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A Acid-catalyzed dehydration, of alcohols, Addition reactions, 337–390 303–308 Absolute configuration, 229–231 of alkenes, 338–373 Acid-catalyzed esterification, 778–780 Absorption spectrum, 590 Adduct, 599 Acid-catalyzed halogenation, of aldehydes Acetals, 728–730 Adenosine diphosphate (ADP), 423 and ketones, 818 Adenosine triphosphate (ATP), 274, 423, Acetaldehyde, 10, 72, 76, 78, 372, 714 Acid-catalyzed hemiacetal formation, 967–968 Acetaldehyde enolate, 53 726–727 Adenylate cyclase, 1095 physical properties, 10 Acid-catalyzed hydration, of alkenes, 354, Adipic acid, 765 Acetic acid, 73–74, 76, 78, 113, 118–119, 496–497 Adipocytes, 1016 126–128, 147, 762 Acid chlorides, see Acyl chlorides Adrenaline, 273, 899 physical properties, 78 Acid derivatives, synthesis of, 775 Adrenocortical hormones, 1032 and pK , 114 a Acidic hydrolysis of a nitrile, 790–791 Adriamycin, see Doxorubicin Acetoacetic synthesis, 825–830 Acidity: Agent Orange, 643–644 acylation, 829–830 carboxylic acids vs. alcohols, 126–132 Aggregation compounds, 163 dialkylation, 826 effect of solvent on, 132 Aglycone, 974–975 substituted methyl ketones, 826–827 hybridization, 122–123 Alanine, 909, 1048, 1051 Acetone, 14, 57, 72, 79, 711 inductive effects, 123 isoelectric point of, 1051 Acetonides, 979, 1007–1008 relationships between structure and, titration curve for, 1052 Acetonitrile, 75 120–123 Albrecht, Walther, 608–609 Acetylcholine, 890–891, 900–901 Acidity constant (Ka), 113–114 Albuterol, 492 Acetylcholinesterase, 900, 1081 Acid strength, 113 Alcohols, 55, 67–68, 132. See also Primary Acetyl-coenzyme A, 773 Acne medications, of, 450 alcohols; Secondary alcohols; Tertiary Acetylenes, 7, 57, 161, 283, 325 Acrylonitrile, anionic polymerization of, 477 alcohols structure of, 40–42 Actin, 168 acid-catalyzed dehydration of, 303–308 Acetylenic hydrogen atom, 161, 312 Activating groups, 677–678, 685, 690 acidity of, 126–128 of terminal , substitution of, Activation energies, 462 as acids, 500 312–313 Active hydrogen compounds, 833–834 addition of: Acetyl group, 713 Active methylene compounds, 833–834 acetals, 728–730 Achiral molecules, 194, 197, 200, 462 Active site, 1076 hemiacetals, 726–727 Acids: of enzyme, 1055 thioacetals, 731 alcohols as, 500 Acyclovir, 1098 alcohol carbon atom, 490 Brønsted–Lowry, 105–106, 139 Acylation, 829–830 from alkenes: Lewis, 109–111 Acylation reaction, 669 through hydroboration–oxidation, in nonaqueous solutions, 135–136 Acyl chlorides (acid chlorides), 670, 349–352 phenols as, 130–131 716–717, 766–767, 774–777 through oxymercuration– relative strength of, 115 aldehydes by reduction of, 716–718 demercuration, 349–350 in water, 106 from, 780 boiling points, 492 Acid anhydrides, reactions of, 800 reactions of, 776–777, 799–800 conversion of: Acid–base reactions, 105–109, 120–123COPYRIGHTEDsynthesis of, 775–776 MATERIAL into halides, 501 acids and bases in water, 106–107 using thionyl chloride, 776 into a mesylate, 507 of amines, 909 Acyl compounds: dehydration of, 303–305 Brønsted–Lowry acids and bases, 105–106 relative reactivity of, 774–775 acid-catalyzed, 303–308 curved arrows, 107 spectroscopic properties of, 768–770 carbocation stability and the transition mechanism for, 107–108 Acyl groups, 669–670 state, 308–312 opposite charges attract, 137 as ortho–para directors, 679–680 ethanol, 490, 493–495 predicting the outcome of, 118–120 Acyl halide, 670 as a biofuel, 495 and the synthesis of deuterium and as insecticide, 676 ethylene, 495 tritium-labeled compounds, Acylium ions, 429 polymerization of, 475 136–137 Acyl substitution, 761, 773–775, 812 from Grignard reagents, 552–560 water solubility as the result of salt by nucleophilic addition–elimination, hydrogen bonding, 493 formation, 119–120 773–774 infrared (IR) spectra of, 93–94 Acid-catalyzed acetal formation, 728–729 Acyl transfer reactions, 773 intermolecular dehydration, ethers by, Acid-catalyzed aldol condensations, 858–859 Adamantane, 182 508–509 Acid-catalyzed aldol enolization, 816 Addition polymers, 474, 797 mesylates, 505–507

I-1 I-2 INDEX

methanol, 493, 494, 500 Aldol reactions, synthetic applications of, ketones from, 720–721 nomenclature, 154–155, 490–491 859–860 Markovnikov additions, 341 oxidation of, 542–547 Aldonic acids, synthesis of, 980–981 regioselective reactions, 344 physical properties of, 492–494 Aldose, 968, 979, 980, 984, 986–987 Markovnikov’s rule, 340–345 primary, 67 Aldose, d-family of, 988 defined, 341 propylene glycols, 493, 495 Aldotetrose, 968–970, 987 theoretical explanation of, 342–343 reactions of, 498–499 Aliphatic aldehydes, 712 mechanism for syn dihydroxylation of, with hydrogen halides, alkyl halides nomenclature of, 712 368–369 from, 501–504 Aliphatic amines, reactions with nitrous in natural chemical syntheses, 381–382 with PBr3 or SOCI2, alkyl halides from, acid, 911 oxidation of, 369, 770 504–505 Aliphatic compounds, 618. See also Aromatic environmentally friendly by reduction of carbonyl compounds, compounds methods, 521 537–541 Aliphatic ketones, nomenclature of, 713 oxidative cleavage of, 371–373 spectroscopic evidence for, 547 Alkadienes, 582 physical properties of, 283 structure, 490–491 Alkaloids, 839, 887, 899 preparation of carboxylic acids by synthesis/reactions, 489–532 Alkanedioic acids, 765 oxidation of, 770 tert-butyl ethers by alkylation of, 511 Alkanes, 56–57, 145 properties/synthesis, 282–336 tosylates, 505–506 bicyclic, 181–182 radical addition to, 472–474 triflates, 505–506 branched-chain, 149 radical polymerization of, 474–478 Alcohol dehydrogenase, 539 nomenclature of, 147–149 rearrangements, 348–349 Aldaric acids, 981–982 chemical reactions of, 182 relative stabilities of, 284–287 Aldehydes, 55, 71–72, 711–760 chlorination of, 455–456 stereochemistry of the ionic addition to, acid-catalyzed halogenation of, 818 combustion of, 479, 481 326–327 α,β -unsaturated, additions to, 869–871 cycloalkanes, 145 stereospecific reactions, 363–364 Baeyer-Villiger oxidation, 741–743 defined, 145 synthesis of alcohols from, 496–499 base-promoted halogenation of, 817 halogenation of, 454–455, 466–467 use in synthesis, 524–525 carbonyl group, 535, 712 IUPAC nomenclature of, 147–149 Alkene diastereomers, (E )-(Z ) system for designating, 283–284 chemical analyses for, 743 multiple halogen substitution, 454–455 Alkenyl, 242, 274–275 from esters and nitriles, 718–720 no functional group, cause of, 64 Alkenylbenzenes, 686–687 IR spectra of, 743–744 nomenclature and conformations of, additions to the double bond of, 687 mass spectra of, 745–746 148–155 petroleum as source of, 145 formation of, by elimination NMR spectra of, 744–745 reactions, 687 physical properties of, 161–163 nomenclature of, 712–714 oxidation of the benzene ring, 688 polycyclic, 181–182 nucleophilic addition to the carbon– oxidation of the side chain, 688 oxygen double bond, 723–726 reactions of, with halogens, 454–456 Alkenyne, 582 oxidation of, 741 shapes of, 146–148 Alkoxides, 289, 500 by oxidation of 1° alcohols, 715–716 sources of, 145–146 Alkoxide ions, 136 oxidation of primary alcohols to, 542 “straight-chain,” 146 Alkoxyl group, 74 by ozonolysis of alkenes, 716 synthesis of, 182–184 Alkoxyl radicals, 449 unbranched, 148–149 in perfumes, 715 Alkoxymercuration–demercuration, synthesis physical properties of, 714–715 Alkanide shift, 310 of ethers by, 511 preparation of carboxylic acids by Alkatrienes, 582 Alkyl alcohols, 491 oxidation of, 770–773 Alkenes, 56, 57 Alkylation, of alkynide anions, 316–317, reduction by hydride transfer, 539 addition of sulfuric acid to, 338, 346 322–323, 336 by reduction of acyl chlorides, esters, and addition of water to, 346–349 Alkylbenzenes: nitriles, 716–718 mechanism, 338 conjugated, stability of, 687 relative reactivity, 725 addition reactions, 338–373 preparation of carboxylic acids by spectroscopic properties of, 743–746 alcohols from, through oxymercuration– oxidation of, 771 summary of addition reactions, 746–747 demercuration, 349–350 reactions of the side chain of, 686 synthesis of, 715–720 aldehydes by ozonolysis of, 716 Alkylboranes: Tollens’ test (silver mirror test), 743 anti 1,2-dihydroxylation of, 519–521 oxidation/hydrolysis of, 353–355 UV spectra, 746 defined, 145, 283 regiochemistry and stereochemistry, Aldehyde hydrates, 542 dipole moments in, 63–64 356–357 Alder, Kurt, 599, 608–609 electrophilic addition, 339–340 protonolysis of, 359 Alditols, 984 of bromine and chlorine, 359–363 Alkyl chlorides, 273 Aldol additions, 857–858 defined, 339 Alkyl chloroformates, 793–794 Aldol addition product, dehydration of, 858 of hydrogen halides, 340–345 Alkyl groups, 257 Aldol addition reactions, 856–857 functional group, 64 branched, nomenclature of, 151–152 Aldol condensations, 856, 858 halohydrin formation from, 364–366 and the symbol R, 64–65 acid-catalyzed, 858–859 heat of reaction, 285 unbranched, 149 crossed, 861–866 how to name, 158–160 nomenclature of, 149 cyclizations via, 867–868 hydrogenation of, 183–184, 317–318 Alkyl halides, 65–66, 240–243 Aldol condensation reactions, 850 ionic addition to, 343 alcohol reactions: INDEX I-3

with hydrogen halides, 501–504 stabilization of, by electron delocalization, heterocyclic, 892 with PBr3 or SOCI2, 504–505 468–469 basicity of, 895–896 conversion of alcohols into, 501 Allylic substitution, 466–469 infrared (IR) spectra of, 94–95 dehydrohalogenation of, 287–289 defined, 466 monoalkylation of, 906 bases used in, 289 Allyl radical, 573 nomenclature, 891–892 defined, 288–291 molecular orbital description of, 573 oxidation of, 910–911 favoring an E2 mechanism, 298–299 resonance description of, 575–576 physical properties of, 892–893 less substituted alkene, formation of, Alpha (α) carbon atom, 288 preparation of, 901–909 using bulky base, 293–296 α-amino acids, 1047, 1051 through Curtius rearrangement, 908 mechanisms, 289 synthesis of, 1053–1055 through Hofmann rearrangement, orientation of groups in the transition from potassium phthalimide, 1053 907–908 state, 294–296 resolution of dl-amino acids, through nucleophilic substitution Zaitsev’s rule, 291–293 1054–1055 reactions, 901–903 E1 reaction, 289, 297–298 Strecker synthesis, 1054 through reduction of nitriles, oximes, E2 reaction, 289–291 α anomer, 971 and amides, 906 elimination reactions of, 288 α carbon, 812 through reduction of nitro nomenclature of, 153 α helices, 1071, 1074, 1077 compounds, 903 physical properties of, 242 α hydrogens, 812, 827 through reductive amination, 904–905 reduction to hydrocarbons, 540 α-keratin, 1046, 1073–1074 primary, 904 simple, 263 α substituents, 1027 oxidation of, 910–911 tertiary, 271 Altman, Sidney, 1076 preparation of, through Curtius Alkylidene, 955 Aluminum chloride, 109 rearrangement, 908 Alkyllithium, 136 Amides, 75, 767, 784–792 preparation of, through Hofmann Alkyloxonium ion, 132, 244 from acyl chlorides, 784–785 rearrangement, 907–908 Alkylpotassium compounds, 547–548 amines vs., 896 preparation of, through reduction of nitriles, oximes, and amides, 904 Alkyl radicals, geometry of, 462 from carboxylic acids and ammonium preparation of, through reductive Alkylsodium compounds, 547–548 carboxylates, 786–787 amination, 904–905 Alkynes, 56, 57, 283 from carboxylic anhydrides, 785–786 quaternary ammonium salts, 897 addition of hydrogen halides to, 374–375 DCC-promoted amide synthesis, 787 reactions of, 909–913 addition reactions, 374–390 from esters, 786 oxidation, 910–911 defined, 145 hydrolysis of, 788–789 primary aliphatic amines with nitrous by enzymes, 789 functional group, 64 acid, 911 lactams, 791–792 hydrogenation of, 183–184, 320–322 primary arylamines with nitrous acid, nitriles: nomenclature of, 160–161 911–913 from the dehydration of, 790 oxidative cleavage of, 375 secondary amines with nitrous acid, physical properties of, 283 hydrolysis of, 790–791 912 synthesis of, 282–336 reactions of, 801 tertiary amines with nitrous acid, 913 by elimination reactions, 313–315 reducing to amines, 906 reactions with sulfonyl chlorides, 919–920 laboratory application, 313–315 synthesis of, 784 as resolving agents, 898–899 terminal, 135 Amines, 70–71, 890–937 secondary, 891–893 acidity of, 312–313, 500 acylation, 910 oxidation of, 910 conversion to nucleophiles for carbon- alkylation, 910 preparation of, through reduction of carbon bond formation, 315–317 amides vs., 896 nitriles, oximes, and amides, 906 substitution of the acetylenic hydrogen amine salts, 894–901 preparation of, through reductive atom of, 312–313 aminium salts, 897 amination, 904–905 Alkynide anions, 316–317 analysis of, 921–923 spectroscopic analysis, 922–923 Allenes, 233–234, 583 in aqueous acids, solubility of, 897–898 structure of, 893 Allopurinol, 1098 arenediazonium salts: summary of preparations and reactions of, Allotropes, 187 coupling reactions of, 917–919 924–928 Allyl cation, 577–578 replacement reactions of, 913–916 tertiary, 906 Allyl group, 159, 573 aromatic, 895–896 oxidation of, 910 Allylic bromination, 576 preparation of, through reduction of preparation of, through reduction of with N-bromosuccinimide, 467–468 nitro compounds, 903 nitriles, oximes, and amides, 906 Allylic carbocations, 573 basicity of, 894–901 preparation of, through reductive Allylic chlorination (high temperature), biologically important, 899–901 amination, 904–905 466–467 antihistamines, 900 Amine salts, 894–901 Allylic group, 466 neurotransmitters, 900–901 Aminium salts, 897 Allylic halides, 264 2-phenylethylamines, 899 Amino acids, 2, 98, 1045 Allylic hydrogens, 466 tranquilizers, 900 α-amino acids, 1047, 1051 Allylic position, 466 vitamins, 900 synthesis of, 1053–1055 Allylic radicals, 466–469 chemical analysis, 921 as dipolar ions, 1050–1053 defined, 467 conjugate addition of, 871, 889 dl-amino acids, resolution of, 1054–1055 resonance delocalization of, 469 diazotization, 911 essential, 1050–1053 I-4 INDEX

Amino acids (cont.) Anti-Markovnikov regioselectivity/syn reduction of, 697–700 l-amino acids, 1048–1050 stereoselectivity, 497 spectroscopy of, 644–650 structures and nomenclature, 1047 Anti-Markovnikov syn hydration, 352 synthetic strategies with, 689–691 Amino acid sequencers, 1058 Antimetabolites, 920 order of reactions, choosing, 689 Aminobenzene, 619 Antioxidants, 480 protecting and blocking groups, use of, Amino cyclitol, 1003 Antisense oligonucleotides, 1116 690–691 α-Aminonitrile, formation of, during Aprotic solvents, 266–267 Aromatic cyclodehydration, 703 Strecker synthesis, 1054 Arbutin, 1007 Aromatic ions, 631–633 Amino sugars, 1000, 1003 Arbuzov reaction, 741 Aromaticity, 623 Ammonia: Arenes, 686 Artificial sweeteners, 237, 993–994 reaction of, with alkyl halide, 244 ketones from, 720–721 Arylamines: reactions of aldehydes and ketones with Arenediazonium salts: basicity of, 895 derivatives of, 734–735 coupling reactions of, 917–919 tertiary, 913 shape of a molecule of, 45 replacement by —F, 914–915 Aryl halides, 241, 672, 911 and water, 13 replacement by hydrogen, 915–916 defined, 241 Ammonium compounds, eliminations replacement by —I, 914 as herbicides, 643–644 involving: replacement by —OH, 915 as insecticides, 676 Cope elimination, 924 replacement reactions of, 913–916 physical properties of, 242 Hofmann elimination, 923–924 salts, instability of, 911 Ascorbic acid (vitamin C), 202 Ammonium cyanate, 3 Arenium ion, 662–668, 702, 703, 706 Ashworth, Linda, 1091 Ammonium ion, 12 Arginine, 479, 1050, 1053, 1062–1063, Asparagine, 1049, 1069, 1074 Ammonium salts, 894 1069 Aspartame (NutraSweet), 947, 993 Ammonolysis, 786 Aromatic amines, 895–896 Aspartic acid, 993, 1049 Ampelopsin D, 700 preparation of, through reduction of nitro Aspirin, 975, 1036 Ampelopsin F, 700 compounds, 903 Asymmetric atoms, see Chirality centers Amphetamine, 70, 899 Aromatic anion, 632 Atoms, 3–4 Amylopectin, 995–996 Aromatic compounds, 56, 617–659 Atomic force microscopy (AFM), 639 Amylose, 965, 995 benzene, 58 Atomic number (Z), 4, 204 Anderson, C. D., 1098 directing effects in disubstituted, 685 Atomic orbitals (AOs), 28, 30–32, 37, 43 Androsterone, 163, 1030 discovery of, 618–619 hybrid, 32 Aneshansley, D., 1025 halogenation of, 664–665 Atomic structure, 3–4 Anet, F. A. L., 413 Kekulé structure for, 58 and quantum mechanics, 27–28 Anethole, 489 modern theories of the structure of, Atropisomers, 228, 233 625–627 Angle strain, 168 Attractive electric forces, summary of, 85 nitration of, 664–666 Angular methyl groups, 1026–1027 Aufbau principle, 29, 47 nomenclature of benzene derivatives, Angular shape, of a molecule of water, 45 Automated peptide synthesis, 1069–1071 619–621 Autoxidation, 479–480, 495 Aniline, 138, 619, 677–679 reactions of, 621–622 acetylation of, 921 Axial bonds, of cyclohexane, 173–174 sulfonation of, 666–667 Azo dyes, 918 Anionic polymerization, 519 thermodynamic stability of, 623–624 Annulenes, 629–630 benzenoid, 636–637 B Anomers, 971 in biochemistry, 641–644 Anomeric carbon atom, 971 Birch reduction, 698–699 Baeyer-Villiger oxidation, 741–743 Anomeric effect, 973 13C NMR spectra, 645–647 Baker, B. R., 1098 Anthracene, 637 defined, 634 Baker, J. T., 516 Anti 1,2-dihydroxylation, of alkenes, 519–521 electrophilic aromatic substitution Ball-and-stick models, 14–16, 45 Anti addition: reactions, 661 Balzani, V., 172 defined, 320 general mechanism for, 662–664 Barger, G., 707 of hydrogen, 321–322 Friedel–Crafts acylation, 669–671 Barton, D.H.R., 172 Antiaromatic compounds, 629, 634–635 Clemmensen reduction, 674 Bases: Antibiotic X-206, 516 synthetic applications of, 673–674 Brønsted–Lowry, 105–106, 139 Antibodies, 522, 864, 1001–1002, 1045 Wolff-Kishner reduction, 675 Lewis, 109–111 Antibonding molecular orbital, 31, 43 Friedel–Crafts alkylation, 668–669 in nonaqueous solutions, 135–136 Anticodon, 1109 Friedel–Crafts reactions, limitations of, organic compounds as, 132–133 Anti conformation, 166, 186 671–673 predicting the strength of, 116–117 Anti coplanar conformation, 294 fullerenes, 638 relative strength of, 115 Antigens, 522, 1001 heterocyclic, 639–641 in water, 106 Antihistamines, and vitamins, 900 1H NMR spectra, 644–645 Base peak, 423, 424 Anti-Markovnikov addition, 345 Hückel’s rule, 628 Base-promoted halogenation, of aldehydes of water to an alkene, 346 infrared spectra of substituted benzenes, and ketones, 817 Anti-Markovnikov addition of hydrogen 647–648 Base strength, 116 bromide, 472–474 mass spectra of, 649–650 Basic hydrolysis of a nitrile, 791 Anti-Markovnikov hydration of a double nonbenzenoid, 638–639 Basicity: bond, 352 reactions of, 660–710 nucleophilicity vs., 266 INDEX I-5

order of, 266 Bertrand, J. A., 1079 Bonding pairs, 44 and polarizability, 299, 301 Beryllium hydride, linear geometry of, 46 Bond length, 30, 42 Basic principles, applications of, 47, 97, Beta (β) carbon atom, 288 Bond-line formulas, 16, 18–19, 492 137–138, 186–188 β-anomer, 971–972 drawing, 18–19 B chains, 1064 β bends, 1073 Bond rotation, 164–166 Beer’s law, 591 β-carotene, 846 Bone growth, organic templates engineered Bends, 18 β-dicarbonyl compounds: to mimic, 86 Benedict’s reagents, 979–980, 1004 by acylation of ketone enolates, 855–856 Born, Max, 28 Bent shape, of a molecule of water, 45 enolates of, 824–825 Borneol, 562 Benzaldehyde, 711, 713 β-dicarboxylic acids, 796 Boron trifluoride, 62 Benzene, 56, 58–59, 242, 274, 617–619, β eliminations, 288 trigonal planar structure of, 45–46 635 β hydrogen atom, 288 Bovine chymotrypsinogen, 1064 directing effects in distributed, 685 β-keto acids, 795 Bovine ribonuclease, 1064 discovery of, 618–619 β-pleated sheets, 1071, 1073, 1077 Bovine trypsinogen, 1064 halogenation of, 664–665 β substituents, 1027 Boyer, Paul D., 523 Kekulé structure for, 58, 622–623 BHA (butylated hydroxyanisole), 705 Bradsher reaction, 703 meta-disubstituted, 648 Bhopal, India, methyl isocyanate accident, Branched alkyl groups, how to name, modern theories of the structure of, 794 151–152 625–627 BHT (butylated hydroxytoluene), 480 Branched-chain alkanes: molecular orbital explanation of the Bicyclic alkanes, 181–182 how to name, 149–151 structure of, 626–627 Bicyclic cycloalkanes, naming, 157–158 nomenclature of, 147–149 monosubstituted, 647 Bicycloalkanes, 158 Breathalyzer alcohol test, 546 nitration of, 665–666 Bijvoet, J. M., 231 Breslow, R., 234 nomenclature of benzene derivatives, Bridge, 157 619–621 Bimolecular reaction, 247 BINAP, 218, 233 Bridgeheads, 157 ortho-disubstituted, 648 Bromides, 273 para-disubstituted, 648 Biochemistry: aromatic compounds in, 641–644 Bromine, 456 reactions of, 621–622 addition to cis- and trans-2-butene, intermolecular forces in, 85 resonance explanation of the structure of, 359–360 Biologically active natural products, 362 625–626 electrophilic addition of bromine to sulfonation of, 666–667 Biologically important amines, 899–901, alkenes, 359–363 931 thermodynamic stability of, 623–624 principal stable isotopes of, 432 2-phenylethylamines, 899 Benzene ring, 469 reaction with alkanes, 454 antihistamines, 900 carbon side chains, reactions of, 686–688 selectivity of, 461–462 functional groups in, 77 oxidation of the, 688 Bromine water, 987, 992, 1004 preparation of carboxylic acids by neurotransmitters, 900–901 Bromobenzene, 664 oxidation of, 771 tranquilizers, 900 2-Bromobutane, 363 Benzene substitution, 622 vitamins, 900 Bromoform, 818–819 Benzenoid aromatic compounds, 636–637 Biological methylation, 273–274 Bromohydrin, 365 Benzenoid polycyclic aromatic hydrocarbons, Biomolecules, mass spectrometry (MS) of, Bromonium ion, 361 436 636–637 Brønsted–Lowry acids and bases, 105–106, Benzoic acid, 73 Biphenyl, 706 139 p-benzoquinone, 1024–1025 Birch, A. J., 698 strength of, 113–118 Birch reduction, 698–699 Benzoyl peroxide, 450 acidity and pKa, 114–116 Black biting, 475 Benzyl, 621 acidity constant (Ka), 113–114 Benzyl bromide, 686 Bloch, Felix, 392 predicting the strength of bases, Benzyl chloride, 686 Blocking groups, 690–691 116–117 Benzyl chloroformates, 793 Boat conformation, 170–172 Brønsted–Lowry acid-base chemistry, 316 Benzyl groups, 65 Boduszek, B., 1079 Brønsted–Lowry theory, 109 Benzylic cations, 687 Boiling points, 82, 97 Brown, Herbert C., 353 Benzylic chlorination of methylbenzene, 470 alcohols, 492 Buckminsterfullerene, 144, 188, 638 Benzylic groups, 469–470 ethers, 492 1,3-Butadiene, 583–585 Benzylic halides, 264 intermolecular forces (van der Waals bond lengths, 583–585 Benzylic halogenation, 471 forces), 82 conformations of, 584 of the side chain, 686 ionic compounds, 78 molecular orbitals of, 584–585 Benzylic hydrogens, 470 neopentane, 81 Butane, 146, 148, 285 Benzylic hydrogen atoms, 688 nonpolar compounds, 82 conformational analysis of, 165–166 Benzylic radicals, 469–470, 686 unbranched alkanes, 162 Butanoic acid, 762 halogenation of the side chain, 686 Bombardier beetle, 1025 Butanone, synthesis of 2-butanol by the Benzyne, 694–697 Bombykol, 949–950 nickel-catalyzed hydrogenation of, 215 Berg, Paul, 1114 Bond angles, 16 Butenandt, Adolf, 1030 Bergman, R. G., 482, 483 Bond breaking, as endothermic process, 451 Butlerov, Alexander M., 618 Bergman cycloaromatization, 482–483 Bond dissociation energies, 451–454 Butyl alcohol, 134, 493 Bergström, S. K., 1036 Bonding molecular orbital, 31–35, 37 Butyric acid, 762 I-6 INDEX

C Carbon–carbon double bond, 7, 56, 64, 92 acidity of, 126–128, 763–765 Cahn, R. S., 204 Carbon–carbon single bond, 7 acyl chlorides, 766–767 Cahn–Ingold–Prelog system of naming Carbon–carbon triple bond, 7 acyl compounds: enantiomers, 204–208, 235, 283 Carbon compounds: relative reactivity of, 774–775 Calicheamicin γ1l, 482–483 alkyl halides (haloalkanes), 65–66 spectroscopic properties of, 768–770 Camphene, 311 amides, 75 acyl substitution, 773–775 Camphor, 562 carboxylic acids, 73–74 α-halo, 820–821 Cannizzaro reaction, 843 esters, 74 amides, 767 Cantharidin, 808 families of, 55–103 carboxylic anhydrides, 766 Capillary electrophoresis, 1115 functional groups, 62–64 decarboxylation of, 795–796 Capillin, 57 hydrocarbons, 56–59 dicarboxylic acids, 765–766 , 48–49 nitriles, 75 esterification, 778–781 Carbaldehyde, 712 polar and nonpolar molecules, 61–63 esters, 766 -carbaldehyde, suffix added to aldehydes, polar covalent bonds, 59–61 infrared (IR) spectra of, 94 712 Carbon dating, 4 lactams, 791–792 Carbamates (urethanes), 793 Carbon dioxide, 46–47 lactones, 783–784 Carbanions, 111, 121–123, 536 Carbonic acid, derivatives of, 792–793 nitriles, 768 relative acidity of, 123 Carbonic anhydrase, 1073–1075, 1079 nomenclature, 762–763 relative basicity of, 123 Carbon–oxygen double bond: oxidation of primary alcohols to, 542 Carbenes, 366–368 nucleophilic addition of ketones to, physical properties, 762–763 Carbenoids, 368 723–726 polyamides, 797–798 Carbocations, 111, 133, 165, 257–259 reversibility of nucleophilic additions to, polyesters, 797–798 relative stabilities of, 257–259 725 preparation of, 770–773 structure of, 257 Carbon side chains, reactions of benzene reactions of, 798–799 ring, 686–688 Carbohydrates, 275, 965–1010. See also Carboxylic acid anhydrides, 777–778 benzylic halogenation, 686 Disaccharides; Monosaccharides; reactions of, 778 Carbon tetrachloride, 242 Polysaccharides synthesis of, 777–778 Carbonyl compounds, 811–848 amino sugars, 1000 Carboxylic acid derivatives, 762, 775 acetoacetic ester synthesis, 825–830 carbohydrate antibiotics, 1003 Carboxylic anhydrides, 766 acidity of the α hydrogens of, 812–813 classification of, 966–967 Carboxyl radicals, decarboxylation of, 796 alcohols by reduction of, 537–541 defined, 966 Carboxypeptidases, 1060–1061 alcohols from, 534– 571 disaccharides, 966, 990–994 Carboxypeptidase A, 1076 condensation and conjugate addition Fischer’s proof of the configuration of Carcinogens, epoxides and, 525 d-(+)-glucose, 988–990 reactions of, 849–889 defined, 535 Carcinogenic compounds, 643 glycolipids and glycoproteins of the cell Carotenes, 1023 surface, 1001–1002 enamines, synthesis of, 834–839 Carrier ionophore, 523 glycoside formation, 974–975 haloform reaction, 818–819 Carvone, 72, 201, 213 glycosylamines, 999–1000 halogenation at the α carbon, 817–818 Catalytic antibodies, 1081–1082 as a major chemical repository for solar Hell–Volhard–Zelinski (HVZ) reaction, energy, 967 820–821 Catalytic asymmetric dihydroxylation, 370–371 monosaccharides, 966, 988–989, 994, lithium enolates, 821 1001–1002, 1004 oxidation and reduction of, 536 Catalytic hydrogenation, 317–318 mutarotation, 973 racemization via enols and enolates, Catalytic triad, 1079–1080 oligosaccharides, 966 815–817 Catenanes, 172 photosynthesis and carbohydrate reactions at the α carbon of, 811–848 Cation-anion forces, 85 metabolism, 967–968 reactions of Grignard reagents with, Cation-exchange resins, 1056–1057 polysaccharides, 966, 994–998 551–552 Cationic carbon, 256 summary of reactions of, 1004 reactions with nucleophiles, 536 C—C bond-forming events, 939 trisaccharides, 966 substituted acetic acids, synthesis of, Celera Genomics Company, 1120 Carbolic acids, see Phenols 830–833 Cellobiose, 993 Carbon, 6, 8 Carbonyl dichloride, 792 Cellulose, 994, 997–998 origin of, 2 Carbonyl functional groups, 534 Cellulose derivatives, 998 principal stable isotopes of, 432 infrared (IR) spectra of, 92–93 Cellulose trinitrate, 998 Carbon-13 (13C) NMR spectroscopy, 396, Carbonyl groups, 71–72, 712 Chain branching, 475–476 414–421 nucleophilic addition to, 536 Chain-growth polymers, 474–476 broadband (BB) proton decoupled, 414– stereoselective reductions of, 541 Chain-initiating step, in fluorination, 457, 415, 418–419 structure of, 535–536 481 chemical shifts, 415–417 Carbowaxes, 519 Chain mechanism, 459 DEPT 13C NMR spectra, 417–419 Carboxylate anion, 743, 763–764, 819, Chain-propagating steps, 457, 467, 481 interpretation of, 414 1018 Chain reaction, 457, 473 one peak for each magnetically distinct Carboxylate salts, 763 Chain-terminating (dideoxynucleotide) carbon atom, 414–415 Carboxyl group, 73 method, 1113–1116 spin decoupling, 412–413 activation of, 1067–1068 Chain-terminating steps, 458, 467 Carbon atom, 243–244, 248–249 Carboxylic acids, 73–74, 761–810 Chair conformation, 170–172 INDEX I-7

Chair conformational structures, drawing, reaction with alkanes, 454 with hot basic potassium permanganate, 174 Chlorine selectivity, lack of, 455–456 371–372 Chaires, J. B., 218 Chlorobenzene, 664 with ozone, 372–373 Chargaff, Erwin, 1100 Chloroethane, 153, 403–405 Clemmensen reduction, 674, 731 Chauvin, Yves, 955, 957 physical properties, 78 Clostridium botulinum, 912 13 C—H bonds, 959–960 Chlorofluorocarbons (CFCs), 481 C (carbon-13) NMR Spectroscopy, see 13 Chemical Abstracts Service (CAS), 181 Chloroform, 242, 818 Carbon-13 ( C) NMR spectroscopy Chemical bonds, 5 dipole moment, 63 Codeine, 562 Chemical energy, defined, 124 in drinking water, 820 Codon, 1109 Chemical exchange, 412 Chlorohydrin, 365 Coenzymes, 641–642, 1076, 1095 Chemical shift, 393–395, 415–417 Chloromethane, 246–249, 251–252, 262 Cofactor, 1076 carbon-13 NMR spectroscopy, 415–417 physical properties, 78 Collagen, 86 equivalent and nonequivalent protons, Chloromethane molecule, net dipole Collision-induced dissociation (CID), 1061 403–406 moment, 62 Combination bands, 90 parts per million (ppm) and the δ scale, Chloromethylation, 809 Combustion of alkanes, 479, 481 394 Chlorophyll, 48–49 Common names, for compounds, 147 shielding and deshielding of protons, Chloroplasts, 967 Competitive inhibitor, 496, 1076 401–402 Chlorpheniramine, 900 Complete sequence analysis, 1060–1061 Chemical shift equivalent protons, 403 Cholesterol, 218, 490, 1028–1029 Compounds, 3 Chemotherapy, 927–928 chemistry of, 496 Concerted reaction, 249 Chiral drugs, 216–218 Cholic acid, 1033 Condensation reactions, 797, 849, 850 Chirality: Choline, 273 Condensed formula, 15–17 biological significance of, 195, 201–202 Cholinergic synapses, 900 Condensed structural formulas, 17 importance of, 195 Configurations: in molecules, 195, 198 Chromate ester, formation of, 544, 545 Chromate oxidations, mechanism of, 545 (R) and (S), 228–231 potential origin of, 234 inversion of, 273 and stereochemistry, 194–195 Chromatography using chiral media, 232 relative and absolute, 229–231 testing for, 203 Chromic acid oxidation, 544–546 Conformations, 164 Chirality centers, 198, 462 Chylomicrons, 1029 eclipsed, 165 compounds other than carbon with, 233 Chymotrypsin, 789, 1064, 1076, staggered, 164 molecules with multiple, 218–224 1079–1081 Conformational analysis, 164–166 meso compounds, 221–222 Chymotrypsinogen, 1079 of butane, 165–166 naming compounds with, 223–224 Cialis, 448, 479 of ethane, 165–166 molecules with one, 198–201 Cinnamaldehyde, 711 hyperconjugation, 165 proceeding with retention of Cis, 283 of methylcyclohexane, 175–176 configuration, 228–231 cis-1-chloro-3-methylcyclopentane, 252 performing, 165–166 Chiral molecules, 195, 197–201 Cis–trans isomers, 39 Fischer projections, 224–225 of cyclohexane derivatives, 226 Conformational isomers, 233 not possessing chirality center, 233–234 physical properties, 62 Conformational stereoisomers, 167, 228 racemic forms (racemic mixture), 214– Cis–trans isomerism, 177–181 Conformer, 164 215 cis 1,2-disubstituted cyclohexanes, Conjugate acid, 116–117, 819, 822 stereoselective reactions, 215–216 180–181 of ammonia, 117 synthesis of, 214–216 cis 1,3-disubstituted cyclohexanes, 180 of methylamine, 117 Chiral object, defined, 194 cis 1,4-disubstituted cyclohexanes, of water, 105 Chiral templates, 208 178–179 Conjugate acid–base strengths, summary and Chitin, 1000 and conformational structures of comparison of, 129 Chloracne, 644 cyclohexanes, 178–181 Conjugate addition, 849 Chlordiazepoxide, 900 trans 1,2-disubstituted cyclohexanes, 180 to activate drugs, 873 Chloride, 276 trans 1,3-disubstituted cyclohexanes, of amines, 871, 889 Chloride ion, 105, 247–248, 255–256, 298, 179–180 of enolates, 871–872 774–776 trans 1,4-disubstituted cyclohexanes, 178, example of, 850 Chlorination: 283 of HCN, 870 of alkanes, 455, 460 Citrus-flavored soft drinks, chemistry of, 366 Conjugate addition reactions, 850, 860 of benzene, 665 Civetone, 163, 715 Conjugate base, 116 of isobutane, 455 Claisen condensation: Conjugated dienes: of methane: crossed, 853–854 electrophilic attack on, 595–598 activation energies, 462 defined, 850 stability of, 586–587 mechanism of reaction, 456–459 examples of, 850 Conjugated double bonds: of pentane, 462 intramolecular, 853 alkadienes, 582–583 of water, 819 mechanism for, 851–852 polyunsaturated hydrocarbons, 582–583 Chlorine, 6, 248, 252, 256, 298, 417 synthesis of β-keto esters, 836, 850–855 Conjugated proteins, 1081 electrophilic addition of bromine to Claisen–Schmidt condensations, 862 Conjugated unsaturated systems, 572–616 alkenes, 344 Cleavage: allyl cation, 577–578 principal stable isotopes of, 432 of ethers, 513–514 allylic substitution, 573 I-8 INDEX

Conjugated unsaturated systems (cont.) C-terminal residues, 1055, 1060 derivatives, 226 allyl radical, 575–576 Cumulated double bonds, 582 Cyclopropane, 57, 168–169 1,3-butadiene/z0, 583–585 qus, 583 Cysteine, 1047, 1049 conjugated dienes: Curl, R. F., 638 Cytochrome P450, 526 defined, 573 Curtius rearrangement, preparation of Cytosine–guanine base pair, 1105 Diels-Alder reaction, 601–609 amines through, 908 Cytosine methylation, 1124 electrophilic attack on, 595–598 alkylation of ammonia, 901 stability of, 586–587 alkylation of azide ion and reduction, 902 D electron delocalization, 583–585 alkylation of tertiary amines, 904 Dacron, 797 resonance theory, 578–582 Gabriel synthesis, 902–903 Dactylyne, 57, 337, 362 ultraviolet-visible spectroscopy, 589–591 Curved arrows, 22 D’Amico, Derin C., 845 Connectivity, 14–16 illustrating reactions with, 107 Darvon (dextropropoxyphene), 217 Constitutional isomers, 14–16, 147, 195, Cyanohydrins, 736–737 Darzens condensation, 884 197, 208 preparation of carboxylic acids by Dash structural formulas, 6–7, 16–17, 49 Constructive interference, 27–28 hydrolysis of, 771–772 Daunorubicin, 218, 868 Coordinatively saturated metals, 940 Cyclamate, 993–994 DDT, 676 Cope elimination, 924, 927 Cycles per second (cps), 588 Deactivating groups, 683 Coplanar, 301 3’,5’-Cyclic adenylic acid (cyclic AMP), Deacylases, 1055 Corey, E. J., 323, 369, 516, 608, 658, 1042 1095 De Broglie, Louis, 28 Corey, R., 1102 Cyclic anhydrides, 777 Debye, 60 Corey, Robert B., 1072 Cyclic compounds, stereoisomerism of, Debye, P.J.W., 60 Corpus luteum, 1031 226–228 Decalin, 181–182 COSY spectrum, 420–422 Cyclic guanosine monophosphate (cGMP), Decane, 148 Coulson, C. A., 628 479 Decarboxylation, 735 Couper, Archibald Scott, 618 Cyclizations, via aldol condensations, of carboxylic acids, 795–796 Coupling, 396–398, 1118 867–868 of carboxyl radicals, 796 Coupling constants (J), 410–411 Cycloalkanes, 145 angle strain, 168 Deconvolution, 1084, 1085 dependence on dihedral angle, 410–411 Decyl alcohol, 84 reciprocity of, 410 defined, 145 disubstituted, 177–181 Degenerate orbitals, 29 Coupling reactions, of arenediazonium salts, Degree of unsaturation, use of term, 184n 917–919 higher, conformations of, 172 Dehydration, 725 Covalent bonds, 5 naming, 155–157 of alcohols, 288, 303–305, 346 formation of, 6 bicyclic, 157–158 monocyclic, 155–156 carbocation stability and the transition homolysis and heterolysis of, 449 state, 305–307 nomenclature of, 155–156 and Lewis structures, 6–7 defined, 303 physical properties, 161–163 multiple, 7 of primary alcohols, 295 ring strain, 168–169 and potential energy (PE), 124–125 mechanism for, 307–308 synthesis of, 182–184 Cracking, 145–146 rearrangement after, 311–312 torsional strain, 168 Crafts, James M., 668 of secondary alcohols, 303–311 Cycloalkenes, 287 Cram, D., 697 mechanism for, 304–305 naming, 158–161 Cram, Donald J., 522 rearrangements during, 309–311 Cycloalkyalkanes, 156 Crick, Francis, 1099–1101, 1105, 1115, 1120 of tertiary alcohols, 303–307 Cyclobutadiene, 59, 630, 634–635 Crixivan, 322 mechanism for, 304–306 Cyclobutane, 169 Cross-coupling reactions, 947–955 Dehydrobenzene, see Benzyne Cycloheptane, 172 defined, 947–955 Dehydrohalogenation: -mediated couplings, Cycloheptatriene, 633–634 of alkenes, 288–289, 313–315 954–955 Cyclohexane, 186 of alkyl halides, 288–289 Heck–Mizoroki reaction, 947–949 conformations of, 170–172 bases used in, 289 Sonogashira coupling, 951–952 substituted, 173–177 defined, 288 Stile coupling reaction, 950–951 Cyclohexane derivatives, 225–226 favoring an E2 mechanism, 289–296 Suzuki–Miyaura reaction, 949 1,2-dimethylcyclohexanes, 227–228 less substituted alkene, formation of, Wacker-Tsuji oxidation, 950 1,3-dimethylcyclohexanes, 227 using bulky base, 293–296 Crossed aldol condensations, 861–866 1,4-dimethylcyclohexanes, 226 mechanisms of, 289, 295, 296 using strong bases, 865–866 cis–trans isomers of, 226 orientation of groups in the transition using weak bases, 862–865 Cyclohexene, 360, 367, 624 state, 294–296 Crossed aldol reaction, 862–863 Cyclononane, 172 Zaitsev’s rule, 291–293 Crossed Claisen condensation, 853–854 Cyclooctadecane, 172 bases used in, 289 Cross peak correlations, 420–423 Cyclooctane, 172 defined, 288 Crown ethers, 522–523 Cyclooctatetraene, 623, 628–629, 635 mechanisms of, 289 defined, 522 Cyclooxygenase, 1036 of vic-dibromides to form alkynes, 314 as phase transfer catalysts, 522 Cyclopentadiene, 602, 631–632 (dn), 940 and transport antibiotics, 523 Cyclopentadienyl anion, 631–633, 635, 638 Delocalization: Crutzen, P. J., 481 Cyclopentane, 169 and acidity of carboxylic acids, 127–128 INDEX I-9

of a charge, 127 Dicyclohexylcarbodiimide, 787, 1095 maltose, 966–967, 991–993 of electrons, 139 Dieckmann condensation, 853 sucrose, 275, 966–967, 990–991, 993 Delocalization effect, 128 Dielectric constants, 268 Dispersion forces, 80–81, 85, 88–89, 167 Deoxyribonucleic acid (DNA), 1091–1092. Diels, Otto, 599, 608–609 Dispersive IR spectrometers, 87 See also DNA sequence Diels–Alder reactions, 572, 584, 601–609, Dissolving metal reduction, 321 defined, 1091 696, 1045, 1082 Disubstituted benzenes, directing effects in, determining the base sequence of, factors favoring, 600–601 685 1113–1116 molecular orbital considerations favoring Disubstituted cycloalkanes, 177–181 DNA sequencing, 1091, 1114–1116 an endo transition state, 612–613 Divalent carbon compounds, 366–367 by the chain-terminating method, predicting the products of, 605–606 dl-amino acids, resolution of, 1054–1055 1114–1116 retrosynthetic analysis, using in, 606–607 DNA, see Deoxyribonucleic acid (DNA) heterocyclic bases, 1093–1094, 1096, stereochemistry of, 601–605 DNA polymerase, 1118 1099 Diene, 599 DNA sequence, 1061–1062, 1091, 1116, microchips, 1120 Dienophile, 599 1120–1121 primary structure of, 1098–1099 Diethyl ether, 490–496, 508, 513 DNA sequencing, by chain-terminating replication of, 1103–1105 physical properties, 82 (dideoxynucleotide) method, secondary structure of, 1099–1103 Difference bands, 90 1114–1116 Deoxy sugars, 999 13 Digitoxigenin, 1033 Dodecahedrane, 188 DEPT C NMR spectra, 417–419, 697, 1,2 Dihalides, 313 Dodecane, 148 707, 745, 754, 807 Dihalocarbenes, 367 Doisy, Edward, 1030 DEPT spectra, 645 Dihedral angle, 164, 410–411 Domagk, Gerhard, 927 DEPT (distortionless enhancement by 1,2-Dihydroxylation, 368 polarization transfer) spectra, 417 Dopamine, 70, 735 Dervan, Peter, 1122 Diisobutylaluminum hydride (DIBAL-H), Double bonds, 21, 274, 290, 298 717 Deshielding: Double-headed arrows (↔), 23–24 Diisopropylcarbodiimide, 787, 1068–1069 atoms, 415 Doublets, 397 Diisopropyl ester, 515 protons, 401–402 Downfield, use of term, 399 Diisopropylphosphofluoridate (DIPF), 1081 Designer catalysts, 1002 Doxorubicin, 868, 1038 1,2-Dimethoxyethane (DME), 493 Destructive interference, 27–28 d-Tubocurarine, 890–891, 901 Dimethoxytrityl (DMTr) group, 1118 Detritylation, 1118 d-Tubocurarine chloride, 890, 901 Dimethylbenzenes, 620 Deuterium atoms, 4 D vitamins, 1032–1033 1,2-Dimethylcyclohexane, 227–228 Dextrorotary, 210, 230 Dyes, 918 d-Fructose, 275 1,3-Dimethylcyclohexanes, 227 d-Glucaric acid, 981, 990 1,4-Dimethylcyclohexanes, 226 E d-Glucosamine, 1000 Dimethyl ether, 69, 493–494 E1 reactions, 289, 297–298 Diacyl peroxide, 474 intermolecular forces, 80 mechanism for, 298 Dialkylation, 826 2,4-Dinitrofluorobenzene, 1059 S 1 reactions vs., 297, 301 Dialkylcarbodiimides, 787 2,4-Dinitrophenylhydrazones, 733, 743 N E2 elimination, 295–296, 316 Dialkyl carbonate, 792–793 Diols, 155 E2 reactions, 289–296 Dialkyl ethers, 513 Diosgenin, 1034 mechanism for, 290, 295, 296 Diamond, 144, 187 1,4-Dioxane, 491–493 S 2 reactions vs., 299–301 Diamox, 1079 Dipeptides, 1055, 1060–1062, 1065 N stereochemistry of, 294–296 Dianeackerone, 752 Dipolar ions: Eclipsed conformation, 165 Diastereomers, 196–197, 220, 226, 463, amino acids as, 1050–1053 464 defined, 1050 Edman, Pehr, 1058 Diastereomeric recrystallization, 232 Dipole, 60 Edman degradation, 1058–1059 Diastereoselective, use of term, 215 Dipole–dipole forces, 79, 85 Ehrlich, Paul, 927 Diastereoselective reactions, 541 Dipole moments, 60 Eicosane, 148 Diastereotopic hydrogens, 405–406, 463 in alkenes, 63 Eisner, T., 1025 Diatomic molecules, 61 permanent, 79 Electromagnetic spectrum, 588–589 1,3-Diaxial interaction: and physical properties of molecules, 97 Electrons, 3–4 of a tert-butyl group, 176–177 simple molecules, 61 configurations, 29–30 Diazo coupling reaction, 917 Diprotic acid, 106 delocalization of, 139 Diazonium salts, 911, 913 Dirac, Paul, 27 donating, as inductive effect, 123 syntheses using, 913–914 Direct alkylation: energy of, 43 Diazotization, 911–912 of esters, 823, 838 sharing, 6 deamination by, 915–916 of ketones, via lithium enolates, 823 in complexes, 940–942 Diborane, 353 Directed aldol reactions, 862 withdrawing, as inductive effect, 123 Dibromobenzenes, 619 and lithium enolates, 865–866 Electron deficient, 453 2,3-Dibromopentane, 218 Disaccharides, 966–994 Electron-deficient atoms, as Lewis acids, 110 Dicarboxylic acids, 765–766 artificial sweeteners, 993–994 Electron delocalization, 583–585 Dichlorocarbene, synthesis of, 367 cellobiose, 993 Electron density surfaces, 36, 258, 264, 269, Dichloromethylbenzene, 686 defined, 966 290 Dicyclohexano-18-crown-6, 522 lactose, 987, 994 Electron-donating groups, 684 I-10 INDEX

Electronegative groups, deshielding, selective binding of drug enantiomers to synthesis of, 514–516 402, 415 left- and right-handed coiled DNA, Equatorial bonds, of cyclohexane, 173–174 Electronegativity, 5, 49, 59 218 Equilibrium, 23 Electronegativity differences polarize bonds separation of, 232 Equilibrium constant (Keq), 113 (principle), 137 Enantiomerically pure, use of term, 254 and standard free-energy change, 125–126 Electronic factors, in aldehydes and Enantiomeric excess, 213–214, 218, 515 Erythromycin, 784 ketones, 725 Enantiomerism, 232 Eschenmoser, A., 322, 608, 958 Electronic spectra, 591 Enantioselective, 215 Essential amino acids, 641, 1050 Electron impact (EI) ionization, 424 Enantioselective reactions, 215, 541 Essential nutrients, 920 Electron probability density, 28 Enantiotopic hydrogens, 405 Essential oils, 1021 Electron-withdrawing effect of a phenyl Enantiotopic hydrogen atoms, 463 Esters, 74, 717, 761–810 group, 895 Endergonic reactions, 249–250 from acyl chlorides, 780 Electron-withdrawing groups, 684 Endo, 602, 604 aldehydes by reduction of, 718–720 Electrophiles, 112–113, 317, 339–340 Endothermic reactions, 125, 451 amides from, 786 Electrophilic addition, 339–340 Energies of activation, 462 from carboxylic acid anhydrides, 780–781 of bromine and chlorine to alkenes, Energy, 27 direct alkylation of esters, 823, 838 359–363 defined, 123 esterification, 778–781 defined, 339 Energy changes, 123–125 acid-catalyzed, 778–780 of hydrogen halides to alkenes, 340–345 Energy of activation, 462 reactions of, 800–801 Electrophilic aromatic substitutions (EAS), Energy state, 27 saponification, 781–783 709, 910, 913, 917, 921 Enols (alkene alcohols), 811–812 synthesis of, 778–781 substituents and position of, 677–683 racemization via, 824–826 Esterifications, 778–781 electron-donating and electron- reactions via, 815–824 Fischer, 778 withdrawing groups, 684 Enolates: transesterification, 781 meta directors, 681–683 of β-dicarbonyl compounds, 824–825 Estradiol, 68, 202, 1030–1032 ortho–para directors, 677–681 defined, 812 Estrogens, 1030 table, 683 racemization via, 815–817 synthetic, 1031 and sulfonation–desulfonation, 667 reactions via, 815–824 Ethanal, 712 and thyroxine biosynthesis, 661, 665 regioselective formation of, 822–823 Ethane, 7, 115, 148 Electrospray ionization (ESI), 436–437, Enolate anions, 812–813 bond length, 42 1084 Enolate chemistry, summary of, 837–838 carbon–carbon bond of, 57 mass spectrometry (MS) with (ESI-MS), Enol form, 813 conformational analysis of, 165–166 1085 Enol tautomers, 852 physical properties, 78 Electrostatic potential, 110. See also Map of Enone, 858 radical halogenation of, 459 electrostatic potential (MEP) Enthalpies, 125 sp2 hybridization, 30 Elements, 3–4 Enthalpy change, 125, 137 structure of, 35 defined, 3–4 Entropy change (ΔS), 125 Ethanoic acid, 147, 762 electronegativities of, 5 Environmentally friendly alkene oxidation Ethanol, 490, 493–495 periodic table of, 2, 4, inside front cover methods, 521 as an hypnotic, 495 Eleutherobin, 362 Enzymes, 195, 215–216 as a biofuel, 495 Eliminations: defined, 1075 miscibility of, 84, 494 β eliminations, 288 resolution by, 232 Ethanoyl group, 713 1,2 eliminations, 288 Enzyme-substrate complex, 1075 Ethene (ethylene), 7, 57 Elimination–addition, 694–696 Epichlorohydrin (1-(chloromethyl) oxirane), anionic polymerization of, 474 Elimination reactions, 290, 299–303, 725 518, 529 bond length, 42 of alkyl halides, 288 Epimerization, 816–817, 848, 1004 physical properties, 36–40, 78 defined, 287 Epimers, 816, 985 radical polymerization of, 474–476 synthesis of alkenes via, 287–288 Epoxidation: structure of, 36–40 synthesis of alkynes by, 313–315 alkene epoxidation, 515 Ethers, 69. See also Epoxides Elion, Gertrude, 1098 Sharpless asymmetric epoxidation, boiling points, 492 Enal, 858 515–516 cleavage of, 513–514 Enamines, 731, 733–734, 736, 747, 834 stereochemistry of, 516 crown, 522–523 synthesis of, 834–836 Epoxides, 514–521 cyclic, naming, 491 Enantiomers, 196–198, 204, 208 acid-catalyzed ring opening of, 516–517 dialkyl, 513 and chiral molecules, 197–198 anti 1,2-dihydroxylation of alkenes via, diethyl ether, 82, 493, 495–496, 513 naming, 204–208 519–521 as general anesthetics, 69 optical activity, 208–213 base-catalyzed ring opening of, 517 hydrogen bonding, 493 plane-polarized light, 209–210 carcinogens and biological oxidation, 525 by intermolecular dehydration of polarimeter, 210–211 defined, 514 alcohols, 509 specific rotation, 211–213 epoxidation, 514–516 nomenclature, 491–492 Pasteur’s method for separating, 232 hidden, 525–526 oxygen atom, 490 properties of, 208–213 polyethers from, 519 physical properties of, 492–494 resolution methods for, 232 reactions of, 516–519 protecting groups, 511–512 INDEX I-11

silyl, 512 drawing/using, 224–225 Galactan, 994 reactions of, 513–514 Fleet, G.W. J., 1009 Gamma globulin, 1064 synthesis of, 507–512 Fleming, Alexander, 436 Garfield, S., 139 by alkoxymercuration–demercuration, Floss, H., 1009 Gas chromatography (GC), 350, 435, 512 511 Fluoride anion, 268 Gates, M., 608 synthesis/reactions, 489–532 Fluorination, chain-initiating step in, 457 Gauche-butane, 176 trimethylsilyl, 512 Fluorine, 665 Gauche conformations, 166 Williamson synthesis of, 509–510 electronegativity of, 5 Gauche interaction, 176 Ethinyl estradiol, 57 principal stable isotopes of, 432 GC/MS (gas chromatography with mass Ethyl acetate, 74 reaction with alkanes, 454 spectrometry), 392 physical properties, 78 Fluorobenzene, 665 GC/MS (gas chromatography with mass Ethyl alcohol, 67, 155 Fluorocarbons, chemistry of, 81 spectrometry) analysis, 435 physical properties, 78 Fokt, I., 218 Gelb, M. H., 1065n Ethylamine, 70 Folic acid, 920, 1076 Gel electrophoresis, 1083–1084, 1090, Ethylbenzene, 669, 686 Formal charges, 49 1115, 1116 Ethyl bromide, 378 calculating, 12–13 gem-diols, 727 Ethylene, 495 summary of, 13 Geminal coupling, 422 polymerization of, 474–475 Formaldehyde, 25, 711, 714 Geminal dihalide (gem-dihalide), 315 Ethylene oxide, 492 bond angles, 72 Geminal hydrogens, 397, 407 Ethyl group, 65 Formic acid, 73, 147, 762 Genes: Ethyllithium, 136 Formyl group, 713 defined, 1092, 1105 Ethyl methyl ether, 493 Fourier transform, 87, 423 location of, for diseases on chromosome 19 (schematic map), 1092 Ethyne (acetylene), 7, 57 Fourier transform infrared (FTIR) bond length, 42 spectrometer, 87 General statement of Markovnikov’s rule, 344 physical properties, 78 Fourier transform NMR spectrometers, 392 2 Genetic code, 1062, 1087, 1106, sp hybridization, 40–42 Fourneau, Ernest, 928 1108–1111 structure of, 40–42 [4+2] cycloaddition, 600 Genetics, basics of, 1091–1092 Ethynylestradiol, 1031 Franklin, Rosalind, 1099, 1100 Genomics, 1085 Ethynyl group, 161 Free energy change: Gentamicins, 1003 Eucalyptol, 381–382 for the reaction, 249 Geometric specificity, 1076 Eugenol, 70, 618 relationship between the equilibrium Geranial, 385 Exchangeable protons, 412 constant and, 125–126 Gibbs, J. W., 125n Excited states, 32 Free-energy diagrams, 249–250 Gibbs free-energy change, 125n Exergonic reactions, 249–250 Free energy of activation, 249 Gilbert, W., 1114 Exhaustive methylation, 977 Free radicals, see Radicals Gilman reagents, 954 Exo, 602, 604 Freons, 481 Gilman reagent-mediated couplings, Exons, 1106 Frequency (ν), 88–89, 588 954–955 Exothermic reactions, 125, 451 Frequency of radiation, 88 Globular tertiary structures, 1074 Extremozymes, 541 Friedel, Charles, 668 Glucan, 994 (E)–(Z) system for designating alkene Friedel–Crafts acylation, 669–671 Glucoside, 974 diastereomers, 283–284 Clemmensen reduction, 674 Glutamic acid, 1049, 1053, 1057 synthetic applications of, 673–674 Glutamine, 1049, 1074, 1087 Wolff-Kishner reduction, 675 F Glutathione, 1062 Friedel–Crafts alkylation, 668–669 Faraday, Michael, 618 Glycans, see Polysaccharides Friedel–Crafts reactions, limitations of, Farnesene, 385 Glycaric acid, 981 671–673 Fats, 1012–1013 Glyceraldehyde-3-phosphate dehydrogenase Fructose, 966 trans, 1016 (GAPDH), 642 Fructosides, 974 Fat substitutes, 1016–1017 Glyceraldehyde entantiomer, 230–231 Fullerenes, 638–639 Fatty acids, 75, 318, 1012–1021 Glycerol, 493 Fumaric acid, 778 composition, 1013, 1015 Glycidic ester, 884 Functional class nomenclature, 153 omega-3, 1013–1014 Glycine, 1047 Functional groups, 55, 60, 64–65 reactions of the carboxyl group of, Glycogen, 994, 996–997 in biologically important compounds, 77 1019–1020 Glycols, 155, 368 defined, 64 saturated, 1013 Glycolipids, 1001–1002 interconversion (functional group unsaturated, 1013 lipids, 1039 transformation), 272–273, 939 reactions of the alkenyl chain of, 1020 Glycolysis, 811, 860–861 Furan, 640–641 Fehling’s solution, 979 Glycoproteins, 1001–1002 Furanose, 972–973, 991, 1004 Fexofenadine (Allegra), 217 Glycosides: Furchgott, R. F., 478 Fibrous tertiary structures, 1074 defined, 974 Fischer, Emil, 970, 1075 formation, 974–975 Fischer esterifications, 778 G hydrolysis of, 975 Fischer projections, 970–971 Gabriel synthesis of amines, 902–903, Glycosylamines, 999–1000 defined, 224 924, 1053 Glycylvalylphenylalanine, 1056 I-12 INDEX

Goodman, L., 1098 Hemoglobin, 85, 1046, 1064, 1075, 1081, Hot basic potassium permanganate, cleavage Gramicidin, 523 1083, 1113 with, 371–372 Graphene, 187, 188 Henderson–Hasselbalch equation, 1051 HSQC, 420 Graphite, 187, 188 Heparin, 1000 Hückel’s rule, 631, 634–637, 649, 652 Grignard, Victor, 548 Heptadecane, 148 annulenes, 629–630 , mechanism for, 552 Heptane, 148 aromatic ions, 631–633 Grignard reagents, 548–550, 939 Herbicides, organic halides as, 643–644 diagramming the relative energies of alcohols from, 552–560 Hertz (Hz), 410, 588 orbitals in monocyclic conjugated Grignard synthesis, planning, 555–556 Hertz, H. R., 588n systems based on, 628 preparation of carboxylic acids by Heteroatoms, 60 NMR spectroscopy, 630–631 of, 772–773 Heterocyclic amines, 892 Huffman, D., 638 reactions with carbonyl compounds, basicity of, 895–896 Hughes, Edward D., 247 551–552 Heterocyclic aromatic compounds, 639–641 Human genome, sequencing of, 1085 reactions with epoxides (oxiranes), 551 Heterogeneous catalysis, 317 Human Genome Project, 1091, 1115 restrictions on the use of, 558–559 Heterogeneous catalyst, 320 Human hemoglobin, 1064 Ground state, 32 Heterolysis, 111, 137 Hund’s rule, 29, 47, 628 Group numbers, atoms, 4 Heterolytically, use of term, 134, 135, Hybrid atomic orbitals, 32, 43 Grubbs, Robert, 956, 957 305, 449 Hybridization, and acidity, 122–123 Heteronuclear correlation spectroscopy Hybrid of resonance structures, 22 H (HETCOR, or C-H HETCOR), Hydrating ions, 83 Hydration, of alkenes, 346, 496 1H–1H correlation spectroscopy, 420 420, 428–430 Hydrazones, 733 Half-chair conformations, 171 Heteropolysaccharides, 994 Hydride ions, 119, 536 Halo alcohol, 364 Heterotopic atoms, 403–405 Hydride shift, 310 α-Haloalcohols, 530 Hexadecane, 148 Hydroboration: Haloalkanes, 65, 76 Hexane isomers, physical constants of, 148 defined, 352 Haloform reaction, 774, 818–819 Hexanoic acid, 762 Halogens: Hexose, 968, 991 mechanism of, 353–354 compounds containing, 185 High-density lipoproteins (HDLs), 1029 stereochemistry of, 355 reactions of alkanes with, 454–456 Highest occupied molecular orbital synthesis of alkylboranes, 353–355 Halogen addition, mechanism of, 360–363 (HOMO), 248, 462, 585, 592, 616 Hydroboration–oxidation, 496–497 Halogenation at the α carbon, 821–824 High-performance liquid chromatography alcohols from alkenes through, 352 Halogen atoms, 241, 244, 274–275, 449 (HPLC), 232, 594, 1057–1058 as regioselective reactions, 356–357 Halogen molecules, 449 High-resolution mass spectrometry, 434–435 Hydrocarbons, 56–59, 92, 145, 283 Halogen substituents, 706 Hirst, E. L., 971n IR spectra of, 91–92 Halohydrin: Histamine, 735, 900 relative acidity of, 123 defined, 365 Histidine, 1050, 1060 Hydrogen, 6, 8 formation, 364–366 Histrionicotoxin, 890, 901 anti addition of, 321–322 mechanism for, 365–366 Hitchings, George, 1098 atomic number, 204 Halomon, 362 Hodgkin, Dorothy Crowfoot, 436, 437, 958 principal stable isotopes of, 432 Halonium ions, 363 Hofmann, August W. von, 923 syn addition of, 320–321 Haloperoxidases (HPO), 362, 959 Hofmann elimination, 897, 923–924, 927 Hydrogen abstraction, 449–450 Halothane, 496 Hofmann product, 295 Hydrogenases, 216 Hammond–Leffler postulate, 264–265, 293 Hofmann rearrangement, preparation of Hydrogenation, 285, 286 Haptens, 1082 amines through, 907–908 of alkenes, 183–184, 317–318, 338 Harington, C., 707 Hofmann rule, 294, 923 of alkynes, 183–184, 320–322 Hassel, O., 172 Homogeneous catalysis, 317 in the food industry, 318 Haworth, W. N., 756 Homogeneous hydrogenation, 944–947 function of the catalyst, 319–320 Haworth formulas, 970–971 Homologous series, 161 homogeneous, 944–947 HCN, conjugate addition of, 889 Homologues, 161 Hydrogen atoms, 257, 263, 266–267, 288 Heat contents, 125 Homolysis, 449 classification of, 153 Heat of hydrogenation, 285 Homolytic bond dissociation energies Hydrogen bonds, 79–80, 97, 493–494, 714 Heat of reaction, 285 (DH°), 451–454 formation of, 84, 85 Heck, Richard F., 949 calculating, 451 Hydrogen bromide, 106, 288, 374–375, 687 Heck–Mizoroki reaction, 947–949, 952, 953 defined, 451 anti-Markovnikov addition of, 472–474 Heisenberg, Werner, 27 using to determine the relative stabilities Hydrogen chloride, 106, 107 Heisenberg uncertainty principle, 30 of radicals, 451–452 Hydrogen halides, 501 Hell–Volhard–Zelinski (HVZ) reaction, Homopolysaccharides, 994 addition to alkynes, 340 820–821 Homotopic atoms, 404 electrophilic addition to alkenes, 339–340 Heme, 649, 1081 Homotopic hydrogen atoms, 455 Hydrogenolysis, 755 Hemiacetals, 726–727, 971–973 Hooke’s law, 88 Hydrogen peroxide, 476, 478 acid-catalyzed formation, 726–727 Horner–Wadsworth–Emmons reaction, Hydrolysis, 216, 261 essential structural features of, 726 740–741, 753 acetals, 728 formation, 726–727 Host-guest relationship, 522 acid-catalyzed, 516, 520–521, 524 INDEX I-13

of alkylboranes, 355–358, 497 Interferogram, 87 Isooctane, 146 regiochemistry and stereochemistry, Intermediates, 104, 255 Isopentane, 147 356–358 Intermolecular dehydration: Isoprene units, 1021 of amides, 788–789 of alcohols, ethers by, 508–509 Isopropyl, 152 by enzymes, 789 complications of, 508–509 Isopropyl alcohol, 490, 493 Hydronium ion, 106 Intermolecular forces (van der Waals forces), condensed structural formula for, 17 Hydrophilic, use of term, 84, 1018 79–80, 85 equivalent dash formulas for, 16 Hydrophobic, use of term, 84, 1018 in biochemistry, 85 Isopropylamine, 71 Hydrophobic effect, 84 boiling points, 82 Isopropylbenzene, 686 Hydrophobic group, 84 dipole–dipole forces, 79 Isopropyl group, 151 Hydroxide ion, 106 dispersion forces, 80–81 Isotopes, 4 Hydroxybenzene, 619 hydrogen bonding, 79–80 in mass spectra, 432–435 3-Hydroxybutanal, 856, 858, 860, 861 organic templates engineered to mimic Isotope-coded affinity tags (ICAT), 1087 Hydroxyl group, alcohols, 67 bone growth, 86 IUPAC system, for naming alkanes, 147–149 Hydroxyproline, 1047, 1057, 1074 solubilities, 83–84 4-Hydroxyproline, 1049 International Union of Pure and Applied J Hyperconjugation, 165, 257–258, 264 Chemistry (IUPAC), 15n, 148 system for naming alkanes, 148–149 Jones reagent, 545 I Intramolecular Claisen condensation, 853 Joule (J), 125n Introns, 1106 Jung, Michael E., 845 Ibuprofen, 216 Inversion, 248, 735 Ignarro, L. J., 478 Inversion of configuration, 253, 273 K Imides, 786 Iodide, 266 Imines, 731–732 Kam, C. M., 1079 Iodination, 665, 818 Index of hydrogen deficiency (IHD): Kanamycins, 1003 Iodine: calculating for compounds, 185–186 Karplus, Martin, 411 principal stable isotopes of, 432 defined, 184 Karplus correlation, 411 reaction with alkanes, 466 gaining structural information from, Katz, T., 652 Iodomethane, 241, 265, 932 184–186 Kekulé, August, 58, 622–623 Ions, 5 Indole system, 641 Kekulé–Couper–Butlerov theory of valence, Ion–dipole forces, 83, 85 Induced field, 401, 402, 631, 644–645 618–619 Ionic bonds, 5–6 Induced fit, 1075 Kekulé structures, 58 Ionic compounds, 6 Inductive effects, 123, 137, 600–601, for benzene, 622–623 694, 696 boiling points, 78 Ketene, 809 and acidity of carboxylic acids, 128 ion–ion forces, 78–79 Keto form, 813–814 of other groups, 129 Ionic reactions, 106, 449 Ketones, 55–56, 71–72, 711–760 Inductive electron-withdrawing effects, 128 carbocations, 133, 165 acid-catalyzed halogenation of, 817–818 Industrial styrene synthesis, 669 organic halides, 548, 558, 740 from alkenes, arenes, and 2° alcohols, Infrared spectra: Ion–ion forces, 78–79 720–721 interpreting, 90–97 Ionization, 424 α,β -unsaturated, additions to, 856, of substituted benzenes, 647–648 Ionophore antibiotics, 523 869–871 Infrared (IR) spectroscopy, 86–90 Ionophores, 523 Baeyer-Villiger oxidation, 741–743 alcohols, 93–94 Ion sorting, 435 base-promoted halogenation of, 817–818 amines, 94–95 Ion trapping, 523 carbonyl group, 535, 712 carbonyl functional groups, 92–93 Ipatiew, W., 846 chemical analyses for, 743 carboxylic acids, 94, 768 Ipecacuanha, 927 direct alkylation of, via lithium enolates, defined, 86 Iron(III) halides (ferric halides), 110, 823 dispersive IR spectrometers, 87 941–942 IR spectra of, 743–744 Fourier transform infrared (FTIR) Isoborneol, 311, 562 mass spectra of, 745–746 spectrometer, 87 Isobutane, 147 from nitriles, 721–722 functional groups containing heteroatoms, Isobutyl, 152 NMR spectra of, 744–745 92–93 Isobutyl alcohol, 493 nomenclature of, 712–714 hydrocarbons, 91–92 Isobutylene, polymerization of, 476 nucleophilic addition to the carbon– interpreting IR spectra, 90–97 Isoelectric focusing, 1085 oxygen double bond, 723–726 phenols, 93–94 Isoelectric point, 1050–1051, 1083, 1085 oxidation of, 751 wavenumbers, 87 Isolable stereoisomers, 228 oxidation of secondary alcohols to, 542 Ingold, Christopher K., 204, 247 Isolated double bonds, 582–583 in perfumes, 715 Inhibitors, aromatase, 1032 Isoleucine, 1073, 1087 physical properties, 714–715 Initial ozonides, 373 Isomaltose, 1007 relative reactivity, 725 Initial rates, 247 Isomers, 14–15 spectroscopic properties of, 743–746 Insecticides, aryl halides as, 676 constitutional, 195, 208 summary of addition reactions, 746–747 Insertion–deinsertion (ligands), 943–944 defined, 195 synthesis of, 720–722 Insulin, 1063–1064 stereoisomers, 196–197 Tollens’ test (silver mirror test), 743 Integration of signal areas, 396 subdivision of, 197 UV spectra, 746 I-14 INDEX

Ketone enolates, b-dicarbonyl compounds defined, 7 isolectric point of, 1053 by acylation of, 855–856 formal charge, 12 Lysozyme, 1046, 1061 Ketopentose, 968, 970 rules for writing/drawing, 7–8 mode of action, 1077–1079 Ketose, 968, 979 Ligands: Keto tautomers, 852 BINAP, 218, 233 M Kharasch, M. S., 472 in transition metal complexes, 939, 941 Kiliani–Fischer synthesis, 736, 986–990 Ligand dissociation–association (ligand McLafferty rearrangement, 431 Kilocalorie of energy, 125 exchange), 943 Macrocyclic lactones, 784 Kinetic control, 293 Light, as electromagnetic phenomenon, 209 Macromolecules, 474 defined, 596 Like charges repel (principle), 47, 186 Magnetic resonance, 392 thermodynamic control of a chemical , 201, 385 Magnetic resonance imaging (MRI), reaction vs., 596–598 Linalool, 843 391, 423 Kinetic energy (KE), 123 Lindlar’s catalyst, 321 Malaria, 676 Kinetic enolate, 822–823 Linear polymers, 1055 MALDI (matrix-assisted laser desorption formation of, 822, 855 Linoleic acid, 480 ionization), 1085 Kinetic products, 596 Lipase, 216 MALDI mass spectrometry, 436 Kinetic resolution, 216 Lipids, 523, 809, 1011–1044 Malonic acids, 796 Kinetics, defined, 246 defined, 1012 Malonic ester synthesis: Knowles, William S., 217, 370, 515, 946 fatty acids, 75, 318, 1019–1020 of substituted acetic acids, 830–833 Kössel, W., 5 glycolipids, 1039 Maltose, 966–967, 991–993 Krätschmer, W., 638 in materials science and bioengineering, Mannich bases, 874 Kroto, H. W., 638 1020–1021 Mannich reaction, 874 Kumepaloxane, 362 phosphatides, 1037–1039 Mannosides, 974 phospholipids, 1036–1041 Map of electrostatic potential (MEP), 23, L prostaglandins, 1035–1036 53, 60–61, 121–128, 317 sphingosine, derivatives of, 1039 Markovnikov, V., 341 Lactams, 791–792 steroids, 1026–1035 Markovnikov additions, 341 Lactones, 783–784 terpenes, 1021 anti-, 345 Lactose, 987, 994 terpenoids, 1021 exception to, 345 Ladder sequencing, 1061 triacylglycerols, 1012–1019 regioselective reactions, 344 l-amino acids, 234, 1048–1050, 1054 waxes, 1040 Markovnikov regioselectivity, 496–497 Langmuir–Blodgett (LB) films, 1020–1021 Lipid bilayers, 1037 Markovnikov’s rule, 340–345, 472 Laqueur, Ernest, 1030 Lithium, electronegativity of, 5 defined, 341 (3E)-Laureatin, 337, 362 Lithium aluminum hydride, 538 general statement of, 344 LCAO (linear combination of atomic overall summary of, 539–540 theoretical explanation of, 342–343 orbitals) method, 31 Lithium dialkylcuprate, 954 Masamune, S., 994 l-DOPA, 946 Lithium diisopropylamide (LDA), 822, Mass, atoms, 4 Leaving groups, 242–243, 246 855, 865 Mass spectrometry (MS), 423–437, defined, 242–243, 246 Lithium enolates, 821–824 439–440 ionization of, 264–265 direct alkylation of ketones via, 822–823 base peak, 423, 424 nature of, 269–271 and directed aldol reactions, 865–866 of biomolecules, 436 Le Bel, J. A., 20, 232, 988 regioselective formation of enolates, 822 determining molecular formulas and Lecithins, 1037 Lithium reagents, use of, 559 molecular weights using, 434–435 Left-handed coiled DNA, selective binding Lithium tri-tert-butoxyaluminum hydride, electron impact (EI) ionization, 424 of drug enantiomers to, 218 717 electrospray ionization (ESI), 436–437, Lehn, Jean-Marie, 522 Lobry de Bruyn–Alberda van Ekenstein 1084 Less substituted alkene: transformation, 976 electrospray ionization with mass defined, 293 Lock-and-key hypothesis, 1075 spectrometry (ESI-MS), 1085 formation of, using bulky base, London forces, see Dispersion forces fragmentation, 425–432 293–296 Lone pairs, 38 by cleavage at single bond, 425–427 Leucine, 1073, 1087 Loop conformations, 1071, 1073 by cleavage of two bonds, 431–432 Leveling effect, 115n Loschmidt, Johann Josef, 622n to form resonance-stabilized cations, of a solvent, 312 Lovastatin, 48–49, 496 429–431 Levitra, 448, 479 Low-density lipoproteins (LDLs), 1029 of longer chain and branched alkanes, Levorotary, 210 Lowest occupied molecular orbital 427–428 Lewis, G. N., 5, 109–111 (LOMO), 592 GC/MS (gas chromatography with mass Lewis acids, 109–111 Lowest unoccupied molecular orbital spectrometry) analysis, 435 as electrophiles, 110 (LUMO), 248 high-resolution, 434–435 Lewis acid–base reactions, 137, 140 “Low-resolution” mass spectrometers, 434 ion sorting and detection, 435 Lewis acid–base theory, 109 Lucas, H. J., 531 ion trap mass analyzers, 523 Lewis bases, 109–111 Lucite, 418, 476 isotopes in mass spectra, 432–435 as nucleophiles, 112 , 592 matrix-assisted laser desorption-ionization Lewis structures, 22, 49 Lycopodine, 887 (MALDI), 436 and covalent bonds, 6–7 Lysine, 861, 1052–1053, 1057 molecular formula, determining, 434–435 INDEX I-15

molecular ion, 424 Methylene chloride, 242 carbohydrate synthesis, use of protecting depicting, 424–425 Methylene group, 65 groups in, 977 fragmentation of, 425–432 1-methylethyl, 151 classification of, 966–967 and isotopic peaks, 432 Methyl group, 65 conversion to cyclic acetals, 979 peptide sequencing using, 1061–1062 Methyl halides, 262–263, 826 conversion to esters, 978 polypetides/proteins, 1061–1062 Methylheptadecane, 163 d and l designations of, 969–970 quadrupole mass analyzer, 436 2-methylhexane, retrosynthetic analysis for, deoxy sugars, 999 time-of-flight (TOF) mass analyzer, 436 325 enolization, 976 Matrix-assisted laser desorption-ionization Methyl ketones, 745 ethers, formation of, 977–978 (MALDI), 436, 1085 converting to carboxylic acids, 819 isomerization, 976 Mauveine, 138–139 synthesis of, 826–827 Kiliani–Fischer synthesis, 736, 986–990 Maxam, A., 1114 Methyloxirane, 517 nitric acid oxidation, 981 Mayo, F. R., 472 2-methylpropene, addition of HBr to, 343 oxidation reactions of, 979–984 Meisenheimer intermediate, 692 Methyl salicylate, 618 Benedict’s reagents, 979–980 Melting point, 63, 78 Mevalonate ion, 496 Tollens’ reagents, 979–980 , 489 Micelles, 1017–1018 oxidative cleavage of polyhydroxy Mercapto group, 641 Michael, Arthur, 871 compounds, 982–984 6-Mercaptopurine, 641, 1098 Michael additions, 835, 871–872 periodate oxidations, 982–984 Merrifield, R. B., 810, 1069 Michelson interferometer, 87 reducing sugars, 979–980 Mescaline, 899 Micrometers, 87 Ruff degradation, 987 Meso compounds, 221–222 Micron, 588 structural formulas for, 970–972 Messenger RNA (mRNA) synthesis, 1106, Miller, S., 234 tautomerization, 976 1109–1110 Millimicron, 588 uronic acids, 998 synthesis-transcription, 1106 Mirror planes of symmetry, 203, 235 Monosubstituted benzenes, 647 Mesylates, 505–507 Mitomycin, 873, 1023, 1122 Montagnon, T., 139 meta-Chloroperoxybenzoic acid (MCPBA), Mitscherlich, Eilhardt, 618 Montreal Protocol, 481 514 Mixed triacylglycerold triacylglycerol, 1013 Moore, S., 1057 Meta directors, 681–683 MOs, see Molecular orbitals (MOs) Morphine, 608, 899 Meta-disubstituted benzenes, 648 Molar absorptivity, 591 MRI (magnetic resonance imaging) scan, Metarhodopsin, 327 Molecular formulas, 14 391, 423 MudPIT (multidimensional protein Methane, 6, 145, 148 determining, 434–435 identification technology), 1085 chlorination of: gaining structural information from, Mullis, Kary B., 1118 activation energies, 462 184–186 Multidimensional FTNMR spectroscopy, mechanism of reaction, 456–459 Molecular handedness, 201 420 orbital hybridization, 32 Molecular ion: Multiple covalent bonds, 7 physical properties, 78 depicting, 424–425 Multiple halogen substitution, 454–455 structure of, 32–34 and isotopic peaks, 432 Murad, F., 478 tetrahedral structure of, 20 Molecularity, 247 Murchison meteorite, 234 valance shell of, 44–45 Molecular orbitals (MOs), 30–32, 43, 47, 49 Muscalure, 163, 325 Methanide ion, 121 antibonding, 43 Muscle action, chemistry of, 168 Methanide shift, 309 bonding, 31 Muscone, 715 Methanogens, 56 explanation of the structure of benzene, Mutagens, 1105 Methanoic acid, 762 626–627 Mutarotation, 973 Methanol, 243, 247, 261, 266, 268, theory, 47 Myelin, 1039 494, 500 Molecular oxygen, 478 Myelin sheath, 1011 miscibility of, 83–84, 494 Molecular recognition, 522 Mylar, 797 physical properties, 493 Molecular structure determines properties Myoglobin, 1074–1075 Methanolysis, 261–262 (principle), 97 Myosin, 168, 1073 Methanoyl group, 713 Molecules: Myrcene, 385 Meth-Cohn, O., 139 composition of, 6 Methionine, 274, 1073 with Nobel Prize in synthetic lineage, 608 synthesis of, 1053, 1054 Molina, M. J., 481 N Methotrexate, 920 Molozonides, 373 N-acetyl-d-glucosamine, 1000 Methoxide anion, 265 Monensin, 523 N-acetylglucosamine, 1000, 1002, 1077 Methyl alcohol (methanol), 67, 155 Monoalkylation, of an amine, 906 N-acetylmuramic acid, 1000, 1077 Methylaminium ion, 117 Monomers, 474 N-acylamino acids, 1055 Methylbenzene, 470, 619 Mononitrotoluenes, 680 NAD+, 641–643 Methyl carbocation, 258, 264 Monosaccharides, 275, 994, 1001–1002, NADH, 642–643 Methyl cyanoacrylate, 478 1004 Naming enantiomers, 204–208 Methylcyclohexane, 186 aldaric acids, 981–982 Nanoscale motors and molecular conformational analysis of, 175–176 alditols, 984 switches, 172 Methyldopa, 216 aldonic acids, synthesis of, 980–981 Nanotubes, 187, 639 Methylene, structure and reactions of, 367 bromine water, 981, 987, 992 Naphthalene, 637 I-16 INDEX

Naproxen, 217 Nonadecane, 148 heteronuclear correlation spectroscopy (S)-Naproxen, 946–947 Nonane, 148 (HETCOR, or C–H HETCOR), Natta, Guilio, 475 Nonaqueous solutions, acids and bases in, 422–423 Natural products, and treatment of disease, 135–136 Nuclear magnetic resonance (NMR) 48–49 Nonaromatic compounds, 634–635 spectrum, 392–398 Natural products chemistry, 3 Nonaromatic cyclohexadienyl carbocation, 662 Nucleic acids. See also Deoxyribonucleic acid Natural rubber, 1024 Nonbenzenoid aromatic compounds, (DNA); Ribonucleic acid (RNA) Nature prefers disorder to order (principle), 638–639 and protein synthesis, 1090–1124 138 Nonbonding pairs, 44 water solubility, 85 Nature prefers states of lower potential Nonpolar compounds, boiling point, 82 Nucleophiles, 112–113, 242–246, 317, 499, energy (principle), 137–138, 186 Nonpolar molecules, 61–63 502–503, 513, 788, 821 Nature tends toward states of lower potential Nonreducing sugars, 980 in acylation reactions, 910 energy (principle), 47 Noradrenaline, 899 concentration and strength of, 265–266 N-bromosuccinimide (NBS), 470, 685 Norethindrone, 68, 1031 conversion of terminal alkynes to, Negishi, Ei-ichi, 949 Novestrol, 1031 315–317 Neighboring-group effects, 531 Noyori, R., 217, 370, 515 defined, 243 Neighboring-group participation, 279 Noyori, Ryoji, 946 reactions of carbonyl compounds with, Neomycins, 1003 N-terminal, 1055, 1058–1059 536 Neopentane, 147, 153, 456 Nuclear magnetic resonance (NMR) Nucleophilic addition, 536 boiling point, 81 spectrometry, 391–423, 437–439 Nucleophilic addition–elimination, 773–774 Neopentyl group, 152 13C (carbon-13) NMR spectroscopy, Nucleophilic aromatic substitution (SNAr), Neopentyl halides, 263 414–421 692–694 Neurotransmitters, 900–901 broadband (BB) proton decoupled, by addition–elimination, 692–693 Neutrons, 3–4 414–415, 418–419 by elimination–addition, 694–696 Newman projections, 164–165 chemical shifts, 415–417 Nucleophilicity, 266 Newman projection formula, 164 DEPT 13C NMR spectra, 417–419 basicity vs., 266 Niacin (nicotinic acid), 900, 1076 interpretation of, 414 Nucleophilic reactions, 240–281 Nicolaou, K. C., 139, 483, 516, 600, 608, one peak for each magnetically distinct carbocations, 257–259 614, 749, 802 carbon atom, 414–415 relative stabilities of, 257–259 Nicotinamide adenine dinucleotide, chemical shift, 393–395, 415–417 structure of, 257 ­641–643 parts per million (ppm) and the δ scale, free-energy diagrams, 249–250 Nicotine, 70, 900 394 leaving groups, 246 Ninhydrin, 1057 chemical shift equivalent, 403–406 nucleophiles, 243–246 Nitrates, 912 heterotopic atoms, 403–404 organic halides, 264 Nitrate ion, 12 homotopic hydrogens, 403–404 SN1 reaction, 247–249 Nitric acid, 10, 665–666 conformational changes, 413–414 mechanism for, 248–249 oxidation, 981 coupling (signal splitting), 396–398 rate-determining step, 247–248 Nitric oxide, 448, 478, 479 defined, 391 SN2 reaction, 246–249 Nitriles, 75, 717 diastereotopic hydrogen atoms, 405–406 measuring, 246–247 acidic hydrolysis of, 790–791 enantiotopic hydrogen atoms, 405–406, mechanism for, 247–249 aldehydes by reduction of, 719 463 stereochemistry of, 273 1 basic hydrolysis of, 791 H NMR spectra, 407, 410, 413–414 transition state, 248–252 ketones from, 720–721 magnetic resonance imaging (MRI), 391, temperature and reaction rate, 250–251 preparation of carboxylic acids by 423 Nucleophilic substitution, 240 hydrolysis of, 771–772 multidimensional FTNMR spectroscopy, substrates for, 506 reactions of, 801 420 Nucleophilic substitution reactions, Nitrites, 912 proton NMR spectra: 242–243, 273–274 Nitrogen, 8 interpreting, 398–401 Nucleotides/nucleosides, 999–1000, principal stable isotopes of, 432 and rate processes, 412–414 1092–1095 Nitrogen, compounds containing, 186 protons, shielding/deshielding, 401–402 defined, 1092–1093 Nitrogen inversion, 894 signal areas, integration of, 396 laboratory synthesis, 1095–1098 1-Nitropropane, 409–410 signal splitting, 396–398 medical applications, 1098 Nitrous acid, reactions of amines with, spin decoupling, chemical exchange as silyl–Hilbert–Johnson nucleosidation, 911–913 cause of, 412–413 1095, 1122 primary aliphatic amines, 911 spin–spin coupling, 407–411 Number of double-bond equivalencies, use primary arylamines, 911–912 coupling constants, 410–411 of term, 184n secondary amines, 912 origin of, 407 Nylon, 797–798 tertiary amines, 913 vicinal coupling, 407 Nitrous oxide (laughing gas), 69 splitting patterns, recognizing, 410 O N-methylmorpholine N-oxide (NMO), 369 two-dimensional NMR (2D NMR) N-nitrosoamines, 912 techniques, 420–423 Octadecane, 148 Noble gas structure, 25 1H-1H COSY spectrum, 420–422 Octadecanoic acid, 762 Nodes, 27, 43 heteronuclear correlation cross-peak Octahedral rhodium complex, 939, 940 Nonactin, 523 correlations, 422–423 Octane, 148 INDEX I-17

Octet rule, 5 and potential energy, 124–125 Oxymercuration–demercuration, 497 exceptions to, 11–12 electrophiles, 112–113 alcohols from alkenes from, 349–352 Oils, 1013, 1015 eliminations, 288 defined, 349, 353, 496 Olah, George A., 257 energy changes, 123–125 mechanism of oxymercuration, 350–352 Olefiant gas, 283 illustrating using curved arrows, 107–108 rearrangements, 350 Olefins, 283 intermediates, 104 regioselectivity of, 349–350 , 955–958 Lewis acids and bases, 109–111 Oxytocin, 1062–1063 Oleksyszyn, J., 1079 mechanisms, 107–108, 134–135 Ozone, cleavage with, 372–373 Olestra, 1016–1017 nucleophiles, 112–113 Ozone depletion and chlorofluorocarbons Oligonucleotides, laboratory synthesis of, reaction mechanism, 104 (CFCs), 481 1116–1118 rearrangements, 104 Ozonides, 373 Oligopeptides, 435, 1055 relationship between the equilibrium Ozonolysis, 372 Oligosaccharides, 966 constant and the standard free- of an alkene, 373 Olympiadane, 172 energy change, 125–126 Omega-3 fatty acids, 1013–1014 Organic synthesis, 322–327 P Opposite charges attract (principle), 47, 97, defined, 322 P-2 catalyst, 320 137 planning, 323 p53 (anticancer protein), 1064–1065 and acid–base reactions, 110, 137 retrosynthetic analysis, 323–327 Paclitaxel (Taxol), 370 Optical activity, 208–213 Organic templates, engineered to mimic Palindromes, 1114 plane-polarized light, 209–210, 232, 235 bone growth, 86 polarimeter, 210–211, 220, 232 Palladium-catalyzed coupling reactions, Organic vitamin, 3 947–953 specific rotation, 211–213 Organolithium compounds, 548–552 Pallidol, 699 Optically active compounds, 209 reactions of, 548 p-Aminobenzoic acid, 920 Optical purity, 214 synthesis of, 939 Pantothenic acid, 931, 1076 Optical rotatory dispersion, 212 Organolithium reagents, 939 Para-disubstituted benzenes, 648 Orange II, 918 Organomagnesium compounds, 549–552 Paraffins, 182 Orbitals, 28 reactions of, 549–552 Parent compound, 154 Orbital hybridization, 32 Organometallic compounds, 547–548, 939 Partial hydrolysis, 1060 Orbital overlap stabilized molecules Orientation, 602–604, 685, 695 and sequence comparison, 1061–1062 (principle), 47 Orlon, 476 Organic chemistry: Pasteur, Louis, 232 Ortho-disubstituted benzenes, 648 method for separating enantiomers, 232 defined, 2 Orthogonal protecting groups, 1069 development of the science of, 3 Pauli exclusion principle, 29, 31, 47 Ortho–para directors, 677–681, 683, 910 Pauling, I., 1102 oxidation–reduction reactions in, Osazones, 985 536–537 Pauling, Linus, 1072 Osmium tetroxide, 368–369, 371 structural formulas, writing/interpreting, Pedersen, Charles J., 522 Oxetane, 491 15–18 Penicillamine, 216 Organic compounds: Oxidation, 1118 Penicillins, 792, 802 as bases, 132–133 of alcohols, 542–547 Penicillinase, 792 families of, 76–77 of alkenes, 369, 770 Pentadecane, 148 ion–ion forces, 78–79 environmentally friendly methods, 521 Pentalide, 163 molecular structure, 77–85 of alkylboranes, 355–358 Pentane, 146, 148 physical properties, 77–85 regiochemistry and stereochemistry, insolubility in water, 494 356–358 Organic halides, 264, 548, 740 radical chlorination of, 462 analogous, 558 defined, 537, 542 stereochemistry of chlorination at C2 of, as herbicides, 643–644 Swern, 543–544, 715–716 463 Organic molecules, 4 Oxidation–reduction reaction, 289 Pentanoic acid, 371, 762, 770, 772 Organic reactions, 104–143 –, Pentose, 968, 1099 944 acid–base reactions, 120–123 Peptides, 98, 435, 767, 901, 1055 Oxidative cleavage, 371–372, 376 predicting the outcome of, 118–120 chemical synthesis of, 809–810 of alkenes, 371–373 and the synthesis of deuterium and defined, 810 tritium-labeled compounds, of alkynes, 375 synthesis of, 787, 793, 802, 809–810 136–137 Oxidizing agents, 537, 665, 688, 690 Peptide bonds, 1055 acidity, effect of the solvent on, 132 Oximes, 733, 906 Peptide linkages, 1046, 1055 acids and bases: reducing to amines, 925 Peptide synthesizers, 810, 1070 in nonaqueous solutions, 135–136 Oxirane, 491, 493 Perfumes: in water, 106 Oxonium cation, 724 aldehydes in, 715 Brønsted–Lowry acids and bases, Oxonium ion, 132 ketones in, 715 105–106, 113–118 Oxonium salts, 513 Pericyclic reactions, 599–600 carbanions, 111–113 Oxygen, 8 Periodic table of the elements, 2, 4 carbocations, 111–113 atomic number, 204 Perkin, W., Jr., 842 carboxylic acids, acidity of, 126–128 compounds containing, 186 Perkin, William Henry, 138–139 covalent bonds: principal stable isotopes of, 432 Permanent dipole moment, 79 homolysis and heterolysis of, 445 as a radical, 478 Peroxides, 449 I-18 INDEX

Peroxy acid (peracid), 514 Plexiglas, 418, 476 cellulose derivatives, 998 Perspex, 476 Poison ivy, 1019 defined, 994 Petroleum: Polar aprotic solvents, 266–269 glycogen, 994, 996–997 refining, 145–146 Polar bonds, electronegativity differences as heteropolysaccharides, 994 as source of alkanes, 145 causes of, 97 homopolysaccharides, 994 typical fractions obtained by distillation Polar covalent bonds, 59–61 starch, 994–996 of, 146 maps of electrostatic potential (MEP), water solubility, 85 Pettit, R., 630 60–61 Polystyrene, 476, 669 Pfizer, 48–49 as part of functional groups, 59–60 Polytetrafluoroethene, 476 Phase sign, 27 Polarimeter, 209–211, 220, 232 Polyunsaturated fats/oils, 479, 1013 Phase transfer catalysts, 522 Polarizability, 269, 299 Polyunsaturated hydrocarbons, 582–583 Phenacetin, 806 and basicity, 301 Polyvinyl chloride (PVC), 476 Phenanthrene, 636–638 Polarized bonds underlie inductive effects p orbitals, 29 Phenols, 68, 490, 619, 730, 763, 804 (principle), 137 Positive entropy change, 138 as acids, 130–131 Polar molecules, 61–63 Potassium dichromate, 138 converted to ethers, 510 Polar protic solvents, 266–269 Potassium permanganate, 368, 371, distinguished/separated from alcohols and Polyacrylonitrile, 476 546–547 carboxylic acids, 131 Polyamides, 797–798, 1046 Potential energy (PE): infrared (IR) spectra of, 93 Polybrominated biphenyls (PBBs), 644 and covalent bonds, 124–125 synthesis of, 915 Polybrominated biphenyl ethers (PBDEs), defined, 123–124 in Williamson synthesis, 510 644 Potential energy diagram, 165 Phenyl acetate, 679 Polybromodiphenyl ethers (PBDEs), 644 Powers, J. C., 1079 Phenylalanine, 641, 993, 1048 Polychlorinated biphenyls (PCBs), 644, Precursors, identifying, 324–326 693–694 Phenylalanine hydroxylase, 641 Pregnenolone, 562 Polycyclic alkanes, 181–182 Phenylethanal, infrared spectrum of, 744 Prelog, V., 204 Phenylethene, 476, 686 Polycyclic aromatic hydrocarbons (PAH), 636–637 Prenylated proteins, 1065 2-Phenylethylamines, 899 Polyesters, 797–798 Presnell, S., 1079 Phenyl groups, 65, 620 Polyethers, from epoxides, 519 Priebe, W., 218 Phenyl halides, 242 Polyethylene, 448, 474–476 Primary alcohols, 67 unreactivity of, 274–275 Polyethylene glycol (PEG), 492 chemical test for, 545–546 Phenylhydrazones, 733 Polyethylene oxide (PEO), 492 dehydration of, 303–304 Phenylosazones, 984–985, 1006 Polyhydroxy compounds, oxidative cleavage mechanism for, 307–308 Pheromones, 163 of, 982–984 rearrangement after, 311–312 Phillips, S. E., 1075 Polyketide biosynthesis, 868–869 preparation of carboxylic acids by Phillips triolefin process, 957–958 Polymers, defined, 474 oxidation of, 770–771 Phosgene, 792 Polymerase chain reaction (PCR), Primary alkyl halide, 65 Phosphatides, 1037–1039 1118–1120 Primary amines: Phosphatidic acid, 1036 Polymerizations, 474–476 addition of, 731–735 Phosphatidylserines, 1037 Polymer polypropylene, 57 preparation of: Phosphodiesterase V (PDE5), 479 Polymethyl methacrylate, 476 through Curtius rearrangement, 926 Phospholipids, 1036–1041 Polypeptides, 1055–1071, 1083–1085 through Hofmann rearrangement, Phosphoramidite, 1117 analysis of, 1083–1085 907–908 Phosphoranes, 737 as linear polymers, 1055 through reduction of nitriles, oximes, Phosphoric acid, 1036 primary structure of, 1058–1062 and amides, 906 Phosphorus, principal stable isotopes of, 432 complete sequence analysis, 1060–1061 through reductive amination, 904–905 Phosphorus pentoxide, 790 C-terminal residues, 1060 Primary carbocations, 258, 264 Phosphorus tribromide, 501 Edman degradation, 1058–1059 Primary carbon, 67, 153 Phosphorus ylides, 737 examples of, 1062–1065 Primary carbon atom, 65 Photons, 588 peptide sequencing using mass Primary structure: Photosynthesis and carbohydrate spectrometry and sequence databases, of polypeptides and proteins, metabolism, 967–968 1061–1062 1058–1062 Phthalic acid, 765 Sanger N-terminal analysis, 1059–1061 of a protein, 1046, 1062–1065, 1071 Phthalimide, 786, 902 purification of, 1083 Primer, 1114–1115 Physical properties, 77–78 synthesis of, 1065–1071 Prochirality, 541 Phytostanols, 1029 activation of the carboxyl group, Progesterone, 562, 1031 Phytosterols, 1029 1067–1068 Progestins, 1030–1031 Pi (π) bonds (π bonds), 37, 44 automated peptide synthesis, 1069– Proline, 1047, 1049, 1057, 1074, 1076 Pitsch, S., 1096 1071 Prontosil, 927–928 Plane of symmetry (mirror plane), 203 peptide synthesis, 1068–1069 Propane, 148 Plane-polarized light, 209–210, 213, 232, protecting groups, 1066–1067 Propene (propylene), 36, 56–57, 158, 340 235 Polypropylene, 476 Propyl alcohol, 493 Plaskon, R. R., 1079 Polysaccharides, 994–998 structural formulas for, 15 Plasmalogens, 1037 cellulose, 994, 997–998 Propylene glycols, 493, 495 INDEX I-19

Propylene oxide alginates, 14 Q autooxidation, 479 Propyl group, 151 Qu, X., 218 benzylic substitution, 469–471 Prostaglandins, 1035–1036 Quadrangularin A, 699 Bergman cycloaromatization reaction, 482–483 Prosthetic group, 1076, 1081 Quadrupole mass analyzer, 436 chlorination of methane, 456–458 Protecting groups, 561, 690–691 Quanta, 588 combustion of alkanes, 479–480 acetals, 729–730 Quantum mechanics, atomic structure and, amino acids, 1066–1067 27–28 halogenation of higher alkanes, 459–462 ethers, 511–512 Quaternary ammonium hydroxides, 923 homolytic bond dissociation energies, 451–454 orthogonal, 1069 Quaternary ammonium salts, 894, 897 molecular oxygen and superoxide, 478 tert-butyl ethers, 511 Quaternary structure, of a protein, 1071– Proteins, 1045, 1079–1087 1075 nitric oxide, 478–479 analysis of, 1083–1085 Quinine, 138–139, 436, 899, 927 radical polymerization of alkenes, 474– conjugated, 1081–1083 478 defined, 1055 that generation tetrahedral chirality R centers, 462–465 prenylated, 1065 Racemic forms (racemic mixture), 213–214, Random coil arrangement, 1074 primary structure of, 1046, 1062–1065, 462 Raney nickel, defined, 731 1071 and enantiomeric excess, 213–214 Ras proteins, 1065 complete sequence analysis, 1060–1061 and synthesis of chiral molecules, 214– Rate constant, 247 215 C-terminal residues, 1055 Rate-determining step, 255, 341 Racemization, 259–261 Edman degradation, 1082–1083 Rate-limiting step, 255, 270 partial, 259 examples of, 1062–1065 (R)-carvone, 711 via enols and enolates, 815–821 peptide sequencing using mass Reaction coordinate, 249 Radicals, 449. See also Radical reactions spectrometry and sequence databases, Reaction mechanism, defined, 104 1061–1062 alkanes: Rearrangements, 104 Sanger N-terminal analysis, chlorination of, 455–456 alkenes, 348–349 1060–1061 combustion of, 481 during dehydration of primary alcohols, proteomics, 1061, 1085–1087 alkyl radicals, geometry of, 462 311–312 purification of, 1083–1085 antioxidants, 480 during dehydration of secondary alcohols, quaternary structure, 1075 autoxidation, 479–480 309–311 secondary structure, 1071–1074 bromine, selectivity of, 462 McLafferty rearrangement, 431 organic reactions, 104, 107, 109–111 synthesis of, 1065–1071 chain reaction, 457–458 oxymercuration–demercuration, 350 activation of the carboxyl group, chlorination: 1067–1068 of alkanes, 455 Reducing agent, 537 protecting groups, 1066–1067 of methane, 456–459 Reducing sugars, 979–980 tertiary structure, 1074–1075 chlorine selectivity, lack of, 455–456 Reduction, 318 water solubility, 85 formation/production of, 449 defined, 536 Proteome, 1085–1087, 1092 homolytic bond dissociation energies dissolving metal reduction, 321 (DH°), 451–454 Proteomics, 435, 1061, 1085–1087, 1121 Reductive amination: calculating, 451 Protic solvent, 132, 267–269 mechanism for, 904–905 to determine the relative stabilities of preparation of primary, secondary, and Protons, 3–4 radicals, 451–453 tertiary amines through, 904–905 shielding/deshielding, 401–402 methane chlorination, 456–459 Regioselectivity, of oxymercuration– Protonated alcohol, 132, 134–135, 260, activation energies, 462 demercuration, 349–350 304, 306, 499, 502, 503, 726 molecular oxygen and superoxide, 478 Reinforcing effect, 28 Proton NMR spectra: multiple halogen substitution, 454–455 Relative configuration, 229–231 interpreting, 398–401 nitric oxide, 448, 478, 479 Relative potential energy, 124 and rate processes, 412–414 radical halogenation, 454–456 Relative probability, 27 Protonolysis, of alkylboranes, 359 radical polymerization of alkenes, Relative reactivity, aldehydes vs. ketones, 725 Pseudoephedrine, 120 475–476 Relative stability, 124 Psicose, 1006 tetrahedral chirality centers, 605, 1028 Relaxation process, 423 Purcell, Edward M., 392 Radical addition: Relaxation times, 423 Purine–purine base pairs, 1100 to alkenes, 472–474 Replacement nomenclature, defined, 491 Pyramidal inversion, 894 to a π bond, 450 Replacement reactions, of arenediazonium Pyranose, 972–973 Radical anion, 321 salts, 913–916 Pyrene, 637 Radical cation, 424 Resolution, 894, 898–899 Pyridine, 639–640 Radical chain reaction, 472 by enzymes, 232 Pyridinium chlorochromate (PCC), 546 Radical halogenation, 454–456 kinetic, 216 Pyridoxal phosphate (PLP), 735 Radical polymerization, of alkenes, 475–476 Resonance, 23 Pyridoxine (vitamin B6), 735 Radical reactions, 448–488 Resonance contributors, 625. See also Pyrimidine, 641, 892, 896, 920, 1093 of alkanes with halogens, 454–456 Resonance structures Pyrimidine-pyrimidine base pairs, 1100 allylic chlorination, 466–468 Resonance effects, 138, 679, 696 Pyrolysis, 1024 anti-Markovnikov addition of hydrogen Resonance effects can stabilize molecules and Pyrrole, 639–640 bromide, 472–474 ions (principle), 138 I-20 INDEX

Resonance energy, 624, 626 Ruh-Pohlenz, C., 1096 Sex hormones, 1030–1032 Resonance stabilization, 24–25, 579–581 Ruthenium, 218, 233, 317 Sharing electrons, 6 Resonance structures (resonance Sharpless, Barry, 217 contributors), 22 S Sharpless, K. B., 370, 515, 946, 994 estimating the relative stability of, Sharpless asymmetric epoxidation, 515–516 Saccharic acid, 981 588–589 Sheehan, John C., 802 Saccharin, 993–994 rules for writing, 24–25, 586–588 Shells, 4 S-adenosylmethionine, 274 Resonance theory, 22, 58, 578–582 Shielding: Restricted rotation, and the double bond, 39 Salicylic acid, 48–49 atoms, 415 Restriction endonucleases, 1114 Salts, 6 protons, 401–402 Resveratrol, 699 Salt formation, water solubility as a result of, 1,2 shift, 309 119–120 Retention times, 435 Shikimic acid, 1009 Salvarsan, 927 Retinal, 72, 326–327 Sialyl Lewisx acids, 965, 1001–1003 Samuelsson, B. I., 1036 Retro-aldol reaction, 857–858 Sickle-cell anemia, 1064 Sandmeyer reaction, 914–915 in glycolysis, 860–861 Side chain: Sanger, Frederick, 1059, 1064, 1114 Retrosynthetic analysis, 323–327, 377–378 benzylic halogenation of, 686 disconnections/synthons/synthetic Sanger N-terminal analysis, 1059 defined, 686 equivalents, 378–379 Saponification, 781–783 oxidation of the, 688 key to, 377 of triacylglycerols, 1017–1019 Sigma bonds (σ bonds), 34–35, 44 stereochemical considerations, 378–382 Saturated compounds, 56, 318 and bond rotation, 164–166 Retrosynthetic arrow, 323 Saturated fatty acids, 1013 Signal splitting, 396–398 Reverse turns, 1073 Sawhorse formula, 164 Silicon, principal stable isotopes of, 432 Rhodium, 233, 317, 319 (S)-BINAP, 218, 233 Silyl ether protecting groups, 512 geometries of, 939–940 σ-bond framework, 37 Silyl–Hilbert–Johnson nucleosidation, Rhodium complex Rh(Ph3P)3H2Cl, 942 Schardinger dextrins, 1007 1095–1096, 1122 Ribonucleic acid (RNA), 3 Schoenberg, B. P., 1075 Simmons, H. E., 368 defined, 1091 Schrock, Richard, 956, 957 Simmons–Smith cyclopropane synthesis, genetic code, 1062, 1087, 1106, 1108, Schrödinger, Erwin, 27 368 1109–1111 Schultz, Peter G., 1082 Simple addition, 869 messenger RNA (mRNA) synthesis, 1106 SDS–PAGE (sodium dodecyl sulfate– Simple triacylglycerols, 1013 and protein synthesis, 1065–1071 polyacrylamide gel electrophoresis), Single-barbed curved arrows, 449 ribosomes, 1107–1108 1084 Single bonds, 34 RNA polymerase, 1106 sec-butyl, 152 Singlets, 397 transcription, 1106 sec-butyl alcohol, 493 Site-specific cleavage, of peptide bonds, 1061 transfer RNAs (tRNAs), 1108–1110, Secondary alcohols, 67 Skeletal formulas, 18 1112, 1113 chemical test for, 545–546 Skou, Jens, 523 translation, 1111–1113 dehydration of, 303–311 Smalley, R. E., 638 Ribosomal RNA (rRNA), 1107–1109 mechanism for, 304–305 Smith, D. C. C., 1008 Ribosomes, 1107–1108 rearrangements during, 309–311 Smith, M., 139 Ribozymes, 1076, 1107 Secondary alkyl halide, 65–66, 272 Smith, R. D., 368 Right-handed coiled DNA, selective binding Secondary amines: SN1 reactions, 255 of drug enantiomers to, 218 addition of, 731–735 E1 reactions vs., 297, 301 Ring-closing metathesis (RCM), 956–957 preparation of: effect of the concentration and strength of Ring current, 630 through reduction of nitriles, oximes, the nucleophile, 265–266 Ring flip, 174 and amides, 906 effect of the structure of the substrate, Ring fusion, 636 through reductive amination, 904–905 262–263 Ring-opening metathesis polymerization Secondary carbocations, 258, 264 mechanism for, 255–257 (ROMP), 957 Secondary carbon, 65, 67, 153 rate-determining step, 255 Ring strain, 168–169 Secondary halides, 264, 300 reactions involving racemization, 259–261 see RNA, Ribonucleic acid (RNA) Secondary structure: SN2 reactions vs., factors favoring, 271 RNA polymerase, 1106 of DNA, 1099–1103 solvent effects on, 266, 267 Roberts, J. D., 412, 695 of a protein, 1072 solvolysis, 244, 246, 261–262 Robertson, A., 658 Second chirality center, in a radical stereochemistry of, 259–262 Robinson, Robert, 436, 658 halogenation, generation of, 463– SN2 reactions, 246–249 Robinson annulation, 872–873, 882 464 E2 reactions vs., 299–301 Rosanoff, M. A., 969 Self-assembled monolayers (SAMs), 1020– effect of the concentration and strength of Rotaxanes, 172 1021 the nucleophile, 265–266 Rowland, F. S., 481 Semicarbazone, 753 effect of the structure of the substrate, R,S-system of naming enantiomers, 204–208 Sequence databases, peptide sequencing 262–263 assigning (R) and (S) configurations, using, 1061–1062 functional group interconversion using, 204–205 Serine, 1048, 1074 271–272 Rubber, natural, 1024 Serine proteases, 1079–1081 measuring, 246–247 Ruff, Otto, 987n Serotonin, 735, 899 mechanism for, 247–249 Ruff degradation, 987 Sevin, 794 reactions involving racemization, 259–261 INDEX I-21

solvent effects on, 266–269 Stachyose, 1007 Streptomycin, 238, 1003 stereochemistry of, 252–254, 273 Staggered conformations, 164 Strong acids, 724 Sodioacetoacetic ester, 825, 851 Starch, 994–996 Structural formulas, 14 Sodium acetate, physical properties, 78 Staudinger, Hermann, 609 bond-line, 18–19 Sodium alkynides, 559–560 STEALTH® liposomes, 1038 condensed, 17 Sodium amide, 313 Stein, W. H., 1057 dash, 16–17 Sodium borohydride, 538 Step-growth polymers, 798 three-dimensional, 20–21 overall summary of, 539–540 Stephens–Castro coupling, 951–952 writing/interpreting, 16–18 Sodium ethynide, 378 Stereocenters, see Chirality centers Structural isomers, 15n Sodium hydride, 136, 243, 289, 829–830 Stereochemistry, 167, 193–239, 273 Stupp, S. I., 86 Sodium nitrite, 911 biological importance of chirality, Styrene, 476, 669 Solid-phase peptide synthesis (SPPS), 1069 201–202 Substituent effect, 129 Solubilities: and chirality, 194–195. See also Chirality on electrophilic aromatic substitution, of substances, 83–85 constitutional isomers, 195, 208 661 in water, 493, 519, 714 defined, 196 Substituted acetic acids, synthesis of, water solubility guidelines, 84–85 diastereomers, 196–197 830–833 Solvating ions, 83 enantiomers, 196–198. See also Substituted benzenes, infrared spectra of, Solvent effects, 266–269 Enantiomers 647–648 Solvolysis, 244, 246, 261–262 of epoxidation, 516 Substituted cyclohexanes, 168–169 Solvomercuration–demercuration, of hydroboration, 355 Substituted methyl ketones, 826–827 352, 511 of the ionic addition, to alkenes, 343 Substitution reactions, 134, 299–303, 499, 506, 623. See also specific reactions Sonogashira coupling, 951–954 of SN1 reaction, 259–262 Substrate, 242, 245, 246 s orbitals, 28 of SN2 reaction, 252–254, 273 sp orbitals, 41, 44 stereoisomers, 196, 197 Subtractive effect, 27 2 sp hybridization: testing for chirality, 203–204 Sucralose, 275, 993 alkanes/cycloalkanes, 146 Stereogenic atoms, see Chirality centers Sucronic acid, 994 ethene, 36–37 Stereogenic carbon, 199 Sucrose, 275–276, 966–967, 990–991, 993 ethyne, 40–42 Stereogenic centers, 199, 226 Suddath, F. L., 1079 2 sp orbitals, 36–38, 43 tetrahedral vs. trigonal, 201 Suicide enzyme substrate, 850, 871, 875 3 sp orbitals, 35, 43, 122, 169 Stereoisomers, 39, 167–168, 177, 196–197 Sulfacetamide, 928 Spackman, D. H., 1057 defined, 196 Sulfadiazene, 928 Specific rotation, 211–213 Stereoisomerism, of cyclic compounds, Sulfa drugs: Spectator ions, 106, 245 226–228 origin of, 927–928 Spectroscopic evidence, for alcohols, 547 Stereoselective reactions, 215–216, 380 synthesis of, 921 13 Spectroscopy, 392. See also Carbon-13 ( C) Stereoselective reductions, of carbonyl Sulfanilamides, synthesis of, 920 NMR spectroscopy; Infrared (IR) groups, 541 Sulfapyradine, 928 spectroscopy; Multidimensional Stereospecific, use of term, 516 Sulfonamides, alkylation of, 919–920 FTNMR spectroscopy; Nuclear Stereospecific reactions, 380, 516 Sulfonyl chlorides, 505, 919–920 magnetic resonance (NMR) alkenes, 363–364 Sulfur, principal stable isotopes of, 432 spectrometry Steric effect, 262, 473, 685 Sulfur dioxide, dipole moment, 61 Sphingolipids, defined, 1039 Steric factors, 186 Sulfuric acid, 106, 133 Sphingosine, derivatives of, 1039 addition to alkenes, 338 Spin decoupling, chemical exchange as in aldehydes and ketones, 725 cause, 413 Steric hindrance, 166, 186, 263, 299 Sunscreens, 648–649 Spin–lattice relaxation, 423 Steroids, 888, 1011, 1026–1035 Superacids, 115 Spin–spin coupling, 407–422 adrenocortical hormones, 1032 Superglue, 478 coupling constants, 410–411 cholesterol, 1028–1029 Supernovae, 2 dependence on dihedral angle, cholic acid, 1033 Superoxide, 478 410–411 defined, 1026 Superposable, use of term, 39, 194 reciprocity of, 410 digitoxigenin, 1033 Suzuki, Akira, 949 origin of, 407 diosgenin, 1034 Suzuki–Miyaura reaction, 949, 952–953 vicinal coupling, 407–410 D vitamins, 1032–1033 Swern oxidation, 543–544, 715–716 Spin–spin relaxation, 423 reactions of, 1034–1035 Syn 1,2-dihydroxylation, 368–370 Spin–spin splitting, 407 sex hormones, 1030–1032 Syn addition, 368–369 Spiranes, 189 stigmasterol, 1034 defined, 319–320 Splenda, 275 structure and systematic nomenclature of, of hydrogen, 320–321 Splitting patterns, recognizing, 410 1026–1027 Synapses, 900 S prefix, 274n Stigmasterol, 1034 Syn coplanar transition state, 294 Squalestatin S1, 516 Stile coupling reaction, 950–951, 953 Syn dihydroxylation, 370 Square planar configuration, 44 Stoddart, J. F., 172 Synthesis, planning, 323–327 Square planar rhodium complex, Stork, Gilbert, 808, 835, 846, 887 Synthetic detergents, 1018–1019 939, 940 Stork enamine reactions, 834–836, 838 Synthetic equivalents, 378, 827 Squaric acid, 141 “Straight-chain” alkanes, 146 Synthetic estrogens, 1031 Stability, 124 Strecker synthesis, 1054 Synthons, 378 I-22 INDEX

T Tetrahydrofuran (THF), 491–493, 510 Trent, J. O., 218 Table sugar, substituting the calories of, Tetrose, 968 Triacylglycerols, 1012–1019 275–276 Thalidomide, 202 biological functions of, 1016–1017 Tagatose, 1006 Thermal cracking, 145–146 hydrogenation of, 1016 Tandem mass spectrometry (MS/MS), 1061 Thermodynamic (equilibrium) control, 598 mixed, 1013 Taq polymerase, 1120 Thermodynamic enolate, 866 saponification of, 1017–1019 Tartaric acid, 232 formation of, 822 simple, 1013 Tautomers, 852 Thermodynamic (equilibrium) products, Trialkylboranes, oxidation of, 356 Tautomerization, 976 596, 598 Trichloromethane, dipole moment, 63 Taxol, 600 Thermophilic bacteria, 541 Trichloromethylbenzene, 686 Teflon, 476 Thiele, Johannes, 608–609 Tridecane, 148 chemistry of, 81 Thioacetals, 731 Triflate ion, 271 Temperature and reaction rate, 250–251 Thiols, 269, 731, 1047 Trigonal bipyramidal rhodium complex, 939, 940 Template, 1118 Thionyl chloride, 501 Trigonal pyramid, 45 Terelene, 797 , 640–641 Trigonal stereogenic centers, tetrahedral Terminal alkynes, 135 Three-dimensional formulas, 20–21 stereogenic centers vs., 201 acidity of, 312–313, 500 Threonine, 1048, 1064 Trimethylene glycol, 493 conversion to nucleophiles for carbon- , 68 Trimethylsilyl ethers, 512 carbon bond formation, 315–317 Thyroxine, 660 Trinitrotoluene (TNT), 660 substitution of the acetylenic hydrogen Thyroxine biosynthesis, 665 atom of, 312–313 iodine incorporation in, 661 Triose, 814, 968 Terminal hydrogen atom, 149 Tifluoromethanesulfonate ion, 271 Tripeptides, 1055 Terminal residue analysis, 1058 Time-of-flight (TOF) mass analyzer, 436 Triple bonds, 7, 21, 88 Terminus, 18 Tollens’ reagent, 743, 844, 979–980, 1004 Triplets, 397 Terpenes, 1021 Tollens’ test (silver mirror test), 743, 754, of nucleotides, 1109 Terpenoids, 1021 844 Trisaccharides, 966 tert-butyl, 152 Toluene, 90, 619, 679–680, 686 Tritium, 4 tert-butyl alcohol, 68, 134, 254, 490, 493 Tomasz, Maria, 1122 Trivial names, for compounds, 147 tert-butyl chloride, 254–256 Tool Kit for Organic Synthesis, 377 Tropylium bromide, 634 tert-butyl ethers by alkylation of alcohols, Torsional barrier, 166 Tryptophan, 641, 1048, 1074 511 Torsional strain, 166, 168 Tscherning, Kurt, 1030 protecting groups, 511 Tranquilizers, 900 Tumor suppressor, 1064–1065 Tertiary alcohols, dehydration of, 303–307 Trans, 283 Two-dimensional NMR (2D NMR) Transaminations, 735 techniques, 420–423 mechanism for, 304–306 1 1 Tertiary amines, 70, 94, 734 Transannular strain, 172 H- H COSY spectrum, 420–422 alkylation of, 904 Transcription, 1106, 1111 heteronuclear correlation cross-peak correlations, 422–423 nomenclature, 891 gene, 525 heteronuclear correlation spectroscopy oxidation of, 910 trans-Cycloheptene, 287 trans-Cyclohexene, 287 (HETCOR, or C–H HETCOR), preparation of: 422–423 trans-Cyclooctene, 287 through reduction of nitriles, oximes, Two-dimensional polyacrylamide gel Transesterification, 781 and amides, 906 electrophoresis (2D PAGE), 1085 Transfer RNAs (tRNAs), 1108–1110, 1112, through reductive amination, 904–905 [2+2] cycloaddition, 600 1113 reactions of, with nitrous acid, 913 Tyrosine, 641, 661, 861, 1048, 1074 Tertiary amine oxides, 910, 924 Transition metal complexes, 938–964 Tertiary carbocations, 257–258, 264 counting electrons in, 940–942 Tertiary carbon, 65–66, 68, 153 cross-coupling reactions, 947–955 U Tertiary halides, 254, 263, 264 Gilman reagent-mediated couplings, Ubiquinones, 1024–1026 Tertiary structure, of a protein, 1073, 1074 954–955 Ultraviolet-visible (UV–Vis) spectroscopy, Tertiary substrates, 263 Heck–Mizoroki reaction, 947–949 589–591 Testosterone, 1030–1032 Sonogashira coupling, 951–952 absorption maxima for nonconjugated Tetrachloroethene, dipole moment, 62 Stile coupling reaction, 950–951 and conjugated dienes, 591–593 Tetrachloromertensene, 362 Suzuki–Miyaura reaction, 949 analytical uses of, 593–595 Tetracycline antibiotics, 68 Wacker-Tsuji oxidation, 950 electromagnetic spectrum, 588–589 Tetradecane, 148 mechanistic steps in reactions of, 942–944 UV–Vis spectrophotometer, 589–591 Tetraethyllead, 548 olefin metathesis, 955–958 Unbranched alkanes, 147–149 Tetrahedral carbon atoms, 146 Wilkinson’s catalyst, 944–947 boiling points, 162 Tetrahedral chirality centers, 605, 1028 Transition metals, 939–940 density, 163 Tetrahedral geometry, 21, 34 defined, 939 melting points, 162 Tetrahedral intermediate, 724, 732, 734, in nature, 958–959 solubilities, 163 742, 759, 773–774, 779, 1080, Transition state, 248–252 Unbranched alkyl groups, how to name, 149 1108 orientation of groups in, 294–296 Undecane, 148, 163 Tetrahedral stereogenic centers, trigonal Translation, 1111–1113 Under equilibrium control, use of term, 118 stereogenic centers vs., 201 Transport antibiotics, and crown ethers, 523 Unfavorable entropy change, 84 INDEX I-23

Unimolecular reactions, 255 Vitamins, 900, 920, 1016 crossed aldol condensations using, Unsaturated compounds, 56, 318 organic, 3 862–865 Unsaturated fatty acids, 1013 water-soluble, 1076–1077 Weak nucleophiles, 724 reactions of the alkenyl chain of, 1020 Vitamin A, 1023 Whitmore, F., 304 Wieland, Heinrich, 1028 Unshared pairs, 44 Vitamin B12, 322, 958 Upfield, use of term, 399 Vitamin C, 48–49, 202, 784 Wilkins, Maurice, 1099, 1120 Urea, 3, 792–793 Vitamin D, 1032–1033 Wilkinson, Geoffrey, 946 Urethanes, 793 Vitamin E, 480 Wilkinson’s catalyst, 317, 944–947 Urey, H., 234 Vitamin K, 1025 Wilkinson’s catalyst tris(triphenylphosphine) rhodium chloride), 317 Uronic acids, 998 Voet, D., 523, 967, 1001, 1029, 1071, Urushiols, 1019 1077, 1116 Williams, L. D., 1079 Williamson ether synthesis, 509–510 UV-A, UV-B, and UV-C regions, 648 Voet, J. G., 523, 967, 1001, 1029, 1071, 1077, 1116 Willstätter, Richard, 623 V Volatize, defined, 81 Windaus, Adolf, 1028 Volume, atoms, 4 Winstein, S., 531 Valence electrons, 4, 7, 12 Withers, Stephen, 1078 Von Hofmann, August W., 138 Valence shell, 4–5 Wittig reaction, 737–739 Vorbrüggen, H., 1096 Valence shell electron pair repulsion Horner–Wadsworth–Emmons reaction, Vulcanization, natural rubber, 1024 (VSEPR) model, 44, 47 740–741 Valeric acid, 762 how to plan, 739–740 Valine, 1048, 1060, 1064, 1087, 1111 W Wöhler, Friedrich, 3, 324 Valinomycin, 523 Wacker-Tsuji oxidation, 950 Wolff-Kishner reduction, 675, 731, 733 Valium, 900 Walden, Paul, 248n, 279 Wood alcohol, see Methanol Vanadium, 959 Walden inversions, 248n Woodward, R. B., 322, 436, 607, 958 Vancomycin, antibiotic resistance and, Walker, John E., 523 97–98 X Van der Waals forces, 79–81 Warmuth, R., 697 Van der Waals radii, 167 Water: X-rays, 588 Van der Waals surface, 36, 61 acid-catalyzed addition of, to alkenes, 346 X-ray crystallography, 1071, 1087 Vane, J. R., 1036 and ammonia, 13 Xylenes, 620 Vanillin, 489, 492, 711 bromine, 987, 992, 1004 Van’t Hoff, J. H., 20, 166, 232, 988 miscibility of, 83–84 Y Vasopressin, 1062–1063 tetrahedral structure for the electron pairs of a molecule of, 45 Yates, John, 1085, 1087 Vedejs, E., 738 Ylides: Viagra, 448, 479 Water solubility: guidelines for, 84–85 addition of, 737–741 Vibrational absorption, 87 phosphorus, 737 Vicinal coupling, 407, 422 as the result of salt formation, 119–120 Vicinal dihalide (vic-dihalide), 313, 359 Watson, James, 1099–1101, 1115, 1120 Vicinal hydrogens, 397 Wave function (ψ), 27 Z Vinyl chloride, 360, 476–477, − and + signs of, 29 Zaitsev, A. N., 292 581, 613 Wavelength (λ), 87, 588 Zaitsev’s rule, 291–293, 295, 309, 923 Vinyl group, 159, 206–207 Wave mechanics, 27 Z-Ala, 810 Vinylic anion, 321 Wavenumbers, 87, 588n Zaragozic acid A (squalestatin S1), 516 Vinylic halides, 241, 672 Waxes, 1040 Ziegler, Karl, 475 unreactivity of, 274–275 Weak bases, 71, 117, 269–271, 501, Ziegler–Natta catalysts, 475–476, 1024 Vitalism, 3 506, 774 Zinc, 110

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