xxii Contents MECHANISM BOXES (otinued) CHAPTER 10 Hydride Reduction of a Carbonyl Group 454 CHAPTER 11 with HBr w1)480 Reaction of a Primary Ald ol with HBr (SN2)480 Reaction of Alcohols with PBr3 485 (Review):Acid-Catalyzed Dehydration of an Alcohol 487 The Pinacol Rearrangement 495 CHAPTER 14 Cleavage of an Ether by HBr or HI 639 Acid-Catalyzed Opening of Epoxides in Water 649 SSCi8nauOpenmngofanEpocdenanAucohal Acid-Catal Base-Catalyzed Openina of Epoxides 653 CHAPTER 15 1.2-and 1,4-Addition to a Conjugated Diene 675 678 CHAPTER 17 Sulfonation of Benzene 762 Friedel-Crafts Alkylation 778 Friedel-Crafts Acylation 782 Nucleophilic Aromatic Substitution (Addition-Elimination)787 Nucleophilic Aromatic Substitution (Benzyne Mechanism)789 The Birch Reduction 79 CHAPTER 18 The Wittig Reaction 844 Hydration of Ketones and Aldehydes 847 Formation of Cyanohydrins 849 Wolff-Kishner Reduction 864 CHAPTER 19 Electrophilic Aromatic Substitution of Pyridine 897 ridine 899 Acid Chloride 901 The Cope Elimination of an Amine Oxide 908 Diazotization of an Amine 910 CHAPTER 20 Nucleophilic Acyl Substitution in the Basic Hydrolysis of an Ester 960 Esterification Using Diazomethane 966 CHAPTER 21 Conversion of an Acid Chloride to an Anhydride 1001 Conversion of an Acid Chloride to an Ester 1001 Conversion of an Acid Chloride to an Amide 1002 Conversion of an Acid Anhydride to an Ester 1002 Conversion of an Acid Anhydride to an Amide 1003 of an Est Transesterification 1008 Saponification of an Ester 1010 sic Hydrolysis of an mide 1012 Acidic Hydrolysis of an Amide 1012
xxii Contents MECHANISM BOXES (continued) CHAPTER 10 Hydride Reduction of a Carbonyl Group 454 CHAPTER 11 Reaction of a Tertiary Alcohol with HBr (SN1) 480 Reaction of a Primary Alcohol with HBr (SN2) 480 Reaction of Alcohols with PBr3 485 (Review): Acid-Catalyzed Dehydration of an Alcohol 487 The Pinacol Rearrangement 495 CHAPTER 14 Cleavage of an Ether by HBr or HI 639 Acid-Catalyzed Opening of Epoxides in Water 649 Acid-Catalyzed Opening of an Epoxide in an Alcohol Solution 650 Base-Catalyzed Opening of Epoxides 653 CHAPTER 15 1,2- and 1,4-Addition to a Conjugated Diene 675 Free-Radical Allylic Bromination 678 CHAPTER 17 Bromination of Benzene 758 Nitration of Benzene 760 Sulfonation of Benzene 762 Friedel–Crafts Alkylation 778 Friedel–Crafts Acylation 782 Nucleophilic Aromatic Substitution (Addition–Elimination) 787 Nucleophilic Aromatic Substitution (Benzyne Mechanism) 789 The Birch Reduction 797 CHAPTER 18 The Wittig Reaction 844 Hydration of Ketones and Aldehydes 847 Formation of Cyanohydrins 849 Wolff–Kishner Reduction 864 CHAPTER 19 Electrophilic Aromatic Substitution of Pyridine 897 Nucleophilic Aromatic Substitution of Pyridine 899 Acylation of an Amine by an Acid Chloride 901 Hofmann Elimination 904 The Cope Elimination of an Amine Oxide 908 Diazotization of an Amine 910 CHAPTER 20 Nucleophilic Acyl Substitution in the Basic Hydrolysis of an Ester 960 Esterification Using Diazomethane 966 CHAPTER 21 Conversion of an Acid Chloride to an Anhydride 1001 Conversion of an Acid Chloride to an Ester 1001 Conversion of an Acid Chloride to an Amide 1002 Conversion of an Acid Anhydride to an Ester 1002 Conversion of an Acid Anhydride to an Amide 1003 Conversion of an Ester to an Amide (Ammonolysis of an Ester) 1003 Transesterification 1008 Saponification of an Ester 1010 Basic Hydrolysis of an Amide 1012 Acidic Hydrolysis of an Amide 1012
Contents xxiii MECHANISM BOXES (tined) Base-Catalyzed Hydrolysis of a Nitrile 1014 Hydride Reduction of an Ester 1015 Reduction of an Amide to an Amine 1016 of an Ester with Two Moles of a Grignard Reagent 1018 CHAPTER 22 Alpha Substitution 1045 Additio Substitution of an Enolate on an Ester (a Condensation)1046 Base-Catalyzed Keto-Enol Tautomerism 1047 Acid-Catalyzed Keto-Enol Tautomerism 1047 1054 1056 Acid-c Catalyzed Alpha Halogenation 1058 Acid-Catalyzed Aldol Condensation 1063 CHAPTER 23 Formation of a Cyclic Hemiacetal 1108 Base-Catalyzed Epimerization of Glucose 1115 Base-Catalyzed Enediol Rearrangement 1115 CHAPTER 26 Free-Radical Polymerization 1225 Cationic Polymerization 1226 Anionic Polymerization 1228
Contents xxiii Base-Catalyzed Hydrolysis of a Nitrile 1014 Hydride Reduction of an Ester 1015 Reduction of an Amide to an Amine 1016 Reaction of an Ester with Two Moles of a Grignard Reagent 1018 CHAPTER 22 Alpha Substitution 1045 Addition of an Enolate to Ketones and Aldehydes (a Condensation) 1046 Substitution of an Enolate on an Ester (a Condensation) 1046 Base-Catalyzed Keto–Enol Tautomerism 1047 Acid-Catalyzed Keto–Enol Tautomerism 1047 Base-Promoted Halogenation 1054 Final Steps of the Haloform Reaction 1056 Acid-Catalyzed Alpha Halogenation 1058 Acid-Catalyzed Aldol Condensation 1063 1,2-Addition and 1,4-Addition (Conjugate Addition) 1085 CHAPTER 23 Formation of a Cyclic Hemiacetal 1108 Base-Catalyzed Epimerization of Glucose 1115 Base-Catalyzed Enediol Rearrangement 1115 CHAPTER 26 Free-Radical Polymerization 1225 Cationic Polymerization 1226 Anionic Polymerization 1228 MECHANISM BOXES (continued)
New to this Edition y re re ognized by otecao8bab8moneShoemstnNedisesions organometal to reducing noaicieysdets2canplenidnaamanerthet No standards unifying mechanism that covers the ma 0 ng students make visual Chapter 1). ohols to aldehydes and ketones cusiecnwegngoceig2。nhancngther carbohydr nds is added in added throughout,includinganewsec tion on biochemistry.and medicine. xxiv
New to this Edition Cutting-edge coverage of organometallic reactions and reagents includes the palladium-catalyzed Suzuki and Heck reactions that were recognized by the 2010 Nobel Prize in Chemistry. New discussions of carbon-carbon bond formation, including organometallic reagents in addition to reducing agents like DIBAL-H, are presented in a manner that introductory students can understand. Modern methods of oxidizing alcohols like DessMartin and Swern oxidations are explained by a unifying mechanism that covers the major methods to oxidize alcohols to aldehydes and ketones (Chapter 11). Additional coverage on silyl ethers addresses their use as protecting groups for alcohols and carbohydrates. A new section on colored compounds is added in Chapter 15, including natural and synthetic dyes, and also a new section on biochemical and clinical applications of UV-visible spectroscopy. Chapter Goals (Learning Outcomes) added to each chapter align with the Essential ProblemSolving Skills at the end of each chapter as well as the Study Problems in the text and in MasteringChemistry. Nomenclature has been updated selectively to reflect the latest IUPAC naming convention standards. A new visual format throughout ensures consistency in the art, helping students make visual connections between concepts and enhancing their accurate understanding of the figures. Approximately 100 new problems have been added, both within the chapters and in the Study Problems at the ends of the chapters. New sections and notes of interest to biology majors and premedical students have been added throughout, including a new section on clinical analysis, as well as numerous applications relating to cancer and toxicology, green chemistry, biochemistry, and medicine. xxiv
Preface To the Student As you begin your study of organic chemistry.you might feel overwhelmed by the number 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 e concepts.Frankly,I have a poor memory,and Ihate lists Ican work them out by rememberina few basic principles.such as"ac dehydrations usually go by EI mechanisms." Still.you'll have to learn some facts and fundamental principles to serve as the work ing"vocabulary"of ch chapter.As a student. way when I made a way thro h the exams for nRT.and I was good to go learned a lot in organ e for solving 一phbe eamod to0网 mhmcated echanisisvdh Key Me es to alert you to thei ouln'tdo 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 icalquencies in Table 12-2 and the important It doeen'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 兴edthe chap红he一 work the probi The pr whether o not you kr eria 8dbhepobics.haiemisagodoneo1eam Here are some hints I give my students at the beginning of the course: .Read the 2.After the lecture,review your notes and the book,and do the in-chapter problems.Also,read the material for the next lecture immediately.before you fall behind.Brin your attempted solutions to probems with you to show the instructor where you are having trouble. eam,beeinby ober
xxv Preface 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 E1 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. Many students find that working in a study group and posing problems for each other is particularly helpful. =
xxvi Preface 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 intere sted to hear from students using this book.If you have any ons abou how the book might be made better or if you've found an eo please let me know (LG Wade,Whitman College,Walla Walla,WA 99362:E-mail wadelg@whitman.edu).I take y and hund appea driver)lim Colem fact n the especially if you let yourself relax and develop an interest in how organic comp ounds influ My goal in writing this boc been to make the pro ext.The hin ceped sug op roblem solving have helped my students in the I hope some of them will help you to learn and use the material.Even if your memory is iaepeiohenoaenr To the Instructor organic chem y at the level needed for chemistry and bioche istry maiors but one tha presents and explains the material in ways that facilitate success for all the many different kinds of students who take the course.Subsequent editions have extended and refined thes goals,with substantial rewritingan organizaiomwTmtngaagaphiC ons in NEW TO THIS EDITION In order to help students navigate the material and study more effectively,summarized Chapter Goals have been added to the start of each chapter to reflect the major focus ssential Problen kills they ch cha with the Essential Problem-Solving Skills enable students to identify which in-chapte and end-of-chapter problems will help them master each of the skills.Updated Applications,inclu ding cases relating to cancer and toxicology,green che nistry. has been updated throughout,including the palladium catalyzed Suzuki and Heck reac tions,biochemical and clinical applications of UV-visible spectroscopy,a brief intro and th e use of silyl ethers as a protecting group for alcohols e most up-to ake visu nd a hemistry resour o le. KEY FEATURES Up-to-Date Treatment:In addition to the classical reactions.this book covers many chemists.M tronic effect NMR s tine tool it has he cop laboratories,and the DEPT technique is included in this edition.Many of the newer
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 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. I wanted a book that presents organic chemistry at the level needed for chemistry and biochemistry majors, but one that presents and explains the material in ways that facilitate success for all the many different kinds of students who take the course. Subsequent editions have extended and refined these goals, with substantial rewriting and reorganizing and with many new features. This eighth edition incorporates even more refinements than the seventh edition with revisions in the organization, writing, and graphics. NEW TO THIS EDITION In order to help students navigate the material and study more effectively, summarized Chapter Goals have been added to the start of each chapter to reflect the major focus and breadth of the chapter content. Revised Essential Problem-Solving Skills at the end of each chapter reinforce the Chapter Goals and provide students with a guide to major take-away skills they need from each chapter. New problem references with the Essential Problem-Solving Skills enable students to identify which in-chapter and end-of-chapter problems will help them master each of the skills. Updated Applications, including cases relating to cancer and toxicology, green chemistry, biochemistry, and medicine, now have descriptive titles to help students understand the relevance of an example to what they are learning in the text. Contemporary content has been updated throughout, including the palladium catalyzed Suzuki and Heck reactions, biochemical and clinical applications of UV-visible spectroscopy, a brief introduction to graphene, and the use of silyl ethers as a protecting group for alcohols ensuring that this edition is the most up-to-date organic chemistry resource possible. A revised visual program helps students make visual and accurate connections between concepts and from one figure to the next. KEY FEATURES Up-to-Date Treatment: In addition to the classical reactions, this book covers many techniques and reactions that have more recently gained wide use among practicing chemists. Molecular-orbital theory is included early and used to explain electronic effects in conjugated and aromatic systems, pericyclic reactions, and ultraviolet spectroscopy. Carbon-13 NMR spectroscopy is treated as the routine tool it has become in most research laboratories, and the DEPT technique is included in this edition. Many of the newer xxvi Preface