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Joel Karty has dedicated nearly a decade developing a teaching approach and textbook that is organized by mechanism, promotes learning by doing, and provides students with the background and support they need to be successful in organic chemistry as well as pre-professional placement exams like the MCAT. Karty's organization, conversational writing style, and interactive pedagogy facilitate understanding rather than memorization and place the emphasis back on mechanisms.
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Organic Chemistry
Principles and Mechanisms
s eco n d e d i t i o n

Joel M. Karty
Elon University


W. W. N o r t o n
N e w yo r k • L o n d o n

To Pnut, Fafa, and Jakers

W. W. Norton & Company has been independent since its founding in 1923, when William Warder
Norton and Mary D. Herter Norton first published lectures delivered at the People’s Institute,
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Copyright © 2018, 2014 by W. W. Norton & Company, Inc.
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Library of Congress Cataloging-in-Publication Data
Names: Karty, Joel, author.
Title: Organic chemistry : principles and mechanisms / Joel M. Karty, Elon
Description:;  Second edition. | New York : W.W. Norton & Company, [2018] |
Includes index.
Identifiers: LCCN 2017042262 | ISBN 9780393630756 (hardcover)
Subjects: LCSH: Chemistry, Organic—Textbooks.
Classification: LCC QD253.2 .K375 2018 | DDC 547—c23 LC record available at
W. W. Norton & Company, Inc., 500 Fifth Avenue, New York, NY 10110
W. W. Norton & Company Ltd., 15 Carlisle Street, London W1D 3BS

About the Author
JOE L KARTY earned his B.S. in chemistry at the University of

Puget Sound and his Ph.D. at Stanford University. He joined the
faculty of Elon University in 2001, where he currently holds the
rank of full professor. He teaches primarily the organic chemistry

sequence and also teaches general chemistry. In the summer, Joel
teaches at the Summer Biomedical Sciences Institute through the
Duke University Medical Center. His research interests include in-

vestigating the roles of resonance and inductive effects in funda-

mental chemical systems and studying the mechanism of pattern

formation in Liesegang reactions. He has written a very successful
student supplement, Get Ready for Organic Chemistry, Second Edition (formerly called The Nuts and Bolts of Organic Chemistry).


Brief Contents
1 ​Atomic and Molecular Structure 1
Interchapter A ​Nomenclature: The Basic
System for Naming Organic Compounds: Alkanes,
Haloalkanes, Nitroalkanes, Cycloalkanes, and
Ethers 52

10 ​Nucleophilic Substitution and Elimination
Reactions 2: Reactions That Are Useful for
Synthesis 515
11 ​Electrophilic Addition to Nonpolar π Bonds 1:
Addition of a Brønsted Acid 563

2 ​Three-Dimensional Geometry, Intermolecular
Interactions, and Physical Properties 70

12 ​Electrophilic Addition to Nonpolar π Bonds 2:
Reactions Involving Cyclic Transition States 601

3 ​Orbital Interactions 1: Hybridization and

13 ​Organic Synthesis 1: Beginning Concepts in

Two-Center Molecular Orbitals 119

Designing Multistep Synthesis 641

Interchapter B ​Naming Alkenes, Alkynes, and
Benzene Derivatives 152

14 ​Orbital Interactions 2: Extended π Systems,
Conjugation, and Aromaticity 682

4 ​Isomerism 1: Conformers and Constitutional
Isomers 165

15 ​Structure Determination 1: Ultraviolet–Visible
and Infrared Spectroscopies 723

5 ​Isomerism 2: Chirality, Enantiomers, and
Diastereomers 208

16 ​Structure Determination 2: Nuclear
Magnetic Resonance Spectroscopy and Mass
Spectrometry 771

Interchapter C ​Stereochemistry in
Nomenclature: R and S Configurations about
Asymmetric Carbons and Z and E Configurations
about Double Bonds 258

17 ​Nucleophilic Addition to Polar π Bonds 1:
Addition of Strong Nucleophiles 839

6 ​The Proton Transfer Reaction: An Introduction
to Mechanisms, Thermodynamics, and Charge
Stability 274

Nucleophiles and Acid and Base Catalysis 888

7 ​An Overview of the Most Common Elementary
Steps 328
Interchapter D ​Molecular Orbital Theory,
Hyperconjugation, and Chemical Reactions 364

Interchapter E ​Naming Compounds with
a Functional Group That Calls for a Suffix 1:
Alcohols, Amines, Ketones, and Aldehydes 377
8 ​An Introduction to Multistep Mechanisms: SN1
and E1 Reactions and Their Comparisons to SN2
and E2 Reactions 393

18 ​Nucleophilic Addition to Polar π Bonds 2: Weak
19 ​Organic Synthesis 2: Intermediate Topics in
Synthesis Design, and Useful Redox and
Carbon–Carbon Bond-Forming Reactions 946
20 ​Nucleophilic Addition–Elimination Reactions
1: The General Mechanism Involving Strong
Nucleophiles 1000
21 ​Nucleophilic Addition–Elimination Reactions 2:
Weak Nucleophiles 1045
22 ​Aromatic Substitution 1: Electrophilic Aromatic
Substitution on Benzene; Useful Accompanying
Reactions 1104

9 ​Nucleophilic Substitution and Elimination

23 ​Aromatic Substitution 2: Reactions of
Substituted Benzenes and Other Rings 1144

Reactions 1: Competition among SN2, SN1, E2, and
E1 Reactions 442

24 ​The Diels–Alder Reaction and Other Pericyclic
Reactions 1198

Interchapter F ​Naming Compounds with
a Functional Group That Calls for a Suffix 2:
Carboxylic Acids and Their Derivatives 503

25 ​Reactions Involving Free Radicals 1247
Interchapter G Fragmentation Pathways in Mass


26 Polymers


List of Biochemistry Topics xxiii
List of Interest Boxes xxv
List of Connections Boxes xxvi
List of Green Chemistry Boxes xxix
List of Mechanisms xxx
Preface xxxiii


Atomic and Molecular Structure


What Is Organic Chemistry? 1
Why Carbon? 3
Atomic Structure and Ground State Electron Configurations 4
The Covalent Bond: Bond Energy and Bond Length 8
Lewis Dot Structures and the Octet Rule 12
Strategies for Success: Drawing Lewis Dot Structures Quickly 14
Electronegativity, Polar Covalent Bonds, and Bond Dipoles 16
Ionic Bonds 18
Assigning Electrons to Atoms in Molecules: Formal Charge 19
Resonance Theory 21
Strategies for Success: Drawing All Resonance Structures 25
Shorthand Notations 30
An Overview of Organic Compounds: Functional Groups 34


An Introduction to Proteins, Carbohydrates, and Nucleic Acids:
Fundamental Building Blocks and Functional Groups 37
Chapter Summary and Key Terms 45
Problems 45


Nomenclature: The Basic System
for Naming Organic Compounds
Alkanes, Haloalkanes, Nitroalkanes, Cycloalkanes,
and Ethers 52
The Need for Systematic Nomenclature: An Introduction to
the IUPAC System 52


Alkanes and Substituted Alkanes 53
Haloalkanes and Nitroalkanes: Roots, Prefixes, and Locator Numbers 54
Alkyl Substituents: Branched Alkanes and Substituted Branched
Alkanes 58
Cyclic Alkanes and Cyclic Alkyl Groups 60
Ethers and Alkoxy Groups 62
Trivial Names or Common Names 63
Problems 67


Three-Dimensional Geometry,
Intermolecular Interactions, and
Physical Properties 70
Valence Shell Electron Pair Repulsion (VSEPR) Theory:
Three-Dimensional Geometry 71
Dash–Wedge Notation 75
Strategies for Success: The Molecular Modeling Kit 77
Net Molecular Dipoles and Dipole Moments 78
Physical Properties, Functional Groups, and Intermolecular
Interactions 80
Melting Points, Boiling Points, and Intermolecular Interactions 82
Solubility 91
Strategies for Success: Ranking Boiling Points and Solubilities of
Structurally Similar Compounds 96
Protic and Aprotic Solvents 99
Soaps and Detergents 101

An Introduction to Lipids 105
Chapter Summary and Key Terms 112
Problems 113


viii   Contents

Orbital Interactions 1
Hybridization and Two-Center Molecular Orbitals


Atomic Orbitals and the Wave Nature of Electrons 120
Interaction between Orbitals: Constructive and Destructive
Interference 122
An Introduction to Molecular Orbital Theory and σ Bonds: An Example
with H2 124
Hybrid Atomic Orbitals and Geometry 128
Valence Bond Theory and Other Orbitals of σ Symmetry:
An Example with Ethane (H3C i CH3) 133
An Introduction to π Bonds: An Example with
Ethene (H2C w CH2) 136

Nonbonding Orbitals: An Example with Formaldehyde (H2C w O) 139
Triple Bonds: An Example with Ethyne (HC { CH) 140
Bond Rotation about Single and Double Bonds: Cis and
Trans Configurations 141
Strategies for Success: Molecular Models and Extended Geometry
about Single and Double Bonds 144
Hybridization, Bond Characteristics, and Effective
Electronegativity 145
Chapter Summary and Key Terms 148
Problems 149



Naming Alkenes, Alkynes, and Benzene
Derivatives 152


Alkenes, Alkynes, Cycloalkenes, and Cycloalkynes: Molecules with
One C w C or C { C 152
Molecules with Multiple C w C or C { C Bonds 155
Benzene and Benzene Derivatives 157
Trivial Names Involving Alkenes, Alkynes, and Benzene
Derivatives 159
Problems 162


Isomerism 1
Conformers and Constitutional Isomers


Isomerism: A Relationship 165
Conformers: Rotational Conformations, Newman Projections, and
Dihedral Angles 166
Conformers: Energy Changes and Conformational Analysis 169
Conformers: Cyclic Alkanes and Ring Strain 174
Conformers: The Most Stable Conformations of Cyclohexane,
Cyclopentane, Cyclobutane, and Cyclopropane 178
Conformers: Cyclopentane, Cyclohexane, Pseudorotation,
and Chair Flips 179
Strategies for Success: Drawing Chair Conformations
of Cyclohexane 182
Conformers: Monosubstituted Cyclohexanes 184
Conformers: Disubstituted Cyclohexanes, Cis and Trans
Isomers, and Haworth Projections 188
Strategies for Success: Molecular Modeling Kits and
Chair Flips 189
Constitutional Isomerism: Identifying Constitutional
Isomers 190
Constitutional Isomers: Index of Hydrogen
Deficiency (Degree of Unsaturation) 193


Strategies for Success: Drawing All Constitutional Isomers of a Given
Formula 195

Constitutional Isomers and Biomolecules: Amino Acids and
Monosaccharides 198
Saturation and Unsaturation in Fats and Oils 199
Chapter Summary and Key Terms 201
Problems 202


Isomerism 2
Chirality, Enantiomers, and Diastereomers


Defining Configurational Isomers, Enantiomers, and
Diastereomers 208
Enantiomers, Mirror Images, and Superimposability 210
Strategies for Success: Drawing Mirror Images 212
Chirality 214
Diastereomers 224
Fischer Projections and Stereochemistry 229
Strategies for Success: Converting between Fischer Projections and
Zigzag Conformations 231
Physical and Chemical Properties of Isomers 234
Stability of Double Bonds and Chemical Properties of Isomers 238
Separating Configurational Isomers 240
Optical Activity 241

The Chirality of Biomolecules 245
The d/l System for Classifying Monosaccharides and
Amino Acids 247
The d Family of Aldoses 248
Chapter Summary and Key Terms 250
Problems 251


Stereochemistry in Nomenclature
R and S Configurations about Asymmetric Carbons
and Z and E Configurations about Double Bonds 258

Priority of Substituents and Stereochemical Configurations at
Asymmetric Carbons: R/S Designations 258
Stereochemical Configurations of Alkenes: Z/E Designations 268
Problems 272

x   Contents


The Proton Transfer Reaction
An Introduction to Mechanisms, Thermodynamics, and
Charge Stability 274
An Introduction to Reaction Mechanisms: The Proton Transfer Reaction
and Curved Arrow Notation 275
Chemical Equilibrium and the Equilibrium Constant, Keq 277
Thermodynamics and Gibbs Free Energy 287
Strategies for Success: Functional Groups and Acidity 289
Relative Strengths of Charged and Uncharged Acids: The Reactivity of
Charged Species 291
Relative Acidities of Protons on Atoms with Like Charges 293
Strategies for Success: Ranking Acid and Base Strengths — ​The
Relative Importance of Effects on Charge 308
Strategies for Success: Determining Relative Contributions by
Resonance Structures 312

The Structure of Amino Acids in Solution as a Function of pH 314
Electrophoresis and Isoelectric Focusing 317
Chapter Summary and Key Terms 320
Problems 321


An Overview of the Most Common
Elementary Steps 328

Mechanisms as Predictive Tools: The Proton Transfer Step
Revisited 329
Bimolecular Nucleophilic Substitution (SN2) Steps 334
Bond-Forming (Coordination) and Bond-Breaking (Heterolysis)
Steps 337
Nucleophilic Addition and Nucleophile Elimination Steps 339
Bimolecular Elimination (E2) Steps 341
Electrophilic Addition and Electrophile Elimination Steps 343
Carbocation Rearrangements: 1,2-Hydride Shifts and 1,2-Alkyl
Shifts 345
The Driving Force for Chemical Reactions 347
Keto–Enol Tautomerization: An Example of Bond Energies as the Major
Driving Force 350
Chapter Summary and Key Terms 355
Problems 356



Molecular Orbital Theory,
Hyperconjugation, and Chemical
Reactions 364

Relative Stabilities of Carbocations and Alkenes: Hyperconjugation 364
MO Theory and Chemical Reactions 366
Problems 376


Naming Compounds with a Functional
Group That Calls for a Suffix 1
Alcohols, Amines, Ketones, and Aldehydes



The Basic System for Naming Compounds Having a Functional Group
That Calls for a Suffix: Alcohols and Amines 378
Naming Ketones and Aldehydes 384
Trivial Names of Alcohols, Amines, Ketones, and Aldehydes 386
Problems 390


An Introduction to Multistep Mechanisms
SN1 and E1 Reactions and Their Comparisons to SN2
and E2 Reactions 393


The Unimolecular Nucleophilic Substitution (SN1) Reaction 394
The Unimolecular Elimination (E1) Reaction 398
Direct Experimental Evidence for Reaction Mechanisms 400
The Kinetics of SN2, SN1, E2, and E1 Reactions 400
Stereochemistry of Nucleophilic Substitution and Elimination
Reactions 406
The Reasonableness of a Mechanism: Proton Transfers and
Carbocation Rearrangements 421
Resonance-Delocalized Intermediates in Mechanisms 432
Chapter Summary and Key Terms 434
Problems 434

xii   Contents

Nucleophilic Substitution and Elimination
Reactions 1
Competition among SN2, SN1, E2, and E1
Reactions 442
The Competition among SN2, SN1, E2, and E1 Reactions 443
Rate-Determining Steps Revisited: Simplified Pictures of the SN2, SN1,
E2, and E1 Reactions 445


Factor 1: Strength of the Attacking Species 447
Factor 2: Concentration of the Attacking Species 456
Factor 3: Leaving Group Ability 458
Factor 4: Type of Carbon Bonded to the Leaving Group 464
Factor 5: Solvent Effects 470
Factor 6: Heat 476
Predicting the Outcome of an SN2/SN1/E2/E1 Competition 477
Regioselectivity in Elimination Reactions: Zaitsev’s Rule 482
Intermolecular Reactions versus Intramolecular Cyclizations 485
Kinetic Control, Thermodynamic Control, and Reversibility 487

Nucleophilic Substitution Reactions and Monosaccharides: The
Formation and Hydrolysis of Glycosides 490
Chapter Summary and Key Terms 493
Reaction Tables 494
Problems 495


Naming Compounds with a Functional
Group That Calls for a Suffix 2
Carboxylic Acids and Their Derivatives


Naming Carboxylic Acids, Acid Chlorides, Amides, and Nitriles 503
Naming Esters and Acid Anhydrides 507
Trivial Names of Carboxylic Acids and Their Derivatives 510
Problems 513


Nucleophilic Substitution and
Elimination Reactions 2
Reactions That Are Useful for Synthesis


Nucleophilic Substitution: Converting Alcohols into Alkyl Halides
Using PBr3 and PCl3 516
Nucleophilic Substitution: Alkylation of Ammonia and Amines 520
Nucleophilic Substitution: Alkylation of α Carbons 523
Nucleophilic Substitution: Halogenation of α Carbons 528
Nucleophilic Substitution: Diazomethane Formation of Methyl
Esters 533
Nucleophilic Substitution: Formation of Ethers and Epoxides 535
Nucleophilic Substitution: Epoxides and Oxetanes as Substrates 540
Elimination: Generating Alkynes via Elimination Reactions 548

Contents   xiii

Elimination: Hofmann Elimination 551
Chapter Summary and Key Terms 554
Reaction Tables 555
Problems 557


Electrophilic Addition to Nonpolar
π Bonds 1
Addition of a Brønsted Acid


The General Electrophilic Addition Mechanism: Addition of a Strong
Brønsted Acid to an Alkene 565
Benzene Rings Do Not Readily Undergo Electrophilic Addition of
Brønsted Acids 568
Regiochemistry: Production of the More Stable Carbocation and
Markovnikov’s Rule 569
Carbocation Rearrangements 573
Stereochemistry 574
Addition of a Weak Acid: Acid Catalysis 576
Electrophilic Addition of a Strong Brønsted Acid to an Alkyne 578
Acid-Catalyzed Hydration of an Alkyne: Synthesis of a Ketone 581
Electrophilic Addition of a Brønsted Acid to a Conjugated Diene:
1,2-Addition and 1,4-Addition 583
Kinetic versus Thermodynamic Control in Electrophilic Addition to a
Conjugated Diene 586

Terpene Biosynthesis: Carbocation Chemistry in Nature 589
Chapter Summary and Key Terms 594
Reaction Table 595
Problems 596


xiv   Contents

Electrophilic Addition to Nonpolar
π Bonds 2
Reactions Involving Cyclic Transition States


Electrophilic Addition via a Three-Membered Ring: The General
Mechanism 602
Electrophilic Addition of Carbenes: Formation of Cyclopropane
Rings 604
Electrophilic Addition Involving Molecular Halogens: Synthesis of
1,2-Dihalides and Halohydrins 607
Oxymercuration–Reduction: Addition of Water 614
Epoxide Formation Using Peroxyacids 620
Hydroboration–Oxidation: Anti-Markovnikov Syn Addition of Water to
an Alkene 623

Hydroboration–Oxidation of Alkynes 631
Chapter Summary and Key Terms 632
Reaction Tables 633
Problems 635


Organic Synthesis 1
Beginning Concepts in Designing Multistep
Synthesis 641


Writing the Reactions of an Organic Synthesis 642
Cataloging Reactions: Functional Group Transformations and
Carbon–Carbon Bond-Forming/Breaking Reactions 647
Retrosynthetic Analysis: Thinking Backward to Go Forward 649
Synthetic Traps 654
Choice of the Solvent 662
Considerations of Stereochemistry in Synthesis 664
Strategies for Success: Improving Your Proficiency with Solving
Multistep Syntheses 668
Choosing the Best Synthesis Scheme 671
Chapter Summary and Key Terms 676
Problems 677


Orbital Interactions 2
Extended π Systems, Conjugation, and
Aromaticity 682
The Shortcomings of VB Theory 683
Multiple-Center MOs 686
Aromaticity and Hückel’s Rules 695
The MO Picture of Benzene: Why It’s Aromatic 700
The MO Picture of Cyclobutadiene: Why It’s Antiaromatic 702
Aromaticity in Larger Rings: [n]Annulenes 705
Aromaticity and Multiple Rings 706
Heterocyclic Aromatic Compounds 707
Aromatic Ions 710
Strategies for Success: Counting π Systems and π Electrons Using
the Lewis Structure 710

Aromaticity and DNA 714
Chapter Summary and Key Terms 718
Problems 718

Contents   xv


Structure Determination 1
Ultraviolet–Visible and Infrared Spectroscopies



An Overview of Ultraviolet–Visible Spectroscopy 724
The UV–Vis Spectrum: Photon Absorption and Electron
Transitions 726
Effects of Structure on λmax 730
IR Spectroscopy 736
A Closer Look at Some Important IR Absorption Bands 745
Structure Elucidation Using IR Spectroscopy 756
Chapter Summary and Key Terms 762
Problems 763


Structure Determination 2
Nuclear Magnetic Resonance Spectroscopy
and Mass Spectrometry 771

NMR Spectroscopy: An Overview 772
Nuclear Spin and the NMR Signal 773
Chemical Distinction and the Number of NMR Signals 776
Strategies for Success: The Chemical Distinction Test and Molecular
Symmetry 778
The Time Scale of NMR Spectroscopy 781
Chemical Shift 783
Characteristic Chemical Shifts, Inductive Effects, and Magnetic
Anisotropy 784
Trends in Chemical Shift 789
Integration of Signals 790
Splitting of the Signal by Spin–Spin Coupling: The N 1 1 Rule 792
Coupling Constants and Signal Resolution 797
Complex Signal Splitting 801
C NMR Spectroscopy 804
DEPT 13C NMR Spectroscopy 809
Structure Elucidation Using NMR Spectroscopy 811
Mass Spectrometry: An Overview 818
Features of a Mass Spectrum, the Nitrogen Rule, and
Fragmentation 820
Isotope Effects: M 1 1 and M 1 2 Peaks 823
Determining a Molecular Formula of an Organic Compound from the
Mass Spectrum 826
Chapter Summary and Key Terms 829
Problems 830

xvi   Contents


Nucleophilic Addition to
Polar π Bonds 1
Addition of Strong Nucleophiles



An Overview of the General Mechanism: Addition of Strong
Nucleophiles 841
Substituent Effects: Relative Reactivity of Ketones and Aldehydes in
Nucleophilic Addition 842
Reactions of LiAlH4 and NaBH4 844
Sodium Hydride: A Strong Base but a Poor Nucleophile 852
Reactions of Organometallic Compounds: Alkyllithium Reagents and
Grignard Reagents 854
Limitations of Alkyllithium and Grignard Reagents 857
Wittig Reagents and the Wittig Reaction: Synthesis
of Alkenes 858
Generating Wittig Reagents 861
Direct Addition versus Conjugate Addition 863
Lithium Dialkylcuprates and the Selectivity of
Organometallic Reagents 869
Organic Synthesis: Grignard and Alkyllithium Reactions in
Synthesis 872
Organic Synthesis: Considerations of Direct Addition
versus Conjugate Addition 874
Organic Synthesis: Considerations of Regiochemistry
in the Formation of Alkenes 877
Chapter Summary and Key Terms 878
Reaction Tables 879
Problems 880


Nucleophilic Addition to
Polar π Bonds 2
Weak Nucleophiles and Acid and Base Catalysis


Weak Nucleophiles as Reagents: Acid and Base Catalysis 888
Formation and Hydrolysis Reactions Involving Acetals, Imines,
Enamines, and Nitriles 897
The Wolff–Kishner Reduction 906
Enolate Nucleophiles: Aldol and Aldol-Type Additions 908
Aldol Condensations 911
Aldol Reactions Involving Ketones 913
Crossed Aldol Reactions 914
Intramolecular Aldol Reactions 919
Aldol Additions Involving Nitriles and Nitroalkanes 922
The Robinson Annulation 924
Organic Synthesis: Aldol Reactions in Synthesis 925
Contents   xvii


Organic Synthesis: Synthesizing Amines via Reductive
Amination 927

Ring Opening and Closing of Monosaccharides; Mutarotation 929
Chapter Summary and Key Terms 933
Reaction Tables 934
Problems 937


Organic Synthesis 2
Intermediate Topics in Synthesis Design, and
Useful Redox and Carbon–Carbon Bond-Forming
Reactions 946


Umpolung in Organic Synthesis: Forming Bonds between Carbon
Atoms Initially Bearing Like Charge; Making Organometallic
Reagents 947
Relative Positioning of Heteroatoms in Carbon–Carbon Bond-Forming
Reactions 951
Reactions That Remove a Functional Group Entirely from a Molecule:
Reductions of C w O to CH2 955
Avoiding Synthetic Traps: Selective Reagents and Protecting
Groups 960
Catalytic Hydrogenation 969
Oxidations of Alcohols and Aldehydes 976
Useful Reactions That Form Carbon–Carbon Bonds: Coupling and
Alkene Metathesis Reactions 982
Chapter Summary and Key Terms 988
Reaction Tables 989
Problems 991


xviii   Contents

Nucleophilic Addition–Elimination
Reactions 1
The General Mechanism Involving Strong
Nucleophiles 1000
An Introduction to Nucleophilic Addition–Elimination Reactions:
Transesterification 1001
Acyl Substitution Involving Other Carboxylic Acid Derivatives: The
Thermodynamics of Acyl Substitution 1006
Reaction of an Ester with Hydroxide (Saponification) and the Reverse
Reaction 1009
Carboxylic Acids from Amides; the Gabriel Synthesis of Primary
Amines 1013
Haloform Reactions 1017


Hydride Reducing Agents: Sodium Borohydride (NaBH4) and Lithium
Aluminum Hydride (LiAlH4) 1021
Specialized Reducing Agents: Diisobutylaluminum Hydride (DIBAH)
and Lithium Tri-tert-butoxyaluminum Hydride (LTBA) 1029
Organometallic Reagents 1032
Chapter Summary and Key Terms 1035
Reaction Tables 1036
Problems 1039



Nucleophilic Addition–Elimination
Reactions 2
Weak Nucleophiles


The General Nucleophilic Addition–Elimination Mechanism
Involving Weak Nucleophiles: Alcoholysis and Hydrolysis of Acid
Chlorides 1046
Relative Reactivities of Acid Derivatives: Rates of Hydrolysis 1049
Aminolysis of Acid Derivatives 1052
Synthesis of Acid Halides: Getting to the Top of the Stability
Ladder 1054
The Hell–Volhard–Zelinsky Reaction: Synthesizing α-Bromo Carboxylic
Acids 1057
Sulfonyl Chlorides: Synthesis of Mesylates, Tosylates, and
Triflates 1059
Base and Acid Catalysis in Nucleophilic Addition–Elimination
Reactions 1061
Baeyer–Villiger Oxidations 1067
Claisen Condensations 1069
Organic Synthesis: Decarboxylation, the Malonic Ester Synthesis,
and the Acetoacetic Ester Synthesis 1078
Organic Synthesis: Protecting Carboxylic Acids and Amines 1082

Determining a Protein’s Primary Structure via Amino Acid
Sequencing: Edman Degradation 1084
Synthesis of Peptides 1087
Chapter Summary and Key Terms 1090
Reaction Tables 1091
Problems 1093


Aromatic Substitution 1
Electrophilic Aromatic Substitution on Benzene;
Useful Accompanying Reactions 1104
The General Mechanism of Electrophilic Aromatic Substitutions 1106
Halogenation 1109
Contents   xix


Friedel–Crafts Alkylation 1111
Limitations of Friedel–Crafts Alkylations 1114
Friedel–Crafts Acylation 1118
Nitration 1121
Sulfonation 1122
Organic Synthesis: Considerations of Carbocation Rearrangements
and the Synthesis of Primary Alkylbenzenes 1125
Organic Synthesis: Common Reactions Used in Conjunction with
Electrophilic Aromatic Substitution Reactions 1126
Chapter Summary and Key Terms 1134
Reaction Tables 1135
Problems 1137


Aromatic Substitution 2
Reactions of Substituted Benzenes and
Other Rings 1144


Regiochemistry of Electrophilic Aromatic Substitution: Defining
Ortho/Para and Meta Directors 1145
What Characterizes Ortho/Para and Meta Directors and Why? 1147
The Activation and Deactivation of Benzene toward Electrophilic
Aromatic Substitution 1155
The Impacts of Substituent Effects on the Outcomes of Electrophilic
Aromatic Substitution Reactions 1159
The Impact of Reaction Conditions on Substituent Effects 1162
Electrophilic Aromatic Substitution on Disubstituted Benzenes 1164
Electrophilic Aromatic Substitution Involving Aromatic Rings Other
than Benzene 1168
Azo Coupling and Azo Dyes 1172
Nucleophilic Aromatic Substitution Mechanisms 1173
Organic Synthesis: Considerations of Regiochemistry; Attaching
Groups in the Correct Order 1179
Organic Synthesis: Interconverting Ortho/Para and Meta
Directors 1180
Organic Synthesis: Considerations of Protecting Groups 1183
Chapter Summary and Key Terms 1186
Reaction Table 1187
Problems 1188

xx   Contents

The Diels–Alder Reaction and Other
Pericyclic Reactions 1198
Curved Arrow Notation and Examples 1199
Conformation of the Diene 1203
Substituent Effects on the Reaction 1206


Stereochemistry of Diels–Alder Reactions 1208
Regiochemistry of Diels–Alder Reactions 1213
The Reversibility of Diels–Alder Reactions; the Retro Diels–Alder
Reaction 1216
Syn Dihydroxylation of Alkenes and Alkynes Using OsO4 or
KMnO4 1218
Oxidative Cleavage of Alkenes and Alkynes 1220
Organic Synthesis: The Diels–Alder Reaction in Synthesis 1226
A Molecular Orbital Picture of the Diels–Alder Reaction 1228
Chapter Summary and Key Terms 1235
Reaction Tables 1235
Problems 1237


Reactions Involving Free Radicals



Homolysis: Curved Arrow Notation and Radical Initiators 1248
Structure and Stability of Alkyl Radicals 1252
Common Elementary Steps That Free Radicals Undergo 1257
Radical Halogenation of Alkanes: Synthesis of Alkyl Halides 1260
Radical Addition of HBr: Anti-Markovnikov Addition 1275
Stereochemistry of Free Radical Halogenation and HBr
Addition 1278
Dissolving Metal Reductions: Hydrogenation of Alkenes and
Alkynes 1279
Organic Synthesis: Radical Reactions in Synthesis 1283
Chapter Summary and Key Terms 1286
Reaction Table 1287
Problems 1287


Fragmentation Pathways in Mass
Spectrometry 1295

Alkanes 1296
Alkenes and Aromatic Compounds 1298
Alkyl Halides, Amines, Ethers, and Alcohols 1300
Carbonyl-Containing Compounds 1304
Problems 1306




Free Radical Polymerization: Polystyrene as a Model 1308
Anionic and Cationic Polymerization Reactions 1320
Contents   xxi


Ring-Opening Polymerization Reactions 1323
Step-Growth Polymerization 1325
Linear, Branched, and Network Polymers 1330
Chemical Reactions after Polymerization 1332
General Aspects of Polymer Structure 1338
Properties of Polymers 1344
Uses of Polymers: The Relationship between Structure and Function
in Materials for Food Storage 1351
Degradation and Depolymerization 1353

Biological Macromolecules 1355
Chapter Summary and Key Terms 1362
Problems 1363

A: Values of Ka and pKa for Various Acids APP-1
B: Characteristic Reactivities of Particular Compound Classes APP-4
C: Reactions That Alter the Carbon Skeleton APP-9
D: Synthesizing Particular Compound Classes via Functional Group
Transformations APP-15

Glossary G-1
Answers to Your Turns ANS-1
Credits C-1
Index I-1

xxii   Contents

Biochemistry Topics

Proteins and Amino Acids

Nucleic Acids

An introduction to proteins 37
Amino acid structure and polypeptides 38
Constitutional isomers of amino acids 198
The D/L system for classifying amino acids 247
The structure of amino acids in solution as a function of
pH 314
Electrophoresis and isoelectric focusing 317
Determining a protein’s primary structure via amino acid
sequencing: Edman degradation 1084
Synthesis of peptides 1087
Polypeptides: Primary, secondary, tertiary, and
quaternary structures 1355
α-Helix; β-sheet 1357
Planarity of a peptide 1358
Ribbon structures 1359
Hydrophobic effect 1359

An introduction to nucleic acids 37
Nucleotide structure, RNA and DNA 42
Aromaticity and DNA 714
The structure of DNA; complementarity of DNA base
pairs 715
Pi stacking 716
The story of Watson and Crick 717

Organic Chemistry of Biomolecules

Interest Boxes
Enzyme active sites 103
Phosphorylation of an enzyme’s active site 420
Using proton transfer reactions to discover new
drugs 427
How an enzyme can manipulate the reactivity of a
nucleophile and substrate 475
Kinetic control, thermodynamic control, and mad cow
disease 589
Aromaticity helping us breathe: A look at
hemoglobin 709
Imine formation and hydrolysis in biochemical
reactions 903

Organic Chemistry of Biomolecules

Interest Boxes
DNA alkylation: Cancer causing and cancer curing 547
Benzo[a]pyrene: Smoking, epoxidation, and cancer 623
UV–Vis spectroscopy and DNA melting points 735
Michael addition in the fight against cancer 869
Protecting groups in DNA synthesis 969
Biological cycloaddition reactions 1202


Organic Chemistry of Biomolecules
An introduction to carbohydrates 37
Monosaccharide structure and polysaccharides 40
Constitutional isomers of monosaccharides 198
Acyclic and cyclic structures of monosaccharides 198
Structures of aldoses, ketoses, pentoses, and
hexoses 199
The D/L system for classifying monosaccharides 247
The D family of aldoses 248
The formation and hydrolysis of glycosides 490
α- and β-glycosidic linkages; 1,4- and 1,6-glycosidic
linkages 491


Ring opening and closing of monosaccharides;
mutarotation 929
Nomenclature involving pyranoses and furanoses 930
Anomers and the anomeric carbon 931
Polysaccharides 1355
Amylose, amylopectin 1360

Interest Boxes
Sugar transformers 354


Organic Chemistry of Biomolecules
An introduction to lipids 105
Structures of fats, oils, and fatty acids 105
Phospholipids and cell membranes 106

xxiv   Biochemistry Topics

Steroids, terpenes, and terpenoids 109
Classifications of terpenes (mono, sesqui, di, tri) 110
Waxes 111
Saturation and unsaturation in fats and oils 199
Effect of unsaturation on boiling point and melting
point 200
Terpene biosynthesis: Carbocation chemistry in
nature 589
Biosynthesis of cholesterol and other
terpenes/terpenoids 592

Interest Boxes
Conjugated linoleic acids 697
Biodiesel and transesterification 1005
Biological Claisen condensations 1077
Free radicals in the body: Lipid peroxidation and
vitamin E 1274

Interest Boxes
Chemistry with Chicken Wire 5
Turning an Inorganic Surface into an Organic
Surface 11
Climbing Like Geckos 89
Enzyme Active Sites: The Lock-and-Key Model 103
Quantum Teleportation 123
Carbyne: The World’s Strongest Material 147
An All-Gauche Alkane 177
Cubane: A Useful “Impossible” Compound? 183
Nanocars 225
Mapping the Earth with Polarimetry 245
pKa and the Absorption and Secretion of Drugs 286
Superacids: How Strong Can an Acid Be? 307
“Watching” a Bond Break 347
Sugar Transformers: Tautomerization in the Body 354
Phosphorylation: An Enzyme’s On/Off Switch 420
Using Proton Transfer Reactions to Discover New
Drugs 427
Rotaxanes: Exploiting Steric Hindrance 470
How an Enzyme Can Manipulate the Reactivity of a
Nucleophile and Substrate 475
DNA Alkylation: Cancer Causing and Cancer Curing 547
Mechanically Generated Acid and Self-Healing
Polymers 553
Electrophilic Addition and Laser Printers 572
Kinetic Control, Thermodynamic Control, and Mad Cow
Disease 589
Halogenated Metabolites: True Sea Treasures 615
Benzo[a]pyrene: Smoking, Epoxidation, and
Cancer 623
Manipulating Atoms One at a Time: Single-Molecule
Engineering 661

Conjugated Linoleic Acids 697
Aromaticity Helping Us Breathe: A Look at
Hemoglobin 709
UV–Vis Spectroscopy and DNA Melting Points 735
IR Spectroscopy and the Search for Extraterrestrial
Life 758
Magnetic Resonance Imaging 803
Mass Spectrometry, CSI, and Grey’s Anatomy 828
NADH as a Biological Hydride Reducing Agent 852
Michael Addition in the Fight against Cancer 869
Imine Formation and Hydrolysis in Biochemical
Reactions 903
Protecting Groups in DNA Synthesis 969
Chromic Acid Oxidation and the Breathalyzer Test 981
Biodiesel and Transesterification 1005
The Stability Ladder in Biochemical Systems 1010
Biological Claisen Condensations 1077
Aromatic Sulfonation: Antibiotics and Detergents 1124
Sodium Nitrite and Foods: Preventing Botulism but
Causing Cancer? 1132
Iodized Salt and Electrophilic Aromatic
Substitution 1152
2,4,6-Trinitrotoluene (TNT) 1160
Biological Cycloaddition Reactions 1202
Ethene, KMnO4, and Fruit Ripening 1225
Halogenated Alkanes and the Ozone Layer 1265
Free Radicals in the Body: Lipid Peroxidation and
Vitamin E 1274
Supramolecular Polymers: Polymers That Can Heal
Themselves 1333
Plastic Made from Corn?


Connections Boxes
Molecular hydrogen and the Hindenburg 8
Bonds as springs; greenhouse gases 9
Chlorine radicals in the stratosphere breaking down
ozone 12
Methanol and the production of plastics, paints,
explosives, and fuel 13
Borane and thionyl chloride as reagents in organic
synthesis 14
The formate anion and the mitochondria of cells 20
Oximes: nylon-6, nerve-agent antidotes, and artificial
sweeteners 21
Cationic species as reactive intermediates in organic
reactions 24
Benzene and crude oil 25
Acetic acid, vinegar, and organic chemistry 25
Naphthalene and mothballs 29
Acetamide as a plasticizer or solvent 30
Crotonaldehyde in foodstuffs 31
Pyrrole and the heme group; benzoic acid and skin
ointments 33
Cyclohexanone and nylon 36
δ-Valerolactone and polyesters; pentanoic acid and
fragrant esters 36
Bromomethane as a pesticide 56
Freon 142b as a refrigerant 57
Diethyl ether as a common organic solvent and an
anesthetic 67
Acetonitrile and acetone as organic solvents; ethane in
the petrochemical industry 73
2-Aminoethanol in the production of shampoos and
detergents 73
Butan-2-ol as a precursor to butan-2-one 76
The pros and cons of carbon tetrachloride 79
Methylene chloride: industrial uses and the drinking
bird 80
Chloromethane as a refrigerant, local anesthetic, and
herbicide 80
Sodium methanoate with fabric dye and as a flavor
enhancer 81
Formic acid in ant venom and its uses 81
Ethanol as more than an alcoholic beverage 84
Elemental iodine as a disinfectant and its use in
analytical chemistry 89

Toluene: an organic solvent, a precursor to TNT, and its
use in extracting hemoglobin 92
2-Naphthol as a precursor in dye production 96
DMSO and its medicinal uses 99
H2 and its wide variety of uses 125
Ethane in the industrial production of ethene 133
Methane and natural gas 135
Ethene: a precursor to polyethylene, and its importance
in the laboratory 136
The high temperature of burning acetylene 140
HCN: industrial uses and eucalyptus leaf beetles 141
Fluoroethene, Tedlar, and the Goodyear blimp 143
α-Linolenic acid as a dietary supplement 144
1,2,3-Trimethylbenzene as a fuel stabilizer 158
Propylene as a precursor of polypropylene, a plastic with
many applications 159
Isobutylene as a fuel additive and a precursor to butyl
rubber 159
The sweetness of anisole 160
Styrene in Styrofoam, coffee beans, and cinnamon 161
Xylene: crude oil, industrial uses, and root canals 161
1,2-Dibromoethane to control insect infestation 172
Cooling cyclohexane to slow chair flips 181
Methylcyclohexane as a solvent for cellulose
ethers 185
But-1-ene and plastic plumbing pipes 191
Cyclobutane and the thymine dimer 191
Acetaldehyde as an intermediate in the metabolism of
ethanol 194
Oxirane: production of antifreeze and the sterilization of
medical devices 194
Butanediol fermentation 220
1-Bromopropane: from asphalt production to dry
cleaning 222
Tetrahydrofuran and Spandex 235
Ammonia, window cleaners, and the Haber–Bosch
process 277
4-Methylphenol: pig odor and the production of
antioxidants 279
Phenol, from plastics to antiseptics 281
Methanamine: industrial uses and putrefaction 282

Isopropyl alcohol: an antiseptic, a solvent, and a
gasoline additive 290
Trichloroacetic acid in biochemistry and cosmetics 291
Aniline: Tylenol and blue jeans 310
Trimethylamine and the freshness of fish 331
Nitrobenzene: a fragrance and a precursor to
explosives, dyes, and drugs 344
Cyclohexanol as a nylon precursor 378
5-Aminopentan-1-ol in the synthesis of antitumor
manzamines 381
Propane-1,2-diol in antifreeze 383
Butanal in natural oils and as a feedstock in industrial
synthesis 386
tert-Butyl alcohol in the synthesis of fuel additives 386
Benzyl alcohol: uses in industry and as a food and
perfume additive 387
Ethylamine: solvated electrons and the production of
herbicides 388
Dimethylamine: rubber vulcanization and allergy
medicines 388
Formaldehyde: uses in industry, medicine, and
embalming 389
Benzaldehyde in the synthesis of dyes and
pharmaceuticals and as a flavoring agent 389
Butanone as an industrial solvent and in dry-erase
markers 389
Acetophenone in the production of inks, coatings, and
pharmaceuticals 390
Benzyl chloride in synthesis, from flavoring agents to
cleaning products 401
Methoxyphenylmethane as a fragrance 422
Cyclohexene and synthetic fibers 425
β-Propiolactone in medicine: blood plasma, tissue
grafts, and flu vaccines 426
2-Methylbutan-2-ol once used as an anesthetic 429
2-Methylbut-3-en-2-ol and the bark beetle 432
HCN: cherries, apples, and mining precious
metals 452
Bromocyclohexane and confocal microscopy 454
2-Methoxyphenol and swarming locusts 462
Allyl halides, from pharmaceuticals to boats 469
Styrene and your take-out meal 477
Hex-1-ene and plastics 483
Tetrahydropyran: organic synthesis and sugars 485
(E)-9-Oxodec-2-enoic acid and bees 504
Natural compounds from watercress and fungi 506
Shikimic acid and antiviral medication 507
Ethyl butanoate as a flavoring agent 508
Acetic anhydride in the synthesis of aspirin and other
compounds 510

Phosphorus tribromide in the synthesis of the
anesthetic Brevital 517
Tetraethylammonium bromide and the treatment of
hypertension 522
Methyl acetate as a nail polish remover 534
The oxetane ring in the treatment of cancer 540
2-Methoxyethanol and safety in air travel 541
2-Phenylethanol in flowers and perfumes 542
3-Hydroxypropanenitrile and knitted clothing 542
Indene as a protective fruit coating 571
1,2-Diphenylethene and keeping your color laundry
bright 575
Propyne as a rocket fuel 580
Buta-1,3-diene and the making of car tires 584
Heptan-2-one: insect bites and gorgonzola cheese 619
Cyclohexane-1,2-diol and the North American
beaver 622
Heptan-1-ol and understanding the heart 624
Borane and fuel cells in automobiles 625
Hexanal and the flavor of cooked meats 631
Butanoic acid and rancid butter 646
(Bromomethyl)benzene and chemical warfare 654
Overcoming synthetic traps in biochemical
reactions 656
Methylenecyclopentane in the synthesis of an antiviral
and antitumor agent 656
(S)-Naproxen as the painkiller Aleve 664
Using diisopinocampheylborane to carry out an
enantioselective hydroboration–oxidation 668
Cyclooctene as trans and cis isomers 674
Buta-1,3-diene and 3-D printers 685
Cycloocta-1,3,5,7-tetraene from fungus in the Eucryphia
cordifolia tree 700
Biphenyl as a citrus fruit preservative 706
Anthracene: insecticidal and fungicidal properties and
the Sistine Chapel 707
Pyridine: numerous chemical applications; found in
marshmallow plants 707
Furan and your morning coffee 708
trans-Penta-1,3-diene and soft drinks 732
Methanimine and extraterrestrial life 733
4-Methylpentan-2-one and mining silver and gold 749
1-Phenylpropan-2-one and the manufacture of
amphetamine and methamphetamine 750
Heptanal as a flavoring agent and in cosmetics 752
Benzophenone and plastic packaging 754
Dichloroacetic acid, from tattoo removal to cancer
treatment 778
Chloroethene in the production of pipes for
plumbing 780

Connections Boxes   xxvii

Ethylbenzene to make styrene and to recover natural
gas 790
1,4-Dimethylbenzene and plastic water bottles 791
Propanal in the manufacture of alkyd resins 803
Benzyl chloride and pharmaceuticals 808
Dodecane as a substitute for jet fuel 823
3-Methylbutanal in cheese, beer, chicken, and fish 841
Butyllithium and the production of some types of
rubber 854
Benzonitrile, resins and pharmaceuticals 855
Propenal, from herbicides to fried food 863
Cyclohex-2-en-1-one and the total synthesis of
morphine 865
Pentanal as a fruity flavor additive and in the
vulcanization of rubber 897
3-Hydroxybutanal as a hypnotic 908
4-Hydroxy-4-methylpentanone in gravure printing
inks 913
Cinnamaldehyde in cinnamon 916
Bromobenzene as an additive to motor oils 948
3-Methylpentan-3-ol and anxiety and tension 951
1-Phenylpropan-1-one in the synthesis of
ephedrine 955
3-Hydroxypropanal and the health benefits of probiotic
bacteria 966
Benzene-1,2-diol and the synthesis of vanilla
flavoring 968
Limonene in the rinds of citrus fruits 975
Ethyl indole-2-carboxylate in the synthesis of
intracellular signaling compounds 1002
Benzoyl chloride and the synthesis of acne
medicine 1006
Ethyl acetate and decaffeinated coffee 1011
The monopotassium salt of phthalic acid and analytical
chemistry 1049
Phenylalanine as an essential dietary amino acid 1059
Hexyl acetate in hard candy 1063
1,3-Diphenylpropane-1,3-dione in licorice and as an
anticancer agent 1074

xxviii   Connections Boxes

Diethyl malonate in the synthesis of barbiturates 1078
Cyclohexylbenzene and lithium ion batteries 1113
(1-Methylethyl)benzene and polycarbonate
plastics 1115
1-Phenylbutan-1-one in the synthesis of the
antipsychotic haloperidol 1121
Benzenesulfonic acid and the treatment of
angina 1122
N-Phenylbenzamide to counter effects of hardening
arteries 1129
p-Nitrophenol in the synthesis of fever and pain
relievers 1146
m-Dinitrobenzene, from an explosive to the synthesis of
dyes 1146
o-Nitrotoluene in the manufacture of herbicides 1151
2,4,6-Tribromophenol as a wood preservative
and fungicide and in the manufacture of flame
retardants 1162
Prontosil, the first sulfa drug discovered 1173
p-Nitrobenzoic acid and Novocain dental
anesthetic 1181
4-Vinylcyclohexene in the manufacture of soaps and
cosmetics 1203
Bicyclo[2.2.1]hept-2-ene and motorcycle riders 1206
The cyclopentadienyl anion as a valuable ligand for
organometallic complexes 1217
Dicyclopentadiene and fiberglass/polyester composites
in heavy vehicles 1218
(2R,3S)-2,3-Dihydroxybutanoic acid as a naturally
occurring metabolite in humans 1218
Diphenylethanedione and the breakdown of
neurotransmitters 1220
Chlorine and clean water 1249
Ethers and the hazards on exposure to air in the
laboratory 1251
A solvated electron and the absorption of visible
light 1279
Polyacrylonitrile and safe drinking water 1314
Polypropylenes: roofing adhesives and Rubbermaid
containers 1318
Bakelite, from kitchenware to billiard balls 1332

Green Chemistry Boxes
NaBH4 as a greener alternative to LiAlH4 847
Green alternatives to Grignard reactions 855
Weighing E1 and E2 reactions against Wittig
reactions 877
Aldol addition reactions as highly atom efficient 908
Avoiding the use of solvents in crossed aldol
reactions 914
Weighing Raney-nickel reductions against Wolff–Kishner
and Clemmensen reductions 958
Selective reactions versus the use of protecting
groups 962
KMnO4 as a less toxic but less selective oxidizing agent
than H2CrO4 982

Hydrogen peroxide as a green oxidizing agent in
Baeyer–Villiger reactions 1068
Graphite as a green catalyst in Friedel–Crafts
alkylations 1112
Using a room temperature ionic liquid as the solvent in
nucleophilic aromatic substitution reactions 1176
Diels–Alder reactions minimizing waste 1200
Zeolite catalysts, a green alternative to OsO4 in syn
dihydroxylation 1219
Weighing KMnO4 against OsO4 in syn
dihydroxylation 1219
Reducing waste in dissolving metal reductions 1280


General SN2 mechanism (Equation 8-1) 394
General SN1 mechanism (Equation 8-2) 394
General E2 mechanism (Equation 8-4) 398
General E1 mechanism (Equation 8-5) 398
SN1 mechanism and stereochemistry
(Equation 8-18) 407
SN2 mechanism under basic conditions
(Equation 8-28) 423
SN1 mechanism under acidic conditions
(Equation 8-31) 424
Solvent-mediated proton transfer in SN2
(Equations 8-34 and 8-35) 426
SN1 mechanism with a carbocation rearrangement
(Equation 8-38) 430
SN1 mechanism proceeding through a
resonance-delocalized carbocation intermediate
(Equation 8-42) 433
Competition among SN2, SN1, E2, and E1 mechanisms
(Equations 9-1 through 9-4) 443
Rate-determining steps in SN2, SN1, E2, and
E1 mechanisms (Equations 9-5 through 9-8) 445
SN2 conversion of a 1° alcohol to an alkyl bromide using
HBr (Equation 9-21) 462
SN2 conversion of a phenyl methyl ether to a phenol and
bromomethane using HBr (Equation 9-24) 463
Acid-catalyzed dehydration of an alcohol
(Equation 9-26) 463
SN2 conversion of an alkyl chloride to an alkyl bromide
(Equation 9-36) 479
Solvolysis of an alkyl halide (Equations 9-38 and
9-39) 480
E2 conversion of a substituted cyclohexyl tosylate to a
substituted cyclohexene (Equation 9-41) 481
Acid-catalyzed glycoside formation of a sugar
(Equation 9-54) 491
SN2 conversion of a 1° alcohol to an alkyl bromide using
HBr (Equation 10-2) 516
PBr3 conversion of an alcohol to an alkyl bromide
(Equation 10-8) 518
SN2 alkylation of an amine (Equation 10-13) 521
Alkylation of an α carbon of a ketone or aldehyde
(Equation 10-19) 524
Regioselective alkylation of an α carbon of a ketone
using LDA (Equation 10-22) 526

Regioselective alkylation of an α carbon of a ketone
using a bulky alkoxide base (Equation 10-25) 527
Halogenation of an α carbon of a ketone or aldehyde
under basic conditions (Equation 10-27) 529
Polyhalogenation of an α carbon of a ketone or aldehyde
under basic conditions (Equation 10-29) 530
Halogenation of an α carbon of a ketone or aldehyde
under acidic conditions (Equation 10-31) 532
Diazomethane formation of a methyl ester
(Equation 10-33) 534
Williamson ether synthesis (Equation 10-36) 536
Formation of a cyclic ether from a haloalcohol under
basic conditions (Equation 10-39) 537
Formation of a symmetric ether from an alcohol under
acidic conditions (Equation 10-42) 538
Ring opening of an epoxide under basic conditions
(Equation 10-48) 541
Alkylation and ring opening of an epoxide using
alkyllithium or Grignard reagents (Equation 10-51) 542
Ring opening of an unsymmetric epoxide under basic
conditions (Equation 10-56) 543
Ring opening of an unsymmetric epoxide under acidic
conditions (Equation 10-58) 545
Formation of a terminal alkyne from a vinylic halide
(Equation 10-66) 549
Hofmann elimination (Equation 10-70) 551
Addition of a Brønsted acid to an alkene
(Equation 11-3) 565
Addition of a Brønsted acid to an alkene, with
carbocation rearrangement (Equation 11-9) 573
Acid-catalyzed hydration of an alkene
(Equation 11-15) 577
Addition of a Brønsted acid to an alkyne to produce a
geminal dihalide (Equation 11-17) 579
Addition of a Brønsted acid to an alkyne to produce a
vinylic halide (Equation 11-19) 581
Acid-catalyzed hydration of an alkyne
(Equation 11-21) 582
Addition of a Brønsted acid to a conjugated diene
(Equation 11-25) 584
Addition of carbene to an alkene (Equation 12-5) 605
Addition of dichlorocarbene to an alkene
(Equation 12-8) 606

Addition of a molecular halogen to an alkene, including
stereochemistry (Equations 12-10 and 12-11) 608
Addition of HOX to a symmetric alkene
(Equation 12-18) 612
Addition of HOX to an unsymmetric alkene
(Equation 12-20) 614
Oxymercuration–reduction of an alkene
(Equation 12-23) 616
Epoxidation of an alkene using a peroxyacid
(Equation 12-33) 621
Hydroboration of an alkene (Equation 12-36) 625
Oxidation of a trialkylborane (Equation 12-40) 629
Generic addition of a strong nucleophile to a π polar
bond (Equation 17-1) 841
Simplified picture of the NaBH4 reduction of a ketone
(Equation 17-7) 846
Simplified picture of the LiAlH4 reduction of an aldehyde
(Equation 17-8) 846
More accurate picture of the NaBH4 reduction of a
ketone (Equation 17-9) 846
Proton transfer involving alkyllithium reagents
(Equation 17-18) 854
Alkyllithium reaction involving a ketone
(Equation 17-21) 856
Grignard reaction involving a nitrile
(Equation 17-22) 856
Wittig reaction (Equation 17-26) 860
Generating a Wittig reagent (Equation 17-29) 861
Direct addition of a nucleophile to a conjugated
aldehyde (Equation 17-31) 864
Conjugate addition of a nucleophile to a conjugated
aldehyde (Equation 17-32) 864
Uncatalyzed nucleophilic addition of a weak nucleophile
to a ketone (Equation 18-3) 890
Base-catalyzed nucleophilic addition of a weak
nucleophile to a ketone (Equation 18-4) 890
Acid-catalyzed nucleophilic addition of a weak
nucleophile to a ketone (Equation 18-5) 891
Addition of HCN to a ketone (Equation 18-7) 893
Conjugate addition of a weak nucleophile to a
conjugated ketone (Equation 18-10) 895
Acid-catalyzed formation of an acetal
(Equation 18-13) 898
Acid-catalyzed formation of an imine
(Equation 18-19) 900
Acid-catalyzed formation of an enamine
(Equation 18-22) 902
Acid-catalyzed hydrolysis of a nitrile to form an amide
(Equation 18-25) 905
Base-catalyzed hydrolysis of a nitrile to form an amide
(Equation 18-26) 905
Wolff–Kishner reduction of a ketone
(Equation 18-28) 907

Self-aldol addition involving an aldehyde
(Equation 18-31) 909
Dehydration of an aldol product under basic conditions:
An E1cb mechanism (Equation 18-33) 911
Dehydration of an aldol product under acidic conditions
(Equation 18-35) 912
Self-aldol addition involving a ketone
(Equation 18-38) 914
Aldol condensation forming a ring
(Equation 18-48) 920
Reductive amination of an aldehyde
(Equation 18-63) 928
Ring formation in a monosaccharide
(Equation 18-66) 930
Catalytic hydrogenation of an alkene (Figure 19-2) 971
Chromic acid oxidation of a 2° alcohol
(Equation 19-33) 978
Suzuki coupling reaction (Equation 19-44) 985
Heck coupling reaction (Equation 19-46) 986
General mechanism for alkene metathesis reactions
(Equation 19-50) 988
Transesterification under basic conditions
(Equation 20-2) 1002
Esterification of an acid chloride under basic conditions
(Equation 20-4) 1006
Saponification: Conversion of an ester into a
carboxylate anion (Equation 20-9) 1012
Hydrolysis of an amide under basic conditions
(Equation 20-11) 1014
Gabriel synthesis of a 1° amine (Equation 20-13) 1016
Haloform reaction (Equation 20-16) 1018
NaBH4 reduction of an acid chloride to a 1° alcohol
(Equation 20-20) 1021
LiAlH4 reduction of a carboxylic acid to a 1° alcohol
(Equation 20-24) 1026
LiAlH4 reduction of an amide to an amine
(Equation 20-26) 1027
Reduction of an acid chloride to an aldehyde using
LiAlH(O-t-Bu)3 (Equation 20-29) 1030
Reduction of an ester to an aldehyde using DIBAH
(Equation 20-31) 1031
Conversion of an acid chloride to a 3° alcohol
(Equation 20-35) 1033
Hydrolysis of an acid chloride under neutral conditions
(Equation 21-4) 1047
Aminolysis of an acid chloride (Equation 21-9) 1053
SOCl2 conversion of a carboxylic acid to an acid chloride
(Equation 21-14) 1055
Hell–Volhard–Zelinsky reaction to form an α-bromo acid
(Equation 21-18) 1058
Sulfonation of an alcohol (Equation 21-21) 1060
Base-catalyzed transesterification
(Equation 21-25) 1062
Mechanisms   xxxi

Acid-catalyzed transesterification
(Equation 21-29) 1063
Amide hydrolysis under acidic conditions
(Equation 21-33) 1066
Baeyer–Villiger oxidation (Equation 21-35) 1067
Claisen condensation (Equation 21-37) 1069
Decarboxylation of a β-keto ester
(Equation 21-49) 1079
Amide formation via dicyclohexylcarbodiimide coupling
(Equation 21-56) 1087
General mechanism of electrophilic aromatic
substitution on benzene (Equation 22-4) 1106
Bromination of benzene (Equation 22-8) 1109
Friedel–Crafts alkylation of benzene
(Equation 22-12) 1112
Friedel–Crafts alkylation of benzene involving a
carbocation rearrangement (Equation 22-16) 1115
Friedel–Crafts alkylation involving a 1° alkyl halide
(Equation 22-18) 1116
Friedel–Crafts acylation of benzene
(Equation 22-22) 1118
Nitration of benzene (Equation 22-24) 1121
Sulfonation of benzene (Equation 22-26) 1123
Diazotization of benzene (Equation 22-35) 1131

xxxii   Mechanisms

Nucleophilic aromatic substitution on benzene, via
nucleophilic addition–elimination
(Equation 23-35) 1174
Nucleophilic aromatic substitution on benzene, via a
benzyne intermediate (Equation 23-40) 1177
Diels–Alder reaction (Equation 24-2) 1199
Syn dihydroxylation of an alkene involving OsO4
(Equation 24-31) 1219
Oxidative cleavage of an alkene involving KMnO4
(Equation 24-37) 1221
Oxidative cleavage of a cis-1,2-diol involving periodate
(Equation 24-41) 1223
Ozonolysis of an alkene (Equation 24-45) 1225
Radical chlorination of an alkane (Equations 25-18
through 25-20) 1261
Production of Br2 from N-bromosuccinimide
(Equation 25-28) 1272
Radical addition of HBr to an alkene
(Equation 25-33) 1275
Radical hydrogenation of an alkyne via dissolving metal
reduction (Equation 25-41) 1281
Birch reduction of benzene (Equation 25-45) 1282
Free-radical polymerization (Equations 26-3 through
26-8) 1311

Focused on the Student, Organized
by Mechanism
When an organic reaction is presented to a novice, only the structural differences between
the reactants and products are immediately apparent. Students tend to see only what
happens, such as the transformation of one functional group into another, changes in
connectivity, and aspects of stereochemistry. It should therefore not be surprising that
students, when presented reactions, are tempted to commit the reactions to memory. But
there are far too many reactions and accompanying details for memorization to work in
organic chemistry.
This is where mechanisms come into play. Mechanisms allow us to understand the
sequences of elementary steps — ​the step-by-step pathways — ​that convert the reactants
to products, so we can see how and why reactions take place as they do. Moreover, the
mechanisms that describe the large number of reactions in the course are constructed
from just a handful of elementary steps, so mechanisms allow us to see similarities among
reactions that are not otherwise apparent. In other words, mechanisms actually simplify
organic chemistry. Thus, teaching students mechanisms — ​enabling students to understand and simplify organic chemistry — ​is an enormous key to success in the course.
At the outset of my teaching career, I fully appreciated the importance of mechanisms, so during my first couple years of teaching, I emphasized mechanisms very
heavily. I did so under a functional group organization where reactions are pulled
together according to the functional groups that react. That is the organization under
which I learned organic chemistry, and it is also the way that most organic chemistry
textbooks are organized. Despite my best efforts, the majority of my students struggled
with even the basics of mechanisms and, consequently, turned to flash cards as their
primary study tool. They tried to memorize their way through the course, which made
matters worse.
I began to wonder what impact the organization — an organization according to
functional group — ​had on deterring my students from mechanisms. I had good reason
to be concerned because, as I alluded to earlier, functional groups tend to convey what,
whereas mechanisms convey how and why. What kinds of mixed messages were my students receiving when I was heavily emphasizing mechanisms, while the organization of
the material was giving priority to functional groups? To probe that question, I made a
big change to my teaching.
The third year I taught organic chemistry, I rearranged the material to pull together
reactions that had the same or similar mechanisms — ​that is, I taught under a mechanistic
organization. I made no other changes that year; the course content, course structure, and
my teaching style all remained the same. I even taught out of the same textbook. But that
year I saw dramatic improvements in my students’ mastery of mechanisms.1 Students had
control over the material, which proved to be a tremendous motivator. They were better
able to solve different kinds of problems with confidence. Ultimately, I saw significant

Bowman, B. G.; Karty, J. M.; Gooch, G. Teaching a Modified Hendrickson, Cram and Hammond Curriculum in Organic
Chemistry. J. Chem. Educ. 2007, 84, 1209.


improvements in student performance, morale, and retention. I was convinced that students benefit remarkably from learning under a mechanistic organization.
My goal in writing this book is to support instructors who are seeking what I was
seeking: getting students to use mechanisms to learn organic chemistry in order to
achieve better performances and to have better experiences in their organic courses.
Using a functional group organization to achieve these outcomes can be an uphill battle
because of the high priority that it inherently places on functional groups. This textbook,
on the other hand, allows students to receive the same message from both their instructor
and their textbook — ​a clear and consistent message that mechanisms are vital to success
in the course.

A Closer Look: Why Is a Mechanistic
Organization Better?
Consider what the novice sees when they begin a new functional group chapter. In an
alcohols chapter, for example, students first learn how to recognize and name alcohols,
then they study the physical properties of alcohols. Next, students might spend time on
special spectroscopic characteristics of alcohols, after which they learn various routes that
can be used to synthesize alcohols from other species. Finally, students move into the
heart of the chapter: new reactions that alcohols undergo and the mechanisms that
describe them. Within a particular functional group chapter, students find themselves
bouncing among several themes.
Even within the discussion of new reactions and mechanisms that a particular functional group can undergo, students are typically faced with widely varying reaction types
and mechanisms. Take again the example of alcohols. Students learn that alcohols can act
as an acid or as a base; alcohols can act as nucleophiles to attack a saturated carbon in a
substitution reaction, or to attack the carbon atom of a polar π bond in a nucleophilic
addition reaction; protonated alcohols can act as electrophiles in an elimination reaction;
and alcohols can undergo oxidation, too.
With the substantial jumping around that takes place within a particular functional
group chapter, it is easy to see how students can become overwhelmed. Under a functional group organization, students don’t receive intrinsic and clear guidance as to what
they should focus on, not only within a particular functional group chapter, but also from
one chapter to the next. Without clear guidance, and without substantial time for focus,
students often see no choice but to memorize. And they will memorize what they perceive to be most important — ​predicting products of reactions, typically ignoring, or giving short shrift to, fundamental concepts and mechanisms.
Under the mechanistic organization in this book, students experience a coherent story
of chemical reactivity. The story begins with molecular structure and energetics, and then
guides students into reaction mechanisms through a few transitional chapters. Thereafter,
students study how and why reactions take place as they do, focusing on one type of
mechanism at a time. Ultimately, students learn how to intuitively use reactions in synthesis. In this manner, students have clear and consistent guidance as to what their focus
should be on, both within a single chapter and throughout the entire book.

xxxiv   Preface

The patterns we, as experts, see become clear to students when they learn under this
mechanistic organization. Consider the following four mechanisms:










+ H2






+ H2








+ Br


R + HNR2 R′


R + Br


















+ Br







+ H3C







+ N2


The mechanism in Equation P-1 is for a Williamson synthesis of an ether; the one in
Equation P-2 is for an alkylation of a terminal alkyne; the one in Equation P-3 is for an
alkylation of a ketone; and the one in Equation P-4 is for the conversion of a carboxylic
acid to a methyl ester. In these four reactions, the reactants are an alcohol, an alkyne, a
ketone, and a carboxylic acid. In a functional group organization, these reactions will be
taught in four separate chapters. Because all four reaction mechanisms are identical — ​a
deprotonation followed by an SN2 step — ​all four reactions are taught in the same chapter
in this book: Chapter 10.
Seeing these patterns early, students more naturally embrace mechanisms and use
them when solving problems. Moreover, as students begin to see such patterns unfold in
one chapter, they develop a better toolbox of mechanisms to draw on in subsequent chapters. Ultimately, students gain confidence in using mechanisms to predict what will happen
and why. I believe this is vital to their success throughout the course and later on admission exams such as the MCAT.

Details about the Organization
Continuing with the success of the first edition, the book remains divided into three
major parts:
Part I: Atomic and molecular structure




Chapter 1: Atomic structure, Lewis structures and the covalent bond, and
resonance theory, culminating in an introduction to functional groups
Chapter 2: Aspects of three-dimensional geometry and its impacts on
intermolecular forces
Chapter 3: Structure in terms of hybridization and molecular orbital (MO)
Chapters 4 and 5: Isomerism in its entirety, including constitutional isomerism,
conformational isomerism, and stereoisomerism

Preface   xxxv

Much of the material in Chapters 1–5 will be new to students, such as organic functional
groups, protic and aprotic solvents, effective electronegativity, conformers and cyclohexane chair structures, and stereoisomers. Chapters 1–5 also contain a significant amount
of material that students will recognize from general chemistry, such as electronic configurations, Lewis structures and resonance, intermolecular forces, VSEPR theory and
hybridization, and constitutional isomers. Because most students do not retain everything they should from general chemistry, I have made the general chemistry topics in
this textbook more extensive than in other textbooks. Knowing that this extended coverage is in the book, instructors should feel comfortable covering as much or as little of it
as they see fit for their students.
Part II: Developing a toolbox for working with mechanisms

Chapters 6 and 7: Ten common elementary steps of mechanisms
Chapter 8: Beginnings of multistep mechanisms using SN1 and E1 reactions as

Mechanisms are vital to succeeding in organic chemistry, but before tackling mechanisms, students must have the proper tools. Chapters 6–8 give students those tools, dealing with aspects of elementary steps in Chapters 6 and 7 before dealing with aspects of
multistep mechanisms in Chapter 8. Therefore, the chapters in Part II act a transition
from Part I to Part III, which deals more intently with reactions.
Chapter 7 is a particularly important part of this transition. Students learn how to
work with elementary steps in Chapter 7 in a low-risk environment, where there are no
demands to predict products. Thus, there is no pressure to memorize overall reactions.
Furthermore, the fact that Chapter 7 brings together the 10 most common elementary
steps — ​making up the mechanisms of the many hundreds of reactions students will
encounter through Chapter 23 — ​sends a strong message to students that mechanisms
simplify organic chemistry. In turn, students take to heart from the outset that mechanisms are worthwhile to learn.
Part III: Major reaction types

Chapters 9 and 10: Nucleophilic substitution and elimination
Chapters 11 and 12: Electrophilic addition
Chapters 17 and 18: Nucleophilic addition
Chapters 20 and 21: Nucleophilic addition–elimination
Chapters 22 and 23: Aromatic substitution
Chapter 24: Diels–Alder reactions and other pericyclic reactions
Chapter 25: Radical reactions
Chapter 26: Polymerization

Several of these chapters come in pairs, where the first chapter is used to introduce key
ideas about the reaction or mechanism and the second chapter explores the reaction or
mechanism to greater depth and breadth.
Pairing the chapters this way provides flexibility. An instructor could teach all of the
chapters in order. Alternatively, following the guidelines set by the American Chemical
Society, an instructor could teach the first of each paired chapter in the first semester as
part of “foundational” coursework. Then, the remaining chapters would represent “indepth” coursework for the second semester. Teaching the chapters in this order would
also allow an instructor to teach carbonyl chemistry in the first semester.
Interspersed in Part III are chapters dealing with multistep synthesis (Chapters 13 and
19), conjugation and aromaticity (Chapter 14), and spectroscopy (Chapters 15 and 16).
The spectroscopy chapters are self-contained and can be taught earlier, at the instructor’s
discretion. They can even be taught separately in the laboratory. The spectroscopy chapters
are movable like this because, with the mechanistic organization of the book, important
aspects of spectroscopy are not integrated in reaction chapters like they typically are in a
functional group text.

xxxvi   Preface

The two chapters devoted to multistep synthesis (Chapters 13 and 19), on the other
hand, are strategically located. Chapter 13 appears after students have spent several chapters working with reactions. Having quite a few reactions under their belts, students can
appreciate retrosynthetic analysis, as well as cataloging reactions as functional group
transformations or reactions that alter the carbon skeleton. Moreover, Chapter 13 appears
early enough so students can practice their skills devising multistep syntheses throughout
the entire second half of the book; each subsequent chapter has multiple synthesis
problems. Additionally, Chapter 13 is an excellent review of reactions students learned to
that point in the book, so it could be taught at the end of the first semester as a capstone,
or it could be taught at the beginning of the second semester to help jog students’ memories in preparation for second semester.
Chapter 19 is delayed a few more chapters because it deals with content related to
reactions from Chapter 18, including protecting groups and choosing carbon–carbon
bond-forming reactions that result in the desired relative positioning of functional
groups. The multistep synthesis topics in Chapter 19 are somewhat more challenging
than the ones in Chapter 13, so whereas Chapter 13 should be covered in most mainstream courses, instructors can choose to cover only certain sections of Chapter 19.
I have found that treating multisynthesis in dedicated chapters makes it more meaningful to students. When I taught synthesis under a functional group organization, it
became a distraction to the reactions that students were simultaneously learning. I also
found that students often associated a synthetic strategy only with the functional group
for which it was introduced. For example, when the idea of protecting groups is introduced in the ketones/aldehydes chapter of a textbook organized by functional group,
students tended to associate protecting groups with ketones and aldehydes only. My
dedicated synthesis chapters help students focus on synthesis without compromising
their focus on reactions. Furthermore, synthesis strategies are discussed more holistically,
so students can appreciate them in a much broader context rather than being applicable
to just a single functional group.
Another major organizational feature of the book pertains to nomenclature. Nomen­
clature is separated out from the main chapters, in five relatively short interchapters — ​
Interchapters A, B, C, E, and F. Separating nomenclature from the main chapters in this way
removes distractions. It also allows students to focus on specific rules of nomenclature instead
of specific compound classes. With each new nomenclature interchapter, the complexity of
the material increases by applying the new rules to the ones introduced earlier.
The instructor has flexibility as to how to work with these nomenclature interchapters. They can be covered in lecture or easily assigned for self-study. They can be split over
two semesters or could all be covered in the first semester. The locations of the interchapters in the book (i.e., immediately after Chapters 1, 3, 5, 7, and 9), however, should be
taken as indicators as to the earliest that each interchapter should be assigned or taught.
Covering a nomenclature interchapter substantially earlier than it appears in the book
would expose students to compound classes well before those types of compounds are
dealt with in the main chapters.
Finally, the application of MOs toward chemical reactions is separated from the main
reaction chapters, and is presented, instead, as an optional, self-contained unit — ​
Interchapter D. This interchapter appears just after Chapter 7, the overview of the
10 most common elementary steps. Each elementary step from Chapter 7 is revisited
from the perspective of frontier MO theory. Because this interchapter is optional, chapters later in the book do not rely on coverage of this material.
Presenting this frontier MO theory material together in an optional unit, as I have
done in Interchapter D in this book, offers two main advantages to students. First, it
removes a potential distraction from the main reaction chapters and, being optional,
instructors have the choice of not covering it at all. Another advantage comes from the fact
that the MO pictures of all 10 common elementary steps appear together in the interchapter. Therefore, instructors who wish to cover this interchapter can expect their students to come away with a better understanding of the bigger picture of MO theory as it
pertains to chemical reactions.
Preface   xxxvii

Focused on the Student
While the organization provides a coherent story, I’ve included pedagogy that promotes
active learning and makes this book a better tool for students.
Strategies for Success. I wrote these sections to help students build specialized skills
they need in this course. For example, Chapter 1 provides strategies for drawing all resonance structures of a given species, and sections in Chapters 2 and 3 are devoted to the
importance of molecular modeling kits in working with
the three-dimensional aspects of molecules and also with
the different rotational characteristics of single and double
bonds. In Chapter 4, students are shown step by step how to
draw chair conformations of cyclohexane and how to draw
all constitutional isomers of a given formula. Chapter 5 provides help with drawing mirror images of molecules. One
Strategies for Success section in Chapter 6 helps students
estimate pKa values and another helps students rank acid
and base strengths based only on their Lewis structures. In Chapter 14, I include a section that shows students how to use the Lewis structure to assess conjugation and aromaticity, and Chapter 16 has a section that teaches students the chemical distinction test
for nuclear magnetic resonance.
Your Turn exercises. Getting students to read actively can be challenging, so I wrote
the Your Turns in each chapter to motivate this type of behavior. Your Turns are basic
exercises that ask students to either answer a question, look something up in a table, construct a molecule using a model kit, or interact with art in a figure or data in a plot. These
exercises are also intended to be “reality checks” for students as they read. If a student cannot solve or answer a Your Turn exercise easily, then that student should interpret this as a
signal to either reread the previous section(s) or seek help. Short answers to all Your Turns
are provided in the back of the book and complete solutions to these exercises are provided
in the Study Guide and Solutions Manual.

Consistent and effective problem-solving approach. Helping students become expert
problem solvers, in this course and beyond, is one of my major goals. I have developed the
Solved Problems in the book to train students how to approach a problem. Each Solved
Problem is broken down into two parts: Think and Solve. In the Think part, students are
provided a handful of guiding questions that I want them to be asking as they approach the
problem. In the Solve part, those questions are answered and the problem is solved. This
xxxviii   Preface

mirrors the strategy I use to help students during office hours,
and we have used these same steps for every problem in the Study
Guide and Solutions Manual that accompanies the book.
Biochemistry and the MCAT. Most students taking
organic chemistry are biology majors or are seeking a career in
a health profession. They appreciate seeing how organic chemistry relates to their interests and look for ways in which this
course will prepare them for the admissions exams (such as the
MCAT) that may have a large impact on their future.
Rather than relegating biochemistry to the end of the book, I have placed selfcontained Organic Chemistry of Biomolecules sections at the ends of several chapters,
beginning with Chapter 1. The topics chosen for these sections cover many of the topics
dealt with on the MCAT, which means that the Organic
Chemistry of Biomolecules sections are not in addition to
what students are expected to know for the MCAT; they are
topics that students should know for the test. In even the earliest of chapters, students have the tools to start learning aspects
of this traditional biochemistry coverage. More importantly,
these sections provide reinforcement of topics. In each biomolecules section, the material is linked directly back to concepts encountered earlier in the chapter.
These Organic Chemistry of Biomolecules sections are both optional and flexible.
Instructors can decide to cover only a few of these topics or none at all, and can do so
either as they appear in the book or as special topics at the end of the second semester.
A range of interesting applications. In addition to the Organic Chemistry of Biomolecules sections, most chapters have two special interest boxes. These boxes apply a concept
in the chapter to some depth toward a discovery or process that can have significant appeal
to students, perhaps delving into a biochemical process or examining new and novel materials. In addition to reinforcing concepts from the chapter, these boxes are intended to
provide meaning to what students are learning, and to motivate students to dig deeper.
In addition to these special interest boxes, several Connections boxes in each chapter
provide glimpses into the everyday utility of molecules that students have just seen.

New to the Second Edition
Organization of end-of-chapter problems. At the end of each chapter, problems are
grouped by concept or section so students can easily identify the types of problems they
need to work on. A set of Integrated Problems follows those sets of focused problems.
These Integrated Problems require students to bring together major concepts from multiple sections within the chapter, or from multiple chapters, as they would on an exam.
These problems also help students stay familiar with material from earlier in the book,
thus reducing the time that students would need to spend separately for review. In addition to organizing problems this way, problems that relate to aspects of synthesis are
labeled (SYN), so students and instructors can find those types of problem quickly.
More than 300 new problems. Based on user and reviewer feedback, several new
problems have been added to each chapter to provide students even more opportunities
to hone their problem-solving skills and to assess their mastery of the material. Some of
these new problems are specifically geared toward material from the Organic Chemistry
of Biomolecules sections from within the chapter, and are grouped together among the
end-of-chapter problems to make them easily identifiable.
More Solved Problems. The first edition provided students with about seven Solved
Problems per chapter on average. Several new Solved Problems have been added, bringing the average to about eight per chapter. This gives students more opportunities to
receive guidance on the strategies they should use when solving a problem. In addition,
Solved Problems have been added to each nomenclature interchapter. Nomenclature
builds in complexity as new rules are introduced, and each Solved Problem is designed to
help students navigate those new rules.
Preface   xxxix

Nomenclature presented in five interchapters rather than four. In the first edition,
nomenclature was presented in four interchapters. The fourth nomenclature interchapter
dealt with all compound classes that call for the addition of a suffix, including amines,
alcohols, ketones, aldehydes, and carboxylic acids and their derivatives. Users found this
to be too much material for one chapter, so in the second edition, that interchapter has
been split into two: Interchapters E and F. Interchapter E deals with alcohols, amines,
ketones, and aldehydes; Interchapter F deals with carboxylic acids and their derivatives.
Addition of green chemistry. Based on user feedback, I have added a new section on
green chemistry to Chapter 13, the first devoted chapter on multistep synthesis.
Section 13.8b provides an overview of green chemistry and its importance, and then
delves into three of the 12 main principles of green chemistry outlined by the American
Chemical Society: less toxic reagents and solvents; safer synthesis routes; and minimizing
by-products and other waste. In subsequent reaction chapters, students will find Green
Chemistry boxes in the margin notes, which highlight green aspects of some reactions
and provide green alternatives to others. For students planning on a career in chemistry,
the goal is to instill in them the importance of considering green chemistry when designing and carrying out a synthesis. All students should know what green chemistry is, and
should come to appreciate the fact that chemists in the 21st century are increasingly
prioritizing the well-being of our planet.
New strategies to help students analyze IR, NMR, and mass spectra. Even with a
strong foundation in the principles that underlie IR and NMR spectroscopy and mass
spectrometry, it can still be quite a challenge for students to analyze a spectrum in a way
that brings the individual pieces of information together. To help students along these
lines in the first edition, I presented spectra of unknowns and then brought students
through the analysis methodically, although somewhat passively. New to the second edition, I now present separate strategies up front to analyze IR, NMR, and mass spectra,
with sequential steps that students can follow. Then I show students how to apply these
strategies toward the analysis of spectra of unknowns. Students are encouraged to develop
other strategies that might work better for them, but until then, students have an effective
strategy that they can use and rely on.
Oxidation states moved to Chapter 17. In the first edition, calculating oxidation
states of atoms was presented in Chapter 1 alongside the calculation of formal charges.
Although grouping those two topics together makes sense because of the similarities
between the two methods, users reported that students weren’t sufficiently applying the
ideas of oxidation states toward redox reactions until Chapter 17. Therefore, in the second
edition, I moved the calculation of oxidation states to Section 17.3b, where hydride
reductions are discussed.
Nobel Prize–winning coupling and metathesis reactions. Because of their importance to organic chemistry, transition metal coupling reactions and alkene metathesis
reactions have been added to the second edition. These include: coupling reactions involving dialkylcurprates; the Suzuki reaction; the Heck reaction; and the Grubbs reaction.
The utility of these reactions is primarily in organic synthesis, specifically in the formation of new carbon–carbon bonds, so these reactions have been added to Chapter 19, the
second chapter devoted to organic synthesis.
Azo coupling and azo dyes. The presentation of azo coupling and a short discussion
on azo dyes have been added to Chapter 23, the second chapter on aromatic substitution
reactions. The benefits of this section are twofold. First, it is an application of diazotization
(Chapter 22) and substituent effects in aromatic substitution (Chapter 23), so it provides
reinforcement of newly learned concepts. Second, students can easily relate to dyes, so it is
an excellent example of the daily impacts organic chemistry has on students’ lives.
Connections boxes. Students often ask, “How does organic chemistry apply to me?”
or, “Why should I care about organic chemistry?” For the chemistry major or the student
going on to medical school or another health profession, the long-term answer might be
apparent. Connections boxes, which are new to the second edition, are designed to help
answer that question as it relates to the immediate. In the margins of each chapter, students will find several Connections boxes that highlight the importance or application of
xl   Preface

a molecule that was just encountered. Students might see that the molecule is integral in
the synthesis of a pharmaceutical drug, or that the molecule is important in the manufacture of a material that students use daily. More than just helping provide an answer to the
above questions, these Connections boxes also help keep students interested in the material, and an interested student is a more successful student.

Special thanks to my wife Valerie and my boys Joshua and Jacob for being my biggest
fans. Their love and immense support throughout my work on the second edition not
only helped push me to the finish line, but they continue to make my achievements
Many thanks to my colleagues in the chemistry department at Elon for your understanding, especially Dan Wright and Karl Sienerth, who served as my department chairs
during this endeavor. And a tremendous thank-you to Kathy Matera for the real-time
feedback you have given me over the years, and for all the times I barged into your office
to pick your brain when I was in the midst of working through a quandary with the book.
I remain indebted to my students. Thank you for bringing such great energy to learning
organic chemistry year in and year out, and thank you for allowing me to learn from you.
I continue to be amazed with the members of the Norton team. Erik Fahlgren, thank
you for your continued belief in me and in the potential this book has to help teachers
teach and to help students learn. John Murdzek, your insights in the developmental process have truly enabled me to reach students more effectively and meaningfully. Arielle
Holstein and Sara Bonacum, thank you for being the glue that has held this entire project
together. And a further congratulations to Arielle for your new position as Associate
Media Editor; thank you for the great work you have done on the book’s ancillaries. To
Carla Talmadge and Connie Parks, many thanks for holding me to a high standard in the
copyediting and page proofing stages. Travis Carr and Elyse Rieder, I admire your patience
and persistence when I need just the right photo. Christopher Rapp and Christine Pruis,
thank you for your work on the online resources for the book, which not only add value to
the book but also make the book more effective. Lisa Buckley, what a fantastic job on the
interior design, giving the book a warm and inviting feel. And Stacy Loyal, you continue
to amaze me with your vision and the creativity you bring to marketing the book.
A special thanks, once again, to Marie Melzer. With the energy and the insight that
you have continued to bring, I could not imagine a better coauthor on the Study Guide
and Solutions Manual. And to Steve Pruett, I truly value your work on the polymers chapter in the first edition.
Finally, I am indebted to the many reviewers, whose feedback has been instrumental
in making several significant improvements over the first edition. I am especially grateful
to Joachim Schantl, who accuracy-checked nearly the entire book! I am in awe of your
breadth and depth of knowledge, as well as your attention to detail. Many, many thanks.

Reviewers of Second Edition
Aron Anderson, Gustavus Adolphus College
Niels Andersen, University of Washington
Amelia Anderson-Wile, Ohio Northern
Christina Bagwill, Saint Louis University
Joshua Beaver, University of North Carolina,
Chapel Hill
David Bergbreiter, Texas A & M University
Shannon Biros, Grand Valley State
Dan Blanchard, Kutztown University

Elizabeth Blue, Campbell University
Luc Boisvert, University of Puget Sound
Michelle Boucher, Utica College
Rick Bunt, Middlebury College
Nancy Carpenter, University of Minnesota,
Timothy Clark, University of San Diego
Kimberly Cousins, California State University,
San Bernardino
Ashton Cropp, Virginia Commonwealth

Anna Drotor, Metropolitan State University
of Denver
Nathan Duncan, Maryville College
Brendan Dutmer, Highland Community
Todd Eckroat, Penn State, Behrend
Daniel Esterline, Thomas More College
Amanda Evans, California State University,
Christoph Fahrni, Georgia State Institute of
Preface   xli

Suzanne Fernandez, Lehigh University
Michael Findlater, Texas Tech University
Abbey Fischer, University of Wisconsin–
Barron County
Stephen Foley, University of Saskatchewan
Malcolm Forbes, Bowling Green State
Denis Fourches, North Carolina State
Andrew Frazer, University of Central Florida
Gregory Friestad, University of Iowa
Brian Frink, Lakeland College
Brian Ganley, University of Missouri
Kevin Glaeske, Wisconsin Lutheran College
Sarah Goforth, Campbell University
Harold Goldston Jr., Des Moines Area
Community College
Anne Gorden, Auburn University
Dustin Gross, Sam Houston State University
Matthew Hart, Grand Valley State University
Allan Headley, Texas A & M University
Ian Hill, Gustavus Adolphus College
Daniel Holley, Columbus State University
Robert Hughes, East Carolina State
Philip Hultin, University of Manitoba
William Jenks, Iowa State University
Bob Kane, Baylor University
Kristopher Keuseman, Mount Mercy
Brett Kite, Shenandoah University
Jeremy Klosterman, University of California,
San Diego
Kazunori Koide, University of Pittsburgh
Shane Lamos, St. Michael’s College
Nicholas Leadbeater, University of
Carl Lecher, Marian University
Larry Lee, Camosun College

Diana Leung, University of Alabama,
Nicholas Llewellyn, Emory University
Carl Lovely, University of Texas, Arlington
Breeyawn Lybbert, University of Wisconsin
Helena Malinakova, University of Kansas
Richard Manderville, University of Guelph
Kristen Mascall, Brandeis University
Eugene Mash, University of Arizona
Daniell Mattern, University of Mississippi
Jimmy Mays, University of Tennessee,
Vanessa McCaffrey, Albion College
Justin Mohr, University of Illinois, Chicago
Suazette Mooring, Georgia State University
Jesse More, Loyola University
Andrew Morehead, East Carolina University
Cheryl Moy, University of North Carolina,
Chapel Hill
R. Scott Murphy, Regina University
Joan Mutanyatta-Comar, Georgia State
David Nagib, Ohio State University
Felix Ngassa, Grand Valley State University
Taeboem Oh, California State University,
Joshua Osbourn, West Virginia University
Keith Pascoe, Georgia State University
Gitendra Paul, Malcolm X College
Michael Pelter, Purdue University Northwest
Angela Perkins, University of Minnesota
Joanna Petridou-Fischer, Spokane Falls
Community College
Tarakeshwar Pilarsetty, Arizona State
Smitha Pillai, Arizona State University
Kyle Plunkett, Southern Illinois University
Pamela Pollet, Georgia Institute of Technology

Brian Popp, West Virginia University
Walda Powell, Meredith College
Stephen Pruett, Jefferson Community and
Technical College
Frank Rossi, State University of New York,
Nicholas Salzameda, California State
University, Fullerton
Robert Sammelson, Ball State University
Joachim Schantl, University of Florida
Jacob Schroeder, Clemson University
Reza Sedaghat-Herati, Missouri State
Jia Sheng, University of Albany
Abbas Shilabin, East Tennessee State
Matthew Siebert, Missouri State University
Chatu Sirimanne, California State University,
Los Angeles
Heather Sklenicka, Rochester Community and
Technical College
Mike Slade, University of Evansville
Greg Slough, Kalamazoo College
Gary Spessard, University of Arizona
Nicholas Stephanopoulos, Arizona State
Robert Ternansky, University of California,
San Diego
Sadanandan Velu, University of Alabama,
Martin Walker, The State University of New
York, Potsdam
Don Warner, Boise State University
Michael Weaver, University of Florida
Lyndon West, Florida Atlantic University
Anne Wilson, Butler University
Kai Ylijoki, Saint Mary’s University
Yimin Zhu, Pennsylvania State University,

Reviewers of the First Edition
Robert Allen, Arkansas Tech University
Herman Ammon, University of Maryland
Carolyn Anderson, Calvin College
Aaron Aponick, University of Florida
Phyllis Arthasery, Ohio University
Jared Ashcroft, Pasadena City College
Athar Ata, University of Winnipeg
Jovica Badjic, Ohio State University
John Bellizzi, University of Toledo
Daniel Berger, Bluffton University
Anthony Bishop, Amherst College
Rebecca Broyer, University of Southern

xlii   Preface

Larry Calhoun, University of New Brunswick
Shawn Campagna, University of Tennessee,
Nancy Carpenter, University of Minnesota,
Brad Chamberlain, Luther College
Robert Coleman, Ohio State University
Tammy Davidson, University of Florida
Lorraine Deck, University of New Mexico
Sergei Dzyuba, Texas Christian University
Jeff Elbert, University of Northern Iowa
Seth Elsheimer, University of Central Florida
Eric Finney, University of Washington

Andrew Frazer, University of Central Florida
Larry French, St. Lawrence University
Gregory Friestad, University of Iowa
Brian Frink, Lakeland University
Anne Gorden, Auburn University
Christopher Gorman, North Carolina State
Oliver Graudejus, Arizona State University
Robert Grossman, University of Kentucky
Daniel Gurnon, DePauw University
Jeffrey Hansen, DePauw University
Bryan Hanson, DePauw University
Andrew Harned, University of Minnesota

Stewart Hart, Arkansas Tech University
John Hershberger, Arkansas State University
Gail Horowitz, Brooklyn College
Roger House, Auburn University
Philip Hultin, University of Manitoba
Kevin Jantzi, Valparaiso University
Amanda Jones, Wake Forest University
Jeff Jones, Washington State University
Paul Jones, Wake Forest University
Robert Kane, Baylor University
Arif Karim, Austin Community College
Steven Kass, University of Minnesota
Stephen Kawai, Concordia University
Valerie Keller, University of Chicago
Mark Keranen, University of Tennessee at
Kristopher Keuseman, Mount Mercy College
Angela King, Wake Forest University
Jesudoss Kingston, Iowa State University
Francis Klein, Creighton University
Jeremy Klosterman, Bowling Green State
Dalila Kovacs, Grand Valley State University
Jason Locklin, University of Georgia
Brian Long, University of Tennessee, Knoxville
Claudia Lucero, California State University,
David Madar, Arizona State University
Kirk Manfredi, University of Northern Iowa

Eric Masson, Ohio University
Anita Mattson, Ohio State University
Gerald Mattson, University of Central Florida
Jimmy Mays, University of Tennessee,
Alison McCurdy, California State University,
Los Angeles
Dominic McGrath, University of Arizona
Mark McMills, Ohio University
Marie Melzer, Old Dominion University
Ognjen Miljanic, University of Houston
Justin Miller, Hobart and William Smith
Stephen Miller, University of Florida
Barbora Morra, University of Toronto
Joseph O’Connor, University of California,
San Diego
James Parise, University of Notre Dame
Gitendra Paul, Malcolm X Community
Noel Paul, Ohio State University
James Poole, Ball State University
Christine Pruis, Arizona State University
Harold Rogers, California State University,
Sheryl Rummel, Pennsylvania State University
Nicholas Salzameda, California State
University, Fullerton
Adrian Schwan, University of Guelph
Colleen Scott, Southern Illinois University,

Alan Shusterman, Reed College
Joseph Simard, University of New England
Chad Snyder, Western Kentucky University
John Sorensen, University of Manitoba
Levi Stanley, Iowa State University
Laurie Starkey, California State University,
Tracy Thompson, Alverno College
Nathan Tice, Butler University
John Tomlinson, Wake Forest University
Melissa VanAlstine-Parris, Adelphi University
Nanine Van Draanen, California Polytechnic
State University
Qian Wang, University of South Carolina
Don Warner, Boise State University
Haim Weizman, University of California, San
Lisa Whalen, University of New Mexico
James Wilson, University of Miami
Laurie Witucki, Grand Valley State University
James Wollack, St. Catherine University
Andrei Yudin, University of Toronto
Michael Zagorski, Case Western Reserve
Rui Zhang, Western Kentucky University
Regina Zibuck, Wayne State University
Eugene Zubarev, Rice University
James Zubricky, University of Toledo

Additional Resources
For Students
Study Guide and Solutions Manual
by Joel Karty, Elon University, and Marie Melzer
Written by two dedicated teachers, this guide provides students with fully worked solutions to all unworked problems in the text. Every solution follows the Think and Solve
format used in the textbook, so the approach to problem solving is modeled consistently.

Smartwork5 (
Smartwork5 is the most intuitive online tutorial and homework system available for
organic chemistry. A powerful engine supports and grades a wide variety of problems
written for the text, including numerous arrow-pushing problems. Every problem in
Smartwork5 has hints and answer-specific feedback to coach students and provide the
help they need, when they need it. Problems in Smartwork5 link directly to the appropriate page in the ebook so students have an instant reference and are prompted to read.
Assigning, editing, and administering homework within Smartwork5 is easy. Instructors can select from Norton’s bank of more than 3200 high-quality, class-tested problems.
Using the sort and search features, instructors can identify problems by chapter section,
learning objective, question type, and more. Instructors can use premade assignments
provided by Norton authors, modify those assignments, or create their own. Instructors
Preface   xliii

also have access to intuitive question authoring tools — ​the same ones Norton authors
use. These tools make it easy to customize the question content to fit the course needs.
Smartwork5 integrates seamlessly with most campus learning management systems and
can be used on computers and tablets.
The Smartwork5 course features:






An expert author team. The Smartwork5 course was authored by instructors who
teach at a diverse group of schools: Arizona State University, Florida State University,
Brigham Young University, Butler University, and Mesa Community College. The
authors have translated their experience in teaching a diverse student population by
creating a library of problems that will appeal to instructors at all schools.
An upgraded drawing tool. Smartwork5 contains an upgraded 2-D drawing tool
that mimics drawing on paper, reduces frustration, and helps students focus on the
problem at hand. This intuitive drawing tool supports multistep mechanism and multistep synthesis problems and provides students with answer-specific feedback for
every problem.
Ease of use for students. The 2-D drawing tool has a variety of features that make
drawing easy and efficient. Students are provided with templates including a variety
of common rings and a carbon chain drawing tool. In addition, Smartwork5 presents
students with commonly used elements, a simple click to add lone pairs option, and
ease-of-use features such as undo, redo, simple-click erase, and zoom-in/zoom-out.
Question variety. The Smartwork5 course offers a diverse set of problems including:
● Nomenclature problems
● Multistep Mechanism problems
● Multistep Synthesis problems
● Reaction problems
● Spectroscopy problems
Conceptual question types include:
● Multiple-choice/multiple select
● Ranking
● Sorting
● Labeling
● Numeric entry
● Short answer
Pooled problems. Smartwork5 features sets of pooled problems for multistep mechanisms and nomenclature to promote independent work. Groups of similar problems
are “pooled” into one problem so different students receive different problems from
the pool. Instructors can choose our preset pools or create their own.

Ebook (
An affordable and convenient alternative to the print text, the Norton Ebook lets students access the entire book and much more: They can search, highlight, and take notes
with ease. The Norton Ebook allows instructors to share their notes with students. The
ebook can be viewed on computers and tablets and will stay synced between devices. The
online ebook is available at no extra cost with the purchase of a new print text or it may
be purchased stand-alone with Smartwork5.

Molecular Model Kits
Norton partners with two model kits and can package either with the textbook for an
additional cost.
Darling Molecular Model Kit. Atoms with their valences already attached are constructed by snapping together V-shaped pieces in a jigsaw style, emphasizing bond
angles and symmetry elements of the atoms. Double bonds are independent, rectangular units to emphasize the planarity of sp2-h