CHAPTER 15 ALCOHOLS DIOLS, AND THIOLS next several chapters deal with the chemistry of various oxygen-containing tional groups. The interplay of these important classes of compounds--alco- ethers, aldehydes, ketones, carboxylic acids, and derivatives of carboxylic Undamental to organic chemistry and biochemistry. ROH ROR RCH RCR RCOH Alcohol Ether Aldehyde Ketone Carboxylic acid We'll start by discussing in more detail a class of compounds already familiar to us,alcohols. Alcohols were introduced in Chapter 4 and have appeared regularly since then. With this chapter we extend our knowledge of alcohols, particularly with respect to their relationship to carbonyl-containing compounds. In the course of studyi hols. we shall also look at some relatives diols are alcohols in which two groups(-OH) are present; thiols are compounds that contain an-SH group Phenols, compounds of the type ArOH, share many properties in common with alcohols but are ufficiently different from them to warrant separate discussion in Chapter 24 This chapter is a transitional one. It ties togethe ch of the earlier and sets the stage for our study of other oxygen-containing functional groups in the chapters that follow 15.1 SOURCES OF ALCOHOLS Until the 1920s, the major source of methanol was as a byproduct in the production of charcoal from wood-hence the name wood alcohol. Now most of the more than 10 579 Back Forward Main MenuToc Study Guide ToC Student o MHHE Website
579 CHAPTER 15 ALCOHOLS, DIOLS, AND THIOLS The next several chapters deal with the chemistry of various oxygen-containing functional groups. The interplay of these important classes of compounds—alcohols, ethers, aldehydes, ketones, carboxylic acids, and derivatives of carboxylic acids—is fundamental to organic chemistry and biochemistry. We’ll start by discussing in more detail a class of compounds already familiar to us, alcohols. Alcohols were introduced in Chapter 4 and have appeared regularly since then. With this chapter we extend our knowledge of alcohols, particularly with respect to their relationship to carbonyl-containing compounds. In the course of studying alcohols, we shall also look at some relatives. Diols are alcohols in which two hydroxyl groups (±OH) are present; thiols are compounds that contain an ±SH group. Phenols, compounds of the type ArOH, share many properties in common with alcohols but are sufficiently different from them to warrant separate discussion in Chapter 24. This chapter is a transitional one. It ties together much of the material encountered earlier and sets the stage for our study of other oxygen-containing functional groups in the chapters that follow. 15.1 SOURCES OF ALCOHOLS Until the 1920s, the major source of methanol was as a byproduct in the production of charcoal from wood—hence, the name wood alcohol. Now, most of the more than 10 ROH Alcohol ROR Ether RCH O X Aldehyde RCR O X Ketone RCOH O X Carboxylic acid Back Forward Main Menu TOC Study Guide TOC Student OLC MHHE Website
CHAPTER FIFTEEN Alcohols, Diols, and Thiols Carbon monoxide is ob. billion Ib of methanol used annually in the United States is synthetic, prepared by reduc tained from coal, and hydro- tion of carbon monoxide with hydrogen is one of the produ natural gas is converted to ethylene and CO +2H, 2, CHOH 5.1) Almost half of this methanol is converted to formaldehyde as a starting material for various resins and plastics. Methanol is also used as a solvent, as an antifreeze, and s a convenient clean-burning liquid fuel. This last property makes it a candidate as a fuel for automobiles--methanol is already used to power Indianapolis-class race cars but extensive emissions tests remain to be done before it can be approved as a gasoline substitute. Methanol is a colorless liquid, boiling at 65C, and is miscible with water in all proportions. It is poisonous: drinking as little as 30 mL has been fatal. Ingestion of sublethal amounts can lead to blindness When vegetable matter ferments, its carbohydrates are converted to ethanol and carbon dioxide by enzymes present in yeast. Fermentation of barley produces beer grapes give wine. The maximum ethanol content is on the order of 15%0, because higher concentrations inactivate the enzymes, halting fermentation. Since ethanol boils at 78C CH HOCH HO- HO CH(CH3)2 Menthol (obtained from oil of Glucose(a carbohydrate) H3C H CH Cholesterol (principal constituent of HC CH, CH3 H3 H3C OH H3 Retinol(vitamin A, an important FIGURE 15.1 Some geranium oil and used in perfumery) substance in vision naturally occurring alcohols. Back Forward Main MenuToc Study Guide ToC Student o MHHE Website
billion lb of methanol used annually in the United States is synthetic, prepared by reduction of carbon monoxide with hydrogen. Almost half of this methanol is converted to formaldehyde as a starting material for various resins and plastics. Methanol is also used as a solvent, as an antifreeze, and as a convenient clean-burning liquid fuel. This last property makes it a candidate as a fuel for automobiles—methanol is already used to power Indianapolis-class race cars— but extensive emissions tests remain to be done before it can be approved as a gasoline substitute. Methanol is a colorless liquid, boiling at 65°C, and is miscible with water in all proportions. It is poisonous; drinking as little as 30 mL has been fatal. Ingestion of sublethal amounts can lead to blindness. When vegetable matter ferments, its carbohydrates are converted to ethanol and carbon dioxide by enzymes present in yeast. Fermentation of barley produces beer; grapes give wine. The maximum ethanol content is on the order of 15%, because higher concentrations inactivate the enzymes, halting fermentation. Since ethanol boils at 78°C CO Carbon monoxide 2H2 Hydrogen CH3OH Methanol ZnO/Cr2O3 400°C 580 CHAPTER FIFTEEN Alcohols, Diols, and Thiols Carbon monoxide is obtained from coal, and hydrogen is one of the products formed when natural gas is converted to ethylene and propene (Section 5.1). CH3 HO CH(CH3)2 HO O HO HOCH2 OH HO HO H3C CH3 CH3 CH3 CH3 CH3 OH CH3 CH3 CH3 CH3 OH Menthol (obtained from oil of peppermint and used to flavor tobacco and food) Cholesterol (principal constituent of gallstones and biosynthetic precursor of the steroid hormones) Citronellol (found in rose and geranium oil and used in perfumery) Retinol (vitamin A, an important substance in vision) Glucose (a carbohydrate) H3C H3C H3C FIGURE 15.1 Some naturally occurring alcohols. Back Forward Main Menu TOC Study Guide TOC Student OLC MHHE Website
15.1 Sources of alcohols and water at 100C, distillation of the fermentation broth can be used to give"distilled spirits"of increased ethanol content. Whiskey is the aged distillate of fermented grain nd contains slightly less than 50% ethanol. Brandy and cognac are made by aging the distilled spirits from fermented grapes and other fruits. The characteristic flavors, odors nd colors of the various alcoholic beverages depend on both their origin and the way Synthetic ethanol is derived from petroleum by hydration of ethylene In the United States, some 700 million Ib of synthetic ethanol is produced annually. It is relatively inexpensive and useful for industrial applications. To make it unfit for drinking, it is denatured by adding any of a number of noxious materials, a process that exempts it Some of the Our bodies are reasonably well equipped to metabolize ethanol, making it less dan- methanol, benzene, pm e from the high taxes most governments impose on ethanol used in beverages to denature ethanol includ gerous than methanol. Alcohol abuse and alcoholism, however, have been and remain dine, castor oil, and gasoline. persistent proble Isopropyl alcohol is prepared from petroleum by hydration of propene. With a boil ing point of 82C, isopropyl alcohol evaporates quickly from the skin, producing a cool- ing effect. Often containing dissolved oils and fragrances, it is the major component of rubbing alcohol. Isopropyl alcohol possesses weak antibacterial properties and is used to maintain medical instruments in a sterile condition and to clean the skin before minor surge Methanol, ethanol, and isopropyl alcohol are included among the readily available starting materials commonly found in laboratories where organic synthesis is carried out So, too, are many other alcohols. All alcohols of four carbons or fewer, as well as most of the five- and six-carbon alcohols and many higher alcohols, are commercially avail- able at low cost. Some occur naturally; others are the products of efficient syntheses Figure 15.1 presents the structures of a few naturally occurring alcohols. Table 15.1 sum marizes the reactions encountered in earlier chapters that give alcohols and illustrates a thread that runs through the fabric of organic chemistry: a reaction that is characteris- tic of one functional group often serves as a synthetic method for preparing another As Table 15.1 indicates, reactions leading to alcohols are not in short supply. Nev- ertheless, several more will be added to the list in the present chapter--testimony to the TABLE 15.1 Summary of Reactions Discussed in Earlier Chapters That Yield Alcohols Reaction(section) and comments General equation and specific example (Section 6.10) The elements of water R2C=CR2+ H20-R2CHCR2 add to the double bond in accord ance with markovnikov's rule Alkene Water CH3 (CH3)2C=CHCH3 (0 CH3 CCH2 CH3 2-Methyl-2-butene 2-Methyl-2-butanol (90%) (Continued) Back Forward Main MenuToc Study Guide ToC Student o MHHE Website
TABLE 15.1 Summary of Reactions Discussed in Earlier Chapters That Yield Alcohols Reaction (section) and comments (Continued) Acid-catalyzed hydration of alkenes (Section 6.10) The elements of water add to the double bond in accordance with Markovnikov’s rule. General equation and specific example Alkene R2CœCR2 Water H2O Alcohol R2CHCR2 OH W H 2-Methyl-2-butene (CH3)2CœCHCH3 2-Methyl-2-butanol (90%) CH3CCH2CH3 OH CH3 W W H2O H2SO4 15.1 Sources of Alcohols 581 and water at 100°C, distillation of the fermentation broth can be used to give “distilled spirits” of increased ethanol content. Whiskey is the aged distillate of fermented grain and contains slightly less than 50% ethanol. Brandy and cognac are made by aging the distilled spirits from fermented grapes and other fruits. The characteristic flavors, odors, and colors of the various alcoholic beverages depend on both their origin and the way they are aged. Synthetic ethanol is derived from petroleum by hydration of ethylene. In the United States, some 700 million lb of synthetic ethanol is produced annually. It is relatively inexpensive and useful for industrial applications. To make it unfit for drinking, it is denatured by adding any of a number of noxious materials, a process that exempts it from the high taxes most governments impose on ethanol used in beverages. Our bodies are reasonably well equipped to metabolize ethanol, making it less dangerous than methanol. Alcohol abuse and alcoholism, however, have been and remain persistent problems. Isopropyl alcohol is prepared from petroleum by hydration of propene. With a boiling point of 82°C, isopropyl alcohol evaporates quickly from the skin, producing a cooling effect. Often containing dissolved oils and fragrances, it is the major component of rubbing alcohol. Isopropyl alcohol possesses weak antibacterial properties and is used to maintain medical instruments in a sterile condition and to clean the skin before minor surgery. Methanol, ethanol, and isopropyl alcohol are included among the readily available starting materials commonly found in laboratories where organic synthesis is carried out. So, too, are many other alcohols. All alcohols of four carbons or fewer, as well as most of the five- and six-carbon alcohols and many higher alcohols, are commercially available at low cost. Some occur naturally; others are the products of efficient syntheses. Figure 15.1 presents the structures of a few naturally occurring alcohols. Table 15.1 summarizes the reactions encountered in earlier chapters that give alcohols and illustrates a thread that runs through the fabric of organic chemistry: a reaction that is characteristic of one functional group often serves as a synthetic method for preparing another. As Table 15.1 indicates, reactions leading to alcohols are not in short supply. Nevertheless, several more will be added to the list in the present chapter—testimony to the Some of the substances used to denature ethanol include methanol, benzene, pyridine, castor oil, and gasoline. Back Forward Main Menu TOC Study Guide TOC Student OLC MHHE Website
CHAPTER FIFTEEN Alcohols, Diols, and Thiols TABLE 15.1 Summary of Reactions Discussed in Earlier Chapters That Yield Alcohols( Continued) Reaction(section) and comments General equation and specific example Hydroboration-oxidation of alkenes (Section 6.11) The elements of water R2 C=CR2 →> RCHCR add to the double bond with regio- lectivity opposite to that of mar kovnikov' s rule. This is a very good Alkene Alcohol synthetic method; addition is syn, CH3(CH2)7 CH=CH2 CH3(CH2)7 CH2CH2OH 1-Decene 1-Decanol (93%) Hydrolysis of alkyl halides(Section 8.1) a reaction useful only with sub strates that do not undergo E2 elimi- Alkyl Hydroxide Alcoh nation readily. It is rarely used for e synthesis of alcohols, since alkyl CH CH alides are normally prepared from H3C H 2, 4, 6-Trimethylbe 2,4.6-T alcohol (78%) Reaction of Grignard reagents with aldehydes and ketones(Section 14.6) A method that allows for alcohol RMgX R'CR preparation with formation of new carbon-carbon bonds. Primary, sec- R ondary, and tertiary alcohols can all Grignard Aldehyde Alcohol be prepared gent or ketone H CH2OH Cyclopentylmagnesium Formaldehyde Cyclopentylmethanol Reaction of organolithium reagents with aldehydes and ketones (Section 14.7)Organolithium reagents react RLi + RCR RCOH with aldehydes and ketones in a manner similar to that of Grignard reagents to form alcohols. Aldehyde Alcohol or ketone CHa CH2 CH2 CH2Li CH3 CH2 CH2CI Butyllithium Acetophenone 2-Phenyl-2-hexanol(67%) Back Forward Main MenuToc Study Guide ToC Student o MHHE Website
TABLE 15.1 Summary of Reactions Discussed in Earlier Chapters That Yield Alcohols (Continued) Reaction (section) and comments General equation and specific example Reaction of Grignard reagents with aldehydes and ketones (Section 14.6) A method that allows for alcohol preparation with formation of new carbon–carbon bonds. Primary, secondary, and tertiary alcohols can all be prepared. Aldehyde or ketone RCR O X Grignard reagent RMgX Alcohol RCOH W W R R 1. diethyl ether 2. H3O 1. diethyl ether 2. H3O H MgBr Cyclopentylmagnesium bromide H CH2OH Cyclopentylmethanol (62–64%) HCH O X Formaldehyde Reaction of organolithium reagents with aldehydes and ketones (Section 14.7) Organolithium reagents react with aldehydes and ketones in a manner similar to that of Grignard reagents to form alcohols. Aldehyde or ketone RCR O X Organolithium reagent RLi Alcohol RCOH W W R R 1. diethyl ether 2. H3O CH3CH2CH2CH2Li Butyllithium 2-Phenyl-2-hexanol (67%) CH3CH2CH2CH2±C±OH CH3 Acetophenone CCH3 O X 1. diethyl ether 2. H3O Hydrolysis of alkyl halides (Section 8.1) A reaction useful only with substrates that do not undergo E2 elimination readily. It is rarely used for the synthesis of alcohols, since alkyl halides are normally prepared from alcohols. Alkyl halide RX Hydroxide ion HO Alcohol ROH Halide ion X H3C CH3 CH2Cl CH3 2,4,6-Trimethylbenzyl chloride H3C CH3 CH2OH CH3 2,4,6-Trimethylbenzyl alcohol (78%) H2O, Ca(OH)2 heat (Continued) Hydroboration-oxidation of alkenes (Section 6.11) The elements of water add to the double bond with regioselectivity opposite to that of Markovnikov’s rule. This is a very good synthetic method; addition is syn, and no rearrangements are observed. 1. B2H6 2. H2O2, HO Alkene R2CœCR2 Alcohol R2CHCR2 OH W 1. B2H6, diglyme 2. H2O2, HO 1-Decene CH3(CH2)7CHœCH2 1-Decanol (93%) CH3(CH2)7CH2CH2OH 582 CHAPTER FIFTEEN Alcohols, Diols, and Thiols Back Forward Main Menu TOC Study Guide TOC Student OLC MHHE Website
15.2 Preparation of Alcohols by Reduction of Aldehydes and Ketones TABLE 15.1 Summary of Reactions Discussed in Earlier Chapters That Yield Alcohols( Continued) Reaction(section) and comments General equation and specific example Reaction of Grignard reagents with ary alcohols in which two of the sub- 2RMgX+ R' COR"1. diethyl ethe rCoh+R"OH esters(Section 14.10) Produces teri stituents on the hydroxyl-bearing carbon are derived from the Gr 2CH3 CH2 CH2 CH2 CH2 MgBr CH3 CH diethyl ether 2.H2O Pentylmagnesium CH3CCH2 CH2 CH2CH2 CH3 CH2 CH2 CH2CH2 CH3 6-Methyl-6-undecanol (75%) importance of alcohols in synthetic organic chemistry. Some of these methods involve Recall from Section 2.16that reduction of carbonyl groups ecrease in the nu OH bonds between car oxygen educing agent number of bond arbon and hydrogen(or We will begin with the reduction of aldehydes and ketones 15.2 PREPARATION OF ALCOHOLS BY REDUCTION OF ALDEHYDES AND KETONES The most obvious way to reduce an aldehyde or a ketone to an alcohol is by hydro- genation of the carbon-oxygen double bond. Like the hydrogenation of alkenes, the reac tion is exothermic but exceedingly slow in the absence of a catalyst. Finely divided met als such as platinum, palladium, nickel, and ruthenium are effective catalysts for the hydrogenation of aldehydes and ketones. Aldehydes yield primary alcohols RCH+ RCHOH Aldehyde Hydrogen Primary alcoho CHO CH -->CH3O- CHOH p-Methoxybenzaldehyde Methoxybenzyl alcohol (92 Back Forward Main MenuToc Study Guide ToC Student o MHHE Website
importance of alcohols in synthetic organic chemistry. Some of these methods involve reduction of carbonyl groups: We will begin with the reduction of aldehydes and ketones. 15.2 PREPARATION OF ALCOHOLS BY REDUCTION OF ALDEHYDES AND KETONES The most obvious way to reduce an aldehyde or a ketone to an alcohol is by hydrogenation of the carbon–oxygen double bond. Like the hydrogenation of alkenes, the reaction is exothermic but exceedingly slow in the absence of a catalyst. Finely divided metals such as platinum, palladium, nickel, and ruthenium are effective catalysts for the hydrogenation of aldehydes and ketones. Aldehydes yield primary alcohols: RCH O Aldehyde H2 Hydrogen Pt, Pd, Ni, or Ru RCH2OH Primary alcohol H2, Pt ethanol CH3O CH O p-Methoxybenzaldehyde CH3O CH2OH p-Methoxybenzyl alcohol (92%) reducing agent C O C H OH 15.2 Preparation of Alcohols by Reduction of Aldehydes and Ketones 583 TABLE 15.1 Summary of Reactions Discussed in Earlier Chapters That Yield Alcohols (Continued) Reaction (section) and comments General equation and specific example Reaction of Grignard reagents with esters (Section 14.10) Produces tertiary alcohols in which two of the substituents on the hydroxyl-bearing carbon are derived from the Grignard reagent. RCOR O X 2RMgX RCOH ROH W W R R 1. diethyl ether 2. H3O Ethyl acetate CH3COCH2CH3 O X Pentylmagnesium bromide 2CH3CH2CH2CH2CH2MgBr 1. diethyl ether 2. H3O 6-Methyl-6-undecanol (75%) CH3CCH2CH2CH2CH2CH3 W W OH CH2CH2CH2CH2CH3 Recall from Section 2.16 that reduction corresponds to a decrease in the number of bonds between carbon and oxygen or an increase in the number of bonds between carbon and hydrogen (or both). Back Forward Main Menu TOC Study Guide TOC Student OLC MHHE Website
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
