12. Alcohols, Ethers, Epoxides and Thiols

There are two different ways of making 2-ethoxyoctane from octan-2-ol using the Williamson ether synthesis. When pure (–)-octan-2-ol of specific rotation -8.24° is treated with sodium metal and then ethyl iodide, the product is 2-ethoxyoctane with a specific rotation of -15.6°. When pure (–)-octan-2-ol is treated with tosyl chloride and pyridine and then with sodium ethoxide, the product is also 2-ethoxyoctane. Predict the rotation of the 2-ethoxyoctane made using the tosylation/sodium ethoxide procedure, and propose a detailed mechanism to support your prediction.

Propose a Williamson synthesis of 3-butoxy-1,1-dimethylcyclohexane from 3,3-dimethyl-cyclohexanol and butan-1-ol.

Fluoxetine hydrochloride (Prozac®) is a widely used antidepressant. How might you stereoselectively install the indicated ether functional group (ROR) in (R)-fluoxetine?

Predict the product when the dihydroxybenzene shown is treated with a single equivalent of both base and haloalkane.

What is the product of the following reaction?

Predict the product of the following substitution/addition reactions involving phenoxides.

(a)

Predict the product of the following reactions. [Two of them are Williamson ether syntheses. Why isn't the other?].

(a)

Identify the alkene and alcohol partners that could be used to make the following ethers.

(a)

Predict the product of the following reactions. [Two of them are Williamson ether syntheses. Why isn't the other?].

(c)

Suggest a phenoxide and an alkyl halide to make the following aryl alkyl ethers.

(b)

Two different Williamson ether syntheses can be used to make the compound in (a). Show them. The compound in (b), however, can only be made one way. Show it and explain why a second Williamson ether synthesis is not possible.

(a)

In contrast to Assessment 13.102, only one combination of haloalkane and alkoxide can be used in the Williamson ether synthesis to make the ether shown. Identify the combination and explain why it is the only combination that works.

Predict the product of the following reactions. [Two of them are Williamson ether syntheses. Why isn't the other?].

(b)

In Chapter 12, we learned that crown ethers were used to increase the rate of S_N2 reactions (Assessment 12.80). Suggest a synthesis of 15-crown-5 using the reactions learned here in Chapter 13.

Suggest a phenoxide and an alkyl halide to make the following aryl alkyl ethers.

(a)