xvi Contents 25.17 Application:Sulfa Drugs 990 Key Concepts 991 Problems 994 26 Carbon-Carbon Bond-Forming Reactions in Organic Synthesis 1002 26.1 Coupling Reactions of Organocuprate Reagents 1003 26.2 Suzuki Reaction 1005 26.3 Heck Reaction 1009 26.4 Carbenes and Cyclopropane Synthesis 1012 26.5 Simmons-Smith Reaction 1014 26.6 Metathesis 1015 27 Carbohydrates 1027 271 Introduction 1028 附 Monosaccharides 1028 The Family of D-Aldoses 1034 27.4 The Family of D-Ketoses 1035 27.5 Physical Properties of Monosaccharides 1036 27.6 The Cyclic Forms of Monosaccharides 1036 27.7 Glycosides 1042 27.8 Reactions of Monosaccharides at the OH Groups 1046 27.9 Reactions at the Carbonyl Group-Oxidation and Reduction 1047 27.10 React s at the Carbonyl Gr -Adding or Removing One Carbor △t0m104g 27.11 The Fischer Proof of the Structure of Glucose 1053 2712 Disaccharides 1056 28 Amino Acids and Proteins 1074 28.1 Amino Acids 1075 28.2 Synthesis of Amino Acids 1078 28.3 Separation of Amino Acids 1081 28.4 Enantioselective Synthesis of Amino Acids 1085 28.5 Peptides 1086 28.6 Peptide Sequencing 1090 28.7 28 Peptid Synthesi 1094 nthesis 1099
xvi Contents 25.17 Application: Sulfa Drugs 990 Key Concepts 991 Problems 994 26 Carbon–Carbon Bond-Forming Reactions in Organic Synthesis 1002 26.1 Coupling Reactions of Organocuprate Reagents 1003 26.2 Suzuki Reaction 1005 26.3 Heck Reaction 1009 26.4 Carbenes and Cyclopropane Synthesis 1012 26.5 Simmons–Smith Reaction 1014 26.6 Metathesis 1015 Key Concepts 1020 Problems 1021 27 Carbohydrates 1027 27.1 Introduction 1028 27.2 Monosaccharides 1028 27.3 The Family of D-Aldoses 1034 27.4 The Family of D-Ketoses 1035 27.5 Physical Properties of Monosaccharides 1036 27.6 The Cyclic Forms of Monosaccharides 1036 27.7 Glycosides 1042 27.8 Reactions of Monosaccharides at the OH Groups 1046 27.9 Reactions at the Carbonyl Group—Oxidation and Reduction 1047 27.10 Reactions at the Carbonyl Group—Adding or Removing One Carbon Atom 1049 27.11 The Fischer Proof of the Structure of Glucose 1053 27.12 Disaccharides 1056 27.13 Polysaccharides 1059 27.14 Other Important Sugars and Their Derivatives 1061 Key Concepts 1066 Problems 1068 28 Amino Acids and Proteins 1074 28.1 Amino Acids 1075 28.2 Synthesis of Amino Acids 1078 28.3 Separation of Amino Acids 1081 28.4 Enantioselective Synthesis of Amino Acids 1085 28.5 Peptides 1086 28.6 Peptide Sequencing 1090 28.7 Peptide Synthesis 1094 28.8 Automated Peptide Synthesis 1099 28.9 Protein Structure 1101 smi75625_fm_00i-xxxiv.indd xvi 11/17/09 11:21:38 AM
Contents 28.10 Important Proteins 1106 29 Lipids 1119 291 Introduction 1120 29.2 Waxes 1121 29.3 Triacylglycerols 1122 29.4 Phospholipids 1126 29.5 Fat-Soluble Vitamins 1128 29.6 Eicosanoids 1129 29.7 Terpenes 1132 29.8 Steroids 1138 1143 30 Synthetic Polymers 1148 30.1 Introduction 1149 30.2 Chain-Growth Polymers-Addition Polymers 1150 30.3 Anionic Polymerization of Epoxides 1156 30.4 Ziegler-Natta Catalysts and Polymer Stereochemistry 1157 30.5 Natural and Synthetic Rubbers 1159 30.6 Step-Growth Polymers-Condensation Polymers 1160 30.7 Polymer Structure and Properties 1164 30.8 Green Polymer Synthesis 1166 30.9 Polymer Recycling and Disposal 1169 172 13 Appendix A pK,Values for Selected Compounds A-1 Appendix B Nomenclature A-3 Appendix C Bond Dissociation Energies for Some Common Bonds A-7 Appendix D Reactions that Form Carbon-Carbon Bonds A-9 AppendixE Characteristic IR Absorption Frequencies A-10 Appendix F Characteristic NMR Absorptions A-11 Appendix G General Types of Organic Reactions A-13 Appendix H How to Synthesize Particular Functional Groups A-15 Glossary G-1 Credits C-1 Index 1-1
Contents xvii 28.10 Important Proteins 1106 Key Concepts 1111 Problems 1113 29 Lipids 1119 29.1 Introduction 1120 29.2 Waxes 1121 29.3 Triacylglycerols 1122 29.4 Phospholipids 1126 29.5 Fat-Soluble Vitamins 1128 29.6 Eicosanoids 1129 29.7 Terpenes 1132 29.8 Steroids 1138 Key Concepts 1143 Problems 1144 30 Synthetic Polymers 1148 30.1 Introduction 1149 30.2 Chain-Growth Polymers—Addition Polymers 1150 30.3 Anionic Polymerization of Epoxides 1156 30.4 Ziegler–Natta Catalysts and Polymer Stereochemistry 1157 30.5 Natural and Synthetic Rubbers 1159 30.6 Step-Growth Polymers—Condensation Polymers 1160 30.7 Polymer Structure and Properties 1164 30.8 Green Polymer Synthesis 1166 30.9 Polymer Recycling and Disposal 1169 Key Concepts 1172 Problems 1173 Appendix A pKa Values for Selected Compounds A-1 Appendix B Nomenclature A-3 Appendix C Bond Dissociation Energies for Some Common Bonds A-7 Appendix D Reactions that Form Carbon–Carbon Bonds A-9 Appendix E Characteristic IR Absorption Frequencies A-10 Appendix F Characteristic NMR Absorptions A-11 Appendix G General Types of Organic Reactions A-13 Appendix H How to Synthesize Particular Functional Groups A-15 Glossary G-1 Credits C-1 Index I-1 smi75625_fm_00i-xxxiv.indd xvii 11/17/09 11:21:40 AM
Preface notes and handouts that were developed in my own organic chemistry courses over my 30-vea teaching career.I have followed two guiding principles:use relevant and interesting applications chemical phenomena.and present the material in a student-friendly fashion using is my attemnt to simnlify and clarify e that intimid、 chemistry interesting.relevant,and accessible to all students,both chemistry majors and those interested in pursuing careers in biology.medicine,and other disciplines,without sacrificing the rigor they need to be successful in the future The Basic Features .Style This text is differen -by design.Today's students rely more heavily on visual of organic chemistry Content Organic Chemistry accents basic themes in an effort to keep memorization at a nt exa Sample problems are used as a tool to illustrate stepwise problem solving.Exceptions to the 上oeo Organic Chemistry donal groups with different functional groups undergo.not on the are them.Moreover similar reactions are grouped together so that parallels can be emphasized.These include acid-base reactions (Chapter 2 oxidation and red action (Chapters 12 and 20),radica reactions (Chapter 15),and reactions of organometallic reagents(Chapter 20) By introducin one new concept at a time.keeping the basic themes in focu and breaking plex problems down into small pieces.I have found that many students find organic chemistry an intense but learable subject.Many,in fact,end the year-long course surprised that they have actually enjoyed their organic chemistry experience. Organization and Presentation For the most part,the overall order of topics in the text is consistent with the way most instru to make them ate be een in the following areas Review material Chapter 1 presents a healthy dose of review material covering Lewis ar geometry and hy ization,bond polarity.and types of bonding here from an organic chemist's perspective.I have found that giving students a firm g Acids and h es Chapter 2 on acids and 1 bases serves two purposes It gives student nusing some this case an acid-base reaction.Since many mechanisms involve one or more acid bas reactions.I emphasize proton transfer reactions early and come back to this topic often throughout the text
Preface My goal in writing Organic Chemistry was to create a text that showed students the beauty and logic of organic chemistry by giving them a book that they would use. This text is based on lecture notes and handouts that were developed in my own organic chemistry courses over my 30-year teaching career. I have followed two guiding principles: use relevant and interesting applications to illustrate chemical phenomena, and present the material in a student-friendly fashion using bulleted lists, solved problems, and extensive illustrations and summaries. Organic Chemistry is my attempt to simplify and clarify a course that intimidates many students—to make organic chemistry interesting, relevant, and accessible to all students, both chemistry majors and those interested in pursuing careers in biology, medicine, and other disciplines, without sacrifi cing the rigor they need to be successful in the future. The Basic Features • Style This text is different—by design. Today’s students rely more heavily on visual imagery to learn than ever before. The text uses less prose and more diagrams, equations, tables, and bulleted summaries to introduce and reinforce the major concepts and themes of organic chemistry. • Content Organic Chemistry accents basic themes in an effort to keep memorization at a minimum. Relevant examples from everyday life are used to illustrate concepts, and this material is integrated throughout the chapter rather than confi ned to a boxed reading. Each topic is broken down into small chunks of information that are more manageable and easily learned. Sample problems are used as a tool to illustrate stepwise problem solving. Exceptions to the rule and older, less useful reactions are omitted to focus attention on the basic themes. • Organization Organic Chemistry uses functional groups as the framework within which chemical reactions are discussed. Thus, the emphasis is placed on the reactions that different functional groups undergo, not on the reactions that prepare them. Moreover, similar reactions are grouped together so that parallels can be emphasized. These include acid–base reactions (Chapter 2), oxidation and reduction (Chapters 12 and 20), radical reactions (Chapter 15), and reactions of organometallic reagents (Chapter 20). By introducing one new concept at a time, keeping the basic themes in focus, and breaking complex problems down into small pieces, I have found that many students fi nd organic chemistry an intense but learnable subject. Many, in fact, end the year-long course surprised that they have actually enjoyed their organic chemistry experience. Organization and Presentation For the most part, the overall order of topics in the text is consistent with the way most instructors currently teach organic chemistry. There are, however, some important differences in the way topics are presented to make the material logical and more accessible. This can especially be seen in the following areas. • Review material Chapter 1 presents a healthy dose of review material covering Lewis structures, molecular geometry and hybridization, bond polarity, and types of bonding. While many of these topics are covered in general chemistry courses, they are presented here from an organic chemist’s perspective. I have found that giving students a fi rm grasp of these fundamental concepts helps tremendously in their understanding of later material. • Acids and bases Chapter 2 on acids and bases serves two purposes. It gives students experience with curved arrow notation using some familiar proton transfer reactions. It also illustrates how some fundamental concepts in organic structure affect a reaction, in this case an acid–base reaction. Since many mechanisms involve one or more acid–base reactions, I emphasize proton transfer reactions early and come back to this topic often throughout the text. xviii smi75625_fm_00i-xxxiv.indd xviii 11/17/09 11:21:42 AM
Preface xix .Functional groups Chapter 3 uses the functional groups to introduce important prop ties of oane cocy practical topics that reome out of time)are introduced early so that students can better grasp why they are studying the discipline. Stereochemistry Stereochemistry(the three-dime sional structure of molecules)is intro early (Chapter S)and re ent in an organic chemistry text.I have chosen to concentrate on new methods that introduce particular thre ter 28) .Grouping reactions Since certain types of reactions have their own unique characteristics 山心 ve groupe rganometallic reagents (Chapter 20).I have found that focusin on a group of reactions that hare a common theme helps students to better see their similarities. in Chng in augmente is given to the retrosynthetic analysis of compounds prepared byca carbon bond. orming reactions (for example,Sections 20.11 and 21.10C). spectroscopy Since spect scopy is such a po werful ructure determination Key Con End of chant es succinctly summarize the main concepts and themes of the chapter.making them ideal for review prior to working the end-of-chapter problems or taking an exam. New to the Third Edition In response to reviewer feedback,new sections have been added on fragmentation pat 28.6).nad ng in 1g0 scopy (Se Some mechanisms have been modified by adding electron pairs to nucleophiles and leaving groups to more clearly indicate the course of the chemical reaction. Twenty newN spectra have been a ded in Chapters 14-25 to give students addi are written at the intermediate level-more advanced than the easier drill problems,but 山心 ior dsynt has prob ified so students can focus more cl ts in sim the in Newrneorogondngn DNA(Chaper) 2 vera as biological catalysts in Chapter 6 has been redone to use an actual reaction the conver. sion of the lactose in milk to glucose and galactose. New health-related the he ntal applications are d in margin note skin can dryl tha oxy ac alocal anesthetic.rebaudiosideA(trade name Truvia)asweetening aent isolated froma plant source.and many others
• Functional groups Chapter 3 uses the functional groups to introduce important properties of organic chemistry. Relevant examples—PCBs, vitamins, soap, and the cell membrane—illustrate basic solubility concepts. In this way, practical topics that are sometimes found in the last few chapters of an organic chemistry text (and thus often omitted because instructors run out of time) are introduced early so that students can better grasp why they are studying the discipline. • Stereochemistry Stereochemistry (the three-dimensional structure of molecules) is introduced early (Chapter 5) and reinforced often, so students have every opportunity to learn and understand a crucial concept in modern chemical research, drug design, and synthesis. • Modern reactions While there is no shortage of new chemical reactions to present in an organic chemistry text, I have chosen to concentrate on new methods that introduce a particular three-dimensional arrangement in a molecule, so-called asymmetric or enantioselective reactions. Examples include Sharpless epoxidation (Chapter 12), CBS reduction (Chapter 20), and enantioselective synthesis of amino acids (Chapter 28). • Grouping reactions Since certain types of reactions have their own unique characteristics and terminology that make them different from the basic organic reactions, I have grouped these reactions together in individual chapters. These include acid–base reactions (Chapter 2), oxidation and reduction (Chapters 12 and 20), radical reactions (Chapter 15), and reactions of organometallic reagents (Chapter 20). I have found that focusing on a group of reactions that share a common theme helps students to better see their similarities. • Synthesis Synthesis, one of the most diffi cult topics for a beginning organic student to master, is introduced in small doses, beginning in Chapter 7 and augmented with a detailed discussion of retrosynthetic analysis in Chapter 11. In later chapters, special attention is given to the retrosynthetic analysis of compounds prepared by carbon–carbon bondforming reactions (for example, Sections 20.11 and 21.10C). • Spectroscopy Since spectroscopy is such a powerful tool for structure determination, four methods are discussed over two chapters (Chapters 13 and 14). • Key Concepts End-of-chapter summaries succinctly summarize the main concepts and themes of the chapter, making them ideal for review prior to working the end-of-chapter problems or taking an exam. New to the Third Edition • In response to reviewer feedback, new sections have been added on fragmentation patterns in mass spectrometry (Section 13.3) and peptide sequencing (Section 28.6). In addition, sections on splitting in NMR spectroscopy (Section 14.7) and substituent effects in substituted benzenes (Section 18.6) have been rewritten to clarify and focus the material. Some mechanisms have been modifi ed by adding electron pairs to nucleophiles and leaving groups to more clearly indicate the course of the chemical reaction. • Twenty new NMR spectra have been added in Chapters 14–25 to give students additional practice in this important type of analysis. • Over 350 new problems are included in the third edition. The majority of these problems are written at the intermediate level—more advanced than the easier drill problems, but not as complex as the challenge problems. Beginning with Chapter 11, there are additional multi-step synthesis problems that rely on reactions learned in earlier chapters. • The interior design has been modifi ed to tidy margins, and art labeling has been simplifi ed, so students can focus more clearly on the important concepts in a section. • New micro-to-macro illustrations are included on hydrogen bonding in DNA (Chapter 3), the production of ethanol from corn (Chapter 9), partial hydrogenation of vegetable oils (Chapter 12), artifi cial sweeteners (Chapter 27), and insulin (Chapter 28). Several 3-D illustrations of proteins have been added to Chapter 28 as well. The depiction of enzymes as biological catalysts in Chapter 6 has been redone to use an actual reaction—the conversion of the lactose in milk to glucose and galactose. • New health-related and environmental applications are included in margin notes and problems. Topics include the health benefi ts of omega-3 fatty acids, α-hydroxy acids in skin care products, drugs such as Benadryl that contain ammonium salts, chloroethane as a local anesthetic, rebaudioside A (trade name Truvia), a sweetening agent isolated from a plant source, and many others. Preface xix smi75625_fm_00i-xxxiv.indd xix 11/17/09 11:21:42 AM
Tools to Make Learning Organic Chemistry Easier lllustrations kCmmcmar otentia e e :to hel stereochemistry)and to better understand the distribution of electronic charge Micro-to-Macro lllustrations Unique to Organic Chemistry are micro-to-macro llustrations,where line art a d photos combine of common phenomena.Examples include starch and cellulose (Chapter 5),adrenaline (Chapter 7),partial ve5) able oil (Chapter 12).and Spectra Over 100 spectra created specifically for Organi Chemistry are presented throughout the text.The pre blue. rmagnetic resonance spectra Mechanisms ·
Tools to Make Learning Organic Chemistry Easier xx Illustrations Organic Chemistry is supported by a well-developed illustration program. Besides traditional skeletal (line) structures and condensed formulas, there are numerous ball-and-stick molecular models and electrostatic potential maps to help students grasp the three-dimensional structure of molecules (including stereochemistry) and to better understand the distribution of electronic charge. Micro-to-Macro Illustrations Unique to Organic Chemistry are micro-to-macro illustrations, where line art and photos combine with chemical structures to reveal the underlying molecular structures giving rise to macroscopic properties of common phenomena. Examples include starch and cellulose (Chapter 5), adrenaline (Chapter 7), partial hydrogenation of vegetable oil (Chapter 12), and dopamine (Chapter 25). m /z Relative abundance 100 50 0 0 10 20 30 40 50 60 70 80 90 100 radical cation derived from hexane m /z = 86 [1] [2] [3] [4] [1] [2] [3] [4] CH3 CH2 CH2 CH2 CH2 CH3 CH3CH2CH2CH2CH2 m /z = 71 CH3CH2CH2CH2 m /z = 57 CH3CH2CH2 m /z = 43 CH3CH2 m /z = 29 + + + + + • Cleavage of C – C bonds (labeled [1]–[4]) in hexane forms lower molecular weight fragments that correspond to lines in the mass spectrum. Although the mass spectrum is complex, possible structures can be assigned to some of the fragments, as shown. 11-cis-retinal bound to opsin rhodopsin disc membrane 11-cis crowding N CH3 H N opsin + rhodopsin hν cross-section of the eye rod cell in rhodopsin in a rod cell the retina The nerve impulse travels along the optic nerve to the brain. optic nerve retina pupil plasma membrane opsin nerve impulse 11-trans • Rhodopsin is a light-sensitive compound located in the membrane of the rod cells in the retina of the eye. Rhodopsin contains the protein opsin bonded to 11-cis-retinal via an imine linkage. When light strikes this molecule, the crowded 11-cis double bond isomerizes to the 11-trans isomer, and a nerve impulse is transmitted to the brain by the optic nerve. Spectra Over 100 spectra created specifi cally for Organic Chemistry are presented throughout the text. The spectra are color-coded by type and generously labeled. Mass spectra are green; infrared spectra are red; and proton and carbon nuclear magnetic resonance spectra are blue. Mechanisms Curved arrow notation is used extensively to help students follow the movement of electrons in reactions. Where appropriate, mechanisms are presented in parts to promote a better conceptual understanding. C H H H H O O C O O Add H2 to one = an allylic carbon—a C adjacent to a C C Unsaturated vegetable oil • two C • lower melting • liquid at room temperature Partially hydrogenated oil in margarine • one C • higher melting • semi-solid at room temperature H2 (1 equiv) Pd-C H H C C s C C only. • Decreasing the number of degrees of unsaturation increases the melting point. Only one long chain of the triacylglycerol is drawn. • When an oil is partially hydrogenated, some double bonds react with H2, whereas some double bonds remain in the product. • Partial hydrogenation decreases the number of allylic sites (shown in blue), making a triacylglycerol less susceptible to oxidation, thereby increasing its shelf life. Mechanism 9.2 Dehydration of a 1° ROH—An E2 Mechanism Step [1] The O atom is protonated. C CH2 OH2 CH3 H H + C CH2 OH CH3 H H good leaving group + H OSO3H proton transfer HSO4 – • Protonation of the oxygen atom of the alcohol converts a poor leaving group ( – OH) into a good leaving group (H2O). Step [2] The C – H and C – O bonds are broken and the o bond is formed. good leaving group CH3CH CH2 β HSO4 – C CH2 + + H2SO4 OH2 CH3 H H + H2O • Two bonds are broken and two bonds are formed in a single step: the base (HSO4 – or H2O) removes a proton from the β carbon; the electron pair in the β C – H bond forms the new π bond; the leaving group (H2O) comes off with the electron pair in the C – O bond. smi75625_fm_00i-xxxiv.indd xx 11/17/09 11:21:42 AM