# 15.E: Alcohols and Ethers (Exercises)

Exercise 15-1

a. Draw the structure of 4-methoxy-1-penten-3-ol.

b. Name the following structure by the IUPAC system:

Exercise 15-2 Explain how hydrogen bonding makes cis-cyclopentane-1,2-diol substantially more volatile (bp $$119^\text{o}$$ at $$22 \: \text{mm}$$ of $$\ce{Hg}$$) than trans-cyclopentane-1,2-diol (bp $$136^\text{o}$$ at $$22 \: \text{mm}$$ of $$\ce{Hg}$$).

Exercise 15-3 What type of infrared absorption bands due to hydroxyl groups would you expect for trans-cyclobutane-1,2-diol and butane-1,2-diol (a) in very dilute solution, (b) in moderately concentrated solution, and (c) as pure liquids? Give your reasoning.

Exercise 15-4 Suggest a likely structure for the compound of molecular formula $$\ce{C_4H_6O}$$ whose proton NMR and infrared spectra are shown in Figure 15-3a. Show your reasoning. Do the same for the compound of formula $$\ce{C_3H_8O_2}$$, whose spectra are shown in Figure 15-3b.

Figure 15-3: Proton NMR and infrared spectra of (a) of $$\ce{C_4H_6O}$$ and (b) of $$\ce{C_3H_8O_2}$$; see Exercise 15-4.

Exercise 15-5 Pure, dry ethanol has a triplet NMR resonance for its $$\ce{OH}$$ proton and a quintet resonance for its $$\ce{CH_2}$$ protons. If $$5\%$$ by weight of water is added to the ethanol, a new single peak is observed about $$0.8 \: \text{ppm}$$ upfield of the ethanol $$\ce{OH}$$ triplet. If $$30\%$$ by weight of water is added, there is only a single large $$\ce{OH}$$ resonance, and the $$\ce{CH_2}$$ resonance becomes a quartet. Explain the changes produced in the NMR spectrum by adding water.

Exercise 15-6 Show how the following alcohols may be prepared from cyclohexene and any other needed reagents. Several steps may be necessary.

a.

b.

c.

d.

Exercise 15-7 What order of basicity would you predict for water, methanol, isopropyl alcohol, and tert-butyl alcohol in the gas phase? Give your reasoning.

Exercise 15-8 Suggest a practical method for preparation of the following ethers. Show the reaction conditions as closely as possible.

a. methoxyethane
b. 3-ethoxy-1-butene
c. methoxycyclohexane

Exercise 15-9 An alternative and plausible mechanism for esterification of carboxylic acids is shown by the following steps:

This mechanism corresponds to an $$S_\text{N}2$$ displacement of water from the methyloxonium ion by the acid. How could you distinguish between this mechanism and the addition-elimination mechanism using heavy oxygen $$\left( \ce{^{18}O} \right)$$ as a tracer?

Exercise 15-10 Formation of tert-butyl ethanoate by direct esterification goes very poorly:

Explain why the reaction fails, and indicate the products you actually expect to form on heating a mixture of ethanoic acid and tert-butyl alcohol with sulfuric acid as a catalyst.

Exercise 15-11 A suitable method of preparing tert-butyl esters is to add the carboxylic acid to 2-methylpropene. Good yields can be obtained if a strong acid catalyst is used, if water is excluded, and if the temperature is kept low:

Write a mechanism for the reaction that accounts for the need for a strong acid catalyst, and why anhydrous conditions and low temperatures are necessary.

Exercise 15-12 The diethyl ester of cis-butenedioic acid can be prepared by heating the corresponding anhydride with ethanol and concentrated $$\ce{H_2SO_4}$$ in benzene in a mole ratio of perhaps 1:2.5:0.25.

Write the steps that occur in this reaction and explain how the use of benzene and more than a catalytic amount of $$\ce{H_2SO_4}$$ makes the formation of the diethyl ester thermodynamically more favorable than with just a catalytic amount of $$\ce{H_2SO_4}$$.

Exercise 15-13 Complete the following reactions by drawing structures for the major organic products expected.

a. $$D$$-$$\ce{CH_3CH_2CH(OH)CH_3} + \ce{CH_3CO_2H} \overset{\ce{H}^\oplus}{\longrightarrow}$$

b. $$\ce{CH_3COCl} + \ce{CH_2=CH-CH_2OH} \rightarrow$$

c.

Exercise 15-14 One can conceive of an esterification procedure involving the reaction of ethanol with ethanoate ion in accord with the following mechanism:

Assess the likelihood of the occurrence of this reaction at a reasonable rate and the favorableness of its overall equilibrium constant.

Exercise 15-15 How can $$D$$-glucose, $$D$$-fructose, and $$D$$-ribose be considered products of the addition of an alcohol to the carbonyl group of an aldehyde or ketone? Name each of the carbonyl compounds by the IUPAC system. For the ribose carbonyl structure, determine the configuration at each chiral center, using the $$D$$,$$L$$ system.

Exercise 15-16 Hemiacetal formation is catalyzed by both acids and bases, but acetal formation is catalyzed only by acids. Write the steps involved in the formation of 1-methoxyethanol from ethanal in methanol containing sodium methoxide:

$\ce{CH_3CHO} + \ce{CH_3OH} \overset{\ce{NaOCH_3}}{\longrightarrow} \ce{CH_3CH(OH)OCH_3}$

Explain why 1,1-dimethoxymethane cannot be prepared from ethanal and methanol with a basic catalyst.

Exercise 15-17 The slow step in an alternative mechanism for acetal formation may be as follows:

How could this mechanism be distinguished experimentally from the one give in Section 15-4E?

Exercise 15-18 Ketals are not always capable of being made in practical yields by the direct reaction of alcohols with ketones because of unfavorable equilibria. Satisfactory preparations of $$\ce{RO-C-OR}$$ with $$\ce{R} =$$ methyl or ethyl are possible through the reactions of ketones with trimethoxy- or triethoxymethane. This process requires an acid catalyst:

Write the mechanistic steps involved in this acid-induced methoxy exchange reaction.

Exercise 15-19 Look at the structure of tetrodotoxin in Section 15-0. What would you expect to happen to the hydroxyl at the bridgehead position in dilute base?

Exercise 15-20 If you wished to convert $$D$$-1-phenylethanol to $$L$$-1-chloro-1-phenylethane, which of the following reagents and conditions would you use? Give reasons for your choice.

a. $$\ce{HCl}$$ and $$\ce{ZnCl_2}$$
b. $$\ce{SOCl_2}$$ alone
c. $$\ce{SOCl_2}$$ with pyridine

Exercise 15-21 Write the steps that could plausibly take place in the reaction of a primary alcohol with phosphorus tribromide in the presence of the weak base pyridine to give an alkyl bromide.

Exercise 15-22 Methylmagnesium iodide with 2-butenal gives an addition product that, when hydrolyzed with dilute sulfuric acid and extracted with ether, yields an ether solution of impure 3-penten-2-ol. Attempted purification by distillation of the ether extract gives only 1,3-pentadiene and di(1-methyl-2-butenyl) ether. Write equations for each of the reactions involved. How could you avoid ether and diene formation in the preparation of 3-penten-2-ol by this method?

Exercise 15-23 What are the expected products on heating the following alcohols with strong sulfuric acid? Give your reasoning.

a. cyclohexanol
b. a mixture of methanol and 1-methylcyclohexanol
c. $$\ce{(CH_2)_2C=CHCH_2OH}$$

Exercise 15-24* It is possible to prepare amides from tertiary alcohols and alkanenitriles, $$\ce{RCN}$$, in concentrated sulfuric acid as the catalyst (Ritter reaction), as illustrated in the equation for the synthesis of $$\ce{N}$$-tert-butylethanamide:

$\ce{(CH_3)_2COH} + \ce{CH_3CN} \overset{\ce{H_2SO_4}}{\longrightarrow} \ce{CH_3CONHC(CH_3)_3}$

Show the steps in the mechanism of this reaction, given the fact that nitrilium ions of structure $$\ce{R-C \equiv} \overset{\oplus}{\ce{N}} \ce{-R}$$ are likely to be intermediates.

Exercise 15-25* The equilibrium for the formation of urea compounds from the hydrolysis of substances called "carbodiimides" is a thermodynamically favorable reaction:

When coupled with an esterification involving an acid and an alcohol this reaction gives excellent conversions, although not in aqueous solution because the nucleophilic reactivities of water and alcohols are rather similar. Show the possible steps by which carbodiimides can achieve this conversion:

$\ce{CH_3CO_2H} + \ce{CH_3OH} + \ce{RN=C=NR} \rightleftharpoons \ce{CH_3CO_2CH_3} + \ce{RNHCONHR}$

(In Chapter 25 we shall encounter reactions of amines and amino acids in which carbodiimides can be used in the presence of water. The difference is that amine nitrogen generally is more nucleophilic than water.)

Exercise 15-26* Trialkoxyalkanes, $$\ce{R'C(OR)_3}$$, sometimes are called "orthoesters". They may be regarded as derived from alcohols and esters, although they seldom are prepared by this direct route because the following equilibrium is quite unfavorable:

a. On the basis of the resonance theory, why should we expect the equilibrium for orthoester formation to be unfavorable?

b. Explain why trimethoxymethane and methanol together give a higher conversion of a ketone to the corresponding ketal than methanol alone does in the presence of an acid catalyst.

c. How many one synthesize $$\ce{HC(OC_2H_5)_3}$$ from $$\ce{CHCl_3}$$? (Review Section 14-7B.)

Exercise 15-27 A possible mechanism for producing esterification of an alcohol coupled with ATP hydrolysis would be the following:

Work out possible mechanisms for each of these steps and decide whether this sequence is likely to be as feasible as the one described by Equations 15-5 and 15-6. Give your reasoning. How could you determine experimentally which mechanistic path was being followed?

Exercise 15-28 In the conversion of 2-propanol to 2-propanone with chromic acid, which is the redox step, esterification or elimination? What is the change in oxidation level of carbon in this reaction?

Exercise 15-29* The ring system, $$11$$, is found in many naturally occurring compounds known as steroids. Several important representatives of this class of compound have secondary hydroxyl groups at $$\ce{C_3}$$ and $$\ce{C_{11}}$$, with configurations represented by the sawhorse drawing, $$12$$:

Explain in detail how steric hindrance would lead you to expect that the relative reactivity of these two hydroxyl groups in esterification is $$\ce{C_3} > \ce{C_{11}}$$. and in chromic acid oxidation is $$\ce{C_{11}}$$ > \ce{C_3}\).

Exercise 15-30 How many moles of permanganate would be required to oxidize (a) one mole of cyclohexanol to cyclohexanone and (b) one mole of phenylmethanol (benzyl alcohol) to benzenecarboxylic acid in basic solution? (Review Section 11-1 if you have difficulty.)

Exercise 15-31 Show the mechanistic steps you expect to be involved in the oxidation of benzenecarbaldehyde (benzaldehyde) to benzenecarboxylic (benzoic) acid in an alkaline solution of potassium permanganate.

Exercise 15-32 Explain why oxidation of secondary alcohols with $$\ce{^{18}O}$$-labeled potassium permanganate produces an $$\ce{^{18}O}$$-containing ketone in acidic solution, but not in basic solution.

Exercise 15-33 The oxidation of $$\ce{(CH_3)_2CDOH}$$ is one seventh as fast as the oxidation of $$\ce{(CH_3)_2CHOH}$$ using potassium permanganate in acidic solution. What does this tell us about the mechanism of the reaction in acidic solution?

Exercise 15-34* For the transformations $$\ce{NAD}^\oplus + \ce{H}^\oplus + 2 \ce{e}^\ominus \rightleftharpoons \ce{NADH}$$ and $$\ce{FAD} + 2 \ce{H}^\oplus + 2 \ce{e}^\ominus \rightarrow \ce{FADH_2}$$, determine which atoms undergo a change in oxidation level, and by how much, according to the rules set up in Section 11-1.

Exercise 15-35 How would you synthesize (a) meso-2,3-butanediol and (b) $$D$$,$$L$$-2,3-butanediol from cis-2-butene?

Exercise 15-36* Write equations for the dissociation of ascorbic acid to give progressively a monoanion and a dianion. Assigna p$$K_a$$ to each dissociation and make your structures clear as to which are the acidic protons. Why is ascorbic acid a stronger diacid than cyclopentane-1,2-diol?

Exercise 15-37 The $$\ce{O-C}$$ bond of phenylmethyl ethers is reduced more readily by hydrogen over a metal catalyst than the $$\ce{O-C}$$ bond of methyl or ethyl esters. How do you account for this?

Exercise 15-38 Devise suitable reactions for the following conversions. (Indicate the specific protecting groups for the $$\ce{OH}$$ function appropriate for the reactions that you use.)

a. $$\ce{HOCH_2CH_2CHO} \rightarrow \ce{HO_2CCH_2CH(CH_3)OH}$$

b.

c.

Exercise 15-39 Write the mechanistic steps involved in the acid-catalyzed addition of alcohols to the cyclic ether $$16$$. Why does cyclohexene react far less readily than $$16$$ with alcohols under acidic conditions? Write equations for the steps involved in the hydrolysis of $$17$$ with aqueous acid.

Would you anticipate ethoxyethene to be a comparably useful reagent for the protection of hydroxyl groups? Explain.

Exercise 15-40 Predict the products likely to be formed on cleavage of the following ethers with hydroiodic acid:

a. $$\ce{CH_2=CH-CH_2-O-CH_3}$$
b. $$\ce{CH_3CH_2-O-CH=CH_2}$$
c. $$\ce{(CH_3)_3CCH_2-O-CH_3}$$
d. $$\ce{(CH_3)_3COCH_3}$$
e.
f.

Exercise 15-41

a. Explain why trimethyloxonium salts will convert alcohols to methyl ethers at neutral or acidic pH, whereas either methyl iodide or dimethyl sulfate requires strongly basic reaction conditions.

b. What products would you expect from the reactions of trimethyloxonium fluoroborate with (1) ethanethiol, $$\ce{C_2H_5SH}$$, (2) diethylamine, $$\ce{(C_2H_5)_2NH}$$, and (3) hydrogen bromide.

Exercise 15-42 The amino acid methionine is a methyl donor in biological methylation of hydroxyl groups. However, direct methylation has an unfavorable free energy change:

When coupled with hydrolysis of ATP (Section 15-5F) methylation becomes favorable as the result of the overall process:

Suggest a sequence of reasonable steps for this process on the basis that sulfides, $$\ce{RSR}$$, are both excellent nucleophiles and good leaving groups. It is implicit that all steps will be enzyme-catalyzed, although the way the enzymes function is unknown. Each step must be energetically reasonable because enzymes, like other catalysts, cannot induce thermodynamically unfavorable reactions.

Exercise 15-43 Draw structures for the following compounds and name each as an oxa-, aza-, or thiacycloalkane (cycloalkene, cycloalkadiene, and so on, as appropriate).

a. aziridine
b. thiirane
c. oxetan-2-one
d. 1,3-diazole
e. 1,3,5-trioxan
f. 3-phenyloxolane
g. perhydroazepine

Exercise 15-44 Which member of the following pairs of compounds would you expect to react faster with hydroxide ion?

a. or

b. or

c. $$\ce{HOC_2CH_2Cl}$$ or $$\ce{HOCH(Cl)CH=CH_2}$$

Exercise 15-45 Oxacyclopropanes tend to polymerize under basic conditions. Draw the structure of the polymer obtained on polymerization of $$D$$-2-methyloxacyclopropane catalyzed by $$\ce{Na}^\oplus \: ^\ominus \ce{OCH_3}$$. Would you expect it to be formed with all $$D$$, all $$L$$, alternating $$D$$ and $$L$$, or with random configurations of the chiral atoms in the chain?

Exercise 15-46 Draw the structures, showing the stereochemistry where necessary, for the products you would expect from the following reactions:

a.

b.

c. meso-dimethyloxacyclopropane + $$\ce{(CH_3)_3O}^\oplus + \ce{BF_4^-} + \ce{CH_3OH} \rightarrow$$

d.

Exercise 15-47 Show how you would synthesize each of the following alcohols, ethers, or acetals from the given organic starting materials and other necessary organic or inorganic reagents. Specify reagents and conditions as closely as possible.

a. $$\ce{CH_3OCH_2CH_2OCH_3}$$ from ethene

b. from 1-propanol

c. $$\ce{(CH_2=CHCH_2)_2O}$$ from $$\ce{CH_2=CHCH_2Cl}$$

d. trans-1,2-cyclohexanediol from cyclohexene

e. from cyclohexanol

f. from cyclohexanol and 1,2-ethanediol

Exercise 15-48 Show how you would convert each of the following alcohols to the indicated products. Specify necessary reagents and conditions.

a. 1-propanol to $$\ce{CH_3CH_2CH_2CH(CH_3)Cl}$$

b. ethanol to

c. $$\ce{(CH_3)_3COH}$$ to $$\ce{(CH_3)_2CHCH_2Br}$$

d. 1-butanol to $$\ce{CH_3CH_2CH(OSO_3H)CH_3}$$

e. $$\ce{(CH_3)_2C(OH)CH_2CH_3}$$ to $$\ce{CH_3CH_2C(CH_3)_2CHO}$$

f. to

g. to

Exercise 15-49 Give for each of the following pairs of compounds a chemical test, preferably a test-tube reaction, that will distinguish between the two substances. Describe the observation by which the distinction is made and write an equation for each reaction.

a. and

b. $$\ce{CH_2=CH-CH_2CH_2OH}$$ and $$\ce{CH_3CH=CH-CH_2OH}$$

c. and $$\ce{CH_3-CH(CH_3)-CH_2CH_2OH}$$

d. $$\ce{CH_3CH_2-O-SO_2-O-CH_2CH_3}$$ and $$\ce{CH_3CH_2CH_2CH_2-O-SO_3H}$$

e. $$\ce{CH_3COCl}$$ and $$\ce{ClCH_2COOH}$$

f. and

g. and

h. and

i. and

j. and

Exercise 15-50 Suppose you were given unlabeled bottles, each of which is known to contain one of the following compounds: 1-pentanol, 2-pentanol, 2-methyl-2-butanol, 3-penten-1-ol, 4-pentyn-1-ol, 1-butoxybutane, and 1-pentyl acetate. Explain how you could use simple chemical tests (test-tube reactions only) to identify the contents of each bottle.

Exercise 15-51 Either tert-butyl alcohol or 2-methylpropene treated with strong sulfuric acid and hydrogen peroxide $$\left( \ce{H_2O_2} \right)$$ gives a mixture of two reasonably stable liquid compounds (A and B), the ratio of which depends on whether the hydrogen peroxide or organic starting material is in excess. The molecular formula of A is $$\ce{C_4H_{10}O_2}$$, whereas B is $$\ce{C_8H_{18}O_2}$$.

Treatment of A and B with hydrogen over a nickel catalyst results in quantitative conversion of each compound to tert-butyl alcohol. A reacts with acyl halides and anhydrides, whereas B is unaffected by these reagents. Treatment of 1 mole of A with excess methylmagnesium iodide in diethyl ether solution produces 1 mole of methane and 1 mole each of tert-butyl alcohol and methanol. One mole of B with excess methylmangesium iodide produces 1 mole of 2-methoxy-2-methylpropene and 1 mole of tert-butyl alcohol.

When B is heated with chloroethane, it causes chloroethane to polymerize. When B is heated alone, it yields 2-propanone and ethane, and if heated in the presence of oxygen, it forms methanol, 2-propanone, methanal, and water.

Determine the structure of A an dB and write equations for all reactions involved, showing the mechanisms and intermediates that are important for each. Write at least one structure for A and for B that is isomeric with your preferred structures and show how these substances would behave in each of the given reactions.

Exercise 15-52 The reaction of methyl ethanoate with water to give methanol and ethanoic acid is catalyzed by strong mineral acids such as sulfuric acid. Furthermore, when hydrolysis is carried out in water enriched in the rare oxygen isotope, $$\ce{^{18}O}$$, the following exchange takes place faster than formation of methanol:

No methanol-$$\ce{^{18}O}$$ $$\left( \ce{CH_3} \ce{^{18}OH} \right)$$ is formed in hydrolysis under these conditions.

a. Write a stepwise mechanism that is in harmony with the acid catalysis and with the results obtained in $$\ce{^{18}O}$$ water. Mark the steps of the reaction that are indicated to be fast or slow.

b. The reaction depends on methyl ethanoate having a proton-accepting ability comparable to that of water. Why? Consider different ways of adding a proton to methyl ethanoate and decide which is most favorable on the basis of structural theory. Give your reasoning.

c. Explain why the reaction is slowed down in the presence of very high concentrations of sulfuric acid.

Exercise 15-53 Write a mechanism for the reaction of trans-2-butene with trifluoroperoxoethanoic acid to give trans-2,3-dimethyloxacyclopropane that is consistent with the fact that the reaction is first order in each participant and gives suprafacial addition.

Exercise 15-54 2,2,4,4-Tetramethyl-3-oxapentane (di-tert-butyl ether) is very unstable to acidic reagents. Devise a synthesis of the compound that you think might have a reasonable chance for success. Give your reasoning.

Exercise 15-55 How would you expect the fraction of elimination toward the methyl groups, as opposed to elimination toward the methylene group, to compare in $$E1$$ and $$E2$$ reactions of 2-chloro-2-methylbutane and the corresponding deuterium-labeled chloride, 2-chloro-2-methylbutane-3-$$\ce{D_2}$$? Give your reasoning. (Review Sections 8-8 and 15-6B.)

Exercise 15-56 Triethyloxonium fluoroborate can be prepared from 1-chloromethyloxacyclopropane and a $$\ce{BF_3}$$-etherate according to the equation

The boron in the complex boron anion ends up as $$\ce{BF_4^-}$$, but the details of this reaction need not concern you. Write the steps that you expect to be involved in the reaction to form $$\ce{R_3O}^\oplus$$ and that you can support by analogy with other reactions discussed in this chapter.

Exercise 15-57 Support your explanation of each of the following facts by reasoning based on mechanistic considerations:

a. $$D$$-1-Phenylethanol reacts with thionyl chloride, $$\ce{SOCl_2}$$, in pyridine to give $$L$$-1-phenylethyl chloride by way of an intermediate chlorosulfite ester,

b. 2-Buten-1-ol and $$\ce{SOCl_2}$$ in ether and a one-molar equivalent of tributylamine gives 1-chloro-2-butene. In the absence of the base, the rearrangement product, 3-chloro-1-butene, is obtained.

Exercise 15-58 1,2-Ethanediol (ethylene glycol) is a familiar "antifreeze". However, it also is used in automotive cooling systems in climates that rarely, if ever, reach temperatures at which water would freeze. What other function, as important as lowering the freezing point, does the diol serve when added to automotive cooling systems?

## Contributors

• John D. Robert and Marjorie C. Caserio (1977) Basic Principles of Organic Chemistry, second edition. W. A. Benjamin, Inc. , Menlo Park, CA. ISBN 0-8053-8329-8. This content is copyrighted under the following conditions, "You are granted permission for individual, educational, research and non-commercial reproduction, distribution, display and performance of this work in any format."