CHAPTER 15 ALCOHOLS DIOLS, AND THIOLS SOLUTIONS TO TEXT PROBLEMS 15.1 The two primary alcohols, 1-butanol and 2-methyl-1-propanol, can be prepared by hydrogenation of the corresponding aldehydes CHCHCH CH CH, CHCHCHO l-Butanol (CH3)2CHCH (CH3)2CHCH2OH The secondary alcohol 2-butanol arises by hydrogenation of a ketone CH3CCH, CH3 CH3 CHCH, CH3 Tertiary alcohols such as 2-methyl-2-propanol,(CH3)3COH, cannot be prepared by hydrogenation 15.2 (b) A deuterium atom is transferred from NaB D4 to the carbonyl group of acetone D-BD D 3(CH3)2C=0 →CH3C一OBD3 ICH CO H3 364 Back Forward Main Menu TOC Study Guide Toc Student OLC MHHE Website
CHAPTER 15 ALCOHOLS, DIOLS, AND THIOLS SOLUTIONS TO TEXT PROBLEMS 15.1 The two primary alcohols, 1-butanol and 2-methyl-1-propanol, can be prepared by hydrogenation of the corresponding aldehydes. The secondary alcohol 2-butanol arises by hydrogenation of a ketone. Tertiary alcohols such as 2-methyl-2-propanol, (CH3)3COH, cannot be prepared by hydrogenation of a carbonyl compound. 15.2 (b) A deuterium atom is transferred from NaBD4 to the carbonyl group of acetone. 3(CH3)2C O CH3C CH3 O D BD3 CH3CO CH3 D B 4 CH3C CH3 D OBD3 H2, Ni 2-Butanone CH3CCH2CH3 O 2-Butanol CH3CHCH2CH3 OH H2, Ni (CH3)2CHCH2OH 2-Methylpropanal 2-Methyl-1-propanol (CH3)2CHCH O H2, Ni CH3CH2CH2CH2OH Butanal 1-Butanol CH3CH2CH2CH O 364 Back Forward Main Menu TOC Study Guide TOC Student OLC MHHE Website
ALCOHOLS. DIOLS AND THIOLS 365 On reaction with CH,OD. deuterium is trar from the alcohol to the oxygen of CH),CDOJB CH3)23- CH3 COD+ B[OCD(CH,)2I3 CH3 D-OCH OCH NabDa (CH3)2C=0 CHOD( CH3)2COD Acetol 2-Propanol-2-d-O-d (c) In this case NaBDa serves as a deuterium donor to carbon, and CD,oh is a proton(not deu erium) donor to oxygen. O NaBDa C6HSCH CD,OH C6HSCHOH Benzyl alcohol (d) Lithium aluminum deuteride is a deuterium donor to the carbonyl carbon of formaldehyde D一AD3 HC-OAID 3HCH (CH,O)Al H H On hydrolysis with D,O, the oxygen-aluminum bond is cleaved and DCH,Od is formed. Al(OCH, D)4 4DCH,OD+ Al(OD) 15.3 The acyl portion of the ester gives a primary alcohol on reduction. The alkyl group bonded to oxy gen may be primary, secondary, or tertiary and gives the corresponding alcohol L. LIA CH3CH, COCH(CH3) CH, CH, CH,OH HOCH(CH,)2 Isopropyl propanoate 1-Propanol 2-Propanol 15.4(b) Reaction with ethylene oxide results in the addition of a-CH, CH,OH unit to the grignard reagent. Cyclohexylmagnesium bromide (or chloride)is the appropriate reagent. CH CHOH t h,c--CH, nexymagnesum Ethylene oxide 2-Cyclohexylethano 15.5 Lithium aluminum hydride is the appropriate reagent for reducing carboxylic acids or esters to L. LiAIHa HOCCHCHCHCOH HOCH, CH, CHCH, CH,OH CH Back Forward Main Menu TOC Study Guide Toc Student OLC MHHE Website
ALCOHOLS, DIOLS, AND THIOLS 365 On reaction with CH3OD, deuterium is transferred from the alcohol to the oxygen of [(CH3)2CDO]4B . Overall: (c) In this case NaBD4 serves as a deuterium donor to carbon, and CD3OH is a proton (not deuterium) donor to oxygen. (d) Lithium aluminum deuteride is a deuterium donor to the carbonyl carbon of formaldehyde. On hydrolysis with D2O, the oxygen–aluminum bond is cleaved and DCH2OD is formed. 15.3 The acyl portion of the ester gives a primary alcohol on reduction. The alkyl group bonded to oxygen may be primary, secondary, or tertiary and gives the corresponding alcohol. 15.4 (b) Reaction with ethylene oxide results in the addition of a @CH2CH2OH unit to the Grignard reagent. Cyclohexylmagnesium bromide (or chloride) is the appropriate reagent. 15.5 Lithium aluminum hydride is the appropriate reagent for reducing carboxylic acids or esters to alcohols. 1. LiAlH4 2. H2O 3-Methyl-1,5-pentanedioic acid 3-Methyl-1,5-pentanediol HOCCH2CHCH2COH O O CH3 HOCH2CH2CHCH2CH2OH CH3 1. diethyl ether 2. H3O Cyclohexylmagnesium bromide MgBr 2-Cyclohexylethanol CH2CH2OH Ethylene oxide H2C CH2 O 1. LiAlH4 2. H2O CH3CH2CH2OH Isopropyl propanoate 2-Propanol 1-Propanol HOCH(CH3) CH3CH2COCH(CH3 2 )2 O 4D2O Methanol-d-O-d 4DCH2OD Al(OD)4 Al(OCH2D)4 HC H O D AlD3 HC H D OAlD3 (DCH2O)4Al 3HCH O NaBD4 CD3OH Benzaldehyde C6H5CH O Benzyl alcohol-1-d C6H5CHOH D NaBD4 CH3OD (CH3)2C (CH3)2COD Acetone 2-Propanol-2-d-O-d O D CH3COD CH3 D CH3C CH3 D O B[OCD(CH3)2]3 D OCH3 OCH3 B[OCD(CH3)2]3 Back Forward Main Menu TOC Study Guide TOC Student OLC MHHE Website
366 ALCOHOLS, DIOLS. AND THIO Any alkyl group may be attached to the oxygen of the ester function. In the following example, it is a methyl group I LiANHe CH3OCCH, CHCH,COCH 2.H2O HOCHCHCHCHCHOH 2CH,, OH CH H3 Dimethyl 3-methyl-1, 5-pentanedioate 3-Methyl-1, 5-pentanediol Methanol 15.6 Hydroxylation of alkenes using osmium tetraoxide is a syn addition of hydroxyl groups to the dou- ble bond. cis-2-Butene yields the meso diol OsOa(CH:)COOH H3C CH3 H,C CH cis-2-Butene trans-2-Butene yields a racemic mixture of the two enantiomeric forms of the chiral diol OH H H3C OsO4(CH3),COOH H3C (2R, 3R).2, 3-Butanediol (2S, 3S)2,3-Butanediol The Fischer projection formulas of the three stereoisomers are CH HO-H H H3 H3 meso-2, 3-Butanediol (2R, 3R)-2 3-Butanediol (2S.3S)-2, 3-Butanediol 15.7 The first step is proton transfer to 1, 5-pentanediol to form the corresponding alkyloxonium ion HOCH2CH_CH_CH2CH2OH HT-OSO2OH HOCH2CHCH2CH,CH2一 OSO.OH 1. 5-Pentanediol Sulfuric acid Conjugate acid of 1, 5-pentanediol Hydrogen sulfate Rewriting the alkyloxonium ion gives H HQ一CH2CH2CH2CH2CH2O is equivalent to H Back Forward Main Menu TOC Study Guide Toc Student OLC MHHE Website
366 ALCOHOLS, DIOLS, AND THIOLS Any alkyl group may be attached to the oxygen of the ester function. In the following example, it is a methyl group. 15.6 Hydroxylation of alkenes using osmium tetraoxide is a syn addition of hydroxyl groups to the double bond. cis-2-Butene yields the meso diol. trans-2-Butene yields a racemic mixture of the two enantiomeric forms of the chiral diol. The Fischer projection formulas of the three stereoisomers are 15.7 The first step is proton transfer to 1,5-pentanediol to form the corresponding alkyloxonium ion. Rewriting the alkyloxonium ion gives HO is equivalent to CH2CH2CH2CH2CH2 O H H O H O H H HOCH2CH2CH2CH2CH2 OH 1,5-Pentanediol H OSO2OH Sulfuric acid OSO2OH Conjugate acid of 1,5-pentanediol Hydrogen sulfate HOCH2CH2CH2CH2CH2 O H H CH3 CH3 H HO H OH (2S,3S)-2,3-Butanediol CH3 CH3 HO H OH H (2R,3R)-2,3-Butanediol CH3 CH3 H H OH OH meso-2,3-Butanediol C C H3C H H CH3 trans-2-Butene OsO4, (CH3)3COOH (CH3)3COH, HO (2R,3R)-2,3-Butanediol (2S,3S)-2,3-Butanediol C HO OH C H3C H H CH3 HO OH C H H3C H3C H C C C H3C H CH3 H cis-2-Butene OsO4, (CH3)3COOH (CH3)3COH, HO meso-2,3-Butanediol C H3C CH3 H H HO OH C 1. LiAlH4 2. H2O HOCH2CH2CHCH2CH2OH Dimethyl 3-methyl-1,5-pentanedioate 3-Methyl-1,5-pentanediol CH3OCCH2CHCH2COCH3 O O CH3 CH3 2CH3OH Methanol Back Forward Main Menu TOC Study Guide TOC Student OLC MHHE Website
ALCOHOLS. DIOLS AND THIOLS 367 The oxonium ion undergoes cyclization by intramolecular nucleophilic attack of its alcohol function on the carbon that bears the leaving group HH H id of Loss of a proton gives oxane OSOOH + H-OSOOH H Conjugate acid Hydrogen Oxane Sulfuric acid 15.8(b) The relationship of the molecular formula of the ester(CioHgoo4) to that of the starting dicar boxylic acid(C& O4) indicates that the diacid reacted with 2 moles of methanol to form a O O 2CH OH HOC COH—CH2OC -COCH Methanol 1. 4-Benzenedicarboxylic acid Dimethyl 1. 4-benzenedicarboxylate 15.9 While neither cis- nor trans-4-tert-butylcyclohexanol is a chiral molecule, the stereochemical course of their reactions with acetic anhydride becomes evident when the relative stereochemist of the ester function is examined for each case. The cis alcohol yields the cis acetate. OH OCCH3 (CH3) CH.COCCH (CH3)3C cis-4-IerI-Butylcyclohexanol Acetic anhydride cis-4-tert-Butylcyclohexyl acetate The trans alcohol yields the trans acetate OH (CH3)C CH COCCI (CH3)2C~ trans-4-1ert-Butylcyclohexanol Acetic anhydride rrans-4-tert-Butylcyclohexyl acetate 15.10 Glycerol has three hydroxyl groups, each of which is converted to a nitrate ester function in nitro- glycerin 3HNO3 CHOH CHONO H,SO CHO CH,ONO Glycerol Back Forward Main Menu TOC Study Guide Toc Student OLC MHHE Website
ALCOHOLS, DIOLS, AND THIOLS 367 The oxonium ion undergoes cyclization by intramolecular nucleophilic attack of its alcohol function on the carbon that bears the leaving group. Loss of a proton gives oxane. 15.8 (b) The relationship of the molecular formula of the ester (C10H10O4) to that of the starting dicarboxylic acid (C8H6O4) indicates that the diacid reacted with 2 moles of methanol to form a diester. 15.9 While neither cis- nor trans-4-tert-butylcyclohexanol is a chiral molecule, the stereochemical course of their reactions with acetic anhydride becomes evident when the relative stereochemistry of the ester function is examined for each case. The cis alcohol yields the cis acetate. The trans alcohol yields the trans acetate. 15.10 Glycerol has three hydroxyl groups, each of which is converted to a nitrate ester function in nitroglycerin. CH2ONO2 CHONO2 CH2ONO2 Nitroglycerin CH2OH CHOH CH2OH Glycerol 3HNO3 H2SO4 (CH3)3C OH trans-4-tert-Butylcyclohexanol CH3COCCH3 O O Acetic anhydride (CH3)3C OCCH3 O trans-4-tert-Butylcyclohexyl acetate (CH3)3C OH cis-4-tert-Butylcyclohexanol CH3COCCH3 O O Acetic anhydride (CH3)3C OCCH3 O cis-4-tert-Butylcyclohexyl acetate HOC COH O O H 2CH3OH Methanol 1,4-Benzenedicarboxylic acid CH3OC COCH3 O O Dimethyl 1,4-benzenedicarboxylate O Oxane O H Conjugate acid of oxane OSO2OH Hydrogen sulfate Sulfuric acid H OSO2OH H2O O H O H O H Conjugate acid of 1,5-pentanediol Conjugate acid of oxane Water H Back Forward Main Menu TOC Study Guide TOC Student OLC MHHE Website
368 ALCOHOLS, DIOLS AND THIOLS 15.11 (b) The substrate is a secondary alcohol and so gives a ketone on oxidation with sodium dichro mate.2-Octanone has been prepared in 92-96%o yield under these reaction conditions CH3 CH(CH2)_CH3 H( Na2C2→CH3C(CH2)CH OH 2-Octanol 2-Octanone (c) The alcohol is primary, and so oxidation can produce either an aldehyde or a carboxylic acid, depending on the reaction conditions. Here the oxidation is carried out under anhydrous condi tions using pyridinium chlorochromate(PCC), and the product is the corresponding aldehyde CHaCHCH,CH, CH,CH,CH,OH CHaCH,CH,CH,,,CH Heptanal 15.12 (b) Biological oxidation of CH,CD,OH leads to loss of one of the C-1 deuterium atoms to NAD The dihydropyridine ring of the reduced form of the coenzyme will bear a single deuterium CNH alcohol CNH CH CD.OH+ - Ch cd+ L.I-Dideuterio- NAD 1-Deuterio NADD ethanal (c) The deuterium atom of CHa CH,OD is lost as D. The reduced form of the coenzyme contains no deuterium CNH, alcohol CNH, CH CHOD CHCH D Ethanol-O-d NAD Ethanal NADH 15.13 (b) Oxidation of the carbon-oxygen bonds to carbonyl groups accompanies their cleav (CH3)2CHCHCH--CHCH,C6H5 HIO:(CH ),CHCH CH+ HCCH2C6H5 I-Phenyl-5-methyl-2, 3-hexanediol 3-Methylbutanal 2-Phenylethanal (c) The Ch,OH group is cleaved from the ring as formaldehyde to leave cyclopentanone O 0+ HCH CHOH Back Forward Main Menu TOC Study Guide Toc Student OLC MHHE Website
15.11 (b) The substrate is a secondary alcohol and so gives a ketone on oxidation with sodium dichromate. 2-Octanone has been prepared in 92–96% yield under these reaction conditions. (c) The alcohol is primary, and so oxidation can produce either an aldehyde or a carboxylic acid, depending on the reaction conditions. Here the oxidation is carried out under anhydrous conditions using pyridinium chlorochromate (PCC), and the product is the corresponding aldehyde. 15.12 (b) Biological oxidation of CH3CD2OH leads to loss of one of the C-1 deuterium atoms to NAD. The dihydropyridine ring of the reduced form of the coenzyme will bear a single deuterium. (c) The deuterium atom of CH3CH2OD is lost as D. The reduced form of the coenzyme contains no deuterium. 15.13 (b) Oxidation of the carbon–oxygen bonds to carbonyl groups accompanies their cleavage. (c) The CH2OH group is cleaved from the ring as formaldehyde to leave cyclopentanone. HIO4 OH CH2OH 1-(Hydroxymethyl)- cyclopentanol O Cyclopentanone O HCH Formaldehyde (CH3)2CHCH2CH CHCH2C6H5 OH OH 1-Phenyl-5-methyl-2,3-hexanediol (CH3)2CHCH2CH O HCCH2C6H5 O 3-Methylbutanal 2-Phenylethanal HIO4 CH3CH2OD D CH3CH O alcohol dehydrogenase CNH2 N R O CNH2 H H N R O Ethanol-O-d Ethanal NADH NAD CH3CD2OH H CH3CD O alcohol dehydrogenase CNH2 N R O CNH2 H D N R O 1,1-Dideuterioethanol 1-Deuterioethanal NAD NADD CH3CH2CH2CH2CH2CH2CH2OH 1-Heptanol Heptanal CH3CH2CH2CH2CH2CH2CH O PCC CH2Cl2 CH3CH(CH2)5CH3 OH 2-Octanol CH3C(CH2)5CH3 O 2-Octanone Na2Cr2O7 H2SO4, H2O 368 ALCOHOLS, DIOLS, AND THIOLS Back Forward Main Menu TOC Study Guide TOC Student OLC MHHE Website
ALCOHOLS. DIOLS AND THIOLS 369 15.14 Thiols may be prepared from the corresponding alkyl halide by reaction with thiourea followed by treatment of the isothiouronium salt with base RBr (hnC=s Isothiouronium salt RSH bromide Thus, an acceptable synthesis of 1-hexanethiol from 1-hexanol would be 1.(H2N)2C= CH(CH,)CH,OH CH3(CH,)CH,Br CH3(CH2)4CH,SH 1-Hexanol 1-Hexanethiol 15.15 The three main components of"essence of skunk"are H2C、 CH,CHCH, CH,SH CH SH 3-Methyl-1-butanethiol is- 2-Butene.l-thiol 15.16 The molecular weight of 2-methyl-2-butanol is 88. A peak in its mass spectrum at m/z 70 corre ponds to loss of water from the molecular ion. The peaks at m/z 73 and m/z 59 represent stable cations corresponding to the cleavages shown in the equation CH, CH3 CH3+ CH3 CCH, CH3 CH2CCH3+“CH2CH m/z73 m/259 15.17 (a) The appropriate alkene for the preparation of 1-butanol by a hydroboration-oxidation sequence is 1-butene. Remember, hydroboration-oxidation leads to hydration of alkenes with a regioselectivity opposite to that seen in acid-catalyzed hydration. L B CH, CHCH=CH2 2.H202HO CH CHCH.OH 1-Butene 1-Butanol (b) 1-Butanol can be prepared by reaction of a Grignard reagent with formaldehyde. CH3 CH,CH,CH,OH CHaCH,CH2+ HCH An appropriate Grignard reagent is propylmagnesium bromide CH CH,CH, Br CH CH, CH,Mgl 1-Bromopropane Propylmagnesium bromide Back Forward Main Menu TOC Study Guide Toc Student OLC MHHE Website
ALCOHOLS, DIOLS, AND THIOLS 369 15.14 Thiols may be prepared from the corresponding alkyl halide by reaction with thiourea followed by treatment of the isothiouronium salt with base. Thus, an acceptable synthesis of 1-hexanethiol from 1-hexanol would be 15.15 The three main components of “essence of skunk” are 15.16 The molecular weight of 2-methyl-2-butanol is 88. A peak in its mass spectrum at mz 70 corresponds to loss of water from the molecular ion. The peaks at mz 73 and mz 59 represent stable cations corresponding to the cleavages shown in the equation. 15.17 (a) The appropriate alkene for the preparation of 1-butanol by a hydroboration–oxidation sequence is 1-butene. Remember, hydroboration–oxidation leads to hydration of alkenes with a regioselectivity opposite to that seen in acid-catalyzed hydration. (b) 1-Butanol can be prepared by reaction of a Grignard reagent with formaldehyde. An appropriate Grignard reagent is propylmagnesium bromide. 1. diethyl ether 2. H3O CH3CH2CH2MgBr CH 3CH2CH2CH2OH 1-Butanol HCH O Mg diethyl ether CH3CH2CH2Br CH3CH2CH2MgBr 1-Bromopropane Propylmagnesium bromide CH3CH2CH2CH2OH HCH CH3CH2CH2 O CH3CH2CH CH2 CH3CH2CH2CH2OH 1. B2H6 2. H2O2, HO 1-Butene 1-Butanol CH3 CH2CH3 CH3 OH C CH3 CH3CCH2CH3 OH CH3CCH3 OH CH2CH3 m/z 73 m/z 59 C C H3C H CH2SH H trans-2-Butene-1-thiol H H C C H3C CH2SH 3-Methyl-1-butanethiol cis-2-Butene-1-thiol CH3CHCH2CH2SH CH3 CH3(CH2)4CH2OH 1-Hexanol CH3(CH2)4CH2Br 1-Bromohexane CH3(CH2)4CH2SH 1-Hexanethiol PBr3 HBr, heat 1. (H2N)2C S 2. NaOH Isothiouronium salt (not isolated) NaOH RBr Alkyl bromide (H2N)2C S Thiourea RSH Thiol Back Forward Main Menu TOC Study Guide TOC Student OLC MHHE Website
370 ALCOHOLS, DIOLS, AND THIOLS (c) Alternatively, 1-butanol may be prepared by the reaction of a Grignard reagent with ethylene CHaCHLCH,CH,OH CHa CH2+ H,C--CH2 In this case, ethylmagnesium bromide would be used CHaCH2Br diethyl ether CH CH2MgBr Ethyl bromide Ethylmagnesium bromide I. diethyl ether CH3 CH2 MgBr H2C CH 2.HO+ CHCH,CH, CH,OH Ethylene oxide 1-Butanol (d) Primary alcohols may be prepared by reduction of the carboxylic acid having the same num- ber of carbons. Among the reagents we have discussed, the only one that is effective in the reduction of carboxylic acids is lithium aluminum hydride. The four-carbon carboxylic acid butanoic acid is the proper substrate CH..CH 1. LiAlHy diethyl ether 2.H,O CHCH,CH,CH,OH (e) Reduction of esters can be accomplished using lithium aluminum hydride. The correct methyl ester is methyl butanoate L LiAlH4 CH3CH2CH,COCH3 2.H-O CH3CH,CH, CH,OH CH,OH Methyl butanoate Methanol Cf) A butyl ester such as butyl acetate may be reduced with lithium aluminum hydride to prepare CHI COCH,CH2CH2..O CH CH_CH,CH2OH CH3CH2OH Butyl acetate 1-Butanol Ethanol (g) Because 1-butanol is a primary alcohol having four carbons, butanal must be the aldehyde that is hydrogenated. Suitable catalysts are nickel, palladium, platinum, and ruthenium CH. CHCHCH CHaCH,CH,CH,OH h) Sodium borohydride reduces aldehydes and ketones efficiently. It does not reduce carboxylic CHaCHaCHLCH water. ethan CHaCH,,CHLOH 1-Butanol Back Forward Main Menu TOC Study Guide Toc Student OLC MHHE Website
(c) Alternatively, 1-butanol may be prepared by the reaction of a Grignard reagent with ethylene oxide. In this case, ethylmagnesium bromide would be used. (d) Primary alcohols may be prepared by reduction of the carboxylic acid having the same number of carbons. Among the reagents we have discussed, the only one that is effective in the reduction of carboxylic acids is lithium aluminum hydride. The four-carbon carboxylic acid butanoic acid is the proper substrate. (e) Reduction of esters can be accomplished using lithium aluminum hydride. The correct methyl ester is methyl butanoate. (f ) A butyl ester such as butyl acetate may be reduced with lithium aluminum hydride to prepare 1-butanol. (g) Because 1-butanol is a primary alcohol having four carbons, butanal must be the aldehyde that is hydrogenated. Suitable catalysts are nickel, palladium, platinum, and ruthenium. (h) Sodium borohydride reduces aldehydes and ketones efficiently. It does not reduce carboxylic acids, and its reaction with esters is too slow to be of synthetic value. CH3CH2CH2CH2OH Butanal 1-Butanol CH3CH2CH2CH O NaBH4 water, ethanol, or methanol H2, Pt CH3CH2CH2CH2OH Butanal 1-Butanol CH3CH2CH2CH O 1. LiAlH4 2. H2O CH3CH2CH2CH2OH CH3CH2OH Butyl acetate 1-Butanol Ethanol CH3COCH2CH2CH2CH3 O 1. LiAlH4 2. H2O CH3CH2CH2COCH3 CH3CH2CH2CH2OH CH3OH Methyl butanoate 1-Butanol Methanol O 1. LiAlH4, diethyl ether 2. H2O CH3CH2CH2COH CH3CH2CH2CH2OH Butanoic acid 1-Butanol O CH3CH2MgBr CH3CH2CH2CH2OH Ethylene oxide 1-Butanol 1. diethyl ether 2. H3O H2C CH2 O Mg diethyl ether CH3CH2Br CH3CH2MgBr Ethyl bromide Ethylmagnesium bromide CH3CH2CH2CH2OH CH3CH2 H2C CH2 O 370 ALCOHOLS, DIOLS, AND THIOLS Back Forward Main Menu TOC Study Guide TOC Student OLC MHHE Website
ALCOHOLS. DIOLS AND THIOLS 371 15.18(a) Both(2)-and (E)-2-butene yield 2-butanol on hydroboration-oxidation 1. B,H6 CHaCH=CHCH3 CH, CHCH,CH (Z)or(E)-2-butene Butanol (b) Disconnection of one of the bonds to the carbon that bears the hydroxyl group reveals a feasi ble route using a grignard reagent and propanal Disconnect this bond LC-HCHCH,CH,>:CH,+HCCH,CH OH The synthetic sequence CHICH,CH CH,B diethyl ether CHaMgBr 2hot CH,CHCH,CH Methyl 2-Butanol (c) Another disconnection is related to a synthetic route using a grignard reagent and acetaldehyde Disconnect this bond CH, CH-CH. CH CHCH CH OH CH3 CH diethyl ether CH3CH,MgB CHa CH, CHCH3 Ethyl bromide Ethylmagnesium 2-Butanol (d-f) Because 2-butanol is a secondary alcohol, it can be prepared by reduction of a ketone having the same carbon skeleton, in this case 2-butanone. All three reducing agents indicated in the O H, Pd CH3; (or Pt. Ni. Ru) CH3CHCH2 CH3 2-Butanone CH3 CCH2CH3 CHOH CH_ CHCH,CH CH-CCH2CH32H。O CH3 CHCH, CH3 2-Butanon 2-Butanol Back Forward Main Menu TOC Study Guide Toc Student OLC MHHE Website
ALCOHOLS, DIOLS, AND THIOLS 371 15.18 (a) Both (Z)- and (E)-2-butene yield 2-butanol on hydroboration–oxidation. (b) Disconnection of one of the bonds to the carbon that bears the hydroxyl group reveals a feasible route using a Grignard reagent and propanal. The synthetic sequence is (c) Another disconnection is related to a synthetic route using a Grignard reagent and acetaldehyde. (d–f ) Because 2-butanol is a secondary alcohol, it can be prepared by reduction of a ketone having the same carbon skeleton, in this case 2-butanone. All three reducing agents indicated in the equations are satisfactory. OH CH3CHCH2CH3 1. LiAlH4 2. H2O 2-Butanone 2-Butanol CH3CCH2CH3 O OH CH3CHCH2CH3 NaBH4 CH3OH 2-Butanone 2-Butanol CH3CCH2CH3 O OH CH3CHCH2CH3 H2, Pd (or Pt, Ni, Ru) 2-Butanone 2-Butanol CH3CCH2CH3 O CH3CH2Br Ethylmagnesium bromide OH CH3CH2MgBr CH3CH2CHCH3 Mg diethyl ether 1. CH3CH 2. H3O O Ethyl bromide 2-Butanol CH3CH CH2CH3 Acetaldehyde OH CH3CH O Disconnect this bond. CH3CH2 CH3MgBr Methylmagnesium bromide Methyl bromide CH3Br Mg diethyl ether 2-Butanol CH3CHCH2CH3 OH 1. CH3CH2CH 2. H3O O CH3 Propanal HCCH2CH3 O H3C CHCH2CH3 OH Disconnect this bond. 1. B2H6 2. H2O2, HO (Z)- or (E)-2-butene CH3CH CHCH3 2-Butanol CH3CHCH2CH3 OH Back Forward Main Menu TOC Study Guide TOC Student OLC MHHE Website
372 ALCOHOLS, DIOLS. AND 15.19(a) All the carbon-carbon disconnections are equivalent. CH Hc--o□>cH3+cHcH H Acetone The synthesis via a grignard reagent and acetone is diethyl ether 2.HO+ (CH3), COH Methyl (b) An alternative route to tert-butyl alcohol is addition of a grignard reagent to an ester. Esters react with 2 moles of Grignard reagent. Thus, tert-butyl alcohol may be formed by reacting nethyl acetate with 2 moles of methylmagnesium iodide. Methyl alcohol is formed as a by product of the reaction. 2CH, Mgl + CH,COCH3 2 H,0+. diethyl C-OH t CHOH Methy magnesium Methyl acetate tert-Butyl alcohol Meth 15.20(a) All of the primary alcohols having the molecular formula CsHno may be prepared by redu on of aldehydes. The CHCH,, CH 1. LiAlH4- diethyl et CH3 CH2CHCH,CH,C 1-Pentanol LiAIHg, diethyl ether CHCH, CHCH 2.H,O CHa CH,CHCH,OH CH 2-Methylbutanal 2-Methyl-1-butanol 1. LiAlH4, diethyl eth (CH,),CHCH,CH (CH3), CHCH,CH,OH 3-Methylbutanal 3. Me 1. LiAIHa, diethyl ether (CH3),CCH (CH3)CCH,OH 2-Dimethylpropanal 2. 2-Dimethyl-1-propanol Back Forward Main Menu TOC Study Guide Toc Student OLC MHHE Website
15.19 (a) All the carbon–carbon disconnections are equivalent. The synthesis via a Grignard reagent and acetone is (b) An alternative route to tert-butyl alcohol is addition of a Grignard reagent to an ester. Esters react with 2 moles of Grignard reagent. Thus, tert-butyl alcohol may be formed by reacting methyl acetate with 2 moles of methylmagnesium iodide. Methyl alcohol is formed as a byproduct of the reaction. 15.20 (a) All of the primary alcohols having the molecular formula C5H12O may be prepared by reduction of aldehydes. The appropriate equations are 1. LiAlH4, diethyl ether 2. H2O 2,2-Dimethylpropanal O (CH3)3CCH 2,2-Dimethyl-1-propanol (CH3)3CCH2OH 1. LiAlH4, diethyl ether 2. H2O 3-Methylbutanal O (CH3)2CHCH2CH 3-Methyl-1-butanol (CH3)2CHCH2CH2OH 2-Methyl-1-butanol 1. LiAlH4, diethyl ether 2. H2O 2-Methylbutanal CH3CH2CHCH O CH3 CH3CH2CHCH2OH CH3 CH3CH2CH2CH2CH2OH 1-Pentanol 1. LiAlH4, diethyl ether 2. H2O Pentanal CH3CH2CH2CH2CH O Methylmagnesium Methyl acetate tert-Butyl alcohol iodide C CH3 CH3 OH CH3 CH3COCH3 O Methyl alcohol 2CH3MgI CH3OH 1. diethyl ether 2. H3O CH3Br Methylmagnesium bromide CH3MgBr (CH3)3COH Mg diethyl ether 1. CH3CCH3 2. H3O O Methyl tert-Butyl alcohol bromide CH3CCH3 Acetone C CH3 H3C OH CH3 O CH3 372 ALCOHOLS, DIOLS, AND THIOLS Back Forward Main Menu TOC Study Guide TOC Student OLC MHHE Website
ALCOHOLS. DIOLS AND THIOLS (b) The secondary alcohols having the molecular formula CsHno may be prepared by reduction of ketones 1. LiAlH diethyl ether CH,CH,CH,CCH CH..CHCH 2-Pentanol CH3CH, CCH,CH3 CH, CHCHCHCH 2.H-O 3-Pentanone 3-Pentanol 1. LiAIH, diethyl ethe (CH3),CHCCH 2.H2O (CH3),CHCHCH 3-Methyl-2-butano 3-Methyl-2-butanol (c) As with the reduction of aldehydes in part (a), reduction of carboxylic acids yields primary alcohols. For example, I-pentanol may be prepared by reduction of pentanoic acid. CH COH CH3 CH,CH,CH2CH2OH The remaining primary alcohols, 2-methyl-1-butanol, 3-methyl-1-butanol, and 2, 2-dimethyl 1-propanol, may be prepared in the same way. (d) As with carboxylic acids, esters may be reduced using lithium aluminum hydride to give primary alcohols. For example, 2, 2-dimethyl-l-propanol may be prepared by reduction of methyl 2, 2-dimethylpropanoate 1. LiAIH4. diethyl ether ( CH,),CCOCH3 2H,O (CH3)3CCH,OH Methyl Dimethyl-1-propano 2.2-dimethylpropanoate 15.21(a) The suggested synthesis CH-CHCHCH ight or heat CH_ CH2Br KOH CH CH, CH, CH,OH Butane 1-Butanol e a poor one because bromination of butane yields a mixture of 1-bromobutane and bromobutane, 2-bromobutane being the major product. CH- CH CH, CH, light or he CH3,CH, CH, Br CH,CHCHaCH 1-Bromobutane 2-Bro atone Back Forward Main Menu TOC Study Guide Toc Student OLC MHHE Website
ALCOHOLS, DIOLS, AND THIOLS 373 (b) The secondary alcohols having the molecular formula C5H12O may be prepared by reduction of ketones. (c) As with the reduction of aldehydes in part (a), reduction of carboxylic acids yields primary alcohols. For example, 1-pentanol may be prepared by reduction of pentanoic acid. The remaining primary alcohols, 2-methyl-1-butanol, 3-methyl-1-butanol, and 2,2-dimethyl- 1-propanol, may be prepared in the same way. (d) As with carboxylic acids, esters may be reduced using lithium aluminum hydride to give primary alcohols. For example, 2,2-dimethyl-1-propanol may be prepared by reduction of methyl 2,2-dimethylpropanoate. 15.21 (a) The suggested synthesis is a poor one because bromination of butane yields a mixture of 1-bromobutane and 2-bromobutane, 2-bromobutane being the major product. Br2 light or heat CH3CH2CH2CH3 Butane CH3CH2CH2CH2Br 1-Bromobutane (minor product) 2-Bromobutane (major product) CH3CHCH2CH3 Br Br2 light or heat KOH CH3CH2CH2CH3 Butane CH3CH2CH2CH2Br 1-Bromobutane CH3CH2CH2CH2OH 1-Butanol 1. LiAlH4, diethyl ether 2. H2O Methyl 2,2-dimethylpropanoate O (CH3)3CCOCH3 2,2-Dimethyl-1-propanol (CH3)3CCH2OH 1. LiAlH4, diethyl ether 2. H2O Pentanoic acid O CH3CH2CH2CH2COH 1-Pentanol CH3CH2CH2CH2CH2OH 1. LiAlH4, diethyl ether 2. H2O 3-Methyl-2-butanone O (CH3)2CHCCH3 3-Methyl-2-butanol OH (CH3)2CHCHCH3 1. LiAlH4, diethyl ether 2. H2O 3-Pentanone O CH3CH2CCH2CH3 3-Pentanol OH CH3CH2CHCH2CH3 1. LiAlH4, diethyl ether 2. H2O 2-Pentanone O CH3CH2CH2CCH3 2-Pentanol OH CH3CH2CH2CHCH3 Back Forward Main Menu TOC Study Guide TOC Student OLC MHHE Website
