12. Alcohols, Ethers, Epoxides and Thiols

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

(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 chemist wanted to synthesize the anesthetic 2-ethoxy-2-methylpropane. He used ethoxide ion and 2-chloro-2-methylpropane for his synthesis and ended up with no ether. What was the product of his synthesis? What reagents should he have used?

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.)

(e) 1-isopropoxy-1-methylcyclopentane

Show how you would accomplish the following transformations. Some of these examples require more than one step.

(e) 2-chlorohexan-1-ol → 1,2-epoxyhexane

Both LiAlH₄ and Grignard reagents react with carbonyl compounds to give alkoxide ion intermediates (that become protonated in an aqueous workup). Those alkoxides can react with 1° or methyl alkyl halides or tosylates to give ethers. Show how the following ethers can be formed in this two-step process. As starting materials you may use any reactants containing 7 carbons or fewer.

(c)

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.

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

(a)

What is the best way to prepare the following ethers using an alkyl halide and an alkoxide ion?

a.

b.

How could you synthesize isopropyl propyl ether, using isopropyl alcohol as the only carbon-containing reagent?

Show how you would accomplish the following transformations. Some of these examples require more than one step.

(d) 5-chloropent-1-ene → 2-methyltetrahydrofuran 

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

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

(b)