Solomons & Fryhles

Organic Chemistry For IIT-JEE

Second Edition

Solomons & Fryhles

Organic Chemistry For IIT-JEE
Second Edition

Adapted by M.S. Chouhan

Solomons & Fryhles Organic Chemistry For IIT-JEE Second Edition

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. Limits of Liability: While the publisher and the author have used their best efforts in preparing this book, Wiley and the author make no representation or warranties with respect to the accuracy or completeness of the contents of this book, and specifically disclaim any implied warranties of merchantability or fitness for any particular purpose. There are no warranties which extend beyond the descriptions contained in this paragraph. No warranty may be created or extended by sales representatives or written sales materials. The accuracy and completeness of the information provided herein and the opinions stated herein are not guaranteed or warranted to produce any particular results, and the advice and strategies contained herein may not be suitable for every individual. Neither Wiley India nor the author shall be liable for any loss of profit or any other commercial damages, including but not limited to special, incidental, consequential, or other damages. Disclaimer: The contents of this book have been checked for accuracy. Since deviations cannot be precluded entirely, Wiley or its author cannot guarantee full agreement. As the book is intended for educational purpose, Wiley or its author shall not be responsible for any errors, omissions or damages arising out of the use of the information contained in the book. This publication is designed to provide accurate and authoritative information with regard to the subject matter covered. It is sold on the understanding that the Publisher is not engaged in rendering professional services. Trademarks: All brand names and product names used in this book are trademarks, registered trademarks, or trade names of their respective holders. Wiley is not associated with any product or vendor mentioned in this book. Other Wiley Editorial Offices: John Wiley & Sons, Inc. 111 River Street, Hoboken, NJ 07030, USA Wiley-VCH Verlag GmbH, Pappellaee 3, D-69469 Weinheim, Germany John Wiley & Sons Australia Ltd, 42 McDougall Street, Milton, Queensland 4064, Australia John Wiley & Sons (Asia) Pte Ltd, 1 Fusionopolis Walk #07-01 Solaris, South Tower Singapore 138628 John Wiley & Sons Canada Ltd, 22 Worcester Road, Etobicoke, Ontario, Canada, M9W 1L1 First Edition: 2009 Second Edition: 2012 ISBN: 978-81-265-3099-1 www.wileyindia.com Printed at: Radha Offset, Delhi

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

O R G A N I Z AT I O N
A central theme of our approach to organic chemistry is to emphasize the relationship between structure and reactivity. To accomplish this, we have chosen an organization that combines the most useful features of the traditional functional group approach with one based on reaction mechanisms. Our philosophy is to emphasize mechanisms and their common aspects as often as possible, and at the same time to use the unifying features of functional groups as the basis for most chapters. The structural aspects of our approach show students what organic chemistry is. Mechanistic aspects of our approach show students how it works. And wherever an opportunity arises, we show them what it does in living systems and the physical world around us. Most important is for students to have a solid understanding of structure of hybridization and geometry, steric hindrance, electronegativity, polarity, and formal charges so that they can make intuitive sense of mechanisms. It is with these topics that we begin in Chapter 1. In Chapter 2 we introduce all of the important functional groups and intermolecular 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 at from the point of view of Lewis acid-base theory, the steps of most organic reaction mechanisms are acid-base reactions. Acid-base reactions, moreover, are relatively simple and they are reactions that students will nd familiar. Acid-base reactions also lend themselves to an introduction of several important topics that students need to know about early in the course: (1) the curved arrow notation for illustrating mechanisms, (2) the relationship between free-energy changes and equilibrium constants, (3) how enthalpy and entropy changes affect reactions under equilibrium control, and (4) the importance of inductive and resonance effects and of solvent effects. In Chapter 3, we also begin to show students how organic chemistry works by presenting the rst of many boxes called A Mechanism for the Reaction. All through the book, these boxes highlight and bring forth the details of important reaction mechanisms. Throughout our study we use various opportunities to show what organic chemistry does in life, both in biological terms and in our physical environment, through real world applications. As students come to realize that life and much of the world around us involves organic chemistry, their fascination with the subject cannot help but increase.

K E Y F E AT U R E S

OF THE

THIS EDITION

Some major highlights of the this edition include: Concept Maps, Mechanism Reviews, and Synthetic Connections: Comprehensive new summary and review tools to enhance student learning. Concepts related to carbenes, carbenoids and nitrenes have been introduced in form of two chapters at the end.

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Concepts not relevant to joint engineering entrance examinations for IIT have been deleted to make the book more concise. Solved problems have been added after related section in some chapters and at the end of some chapters for better understanding of the subject. New end-of-chapter material comprising IIT-JEE specic questions and an answer key to 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 prepare for examinations.

Concept Maps, Mechanism Summaries, and Synthetic Connections

We introduce, for the rst time with this edition, comprehensive visual summary and review tools for students. These tools come in three forms: Concept Maps, Mechanism Summaries, and Synthetic Connections. Concept Maps are hierarchical owcharts that join one key concept 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 tie together common themes and highlight key attributes of important mechanisms. They highlight factors inuencing the type of mechanism by which a molecule will react, as well as show regiochemical and stereochemical aspects of mechanisms. Synthetic Connections are roadmaps that show pathways for converting molecules from one type to another. Using our Synthetic Connections, students can see how reactions they have learned are part of their growing repertoire for synthesis.
CONCEPT MAP Curved arrow notation (Section 3.4) is used to show Acids can be Reaction mechanisms (Section 3.1) often involve Bases can be

Br nsted-Lowry acids (Section 3.2A) are Proton donors

are a subcategory of

Lewis acids (Section 3.2B) are Electron pair acceptors are

Lewis bases (Section 3.2B) are Electron pair donors can be are

are a subcategory of

Br nsted-Lowry bases (Section 3.2A) are Proton acceptors contain/have

contain/have Small or negative pKa values and large Ka values (Section 3.5) are associated with Strong acids have Weak conjugate bases

Electrophiles (Section 3.3) can be Carbocations

Nucleophiles (Section 3.3) can be Carbanions

Large and positive pKa values and small Ka values (Section 3.5) are associated with Strong bases have Weak conjugate acids

Part of the Chapter 3 Concept Map

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Orbital Hybridization and the Structure of Organic Molecules

Students must develop a sound understanding of the structure and shape of organic molecules. We build the foundation for their understanding of structure by introducing orbital hybridization and VSEPR theory in Chapter 1. We begin with methane for sp3 hybridization, move directly to ethene for sp2 hybridization, and then to ethyne for sp hybridization. We also use calculated molecular orbitals, and electron density surfaces to illustrate regions of bonding electron density and overall molecular shape. In this edition we improved our presentation of resonance in Chapter 1 by including some additional rules for drawing proper resonance structures. Students will consider these rules further when they study conjugated systems in Chapter 12.

H 10928 C H H H

Early Introduction to Retrosynthetic Analysis and Organic Synthesis

We use the alkylation of alkynide anions in Chapter 4 to introduce organic synthesis and retrosynthetic analysis. One advantage of using alkynide anions to introduce synthesis is that the reactivity of terminal alkynes and alkyl halides is readily understood on the basis of concepts students have learned in the beginning chapters of the book, namely acid-base chemistry and polarity. Students will use Brnsted-Lowry acid-base chemistry to outline the preparation of alkynide anions from alkynes, and they will recall Lewis acid-base concepts when they consider the reaction of an alkynide anion with an alkyl halide. They will also nd reinforcement of a common theme in many organic reactions the interaction between molecules or groups bearing opposite charges. The alkylation of alkynide anions also gives students a method for carboncarbon bond formation very early in their study of organic chemistry. And, it gives them a product that contains a functional group from which they can make many other compounds as their synthetic repertoire grows. Finally, because better or worse retrosynthetic pathways using alkynide-anion alkylation are conceivable for a given molecule, this reaction is a realistic vehicle for teaching the logic of retrosynthetic analysis.

Substitution and Elimination Reactions

Substitution and elimination reactions provide an opportunity for students to encounter one of the important realities of organic chemistry. Reactions almost never follow exclusively one path, much as we would like them to. As chemists, we know very well how frequently one kind of reaction competes with another to complicate our synthetic plans. Therefore, bringing students to the point where they can propose reasonable syntheses using substitutions or eliminations requires a careful orchestration of topics. In this edition, as in the last, Chapter 6 focuses on substitution, but it also briey introduces elimination reactions. We have done this because the two reactions nearly always occur together, and it 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 reactions, including stereochemistry, regiochemistry, and overall product distribution.

Synthesis Updates
The 2001 Nobel Prize in Chemistry was awarded to K. Barry Sharpless, William Knowles, and Ryoji Noyori for their work on catalytic asymmetric methods for oxidation and reduction. We have highlighted these powerful synthesis tools in several new or

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revised boxes in the this edition, including mention of their relevance to well-known compounds such as Naproxen and L-DOPA. We have also included information on green catalytic methods such as the oxidation of alkenes using catalytic rather than stoichiometric amounts of osmium, and oxidation using Jacobsens catalyst. In this edition we introduce oxymercurationdemercuration and hydroborationoxidation in Chapter 8 because these reactions belong with other addition reactions of alkenes. This change also groups these reactions with acid-catalyzed hydration of alkenes as a collection of methods for alcohol synthesis from alkenes. Then, when alcohols and ethers are discussed in Chapter 10, we briey review the ensemble of methods given in Chapter 8 for synthesis of alcohols from alkenes. We have also deleted some sections that, although dear to us as chemists, provided reasonable 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, enolate ions, biochemistry and green chemistry.

Other Pedagogical Features

Concept Maps, Mechanism Reviews, and Synthetic Connections These new features appear at the end of chapters as summary and review tools. A Mechanism for the Reaction These specially designed mechanism presentations give detailed explanations for every key mechanism in the book. Curved arrows show precisely and unambiguously how electrons flow in each step of a mechanism. Steps are identified and annotated in the mechanisms to further explain each transformation. Solved Problems Sample problems with solutions are included at key points to show students how to approach problems in organic chemistry. Various solved problems have been added in the chapters for this edition. In-Chapter Problems Numbered problems appear at the end of sections to reinforce students learning immediately after each topic is introduced. Key Terms and Concepts A list of key terms and concepts with section references at the end of each chapter allows students to test their memory regarding key ideas and if necessary to easily refer back to a full presentation of the concept in the chapter. The key terms and concepts listed are also dened in the glossary. End-of-Chapter Problems have been modied as per IIT-JEE requirements to include Single Correct Choice Type, Multiple Correct Choice Type, Linked Comprehension Type, Integer Answer Type and MatrixMatch Type questions. The number of these question types vary across all chapters. Craig B. Fryhle T. W. Graham Solomons

44254 Solomons Wiley FM_pv-xxxii.qxp:FM_pi-xxxii.qxp 18/04/12 10:54 frontmatter AM Page ix

first pages bb 10/30/03 p ix application file

Preface to the Adapted Version

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 corresponds closely to the course that I teach. Although the book is organized along tried-andtrue functional-group lines, it contains some unique features that have served me well in both my teaching and understanding of Organic Chemistry. My four major concerns in both the initial writing and the revision of this text were readability, presentation, organization, and accuracy. In the current scenario of stiff competition especially for IIT-JEE, one must be clear that almost all the sincere applicants are well equipped with the facts of subject; yet, the winner is the one who knows how to use these facts with accuracy and efciency. As an experienced teacher, I would like to suggest students 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 of fact, they will enjoy the present venture and I would feel rewarded if this book is helpful for the students and teachers in real terms. All efforts have been made to make the book error-free; however, a few misprints may inadvertently creep. I acknowledge the blessing and support of my mother Smt. Raj Kanwar, father Shri 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 acknowledged. I also pay my sincere thanks to all the esteemed members of Wiley India and specially Mr. Paras Bansal, Ms. Anjali Chadha, Ms. Sruthi Guru and Mr. Rakesh Poddar in bringing out this book in such a nice form. In the end, constructive criticism and valuable suggestions from the readers are most welcome to make the book more useful. M.S.Chouhan (MSC Sir) Email: mahen_chouhan@yahoo.com Mobile: 9828025625

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Contents
Chapter 1
1.1 1.2 1.3 1.4 1.5 1.6 1.7 1.8 1.9 1.10 1.11 1.12 1.13 1.14 1.15

Carbon Compounds and Chemical Bonds 1

(Molecular graphic: Glycine, an organic molecule found in space) Introduction 1 The Development of Organic Chemistry as a Science 2 The Structural Theory of Organic Chemistry 3 Chemical Bonds: The Octet Rule 6 Writing Lewis Structures 8 Exceptions to the Octet Rule 9 Formal Charge 11 Resonance 13 Hyperconjugation 25 The Structure of Methane and Ethane: sp3 Hybridization 32 The Structure of Ethene (Ethylene): sp2 Hybridization 33 The Structure of Ethyne (Acetylene): sp Hybridization 36 A Summary of Important Concepts That Come from Quantum Mechanics 38 Molecular Geometry: The Valence Shell Electron Pair Repulsion Model 39 Representation of Structural Formulas 40

Chapter 2

Representative Carbon Compounds: Functional Groups and Intermolecular Forces 56

2.1 2.2 2.3 2.4 2.5 2.6 2.7 2.8 2.9 2.10 2.11 2.12 2.13 2.14 2.15

(Molecular graphic: A molecular template for bone growth) CarbonCarbon Covalent Bonds 56 Hydrocarbons: Representative Alkanes, Alkenes, Alkynes, and Aromatic Compounds 57 Polar Covalent Bonds 60 Polar and Nonpolar Molecules 61 Functional Groups 63 Alkyl Halides or Haloalkanes 65 Alcohols 65 Ethers 67 Amines 67 Aldehydes and Ketones 68 Carboxylic Acids, Esters, and Amides 69 Nitriles 70 Summary of Important Families of Organic Compounds 71 Physical Properties and Molecular Structure 72 Summary of Attractive Electric Forces 78

Chapter 3
3.1 3.2 3.3 3.4 3.5 3.6 3.7 3.8 3.9

An Introduction to Organic Reactions: Acids and Bases 89

(Molecular graphic: Diamox, a drug that prevents altitude sickness) Reactions and Their Mechanisms 89 AcidBase Reactions 91 Heterolysis of Bonds to Carbon: Carbocations and Carbanions 94 The Use of Curved Arrows in Illustrating Reactions 95 The Strength of Acids and Bases: Ka and pKa 97 Predicting the Outcome of AcidBase Reactions 100 The Relationship Between Structure and Acidity 102 Energy Changes 106 The Relationship Between the Equilibrium Constant and the Standard Free-Energy Change, DG 107
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3.10 3.11 3.12 3.13 3.14 3.15 3.16 3.17 3.18

The Acidity of Carboxylic Acids 108 The Effect of the Solvent on Acidity 112 Organic Compounds as Bases 113 Acids and Bases in Nonaqueous Solutions 114 AcidBase Reactions and the Synthesis of Deuterium- and Tritium-Labeled Compounds 116 Reaction of NaHCO3 117 Steric Inhibition of Resonance (SIR) Effect 118 Ortho and Para Effects 120 Representation of Change in Electronic Conguration 137

Chapter 4

Alkanes: Nomenclature, Conformational Analysis, and an Introduction to Synthesis 157

4.1 4.2 4.3 4.4 4.5 4.6 4.7 4.8 4.9 4.10 4.11 4.12 4.13 4.14 4.15 4.16 4.17 4.18

(Molecular graphic: A portion of the structure of diamond, an exceptionally rigid molecule) Introduction to Alkanes and Cycloalkanes 157 Shapes of Alkanes 159 IUPAC Nomenclature of Alkanes, Alkyl Halides, and Alcohols 162 Nomenclature of Cycloalkanes 169 Nomenclature of Alkenes and Cycloalkenes 171 Nomenclature of Alkynes 173 Physical Properties of Alkanes and Cycloalkanes 174 Sigma Bonds and Bond Rotation 176 Conformational Analysis of Butane 178 The Relative Stabilities of Cycloalkanes: Ring Strain 187 The Origin of Ring Strain in Cyclopropane and Cyclobutane: Angle Strain and Torsional Strain 189 Conformations of Cyclohexane 191 Substituted Cyclohexanes: Axial and Equatorial Hydrogen Atoms 196 Disubstituted Cycloalkanes: CisTrans Isomerism 198 Bicyclic and Polycyclic Alkanes 203 Chemical Reactions of Alkanes 205 Synthesis of Alkanes and Cycloalkanes 205 Retrosynthetic AnalysisPlanning an Organic Synthesis 208

Chapter 5
5.1 5.2 5.3 5.4 5.5 5.6 5.7 5.8 5.9 5.10 5.11 5.12 5.13 5.14 5.15

Stereochemistry: Chiral Molecules 225

(Molecular graphic: The mirror-image stereoisomers of alanine, a chiral amino acid) The Biological Signicance of Chirality 225 Isomerism: Constitutional Isomers and Stereoisomers 226 Enantiomers and Chiral Molecules 228 More about the Biological Importance of Chirality 231 Historical Origin of Stereochemistry 233 Tests for Chirality: Planes of Symmetry 234 Nomenclature of Enantiomers: The R,S-System 234 Properties of Enantiomers: Optical Activity 239 The Origin of Optical Activity 243 The Synthesis of Chiral Molecules 246 Chiral Drugs 248 Molecules with More than One Stereogenic Center 249 Fischer Projection Formulas 253 Stereoisomerism of Cyclic Compounds 254 Relating Congurations through Reactions in Which No Bonds to the Stereogenic Carbon Are Broken 257

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5.16 Separation of Enantiomers: Resolution 260 5.17 Compounds with Stereogenic Centers Other than Carbon 263 5.18 Chiral Molecules that Do Not Possess a Tetrahedral Atom with 5.19 5.20 5.21 5.22 5.23
Four Different Groups 263 Elements of Symmetry 264 Biphenyl 271 Racemization of Biphenyl Compounds 274 Tautomerism 276 Gero Entropy 279

Chapter 6

Ionic Reactions Nucleophilic Substitution and Elimination Reactions of Alkyl Halides 300

6.1 6.2 6.3 6.4 6.5 6.6 6.7 6.8 6.9 6.10 6.11 6.12 6.13 6.14 6.15 6.16 6.17 6.18 6.19

(Molecular graphic: The SN2 transition state resulting from collision of a hydroxide anion with chloromethane) Introduction 300 Nucleophilic Substitution Reactions 302 Nucleophiles 303 Leaving Groups 304 Kinetics of a Nucleophilic Substitution Reaction: An SN2 Reaction 304 A Mechanism for the SN2 Reaction 306 Transition State Theory: Free-Energy Diagrams 307 The Stereochemistry of SN2 Reactions 310 The Reaction of tert-Butyl Chloride with Hydroxide Ion: An SN1 Reaction 312 A Mechanism for the SN1 Reaction 313 Carbocations 315 The Stereochemistry of SN1 Reactions 317 Factors Affecting the Rates of SN1 and SN2 Reactions 319 Organic Synthesis: Functional Group Transformations Using SN2 Reactions 330 Elimination Reactions of Alkyl Halides 331 The E2 Reaction 336 The E1 Reaction 337 Substitution versus Elimination 339 Overall Summary 341

Chapter 7

Alkenes and Alkynes I: Properties and Synthesis. Elimination Reactions of Alkyl Halides 357

7.1 7.2 7.3 7.4 7.5 7.6 7.7 7.8 7.9 7.10 7.11 7.12 7.13 7.14 7.15

(Molecular graphic: cis-9-Octadecenoic acid, an unsaturated fatty acid incorporated into cell membrane phospholipids) Introduction 357 The (E )(Z) System for Designating Alkene Diastereomers 358 Relative Stabilities of Alkenes 359 Cycloalkenes 361 Synthesis of Alkenes via Elimination Reactions 362 Dehydrohalogenation of Alkyl Halides 362 Acid-Catalyzed Dehydration of Alcohols 367 Carbocation Stability and the Occurrence of Molecular Rearrangements 374 Synthesis of Alkynes by Elimination Reactions 377 The Acidity of Terminal Alkynes 379 Replacement of the Acetylenic Hydrogen Atom of Terminal Alkynes 380 Hydrogenation of Alkenes 381 Hydrogenation: The Function of the Catalyst 382 Hydrogenation of Alkynes 383 Structural Information from Molecular Formulas and the Index of Hydrogen Deciency 385

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Chapter 8
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 8.16 8.17 8.18 8.19 8.20 8.21 8.22

Alkenes and Alkynes II: Addition Reactions 406

(Molecular graphic: Dactylyne, a halogenated marine natural product) Introduction: Additions to Alkenes 406 Addition of Hydrogen Halides to Alkenes: Markovnikovs Rule 408 Stereochemistry of the Ionic Addition to an Alkene 413 Addition of Sulfuric Acid to Alkenes 413 Addition of Water to Alkenes: Acid-Catalyzed Hydration 414 Alcohols from Alkenes through OxymercurationDemercuration: Markovnikov Addition 416 Alcohols from Alkenes through HydroborationOxidation: Anti-Markovnikov Syn Hydration 419 Hydroboration: Synthesis of Alkylboranes 420 Oxidation and Hydrolysis of Alkylboranes 422 Summary of Alkene Hydration Methods 424 Protonolysis of Alkylboranes 424 Addition of Bromine and Chlorine to Alkenes 425 Stereochemistry of the Addition of Halogens to Alkenes 427 Halohydrin Formation 430 Oxidations of Alkenes: Syn 1,2-Dihydroxylation 432 Oxidative Cleavage of Alkenes 434 Addition of Bromine and Chlorine to Alkynes 438 Addition of Hydrogen Halides to Alkynes 439 Oxidative Cleavage of Alkynes 440 Synthetic Strategies Revisited 440 Dimerization of Alkene 444 Prins Reaction 445

Chapter 9

Radical Reactions 475

(Molecular graphic: Calicheamicin g1I, a molecule capable of double-strand DNA cleavage, bound to DNA) 9.1 Introduction 475 9.2 Homolytic Bond Dissociation Energies 476 9.3 The Reactions of Alkanes with Halogens 480 9.4 Chlorination of Methane: Mechanism of Reaction 482 9.5 Chlorination of Methane: Energy Changes 485 9.6 Halogenation of Higher Alkanes 491 9.7 Reactions that Generate Tetrahedral Stereogenic Carbons 494 9.8 Radical Addition to Alkenes: The Anti-Markovnikov Addition of Hydrogen Bromide 496 9.9 Radical Polymerization of Alkenes: Chain-Growth Polymers 498 9.10 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 520 10.2 Physical Properties of Alcohols and Ethers 522 10.3 Synthesis of Alcohols from Alkenes 524 10.4 Reactions of Alcohols 526 10.5 Alcohols as Acids 526 10.6 Conversion of Alcohols into Alkyl Halides 527 10.7 Alkyl Halides from the Reaction of Alcohols with Hydrogen Halides 528 10.8 Alkyl Halides from the Reaction of Alcohols with PBr3 or SOCl2 531 10.9 Tosylates, Mesylates, and Triates: Leaving Group Derivatives of Alcohols 533 10.10 Synthesis of Ethers 539

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10.11 10.12 10.13 10.14 10.15

Reactions of Ethers 543 Epoxides 545 Reactions of Epoxides 546 Anti 1,2-Dihydroxylation of Alkenes via Epoxides 550 Crown Ethers: Nucleophilic Substitution Reactions in Relatively Nonpolar Aprotic Solvents by Phase-Transfer Catalysis 552 10.16 Summary of Reactions of Alkenes, Alcohols, and Ethers 554

Chapter 11 Alcohols from Carbonyl Compounds. OxidationReduction and Organometallic Compounds 579
11.1 11.2 11.3 11.4 11.5 11.6 11.7 11.8 11.9
(Molecular graphic: Nicotinamide [niacin]) Introduction 579 OxidationReduction Reactions in Organic Chemistry 581 Alcohols by Reduction of Carbonyl Compounds 582 Oxidation of Alcohols 583 Organometallic Compounds 587 Preparation of Organolithium and Organomagnesium Compounds 588 Reactions of Organolithium and Organomagnesium Compounds 590 Alcohols from Grignard Reagents 592 Lithium Dialkylcuprates: The CoreyPosner, WhitesidesHouse Synthesis 605

Chapter 12 Conjugated Unsaturated Systems 629

12.1 12.2 12.3 12.4 12.5 12.6
(Molecular graphic: Morphine, the synthesis of which involved the DielsAlder reaction) Introduction 629 Allylic Substitution and the Allyl Radical 629 Alkadienes and Polyunsaturated Hydrocarbons 633 1,3-Butadiene: Electron Delocalization 635 Electrophilic Attack on Conjugated Dienes: 1,4 Addition 636 The DielsAlder Reaction: A 1,4-Cycloaddition Reaction of Dienes 640

Chapter 13 Aromatic Compounds 653

13.1 13.2 13.3 13.4 13.5 13.6 13.7 13.8 13.9
(Molecular graphic: Benzene, parent molecule in the family of aromatic hydrocarbons) Introduction 653 Nomenclature of Benzene Derivatives 654 Reactions of Benzene 656 The Kekul Structure for Benzene 657 The Stability of Benzene 658 Modern Theories of the Structure of Benzene 660 Hckels Rule: The 4n + 2 Electron Rule 662 Other Aromatic Compounds 667 Heterocyclic Aromatic Compounds 669

Chapter 14 Reactions of Aromatic Compounds 680

14.1 14.2 14.3 14.4
(Molecular graphic: Thyroxine, an aromatic iodine-containing hormone associated with regulation of metabolic rate) Electrophilic Aromatic Substitution Reactions 680 A General Mechanism for Electrophilic Aromatic Substitution: Arenium Ions 681 Halogenation of Benzene 683 Nitration of Benzene 684

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14.5 14.6 14.7 14.8 14.9 14.10 14.11 14.12 14.13 14.14 14.15 14.16

Sulfonation of Benzene 685 FriedelCrafts Alkylation 687 FriedelCrafts Acylation 689 Limitations of FriedelCrafts Reactions 691 Synthetic Applications of FriedelCrafts Acylations: The Clemmensen Reduction 692 Effect of Substituents on Reactivity and Orientation 694 Theory of Substituent Effects on Electrophilic Aromatic Substitution 696 Reactions of the Side Chain of Alkylbenzenes 706 Alkenylbenzenes 710 Synthetic Applications 713 Allylic and Benzylic Halides in Nucleophilic Substitution Reactions 716 Reduction of Aromatic Compounds 718

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

15.1 15.2 15.3 15.4 15.5 15.6 15.7 15.8 15.9 15.10 15.11 15.12 15.13

Introduction 746 Nomenclature of Aldehydes and Ketones 747 Physical Properties 748 Synthesis of Aldehydes 749 Synthesis of Ketones 753 Nucleophilic Addition to the CarbonOxygen Double Bond 756 The Addition of Alcohols: Hemiacetals and Acetals 759 The Addition of Primary and Secondary Amines 768 The Addition of Hydrogen Cyanide 772 The Addition of Ylides: The Wittig Reaction 773 The Addition of Organometallic Reagents: The Reformatsky Reaction 777 Oxidation of Aldehydes and Ketones 779 Chemical Analyses for Aldehydes and Ketones 785

Chapter 16 Aldehydes and Ketones II. Aldol Reactions 806

16.1 16.2 16.3 16.4 16.5 16.6 16.7
L (Molecular graphic: Glyceraldehyde-3-phosphate, a key intermediate in metabolic energy production) The Acidity of the -Hydrogens of Carbonyl Compounds: Enolate Anions 806 Keto and Enol Tautomers 807 Reactions via Enols and Enolate Anions 808 The Aldol Reaction: The Addition of Enolate Anions to Aldehydes and Ketones 814 Crossed Aldol Reactions 818 Cyclizations via Aldol Condensations 823 Lithium Enolates 825

Chapter 17 Carboxylic Acids and Their Derivatives. Nucleophilic Addition Elimination at the Acyl Carbon 845
17.1 17.2 17.3 17.4 17.5 17.6 17.7 17.8 17.9
L (Molecular graphic: A portion of nylon 6, 6, a polyamide) Introduction 845 Nomenclature and Physical Properties 846 Preparation of Carboxylic Acids 852 Nucleophilic AdditionElimination at the Acyl Carbon 855 Acyl Chlorides 857 Carboxylic Acid Anhydrides 859 Esters 860 Amides 866 Derivatives of Carbonic Acid 872

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17.10 17.11 17.12 17.13

Decarboxylation of Carboxylic Acids 875 Chemical Tests for Acyl Compounds 878 The Hunsdiecker Reaction 881 Step-Growth Polymers 881

Chapter 18 Amines 902

(Molecular graphic: Histrionicatoxin, a paralyzing neurotoxin from certain poison dart frogs) 18.1 Nomenclature 902 18.2 Physical Properties and Structure of Amines 904 18.3 Basicity of Amines: Amine Salts 905 18.4 Preparation of Amines 911 18.5 Reactions of Amines 919 18.6 Reactions of Amines with Nitrous Acid 920 18.7 Replacement Reactions of Arenediazonium Salts 923 18.8 Coupling Reactions of Arenediazonium Salts 926 18.9 Reactions of Amines with Sulfonyl Chlorides 928 18.10 The Sulfa Drugs: Sulfanilamide 930 18.11 Eliminations Involving Ammonium Compounds 930

Chapter 19 Phenols and Aryl Halides: Nucleophilic Aromatic Substitution 949

19.1 19.2 19.3 19.4 19.5 19.6 19.7 19.8 19.9 19.10 19.11
(Molecular graphic: 4-tert-Butylcalix[4]arene, a chalice-shaped molecule) Structure and Nomenclature of Phenols 949 Naturally Occurring Phenols 950 Physical Properties of Phenols 951 Synthesis of Phenols 952 Reactions of Phenols as Acids 954 Other Reactions of the OH Group of Phenols 957 Cleavage of Alkyl Aryl Ethers 957 Reactions of the Benzene Ring of Phenols 958 The Claisen Rearrangement 960 Quinones 961 Aryl Halides and Nucleophilic Aromatic Substitution 962

Chapter 20 Carbohydrates 978

20.1 20.2 20.3 20.4 20.5 20.6 20.7 20.8 20.9 20.10 20.11 20.12 20.13 20.14 20.15 20.16
(Molelcular graphic: Sialyl Lewis,x a carbohydrate that is important in the recognition and healing of traumatized tissue) Introduction 978 Monosaccharides 981 Mutarotation 986 Glycoside Formation 987 Other Reactions of Monosaccharides 989 Oxidation Reactions of Monosaccharides 993 Reduction of Monosaccharides: Alditols 998 Reactions of Monosaccharides with Phenylhydrazine: Osazones 999 Synthesis and Degradation of Monosaccharides 1000 The D Family of Aldoses 1002 Fischers Proof of the Conguration of D-(1)-Glucose 1002 Disaccharides 1005 Polysaccharides 1008 Other Biologically Important Sugars 1012 Sugars That Contain Nitrogen 1013 Carbohydrate Antibiotics 1014

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Chapter 21 Amino Acids and Proteins 1028

21.1 21.2 21.3 21.4 21.5 21.6
(Molecular graphic: A synthetic Diels-Alderase catalytic antibody with a bound hapten) Introduction 1028 Amino Acids 1029 Synthesis of -Amino Acids 1034 Polypeptides and Proteins 1037 Primary Structure of Polypeptides and Proteins 1039 Secondary, Tertiary, and Quaternary Structures of Proteins 1040

Chapter 22 Carbene and Carbenoids 1049

22.1 22.2 22.3 22.4 22.5 22.6
Introduction 1049 Existence of Carbenes 1049 Formation of Carbenes 1049 Types of Carbenes 1051 Reactions of Carbenes 1052 Rearrangement in Carbenes 1066

Chapter 23 Reaction of Nitrene and Electron Deficient Oxygen 1078

23.1 23.2 23.3 23.4 23.5 23.6 23.7 23.8
Migration to Electron Decient Nitrogen 1078 Nitrene Formation 1078 HofmannCurtiusLossenSchmidt Group of Rearrangements 1079 Curtius Reaction 1080 Schmidt Reaction 1080 Hofmann-Bromamide Reaction or Hofman Rearrangement 1081 Beckmann Rearrangement 1083 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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About the Authors

T. W. Graham Solomons
T. W. Graham Solomons did his undergraduate work at The Citadel and received his doctorate in organic chemistry in 1959 from Duke University where he worked with C. K. Bradsher. Following this he was a Sloan Foundation Postdoctoral Fellow at the University of Rochester where he worked with V. Boekelheide. In 1960 he became a charter member of the faculty of the University of South Florida and became Professor of Chemistry in 1973. In 1992 he was made Professor Emeritus. In 1994 he was a visiting professor with the Facult des Sciences Pharmaceutiques et Biologiques, Universit Ren Descartes (Paris V). He is a member of Sigma Xi, Phi Lambda Upsilon, and Sigma Pi Sigma. He has received research grants from the Research Corporation and the American Chemical Society Petroleum Research Fund. For several years he was director of an NSF-sponsored Undergraduate Research Participation Program at USF. His research interests have been in the areas of heterocyclic chemistry and unusual aromatic compounds. He has published papers in the Journal of the American Chemical Society, the Journal of Organic Chemistry, and the Journal of Heterocyclic Chemistry. He has received several awards for distinguished teaching. His organic chemistry textbooks have been widely used for 20 years and have been translated into French, Japanese, Chinese, Korean, Malaysian, Arabic, Portuguese, Spanish, Turkish, and Italian. He and his wife Judith have a daughter who is a building conservator, a son who is an artist, and another son who is a graduate student studying biochemistry.

Craig Barton Fryhle

Craig Barton Fryhle is Chair and Professor of Chemistry at Pacic Lutheran University. He earned his B.A. degree from Gettysburg College and Ph.D. from Brown University. His experiences at these institutions shaped his dedication to mentoring undergraduate students in chemistry and the liberal arts, which is a passion that burns strongly for him. His research interests have been in areas relating to the shikimic acid pathway, including molecular modeling and NMR spectrometry of substrates and analogues, as well as structure and reactivity studies of shikimate pathway enzymes using isotopic labeling and mass spectrometry. He has mentored many students in undergraduate research, a number of whom have later earned their Ph.D. degrees and gone on to academic or industrial positions. He has participated in workshops on fostering undergraduate participation in research, and has been an invited participant in efforts by the National Science Foundation to enhance undergraduate research in chemistry. He has received research and instrumentation grants from the National Science Foundation, the M J. Murdock Charitable Trust, and other private foundations. His work in chemical education, in addition to textbook co-authorship, involves incorporation of student-led teaching in the classroom and technology-based strategies in organic chemistry. He has also developed experiments for undergraduate students in organic laboratory and instrumental analysis courses. He has been a volunteer with the hands-on science program in Seattle public schools, and Chair of the Puget Sound Section of the American Chemical Society. He lives in Seattle with his wife and two daughters.

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To the Student
Contrary to what you may have heard, organic chemisty does not have to be a difcult course. It will be a rigorous course, and it will offer a challenge. But you will learn more in it than in almost any course you will takeand what you learn will have a special relevance to life and the world around you. However, because organic chemistry can be approached in a logical and systematic way, you will nd that with the right study habits, mastering organic chemistry can be 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 that has gone before. It is essential, therefore, that you keep up with, or better yet, be a little ahead of your instructor. Ideally, you should try to stay one day ahead of your instructors lectures in your own class preparations. The lecture, then, will be much more helpful because you will already have some understanding of the assigned material. 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 section before you go on to the next. Again, because of the cumulative nature of organic chemistry, your studying will be much more effective if you take each new idea as it comes 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 progress is to work each of the in-chapter problems when you come to it. These problems have been written just for this purpose and are designed to help you decide whether or not you understand the material that has just been explained. If you can work the in-chapter problem, then you should go on; if you cannot, then you should go back and study the preceding material again. Work all of the problems assigned by your instructor from the end of the chapter, as well. Do all of your problems in a notebook and bring this 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 and over again. Organic chemistry is best assimilated through the ngertips by writing, and not through the eyes by simply looking, or by highlighting material in the text, or by referring to ash cards. There is a good reason for this. Organic structures, mechanisms, and reactions are complex. If you simply examine them, you may think you understand them thoroughly, but that will be a misperception. The reaction mechanism may make sense to you in a certain way, but you need a deeper understanding than this. You need to know the material so thoroughly that you can explain it to someone else. This level of understanding comes to most of us (those of us without photographic memories) through writing. Only by writing the reaction mechanisms do we pay sufcient attention to their details, such as which atoms are connected to which atoms, which bonds break in 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 provide the long-term memory needed for success in organic chemistry. We virtually guarantee that your grade in the course will be directly proportional to the number of pages of paper that your ll with your own writing in studying during the term. 5. Learn by teaching and explaining. Study with your student peers and practice explaining concepts and mechanisms to each other. Use exercises your instructor may assign as vehicles for teaching and learning interactively with your peers.