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