1559T_ch08_132-14710/30/0511:59Pa9e132 EQA 8 Hydroxy Functional Group:Alcohols: Properties,Preparation,and Strategy of Synthesis an be prepared from m inerent types or compound nd,in tum they can be co compounds. n ocn me an boeec 11-x Substitution e-c Substitution breaks bond 3.Elimination breaks bonds 1 and 3.and"doubles"bond 2.By comparison.five bonds may participate in chemical reactions of alcohols: -4- amine the general prablem of synthene we cy We focus first on e this discussion to ex and efficient sequence of rting material into an organic product 鸟
8 Hydroxy Functional Group: Alcohols: Properties, Preparation, and Strategy of Synthesis With this chapter we begin a detailed examination of alcohols, molecules containing the hydroxy functional group. Apart from carbonyl compounds, alcohols are the most important molecules in organic chemistry. They can be prepared from many different types of compounds, and, in turn, they can be converted into many different types of compounds. They therefore play a central role in organic chemistry. Moreover, their preparations, properties, and reactions serve as excellent illustrations of the logic underlying the behavior of organic compounds. The approach to Chapters 8 and 9 is similar to that used in Chapters 6 and 7. However—and this is very important—alcohols have much more potential for chemical conversion than haloalkanes do. You must be prepared even more than before to focus on the functional groups and their polar bonds as sites of possible reactivity. A comparison of, first, the bonds and, second, the potential bonding changes available in alcohols and haloalkanes is useful. Haloalkane chemistry involves mainly three bonds: Substitution breaks bond 3. Elimination breaks bonds 1 and 3, and “doubles” bond 2. By comparison, five bonds may participate in chemical reactions of alcohols: We focus first on properties of alcohols. Then we examine their preparation, using this discussion to examine the general problem of synthetic strategy: how to logically plan a practical and efficient sequence of chemical steps that allows the conversion of a starting material into an organic product. H H H C C O 1 2 3 5 4 H C C X H C C Y C C 1 2 3 Substitution Elimination 132 1559T_ch08_132-147 10/30/05 11:59 Page 132
1559r.ah08.132-14710/30/0511:59Page133 Keyso the Chapter·133 Outline of the Chapter uced:hydrogen bonding 8的eannacckchotetputnweasne 8-4 Industrial Preparation of Alcohols A brief survey of methods for the preparation of commercially useful alcohols. 8-5 Synthesis of Alcohols by Nucleophilic Substitution 8-6 Oxidation and Reduction Alcohols and carbonyl compounds are interconverted in oxidation-reduction processes,opening up many synthctic possibilities. 8782gCaemeacRaogpaomigeaht女pritadamrtntikcaam addition of nucleophilic carbon compounds to carbonyl groups」 8-9 ule and ically"plan"its synthesis using sequences of several reactions. Keys to the Chapter 8-1and8-2. Nomenclature and Physical Properties Second,there is an order of precedence when there are two or more different functio onal groups in a mole cule.Thi CI OH CH CHCH-CHCH: OH the ring. The physical properties of alcohols are strongly influenced by the hydrogen bonding ability of the OH group.Asn the hydroxy hydrogen in an hol and a lone panr on a
Keys to the Chapter • 133 Outline of the Chapter 8-1 Nomenclature A description of both systematic and common naming systems for these very common molecules. 8-2 Physical Properties A new factor is introduced: hydrogen bonding. 8-3 Acidity and Basicity of Alcohols Similarities and differences with water, the simplest inorganic relative. 8-4 Industrial Preparation of Alcohols A brief survey of methods for the preparation of commercially useful alcohols. 8-5 Synthesis of Alcohols by Nucleophilic Substitution 8-6 Oxidation and Reduction Alcohols and carbonyl compounds are interconverted in oxidation–reduction processes, opening up many synthetic possibilities. 8-7 Organometallic Reagents A detour, introducing compounds containing negatively polarized, nucleophilic carbon atoms. 8-8 Organometallic Reagents in the Synthesis of Alcohols The most important general alcohol syntheses: addition of nucleophilic carbon compounds to carbonyl groups. 8-9 An Introduction to Synthetic Strategy How to look at a “target” molecule and logically “plan” its synthesis using sequences of several reactions. Keys to the Chapter 8-1 and 8-2. Nomenclature and Physical Properties Two points need to be made concerning nomenclature. First, alcohols have been around for a long time, and the common names given in this section are still in widespread use and need to be learned and understood. Second, there is an order of precedence when there are two or more different functional groups in a molecule. This precedence order determines the numbering. The alcohol group is of fairly high ranking on this list, whereas halogens are near the bottom. So, The physical properties of alcohols are strongly influenced by the hydrogen bonding ability of the OH group. As in water, the hydroxy hydrogen in an alcohol and a lone pair on a highly electronegative atom (typically F, O, or N) can participate in an unusually strong form of dipole–dipole (electrostatic) interaction. Although much weaker than an ordinary covalent bond, this effect may be worth several kcal mol1 and is Cl Br OH This compound is 4-bromo-2-chlorocyclopentanol. Note that the OH is understood to be attached to carbon 1 in the ring. Cl OH CH3CHCH2CHCH3 This compound is 4-chloro-2-pentanol (not 2-chloro-4-pentanol). 1559T_ch08_132-147 10/30/05 11:59 Page 133
1559T_ch08_132-14710/30/0511:59Pa9e134 ⊕ EQA 134.Chapter 8 HYDROXY FUNCTIONAL GROUP:ALCOHOLS:PROPERTIES,PREPARATION,AND STRATEGY OF SYNTHESIS onge han any other dipole-dipole attraction.which is why it merits the special name ydroger CH3 CHs 08- dimcylche Remember.the requireme y elec tract them 8-3.Acidity and Basicity of Alcohols If you understa the acidic and basic nature of water,then you will need to leam only a little bit that is new here with alcohols.The equilibrium processes are qualitatively similar: H0+H20H0 As a ROH RO The differences arise from the presence of the R group (instead of an H).which can affect the relative stabil- n substituents in R(such as halogens) will stabilize RO，however,there y making ROH a stronger acid(see entries in Table 8-2). The acidity and n many or their re hen an alcohol d i ts as an cid and loses a proton,it be .a good nucleophile and strong base capable ceaterimgint 2 and SN reaction of alcohols coming up later. 85 Synthesis of Alcohols by Nucleop philic subs be prepared by 2displacement reactions of HOth appropriate substrates (.gprima haloalkanes).This approach sor netimes work secondar but elir n often inter eres.To phile.However.the chemistr n the ofhe c vid much more versatile and reliable means of synthesizing alcohols. nd Redu ecursors (starting materials)for the synthe The same process converts ketones to secondary alcohol
much stronger than any other dipole–dipole attraction, which is why it merits the special name hydrogen bonding. Remember, the requirements for hydrogen bonding are hydrogens, such as those attached to very electronegative atoms (e.g., N, O, F), and electronegative atoms with lone pairs (again, mainly N, O, and F) to attract them. 8-3. Acidity and Basicity of Alcohols If you understand the acidic and basic nature of water, then you will need to learn only a little bit that is new here with alcohols. The equilibrium processes are qualitatively similar: The differences arise from the presence of the R group (instead of an H), which can affect the relative stabilities of the three species involved. Simple alkyl groups generally destabilize both ROH2 and RO in solution, relative to ROH, more than H3O and OH are destabilized, relative to water. So most ordinary alcohols are both weaker acids and weaker bases than water. Electron-withdrawing substituents in R (such as halogens) will stabilize RO, however, thereby making ROH a stronger acid (see entries in Table 8-2). The acidity and basicity of alcohols will play major roles in many of their reactions. When an alcohol acts as a base and is protonated by a strong acid, becoming ROH2 , it then contains a good leaving group and is capable of both substitution and elimination reactions (Chapter 9). When an alcohol acts as an acid and loses a proton, it becomes RO, a good nucleophile and strong base capable of entering into E2 and SN2 reactions (Chapters 6 and 9). So this chemistry really serves as a general entry to the more extensive survey of reactions of alcohols coming up later. 8-5. Synthesis of Alcohols by Nucleophilic Substitution After a section on industrial methods, a review covering SN2 and SN1 routes to alcohols is presented. Primary alcohols may be prepared by SN2 displacement reactions of HO with appropriate substrates (e.g., primary haloalkanes). This approach sometimes works for secondary systems, but elimination often interferes. To a limited extent, both secondary and tertiary alcohols may be formed in SN1 reactions with water as the nucleophile. However, the chemistry described in the remainder of the chapter provides much more versatile and reliable means of synthesizing alcohols. 8-6. Oxidation and Reduction Carbonyl compounds such as ketones and aldehydes are useful precursors (starting materials) for the synthesis of alcohols. Reaction with the hydride reagents NaBH4 and LiAlH4 converts aldehydes to primary alcohols. The same process converts ketones to secondary alcohols. These hydride reductions are the first of many H3O H2O HO ROH2 ROH RO As a base (adds H) As an acid (loses H) O O CH3 CH3 CH3 CH3 O O O O H H H CH3 CH3 H CH3 CH3 Strong “hydrogen bonding” type dipole–dipole attractions in methanol Weak dipole–dipole attractions in dimethyl ether 134 • Chapter 8 HYDROXY FUNCTIONAL GROUP: ALCOHOLS: PROPERTIES, PREPARATION, AND STRATEGY OF SYNTHESIS 1559T_ch08_132-147 10/30/05 11:59 Page 134
1559Tch08132-14710/30/0511:59Page135 EQA Keyso the Chapter·135 examples that you will see of nucleophilic additions to the electrophilic carbons of carbonyl groups.This is to aldehydes and ketones.the reverse of reduction.Alcohol oxidation is very useful in that it produces a carbonyl group.the most important Cr(vD: icrom which ondary alcohols to ketones,but ov 8-7.Organometallic Reagents 0=N Alcohol Ether Nitrile dIf we were to seek a logicalns which od proce s.we would try to take find bine with ment to electronegative atoms,then carbons should result from attachment to electropositive atoms Metals are the most mntsso the way toget ophilic)carbon would be to attac tions are easy to do,and the reagents you get are very useful in synthesis.The R groups in RLi and RMgX R”+ H →RH Weak acid 8-8.Organometallic Reagents in the Synthesis of Alcohols We now come to the primary value of these reagents:their ability to react as nucleophiles toward the el trophilic carbon in carbonyl compounds (C=O).In a reaction mechanistically analogous to the hydride you 8-9.An Introduction to Synthetic Strategy In order to learn how to levise sen e the pro n systen 1.Reactions CH:I+NaOH→CHOH+Nal
Keys to the Chapter • 135 examples that you will see of nucleophilic additions to the electrophilic carbons of carbonyl groups. This is one of the most important classes of reactions in organic chemistry. The second part of this text section introduces the oxidation of alcohols to aldehydes and ketones, the reverse of reduction. Alcohol oxidation is very useful in that it produces a carbonyl group, the most important functional group of all. Note the two types of reagents based on Cr(VI): PCC (pyridinium chlorochromate, pyH CrO3Cl), which is specifically intended for oxidation of primary alcohols to aldehydes, and aqueous dichromate, which oxidizes secondary alcohols to ketones, but overoxidizes 1° alcohols to carboxylic acids. With these aspects of alcohol preparation and chemistry as background, we now turn to a discussion of molecules that will greatly expand our ability to make bonds: compounds with nucleophilic carbon atoms. 8-7. Organometallic Reagents So far the only kind of polarized carbons we’ve looked at in any detail is the (electrophilic) carbon that results from its attachment to a very electronegative atom: If we were to seek a logical way to link two carbon atoms in a synthetic process, we would try to take advantage of electrostatics and find molecules with carbons, which could combine with the carbons above. That’s very nice, but where can we find carbon atoms? Logically, if carbons result from attachment to electronegative atoms, then carbons should result from attachment to electropositive atoms. Metals are the most electropositive elements, so the way to get a (nucleophilic) carbon would be to attach it to a metal. Compounds with carbon–metal bonds are called organometallic compounds and are sources of nucleophilic carbons. This section describes the preparations of some organometallic compounds. These reactions are easy to do, and the reagents you get are very useful in synthesis. The R groups in RLi and RMgX also act as very strong bases. They are protonated by even weak acids like water or ammonia, giving the hydrocarbon RH as the product: 8-8. Organometallic Reagents in the Synthesis of Alcohols We now come to the primary value of these reagents: their ability to react as nucleophiles toward the electrophilic carbon in carbonyl compounds In a reaction mechanistically analogous to the hydride additions of Section 8-6, organometallic reagents add nucleophilic carbon to aldehydes and ketones, resulting in alcohols, and making a new carbon–carbon bond in the process. At the end of the next section, you will find a summary chart of the major types of reactions that convert carbonyl compounds to alcohols. 8-9. An Introduction to Synthetic Strategy In order to learn how to devise sensible ways to make large organic molecules from small ones (a typical task of synthesis), you need to approach the problem systematically. First, note that the reactions you are learning can be classified into two categories: 1. Reactions that exchange one functional group for another but do not make or break any carbon–carbon bonds. These are called functional group interconversions, and a simple example is CH3I NaOH n CH3OH NaI C O). ( “H “R ” ” RH From even weakly Weak acid acidic molecules (e.g., H2O, ROH, NH3) Strong base (as in ROM) C X C O Haloalkane C OH Alcohol C OR Ether Carbonyl C N Nitrile 1559T_ch08_132-147 10/30/05 11:59 Page 135
1559T_ch08_132-14710/30/0511:59Pa9e136 ⊕ EQA 136.Chapter 8 HYDROXY FUNCTIONAL GROUP:ALCOHOLS:PROPERTIES,PREPARATION,AND STRATEGY OF SYNTHESIS 2.Reac carbon-carbon bonds.In the text Section8 you saw several very typical Next,you sh ould draw a chart of the general functional group interconversions that we've seen so far.This is how it would look at the moment: Functional Group Interconversion Haloalkanes Lots of other things Carbonyl compounds we see immediately thate have no direct method for alkanes to alcohols.We must first make CH3OH No direct method Note that it is not enough to use the general labels"radical halogenation"or"S2 reaction"in the synthesis have o e given paper,imagining disconneeting bonds in the desired product molecule.looking for methods that can put carbon-carbon bond-f orming reaction you've had so far-addition of Grignard reagents to carbonyl com- es of ev Alcohols with Oxidation Aldehyde or ketone New alcohol with n carbons with n carbons n+m carbons
136 • Chapter 8 HYDROXY FUNCTIONAL GROUP: ALCOHOLS: PROPERTIES, PREPARATION, AND STRATEGY OF SYNTHESIS 2. Reactions that make or break carbon–carbon bonds. In the text Section 8-8 you saw several very typical examples of this kind of reaction. There are transformations that overlap the two categories (for instance, SN2 reactions with cyanide), but let’s just keep things simple for now. Next, you should draw a chart of the general functional group interconversions that we’ve seen so far. This is how it would look at the moment: It is absolutely necessary to know these interconversion patterns, because they provide the framework for designing synthetic strategy. Suppose we wish to synthesize an alcohol starting with an alkane. From this chart, we see immediately that we have no direct method for converting alkanes to alcohols. We must first make a haloalkane and then use it in another reaction to make an alcohol. We set up the proposed synthesis in just that way and insert the specific reagents necessary to carry out the two synthetic steps: Note that it is not enough to use the general labels “radical halogenation” or “SN2 reaction” in the synthesis equations; the actual reagents have to be given. All right. What about carbon–carbon bond-forming reactions? Syntheses requiring the formation of new bonds are best approached via the retrosynthetic analysis described in the text. One works backward on paper, imagining disconnecting bonds in the desired product molecule, looking for methods that can put together the necessary bonds in an efficient way from reasonable starting molecules. Functional group interconversions are applied as necessary. Notice that by combining the oxidation of alcohols with the one main carbon–carbon bond-forming reaction you’ve had so far—addition of Grignard reagents to carbonyl compounds to make alcohols—you can now assemble pretty big molecules via synthetic schemes of several steps. The key is the following sequence, made possible by the capability to oxidize alcohols to carbonyl compounds: Take some time to look over the examples in the text. Note the preferability of some routes over others, based on efficient incorporation of small molecules into large ones. Finally, apply the techniques to the probOxidation Addition of Grignard with m Alcohols with carbons n carbons Aldehyde or ketone with n carbons New alcohol with n m carbons CH4 Cl2, hv HO CH4 CH3OH CH3Cl CH3OH No direct method A sensible synthesis Alkanes Haloalkanes Alcohols Carbonyl compounds Lots of other things Halogenation Reduction SN reactions SN reactions Alkenes E reactions Reduction reactions Oxidation reactions Functional Group Interconversions 1559T_ch08_132-147 10/30/05 11:59 Page 136
1559reh08132-14710/30/0511:59Pag0137 Solutions to Problems137 have to know them in the end Alsohol produst from reaction with NaBH,or LiAlH R"Li or R"MgX me H.OH RCH-OH) 1 (RCH OH) CHOH R R'-COH Solutions to Problems ⊕ 21.(a)2-Butanol.2 (b)5-Bromo-3-hexanol,2 (c)2-Propy1-1-pentanol,1 (d)(5)-1-Chloro-2-propanol,2 (e)1-Ethylcyclobutanol,3 (f)(IR,2R)-2-Bromocyclodecanol,2 (h)meso-1.2.3.4-Butanetetraol,1 on CI and C4.2 on C2 and C3 (i)(IR.2R)-2-(2-Hydroxyethyl)cyclopentanol.2 on ring.1 on side chain (j)(R)-2-Chloro-2-methyl-1-butanol1 22.(a)(CHa)SiCHCH2OH △Y% OH CH(CH3)z CH.CH,CH (e)CHCHOHCHCH2CH2CHs (d)H--OH CH, (e) 〉-OH Br Br (b)2-Heptanol >2-methyl-2-hexanol >2.3-dimethyl-2-pentanol (branching)
Solutions to Problems • 137 lems that follow. The practice will not only help you develop and improve your ability to analyze synthesis problems, it will also help you become more and more familiar with all the reactions and reagents. You will have to know them in the end. SUMMARY CHART Synthesis of alcohols from carbonyl compounds Alcohol product from reaction with Carbonyl compounds NaBH4 or LiAlH4 R''Li or R''MgX Formaldehyde methanol 1° alcohol (HCHO) (CH3OH) (R''CH2OH) Aldehyde 1° alcohol (RCHO) (RCH2OH) Solutions to Problems 21. (a) 2-Butanol, 2° (b) 5-Bromo-3-hexanol, 2° (c) 2-Propyl-1-pentanol, 1° (d) (S)-1-Chloro-2-propanol, 2° (e) 1-Ethylcyclobutanol, 3° (f ) (1R,2R)-2-Bromocyclodecanol, 2° (g) 2,2-Bis(hydroxymethyl)-1,3-propanediol, 1° [“Bis” is used as the prefix instead of “di” when the name that follows is complicated enough to be in parentheses.] (h) meso-1,2,3,4-Butanetetraol, 1° on C1 and C4, 2° on C2 and C3 (i) (1R,2R)-2-(2-Hydroxyethyl)cyclopentanol, 2° on ring, 1° on side chain (j) (R)-2-Chloro-2-methyl-1-butanol, 1° 22. (a) (CH3)3SiCH2CH2OH (b) CH(CH3)2 CH2CH2CH3 A (c) CH3CHOHCHCH2CH2CH3 (d) HOOOH CH3 (e) 23. (a) Cyclohexanol chlorocyclohexane cyclohexane (polarity) (b) 2-Heptanol 2-methyl-2-hexanol 2,3-dimethyl-2-pentanol (branching) OH Br Br CH3 OH COH R R R 3 alcohol CHOH R R 2 alcohol CO R R Ketone CHOH R R 2 alcohol 1559T_ch08_132-147 10/30/05 11:59 Page 137
1559T_ch08_132-14710/30/0511:59Pa9e138 ⊕ EQA 138.Chapter 8 HYDROXY FUNCTIONAL GROUP:ALCOHOLS:PROPERTIES,PREPARATION,AND STRATEGY OF SYNTHESIS (b)Solubility decreases as the relative size of the nonpolar portion of a molecule increases. 25.Intram shown at right H a H So th ethanol should be more like that of 1.-ethanedio than 1.2-dichlorocthanc.in which hydrogen bonding is absent. H 26.(a)The diequatorial conformation of the diol is shown below.left.It is stabilized in two ways.relative form.First.the OH groups are larger than- andhcrcforc,stcnicsfa rs the ormation to form an internal hydre ().The of this conformation is further lowered by the strength of this hydrogen bond.about 2 keal mol- awi9teasa ()hof the dio in part (a)hodcnt icqutrilrin rale this point,re H osS92 OSi[CH(CH3)2ls Diequatorial OSi[CH(CHa)2 OSi[CH(CH3)2]s CH(CHs) H os OSi[CH(CH3)2l Diaxial
138 • Chapter 8 HYDROXY FUNCTIONAL GROUP: ALCOHOLS: PROPERTIES, PREPARATION, AND STRATEGY OF SYNTHESIS 24. (a) Ethanol hydrogen bonds to water. Chloroethane is attracted to water by dipole forces. Ethane is nonpolar and attracted least to water. (b) Solubility decreases as the relative size of the nonpolar portion of a molecule increases. 25. Intramolecular hydrogen bonding stabilizes the gauche conformation of 1,2-ethanediol, shown at right, but not the anti form. In 2-chloroethanol, similar hydrogen bonding can occur (although it is weaker because of poorer overlap between the large Cl 3p lone pair orbital with the small hydrogen): So the conformational ratio of 2-chloroethanol should be more like that of 1,2-ethanediol than 1,2-dichloroethane, in which hydrogen bonding is absent. 26. (a) The diequatorial conformation of the diol is shown below, left. It is stabilized in two ways, relative to the diaxial form. First, the OOH groups are larger than OH, and therefore sterics favors the diequatorial. Second, the two hydroxy groups are close enough in the trans-1,2-diequatorial conformation to form an internal hydrogen bond (below, right). The energy of this conformation is further lowered by the strength of this hydrogen bond, about 2 kcal mol1 . (b) As the models of the diol in part (a) show, adjacent diequatorial substituents are in rather close proximity. A Newman projection view further illustrates this point, revealing that the groups are in a gauche relationship. Replacement of the two hydroxy hydrogens with very bulky silyl groups makes the diequatorial form less stable than the diaxial, because the 1,2-silyl-silyl steric interference is greater than the alternative, two pairs of 1,3-silyl-hydrogen diaxial interactions. In addition, with the hydrogens gone from the oxygen atoms no hydrogen bonding is possible to help lower the energy of the diequatorial form. Compare the structures: Diequatorial Diaxial OSi[CH(CH3)2]3 H OSi[CH(CH3)2]3 H H H H H H H OSi[CH(CH3)2]3 OSi[CH(CH3)2]3 OSi[CH(CH3)2]3 OSi[CH(CH3)2]3 H H H OSi[CH(CH3)2]3 OSi[CH(CH3)2]3 H H H O O H H H OH OH H trans-1,2-Cyclohexanediol (both _ OH groups equatorial) O H H H H H Cl O H H H H H HO 1559T_ch08_132-147 10/30/05 11:59 Page 138
1559Tch08132-14711/03/0518:42Page139 EQA Solutions to Problems139 27.Three factors are involved:the elctrogativity of the elctron-withdrawing atoms how many there are,and their distance from the hydroxy group. (a)CH CHCICH OH>CH CHBICHOH>BrCH,CH,CH OH (b)CCl,CH,OH>CH,CCICH,OH>(CH)CCICH,OH (e)(CF3)2CHOH>(CCl)CHOH>(CH)CHOH 28.()(CH,)CHOH (CHs)CHOHs (CH3)CHO- 2-Propanol is botha weaker acid and a weaker base than methanol (Tables8-2 and 8-3) ()CH.CHFCHOHCH,CHFCH,OH CH.CHFCHO- 29.(a)Halfwa b)pH-2.2(cpH+15.5 ⊕ on oxygen in alkyloxonium ions:therefore such overlap is not possible. 31.(a)Worthless.H is a very poor nucleophile in S2 reactions (b)Good.Excellent Sx2 reaction-CH,attached to sulfonate leaving group (c)Not so good.Bases give much elimination with 2 haloalkanes. (d)Good,but slow,viaan S mechanism. (e)Worthless.-CN isa bad leaving group. (f)Worthless.OCH,isa bad leaving group (g)Good.S first step. (h)Not so good.Branching reduces S2 reactivity.and E2occurs. 32.(a)CH,CH:CHOHCH (b)CH,CHOHCH-CH.CHOHCHs -CH2OH CH; (e)(CH3)CH From addition of hydride to less sterically hindered (bottom)face of ring
Solutions to Problems • 139 27. Three factors are involved: the electronegativity of the electron-withdrawing atoms, how many there are, and their distance from the hydroxy group. (a) CH3CHClCH2OH CH3CHBrCH2OH BrCH2CH2CH2OH (b) CCl3CH2OH CH3CCl2CH2OH (CH3)2CClCH2OH (c) (CF3)2CHOH (CCl3)2CHOH (CH3)2CHOH 28. (a) 2-Propanol is both a weaker acid and a weaker base than methanol (Tables 8-2 and 8-3). (b) (c) The last two alcohols are both stronger acids and weaker bases than methanol. In each, the alkoxide is stabilized and the alkyloxonium ion destabilized by the electronegative halogens. 29. (a) Halfway between the two pKa values: pH 6.7. (Compare H2O: At pH 7, equal amounts of H3O and HO are present.) (b) pH 2.2 (c) pH 15.5 30. No. Recall that stabilization of carbocations by hyperconjugation involves overlap between a bonding hybrid orbital and an empty p orbital on carbon (Section 7-5). There aren’t any empty p orbitals on oxygen in alkyloxonium ions; therefore such overlap is not possible. 31. (a) Worthless. H2O is a very poor nucleophile in SN2 reactions. (b) Good. Excellent SN2 reaction—CH3 attached to sulfonate leaving group. (c) Not so good. Bases give much elimination with 2° haloalkanes. (d) Good, but slow, via an SN1 mechanism. (e) Worthless. CN is a bad leaving group. (f ) Worthless. OCH3 is a bad leaving group. (g) Good. SN1 first step. (h) Not so good. Branching reduces SN2 reactivity, and E2 occurs. 32. (a) CH3CH2CHOHCH3 (b) CH3CHOHCH2CH2CHOHCH3 (c) (d) (e) From addition of hydride to less sterically hindered (bottom) face of ring (CH3)2CH CH3 OH H CH2OH CCl3CH2OH2 CCl3CH2OH CCl3CH2O H HO, (–H ) CH3CHFCH2OH2 CH3CHFCH2OH CH3CHFCH2O H HO, (–H ) (CH3)2CHOH2 (CH3)2CHOH (CH3)2CHO As a base, add H As an acid, add HO 1559T_ch08_132-147 11/03/05 18:42 Page 139
1559T_ch08_132-14710/30/0511:59Pa9e140 ⊕ EQA 140.Chapter 8 HYDROXY FUNCTIONAL GROUP:ALCOHOLS:PROPERTIES,PREPARATION,AND STRATEGY OF SYNTHESIS eric interf redominant alcohol diastereome 33.To the right.H2 is a weaker acid than HO,and HO-is a weaker base than H- 34.(a)CH:CHDOH (b)CH,CHOD.from reaction of CH,CH2O with D' 假2 eiae,D, MgCI 35.(a)CHa(CH2)sCHCHs (b)CH:(CH2)sCHDCH ⊕ .0 (e)CHaCH2CH2MgCI 《 -CH2CH2CHs CH Li OHOH (h)CH;CCH2CH2CCH3 ◇◇ 37.Only the co wil Grignard reagent that forms:similarly,the terminal hydrogen on the alkyne function in (e)is acidic is about 25,alth em 4 not a problem,because it does not contain any acidic hydrogen atoms
140 • Chapter 8 HYDROXY FUNCTIONAL GROUP: ALCOHOLS: PROPERTIES, PREPARATION, AND STRATEGY OF SYNTHESIS (f ) Make a model. Here the main steric interference with hydride addition is by the axial hydrogens on the “top” side of the ring in the chair conformation: 33. To the right. H2 is a weaker acid than H2O, and HO is a weaker base than H. 34. (a) CH3CHDOH (b) CH3CH2OD, from reaction of CH3CH2O with D (c) CH3CH2D, from SN2 reaction. (LiAlD4 serves as a source of “deuteride” nucleophile, D, just as LiAlH4 is a source of hydride nucleophile, H.) MgCl A 35. (a) CH3(CH2)5CHCH3 (b) CH3(CH2)5CHDCH3 (c) (d) (e) CH3CH2CH2MgCl (f ) (g) (h) 36. The desired reaction is CH3MgI C6H5CHO n CH3CH(OH)C6H5, a synthesis of a secondary alcohol by addition of a Grignard reagent to an aldehyde. The unexpected and undesired side reaction is the addition of methylmagnesium iodide to acetone: CH3MgI CH3COCH3 n (CH3)3COH, forming 2-methyl-2-propanol (tert-butyl alcohol). 37. Only the compounds pictured in parts (a) and (c) will form Grignard reagents in a problem-free manner. In (b) the OOH group contains an acidic hydrogen that will destroy the carbon–metal bond of any Grignard reagent that forms; similarly, the terminal hydrogen on the alkyne function in (e) is acidic enough to do the same (the pKa is about 25, although all you need to know—from the information in Problem 42 of Chapter 1Ois that such hydrogens are much more acidic than hydrogens on alkane carbons). Finally, in (d) the carbonyl function contains a strongly electrophilic carbon and will interfere. The ether function in (c) is not a problem, because it does not contain any acidic hydrogen atoms. OH OH CH3CCH2CH2CCH3 Li CH2CH2CH3 CH3 OH C HO Li H H H H H H O H HO H H H Less hindered Predominant alcohol diastereomer Hindered 1559T_ch08_132-147 10/30/05 11:59 Page 140
1559reh09.132-14710/30/0511:59Page141 Solutions to Problems141 38.Products after hydrolysis are given. (a)CH.OH (c)C.H,CH,CHOHC.Hs e○一CHOHCHCH,ct 39.a) MgBr H0:一-aH-"MeBe n H、 CH2-OH HO-'MgB (b) (CHs)CHCH,∠MgC (CH)2CHCH2-CH-OH +HO-+MgCI C.H,CH ZLi cr令一clct-q-hm CoH CH2-CH-OH HO-+Li (CH)CH-MgCI 一(CH6hCH、:+MeBr n (CHa)zCH、H +HO-+MgBr
Solutions to Problems • 141 38. Products after hydrolysis are given. (a) (b) (CH3)2CHCH2CHOHCH3 (c) C6H5CH2CHOHC6H5 (d) (e) 39. (a) (b) (c) (d) O O MgCl MgBr (CH3)2CH (CH3)2CH OH HO MgBr (CH3)2CH H OH C6H5CH2 Li C O C6H5CH2 H C6H5 C6H5 O Li CH C6H5CH2 C6H5 OH HO CH Li H OH (CH3)2CHCH2 MgCl (CH3)2CHCH2 CH3 C O H CH3 O MgCl CH (CH3)2CHCH2 CH3 OH HO CH MgCl H OH MgBr C CH2 The C—Mg bond is source of the nucleophilic electron pair O H H O MgBr CH2 OH HO MgBr H OH CHOHCH(CH2CH3)2 CH(CH3)2 OH CH2OH 1559T_ch08_132-147 10/30/05 11:59 Page 141
