Organic chemistry

2403 Pages·2020·51.533 MB·English

by  David Klein

EXAMPLES OF COMMON FUNCTIONAL GROUPS
FUNCTIONAL GROUP* CLASSIFICATION EXAMPLE CHAPTER FUNCTIONAL GROUP* CLASSIFICATION EXAMPLE CHAPTER
O
O
R X Cl
Alkyl halide 7 Ketone 19
(X = Cl, Br or ) n-Propyl chloride R R
2-Butanone
R R O O
C C Alkene 7, 8 Aldehyde 19
R R 1-Butene R H H
Butanal
O
O
R C C R Alkyne 9 Carboxylic H 20
H acid O
1-Butyne R O
Pentanoic acid
O
O
OH
R OH Alcohol 12 Acyl halide 20
Cl
1-Butanol R X
Acetyl chloride
O O
O O
O
R O R Ether 13 Anhydride 20
O
Diethyl ether R O R
Acetic anhydride
O
O
SH
R SH Thiol 13 Ester 20
R O
1-Butanethiol R O
Ethyl acetate
O O
S R
R S R Sulfi de 13 Amide 20
R N NH
Diethyl sulfide 2
R Butanamide
H
R
Aromatic
(or arene) 17, 18 N Amine N 22
R R
Methylbenzene Diethylamine
* The “R” refers to the remainder of the compound, usually carbon and hydrogen atoms.
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Approximate pK Values for Commonly Encountered Structural Types
a
X pKa −10 R1 R2 pKa
Me H –8.0
–10 H X
Me Me –7.3
BCrl ––97..00 +O H Me OMe –6.5
Me Ph –6.2
F 3.2
R1 R2 Me OH –6.1
−5
R pKa O H R1 R2 pKa
CF3 –14 R S OH O Me Me –3.8
OH –9.0 O R1 + R2 Et Et –3.6
Me –1.2 Et H –2.4
O
Ph –0.6 Me H –2.2
0 −O+N OH (–1.3) H H –1.7
R pKa
CF3 –0.25 H F(3.2)
H 3.8 −
Me 4.8 O N +N N H (4.7)
t-Bu 5.0
OH 6.4 R OH 5 N H (5.3)
+
R1 R2 R3 pKa OH H S H (7.0)
HH NHO2 NHO2 78..14 R1 CH3CO3H (8.2) R1 R2 R3 pKa
H H H 9.9 H H H 9.2
H H OMe 10.2 R3 R2 10 +R1 Me H H 10.5
R2 N H Me Me H 10.6
R1 R2 pKa O O R3 Me Me Me 9.8
Me Me 9.0 R1 R2 PErt PErt EHt 1101..81
OEt Me 11 H H
OMe OMe 13 H
OEt OEt 13.3 R1 15 H (15)
R1 R2 R3 pKa R2 C O H H O H (15.7)
Me Me Me 18.0 R3 O R pKa
Me Me H 16.5 H Ph 16.0
Me H H 16.0 R H 17.0
H H H 15.5 20 H H Me 19.2
CF3 H H 12.5
CF3 CF3 H 9.3
O R pKa
R pKa R C C H Ph 23
t-Bu 24.5 RO H 25 H 25
Et 25.0
H H
O
S H
35 H3C C (35)
DMSO H H
R1 R2 pKa
H H 38 H H H (36)
Et H 38 N
Et Et 40 R1 R2
40
H H
C C (44)
H H
R1 R2 R3 pKa 45
Ph H H 41
CH=CH2 H H 43 R1
H H H 48 R2 C H
Me H H 50 R3
Me Me H 51
50
Me Me Me 53
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ISBN 978-1-119-659594
Library of Congress Cataloging-in-Publication Data
Names: Klein, David R., 1972- author.
Title: Organic chemistry / David Klein.
Description: Fourth edition. | Hoboken, NJ : Wiley, [2021] | Includes
bibliographical references and index.
Identifiers: LCCN 2020044903 (print) | LCCN 2020044904 (ebook) | ISBN
9781119659594 (paperback) | ISBN 9781119316152 | ISBN 9781119760825
(adobe pdf) | ISBN 9781119659402 (epub)
Subjects: LCSH: Chemistry, Organic—Textbooks.
Classification: LCC QD253.2 .K55 2021 (print) | LCC QD253.2 (ebook) | DDC
547--dc23
LC record available at https://lccn.loc.gov/2020044903
LC ebook record available at https://lccn.loc.gov/2020044904
Printed in the United States of America 10 9 8 7 6 5 4 3 2 1
The inside back cover will contain printing identification and country of origin if omitted from this
page. In addition, if the ISBN on the back cover differs from the ISBN on this page, the one on the
back cover is correct.
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Dedication
To my father and mother,
You have saved me (quite literally) on so many occasions, always steering me in the right
direction. I have always cherished your guidance, which has served as a compass for me in all of
my pursuits. You r epeatedly urged me to work on this textbook (“write the book!”, you would say
so often), with full confidence that it would be appreciated by students around the world. I will
forever rely on the life lessons that you have taught me and the values that you have instilled in me.
I love you.
To Larry,
By inspiring me to pursue a career in organic chemistry instruction, you served as the spark
for the creation of this book. You showed me that any subject can be fascinating (even organic
chemistry!) when presented by a masterful teacher. Your mentorship and friendship have pro-
foundly shaped the course of my life, and I hope that this book will always serve as a source of
pride and as a reminder of the impact you’ve had on your students.
To my wife, Vered,
This book would not have been possible without your partnership. As I worked for years in
my office, you shouldered all of our life responsibilities, including taking care of all of the needs
of our five amazing children. This book is our collective accomplishment and will forever serve
as a testament of your constant support that I have come to depend on for everything in life.
You are my rock, my partner, and my best friend. I love you.
Klein4e_FM.indd 3 31/10/20 8:53 PM
Contents
Review of Concepts & Vocabulary • SkillBuilder Review
Practice Problems • ACS-Style Problems (Multiple Choice)
Integrated Problems • Challenge Problems
3
1
Acids and Bases 93
A Review of General Chemistry:
Electrons, Bonds, and Molecular Properties 1 3.1 Introduction to Brønsted-Lowry Acids and Bases 94
3.2 Flow of Electron Density: Curved-Arrow Notation 94
1.1 Introduction to Organic Chemistry 2
BioLinks Antacids and Heartburn 96
1.2 The Structural Theory of Matter 3
3.3 Brønsted-Lowry Acidity: Comparing pK values 97
1.3 Electrons, Bonds, and Lewis Structures 4 a
BioLinks Drug Distribution and pK 103
1.4 Identifying Formal Charges 7 a
3.4 Brønsted-Lowry Acidity: Factors Affecting the Stability of
1.5 Induction and Polar Covalent Bonds 8
Anions 104
1.6 Reading Bond-Line Structures 11
3.5 Brønsted-Lowry Acidity: Assessing the Relative Acidity of
1.7 Atomic Orbitals 14
Cationic Acids 115
1.8 Valence Bond Theory 17
3.6 Position of Equilibrium and Choice of Reagents 120
1.9 Molecular Orbital Theory 18
3.7 Leveling Effect 123
1.10 Hybridized Atomic Orbitals 20
3.8 Solvating Effects 124
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Gecko Feet 37 Review of Concepts & Vocabulary • SkillBuilder Review
Practice Problems • ACS-Style Problems (Multiple Choice)
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Selma ARSLAN/Shutterstock.com
Alkanes and Cycloalkanes 138
2
4.1 Introduction to Alkanes 139
4.2 Nomenclature of Alkanes 139
Molecular Representations 50
WorldLinks Pheromones: Chemical Messengers 143
2.1 Molecular Representations 51 BioLinks Naming Drugs 151
2.2 Drawing Bond-Line Structures 53 4.3 Constitutional Isomers of Alkanes 152
2.3 Identifying Functional Groups 55 4.4 Relative Stability of Isomeric Alkanes 153
BioLinks Marine Natural Products 56 4.5 Sources and Uses of Alkanes 154
2.4 Carbon Atoms with Formal Charges 58 WorldLinks An Introduction to Polymers 156
2.5 Identifying Lone Pairs 58 4.6 Drawing Newman Projections 156
2.6 Three-Dimensional Bond-Line Structures 61 4.7 Conformational Analysis of Ethane
and Propane 158
BioLinks The Opioids 62
4.8 Conformational Analysis of Butane 160
2.7 Introduction to Resonance 63
2.8 Curved Arrows 65 BioLinks Drugs and Their Conformations 164
2.9 Formal Charges in Resonance Structures 68 4.9 Cycloalkanes 164
2.10 Drawing Resonance Structures via Pattern Recognition 70 BioLinks Cyclopropane as an Inhalation Anesthetic 166
2.11 Assessing the Relative Importance of Resonance 4.10 Conformations of Cyclohexane 167
Structures 75 4.11 Drawing Chair Conformations 168
2.12 The Resonance Hybrid 79 4.12 Monosubstituted Cyclohexane 170
2.13 Delocalized and Localized Lone Pairs 81 4.13 Disubstituted Cyclohexane 172
iv
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CONTENTS v
4.14 cis-trans Stereoisomerism 176 6.12 Reversible and Irreversible Reaction Arrows 268
4.15 Polycyclic Systems 177 Review of Concepts & Vocabulary • SkillBuilder Review
Review of Concepts & Vocabulary • SkillBuilder Review Practice Problems • ACS-Style Problems (Multiple Choice)
Practice Problems • ACS-Style Problems (Multiple Choice) Integrated Problems • Challenge Problems
Integrated Problems • Challenge Problems
7
5
Alkyl Halides: Nucleophilic Substitution and Elimination
Stereoisomerism 188
Reactions 280
5.1 Overview of Isomerism 189
7.1 Introduction to Substitution and Elimination Reactions 281
5.2 Introduction to Stereoisomerism 190
7.2 Nomenclature and Uses of Alkyl Halides 282
WorldLinks The Sense of Smell 195
7.3 S 2 Reactions 286
N
5.3 Designating Configuration Using the
BioLinks Pharmacology and Drug Design 292
Cahn-Ingold-Prelog System 195
7.4 Nucleophilic Strength in S 2 Reactions 294
N
BioLinks Chiral Drugs 200
BioLinks S 2 Reactions in Biological Systems—Methylation 295
N
5.4 Optical Activity 201
7.5 Introduction to E2 Reactions 296
5.5 Stereoisomeric Relationships: Enantiomers and
7.6 Stability of Alkenes and Cycloalkenes 299
Diastereomers 207
7.7 Regiochemical and Stereochemical Outcomes for E2
5.6 Symmetry and Chirality 210
Reactions 301
5.7 Fischer Projections 214
7.8 Unimolecular Reactions (S 1 and E1) 311
N
5.8 Conformationally Mobile Systems 216
7.9 Predicting Products: Substitution vs. Elimination 320
5.9 Chiral Compounds that Lack a Chiral Center 217
7.10 Substitution and Elimination Reactions with Other
5.10 Resolution of Enantiomers 218 Substrates 327
5.11 E and Z Designations for Diastereomeric Alkenes 220 7.11 Synthesis Strategies 331
BioLinks Phototherapy Treatment for Neonatal Jaundice 222 BioLinks Radiolabeled Compounds in Diagnostic Medicine 338
Review of Concepts & Vocabulary • SkillBuilder Review 7.12 Solvent Effects in Substitution Reactions 339
Practice Problems • ACS-Style Problems (Multiple Choice) SpecialTopic Kinetic Isotope Effects 343
Integrated Problems • Challenge Problems
Review of Reactions • Review of Concepts & Vocabulary
Lukiyanova Natalia/frenta/Shutterstock SAkCilSlB-Sutilydlee rP Rroebvileewm s• ( MPuraltciptilcee CPhroobiclee)m •s Integrated Problems
Challenge Problems
6
8
kcotsrettuhS/.D.V.O
Chemical Reactivity and Mechanisms 233
6.1 Enthalpy 234 Addition Reactions of Alkenes 356
6.2 Entropy 237
6.3 Gibbs Free Energy 239 8.1 Introduction to Addition Reactions 357
WorldLinks Explosives 240 8.2 Alkenes in Nature and in Industry 358
WorldLinks Do Living Organisms Violate the Second Law of WorldLinks Pheromones to Control Insect Populations 358
Thermodynamics? 242 8.3 Nomenclature of Alkenes 359
6.4 Equilibria 242 8.4 Addition vs. Elimination: A Thermodynamic Perspective 361
6.5 Kinetics 244 8.5 Hydrohalogenation 363
BioLinks Nitroglycerin: An Explosive WorldLinks Cationic Polymerization and Polystyrene 370
with Medicinal Properties 247 8.6 Acid-Catalyzed Hydration 371
WorldLinks Beer Making 248 8.7 Oxymercuration-Demercuration 375
6.6 Reading Energy Diagrams 249 8.8 Hydroboration-Oxidation 376
6.7 Nucleophiles and Electrophiles 252 8.9 Catalytic Hydrogenation 382
6.8 Mechanisms and Arrow Pushing 256 WorldLinks Partially Hydrogenated Fats and Oils 387
6.9 Combining the Patterns of Arrow Pushing 261 8.10 Halogenation and Halohydrin Formation 388
6.10 Drawing Curved Arrows 263 8.11 Anti Dihydroxylation 392
6.11 Carbocation Rearrangements 266 8.12 Syn Dihydroxylation 395
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vi CONTENTS
8.13 Oxidative Cleavage 396 10.13 Halogenation as a Synthetic
8.14 Predicting the Products of an Addition Reaction 398 Technique 489
8.15 Synthesis Strategies 400 Review of Reactions • Review of Concepts & Vocabulary
Review of Reactions • Review of Concepts & Vocabulary SkillBuilder Review • Practice Problems
SkillBuilder Review • Practice Problems ACS-Style Problems (Multiple Choice)
ACS-Style Problems (Multiple Choice) Integrated Problems • Challenge Problems
Integrated Problems • Challenge Problems
11
9 pokki77/Shutterstock
Synthesis 499
Alkynes 417
11.1 One-Step Syntheses 500
9.1 Introduction to Alkynes 418 11.2 Functional Group Transformations 501
BioLinks The Role of Molecular Rigidity 420 11.3 Reactions That Change the Carbon Skeleton 505
WorldLinks Conducting Organic Polymers 421 BioLinks Vitamins 507
9.2 Nomenclature of Alkynes 421 11.4 How to Approach a Synthesis Problem 508
9.3 Acidity of Acetylene and Terminal Alkynes 423 BioLinks The Total Synthesis of Vitamin B 512
12
9.4 Preparation of Alkynes 426 11.5 Multi-step Synthesis and Retrosynthetic Analysis 514
9.5 Reduction of Alkynes 428 WorldLinks Retrosynthetic Analysis 519
9.6 Hydrohalogenation of Alkynes 431 11.6 Green Chemistry 519
9.7 Hydration of Alkynes 433 11.7 Practical Tips for Increasing Proficiency 520
9.8 Halogenation of Alkynes 439
BioLinks Total Synthesis of Taxol 521
9.9 Ozonolysis of Alkynes 439
Review of Concepts & Vocabulary • SkillBuilder Review
9.10 Alkylation of Terminal Alkynes 440
Practice Problems • ACS-Style Problems (Multiple Choice)
9.11 Synthesis Strategies 442
Integrated Problems • Challenge Problems
Review of Reactions • Review of Concepts & Vocabulary
SkillBuilder Review • Practice Problems
ACS-Style Problems (Multiple Choice)
Integrated Problems • Challenge Problems
mg7/Getty Images
12
SciePro/Shutterstock
Alcohols and Phenols 52mag9netcreative/Getty Images
10
pokki77/Shutterstock
richcano/Getty Images
12.1 Structure and Properties of Alcohols 530
BioLinks Chain Length as a Factor in Drug Design 534
Radical Reactions 454
12.2 Acidity of Alcohols and Phenols 535
10.1 Radicals 455 12.3 Preparation of Alcohols via Substitution or Addition 538
10.2 Common Patterns in Radical Mechanisms 460 12.4 Preparation of Alcohols via Reduction 539
10.3 Chlorination of Methane 463 12.5 Preparation of Diols 546
10.4 Thermodynamic Considerations WorldLinks Antifreeze 547
for Halogenation Reactions 467 12.6 Preparation of Alcohols via Grignard
10.5 Selectivity of Halogenation 469 Reagents 547
10.6 Stereochemistry of Halogenation 472 12.7 Protection of Alcohols 552
10.7 Allylic Bromination 474 12.8 Preparation of Phenols 553
10.8 Atmospheric Chemistry and the Ozone Layer 477 12.9 Reactions of Alcohols: Substitution and Elimination 554
WorldLinks Fighting Fires with Chemicals 479 BioLinks Drug Metabolism 557
10.9 Autooxidation and Antioxidants 480 12.10 Reactions of Alcohols: Oxidation 559
BioLinks Why Is an Overdose of Acetaminophen Fatal? 482 12.11 Biological Redox Reactions 563
10.10 Radical Addition of HBr: Anti-Markovnikov Addition 483 BioLinks Biological Oxidation of Methanol and Ethanol 565
10.11 Radical Polymerization 487 12.12 Oxidation of Phenol 565
10.12 Radical Processes in the Petrochemical Industry 489 12.13 Synthesis Strategies 567
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