List of Selected Applications xxxi B S-Adenosylmethionine(SAM).a nutritional supplement used by the cell in key nucleophilic substitutions that MThemrofyh preparing fg,n anieancerdg M Alkyl halides and elimination reaction DDE.a degradation product of the pesticide DDT(Opener.Section8.1) B.M Chapter 9 Alcohols.Ethers.and Epoxides G.E arbohydrates in grains(Section 95) t can be produced from the fermentation of M B carbons (PAHs)to carcinogens that disrupt normal cell function ulting in cancer or Chapter 10 Alkenes G ety of other polymers B (Section 106,Problem 10.12 (Section 10.16) Chapter 11 Alkynes Plan B.drugs that prevent pregnancy (Section 11.4) Chapter12 Oxidation and reduction The metabolism of ethanol,the alcohol in alcoholic beverages (Opener,Section 12.14 /。112 The synthesis of insect pheromones usine asymmetric epoxidation (Section 12 15) Chapter 13 MMB nfrared spectroscopy of penicillin (Opener.Section 13.8) rugs(Section 13.4B Chapter 14 Nuclear Magnetic Resonance Spectroscopy Chapter Polystyrene,a common nthetic polymer used in packaging materials and beverage cups(Opener) Ozone on and CR n13 of un actions (Section 15 1 turally oecur ng vitamin Eand synthetic BHT (Section 15.12) on of useful polymers from monomers by radical reactions(Section 15.14) Chapter 10 Conjugatic 0m16.刀 melon.and other fruits(Opene B The Die
List of Selected Applications xxxi B S-Adenosylmethionine (SAM), a nutritional supplement used by the cell in key nucleophilic substitutions that synthesize amino acids, hormones, and neurotransmitters (Section 7.12) B How nitrosamines, compounds formed in cured meats preserved with sodium nitrite, are thought to be cancercausing (Section 7.16) M The importance of organic synthesis in preparing useful drugs such as aspirin and taxol, an anticancer drug used to treat breast cancer (Section 7.19) Chapter 8 Alkyl Halides and Elimination Reactions E DDE, a degradation product of the pesticide DDT (Opener, Section 8.1) B, M Elimination reactions in the synthesis of a prostaglandin, an antimalarial drug, and a female sex hormone (Section 8.4) Chapter 9 Alcohols, Ethers, and Epoxides B Palytoxin, a toxic component isolated from marine soft corals of the genus Palythoa (Opener, Problem 9.80) G, E Ethanol, a gasoline additive and renewable fuel source that can be produced from the fermentation of carbohydrates in grains (Section 9.5) M The design of asthma drugs that block the synthesis of leukotrienes, highly potent molecules that contribute to the asthmatic response (Section 9.16) B The metabolism of polycyclic aromatic hydrocarbons (PAHs) to carcinogens that disrupt normal cell function resulting in cancer or cell death (Section 9.17) Chapter 10 Alkenes B Fats and oils—the properties of saturated and unsaturated fatty acids (Opener, Section 10.6) G Ethylene, the starting material for preparing the polymer polyethylene and many other simple compounds used to make a variety of other polymers (Section 10.5) B Omega-3 fatty acids, highly unsaturated fatty acids thought to be benefi cial for individuals at risk of developing coronary artery disease (Section 10.6, Problem 10.12) B The synthesis of the female sex hormone estrone (Section 10.15B) M The synthesis of artemisinin, an antimalarial drug isolated from qinghao, a Chinese herbal remedy (Section 10.16) Chapter 11 Alkynes M Oral contraceptives (Opener, Section 11.4) M Synthetic hormones mifepristone and Plan B, drugs that prevent pregnancy (Section 11.4) Chapter 12 Oxidation and Reduction B The metabolism of ethanol, the alcohol in alcoholic beverages (Opener, Section 12.14) B The partial hydrogenation of vegetable oils and the formation of “trans fats” (Section 12.4) B The use of disparlure, a sex pheromone, in controlling the spread of gypsy moths (Section 12.8) G Blood alcohol screening (Section 12.12) E Green chemistry—environmentally benign oxidation reactions (Section 12.13) B The synthesis of insect pheromones using asymmetric epoxidation (Section 12.15) Chapter 13 Mass Spectrometry and Infrared Spectroscopy M Infrared spectroscopy and the structure determination of penicillin (Opener, Section 13.8) M Using instrumental analysis to detect THC, the active component in marijuana, and other drugs (Section 13.4B) B Mass spectrometry and high molecular weight biomolecules (Section 13.4C) Chapter 14 Nuclear Magnetic Resonance Spectroscopy M Modern spectroscopic methods and the structure of the hormone melatonin (Opener, Problem 14.26) M Magnetic resonance imaging (MRI) and medicine (Section 14.12) Chapter 15 Radical Reactions G Polystyrene, a common synthetic polymer used in packaging materials and beverage cups (Opener) E Ozone destruction and CFCs (Section 15.9) B The oxidation of unsaturated lipids by radical reactions (Section 15.11) M, B Two antioxidants—naturally occurring vitamin E and synthetic BHT (Section 15.12) G The formation of useful polymers from monomers by radical reactions (Section 15.14) Chapter 16 Conjugation, Resonance, and Dienes M Lycopene, a highly unsaturated red pigment found in tomatoes, watermelon, and other fruits (Opener, Section 16.7) B The Diels–Alder reaction and the synthesis of tetrodotoxin, a toxin isolated from the puffer fi sh (Section 16.12) M The synthesis of steroids by Diels–Alder reactions (Section 16.14C) G Why lycopene and other highly conjugated compounds are colored (Section 16.15A) G How sunscreens work (Section 16.15B) smi75625_fm_00i-xxxiv.indd xxxi 11/25/09 1:11:40 PM
xxxii List of Selected Applications Chapte Benzene and Aromatic Compounds mpone ofh peppers and active ingredient in topical reams for of Claritin (Section 17.5) B ind and 17 11) Chapter18 The synthesis of the hallucinogen LSD (Opener.Section 18.5D) 245-9 rugs bup icide chlorphenraminend-Dn Chapter 19 Carboxylic Acids and the Acidity of the O-H Bond GHB(4-hdrobuanoic blem 19.51 e(Section 19.5 b n19. Ston19.14） Chapter20 tallic Re nts:Oxidation and Reduction B The use of juvenile hormo mimics to control certain in B.M ofen and the perfume component muscone 20.4) the erol (Sec B Biologicaloidatiom-Tedictionreacionswiththccoc s NADH and NAD(Section 20.6B) M T e synthesis of th ne neurotoxin cig (Section 20.7 。 M Digoxin.a naturallyo Opener,Prob 21 drug isolated from the woolly foxglove plant and used to treat congestive heart ssava root:and a rry pits Section 21.9B B The rl f hemi range pigment in carrots(Section 21.10B Chapter 22 Carboxylic Acids and Their Derivatives-Nucleophilic Acyl Substitution M. Nylon,the first synthetic fiber (Opener) M.B The synthesis of the insect repellent DEET() 22. ylation in the synthesis of aspirin.acetaminophen (the active ingredient in Tylenol).and heroin B The hydro the metabolism of lipids (ctiA) 2212B The mechar ection 22.14) ation reactions (sectior 02217 M Cholesteryl esters in plaque,the deposits that form on the walls of arteries (Section 22.17 Chapter 23 Reactionsof Carbonyl Compounds at the Carbon tion 23.8C Chapter 24 Carbonyl Condensation Reactions The synthesis of the anti-inflammatory agent ibuprofen(Opener.Problem 24.19) is of
Chapter 17 Benzene and Aromatic Compounds B, M Capsaicin, the spicy component of hot peppers and active ingredient in topical creams for the treatment of chronic pain (Opener) G Polycyclic aromatic hydrocarbons (PAHs), constituents of cigarette smoke and diesel exhaust (Section 17.5) M Examples of common drugs that contain an aromatic ring—Zoloft, Valium, Novocain, Viracept, Viagra, and Claritin (Section 17.5) B Histamine and scombroid fi sh poisoning (Section 17.8) G Diamond, graphite, and buckminsterfullerene (Section 17.11) Chapter 18 Electrophilic Aromatic Substitution M The synthesis of the hallucinogen LSD (Opener, Section 18.5D) M, E Examples of biologically active aryl chlorides—the drugs bupropion and chlorpheniramine, and 2,4-D and 2,4,5-T, herbicide components of the defoliant Agent Orange (Section 18.3) M Benzocaine, the active ingredient in the over-the-counter topical anesthetic Orajel (Section 18.14C) Chapter 19 Carboxylic Acids and the Acidity of the O–H Bond G Hexanoic acid, the foul-smelling carboxylic acid in ginkgo seeds (Opener, Problem 19.51) B GHB (4-hydroxybutanoic acid), an illegal recreational intoxicant used as a “date rape” drug (Section 19.5) M, B How NSAIDs block the synthesis of prostaglandins to prevent infl ammation (Section 19.6) B An introduction to amino acids, the building blocks of proteins; why vegetarians must have a balanced diet (Section 19.14) Chapter 20 Introduction to Carbonyl Chemistry; Organometallic Reagents; Oxidation and Reduction B The use of juvenile hormone mimics to control certain insect populations; the use of organometallic reagents to synthesize the C18 juvenile hormone (Opener, Section 20.10C) B, M Reduction reactions in the synthesis of the analgesic ibuprofen and the perfume component muscone (Section 20.4) M The synthesis of the long-acting bronchodilator salmeterol (Section 20.6A) B Biological oxidation–reduction reactions with the coenzymes NADH and NAD+ (Section 20.6B) B The synthesis of the marine neurotoxin ciguatoxin CTX3C (Section 20.7) M The use of organometallic reagents to synthesize the oral contraceptive ethynylestradiol (Section 20.10C) Chapter 21 Aldehydes and Ketones—Nucleophilic Addition M Digoxin, a naturally occurring drug isolated from the woolly foxglove plant and used to treat congestive heart failure (Opener, Problem 21.40) B Naturally occurring cyanohydrin derivatives—linamarin, from cassava root; and amygdalin, often called laetrile, from apricot, peach, and wild cherry pits (Section 21.9B) B The use of the Wittig reaction in the synthesis of β-carotene, the orange pigment in carrots (Section 21.10B) B The role of rhodopsin in the chemistry of vision (Section 21.11B) Chapter 22 Carboxylic Acids and Their Derivatives—Nucleophilic Acyl Substitution G Nylon, the fi rst synthetic fi ber (Opener) M, B Compounds that contain an ester—vitamin C; cocaine, addictive stimulant from the leaves of the coca plant; and FK506, an immunosuppressant (Section 22.6) M, B Useful amides—proteins, the polyamide met-enkephalin, the anticancer drug Gleevec, the penicillin antibiotics, and the cephalosporin antibiotics (Section 22.6) G The synthesis of the insect repellent DEET (Section 22.8) M The use of acylation in the synthesis of aspirin, acetaminophen (the active ingredient in Tylenol), and heroin (Section 22.9) B The hydrolysis of triacylglycerols in the metabolism of lipids (Section 22.12A) G Olestra, a fake fat (Section 22.12A) G The synthesis of soap (Section 22.12B) M The mechanism of action of β-lactam antibiotics like penicillin (Section 22.14) G Natural and synthetic fi bers—nylon and polyesters (Section 22.16) B Biological acylation reactions (Section 22.17) M Cholesteryl esters in plaque, the deposits that form on the walls of arteries (Section 22.17) Chapter 23 Substitution Reactions of Carbonyl Compounds at the ` Carbon M The synthesis of tamoxifen, an anticancer drug used in the treatment of breast cancer (Opener, Section 23.8C) M The synthesis of the antimalarial drug quinine by an intramolecular substitution reaction (Section 23.7C) Chapter 24 Carbonyl Condensation Reactions M The synthesis of the anti-infl ammatory agent ibuprofen (Opener, Problem 24.19) B The synthesis of periplanone B, sex pheromone of the female American cockroach (Section 24.3) B Synthesis of ar-turmerone, a component of turmeric, a principal ingredient in curry powder (Section 24.3) xxxii List of Selected Applications smi75625_fm_00i-xxxiv.indd xxxii 11/17/09 11:21:48 AM
List of Selected Applications xxxiii The synthesis of the steroid progesterone by an intramolecular aldol reaction (Section 24.4) The synthesis of the female sex hormone estrone by a Michael reaction (Section 24.8 Chapter 25 n alkaloid found in coffee Hista es,and antiulcer drugs like Taga ropine from the pois sonous nightshade plant.from coniin 5.6B B.M ogicaly active deriv es of 2-phenylethylamine-adrenaline.noradrenaline.methamphetamine.mescaline B.M in and widely used antidepressants called SSRIs (selective serotonin reuptake Dru such as the anthistamins dinsnhydrodas watcr-solubls ammonium alts (Section 259 ection 25.16A) tion 25.17 Chapte ond-Formi ons in Organic Synthe 126.2B sectic esis of epotl Chapter 27 Carbohydrat B.M plant (Section 27.7C Common disaccharides 7.12 G 710 ellulose.starch.and gly gen (Se ction 27.13) nter remedy used for n27.14A and chitin.the carbohydrate that gives rigidity B N-Glycosides and the structure of DNA (Section 27.14B) Chapter 28 Amino Acids and Proteins he protein that store s(Opener.Section 28.10C) on of polypeptides and proteins using automated peptide synthesis-the Merrifield method The structure of spider silk (Section 28 9B) e structure of insulin (S ci0n28.90 2810A Collagen.the ue(Section 28.10B) bular protein hemoglobin:the structure of sickle cel (Section28.10C) Chapter 2 Triacylglycerols.the components of fats and oils(Section 29.3) ergy sto and he 29.3 B8B nins-A.D.E and K (See cortical steroid nabolic steroids,and oral contraceptives (Section 298) M Cholesterol and cholesterol-lowering drugs atorvastatin(Lipitor)and simvastatin (Zocor)(Section 29.8B)
List of Selected Applications xxxiii B The synthesis of the steroid progesterone by an intramolecular aldol reaction (Section 24.4) B The synthesis of the female sex hormone estrone by a Michael reaction (Section 24.8) Chapter 25 Amines B Caffeine, an alkaloid found in coffee, tea, and cola beverages (Opener) M Histamine, antihistamines, and antiulcer drugs like Tagamet (cimetidine) (Section 25.6B) B Naturally occurring alkaloids—atropine from the poisonous nightshade plant, nicotine from tobacco, and coniine from hemlock (Section 25.6B) B, M Biologically active derivatives of 2-phenylethylamine—adrenaline, noradrenaline, methamphetamine, mescaline, and dopamine (Section 25.6C) B, M The neurotransmitter serotonin and widely used antidepressants called SSRIs (selective serotonin reuptake inhibitors) (Section 25.6C) M The synthesis of methamphetamine (Section 25.7C) M Drugs such as the antihistamine diphenhydramine, sold as water-soluble ammonium salts (Section 25.9) G Azo dyes (Section 25.15) G Perkin’s mauveine and synthetic dyes (Section 25.16A) G How dyes bind to fabric (Section 25.16B) M Sulfa drugs (Section 25.17) Chapter 26 Carbon–Carbon Bond-Forming Reactions in Organic Synthesis B, E Bombykol, the sex pheromone of the female silkworm moth (Opener, Section 26.2B) E Pyrethrin I, a biodegradable insecticide isolated from chrysanthemums (Section 26.4, Problem 26.33) M Ring-closing metathesis and the synthesis of epothilone A, an anticancer drug, and Sch38516, an antiviral agent (Section 26.6) Chapter 27 Carbohydrates B Lactose, the carbohydrate in milk (Opener) B Glucose, the most common simple sugar (Section 27.6) B, M Naturally occurring glycosides—salicin from willow bark and solanine, isolated from the deadly nightshade plant (Section 27.7C) G Rebaudioside A (trade name Truvia), a sweet glycoside from the stevia plant (Section 27.7C) B Common disaccharides—maltose from malt, lactose from milk, and sucrose, common table sugar (Section 27.12) G Artifi cial sweeteners (Section 27.12C) B Common polysaccharides—cellulose, starch, and glycogen (Section 27.13) B, M Glucosamine, an over-the-counter remedy used for osteoarthritis, and chitin, the carbohydrate that gives rigidity to crab shells (Section 27.14A) B N-Glycosides and the structure of DNA (Section 27.14B) Chapter 28 Amino Acids and Proteins B Myoglobin, the protein that stores oxygen in tissues (Opener, Section 28.10C) B The naturally occurring amino acids (Section 28.1) B The preparation of polypeptides and proteins using automated peptide synthesis—the Merrifi eld method (Section 28.8) B The structure of spider silk (Section 28.9B) M The structure of insulin (Section 28.9C) B β-Keratin, the protein in hair (Section 28.10A) B Collagen, the protein in connective tissue (Section 28.10B) B The globular protein hemoglobin; the structure of sickle cell hemoglobin (Section 28.10C) Chapter 29 Lipids B Cholesterol, the most prominent steroid (Opener, Section 29.8B) B Triacylglycerols, the components of fats and oils (Section 29.3) B Energy storage and the metabolism of fats (Section 29.3) B The phospholipids in cell membranes (Section 29.4) B Fat-soluble vitamins—A, D, E, and K (Section 29.5) B The eicosanoids, a group of biologically active lipids that includes the prostaglandins and leukotrienes (Section 29.6) M Vioxx, Bextra, and Celebrex—anti-infl ammatory drugs (Section 29.6) B, M The structure of steroids—cholesterol, female sex hormones, male sex hormones, adrenal cortical steroids, anabolic steroids, and oral contraceptives (Section 29.8) M Cholesterol and cholesterol-lowering drugs atorvastatin (Lipitor) and simvastatin (Zocor) (Section 29.8B) smi75625_fm_00i-xxxiv.indd xxxiii 11/17/09 11:21:48 AM
xxxiv Contents Chape Synthetic Polymers Natural and synthetie rubber (Section 30.5) The synthesis of polym olving sutures (Sec n30.6B nvironmentally benign methods for preparing polymers (Section30.8)
xxxiv Contents Chapter 30 Synthetic Polymers G Polyethylene terephthalate, an easily recycled synthetic polymer used in transparent soft drink containers (Opener, Sections 30.6B and 30.9A) G Polyethylene, the plastic in milk jugs and plastic bags, and other chain-growth polymers (Section 30.2) G Using Ziegler–Natta catalysts to make high-density polyethylene (Section 30.4) B Natural and synthetic rubber (Section 30.5) G The synthesis of step-growth polymers—polyamides such as nylon and Kevlar, polyesters such as Dacron, polyurethanes such as spandex, and polycarbonates such as Lexan (Section 30.6) M Dissolving sutures (Section 30.6B) G Epoxy resins (Section 30.6E) E Green polymer synthesis—environmentally benign methods for preparing polymers (Section 30.8) E Polymer recycling (Section 30.9A) E Biodegradable polymers (Section 30.9B) smi75625_fm_00i-xxxiv.indd xxxiv 11/17/09 11:21:48 AM
Prologue 6 。A century. rgani or a m ment the .You likely showered wit aper.listened toa CD.and aveled in a vehicle that had rubber tiresand was powered by fossil fuels.If you did any one of these,your life was touched by organic chemistry. What Is Organic Chemistry? Organic chemistry is the chemistry of compounds that contain the element carbon. It is one hranch in the entire feld of h s many classical subdiscipline including inorganic,physical,and analytical chemistry,and newer fields such as bioinorgani chemistry,physical biochemistry,polymer chemistry,and materials science. stry was s ut as a .Originall term ref found in living organisms. It may seem odd that a whole discipline is devoted to the study of a single element in the periodic table.when more than 100 elements exist.It turns out,though,that there are far more organic r type.Organic che ally et of our lives Clothes.foods.medicines.gasoline.refrigerants.and soaps are composed almost solely of molecules.Some,like coton,wool or silk are naturally occumring:that is,they can be ted directly from natural source s,such a s nylon and polyester are synthetic,mean h about nds sucng world around you. nes that were ly none 47 the wea thy.w To a large extent this is due to the isolation and synthesis of new drugs to fight infections and the acc心so e.andheresmoeioodor mnany pro resu from organic chemistry ()
1 Prologue Organic chemistry. You might wonder how a discipline that conjures up images of eccentric old scientists working in basement laboratories is relevant to you, a student in the twenty-fi rst century. Consider for a moment the activities that occupied your past 24 hours. You likely showered with soap, drank a caffeinated beverage, ate at least one form of starch, took some medication, read a newspaper, listened to a CD, and traveled in a vehicle that had rubber tires and was powered by fossil fuels. If you did any one of these, your life was touched by organic chemistry. What Is Organic Chemistry? • Organic chemistry is the chemistry of compounds that contain the element carbon. It is one branch in the entire fi eld of chemistry, which encompasses many classical subdisciplines including inorganic, physical, and analytical chemistry, and newer fi elds such as bioinorganic chemistry, physical biochemistry, polymer chemistry, and materials science. Organic chemistry was singled out as a separate discipline for historical reasons. Originally, it was thought that compounds in living things, termed organic compounds, were fundamentally different from those in nonliving things, called inorganic compounds. Although we have known for more than 150 years that this distinction is artifi cial, the name organic persists. Today the term refers to the study of the compounds that contain carbon, many of which, incidentally, are found in living organisms. It may seem odd that a whole discipline is devoted to the study of a single element in the periodic table, when more than 100 elements exist. It turns out, though, that there are far more organic compounds than any other type. Organic chemicals affect virtually every facet of our lives, and for this reason, it is important and useful to know something about them. Clothes, foods, medicines, gasoline, refrigerants, and soaps are composed almost solely of organic molecules. Some, like cotton, wool, or silk are naturally occurring; that is, they can be isolated directly from natural sources. Others, such as nylon and polyester, are synthetic, meaning they are produced by chemists in the laboratory. By studying the principles and concepts of organic chemistry, you can learn more about compounds such as these and how they affect the world around you. Realize, too, what organic chemistry has done for us. Organic chemistry has made available both comforts and necessities that were previously nonexistent, or reserved for only the wealthy. We have seen an enormous increase in life span, from 47 years in 1900 to over 70 years currently. To a large extent this is due to the isolation and synthesis of new drugs to fi ght infections and the availability of vaccines for childhood diseases. Chemistry has also given us the tools to control insect populations that spread disease, and there is more food for all because of fertilizers, pesticides, and herbicides. Our lives would be vastly different today without the many products that result from organic chemistry (Figure 1). What is organic chemistry? Some representative organic molecules Ginkgolide B—A complex organic compound from the ginkgo tree smi75625_001-005prologue.indd 1 10/15/09 9:02:42 AM