12. Alcohols, Ethers, Epoxides and Thiols

a. Propose a mechanism for the following reaction:

(a) Show how ethanol and cyclohexanol may be used to synthesize cyclohexyl ethyl ether (tosylation followed by the Williamson ether synthesis).

(b) Why can't we synthesize this product simply by mixing the two alcohols, adding some sulfuric acid, and heating?

A good Williamson synthesis of ethyl methyl ether would be

What is wrong with the following proposed synthesis of ethyl methyl ether? First, ethanol is treated with acid to protonate the hydroxy group (making it a good leaving group), and then sodium methoxide is added to displace water.

Phenols (pK_a ≈ 10) are more acidic than other alcohols, so they are easily deprotonated by sodium hydroxide or potassium hydroxide. The anions of phenols (phenoxide ions) can be used in the Williamson ether synthesis, especially with very reactive alkylating reagents such as dimethyl sulfate. Using phenol, dimethyl sulfate, and other necessary reagents, show how you would synthesize methyl phenyl ether.

Identify the two possible combinations of haloalkane and alkoxide that can be used to make the following ether.

The reaction of alkoxides with haloalkanes is not a viable way to form ethers. (a) Why? (b) Why can thioethers be formed by an analogous reaction?

How could the reaction in Figure 13.67(b) be modified to produce the following ether?

Show how the following ethers might be synthesized using (1) alkoxymercuration– demercuration and (2) the Williamson synthesis. (When one of these methods cannot be used for the given ether, point out why it will not work.)

a. 2-methoxybutane

b. ethyl cyclohexyl ether

c. 1-methoxy-2-methylcyclopentane

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)