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14 Aldehydes and Ketones: Nucleophilic Addition Reactions Phosphoglucoisomerase catalyzes the isomerization of glucose 6-phosphate to fructose 6-phosphate, the second step in glucose metabolism contents 14.1 Naming Aldehydes and Ketones 14.2 Preparing Aldehydes and Ketones 14.3 Oxidation of Aldehydes 14.4 Nucleophilic Addition Reactions of Aldehydes and Ketones 14.5 Nucleophilic Addition of H2O: Hydration 14.6 Nucleophilic Addition of Grignard and Hydride Reagents: Alcohol Formation 14.7 Nucleophilic Addition of Amines: Imine and Enamine Formation 14.8 14.9 Nucleophilic Addition of Phosphorus Ylides: The Wittig Reaction Conjugate Nucleophilic Addition to ␣,-Unsaturated Aldehydes and Ketones 14.12 Spectroscopy of Aldehydes and Ketones Lagniappe—Enantioselective Synthesis 564 CH2OH 2–O PO CH3 H H HO CH3 O O OH C Nucleophilic Addition of Alcohols: Acetal Formation 14.10 Biological Reductions 14.11 Aldehydes (RCHO) and ketones (R2CO) are among the most widely occurring of all compounds In nature, many substances required by living organisms are aldehydes or ketones The aldehyde pyridoxal phosphate, for instance, is a coenzyme involved in a large number of metabolic reactions; the ketone hydrocortisone is a steroid hormone secreted by the adrenal glands to regulate fat, protein, and carbohydrate metabolism H +N OH H CH3 Pyridoxal phosphate (PLP) H H O Hydrocortisone In the chemical industry, simple aldehydes and ketones are produced in large quantities for use as solvents and as starting materials to prepare a host of other compounds For example, more than 1.9 million tons per year of formaldehyde, H2CUO, are produced in the United States for use in building insulation materials and in the adhesive resins that bind particle board and plywood Online homework for this chapter can be assigned in Organic OWL 14.1 naming aldehydes and ketones Acetone, (CH3)2CUO, is widely used as an industrial solvent; approximately 1.2 million tons per year are produced in the United States why this chapter? The chemistry of living organisms is, in many ways, the chemistry of carbonyl compounds Aldehydes and ketones, in particular, are intermediates in almost all biological pathways, so an understanding of their properties and reactions is essential We’ll look in this chapter at some of their most important reactions 14.1 Naming Aldehydes and Ketones Aldehydes are named by replacing the terminal -e of the corresponding alkane name with -al The parent chain must contain the –CHO group, and the –CHO carbon is numbered as C1 In the following examples, note that the longest chain in 2-ethyl-4-methylpentanal is actually a hexane, but this chain does not include the –CHO group and thus is not considered the parent O CH3 O CH3CH O CH3CH2CH CH3CHCH2CHCH CH2CH3 Ethanal (acetaldehyde) Propanal (propionaldehyde) 2-Ethyl-4-methylpentanal For cyclic aldehydes in which the –CHO group is directly attached to a ring, the suffix -carbaldehyde is used: CHO Cyclohexanecarbaldehyde CHO Naphthalene-2-carbaldehyde A few simple and well-known aldehydes have common names that are recognized by IUPAC Several that you might encounter are listed in Table 14.1 TABLE 14.1 Common Names of Some Simple Aldehydes Formula Common name Systematic name HCHO Formaldehyde Methanal CH3CHO Acetaldehyde Ethanal H2CUCHCHO Acrolein Propenal CH3CHUCHCHO Crotonaldehyde But-2-enal Benzaldehyde Benzenecarbaldehyde CHO 565 566 chapter 14 aldehydes and ketones: nucleophilic addition reactions Ketones are named by replacing the terminal -e of the corresponding alkane name with -one The parent chain is the longest one that contains the ketone group, and the numbering begins at the end nearer the carbonyl carbon As with alkenes (Section 7.2) and alcohols (Section 13.1), the numerical locant is placed before the parent name in older rules but before the suffix in newer IUPAC recommendations For example: O O CH3CH2CCH2CH2CH3 34 CH3CH 6 Hexan-3-one CHCH2CCH3 O O CH3CH2CCH2CCH3 21 Hex-4-en-2-one 43 21 Hexane-2,4-dione A few ketones are allowed by IUPAC to retain their common names: O O C CH3CCH3 Acetone O C CH3 Acetophenone Benzophenone When it’s necessary to refer to the R–C=O as a substituent, the name acyl (a-sil) group is used and the name ending -yl is attached Thus, CH3CO– is an acetyl group, –CHO is a formyl group, and C6H5CO– is a benzoyl group O O C C H3C R An acyl group O O C C H Acetyl Formyl Benzoyl If other functional groups are present and the doubly bonded oxygen is considered a substituent on a parent chain, the prefix oxo- is used For example: O O CH3CH2CH2CCH2COCH3 32 Methyl 3-oxohexanoate Problem 14.1 Name the following aldehydes and ketones: O (a) (b) CH2CH2CHO (c) O O CH3CCH2CH2CH2CCH2CH3 CH3CH2CCHCH3 CH3 (d) H (e) CH3 H CHO O CH3CH CHCH2CH2CH O (f) H3C H H CH3 14.2 preparing aldehydes and ketones Problem 14.2 Draw structures corresponding to the following names: (a) 3-Methylbutanal (b) 4-Chloropentan-2-one (c) Phenylacetaldehyde (d) cis-3-tert-Butylcyclohexanecarbaldehyde (e) 3-Methylbut-3-enal (f) 2-(1-Chloroethyl)-5-methylheptanal 14.2 Preparing Aldehydes and Ketones One of the best methods of aldehyde synthesis is by oxidation of primary alcohols, as we saw in Section 13.5 The reaction is often carried out using the Dess–Martin periodinane reagent in dichloromethane solvent at room temperature: AcO I OAc OAc O H O CH2OH C CH2Cl2 Geraniol O Geranial (84%) A second method of aldehyde synthesis is one that we’ll mention here just briefly and then return to in Section 16.6 Certain carboxylic acid derivatives can be partially reduced to yield aldehydes The partial reduction of an ester by diisobutylaluminum hydride (DIBAH), for instance, is an important laboratory-scale method of aldehyde synthesis, and mechanistically related processes also occur in biological pathways O CH3(CH2)10COCH3 O DIBAH, toluene, –78 °C H O+ Methyl dodecanoate CH3(CH2)10CH Dodecanal (88%) H where DIBAH = CH3CHCH2 Al CH2CHCH3 CH3 CH3 For the most part, methods of ketone synthesis are similar to those for aldehydes Secondary alcohols are oxidized by a variety of reagents to give ketones (Section 13.5) The choice of oxidant depends on such factors as reaction scale, cost, and acid or base sensitivity of the alcohol, with either the Dess–Martin periodinane or a Cr(VI) regent such as CrO3 being a common choice O OH CrO3 H3C H3C CH2Cl2 C CH3 4-tert-Butylcyclohexanol H3C H3C C CH3 4-tert-Butylcyclohexanone (90%) 567 568 chapter 14 aldehydes and ketones: nucleophilic addition reactions Aryl ketones can be prepared by Friedel–Crafts acylation of an aromatic ring with an acid chloride in the presence of AlCl3 catalyst (Section 9.7): O O + Benzene C AlCl3 CH3CCl CH3 Heat Acetyl chloride Acetophenone (95%) In addition, ketones can be prepared from certain carboxylic acid derivatives, just as aldehydes can Among the most useful reactions of this type is that between an acid chloride and a lithium diorganocopper reagent, R2CuLi We’ll discuss lithium diorganocopper reagents later in this chapter (Section 14.11) and will look at preparing ketones from acid chlorides in Section 16.4 O O (CH3)2Cu– Li+ C CH3CH2CH2CH2CH2 C Ether Cl CH3CH2CH2CH2CH2 Hexanoyl chloride CH3 Heptan-2-one (81%) Problem 14.3 How would you carry out the following reactions? More than one step may be required (a) Benzene n m-Bromoacetophenone (b) Bromobenzene n Acetophenone (c) 1-Methylcyclohexene n 2-Methylcyclohexanone 14.3 Oxidation of Aldehydes Aldehydes are easily oxidized to yield carboxylic acids, but ketones are generally inert toward oxidation The difference is a consequence of structure: aldehydes have a –CHO hydrogen that can be abstracted during oxidation, but ketones not Hydrogen here Not hydrogen here O O [O] C R C R H An aldehyde O [O] C OH R A carboxylic acid No reaction RЈ A ketone Many oxidizing agents, including KMnO4 and hot HNO3, convert aldehydes into carboxylic acids, but CrO3 in aqueous acid is a more common choice The oxidation takes place rapidly at room temperature O CH3CH2CH2CH2CH2CH Hexanal O CrO3, H3O+ Acetone, °C CH3CH2CH2CH2CH2COH Hexanoic acid (85%) 14.4 nucleophilic addition reactions of aldehydes and ketones 569 Aldehyde oxidations occur through intermediate 1,1-diols, or hydrates, which are formed by a reversible nucleophilic addition of water to the carbonyl group Even though formed to only a small extent at equilibrium, the hydrate reacts like any typical primary or secondary alcohol and is rapidly oxidized to a carbonyl compound OH O H2O C R H An aldehyde C R O OH CrO3 H O+ C R H A hydrate OH A carboxylic acid 14.4 Nucleophilic Addition Reactions of Aldehydes and Ketones As we saw in the Preview of Carbonyl Chemistry, the most general reaction of aldehydes and ketones is the nucleophilic addition reaction A nucleophile, :Nu؊, approaches along the C=O bond from an angle of about 75° to the plane of the carbonyl group and adds to the electrophilic C=O carbon atom At the same time, rehybridization of the carbonyl carbon from sp2 to sp3 occurs, an electron pair from the C=O bond moves toward the electronegative oxygen atom, and a tetrahedral alkoxide ion intermediate is produced (Figure 14.1) FIGURE 14.1 M E C H A N I S M : A nucleophilic addition reaction to an aldehyde or ketone The nucleophile approaches the carbonyl group from an angle of approximately 75° to the plane of the sp2 orbitals, the carbonyl carbon rehybridizes from sp2 to sp3, and an alkoxide ion is formed O An electron pair from the nucleophile adds to the electrophilic carbon of the carbonyl group, pushing an electron pair from the C=O bond onto oxygen and giving an alkoxide ion intermediate The carbonyl carbon rehybridizes from sp2 to sp3 Aldehyde or ketone C Nu – R RЈ 75° O Nu C – R RЈ Alkoxide ion H3O+ OH Nu C R RЈ Alcohol + H2O © John McMurry Protonation of the alkoxide anion intermediate gives the neutral alcohol addition product 570 chapter 14 aldehydes and ketones: nucleophilic addition reactions The nucleophile can be either negatively charged (:Nu؊) or neutral (:Nu) If it’s neutral, however, it usually carries a hydrogen atom that can subsequently be eliminated, :Nu–H For example: HO – (hydroxide ion) H – (hydride ion) Some negatively charged nucleophiles R3C – (a carbanion) RO – (an alkoxide ion) C – (cyanide ion) N HOH (water) ROH (an alcohol) Some neutral nucleophiles H3N (ammonia) RNH2 (an amine) Nucleophilic additions to aldehydes and ketones have two general variations, as shown in Figure 14.2 In one variation, the tetrahedral intermediate is protonated by water or acid to give an alcohol as the final product; in the second variation, the carbonyl oxygen atom is protonated and then eliminated as HO؊ or H2O to give a product with a C=Nu bond FIGURE 14.2 Two general reaction pathways following addition of a nucleophile to an aldehyde or ketone The top pathway leads to an alcohol product; the bottom pathway leads to a product with a C=Nu bond O Nu– R ؊ OH H C C R Nu Nu RЈ RЈ O A C R RЈ H Aldehyde or ketone Nu O H R C RЈ ؊ OH + Nu H H R C RЈ Nu –H2O Nu H C R RЈ Aldehydes are generally more reactive than ketones in nucleophilic addition reactions for both steric and electronic reasons Sterically, the presence of only one large substituent bonded to the C=O carbon in an aldehyde versus two large substituents in a ketone means that a nucleophile is able to approach the aldehyde more readily Thus, the transition state leading to the tetrahedral intermediate is less crowded and lower in energy for an aldehyde than for a ketone (Figure 14.3) Electronically, aldehydes are more reactive than ketones because of the greater polarization of aldehyde carbonyl groups To see this polarity difference, recall the stability order of carbocations (Section 7.8) A primary carbocation is higher in energy and thus more reactive than a secondary carbocation because it has only one alkyl group inductively stabilizing the positive charge rather than two In the same way, an aldehyde has only one alkyl group inductively stabilizing the partial positive charge on the carbonyl 14.4 nucleophilic addition reactions of aldehydes and ketones (a) FIGURE 14.3 (a) Nucleophilic addition to an aldehyde is sterically less hindered because only one relatively large substituent is attached to the carbonyl-group carbon (b) A ketone, however, has two large substituents and is more hindered The approach of the nucleophile is along the C=O bond at an angle of about 75° to the plane of the carbon sp2 orbitals (b) Nu Nu 75° carbon rather than two, is a bit more electrophilic, and is therefore more reactive than a ketone H R H C+ 1° carbocation (less stable, more reactive) O R C C+ R H RЈ 2° carbocation (more stable, less reactive) ␦– O ␦+ C R H Aldehyde (less stabilization of ␦+, more reactive) ␦– ␦+ RЈ Ketone (more stabilization of ␦+, less reactive) One further comparison: aromatic aldehydes, such as benzaldehyde, are less reactive in nucleophilic addition reactions than aliphatic aldehydes because the electron-donating resonance effect of the aromatic ring makes the carbonyl group less electrophilic Comparing electrostatic potential maps of formaldehyde and benzaldehyde, for example, shows that the carbonyl carbon atom in the aromatic aldehyde is less positive (less blue) O O C C H + Formaldehyde – O C H 571 – O + H + Benzaldehyde C – H 572 chapter 14 aldehydes and ketones: nucleophilic addition reactions Problem 14.4 Treatment of an aldehyde or ketone with cyanide ion (؊:CϵN), followed by protonation of the tetrahedral alkoxide ion intermediate, gives a cyanohydrin Show the structure of the cyanohydrin obtained from cyclohexanone Problem 14.5 p-Nitrobenzaldehyde is more reactive toward nucleophilic additions than p-methoxybenzaldehyde Explain 14.5 Nucleophilic Addition of H2O: Hydration Aldehydes and ketones react with water to yield 1,1-diols, or geminal (gem) diols The hydration reaction is reversible, and a gem diol can eliminate water to regenerate the aldehyde or ketone OH O + C H3C H2O CH3 Acetone (99.9%) H3C H3C C OH Acetone hydrate (0.1%) The position of the equilibrium between a gem diol and an aldehyde or ketone depends on the structure of the carbonyl compound The equilibrium generally favors the carbonyl compound for steric reasons, but the gem diol is favored for a few simple aldehydes For example, an aqueous solution of formaldehyde consists of 99.9% gem diol and 0.1% aldehyde at equilibrium, whereas an aqueous solution of acetone consists of only about 0.1% gem diol and 99.9% ketone OH O + C H H H2O Formaldehyde (0.1%) C H OH H Formaldehyde hydrate (99.9%) The nucleophilic addition of water to an aldehyde or ketone is slow under neutral conditions but is catalyzed by both base and acid The base-catalyzed hydration reaction takes place as shown in Figure 14.4 The nucleophile is the hydroxide ion, which is much more reactive than neutral water because of its negative charge 14.5 nucleophilic addition of h2o: hydration O – FIGURE 14.4 M E C H A N I S M : The mechanism of basecatalyzed hydration of an aldehyde or ketone Hydroxide ion is a more reactive nucleophile than neutral water OH C The nucleophilic hydroxide ion adds to the aldehyde or ketone and yields a tetrahedral alkoxide ion intermediate O – H C The alkoxide ion is protonated by water to give the gem diol product and regenerate the hydroxide ion catalyst 573 O H OH C –OH + OH A hydrate, or gem diol © John McMurry OH The acid-catalyzed hydration reaction begins with protonation of the carbonyl oxygen atom, which places a positive charge on oxygen and makes the carbonyl group more electrophilic Subsequent nucleophilic addition of water to the protonated aldehyde or ketone then yields a protonated gem diol, which loses H؉ to give the neutral product (Figure 14.5) Acid catalyst protonates the basic carbonyl oxygen atom, making the aldehyde or ketone a better acceptor for nucleophilic addition O + H H O C H FIGURE 14.5 M E C H A N I S M : The mechanism of acid-catalyzed hydration of an aldehyde or ketone Acid protonates the carbonyl group, making it more electrophilic and more reactive + H O O H C H Addition of water to the protonated carbonyl compound gives a protonated gem diol intermediate OH C OH2 + H O H OH C + OH A hydrate, or gem diol H3O+ © John McMurry Deprotonation of the intermediate by reaction with water yields the neutral gem diol and regenerates the acid catalyst i-18 index Ketone(s) (continued) alkylation of, 713– 714 amines from, 761– 762 biological halogenation of, 700 biological reduction of, 511, 588 carbonyl condensation reactions of, 716– 719 common names of, 566 conjugate addition reactions of, 588– 592 enamines from, 576– 579 enols of, 696– 698 enones from, 719– 721 from acetoacetic ester, 710– 711 from acid chlorides, 568, 662– 663 from alcohols, 520– 522 from alkenes, 270– 271 from nitriles, 626 Grignard reaction of, 514– 515 hydrates of, 572– 574 imines from, 576– 579 IR spectroscopy of, 387, 593 mass spectrometry of, 374, 594– 595 McLafferty rearrangement of, 374, 594 naming, 566 NMR spectroscopy of, 594 pKa of, 705 polarity of, 75 protection of, 582 reaction summary of, 597– 598 reaction with alcohols, 580– 582 reaction with amines, 576– 579 reaction with Br2, 700– 701 reaction with Grignard reagents, 514– 515, 574– 575 reaction with H2O, 572– 574 reaction with LDA, 713– 714 reaction with LiAlH4, 510– 511, 575 reaction with NaBH4, 510, 575 reactivity versus aldehydes, 570– 571 reduction of, 349, 510– 511, 575 reductive amination of, 761– 762 Wittig reaction of, 583– 585 Ketone bodies, 846 Ketoreductase domain, polyketide synthase and, 1035 Ketose, 864 Ketosynthase domain, polyketide synthase and, 1035 Kiliani– Fischer reaction, 898 Kilojoule (kJ), 11 Kinetics, 457 E1 reaction and, 485 E2 reaction and, 481 SN1 reaction and, 467– 468 SN2 reaction and, 457– 458 Knowles, William, 599, 801 Krebs, Hans, 915 Krebs cycle, see Citric acid cycle Amino acid, 796 Sugar, 869 Labetalol, stereochemistry of, 753 structure of, 753 synthesis of, 753 Laboratory reaction, comparison with biological reactions, 202– 204 L L Lactam(s), 673 cyclic amines from, 673 reaction with LiAlH4, 673 Lactic acid, configuration of (ϩ) enantiomer, 145– 146 configuration of (– ) enantiomer, 145– 146 enantiomers of, 135– 136 molecular model of, 136, 137 resolution of, 154– 155 Lactone(s), 666 alkylation of, 713 reaction with LDA, 713 molecular model of, 885 Lactose, occurrence of, 885 structure of, 885 sweetness of, 892 Lagging strand, DNA replication and, 994 Lanosterol, cholesterol from, 975 structure of, 242 biosynthesis of, 969– 975 Lard, composition of, 938 Latex, rubber from, 298 Lauric acid, structure of, 938 LD50, 25 table of, 25 LDA, see Lithium diisopropylamide LDL, heart disease and, 978– 979 Le Bel, Joseph, Leading strand, DNA replication and, 994 Leaving group, 463 reactivity of, 463– 464 SN1 reaction and, 472– 473 SN2 reactions and, 463– 464 LeBlanc process, 940 Leucine, biosynthesis of, 746, 861 metabolism of, 743 structure and properties of, 794 Leuprolide, structure of, 828 Levorotatory, 140 Lewis, G N., Lewis acid, 56 examples of, 57 reactions of, 56– 57 Lewis base, 56 examples of, 58 reactions of, 58– 59 Lewis structure, Lewis Y hexasaccharide, structure of, 889 Lexan, structure of, 678 uses of, 677– 678 Lidocaine, molecular model of, 99 Ligase, 816 Light, plane-polarized, 140 speed of, 378 Limit dextrin, from starch, 902– 903 Limonene, biosynthesis of, 249, 964 molecular model of (ϩ) enantiomer, 162 molecular model of (– ) enantiomer, 162 odor of, 162 Linalyl diphosphate, biosynthesis of, 964 Lindlar catalyst, 290 Line-bond structure, resonance and, 42 Linear metabolic pathways, reasons for, 919– 920 1→4-Link, 884 Linoleic acid, structure of, 938 Linolenic acid, molecular model of, 939 structure of, 938 Lipase, function of, 943 mechanism of action of, 668– 669, 943– 945 Lipid, 936 classification of, 936 Lipid bilayer, 943 structure of, 943 Lipitor, see Atorvastatin Lipoamide, structure and function of, 914 Lipoic acid, structure and function of, 818, 914 Lipoprotein, 978– 979 heart disease and, 978– 979 table of, 979 Liquid chromatography, 395 Lithium aluminum hydride, danger of, 511 reaction with aldehydes, 510– 511 reaction with carboxylic acids, 512, 657 reaction with esters, 512 reaction with ketones, 510– 511 Lithium diisopropylamide, formation of, 704 properties of, 704 reaction with cyclohexanone, 704 reaction with esters, 713 reaction with ketones, 713– 714 reaction with lactones, 713 reaction with nitriles, 714 Lithium diorganocopper reagent, conjugate addition reaction to enones, 590– 592 reaction with acid chlorides, 568 reaction with enones, 590– 592 synthesis of, 591 Lithocholic acid, structure of, 638, 967 Liver alcohol dehydrogenase, function of, 501 molecular model of, 501 Loading reaction, fatty acid biosynthesis and, 953 Locant (nomenclature), 84 position of in chemical names, 216– 217 Lone-pair electrons, Loratadine, structure of, 245 Lotaustralin, structure of, 623 Lovastatin, biosynthesis of, 289 mechanism of action of, 2, 977 structure of, 1032 Lowest unoccupied molecular orbital (LUMO), 389 LUMO, see Lowest unoccupied molecular orbital, 389 Lyase, 816 Lysine, catabolism of, 859 saccharopine from, 859 structure and properties of, 795 Lysozyme, isoelectric point of, 799 MALDI– TOF mass spectrum of, 376 Lyxose, configuration of, 871 Magnetic field, NMR spectroscopy and, 405– 406 Magnetic resonance imaging, 432 uses of, 432 Major groove (DNA), 991 index Malate, molecular model of, 420 oxaloacetate from, 919 oxidation of, 919 Malate dehydrogenase, function of, 919 MALDI– TOF mass spectrometry, 376 MALDI– TOF mass spectrum, lysozyme, 376 Maleic acid, structure of, 612 Malic acid, structure of, 612 Walden inversion of, 455 Malonic ester, pKa of, 705 Malonic ester synthesis, 707– 709 decarboxylation in, 708 intramolecular, 709 Malonyl CoA, from acetyl CoA, 953– 954 Maltose, molecular model of, 884 mutarotation of, 884 Maltotriose, from starch, 902– 903 Manicone, synthesis of, 663 Mannich reaction, 748 Mannose, biosynthesis of, 933 configuration of, 871 molecular model of, 124 Margarine, manufacture of, 939 Markovnikov, Vladimir, 230 Markovnikov’s rule, 230– 231 alkene additions and, 230– 231 alkyne additions and, 290– 291 carbocation stability and, 233– 235 hydroboration and, 259 oxymercuration and, 258 Mass analyzers, mass spectrometry and, 368 Mass number (A), Mass spectrometer, detectors in, 368 double-focusing, 370 exact mass measurement in, 370 ionization sources in, 368 kinds of, 368 mass analyzers in, 368 operation of, 368– 369 soft ionization in, 370, 376 Mass spectrometry (MS), 368 alcohols and, 373– 374, 538 aldehydes, 374, 594– 595 alkanes and, 370– 371 alpha cleavage of alcohols in, 373, 538 alpha cleavage of aldehydes in, 374, 595 alpha cleavage of amines in, 374, 777 alpha cleavage of ketones in, 374, 595 amines and, 374, 777– 778 base peak in, 369 biological, 376 carbonyl compounds and, 374 cation radicals in, 368 dehydration of alcohols in, 373– 374 electron-impact, 368– 369 ESI source in, 376 fragmentation in, 730– 372 ketones, 374, 594– 595 MALDI source in, 376 McLafferty rearrangement in, 374, 594 molecular ion in, 369 nitrogen rule and, 396, 777 parent peak in, 369 peptide sequencing with, 805 time-of-flight, 376 Mass spectrum, 369 butan-1-ol, 538 2,2-dimethylpropane, 370 ethylcyclopentane, 372 N-ethylpropylamine, 778 hexane, 371 hex-2-ene, 373 lysozyme, 376 methylcyclohexane, 372 5-methylhexan-2-one, 595 2-methylpentane, 397 2-methylpentan-2-ol, 375 2-methylpent-2-ene, 373 propane, 369 Matrix-assisted laser-desorption ionization mass spectrometry, see MALDI Maxam– Gilbert DNA sequencing, 999 McLafferty rearrangement, 374, 594 Mechanism, 177 a bromination of aldehydes, 700– 701 a bromination of carboxylic acids, 702 a bromination of ketones, 700– 701 a-substitution reaction, 699– 700 acetal formation, 580– 582 acid-catalyzed enol formation, 697 acid-catalyzed epoxide cleavage, 268 acid-catalyzed ester hydrolysis, 668 alcohol dehydration with acid, 517 alcohol dehydration with POCl3, 518 alcohol oxidation, 521– 522 aldehyde hydration, 572– 574 aldehyde oxidation, 569 aldehyde reduction, 575 aldol dehydration, 720 aldol reaction, 717 alkene bromination, 255 alkene epoxidation, 266 alkene oxymercuration, 258 alkene ozonolysis, 270 alkene polymerization, 275– 276 allylic bromination with NBS, 448– 450 amide dehydration, 624 amide hydrolysis, 626, 671– 672 amide reduction, 673 amide synthesis with DCC, 656 argininosuccinate biosynthesis, 845 aromatic bromination, 326 aromatic chlorination, 327 aromatic iodination, 327 aromatic nitration, 328 aromatic sulfonation, 329 base-catalyzed enol formation, 698 base-catalyzed epoxide cleavage, 532 base-catalyzed ester hydrolysis, 667 -ketoacyl-CoA thiolase, 949– 950 -oxidation pathway, 946– 950 biological epoxidation, 266– 267, 970– 971 biological hydroxylation, 329– 330, 1024, 1027– 1028 biological oxidation with FAD, 946– 948 biological oxidation with NAD؉, 522 biological reduction with NADH, 511 biological reduction with NADPH, 265, 511 biotin-mediated carboxylation, 953– 954 bromohydrin formation, 256– 257 i-19 bromonium ion formation, 254 Cannizzaro reaction, 587 carbonyl condensation reaction, 715– 716 carboxylic acid reduction, 657 citrate synthase, 819– 820 citric acid cycle, 915– 920 Claisen condensation reaction, 723– 724 Claisen rearrangement, 533– 534 conjugate addition of lithium diorganocopper reagents, 591 conjugate nucleophilic additions to enones, 588– 589 deamination, 837– 841 dichlorocarbene formation, 272– 273 Dieckmann cyclization reaction, 726– 727 Diels– Alder reaction, 285– 286 DNA replication, 992– 994 DNA transcription, 994– 995 E1 reaction, 485 E1cB reaction, 485– 486 E2 reaction, 481– 482 Edman degradation, 805– 806 electrophilic addition reaction, 187– 188, 227– 228 electrophilic aromatic substitution, 325– 326 enamine formation, 578 ester reduction, 669 ether cleavage with HI, 531 FAD reactions, 948 fat hydrolysis, 668– 669, 943– 945 fatty acid biosynthesis, 951– 955 fatty acyl CoA biosynthesis, 657– 659 Fischer esterification reaction, 654– 655 Friedel– Crafts acylation reaction, 334 Friedel– Crafts alkylation reaction, 331 geranyl diphosphate biosynthesis, 963 glycoconjugate biosynthesis, 878– 879 Grignard carboxylation, 621 Grignard reaction, 574– 575 guanine hydrolysis, 1006 guanosine phosphorolysis, 1006 Hofmann elimination reaction, 765 hydroboration, 259 hydrogenation, 262– 263 L-3-hydroxyacyl-CoA dehydrogenase, 949 imine formation, 576– 577 intramolecular aldol reaction, 722 inverting glycosidase, 902– 903 isopentenyl diphosphate biosynthesis, 958– 961 ketone hydration, 572– 574 ketone reduction, 575 lipase, 943– 945 mevalonate decarboxylation, 961 Michael reaction, 728– 729 mutarotation, 874 nitrile hydrolysis, 625 nucleophilic acyl substitution reaction, 647– 648 nucleophilic addition reaction, 569 nucleophilic aromatic substitution reaction, 345 oxidative deamination, 841 oxidative decarboxylation, 911– 913 oxymercuration, 258 i-20 index Mechanism (continued) phosphorylation with ATP, 835 pyruvate decarboxylation, 911– 913 reductive amination, 761– 762 retaining glycosidase, 902– 903 saponification, 667 SN1 reaction, 467– 468, 473 SN2 reaction, 458– 459 starch hydrolysis, 902– 903 steroid biosynthesis, 969– 975 Stork enamine reaction, 731– 732 transamination, 837– 841 transimination, 839 Williamson ether synthesis, 529– 530 Wittig reaction, 583– 584 xanthine oxidation, 1007 Meerwein– Ponndorf– Verley reaction, 605 Meisenheimer complex, 345 Membrane channel protein, function of, 70, 105 molecular model of, 70, 105 Menthene, electrostatic potential map of, 71 functional groups in, 71 Menthol, molecular model of, 115 structure of, 139 Meperidine, structure of, 1023 Mercapto group, 504 Mercurinium ion, 258 Merrifield solid-phase synthesis, 809– 811 Fmoc protecting group in, 811 PAM resin in, 811 steps in, 810– 811 Wang resin in, 811 Meso compound, 152 plane of symmetry in, 152 Messenger RNA, 994 codons in, 996 translation of, 996– 998 Mestranol, structure of, 302 Meta (m), 311 Meta-directing group, 337 Metabolic pathways, cyclic, 919– 920 linear, 919– 920 Metabolism, 833 overview of, 833– 834 Methadone, structure of, 1023 Methandrostenolone, structure and function of, 969 Methane, bond angles in, 13 bond lengths in, 13 bond strengths in, 13 molecular model of, 7, 13, 78 pKa of, 292 reaction with Cl2, 179– 180 sp3 hybrid orbitals in, 12– 13 structure of, 13 Methanethiol, bond angle in, 19 dipole moment of, 37 electrostatic potential map of, 207 molecular model of, 19 pKa of, 506 sp3 hybrid orbitals in, 19 structure of, 19 Methanol, annual U.S production of, 501 bond angle in, 19 dipole moment of, 37 electrostatic potential map of, 35, 54, 55, 183, 505 industrial synthesis of, 501 molecular model of, 19, 501 pKa of, 506 polar covalent bond in, 34– 35 sp3 hybrid orbitals in, 19 structure of, 19 toxicity of, 501 uses of, 501 Methionine, biosynthesis of, 603 molecular model of, 149 reaction with ATP, 535 S-adenosylmethionine from, 535 structure and properties of, 794 Methoxide ion, electrostatic potential map of, 55 p-Methoxybenzoic acid, pKa of, 618 p-Methoxypropiophenone, 1H NMR spectrum of, 427 Methyl acetate, electrostatic potential map of, 649 13C NMR spectrum of, 407 1H NMR spectrum of, 407 pKa of, 705 Methyl anion, electrostatic potential map of, 292 Methyl 2,2-dimethylpropanoate, 1H NMR spectrum of, 423 Methyl group, 81 chiral, 500 directing effect of, 341 inductive effect of, 339– 340 orienting effect of, 343 Methyl phosphate, bond angle in, 19 molecular model of, 19 sp3 hybrid orbitals in, 19 structure of, 19 Methyl propanoate, 13C NMR spectrum of, 414 Methyl thioacetate, electrostatic potential map of, 649 pKa of, 705 9-Methyladenine, electrostatic potential map of, 1011 Methylamine, bond angles in, 18 dipole moment of, 37 electrostatic potential map of, 36, 55, 65, 756 molecular model of, 18 sp3 hybrid orbitals in, 18 structure of, 18 2-Methylbutane, molecular model of, 78 2-Methylbutan-2-ol, 1H NMR spectrum of, 428 Methylcyclohexane, 1,3-diaxial interactions in, 121– 122 conformations of, 121– 122 mass spectrum of, 372 molecular model of, 138 1-Methylcyclohexanol, 1H NMR spectrum of, 431 2-Methylcyclohexanone, chirality of, 138 molecular model of, 138 Methylcyclohex-1-ene, 13C NMR spectrum of, 418 N-Methylcyclohexylamine, 13C NMR spectrum of, 777 1H NMR spectrum of, 777 Methylene group, 217 9-Methylguanine, electrostatic potential map of, 1011 6-Methylhept-5-en-2-ol, DEPT-NMR spectra of, 415– 416 5-Methylhexan-2-one, mass spectrum of, 595 Methyllithium, electrostatic potential map of, 35, 182 polar covalent bond in, 35 Methylmagnesium chloride, electrostatic potential map of, 574 Methylmagnesium iodide, electrostatic potential map of, 453 N-Methylmorpholine N-oxide, alkene hydroxylation with OsO4 and, 269 2-Methylpentane, mass spectrum of, 397 2-Methylpentan-3-ol, mass spectrum of, 375 2-Methylpent-2-ene, mass spectrum of, 373 p-Methylphenol, pKa of, 506 2-Methylpropane, molecular model of, 78 2-Methylpropene, heat of hydrogenation of, 226 Mevacor, mechanism of action of, 2, 977 Mevaldehyde, biosynthesis of, 675 Mevalonate, biosynthesis of, 958– 960 decarboxylation of, 961 isopentenyl diphosphate from, 958– 961 phosphorylation of, 960– 961 Mevalonate-5-diphosphate decarboxylase, function of, 961 Micelle (soap), 940– 941 Michael reaction, 728– 729 acceptors in, 729 donors in, 729 mechanism of, 728– 729 Stork enamine reaction and, 731– 732 Microwaves, electromagnetic spectrum and, 377 Mineralocorticoid, 968– 969 Minor groove (DNA), 991 Mitomycin C, structure of, 789 Mobile phase, chromatography and, 395 Molar absorptivity, 391 Molecular ion (M؉), 369 Molecular mechanics, 128 Molecular model, ␣ helix (protein), 813 acetaminophen, 27 acetyl CoA carboxylase, 610 acetylene, 17 acyl CoA dehydrogenase, 212 adenine, 64 N6-adenine methyltransferase, 444 adrenaline, 167 alanine, 26, 791 alanylserine, 802 D-amino-acid aminotransferase 832 p-aminobenzoic acid, 24 anisole, 502 anti periplanar geometry, 482 index arecoline, 76 aspartame, 27 aspirin, 16 bacteriorhodopsin, 367 -ketoacyl-CoA thiolase, 695 -pleated sheet (protein), 813 p-bromoacetophenone, 413 bromocyclohexane, 119 butane, 78 cis-but-2-ene, 220, 224 trans-but-2-ene, 220, 224 tert-butyl carbocation, 233 cellulose, 884 chair cyclohexane, 116 cholesterol, 967 cholic acid, 611 citrate synthase, 791, 819 citric acid, 27 coniine, 26 cyclobutane, 114 cyclodecapentaene, 317 cyclohexane ring flip, 119 cyclopentane, 115 cyclopropane, 109, 113 cytosine, 64 cis-decalin, 126, 966 trans-decalin, 126, 966 decane, 96 diethyl ether, 502 dimethyl sulfide, 19 cis-1,2-dimethylcyclopropane, 110 trans-1,2-dimethylcyclopropane, 110 2,2-dimethylpropane, 78 DNA, 991 dopamine, 761 eclipsed ethane conformation, 92 enflurane, 140 enoyl CoA hydratase, 251 ethane, 9, 14, 78 ethanol, 502 ethylene, 15 (S)-fluoxetine, 163 fructose-1,6-bisphosphate aldolase, 739 ␣-D-glucopyranose, 873 -D-glucopyranose, 873 glucose, 117, 124 glutamine synthase, 749 R-glyceraldehyde, 865– 866 glycogen synthase, 134 halomon, 445 hemoglobin, 309 hexane, 14 hexokinase, 203, 862 HIV protease, 33 HMG-CoA reductase, hydroxyacyl-CoA dehydrogenase, 936 (S)-ibuprofen, 166 isobutane, 78 isoleucine, 151, 824 lactic acid, 136, 137 lactose, 885 lidocaine, 99 (ϩ)-limonene, 162 (– )-limonene, 162 linolenic acid, 939 liver alcohol dehydrogenase, 501 S-malate, 420 maltose, 884 mannose, 124 membrane channel protein, 70, 105 menthol, 115 methane, 7, 13, 78 methanethiol, 19 methanol, 19, 501 methionine, 149 methyl phosphate, 19 methylamine, 18 2-methylbutane, 78 methylcyclohexane, 138 2-methylcyclohexanone, 138 2-methylpropane, 78 naphthalene, 64 Newman projections, 91 norcoclaurine synthase, 1015 oseltamivir, 128 pancreatic lipase, 643 pentane, 78 phenylalanine, 99 phosphoglucoisomerase, 564 phosphoribosyl-diphosphate synthetase, 987 piperidine, 767 propane, 78 propane conformations, 93 protein kinase A, 175 pseudoephedrine, 167 serine, 167 serylalanine, 802 staggered ethane conformation, 92 stearic acid, 938 steroid, 965 sucrose, 886 syn periplanar geometry, 482 Tamiflu, 128 meso-tartaric acid, 152 testosterone, 127 tetrahydrofuran, 502 threose, 140 trimethylamine, 752 triose-phosphate isomerase, 901 tRNA, 997 twist-boat cyclohexane, 117 ubiquinone– cytochrome c reductase, 404 urocanase, 856 vitamin C, 631 Molecular orbital, 20 algebraic signs of lobes in, 21, 219 antibonding, 21 bonding, 21 Molecular orbital (MO) theory, 20– 21 benzene and, 314– 315 buta-1,3-diene and, 282 conjugated dienes and, 282– 283 Hückel 4n ϩ rule and, 317 Molecular weight, determination of, 370 Molecule, electron-dot structures of, 8– lone-pair electrons in, Molozonide, 270 Monomer, 274 Monosaccharide(s), 863 aldaric acids from, 881 i-21 alditols from, 879– 880 aldonic acids from, 880– 881 anomers of, 873– 874 configurations of, 870– 871 cyclic forms of, 873– 874 essential, 882– 883 esters from, 876– 877 ethers from, 877 Fischer projections of, 865– 867 glycosides of, 877– 878 hemiacetal forms of, 873– 874 osazones from, 898 oxidation of, 880– 881 phosphorylation of, 878– 879 reaction with acetic anhydride, 876– 877 reaction with iodomethane, 877 reaction with NaBH4, 879– 880 reaction summary of, 876– 881 reduction of, 879– 880 see also Aldose uronic acids from, 881 Monoterpene, 242 Monoterpenoid, 957 Morphine, biosynthesis of, 1022– 1030 from opium, 1022 mechanism of action of, 1023 specific rotation of, 141 structure of, 63 Morphine alkaloids, 1022– 1023 Morphine rule, 1023 MRI, see Magnetic resonance imaging, 432 mRNA, see Messenger RNA MS, see Mass spectrometry Mullis, Kary, 1004 Multiplet (NMR), 423– 425 table of, 426 Mutarotation, 874 glucose and, 874 mechanism of, 874 L-Mycarose, structure of, 1039 3-O-Mycarosylerythronolide B, structure of, 1039 Mycomycin, stereochemistry of, 172 Mylar, structure of, 677 myo-Inositol, structure of, 133 Myoglobin, ␣ helix in, 813 ribbon model of, 813 Myrcene, structure of, 242 Myristic acid, catabolism of, 950 structure of, 938 n (normal), 79 n ϩ rule (NMR), 425 N-terminal amino acid, 803 NAD؉, see Nicotinamide adenine dinucleotide NADH, see Nicotinamide adenine dinucleotide (reduced) NADPH, see Nicotinamide adenine dinucleotide phosphate (reduced) Naming, acid anhydrides, 644 acid chlorides, 644 acid halides, 644 acyl groups, 612 acyl phosphates, 646 alcohols, 503– 504 i-22 index Naming (continued) aldehydes, 565 aldoses, 870– 871 alkanes, 79– 80, 84– 88 alkenes, 216– 217 alkyl groups, 81– 82, 86– 87 alkyl halides, 445– 446 alkynes, 218 alphabetization and, 86, 88 amides, 645 amines, 750– 751 aromatic compounds, 310– 312 carboxylic acid derivatives, 644– 646 carboxylic acids, 611– 612 cycloalkanes, 106– 108 cycloalkenes, 217 enzymes, 816 esters, 645 ethers, 528 heterocyclic amines, 751 ketones, 566 nitriles, 613 phenols, 504 sulfides, 528 thioesters, 645 thiols, 504 Naphthalene, aromaticity of, 323 electrostatic potential map of, 323 Hückel 4n ϩ rule and, 323 molecular model of, 64 orbitals in, 323 reaction with Br2, 323 resonance in, 322 Naproxen, structure of, 32, 358 Natural gas, composition of, 98 thiols in, 526 Natural product, 1015 alkaloids, 1016– 1017 bioprospecting for, 1041 classification of, 1016– 1017 drugs from, 205 enzyme cofactors, 1016– 1017 fatty-acid derived substances, 1016– 1017 nonribosomal polypeptides, 1016– 1017 polyketides, 1016– 1017 terpenoids and steroids, 1016– 1017 Natural rubber, structure of, 298 vulcanization of, 298 NBS, see N-Bromosuccinimide NDA, see New drug application, 205– 206 Neopentyl group, 87 SN2 reaction and, 461 Neuraminic acid, biosynthesis of, 883 influenza virus and, 883 Neuraminidase, influenza virus and, 930 New drug application (NDA), 205– 206 New molecular entity (NME), number of, 205 Newman projection, 91 molecular model of, 91 Nicotinamide adenine dinucleotide (NAD؉), oxidative deamination and, 841 biological oxidation with, 522, 817 yeast alcohol dehydrogenase and, 161 Nicotinamide adenine dinucleotide (reduced), biological reduction with, 511, 587– 588 structure of, 203 Nicotinamide adenine dinucleotide phosphate (reduced), biological reduction with, 265, 511 Nicotine, structure of, 28, 749 Ninhydrin, reaction with amino acids, 804 Nitration (aromatic), 328– 329 Nitric acid, pKa of, 50 Nitrile(s), 613 alkylation of, 714 amides from, 625 amines from, 626 carboxylic acids from, 620, 625– 626 from alkyl halides, 620 from amides, 624 Grignard reaction of, 626 hydrolysis of, 620, 625– 626 IR spectroscopy of, 627 ketones from, 626 mechanism of hydrolysis of, 625 naming, 613 naturally occurring, 623 NMR spectroscopy of, 628 nucleophilic additions to, 624 pKa of, 705 reaction summary of, 630– 631 reaction with LDA, 714 reaction with LiAlH4, 626 reduction of, 626 synthesis of, 624 Nitrile group, directing effect of, 342– 343 inductive effect of, 339– 340 orienting effect of, 343 resonance effect of, 339– 340 Nitro group, directing effect of, 342– 343 inductive effect of, 339– 340 orienting effect of, 343 resonance effect of, 339– 340 Nitroarene, arylamines from, 760 reaction with iron, 760 reaction with tin, 760 reduction of, 760 Nitrobenzene, aniline from, 328– 329 reduction of, 328– 329 synthesis of, 328 p-Nitrobenzoic acid, pKa of, 618 Nitrogen rule (mass spectrometry), 396, 777 Nitronium ion, 328– 329 electrostatic potential map of, 328 p-Nitrophenol, pKa of, 506 p-Nitrophenoxide ion, resonance in, 507 NME, see New molecular entity NMR, see Nuclear magnetic resonance Node, Nomenclature, see Naming Nonbonding electrons, Noncoding strand (DNA), 995 Noncovalent interaction, 60 dipole– dipole forces and, 60 dispersion forces and, 60 hydrogen bonds and, 60– 61 kinds of, 60– 62 van der Waals forces and, 60 Nonequivalent protons, spin– spin splitting and, 428– 430 tree diagram in NMR of, 429– 430 Nonessential amino acid, 850– 851 biological precursors of, 851 Nonribosomal polypeptide, 1017 Nootkatone, structure of, 139 (S)-Norcoclaurine, biosynthesis of, 1026– 1027 Norcoclaurine synthase, function of, 1015, 1026 molecular model of, 1015 Norepinephrine, biosynthesis of, 348 Norethindrone, structure and function of, 969 Normal (n) alkane, 79 Noyori, Ryoji, 599 NSAID, 357– 358 Nuclear magnetic resonance spectrometer, operation of, 408 Nuclear magnetic resonance spectroscopy (NMR), 404 acid anhydrides, 680 acid chlorides, 680 alcohols, 537 aldehydes, 594 amides, 680 amines, 776– 777 13C chemical shifts in, 412 calibration peak for, 409 carboxylic acid derivatives, 680 carboxylic acids, 628 chart for, 409 coupling constants in, 425– 426 delta scale for, 409 DEPT-NMR and, 415– 416 diastereotopic protons and, 420 enantiotopic protons and, 419 energy levels in, 405 esters, 680 ethers, 537 field strength and, 405– 406 FT-NMR and, 411– 412 1H chemical shifts in, 421– 422 homotopic protons and, 419 integration of 1H spectra, 423 ketones, 594 multiplets in, 424– 426 n ϩ rule and, 425 nitriles, 628 overlapping signals in, 429 peak assigning in 13C spectra, 412, 415– 416 peak size in 13C spectra, 413 peak size in 1H spectra, 423 phenols, 537 principle of, 405– 406 proton equivalence and, 418– 420 radiofrequency energy and, 405– 406 shielding in, 406– 408 signal averaging in, 411– 412 spin-flips in, 405 spin– spin splitting in, 424– 427 time scale of, 408 uses of 13C spectra in, 417– 418 uses of 1H spectra in, 430– 431 index 13C Nuclear magnetic resonance spectrum, acetaldehyde, 594 acetophenone, 594 benzaldehyde, 594 benzoic acid, 628 p-bromoacetophenone, 413 butan-2-one, 413, 594 crotonic acid, 628 cyclohexanone, 594 cyclohexanol, 537 ethyl benzoate, 439 methyl acetate, 407 methyl propanoate, 414 1-methylcyclohexene, 418 N-methylcyclohexylamine, 777 pentan-1-ol, 411 propanenitrile, 628 propanoic acid, 628 1H Nuclear magnetic resonance spectrum, acetaldehyde, 594 anethole, 551 bromoethane, 424 2-bromopropane, 425 trans-cinnamaldehyde, 429 cyclohexylmethanol, 431 ethyl acetate, 680 methyl acetate, 407 methyl 2,2-dimethylpropanoate, 423 2-methylbutan-2-ol, 428 1-methylcyclohexanol, 431 N-methylcyclohexylamine, 777 p-methoxypropiophenone, 427 phenacetin, 789 phenylacetic acid, 628 propan-1-ol, 537 toluene, 429 Nuclear spin, common nuclei and, 406 NMR and, 405– 406 Nuclease, function of, 1005 Nucleic acid, 987-990 biosynthesis of, 1008– 1009 catabolism of, 1005– 1007 hydrolysis of, 1005 phosphodiester bonds in, 989 see also Deoxyribonucleic acid, Ribonucleic acid structure of, 989– 990 synthesis of, 1001– 1003 Nucleophile, 184– 185 characteristics of, 189– 190 curved arrows and, 183– 184, 189– 190 electrostatic potential maps of, 184 examples of, 184 SN1 reaction and, 473 SN2 reaction and, 462– 463 Nucleophilic acyl substitution reaction, 560, 647– 648 abbreviated mechanism for, 852– 853 acid anhydrides, 664– 665 acid chlorides, 659– 663 acid halides, 659– 663 amides, 671– 673 biological example of, 657– 659 carboxylic acids and, 652– 657 esters, 666– 670 kinds of, 650– 651 mechanism of, 647– 648 reactivity in, 649– 650 Nucleophilic carbonyl addition reaction, 558– 559, 569– 571 acid catalysis of, 572– 574 base catalysis of, 572– 574 kinds of, 570 mechanism of, 569 steric hindrance in, 570– 571 trajectory of, 571 Nucleophilic aromatic substitution reaction, 344– 346 characteristics of, 346 mechanism of, 345 Nucleophilic substitution reaction, 455 biological examples of, 476– 477 see also SN1 reaction, SN2 reaction summary of, 486– 487 Nucleophilicity, 463 basicity and, 463 table of, 463 trends in, 463 Nucleosidase, function of, 1005 Nucleoside, 987-990 Nucleoside phosphorylase, function of, 1006 Nucleotidase, function of, 1005 Nucleotide, 987-990 biosynthesis of, 1008– 1009 catabolism of, 1005– 1007 3Ј end of, 989 5Ј end of, 989 Nucleus, size of, Nylon, 677 naming, 677 uses of, 677 Nylon 6, structure of, 676 Nylon 66, structure of, 676– 677 Ocimene, structure of, 244 Octane number (fuel), 98 Octet rule, -oic acid, name ending for carboxylic acids, 611 Okazaki fragment, DNA replication and, 994 -ol, alcohol name ending, 503 Olefin, 212 Oleic acid, structure of, 938 Oligonucleotide, 1000 synthesis of, 1001– 1003 Olive oil, composition of, 938 -one, ketone name ending, 566 -onitrile, nitrile name ending, 613 Opium, 1022 Optical activity, measurement of, 140– 141 Optical isomers, 143 Optically active, 140 Orbital, energies of, hybridization of, 12– 19 shapes of, 5– d Orbital, shape of, p Orbital, algebraic signs of lobes in, 21, 219 lobes of, nodes in, shape of, 5– i-23 s Orbital, shape of, Organic acids, 53– 55 Organic bases, 55– 56 Organic chemicals, elements found in, number of, 70 size of, toxicity of, 25 Organic chemistry, Organic reactions, conventions for writing, 229 kinds of, 176– 177 Organic synthesis, enantioselective, 599 strategy for, 349– 354 Organoborane, from alkenes, 259 reaction with H2O2, 259 Organodiphosphate, biological SN1 reactions and, 476– 477 Friedel-Crafts reactions and, 334– 335 Organometallic compound, 453 polarity of, 182 Organophosphate, sp3 hybrid orbitals in, 19 structure of, 19 Ornithine, biosynthesis of, 853– 854 citrulline from, 842– 843 from arginine, 845 reaction with carbamoyl phosphate, 842– 843 urea cycle and, 842– 843 Ornithine transcarbamoylase, function of, 843 Ortho (o), 311 Ortho- and para-directing group, 337 Osazone, 898 -ose, carbohydrate name ending, 864 Oseltamivir, mechanism of, 930 molecular model of, 128 see also Tamiflu -oside, glycoside name ending, 878 Osmium tetroxide, reaction with alkenes, 269 toxicity of, 269 Oxalic acid, structure of, 612 Oxaloacetate, aspartate from, 842, 851– 852 decarboxylation of, 924– 925 from malate, 919 from pyruvate, 923– 924 phosphoenolpyruvate from, 924– 925 reaction with acetyl CoA, 916– 917 Oxaloacetic acid, structure of, 612 Oxalosuccinate, decarboxylation of, 917– 918 from isocitrate, 917– 918 Oxidation, alcohols, 520– 522 aldehydes, 568– 569 FAD and, 946– 948 NAD؉ and, 522, 817 organic, 265– 266 phenols, 523 Oxidative deamination, 841 mechanism of, 841 Oxidative decarboxylation, 911 a-ketoglutarate and, 918 mechanism of, 912 pyruvate and, 911– 915 thiamin diphosphate and, 911– 913 i-24 index Oxidoreductase, 816 Oxidosqualene:lanosterol cyclase, function of, 970 Oxirane, 266 see also Epoxide Oxo group, 566 Oxymercuration, 258 mechanism of, 258 regiochemistry of, 258 Oxytocin, structure of, 830 -oyl, name ending for acyl groups, 612 Ozone, laboratory preparation of, 270 reaction with alkenes, 270 Ozonide, 270 dangers of, 270 reduction of with zinc, 270 Paclitaxel, origin of, 1041 structure and function of, 1041 Palmitic acid, fatty acid biosynthesis and, 956 structure of, 938 Palmitoleic acid, structure of, 938 PAM resin, peptide synthesis and, 811 Pancreatic lipase, function of, 643 molecular model of, 643 Papaver somniferum, morphine from, 1022 Para (p), 311 Paraffin, 89 Parent (nomenclature), 84 Parent peak (mass spectrum), 369 Partial charge, 34– 35 Pasteur, Louis, 142 enantiomers and, 142– 143 Patchouli alcohol, structure of, 957 Pauli exclusion principle, Pauling, Linus, 12 PCR, see Polymerase chain reaction, 1004– 1005 PDB, see Protein Data Bank Peanut oil, composition of, 938 Penicillin, discovery of, 683 mechanism of action of, 684 Penicillin G, structure of, 671 Penicillin V, specific rotation of, 141 stereochemistry of, 165 Penta-1,4-diene, electrostatic potential map of, 282 Pentadienyl radical, resonance forms of, 46– 47 Pentalene dianion, aromaticity of, 363 Pentane, molecular model of, 78 Pentane-2,4-dione, pKa of, 704 Pentane-2,4-dione anion, resonance forms of, 45– 46 Pentan-1-ol, 13C NMR spectrum of, 411 Pentose phosphate pathway, 934, 925 PEP, see Phosphoenolpyruvate Pepsin, isoelectric point of, 799 Peptide, 791 amino acid analysis of, 804– 805 backbone of, 803 covalent bonding in, 803 disulfide bonds in, 803– 804 Edman degradation of, 805– 806 hydrolysis of, 804 partial hydrolysis of, 807 reaction with phenylisothiocyanate, 805– 806 see also Protein sequencing of, 805– 807 solid-phase synthesis of, 809– 811 synthesis of, 807– 812 Peptide bond, 802 DCC formation of, 809 restricted rotation in, 803 Pericyclic reaction, 285– 289 Diels– Alder reaction and, 285– 289 Claisen rearrangement and, 533– 534 Periodic acid, diol cleavage with, 271 Periplanar, 482 E2 reactions and, 482– 483 Perlon, structure of, 676 Peroxyacid, 266 reaction with alkenes, 266 Petroleum, catalytic cracking of, 98 composition of, 98 gasoline from, 98 refining of, 98 Pfu DNA polymerase, 1004 PGA, see Poly(glycolic acid), 678 Pharmaceuticals, approval procedure for, 205– 206 origin of, 205 PHB, see Poly(hydroxybutyrate), 678 Phenacetin, 1H NMR spectrum of, 789 Phenol(s), 501 acidity of, 505– 507 electrophilic aromatic substitution of, 341– 342 electrostatic potential map of, 338 hydrogen bonds in, 505 IR spectroscopy of, 536 IR spectrum of, 536 naming, 504 NMR spectroscopy of, 537 oxidation of, 523 phenoxide ions from, 505– 507 pKa of, 506, 615 properties of, 504– 507 quinones from, 523 reaction summary of, 541 uses of, 502 Phenoxide ion, 505 resonance in, 507 Phenyl group, 311 Phenylacetaldehyde, aldol reaction of, 716– 717 IR spectrum of, 388 Phenylacetic acid, 1H NMR spectrum of, 628 Phenylalanine, from chorismate, 533– 534 molecular model of, 99 pKa of, 51 structure and properties of, 794 Phenylisothiocyanate, Edman degradation and, 805– 806 Phenylthiohydantoin, Edman degradation and, 805– 806 Phosphate, electrostatic potential map of, 74 polarity of, 74 Phosphatidic acid, structure of, 942 Phosphatidylcholine, structure of, 942 Phosphatidylethanolamine, structure of, 942 Phosphatidylserine, structure of, 942 Phosphine(s), chirality of, 158, 801 Phosphite, 1002 oxidation of, 1002– 1003 Phosphodiester, nucleic acid and, 989 Phosphoenolpyruvate, from 2phosphoglycerate, 909– 910 from oxaloacetate, 924– 925 2-phosphoglycerate from, 925 pyruvate from, 910 Phosphoenolpyruvate carboxykinase, function of, 925 Phosphofructokinase, function of, 906 Phosphoglucoisomerase, function of, 564 molecular model of, 564 2-Phosphoglycerate, from 3-phosphoglycerate, 909 from phosphoenolpyruvate, 925 3-Phosphoglycerate, from 1,3-bisphosphoglycerate, 909 isomerization of, 909 Phosphoglycerate kinase, function of, 909 Phosphoglycerate mutase, function of, 909 Phospholipid, 942– 943 abundance of, 943 classification of, 942 function of, 943 Phosphopantetheine, structure of, 674, 834 Phosphoramidite, 1002 Phosphorane, 583 Phosphoribosyl-diphosphate synthetase, function of, 987 molecular model of, 987 Phosphoric acid, pKa of, 50 Phosphoric acid anhydride, 834 Phosphorus, ground-state electron configuration of, Phosphorus oxychloride, alcohol dehydration with, 518 Phosphorus tribromide, reaction with alcohols, 452, 464, 516 Phosphorylation, ATP and, 834– 835 mechanism of, 834– 835 Photon, 377– 378 energy of, 378 Photosynthesis, 862– 863 Phthalic acid, structure of, 612 Phylloquinone, biosynthesis of, 335 Physiological pH, 617 Phytyl diphosphate, vitamin K1 biosynthesis and, 334– 335 Pi () bond, 15 acetylene and, 17 ethylene and, 15– 16 molecular orbitals in, 21 Picometer, Pinacol rearrangement, 549 Pineapple, esters in, 665 Piperidine, molecular model of, 767 structure of, 751 PITC, see Phenylisothiocyanate, 805– 806 pKa, 49 table of, 50 PKS, see Polyketide synthase PLA, see Poly(lactic acid), 678 index Planck equation, 378 Plane of symmetry, 136– 137 meso compounds and, 152 Plane-polarized light, 140 Plasmalogen, structure of, 980 Plasticizer, 666 Plexiglas, 304 Plocamium cartilagineum, alkyl halides in, 255 PLP, see Pyridoxal phosphate PMP, see Pyridoxamine phosphate Poison ivy, urushiols in, 502 Polar aprotic solvent, 465 SN1 reaction and, 474 SN2 reaction and, 465 Polar covalent bond, 34 dipole moments and, 36– 37 electronegativity and, 34– 35 electrostatic potential maps and, 35 polar reactions and, 181– 183 Polar reaction, 178, 181– 185 characteristics of, 181– 185 curved arrows in, 183– 184, 189– 190 electrophiles in, 184– 185 example of, 186– 188 nucleophiles in, 184– 185 Polarimeter, 140– 141 Polarizability, 183 Polyamide, 675 Polycyclic aromatic compound, 322– 324 Polycyclic compound, 126 conformations of, 126– 127 Polyester, 675 uses of, 677 Polyethylene, synthesis of, 275– 276 Poly(glycolic acid), 678 Poly(hydroxybutyrate), 678 Polyimide, structure of, 692 Polyketide(s), 1016– 1017 biosynthesis of, 1031– 1032 examples of, 1031– 1032 number of, 1017 Polyketide synthase, 1033 domains in, 1034 modules in, 1034 size of, 1034 Poly(lactic acid), 678 Polymer, 274 biodegradable, 678 biological, 274– 275 chain-growth, 275– 277, 676 step-growth, 676 Polymerase chain reaction (PCR), 1004– 1005 amplification factor in, 1004 taq DNA polymerase in, 1004 Polymerization, mechanism of, 275– 276 radical, 275– 277 Polypeptide, nonribosomal, 1016– 1017 Polysaccharide, 863, 886– 888 synthesis of, 888– 889 Polyunsaturated fatty acid, 937 Polyurethane, structure of, 676 Poly(vinyl pyrrolidone), 305 Porphobilinogen, biosynthesis of, 786 Potassium nitrosodisulfonate, reaction with phenols, 523 Potassium permanganate, reaction with alkenes, 271 Pravachol, mechanism of action of, 2, 977 structure of, 104 Pravadoline, green synthesis of, 781 Pravastatin, mechanism of action of, 2, 977 structure of, 104 Preeclampsia, Viagra and, 205 Prefix (nomenclature), 84 Prelaureatin, biosynthesis of, 306 Priestley, Joseph, 298 Primary alcohol, 503 Primary amine, 750 Primary carbon, 82– 83 Primary hydrogen, 82– 83 Primary protein structure, 812 Priming reaction, fatty acid biosynthesis and, 951– 952 pro-R prochirality center, 160 pro-S prochirality center, 160 Problems, how to work, 26 Procaine, structure of, 30 Prochirality, 159– 161 assignment of, 159– 160 biological reactions and, 160– 161 Re descriptor for, 159 Si descriptor for, 160 Prochirality center, 160 pro-R, 160 pro-S, 160 Progesterone, structure and function of, 968 Progestin, 968 function of, 968 Proline, biosynthesis of, 762– 763, 853– 854 catabolism of, 858 from glutamate, 853– 854 structure and properties of, 794 Promotor sequence (DNA), 994 Propagation step (radical), 179 Propane, bond rotation in, 92– 93 conformations of, 92– 93 mass spectrum of, 369 molecular model of, 78 Propane conformation, molecular model of, 93 Propanenitrile, 13C NMR absorptions in, 628 Propanoic acid, 13C NMR absorptions in, 628 Propan-1-ol, 1H NMR spectrum of, 537 Propenal, electrostatic potential maps of, 287 Propenenitrile, electrostatic potential maps of, 287 Propionyl CoA, catabolism of, 951 Propyl group, 82 Propylene, annual U.S production of, 212 heat of hydrogenation of, 226 industrial uses of, 213 Prostaglandin(s), biological functions of, 180 Prostaglandin E1, structure of, 105 Prostaglandin F2␣, structure of, 111 Prostaglandin H2, biosynthesis of, 180– 181, 278– 279 Protease, mechanism of action of, 672 i-25 Protecting group, 525 alcohols and, 524– 526 aldehydes and, 582 amino acids, 808– 809, 811 DNA synthesis and, 1001 ketones and, 582 Protein(s), 791 ␣ helix in, 812– 813 backbone of, 803 biological hydrolysis of, 672 biosynthesis of, 996– 998 classification of, 812 denaturing, 814 electrophoresis of, 799– 800 fibrous, 812 globular, 812 isoelectric point of, 799 number of in humans, 832 primary structure of, 812 purification of, 799– 800 quaternary structure of, 812 reaction with Sanger’s reagent, 345 secondary structure of, 812– 813 see also Peptide structure of, 812– 814 tertiary structure of, 812, 814 X-ray crystallography of, 739 Protein Data Bank, 823 uses of, 823 visualizing enzyme structures and, 855–856 X-ray crystallographic structures in, 739 Protein kinase A, function of, 175 molecular model of, 175 Protic solvent, SN1 reaction and, 474 SN2 reaction and, 465 Proton equivalence, 1H NMR spectroscopy and, 418– 420 Protonated methanol, electrostatic potential map of, 183 Protosteryl cation, steroid biosynthesis and, 974 Prozac, structure of, 163 see also Fluoxetine Pseudoephedrine, molecular model of, 167 PTH, see Phenylthiohydantoin, 805– 806 PUFA, see Polyunsaturated fatty acid, 937 Purification, organic compounds, 395 Purine, aromaticity of, 323 basicity of, 775 catabolism of, 1005– 1007 electrostatic potential map of, 775 Purine nucleoside phosphorylase, function of, 1006 Pyramidal inversion, amines and, 752– 753 energy barrier to, 752– 753 Pyran, structure of, 873 Pyranose, 873 Pyridine, aromaticity of, 319– 320, 772 basicity of, 755 bond lengths in, 772 dipole moment of, 773 electrophilic substitution reactions of, 772– 773 electrostatic potential map of, 320 Hückel 4n ϩ rule and, 319– 320 pKa of, 772 i-26 index Pyridoxal phosphate (PLP), 818 alanine catabolism and, 847 amino acid deamination and, 837– 841 amino acid transamination and, 837– 841 asparagine catabolism and, 848 aspartate catabolism and, 848 biosynthesis of, 1017– 1022 from PMP, 840 imine formation from, 576 imines of, 839 serine catabolism and, 847– 848 structure of, 31, 564, 769 threonine catabolism and 849– 850 Pyridoxamine phosphate (PMP), structure of, 833 transamination of, 840 Pyridoxine, structure of, 837 Pyrimidine, aromaticity of, 319– 320 basicity of, 755, 773 electrostatic potential map of, 320 Hückel 4n ϩ rule and, 319– 320 Pyrrole, aromaticity of, 320, 770 basicity of, 755, 770 electrophilic substitution reactions of, 770– 771 electrostatic potential map of, 320, 770 Hückel 4n ϩ rule and, 320 industrial synthesis of, 769– 770 Pyrrolidine, electrostatic potential map of, 770 enamines from, 731 structure of, 751 Pyrrolysine, structure of, 793 Pyruvate, acetyl CoA from, 911– 915 alanine from, 851– 852 carboxylation of, 923– 924 catabolism of, 911– 915 decarboxylation of, 911– 915 ethanol from, 932 from alanine, 847 from phosphoenolpyruvate, 910 from serine, 847– 848 oxaloacetate from, 923– 924 reaction with thiamine diphosphate, 911– 913 Pyruvate carboxylase, function of, 923 Pyruvate dehydrogenase complex, function of, 911– 915 Pyruvate kinase, function of, 910 Pyruvic acid, structure of, 612 Qiana, structure of, 692 Quantum mechanical model, 4– Quartet (NMR), 426 Quaternary ammonium salt, 750 Hofmann elimination and, 764– 765 Quaternary carbon, 82– 83 Quaternary protein structure, 812 Quinine, structure of, 324, 774 Quinoline, aromaticity of, 323 electrophilic substitution reaction of, 774 Quinone(s), 523 from phenols, 523 hydroquinones from, 523 reduction of, 523 R configuration, 145 assignment of, 143– 145 R group, 82 Racemate, 154 Racemic mixture, 154 Radical, 178 reactivity of, 178– 181 Radical reaction, 178– 181 addition to alkenes, 275– 277 biological additions, 180– 181, 278– 279 characteristics of, 178– 180 fishhook arrows and, 177– 178 initiation steps in, 179 polymerization and, 275– 277 propagation steps in, 179– 180 prostaglandin biosynthesis and, 278– 279 termination steps in, 180 Radio waves, electromagnetic spectrum and, 377 Radiofrequency energy, NMR spectroscopy and, 405– 406 Rapa Nui, rapamycin from, 1041 Rapamycin, immunosuppressant activity of, 1041 structure and function of, 1032 Rate equation, 458 Rate-determining step, 467 Rate-limiting step, 467 Rayon, synthesis of, 886 Re prochirality, 159 Reaction (polar), 178, 181– 185 Reaction (radical), 178– 181 Reaction coordinate, 198 Reaction energy diagram, 197– 199 biological reactions and, 201 electrophilic addition reactions and, 198– 199 endergonic reactions and, 198– 199 exergonic reactions and, 198– 199 intermediates and, 200– 201 Reaction intermediate, 200 electrophilic addition reactions and, 200– 201 Reaction mechanism, 177 Reaction rate, activation energy and, 198– 199 Rearrangement reaction, 177 Red fox, scent marker in, 551 Reducing sugar, 880 Reduction, acid chlorides, 662 aldehydes, 510– 511, 575 alkene, 261– 265 alkyne, 290– 291 amides, 673 aromatic compounds and, 348– 349 biological reactions with NADH and NADPH, 265 carboxylic acids, 512 esters, 512, 669– 670 ketones, 510– 511, 575 lactams, 673 nitriles, 626 organic, 262 quinones, 523 Reductive amination, 761– 763 biological example of, 762– 763 mechanism of, 761– 762 Refining (petroleum), 98 Regiospecific, 230 Replication (DNA), 992– 994 Replication fork (DNA), 993 Reserpine, structure of, 63 Residue (protein), 802 Resolution (enantiomers), 154– 155 Resonance, acetate ion and, 41– 42 acetyl CoA anion and, 44 acyl cations and, 334 allylic carbocations and, 283– 284 allylic radicals and, 449 arylamines and, 757 benzene and, 42, 314 benzylic carbocation and, 471 benzylic radical and, 347 carboxylate ions and, 615– 616 enolate ions and, 703 naphthalene and, 322 p-nitrophenoxide ion and, 507 pentadienyl radical and, 46– 47 pentane-2,4-dione anion and, 45– 46 phenoxide ion and, 507 Resonance effect (electrophilic aromatic substitution), 339– 340 Resonance form, 42 drawing, 45– 47 electron movement and, 43– 44 rules for, 43– 44 stability of, 44 three-atom groupings in, 45– 47 Resonance hybrid, 42 Restriction endonuclease, 999 Reticuline, biosynthesis of, 1027– 1028 epimerization of, 1027– 1028 Retinal, vision and, 393– 394 Reye’s syndrome, aspirin and, 358 Rhodopsin, isomerization of, 393– 394 vision and, 393– 394 Ribavirin, structure of, 362 Ribonucleic acid (RNA), 987-990 bases in, 988 biosynthesis of, 994– 995 3Ј end of, 989 5Ј end of, 989 functional, 994 kinds of, 994 messenger, 994 ribosomal, 994 size of, 988 small, 994 structure of, 989– 990 transfer, 994 translation of, 996– 998 Ribonucleotide, biosynthesis of, 1008– 1009 catabolism of, 1005– 1007 structures of, 989 Ribose, configuration of, 871 Ribosomal RNA, 994 function of, 996 Ring-flip (cyclohexane), 119 energy barrier to, 119 molecular model of, 119 index Risk, chemicals and, 25 RNA, see Ribonucleic acid Robinson, Robert, 1023 Rod cells, vision and, 393– 394 Rofecoxib, structure of, 358 Rosuvastatin, mechanism of action of, 2, 977 rRNA, see Ribosomal RNA Rubber, history of, 298 vulcanization of, 298 S configuration, 145 assignment of, 143– 145 s-Cis conformation, 287– 288 Diels– Alder dienes and, 287– 288 Saccharin, structure of, 892 sweetness of, 892 Saccharopine, from lysine, 859 oxidative deamination of, 860 SAH, see S-Adenosylhomocysteine Salt bridge (protein), 814 Salutaridine, biosynthesis of, 1028– 1029 Salutaridine reductase, function of, 1029 SAM, see S-Adenosylmethionine Sanger, Frederick, 999 Sanger dideoxy DNA sequencing, 999– 1000 Sanger’s reagent, 345 uses of, 345 Saponification, 667, 940 mechanism of, 667 Saturated, 77 Sawhorse representation, 91 Schiff base, 907 see also Imine Scurvy, vitamin C and, 631 sec-Butyl group, 82 Second-order reaction, 458 Secondary alcohol, 503 Secondary amine, 750 Secondary carbon, 82– 83 Secondary hydrogen, 82– 83 Secondary metabolite, 1015 examples of, 1015– 1016 function of, 1015 number of, 1015 Secondary protein structure, 812– 813 ␣ helix in, 812– 813  sheet in, 812– 813 Sedoheptulose, structure of, 864 Selenocysteine, structure of, 793 Semiconservative replication (DNA), 993 Sense strand (DNA), 995 Sequence rules (Cahn– Ingold– Prelog), 143– 145 alkenes and, 221– 222 enantiomers and, 143– 145 Serine, catabolism of, 847– 848, 858 molecular model of, 167 pyruvate from, 847– 848 structure and properties of, 795 Serine dehydratase, function of, 847 Serylalanine, molecular model of, 802 Sesquiterpene, 242 Sesquiterpenoid, 957 Sex hormone, 968 Sharpless, K Barry, 599 Sharpless epoxidation, 599 Shell (electron), capacity of, Shielding (NMR), 406– 408 Si prochirality, 160 Sialic acid, 883 Side chain (amino acid), 793 Sigma () bond, 11 cylindrical symmetry of, 11 Signal averaging, FT-NMR spectroscopy and, 411– 412 Sildenafil, preeclampsia and, 205 structure of, 769 Silver oxide, Hofmann elimination reaction and, 764 Silyl ether, alcohol protecting group, 525– 526 Simple sugar, 863 Simvastatin, mechanism of action of, 2, 977 structure of, 104 Single bond, electronic structure of, 13– 14 length of, 13– 14 see also Alkane strength of, 13– 14 Skeletal structure, 22 rules for drawing, 22– 23 Skunk scent, cause of, 526 Small RNAs, 994 sn-, naming prefix, 946 SN1 reaction, 467 allylic halides in, 471– 472 benzylic halides in, 471– 472 biological example of, 476– 477 carbocation stability and, 471– 472 characteristics of, 471– 475 energy diagram for, 468 Hammond postulate and, 471 ion pairs in, 469– 470 kinetics of, 467 leaving groups in, 472– 473 mechanism of, 467– 468, 473 nucleophiles and, 473 racemization in, 469– 470 rate law for, 467 rate-limiting step in, 467– 468 solvent effects on, 474 stereochemistry of, 469– 470 substrate structure and, 471– 472 summary of, 474– 475 SN2 reaction, 458 allylic halides in, 472 amines and, 760– 761 benzylic halides in, 472 biological example of, 476– 477 characteristics of, 460– 467 electrostatic potential maps of, 459 inversion of configuration in, 458– 459 kinetics of, 457– 458 leaving groups and, 463– 464 mechanism of, 458– 459 nucleophiles in, 462– 463 rate law for, 458 solvent effects and, 465 stereochemistry of, 458– 459 steric hindrance in, 460– 461 substrate structure and, 460– 461 i-27 summary of, 466 table of, 462 Williamson ether synthesis and, 529– 530 epoxide cleavage and, 532 Soap, 940– 941 history of, 940 manufacture of, 940 mechanism of action of, 940– 941 micelles and, 940– 941 Sodium amide, reaction with alcohols, 506– 507 Sodium ammonium tartrate, optical activity of, 142– 143 Sodium bisulfite, osmate reduction with, 269 Sodium borohydride, reaction with aldehydes, 510 reaction with ketones, 510 reaction with organomercury compounds, 258 reductive amination with, 761– 762 Sodium chloride, dipole moment of, 37 Sodium cyclamate, LD50 of, 25 Sodium hydride, reaction with alcohols, 506– 507 Solid-phase synthesis, DNA and, 1001– 1003 peptides and, 809– 811 see also Merrifield, 809– 811 Solvation, 465 carbocations and, 474 SN2 reaction and, 465 Solvent, polar aprotic, 465 SN1 reaction and, 474 SN2 reaction and, 465 Soot, carcinogenic compounds in, 268 Sorbitol, from glucose, 609 structure of, 879 Spandex, structure of, 676 Specific rotation, 141 table of, 141 Sphingomyelin, 942 function of, 942 Sphingosine, structure of, 943 Spin-flip, NMR spectroscopy and, 405 Spin– spin splitting (NMR), 424– 427 alcohols and, 537 bromoethane and, 424– 425 2-bromopropane and, 425 13C NMR spectroscopy and, 427 1H NMR spectroscopy and, 424– 427 n ϩ rule and, 425 nonequivalent protons and, 426– 427 origin of, 424– 427 rules for, 426– 427 tree diagrams and, 429– 430 Squalene, biological epoxidation of, 266– 267, 970– 971 from farnesyl diphosphate, 962, 970 steroid biosynthesis and, 970– 971 Squalene epoxidase, function of, 970 Staggered conformation, 91 molecular model of, 92 Standard state, biological, 193 thermodynamic, 193 i-28 index Starch, digestion of, 887– 888 glucose from, 902– 903 hydrolysis of, 902– 903 limit dextrin from, 902– 903 maltotriose from, 902– 903 structure of, 887– 888 Statins, mechanism of action of, 2, 977 Stationary phase, chromatography and, 395 Stearic acid, molecular model of, 938 structure of, 938 Step-growth polymer, 676 table of, 676 Stereochemistry, 90 absolute configuration and, 147 cis– trans cycloalkane isomers and, 109– 110 cis– trans alkene isomers and, 219– 220 diastereomers and, 150 Diels– Alder reaction and, 287 E, Z alkene isomers and, 221– 222 E1 reaction and, 485 E2 reactions and, 482– 483 enantiomers and, 135– 136 epimers and, 150 R,S configuration and, 143– 145 SN1 reaction and, 469– 470 SN2 reactions and, 458– 459 Stereogenic center, 137 Stereoisomers, 110 cis– trans isomers and, 109– 110, 219– 220 diastereomers and, 150 enantiomers and, 142– 143 epimers and, 150 kinds of, 157– 158 properties of, 152 Stereospecific, 273 Stereospecific numbering (sn-), 946 Steric hindrance, SN2 reaction and, 460– 461 Steric strain, 94 cis alkenes and, 223– 224 substituted cyclohexanes and, 121– 122 Steroid, 965– 969 adrenocortical, 968– 969 anabolic, 969 biosynthesis of, 969– 975 classification of, 967– 968 conformations of, 127, 966– 967 molecular model of, 965 numbering of, 965 shape of, 965 synthetic, 969 Steroid hormones, 967– 969 Stork enamine reaction, 731– 732 mechanism of, 731– 732 STR loci, DNA fingerprinting and, 1010 Straight-chain alkane, 78 Strecker synthesis, 790 Structure, condensed, 21 electron-dot, Kekulé, Lewis, line-bond, skeletal, 22 Strychnine, LD50 of, 25 Substituent effect, electrophilic aromatic substitution and, 336– 343 summary of, 343 Substitution reaction, 176 Substrate (enzyme), 815 Succinate, dehydrogenation of, 919 from succinyl CoA, 918 fumarate from, 919 Succinate dehydrogenase, function or, 919 Succinic acid, structure of, 612 Succinyl CoA, from ␣-ketoglutarate, 918 succinate from, 918 Succinyl CoA synthetase, function of, 918 Sucralose, structure of, 892 sweetness of, 892 Sucrose, molecular model of, 886 sources of, 885 specific rotation of, 141 structure of, 886 sweetness of, 892 Suffix (nomenclature), 84 Sugar, complex, 863 D, 869 L, 869 see also Aldose, Carbohydrate, Monosaccharide simple, 863 Sulfa drugs, 768 synthesis of, 329 Sulfanilamide, structure of, 329 synthesis of, 768 Sulfathiazole, structure of, 768 Sulfide(s), 501 electrostatic potential map of, 75 from thiols, 534 naming, 528 occurrence of, 502 oxidation of, 535 polarity of, 74 reaction with alkyl halides, 534– 535 sp3 hybrid orbitals in, 19 structure of, 19 sulfoxides from, 535 Sulfonamides, synthesis of, 329 Sulfonation (aromatic), 329 Sulfone, 535 from sulfoxides, 535 Sulfonium salt, 159 chirality of, 159 Sulfoxide(s), 535 from sulfides, 535 oxidation of, 535 Sutures, absorbable, 678 Sweeteners, synthetic, 892 Swine flu, 929– 930 Swine H1N1 virus, 929 Symmetry plane, 136– 137 Syn periplanar, 482 molecular model of, 482 Syn stereochemistry, 259 Synthase, 951, 1031 Synthesis, trisubstituted aromatic compounds and, 349– 354 Table sugar, see Sucrose Talose, configuration of, 871 Tamiflu, influenza virus and, 930 mechanism of, 930 molecular model of, 128 Tamoxifen, synthesis of, 604 Taq DNA polymerase, PCR and, 1004 Tartaric acid, stereoisomers of, 151– 152 meso-Tartaric acid, molecular model of, 152 Tautomer, 696 Tautomerism, 696 Tazobactam, structure of, 691 Termination step (radical), 180 Terpene, 242, 956 biosynthesis of, 242– 243 number of, 242 see also Terpenoid Terpene cyclase, function of, 964 Terpenoid, 242, 956– 964 biosynthesis of, 956– 964 classification of, 957 number of, 1016 occurrence of, 957 ␣-Terpineol, biosynthesis of, 964 tert-Amyl group, 87 tert-Butyl group, 82 Tertiary alcohol, 503 Tertiary amine, 750 Tertiary carbon, 82– 83 Tertiary hydrogen, 82– 83 Tertiary protein structure, 812, 814 hydrophilic interactions in, 814 hydrophobic interactions in, 814 noncovalent interactions in, 814 salt bridges in, 814 Testosterone, conformation of, 127 molecular model of, 127 structure and function of, 968 Tetracycline, structure and function of, 1032 Tetrahedral geometry, conventions for drawing, Tetrahydrobiopterin, monooxygenase activity and, 1024 Tetrahydrofolate, structure and function of, 818 Tetrahydrofuran, as reaction solvent, 253 molecular model of, 502 Tetramethylsilane, NMR spectroscopy and, 409 Tetrapyrroles, biosynthesis of, 1042 Tetraterpenoid, 957 Tetrazole, DNA synthesis and, 1002 Thebaine, biosynthesis of, 1030– 1031 Thermodynamic quantities, 194– 195 Thermodynamic standard state, 193 Thiamin, aromaticity of, 322 basicity of, 771 Thiamin diphosphate, decarboxylations with, 911– 913 pKa of, 911– 913 reaction with pyruvate, 911– 913 structure and function of, 818 structure of, 913 ylide from, 911– 913 Thiazole, basicity of, 771 Thiazolium ring, aromaticity of, 322 pKa of, 911– 913 Thioacetal, synthesis of, 603 index Thioanisole, electrostatic potential map of, 634 -thioate, thioester name ending, 645 Thioester(s), 643 biological hydrolysis of, 690 biological partial reduction of, 675 biological reactivity of, 674– 675 electrostatic potential map of, 649 naming, 645 pKa of, 705 polarity of, 75 Thioesterase domain, polyketide synthase and, 1035 Thioglycolic acid, pKa of, 635 Thiol(s), 501 acidity of, 506 disulfides from, 527 electrostatic potential map of, 75 from alkyl halides, 527 hydrogen bonding in, 505 naming, 504 occurrence of, 502 odor of, 526 oxidation of, 527 polarity of, 74 polarizability of, 183 reaction summary of, 541 reaction with alkyl halides, 534 reaction with Br2, 527 reaction with NaH, 534 sp3 hybrid orbitals in, 19 structure of, 19 sulfides from, 534 thiolate ions from, 534 -thiol, thiol name ending, 504 Thionyl chloride, reaction with alcohols, 452, 464, 516 reaction with amides, 624 reaction with carboxylic acids, 652– 653 Thiophene, aromaticity of, 321 Thiophenol, 501 Thiourea, reaction with alkyl halides, 527 Threonine, catabolism of, 849– 850, 858 glycine from, 849– 850 stereoisomers of, 149 structure and properties of, 795 Threose, configuration of, 871 molecular model of, 140 Thymine, electrostatic potential map of, 991 structure of, 988 Thyroxine, biosynthesis of, 327– 328 structure of, 793 Time-of-flight (TOF) mass spectrometry, 376 sensitivity of, 376 Tin, reaction with nitroarenes, 760 Titration curve, amino acids and, 798 TMS, see Tetramethylsilane, 409 Tollens test, 880 Toluene, electrostatic potential map of, 340 1H NMR spectrum of, 429 IR spectrum of, 386 Torsional strain, 92 Tosylate, 455– 456 from alcohols, 464 Toxicity, chemicals and, 25 TPP, see Thiamin diphosphate Trans fatty acid, formation of, 264 from hydrogenation of fats, 939 Transamination, 837 amino acids and, 837– 841 mechanism of, 837– 841 PMP and, 840 Transcription (DNA), 994– 995 Transesterification, 668– 669 Transfer RNA, 994 anticodons in, 997 function of, 996– 998 molecular model of, 997 shape of, 996– 997 Transferase, 816 Transimination, 839 amino acids and, 839 mechanism of, 839 Transition state, 198 Hammond postulate and, 236– 238 Translation (RNA), 996– 998 Tree diagram (NMR), 429– 430 Triacylglycerol, 937 catabolism of, 943– 951 Trialkylsulfonium salt, alkylations with, 535 from sulfides, 534– 535 1,2,4-Triazole, aromaticity of, 362 Tricarboxylic acid cycle, see Citric acid cycle Trichodiene, biosynthesis of, 986 Trifluoroacetic acid, ether cleavage with, 531 pKa of, 615 (Trifluoromethyl)benzene, electrostatic potential map of, 340 Triglyceride, see Triacylglycerol, 937 Trimethylamine, bond angles in, 752 electrostatic potential map of, 754 molecular model of, 752 Trimetozine, synthesis of, 661 2,4,6-Trinitrochlorobenzene, electrostatic potential map of, 345 Triose phosphate isomerase, function of, 901, 908 molecular model of, 901 Triphenylphosphine, reaction with alkyl halides, 584 Triple bond, electronic structure of, 17– 18 length of, 17– 18 see also Alkyne strength of, 17– 18 Triplet (NMR), 426 Trisubstituted aromatic compound, synthesis of, 349– 354 Triterpenoid, 957 tRNA, see Transfer RNA Trypsin, peptide cleavage with, 807 Tryptophan, pKa of, 51 structure and properties of, 795 Tswett, Mikhail, 395 Turnover number (enzyme), 815 Twist-boat cyclohexane, 116– 117 molecular model of, 117 Tyrosine, aromatic hydroxylation of, 1024– 1025 biological iodination of, 327– 328 biosynthesis of, 518– 519 catabolism of, 859 structure and properties of, 795 i-29 Tyrosine 3-monooxygenase, function of, 1024 Ubiquinones, function of, 523– 524 structure of, 524 Ubiquinone– cytochrome c reductase, function of, 404 molecular model of, 404 Ultraviolet light, electromagnetic spectrum and, 377 wavelength of, 389 Ultraviolet spectroscopy, 389– 392 absorbance and, 390 conjugation and, 391– 392 HOMO– LUMO transition in, 389– 390 interpretation of, 391– 392 molar absorptivity and, 391 Ultraviolet spectrum, benzene, 392 -carotene, 393 but-3-en-2-one, 392 buta-1,3-diene, 390 cyclohexa-1,3-diene, 392 ergosterol, 400 hexa-1,3,5-triene, 392 Unimolecular, 467 Unsaturated, 213 Unsaturated aldehyde, conjugate addition reactions of, 588– 592 Unsaturated ketone, conjugate addition reactions of, 588– 592 Unsaturation, degree of, 213 Upfield (NMR), 409 Uracil, structure of, 988 Urea, from ammonia, 841– 845 Urea cycle, 842– 845 steps in, 843 Uric acid, from xanthine, 1007 pKa of, 636 structure of, 636, 841 Uridine triphosphate, glycoconjugate biosynthesis and, 878– 879 Urocanase, active site of, 856 molecular model of, 856 ribbon model of, 856 Uronic acid(s), 881 from aldoses, 881 Urushiols, structure of, 502 UV, see Ultraviolet Valence bond theory, 10– 19 orbital hybridization and, 12– 19 orbital overlap in, 10– 12 Valence shell, Valine, structure and properties of, 795 Valium, see Diazepam van der Waals forces, 60 alkanes and, 90 van’t Hoff, Jacobus, Vasopressin, structure of, 804 Vegetable oil, 937 hydrogenation of, 264, 939 table of, 938 Vent DNA polymerase, 1004 Viagra, see Sildenafil Vinyl group, 217 Vinyl monomer, 276 i-30 index Vinylic, 332 Vinylic anion, electrostatic potential map of, 292 Vinylic carbocation, 332 Vinylic halide, SN2 reaction and, 461 Vioxx, see Rofecoxib Virion, 930 Visible light, electromagnetic spectrum and, 377 Vision, chemistry of, 393– 394 retinal and, 393– 394 Vitamin, 816 chromatography of, 395 coenzymes from, 816 Vitamin A acetate, industrial synthesis of, 585 Vitamin B6, structure of, 837 Vitamin B12, structure of, 976 Vitamin C, from glucose, 632 history of, 631 industrial synthesis of, 632 molecular model of, 631 scurvy and, 631 uses of, 631 Vitamin K1, biosynthesis of, 335 VLDL, heart disease and, 978– 979 Volcano, chloromethane from, 444 Vulcanization, 298 rubber and, 298 Walden, Paul, 455 Walden inversion, 455– 457 Wang resin, peptide synthesis and, 811 Water, acid– base behavior of, 49 conjugate addition reactions to enones, 590 dipole moment of, 37 electrophilicity of, 185 electrostatic potential map of, 52, 184 hydrogen bond in, 60– 61 nucleophilic addition reactions of, 572– 574 nucleophilicity of, 185 pKa of, 50 reaction with aldehydes, 572– 574 reaction with enones, 590 reaction with ketones, 572– 574 Watson, James, 990 Watson– Crick DNA model, 990– 991 Wave equation, Wave function, molecular orbitals and, 20– 21 Wavelength (), 377– 378 Wavenumber, 380 Wax, 937 Whale blubber, composition of, 938 Williamson ether synthesis, 529– 530 Ag2O in, 530 carbohydrates and, 877 mechanism of, 529– 530 Wittig reaction, 583– 585 mechanism of, 583– 584 uses of, 585 ylides in 583– 584 Wohl degradation, 898 Wood alcohol, 501 X rays, electromagnetic spectrum and, 377 X-ray crystallography, 738– 739 X-ray diffractometer, 738 Xanthine, biological oxidation of, 1007 from guanine, 1006 Xanthine oxidase, function of, 1007 Xylose, configuration of, 871 Yeast alcohol dehydrogenase, stereochemistry of, 161 -yl, alkyl group name ending, 81 Ylide, 583 synthesis of, 584 -yne, alkyne name ending, 218 Z configuration, 221 assignment of, 221– 222 Zaitsev, Alexander, 478 Zaitsev’s rule, 478 alcohol dehydration and, 516– 517 Hofmann elimination and, 765 NMR proof for, 417– 418 Zocor, mechanism of action of, 2, 977 structure of, 104 Zusammen (Z configuration), 221 Zwitterion, 56, 792 amino acids and, 792 electrostatic potential map of, 792 Periodic Table of the Elements Key 79 Au Gold 196.9665 Group number, U.S system IUPAC system Metals Atomic number Symbol Name Atomic mass Semimetals Nonmetals An element 1A (1) 8A (18) Period number H He 1.0079 Helium 4.0026 3A (13) 2A (2) 4A (14) 5A (15) 6A (16) 7A (17) 10 Li Be B C N O F Ne Lithium 6.941 Beryllium 9.0122 Boron 10.811 Carbon 12.011 Nitrogen 14.0067 Oxygen 15.9994 Fluorine 18.9984 Neon 20.1797 11 12 13 14 15 16 17 18 Na Mg Al Si P S Cl Ar Sodium 22.9898 Magnesium 24.3050 Aluminum 26.9815 Silicon 28.0855 Phosphorus 30.9738 Sulfur 32.066 Chlorine 35.4527 Argon 39.948 19 Hydrogen 20 3B (3) 21 4B 5B 6B 7B 8B 8B 8B 1B 2B (4) (5) (6) (7) (8) (9) (10) (11) (12) 22 23 24 25 26 27 28 29 30 31 32 33 34 35 Ca Sc Ti V Cr Mn Fe Co Ni Cu Zn Ga Ge As Se Br Kr Calcium 40.078 Scandium 44.9559 Titanium 47.88 Vanadium 50.9415 Chromium 51.9961 Manganese 54.9380 Iron 55.847 Cobalt 58.9332 Nickel 58.693 Copper 63.546 Zinc 65.39 Gallium 69.723 Germanium 72.61 Arsenic 74.9216 Selenium 78.96 Bromine 79.904 Kyrpton 83.80 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 Rb Sr Y Zr Nb Mo Tc Ru Rh Pd Ag Cd In Sn Sb Te I Xe Rubidium 85.4678 Strontium 87.62 Yttrium 88.9059 Zirconium 91.224 Niobium 92.9064 Ruthenium 101.07 Rhodium 102.9055 Palladium 106.42 Silver 107.8682 Cadmium 112.411 Indium 114.82 Tin 118.710 Antimony 121.757 Tellurium 127.60 Iodine 126.9045 Xenon 131.29 55 56 57 72 73 74 75 76 77 78 79 80 81 82 83 84 85 86 Cs Ba La Hf Ta W Re Os Ir Pt Au Hg Tl Pb Bi Po At Rn Cesium 132.9054 Barium 137.327 Lanthanum 138.9055 Hafnium 178.49 Tantalum 180.9479 Tungsten 183.85 Rhenium 186.207 Osmium 190.2 Iridium 192.22 Platinum 195.08 Gold 196.9665 Mercury 200.59 Thallium 204.3833 Lead 207.2 Bismuth 208.9804 Polonium (209) Astatine (210) Radon (222) 87 88 89 104 105 106 107 108 109 110 111 Fr Ra Ac Rf Db Sg Bh Hs Mt Ds Rg Francium (223) Radium 227.0278 Rutherfordium Dubnium (262) Seaborgium (263) Bohrium (262) Hassium (265) Actinium (227) (261) 58 Lanthanides Numbers in parentheses are mass numbers of radioactive isotopes Actinides Ce Cerium 140.115 59 60 61 Pr Nd Pm Praseodymium Neodymium Promethium 140.9076 144.24 (145) 63 64 65 66 67 68 69 70 71 Sm Eu Gd Tb Dy Ho Er Tm Yb Lu Samarium 150.36 Europium Gadolium 157.25 Terbium 158.9253 Dysprosium 162.50 Holmium 164.9303 Erbium 167.26 Thulium 168.9342 Ytterbium 173.04 Lutetium 174.967 103 151.965 Meitnerium Darmstadtium Roentgenium (269) (272) (266) 62 36 K Potassium 39.0983 Molybdenum Technetium 95.94 (98) 90 91 92 93 94 95 96 97 98 99 100 101 102 Th Pa U Np Pu Am Cm Bk Cf Es Fm Md No Lr Thorium 232.0381 Protactinium 231.0359 Uranium 238.00289 Neptunium (237) Plutonium (244) Americium (243) Curium (247) Berkelium (247) Californium (251) Einsteinium (252) Fermium (257) Mendelevium Nobelium (259) Lawrencium (260) (258) Structures of Some Common Functional Groups Name Alkene (double bond) Alkyne (triple bond) Structure C Name ending Name -ene Sulfide Structure C C -yne XCmCX disulfide C None X Aldehyde C -ol OH Ketone O Carboxylic acid O P O– O– Ester C C -oic acid C OH -oate O C O C N Thioester Imine (Schiff base) C Amide C C C -amide C N -nitrile Acid chloride SH S O C XCmN C None N C -thioate O C Thiol -one -amine C Nitrile H O C Amine -al phosphate O C C ether C C Monophosphate sulfoxide O C C S+ O C Ether S C O– Sulfoxide (X ϭ F, Cl, Br, I) Alcohol S None C Halide sulfide C Disulfide C Arene (aromatic ring) S Name ending -oyl chloride O -thiol C C Cl ... carbonyl carbons absorb in the 190 to 20 0 ␦ region 136.5 O C O 1 92 O H C CH3CCH2CH3 130, 129 134 198 CH3 O CH3CH 31 20 0 137 O 21 1 29 .5 20 9 37 26 .5 25 27 42 128 .5, 128 133 Mass Spectrometry Aliphatic... monoalcohol.) O HOCH2CH2OH C O O Acid catalyst OCH2CH3 C O OCH2CH3 + H2O O Ethyl 4-oxopentanoate LiAlH4 H3O+ Can’t be done directly O HOCH2CH2OH H3O+ + O O CH2OH + CH3CH2OH CH2OH 5-Hydroxypentan -2- one Acetal... For example: O O CH3CH2CH2CCH2COCH3 32 Methyl 3-oxohexanoate Problem 14.1 Name the following aldehydes and ketones: O (a) (b) CH2CH2CHO (c) O O CH3CCH2CH2CH2CCH2CH3 CH3CH2CCHCH3 CH3 (d) H (e)