Selected Applications Helium 5 Carcinogenesis 614 Methane 60 Aniline 648 Ethylene:A Plant Hormone 106 Magnetic resonance imaging(MRI)713 Strychnine 172 Maitotoxin 745 Thalidomide 180 Civetone 769 Carboranes:Weird Bonding 217 Salicylic Acid 838 Synthetic diamonds 219 Nylon and polyesters 852 Ajoene 252 Fats,oils,soaps,and detergents 862 Malic Acid 274 Velcro 898 Cholesterol Formation 358 Eat Your Broccoli!921 Ethyl Alcohol 400 Anticancer drugs 980 Pyrethrins 456 Palytoxin 1009 Radical inhibitors as food preservatives 484 Chorismate to Prephenate: Vitamin E 505 A Biological Cope Rearrangement 1063 Vitamin A and vision 533 Mustard Gas 1089 Bombykol 534 Sugar Substitutes 1164 The birth-control pill 562 Cellulose and starch 1168 Vanillin 582 Canavanine:An Unusual Amino Acid 1177 Carcinogens 605 DNA and RNA 1211 xix
xix Helium 5 Methane 60 Ethylene: A Plant Hormone 106 Strychnine 172 Thalidomide 180 Carboranes: Weird Bonding 217 Synthetic diamonds 219 Ajoene 252 Malic Acid 274 Cholesterol Formation 358 Ethyl Alcohol 400 Pyrethrins 456 Radical inhibitors as food preservatives 484 Vitamin E 505 Vitamin A and vision 533 Bombykol 534 The birth-control pill 562 Vanillin 582 Carcinogens 605 Carcinogenesis 614 Aniline 648 Magnetic resonance imaging (MRI) 713 Maitotoxin 745 Civetone 769 Salicylic Acid 838 Nylon and polyesters 852 Fats, oils, soaps, and detergents 862 Velcro 898 Eat Your Broccoli! 921 Anticancer drugs 980 Palytoxin 1009 Chorismate to Prephenate: A Biological Cope Rearrangement 1063 Mustard Gas 1089 Sugar Substitutes 1164 Cellulose and starch 1168 Canavanine: An Unusual Amino Acid 1177 DNA and RNA 1211 Selected Applications
Organic Reaction Animations Bimolecular nucleophilic substitution:SN2 267 Arene halogenation 670 Halide formation 285 Nucleophilic aromatic substitution 674 Unimolecular nucleophilic substitution:SN1 289 Benzyne formation 681 Unimolecular elimination:E1 298 Carbonyl hydration 775 Bimolecular elimination:E2 301 Acetal formation 786 Hofmann elimination 308 Imine formation 792 Acetylide addition 312 Grignard reaction 801 Intramolecular SN2 316 Carbonyl reduction 802 Sx2 with cyanide 344 Alcohol oxidation 804 Alkene hydrohalogenation 365 Cleavage of vicinal diols 807 Alkene hydration 381 Wittig reaction 812 Alkene polymerization 385 Fischer esterification 841 Carbocation rearrangement E1 389 Acid chloride formation 854 Alkene hydroboration 390 Acid chloride aminolysis 854 Alkene halogenation 414 Acid chloride aminolysis 889 Stabilized alkene halogenation 417 Ester hydrolysis 895 Halohydrin formation 418 Nitrile hydrolysis 904 Alkene epoxidation 424 Baeyer-Villiger reaction 907 Basic epoxide ring opening 426 Enol halogenation 947 Acidic epoxide ring opening 427 Decarboxylation 960 Dihydroxylation of alkenes 443 Malonate alkylation 962 Radical alkene hydrohalogenation 485 Aldol condensation 965 Alkane halogenation 494 Michael addition 976 1,2-Hydrohalogenation of dienes 534 Mixed aldol condensation 983 1,4-Hydrohalogenation of dienes 534 Claisen condensation 987 Diels-Alder reaction 544 Cope rearrangement 1063 Benzylic oxidation 613 Intramolecular SN2 1081 Friedel-Crafts acylation 644 xxi
xxi Organic Reaction Animations Bimolecular nucleophilic substitution: SN2 267 Halide formation 285 Unimolecular nucleophilic substitution: SN1 289 Unimolecular elimination: E1 298 Bimolecular elimination: E2 301 Hofmann elimination 308 Acetylide addition 312 Intramolecular SN2 316 SN2 with cyanide 344 Alkene hydrohalogenation 365 Alkene hydration 381 Alkene polymerization 385 Carbocation rearrangement E1 389 Alkene hydroboration 390 Alkene halogenation 414 Stabilized alkene halogenation 417 Halohydrin formation 418 Alkene epoxidation 424 Basic epoxide ring opening 426 Acidic epoxide ring opening 427 Dihydroxylation of alkenes 443 Radical alkene hydrohalogenation 485 Alkane halogenation 494 1,2-Hydrohalogenation of dienes 534 1,4-Hydrohalogenation of dienes 534 Diels–Alder reaction 544 Benzylic oxidation 613 Friedel–Crafts acylation 644 Arene halogenation 670 Nucleophilic aromatic substitution 674 Benzyne formation 681 Carbonyl hydration 775 Acetal formation 786 Imine formation 792 Grignard reaction 801 Carbonyl reduction 802 Alcohol oxidation 804 Cleavage of vicinal diols 807 Wittig reaction 812 Fischer esterification 841 Acid chloride formation 854 Acid chloride aminolysis 854 Acid chloride aminolysis 889 Ester hydrolysis 895 Nitrile hydrolysis 904 Baeyer–Villiger reaction 907 Enol halogenation 947 Decarboxylation 960 Malonate alkylation 962 Aldol condensation 965 Michael addition 976 Mixed aldol condensation 983 Claisen condensation 987 Cope rearrangement 1063 Intramolecular SN2 1081
Preface to the Fourth Edition Most students in our organic chemistry courses are not chemistry majors.We wrote this book for anyone who wants a broad yet modern introduction to the subject.We stress general principles because it is impossible to memorize all the details of this vast subject.We want students to learn to make connections and to apply a set of broad organizing principles in order to make the material more manageable and understandable. The Fourth Edition Quite a bit has changed from the third to the fourth edition.New coauthor Steven Fleming brought his experience with this book and with his students to this revi- sion.Developmental editor Irene Nunes read the third edition from the student per- spective and made extensive comments.Irene helped us identify places where we may have assumed knowledge some students would not have or where we could further clarify a point or figure.We made substantial changes that will benefit students using this book. The voice of the book remains the same.It is personal,and talks directly to the student not only about the material at hand,but also about the"how and why"of organic chemistry.We think it is much easier to enjoy,and learn,organic chemistry if a strong focus on"Where are we and why are we here?"and"What is the best way to do this?"is maintained.On occasion,we try to help students through a tough part of the subject by pointing out that it is tough and then suggesting ways to deal with it.Everyone who has taught this subject knows there are such places-when we talk to students ourselves,we try to use our experi- ence to help students succeed,even when we know the going is likely to be difficult for some,and the book tries ESSENTIAL SKILLS AND DETAILS to do the same thing. L Sidedness and Handedness.You have the broad outlines of structure under control Every chapter begins with a Preview section in acyclic alkanes,alkenes,and alkynes have appeared,as have rings.Now we come which the coming chapter is outlined.At the end of the to the details,to stereochemistry."Sidedness"-cis/trans isomerism-is augmented by Preview,we describe the Essential Skills and Details mimRaicengooac6ndoprhohr students will need for the chapter.At exam time,stu- 2.Difference.The topic of difference and how difference is determined arises in this chapter.The details may be nuts and bolts,and,indeed,any way that you work out to dents can use these sections as guides for study and do the job will be just fine,but there isnoavoidin the seriousness of the quesio Whenare two atoms the same (in exactly the same envroment)or different (not in review. the same environment)?This question gets to the heart of structure and is much Organic chemistry is a highly visual subject.Organic tougher toanswer than it sem By all means,n this point.This chapter ill help you ou by intrducingethodthfor determining whethero chemists think by constructing mental pictures of mol- not two atoms are in different environments.It is well worth knowing how it works. ecules and communicate with each other by drawing pic- 3There is no way out-the (R)and(s)priority system must be learned. Words-Jargon.This chapter is filled with jargon:Be certain that you earn the tures.This book favors series of figures over long differe nce between enan chiral,""racemic,"and "meso mean. discussions in the text.The text serves to point out the changes in successive figures.Color is used to highlight xxiii
Most students in our organic chemistry courses are not chemistry majors. We wrote this book for anyone who wants a broad yet modern introduction to the subject. We stress general principles because it is impossible to memorize all the details of this vast subject. We want students to learn to make connections and to apply a set of broad organizing principles in order to make the material more manageable and understandable. The Fourth Edition Quite a bit has changed from the third to the fourth edition. New coauthor Steven Fleming brought his experience with this book and with his students to this revision. Developmental editor Irene Nunes read the third edition from the student perspective and made extensive comments. Irene helped us identify places where we may have assumed knowledge some students would not have or where we could further clarify a point or figure.We made substantial changes that will benefit students using this book. The voice of the book remains the same. It is personal, and talks directly to the student not only about the material at hand, but also about the “how and why” of organic chemistry. We think it is much easier to enjoy, and learn, organic chemistry if a strong focus on “Where are we and why are we here?” and “What is the best way to do this?”is maintained. On occasion, we try to help students through a tough part of the subject by pointing out that it is tough and then suggesting ways to deal with it. Everyone who has taught this subject knows there are such places—when we talk to students ourselves, we try to use our experience to help students succeed, even when we know the going is likely to be difficult for some, and the book tries to do the same thing. Every chapter begins with a Preview section in which the coming chapter is outlined. At the end of the Preview, we describe the Essential Skills and Details students will need for the chapter. At exam time, students can use these sections as guides for study and review. Organic chemistry is a highly visual subject. Organic chemists think by constructing mental pictures of molecules and communicate with each other by drawing pictures. This book favors series of figures over long discussions in the text. The text serves to point out the changes in successive figures. Color is used to highlight xxiii Preface to the Fourth Edition ESSENTIAL SKILLS AND DETAILS 1. Sidedness and Handedness. You have the broad outlines of structure under control now—acyclic alkanes, alkenes, and alkynes have appeared, as have rings. Now we come to the details, to stereochemistry. “Sidedness”—cis/trans isomerism—is augmented by questions of chirality—“handedness.” Learning to see one level deeper into threedimensionality is the next critical skill. 2. Difference. The topic of difference and how difference is determined arises in this chapter. The details may be nuts and bolts, and, indeed, any way that you work out to do the job will be just fine, but there is no avoiding the seriousness of the question. When are two atoms the same (in exactly the same environment) or different (not in the same environment)? This question gets to the heart of structure and is much tougher to answer than it seems. By all means, concentrate on this point. This chapter will help you out by introducing a method—an algorithm for determining whether or not two atoms are in different environments. It is well worth knowing how it works. 3. There is no way out—the (R) and (S) priority system must be learned. 4. Words—Jargon. This chapter is filled with jargon: Be certain that you learn the difference between enantiomers and diastereomers. Learn also what “stereogenic,” “chiral,” “racemic,” and “meso” mean