Ebook Organic chemistry (2nd edition) Part 1

Structures of Common Coenzymes
The reactive parts of the molecules are darkened, while nonreactive parts are ghosted.

Adenosine triphosphate—ATP (phosphorylation)
NH2
N
O
–O

P
O–

O

P

N

O

O

P

O

N

OCH2

N

O

O–

O–

OH

OH
Coenzyme A (acyl transfer)

NH2
N
O

O

CH3

N

O O
N

HSCH2CH2NHCCH2CH2NHCCHCCH2OPOPOCH2
HO CH3

N

O

O– O–
2–O PO
3

OH

Nicotinamide adenine dinucleotide—NAD+ (oxidation/reduction)
(NADP+)
NH2
CONH2

N

N

O O
+

N

CH2OPOPOCH2

N
OH HO
O

N

O

O– O–

OH

OH (OPO32–)

Flavin adenine dinucleotide—FAD (oxidation/reduction)
NH2
N
HO OH
HO

CHCHCHCH2OPOPOCH2
O– O–

CH2
H3C

N

H3C

N

N

N

O

O
OH
N

O

N

O O

H

OH

N


Tetrahydrofolate (transfer of C1 units)
H
H2N

H

N

N

H

N

N

N

CO2–

H

O

H

O

NHCHCH2CH2C

O–
1–5

O
S-Adenosylmethionine (methyl transfer)
NH2
N

N

CH3

O
–OCCHCH CH
2
2
+NH

S
+

CH2

N

N

O

3

OH

OH

Lipoic acid (acyl transfer)

S

Pyridoxal phosphate
(amino acid metabolism)
CH2OPO32–

S

CHO

CH2CH2CH2CH2CO2–
+
H

N
OH
CH3

Biotin (carboxylation)

Thiamin diphosphate
(decarboxylation)
H
S

O

NH2
+
N

H

N

O O
–OPOPOCH CH
2
2
O– O–

N

N

H
CH3

N

H
H
H

CH3
S

CH2CH2CH2CH2CO2–


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Sincerely,
John McMurry

All royalties from Organic Chemistry with Biological Applications will be donated to the Cystic Fibrosis (CF) Foundation. This
book and donation are dedicated to the author’s eldest son and to the thousands of others who daily fight this disease.
To learn more about CF and the programs and services provided by the CF Foundation, please visit .



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Organic Chemistry
with Biological Applications 2e

John McMurry
Cornell University

Australia • Brazil • Japan • Korea • Mexico • Singapore • Spain • United Kingdom • United States


Organic Chemistry with Biological
Applications 2e
John McMurry
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Brief Contents
1

Structure and Bonding

2

Polar Covalent Bonds; Acids and Bases

3

Organic Compounds: Alkanes and Their Stereochemistry

4

Organic Compounds: Cycloalkanes and Their Stereochemistry

5

Stereochemistry at Tetrahedral Centers

6

An Overview of Organic Reactions

7

Alkenes and Alkynes

8

Reactions of Alkenes and Alkynes

9

Aromatic Compounds

10

1
33
70
105

134

175

212
251

309

Structure Determination:
Mass Spectrometry, Infrared Spectroscopy, and Ultraviolet Spectroscopy

11

Structure Determination: Nuclear Magnetic Resonance Spectroscopy

12

Organohalides: Nucleophilic Substitutions and Eliminations

13

Alcohols, Phenols, and Thiols; Ethers and Sulfides
Preview of Carbonyl Chemistry

367

404

444

501

555

14

Aldehydes and Ketones: Nucleophilic Addition Reactions

15

Carboxylic Acids and Nitriles

16

Carboxylic Acid Derivatives: Nucleophilic Acyl Substitution Reactions

17

Carbonyl Alpha-Substitution and Condensation Reactions

18

Amines and Heterocycles

19

Biomolecules: Amino Acids, Peptides, and Proteins

20

Amino Acid Metabolism

21

Biomolecules: Carbohydrates

22

Carbohydrate Metabolism

23

Biomolecules: Lipids and Their Metabolism

24

Biomolecules: Nucleic Acids and Their Metabolism

25

Secondary Metabolites: An Introduction to Natural Products Chemistry

564

610
643

695

749
791

832

862

901
936
987
1015

Key to Sequence of Topics (chapter numbers are color coded as follows):
• Traditional foundations of organic chemistry
• Organic reactions and their biological counterparts
• The organic chemistry of biological molecules and pathways

v


Detailed Contents

1

Structure and Bonding
1.1
1.2
1.3
1.4
1.5
1.6
1.7
1.8
1.9
1.10

1.11
1.12

1

Atomic Structure: The Nucleus 3
Atomic Structure: Orbitals 4
Atomic Structure: Electron Configurations 6
Development of Chemical Bonding Theory 7
The Nature of Chemical Bonds: Valence Bond Theory 10
sp3 Hybrid Orbitals and the Structure of Methane 12
sp3 Hybrid Orbitals and the Structure of Ethane 13
sp2 Hybrid Orbitals and the Structure of Ethylene 14
sp Hybrid Orbitals and the Structure of Acetylene 17
Hybridization of Nitrogen, Oxygen, Phosphorus, and Sulfur 18
The Nature of Chemical Bonds: Molecular Orbital Theory 20
Drawing Chemical Structures 21
Summary 24
Lagniappe—Chemicals, Toxicity, and Risk 25
Working Problems 26
Exercises 26

2

Polar Covalent Bonds; Acids and Bases
2.1
2.2
2.3
2.4
2.5

2.6
2.7

vi

Polar Covalent Bonds: Electronegativity 33
Polar Covalent Bonds: Dipole Moments 36
Formal Charges 38
Resonance 41
Rules for Resonance Forms 43
Drawing Resonance Forms 45
Acids and Bases: The Brønsted–Lowry Definition 48

33


detailed contents

2.8
2.9
2.10
2.11
2.12

Acid and Base Strength 49
Predicting Acid–Base Reactions from pKa Values 51
Organic Acids and Organic Bases 53
Acids and Bases: The Lewis Definition 56
Noncovalent Interactions between Molecules 60
Summary 62

Lagniappe—Alkaloids: Naturally Occurring Bases 63
Exercises 64

Organic Compounds: Alkanes and Their
Stereochemistry 70
3.1
3.2
3.3
3.4
3.5
3.6
3.7

3

Functional Groups 70
Alkanes and Alkane Isomers 77
Alkyl Groups 81
Naming Alkanes 84
Properties of Alkanes 89
Conformations of Ethane 90
Conformations of Other Alkanes 92
Summary 97
Lagniappe—Gasoline 98
Exercises 99

Organic Compounds: Cycloalkanes and Their
Stereochemistry 105
4.1
4.2

4.3
4.4
4.5
4.6
4.7
4.8
4.9

Naming Cycloalkanes 106
Cis–Trans Isomerism in Cycloalkanes 109
Stability of Cycloalkanes: Ring Strain 112
Conformations of Cycloalkanes 113
Conformations of Cyclohexane 115
Axial and Equatorial Bonds in Cyclohexane 117
Conformations of Monosubstituted Cyclohexanes 120
Conformations of Disubstituted Cyclohexanes 123
Conformations of Polycyclic Molecules 126
Summary 127
Lagniappe—Molecular Mechanics 128
Exercises 129

4

vii


viii

detailed contents

5

Stereochemistry at Tetrahedral Centers
5.1
5.2
5.3
5.4
5.5
5.6
5.7
5.8
5.9
5.10
5.11
5.12

134

Enantiomers and the Tetrahedral Carbon 135
The Reason for Handedness in Molecules: Chirality 136
Optical Activity 140
Pasteur’s Discovery of Enantiomers 142
Sequence Rules for Specifying Configuration 143
Diastereomers 149
Meso Compounds 151
Racemic Mixtures and the Resolution of Enantiomers 154
A Review of Isomerism 156
Chirality at Nitrogen, Phosphorus, and Sulfur 158
Prochirality 159
Chirality in Nature and Chiral Environments 162

Summary 164
Lagniappe—Chiral Drugs 165
Exercises 166

6

An Overview of Organic Reactions
6.1
6.2
6.3
6.4
6.5
6.6
6.7
6.8
6.9
6.10
6.11

175

Kinds of Organic Reactions 176
How Organic Reactions Occur: Mechanisms 177
Radical Reactions 178
Polar Reactions 181
An Example of a Polar Reaction: Addition of H2O to Ethylene 186
Using Curved Arrows in Polar Reaction Mechanisms 189
Describing a Reaction: Equilibria, Rates, and Energy Changes 192
Describing a Reaction: Bond Dissociation Energies 195
Describing a Reaction: Energy Diagrams and Transition States 197

Describing a Reaction: Intermediates 200
A Comparison between Biological Reactions and Laboratory Reactions 202
Summary 204
Lagniappe—Where Do Drugs Come From? 205
Exercises 206

7

Alkenes and Alkynes
7.1
7.2
7.3
7.4
7.5

212

Calculating a Degree of Unsaturation 213
Naming Alkenes and Alkynes 216
Cis–Trans Isomerism in Alkenes 219
Alkene Stereochemistry and the E,Z Designation 221
Stability of Alkenes 223


detailed contents

7.6
7.7
7.8
7.9

7.10

Electrophilic Addition Reactions of Alkenes 227
Writing Organic Reactions 229
Orientation of Electrophilic Addition: Markovnikov’s Rule 230
Carbocation Structure and Stability 233
The Hammond Postulate 235
Evidence for the Mechanism of Electrophilic Additions: Carbocation
Rearrangements 238
Summary 241
Lagniappe—Terpenes: Naturally Occurring Alkenes 242
Exercises 243

Reactions of Alkenes and Alkynes
8.1
8.2
8.3
8.4
8.5
8.6
8.7
8.8
8.9
8.10
8.11
8.12
8.13
8.14
8.15

251

8

Preparing Alkenes: A Preview of Elimination Reactions 252
Halogenation of Alkenes 254
Halohydrins from Alkenes 256
Hydration of Alkenes 257
Reduction of Alkenes: Hydrogenation 261
Oxidation of Alkenes: Epoxidation 265
Oxidation of Alkenes: Hydroxylation 267
Oxidation of Alkenes: Cleavage to Carbonyl Compounds 270
Addition of Carbenes to Alkenes: Cyclopropane Synthesis 272
Radical Additions to Alkenes: Alkene Polymers 274
Biological Additions of Radicals to Alkenes 278
Conjugated Dienes 279
Reactions of Conjugated Dienes 283
The Diels–Alder Cycloaddition Reaction 285
Reactions of Alkynes 290
Summary 293
Learning Reactions 294
Summary of Reactions 295
Lagniappe—Natural Rubber 298
Exercises 299

Aromatic Compounds
9.1
9.2
9.3
9.4

9.5
9.6

309

Naming Aromatic Compounds 310
Structure and Stability of Benzene 313
Aromaticity and the Hückel 4n ϩ 2 Rule 315
Aromatic Ions and Aromatic Heterocycles 317
Polycyclic Aromatic Compounds 322
Reactions of Aromatic Compounds: Electrophilic Substitution 324

9

ix


x

detailed contents

9.7
9.8
9.9
9.10
9.11

Alkylation and Acylation of Aromatic Rings: The Friedel–Crafts
Reaction 331
Substituent Effects in Electrophilic Substitutions 336

Nucleophilic Aromatic Substitution 344
Oxidation and Reduction of Aromatic Compounds 347
An Introduction to Organic Synthesis: Polysubstituted Benzenes 349
Summary 355
Summary of Reactions 356
Lagniappe—Aspirin, NSAIDs, and COX-2 Inhibitors 357
Exercises 359

10

Structure Determination: Mass Spectrometry,
Infrared Spectroscopy, and Ultraviolet
Spectroscopy 367
10.1
10.2
10.3
10.4
10.5
10.6
10.7
10.8
10.9
10.10
10.11

Mass Spectrometry of Small Molecules: Magnetic-Sector Instruments 368
Interpreting Mass Spectra 369
Mass Spectrometry of Some Common Functional Groups 373
Mass Spectrometry in Biological Chemistry: Time-of-Flight (TOF)
Instruments 376

Spectroscopy and the Electromagnetic Spectrum 377
Infrared Spectroscopy 380
Interpreting Infrared Spectra 381
Infrared Spectra of Some Common Functional Groups 384
Ultraviolet Spectroscopy 389
Interpreting Ultraviolet Spectra: The Effect of Conjugation 391
Conjugation, Color, and the Chemistry of Vision 392
Summary 394
Lagniappe—Chromatography: Purifying Organic Compounds 395
Exercises 396

11

Structure Determination: Nuclear Magnetic
Resonance Spectroscopy 404
11.1
11.2
11.3
11.4
11.5
11.6
11.7

Nuclear Magnetic Resonance Spectroscopy 405
The Nature of NMR Absorptions 406
Chemical Shifts 409
13C NMR Spectroscopy: Signal Averaging and FT–NMR 411
Characteristics of 13C NMR Spectroscopy 412
DEPT 13C NMR Spectroscopy 415
Uses of 13C NMR Spectroscopy 417

detailed contents

11.8
11.9
11.10
11.11
11.12
11.13

1H NMR Spectroscopy and Proton Equivalence

418

Chemical Shifts in 1H NMR Spectroscopy 421
Integration of 1H NMR Absorptions: Proton Counting 423
Spin–Spin Splitting in 1H NMR Spectra 423
More Complex Spin–Spin Splitting Patterns 428
Uses of 1H NMR Spectroscopy 430
Summary 431
Lagniappe—Magnetic Resonance Imaging (MRI) 432
Exercises 433

Organohalides: Nucleophilic Substitutions
and Eliminations 444
12.1
12.2
12.3
12.4

12.5
12.6
12.7
12.8
12.9
12.10
12.11
12.12
12.13
12.14
12.15

12

Names and Structures of Alkyl Halides 445
Preparing Alkyl Halides from Alkenes: Allylic Bromination 447
Preparing Alkyl Halides from Alcohols 451
Reactions of Alkyl Halides: Grignard Reagents 453
Discovery of the Nucleophilic Substitution Reaction 454
The SN2 Reaction 457
Characteristics of the SN2 Reaction 460
The SN1 Reaction 467
Characteristics of the SN1 Reaction 471
Biological Substitution Reactions 476
Elimination Reactions: Zaitsev’s Rule 478
The E2 Reaction 481
The E1 and E1cB Reactions 484
Biological Elimination Reactions 486
A Summary of Reactivity: SN1, SN2, E1, E1cB, and E2 486
Summary 488

Summary of Reactions 489
Lagniappe—Green Chemistry 491
Exercises 492

Alcohols, Phenols, and Thiols; Ethers
and Sulfides 501
13.1
13.2
13.3
13.4
13.5
13.6

Naming Alcohols, Phenols, and Thiols 503
Properties of Alcohols, Phenols, and Thiols 504
Preparing Alcohols from Carbonyl Compounds 508
Reactions of Alcohols 516
Oxidation of Alcohols and Phenols 520
Protection of Alcohols 524

13

xi


xii

detailed contents

13.7

13.8
13.9
13.10
13.11
13.12

Preparation and Reactions of Thiols 526
Ethers and Sulfides 528
Preparing Ethers 529
Reactions of Ethers 531
Preparation and Reactions of Sulfides 534
Spectroscopy of Alcohols, Phenols, and Ethers 536
Summary 538
Summary of Reactions 539
Lagniappe—Ethanol: Chemical, Drug, and Poison 542
Exercises 543

Preview of Carbonyl Chemistry
I
II
III
IV

14

555

Kinds of Carbonyl Compounds 555
Nature of the Carbonyl Group 557
General Reactions of Carbonyl Compounds 557

Summary 562
Exercises 563

Aldehydes and Ketones: Nucleophilic Addition
Reactions 564
14.1
14.2
14.3
14.4
14.5
14.6
14.7
14.8
14.9
14.10
14.11
14.12

Naming Aldehydes and Ketones 565
Preparing Aldehydes and Ketones 567
Oxidation of Aldehydes 568
Nucleophilic Addition Reactions of Aldehydes and Ketones 569
Nucleophilic Addition of H2O: Hydration 572
Nucleophilic Addition of Grignard and Hydride Reagents:
Alcohol Formation 574
Nucleophilic Addition of Amines: Imine and Enamine Formation 576
Nucleophilic Addition of Alcohols: Acetal Formation 580
Nucleophilic Addition of Phosphorus Ylides: The Wittig Reaction 583
Biological Reductions 587
Conjugate Nucleophilic Addition to ␣,␤-Unsaturated Aldehydes and

Ketones 588
Spectroscopy of Aldehydes and Ketones 593
Summary 596
Summary of Reactions 597
Lagniappe—Enantioselective Synthesis 599
Exercises 600


detailed contents

Carboxylic Acids and Nitriles
15.1
15.2
15.3
15.4
15.5
15.6
15.7
15.8

610

15

Naming Carboxylic Acids and Nitriles 611
Structure and Properties of Carboxylic Acids 613
Biological Acids and the Henderson–Hasselbalch Equation 617
Substituent Effects on Acidity 618
Preparing Carboxylic Acids 620
Reactions of Carboxylic Acids: An Overview 622

Chemistry of Nitriles 623
Spectroscopy of Carboxylic Acids and Nitriles 627
Summary 629
Summary of Reactions 630
Lagniappe—Vitamin C 631
Exercises 633

Carboxylic Acid Derivatives: Nucleophilic Acyl
Substitution Reactions 643
16.1
16.2
16.3
16.4
16.5
16.6
16.7
16.8
16.9
16.10

16

Naming Carboxylic Acid Derivatives 644
Nucleophilic Acyl Substitution Reactions 647
Nucleophilic Acyl Substitution Reactions of Carboxylic Acids 652
Chemistry of Acid Halides 659
Chemistry of Acid Anhydrides 664
Chemistry of Esters 665
Chemistry of Amides 671
Chemistry of Thioesters and Acyl Phosphates: Biological Carboxylic Acid

Derivatives 674
Polyamides and Polyesters: Step-Growth Polymers 675
Spectroscopy of Carboxylic Acid Derivatives 679
Summary 680
Summary of Reactions 681
Lagniappe—␤-Lactam Antibiotics 683
Exercises 684

Carbonyl Alpha-Substitution and Condensation
Reactions 695
17.1
17.2
17.3
17.4
17.5

Keto–Enol Tautomerism 696
Reactivity of Enols: ␣-Substitution Reactions 699
Alpha Bromination of Carboxylic Acids 702
Acidity of ␣ Hydrogen Atoms: Enolate Ion Formation 703
Alkylation of Enolate Ions 706

17

xiii


xiv

detailed contents

17.6
17.7
17.8
17.9
17.10
17.11
17.12
17.13

Carbonyl Condensations: The Aldol Reaction 715
Dehydration of Aldol Products 719
Intramolecular Aldol Reactions 722
The Claisen Condensation Reaction 723
Intramolecular Claisen Condensations 726
Conjugate Carbonyl Additions: The Michael Reaction 728
Carbonyl Condensations with Enamines: The Stork Reaction 730
Biological Carbonyl Condensation Reactions 733
Summary 735
Summary of Reactions 736
Lagniappe—X-Ray Crystallography 738
Exercises 739

18

Amines and Heterocycles
18.1
18.2
18.3
18.4

18.5
18.6
18.7
18.8
18.9
18.10

749

Naming Amines 750
Properties of Amines 752
Basicity of Amines 754
Basicity of Arylamines 757
Biological Amines and the Henderson–Hasselbalch Equation 758
Synthesis of Amines 759
Reactions of Amines 764
Heterocyclic Amines 769
Fused-Ring Heterocycles 773
Spectroscopy of Amines 776
Summary 778
Summary of Reactions 779
Lagniappe—Green Chemistry II: Ionic Liquids 780
Exercises 782

19

Biomolecules: Amino Acids, Peptides,
and Proteins 791
19.1
19.2

19.3
19.4
19.5

Structures of Amino Acids 792
Amino Acids and the Henderson–Hasselbalch Equation: Isoelectric
Points 797
Synthesis of Amino Acids 800
Peptides and Proteins 802
Amino Acid Analysis of Peptides 804


detailed contents

19.6
19.7
19.8
19.9
19.10

Peptide Sequencing: The Edman Degradation 805
Peptide Synthesis 807
Protein Structure 812
Enzymes and Coenzymes 814
How Do Enzymes Work? Citrate Synthase 818
Summary 821
Summary of Reactions 822
Lagniappe—The Protein Data Bank 823
Exercises 824

Amino Acid Metabolism
20.1
20.2
20.3
20.4
20.5

20

832

An Overview of Metabolism and Biochemical Energy 833
Catabolism of Amino Acids: Deamination 836
The Urea Cycle 841
Catabolism of Amino Acids: The Carbon Chains 845
Biosynthesis of Amino Acids 850
Summary 854
Lagniappe—Visualizing Enzyme Structures 855
Exercises 857

Biomolecules: Carbohydrates
21.1
21.2
21.3
21.4
21.5
21.6
21.7
21.8
21.9

21.10

862

Classification of Carbohydrates 863
Depicting Carbohydrate Stereochemistry: Fischer Projections 864
d,l Sugars 868
Configurations of the Aldoses 870
Cyclic Structures of Monosaccharides: Anomers 872
Reactions of Monosaccharides 876
The Eight Essential Monosaccharides 882
Disaccharides 883
Polysaccharides and Their Synthesis 886
Cell-Surface Carbohydrates and Carbohydrate Vaccines 889
Summary 890
Summary of Reactions 891
Lagniappe—Sweetness 892
Exercises 893

21

xv


xvi

detailed contents

22

Carbohydrate Metabolism
22.1
22.2
22.3
22.4
22.5

901

Hydrolysis of Complex Carbohydrates 902
Catabolism of Glucose: Glycolysis 904
Conversion of Pyruvate to Acetyl CoA 911
The Citric Acid Cycle 915
Biosynthesis of Glucose: Gluconeogenesis 921
Summary 929
Lagniappe—Influenza Pandemics 929
Exercises 931

23

Biomolecules: Lipids and Their Metabolism
23.1
23.2
23.3
23.4
23.5
23.6
23.7
23.8
23.9

23.10

936

Waxes, Fats, and Oils 937
Soap 940
Phospholipids 942
Catabolism of Triacylglycerols: The Fate of Glycerol 943
Catabolism of Triacylglycerols: ␤-Oxidation 947
Biosynthesis of Fatty Acids 951
Terpenoids 956
Steroids 965
Biosynthesis of Steroids 969
Some Final Comments on Metabolism 975
Summary 978
Lagniappe—Saturated Fats, Cholesterol, and Heart Disease 978
Exercises 979

24

Biomolecules: Nucleic Acids and Their
Metabolism 987
24.1
24.2
24.3
24.4
24.5
24.6
24.7
24.8

24.9
24.10

Nucleotides and Nucleic Acids 987
Base Pairing in DNA: The Watson–Crick Model 990
Replication of DNA 992
Transcription of DNA 994
Translation of RNA: Protein Biosynthesis 996
DNA Sequencing 999
DNA Synthesis 1000
The Polymerase Chain Reaction 1004
Catabolism of Nucleotides 1005
Biosynthesis of Nucleotides 1008
Summary 1009
Lagniappe—DNA Fingerprinting 1010
Exercises 1011


detailed contents

Secondary Metabolites: An Introduction
to Natural Products Chemistry 1015
25.1
25.2
25.3
25.4

Classification of Natural Products 1016
Biosynthesis of Pyridoxal Phosphate 1017
Biosynthesis of Morphine 1022

Biosynthesis of Erythromycin 1031
Summary 1040
Lagniappe—Bioprospecting: Hunting for Natural Products 1041
Exercises 1041

Appendices
A
B
C
D

Nomenclature of Polyfunctional Organic Compounds A-1
Acidity of Constants for Some Organic Compounds A-7
Glossary A-9
Answers to In-Text Problems A-28
Index I-1

25

xvii


Preface

I’ve taught organic chemistry many times for many years, and it has often
struck me what a disconnect there is between the interests and expectations
of me—the teacher—and the interests and expectations of those being taught—
my students. I love the logic and beauty of organic chemistry, and I want to
pass that feeling on to others. My students, however, seem to worry primarily
about getting into medical school. That may be an exaggeration, but there is

also a lot of truth in it. All of us who teach organic chemistry know that the
large majority of our students—90% or more, including many chemistry
majors—are interested primarily in medicine, biology, and other life sciences
rather than in pure chemistry.
But if we are primarily teaching future physicians, biologists, biochemists, and others in the life sciences (not to mention the occasional lawyer and
businessperson), why do we continue to teach the way we do? Why do we
spend so much time discussing details of topics that interest research chemists but have no connection to biology? Wouldn’t the limited amount of time
we have be better spent paying more attention to the organic chemistry of living organisms and less to the organic chemistry of the research laboratory? I
believe so, and I have written this book, Organic Chemistry with Biological
Applications, to encourage others who might also be thinking that the time
has come to try doing things a bit differently.
This is, first and foremost, a textbook on organic chemistry, and you will
find that almost all of the standard topics are here. Nevertheless, my guiding
principle in writing this text has been to emphasize organic reactions and topics that are relevant to biological chemistry.

Organization of the Text

xviii

When looking through the text, three distinct groups of chapters are apparent. The first group (Chapters 1–6 and 10–11) covers the traditional principles of organic chemistry that are essential for building the background
necessary to further understanding. The second group (Chapters 7–9 and
12–18) covers the common organic reactions found in all texts. As each laboratory reaction is discussed, however, a biological example is also shown to
make the material more interesting to students. As an example, trans fatty
acids are described at the same time that catalytic hydrogenation is discussed


preface

(see Section 8.5, page 261). The third group of chapters (19–25) is unique to
this text in their depth of coverage. These chapters deal exclusively with the

main classes of biomolecules—amino acids and proteins, carbohydrates, lipids, and nucleic acids—and show how thoroughly organic chemistry permeates biological chemistry. Following an introduction to each class, major
metabolic pathways for that class are discussed from the perspective of
mechanistic organic chemistry. Finally, the book ends with a chapter devoted
to natural products and their biosynthesis.

Content Changes in the Second Edition
Text content has been revised substantially for this second edition as a result
of user feedback. Consequently, the text covers most of the standard topics
found in typical organic courses yet still retains an emphasis on biological
reactions and molecules. Perhaps the most noticeable change is that the book
is now titled Organic Chemistry with Biological Applications to emphasize
that it is, above all, written for the standard organic chemistry course found in
colleges and universities everywhere.
Within the text itself, a particularly important change is that the chapter
on chirality and stereochemistry at tetrahedral centers, a topic crucial to
understanding biological chemistry, has been moved forward to Chapter 4
from its previous placement in Chapter 9. In addition, the chapter on organohalides has been moved from Chapter 10 to Chapter 12, thereby placing spectroscopy earlier (Chapters 10 and 11).

Other Changes and Newly Added Content
•

Alkene ozonolysis and diol cleavage—added in Section 8.8

•

Addition of carbenes to alkenes—added in Section 8.9

•

The Diels–Alder cycloaddition reaction—added in Section 8.14

•

Acetylide alkylations—added in Section 8.15

•

Aromatic ions—added in Section 9.4

•

Nucleophilic aromatic substitution—added in Section 9.9

•

Aromatic hydrogenation—added in Section 9.10

•

Allylic bromination of alkenes—added in Section 12.2

•

Dess–Martin oxidation of alcohols—added in Section 13.5

•

Protection of alcohols as silyl ethers—added in Section 13.6

•

Claisen rearrangement—added in Section 13.10

•

Protection of ketones and aldehydes as acetals—added in Section 14.8

•

Conjugate addition of diorganocuprates to enones—added in Section 14.11

•

Grignard reaction of nitriles—added in Section 15.7

•

Reaction of diorganocuprates with acid halides—added in Section 16.4

•

Alpha bromination of carboxylic acids—added in Section 17.3

•

Amino acid metabolism—simplified coverage, Section 20.4

•

Amino acid biosynthesis—simplified coverage, Section 20.5

•

Final comments on metabolism—added in Section 23.10

•

Nucleotide metabolism—simplified coverage, Section 24.9

xix


xx

preface

•

Nucleotide biosynthesis—simplified coverage, Section 24.10

•

“Secondary Metabolites: An Introduction to Natural Products Chemistry”—new Chapter 25

There is more than enough organic chemistry in this book, along with a
coverage of biological chemistry that far surpasses what is found in any other
text. My hope is that all the students we teach, including those who worry about
medical school, will come to agree that there is also logic and beauty here.

Features of the Second Edition

Reaction Mechanisms
The innovative vertical presentation of reaction mechanisms that has become
a hallmark of all my texts in retained in Organic Chemistry with Biological
Applications. Mechanisms in this format have the reaction steps printed vertically, while the changes taking place in each step are explained next to the
reaction arrows. With this format, students can see what is occurring at each
step in a reaction without having to jump back and forth between structures
and text. See Figure 14.10 on page 581 for a chemical example and Figure 22.7
on page 912 for a biochemical example.

Visualization of Biological Reactions
One of the most important goals of this book is to demystify biological chemistry—to show students how the mechanisms of biological reactions are the
same as those of laboratory organic reactions. Toward this end, and to let
students more easily visualize the changes that occur during reactions of
large biomolecules, I use an innovative method for focusing attention on the
reacting parts in large molecules by “ghosting” the nonreacting parts. See
Figure 13.6 on page 522, for example.

Other Features
•

“Why do we have to learn this?” I’ve been asked this question by students
so many times that I thought I should answer it upfront. Thus, the introduction to every chapter now includes “Why This Chapter?”—a brief
paragraph that tells students why the material about to be covered is
important and explains how the organic chemistry in each chapter relates
to biological chemistry.

•

The Worked Examples in each chapter are titled to give students a frame
of reference. Each Worked Example includes a Strategy and worked-out

Solution, followed by Problems for students to try on their own.

•

A Lagniappe—a Louisiana Creole word meaning “something extra”—is
provided at the end of each chapter to relate real-world concepts to students’ lives. New Lagniappes in this edition include essays on Green
Chemistry and Ionic Liquids as green reaction solvents.

•

Visualizing Chemistry problems at the end of each chapter offer students
an opportunity to see chemistry in a different way by visualizing molecules rather than simply interpreting structural formulas.

•

Summaries and Key Word lists at the ends of chapters help students focus
on the key concepts in that chapter.


preface

•

Reaction Summaries at the ends of chapters bring together the key reactions from that chapter into one complete list.

•

An overview titled “A Preview of Carbonyl Chemistry,” following Chapter 13, highlights the idea that studying organic chemistry works by both
summarizing past ideas and looking ahead to new ones.

•

The latest IUPAC nomenclature rules, as updated in 1993, are used in this
text.

•

Thorough media integration with OWL for Organic Chemistry, an online
homework assessment program, is provided to help students practice
and test their knowledge of important concepts. For this second edition, OWL includes parameterized end-of-chapter questions from the
text (marked in the text with ). An access code is required. Visit www
.cengage.com/owl to register.

•

Students can work through animated versions of the text’s Active Figures
at the Student Companion site, which is accessible from www.cengage
.com/chemistry/mcmurry.

xxi

Acknowledgments
I thank all the people who helped to shape this book and its message. At
Brooks/Cole Cengage Learning they include: Lisa Lockwood, executive editor; Sandra Kiselica, senior development editor; Amee Mosley, executive marketing manager; Teresa Trego, senior production manager; Lisa Weber, senior
media editor; Elizabeth Woods, assistant editor, and Suzanne Kastner at
Graphic World.
I am grateful to colleagues who reviewed the manuscript for this book.
They include:
REVIEWERS OF THE SECOND EDITION
Peter Alaimo, Seattle University

Rizalia Klausmeyer, Baylor University

Paul Sampson, Kent State University

Sheila Browne, Mount Holyoke
College

Bette Kreuz, University of Michigan–
Dearborn

Martin Semmelhack, Princeton
University

Gordon Gribble, Dartmouth College

Megan Tichy, Texas A&M University

John Grunwell, Miami University

Manfred Reinecke, Texas Christian
University

Eric Kantorowski, California
Polytechnic State University

Frank Rossi, State University of New
York, Cortland

Kevin Kittredge, Siena College

Miriam Rossi, Vassar College

Bernhard Vogler, University of
Alabama, Huntsville

REVIEWERS OF FIRST EDITION
Helen E. Blackwell, University of
Wisconsin

Thomas Lectka, Johns Hopkins
University

Kevin Minbiole, James Madison
University

Joseph Chihade, Carleton College

Paul Martino, Flathead Valley
Community College

Andrew Morehead, East Carolina
University

Eugene Mash, University of Arizona

K. Barbara Schowen, University of
Kansas

Robert S. Coleman, Ohio State

University
John Hoberg, University of Wyoming
Eric Kantorowski, California
Polytechnic State University

Pshemak Maslak, Pennsylvania State
University