Solomons & Fryhle’sOrganic Chemistry

For IIT-JEE

Second Edition

Solomons & Fryhle’sOrganic Chemistry

For IIT-JEE

Second Edition

Adapted byM.S. Chouhan

Copyright © 2012 by Wiley India Pvt. Ltd., 4435-36/7, Ansari Road, Daryaganj, New Delhi-110002.

All rights reserved. No part of this book may be reproduced, stored in a retrieval system, or transmitted in any form or by any means, electronic, mechanical, photocopying, recording or scanning without the written permission of the publisher. This book is an adaptation of Organic Chemistry, 8/e by T.W. Graham Solomons and Craig B. Fryhle (ISBN: 978-0471-417996). All rights remain with their respective holders.

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Solomons & Fryhle’s Organic Chemistry For IIT-JEESecond Edition

The goal of our book is to bring organic chemistry to students in the most interestingand comprehensible way possible. We believe that the this edition offers our strongestpedagogy yet for achieving these goals. The text includes many visual tools for learning,including Concept Maps, details of reaction mechanisms and thematic MechanismReview summaries, Synthetic Connections, enlightening illustrations, and abundantproblems.

O R G A N I Z A T I O NA central theme of our approach to organic chemistry is to emphasize the relationship be-tween structure and reactivity. To accomplish this, we have chosen an organization thatcombines the most useful features of the traditional functional group approach with onebased on reaction mechanisms. Our philosophy is to emphasize mechanisms and theircommon aspects as often as possible, and at the same time to use the unifying features offunctional groups as the basis for most chapters. The structural aspects of our approachshow students what organic chemistry is. Mechanistic aspects of our approach show stu-dents how it works. And wherever an opportunity arises, we show them what it does inliving systems and the physical world around us.

Most important is for students to have a solid understanding of structure—of hybridiza-tion and geometry, steric hindrance, electronegativity, polarity, and formal charges—so thatthey can make intuitive sense of mechanisms. It is with these topics that we begin inChapter 1. In Chapter 2 we introduce all of the important functional groups and intermolec-ular forces.

We begin our study of mechanisms in Chapter 3 in the context of acid-base chemistry.Why? Because acid-base reactions are fundamental to organic chemistry. When looked atfrom the point of view of Lewis acid-base theory, the steps of most organic reactionmechanisms are acid-base reactions. Acid-base reactions, moreover, are relatively simpleand they are reactions that students will find familiar. Acid-base reactions also lend them-selves to an introduction of several important topics that students need to know aboutearly in the course: (1) the curved arrow notation for illustrating mechanisms, (2) the rela-tionship between free-energy changes and equilibrium constants, (3) how enthalpy andentropy changes affect reactions under equilibrium control, and (4) the importance ofinductive and resonance effects and of solvent effects. In Chapter 3, we also begin toshow students how organic chemistry works by presenting the first of many boxes called “A Mechanism for the Reaction.” All through the book, these boxes highlight and bringforth the details of important reaction mechanisms.

Throughout our study we use various opportunities to show what organic chemistrydoes in life, both in biological terms and in our physical environment, through real worldapplications. As students come to realize that life and much of the world around us in-volves organic chemistry, their fascination with the subject cannot help but increase.

K E Y F E A T U R E S O F T H E T H I S E D I T I O NSome major highlights of the this edition include:

• Concept Maps, Mechanism Reviews, and Synthetic Connections: Comprehensive newsummary and review tools to enhance student learning.

• Concepts related to carbenes, carbenoids and nitrenes have been introduced in form oftwo chapters at the end.

Preface

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vi Preface

• Concepts not relevant to joint engineering entrance examinations for IIT have beendeleted to make the book more concise.

• Solved problems have been added after related section in some chapters and at the endof some chapters for better understanding of the subject.

• New end-of-chapter material comprising IIT-JEE specific questions and an answer keyto both in text problems as well as end-of-chapter problems.

• Review problem sets have been provided at the end of the book to help students preparefor examinations.

C o n c e p t M a p s , M e c h a n i s m S u m m a r i e s ,a n d S y n t h e t i c C o n n e c t i o n sWe introduce, for the first time with this edition, comprehensive visual summary and reviewtools for students. These tools come in three forms: Concept Maps, Mechanism Summaries,and Synthetic Connections. Concept Maps are hierarchical flowcharts that join one keyconcept to the next with a linking phrase. Our Concept Maps help students summarize,review, and organize the material in a chapter. Our new Mechanism Summaries tietogether common themes and highlight key attributes of important mechanisms. They high-light factors influencing the type of mechanism by which a molecule will react, as well asshow regiochemical and stereochemical aspects of mechanisms. Synthetic Connections areroadmaps that show pathways for converting molecules from one type to another. Using ourSynthetic Connections, students can see how reactions they have learned are part of theirgrowing repertoire for synthesis.

Curved arrow notation(Section 3.4)

is used to show

often involvecan be

are asubcategory

of

are asubcategory

ofare are

are

can be

Reaction mechanisms(Section 3.1)Acids

Brønsted-Lowry acids(Section 3.2A)

Lewis acids(Section 3.2B)

contain/have

are associated with

Small or negative pKavalues and large Ka values

(Section 3.5)

Protondonors

Strong acids

have

Weak conjugate bases

Electron pairacceptors

Electrophiles(Section 3.3)

Carbocations

can be

areare

can be are

can be

Bases

Brønsted-Lowry bases(Section 3.2A)

Lewis bases(Section 3.2B)

contain/have

are associated with

Large and positive pKavalues and small Ka values

(Section 3.5)

Protonacceptors

Strong bases

have

Weak conjugate acids

Electron pairdonors

Nucleophiles(Section 3.3)

Carbanions

CONCEPT MAP

Part of the Chapter 3 Concept Map

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Preface vii

O r b i t a l H y b r i d i z a t i o n a n dt h e S t r u c t u r e o f O r g a n i c M o l e c u l e sStudents must develop a sound understanding of the structure and shape of organic mole-cules. We build the foundation for their understanding of structure by introducing orbitalhybridization and VSEPR theory in Chapter 1. We begin withmethane for sp3 hybridization, move directly to ethene for sp2 hy-bridization, and then to ethyne for sp hybridization. We also usecalculated molecular orbitals, and electron density surfaces toillustrate regions of bonding electron density and overall molecu-lar shape. In this edition we improved our presentation of reso-nance in Chapter 1 by including some additional rules for drawingproper resonance structures. Students will consider these rules fur-ther when they study conjugated systems in Chapter 12.

E a r l y I n t r o d u c t i o n t o R e t r o s y n t h e t i cA n a l y s i s a n d O r g a n i c S y n t h e s i sWe use the alkylation of alkynide anions in Chapter 4 to introduce organic synthesis andretrosynthetic analysis. One advantage of using alkynide anions to introduce synthesis isthat the reactivity of terminal alkynes and alkyl halides is readily understood on the basisof concepts students have learned in the beginning chapters of the book, namely acid-basechemistry and polarity. Students will use Brønsted-Lowry acid-base chemistry to outlinethe preparation of alkynide anions from alkynes, and they will recall Lewis acid-baseconcepts when they consider the reaction of an alkynide anion with an alkyl halide. Theywill also find reinforcement of a common theme in many organic reactions—the interac-tion between molecules or groups bearing opposite charges.

The alkylation of alkynide anions also gives students a method for carbon–carbonbond formation very early in their study of organic chemistry. And, it gives them a prod-uct that contains a functional group from which they can make many other compounds astheir synthetic repertoire grows. Finally, because ‘better’ or ‘worse’ retrosynthetic path-ways using alkynide-anion alkylation are conceivable for a given molecule, this reactionis a realistic vehicle for teaching the logic of retrosynthetic analysis.

S u b s t i t u t i o n a n d E l i m i n a t i o n R e a c t i o n sSubstitution and elimination reactions provide an opportunity for students to encounterone of the important realities of organic chemistry. Reactions almost never follow exclu-sively one path, much as we would like them to. As chemists, we know very well howfrequently one kind of reaction competes with another to complicate our synthetic plans.Therefore, bringing students to the point where they can propose reasonable syntheses us-ing substitutions or eliminations requires a careful orchestration of topics. In this edition,as in the last, Chapter 6 focuses on substitution, but it also briefly introduces eliminationreactions. We have done this because the two reactions nearly always occur together, andit is vitally important that students gain a chemically accurate understanding of this.Chapter 7, then, rounds out the discussion by giving detailed treatment of E2 and E1 reac-tions, including stereochemistry, regiochemistry, and overall product distribution.

S y n t h e s i s U p d a t e sThe 2001 Nobel Prize in Chemistry was awarded to K. Barry Sharpless, WilliamKnowles, and Ryoji Noyori for their work on catalytic asymmetric methods for oxida-tion and reduction. We have highlighted these powerful synthesis tools in several new or

CH

H

H

H

109°28´

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revised boxes in the this edition, including mention of their relevance to well-knowncompounds such as Naproxen™ and L-DOPA. We have also included information on“green” catalytic methods such as the oxidation of alkenes using catalytic rather thanstoichiometric amounts of osmium, and oxidation using Jacobsen’s catalyst.

In this edition we introduce oxymercuration–demercuration and hydroboration–oxidationin Chapter 8 because these reactions belong with other addition reactions of alkenes. Thischange also groups these reactions with acid-catalyzed hydration of alkenes as a collection ofmethods for alcohol synthesis from alkenes. Then, when alcohols and ethers are discussed inChapter 10, we briefly review the ensemble of methods given in Chapter 8 for synthesis ofalcohols from alkenes.

We have also deleted some sections that, although dear to us as chemists, providedreasonable opportunities to trim material from the book. We have removed chapters 9, 18,23 and 25 of the previous edition and introduced two chapters on Carbenes and Nitrenes.Also we have deleted sections on IR, UV-Vis and NMR spectroscopy, fullerenes, enolateions, biochemistry and green chemistry.

O t h e r P e d a g o g i c a l F e a t u r e sConcept Maps, Mechanism Reviews, and Synthetic Connections These new featuresappear at the end of chapters as summary and review tools.

“A Mechanism for the Reaction” These specially designed mechanism presenta-tions give detailed explanations for every key mechanism in the book. Curvedarrows show precisely and unambiguously how electrons flow in each step of amechanism. Steps are identified and annotated in the mechanisms to further explaineach transformation.

Solved Problems Sample problems with solutions are included at key points to showstudents how to approach problems in organic chemistry. Various solved problems havebeen added in the chapters for this edition.

In-Chapter Problems Numbered problems appear at the end of sections to reinforcestudents’ learning immediately after each topic is introduced.

Key Terms and Concepts A list of key terms and concepts with section references at theend of each chapter allows students to test their memory regarding key ideas and if neces-sary to easily refer back to a full presentation of the concept in the chapter. The key termsand concepts listed are also defined in the glossary.

End-of-Chapter Problems have been modified as per IIT-JEE requirements to includeSingle Correct Choice Type, Multiple Correct Choice Type, Linked Comprehension Type,Integer Answer Type and Matrix–Match Type questions. The number of these questiontypes vary across all chapters.

—Craig B. Fryhle—T. W. Graham Solomons

viii Preface

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44254 Solomons Wiley frontmatter first pages bb 10/30/03 p ix application file

This book is dedicated to the lotus feet of Revered Guruji SHRI KESARAM JI MAHARAJ

It is a matter of great pleasure for me to present the second edition of the book before IIT-JEE aspirants. This book was written because I felt the need for a textbook that corre-sponds closely to the course that I teach. Although the book is organized along tried-and-true functional-group lines, it contains some unique features that have served me well inboth my teaching and understanding of Organic Chemistry.

My four major concerns in both the initial writing and the revision of this text werereadability, presentation, organization, and accuracy. In the current scenario of stiff compe-tition especially for IIT-JEE, one must be clear that almost all the sincere applicants arewell equipped with the facts of subject; yet, the winner is the one who knows how to usethese facts with accuracy and efficiency. As an experienced teacher, I would like to suggeststudents three golden rules to score high in Organic Chemistry:

1. Do not lag behind in schedule.

2. Work out a number of problems of different types.

3. Revise through short notes.

I hope that the present book will cater to the needs of IIT-JEE aspirants. As a matter offact, they will enjoy the present venture and I would feel rewarded if this book is helpfulfor the students and teachers in real terms. All efforts have been made to make the bookerror-free; however, a few misprints may inadvertently creep.

I acknowledge the blessing and support of my mother Smt. Raj Kanwar, fatherShri B.S. Chouhan, brother Dr. V.S. Chouhan, wife Ms. Meena Chouhan and daughter.They inspired me all the time during the preparation of this book.

The support and valuable suggestions from Mr. V.K. Jaiswal, Mr. N. Avasthi,Mr. Akshay Chawdhary, Dr. S. Kothari, Mr. Navneet Jethwani, Ms. Neha Joshi, Mr.Ashish Mishra, Mr. Kumud Ranjan, Mr. Mohit Sayal, Mr. Hanuman Prasad Sahay,Mr. Vineet Khatri, Mr. Govind Khadelwal and Mr. Manish Arora are highly acknowl-edged. I also pay my sincere thanks to all the esteemed members of Wiley India and spe-cially Mr. Paras Bansal, Ms. Anjali Chadha, Ms. Sruthi Guru and Mr. Rakesh Poddar inbringing out this book in such a nice form.

In the end, constructive criticism and valuable suggestions from the readers are mostwelcome to make the book more useful.

M.S.Chouhan(MSC Sir)

Email: mahen_chouhan@yahoo.comMobile: 9828025625

Preface to the Adapted Version

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xi

Chapter 1 Carbon Compounds and Chemical Bonds 1▲ (Molecular graphic: Glycine, an organic molecule found in space)

1.1 Introduction 11.2 The Development of Organic Chemistry as a Science 21.3 The Structural Theory of Organic Chemistry 31.4 Chemical Bonds: The Octet Rule 61.5 Writing Lewis Structures 81.6 Exceptions to the Octet Rule 91.7 Formal Charge 111.8 Resonance 131.9 Hyperconjugation 251.10 The Structure of Methane and Ethane: sp3 Hybridization 321.11 The Structure of Ethene (Ethylene): sp2 Hybridization 331.12 The Structure of Ethyne (Acetylene): sp Hybridization 361.13 A Summary of Important Concepts That Come from Quantum Mechanics 381.14 Molecular Geometry: The Valence Shell Electron Pair Repulsion Model 391.15 Representation of Structural Formulas 40

Chapter 2 Representative Carbon Compounds: Functional Groups and Intermolecular Forces 56▲ (Molecular graphic: A molecular template for bone growth)

2.1 Carbon–Carbon Covalent Bonds 562.2 Hydrocarbons: Representative Alkanes, Alkenes, Alkynes, and Aromatic Compounds 572.3 Polar Covalent Bonds 602.4 Polar and Nonpolar Molecules 612.5 Functional Groups 632.6 Alkyl Halides or Haloalkanes 652.7 Alcohols 652.8 Ethers 672.9 Amines 672.10 Aldehydes and Ketones 682.11 Carboxylic Acids, Esters, and Amides 692.12 Nitriles 702.13 Summary of Important Families of Organic Compounds 712.14 Physical Properties and Molecular Structure 722.15 Summary of Attractive Electric Forces 78

Chapter 3 An Introduction to Organic Reactions: Acids and Bases 89▲ (Molecular graphic: Diamox, a drug that prevents altitude sickness)

3.1 Reactions and Their Mechanisms 893.2 Acid–Base Reactions 913.3 Heterolysis of Bonds to Carbon: Carbocations and Carbanions 943.4 The Use of Curved Arrows in Illustrating Reactions 953.5 The Strength of Acids and Bases: Ka and pKa 973.6 Predicting the Outcome of Acid–Base Reactions 1003.7 The Relationship Between Structure and Acidity 1023.8 Energy Changes 1063.9 The Relationship Between the Equilibrium Constant and the Standard Free-Energy

Change, DG° 107

Contents

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3.10 The Acidity of Carboxylic Acids 1083.11 The Effect of the Solvent on Acidity 1123.12 Organic Compounds as Bases 1133.13 Acids and Bases in Nonaqueous Solutions 1143.14 Acid–Base Reactions and the Synthesis of Deuterium- and Tritium-Labeled

Compounds 1163.15 Reaction of NaHCO3 1173.16 Steric Inhibition of Resonance (SIR) Effect 1183.17 Ortho and Para Effects 1203.18 Representation of Change in Electronic Configuration 137

Chapter 4 Alkanes: Nomenclature, Conformational Analysis, and an Introduction to Synthesis 157▲ (Molecular graphic: A portion of the structure of diamond, an exceptionally

rigid molecule)4.1 Introduction to Alkanes and Cycloalkanes 1574.2 Shapes of Alkanes 1594.3 IUPAC Nomenclature of Alkanes, Alkyl Halides, and Alcohols 1624.4 Nomenclature of Cycloalkanes 1694.5 Nomenclature of Alkenes and Cycloalkenes 1714.6 Nomenclature of Alkynes 1734.7 Physical Properties of Alkanes and Cycloalkanes 1744.8 Sigma Bonds and Bond Rotation 1764.9 Conformational Analysis of Butane 1784.10 The Relative Stabilities of Cycloalkanes: Ring Strain 1874.11 The Origin of Ring Strain in Cyclopropane and Cyclobutane: Angle Strain and Torsional

Strain 1894.12 Conformations of Cyclohexane 1914.13 Substituted Cyclohexanes: Axial and Equatorial Hydrogen Atoms 1964.14 Disubstituted Cycloalkanes: Cis–Trans Isomerism 1984.15 Bicyclic and Polycyclic Alkanes 2034.16 Chemical Reactions of Alkanes 2054.17 Synthesis of Alkanes and Cycloalkanes 2054.18 Retrosynthetic Analysis—Planning an Organic Synthesis 208

Chapter 5 Stereochemistry: Chiral Molecules 225▲ (Molecular graphic: The mirror-image stereoisomers of alanine,

a chiral amino acid)5.1 The Biological Significance of Chirality 2255.2 Isomerism: Constitutional Isomers and Stereoisomers 2265.3 Enantiomers and Chiral Molecules 2285.4 More about the Biological Importance of Chirality 2315.5 Historical Origin of Stereochemistry 2335.6 Tests for Chirality: Planes of Symmetry 2345.7 Nomenclature of Enantiomers: The R,S-System 2345.8 Properties of Enantiomers: Optical Activity 2395.9 The Origin of Optical Activity 2435.10 The Synthesis of Chiral Molecules 2465.11 Chiral Drugs 2485.12 Molecules with More than One Stereogenic Center 2495.13 Fischer Projection Formulas 2535.14 Stereoisomerism of Cyclic Compounds 2545.15 Relating Configurations through Reactions in Which No Bonds to the Stereogenic Carbon

Are Broken 257

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5.16 Separation of Enantiomers: Resolution 2605.17 Compounds with Stereogenic Centers Other than Carbon 2635.18 Chiral Molecules that Do Not Possess a Tetrahedral Atom with

Four Different Groups 2635.19 Elements of Symmetry 2645.20 Biphenyl 2715.21 Racemization of Biphenyl Compounds 2745.22 Tautomerism 2765.23 Gero Entropy 279

Chapter 6 Ionic Reactions — Nucleophilic Substitution and Elimination Reactions of Alkyl Halides 300▲ (Molecular graphic: The SN2 transition state resulting from collision

of a hydroxide anion with chloromethane)6.1 Introduction 3006.2 Nucleophilic Substitution Reactions 3026.3 Nucleophiles 3036.4 Leaving Groups 3046.5 Kinetics of a Nucleophilic Substitution Reaction: An SN2 Reaction 3046.6 A Mechanism for the SN2 Reaction 3066.7 Transition State Theory: Free-Energy Diagrams 3076.8 The Stereochemistry of SN2 Reactions 3106.9 The Reaction of tert-Butyl Chloride with Hydroxide Ion: An SN1 Reaction 3126.10 A Mechanism for the SN1 Reaction 3136.11 Carbocations 3156.12 The Stereochemistry of SN1 Reactions 3176.13 Factors Affecting the Rates of SN1 and SN2 Reactions 3196.14 Organic Synthesis: Functional Group Transformations Using SN2 Reactions 3306.15 Elimination Reactions of Alkyl Halides 3316.16 The E2 Reaction 3366.17 The E1 Reaction 3376.18 Substitution versus Elimination 3396.19 Overall Summary 341

Chapter 7 Alkenes and Alkynes I: Properties and Synthesis. Elimination Reactions of Alkyl Halides 357▲ (Molecular graphic: cis-9-Octadecenoic acid, an unsaturated fatty

acid incorporated into cell membrane phospholipids)7.1 Introduction 3577.2 The (E)–(Z) System for Designating Alkene Diastereomers 3587.3 Relative Stabilities of Alkenes 3597.4 Cycloalkenes 3617.5 Synthesis of Alkenes via Elimination Reactions 3627.6 Dehydrohalogenation of Alkyl Halides 3627.7 Acid-Catalyzed Dehydration of Alcohols 3677.8 Carbocation Stability and the Occurrence of Molecular Rearrangements 3747.9 Synthesis of Alkynes by Elimination Reactions 3777.10 The Acidity of Terminal Alkynes 3797.11 Replacement of the Acetylenic Hydrogen Atom of Terminal Alkynes 3807.12 Hydrogenation of Alkenes 3817.13 Hydrogenation: The Function of the Catalyst 3827.14 Hydrogenation of Alkynes 3837.15 Structural Information from Molecular Formulas and the Index of

Hydrogen Deficiency 385

Contents xiii

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Chapter 8 Alkenes and Alkynes II: Addition Reactions 406▲ (Molecular graphic: Dactylyne, a halogenated marine natural product)

8.1 Introduction: Additions to Alkenes 4068.2 Addition of Hydrogen Halides to Alkenes: Markovnikov’s Rule 4088.3 Stereochemistry of the Ionic Addition to an Alkene 4138.4 Addition of Sulfuric Acid to Alkenes 4138.5 Addition of Water to Alkenes: Acid-Catalyzed Hydration 4148.6 Alcohols from Alkenes through Oxymercuration–Demercuration:

Markovnikov Addition 4168.7 Alcohols from Alkenes through Hydroboration–Oxidation: Anti-Markovnikov Syn

Hydration 4198.8 Hydroboration: Synthesis of Alkylboranes 4208.9 Oxidation and Hydrolysis of Alkylboranes 4228.10 Summary of Alkene Hydration Methods 4248.11 Protonolysis of Alkylboranes 4248.12 Addition of Bromine and Chlorine to Alkenes 4258.13 Stereochemistry of the Addition of Halogens to Alkenes 4278.14 Halohydrin Formation 4308.15 Oxidations of Alkenes: Syn 1,2-Dihydroxylation 4328.16 Oxidative Cleavage of Alkenes 4348.17 Addition of Bromine and Chlorine to Alkynes 4388.18 Addition of Hydrogen Halides to Alkynes 4398.19 Oxidative Cleavage of Alkynes 4408.20 Synthetic Strategies Revisited 4408.21 Dimerization of Alkene 4448.22 Prins Reaction 445

Chapter 9 Radical Reactions 475▲ (Molecular graphic: Calicheamicin g1

I, a molecule capable of double-strandDNA cleavage, bound to DNA)

9.1 Introduction 4759.2 Homolytic Bond Dissociation Energies 4769.3 The Reactions of Alkanes with Halogens 4809.4 Chlorination of Methane: Mechanism of Reaction 4829.5 Chlorination of Methane: Energy Changes 4859.6 Halogenation of Higher Alkanes 4919.7 Reactions that Generate Tetrahedral Stereogenic Carbons 4949.8 Radical Addition to Alkenes: The Anti-Markovnikov Addition of Hydrogen Bromide 4969.9 Radical Polymerization of Alkenes: Chain-Growth Polymers 4989.10 Other Important Radical Reactions 500

Chapter 10 Alcohols and Ethers 520▲ (Molecular graphic: Monensin sodium salt, an antibiotic that transports

ions across cell membranes)10.1 Structure and Nomenclature 52010.2 Physical Properties of Alcohols and Ethers 52210.3 Synthesis of Alcohols from Alkenes 52410.4 Reactions of Alcohols 52610.5 Alcohols as Acids 52610.6 Conversion of Alcohols into Alkyl Halides 52710.7 Alkyl Halides from the Reaction of Alcohols with Hydrogen Halides 52810.8 Alkyl Halides from the Reaction of Alcohols with PBr3 or SOCl2 53110.9 Tosylates, Mesylates, and Triflates: Leaving Group Derivatives of Alcohols 53310.10 Synthesis of Ethers 539

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10.11 Reactions of Ethers 54310.12 Epoxides 54510.13 Reactions of Epoxides 54610.14 Anti 1,2-Dihydroxylation of Alkenes via Epoxides 55010.15 Crown Ethers: Nucleophilic Substitution Reactions in Relatively Nonpolar Aprotic

Solvents by Phase-Transfer Catalysis 55210.16 Summary of Reactions of Alkenes, Alcohols, and Ethers 554

Chapter 11 Alcohols from Carbonyl Compounds. Oxidation–Reduction andOrganometallic Compounds 579▲ (Molecular graphic: Nicotinamide [niacin])

11.1 Introduction 57911.2 Oxidation–Reduction Reactions in Organic Chemistry 58111.3 Alcohols by Reduction of Carbonyl Compounds 58211.4 Oxidation of Alcohols 58311.5 Organometallic Compounds 58711.6 Preparation of Organolithium and Organomagnesium Compounds 58811.7 Reactions of Organolithium and Organomagnesium Compounds 59011.8 Alcohols from Grignard Reagents 59211.9 Lithium Dialkylcuprates: The Corey–Posner, Whitesides–House Synthesis 605

Chapter 12 Conjugated Unsaturated Systems 629▲ (Molecular graphic: Morphine, the synthesis of which involved

the Diels–Alder reaction)12.1 Introduction 62912.2 Allylic Substitution and the Allyl Radical 62912.3 Alkadienes and Polyunsaturated Hydrocarbons 63312.4 1,3-Butadiene: Electron Delocalization 63512.5 Electrophilic Attack on Conjugated Dienes: 1,4 Addition 63612.6 The Diels–Alder Reaction: A 1,4-Cycloaddition Reaction of Dienes 640

Chapter 13 Aromatic Compounds 653▲ (Molecular graphic: Benzene, parent molecule in the family

of aromatic hydrocarbons)13.1 Introduction 65313.2 Nomenclature of Benzene Derivatives 65413.3 Reactions of Benzene 65613.4 The Kekulé Structure for Benzene 65713.5 The Stability of Benzene 65813.6 Modern Theories of the Structure of Benzene 66013.7 Hückel’s Rule: The 4n + 2 π Electron Rule 66213.8 Other Aromatic Compounds 66713.9 Heterocyclic Aromatic Compounds 669

Chapter 14 Reactions of Aromatic Compounds 680▲ (Molecular graphic: Thyroxine, an aromatic iodine-containing hormone

associated with regulation of metabolic rate)14.1 Electrophilic Aromatic Substitution Reactions 68014.2 A General Mechanism for Electrophilic Aromatic Substitution: Arenium Ions 68114.3 Halogenation of Benzene 68314.4 Nitration of Benzene 684

Contents xv

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14.5 Sulfonation of Benzene 68514.6 Friedel–Crafts Alkylation 68714.7 Friedel–Crafts Acylation 68914.8 Limitations of Friedel–Crafts Reactions 69114.9 Synthetic Applications of Friedel–Crafts Acylations: The Clemmensen Reduction 69214.10 Effect of Substituents on Reactivity and Orientation 69414.11 Theory of Substituent Effects on Electrophilic Aromatic Substitution 69614.12 Reactions of the Side Chain of Alkylbenzenes 70614.13 Alkenylbenzenes 71014.14 Synthetic Applications 71314.15 Allylic and Benzylic Halides in Nucleophilic Substitution Reactions 71614.16 Reduction of Aromatic Compounds 718

Chapter 15 Aldehydes and Ketones I. Nucleophilic Addition to the CarbonylGroup 746� (Molecular graphic: Pyridoxal phosphate [vitamin B6])

15.1 Introduction 74615.2 Nomenclature of Aldehydes and Ketones 74715.3 Physical Properties 74815.4 Synthesis of Aldehydes 74915.5 Synthesis of Ketones 75315.6 Nucleophilic Addition to the Carbon–Oxygen Double Bond 75615.7 The Addition of Alcohols: Hemiacetals and Acetals 75915.8 The Addition of Primary and Secondary Amines 76815.9 The Addition of Hydrogen Cyanide 77215.10 The Addition of Ylides: The Wittig Reaction 77315.11 The Addition of Organometallic Reagents: The Reformatsky Reaction 77715.12 Oxidation of Aldehydes and Ketones 77915.13 Chemical Analyses for Aldehydes and Ketones 785

Chapter 16 Aldehydes and Ketones II. Aldol Reactions 806� (Molecular graphic: Glyceraldehyde-3-phosphate, a key intermediate in

metabolic energy production)16.1 The Acidity of the α-Hydrogens of Carbonyl Compounds: Enolate Anions 80616.2 Keto and Enol Tautomers 80716.3 Reactions via Enols and Enolate Anions 80816.4 The Aldol Reaction: The Addition of Enolate Anions to Aldehydes and Ketones 81416.5 Crossed Aldol Reactions 81816.6 Cyclizations via Aldol Condensations 82316.7 Lithium Enolates 825

Chapter 17 Carboxylic Acids and Their Derivatives. Nucleophilic Addition –Elimination at the Acyl Carbon 845� (Molecular graphic: A portion of nylon 6, 6, a polyamide)

17.1 Introduction 84517.2 Nomenclature and Physical Properties 84617.3 Preparation of Carboxylic Acids 85217.4 Nucleophilic Addition–Elimination at the Acyl Carbon 85517.5 Acyl Chlorides 85717.6 Carboxylic Acid Anhydrides 85917.7 Esters 86017.8 Amides 86617.9 Derivatives of Carbonic Acid 872

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17.10 Decarboxylation of Carboxylic Acids 87517.11 Chemical Tests for Acyl Compounds 87817.12 The Hunsdiecker Reaction 88117.13 Step-Growth Polymers 881

Chapter 18 Amines 902▲ (Molecular graphic: Histrionicatoxin, a paralyzing neurotoxin from certain

poison dart frogs)18.1 Nomenclature 90218.2 Physical Properties and Structure of Amines 90418.3 Basicity of Amines: Amine Salts 90518.4 Preparation of Amines 91118.5 Reactions of Amines 91918.6 Reactions of Amines with Nitrous Acid 92018.7 Replacement Reactions of Arenediazonium Salts 92318.8 Coupling Reactions of Arenediazonium Salts 92618.9 Reactions of Amines with Sulfonyl Chlorides 92818.10 The Sulfa Drugs: Sulfanilamide 93018.11 Eliminations Involving Ammonium Compounds 930

Chapter 19 Phenols and Aryl Halides: Nucleophilic Aromatic Substitution 949▲ (Molecular graphic: 4-tert-Butylcalix[4]arene, a chalice-shaped molecule)

19.1 Structure and Nomenclature of Phenols 94919.2 Naturally Occurring Phenols 95019.3 Physical Properties of Phenols 95119.4 Synthesis of Phenols 95219.5 Reactions of Phenols as Acids 95419.6 Other Reactions of the O—H Group of Phenols 95719.7 Cleavage of Alkyl Aryl Ethers 95719.8 Reactions of the Benzene Ring of Phenols 95819.9 The Claisen Rearrangement 96019.10 Quinones 96119.11 Aryl Halides and Nucleophilic Aromatic Substitution 962

Chapter 20 Carbohydrates 978▲ (Molelcular graphic: Sialyl Lewis,x a carbohydrate that is important in the

recognition and healing of traumatized tissue)20.1 Introduction 97820.2 Monosaccharides 98120.3 Mutarotation 98620.4 Glycoside Formation 98720.5 Other Reactions of Monosaccharides 98920.6 Oxidation Reactions of Monosaccharides 99320.7 Reduction of Monosaccharides: Alditols 99820.8 Reactions of Monosaccharides with Phenylhydrazine: Osazones 99920.9 Synthesis and Degradation of Monosaccharides 100020.10 The D Family of Aldoses 100220.11 Fischer’s Proof of the Configuration of D-(1)-Glucose 100220.12 Disaccharides 100520.13 Polysaccharides 100820.14 Other Biologically Important Sugars 101220.15 Sugars That Contain Nitrogen 101320.16 Carbohydrate Antibiotics 1014

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Chapter 21 Amino Acids and Proteins 1028▲ (Molecular graphic: A synthetic Diels-Alderase catalytic antibody

with a bound hapten)21.1 Introduction 102821.2 Amino Acids 102921.3 Synthesis of α-Amino Acids 103421.4 Polypeptides and Proteins 103721.5 Primary Structure of Polypeptides and Proteins 103921.6 Secondary, Tertiary, and Quaternary Structures of Proteins 1040

Chapter 22 Carbene and Carbenoids 104922.1 Introduction 104922.2 Existence of Carbenes 104922.3 Formation of Carbenes 104922.4 Types of Carbenes 105122.5 Reactions of Carbenes 105222.6 Rearrangement in Carbenes 1066

Chapter 23 Reaction of Nitrene and Electron Deficient Oxygen 107823.1 Migration to Electron Deficient Nitrogen 107823.2 Nitrene Formation 107823.3 Hofmann–Curtius–Lossen–Schmidt Group of Rearrangements 107923.4 Curtius Reaction 108023.5 Schmidt Reaction 108023.6 Hofmann-Bromamide Reaction or Hofman Rearrangement 108123.7 Beckmann Rearrangement 108323.8 Stieglitz Rearrangement 1086

First Review Problem Set R-1

Second Review Problem Set R-4

Glossary G-1

Photo and Illustration Credits C-1

Index I-1

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T. W. Graham Solomons

T. W. Graham Solomons did his undergraduate work atThe Citadel and received his doctorate in organic chem-istry in 1959 from Duke University where he workedwith C. K. Bradsher. Following this he was a SloanFoundation Postdoctoral Fellow at the University ofRochester where he worked with V. Boekelheide. In 1960he became a charter member of the faculty of theUniversity of South Florida and became Professor ofChemistry in 1973. In 1992 he was made ProfessorEmeritus. In 1994 he was a visiting professor with theFaculté des Sciences Pharmaceutiques et Biologiques,Université René Descartes (Paris V). He is a member ofSigma Xi, Phi Lambda Upsilon, and Sigma Pi Sigma. Hehas received research grants from the ResearchCorporation and the American Chemical SocietyPetroleum Research Fund. For several years he was direc-tor of an NSF-sponsored Undergraduate ResearchParticipation Program at USF. His research interests havebeen in the areas of heterocyclic chemistry and unusualaromatic compounds. He has published papers in theJournal of the American Chemical Society, the Journal ofOrganic Chemistry, and the Journal of HeterocyclicChemistry. He has received several awards for distin-guished teaching. His organic chemistry textbooks havebeen widely used for 20 years and have been translatedinto French, Japanese, Chinese, Korean, Malaysian,Arabic, Portuguese, Spanish, Turkish, and Italian. He andhis wife Judith have a daughter who is a building conser-vator, a son who is an artist, and another son who is agraduate student studying biochemistry.

Craig Barton Fryhle

Craig Barton Fryhle is Chair and Professor of Chemistryat Pacific Lutheran University. He earned his B.A. degreefrom Gettysburg College and Ph.D. from BrownUniversity. His experiences at these institutions shapedhis dedication to mentoring undergraduate students inchemistry and the liberal arts, which is a passion thatburns strongly for him. His research interests have beenin areas relating to the shikimic acid pathway, includingmolecular modeling and NMR spectrometry of substratesand analogues, as well as structure and reactivity studiesof shikimate pathway enzymes using isotopic labelingand mass spectrometry. He has mentored many studentsin undergraduate research, a number of whom have laterearned their Ph.D. degrees and gone on to academic or in-dustrial positions. He has participated in workshops onfostering undergraduate participation in research, and hasbeen an invited participant in efforts by the NationalScience Foundation to enhance undergraduate research inchemistry. He has received research and instrumentationgrants from the National Science Foundation, the M J.Murdock Charitable Trust, and other private foundations.His work in chemical education, in addition to textbookco-authorship, involves incorporation of student-ledteaching in the classroom and technology-based strategiesin organic chemistry. He has also developed experimentsfor undergraduate students in organic laboratory and in-strumental analysis courses. He has been a volunteer withthe hands-on science program in Seattle public schools,and Chair of the Puget Sound Section of the AmericanChemical Society. He lives in Seattle with his wife andtwo daughters.

About the Authors

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Contrary to what you may have heard, organic chemisty does not have to be a difficult course.It will be a rigorous course, and it will offer a challenge. But you will learn more in it than inalmost any course you will take—and what you learn will have a special relevance to life andthe world around you. However, because organic chemistry can be approached in a logical andsystematic way, you will find that with the right study habits, mastering organic chemistry canbe a deeply satisfying experience. Here, then, are some suggestions about how to study:

1. Keep up with your work from day to day—never let yourself get behind.Organic chemistry is a course in which one idea almost always builds on another thathas gone before. It is essential, therefore, that you keep up with, or better yet, be a lit-tle ahead of your instructor. Ideally, you should try to stay one day ahead of your in-structor’s lectures in your own class preparations. The lecture, then, will be muchmore helpful because you will already have some understanding of the assigned ma-terial. Your time in class will clarify and expand ideas that are already familiar ones.

2. Study material in small units, and be sure that you understand each new sectionbefore you go on to the next. Again, because of the cumulative nature of organicchemistry, your studying will be much more effective if you take each new idea as itcomes and try to understand it completely before you move on to the next concept.

3. Work all of the in-chapter and assigned problems. One way to check your progressis to work each of the in-chapter problems when you come to it. These problems havebeen written just for this purpose and are designed to help you decide whether or notyou understand the material that has just been explained. If you can work the in-chap-ter problem, then you should go on; if you cannot, then you should go back and studythe preceding material again. Work all of the problems assigned by your instructorfrom the end of the chapter, as well. Do all of your problems in a notebook and bringthis book with you when you go to see your instructor for extra help.

4. Write when you study. Write the reactions, mechanisms, structures, and so on, over andover again. Organic chemistry is best assimilated through the fingertips by writing, andnot through the eyes by simply looking, or by highlighting material in the text, or by re-ferring to flash cards. There is a good reason for this. Organic structures, mechanisms,and reactions are complex. If you simply examine them, you may think you understandthem thoroughly, but that will be a misperception. The reaction mechanism may makesense to you in a certain way, but you need a deeper understanding than this. You need toknow the material so thoroughly that you can explain it to someone else. This level ofunderstanding comes to most of us (those of us without photographic memories)through writing. Only by writing the reaction mechanisms do we pay sufficient attentionto their details, such as which atoms are connected to which atoms, which bonds breakin a reaction and which bonds form, and the three-dimensional aspects of the structures.When we write reactions and mechanisms, connections are made in our brains that pro-vide the long-term memory needed for success in organic chemistry. We virtually guar-antee that your grade in the course will be directly proportional to the number of pagesof paper that your fill with your own writing in studying during the term.

5. Learn by teaching and explaining. Study with your student peers and practice ex-plaining concepts and mechanisms to each other. Use exercises your instructor mayassign as vehicles for teaching and learning interactively with your peers.

To the Student

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