Organic chemistry structure and function 6th edition by peter 2

THIRTEEN C H A P T E R Alkynes The Carbon – Carbon Triple Bond S  N O  O A lkynes are hydrocarbons that contain carbon – carbon triple bonds It should not come as a surprise that their characteristics resemble the properties and behavior of alkenes, their double-bonded cousins In this chapter we shall see that, like alkenes, alkynes find numerous uses in a variety of modern settings For example, the polymer derived from the parent compound, ethyne (HC q CH), can be fashioned into electrically conductive sheets usable in lightweight, all-polymer batteries Ethyne is also a substance with a relatively high energy content, a property that is exploited in oxyacetylene torches A variety of alkynes, both naturally occurring and synthetic, have found use in medicine for their antibacterial, antiparasitic, and antifungal activities OCq CO Alkyne triple bond Because the O C q C O functional group contains two p linkages (which are mutually perpendicular; recall Figure 1-21), its reactivity is much like that of the double bond For example, like alkenes, alkynes are electron rich and subject to attack by electrophiles Many of the alkenes that serve as monomers for the production of polymeric fabrics, elastics, and plastics are prepared by electrophilic addition reactions to ethyne and other alkynes Alkynes can be prepared by elimination reactions similar to those used to generate alkenes, and they are likewise most stable when the multiple bond is internal rather than terminal A further, and useful, feature is that the alkynyl hydrogen is much more acidic than its alkenyl or alkyl counterpart, a property that permits easy deprotonation by strong bases The resulting alkynyl anions are valuable nucleophilic reagents in synthesis We begin with discussions of the naming, structural characteristics, and spectroscopy of the alkynes Subsequent sections introduce methods for the synthesis of compounds in this class and the typical reactions they undergo We end with an overview of the extensive industrial uses and physiological characteristics of alkynes Scanning tunneling microscopy (STM) is an indirect method for imaging individual atoms and molecules on a solid surface The dialkyne whose structure is shown above glows brightly in the top STM image because it is in a conformation that is highly electrically conductive In contrast, in the bottom image a change in molecular shape has “turned off” its conductivity, and it goes “dark” as a result Such molecules are prototypes for “molecular switches,” which promise to revolutionize the fields of electronic components and computers in the 21st century Chapter 13 Common Names for Alkynes HC q CH Alkynes 13-1 Naming the Alkynes A carbon–carbon triple bond is the functional group characteristic of the alkynes The general formula for the alkynes is CnH2n22, the same as that for the cycloalkenes The common names for many alkynes are still in use, including acetylene, the common name of the smallest alkyne, C2H2 Other alkynes are treated as its derivatives—for example, the alkylacetylenes The IUPAC rules for naming alkenes (Section 11-1) also apply to alkynes, the ending -yne replacing -ene A number indicates the position of the triple bond in the main chain HC q CH CH3C q CCH3 CH3C q CCHCH2CH3 CH3 3A CH3CC q CH Ethyne 2-Butyne 4-Bromo-2-hexyne 3,3-Dimethyl-1-butyne (An internal alkyne) (A terminal alkyne) Br Acetylene CH3C q CCH3 Dimethylacetylene A4 A CH3 Alkynes having the general structure RC q CH are terminal, whereas those with the structure of RC q CR9 are internal Substituents bearing a triple bond are alkynyl groups Thus, the substituent – C q CH is named ethynyl; its homolog – CH2C q CH is 2-propynyl (propargyl) Like alkanes and alkenes, alkynes can be depicted in straight-line notation [ ð CH3CH2CH2C q CH trans-1,2-Diethynylcyclohexane Propylacetylene CH2C q CH 2-Propynylcyclobutane (Propargylcyclobutane) HCq CCH2OH 2-Propyn-1-ol (Propargyl alcohol) In IUPAC nomenclature, a hydrocarbon containing both double and triple bonds is called an alkenyne The chain is numbered starting from the end closest to either of the functional groups When a double bond and a triple bond are at equidistant positions from either terminus, the double bond is given the lower number Alkynes incorporating the hydroxy function are named alkynols Note the omission of the final e of -ene in -enyne and of -yne in -ynol The OH group takes precedence over both double and triple bonds in the numbering of a chain OH CH3CH2CH P CHC q CH 5 CH2 P CHCH2C q CH 3-Hexen-1-yne 1-Penten-4-yne 5-Hexyn-2-ol (Not 3-hexen-5-yne) (Not 4-penten-1-yne) (Not 1-hexyn-5-ol) Exercise 13-1 Give the IUPAC names for (a) all the alkynes of composition C6H10; H3C (b) C G 568 CG C q CH H ( CH PCH2 (c) all butynols Remember to include and designate stereoisomers 13-2 Properties and Bonding in the Alkynes The nature of the triple bond helps explain the physical and chemical properties of the alkynes In molecular-orbital terms, we shall see that the carbons are sp hybridized, and the four singly filled p orbitals form two perpendicular p bonds 13-2 Properties and Bonding in the Alkynes Chapter 13 569 Alkynes are relatively nonpolar Alkynes have boiling points very similar to those of the corresponding alkenes and alkanes Ethyne is unusual in that it has no boiling point at atmospheric pressure; rather, it sublimes at 2848C Propyne (b.p 223.28C) and 1-butyne (b.p 8.18C) are gases, whereas 2-butyne is barely a liquid (b.p 278C) at room temperature The medium-sized alkynes are distillable liquids Care must be taken in the handling of alkynes: They polymerize very easily — frequently with violence Ethyne explodes under pressure but can be shipped in pressurized gas cylinders that contain acetone and a porous filler such as pumice as stabilizers Dissociation Energies of C–C Bonds HC q CH Ethyne is linear and has strong, short bonds DHЊ ϭ 229 kcal molϪ1 (958 kJ molϪ1) In ethyne, the two carbons are sp hybridized (Figure 13-1A) One of the hybrid orbitals on each carbon overlaps with hydrogen, and a s bond between the two carbon atoms results from mutual overlap of the remaining sp hybrids The two perpendicular p orbitals on each carbon contain one electron each These two sets overlap to form two perpendicular p bonds (Figure 13-1B) Because p bonds are diffuse, the distribution of electrons in the triple bond resembles a cylindrical cloud (Figure 13-1C) As a consequence of hybridization and the two p interactions, the strength of the triple bond is about 229 kcal mol21, considerably stronger than either the carbon – carbon double or single bonds (margin) As with alkenes, however, the alkyne p bonds are much weaker than the s component of the triple bond, a feature that gives rise to much of its chemical reactivity The C – H bond-dissociation energy of terminal alkynes is also substantial: 131 kcal mol21 (548 kJ mol21) π bond p orbital H2C P CH2 DHЊ ϭ 173 kcal molϪ1 (724 kJ molϪ1) H3C O CH3 DHЊ ϭ 90 kcal molϪ1 (377 kJ molϪ1) π electron cloud sp orbital H H C C C H C C H C sp orbital π bond p orbital A σ bond B Figure 13-1 (A) Orbital picture of sp-hybridized carbon, showing the two perpendicular p orbitals (B) The triple bond in ethyne: The orbitals of two sp-hybridized CH fragments overlap to create a s bond and two p bonds (C) The two p bonds produce a cylindrical electron cloud around the molecular axis of ethyne (D) The electrostatic potential map reveals the (red) belt of high electron density around the central part of the molecular axis Because both carbon atoms in ethyne are sp hybridized, its structure is linear (Figure 13-2) The carbon – carbon bond length is 1.20 Å, shorter than that of a double bond (1.33 Å, Figure 11-1) The carbon–hydrogen bond also is short, again because of the relatively large degree of s character in the sp hybrids used for bonding to hydrogen The electrons in these orbitals (and in the bonds that they form by overlapping with other orbitals) reside relatively close to the nucleus and produce shorter (and stronger) bonds Alkynes are high-energy compounds The alkyne triple bond is characterized by a concentration of four p electrons in a relatively small volume of space The resulting electron – electron repulsion contributes to the relative weakness of the two p bonds and to a very high energy content of the alkyne molecule itself Because of this property, alkynes often react with the release of considerable amounts of energy In addition to being prone to explosive decomposition, ethyne has a heat of combustion of 311 kcal mol21 As shown in the equation for ethyne combustion on the next page, this energy is distributed among only three product molecules, one of water and two D 1.203 A؇ HO C q C O H 1.061 A؇ 180؇ Linear ethyne Figure 13-2 Molecular structure of ethyne 570 Alkynes Chapter 13 of CO2, causing each to be heated to extremely high temperatures (.25008C), sufficient for use in welding torches Combustion of Ethyne HC q CH ϩ CO2 2.5 O2 ϩ ΔH° ϭ Ϫ311 kcal molϪ1 (Ϫ1301 kJ molϪ1) H2O As we found in our discussion of alkene stabilities (Section 11-5), heats of hydrogenation also provide convenient measures of the relative stabilities of alkyne isomers In the presence of catalytic amounts of platinum or palladium on charcoal, the two isomers of butyne hydrogenate by addition of two molar equivalents of H2 to produce butane Just as we discovered in the case of alkenes, hydrogenation of the internal alkyne isomer releases less energy, allowing us to conclude that 2-butyne is the more stable of the two Hyperconjugation is the reason for the greater relative stability of internal compared with terminal alkynes The high temperatures required for welding are attained by combustion of ethyne (acetylene) CH3CH2C q CH ϩ H2 CH3C q CCH3 ϩ H2 Catalyst Catalyst CH3CH2CH2CH3 ΔH° ϭ Ϫ69.9 kcal molϪ1 (Ϫ292.5 kJ molϪ1) CH3CH2CH2CH3 ΔH° ϭ Ϫ65.1 kcal molϪ1 (Ϫ272.4 kJ molϪ1) Exercise 13-2 Are the heats of hydrogenation of the butynes consistent with the notion that alkynes are highenergy compounds? Explain (Hint: Compare these values with the heats of hydrogenation of alkene double bonds.) Terminal alkynes are remarkably acidic Relative Stabilities of the Alkynes In Section 2-2 you learned that the strength of an acid, H – A, increases with increasing electronegativity, or electron-attracting capability, of atom A Is the electronegativity of an atom the same in all structural environments? The answer is no: Electronegativity varies with hybridization Electrons in s orbitals are more strongly attracted to an atomic nucleus than are electrons in p orbitals As a consequence, an atom with hybrid orbitals high in s character (e.g., sp, with 50% s and 50% p character) will be slightly more electronegative than the same atom with hybrid orbitals with less s character (sp3, 25% s and 75% p character) This effect is indicated below in the electrostatic potential maps of ethane, ethene, and ethyne The increasingly positive polarization of the hydrogen atoms is reflected in their increasingly blue shadings, whereas the carbon atoms become more electron rich (red) along the series The relatively high s character in the carbon hybrid orbitals of terminal alkynes makes them more acidic than alkanes and alkenes The pKa of ethyne, for example, is 25, remarkably low compared with that of ethene and ethane RC q CH , RC q CR9 More stable Deprotonation of 1-Alkynes RC q C O H Ϫ ϩ ðB RC q CðϪ ϩ HB Relative Acidities of Alkanes, Alkenes, and Alkynes H3C Hybridization: pKa: CH3 Ͻ H2C CH2 sp3 sp2 50 44 Increasing acidity Ͻ HC CH sp 25 13-3 Spectroscopy of the Alkynes Chapter 13 This property is useful, because strong bases such as sodium amide in liquid ammonia, alkyllithiums, and Grignard reagents can deprotonate terminal alkynes to the corresponding alkynyl anions These species react as bases and nucleophiles, much like other carbanions (Section 13-5) Deprotonation of a Terminal Alkyne pKa Ϸ 50 pKa Ϸ 25 CH3CH2C q CH (Stronger acid) ϩ CH3CH2CH2CH2Li (CH3CH2)2O H A CH3CH2C q CLi ϩ CH3CH2CH2CH2 (Stronger base) (Weaker base) (Weaker acid) Exercise 13-3 Working with the Concepts: Deprotonation of Alkynes What is the equilibrium constant, Keq, for the acid-base reaction shown above? Does its value explain why the reaction is written with only a forward arrow, suggesting that it is “irreversible”? Strategy Recall how pKa values relate to acid dissociation constants Use this information to determine the value for Keq Solution • The pKa is the negative logarithm of the acid dissociation constant Dissociation of the alkyne therefore has a Ka < 10225, very unfavorable, at least in comparison with the more familiar acids However, butyllithium is the conjugate base of butane, which has a Ka < 10250 As an acid, butane is 25 orders of magnitude weaker than is the terminal alkyne Thus, butyllithium is that much stronger a base compared with the alkynyl anion • The Keq for the reaction is found by dividing the Ka for the acid on the left by the Ka for the acid on the right: 10225y10250 1025 The reaction is very favorable in the forward direction, so much so that for all practical purposes it may be considered to be irreversible (Caution: Use common sense to avoid major errors in solving acid-base problems, such as deciding that the equilibrium lies the wrong direction Use this hint: The favored direction for an acid-base reaction converts the stronger acid/stronger base pair into the weaker acid/weaker base pair.) Exercise 13-4 Try It Yourself Strong bases other than those mentioned here for the deprotonation of alkynes were introduced earlier Two examples are potassium tert-butoxide and lithium diisopropylamide (LDA) Would either (or both) of these compounds be suitable for making ethynyl anion from ethyne? Explain, in terms of their pKa values In Summary The characteristic hybridization scheme for the triple bond of an alkyne controls its physical and electronic features It is responsible for strong bonds, the linear structure, and the relatively acidic alkynyl hydrogen In addition, alkynes are highly energetic compounds Internal isomers are more stable than terminal ones, as shown by the relative heats of hydrogenation 13-3 Spectroscopy of the Alkynes Alkenyl hydrogens (and carbons) are deshielded and give rise to relatively low-field NMR signals compared with those in saturated alkanes (Section 11-4) In contrast, alkynyl hydrogens have chemical shifts at relatively high field, much closer to those in alkanes Similarly, the sp-hybridized carbons absorb in a range between that recorded for alkenes and alkanes Alkynes, especially terminal ones, are also readily identified by IR spectroscopy Finally, mass spectrometry can be a useful tool for identification and structure elucidation of alkynes 571 572 Alkynes Chapter 13 Figure 13-3 300-MHz 1H NMR spectrum of 3,3-dimethyl-1-butyne showing the high-field position (d 2.06 ppm) of the signal due to the alkynyl hydrogen 1H NMR 9H CH3 CH3CC CH (CH3)4Si CH3 1H ppm (δ ) The NMR absorptions of alkyne hydrogens show a characteristic shielding Unlike alkenyl hydrogens, which are deshielded and give 1H NMR signals at d 4.6–5.7 ppm, protons bound to sp-hybridized carbon atoms are found at d 1.7 – 3.1 ppm (Table 10-2) For example, in the NMR spectrum of 3,3-dimethyl-1-butyne, the alkynyl hydrogen resonates at d 2.06 ppm (Figure 13-3) Why is the terminal alkyne hydrogen so shielded? Like the p electrons of an alkene, those in the triple bond enter into a circular motion when an alkyne is subjected to an external magnetic field (Figure 13-4) However, the cylindrical distribution of these electrons (Figure 13-1C) now allows the major direction of this motion to be perpendicular to Local magnetic field hlocal Opposes H0 in this region of space hlocal Local magnetic field R H H hlocal C hlocal C H Strengthens H0 in this region of space C hlocal hlocal C H H π electron movement A hlocal External field, H0 Opposes H0 in this region of space B hlocal π electron movement External field, H0 Figure 13-4 Electron circulation in the presence of an external magnetic field generates local magnetic fields that cause the characteristic chemical shifts of alkenyl and alkynyl hydrogens (A) Alkenyl hydrogens are located in a region of space where hlocal reinforces H0 Therefore, these protons are relatively deshielded (B) Electron circulation in an alkyne generates a local field that opposes H0 in the vicinity of the alkynyl hydrogen, thus causing shielding 13-3 Spectroscopy of the Alkynes Chapter 13 573 that in alkenes and to generate a local magnetic field that opposes H0 in the vicinity of the alkyne hydrogen The result is a strong shielding effect that cancels the deshielding tendency of the electron-withdrawing sp-hybridized carbon and gives rise to a relatively high-field chemical shift The triple bond transmits spin – spin coupling The alkyne functional group transmits coupling so well that the terminal hydrogen is split by the hydrogens across the triple bond, even though it is separated from them by three carbons This result is an example of long-range coupling The coupling constants are small and range from about to Hz Figure 13-5 shows the NMR spectrum of 1-pentyne The alkynyl hydrogen signal at d 1.94 ppm is a triplet (J 2.5 Hz) because of coupling to the two equivalent hydrogens at C3, which appear at d 2.16 ppm The latter, in turn, give rise to a doublet of triplets, representing coupling to the two hydrogens at C4 (J Hz) as well as that at C1 (J 2.5 Hz) CH 1.1 1.0 0.9 ppm 1.6 1.5 ppm 3H 2.0 1.9 ppm 2H 2.2 2.1 ppm J ‫ ؍‬2–4 Hz H A O C O C q COH A Figure 13-5 300-MHz 1H NMR spectrum of 1-pentyne showing coupling between the alkynyl (green) and propargylic (blue) hydrogens 1H NMR CH3CH2CH2C Long-Range Coupling in Alkynes 1H 2H (CH3)4Si ppm (δ ) Exercise 13-5 Working with the Concepts: Predicting an NMR Spectrum Predict the first-order splitting pattern in the 1H NMR spectrum of 3-methyl-1-butyne Strategy First, write out the structure Then identify groups of hydrogens within coupling distance of each other, both neighboring and long range Finally, use information regarding approximate values of coupling constants (and the N 1 rule) to generate expected splitting patterns Solution • The structure of the molecule is CH3 A CH3 O CHO C q CH • The two methyl groups are equivalent and give one signal that is split into a doublet by the single hydrogen atom at C3 (N 1 lines) The coupling constant (J value) for this splitting is the typical – Hz found in saturated systems (Section 10-7) 574 Chapter 13 Alkynes • The alkynyl O CqCH hydrogen at C1 experiences long-range coupling to the same H at C3, appearing also as a doublet, but J is smaller, about Hz • Finally, the signal for the hydrogen at C3 displays a more complex pattern The – 8-Hz splitting by the six hydrogens of the methyl groups gives a septet (N 1 lines) Each line of this septet is further split by the additional 3-Hz coupling to the alkynyl H As the actual spectrum below shows, the outermost lines of this signal, a doublet of septets, are so small that they are barely visible (see Tables 10-4 and 10-5) (Caution: When interpreting 1H NMR spectra, be aware of the very low intensity of the outer lines in highly split signals In fact, it is prudent to assume that such signals may consist of more lines than are readily visible.) 1H NMR 6H H C H3C C CH 1.2 1.1 CH3 ppm 2.1 2.0 1.9 ppm 1H 2.6 2.5 ppm (CH3)4Si 1H ppm (δ ) Exercise 13-6 Try It Yourself Predict the first-order splitting pattern in the 1H NMR spectrum of 2-pentyne The 13C NMR chemical shifts of alkyne carbons are distinct from those of the alkanes and alkenes Carbon-13 NMR spectroscopy also is useful in deducing the structure of alkynes For example, the triple-bonded carbons in alkyl-substituted alkynes resonate in the range of d 65–95 ppm, quite separate from the chemical shifts of analogous alkane (d 5 – 45 ppm) and alkene (d 100 – 150 ppm) carbon atoms (Table 10-6) Typical Alkyne 13C NMR Chemical Shifts HC q CH ␦ ‫ ؍‬71.9 HC q CCH2CH2CH2CH3 68.6 84.0 18.6 31.1 22.4 14.1 CH3CH2C q CCH2CH3 81.1 15.6 13.2 ppm Terminal alkynes give rise to two characteristic infrared absorptions Infrared spectroscopy is helpful in identifying terminal alkynes Characteristic stretching bands appear for the alkynyl hydrogen at 3260 – 3330 cm21 and for the CqC triple bond at 2100 – 2260 cm21 There is also a diagnostic n|Csp–H bending absorption at 640 cm21 13-3 Spectroscopy of the Alkynes Chapter 13 575 Figure 13-6 IR spectrum of 1,7-octadiyne: n| Csp2H stretch 3300 cm21; n| CqC stretch 2120 cm21; n| Csp2H bend 640 cm21 Transmittance (%) 100 2120 H H C C H C C C H C H 3300 C C H H IR 4000 3500 H 640 H H 3000 2500 2000 1500 1000 600 cm−1 Wavenumber (Figure 13-6) Such data are especially useful when 1H NMR spectra are complex and difficult to interpret However, the band for the CqC stretching vibration in internal alkynes is often weak, like that for internal alkenes (Section 11-8), thus reducing the value of IR spectroscopy for characterizing these systems Mass spectral fragmentation of alkynes gives resonance-stabilized cations The mass spectra of alkynes, like those of alkenes, frequently show prominent molecular ions Thus high-resolution measurements can reveal the molecular formula and therefore the presence of two degrees of unsaturation derived from the presence of the triple bond In addition, fragmentation at the carbon once removed from the triple bond is observed, giving resonance-stabilized cations For example, the mass spectrum of 3-heptyne (Figure 13-7) shows an intense molecular ion peak at myz 96 and loss of both methyl CH3CH2C Relative abundance 67 (M − CH2CH3) 81 (M − CH3) MS 100 CCH2CH2CH3 M • 96 50 0 20 40 60 m/z 80 100 Figure 13-7 Mass spectrum of 3-heptyne, showing M1 at myz 96 and important fragments at myz 67 and 81 arising from cleavage of the C1 – C2 and C5 – C6 bonds 576 Chapter 13 Alkynes (cleavage a) and ethyl (cleavage b) fragments to give two different stabilized cations, with myz 81 and 67 (base peak), respectively: Fragmentation of an Alkyne in the Mass Spectrometer ϩ CH2 O C O O C O CH2 O CH2CH3 a a b CH3 O CH2 O C q C O CH2 O CH2CH3 ϩj ϩ ϪCH3j m/z ‫ ؍‬96 ϪC2H5j CH2 O C O C O CH2 O CH2CH3 m/z ‫ ؍‬81 b ϩ CH3 O CH2 O C O O C O CH2 ϩ CH3 O CH2 O C O C O CH2 m/z ‫ ؍‬67 Unfortunately, under the high energy conditions of the mass spectrometry experiment, migration of the triple bond can occur Thus this fragmentation is not typically very useful for identifying the location of the triple bond in a longer-chain alkyne In Summary The cylindrical p cloud around the carbon – carbon triple bond induces local magnetic fields that lead to NMR chemical shifts for alkynyl hydrogens at higher fields than those of alkenyl protons Long-range coupling is observed through the C q C linkage Infrared spectroscopy provides a useful complement to NMR data, displaying characteristic bands for the C q C and qC – H bonds of terminal alkynes In the mass spectrometer, alkynes fragment to give resonance-stabilized cations 13-4 Preparation of Alkynes by Double Elimination The two basic methods used to prepare alkynes are double elimination from 1,2-dihaloalkanes and alkylation of alkynyl anions This section deals with the first method, which provides a synthetic route to alkynes from alkenes; Section 13-5 addresses the second, which converts terminal alkynes into more complex, internal ones Alkynes are prepared from dihaloalkanes by elimination As discussed in Section 11-6, alkenes can be prepared by E2 reactions of haloalkanes Application of this principle to alkyne synthesis suggests that treatment of vicinal dihaloalkanes with two equivalents of strong base should result in double elimination to furnish a triple bond Double Elimination from Dihaloalkanes to Give Alkynes X X C C H H Base (2 equivalents) Ϫ2 HX Cq C Vicinal dihaloalkane Indeed, addition of 1,2-dibromohexane (prepared by bromination of 1-hexene, Section 12-5) to sodium amide in liquid ammonia followed by evaporation of solvent and aqueous work-up gives 1-hexyne I-14 Index Lithium aluminum hydride (cont.) oxacyclopropane and, 361 protic solvents and, 301 Lithium dibutylcuprate, 311 Lithium diisopropylamide, 982 Lithium dimethylcuprate, 850 Lithium organocuprate, 850 Local magnetic fields, 395–396 London, Fritz, 77n London forces, 77–79, 78 Lone electron pairs, 14, 35, 35 Lone pairs, 14 Long-chain carboxylates, 900–901 Long-range coupling, 455 Loschmidt, Josef, 673 Low field, NMR spectroscopy and, 396 Low-density lipoproteins (LDL), 903 Low-density polyethylene, 546 Lowry, Thomas Martin, 58n Lysergic acid, 906 Lysine, 1215–1216 M MacDiarmid, Alan G., 630n Magnetic field strength, resonance frequency and, 392 Magnetic resonance imaging (MRI), 404 Main chains, 1224 Major resonance contributors, 21 Malondialdehyde, 1055 Malonic ester synthesis, 1093 Malonyl CoA, 1086 Maltose, 1144 –1145 Manganese dioxide, 786, 1025 Mannaric acid, 1130 Mannich, Carl U F., 994n Mannich base, 994 Mannich reaction, 994 –996 Mannose, 1130 Mansfield, Sir Peter, 404n Marijuana (cannabis), 370 Markovnikov, Vladimir V., 514n Markovnikov hydration, 525, 786 Markovnikov rule, 514 –515 Masked acyl anions, 1098, 1098–1099 Mass spectra, 473 Mass spectral fragmentation, 475 aldehydes and ketones, 782–784 alkene fragments and, 481 alkynes, 575, 575–576 carboxylic acids, 878 functional group identification and, 480 highly substituted center and, 478–480 organic molecules and, 478–481 patterns, 475 Mass spectrometry, 473–477 aldehydes and ketones, 782–784 alkynes, 575, 575–576 amines, 979–980 base peak and, 475 benzene and, 683, 684 carboxylic acids and, 875–879 detecting performance-enhancing drugs using, 476 distinguishing ions by mass and, 473–474 fragmentation patterns of organic molecules and, 478–481 high resolution, 474 isotopes and, 476–477 molecular formulas and, 474 molecular ion fragmentation and, 475 parent ion and, 473 security technology and, 475 spectrometer diagram, 473 Maxam-Gilbert procedure, 1249 McLafferty, Fred W., 784n McLafferty rearrangement, 783, 784 Mechanisms, 95 Mechanistic grounds, predicting reaction outcomes on, 310–312 Medicinal chemistry origins, 1062–1063 Mercapto group, 365 Mercuration, 525–528 Mercuric ion-catalyzed hydration, 584 –585 Mercury cells, 117 Meridia, 975 Merrifield, Robert B., 1238n Merrifield solid-phase peptide synthesis, 1238–1239 Mescaline, 974 Meso compounds, 191–193 cyclic compounds and, 193 identically substituted stereocenters and, 192 with multiple stereocenters, 192 Messenger RNA synthesis, 1246, 1246–1248 Meta attack on benzenamine, 739 on benzoic acid, 742 on halobenzene, 743 on methylbenzene, 735–736 on (trifluoromethyl)benzene, 737 Meta directing, 737, 744t Meta positions, 732 Meta substitution, 737 Metal-catalyzed alkene metathesis, 548–549 Metal-catalyzed polymerization, 546 Metallation, 306 Methanamine, 973, 973, 986 Methane chlorination of, 104 –109 fragmentation of, 475 mass spectrum of, 476 radical halogenations of, 109–111, 109t Methanol acidity in comparison to acetic acid and, 62 hydrogen bonding in, 291, 291 hydrophobic and hydrophilic parts of, 291, 291 making methoxide from, 334 oxidation of, 882 as precursor of gasoline, 367 spin-spin splitting in, 421, 421 synthesis gas and, 295 Methoxide, 334 Methoxide ion, 293, 294 Methoxybenzene, 675 Methoxybenzoic acid, 1042 Methoxymethane, 37, 37–38 Methoxynaphthalene, 756 Methyl alcohol, 289 Methyl benzoate, 940 Methyl esters, 939 Methyl formate, 940 Methyl group rotation, 400 Methyl isocyanate, 953 Methyl ketones, 1092–1093 Methyl propanoate, 935 Methylamine, 2, 986 Methylammonium bromide, 986 Methylation, 986, 1133 Methylbenzene deprotonation of, 1024 electrophilic bromination of, 735 meta attack on, 735–736 ortho attack on, 735–736 para attack on, 736 Methylbutane, 478, 479 Methyl-1,3-butadiene, 649–650 Methylcyclohexane, 144 –146, 146t, 311 Methylcyclohexanone, 835 Methylene, 531 Methylethanamine, 876 Methylheptanol, 288 Methyllithium, 306 Methylmethanamine, 987 Methylpentanamide, 948 Methylpentanoic acid, 948 Methylpentene, 446 Methylpropanal, 837–839 Methylpropane, 113, 115, 115, 116, 116 Methylpropenamide, 932 Methylpropene, 517, 523 Mevalonic acid, 900, 1087 Micellar effects, 1227 Michael, Arthur, 852n Michael acceptors, 1095 Michael addition, 852–855, 1095–1097 Middle infrared, 468 Migratory aptitude, 808 Mineral acids, 467 Mirror planes, 174 Mirror symmetry in organic molecules, 400, 400 Mirror-image stereoisomerism, 171, 171 Mitochondrial DNA sequencing, 1257 Mixed Claisen condensations, 1084 –1085 Molar absorptivity, 652 Molar extinction coefficient, 652 Molecular alteration, 313 Molecular formulas, mass spectrometry and, 474 Molecular ions, 473, 475 Molecular masses of organic molecules, 474 Molecular orbitals, 28–31, 611, 611–612 Molecular structures, 38–39 acid and base strengths and, 61–64 bond-line formulas and, 36 condensed formulas and, 36 degree of unsaturation and, 482–483, 482t hashed-wedged/solid-wedged line notation, 39, 39 Kekulé structures and, 36 NMR spectroscopy and, 395–400 Molecular symmetry, chemical equivalence tests and, 400 Molina, Mario, 120n Molozonide, 538 Monomers, common polymers and, 544t Monosaccharides, 1119, 1131–1132 Monosubstituted benzenes, 745t Montelucast, 1166t Morphine, 370 Mueller, Paul, 118 Mullis, Kary B., 1258n Multiplets, NMR spectroscopy and, 407–409, 409 Murad, Ferid, 1216n Mutarotation of glucose, 1127 Myoglobin, 1239–1241, 1240 N N 1 rule, 411, 411–412, 417, 417–419, 418 Naphthalene aromaticity and, 691 electrophilic attack, 755–756 electrophilic substitution and, 754 –756 electrostatic potential map, 691 extended pi conjugation in, 690, 691 NMR data for, 691, 692 orbital picture of, 691 spectral properties of, 690–691 Naproxen, 197 Natta, Giulio, 546n Natural pesticides, 1192–1193 Natural products, 152, 370, 430–431 Natural rubber synthesis, 648–649 Natural (2S)-amino acids, 1212t–1213t Newman, Melvin S., 80n Newman projections, 80–82 chloroethane and, 402, 402 Index E2 transition state and, 268 substituted cyclohexane and, 145 Nexium, 1166t Nicotinamide adenine dinucleotide, 298, 1186–1187 Nicotine, 1170–1171 Nicotine patches, 1170 Nitration benzene and, 705–708 methoxynaphthalene and, 756 monosubstituted benzenes and, 745t Nitric acid, 15, 64, 705 Nitric oxide, 1216 Nitrile group hybridization and structure of, 954, 954t hydrolysis to carboxylic acids, 884 –885, 955 ketone synthesis from, 956 orbital picture of, 954 organometallic reagents attack and ketones, 955–956 reduction by hydride reagents, 956–957 Nitroarenes, explosive, 741 Nitrobenzenamine, 753 Nitrobenzene, 734 Nitrogen, modified sugars containing, 1151 Nitrogen bases, 1241, 1241 Nitrogen dioxide, 119 Nitrogen elimination in WolffKishner reduction, 803 Nitrogen heterocycles in nature, 1191–1194 Nitroglycerine, 369 Nitronium ion, electrophilic attack by, 705 Nitrosamines, 998 Nitrosation, 996–1003 Nitrosyl cation, 15, 21, 996, 997 Nitrous acid, 997 N-methylamide, 998 N-methyl-N-nitrosamides, 1002–1003 N-nitrosamines, 997 N-nitrosodialkanamines, cancer and, 998 Nodes, 24 Nonanamide, 951 Nonanol, 940 Nonaromatic heterocycles, 1168–1171 Nonconjugated alkenes, hydrogenation heat and, 619 Nonconjugated dienes, 618–619, 622 Nonconjugated isomers, 617 Nonequivalence of diastereotopic hydrogens, 418–419 Nonequivalent neighbors, 417, 417–419, 418 Nonequivalent resonance forms, 20–21 Non-first-order spectra, 415, 415–416, 416 Norbornane, 150 Norvasc, 1166t Noyori, Ryoji, 197 N-Phenylacetamide, 739 N-terminal amino acid, 1223 Nuclear magnetic resonance (NMR) spectroscopy See also Carbon-13 nuclear magnetic resonance; Mass spectroscopy aldehydes and ketones, 779–784 alkenes and, 453–459 alkynes and, 571–576 amine group and, 977–981 analyzing molecular structure and, 395–400 benzene derivatives and, 683–686 carbon-13 nuclear magnetic resonance, 422–432 carboxylic acid derivatives and, 926–929 carboxylic acids and, 875–878 chemical equivalence tests and, 400–405 chemical shifts and peak and, 396–397, 405–407 coupling constant and, 409 deshielding and, 396, 399, 399t differentiating nuclei of the same element and, 392–394, 394 doublets and, 407–409, 409 FT technique and, 427–430 functional groups and, 397–399 high field and, 396 hydrogen nuclear magnetic resonance, 390–395 integration and, 405–407, 406 local magnetic fields and, 395–396 low field and, 396 medical diagnosis and, 404 multiplets and, 407–408 nitriles and, 954 nonequivalent neighboring hydrogens and, 407–414 nuclei responsive to, 392t, 393 pyridine and, 1180–1181 quartets and, 408 recording an NMR spectrum, 393 shielded nuclei and, 395–396 signal position and, 395, 395–396 spectroscopy defined, 388–390 spectrum recording, 393–394 spin-spin splitting and, 407, 407–414 spin-spin splitting complications, 414 –422 time scale, 401–402, 421–422 triplets and, 408 typical hydrogen chemical shifts, 398t upfield and, 396 Nuclear spins, 390–392 Nucleic acids, 1241–1246 double helix formation and, 1244 –1245, 1245 heterocycles and, 1241–1244 information storage in, 1244 replication and, 1243 Nucleophiles, 65–66 additions, aldehyde and ketones and, 788t alkenyl halides reactivity and, 587 attack on carbonyl carbon, 886 bromonium entrapment by, 521–522 carboxylic acid competing reactions and, 888 haloalkanes reaction with, 273t reactivity of haloalkanes towards, 261, 261t sterically hindered basic, 272–273 strength, SN1 reactions and, 259 strongly basic, 271–272 weak, 270–271 Nucleophilic additionelimination, 935 Nucleophilic additionprotonation, 789 Nucleophilic aromatic substitution, 1030–1041 Nucleophilic atoms, 1099 Nucleophilic attack, 240–243, 254 Nucleophilic carbon, 304 –307 Nucleophilic ring opening of cyclic anhydrides, 935 Nucleophilic ring opening of oxacyclopropane, 360–364 Nucleophilic substitution, 65–66, 218–221 See also SN2 reactions by addition-elimination, 887 alcohol synthesis by, 295–296 allylic halides and, 614 –616 bimolecular substitution and, 224 –225 chloromethane with sodium hydroxide reaction and, 223–224 diversity and, 218–220, 219t electrophilic centers and, 218 leaving groups and, 218 pyridines and, 1185–1186 rate law and, 223 reaction kinetics and, 223–236 simple haloarenes and, 1036 substrates and, 218 Nucleophilic trapping, 621 Nucleophilicity, 233–240 aprotic solvents and, 236–237, 236t basicity and, 234 –235 increasing negative charge and, 233 increasing polarizability and, 237 I-15 periodic table and, 234 reversible substitutions and, 239–240 solvation and, 235–236, 236 sterically hindered nucleophiles and, 238 Nucleosides, 1242, 1243, 1253 Nucleotides, 1241, 1242–1243 Nylon, 1000–1001 O O-acyl isourea, 1236 Observed optical rotation, 175 Octadecenamide, 943 Octadecenoic acid, 901 Octanamine, 951 Octet rule, 7–13 covalent bonds and, 9–10 Lewis structures and, 15–16 periodic table and, 7, polar covalent bonds and, 10–12 pure ionic bonds and, 8–9 valence electron repulsion and, 12–13 Oils, 942 Oil-spills, polymers in clean-up, 545 Olah, George A., 705n Oleic acid, 901 Olestra, 975 Oligomerization, 543 Oligomers, 542 Oligonucleotides, 1250–1251 One-electron reductions, alkynes, 580–582 Open-chain forms of glucose, 1127 Open-shell configurations, 28 Opium, 370 Opsin, 843 Optical activity enantiomeric composition and, 176–177 observed optical rotation, 175 specific rotation, 175–176, 176 stereoisomers and, 174 –177 Optical purity, 176 Optical rotation enantiomeric composition and, 176–177 polarimeters and, 175–176, 176 racemic mixtures and, 176 Optically active, 175 Orbital hybridization, 32 See also Hybrid orbitals Orbital pictures, 228, 228 Organic chemistry functional groups and, 2–3 mechanisms and, –5 reactions and, –5 scope of, 2–5 synthesis and, Organic compounds, carcinogenicity in, 760 Organic esters, 344 Organic light-emitting diodes (OLEDs), 631 I-16 Index Organic molecules characteristics of, constitutional isomers and, 37 elemental analysis and, 37 empirical formulas and, 37 fragmentation patterns and, 478–481 infrared stretching wavenumber ranges of, 469, 470t molecular masses of, 474 molecular structure representations and, 38–39 rotational and mirror symmetry in, 400, 400 structures and formulas of, 37–39 Organocuprates, 850 Organolithium, 850 Organometallic carbonation, 883 Organometallic reagents, 304 –307 1,2- and 1,4-additions to, 850–852 alcohol synthesis and, 307–309 aldehydes and ketones and, 788t attacking acyl halides to give ketones, 933 attacking esters to give ketones, 940 attacking nitriles to give ketones, 955–956 carboxylic acids and, 883 conversion into ketones, 933 deuterium introduction and, 307 hydrolysis and, 306 Orlistat, 975 Ortho and para directing, 735 Ortho attack on benzenamine, 739 on benzoic acid, 742 on halobenzene, 743 on methylbenzene, 735–736 on (trifluoromethyl)benzene, 737 Ortho directors, 744t Ortho positions, 732 Ortho substitution, 735, 738 Osazone, 1132 Osmium tetroxide, 535–537 Out-of-phase antibonding, 29, 29 Ovalicin, 537 Overlap, atomic orbitals, 28–31 Overlap peptides, 1233 Overoxidation, 302–303 Oxa-2-cycloalkanone, 936 Oxacycloalkane, 348 Oxacyclopentane synthesis, 591 Oxacyclopropane acid-catalyzed ring opening, 363–364 formation of, 354, 522, 533 hydride and organometallic reagents and, 360–362 hydrolysis of, 534 hydrolytic kinetic resolution and, 362–363 nucleophilic ring opening and, 360 opening inversion, 361 reactions, 360–364 retrosynthetic analysis and, 361 ring opening by Grignard reagent, 362 ring opening by lithium aluminum hydride, 361 synthesis of, 532–534 Oxaphosphacyclobutane, 806 Oxaphosphetane, 806 Oxidation, 297, 298–299 alcohols and, 316, 785 alkylboranes and, 529–530 peroxycarboxylic acids and, 808 primary alcohols and aldehydes and, 883 Oxidation-reduction processes in nature, 1053–1058 Oxidative chemical tests, 809 Oxidative cleavage, 538–540, 1130–1131 Oxidative damage, 1054 Oxidative decarboxylation, 1137 Oximes, 799–800 Oxonium ions, 336 Oxygen lone electron pairs and alcohols, 294 oxygen debt and lactic acid, 1100 peroxycarboxylic acids and, 533–534 phenols and, 1041–1042 transport by myoglobin and hemoglobin, 1239–1241 Oxymercuration, 525–528 Oxymercuration-demercuration sequence, 525–528 Ozone layer CFC substitutes and, 120 chlorofluorocarbons and, 120 high-energy ultraviolet light and, 119, 119 ozone decrease since 1978, 121 Ozonolysis, 538–540, 786 P 2p orbitals, 25, 26 3p orbitals, 26 p orbitals, benzene ring and, 677–678 Paal, Karl, 1174n Paal-Knorr synthesis, 1174 Paired electrons, 26 Palmitic acid, 901 Para attack on benzenamine, 739 on benzoic acid, 742 on halobenzene, 744 on methylbenzene, 736 on (trifluoromethyl)benzene, 737 Para directors, 744t Para positions, 732 Para substitution, 735, 738 Para-dibromobenzene, 743 Paraldehyde, 794 Parent ion, mass spectrometry and, 473 Parietal cells, 59 Pascal, Blaise, 411n Pascal’s triangle, 411–412, 411t Pasteur, Louis, 190 Pauli, Wolfgang, 26n Pauli exclusion principle, 26 Pauling, Linus, 29n Pd-catalyzed phenol synthesis from haloarenes, 1040–1041 Peak, spectroscopy and, 389 Pedersen, Charles J., 350 Penicillin, 936–947 Penicillinase, 946 Penicillium notatum, 946 Pentanal, 949 Pentane, 77 fragment ions from, 479 infrared spectroscopy and, 470 isomeric, 71 mass spectrum of, 478, 479 Pentanoic acid, 879 Pentanol, 288, 291, 291 Pentanone, 783, 784 Pentanoyl fluoride, 930 Pentene, 447 Pentoses, 1119 Peptic ulcers, 59 Peptide bonds amino acids forming, 1222–1223 formation using carboxy activation, 1236 planarity induced by resonance in, 1223 Peptide hydrolysis, 1228 Peptides, 1222 overlap peptides, 1233 synthesis, 1235–1236 Performance-enhancing drugs, 476 Pericyclic transformations, 640 Periodic acid cleavage, 1130 Periodic acid degradation, 1131 Periodic table, 7, Perkin, William, 1062–1063 Peroxides, 357 Peroxycarboxylic acids epoxidation by, 532–534 oxidation by, 808 oxygen atom delivery to double bonds and, 533–534 Pesticides, natural, 1192–1193 Petroleum as alkane source, 102–103, 102t conversion of, 100–103 greener alternatives to, 944–945 pH, isoelectric, 1215 Phase-transfer catalysis, 1223 Phenanthrene, 592, 757 Phenobarbital, 1184 Phenolic resin, 1046 Phenols acidity of, 1028–1029 alcohol chemistry of, 1041–1043 arenediazonium salts and, 1038–1039 bisphenol A, 1030–1031 derivatives, oxidative damage and, 1054 electrophilic substitution of, 1044 –1047 Friedel-Crafts acylation of, 1044 “green” industrial synthesis, 1041 halogenation of, 1044 as hydroxyarenes, 1027–1028 hydroxymethylation of, 1046 keto and enol forms of, 1027 names and properties of, 1026–1030 nucleophilic aromatic substitution and, 1030–1041 oxygen in, 1041–1042 Pd catalysis and, 1040–1041 protecting oxygen atom in, 752 resveratrol, 1030–1031 retrosynthetic connection to arenes, 1039 Phenoxide ion, 1028, 1047 Phenoxy, 1027 Phenoxy radical, 1051 Phenyl, 676 Phenyl alkanoates, 1042, 1043 Phenylalanine, 1223 Phenylalkanones, 715–716 Phenylethanamine, 974, 981 Phenylhydrazone formation, 1132 Phenylmethanol, 785 Phenylmethoxycarbonyl group, 1235 Phenylmethyl (benzyl) carbon, 1020–1024 Phenylmethyl protection in complex synthesis, 1026 Phenylmethyllithium, 1024 Phenylosazone formation, 1132 Phenyloxonium ions, 1041 Pheromones, 79, 548–550, 936–937 Phosphoglycerides, 942–943 Phospholipids, 942–943 Phosphonium salts, 804 Phosphoric acid, 16 Phosphorus tribromide acyl bromide formation and, 889, 898–899 bromoalkane synthesis and, 345 flame retardant and, 217 Phosphorus trichloride, 16 Phosphorus triiodide iodoalkane synthesis and, 345 Phosphorus betaine, 806 Phosphorus ylides, 804 –807 Photochemical reactions, 640 Photosynthesis, 368, 1138 Pi bonds, 29–30, 30 alkyne reduction and, 299–300 antibonding molecular orbital of, 451 butadiene conjugation and, 619–620 carbocations attack on, 542–543 energy ordering and, 451 in ethene and ethyne, 35, 35, 449–452 nucleophilic character of, 512–516 Index relative strength of, 450 thermal isomerization and, 450–452 Pi electrons, 453–454, 454, 684, 684 Pi systems See also Conjugated Pi systems; Delocalized Pi systems Picric acid, 741 pKa values alcohols and, 292–294, 292t, 294t, 335 aldehydes and ketones and, 828–829, 828 amines and, 981–986t, 983 amino acids and, 1212t–1213t, 1214 –1217 ammonium ions and, 983 benzoic acids and, 881t beta-dicarbonyl compounds and, 1083–1084t carboxylic acids and, 879–882, 881t carboxylic acid derivatives and, 930, 950 cyclopentadiene and, 699 ethene and ethane and, 452–453 ethyne and, 570-571, 570 methyl- and phenyloxonium ion and, 1041 methylbenzene and, 1023 phenol and, 1028–1029 propene and, 610 pyridinium ion and, 1180 pyrrole and, 1177–1178 thioacetals and, 1098 thiols and, 365t Planar cyclohexane, 141, 141 Planck, Max K E L., 24n Plane of symmetry, 174, 174 Plane-polarized light, 175, 175 Plant pesticides, natural, 1192–1193 Plasticizers, 545 Plastics, from biomass-derived hydroxyesters, 905 Plavix, 1166t Pleated sheets, 1226, 1227 Poison arrow frog, 592 Polar aprotic solvents, 236–237, 236t Polar bonds, 10–12, 69–70 Polar reaction mechanisms, 221–223 Polar reagents, 848–849 Polar solvents, 258 Polarimeters, optical rotation and, 175–176, 176 Polarizability, 216, 237 Polarization, 11, 452, 779 Polyacetylene, 630–631 Polyacrylates, 591 Polyalkylation, 712 Polycarbonate plastics, 1030 Polychloroethene, 545 Polycyclic alkanes, 149–152 Polycyclic aromatic hydrocarbons, 687–692, 758–760 Polycyclic benzenoid, 687–692 Polycyclic benzenoid hydrocarbon reactivity, 754 –758 Polycyclic carboxylic acids, 906 Polyenes, conducting, 630–631 Polyethene, 545 Polyethers solvate metal ions, 349–350 Polyfunctional carbohydrates, 1118 Polyisoprene, 648–649 Polymerase chain reaction, 1248–1249 Polymerase DNA replication, 1249 Polymerizations alkene, 543 anionic, 546 butadiene, 647–648 conjugated dienes, 647–650 metal-catalyzed, 546 radical, 544 –546 Polymers, 542 monomers of, 544t oil spill clean-up and, 545 synthesis, 543–546 Polypeptide chains, 1222 Polypeptides affinity chromatography and, 1230 amino acid residues and, 1223–1226 amino end and, 1223 carboxy end and, 1223 cleavage and, 1232–1233, 1232t dialysis and, 1230 electrophoresis and, 1230 gel-filtration chromatography and, 1230 hydrolytic enzymes and, 1232–1233, 1232t information storage and, 1244 ion-exchange chromatography and, 1230 Merrifield solid-phase peptide synthesis and, 1238–1239 oxygen transport and, 1239–1241 peptide bonds and, 1223 primary structure and, 1226 protecting groups and, 1235–1236 purification and, 1230 secondary structure and, 1226 sequencing and, 1230–1234 side chains and, 1224 synthesis of, 1234–1236 tertiary structure and, 1226–1227 Polypropenenitrile, 546 Polysaccharides, 1146–1153 Polystyrene, 1238 Porphine, 1239, 1240 Porphyrin, 1239, 1240 Potassium permanganate test, 535 Potential energies, 81–82, 82 Potential-energy diagrams, 53, 53 Predicting reaction outcomes, 310–312 Pregabalin, 1211 Prescription drugs, 1166t Preservatives, 1057–1058 Prevacid, 1166t Primary alcohols, oxidation of and carboxylic acids, 883 Primary carbon, 72 Primary haloalkanes, 273–274 Primary structure, proteins and, 1226 Products, Progesterone, 157 Propagation steps, 105 Propanal, 780, 780, 841 Propane, 72, 112, 112 Propanedial, 1055 Propanoic acid, 878, 935, 1218 Propanoic anhydride, 935 Propanol, 288 Propene, 514 –515, 515 Propenenitrile, 1001 Propenoic acid, 591 Propenoyl chloride, 932 Propylacetylene, 568 Propylene, 446 Propylhexedrine, 974 Propylmagnesium bromide, 940 Propyloctene, 446 Prostaglandins, 459 Protecting groups, 358, 359, 794, 1235–1236 Protection strategies, 752–753 Proteins, 1211 automated synthesis of, 1238–1239 binding sites and, 1228 cross-linking and, 1055 denaturation and, 1229 fibrous proteins, 1228 globular proteins, 1227 helices and, 1226 nucleic acids and, 1241–1246 pleated sheets and, 1226, 1227 primary structure and, 1226 quaternary structure and, 1229 recombinant DNA technology and, 1234 secondary structure and, 1226 sequencing and, 1234 substrate or ligands and, 1228 superhelix and, 1228, 1229 synthesis of, 1246–1248, 1247t tertiary structure and, 1226–1227 Proteomics, 1252 Protic solvents, 236, 291, 301 Protonated formaldehyde, 15 Protonation, 364, 517–518, 881–882 Protonation, 621, 930, 1177, 1178 Protons, benzene and, 702–703 chemical shifts and, 395–400 flanked by two carbonyl groups, 1083–1084 relaxation times, 404 Proximity effect, 354 Psoralen, 1193 Pure ionic bonds, 8–9 Purification, polypeptide, 1230 I-17 Push-pull transition states, 952 Pyramidal geometry, 973 Pyranose, 1122, 1127, 1133 Pyridines aromatic nature and, 1179–1181 carbon chemical shifts in, 1180 chichibabin reaction and, 1185 condensation reactions and, 1181–1182 electrophilic aromatic substitution and, 1184 –1185 electrostatic potential map of, 1180 Hantzsch pyridine synthesis, 1181–1182 nucleophilic substitution and, 1185–1186 orbital picture of, 1180 reactions of, 1184 –1187 resonance in, 1180 structure and preparation of, 1179–1183 Pyridinium chlorochromate, 303 Pyridinium salts in nature, 1186–1187 Pyridoxamine, 799 Pyridoxine, 799, 1167 Pyrolysis, 100–103 Pyrroles dicarbonyl compounds and, 1174 electron pairs and, 1172–1174, 1173 electrophilic aromatic substitution and, 1176–1177 protonation of, 1177 Pyrrolidine, 835 Pyruvate, 1100–1101 Pyruvic acid, 1100–1101 Q Quanta, 389 Quantized systems, 24 Quantum corral, 26 Quantum mechanics, 24 Quartets, NMR spectroscopy and, 408 Quaternary ammonium salts, 992 Quaternary carbon, 72 Quaternary structure, polypeptide chains and, 1229 Quinine, 1194 Quinoline, 1188–1190 Quinomethanes, 1046 Quinones, 1051–1058 R R symbol, 70 Racemic 2-bromobutane, 198–201 Racemic mixtures, 176 Racemic valine resolution, 1221 Racemization, 176, 832 Radiation absorption, spectroscopy and, 389, 389–390 Radical addition, 540–541 Radical allylic halogenation, 612–614 I-18 Index Radical allylic substitution, 612 Radical brominations, 194 –195, 318 Radical chain mechanisms, methane chlorination and, 107–108 Radical chain sequence, 541 Radical halogenations with fluorine and bromine, 115–116 Radical hydrobromination, 541 Radical polymerizations, 544 –546 Radical reactions, 95 Radical stability, C-H bond strengths and, 98–99, 99 Radicals, homolytic cleavage and, 96–97 Raney, Murray, 509n Raney nickel, 509 Ranitidine, 59 Rapid DNA sequencing, 1249–1252 Rapid magnetic exchange, 421–422 Rapid proton exchange, 421, 421 Rate constant, 54 –55 Rate law, 223 Rate-determining steps, 253, 253 Rational drug design, 1153 Reactants, Reaction barriers, 54 Reaction coordinate, 53 Reaction intermediates, Reaction mechanisms, –5 Reaction rates activation energy and, 53–54 Arrhenius equation and, 55–56 first-order reactions and, 55 rate constant and, 54 –55 reactant concentration and, 54 –55 second-order reactions and, 55 Recombinant DNA technology, 1234, 1249 Redox reactions, 297 Reducing sugars, 1129 Reduction, 297, 298–299 acylarenes to alkylarenes, 750–751 acyl halides and, 933–934 aldehydes and ketones and, 299–301, 802–803 alkynes and, 579–582 amides and, 948–949 annulenes and, 700 azides and, 987 carbon monoxide to methanol, 295 carboxylic acids to alcohols, 897–898 disulfides to thiols, 367 ester to alcohol, 941 ester to aldehyde, 941 monosaccharides to alditols, 1131–1132 nature and, 1053–1058 nitriles to aldehydes and amines, 956–957 nitroarenes to benzenamines, 749 ozonolysis and, 538–539 reductive amination and, 989–991 Reductive amination, 989–991 Regioselective additions, 514 Regioselectivity, 756–757 Regioselectivity in E2 reactions, 462–464, 463 Relative acidities of common compounds, 60t Relative stabilities of alkanes, 122–123 Relenza, 1153 Replication, DNA, 1245–1246, 1246 Residues, 1222 Resolution of enantiomers, 202–204, 203 Resonance, 391, 732 See also Nuclear magnetic resonance (NMR) acceptance from benzene, 733 donation to benzene, 733 enamines and, 836 groups donating electrons and, 738–741 hybrids, 19, 828 polycyclic aromatic hydrocarbons and, 757 resonance energy, 679 resonance frequency, 392 stabilization in oximes, 799 Resonance forms, 18–23 2-butenal and, 846 carbonate ion and, 18–20 major resonance contributors, 21 nonequivalent, 20–21 unsaturated carbonyl compounds and, 848 Restaurant grease, 945 Restriction endonucleases, 1249 Restriction enzymes, 1249 Resveratrol, 1028, 1030–1031 Retention of configuration, 229 Retinal isomerase, 843 Retinol, 843 Retro-Claisen condensation, 1084 Retronecine, 995 Retrosynthetic analysis alcohol construction and, 315–317 Claisen condensations and, 1088 synthesis problems and, 313–315 working backward and, 316–317 Retrosynthetic disconnection, 314 Reverse polarization, 306 Reversibility, nucleophilic substitutions and, 239–240 Reversible sulfonation, 752 Reye’s syndrome, 1043 Rhizobium bacteria, 972 Rhodopsin, 843 Ribavirin, 1243 Ribonucleic acid (RNA), 1241 messenger RNA, 1246, 1246–1248 nucleotides of, 1243 protein synthesis through, 1246–1248 structures of, 1241–1244 transcription and, 1246 transfer RNA, 1246–1248 translation and, 1246 Ribose, 1119 Ribosomes, 1246 Rickets, 1188 Ring current, 684, 684 Ring size, 353–354 Ring strain, 135–137 Ring-fusion carbons, 149 Ring-fusion substituents, 149 Robinson, Sir Robert, 854n Robinson annulation, 854 –855, 1096 Rodbell, Martin, 844n Rotational energy, 81 Rotational symmetry in organic molecules, 400, 400 Rotations in ethane, 79–80, 80 single bonds and, 79–82 steric hindrance and, 82–83, 83 in substituted ethanes, 82–85 Rowland, F Sherwood, 120n R-S sequence rules, 177–182 RU-486, 156–157 Rubber, 647–650 Ruff degradation of sugars, 1137–1138 S Saccharic acid, 1130 Saccharides, 1118 Saccharin, Safety in chemical industry, 953 Salicylic acid, 1043 Salmeterol mixture, 1166t Sandmeyer, Traugott, 1059n Sandmeyer reaction, 1059 Sanger, Frederick, 1249n Sanger DNA sequencing method, 1249–1251, 1250 Saponification, 901 Saturated compounds, 446 Saytzev, Alexander M., 462n Saytzev rule, 462–463 Scanning tunneling microscope, 26, 509 Schiff, Hugo, 707n Schiff base, 797 Schmitt, Rudolf, 1047n Schrock, Richard R., 549n Schrödinger, Erwin, 23n s-cis, 619–620 Secondary alcohols, 336–337 Secondary carbons, 72 Secondary C-H bonds, 111–113 Secondary haloalkanes, 251–252, 274 Secondary N-nitrosammonium salts, 997 Secondary structure, proteins and, 1226 Second-order reactions, 55 Security technology, 475 Selective hydroxylation, 299 Selective mixed Claisen condensation, 1085 Selectivity, 112 Semicarbazones, 799–800 Semiquinone radical anion, 1052 Sequence rules, 177–182 Sequencing, amino acid, 1230 Sequencing, protein, 1234 Serotonin, 1193 Sex hormones, 156–157 “Sexual swindle” phenomenon, 79 Sharpless, K Barry, 197, 536 Sharpless enantioselective oxacyclopropanation and dihydroxylation, 536–537 Shielded nucleus, 395–396 Shirakawa, Hideki, 630n Short tandem repeats (STR), 1256 Sialic acid, 1152–1153 Sibutramine, 975 Side chains, 1224 Sigma bonds, 29–30, 30 Signal position, NMR spectroscopy and, 395, 395–396 Sildenafil citrate, 1167 Simmons, Howard E., 532n Simmons-Smith reagent, 532 Simple sugar, 1119 Simvastatin, 1166t Single bonds, rotations and, 79–82 Singulair, 1166t Skew conformations, 79 Skew-boat cyclohexane, 141, 141 Skin color, 1188–1189 Smalley, Richard E., 688n Smith, Ronald D., 532n Smoking, 1170–1171 SN1 reactions, 614 –615 anticancer drug synthesis and, 263 carbocation stability and, 260–264 green criteria and, 263 leaving groups and, 258 nucleophile strength and, 259 polar solvents and, 258 secondary systems and, 261–263 stereochemical consequences of, 256–257 stereoselective displacement and, 263 transition states and, 258, 258 SN2 reactions, 350–352 branching at reacting carbon and, 240–242, 240t enantiomer synthesis and, 229–231 green criteria and, 263 inversion consequences and, 228–231 leaving-group ability and, 231–233 nucleophilicity and, 233–240 Index one and two carbon lengthening and, 242, 242 potential-energy diagrams and, 255f relative rates of reaction and, 129t, 237t retention of configuration and, 229 secondary systems and, 261–263 stereospecificity and, 226–228 structure and, 231–233 substrates and, 240–243 transition states and, 228, 228, 240, 240, 258, 258 SN2 transition state at benzylic center, 1022–1023, 1023 Soaps from long-chain carboxylates, 900–901 Sodium, reactions with water, 334 Sodium amide, 982 Sodium cation, Sodium chloride, Sodium hydroxide, 65, 223–224 Sodium reduction of alkynes, 581 Solanine, 1192 Solid-state synthesis, dipeptides and, 1238–1239 Solvation, nucleophilicity and, 235–236, 236 Solvolysis carbocation formation and, 253–256 first-order kinetics and, 253 rate-determining step and, 253, 253 rearrangement in, 341 tertiary and secondary haloalkanes and, 251–252 Sondheimer, Franz, 696n Sonogashira, Kenkichi, 588n Sonogashira coupling reaction, 589 Sorbose, 1135 Southern blotting, 1256 Soybean oil, 945 sp hybrids, 32–34, 33, 34 Specific rotations of various chiral compounds, 175–176, 176 Spectinabilin, 644 –645 Spectral characteristics, benzene ring and, 682–687 Spectrometers, 389, 390 Spectroscopy, 388–390 baseline and, 389 carboxylic acids and, 875–878 molecular excitation and, 388 peak and, 389 radiation absorption and, 389, 389–390 spectrum and, 389, 390 Spectrum, spectroscopy and, 389, 390 Speier, Arthur, 892 Spin, 26 Spin states, 390, 391 Spin-spin coupling, 407, 407–414, 573 Spin-spin splitting, 407, 407–414 in common alkyl groups, 413t fast proton exchange and, 421, 421 multiple hydrogens and, 409–410, 410 N 1 rule and, 411, 411–412 nonequivalent neighbor coupling and N 1 rule, 417, 417–419, 418 non-first-order spectra and, 415, 415–416, 416 Pascal’s triangle and, 411, 411t rapid magnetic exchange and, 421–422 Spruce budworm, 581 Squalene, 650, 1087 Staggered conformation, 79 Staphylococcus aureus, 946–947 Starch, 1147 State of equilibrium, 50 Statistical product ratio, 111 Stem chain, 73 Stereocenters, 172, 178, 178–184 Stereochemistry bromination of butane and, 194, 194 –195 in chemical reactions, 193–202 cyclic bromonium ions and, 520–521 SN1 reactions and, 256–257 SN2 reactions and, 226–228 Stereoisomerism, 2, 170 Stereoisomerization, 830–831 Stereoisomers, 133 absolute configuration and, 177–182 chiral molecules, 171–174 diastereomers, 189–190 Fischer projections and, 182–187 meso compounds and, 191–193 more than two stereocenters and, 190–191 optical activity and, 174 –177 optical rotation measurement and, 175–176, 176 resolution of enantiomers and, 202–204, 203 R-S sequence rules and, 177–182 stereochemistry in chemical reactions, 193–202 stereoperception and, 181–182 stereoselectivity and, 201 tartaric acid and, 190 two stereocenters and, 187–189 Stereoperception, 181–182 Stereoselective crossed aldol condensations, 842 Stereoselective dehydrobromination, 465 Stereoselective displacement, 263 Stereospecific 2-butene bromination, 520 Stereospecific intramolecular Williamson synthesis, 354 –355 Stereospecificity catalytic hydrogenation and, 511 Diels-Alder reaction and, 634 –635 electrocyclic reactions and, 643–646 stereospecific process, 226, 465–466 Steric bulk, 271–272 Steric congestion, 461, 461 Steric disruption, 293–294 Steric hindrance, 82–83, 83 Sterically hindered nucleophiles, 238, 272–273 Steroids, 154 –157 See Cycloalkanes angular fusion and, 154 cholesterol and, 155 cyclohexane ring fusion and, 154 nucleus, 154 Stevioside, 1145 Stille, John K., 588n Stille coupling reaction, 588, 645 Stomach acid, food digestion and, 59 Straight-chain alkanes, 70, 77 s-trans, 619–620 Strategic disconnection, 314 Stratospheric ozone layer, 119, 119–121 Strecker, Adolf, 1220n Strecker synthesis, 1220 Streptococcus pneumoniae, 947 Streptomyces, 644 –645 Streptomycin, 1151 Strongly basic nucleophiles, 271–272 Structural isomers, 37 Strychnine, 309, 1194 Substituents, 36, 73–74 activation or deactivation on benzene ring, 732–734 electrophilic aromatic substitution and, 744t keto-enol equilibrium and, 830 Substituted benzenes directing effects of, 738–745 directing power of, 749–751 Friedel-Crafts electrophiles and, 751 groups that donate electrons and, 738–741 groups that withdraw electrons and, 742–743 halogen substituents, 743–745 inductive effects on benzene ring, 733 protection strategies and, 752–753 reversible sulfonation and, 752 synthetic strategies toward, 749–754 I-19 Substituted cyclohexanes, 144–149 axial and equatorial methylcyclohexanes and, 144 –146, 146t competition for equatorial positions and, 147–148 1,3-diaxial interactions and, 145 Newman projection of, 145 Substitution at carboxy carbon, 886–889 Substitution patterns, benzene derivatives and, 683 Substitution reaction, Substrates, 4, 1228 nucleophilic attack and, 240–243 nucleophilic substitution and, 218 Succinimide, 897 Sucralose, 1145 Sucrose inversion, 1142–1143 Sugar substitutes, carbohydratederived, 1144 –1145 Sugars acetals and, 1144 –1146 as aldoses and ketoses, 1118 anomers of, 1127 biochemistry of, 1138–1139 chiral and optically active, 1119–1120 complex sugars, 1119 conformations and cyclic forms of, 1122–1126 containing nitrogen, 1151 cyanohydrin formation and reduction and, 1136 D and L sugar designations, 1119 esterification, 1133–1134 Fehling’s test and, 1128–1129 Fischer projections and, 1112, 1125 Haworth projections and, 1125–1126 intramolecular hemiacetals and, 1122–1124 inversion, 1143 methylated, 1133–1134 neighboring hydroxy groups in, 1134 –1135 oxidative cleavage of, 1130–1131 periodic acid degradation of, 1131 polyfunctional chemistry of, 1128–1130 reducing sugars, 1129 Ruff degradation of, 1137–1138 step-by-step buildup and degradation, 1136–1139 Tollens’s test and, 1128–1129 Sulfa drugs, 370, 707 Sulfadiazine, 370 Sulfate leaving groups, 232 Sulfides, 365–366 Sulfonamides, 370, 707 Sulfonate leaving groups, 232 I-20 Index Sulfonation, 705–708, 752 Sulfones, 367 Sulfonium ions, 366 Sulfonyl chlorides, 707 Sulfoxide, 367 Sulfur, valence-shell expansion of, 366–367 Sulfuric acid, 16, 705 Sun lotions, 682 Super glue, anionic polymerization of, 546 Superhelix, 1228, 1229 Superoxide, 1054 Suzuki, Akira, 588n Suzuki coupling reaction, 588–589 Symmetrical ether, 70 Symmetry, chiral molecules and, 173–174 Synthesis, acetals, 792–793 acetoacetic ester, 1092–1093 acyl halides, 889–890 alcohols, 297–304 alkenes and, 532–534, 543–546 alkyl sulfonates, 346 amines and, 986–992 amino acids, 1217–1220 anticancer drugs, 263 antitumor drugs, 536–537 automated proteins, 1238–1239 benzene derivative, 701–703 bromoalcohol, 522 bromoalkanes, 336, 345 carboxylic acids, 882–883 chloroalkane, 345–346 chloroethene, 547 convergent, 317 dialkylated acetic acid, 1093 dinucleotide, 1253 DNA, 1252–1254 enantiomers, 229–231 enantioselective, 197, 199, 512, 536–537, 1187, 1221–1222 enzymes, 842 ether, 355–357 formic acid, 882 Gabriel synthesis, 988, 1218 haloalkanes, 344 –347 hexanol, 314 hydrazone, 802 hydroxyketone, 1098 iodoalkane, 336 ketones and, 308, 956 Kiliani-Fischer synthesis, 1136 linear synthesis, 317 malonic ester, 1093 Merrifield solid-state peptide synthesis, 1238–1239 messenger RNA, 1246–1248 natural rubber, 648–649 oxacyclopentane, 591 oxacyclopropane, 532–534 Paal-Knorr synthesis, 1174 peptides, 1235–1236 polymers, 543–546 proteins, 1246–1248 Stecker synthesis, 1220 varenicline, 1171 Williamson ether synthesis, 350–355 Wöhler synthesis of urea, 3–4 Synthesis gas, 295 Synthesis problems, retrosynthetic analysis and, 313–315 Synthetic artificial sweeteners, 1144 –1145 Synthetic chemistry, 317–319 Synthetic intermediates, 1090–1095 Synthetic methods, new reactions leading to, 312–313 Synthetic nucleic acid bases, 1243 Synthetic radical halogenation, 116–118 Synthetic rubbers, 648 Synthetic strategies toward substituted benzenes, 749–754 Systematic nomenclature, 71 T Talose, 1141 Taq DNA polymerase, 1258 Tartaric acid, 190 Tautomers, 829 Taxol, 153 Template strands, DNA sequencing and, 1249, 1250 Terminal alkenes, 447 Terminal alkynes, 568 acidity and, 570–571 deprotonation of, 571 hydration of, 584 hydroboration-oxidation of, 586 infrared absorptions and, 574 –575, 575 Termination steps, 107 Terpenes, 152 Tertiary alcohols, 309, 336–337 Tertiary butyl ethers, 358–360 Tertiary carbon, 72 Tertiary C-H bonds, 113 Tertiary haloalkanes, 251–252, 274, 319 Tertiary N-nitrosammonium salts, 997 Tertiary structure, proteins and, 1226–1227 Tesla, Nikola, 391n Testosterone, 157 Tetracyanoethylene, 635 Tetrahedral, 12 Tetrahedral arrangement, amines and, 973–976 Tetrahedral carbon, 469 Tetrahedral carbon compounds, 34, 34 Tetrahedral intermediate, 887 Tetrahedral stereocenter, 178, 178 Tetrahydrocannabinol, 370 Tetrahydrofuran (THF), 529 Tetramethylammonium bromide, 987 Tetroses, 1119 Theobromine, 1194 Thermal isomerization, 450–452, 451 Thermodynamic control, 50, 516–518, 623–625 Thermodynamic feasibility, 507–509 Thermodynamics, simple chemical processes and, 50–56 Thiamine, 1081, 1100–1101 Thiamine pyrophosphate, 1100 Thiazolium salts acidity and, 1102 aldehyde coupling and, 1099–1103 thiamine, 1100–1101 Thioacetal formation, 795–797 Thioacetal hydrolysis, 796 Thioacetals, 795–797, 797 Thiol ester, 902 Thiol-disulfide redox reaction, 367 Thiols, 70, 365–366 acidity of, 365 boiling point of, 365t radical addition of, 541 reactions of, 365–366 thioacetal formation and, 795–797 valence-shell sulfur expansion and, 366–367 Thionyl chloride, 891 Thiophenes dicarbonyl compounds and, 1174 electron pairs and, 1172–1174, 1173 electrophilic aromatic substitution and, 1176–1177 39-end, 1243 Threose, 1120 Thymidylic acid, 1242 Thymine, 1241 Tigecycline, 947 TNT, 741 Tollens, Bernhard C G., 809n Tollens’s test, 809 Torsional angle, 81 Torsional energy, 81 Torsional strain, 81 Total synthesis, 310 trans coupling, 454 –456 Trans fatty acids, 511, 903 trans isomer stability, 460–461 Transannular strain, 141 Transcription, 1246 trans-decalin, 150, 150 Transesterification, 939 Transfer RNA, 1246–1248 Transition metal-catalyzed cross-coupling reactions, 310–311 Transition state, 53, 268–269 Transketolase, 1138 Translation, 1246 Transpeptidase, 946 trans-retinal, 843 Tremorine, 593 Tricarboxylic acid (TCA) cycle, 1100 Trichloroethylene, 446 Triethylamine, 345, 979, 980 (Trifluoromethyl)benzene, 737 Trigonal arrangement, 12 Trigonal structures, 33, 33–34 Trimethylamine, 982 Trimethylbenzene, 675 Trioses, 1119 Tripeptides, 1222, 1224 Triplets, NMR spectroscopy and, 408 Trivial names, 71 Trypsin, insulin hydrolysis and, 1223 Twist-boat cyclohexane, 141, 141 2-Amino acids, 1212–1213 Two-dimensional (2D) NMR, 428 Tygacil, 947 Tylenol, 1043 Tyrosine, 1215 U Ubiquinones, 1053–1054 Ultraviolet light chlorofluorocarbons and, 120 ozone layer and, 119, 119 Ultraviolet spectra, benzene, 682, 682 Ultraviolet spectroscopy, 650–655 electronic excitations and, 651, 651–652 viniferone characterization and, 655 Unimolecular elimination (E1), 264 –266, 265 Unimolecular nucleophilic substitution, 252–256 carbocation formation and, 253–256 first-order kinetics and, 253 stereochemical consequences and, 256–257 Unsaturated aldehydes and ketones, 846–850 Unsaturated aldehydes in nature, 844 –845 Unsaturated carbonyl compounds, 848, 851 Unsaturated compounds, 446 Unsaturation, degree of, 482–483, 482t Unselective chlorination, 113 Unsymmetrical ether, 70 Upfield, NMR spectroscopy and, 396 Uracil, 1241 Urea, Wöhler’s synthesis of, 3–4 Uridylic acid, 1243 Urotropine, 974 V Valence electrons, 8–9 Valence-shell electron-pair repulsion (VSEPR), 12–13 Index Valence-shell expansion, 16, 366–367 Valine, 1221 Valium, 1167 van der Waals, Johannes D., 77n van der Waals forces, 77 Vancomycin, 946, 947 Varenicline synthesis, 1171 Variable-number tandem repeats, 1256–1257 Vegetable oils, fuels from, 944 –945 Venlafaxine, 1166t Veronal, 1184 Viagra, 1167 Vibrational excitation, infrared spectroscopy and, 468, 468–469 Vicinal coupling, 409, 455 Vicinal diols cyclic acetal formation from, 1135 oxidative cleavage of, 1130 periodic acid cleavage of, 1130 Vicinal haloether synthesis, 522 Vicinal syn dihydroxylation, 535–537 Villiger, Victor, 808n Viniferone, 430–431, 655 Visible spectroscopy, 650–655, 651, 651–652 Visible spectrum, 651 Vision chemistry, 844 –845 Vitamin A, 843 Vitamin B6, 1167 Vitamin B12, 1167 Vitamin C, 1056, 1135 Vitamin D, 1188–1189 Vitamin E, 1055–1056 reactions with lipid hydroperoxy and alkoxy radicals, 1056 regeneration by vitamin C, 1056 systemic analogs of, 1057–1058 Volhard, Jacob, 898n von Fehling, Hermann C., 809n Vulcanization, 648 W Wacker, Alexander, 547 Wacker process, 547 Water alcohol overoxidation and, 786 bond and molecular dipoles of, 290 hydrogen bonding and, 290–291 nucleophilic attack by, 254 pKa values of alcohols in, 292, 292t structural similarity with alcohol, 289–290, 291 Watson, James D., 1244n Wave equations, 23–24, 24 Wave functions, 24 Waxes, 942 Weak nucleophiles, 270–271 Weight control, amines and, 974 –975 Williamson ether synthesis, 350–355 cyclic ether preparation and, 352, 352–354 intramolecular, 352–353 ring size and, 353–354 SN2 reactions and, 350–352 stereospecific, 354 –355 Willstätter, Richard, 695n Wittig, Georg, 804n Wittig reaction, 804 –807 Wöhler, Friedrich, Wöhler’s synthesis of urea, 3–4 Wolff, Ludwig, 802n Wolff-Kishner reduction, 802–803 Woodward, Robert B., 643n Woodward-Hoffmann rules, 643–646 X Xenical, 975 X-ray diffraction, 177–178 Y Ylides, 804 –807 Z Zelinsky, Nicolai D., 898n Zeolite catalyst, 101 Zidovudine, 1167, 1243 Ziegler, Karl, 546n Ziegler-Natta catalysts, 546, 648 Zocor, 1166t Zwitterions, 806, 1214 –1215 I-21 This page intentionally left blank Organic Chemistry at the Click of a Button! 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ABOUT THE AUTHORS K PETER C VOLLHARDT was born in Madrid, raised in Buenos Aires and Munich, studied at the University of Munich, got his Ph.D with Professor Peter Garratt at the University College, London, and was a postdoctoral fellow with Professor Bob Bergman (then) at the California Institute of Technology He moved to Berkeley in 1974 when he began his efforts toward the development of organocobalt reagents in organic synthesis, the preparation of theoretically interesting hydrocarbons, the assembly of novel transition metal arrays with potential in catalysis, and the discovery of a parking space Among other pleasant experiences, he was a Studienstiftler, Adolf Windaus medalist, Humboldt Senior Scientist, ACS Organometallic Awardee, Otto Bayer Prize Awardee, A C Cope Scholar, Japan Society for the Promotion of Science Prize Holder, and recipient of the Medal of the University Aix-Marseille and an Honorary Doctorate from The University of Rome Tor Vergata He is the current Chief Editor of Synlett Among his more than 320 publications, he treasures especially this textbook in organic chemistry, translated into 13 languages Peter is married to Marie-José Sat, a French artist, and they have two children, Paloma (b 1994) and Julien (b 1997), whose picture you can admire on p 170 NEIL E SCHORE was born in Newark, New Jersey, in 1948 His education took him through the public schools of the Bronx, New York, and Ridgefield, New Jersey, after which he completed a B.A with honors in chemistry at the University of Pennsylvania in 1969 Moving back to New York, he worked with Professor Nicholas Turro at Columbia University, studying photochemical and photophysical processes of organic compounds for his Ph.D thesis He first met Peter Vollhardt when he and Peter were doing postdoctoral work in Professor Robert Bergman’s laboratory at Cal Tech in the 1970s Since joining the U C Davis faculty in 1976, he has taught organic chemistry to more than 12,000 nonchemistry majors, winning five teaching awards, publishing over 100 papers in various areas related to organic chemistry, and refereeing several hundred local youth soccer games Neil is married to Carrie Erickson, a microbiologist at the U.C Davis School of Veterinary Medicine They have two children, Michael (b 1981) and Stefanie (b 1983), both of whom carried out experiments for this book Text References for Compound Classes and Functional Groups Alkanes A A O C OC OH A A Haloalkanes A O C OX A Alcohols Ethers A O C O O OH A A A O C O O OC O A A Thiols A O C O S OH A Alkenes G D CP C G D Properties 2-6 to 2-8, 3-1, 3-10, 4-2 to 4-6 6-1 Preparations 8-7, 11-5, 12-2, 13-6, 17-10, 18-8, 21-10 3-4 to 3-8, 9-2, 9-4, 12-3, 12-5, 12-6, 12-13, 13-7, 14-2, 19-12 Reactions 3-3 to 3-10, 8-6, 19-5 Compound Class Aldehydes and ketones 6-2, 6-4 to 7-8, 8-5, 8-7, 11-6, 13-9, 14-3, 15-11, 17-12, 19-6, 21-5 9-5 8-4 to 8-6, 8-8, 9-8, 9-9, 12-4, 12-6 to 12-8, 12-11, 13-5, 17-6, 17-7, 17-9, 17-11, 18-5, 18-9, 19-11, 20-4, 23-4, 24-6 8-3, 8-6, 9-1 to 9-4, 9-6, 9-7, 9-9, 11-7, 12-6, 15-11, 17-4, 17-7, 17-11, 18-9, 20-2 to 20-4, 22-2, 24-2, 24-5, 24-8 9-6, 9-7, 12-6, 12-7, 12-10, 12-13, 17-7, 17-8, 18-9, 22-5 9-8, 9-9, 23-4, 25-2 Alkanoyl halides Anhydrides 9-10 9-10, 26-5 9-10, 26-5 Esters 11-2 to 11-5, 11-8 to 11-11 14-5, 14-11 7-6 to 7-9, 9-2, 9-3, 9-7, 11-6, 11-7, 12-14, 12-16, 13-4, 13-6 to 13-10, 17-12, 18-5 to 18-7, 21-8 8-4, 11-5, 12-2 to 12-16, 13-4, 14-2 to 14-4, 14-6 to 14-10, 15-7, 15-11, 16-4, 18-8 to 18-11, 21-10 Amides Nitriles Alkynes Aromatics O C q C OH 13-2, 13-3 15-2 to 15-7 13-4, 13-5 15-8 to 16-6, 22-4 to 22-11, 25-5, 26-7 13-2, 13-3, 13-5 to 13-10, 17-4 14-7, 15-2, 15-9 to 16-6, 22-1 to 22-8, 22-10, 22-11, 25-4, 25-6, 26-7 Red nucleophilic or basic atom; blue electrophilic or acidic atom; green potential leaving group O B H H EC H H AC A Preparations Reactions 17-2, 17-3, 18-1, 23-1 8-6, 12-12, 13-7, 13-8, 15-13, 16-5, 17-4, 17-6 to 17-9, 17-11, 18-1, 18-4, 20-2, 20-4, 20-6, 20-8, 22-2, 22-8, 23-1, 23-2, 23-4, 24-5, 24-9, 25-4 8-6, 8-8, 16-5, 17-5 to 17-14, 18-1 to 18-11, 19-5, 19-6, 21-6, 21-9, 22-8, 23-1 to 23-4, 24-4 to 24-7, 24-9, 25-3 to 25-5, 26-2 19-2 to 19-4, 26-1 8-5, 8-6, 17-14, 19-5, 19-6, 19-9, 20-1 to 20-3, 20-5, 20-6, 20-8, 22-2, 23-2, 24-4 to 24-6, 24-9, 26-2, 26-5, 26-6 9-4, 19-4, 19-7 to 19-12, 21-10, 23-2, 24-9, 26-4, 26-6, 26-7 Properties O B H H EC H E AC A AC A Carboxylic acids 8-2, 8-3 Functional Group Amines O B EC H EH O O B EC H 15-13, 20-2 20-1 X 19-8 O O B B EC H E CH O 19-8 20-1, 20-4, 20-5 O B C E H EH N A 20-1, 20-6 O C qN 20-8 A C E H EH N A 15-13, 20-3 20-1 O A B H H EC H ECH O AC A A Functional Group A Compound Class 7-8, 9-4, 17-13, 19-9, 20-2, 22-5 20-4, 23-1 to 23-3, 26-6 20-6, 20-7, 26-5 19-10, 20-2, 20-4, 26-6 17-11, 18-9, 20-8, 21-10, 22-10, 24-9 21-2 to 21-4, 26-1 16-5, 17-9, 18-9, 20-6 to 20-8, 21-5 to 21-7, 21-9, 22-4, 25-2, 25-6, 26-2, 26-5 17-11, 19-6, 20-8, 21-12, 24-9, 26-2 16-5, 17-9, 18-4, 18-9, 19-10, 20-2 to 20-4, 21-4, 21-5, 21-7 to 21-10, 22-4, 22-10, 22-11, 25-2, 25-3, 26-1, 26-5, 26-6 Periodic Table of the Elements Relative atomic mass (atomic weight), 1995 IUPAC values; * for these radioactive elements, nuclidic mass of an important isotope 1.00794 1, Ϫ1 2.2 H Oxidation states in compounds: important, most important 6.941 9.012182 2 Li 24.3050 Atomic number Element essential to all biological species investigated Element essential to at least one biological species 1.3 0.9 11 Na Electronegativity 26 Fe Be 22.989770 1.8 1.6 1.0 55.845 6, 3, 2, 0, Ϫ2 12 Mg 39.0983 40.078 44.955910 47.867 50.9415 51.9961 54.938049 4, 5, 4, 3, 2, 6, 3, 2, 7, 6, 4, 3, 2, 0, Ϫ1 6, 3, 2, 0, Ϫ2 0.8 1.0 1.4 1.5 1.6 1.7 20 Ca 21 Sc 22 85.4678 87.62 88.90585 91.224 92.90638 95.94 5, 6, 5, 4, 3, 2, 19 K 0.8 1.0 37 Rb 38 132.90545 Sr 24 Cr 1.3 178.49 180.9479 183.84 6, 5, 4, 3, 2, 223.0197* 226.0254* 0.8 1.8 1.9 26 Fe 27 Co 98.9063* 101.07 102.90550 8, 6, 4, 3, 2, 0, Ϫ2 5, 4, 3, 2, 1, 42 Mo 1.3 2.3 44 Ru 45 Rh 186.207 190.23 192.217 7, 6, 4, 2, Ϫ1 8, 6, 4, 3, 2, 0, Ϫ2 6, 4, 3, 2, 1, 0, Ϫ1 43 Tc 2.4 2.2 72 Hf 73 Ta 74 W 75 Re 76 Os 77 261.1088* 262.1142* 266.1219* 264.1247* (277) 268.1388* 104 Rf 105 Db 106 Sg 107 Bh 108 Hs 109 Mt 138.9055 140.116 140.90765 144.24 146.9151* 150.36 151.964 4, 4, 3 3, La–Lu 0.9 3, 2, 0, Ϫ1 2.2 57 to 71 58.933200 1.6 25 Mn 137.327 0.9 Y V 41 Nb 56 Ba Fr 1.2 39 55 Cs 87 23 40 Zr 0.8 Ti 55.845 Ir 89 to 103 88 Ra Ac–Lr Lanthanides 1.1 1.1 1.1 1.1 1.2 3, 1.2 1.2 57 La 58 Ce 59 Pr 60 Nd 61 Pm 62 Sm 63 Eu 227.0278* 232.0381 231.03588* 238.02891 237.0482* 244.0642* 243.0614* 5, 6, 5, 4, 6, 5, 4, 6, 5, 4, 6, 5, 4, Actinides 1.3 1.2 89 Ac 90 Th 1.3 91 Pa 1.4 92 U 1.4 93 Np 1.3 94 Pu 95 Am 18 4.002602 13 s Block elements d Block elements p Block elements f Block elements 14 12.0107 14.0067 15.9994 18.9984032 4, 2, Ϫ4 5, 4, 3, 2, Ϫ3 Ϫ2, Ϫ1 Ϫ1 2.6 B 12 3.0 C N 3.4 O F 39.948 28.0855 30.973761 32.065 35.453 4, Ϫ4 5, 3, Ϫ3 6, 4, 2, Ϫ2 7, 5, 3, 1, Ϫ1 13 Al 14 Si 2.2 15 P 2.6 S 16 3.2 17 18 Ar Cl 58.6934 63.546 65.409 69.723 72.64 74.92160 78.96 79.904 3, 2, 2, 5, 3, Ϫ3 6, 4, Ϫ2 7, 5, 3, 1, Ϫ1 1.9 1.7 1.9 30 Zn 31 Ga 107.8682 112.411 2, 28 Ni 29 Cu 106.42 4, 2, 1.9 2.2 46 Pd 47 Ag 195.078 4, 2, 33 As 114.818 118.710 121.760 4, 5, 3, Ϫ3 1.8 1.7 49 196.96655 200.59 3, 2, 2.5 2.2 32 Ge 48 Cd 2.3 2.0 1.8 83.798 2.6 3.0 3.0 35 Br 36 Kr 127.60 126.90447 131.293 6, 4, Ϫ2 7, 5, 1, Ϫ1 8, 6, 4, 34 Se 2.0 20.1797 10 Ne 1.9 He 4.0 26.981538 1.6 11 17 10.811 2.0 10 16 15 2.1 2.1 51 Sb 52 204.3833 207.2 208.98038 208.9824* 209.9871* 222.0176* 3, 4, 5, 6, 4, 7, 5, 3, 1, Ϫ1 2.0 2.3 2.0 2.0 53 I 2.6 50 Sn In Te 2.7 54 Xe 2.0 79 Au 80 Hg 81 Tl 82 Pb 83 Bi 84 Po (281) 272.1535* (285) (284) (289) (288) (292) (294) 110 Ds 111 Rg 112 Cn (113) Uut (114) Uuq (115) Uup (116) Uuh (118) Uuo 157.25 158.92534 162.500 164.93032 167.259 168.93421 173.04 174.967 4, 3 3 3, 3, 78 Pt 1.2 1.2 1.2 1.2 1.2 64 Gd 65 Tb 66 Dy 67 Ho 68 247.0703* 247.0703* 251.0796* 252.0830* 4, 4, 4, 3 96 Cm 97 Bk 98 Cf 99 Es Er 85 At 86 Rn 1.0 1.3 69 Tm 70 Yb 71 Lu 257.0951* 258.0984* 259.1010* 262.1097* 3 3, 100 Fm 101 Md 102 No 103 Lr ... attained by combustion of ethyne (acetylene) CH3CH2C q CH ϩ H2 CH3C q CCH3 ϩ H2 Catalyst Catalyst CH3CH2CH2CH3 ΔH° ϭ Ϫ69.9 kcal molϪ1 ( 29 2.5 kJ molϪ1) CH3CH2CH2CH3 ΔH° ϭ Ϫ65.1 kcal molϪ1 ( 27 2.4... Deprotonation of a Terminal Alkyne pKa Ϸ 50 pKa Ϸ 25 CH3CH2C q CH (Stronger acid) ϩ CH3CH2CH2CH2Li (CH3CH2)2O H A CH3CH2C q CLi ϩ CH3CH2CH2CH2 (Stronger base) (Weaker base) (Weaker acid) Exercise... 1,7-octadiyne: n| Csp2H stretch 3300 cm21; n| CqC stretch 21 20 cm21; n| Csp2H bend 640 cm21 Transmittance (%) 100 21 20 H H C C H C C C H C H 3300 C C H H IR 4000 3500 H 640 H H 3000 25 00 20 00 1500 1000