Carey - Organic Chemistry - chapt15

Carey - Organic Chemistry - chapt15

(Parte 1 de 5)


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’l 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. Diolsare alcohols in which two hydroxyl groups (±OH) are present; thiolsare 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.


Until the 1920s, the major source of methanolwas as a byproduct in the production of charcoal from wood—hence, the name wood alcohol.Now, most of the more than 10

Ketone RCOH

Carboxylic acid

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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 mLhas been fatal. Ingestion of sublethal amounts can lead to blindness.

When vegetable matter ferments, its carbohydrates are converted to ethanoland 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

COCarbon monoxide 2H2Hydrogen CH3OHMethanol

580CHAPTER FIFTEENAlcohols, 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).









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 andgeranium oil and used in perfumery)Retinol (vitamin A, an important substance in vision)

Glucose (a carbohydrate) H3C

FIGURE 15.1 Some naturally occurring alcohols.

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TABLE 15.1Summary of Reactions Discussed in Earlier Chapters That Yield Alcohols Reaction (section) and comments


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



CH3 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 denaturedby 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 alcoholis 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.

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TABLE 15.1Summary of Reactions Discussed in Earlier Chapters That Yield Alcohols (Continued) Reaction (section) and commentsGeneral 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, sec- ondary, and tertiary alcohols can all be prepared.Aldehyde or ketone

Grignard reagent RMgX Alcohol

1. diethyl ether

Cyclopentylmagnesium bromide



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

Organolithium reagent RLi Alcohol


Butyllithium 2-Phenyl-2-hexanol (67%)

CH3 Acetophenone


OX1. diethyl ether

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

Hydroxide ion ion



2,4,6-Trimethylbenzyl chloride


2,4,6-Trimethylbenzyl alcohol (78%)


Hydroboration-oxidation of alkenes (Section 6.1) 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.

582CHAPTER FIFTEENAlcohols, Diols, and Thiols

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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.


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:


Pt, Pd, Ni, or RuRCH2OH Primary alcohol

H2, PtethanolCHCH3O O p-Methoxybenzaldehyde CH2OHCH3O p-Methoxybenzyl alcohol (92%) reducing agentCOC HO H

TABLE 15.1Summary of Reactions Discussed in Earlier Chapters That Yield Alcohols (Continued)

Reaction (section) and commentsGeneral 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.

Ethyl acetate


Pentylmagnesium bromide

2CH3CH2CH2CH2CH2MgBr 1. diethyl ether

6-Methyl-6-undecanol (75%)


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).

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Ketones yield secondary alcohols:

PROBLEM 15.1Which 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 m-Nitrobenzaldehyde CH2OH m-Nitrobenzyl alcohol (82%)

NaBH4 water, methanol,or ethanol RCH

Aldehyde RCH2OH Primary alcohol

NaBH4 water, methanol,or ethanol RCR

Secondary alcohol

4,4-Dimethyl-2-pentanol (85%)

NaBH4 ethanol


OH Secondary alcohol

H2, Pt methanol

OCyclopentanone OHH Cyclopentanol (93–95%)

584CHAPTER FIFTEENAlcohols, Diols, and Thiols

Compare the electrostatic and AlH4 on Learning By Modeling.Notice how different the electrostatic potentials associated with hydrogen are.

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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 donorsrather 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

Asimilar series of hydride transfers occurs when aldehydes and ketones are treated with lithium aluminum hydride.

3R2CœO H BH3



1. LiAlH4, diethyl ether 2. H2ORCH

Aldehyde RCH2OH Primary alcohol

Heptanal CH3(CH2)5CH2OH1-Heptanol (86%)

1. LiAlH4, diethyl ether 2. H2O


OH Secondary alcohol

1. LiAlH4, diethyl ether 2. H2O


OH 1,1-Diphenyl-2-propanol (84%)

1. LiAlH4, diethyl ether 2. H2O

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Addition of water converts the tetraalkoxyaluminate to the desired alcohol.

PROBLEM 15.2Sodium 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 NaBD4in H2O

(b)Reduction of (acetone) with NaBD4in CH3OD

(c)Reduction of (benzaldehyde) with NaBD4in CD3OH

(d)Reduction of (formaldehyde) with LiAlD4in 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.

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.







3R2CœO H AlH3


R2COH Tetraalkoxyaluminate

586CHAPTER FIFTEENAlcohols, Diols, and Thiols




An undergraduate laboratory experiment related to Problem 15.2 appears in the March 1996 issue of the Journal of Chemical Education, p. 264–266.

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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. Avery 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 15.3Give 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.


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. H2OCOCH2CH3

Ethyl benzoate CH2OHBenzyl alcohol (90%)

CH3CH2OH Ethanol

Ester RCH2OHPrimary alcohol

1. LiAlH4, diethyl ether 2. H2ORCOH

Carboxylic acid RCH2OH Primary alcohol

Cyclopropanecarboxylic acid

CH2OH Cyclopropylmethanol (78%)

(Parte 1 de 5)