.ii. The SN 1 Mechanism
10.A.iii. Ion Pairs in the SN 1 Mechanism
10.A.iv. Mixed SN 1 and SN 2 Mechanisms
10.B. SET Mechanisms
10.C. The Neighboring-Group Mechanism
10.C.i.
Neighboring-Group Participation by π and σ Bonds:
Nonclassical Carbocations
10.D. The SN i Mechanism
10.E. Nucleophilic Substitution at an Allylic Carbon: Allylic
Rearrangements

10.F. Nucleophilic Substitution at an Aliphatic Trigonal Carbon: The
Tetrahedral Mechanism
10.G. Reactivity
10.G.i.
The Effect of Substrate Structure
10.G.ii. The Effect of the Attacking Nucleophile
10.G.iii. The Effect of the Leaving Group
10.G.iv. The Effect of the Reaction Medium
10.G.v. Phase-Transfer Catalysis
10.G.vi. Influencing Reactivity by External Means
10.G.vii. Ambident (Bidentant) Nucleophiles: Regioselectivity
10.G.viii. Ambident Substrates
10.H. Reactions
10.H.i.
Oxygen Nucleophiles
10.H.ii. Sulfur Nucleophiles
10.H.iii. Nitrogen Nucleophiles
10.H.iv. Halogen Nucleophiles
10.H.v. Carbon Nucleophiles
11. Aromatic Substitution, Electrophilic
11.A. Mechanisms
11.A.i.
The Arenium Ion Mechanism
11.A.ii. The SE 1 Mechanism
11.B. Orientation and Reactivity
11.B.i.
Orientation and Reactivity in Monosubstituted Benzene
Rings
11.B.ii. The Ortho/Para Ratio
11.B.iii. Ipso Attack

403
404
404
410
414
418
420
422
425
440
441
445
449
449
457
464
469
474
477
478
481
483
483
506
512
534
545
607
607

608
613
614
614
618
620


x

CONTENTS

11.B.iv.

11.C.
11.D.
11.E.
11.F.

Orientation in Benzene Rings With More Than One
Substituent
11.B.v. Orientation in Other Ring Systems
Quantitative Treatments of Reactivity in the Substrate
A Quantitative Treatment of Reactivity of the Electrophile: The
Selectivity Relationship
The Effect of the Leaving Group
Reactions
11.F.i.
Hydrogen as the Leaving Group in Simple Substitution
Reactions

11.F.ii.
Hydrogen as the Leaving Group In Rearrangement
Reactions
11.F.iii. Other Leaving Groups

12. Aliphatic, Alkenyl, and Alkynyl Substitution: Electrophilic and
Organometallic
12.A. Mechanisms
12.A.i.
Bimolecular Mechanisms. SE 2 and SE i
12.A.ii. The SE 1 Mechanism
12.A.iii. Electrophilic Substitution Accompanied by Double-Bond
Shifts
12.A.iv. Other Mechanisms
12.B. Reactivity
12.C. Reactions
12.C.i.
Hydrogen as Leaving Group
12.C.ii. Metals as Leaving Groups
12.C.iii. Halogen as Leaving Group
12.C.iv. Carbon Leaving Groups
12.C.v. Electrophilic Substitution At Nitrogen
13. Aromatic Substitution: Nucleophilic and Organometallic
13.A. Mechanisms
13.A.i.
The SN Ar Mechanism
13.A.ii. The SN 1 Mechanism
13.A.iii. The Benzyne Mechanism
13.A.iv. The SRN 1 Mechanism
13.A.v. Other Mechanisms

13.B. Reactivity
13.B.i.
The Effect of Substrate Structure
13.B.ii. The Effect of the Leaving Group
13.B.iii. The Effect of the Attacking Nucleophile
13.C. Reactions
13.C.i.
All Leaving Groups Except Hydrogen And N2 +
13.C.ii. Hydrogen as Leaving Group

621
622
624
626
628
629
629
675
680

687
687
688
691
694
695
695
697
697
733

746
751
760
767
768
768
771
772
774
776
776
776
778
779
779
779
823


CONTENTS

13.C.iii.
13.C.iv.

Nitrogen as Leaving Group
Rearrangements

14. Radical Reactions
14.A. Mechanisms
14.A.i.

Radical Mechanisms in General
14.A.ii. Free-Radical Substitution Mechanisms
14.A.iii. Mechanisms at an Aromatic Substrate
14.A.iv. Neighboring-Group Assistance in Free-Radical Reactions
14.B. Reactivity
14.B.i.
Reactivity for Aliphatic Substrates
14.B.ii. Reactivity at a Bridgehead
14.B.iii. Reactivity in Aromatic Substrates
14.B.iv. Reactivity in the Attacking Radical
14.B.v. The Effect of Solvent on Reactivity
14.C. Reactions
14.C.i.
Hydrogen as Leaving Group
14.C.ii. Metals as Leaving Groups
14.C.iii. Halogen as Leaving Group
14.C.iv. Sulfur as Leaving Group
14.C.v. Carbon as Leaving Group
15. Addition to Carbon–Carbon Multiple Bonds
15.A. Mechanisms
15.A.i.
Electrophilic Addition
15.A.ii. Nucleophilic Addition
15.A.iii. Free-Radical Addition
15.A.iv. Cyclic Mechanisms
15.A.v. Addition to Conjugated Systems
15.B. Orientation and Reactivity
15.B.i.
Reactivity
15.B.ii. Orientation

15.B.iii. Stereochemical Orientation
15.B.iv. Addition to Cyclopropane Rings
15.C. Reactions
15.C.i.
Isomerization of Double and Triple Bonds
15.C.ii. Reactions in Which Hydrogen Adds to One Side
15.C.iii. Reactions in Which Hydrogen Adds to Neither Side
15.C.iv. Cycloaddition Reactions
16. Addition to Carbon–Heteroatom Multiple Bonds
16.A. Mechanism and Reactivity
16.A.i.
Nucleophilic Substitution at an Aliphatic Trigonal Carbon:
The Tetrahedral Mechanism

xi

824
834
839
839
839
844
845
847
848
848
853
854
855
856

856
856
880
883
883
885
891
892
892
895
896
898
898
899
899
902
904
906
908
908
910
992
1027
1087
1087
1089


xii

CONTENTS

16.B. Reactions
16.B.i.
Reactions in Which Hydrogen or a Metallic Ion Adds
to the Heteroatom
16.B.ii. Acyl Substitution Reactions
16.B.iii. Reactions in Which Carbon Adds to the Heteroatom
16.B.iv. Addition to Isocyanides
16.B.v. Nucleophilic Substitution at a Sulfonyl Sulfur Atom
17. Elimination Reactions
17.A. Mechanisms and Orientation
17.A.i.
The E2 Mechanism
17.A.ii. The E1 Mechanism
17.A.iii. The E1cB Mechanism
17.A.iv. The E1-E2-E1cB Spectrum
17.A.v. The E2C Mechanism
17.B. Regiochemistry of the Double Bond
17.C. Stereochemistry of the Double Bond
17.D. Reactivity
17.D.i.
Effect of Substrate Structure
17.D.ii. Effect of the Attacking Base
17.D.iii. Effect of the Leaving Group
17.D.iv. Effect of the Medium
17.E. Mechanisms and Orientation in Pyrolytic Eliminations
17.E.i.
Mechanisms
17.E.ii. Orientation in Pyrolytic Eliminations

17.E.iii. 1,4 Conjugate Eliminations
17.F. Reactions
17.F.i.
Reactions in Which C C and C≡C Bonds Are Formed
17.F.ii.
Fragmentations
17.F.iii. Reactions in Which C≡N or C N Bonds Are Formed
17.F.iv. Reactions in Which C O Bonds Are Formed
17.F.v.
Reactions in Which N N Bonds Are Formed
17.F.vi. Extrusion Reactions
18. Rearrangements
18.A. Mechanisms
18.A.i.
Nucleophilic Rearrangements
18.A.ii. The Actual Nature of the Migration
18.A.iii. Migratory Aptitudes
18.A.iv. Memory Effects
18.B. Longer Nucleophilic Rearrangements
18.C. Free-Radical Rearrangements
18.D. Carbene Rearrangements
18.E. Electrophilic Rearrangements
18.F. Reactions

1094
1095
1218
1257
1264
1266

1273
1273
1274
1280
1281
1286
1287
1288
1290
1291
1291
1293
1294
1294
1295
1295
1298
1298
1299
1299
1321
1325
1328
1329
1329
1335
1336
1336
1337
1340

1343
1344
1345
1349
1349
1350


CONTENTS

18.F.i.
18.F.ii.

1,2-Rearrangements
Non 1,2-Rearrangements

xiii

1350
1389

19. Oxidations and Reductions

1439

19.A. Mechanisms
19.B. Reactions
19.B.i.
Oxidations
19.B.ii. Reductions

1440
1442
1442
1510

APPENDIX A: THE LITERATURE OF ORGANIC CHEMISTRY

1607

APPENDIX B: CLASSIFICATION OF REACTIONS BY TYPE OF
COMPOUNDS SYNTHESIZED

1645

INDEXES
AUTHOR INDEX
SUBJECT INDEX

1669
1917



NEW REACTION SECTIONS CORRELATION: 7TH
EDITION → 8TH EDITION

7TH → 8TH
10-1 → 10-1
10-2 → 10-2

10-3 → 10-3
10-4 → 10-4
10-5 → 10-5
10-6 → 10-6
10-7 → 10-7
10-8 → 10-8
10-9 → 10-9
10-10 → 10-10
10-11 → 10-11
10-12 → 10-12
10-13 → 10-13
10-14 → 10-14
10-15 → 10-15
10-16 → 10-16
10-17 → 10-17
10-18 → 10-18
10-19 → 10-19
10-20 → 10-20
10-21 → 10-21
10-22 → 10-22
10-23 → 10-23
10-24 → 10-24
10-25 → 10-25
10-26 → 10-26
10-27 → 10-27
10-28 → deleted, now
with 10-27
10-29 → 10-28
10-30 → 10-29
10-31 → 10-30

10-32 → 10-31
10-33 → 10-32
10-34 → 10-33
10-35 → 10-34

10-36 → 10-35
10-37 → 10-36
10-38 → 10-37
10-39 → 10-38
10-40 → 10-39
10-41 → 10-40
10-42 → 10-41
10-43 → 10-42
10-44 → 10-43
10-45 → 10-44
10-46 → 10-45
10-47 → 10-46
10-48 → 10-47
10-49 → 10-48
10-50 → 10-49
10-51 → 10-50
10-52 → 10-51
10-53 → 10-52
10-54 → 10-53
10-55 → 10-54
New 10-55
10-56 → 10-56
10-57 → 10-57
10-58 → 10-58
10-59 → 10-59

10-60 → 10-60
10-61 → 10-61
10-62 → 10-62
10-63 → 10-63
10-64 → 10-64
10-65 → 10-65
10-66 → 10-66
10-67 → 10-67
10-68 → 10-68
10-69 → 10-69
10-70 → 10-70

10-71 → 10-71
10-72 → 10-72
10-73 → 10-73
10-74 → 10-74
New 10-75
10-75 → 10-76
10-76 → 10-77
10-77 → 10-78
New 10-79
11-1 → 11-1
11-2 → 11-2
11-3 → 11-3
11-4 → 11-6
11-5 → 11-5
11-6 → 11-4
11-7 → 11-7
11-8 → 11-8
11-9 → 11-9

11-10 → 11-10
11-11 → 11-11
11-12 → 11-12
11-13 → 11-13
11-14 → 11-14
11-15 → 11-15
11-16 → 11-16
11-17 → 11-17
11-18 → 11-18
11-19 → 11-19
11-20 → deleted, now
with 11-19
11-21 → 11-20
New 11-21
11-22 → 11-22
11-23 → 11-23
11-24 → 11-24
xv


xvi

NEW REACTION SECTIONS CORRELATION: 7TH EDITION → 8TH EDITION

11-25 → 11-25
11-26 → 11-26
11-27 → 11-27
11-28 → 11-28
11-29 → 11-29
11-30 → 11-30

11-31 → 11-31
11-32 → 11-32
11-33 → 11-33
11-34 → 11-34
11-35 → 11-35
11-36 → 11-36
11-37 → deleted, now
with 19-61
11-38 → deleted, now
with 19-74
11-39 → deleted, now
with 19-58
11-40 → 11-37
11-41 → 11-38
12-1 → 12-1
12-2 → 12-2
12-3 → 12-3
12-4 → 12-4
12-5 → 12-5
12-6 → 12-6
12-7 → 12-7
12-8 → 12-8
12-9 → 12-9
12-10 → 12-10
12-11 → 12-11
12-12 → 12-12
12-13 → 12-13
12-14 → 12-14
12-15 → 12-15
12-16 → 12-16

12-17 → 12-17
12-18 → 12-18
12-19 → 12-19
12-20 → 12-20
12-21 → 12-21
12-22 → 12-22
12-23 → 12-23
12-24 → 12-24
12-25 → 12-25
12-26 → 12-26
12-27 → 12-27

12-28 → deleted now
with 12-27
12-29 → 12-28
12-30 → 12-29
12-31 → 12-30
12-32 → 12-31
12-33 → 12-32
12-34 → 12-33
12-35 → 12-34
12-36 → 12-35
12-37 → 12-36
12-38 → 12-37
12-39 → 12-38
12-40 → 12-39
12-41 → 12-40
12-42 → 12-41
12-43 → 12-42
12-44 → 12-43

12-45 → 12-44
12-46 → 12-45
12-47 → 12-46
12-48 → 12-47
12-49 → 12-48
12-50 → 12-49
12-51 → 12-50
12-52 → 12-51
12-53 → 12-52
13-1 → 13-1
13-2 → deleted, now
with 13-1
13-3 → 13-2
13-4 → 13-3
13-5 → 13-4
13-6 → 13-5
13-7 → 13-6
New 13-7
13-8 → 13-8
13-9 → 13-9
13-10 → 13-13
13-11 → 13-10
13-12 → 13-11
13-13 → 13-14
13-14 → 13-15
13-15 → 13-16
13-16 → 13-17
13-17 → 13-12
13-18 → 13-18

13-19 → 13-19
13-20 → 13-20
13-21 → 13-21
13-22 → 13-22
13-23 → deleted, now
with 13-22
New 13-23
13-24 → 13-24
13-25 → 13-25
New 13-26
13-26 → 13-27
13-27 → 13-28
13-28 → 13-29
13-29 → 13-30
13-30 → 13-31
13-31 → 13-32
13-32 → 13-33
13-34 → 13-34
14-1 → 14-1
14-2 → 14-2
14-3 → 14-3
14-4 → deleted, now
with 14-1
14-5 → 14-4
14-6 → 14-5
14-7 → 14-6
14-8 → 14-7
14-9 → 14-8
14-10 → 14-9
14-11 → 14-10

14-12 → 14-11
14-13 → 14-12
14-14 → 14-13
14-15 → 14-14
14-16 → 14-15
14-17 → 14-16
14-18 → 14-17
14-19 → 14-18
14-20 → moved to
13-22
14-21 → moved to
13-7
14-22 → moved to
13-21
14-23 → moved to
13-26
14-24 → 14-19


NEW REACTION SECTIONS CORRELATION: 7TH EDITION → 8TH EDITION

14-25 → 14-20
14-26 → 14-21
14-27 → 14-22
14-28 → deleted, now
with 14-22
14-29 → 14-23
14-30 → 14-24
14-31 → 14-25
14-32 → 14-26

15-1 → 15-1
15-2 → 15-2
15-3 → 15-3
15-4 → 15-4
15-5 → 15-5
15-6 → 15-6
15-7 → 15-7
15-8 → 15-8
15-9 → 15-9
15-10 → 15-10
15-11 → moved to
19-34
15-12 → moved to
19-35
15-13 → moved to
19-36
15-14 → moved to
19-37
15-15 → moved to
19-38
15-16 → 15-11
15-17 → 15-12
15-18 → 15-13
15-19 → 15-14
15-20 → 15-15
15-21 → 15-16
New 15-17
15-22 → 15-18
15-23 → 15-19
15-24 → 15-20

15-25 → 15-21
15-26 → 15-22
15-27 → 15-23
15-28 → 15-24
15-29 → 15-25
15-30 → 15-26
15-31 → 15-27
15-32 → 15-28

15-33 → 15-29
15-34 → 15-30
15-35 → 15-31
15-36 → 15-32
15-37 → 15-33
15-38 → 15-34
15-39 → 15-35
15-40 → 15-36
15-41 → 15-37
15-42 → 15-38
15-43 → 15-39
15-44 → 15-40
15-45 → 15-41
15-46 → 15-42
15-47 → 15-43
15-48 → 15-44
15-49 → 15-45
15-50 → 15-46
15-51 → 15-47
15-52 → 15-48
15-53 → 15-49

15-54 → 15-50
15-55 → 15-51
15-56 → 15-52
15-57 → 15-53
15-58 → 15-54
15-59 → 15-55
15-60 → 15-56
15-61 → 15-57
15-62 → 15-58
15-63 → 15-59
15-64 → 15-60
15-65 → 15-61
15-66 → 15-62
16-1 → 16-1
16-2 → 16-2
16-3 → 16-3
16-4 → 16-4
16-5 → 16-5
16-6 → deleted, now
with 16-5
16-7 → 16-6
16-8 → 16-7
16-9 → 16-8
16-10 → 16-9
16-11 → 16-10
16-12 → 16-11

16-13 → 16-12
16-14 → 16-13
16-15 → deleted, now

with 16-13
16-16 → 16-14
16-17 → 16-15
16-18 → 16-16
16-19 → 16-17
16-20 → 16-18
16-21 → 16-19
16-22 → 16-20
16-23 → 16-21
16-24 → 16-22
16-25 → 16-23
New 16-24
16-26 → 16-25
16-27 → 16-26
16-28 → 16-27
16-29 → 16-29
16-30 → 16-30
16-31 → 16-31
16-32 → 16-32
16-33 → 16-33
16-34 → 16-34
16-35 → 16-35
16-36 → 16-36
16-37 → 16-37
16-38 → 16-38
16-39 → 16-39
16-40 → 16-40
16-41 → 16-41
16-42 → 16-42
16-43 → 16-43

16-44 → 16-44
16-45 → 16-45
16-46 → 16-46
16-47 → 16-47
16-48 → 16-48
16-49 → deleted, now
with 16-48
16-50 → 16-49
16-51 → 16-50
16-52 → 16-51
16-53 → 16-52
16-54 → 16-53
16-55 → 16-54
16-56 → 16-55
16-57 → 16-56

xvii


xviii

NEW REACTION SECTIONS CORRELATION: 7TH EDITION → 8TH EDITION

16-58 → 16-57
16-59 → 16-58
16-60 → 16-59
16-61 → 16-60
16-62 → 16-61
16-63 → 16-62
16-64 → 16-63

16-65 → 16-64
16-66 → 16-65
16-67 → 16-66
16-68 → 16-67
16-69 → 16-68
16-70 → 16-69
16-71 → 16-70
16-72 → 16-71
16-73 → 16-72
16-74 → 16-73
16-75 → 16-74
16-76 → 16-75
16-77 → 16-76
16-78 → 16-77
16-79 → 16-78
16-80 → deleted, now
with 16-78
16-81 → 16-28
16-82 → moved, now
with 18-29
16-83 → 16-79
16-84 → 16-80
16-85 → 16-81
16-86 → 16-82
16-87 → deleted, now
with 16-82
16-88 → 16-83
16-89 → moved, now
with 12-10
16-90 → 16-84

16-91 → 16-85
16-92 → 16-86
16-93 → 16-87
16-94 → 16-88
16-95 → 16-89
16-96 → 16-90
16-97 → 16-91
16-98 → 16-92
16-99 → 16-93
16-100 → 16-94

16-101 → 16-95
16-102 → 16-96
16-103 → 16-97
16-104 → moved,
now with 19-75
16-105 → 16-98
17-1 → 17-1
17-2 → 17-2
17-3 → 17-3
17-4 → 17-4
17-5 → 17-5
17-6 → deleted, now
with 17-5
17-7 → 17-6
17-8 → deleted, now
with 17-2
17-9 → 17-7
17-10 → 17-8
17-11 → 17-9

17-12 → 17-10
17-13 → 17-11
17-14 → 17-12
17-15 → 17-13
17-16 → 17-14
17-17 → 17-15
17-18 → 17-16
17-19 → 17-17
17-20 → 17-18
17-21 → 17-19
17-22 → 17-20
17-23 → 17-21
17-24 → 17-22
17-25 → 17-23
17-26 → 17-24
17-27 → 17-25
17-28 → 17-26
17-29 → 17-27
17-30 → 17-28
17-31 → 17-29
17-32 → 17-30
17-33 → 17-31
17-34 → 17-32
17-35 → 17-33
17-36 → 17-34
17-37 → 17-35
17-38 → 17-36

18-1 → 18-1
18-2 → 18-2

18-3 → 18-3
18-4 → 18-4
18-5 → 18-5
18-6 → 18-6
18-7 → 18-7
18-8 → 18-8
18-9 → 18-9
18-10 → 18-10
18-11 → 18-11
18-12 → 18-12
18-13 → 18-13
18-14 → 18-14
18-15 → 18-15
18-16 → 18-16
18-17 → 18-17
18-18 → 18-18
18-19 → 18-19
18-20 → 18-20
18-21 → 18-21
18-22 → 18-22
18-23 → 18-23
18-24 → 18-24
18-25 → 18-25
18-26 → 18-26
18-27 → 18-27
18-28 → 18-28
18-29 → 18-29
18-30 → 18-30
18-31 → 18-31
18-32 → 18-32

18-33 → 18-33
18-34 → 18-34
18-35 → 18-35
18-36 → 18-36
18-37 → 18-37
18-38 → 18-38
18-39 → 18-39
18-40 → 18-40
18-41 → 18-41
18-42 → 18-42
18-43 → 18-43
18-44 → 18-44
19-1 → 19-1
19-2 → 19-2


NEW REACTION SECTIONS CORRELATION: 7TH EDITION → 8TH EDITION

19-3 → 19-3
19-4 → 19-4
19-5 → 19-5
19-6 → 19-6
19-7 → 19-7
19-8 → 19-8
19-9 → 19-9
19-10 → 19-10
19-11 → 19-11
19-12 → 19-12
19-13 → 19-13
19-14 → 19-14

19-15 → 19-16
19-16 → 19-17
19-17 → 19-18
19-18 → 19-15
19-19 → 19-19
19-20 → 19-20
19-21 → 19-21
19-22 → 19-22
19-23 → 19-23
19-24 → 19-24
19-25 → 19-25
19-26 → 19-26
19-27 → 19-27
19-28 → deleted, now
with 19-27
19-29 → 19-28

19-30 → 19-29
19-31 → 19-30
19-32 → 19-31
19-33 → 19-32
19-34 → 19-33
19-35 → 19-39
19-36 → 19-40
19-37 → 19-41
19-38 → 19-42
19-39 → 19-43
19-40 → 19-44
19-41 → 19-45
19-42 → 19-46

19-43 → 19-47
19-44 → 19-48
19-45 → 19-49
19-46 → 19-50
19-47 → 19-51
19-48 → 19-52
19-49 → 19-53
19-50 → 19-54
19-51 → 19-55
19-52 → 19-56
19-53 → 19-57
19-54 → 19-59
19-55 → 19-60
19-56 → 19-61
19-57 → 19-63

19-58 → 19-64
19-59 → 19-62
19-60 → 19-65
19-61 → 19-66
19-62 → 19-67
19-63 → deleted, now
with 19-67
19-64 → 19-68
19-65 → 19-69
19-66 → 19-70
19-67 → 19-71
19-68 → 19-72
19-69 → 19-73
19-70 → 19-74

19-71 → 19-75
19-72 → 19-76
19-73 → 19-77
19-74 → 19-78
19-75 → 19-79
19-76 → 19-80
19-77 → 19-81
19-78 → 19-82
19-79 → 19-83
19-80 → 19-84
19-81 → 19-85
19-82 → 19-86
19-83 → 19-87
19-84 → 19-88

xix



PREFACE

This eighth edition of March’s Advanced Organic Chemistry has been thoroughly updated
to include new advances in areas of organic chemistry published between 2011 and 2017.
Every topic retained from the seventh edition has been brought up to date if there was
activity in that area during that six-year period. Changes also include a significant rewrite
of most of the book. More than 5800 new references have been added for work published
since 2011. As with the seventh edition, many older references were deleted to make room
for new ones. In cases where a series of papers by the same principal author were cited, most
but the most recent were deleted. Be aware that the older citations can usually be found by
referring to the more recent publications. It is noted that more than 250 000 articles for the

years 2011–2017, from 31 journals, were scanned for this edition. Of this huge number of
articles, just over 8000 were examined in detail for inclusion in this work, with 5853 finally
chosen. With such numbers, it is inevitable that some work was not included, and it was
impossible to include representative research in many areas. For example, over 2000 of the
8000 articles examined were relevant to the transition metal-catalyzed reactions covered
in reactions 13-3 to 13-13. It was simply impossible to keep a representative number of
articles for this subject area. There were other areas of research that were also too extensive
for complete inclusion of all references.
Many of the reaction drawings considered to be redundant or not very useful were deleted
when compiling the eighth edition. A few new sections of text were added to better reflect
some areas of research. Several of the older sections were moved to new chapters, especially the ones that deal with hydrogenation of alkenes and alkynes; as these are clearly
reductions they were moved to Chapter 19. Some sections were combined with others and
the original section deleted. These actions required renumbering the sections for the eighth
edition. A correlation table of the sections in the seventh edition and their placement in the
eighth edition is provided below. However, the fundamental structure of the eighth edition
is essentially the same as that of all previous editions.
The goal, as in previous editions, is to give equal weight to three fundamental aspects
of the study of organic chemistry: reactions, mechanisms, and structure. References are
provided, and every effort has been given to provide a snapshot of current research.
Specific but specialized areas of organic chemistry—terpenes, carbohydrates, proteins,
many organometallic reagents, combinatorial chemistry, polymerization and electrochemical reactions, steroids, etc.—have been incorporated into a great many pertinent sections
rather than segregated into their own sections.
This book is largely directed at graduate students in their first year of study and to undergraduates advanced in their studies, but previous editions have, for many years, been used
as an off-the-shelf reference book. This practice should continue with the eighth edition. It
is hoped that this book will lead a student to consult the many excellent books and review
articles cited for various topics in order to understand the subject in more detail. Indeed,
most of these topics are so vast they cannot be explained completely in this book.
xxi

xxii

PREFACE

The structure of organic compounds is discussed in Chapters 1–5 (found in Part I); these
chapters provide the background that is necessary for understanding mechanisms, but are
important in their own right. The discussion begins with chemical bonding (Chapter 1) and
ends with a chapter on stereochemistry (Chapter 4). Chapter 5 discusses the structure of
intermediates. Chapters 6 and 7 then address reaction mechanisms in general, Chapter 6
for ordinary reactions and Chapter 7 for photochemical reactions. Other methods related to
reactions are included in Chapter 7, including microwave chemistry, the use of ultrasound,
mechanochemistry, and the relatively new area of reactions done under flow conditions.
Part I concludes with Chapters 8 and 9, which give further background to the study of
mechanisms and reaction conditions.
The Introduction to Part II briefly describes how the second part of the book is organized. The organization is based on reaction types, and a relatively few principles suffice
to explain nearly all the types, despite the large number of organic reactions. Accordingly,
the reactions and mechanisms section of this book (Part II) is divided into ten chapters,
each being concerned with a different type of reaction. In the first part of each chapter the
appropriate basic mechanisms are discussed, along with considerations of reactivity and
orientation. The second part of each chapter is devoted to individual reaction types, where
the scope and the mechanism of each reaction are discussed. Numbered sections are used for
the reactions and theses are set in boldface when given as cross-references. Since the methods for the preparation of individual classes of compounds (e.g., ketones, nitriles, etc.) are
not treated all in one place, an updated and revised index has been provided (Appendix B)
by use of which the synthesis of a given type of compound may be found.
It is important to note that the reaction numbers (e.g., 10-25) for many reactions in the
eighth edition are different from those in the sixth and seventh editions. A table is included
that precedes this Preface that directly correlates the reaction numbers found in the eighth
edition with the reaction numbers that were used in the sixth and seventh editions. Note also
that changes in the sixth edition made the reaction numbers from editions 1–5 different in
many cases to those in the sixth edition. To see the differences between the fifth and sixth

editions, the reader is referred to the sixth edition.
Although IUPAC has published a system for designating reaction mechanisms, the designations for reactions that were featured in editions 1–7 have been removed, in large part
because they are not extensively used and in part because many reactions were deemed by
this author as difficult to categorize using only one designation.
In treating subjects as broad as structure, reactions, and mechanisms of organic chemistry, it is impossible to cover each topic in great depth, though this would not be desirable
even if possible. This book is intended to point the reader to the primary literature (the
original journal publications). Secondary literatures sources, including reviews, books, and
monographs, have also been included.
Appendix A provides a brief introduction to using modern computer-based search
engines such as Reaxys® and SciFinder® .
Although basically designed as a reference text for a one-year course at graduate level,
this book can also be used in advanced undergraduate courses but is most useful after completion of a one-year course in organic chemistry. It has been my experience that students
who have completed the first-year courses often have a hazy recollection of the material and
greatly profit from a re-presentation of the material if it is easily accessible. The material in
the first nine chapters, particularly chapters 1, 2, 4, 6, and 8, may be helpful for reviewing
such material when this book is used in connection with a course.


PREFACE

xxiii

This book is probably most valuable as a reasonably up-to-date reference work. Both
students preparing for qualifying examinations and practicing organic chemists will find
that Part II contains a survey of the mechanism and scope of a large number of reactions,
arranged in an orderly manner based on reaction type and on which bonds are broken and
formed.
IUPAC mandates joules for units of energy, but many journals do not use this unit exclusively. Indeed, organic chemists who publish in United States’ journals commonly use calories. Virtually all energy values are presented here in both calories and joules.
˚ for bond distances, preferring
Although IUPAC does not recommend angstrom units (A)

instead picometers (pm), a vast number of bond distances published in the literature are in
angstrom units, and this book therefore uses angstrom units.
I would like to acknowledge the contributions of those chemists cited and thanked by
Professor March in the first four editions, and those I thanked in the fifth, sixth, and seventh
editions. This book would not be possible without their contributions. I thank the many
people who have contributed comments or have pointed out errors in editions 5–7 that were
invaluable to putting together this edition. I thank Warren Hehre and Sean Ohlinger of
Wavefunction, Inc., Irvine, CA (www.wavefun.com) for providing Spartan 10 Macintosh
(v. 1.0.1), allowing the incorporation of Spartan models for selected molecules and intermediates. All structures and line drawings in this book were done using ChemDraw® Professional 15.1.0.144 (2348350), graciously provided by PerkinElmer Corporation, Waltham,
MA.
Special thanks are due to the Interscience division of John Wiley & Sons and to Stefanie
Volk and to Jonathan Rose, and also to Katrina Maceda at Wiley for their fine work as
editors in turning the manuscript into the finished book. I also thank Tim Jackson for an
excellent job of copy editing the manuscript.
With gratitude, I acknowledge the work of the late Jerry March, upon whose work all the
editions I have authored is built, although updates and changes have been made, beginning
with the fifth edition, However, Jerry is responsible for the concept and fundamental organization of this book and he carried it through four very successful editions. I used Jerry’s
book as a student and it is an honor to continue this tradition.
I encourage those who read and use the eight edition to contact me directly with comments and errors and with publications that might be appropriate for future editions. I hope
that this new edition will do justice to the tradition that Professor March began nearly
60 years ago.
My email address is:



Finally, I want to thank my wife Sarah for her patience and understanding during the
preparation of this manuscript. I also thank my son Steven. Without them, this work would
not have been possible.
Michael B. Smith
Professor Emeritus

October, 2018