The following reaction involves a starting material with a double bond and a hydroxy group, yet its mechanism resembles a pinacol rearrangement. Propose a mechanism, and point out the part of your mechanism that resembles a pinacol rearrangement.

Predict the products formed by periodic acid cleavage of the following diols.

(a) CH₃CH(OH)CH(OH)CH₃

(b)

Predict the products formed by periodic acid cleavage of the following diols.

(c)

(d)

Show the alcohol and the acid chloride that combine to make the following esters.

(c)

(d)

Use resonance forms of the conjugate bases to explain why methanesulfonic acid (CH₃SO₃H, pK_a = –2.6) is a much stronger acid than acetic acid (CH₃COOH, pK_a = 4.8).

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.

(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 student wanted to use the Williamson ether synthesis to make (R)-2-ethoxybutane. He remembered that the Williamson synthesis involves an S_N2 displacement, which takes place with inversion of configuration. He ordered a bottle of (S)-butan-2-ol for his chiral starting material. He also remembered that the S_N2 goes best on primary halides and tosylates, so he made ethyl tosylate and sodium (S)-but-2-oxide. After warming these reagents together, he obtained an excellent yield of 2-ethoxybutane.

a. What enantiomer of 2-ethoxybutane did he obtain? Explain how this enantiomer results from the S_N2 reaction of ethyl tosylate with sodium (S)-but-2-oxide.

b. What would have been the best synthesis of (R)-2-ethoxybutane?

c. How can this student convert the rest of his bottle of (S)-butan-2-ol to (R)-2-ethoxybutane?

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.

To practice working through the early parts of a multistep synthesis, devise syntheses of

(a) pentan-3-one from alcohols containing no more than three carbon atoms.

To practice working through the early parts of a multistep synthesis, devise syntheses of

(b) 3-ethylpentan-2-one from compounds containing no more than three carbon atoms.

Develop syntheses for the following compounds. As starting materials, you may use cyclopentanol, alcohols containing no more than four carbon atoms, and any common reagents and solvents.

(a) trans-cyclopentane-1,2-diol

Develop syntheses for the following compounds. As starting materials, you may use cyclopentanol, alcohols containing no more than four carbon atoms, and any common reagents and solvents.

(b) 1-chloro-1-ethylcyclopentane

Develop syntheses for the following compounds. As starting materials, you may use cyclopentanol, alcohols containing no more than four carbon atoms, and any common reagents and solvents.

(c)

Develop syntheses for the following compounds. As starting materials, you may use cyclopentanol, alcohols containing no more than four carbon atoms, and any common reagents and solvents.

(d)

Develop syntheses for the following compounds. As starting materials, you may use cyclopentanol, alcohols containing no more than four carbon atoms, and any common reagents and solvents.

(e)

Develop syntheses for the following compounds. As starting materials, you may use cyclopentanol, alcohols containing no more than four carbon atoms, and any common reagents and solvents.

(f)

Predict the major products of the following reactions, including stereochemistry where appropriate.

(a) (R)-butan-2-ol + TsCl in pyridine

(b) (S)-2-butyl tosylate + NaBr

Predict the major products of the following reactions, including stereochemistry where appropriate.

(c) cyclooctanol + NaOCl/HOAC

(d) cyclopentylmethanol + CrO₃·pyridine·HCl

Predict the major products of the following reactions, including stereochemistry where appropriate.

(e) cyclopentylmethanol + Na₂Cr₂O₇/H₂SO₄

(f) cyclopentanol + HCl/ZnCl₂

(g) n-butanol + HBr

Predict the major products of the following reactions, including stereochemistry where appropriate.

(h) cyclooctylmethanol + CH₃CH₂MgBr

(i) potassium tert-butoxide + methyl iodide

(j) sodium methoxide + tert-butyl iodide

Predict the major products of the following reactions, including stereochemistry where appropriate.

(k) cyclopentanol + H₂SO₄/heat

(l) product from (k) + OsO₄/H₂O₂, then HIO₄

(m) sodium ethoxide + 1-bromobutane

Predict the major products of the following reactions, including stereochemistry where appropriate.

(n) sodium ethoxide + 2-methyl-2-bromobutane

(o) octan-1-ol + DMSO + oxalyl chloride

(p) 4-cyclopentylhexan-1-ol + DMP reagent

Show how you would convert 2-methylcyclopentanol to the following products. Any of these products may be used as the reactant in any subsequent part of this problem.

a. 1-methylcyclopentene

b. 2-methylcyclopentyl tosylate

c. 2-methylcyclopentanone

Show how you would convert 2-methylcyclopentanol to the following products. Any of these products may be used as the reactant in any subsequent part of this problem.

d. 1-methylcyclopentanol

Show how you would convert 2-methylcyclopentanol to the following products. Any of these products may be used as the reactant in any subsequent part of this problem.

(g) 2-methylcyclopentyl acetate

(h) 1-bromo-1-methylcyclopentane

In each case, show how you would synthesize the chloride, bromide, and iodide from the corresponding alcohol.

(a) 1-halobutane (halo = chloro, bromo, iodo)

(b) halocyclopentane

Show how you would accomplish the following synthetic conversions.

(a)

(b)

Show how you would accomplish the following synthetic conversions.

(c)

Show how you would accomplish the following synthetic conversions.

(d)