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(BQ) Part 2 book Organic chemistry has contents: Reactions of carboxylic acids and carboxylic derivatives, reactions of benzene and substituted benzenes, reactions of heterocyclic compounds, the organic chemistry of carbohydrates, the organic chemistry of amino acids, peptides, and proteins,... and other contents.
PART FIVE Carbonyl Compounds The three chapters in Part focus on the reactions of compounds that contain a carbonyl group Carbonyl compounds can be classified as either those that contain a group that can be replaced by another group (carboxylic acids and carboxylic acid derivatives) or those that contain a group that cannot be replaced by another group (aldehydes and ketones) C H A P T E R Reactions of Carboxylic Acids and Carboxylic Acid Derivatives The reactions of carboxylic acids and carboxylic acid derivatives are discussed in Chapter 16, where you will see that they all react with nucleophiles in the same way—they undergo nucleophilic addition– elimination reactions In a nucleophilic addition–elimination reaction, the nucleophile adds to the carbonyl carbon, forming an unstable tetrahedral intermediate that collapses by eliminating the weaker of two bases As a result, all you need to know to determine the product of one of these reactions—or even whether a reaction will occur—is the relative basicity of the two potential leaving groups in the tetrahedral intermediate C H A P T E R Reactions of Aldehydes and Ketones • More Reactions of Carboxylic Acid Derivatives • Reactions of a, b-Unsaturated Carbonyl Compounds Chapter 17 starts by comparing the reactions of carboxylic acids and carboxylic acid derivatives with the reactions of aldehydes and ketones This comparison is made by discussing their reactions with carbon nucleophiles and hydride ion You will see that carboxylic acids and carboxylic acid derivatives undergo nucleophilic addition–elimination reactions with carbon nucleophiles and hydride ion, just as they did with nitrogen and oxygen nucleophiles in Chapter 16 Aldehydes and ketones, on the other hand, undergo nucleophilic addition reactions with carbon nucleophiles and hydride ion and nucleophilic addition– elimination reactions with oxygen and nitrogen nucleophiles (and the species eliminated is always water) What you learned in Chapter 16 about the partitioning of tetrahedral intermediates is revisited in this chapter The reactions of a,b-unsaturated carbonyl compounds are also discussed C H A P T E R Reactions at the a-Carbon Many carbonyl compounds have two sites of reactivity: the carbonyl group and the a-carbon Chapters 16 and 17 discuss the reactions of carbonyl compounds that take place at the carbonyl group, whereas Chapter 18 examines the reactions of carbonyl compounds that take place at the a-carbon acetamide acetyl chloride acetonitrile acetic anhydride acetone acetic acid acetaldehyde methyl acetate 16 Reactions of Carboxylic Acids and Carboxylic Acid Derivatives Some of the things you will learn in this chapter are the purpose of the large deposit of fat in a whale’s head, how aspirin decreases inflammation and fever, why Dalmatians are the only dogs that excrete uric acid, how bacteria become resistant to penicillin, and why young people sleep better than adults W III O R C Z Z = an atom more electronegative than carbon O R C Z Z = R or H e have seen that the families of organic compounds can be placed in one of four groups, and that all the families in a group react in similar ways (Section 5.5) This chapter begins our discussion of the familes of compounds in Group III—compounds that contain a carbonyl group The carbonyl group (a carbon doubly bonded to an oxygen) is probably the most important functional group Compounds containing carbonyl groups—called carbonyl (“car-bo-neel”) compounds—are abundant in nature, and many play important roles in biological processes Vitamins, amino acids, proteins, hormones, drugs, and flavorings are just a few of the carbonyl compounds that affect us daily An acyl group consists of a carbonyl group attached to an alkyl group (R) or to an aromatic group (Ar), such as benzene O C a carbonyl group O O R C Ar C acyl groups The group (or atom) attached to the acyl group strongly affects the reactivity of the carbonyl compound In fact, carbonyl compounds can be divided into two classes determined by that group The first class are those in which the acyl group is attached to a group (or atom) that can be replaced by another group Carboxylic acids, acyl halides, esters, and amides belong to this class All of these compounds contain a group (OH, Cl, OR, NH2, NHR, NR2) that can be replaced by a nucleophile 720 Introduction carbonyl compounds with groups that can be replaced by a nucleophile O R C O R OH a carboxylic acid C O R OR′ an ester C Cl R C O O O NH2 C R an acyl chloride NHR′ R C NR′2 amides Esters, acyl chlorides, and amides are called carboxylic acid derivatives because they differ from a carboxylic acid only in the nature of the group or atom that has replaced the OH group of the carboxylic acid The second class of carbonyl compounds are those in which the acyl group is attached to a group that cannot be readily replaced by another group Aldehydes and ketones belong to this class The H bonded to the acyl group of an aldehyde and the R group bonded to the acyl group of a ketone cannot be readily replaced by a nucleophile carbonyl compounds with groups that cannot be replaced by a nucleophile O R C O H an aldehyde R¿ C R a ketone We have seen that, when comparing bases of the same type, weak bases are good leaving groups and strong bases are poor leaving groups (Section 9.2) The pKa values of the conjugate acids of the leaving groups of various carbonyl compounds are listed in Table 16.1 Table 16.1 The pKa Values of the Conjugate Acids of the Leaving Groups of Carbonyl Compounds Carbonyl compound Leaving group Conjugate acid of the leaving group pKa Carboxylic Acids and Carboxylic Acid Derivatives a carboxylic acid O R C Cl− Cl HCl -7 R′OH ~15–16 O R C OR′ − OR′ O R C an acyl chloride OH − OH H2O 15.7 NH2 NH3 36* O R C NH2 − Aldehydes and Ketones an ester O R C H H− H2 35 R R− RH > 60 O R C an amide * An amide can undergo substitution reactions only when its leaving group is converted to NH3, giving its conjugate acid (+NH4) a pKa value of 9.4 721 722 CHAPTER 16 Reactions of Carboxylic Acids and Carboxylic Acid Derivatives Notice that the acyl groups of carboxylic acids and carboxylic acid derivatives are attached to weaker bases than are the acyl groups of aldehydes and ketones (Remember that the lower the pKa, the stronger the acid and the weaker its conjugate base.) The hydrogen of an aldehyde and the alkyl group of a ketone are too basic to be replaced by another group This chapter discusses the reactions of carboxylic acids and carboxylic acid derivatives We will see that these compounds undergo substitution reactions, because they have an acyl group attached to a group that can be replaced by a nucleophile The reactions of aldehydes and ketones are discussed in Chapter 17, where we will see that these compounds not undergo substitution reactions because their acyl group is attached to a group that cannot be replaced by a nucleophile 16.1 THE NOMENCLATURE OF CARBOXYLIC ACIDS AND CARBOXYLIC ACID DERIVATIVES First we will look at how carboxylic acids are named, because their names form the basis of the names of the other carbonyl compounds Naming Carboxylic Acids The functional group of a carboxylic acid is called a carboxyl group O C CO2H COOH OH carboxyl groups are frequently shown in abbreviated forms a carboxyl group In systematic (IUPAC) nomenclature, a carboxylic acid is named by replacing the terminal “e” of the alkane name with “oic acid.” For example, the one-carbon alkane is methane, so the one-carbon carboxylic acid is methanoic acid O O C H O C C OH CH3 systematic name: methanoic acid common name: formic acid O OH ethanoic acid acetic acid CH3CH2 C CH3CH2CH2 OH propanoic acid propionic acid O O O OH OH pentanoic acid valeric acid hexanoic acid caproic acid OH butanoic acid butyric acid C CH2 CH OH propenoic acid acrylic acid Carboxylic acids containing six or fewer carbons are frequently called by their common names These names were chosen by early chemists to describe some feature of the compound, usually its origin For example, formic acid is found in ants, bees, and other stinging insects; its name comes from formica, which is Latin for “ant.” Acetic acid— contained in vinegar—got its name from acetum, the Latin word for “vinegar.” Propionic acid is the smallest acid that shows some of the characteristics of the larger fatty acids (Section 16.4); its name comes from the Greek words pro (“the first”) and pion (“fat”) Butyric acid is found in rancid butter; the Latin word for “butter” is butyrum Valeric acid got its name from valerian, an herb that has been used as a sedative since Greco/Roman times Caproic acid is found in goat’s milk If you have ever smelled a goat, then you know what caproic acid smells like Caper is the Latin word for “goat.” In systematic nomenclature, the position of a substituent is designated by a number The carbonyl carbon is always the C-1 carbon In common nomenclature, the position of a substituent is designated by a lowercase Greek letter, and the carbonyl carbon is not The Nomenclature of Carboxylic Acids and Carboxylic Acid Derivatives 723 given a designation Thus, the carbon adjacent to the carbonyl carbon is the a-carbon, the carbon adjacent to the a-carbon is the b-carbon, and so on CH3CH2CH2CH2CH2 O O C C OH CH3CH2CH2CH2CH2 e systematic nomenclature g d b a = alpha b = beta g = gamma d = delta e = epsilon OH a common nomenclature Take a careful look at the following examples to make sure that you understand the difference between systematic (IUPAC) and common nomenclature: O O O Br OH OH OH OCH3 Cl systematic name: 2-methoxybutanoic acid common name: a-methoxybutyric acid 3-bromopentanoic acid b-bromovaleric acid 4-chlorohexanoic acid g-chlorocaproic acid Carboxylic acids in which a carboxyl group is attached to a ring are named by adding “carboxylic acid” to the name of the cyclic compound O O C C OH cyclohexanecarboxylic acid COOH COOH OH benzenecarboxylic acid benzoic acid 1,2-benzenedicarboxylic acid Naming Acyl Chlorides Acyl chlorides have a Cl in place of the OH group of a carboxylic acid Acyl chlorides are named by replacing “ic acid” of the acid name with “yl chloride.” For cyclic acids that end with “carboxylic acid,” “carboxylic acid” is replaced with “carbonyl chloride.” (Acyl bromides exist too, but are less common than acyl chlorides.) O O CH3 C C O Br Cl systematic name: ethanoyl chloride common name: acetyl chloride Cl 3-methylpentanoyl bromide b-methylvaleryl bromide cyclopentanecarbonyl chloride carbonyl oxygen O Naming Esters An ester has an OR group in place of the OH group of a carboxylic acid In naming an ester, the name of the group (RЈ) attached to the carboxyl oxygen is stated first, followed by the name of the acid, with “ic acid” replaced by “ate.” (The prime on RЈ indicates that the alkyl group it designates does not have to be the same as the alkyl group designated by R.) Recall the difference between a phenyl group and a benzyl group (page 438) O O CH3 systematic name: common name: C OCH2CH3 ethyl ethanoate ethyl acetate CH3CH2 C Br O phenyl propanoate phenyl propionate CH3CHCH2 C OR′ carboxyl oxygen The double-bonded oxygen is the carbonyl oxygen; the single-bonded oxygen is the carboxyl oxygen O O C R C OCH3 methyl 3-bromobutanoate methyl b-bromobutyrate OCH2CH3 ethyl cyclohexanecarboxylate 724 CHAPTER 16 Reactions of Carboxylic Acids and Carboxylic Acid Derivatives Salts of carboxylic acids are named in the same way That is, the cation is named first, followed by the name of the acid, again with “ic acid” replaced by “ate.” O O C O− Na+ H systematic name: common name: C CH3 sodium methanoate sodium formate O C O− K+ potassium ethanoate potassium acetate O− Na+ sodium benzenecarboxylate sodium benzoate Frequently, the name of the cation is omitted O COO− O C O− O− CH3 C H3C O acetate pyruvate H OH (S)-(+)-lactate Cyclic esters are called lactones In systematic nomenclature, they are named as “2-oxacycloalkanones” (“oxa” designates the oxygen atom.) For their common names, the length of the carbon chain is indicated by the common name of the carboxylic acid, and a Greek letter specifies the carbon to which the oxygen is attached Thus, six-membered ring lactones are d-lactones (the carboxyl oxygen is on the d-carbon), five-membered ring lactones are g-lactones, and four-membered ring lactones are b-lactones O O O 2-oxacyclopentanone g-butyrolactone a g-lactone a O b d g O O 2-oxacyclohexanone d-valerolactone a d-lactone O O CH3 3-methyl-2-oxacyclohexanone d-caprolactone a d-lactone CH2CH3 3-ethyl-2-oxacyclopentanone g-caprolactone a g-lactone PROBLEM 1♦ The aromas of many flowers and fruits are due to esters such as those shown in this problem What are the common names of these esters? (Also see Problem 66.) O a O O jasmine a-Hydroxycarboxylic acids are found in skin products that claim to reduce wrinkles by penetrating the top layer of the skin, causing it to flake off b O O banana c O apple PROBLEM The word “lactone” has its origin in lactic acid, a three-carbon carboxylic acid with an OH group on the a-carbon Ironically, lactic acid (for its structure, see the structure of lactate near the top of this page) cannot form a lactone Why not? Naming Amides An amide has an NH2, NHR, or NR2 group in place of the OH group of a carboxylic acid Amides are named by replacing “oic acid,” “ic acid,” or “ylic acid” of the acid name with “amide.” 725 The Nomenclature of Carboxylic Acids and Carboxylic Acid Derivatives O CH3 systematic name: common name: C O O NH2 ethanamide acetamide ClCH2CH2CH2 C C NH2 NH2 benzenecarboxamide benzamide 4-chlorobutanamide g-chlorobutyramide If a substituent is bonded to the nitrogen, the name of the substituent is stated first (if there is more than one substituent bonded to the nitrogen, they are stated alphabetically), followed by the name of the amide The name of each substituent is preceded by an N to indicate that the substituent is bonded to a nitrogen O CH3CH2 C O O NH CH3CH2CH2CH2 C CH3CH2CH2 NCH2CH3 NCH2CH3 CH2CH3 CH3 N-cyclohexylpropanamide C N-ethyl-N-methylpentanamide N,N-diethylbutanamide Cyclic amides are called lactams Their nomenclature is similar to that of lactones In systematic nomenclature, they are named as “2-azacycloalkanones” (“aza” designates the nitrogen atom) For their common names, the length of the carbon chain is indicated by the common name of the carboxylic acid, and a Greek letter specifies the carbon to which the nitrogen is attached O a b NH g d 2-azacyclohexanone d-valerolactam a d-lactam O NH 2-azacyclopentanone g-butyrolactam a g-lactam O NH 2-azacyclobutanone b-propiolactam a b-lactam Nature’s Sleeping Pill Melatonin, a naturally occurring amide, is a hormone synthesized by the pineal gland from the amino acid tryptophan An amino acid is an CH3O a-aminocarboxylic acid Melatonin regulates the dark–light clock in our brains that governs such things as the sleep–wake cycle, body temperature, and hormone production Melatonin levels increase from evening to night and then decrease as morning approaches People with high levels of melatonin sleep longer and more soundly than those with low levels The concentration of the hormone in our bodies varies with age—6-year-olds have more than five times the concentration that 80-year-olds have—which is one of the reasons young people have less trouble sleeping than older people Melatonin supplements are used to treat insomnia, jet lag, and seasonal affective disorder H N + NH3 O O− O N H melatonin N H tryptophan 726 CHAPTER 16 Reactions of Carboxylic Acids and Carboxylic Acid Derivatives PROBLEM 3♦ Name the following compounds: O a C CH3CH2CH2 O− K+ d g NH Cl O b O O COOH O e O O O c h OH O f N CH3CH2 C O i NH2 CH3 PROBLEM Draw the structure of each of the following: a phenyl acetate b g-caprolactam c N-benzylethanamide e ethyl 2-chloropentanoate f b-bromobutyramide g cyclohexanecarbonyl chloride d g-methylcaproic acid h a-chlorovaleric acid Derivatives of Carbonic Acid Carbonic acid—a compound with two OH groups bonded to a carbonyl carbon—is unstable, readily breaking down to CO2 and H2O The reaction is reversible, so carbonic acid is formed when CO2 is bubbled into water (Section 1.17) O CO2 + H2O C HO OH carbonic acid The OH groups of carbonic acid, just like the OH group of a carboxylic acid can be substituted by other groups O O C Cl O C Cl phosgene CH3O O C OCH3 dimethyl carbonate H2N C NH2 urea O H2N C OH carbamic acid H2N OCH3 methyl carbamate 16.2 THE STRUCTURES OF CARBOXYLIC ACIDS AND CARBOXYLIC ACID DERIVATIVES The carbonyl carbon in carboxylic acids and carboxylic acid derivatives is sp2 hybridized It uses its three sp2 orbitals to form s bonds to the carbonyl oxygen, the a-carbon, and a substituent (Y) The three atoms attached to the carbonyl carbon are in the same plane, and the bond angles are each approximately 120° The Structures of Carboxylic Acids and Carboxylic Acid Derivatives 727 O ~120° C ~120° ~120° p bond Y The carbonyl oxygen is also sp2 hybridized One of its sp2 orbitals forms a s bond with the carbonyl carbon, and each of the other two sp2 orbitals contains a lone pair The remaining p orbital of the carbonyl oxygen overlaps the remaining p orbital of the carbonyl carbon to form a p bond (Figure 16.1) Esters, carboxylic acids, and amides each have two resonance contributors The resonance contributor on the right makes an insignificant contribution to an acyl chloride (Section 16.6), so it is not shown here − O O C C R OCH3 O C C OH + R OH − O O C R OCH3 − O R + R C NH2 R + NH2 The resonance contributor on the right makes a greater contribution to the hybrid in the amide than in the ester or the carboxylic acid, because the amide’s resonance contributor is more stable It is more stable because nitrogen is less electronegative than oxygen, so nitrogen can better accommodate a positive charge PROBLEM 5♦ Which is a correct statement? A The delocalization energy of an ester is about 18 kcal/mol, and the delocalization energy of an amide is about 10 kcal/mol B The delocalization energy of an ester is about 10 kcal/mol, and the delocalization energy of an amide is about 18 kcal/mol PROBLEM 6♦ Which is longer, the carbon–oxygen single bond in a carboxylic acid or the carbon–oxygen bond in an alcohol? Why? PROBLEM 7♦ There are three carbon–oxygen bonds in methyl acetate a What are their relative lengths? b What are the relative infrared (IR) stretching frequencies of these bonds? PROBLEM 8♦ Match the compound to the appropriate carbonyl IR absorption band: 1800 cm - acyl chloride 1640 cm - ester amide 1730 cm - C O s bond ▲ Figure 16.1 Bonding in a carbonyl group The p bond is formed by the side-to-side overlap of a p orbital of carbon with a p orbital of oxygen 728 CHAPTER 16 Reactions of Carboxylic Acids and Carboxylic Acid Derivatives 16.3 THE PHYSICAL PROPERTIES OF CARBONYL COMPOUNDS The acid properties of carboxylic acids were discussed in Sections 2.3 and 8.15 Recall that carboxylic acids have pKa values of approximately Carbonyl compounds have the following relative boiling points: relative boiling points amide carboxylic acid nitrile W ester ϳ acyl chloride ϳ ketone ϳ aldehyde The boiling points of an ester, acyl chloride, ketone, and aldehyde of comparable molecular weight are similar and are lower than the boiling point of an alcohol of similar molecular weight because only the alcohol molecules can form hydrogen bonds with each other The boiling points of these four carbonyl compounds are higher than the boiling point of the same-sized ether because of the dipole–dipole interactions between the polar carbonyl groups O O C C CH3CH2CH2OH bp = 97.4 °C H O CH3 OCH3 bp = 32 °C O C Cl bp = 51 °C C CH3 CH3 bp = 56 °C O N CH3 bp = 97 °C H bp = 49 °C CH3CH2OCH3 bp = 10.8 °C O C CH3CH2C CH3CH2 C OH CH3 bp = 118 °C NH2 bp = 221 °C The strong dipole–dipole interactions of a nitrile give it a boiling point similar to that of an alcohol Carboxylic acids have relatively high boiling points because each molecule has two groups that can form hydrogen bonds Amides have the highest boiling points because they have strong dipole–dipole interactions, since the resonance contributor with separated charges contributes significantly to the overall structure of the compound (Section 16.2) In addition, if the nitrogen of an amide is bonded to a hydrogen, hydrogen bonds can form between the molecules R d− dipole–dipole interactions N R C d+ d+ C N d− R O R HO C C OH O R R + N intermolecular hydrogen bonds R dipole–dipole interactions C O− C R O− R N + R Carboxylic acid derivatives are soluble in solvents such as ethers, chloroalkanes, and aromatic hydrocarbons Like alcohols and ethers, carbonyl compounds with fewer than four carbons are soluble in water Tables of physical properties can be found in the Study Area of MasteringChemistry Esters, N,N-disubstituted amides, and nitriles are often used as solvents because they are polar but not have reactive OH or NH2 groups We have seen that dimethylformamide (DMF) is a common aprotic polar solvent (Section 9.2) Index Keto-enol tautomer(s), 311 Keto-enol tautomerization, 311, 311–312 Ketones, 263, 311, 499, 789 a,b-unsaturated, 871 formation by dehydration of aldol addition products, 871–872 nucleophilic addition to, 832–836 cross condensation with esters, 878–879 enamine formation secondary amines and, 814–815 fragmentation patterns in mass spectrometry, 608–610, 609f, 610f halogenation of acid-catalyzed, 859–860 base-promoted, 860 imine formation with primary amines, 811f, 811–812 nomenclature of, 791t, 792 reactions of, 795 with alcohols, 820–823 with cyanide ion, 801–803 with Grignard reagents, 796–798 with hydride ion, 803–804 with peroxyacids, 826–827 with water, 817–820, 818f with thiols, 825 unsymmetrical, alkylation of a-carbon of, 864–866 Ketoprofen, 972 Ketoses, 1018 configurations of, 1022t, 1022–1023 Keto tautomers, 857, 857–858 Kevlar, 770, 1255 Kiliani-Fischer synthesis, 1026 Kinetic control, 369 of electrophilic addition to conjugated dienes, 369 of nucleophilic addition to a,-b-unsaturated aldehydes and ketones, 834–835 Kinetic enolate ion, 864 Kinetic product, 369, 369–373 Kinetics, 211, 404 parameters of, calculating, 224 of reactions, 205, 211f, 211–212 Kinetic stability, 212 Klonopin (clonazepam), 817 Knoevenagel condensation, 900 Kodel, 1256 Kolbe-Schmitt carboxylation reaction, 864, 864–865 Kroto, H W., 345 Kursanov, D N., 750 Kuru, 1093 L Lactase, 1039 Lactate, 1184 Lactic acid, 161, 1261 d-(-)-Lactic acid, 1020 Lactonase, 1044 Lactones, 724 G-Lactones, 1044 Lactose, 1038 Lactose intolerance, 1039 Lambert, Johann, 633 l-Amino acid oxidase, reaction catalyzed by, 1143 Lanosterol, biosynthesis of, 1202–1203 Latex, 1250 Lauric acid, 729t LCAO (linear combination of atomic orbitals), 358, 1269 LDL (low-density lipoprotein), 138, 1198 l-DOPA, 300 Lead compounds, 518, 518–519 Leaning, 677 Leaving groups, 402, 482 adenosine triphosphate activation of compounds and, 1172–1174 in nucleophilic-addition elimination reactions, 733 in SN1 reactions, 420 in SN2 reactions, 410 Le Châtelier’s principle, 208, 493 Lecithins, 754 Left-handed helices, 1089 Leinamycin, 1217 Leucine, 167, 1055t, 1057, 1222t pKa value of, 1061t Leucine enkephalin, 1075 Levonorgestrel (Norplant), 302 Levorotatory compounds, 161 Lewis, G N., 77 Lewis acids, 77–78, 78 in halogenation of benzene, 913 Lewis bases, 77–78, 78 Lewis structures, 14–18, 27 Lexan, 770, 1256 Lexapro, 908 Librium, 816 Lidocaine (Xylocaine), 519, 973 Ligation, 1008 Light ultraviolet, 612, 612f, 632 skin cancer and, 1286–1287 sunscreens and, 632–633 vitamin D formation and, 1288 visible, 612, 612f, 632 color and, 635–636, 636t Limeys, 1045 Limonene, 190, 1199 Lindlar catalyst, 314, 321, 324 Linear combination of atomic orbitals (LCAO), 358, 1269 Linezolid (Zyvox), 1044 Linoleic acid, 268, 729t, 730 Linolenic acid, 729t, 730 Lipid(s), 752 Lipid bilayer, 121, 754 Lipitor (atorvastatin), 138, 1198 Lipoate, 1141, 1142, 1147 Lipoic acid (lipoate), 1133t Lipopeptide antibiotics, 1044 Lister, Joseph, 758 Lithium clinical uses of, electronic configuration of, 6t electrons of, natural, deposit of, Living polymers, 1246 Localized electrons, 330 Lock-and-key model, 1114 Lone-pair electrons, 14–15, 15 Long-range coupling, 669 Loop conformation, 1090, 1090f, 1090–1091 Loratadine (Claritin), 1007 Lorazepam (Ativan), 817 Lovastatin (Mevacor), 138, 182, 1198 Low-density lipoprotein (LDL), 138 Lowest unoccupied molecular orbital (LUMO), 359, 634, 634f, 1271 back-side attack and, 405–406, 406f in cycloaddition reactions, 1279–1280, 1280f in electrocyclic reactions, 1272 Lucas test, 484 Luciferase, 1287 Luciferin, 1287 Lucite, 1238t Lufenuron, 1042 Luminescence, 1287 LUMO (lowest unoccupied molecular orbital), 359, 634, 634f, 1271 back-side attack and, 405–406, 406f in cycloaddition reactions, 1279–1280, 1280f in electrocyclic reactions, 1272 Lycopene, 637 lmax value for, 635, 635f Lycra, 1237, 1258 Lysergic acid, synthesis of, 981 Lysine, 1056t, 1057, 1096 pKa value of, 1061t Lysozyme, 219f, 219–220 reaction involving two sequential SN2 reactions catalyzed by, 1121–1125, 1122f d-Lyxose, 1021 M MacDiarmid, Alan, 354 Macintosh, Charles, 1250 Mad cow disease, 1093 Magnetic field, effective, 653 Magnetic resonance imaging (MRI), 698, 698–699, 699f Major groove, 1214 Malate, 284, 498 (S)-Malate, 1188f Malathion, 776 MALDI (matrix-assisted laser desorption ionization), 611 Maleate, 285 Maleic anhydride, 390, 1096 Malonic acid pKa values of, 769t structure of, 769t Malonic ester synthesis, 885, 885–886 retrosynthetic analysis of, 886 Malonyl-CoA, 891, 1150, 1151 Mannich reaction, 903 d-Mannose, 1021, 1023, 1024, 1028, 1029 Marble, acid rain and, 57 Marconi, Guglielmo, 651 Margarine, coloring of, 636 Markovnikov, Vladimir, 244 Markovnikov’s rule, 244 Mass number, Mass spectrometry, 596, 597f, 597–611 chemical ionization, 611 determining structures using, 601 I-15 in forensics, 611 functional group fragmentation patterns and, 604–610 of alcohols, 607–608, 608f of alkyl halides, 604f, 604–605, 605f of ethers, 605–606, 606f, 607f of ketones, 608–610, 609f, 610f gas chromatography and, 611 high-resolution, 603, 603t isotopes in, 602t, 602–603 mass spectrum and fragmentation and, 598–600, 600f molecular formula calculation and, 600–602 nitrogen rule in, 601 operation of, 597f, 597–598, 598f rule of 13 in, 600 Mass spectrum, 598, 598f, 598–600, 600f Materials science, 1237 Matrix-assisted laser desorption ionization (MALDI), 611 McLafferty rearrangement, 609 Mechanism-based inhibitors, 1163 Mechanism of reaction, 203, 238 for acid anhydride reaction with alcohol, 767 for acid-catalyzed acetal formation, 820–821 for acid-catalyzed ester hydrolysis, 1101 for acid-catalyzed hydrolysis of amides, 760–761, 762 for acid-catalyzed keto-enol interconversion, 311–312 for acid-catalyzed proton exchange, 685–686 for acyl chloride reaction with alcohol, 737 for acyl chlorides with hydride ion, 804–805 for addition of bromine to alkene, 257f, 257–258 for addition of hydrogen halide to alkene, 238 for addition reactions, 203 for alcohol conversion into sulfonate ester, 489 for aldehyde reaction with Grignard reagent, 796 for aldehyde with cyanide ion, 802 for aldehyde with hydride ion, 804 for aldol addition, 870 for alkene formation by Wittig reaction, 827–829 for alkene (olefin) metathesis, 549–550 for amide reaction with hydride ion, 807 for anionic polymerization, 1246 for arene oxide rearrangement, 512 for attachment of amino acid to tRNA, 1220 for base-catalyzed enediol rearrangement of monosaccharides, 1023 for base-catalyzed epimerization of monosaccharides, 1023 for base-catalyzed keto-enol interconversion, 314, 858 I-16 Index for Bayer-Villiger oxidation, 826–827 for bromination of benzene, 913, 914 for carboxylic acid reaction with hydride ion, 806 for cationic polymerization, 1244 for chlorination of benzene, 913, 914 for conjugated diene reaction with hydrogen bromide, 367–368 for conversion of alcohol into alkyl bromide using thionyl chloride, 488 for conversion of alkynes to trans alkenes, 315–316, 316f for conversion of isopentyl pyrophosphate to dimethylallyl pyrophosphate, 1198–1199 for cyanogen bromide peptide bond hydrolysis, 1086 for desulfonization, 918 for Dieckmann condensation, 880 for E1cB, 872 for E1 dehydration of alcohols, 492 for electrophilic addition reaction of hydrogen halide to alkenes, 203, 238 for electrophilic addition of hydrogen halide to alkynes, 309–310 for electrophilic aromatic substitution, 996 for electrophilic aromatic substitution reactions, 912–913 for electrophilic aromatic substitution using arenediazonium ion electrophile, 951 for enamine formation, 814–815 for epoxidation of alkenes, 261 for E1 reaction, 453 for E2 reaction, 446 for ester reaction with Grignard reagent, 798–799 for ester reaction with hydride ion, 805 for ether cleavage by SN1 reaction, 502–503 for ether cleavage by SN2 reaction, 503 for Friedel-Crafts acylation, 919 for Friedel-Crafts alkylation of benzene, 920 for cis-glycol formation, 510 for glycoside formation, 1035 for halogenation acid-catalyzed, 859–860 base-promoted, 860 for Heck reaction, 545–546 for hydroboration of alkene, 254–255 for hydrohalin formation, 258–260 for hydrolysis of ester with primary or secondary alkyl group, 742–743 for hydrolysis of ester with tertiary alkyl group, 745 for hydroxide-ion promoted hydrolysis of amides, 762–763 for hydroxide-ion promoted hydrolysis of esters, 746 for imine formation, 811 for iodide-ion catalyzed reaction, 1106 for iodination of benzene, 915 for isolated diene reaction with excess hydrogen bromide, 366 for ketone reaction with Grignard reagent, 796 of ketone with cyanide ion, 802 for ketone with hydride ion, 804 for mercuric-ion-catalyzed hydration of alkynes, 312–313 for Michael reaction, 868 for monobromination of ethane, 559 for monochlorination of methane, 558–559 for nitration of benzene, 916 for nucleophilic additionelimination reactions confirmation of, 749–751 with negatively charged nucleophile, 736 with neutral nucleophile, 736 for nucleophilic aromatic substitution, 956, 1002 for nucleophilic substitution of epoxides under acidic conditions, 505 under neutral or basic conditions, 507–508 for oxidation of alcohol by hypochlorous acid, 500 for oxidation of thiols to disulfides, 1073 for ozonide formation, 263–264 for peroxide formation, 568 for PLP-catalyzed decarboxylation of amino acids, 1153 for PLP-catalyzed racemization of l-amino acids, 1154 for PLP-catalyzed transamination of amino acids, 1154–1155 for radical polymerization, 1239 for reaction catalyzed by aldolase, 1127–1128 for reaction catalyzed by carboxypeptidase A, 1116–1117 for reaction catalyzed by dihydrolipoyl dehydrogenase, 1142 for reaction catalyzed by dioldehydrase, 1158 for reaction catalyzed by d- or l-amino acid oxidase, 1143 for reaction catalyzed by glucose6-phosphate isomerase, 1125–1126 for reaction catalyzed by lysozyme, 1123 for reaction catalyzed by pyruvate decarboxylase, 1145 for reaction catalyzed by pyruvate dehydrogenase complex, 1146–1147 for reaction catalyzed by serine proteases, 1119–1120 for reaction catalyzed by succinate dehydrogenase, 1143 for reaction catalyzed by thymidylate synthase, 1161 for SN1 reactions of alcohols, 483 of alkyl halides, 418 for SN2 reactions, 404–409, 406f of alcohols, 484 of alkyl halides, 405–406 experimental evidence for, 404–405, 406–409, 407f, 408f for sulfonation of benzene, 917 for Suzuki reaction, 543 for terpene biosynthesis, 1199 for vitamin KH2-dependent carboxylation of glutamate, 1164–1165 for Wolff-Kishner reduction, 923–924 for Ziegler-Natta catalyzed polymerization of substituted ethylenes, 1250 Mefegyne (mifepristone), 302 Meisenheimer complexes, 956 Melamine, 1259 Melamine poisoning, 1259 Melanin, 632 Melatonin, 724 Melmac, 1259 Melphalan, 523 Melting points, 118, 118–119, 119f Membranes, 754 phosphoglycerides in, 754 Menthol, 1196, 1199 Menthyl chloride, 464 2-Mercaptoethanol, 1082 Mercuric-ion-catalyzed hydration, of alkynes, 312–313 Merrifield, Bruce, 1079 Mescaline, 908 Meso compounds, 169–173, 170 Messenger RNA (mRNA), 1219 Metabolic pathways, 1170–1206 adenosine triphosphate and See Adenosine triphosphate (ATP) amino acid biosynthesis and, 1195 anabolic, 1170, 1192 carbohydrate catabolism and, 1180–1184, 1181f catabolic, 1170 cholesterol biosynthesis and, 1202–1203 citric acid cycle and, 1187–1190, 1188f fat catabolism and, 1177–1180, 1179f four stages of catabolism and, 1176f, 1176–1177 gluconeogenesis and, 1192–1194, 1193f leaving groups and, 1172–1174 oxidative phosphorylation and, 1191 phosphoanhydride bonds and, 1174–1176 phosphoryl transfer reactions and, 1171–1172 protein catabolism, 1185–1187, 1186f pyruvate fate and, 1184–1185 regulation of, 1194–1195 terpenes and biosynthesis of, 1197–1202 structure of, 1195–1197 Metabolism, 1170 basal metabolic rate and, 1191 differences in, 1171 inborn errors of, phenylketonuria as, 1186–1187 Meta directors, 935 Metal ions, 1107 as catalysts, 1107–1109, 1108t Methadone, enantiomers of, 179 Methamphetamine, 908 Methanal, 790 Methane bonds in, 10, 28–30, 29f, 30f electrostatic potential map for, 39 monochlorination of, mechanism for, 558–559 physical properties of, 91t structure of, 92 Methanesulfonyl chloride, 489, 528 Methanoic acid, 722 Methanol (methyl alcohol), 94, 106, 404, 486, 806 boiling point of, 429t dielectric constant of, 429t pKa of, 63 pKa value of, 58 poisoning by, 501–502 protonated, 58 N5,N10-Methenyl-THF, 1159 Methicillin, 759 Methine protons, 660 Methionine, 1160 pKa value of, 1061t Methionine enkephalin, 1075 Methotrexate, 1163 2-Methoxybutane, 106 2-Methoxybutanoic acid, 723 3-Methoxybutanol, 506 Methoxychlor, 403 2-Methoxy-3-cyclohexanecarbaldehyde, 376 5-Methoxy-3-cyclohexanecarbaldehyde, 376 2-Methoxy-2-methylbutane, 473 1-Methoxy-2-methylpropane, 467 2-Methoxypropane, 660 1-Methoxy-2-propanol, 507 2-Methoxy-1-propanol, 507 N-Methylacetamide, 807 Methyl acetate, 719, 781 Methyl a-cyanoacrylate, 1247 Methylamine, 94, 109, 816, 993 pKa of, 63 pKa value of, 58 protonated, 58 Methyl anion, bonds in, 36–37 Methylating agents, used by chemists vs those used by cells, 436–438 Methylation, exhaustive, 416 2-Methylazacyclohexane, 990 Methyl b-bromobutyrate, 723 Methyl bromide, 105 Methyl 3-bromobutanoate, 723 2-Methyl-1,3-butadiene, 368 3-Methylbutanal, 791 2-Methylbutane, 114 mass spectrum of, 599–600, 600f 3-Methyl-1-butane, 508 Methyl butanoate, 806 2-Methyl-2-butanol, 483 3-Methyl-1-butanol, 256 3-Methyl-2-butanol, 485 2-Methyl-1-butanol, specific rotation of, 162 2-Methyl-1-butene, 572 in elimination reactions, 448, 449, 453 hydrogenation of, 267 Index 2-Methyl-2-butene, 243, 473 in elimination reactions, 448, 449, 453 halogene addition to alkenes and, 258 hydrogenation of, 267 3-Methyl-1-butene, 273, 570 cationic polymerization of, 1245 halogen addition to alkenes and, 257 hydrogenation of, 267 Methyl carbamate, 726 Methyl cation, bonds in, 36 Methyl chloride, 94, 104–105, 105 Methyl cyanide, 764 Methylcyclohexane, 601 axial, 131f Methyl cyclohexanecarboxylate, 826 3-Methylcyclohexanol, 108 2-Methylcyclohexanone, 864 Methylcyclohexene, 266 1-Methylcyclohexene, 266 3-Methylcyclohexene, 574 6-Methyl-2-cyclohexenol, 304 Methylcyclopropane, skeletal structure of, 102 5-Methylcytosine, 1218 Methyldiazonium, 954 1-Methyl-2,4-dinitrobenzene, 946 Methylenecyclohexane, 195, 828 Methylene group, 91 Methylene protons, 660 N5,N10-Methylene-THF, 1159, 1160 N-Methylethanamide, 856 3-(1-Methylethyl)hexane, 99 Methyl fluoride, 105 Methyl group, 94 6-Methyl-1,4-heptadiyne, 303 6-Methylhepta-1,4-diyne, 303 2-Methyl-4-heptanol, 108 4-Methyl-3-heptanone, 888 6-Methyl-2-heptanone, 792 3-Methyl-3-heptene, 193 2-Methyl-1,4-hexadiene, 303 2-Methylhexa-1,4-diene, 303 2-Methyl-1,5-hexadiene, 366 5-Methyl-1,3-hexadiene, 449 5-Methyl-1,4-hexadiene, 449 2-Methylhexane, 93 skeletal structure of, 102 3-Methylhexane, 93, 285 5-Methylhexanenitrile, 764 3-Methyl-1-hexanol, 107 3-Methylhexan-1-ol, 107 3-Methyl-3-hexanol, 797 2-Methyl-3-hexanone, 865 4-Methyl-3-hexanone, 865 4-Methyl-2-hexyne, 301 4-Methylhistidine, 1007 Methyl iodide, 94, 105 Methyl ketones, 899 Methylmagnesium bromide, 796 Methylmalonyl-CoA, 1157, 1168, 1205 Methyl methacrylate, 1241t, 1247t para-Methylnitrobenzene, 946 4-Methyloctane, 97 Methyl orange, 636 3-Methyl-2-oxacyclohexanone, 724 Methyl 3-oxobutanoate, 792 Methyl 5-oxopentanoate, 791 4-Methyl-1,3-pentadiene, 193, 372 2-Methylpentane, 93, 97 3-Methylpentane, 93 4-Methyl-2,3-pentanediol, 107 4-Methylpentane-2,3-diol, 107 3-Methyl-3-pentanol, 797 3-Methylpentanoyl bromide, 723 2-Methyl-1-pentene, 458 2-Methyl-2-pentene, 458 4-Methyl-1-pentene, 251 4-Methyl-2-pentene, 193 4-Methyl-3-penten-1-ol, 304 para-Methylphenol, 946 2-Methyl-2-phenylbutane, 921 3-Methyl-1-phenyl-1-butene, 449 3-Methyl-1-phenyl-2-butene, 449 Methyl phenyl ketone, 792 2-Methylpiperidine, 990 Methyl propanoate, 805, 888 2-Methyl-2-propanol, 417 2-Methylpropene addition of halogen to, 256 addition of hydrogen to, 237 in elimination reactions, 445, 452, 467, 469, 471 Methylpropylamine, 109, 809 1-Methyl-2-propylcyclopentane, skeletal structure of, 102 Methyl propyl ether, 467 3-Methyl-propylheptane, skeletal structure of, 102 Methyl protons, 660 N-Methylpyridinium iodide, 1000 N-Methylpyrrolidine, 807 conjugate acid of, pKa value of, 991 Methyl radical, bonds in, 36 N5-Methyl-THF, 1159 N-Methyltransferase, 1186 Methyl vinyl ether, 1245t Methyl vinyl ketone, 634 Mevacor (lovastatin), 138, 182, 1198 Mevalonic acid, 1197 Mevalonyl phosphate, 1197 Mevalonyl pyrophosphate, 1197, 1198, 1202 Micelles, 753 Michael reaction, 867–869, 868 Micrographis (Hooke), 618 Microwaves, 612, 612f Mifepristone (Mefegyne), 302 Milnamides A and B, 989 Minor groove, 1214 Mitscherlich, Eilhard, 178, 907 Mixed anhydrides, 766 Mixed triglycerides, 751 Molar absorptivity, 633 Molarity, effective, 1109, 1109–1110, 1110t Molecular formulas, high-resolution mass spectrometry and, 603, 603t Molecular geometry, hybridization and, 42–43 Molecular ions, 597 Molecular models, 146 Molecular modification, 518 Molecular orbitals, 23 antibonding, π*, 357 antisymmetric, 359 bonding, π, 357 conservation of, 24 frontier, 1272 highest occupied, 359, 634, 634f, 1271 back-side attack and, 405–406, 406f in cycloaddition reactions, 1279–1280, 1280f in electrocyclic reactions, 1272, 1274, 1275, 1276 in sigmatropic rearrangement, 1286 lowest unoccupied, 359, 634, 634f, 1271 back-side attack and, 405–406, 406f in cycloaddition reactions, 1279–1280, 1280f in electrocyclic reactions, 1272 sigma (s) bonding and antibonding, 24–25, 25f stability and, 356–360, 357f symmetric, 359 Molecular orbital (MO) theory, 23, 23f–27f, 23–27, 1269 pericyclic reactions and, 1269–1272, 1270f, 1271f Molecular recognition, 219, 510–511, 1017, 1114, 1139 Molecular structures, models of, 95 Molecular weight, Molecules dipole moments of, 12, 13t, 47–48 nonpolar, 28 Molozonides, 263 Monobromination of ethane, mechanism of, 559 Monochlorination of methane, mechanism for, 558–559 Monomers, 1236 Monosaccharides, 1018 cyclic hemiacetal formation from, 1030–1032 oxidation-reduction reactions of, 1024–1026 reactions in basic solutions, 1023–1024 Monosodium glutamate, 163 Monoterpenes, 1196 Morachalcone A, 874 Morphine, 3, 518, 768 skeletal structure of, 103 specific rotation of, 163t Morpholine, 1130 conjugate acid of, pKa value of, 991 MO (molecular orbital) theory, 23, 23f–27f, 23–27, 1269 pericyclic reactions and, 1269–1272, 1270f, 1271f Motrin (ibuprofen), 118, 141, 748, 942 enantiomers of, 179 MRI (magnetic resonance imaging), 698, 698–699, 699f MRI scanners, 698 mRNA (messenger RNA), 1219 Multiplets, 666 Multiplicity, of NMR signals, 666 Multistep synthesis, 319–324, 576–578 Muscalure, 191 Mushrooms, 1-octen-3-ol and, 304 Mustard gas, 523 Mutagenesis, site-specific, 1120 Mutarotation, 1031 Myristic acid, 729t N I-17 NAD+ (nicotinamide adenine dinucleotide), 1135, 1135–1138 substrate oxidation by, 1137–1138 NADH, 1135, 1136, 1138, 1177, 1184, 1191 NADP+ (nicotinamide adenine dinucleotide phosphate), 1135, 1135–1138 NADPH, 1135, 1135–1138 substrate reduction by, 1139–1140 Nanocontainers, 1253 Naphthalene, 345 Naphthalene oxide, 513 1-Naphthol, 513 2-Naphthol, 513 Naproxen (Aleve), 118, 285 Natural gas, 28, 557 NBS (N-bromosuccinamide), 574 Neomenthyl chloride, 463 Neon, electronic configuration of, 6t Neoprene, 1251 Neptune, blue color of, 28 Nerve gas, 776 Neurotransmitters, acetylcholine as, 775–776 Newman projections, 121, 121–122 converting perspective formulas to, 189 converting to perspective formulas, 188 N—H absorption bands, 623 N-Hydroxyazo compounds, 953 Niacin, 1134–1140 deficiency of, 1136 pyridine nucleotide coenzymes and, 1135–1137 substrate oxidation by NAD+, 1137–1138 substrate reduction by NADP, 1139–1140 Niacinamide, 1135 Nicotinamide, 1135 Nicotinamide adenine dinucleotide (NAD+), 1135, 1135–1138 substrate oxidation by, 1137–1138 Nicotinamide adenine dinucleotide phosphate (NADP+), 1135, 1135–1138 Nicotine, 51, 518 Nicotinic acid, 1135 Ninhydrin, 903 amino acid reaction with, to form a colored product, 1065 Nitration, of benzene, 916 Nitric acid, 916 Nitriles, 764, 764–766 nomenclature of, 764, 791t reactions of, 764–766 meta-Nitroacetophenone, 944 4-Nitroaniline, 928 para-Nitroaniline, 928 para-Nitroanisole, 956 Nitrobenzene, 909, 916, 942 H NMR spectrum of, 673, 673f Nitroethane, 335, 855 Nitrogen bonds formed by, 10 electronic configuration of, 6t electrons of, 16 natural abundance of, 602t I-18 Index Nitrogen atoms, as asymmetric centers, 180, 180f Nitronium ion, 916 para-Nitrophenyl acetate, 1265 para-Nitrophenyl methacrylate, 1265 Nitrosamines, 953, 953 hazards of, 954 Nitrosonium ion, 953 Nitro substituents, on benzene ring, reduction of, 926–927 Nitrous acid, 953 reaction of amines with, 953–955 NMR See Nuclear magnetic resonance spectroscopy NMR spectrometers, 651 Nobel, Alfred Bernhard, 466 Nobel Prize, 466 Nodal planes, 22 Nodes, 21 Nomenclature (See particular functional group.) E,Z system, 197 R,S system, 155–159, 173–175 Nonane, physical properties of, 91t Nonbonding electrons, 14–15, 15 Noncyclic compounds, 191 N + rule, 665f, 665–667, 666, 667f, 668f Nonpolar covalent bonds, 11, 11–12 Nonpolar molecules, 28 Nonreducing sugars, 1036–1037, 1037 Nonsteroidal anti-inflammatory drugs (NSAIDs), 748 See also specific drugs Noradrenaline, 437 Norethindrone (Aygestin), 302 Norplant (levonorgestrel), 302 Novocain (procaine), 519 NSAIDs (nonsteroidal antiinflammatory drugs), 748 See also specific drugs N-terminal amino acids, 1071, 1071–1072 determination of, 1082–1083 Nuclear magnetic resonance (NMR), 612, 613f, 650 Nuclear magnetic resonance (NMR) spectroscopy, 596, 649, 649–699, 650f, 701–718 13 C, 689, 689t, 689–693, 690f, 691f, 693f–694f chemical shifts in, 656–658, 657f characteristic values of, 659t, 659–661 coupling constants in, 675–678, 676t, 675f–678f DEPT 13C, 694, 694f diamagnetic anisotropy and, 661–663, 662f, 663f diastereotopic hydrogens and, 681–683 Fourier transform, 652, 652f H spectra and deducing chemical structure using, 677f, 677–678 examples of, 670f–673f, 670–675 number of signals and, 654–656 regions of, 660 relative number of protons causing signals and, 663f, 663–666 relative positions of signals and, 658–659 resolution of, 687f, 687–688, 688f splitting of signals and, 665f, 665–670, 667f–669f, 679f, 679–681, 680f medical use of, 698–699, 699f protons bonded to oxygen and nitrogen and, 684–686, 685f, 686f deuterium in, 686–687 shielding and, 653f, 653–654 time dependence of, 683–684, 684f two-dimensional, 695, 695–698, 696f, 697f Nuclear Overhauser Effect Spectroscopy (NOESY), 698 Nucleic acids, 1207, 1207–1234, 1208f See also Deoxyribonucleic acid (DNA); Ribonucleic acid (RNA) bases of, 1207, 1209t nucleotide subunits of, 1211–1214, 1212f–1214f primary structure of, 1212 Nucleophiles, 78, 202, 411, 524 amine reaction as, 993–994 hard and soft, 834–835 reaction with electrophiles, 202, 203 in SN1 reactions, 421 in SN2 reactions, 411t, 411–413, 412f Nucleophilic acyl substitution reactions, 732 Nucleophilic addition-elimination reactions, 795 of acyl chlorides with Grignard reagents, 798 of aldehydes, 795 aromatic substitution as, 955–957 basicity for predicting outcome of, 733 of carboxylic acid and carboxylic acid derivatives, 732 confirmation of mechanism for, 749–751 of esters with Grignard reagents, 798 imine formation from aldehydes and ketones with primary amines, 811–812 of ketones, 795 mechanism for, 736–737 Nucleophilic addition reactions, 795 of aldehydes, 795 to a,b-unsaturated aldehydes and ketones, 832–836 to a,b-unsaturated carboxylic acid derivatives, 837 of ketones, 795 of ketones with Grignard reagents, 798 Nucleophilic aromatic substitution, 955, 955–957, 1001, 1002–1003 Nucleophilic catalysts, 1106, 1106–1107 Nucleophilicity, 411 basicity and, 411 solvent and, 413t, 413–414 steric effects and, 414–416 Nucleophilic substitution reactions, 404 of alcohols to form alkyl halides, 482–486 mechanism for SN1 reaction, 483 mechanism for SN2 reaction, 484 aromatic, 955, 955–957, 1001, 1002–1003 of epoxides, 505–511, 506f under acidic conditions, 506–507 under neutral or basic conditions, 507–509 trans and cis diols and, 509–510 of ethers, 502–505, 503t reactivity of alkyl halides in, 424, 424t Nucleosides, 1209, 1209t in deoxyribonucleic acid, 1209, 1210 in ribonucleic acid, 1209, 1210 Nucleotides, 1209, 1209t, 1211–1214, 1212f–1214f DNA composition of, estimation using UV/Vis spectroscopy, 638–639, 639f Nuprin (ibuprofen), 118, 141, 748, 942 enantiomers of, 179 NutraSweet (aspartame), 1047–1048, 1075, 1187 Nutrition, proteins and, 1058 Nylon, 770 Nylon 6, 1254 Nylon 66, 1254 O Observed rotation, 162 Observed specific rotation, 163 (9Z,12Z)-Octadecadienoic acid, 729t Octadecanoic acid, 729t (9Z,12Z,15Z)-Octadecatrienoic acid, 729t (9Z)-Octadecenoic acid, 729t Octane, physical properties of, 91t Octane number, of gasoline, 100 4-Octanol, 152 (2E,4Z,6E)-Octatriene, 1272, 1273, 1275 1-Octen-3-ol, 304 Octet rule, Odor(s), butanedione and, 793 Odorants, thiols as, 522 O—H absorption bands, 623 Oil(s), 751, 751–752 polyunsaturated, 752 radical reactions in, 579–580 Oil of celery, 1196 Oil of ginger, 1196 Oil spills, 120 Olefin metathesis, 548, 548–551 mechanism of reaction for, 549–550 Oleic acid, 268, 729t, 730 Olestra, 1034 Oligonucleotides, 1211 Oligopeptides, 1053 sequencing of, 1084 Oligosaccharides, 1018 Omega fatty acids, 730 OPEC (Organization of Petroleum Exporting Countries), 557 Operating frequency, of nuclear magnetic spectrometer, 651 Opium, 3, 768 Opsin, 151 Optically active compounds, 161 Optically inactive compounds, 161 Optical purity, 163–164 Orbitals atomic See Atomic orbitals hybrid, 29 hybridization of, length of carboncarbon single bonds and, 352, 353t molecular See Molecular orbitals; Molecular orbital (MO) theory Organic compounds, 2, 2–4, 90–144 See also specific compounds and types of compounds bad-smelling, 110–111 classes of, 596, 596t conducting electricity, 353–354 structure of, pH and, 72–76 synthetic, Organization of Petroleum Exporting Countries (OPEC), 557 Organoboranes, 924 Organoboron compounds, 542, 542–545 Organocuprates, 538, 538–541, 924 Organohalides, naturally occurring, 445 Organolithium compounds, 536, 537–538 Organomagnesium compounds, 536, 537, 538 Organometallic compounds, 535–555, 536, 536t alkene metathesis and, 548–551 alkyne metathesis, 551 organocuprates, 538, 538–541 organolithium, 536, 537–538 organomagnesium, 536, 537, 538 palladium-catalyzed coupling reactions of, 541–548 transmetallation and, 538 Organopalladium compounds, 542 Orientation, substituent effects on, in substituted benzenes, 935–939, 936f, 937f Oriented polymers, 1260 physical properties of, 1260 Orlon, 1238t Ornithine, 1060 Orsellinic acid, 904 Ortho-para directors, 935 Osteoporosis, Fosamax for treatment of, 70 Oxacillin, 759 Oxacyclobutane, 991 Oxacyclohexane, 991 2-Oxacyclohexanone, 724 Oxacyclopentane, 991 2-Oxacyclopentanone, 724 Oxacyclopropane, 991 Index Oxalic acid pKa values of, 769t structure of, 769t Oxaloacetate, 1150, 1188, 1188f, 1193, 1194, 1195 Oxaloacetic acid, 183, 851 Oxalyl chloride, 848 Oxazolidinones, 1044 Oxetane, 991 Oxidation reactions, 255, 255–256 of alcohols, 499–500 mechanism for, 500 b-oxidation as, 1178 of monosaccharides, 1025–1026 of substrates by NAD+ or NADP+ and, 1137–1138 of thiols to disulfides, 1073 Oxidative addition, 543 in Heck reaction, 546 in Suzuki reaction, 543 Oxidative cleavage, 262 determining products of, 264 Oxidative phosphorylation, 1176f, 1177, 1191 Oximes, 813 Oxirane, 991 Oxocarbenium, 1035 2-Oxocyclohexanecarboxylic acid, 884 8-Oxoguanine, 1226 5-Oxohexanamide, 792 3-Oxohexanoic acid, 884 4-Oxopentanal, 792 Oxyacetylene torches, 34 Oxyanion hole, 1120 Oxygen(s) bonds formed by, 10 carbonyl, 727, 727f carboxyl, 723 electronic configuration of, 6t natural abundance of, 602t Oxygen atom, electrons of, 15 Oxyluciferin, 1287 Oxytocin, 1075 Ozone, 263 addition to alkenes, 262–266 in atmosphere, 583–584 Ozone hole, 263, 583, 584 Ozonides, 263 Ozonolysis, 262, 262–266 P PABA (para-aminobenzoic acid), 633, 1159, 1160 Packing, 118 Padimate O, 633 Palladium-catalyzed coupling reactions, 541–548 Heck reaction, 542, 545, 545–548 Suzuki reaction, 542, 542–545 Palmitic acid, 729t Palmitoleic acid, 729t Pantothenic acid (pantothenate), 1133t Pantropazole (Protonix), 1007 Paper chromatography, 1065 determining number of amino acids using, 1065–1066, 1066f Paraffins, 557 Parallel b-pleated sheets, 1089, 1089–1090, 1090f Parathion, 776 Parent hydrocarbon, 97 Parkinson’s disease, synthetic alkynes for treatment of, 300 Partial hydrolysis, 1084 Partial racemization, 419 Pasteur, Louis, 178, 1237 Pauli exclusion principle, 6–7, 357 Pauling, Linus, 29 PCC (pyridinium chlorochromate), 499 PCR (polymerase chain reaction), 1230, 1230f, 1230–1231 PDS (poly[dioxanone]), 771 Pellagra, 1136 Penicillamine, enantiomers of, 179 Penicillin in clinical use, 759 discovery of, 758 drug resistance and, 758–759 resistance to, 1043 semisynthetic, 759 Penicillinase action of, 758, 759 discovery of, 758 Penicillin G, 758, 759 Penicillin O, 759 Penicillin V, 759 specific rotation of, 163t 1,3-Pentadiene, 193, 352, 372 1,4-Pentadiene, 193, 352, 531 stability of, 359–360 1-Pentanamine, 990 Pentane, 114 boiling point of, 305t mass spectrum of, 598, 598f physical properties of, 91t structure of, 92 1,5-Pentanediamine (cadaverine), 111 2,4-Pentanedione, 792 Pentanoic acid, 722 Pentan-3-ol, 107 3-Pentanol, 107 2-Pentanol, 616, 616f 2-Pentanone, 609, 619, 797, 884 3-Pentanone, 797, 865 1-Pentene, 40, 245, 246, 458, 467, 519 boiling point of, 305t 2-Pentene, 40, 244, 245, 246, 322, 458, 459, 519 cis-2-Pentene, 193, 278, 280 trans-2-Pentene, 193, 278, 280 Pentoses, 1018 4-Pentoxy-1-butene, 193 Pentylamine, 990 skeletal structure of, 103 tert-Pentyl bromide, 96 Pentyl group, 94 1-Pentyne, 319 boiling point of, 305t 2-Pentyne, 301, 310 boiling point of, 305t Peppermint oil, 1196 Peptide(s), 1053, 1075–1076 Peptide antibiotic, 1060 Peptide bonds, 1071, 1071–1072, 1072f Peptide synthesis, 1076–1081 automated, 1079–1081 N-protection and C-activation and, 1076–1079 Perfluorocarbons, as blood substitute, 584 Pericyclic reactions, 374, 1266, 1266–1293 in biological systems, 1286–1289 cycloaddition, 1286–1289 cycloaddition, 1267, 1278–1281, 1280f, 1281t in biological systems, 1286–1289 electrocyclic, 1267, 1272–1278, 1277f, 1277t, 1278t molecular orbitals and, 1269–1272, 1270f, 1271f sigmatropic rearrangements, 1267, 1267–1268, 1281–1286, 1283t migration of carbon and, 1285–1286 migration of hydrogen and, 1284–1285 Perkin condensation, 900 Peroxide(s) addition of radicals to alkenes in presence of, 569–570 explosive, formation of, 567–568 formation of, mechanism for, 568 Peroxide effect, 570 Peroxyacids, 260, 260–261, 826 addition to alkene, 260–262 addition to alkenes, stereochemistry of, 278–279 aldehyde reactions with, 826–827 ketone reactions with, 826–827 Perspective formulas, 28, 154 converting other structural representations to, 187, 188 converting to other structural representations, 187, 189 of stereoisomers, 165–166 with more than one asymmetric center, 164–167, 169–176 Perspiration odor, butanedione and, 793 Pesticides, natural versus synthetic, harmfulness of, 290 PET (poly[ethylene terephthalate]), 1238, 1256, 1261 Petroleum, distillation of, 557 pH, 56 of blood, 77 imine formation and, 812f, 812–813 structure affected by, 88 structure of organic compounds and, 72–76 pH-activity profile, 1124, 1124f PHAs (polyhydroxyalkanoates), 1262 Phenanthrene, 345 Phenol, 361, 512, 909, 949, 950, 1107 lmax value for, 635 Phenolate ion, 361 lmax value for, 635 2-Phenoxyethanol, 759 Phenyl acetate, 1107 Phenylacetonitrile, 925 Phenylalanine, 1056t, 1057, 1186, 1187 pKa value of, 1061t N-Phenyl a-d-ribosylamine, 1036 2-Phenylbenzene, 910 N-Phenyl b-d-ribosylamine, 1036 1-Phenylbutane, 921 I-19 2-Phenylbutane, 921 1-Phenyl-1-butanol, 797 2-Phenyl-2-butene, 460 Phenyl cyanide, 764 2-Phenylethanol, 943 Phenylethanolamine, 1186 Phenylethanone, 997 Phenyl groups, 909 2-Phenylindole, 1014 Phenyl isothiocyanate (PITC), in N-terminal amino acid determination, 1082–1083 Phenylketonuria (PKU), 1186–1187 Phenyllithium, 536, 537 3-Phenylpentane, 910 Phenyl propanoate, 723 Phenyl propionate, 723 Phenyl propyl ketone, 792 Phenylpyruvate, in phenylketonuria, 1186 Pheromones, 191 sex, 535, 555 Phosgene, 726 Phosphatases, 1194 Phosphates, 1173 in nature, 1172 Phosphatidylcholines, 754 Phosphatidylethanolamines, 754 Phosphatidylserines, 754 Phosphoacylglycerols, 754 Phosphoanhydride(s), 1171 Phosphoanhydride bonds, 773, 1172 high-energy nature of, 1174–1176 Phosphodiesters, 1171, 1208, 1209f Phosphoenolpyruvate, 498, 1181, 1183, 1193, 1194 2-Phosphoenolpyruvate, 1182 Phosphofructokinase, regulation of metabolic pathways by, 1194 2-Phosphoglycerate, 1181, 1182 3-Phosphoglycerate, 1181, 1182 Phosphoglycerides, 754 Phosphomonoesters, 1171 Phosphonium ylides, 827, 828 Phosphoric acid, 773, 1171 Phosphorus trichloride, 771 Phosphorus trihalides, alcohol conversion into alkyl halide using, 487 Phosphorylation, oxidative, 1191 Phosphoryl transfer reactions, 1171–1172, 1172 Phosphotriesters, 1171 Photochemical reactions, 1268 Photosynthesis, 1018 pH-rate profile, 812, 1124, 1124f Phthalates, 1261 Phthalic acid, 763, 770, 1069 pKa values of, 769t structure of, 769t Phthalic anhydride, 770 Phthalimide, 763 N-Phthalimidomalonic esters, synthesis of, 1069–1070 pI (isoelectric point), 1062, 1062–1064 π* Antibonding molecular orbitals, 357 Pi (π) Bond(s), 26 in pericyclic reactions, 1267 I-20 Index π Bonding molecular orbitals, 357 π-Complex, 307, 307–308 Piperidine, 531, 971, 990, 1000 conjugate acid of, pKa value of, 991 Piperidinium ion, 1000 PITC (phenyl isothiocyanate), in N-terminal amino acid determination, 1082–1083 pKa values, 56 of amines, 991–992 of anilines, 940 of benzoic acids, 939 of carbon acids, 854, 854t delocalized electrons effects on, 360–364, 362t dependence on structure of acid, 63–66 determination using UV/Vis spectroscopy, 638, 638f of enzyme catalytic groups, 1124, 1124f importance of, 59–60, 60t for nitrogen heterocycles, 998t of phenols, 938 substituent effects on, in substituted benzenes, 939–940 table of, A-1 PKU (phenylketonuria), 1186–1187 PLA (polyactide), 1261–1262 Planck, Max, Planck’s constant, 224, 613 Plane of polarization, 160, 160f, 160–161, 161f Plane of symmetry, 170 Plastic(s), 1237 Plasticizers, 1260, 1260–1261 physical properties of, 1260–1261 Plavix, 908 Plexiglas, 1238t PLP (pyridoxal phosphate), 1151, 1151–1156 Polar covalent bonds, 11, 11t, 11–14, 13t Polarimeters, 161, 161–162, 162f Polarizability, 115 boiling points and, 115, 115t Polar reactions, 1266 Polar solvents, aprotic, 412, 412f, 413 (Z)-Poly(1,3-butadiene), 1251 (Z)-Poly(2-methyl-1,3-butadiene), 1250 Poly(acrylonitrile), 1238t Poly(dioxanone) (PDS), 771 Poly(ethylene terephthalate) (PET), 1238, 1256, 1261 Poly(methyl methacrylate), 1238t Poly(p-phenylene vinylene), 354 Poly(tetrafluoroethylene), 1238t Poly(vinyl acetate), 1238t, 1264 Poly(vinyl alcohol), 1264 Poly(vinyl bromide), 1265 Poly(vinyl chloride), 1238t, 1240 Polyacetylene, 354, 1250 Polyactide (PLA), 1261–1262 Polyamides, 1254, 1254–1255 Polycarbonates, 1256 Polyenes, conjugated, lmax values for, 634t Polyesters, 1256 Polyethylene, 1238t properties of, as function of crystallinity, 1258, 1258t Polyhydroxyalkanoates (PHAs), 1262 Polymer(s), 353–354 atactic, 1249 biodegradable, 1261, 1261–1262 conducting, 1250 designing, 1259 isotactic, 1249 living, 1246 oriented, 1260 syndiotactic, 1249 synthesized by cells, 1236, 1237 synthetic See Synthetic polymers thermoplastic, 1259 thermosetting, 1259 Polymerase chain reaction (PCR), 1230, 1230f, 1230–1231 Polymer chemistry, 1237 Polymerization, 353, 354, 1236 Polynucleotides, 1211 Polypeptides, 1053 Polypropylene, 1238t Polypyrrole, 354 Polysaccharides, 132, 1018, 1040f–1042f, 1040–1043 Polystyrene, 1237, 1238t Polythiophene, 354 Polyunsaturated fatty acids, 729 Polyunsaturated oils, 752 Polyurethanes, 1257, 1257–1258 Porphyrin(s), 1008–1009 Porphyrin ring system, 1008, 1008–1009 Positively charged protons, Potassium acetate, 724 Potassium atoms, as asymmetric centers, 180 Potassium ethanoate, 724 Potassium hydrogen tartrate, 179 Potassium phthalimide, 1069 Potential maps, 14 Pott, Percival, 516 Prepolymers, 1257 Preservatives for biological specimens, 819 for food, 582, 954 Primary alcohols, 106 Primary alkyl halides, 104 Primary alkyl radicals, 560 Primary amines, 109 Primary carbocation, 238 Primary carbons, 94 Primary hydrogens, 95 Primary protein structure, 1081 determination of, 1082–1088 C-terminal amino acid determination and, 1083–1084 hydrolysis using endopeptidases and, 1084–1088, 1085t N-terminal amino acid determination and, 1082–1083 partial hydrolysis and, 1084 Primary radicals, 560 Primary structure, of nucleic acids, 1212 Principle of microscopic reversibility, 918 Prions, 1093 Procaine (Novocain), 519 Prochiral carbons, 681 Prodrugs, 952, 953 Products, 55 kinetic, 369, 369–373 thermodynamic, 369, 369–373 Progesterone, 302, 790 specific rotation of, 163t Proline, 1005, 1056t, 1057 pKa value of, 1061t Promoter site, in transcription, 1217 Pronated methyl alcohol, pKa of, 63 Pronated methylamine, pKa of, 63 Prontosil, 951–952 Propadiene, 303 Propagating site, 1239 Propagation steps, 559 of monochlorination of methane reaction, 559 Propanal, 796, 1157 Propane, 94 boiling point of, 305t physical properties of, 91t structure, 92 1,2-Propanediol, 1157 1,3-Propanediol, 823 Propanitrile, 855 Propanoic acid, 722, 806 1-Propanol, 253, 483, 796, 806 2-Propanol, 247, 253, 468 Propanone, 792 Propene, 192, 258, 272, 446, 467, 468 boiling point of, 305t Propenenitrile, 764 2-Propen-1-ol, 304 Propionic acid, 722 Propionyl-CoA, 1205 Propofol, 504 Propoxide ion, 471 Propranolol, enantiomers of, 179 N-Propylacetamide, 738 Propyl alcohol, 106 Propylamine, 94 Propylbenzene, 924, 925 p-Propylbenzenesulfonic acid, 945 Propyl bromide, 94, 467, 471 Propyl chloride, 94 Propylene, 192, 262 Propylene oxide, 262 Propyl group, 94 Propyl halides, 319 2-Propyl-1-hexene, 193 Propylmagnesium bromide, 797 4-Propyloctane, 97 Propyne, boiling point of, 305t Pro-R-hydrogen, 681 Pro-S-hydrogen, 681 Prostaglandin synthase, 748 Prostaglandin synthesis, aspirin blockage of, 748–749 Protecting groups, 823, 823–825 Protective proteins, functions in biological systems, 1054t Protein(s), 1053 See also Enzyme(s); Hormones amino acids and See Amino acid(s) biosynthesis of, 1221t, 1221–1225, 1222f, 1224f from RNA blueprint, 1216 catabolism of, 1185–1187, 1186f denaturation of, 1094 fibrous, 1054 functions in biological systems, 1054t globular, 1054 nutrition and, 1058 prenylation of, 1201 protective, functions in biological systems, 1054t shape of, electron delocalization and, 338 structural, functions in biological systems, 1054t taxonomic relationships between, 1081 Protein prenylation, 1201 Protein structure, 1081–1094 primary See Primary protein structure quaternary, 1081 coil conformation and, 1093f, 1093–1094 secondary, 1081, 1088–1091 a-helix, 1088–1089, 1089f b-pleated sheet, 1089–1090, 1090f coil conformation and, 1090f taxonomic relationship and, 1081 tertiary, 1081 coil conformation 1091f, 1091–1093, 1092f loop conformation, 1091f Protic solvents, 412, 412f, 428 Proton(s), 4, 8–9 bonded to oxygen and nitrogen, NMR spectroscopy and, 684–686, 685f, 686f chemically equivalent, 654 coupled, 666 identification by coupling constants, 675–678, 676t, 675f–678f methine, 660 methyl, 660 methylene, 660 number causing signals, integration of NMR signals and, 663f, 663–665, 665f reduction by addition of electrons and, 809 reduction by addition of hydride ions and, 808 Protonated acetic alcohol, 58 Protonated alcohols, 58 pKa value of, 59, 60t Protonated a-aminocarboxylic acids, 1053 Protonated amines, pKa value of, 60, 60t Protonated anilines, 361–362, 937 pKa values of, 940 Protonated carboxylic acids, 58, 59 pKa value of, 59, 60, 60t Protonated cyclohexylamine, 361–362 Protonated ethyl alcohol, 58 Protonated ethylamine, 58 Protonated imidazole, 1006, 1057 Protonated methyl alcohol, 58 Protonated methylamine, 58 Protonated triethylamine, 111 Protonated water, pKa value of, 59–60, 60t Index Proton-coupled 13C NMR spectra, 691, 692–693 Proton exchange, 684, 684–685 acid-catalyzed, mechanism for, 685–686 Protonix (pantropazole), 1007 Proton magnetic resonance (1H NMR), 649 See also Nuclear magnetic resonance Proton transfer reactions, 54, 54–55 See also Acid-base reactions Protosterol cation, 1202 Provitamin D2, 1288 Provitamin D3, 1288 Proximity effect, 372 Prozac, 46 d-Psicose, 1022t Purine, 349, 387, 1008, 1160, 1208 Pyranoses, 1031 Pyranosides, 1035 Pyridine, 347, 999, 999–1005, 1001f, 1003f orbital structure of, 348 Pyridine nucleotide coenzymes, 1135 Pyridinium chlorochromate (PCC), 499 Pyridinium ion, 1000 Pyridone, 1004 Pyridoxal phosphate (PLP), 1151, 1151–1156 Pyridoxamine, 1154 Pyridoxine (vitamin B6), 1133t, 1151–1156 Pyrimidine, 349, 1008, 1208 Pyrophosphate, 774, 891, 922, 1173, 1174, 1199, 1220 Pyrophosphoric acid, 773, 1171 Pyrosequencing, 1228, 1228–1229 Pyrrole, 347, 387, 906, 994, 994–995, 996f, 998 orbital structure of, 348 reactivity of, 997 resonance contributors of, 348 Pyrrolidine, 906, 990, 995 conjugate acid of, pKa value of, 991 enamine formation from, 993 Pyruvate, 890, 1145, 1146, 1150, 1181, 1183, 1193, 1195 fate of, 1184–1185 Pyruvate carboxylase, regulation of metabolic pathways by, 1194–1195 Pyruvate decarboxylase, reaction catalyzed by, 1145 Pyruvate dehydrogenase complex, reaction catalyzed by, 1146–1147 Q Quantum mechanics, Quartet, 665 Quaternary ammonium ions, 482, 519 elimination reactions of, 519–521 mechanism of, 519 Quaternary protein structure, 1081 Quinoline, 349, 1014 Quinone, 581 Quinuclidine, 441 conjugate acid of, pKa value of, 991 R Racemic mixtures (racemates), 163, 178, 273 resolution of, 178, 178–179 of amino acid mixtures, 1070– 1071 Racemization of amino acids, PLP-catalyzed, 1152–1154 complete, 419 partial, 419 Radial nodes, 21 Radical(s), 16, 558 addition to alkenes, 568–571 alkyl distribution of products and, 561–563 primary, 560 secondary, 560 tertiary, 560 allylic, 573 benzylic, 573 peroxide, explosive, formation of, 567–568 reactions in biological systems, 578–583 reactivity-selectivity principle and, 564–567, 565f, 566 stability of, 560–561, 561f stratosphere and, 583–584 terminology for, 560 vinylic, 315 Radical addition reactions, 570 addition of radicals to alkenes, 568–571 mechanism for, 569–570 stereochemistry of, 571–573 Radical anions, 315, 316f Radical cations, 597 Radical chain reaction, 559 Radical inhibitors, 570, 580, 580–581 Radical initiators, 568, 570, 1241t, 1241–1242 Radical polymerization, 1239, 1239–1242, 1241t Radical reactions, 1266 curved arrows in, 590–591 Radical substitution reactions, 559 of alkanes, 558–567 of benzylic and allylic hydrogens, 573–576 stereochemistry of, 571–573 Radio waves, 612, 612f Random copolymers, 1252–1253 Ranitidine (Zantac), 1007 Rasagiline, 300 Rate constants, 213, 404 first-order, 213 rate of reaction compared with, 213–215 second-order, 214 Rate-determining step, 217 Rate laws, 213, 404 Rate-limiting step, 217 Rayon, 1237 R configuration, 156 RCSB PDB (Research Collaboratory for Structural Bioinformatics Protein Data Bank), 700 Reactants, 55 for synthesis, choosing, 269 Reaction(s) See also specific compounds and types of compounds acid-catalyzed See Acid-catalyzed reactions acylation of a-carbon of carbonyl compounds using enamine intermediate, 866–867 Friedel-Crafts, of benzene, 918–920 acylation-reduction, alkylation of benzene by, 922–924 addition See Addition reactions addition-elimination, nucleophilic See Nucleophilic additionelimination reactions alcoholysis, 739, 739–741 acid-catalyzed, of amides, 760, 762 alkene metathesis, 548, 548–551 alkylation See Alkylation reactions alternate methods for carrying out, 924 amination, reductive, 815, 815–816, 1069 of amines with nitrous acid, 953–955 of amino acids with ninhydrin to form a colored product, 1065 aminolysis, 740 with ammonia, amino acid synthesis and, 1068–1069 anabolic, 1136 Baeyer-Villiger, 826 Baylis-Hillman, 852 bimolecular, 405 biological, enzymes as catalysis of, 1113–1115 bromination of benzene, 913, 914 of ethane, 559 Cannizzaro, 904 carboxylation of glutamate, vitamin KH20dependent, 1164–1165 Kolbe-Schmitt, 864, 864–865 catabolic, 1136 catalysis of See Catalysis chain, 1237 chemoselective, 810 chlorination of benzene, 913, 914 of methane, 558–559 cis-trans interconversion, enzyme-catalyzed, 836 combustion, 558 concerted, 254, 374 condensation See Condensation reactions coupled, 1183 coupling, 538 alkylation of benzene using, 924 cycloaddition, 374, 1278–1281 [4 + 2], 374 degradation Hofmann, 532 Wohl, 1026, 1026–1027 Diels-Alder, 374, 374–381, 1278–1279 diene conformations and, 377–379 I-21 predicting product when both reagents are unsymmetrically substituted and, 376–377 retrosynthetic analysis of, 380–381 stereochemistry of, 379 E1cB, 871, 871–872 elimination See Elimination reactions; E2 reaction(s); E1 reaction(s) endergonic, 207 endothermic, 208 exergonic, 207 exothermic, 208 Favorskii, 903 first-order, 213, 417 Fischer esterification, 755, 755–757 Gatterman-Koch, 919, 919–920 of group I organic compounds, 381 of group II organic compounds, 524 or group III organic compounds, 894 of group IV organic compounds, 1010 halogenation See Halogenation Heck, 545 Hell-Volhard-Zelinski, 861, 861–862 hydrolysis See Hydrolysis reactions intermolecular, 433, 433–435, 1109 intramolecular, 434, 434–435, 1109–1111, 1110t cyclic compound formation by, 957–958 keto-enol interconversion, 858, 858–859 kinetics of, 205, 211f, 211–212 Mannich, 903 Michael, 867–869, 868 nitration, of benzene, 916 overview of, 381 oxidation See Oxidation reactions pericyclic See Pericyclic reactions phosphoryl transfer, 1172 photochemical, 1268 polar, 1266 product of, delocalized electrons and, 364–365 radical, 1266 curved arrows in, 590–591 radical chain, 559 radical substitution, 559 rate-determining step of, 217 rate-limiting step of, 217 reduction See Reduction reactions regioselective, 242–244, 243, 271 reversible, 54 Ritter, 787 Sandmeyer, 948 Schiemann, 949 Sandmeyer reactions, 948 second-order, 404 Simmons-Smith, 296 SNAr, 955 stereoselective, 271, 271–272 stereospecific, 271, 271–272 Strecker synthesis, 1070 substitution See Nucleophilic substitution reactions; SN2 reactions; SN1 reactions; Substitution reactions I-22 Index sulfonation, of benzene, 917–918, 918f summaries of for delocalized electrons and products of reactions, 383 for elimination reactions, 439, 477 for reactions of alcohols, esters, epoxides, amines, and thiols, 526–528 for reactions of aldehydes, 839–843 for reactions of alkanes, 585–586 for reactions of alkenes, 291–292 for reactions of alkynes, 325–326 for reactions of a-carbon of carbonyl compounds, 895–898 for reactions of a,b-unsaturated carbonyl compounds, 839–843 for reactions of benzene and substituted benzenes, 960–962 for reactions of carbohydrates, 1049–1050 for reactions of carboxylic acids and carboxylic acid derivatives, 777–780, 839–843 for reactions of heterocyclic compounds, 1011–1012 for reactions of organometallic compounds, 552 for substitution reactions, 439 Suzuki, 924 thermal, 1268 thermodynamics of, 205–211, 210t transesterification, 739, 739–741 aspirin and, 748–749 transmetallation, 538 unimolecular, 417 Reaction coordinate diagrams, 205, 205–206, 206f energy changes described by, 216f, 216–218, 217f Reaction rates, 212, 213f measurement using UV/Vis spectroscopy, 637f, 637–638, 638f rate constant compared with, 213–215 solvent effects on, 429–430, 430f Reactivity(ies) See also specific compounds of aldehydes and ketones, 794 benzene substituent effects on, 929–935 of carbonyl compounds, 794 of carboxylic acid derivatives, 733–734, 767 in SN1 reactions, 423 in SN2 reactions, 405–407 stereochemistry and, 435 Reactivity-selectivity principle, 564–567, 565f, 566 Rearrangements of arene oxides, mechanism for, 512 carbocation, 250, 250–252 Claisen, 1283 Cope, 1283 enediol, 1023 base-catalyzed, enzymecatalyzed reactions reminiscent of, 1125–1126 base-catalyzed, of monosaccharides, 1023 McLafferty, 609 sigmatropic, 1267, 1267–1268, 1281–1286, 1283t migration of carbon and, 1285–1286 migration of hydrogen and, 1284–1285 Receptors drug binding to, 118 enantiomer differentiation by, 287 Recombinant DNA, 1231 Recycling of polymers, 1261 symbols for, 1243 Reducing sugars, 1036–1037, 1037 Reduction reactions, 266, 266–269, 267f, 804, 808–809 by addition of electrons and protons, 809 by addition of a hydride ion and a proton, 808 by addition of two hydrogen atoms, 808–809 Clemmensen, 923, 960 dissolving metal, 315, 809 of monosaccharides, 1024–1025 of nitro substituents on benzene ring, 926–927 Wolff-Kishner, 923, 923–924, 960 Reductive amination, 815, 815–816, 1069 Reductive elimination, 543 in Suzuki reaction, 543 Reference compound, in nuclear magnetic resonance spectroscopy, 656, 690 Reformatsky reaction, 900–901 Regioselective reactions, 242–244, 243, 271 Regioselectivity, 242–244, 243 degrees of, 243 of E2 reaction, 446–452 Regulatory enzymes, 1194 Relative boiling points, 728 Relative rates, 1109, 1109–1110, 1110t Remsen, Ira, 1047 Replication, 1215, 1215–1216, 1216f semiconservative, 1216 Research Collaboratory for Structural Bioinformatics Protein Data Bank (RCSB PDB), 700 Resolution of 1H NMR spectra, 687f, 687–688, 688f of racemic mixtures, 178, 178–179 Resonance, 341 Resonance contributors (resonance structures), 69, 334, 334–340 contributing, that are radicals, curved arrows in, 591–592 drawing, 335–338, 392–400 moving a lone pair toward a doubly bonded sp2 carbon and, 394–397 moving π electrons toward a doubly bonded sp2 carbon and, 393–394 moving π electrons toward a positively charged sp2 carbon and, 392–393 predicted stabilities of, 338–340, 339f, 340f Resonance electron donation, 364, 930 Resonance electron withdrawal, 363, 931 Resonance energy, 341, 341–342 Resonance hybrid, 69, 334 Resonance structures See Resonance contributors Restricted rotation, cis-trans isomers resulting from, 148–151, 149f Restriction endonucleases, 1228 Restriction fragments, 1228 cis-Retinal, 151 trans-Retinal, 151 Retro-aldol addition, 870–871 Retrosynthetic analysis, 320, 320–324, 829–832 of acetoacetic ester synthesis, 887–888 of alcohol synthesis, 800–801 of alkene synthesis by Wittig reaction, 829 creating a functional group using, 976–977 of crossed aldol addition, 874–875 designing syntheses using relative positions of two functional groups and, 978–980 of Diels-Alder reaction, 380–381 disconnections in, 830, 977–978 of malonic ester synthesis, 886 of Robinson annulation, 883 of substituted benzene synthesis using arenediazonium salts, 949–950 synthetic equivalents in, 830 synthons in, 830 Reversible reactions, 54 Reye’s syndrome, 76 rf radiation, 650 Rhodposin, 151 Ribavirin (Viramid), 1227 Riboflavin, 1133t, 1140–1144 Ribonucleic acid (RNA), 1207 bases in, 1207, 1208, 1208f biosynthesis of (transcription), 1217–1218, 1218f messenger, 1219 nucleosides in, 1209, 1210 as polynucleotide, 1211 ribosomal, 1219 synthesis of (transcription), 1216 transfer, 1219 Ribonucleosides, 1209t Ribonucleotides, 1209, 1209t d-Ribose, 1021 forms of, 1031 Ribose-5'-phosphate, 1168 Ribose-5-phosphate, 1160 Ribosomal RNA (rRNA), 1219 d-Ribulose, 1022t Rickets, 1288 Right-handed helices, 1089 Ring-closing metathesis, 549 Ring-contraction arrangement, 495 Ring-expansion arrangement, 495 Ring flip, 129, 129f Ring-opening polymerizations, 1248, 1248–1249 Ritter reaction, 787 RNA See Ribonucleic acid RNA polymerases, 1212 Robinson annulation, 881, 881–883 determining products of, 882 retrosynthetic analysis of, 883 Rock bending vibration, 614, 614f ROESY (Rotation-frame Overhauser Effect Spectroscopy), 698 Rohypnol (flunitrazepam), 817 Rotation observed, 162 restricted, cis-trans isomers resulting from, 148–151, 149f specific, 162 measurement of, 161–163, 162f, 163t observed, 163 Rotation-frame Overhauser Effect Spectroscopy (ROESY), 698 ROTs (allkyl tosylate), 489 Roundup (glyphosphate), 1231, 1232 rRNA (ribosomal RNA), 1219 R,S system, naming enantiomers by, 156 RU-486 (Mefegyne), 302 Rubber, manufacture of, 1250–1252 Rule of 13, 600 “Runner’s high,” 1075 S Saccharides See Carbohydrates Saccharin (Sweet’N Low), 908, 973, 1047 Salar de Uyuni, Bolivia, Salicylic acid, 118, 747 SAM (S-adenosylmethionine), 436–437 SAMe (S-adenosylmethionine), 436–437 SAN, 1252t Sandmeyer reactions, 948 Sanger, Frederick, 1228 Saponification, 752, 752–753 Saran, 1252t Saturated hydrocarbons, 191, 556 Sawhorse projections, 458 Schiemann reaction, 949 Schiff base, 811 See also Imine(s) Schrock catalyst, 551, 552 Schrödinger, Erwin, s-cis Conformation, 377 Scissor bending vibration, 614, 614f S configuration, 156 Scrapie, 1093 Scurvy, 1045 Sea hare, 445 Secondary alcohol, 106 Secondary alkyl halide, 104 Secondary alkyl radical, 560 Secondary amine, 109 Secondary carbocation, 238 Secondary carbon, 94 Secondary hydrogen, 95 Index Secondary ion mass spectrometry (SIMS), 611 Secondary protein structure, 1081, 1088–1091 a-helix, 1088–1089, 1089f b-pleated sheet, 1089–1090, 1090f coil conformation, 1090f, 1090–1091 loop conformation, 1090f, 1090–1091 Secondary radical, 560 Second-order rate constant, 214 Second-order reaction, 404 Selection rules, for pericyclic reactions cycloaddition, 1280, 1281t electrocyclic, 1276, 1277t sigmatropic rearrangements, 1283, 1283t summary of, 1289 Selectivity factor, radical formation and, 564–567, 565f Selegiline, 300 Selenoxide, 903 Semiconservative replication, 1216 Semiquinone, 581 Semisynthetic drugs, 832 Sense strand, 1217, 1218f Separated charges, 339 Sequencing-by-synthesis, 1228 Serine, 1055t, 1057, 1195, 1222t pKa value of, 1061t Serine proteases, 1118f, 1118–1120 Sesquiterpenes, 1196 Sex pheromones, 535, 555 Sharpless epoxidation, 285 Shielding, 653 diamagnetic, 653 in nuclear magnetic resonance, 653f, 653–654 Shirakawa, Hideki, 354 Sickle cell anemia, 1224 Side chains amino acid, 1054, 1114 Sigma (s) antibonding molecular orbitals, 24–25, 25f Sigma (s) bond(s), 23 in pericyclic reactions, 1267 Sigma (s) bonding molecular orbitals, 24–25, 25f Sigmatropic rearrangements, 1267, 1267–1268, 1281–1286, 1283t migration of carbon and, 1285–1286 migration of hydrogen and, 1284–1285 Silent Spring (Carson), 403 Silicon, carbon versus, in living organisms, 416 Simmons-Smith reaction, 296 Simple carbohydrates, 1018 Simple triglycerides, 751 SIMS (secondary ion mass spectrometry), 611 Simvastatin (Zocor), 138 Single bond, 30 formation of, 28–31 strength of, 44, 44t Singlet, 665 Site-specific mutagenesis, 1120 Skeletal structures, 102, 102–103 converting other structural representations to, 187 converting to other structural representations, 187, 188 Smalley, R E., 345 Snake venom, 754 SNAr, 955 SN1/E1 reactions, 466, 469–471, 470t SN2/E2 reactions, 466, 467t, 467–469 SN1 reaction, 417 of alkyl halides, 417–421 of alcohols, mechanism for, 483 of allylic halides, benzylic halides, 421–424 determining products of, 426–427 ether cleavage by, mechanism for, 502–503 leaving group in, 420 mechanism for, 417–420, 418f experimental evidence for, 417 nucleophile in, 421 predicting, 426–427 reactivity in, predicting, 423 solvent in, reaction rate and, 430–431, 431t SN2 reaction, 405 of alcohols, mechanism for, 484 of alkyl halides, 404–416 of benzylic halides, allylic halides, 421–424 competition between SN1 reactions and, 424t, 424–427 determining products of, 426–427 ether cleavage by, mechanism for, 503 inability to perform, Lesch-Nyhan syndrome due to, 490 leaving group in, 410 mechanism for, 404–406, 406f experimental evidence for, 404–405, 406–409, 407f, 408f nucleophile in, 411t, 411–413, 412f solvent effect on nucleophilicity and, 413t, 413–414 steric effects on nucleophilicity and, 414–416 predicting, 426–427 sequential, enzyme-catalyzed reactions involving, 1121–1125, 1122f solvent in, reaction rate and, 431–433 SN2 reactions, catalysis by crown ethers, 511 Soap, 752, 752–753 Socrates, 58 Sodamide (sodium amide), 317 Sodium electronic configuration of, 6t electrons of, in liquid ammonia, 317 Sodium amide (sodamide), 317 Sodium ammonium tartrate, 178 Sodium benzenecarboxylate, 724 Sodium benzoate, 724 Sodium chloride, bonds in, Sodium cyclamate, 1047 Sodium formate, 724 Sodium lactate, 161 Sodium linoleate, 753 Sodium methanoate, 724 Sodium nitrite, 953 hazards of, 954 Sodium oleate, 753 Sodium pentothal, 504 Sodium stearate, 753 Sodium trichloroacetate, 297 Solubility, 119 See also specific compounds Solvation, 119 effects of, 428 Solvent(s) aprotic, 428 carbonyl compounds as, 728 dielectric constants and boiling points of, 429t ethers used as, 503, 503t nucleophilicity and, 413t, 413–414 polar, aprotic, 412, 412f, 413 protic, 412, 412f, 428 reaction rates and, 429–430, 430f in SN1 reactions, 430–431, 431t in SN2 reactions, 431–433 Solvent-separated ion pairs, 420 d-Sorbose, 1022t Spearmint oil, 790 Specific-acid catalysis, 1102, 1102–1104, 1103f Specific-base catalysis, 1105, 1105–1106 Specific rotation, 162 measurement of, 161–163, 162f, 163t observed, 163 Spectroscopy, 611 electromagnetic spectrum and, 611–613, 612f infrared See Infrared spectroscopy NMR See Nuclear magnetic resonance spectroscopy ultraviolet/visible, 596, 631, 631–639, 632f Beer-Lambert law and, 633 effect of conjugation on lmax and, 634f, 634t, 634–635 uses of, 637–639, 637f–639f visible spectrum and color and, 645–647, 646t “Speed,” 908 SPF (sun protection factor), 633 Spin-spin coupling, 668 Splenda (sucralose), 1047, 1048 Splitting diagrams (splitting trees), 679, 679f, 679–681, 680f Squalene, 1196, 1202 Squalene oxide, 1202 Squalene synthase, 1201 Stability of alkenes, relative, 269–271 of alkynes, 306–307 of carbanions, 451 of carbocations, 238, 307, 356, 451 delocalization energy and, 341–342 delocalized electrons and, 351–364 allylic and benzylic cations and, 355–356 1,3-butadiene and, 357–359, 358f dienes and, 351–353, 352f, 353f, 355 molecular orbital description of, 356–360, 357f 1,4-pentadiene and, 359–360 kinetic, 212 I-23 of radicals, 560 of resonance contributors, predicted, 338–340, 339f, 340f thermodynamic, 212 Stacking interactions, 1214 Stack plots, 695, 696f Staggered conformers, 122, 122f, 122–124 Standing waves, 21–22 Staphylococcus aureus, penicillin resistance of, 1043 Starches, 132 Statins, 138, 1198 Staudinger, Hermann, 1237 Stearic acid, 729t, 730 in chocolate, 582 Step-growth polymers, 1238, 1253–1258, 1254f epoxy resins and, 1257 polyamides and, 1254–1255 polyesters and, 1256 polyurethanes and, 1257–1258 Stereocenters (stereogenic centers), 154 Stereochemistry, 271 See also Stereoisomers of E1 dehydration of alcohol, 497 of electrophilic addition reactions of alkenes, 272–284 forming products with one asymmetric center, 272–274, 273f forming products with two asymmetric centers, 272–284 of glucose, 1027–1029 of polymerization, 1249–1250 of radical addition reactions, 571–573 of radical substitution reactions, 571–573 reactivity and, 435 Stereoisomers, 147, 147–148 addition reactions with alkenes forming, 274–276 cis-trans See Cis-trans isomers of cyclic compounds, 167–169 formed in E2 reactions, 458–461, 459f meso compounds, 170–173 recognizing, 171–172 with more than one asymmetric center, 164–167, 169–173 nomenclature of, 173–178, 175t with one asymmetric center, 153f, 153–154 Stereoselective reactions, 271, 271–272 Stereoselectivity of E1 reactions, 457–458, 461t, 461–462 of E2 reactions, 457–461, 459t Stereospecific reactions, 271, 271–272 Steric effects, 407 nucleophilicity and, 414–416 Steric hindrance, 407 Steric interactions 1,3-diaxial, 131 gauche, 124, 131 Steric strain, 124 Sternbach, Leo, 816 Steroids, 137, 137–138 I-24 Index Stop codons, 1222, 1222f Straight-chain alkanes, 91 Strain energy, of cycloalkanes, 125f, 125–127, 127t s-trans Conformation, 377 Strecker synthesis, 1070 Streptomycin, 1225 Stretching vibrations, 614, 614f, 614–615 C—H absorption bands and, 623–625, 624f–626f, 624t Strong acids, 55 Strong base, 55 Structural databases, 700 Structural proteins, functions in biological systems, 1054t Structural representations See also Fischer projections; Newman projections; Perspective formulas; Skeletal structures interconverting, 187–189 Styrene, 909, 925, 1237, 1241t, 1245t, 1247t, 1252t Substantia nigra, in Parkinson’s disease, 300 Substituents acid strength and, 66–68 activating, 930 of substituted benzenes, 931–934, 932t, 935 deactivating, 930 of substituted benzenes, 933–934, 935, 936 Substituted acetylenes, 301 Substituted benzenes in Agent Orange, 909 alkyl substituent reactions and, 925–926 disubstituted, nomenclature of, 927–929 monosubstituted, nomenclature of, 909–910 nitro substituent reduction and, 926–927 polysubstituted, nomenclature of, 928–929 substituent effects and, 929–943 on orientation, 935–939, 936f, 937f ortho-para ratio and, 941 on pKa, 939–940 on reactivity, 929–935 synthesis of of disubstituted benzenes, 943–945 of monosubstituted benzenes, 943–945 of trisubstituted benzenes, 945–947 using arenedaizonium salts, 947–950 Substitution reactions, 145, 402 See also SN1 reactions; SN2 reactions acyl, nucleophilic, 732 of alkyl halides, 402–443 intermolecular versus intramolecular, 433–435 methylating agents used by chemists and by cells and, 436–438 SN1 See SN1 reactions SN2 See SN2 reactions of allylic halides, 421–422 of benzylic halides, 421–422 electrophilic aromatic substitution, 910, 910–913, 911f, 912, 912f, 996 See also Friedel-Crafts acylation; Friedel-Crafts alkylation; Halogenation; Nitration; Sulfonation nucleophilic See Nucleophilic substitution reactions radical of benzylic and allylic hydrogens, 573–576 stereochemistry of, 571–573 stereochemistry of, 461t in synthesis, 471–472 Substrates, 219, 1113 active site of, 1114 binding of, 1113–1114, 1115f Subunits, 1093, 1093f, 1093–1094 Succinate, 1141, 1143, 1188f, 1189 Succinate dehydrogenase, reaction catalyzed by, 1143 Succinic acid, 770 pKa values of, 769t structure of, 769t Succinic anhydride, 770 Succinimide, 574 Succinyl-CoA, 1157, 1168, 1188f, 1189, 1205 Sucralose (Splenda), 1047, 1048 Sucrose, 1039–1040 specific rotation of, 163t Sugars See also Carbohydrates; Monosaccharides amino, 1043 dental plaque and, 1041 deoxy, 1043 disaccharides, 1037, 1037–1040 invert, 1040 nonreducing, 1036–1037, 1037 polysaccharides, 1040f–1042f, 1040–1043 reducing, 1036–1037, 1037 Suicide inhibitors, 1163 Sulfa drugs, 1160 Sulfanilamide, 952, 1160 Sulfides, 522 Sulfonamides, 1160 Sulfonate esters, 481, 488 alcohol conversion into, 488–491 mechanism for, 489 Sulfonation, of benzenes, 917–918, 918f Sulfonium ions, 481, 523, 917 Sulfonium salts, 522 Sulfonyl chloride, 489 Sulfur, natural abundance of, 602t Sulfuric acid, 917 Sulphur nucleophiles addition to aldehydes, 825 addition to a,b,-unsaturated aldehyes and ketones, 835 addition to ketones, 825 Sunette (acesulfame potassium), 1047, 1048 Sunlight See Ultraviolet light Sun protection factor (SPF), 633 Sunscreens, 632–633 Super Glue, 1235, 1247 Suprafacial bond formation, 1279, 1282, 1285 Sutures, dissolving, 771 Suzuki reaction, 542, 542–545, 924 mechanism of reaction for, 543 Sweet and Safe (acesulfame potassium), 1047, 1048 Sweeteners See also Sugars artificial, 1047–1048 Sweet’N Low (saccharin), 908, 973, 1047 Sweet One (acesulfame potassium), 1047, 1048 Symmetrical ethers, 105 Symmetric anhydrides, 766 Symmetric molecular orbitals, 359, 1271 Symmetry, plane of, 170 Symmetry-allowed pathway, 1275 Symmetry-forbidden pathway, 1275 Syn addition, 275 Syndiotactic polymers, 1249 Syn eliminations, 458 Syn-periplanar arrangement, 458 Synthesis, 974–976 See also Retrosynthetic analysis acetoacetic ester, 887, 887–888 adding carbons to carbon skeleton and, 975–976 of alcohols, retrosynthetic analysis and, 800–801 of alkenes, 288–289 of alkenes by Wittig reaction, 827–829 of alkyl halides, planning, 566 of aspirin, 864–865 of benzenes disubstituted, 943–945 monosubstituted, 943–945 substituted, using arenediazonium salts, 947–950 trisubstituted, 945–947 changing carbon skeleton and, 975 changing functional group and, 974 changing position of functional group and, 975 of cyclic compounds, 957–958 designing approaching the problem, 474–476 multistep, 319–324 designing syntheses using relative positions of two functional groups and, 978–980 elimination reactions in, 472–473 functionalizing carbons and, 974 Kiliani-Fischer, 1026 by living organisms, 773 malonic ester, 885, 885–886 multistep, 576–578 examples of, 981–982 of natural products, 832 of peptide, 1076–1081 automated, 1079–1081 N-protection and C-activation and, 1076–1079 of primary amines by imide hydrolysis, hydrolysis reactions of, 763–764 reactants for, choosing, 269 substitution reactions in, 471–472 Synthetic equivalents, 830 Synthetic organic compounds, Synthetic polymers, 770, 1236, 1236–1265 biodegradable, 1261–1262 chain-growth (addition), 1237, 1238t, 1238–1249 anionic polymerization and, 1239, 1246–1247, 1247t branching of polymer chain and, 1242–1244 cationic polymerization and, 1239, 1244–1246 determination of mechanism for, 1247 radical polymerization and, 1239, 1239–1242, 1241t ring-opening polymerization and, 1248–1249 copolymers and, 1252t, 1252–1253 diene polymerization and, 1250–1252 physical properties of, 1258f, 1258t, 1258–1261 of elastomers, 1260 of oriented polymers, 1260 of plasticizers, 1260–1261 of thermoplastic polymers, 1259 of thermosetting polymers, 1259–1260 recycling, 1261 step-growth (condensation), 1238, 1253–1258, 1254f epoxy resins and, 1257 polyamides and, 1254–1255 polyesters and, 1256 polyurethanes and, 1257–1258 stereochemistry of polymerization and, 1249–1250 Synthons, 830 Système International Units for energy, 24n for length, 13n Systemic nomenclature, 93 2,4,5,-T (2,4,5-trichlorophenoxyacetic acid), 909 T Tagamet (cimetidine), 1007 d-Tagatose, 1022t d-Talose, 1021, 1028 Tamiflu, 1124 Tamoxifen, 199 Tartaric acid, stereoisomers of perspective formulas and Fischer projections of, 175 physical properties of, 175, 175t Tautomer(s), 311, 857 keto-enol, 311, 857–858 Tautomerization, 858, 858–859 keto-enol, 311, 311–312 Taxol, 789, 832 TBME (tert-butyl methyl ether), 503t TCDD (2,4,7,8-tetrachlorodibenzo [b,e][1,4]dioxin acid), 909 TE-AC, 1276, 1289 Teflon, 1238t, 1242 TEM (triethylenemelamine), 534 Temozolamide, 953–954 Template strand, 1217, 1218f Tenormin (atenolol), 80 Terminal alkyne, 301 Index Termination step, 559 Termites, eradicating, 436 Terpenes, 1195, 1195–1202 biosynthesis of, 1197–1202, 1199 structure of, 1195–1197 Terpin hydrate, 1199 Tertiary alcohol, 106 Tertiary alkyl halide, 104 Tertiary alkyl radical, 560 Tertiary amine, 109, 481 Tertiary carbocation, 238 Tertiary carbon, 95 Tertiary hydrogen, 95 Tertiary protein structure, 1081 coil conformation and, 1091f, 1091–1093, 1092f Tertiary radical, 560 Tesla, Nikola, 651 Testosterone, 790 specific rotation of, 163t 2,4,7,8-Tetrachlorodibenzo [b,e][1,4]dioxin (TCDD) acid, 909 Tetracycline, 153, 1225 Tetradecanoic acid, 729t Tetraethyllead, 536 Tetrafluoroethylene, 1242 Tetrahedral bond angle, 30 Tetrahedral carbon, 30f, 30–31, 31f Tetrahedral intermediate, 731, 731–733 Tetrahydrofolate (THF), 1159 Tetrahydrofuran, 991 Tetrahydrofuran (THF), 143, 442, 503t Tetrahydrofuran boiling point of, 429t dielectric constant of, 429t Tetrahydropyran (THP), 503t, 991 Tetramethylammonium hydroxide, 110 2,3,4,6-Tetra-O-methylgalactose, 1038 Tetramethylsilane (TMS), 656–658, 657f Tetraphenylporphyrin, 1015 Tetraterpene, 1196 Tetrose, 1018 Thalidomide (Contergan), enantiomers of, 287–288 Thatcher, Margaret, 700 Thermal reaction, 1268 Thermodynamic control, 369 of nucleophilic addition to a,b-unsaturated aldehydes and ketones, 833–834 Thermodynamic enolate ion, 864 Thermodynamic product, 369, 369–373 Thermodynamics, 205, 206, 206–211, 207f, 210t endergonic reactions and, 207 endothermic reactions and, 208 enthalpy and, 208 entropy and, 209 exergonic reactions and, 207 exothermic reactions and, 208 Le Châtelier’s principle and, 208 Thermodynamic stability, 212 Thermolysin, hydrolysis catalyzed by, 1085t Thermoplastic polymers, 1259 physical properties of, 1259 Thermosetting polymers, 1259 physical properties of, 1259–1260 THF (tetrahydrofolate), 1159 THF (tetrahydrofuran), 143, 442, 503t Thiacyclopropane, 991 Thiamine, 1133t, 1134 curing hangovers by, 1148 Thiamine pyrophosphate (TPP), 1144, 1144–1149 Thiazolinones, 1083 Thiazolium ring, 1145 Thiirane, 991 Thin-layer chromatography, 1066 determining number of amino acids using, 1066 Thioesters, 774, 774–775, 1178 Thioethers, 522 Thiols, 521, 521–522 oxidation to disulfides, 1073 Thionyl chloride, 771 alcohol conversion into alkyl halide using, 488 Thiopental sodium, 504 Thiophene, 347, 906, 994, 996, 997 Thomson, William, 208 THP (tetrahydropyran), 503t, 991 Threo enantiomers, 165 Threonine, 1055t, 1057, 1221 pKa value of, 1061t stereoisomers of, 176 d-Threose, 1020, 1021 l-Threose, 1020 Thromboxanes, 748 Thymidylate synthase, 1160–1161 Thymine, 1008, 1208 in DNA, 1225–1227 Thymine dimers, 1286 Thyroxine, 915 Time dependence, of NMR spectroscopy, 683–684, 684f TMS (tetramethylsilane), 656–658, 657f Toluene, 909, 926, 935, 937, 941 boiling point of, 429t dielectric constant of, 429t para-Toluenediazonium chloride, 948, 949 Toluene-2,6-diisocyanate, 1258 para-Toluenesulfonylchloride, 489, 528 ortho-Toluidine, 928 Toxicity of Agent Orange, 909 of benzene, 910 TPP (thiamine pyrophosphate), 1144, 1144–1149 TPP ylide, 1145 Trans alkenes, 315 alkyne conversion to, 315–316, 316f Transamination of amino acids, PCP-catalyzed, 154-155, 1152 PLP-catalyzed, 1152, 1154–1156, 1185 TRANS-ANTI-(ERYTHRO or CIS), 282 Transcription, 1216, 1217–1218, 1218f Trans 1,2-diols, 509 Transesterification reactions, 739, 739–741, 745 aspirin and, 748–749 Trans fats, 268 Transfer reactions, acyl, 732 Transfer RNA (tRNA), 1219, 1219–1221 amino acid attachment to, 1220 Trans-fused rings, 137 Transimination, 1152–1155 Trans isomers, 133, 149 Transition metals, in organocuprates, 538 Transition state, 206, 217 stability of alkynes and, 306–307 structure of, 240–242, 241f, 242f Translation, 1216, 1221t, 1221–1225, 1222f, 1224f antibiotics inhibiting, 1225 Transmetallation, 538 TRANS-SYN-(ERYTHRO or CIS), 282 Traveling waves, 21 Triacontane, physical properties of, 91t Triacylglycerols, 751 2,4,6-Tribromoanisole, 942 1,3,5-Tribromobenzene, 949 1,1,2-Trichloro-3-methylbutane, 679 2,4,5-Trichlorophenoxyacetic acid (2,4,5-T), 909 Tridecane, physical properties of, 91t Triethylamine, 111, 441, 531 protonated, 111 Triethylene glycol, 531 Triethylenemelamine (TEM), 534 3,3,6-Triethyl-7-methyldecane, 97 Trifluoromethanesulfonyl chloride, 489 Triglycerides, 751, 751–755 mixed, 751 simple, 751 Trigonal planar carbon, 32 Trimethoprim, 1163 Trimethylamine, 109, 519 Trimethylborate, 544 2,2,3-Trimethylbutane, 93 1,1,2-Trimethylcyclopentane, skeletal structure of, 102 2,3,6-Tri-O-methylglucose, 1038 2,2,4-Trimethylpentane, 99 3,4,4-Trimethyl-2-pentene, 460 Trimethylsulfonium iodide, 522 Triose, 1018 Tripeptide, 1053, 1071 Triphenylmethyl chloride, 386 Triphenylphosphine, 828 Triphenylphosphine oxide, 827 Triphosphoric acid, 773, 1171 Triple bonds in ethyne, 34f, 34–35, 35f formation of, 34f, 34–35, 35f strength of, 44, 44t Triterpene, 1196 tRNA (transfer RNA), 1219, 1219–1221 amino acid attachment to, 1220 Trypsin, hydrolysis catalyzed by, 1084–1085, 1085t Tryptophan, 724, 1005, 1056t, 1057 pKa value of, 1061t Twist bending vibration, 614, 614f Twist-boat conformer, 129, 129–130, 130f I-25 Two dimensional (2-D) NMR, 695, 695–698, 696f, 697f Tylenol (acetaminophen), 118, 972 Tyramine, 972 Tyrosine, 300, 915, 1056t, 1057, 1186 pKa value of, 1061t U UDP-galactose, 1205 UDP-glucose, 1205 Ultraviolet (UV) light, 612, 612f, 632 skin cancer and, 1286–1287 sunscreens and, 632–633 vitamin D formation and, 1288 Ultraviolet/visible (UV/Vis) spectroscopy, 596, 631, 631–639, 632f Beer-Lambert law and, 633 effect of conjugation on lmax and, 634f, 634t, 634–635 uses of, 637–639, 637f–639f visible spectrum and color and, 645–647, 646t Undecane, physical properties of, 91t Unimolecular reaction, 417 Unsaturated fatty acid, 752 Unsaturated hydrocarbon, 191 physical properties of, 305, 305t Unsymmetrical ether, 105 Upfield, 654 Uracil, 1008, 1208, 1226 Uranus, blue color of, 28 Urea, 726, 761 Urethane, 1257 Uric acid, Dalmations’ excretion of, 761–762 Uridine, 1209 Urobilinogen, 1009 UV (ultraviolet) light, 612, 612f, 632 skin cancer and, 1286–1287 sunscreens and, 632–633 vitamin D formation and, 1288 UV/Vis (ultraviolet/visible) spectroscopy, 596, 631, 631–639, 632f Beer-Lambert law and, 633 effect of conjugation on lmax and, 634f, 634t, 634–635 uses of, 637–639, 637f–639f visible spectrum and color and, 645–647, 646t V Valence electrons, Valence-shell electron-pair repulsion (VSEPR) model, 27 Valeric acid, 722 Valine, 1054t, 1221 N-protected, 1078 pKa value of, 1061t Valium (diazepam), 817 Van der Waals forces, 114 boiling points and, 113–114, 114f Vanillin, 790 Vinylic halide, 542 Vasopressin, 1075 Venom, of snakes, 754 Vernolepin, 836 Vibrations bending, 614, 614f, 614–615 stretching, 614, 614f, 614–615 uploaded by [stormrg] Periodic Table of the Elements Main groups 1Aa 1 H Main groups B 4A 14 C 5A 15 N 10.811 12.0107 14.0067 13 Al 14 Si 15 P 1.00794 2A 3A 13 Li Be 6.941 9.012182 11 Na 12 Mg 22.989770 24.3050 19 K Transition metals 8B 27 Co 20 Ca 3B 21 Sc 4B 22 Ti 5B 23 V 39.0983 40.078 44.955910 47.867 50.9415 37 Rb 38 Sr 39 Y 40 Zr 41 Nb 42 Mo 43 Tc 44 Ru 45 Rh 46 Pd 85.4678 87.62 88.90585 91.224 92.90638 95.94 [98] 101.07 102.90550 55 Cs 56 Ba 71 Lu 72 Hf 73 Ta 74 W 75 Re 76 Os 77 Ir 132.90545 137.327 174.967 178.49 180.9479 183.84 186.207 190.23 192.217 104 Rf 105 Db 106 Sg 107 Bh 108 Hs 109 Mt 110 Ds [261.11] [262.11] [266.12] [264.12] [269.13] [268.14] 57 *La 58 Ce 59 Pr 60 Nd 61 Pm 144.24 92 U 87 Fr 88 Ra 103 Lr [223.02] [226.03] [262.11] *Lanthanide series 138.9055 †Actinide series 89 †Ac [227.03] a The 6B 24 Cr 26 Fe 91 Pa 1B 11 29 Cu 2B 12 30 Zn 63.546 47 Ag 106.42 78 Pt 10 28 Ni 7A 17 4.002602 O F 10 Ne 15.9994 18.998403 20.1797 16 S 17 Cl 18 Ar 32.065 35.453 39.948 32 Ge 33 As 34 Se 35 Br 36 Kr 65.39 69.723 72.64 74.92160 78.96 79.904 83.80 48 Cd 49 In 50 Sn 51 Sb 52 Te 53 I 54 Xe 107.8682 112.411 114.818 118.710 121.760 127.60 79 Au 80 Hg 81 Tl 82 Pb 83 Bi 84 Po 85 At 86 Rn 200.59 204.3833 207.2 208.98038 [208.98] [209.99] [222.02] 111 Rg 112 Cn 113 114 Fl 115 116 Lv 117 118 [271.15] [272.15] [277] [284] [289] [288] [293] [293] [294] 62 Sm 63 Eu 64 Gd 65 Tb 66 Dy 67 Ho 68 Er 69 Tm 70 Yb [145] 150.36 151.964 157.25 158.92534 162.50 93 Np 94 Pu 95 Am 96 Cm 97 Bk 98 Cf [244.06] [243.06] [247.07] [247.07] [251.08] 232.0381 231.03588 238.02891 [237.05] 58.933200 58.6934 195.078 196.96655 26.981538 28.0855 30.973761 6A 16 31 Ga 51.9961 54.938049 55.845 140.116 140.90765 90 Th 7B 25 Mn 8A 18 He 126.90447 131.293 164.93032 167.259 168.93421 173.04 99 Es 100 Fm 101 Md 102 No [252.08] [257.10] [258.10] [259.10] labels on top (1A, 2A, etc.) are common American usage The labels below these (1, 2, etc.) are those recommended by the International Union of Pure and Applied Chemistry The names for elements 113, 115, 117, and 118 have not yet been decided Atomic weights in brackets are the masses of the longest-lived or most important isotope of radioactive elements Further information is available at http://www.shef.ac.uk/chemistry/web-elements/ Common Functional Groups Alkane RCH3 Alkene C Aniline NH2 Benzene C C Phenol CH2 OH terminal internal O Alkyne RC CR RC CH C Carboxylic acid R terminal internal N Pyridine OH O Nitrile RC Ether R N O R R O C Acid anhydride Epoxide R Cl O O N H Pyrrole C Acyl chloride C R O O Furan R R O Thiol Sulfide RCH2 SH R R S C Ester R O Thioester Disulfide R S S Thiophene OR S O C R SR C R Sulfonium salt R + S C Amide R X R Aldehyde N+ R X− primary R CH2 X tertiary R R CH X R CH2 OH C R CH R OH R C R R R Amine R NH2 X R R R R secondary R R NH R N R O O O NR2 R P O O− Ad O Acyl adenylate (Ad = adenosyl) C R X = F, Cl, Br, or I Alcohol H O Ketone R C C R R Alkyl halide NHR O R Quaternary ammonium salt NH2 R − P O− O− Acyl phosphate O R O OH Approximate pKa Values See Appendix I for more detailed information O +OH protonated carbonyl groups a-carbon (aldehyde) C R protonated alcohols + ROH H protonated water + HOH H ~20 O a-carbon (ketone) C R RCH H O C R H H