Contents xix ◆-KEY MECHANISM BOXES CHAPTER 4 Free-Radical Halogenation 130 CHAPTER 6 The S.2 Reac The SN1 Reaction The E1 Reaction 255 The E2 Reactior 262 CHAPTER7 Acid-Catalyzed Dehydration of an Alcchol 309 CHAPTER 8 Electrophilic Addition to Alkenes 324 CHAPTER 10 Grignard Reactions 439 CHAPTER 11 The Williamson Ether Synthesis 497 CHAPTER 15 The Diels-Alder Reaction 682 CHAPTER 17 Electrophilic Aromatic Substitution 752 CHAPTER 18 Nucleophilic Additions to Carbonyl Groups 833 ation of Imines 812 ation of Acetals 848 CHAPTER 20 Fischer Esterification 91 CHAPTER 21 CHAPTER 22 Base-Catalyzed Aldol Condensatic 1058 a Dehydr Aldol 1061 MECHANISM BOXES CHAPTER 6 Allylic Bromination 225 Inversion of Configuration in the SN2 Reaction 241 Racemization in the s1 reaction 248 Hydride Shift in an SN1 Reaction 250 Methyl shift in an sv1 Reaction 251 ction 258 CHAPTER 7 E2 De CHAPTER 8 lonic Addition of HX to an Alkene 327 Free-Radical Addition of HBr to Alkenes 329 Acid-Catalyzed Hydration of an Alkene 333 Oxymercuration of an Alkene 335 atonof6085oAkeneS345 Hydroboration of an alkene 340 Addition of Hald For hydrins 347 Epoxidation of Alkenes 356 Acid-Catalyzed Opening of Epoxides 357 Olefin Metathesis 372 CHAPTER 9 Metal-Ammonia Reduction of an Alkyre 404 Acid-Catalyzed Keto-Enol Tautomerism 408 Base-Catalyzed Keto-Enol Tautomerism 410
CHAPTER 4 Free-Radical Halogenation 130 CHAPTER 6 The SN2 Reaction 230 The SN 1 Reaction 244 The E1 Reaction 255 The E2 Reaction 262 CHAPTER 7 Acid-Catalyzed Dehydration of an Alcohol 309 CHAPTER 8 Electrophilic Addition to Alkenes 324 CHAPTER 10 Grignard Reactions 439 CHAPTER 11 The Williamson Ether Synthesis 497 CHAPTER 15 The Diels-Aider Reaction 682 CHAPTER 17 Electrophilic Aromatic Substitution 752 CHAPTER 18 Nucleophilic Additions to Carbonyl Groups 833 Formation of lmines 842 Formation of Acetals 848 CHAPTER 20 Fischer Esterification 961 CHAPTER 21 Addition-Elimination Mechanism of Nucleophilic Acyl Substitution 997 CHAPTER 22 Base-Catalyzed Aldol Condensation 1058 Base-Catalyzed Dehydration of an Aldol 1061 The Claisen Ester Condensation 1068 CHAPTER 6 Allylic Bromination 225 Inversion of Configuration in the SN2 Reaction 241 Racemization in the SN1 Reaction 248 Hydride Shift in an SN1 Reaction 250 Methyl Shift in an SN1 Reaction 251 Rearrangement in an E1 Reaction 258 CHAPTER 7 Dehydrohalogenation by the E2 Mechanism 300 Stereochemistry of the E2 Reaction 302 E2 Debromination of a Vicinal Dibromide 306 CHAPTER 8 Ionic Addition of HX to an Alkene 327 Free-Radical Addition of HBr to Alkenes 329 Acid-Catalyzed Hydration of an Alkene 333 Oxymercuration of an Alkene 335 Hydroboration of an Alkene 340 Addition of Halogens to Alkenes 345 Formation of Halohydrins 347 Epoxidation of Alkenes 356 Acid-Catalyzed Opening of Epoxides 357 Olefin Metathesis 372 CHAPTER 9 Metal-Ammonia Reduction of an Alkyne 404 Acid-Catalyzed Keto-Enol Tautomerism 408 Base-Catalyzed Keto-Enol Tautomerism 410 Contents xix
Contents CHAPTER 10 Hydride Reduction of a Carbonyl Group 450 CHAPTER 11 Reaction of a Tertiary Alcohol with HBr(SN1)477 r Alcohol with HBr (S.2)477 Reaction ohols with PB 48 (Review):Acid-Catalyzed Dehydration of an Alcohol 484 The Pinacol Rearrangement 491 CHAPTER 14 Cleavage of an Ether by HBr or HI 639 Acid-Catalyzed Opening of Epoxides in Water 648 Acid-Catalyzed Opening of an Epoxide in an Alcohol Solution 649 Base-Catalyzed Opening of Epoxides 651 CHAPTER 15 1,2-and 1,4-Addition to a Conjugated Diene 673 Free-Radical Allylic Bromination 676 CHAPTER 17 Bro Nitmiontion of Benzengse nzene 757 Friedel Crafts Alkylation 774 Friedel-Crafts Acylation 778 (Benzyne M The Birch Reduction 788 CHAPTER 18 The Wittig Reaction 836 Hydration of Ketones and Aldehydes 839 Formation of Cyanohvdrins 840 Wolff-Kishner Reduction 857 ution of Pyridin e893 Acylation of an Amine by an Acid Chloride 895 Hofmann Elimination 899 The Cope Elimination of an Amine Oxide 903 Diazolization of an Amine 904 The Hofmann Rearrangement of Amides 921 CHAPTER 20 Nucleophilic Acyl Substitution in the Basic Hydrolysis of an Ester 959 Esterification Using Diazomethane 964 CHAPTER 21 Conversion of an Acid Chloride to an Anhydride 1000 Conversion of an Acid Chloride to an Ester 1000 n of an Acid Chloride an Am nide 1001 Conversion of an Acid Anhydride to an Este 100 Conversion of an Acid Anhydride to an Amid Convers 1007 ion of an Ester 1009 Basic Hydrolysis of an Amide 101 Acidic Hydrolysis of an Amide 1011
xx Contents CHAPTER 10 Hydride Reduction of a Carbonyl Group 450 CHAPTER 11 Reaction of a Tertiary Alcohol with HBr (SN1) 477 Reaction of a Primary Alcohol with HBr (SN2) 477 Reaction of Alcohols with PBr3 481 (Review): Acid-Catalyzed Dehydration of an Alcohol 484 The Pinacol Rearrangement 491 CHAPTER 14 Cleavage of an Ether by HBr or HI 639 Acid-Catalyzed Opening of Epoxides in Water 648 Acid-Catalyzed Opening of an Epoxide in an Alcohol Solution 649 Base-Catalyzed Opening of Epoxides 651 CHAPTER 15 1,2- and 1 ,4-Addition to a Conjugated Diene 673 Free-Radical Allylic Bromination 676 CHAPTER 17 Bromination of Benzene 753 Nitration of Benzene 756 Sulfonation of Benzene 757 Friedei-Crafts Alkylation 774 Friedei-Crafts Acylation 778 Nucleophilic Aromatic Substitution (Addition-Elimination) 783 Nucleophilic Aromatic Substitution (Benzyne Mechanism) 786 The Birch Reduction 788 CHAPTER 18 The Wittig Reaction 836 Hydration of Ketones and Aldehydes 839 Formation of Cyanohydrins 840 Wolff-Kishner Reduction 857 CHAPTER 19 Electrophilic Aromatic Substitution of Pyridine 892 Nucleophilic Aromatic Substitution of Pyridine 893 Acylation of an Amine by an Acid Chloride 895 Hofmann Elimination 899 The Cope Elimination of an Amine Oxide 903 Diazotization of an Amine 904 The Hofmann Rearrangement of Amides 921 CHAPTER 20 Nucleophilic Acyl Substitution in the Basic Hydrolysis of an Ester 959 Esterification Using Diazomethane 964 CHAPTER 21 Conversion of an Acid Chloride to an Anhydride 1000 Conversion of an Acid Chloride to an Ester 1000 Conversion of an Acid Chloride to an Amide 1001 Conversion of an Acid Anhydride to an Ester 1001 Conversion of an Acid Anhydride to an Amide 1002 Conversion of an Ester to an Amide (Ammonolysis of an Ester) 1002 Transesterification 1007 Saponification of an Ester 1009 Basic Hydrolysis of an Amide 1011 Acidic Hydrolysis of an Amide 1011
Contents xxi r1013 CHAPTER nsatio 1044 Enolate on n Ester atalyzed Ket -Ep Base-Promoted Halogenatior 1052 Final Steps of the Haloform Reaction 1054 Acid-Catalyzed Alpha Halogenation 1055 Acid-Catalyzed Aldol Condensation 1060 1,2-Addition and 1,4-Addition(Conjugate Addition)1082 CHAPTER 23 Formation of a Cyclic Hemiacetal 1104 Base-Catalyzed Epimerization of Glucose 1111 Base-Catalyzed Enediol Rearrangement 1111 CHAPTER 2 Free-Radical Polym 1225 ationic Polymerizatic 1226 Anionic Polymerization 122
Base-Catalyzed Hydrolysis of a Nitrile 1012 Hydride Reduction of an Ester 1013 Reduction of an Amide to an Amine 1014 Reaction of an Ester with Two Moles of a Grignard Reagent 1016 CHAPTER 22 Alpha Substitution 1043 Addition of an Enolate to Ketones and Aldehydes (a Condensation) 1 044 Substitution of an Enolate on an Ester (a Condensation) 1044 Base-Catalyzed Keto-Enol Tautomerism 1044 Acid-Catalyzed Keto-Enol Tautomerism 1045 Base-Promoted Halogenation 1 052 Final Steps of the Haloform Reaction 1054 Acid-Catalyzed Alpha Halogenation 1055 Acid-Catalyzed Aldol Condensation 1060 1 ,2-Addition and 1 ,4-Addition (Conjugate Addition) 1082 CHAPTER 23 Formation of a Cyclic Hemiacetal 1104 Base-Catalyzed Epimerization of Glucose 1111 Base-Catalyzed Enediol Rearrangement 1111 CHAPTER 26 Free-Radical Polymerization 1225 Cationic Polymerization 1226 Anionic Polymerization 1228 Contents xxi
Contents PREFACE To the Student As you begin your study of organic chemistry.you might feel overwhelmed by the num ber of compounds names. n you.You migh istry consists of a few basic principles and many extensions and applications of these develop fle tions and mechanisms in this book.but I can work them out by rememberinga few basic principlessuchdehydrations ygo by EI mechanism you n the workin have to when I made a D on my se like general chemistry,where I could memorize a couple of equations and fake my the exams.For example,in the ideal gas chapter,I 7.an aD.We s good to In writing this book.I've tried to point out a small number of impo tant facts and principles that should be learned to prepare for solving problems.For example,of the hundreds of reaction me shown in this book. ut 20 are the fundamenta importance.Spectroscopy is another area where a student might feel pressured to mem. orize hundreds of facts.such as NMR chemical shifts and infrared vibration frequer t do out a dozen r Tahea e mpo NMR chemic T1 I've listed thos frequencies ave to youway don'think (like know what nyou can apply th ccures.and.The tel you whether or not you know you can do the problems,you should do well on the exams.If you can't o the problems. you pro oly won f you keep hav ng t 1.Read the material in the book before the lecture (expect 13-15 pages per lecture) ing the lecture t lecture you al od you notes,then if available
xxii Contents PREFACE xxii To the Student As you begin your study of organic chemistry, you might feel overwhelmed by the number of compounds, names, reactions, and mechanisms that confront you. You might even wonder whether you can learn all this material in a single year. The most important function of a textbook is to organize the material to show that most of organic chemistry consists of a few basic principles and many extensions and applications of these principles. Relatively little memorization is required if you grasp the major concepts and develop flexibility in applying those concepts. Frankly, I have a poor memory, and I hate memorizing lists of information. I don't remember the specifics of most of the reactions and mechanisms in this book, but I can work them out by remembering a few basic principles, such as "alcohol dehydrations usually go by El mechanisms." Still, you'll have to learn some facts and fundamental principles to serve as the working "vocabulary" of each chapter. As a student, I learned this the hard way when I made a D on my second organic chemistry exam. I thought organic would be like general chemistry, where I could memorize a couple of equations and fake my way through the exams. For example, in the ideal gas chapter, I would memorize PV = nRT, and I was good to go. When I tried the same approach in organic, I got a D. We learn by making mistakes, and I learned a lot in organic chemistry. In writing this book, I've tried to point out a small number of important facts and principles that should be learned to prepare for solving problems. For example, of the hundreds of reaction mechanisms shown in this book, about 20 are the fundamental mechanistic steps that combine into the longer, more complicated mechanisms. I've highlighted these fundamental mechanisms in Key Mechanism boxes to alert you to their importance. Spectroscopy is another area where a student might feel pressured to memorize hundreds of facts, such as NMR chemical shifts and infrared vibration frequencies. I couldn't do that, so I've always gotten by with knowing about a dozen NMR chemical shifts and about a dozen IR vibration frequencies, and knowing how they are affected by other influences. I've listed those important infrared frequencies in Table 12-2 and the important NMR chemical shifts in Table 13-3. Don't try to memorize your way through this course. It doesn't work; you have to know what's going on so you can apply the material. Also, don't think (like I did) that you can get by without memorizing anything. Read the chapter, listen carefully to the lectures, and work the problems. The problems will tell you whether or not you know the material. If you can do the problems, you should do well on the exams. If you can't do the problems, you probably won't be able to do the exams, either. If you keep having to look up an item to do the problems, that item is a good one to learn. Here are some hints I give my students at the beginning of the course: 1. Read the material in the book before the lecture (expect 13-15 pages per lecture). Knowing what to expect and what is in the book, you can take fewer notes and spend more time listening and understanding the lecture. 2. After the lecture, review your notes and the book, and do the in-chapter problems. Also, read the material for the next lecture. 3. If you are confused about something, visit your instructor during office hours immediately, before you fall behind. Bring your attempted solutions to problems with you to show the instructor where you are having trouble. 4. To study for an exam, begin by reviewing each chapter and your notes, then concentrate on the end-of-chapter problems. Also use old exams for practice, if available
Preface xxii Remember the two"golden rules"of organic chemistry 1.Don't Get Behind!The course moves too fast.and it's hard to catch up. 2.Work Lots of Problems.Everyone needs the practice,and the problems show where you need more work I am always interested to hear from students using this book.if you have an suggestions about how the book might be made better.or if you've found an error 心mc wadelg sbook.Fo 20n0 University of Minnesota student (and race-car driver)Jim Coleman gave me the facts or the use of methanol at Indianapolis. Good luck with your study of chemistry.I'm cerain you will enjoy this cess a little easier:to build the concepts log yonopoteachohes0they have helped my one to the next.The hints and ugproplem solving e past,and I e some o f them p you to lear good learning experience for all of us. .G.Wade,Jr WallaWalla,Washingto wadelg@whitman.edu To the Instructor In writing the first edition of this text.my goal was to produce a moder.readable text at goa ting and reorganiz on and Thi ments than the sixth.with revisions in the organization.writing.and graphics.Some of the modifications made in the most recent editions are: 1.Mechanism Boxes. seventhdition.these boxes have been refned to make heindividul stepsce to students.I've tried to choose most of the standard mechanisms that nearly that that should not be boxed.please let me know what you think. In choosing the Key Mechanisms,I've used two major criteria.If the mechanism is one of the fundamental me amples ar nuceolie addition to arbonls and so on.The otherriterion is more subie tive.If the mechanism is one of the ones I routinely expect students to do on amples are formation of In tha sisth and reeivedtpdted Examples are bond-dissociation enthalpy to replace the more ambiguous bond dissociation energy and the newer transliteration Zaitsey to replace the older
Remember the two "golden rules" of organic chemistry. 1. Don't Get Behind! The course moves too fast, and it's hard to catch up. 2. Work Lots of Problems. Everyone needs the practice, and the problems show where you need more work. I am always interested to hear from students using this book. If you have any suggestions about how the book might be made better, or if you've found an error, please let me know (L. G. Wade, Whitman College, Walla Walla, WA 99362: E-mail wadelg@whitman.edu). I take students' suggestions seriously, and hundreds of them now appear in this book. For example, Whitman student Brian Lian suggested Figure 21-9, and University of Minnesota student (and race-car driver) Jim Coleman gave me the facts on the use of methanol at Indianapolis. Good luck with your study of organic chemistry. I'm certain you will enjoy this course, especially if you let yourself relax and develop an interest in how organic compounds influence our lives. My goal in writing this book has been to make the process a little easier: to build the concepts logically on top of each other, so they flow naturally from one to the next. The hints and suggestions for problem solving have helped my students in the past, and I hope some of them will help you to learn and use the material. Even if your memory is worse than mine (highly unlikely), you should be able to do well in organic chemistry. I hope this will be a good learning experience for all of us. To the Instructor L. G. Wade, Jr. Walla Walla, Washington wadelg@ whitman.edu In writing the first edition of this text, my goal was to produce a modern, readable text that uses the most effective techniques of presentation and review. Subsequent editions extended and refined that goal, with substantial rewriting and reorganization and with the addition of several new features. This seventh edition incorporates even more refinements than the sixth, with revisions in the organization, writing, and graphics. Some of the modifications made in the most recent editions are: 1. Mechanism Boxes. About 100 of the most important mechanisms have been organized into mechanism boxes, with large blue headings for easy review. In this seventh edition, these boxes have been refined to make the individual steps clearer to students. I've tried to choose most of the standard mechanisms that nearly everyone teaches; yet, in some cases, it seems that other mechanisms would be good candidates. If there are additional mechanisms that should be boxed, or some that should not be boxed, please let me know what you think. In choosing the Key Mechanisms, I've used two major criteria. If the mechanism is one of the fundamental mechanisms that make up the longer, more complex mechanisms, then it must be a Key Mechanism. Examples are SN1, SN2, E1 , E2, nucleophilic acyl substitution, electrophilic aromatic substitution, nucleophilic addition to carbonyls, and so on. The other criterion is more subjective. If the mechanism is one of the ones I routinely expect students to do on exams, then it is a Key Mechanism. Examples are formation of imines and acetals, aldol and Claisen condensations, and so on. If you feel I have left one out or included one that should not be a Key Mechanism, please let me know. 2. Updated Coverage. In the sixth and seventh editions, I've updated several terms to those that have gradually received acceptance among organic chemists. Examples are bond-dissociation enthalpy to replace the more ambiguous bonddissociation energy and the newer transliteration Zaitsev to replace the older Saytzeff. Preface xxiii