374 ALCOHOLS, DIOLS AND proceed by elimination rather than by substitution. The first step in thee hydroxide will will fail because the reaction of 2-bromo-2-methylpropane with potassium ocess. selective bromination of 2-methylpropane to 2-bromo-2-methylpropane, is satisfactory because bromi- nation is selective for substitution of tertiary hydrogens in the presence of secondary and pri- (c) Benzyl alcohol, unlike 1-butanol and 2-methyl-2-propanol, can be prepared effectively by this method CH,Br-KOH CHOH Toluene Benzyl bromide Benzyl alcohol Free-radical bromination of toluene is selective for the benzylic position. Benzyl bromide can- not undergo elimination, and so nucleophilic substitution of bromide by hydroxide will work well (d) The desired transformation CHCH phenylethanol ils because it produces more than one enantiomer. The reactant ethylbenzene is achiral and although its bromination will be highly regioselective for the benzylic position, the product will be a racemic mixture of (R) and(S)-l-bromo-l-phenylethane The alcohol produced by hydrolysis will also be racemic. Furthermore, the hydrolysis step will give mostly styrene by an E2 elimination, rather than 1-phenylethanol by nucleophilic substitution. 15.22 Glucose contains five hydroxyl groups and an aldehyde functional group. Its hydrogenation will not affect the hydroxyl groups but will reduce the aldehyde to a primary alcohol. OHOH O H2(120 OHOH Glucose Sorbitol 15.23 (a) 1-Phenylethanol is a secondary alcohol and so can be prepared by the reaction of a grignard reagent with an aldehyde. One combination is phenylmagnesium bromide and ethanal acetaldehyde) C6HSCHCH3 C6Hs Mg Br HCCH3 bromide un Ethanal Back Forward Main Menu TOC Study Guide Toc Student OLC MHHE Website
(b) The suggested synthesis will fail because the reaction of 2-bromo-2-methylpropane with potassium hydroxide will proceed by elimination rather than by substitution. The first step in the process, selective bromination of 2-methylpropane to 2-bromo-2-methylpropane, is satisfactory because bromination is selective for substitution of tertiary hydrogens in the presence of secondary and primary ones. (c) Benzyl alcohol, unlike 1-butanol and 2-methyl-2-propanol, can be prepared effectively by this method. Free-radical bromination of toluene is selective for the benzylic position. Benzyl bromide cannot undergo elimination, and so nucleophilic substitution of bromide by hydroxide will work well. (d) The desired transformation fails because it produces more than one enantiomer. The reactant ethylbenzene is achiral and although its bromination will be highly regioselective for the benzylic position, the product will be a racemic mixture of (R) and (S)-1-bromo-1-phenylethane. The alcohol produced by hydrolysis will also be racemic. Furthermore, the hydrolysis step will give mostly styrene by an E2 elimination, rather than 1-phenylethanol by nucleophilic substitution. 15.22 Glucose contains five hydroxyl groups and an aldehyde functional group. Its hydrogenation will not affect the hydroxyl groups but will reduce the aldehyde to a primary alcohol. 15.23 (a) 1-Phenylethanol is a secondary alcohol and so can be prepared by the reaction of a Grignard reagent with an aldehyde. One combination is phenylmagnesium bromide and ethanal (acetaldehyde). C6H5CHCH3 C6H5MgBr OH 1-Phenylethanol Phenylmagnesium bromide HCCH3 O Ethanal (acetaldehyde) H2 (120 atm) Ni, 140C HO OH OH O OH OH H Glucose HO OH OH OH OH OH Sorbitol Br2 light or heat KOH CH2CH3 Ethylbenzene CHCH3 Br 1-Bromo-1-phenylethane CHCH3 OH 1-Phenylethanol Br2 light or heat KOH CH3 Toluene CH2Br Benzyl bromide CH2OH Benzyl alcohol Br2 light or heat KOH (CH3)3CH 2-Methylpropane (CH3)3CBr 2-Bromo-2- methylpropane (CH3)3COH 2-Methyl-2- propanol 374 ALCOHOLS, DIOLS, AND THIOLS Back Forward Main Menu TOC Study Guide TOC Student OLC MHHE Website
ALCOHOLS. DIOLS AND THIOLS 375 Grignard reagents-phenylmagnesium bromide in this case--are always prepared by reaction of magnesium metal and the corresponding halide. Starting with bromobenzene, a suitable synthesis is described by the sequence cB: CH, MgBr… C,HS,CHCH1 Bromobenzene bromide (b An alternative disconnection of 1-phenylethanol reveals a second route using benzaldehyde d a methyl grignard reagent CH CHCH □>ccm+cmMg Equations representing this approach are ChI diethyl ether CH3Mgl CsH-CHCH 1-Phenylethanol c) Aldehydes are, in general, obtainable by oxidation of the corresponding primary alcohol By recognizing that benzaldehyde can be obtained by oxidation of benzyl alcohol with PCC C6HSCH,OH CC→CH2 1. CH, Mgl, diethyl ether 2.H2O C6HSCHCH3 Benzyl alcohol 1-Phenylethanol (d) The conversion of acetophenone to 1-phenylethanol is a reduction CCH educing agent C6HSCHCH OH Acetophenone 1-Phenylethanol Any of a number of reducing agents could be used. These include 1. NaBH4, CH,OH 2. LiAIH, in diethyl ether, then H,O 3. H, and a Pt, Pd, Ni, or Ru catalyst Back Forward Main Menu TOC Study Guide Toc Student OLC MHHE Website
ALCOHOLS, DIOLS, AND THIOLS 375 Grignard reagents—phenylmagnesium bromide in this case—are always prepared by reaction of magnesium metal and the corresponding halide. Starting with bromobenzene, a suitable synthesis is described by the sequence (b) An alternative disconnection of 1-phenylethanol reveals a second route using benzaldehyde and a methyl Grignard reagent. Equations representing this approach are (c) Aldehydes are, in general, obtainable by oxidation of the corresponding primary alcohol. By recognizing that benzaldehyde can be obtained by oxidation of benzyl alcohol with PCC, we write (d) The conversion of acetophenone to 1-phenylethanol is a reduction. Any of a number of reducing agents could be used. These include 1. NaBH4, CH3OH 2. LiAlH4 in diethyl ether, then H2O 3. H2 and a Pt, Pd, Ni, or Ru catalyst reducing agent Acetophenone O C6H5CCH3 1-Phenylethanol C6H5CHCH3 OH PCC CH2Cl2 Benzyl alcohol 1-Phenylethanol C6H5CH2OH C6H5CHCH3 OH 2. H3O 1. CH3MgI, diethyl ether Benzaldehyde C6H5CH O CH3I Iodomethane CH3MgI Methylmagnesium iodide Mg diethyl ether 1-Phenylethanol C6H5CHCH3 OH 2. H3O 1. C6H5CH O C6H5CHCH3 OH 1-Phenylethanol Benzaldehyde C6H5CH O CH3MgI Methylmagnesium iodide C C6H5MgBr 6H5Br Bromobenzene Phenylmagnesium bromide 1-Phenylethanol Mg diethyl ether 1. CH3CH 2. H3O C6H5CHCH3 OH O Back Forward Main Menu TOC Study Guide TOC Student OLC MHHE Website
376 ALCOHOLS, DIOLS, AND THIOLS ynthesis of 1-phenyl Friedel-Crafts acylation of benzene gives acetophenone, which can then be reduced as in Ch CCi Benzene Acetyl chloride Acetic anhydride(CH, COCCH3)can be used in place of acetyl chloride 15.24 2-Phenylethanol is an ingredient in many perfumes, to which it imparts a rose-like fragrance Numerous methods have been employed for its synthesis (a) As a primary alcohol having two more carbon atoms than bromobenzene, it can be formed by reaction of a Grignard reagent, phenylmagnesium bromide, with ethylene oxide. C,H,CH,CH,OH>C,H,MgBr+H,C-CH2 The desired reaction sequence is therefore C H-Br diethyl CH MgBr CsHSCH, CH,OH Bromobenzene Phenylmagnesium 2-Phenylethanol (b) Hydration of sytrene with a regioselectivity contrary to that of Markovnikov's rule is required This is accomplished readily by hydroboration-oxidation C,H,CH=CH, CBHSCHLCH,OH (c f aldehydes yields primary alcohols. C.,CH redu CH-CHCHOH Among the reducing agents that could be(and have been)used are 1. NaBH4, CH,OH 2. LiAlH4 in diethyl ether, then H,O 3. H, and a Pt, Pd, Ni, or Ru cataly (d)Esters are readily reduced to primary alcohols with lithium aluminum hydride 1. LiAlHr, diethyl ether C6H CH,COCH,CH 2.H,O C6HSCH,CH,OH Ethyl 2-phenylethanoate Back Forward Main Menu TOC Study Guide Toc Student OLC MHHE Website
(e) Benzene can be employed as the ultimate starting material in a synthesis of 1-phenylethanol. Friedel–Crafts acylation of benzene gives acetophenone, which can then be reduced as in part (d). Acetic anhydride can be used in place of acetyl chloride. 15.24 2-Phenylethanol is an ingredient in many perfumes, to which it imparts a rose-like fragrance. Numerous methods have been employed for its synthesis. (a) As a primary alcohol having two more carbon atoms than bromobenzene, it can be formed by reaction of a Grignard reagent, phenylmagnesium bromide, with ethylene oxide. The desired reaction sequence is therefore (b) Hydration of sytrene with a regioselectivity contrary to that of Markovnikov’s rule is required. This is accomplished readily by hydroboration–oxidation. (c) Reduction of aldehydes yields primary alcohols. Among the reducing agents that could be (and have been) used are 1. NaBH4, CH3OH 2. LiAlH4 in diethyl ether, then H2O 3. H2 and a Pt, Pd, Ni, or Ru catalyst (d) Esters are readily reduced to primary alcohols with lithium aluminum hydride. 1. LiAlH4, diethyl ether 2. H2O C6H5CH2COCH2CH3 C6H5CH2CH2OH Ethyl 2-phenylethanoate 2-Phenylethanol O reducing agent 2-Phenylethanol C6H5CH2CH2OH 2-Phenylethanal C6H5CH2CH O 1. B2H6, diglyme 2. H2O2, HO 2-Phenylethanol C6H5CH2CH2OH Styrene C6H5CH CH2 Mg diethyl ether H2C CH2 O 1. 2. H3O C6H5CH2CH2OH 2-Phenylethanol C6H5MgBr Phenylmagnesium bromide C6H5Br Bromobenzene C6H5CH2CH2OH C6H5MgBr H 2C CH2 O O O (CH3COCCH3) O CH3CCl Acetyl chloride AlCl3 Benzene Acetophenone O CCH3 376 ALCOHOLS, DIOLS, AND THIOLS Back Forward Main Menu TOC Study Guide TOC Student OLC MHHE Website