CHAPTER FIFTEEN Alcohols, Diols, and Thiols Ketones yield secondary alcohols: RCR′+H P, Pd, Ni, or R RCHR′ Ketone Secondary alcohol Cyclopentanone Cyclopentanol (93-95%) TPROBLEM 15.1 Which of the isomeric CaH1oo alcohols can be prepared by hydrogenation of aldehydes? Which can be prepared by hydrogenation of stones? Which cannot be prepared by hydrogenation of a carbonyl compound For most laboratory-scale reductions of aldehydes and ketones, catalytic hydro- genation has been replaced by methods based on metal hydride reducing agents. The two most common reagents are sodium borohydride and lithium aluminum hydride H the electrostatic laps of CHa, BH Na*H-B=H Li*H-AI-H ice how different the H lectrostatic potentials associ- ted with hydrog Sodium borohydride(NaBH4) Lithium aluminum hydride (LiAlH4) Sodium borohydride is especially easy to use, needing only to be added to an aque- ous or alcoholic solution of an aldehyde or a ketone: water. methanol RCHO Aldehyde O,N m-Nitrobenzaldehyde m-Nitrobenzyl alcohol (82%o) RCR RCHR Ketone or ethanol Secondary alcohol OH CH3CCH,C(CH3)3 CH3CHCH, C(CH3)3 4, 4-Dimethy l-2-pentanone 4. 4-Dimethy l-2-pentanol(85%) Back Forward Main MenuToc Study Guide ToC Student o MHHE Website
Ketones yield secondary alcohols: PROBLEM 15.1 Which of the isomeric C4H10O alcohols can be prepared by hydrogenation of aldehydes? Which can be prepared by hydrogenation of ketones? Which cannot be prepared by hydrogenation of a carbonyl compound? For most laboratory-scale reductions of aldehydes and ketones, catalytic hydrogenation has been replaced by methods based on metal hydride reducing agents. The two most common reagents are sodium borohydride and lithium aluminum hydride. Sodium borohydride is especially easy to use, needing only to be added to an aqueous or alcoholic solution of an aldehyde or a ketone: NaBH4 methanol O2N CH O m-Nitrobenzaldehyde CH2OH O2N m-Nitrobenzyl alcohol (82%) NaBH4 water, methanol, or ethanol RCH O Aldehyde RCH2OH Primary alcohol NaBH4 water, methanol, or ethanol RCR O Ketone RCHR OH Secondary alcohol CH3CCH2C(CH3)3 O 4,4-Dimethyl-2-pentanone CH3CHCH2C(CH3)3 OH 4,4-Dimethyl-2-pentanol (85%) NaBH4 ethanol Sodium borohydride (NaBH4) Na H±B±H H W W H Li H±Al±H H W W H Lithium aluminum hydride (LiAlH4) RCR O Ketone H2 Hydrogen Pt, Pd, Ni, or Ru RCHR OH Secondary alcohol H2, Pt methanol O Cyclopentanone H OH Cyclopentanol (93–95%) 584 CHAPTER FIFTEEN Alcohols, Diols, and Thiols Compare the electrostatic potential maps of CH4, BH4 , and AlH4 on Learning By Modeling. Notice how different the electrostatic potentials associated with hydrogen are. Back Forward Main Menu TOC Study Guide TOC Student OLC MHHE Website
15.2 Preparation of Alcohols by Reduction of Aldehydes and Ketones Lithium aluminum hydride reacts violently with water and alcohols, so it must be used in solvents such as anhydrous diethyl ether or tetrahydrofuran. Following reduc tion, a separate hydrolysis step is required to liberate the alcohol product 1. LiAlH, diethyl ether →>RCH2OH Aldehyde Primary alcohol CH3(CH,)sCH- LiAIH CH3(CH2)5CH,OH Heptanal I-Heptanol (86%) RCR’ LiAIH,diethyl eth (C6H5)2CHCCH3 (C6H5)2CHCHCH3 1. 1-Diphenyl-2-propanol (84%) Sodium borohydride and lithium aluminum hydride react with carbonyl compounds in much the same way that Grignard reagents do, except that they function as hydride donors rather than as carbanion sources. Borohydride transfers a hydrogen with its pair of bonding electrons to the positively polarized carbon of a carbonyl group. The nega tively polarized oxygen attacks boron. Ultimately, all four of the hydrogens of borohy- dride are transferred and a tetraalkoxyborate is formed H-BH3 H BH3 (R2CHO)4B RC-O RC=O Tetraalkoxyborate Hydrolysis or alcoholysis converts the tetraalkoxyborate intermediate to the corre- sponding alcohol. The following equation illustrates the process for reactions carried out in water. An analogous process occurs in methanol or ethanol and yields the alcohol and (CH3O)4B or(CH3 CH,O)4B R2CHO—B(OCHR2)3 ?R2CHOH+ HOb(OCHR2)3->3R,CHOH +(HO)4B A similar series of hydride transfers occurs when aldehydes and ketones are treated with lithium aluminum hydride Back Forward Main MenuToc Study Guide ToC Student o MHHE Website
Lithium aluminum hydride reacts violently with water and alcohols, so it must be used in solvents such as anhydrous diethyl ether or tetrahydrofuran. Following reduction, a separate hydrolysis step is required to liberate the alcohol product: Sodium borohydride and lithium aluminum hydride react with carbonyl compounds in much the same way that Grignard reagents do, except that they function as hydride donors rather than as carbanion sources. Borohydride transfers a hydrogen with its pair of bonding electrons to the positively polarized carbon of a carbonyl group. The negatively polarized oxygen attacks boron. Ultimately, all four of the hydrogens of borohydride are transferred and a tetraalkoxyborate is formed. Hydrolysis or alcoholysis converts the tetraalkoxyborate intermediate to the corresponding alcohol. The following equation illustrates the process for reactions carried out in water. An analogous process occurs in methanol or ethanol and yields the alcohol and (CH3O)4B or (CH3CH2O)4B. A similar series of hydride transfers occurs when aldehydes and ketones are treated with lithium aluminum hydride. 3H2O B(OCHR2)3 H OH R2CHO R2CHOH HOB(OCHR2)3 3R2CHOH (HO)4B 3R2CœO H BH3 R2C O BH3 R2C O H (R2CHO)4B Tetraalkoxyborate 1. LiAlH4, diethyl ether 2. H2O RCH O Aldehyde RCH2OH Primary alcohol CH3(CH2)5CH O Heptanal CH3(CH2)5CH2OH 1-Heptanol (86%) 1. LiAlH4, diethyl ether 2. H2O RCR O Ketone RCHR OH Secondary alcohol 1. LiAlH4, diethyl ether 2. H2O (C6H5)2CHCCH3 O 1,1-Diphenyl-2-propanone (C6H5)2CHCHCH3 OH 1,1-Diphenyl-2-propanol (84%) 1. LiAlH4, diethyl ether 2. H2O 15.2 Preparation of Alcohols by Reduction of Aldehydes and Ketones 585 Back Forward Main Menu TOC Study Guide TOC Student OLC MHHE Website
CHAPTER FIFTEEN Alcohols, Diols, and Thiols H-AIH H AlH RC=O Tetraalkoxyaluminate Addition of water converts the tetraalkoxyaluminate to the desired alcohol (R,CHO) 4H,0->4R CHOH Al(Od) Tetraalkoxyaluminate PROBLEM 15.2 Sodium borodeuteride(naBD) and lithium aluminum deuteride (LiAID) are convenient reagents for introducing deuterium, the mass 2 isotope of hydrogen, into organic compounds. Write the structure of the organic product of the following reactions, clearly showing the position of all the deuterium atoms in each p.264-266 (a)Reduction of CH3 CH (acetaldehyde)with NaBDa in H2O (b) Reduction of ch3CCH3(acetone) with NaBDa in CH3OD (c)Reduction of CHs cH( benzaldehyde)with NaBDa in CD3OH ( d)Reduction of HCH (formaldehyde) with LiAIDa in diethyl ether, followed by addition of d2O SAMPLE SOLUTION (a) Sodium borodeuteride transfers deuterium to the car bonyl group of acetaldehyde, forming a c-D bond CH3C=O CH3 O ->CH CHO)B he C-D bond formed in the preceding step while forming an o-H bonds Hydrolysis of (CH3 CHDO)4B in H2O leads to the formation of ethanol, retain CHH-o- B(OCHDCH2)3→→cH2cH+ OCHDCH2)2°3 CHaCHOH+BoHa Neither sodium borohydride nor lithium aluminum hydride reduces isolated car- bon-carbon double bonds. This makes possible the selective reduction of a carbonyl group in a molecule that contains both carbon-carbon and carbon-oxygen double bonds Back Forward Main MenuToc Study Guide ToC Student o MHHE Website
Addition of water converts the tetraalkoxyaluminate to the desired alcohol. PROBLEM 15.2 Sodium borodeuteride (NaBD4) and lithium aluminum deuteride (LiAlD4) are convenient reagents for introducing deuterium, the mass 2 isotope of hydrogen, into organic compounds. Write the structure of the organic product of the following reactions, clearly showing the position of all the deuterium atoms in each: (a) Reduction of (acetaldehyde) with NaBD4 in H2O (b) Reduction of (acetone) with NaBD4 in CH3OD (c) Reduction of (benzaldehyde) with NaBD4 in CD3OH (d) Reduction of (formaldehyde) with LiAlD4 in diethyl ether, followed by addition of D2O SAMPLE SOLUTION (a) Sodium borodeuteride transfers deuterium to the carbonyl group of acetaldehyde, forming a C±D bond. Hydrolysis of (CH3CHDO)4B in H2O leads to the formation of ethanol, retaining the C±D bond formed in the preceding step while forming an O±H bond. Neither sodium borohydride nor lithium aluminum hydride reduces isolated carbon–carbon double bonds. This makes possible the selective reduction of a carbonyl group in a molecule that contains both carbon–carbon and carbon–oxygen double bonds. D BD3 CH3C O H C O D BD3 H CH3 3CH3CH O X (CH3CHO)4B D HCH O X C6H5CH O X CH3CCH3 O X CH3CH O X Tetraalkoxyaluminate (R2CHO)4Al Al(OH)4 Alcohol 4H2O 4R2CHOH 3R2CœO H AlH3 R2C O AlH3 R2C O H Tetraalkoxyaluminate (R2CHO)4Al 586 CHAPTER FIFTEEN Alcohols, Diols, and Thiols CH3CH B(OCHDCH3)3 H OH D O D OH CH3CH Ethanol-1-d 3H2O 3CH3CHOH D B(OH)4 OH B(OCHDCH3)3 An undergraduate laboratory experiment related to Problem 15.2 appears in the March 1996 issue of the Journal of Chemical Education, pp. 264–266. Back Forward Main Menu TOC Study Guide TOC Student OLC MHHE Website
15.4 Preparation of Alcohols from Epoxides (CH3)C=CHCH, CH-CCH 2.H2O CH3)2C=CHCH,CH,CHCH3 this transformation because 6-Methyl-5-hepten-2-one 6-Methyl-5-hepten-2-ol(90%) double bonds faster than it reduces carbonyl groups. 15.3 PREPARATION OF ALCOHOLS BY REDUCTION OF CARBOXYLIC ACIDS AND ESTERS Carboxylic acids are exceedingly difficult to reduce. Acetic acid, for example, is often used as a solvent in catalytic hydrogenations because it is inert under the reaction con- ditions. A very powerful reducing agent is required to convert a carboxylic acid to a pri mary alcohol. Lithium aluminum hydride is that reducing agent RCOH RCH,OH Carboxylic acid Primary alcohol Cyclopropylmethar Sodium borohydride is not nearly as potent a hydride donor as lithium aluminum hydride and does not reduce carboxylic acids Esters are more easily reduced than carboxylic acids. Two alcohols are formed from each ester molecule. The acyl group of the ester is cleaved, giving a primary alcohol. RCOR RCH,OH R'OH Ester Primary alcohol Alcohol Lithium aluminum hydride is the reagent of choice for reducing esters to alcohols LiAlH4, diethyl etl COCH, CH -CH,OH CH3 CH,OH Ethyl benzoate Benzyl alcohol (90%) Ethanol PROBLEM 15.3 Give the structure of an ester that will yield a mixture contain- ing equimolar amounts of 1-propanol and 2-propanol on reduction with lithium aluminum hydride. Sodium borohydride reduces esters, but the reaction is too slow to be useful Hydrogenation of esters requires a special catalyst and extremely high pressures and tem- peratures; it is used in industrial settings but rarely in the laboratory 15.4 PREPARATION OF ALCOHOLS FROM EPOXIDES Although the chemical reactions of epoxides will not be covered in detail until the fol lowing chapter, we shall introduce their use in the synthesis of alcohols here Back Forward Main MenuToc Study Guide ToC Student o MHHE Website
15.3 PREPARATION OF ALCOHOLS BY REDUCTION OF CARBOXYLIC ACIDS AND ESTERS Carboxylic acids are exceedingly difficult to reduce. Acetic acid, for example, is often used as a solvent in catalytic hydrogenations because it is inert under the reaction conditions. A very powerful reducing agent is required to convert a carboxylic acid to a primary alcohol. Lithium aluminum hydride is that reducing agent. Sodium borohydride is not nearly as potent a hydride donor as lithium aluminum hydride and does not reduce carboxylic acids. Esters are more easily reduced than carboxylic acids. Two alcohols are formed from each ester molecule. The acyl group of the ester is cleaved, giving a primary alcohol. Lithium aluminum hydride is the reagent of choice for reducing esters to alcohols. PROBLEM 15.3 Give the structure of an ester that will yield a mixture containing equimolar amounts of 1-propanol and 2-propanol on reduction with lithium aluminum hydride. Sodium borohydride reduces esters, but the reaction is too slow to be useful. Hydrogenation of esters requires a special catalyst and extremely high pressures and temperatures; it is used in industrial settings but rarely in the laboratory. 15.4 PREPARATION OF ALCOHOLS FROM EPOXIDES Although the chemical reactions of epoxides will not be covered in detail until the following chapter, we shall introduce their use in the synthesis of alcohols here. 1. LiAlH4, diethyl ether 2. H2O COCH2CH3 O Ethyl benzoate CH2OH Benzyl alcohol (90%) CH3CH2OH Ethanol RCOR O Ester RCH2OH Primary alcohol ROH Alcohol 1. LiAlH4, diethyl ether 2. H2O RCOH O Carboxylic acid RCH2OH Primary alcohol 1. LiAlH4, diethyl ether 2. H2O CO2H Cyclopropanecarboxylic acid CH2OH Cyclopropylmethanol (78%) CHCH2CH2CCH3 (CH3)2C O 6-Methyl-5-hepten-2-one CHCH2CH2CHCH3 (CH3)2C OH 6-Methyl-5-hepten-2-ol (90%) 1. LiAlH4, diethyl ether 2. H2O 15.4 Preparation of Alcohols from Epoxides 587 Catalytic hydrogenation would not be suitable for this transformation, because H2 adds to carbon–carbon double bonds faster than it reduces carbonyl groups. Back Forward Main Menu TOC Study Guide TOC Student OLC MHHE Website
CHAPTER FIFTEEN Alcohols, Diols, and Thiols gnard reagents react with ethylene oxide to yield primary alcohols containing two carbon atoms than the alkyl halide from which the organometallic compound was prepared RMgX HC CH RCH, CH,OH Grignard Ethylene oxide Primary alcohol CH3(CH2)4CH,MgBr H2C-CH2-0 u >CH3(CH2)4CH2CH2,OH Hexylmagnesium Ethylene oxide Octanol (71%) Organolithium reagents react with epoxides in a similar manner. PROBLEM 15.4 Each of the following alcohols has been prepared by reaction of a Grignard reagent with ethylene oxide. Select the appropriate Grignard read nt in each case TCH2CH2OH SAMPLE SOLUTION (a)Reaction with oxide results in the addition of a - CH,OH unit to the grignard rea Grignard reagent derived from O-bromotoluene(or o-chlorotoluene or o luene)is appropriate here Hc、ch2 CHCHOH o-Methylphenylmagnesium Ethylene oxide 2(o-Methylphenyl)ethanol bromide (66%) Epoxide rings are readily opened with cleavage of the carbon-oxygen bond when attacked by nucleophiles. Grignard reagents and organolithium reagents react with eth ylene oxide by serving as sources of nucleophilic carbon RM2x→RcH2-CH2-0Mx→p RCH2 CH2OH HoC-CH ( may be written as RCH,CH,OMgX This kind of chemical reactivity of epoxides is rather general Nucleophiles other than Grignard reagents react with epoxides, and epoxides more elaborate than ethylene oxide may be used. All these features of epoxide chemistry will be discussed in Sections 16.11 d16.12 Back Forward Main MenuToc Study Guide ToC Student o MHHE Website
Grignard reagents react with ethylene oxide to yield primary alcohols containing two more carbon atoms than the alkyl halide from which the organometallic compound was prepared. Organolithium reagents react with epoxides in a similar manner. PROBLEM 15.4 Each of the following alcohols has been prepared by reaction of a Grignard reagent with ethylene oxide. Select the appropriate Grignard reagent in each case. (a) (b) SAMPLE SOLUTION (a) Reaction with ethylene oxide results in the addition of a ±CH2CH2OH unit to the Grignard reagent. The Grignard reagent derived from o-bromotoluene (or o-chlorotoluene or o-iodotoluene) is appropriate here. Epoxide rings are readily opened with cleavage of the carbon–oxygen bond when attacked by nucleophiles. Grignard reagents and organolithium reagents react with ethylene oxide by serving as sources of nucleophilic carbon. This kind of chemical reactivity of epoxides is rather general. Nucleophiles other than Grignard reagents react with epoxides, and epoxides more elaborate than ethylene oxide may be used. All these features of epoxide chemistry will be discussed in Sections 16.11 and 16.12. R MgX RCH2CH2OH H2C O CH2 R CH2 MgX CH2 O (may be written as RCH2CH2OMgX) H3O CH3 MgBr o-Methylphenylmagnesium bromide H2C O CH2 Ethylene oxide 1. diethyl ether 2. H3O CH3 CH2CH2OH 2-(o-Methylphenyl)ethanol (66%) CH2CH2OH CH3 CH2CH2OH 1. diethyl ether 2. H3O RMgX Grignard reagent H2C O CH2 Ethylene oxide RCH2CH2OH Primary alcohol 1. diethyl ether 2. H3O H2C O CH2 Ethylene oxide CH3(CH2)4CH2MgBr Hexylmagnesium bromide CH3(CH2)4CH2CH2CH2OH 1-Octanol (71%) 588 CHAPTER FIFTEEN Alcohols, Diols, and Thiols Back Forward Main Menu TOC Study Guide TOC Student OLC MHHE Website