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