22. Carboxylic Acid Derivatives: NAS

Show how you would accomplish the following syntheses.

c. hexan-1-ol → 2-hydroxyheptanoic acid

Predict the products and propose mechanisms for the following reactions.

(a)

Suppose we have some optically pure (R)-2-butyl acetate that has been "labeled" with the heavy ¹⁸O isotope at one oxygen atom as shown.

(b) Repeat part (a) for the acid-catalyzed hydrolysis of this compound.

Propose a mechanism for the acid-catalyzed hydrolysis of phenylalanine ethyl ester.

The Reformatsky reaction is an addition reaction in which an organozinc reagent is used instead of a Grignard reagent to add to the carbonyl group of an aldehyde or a ketone. Because the organozinc reagent is less reactive than a Grignard reagent, a nucleophilic addition to the ester group does not occur.

The organozinc reagent is prepared by treating an α-bromo ester with zinc.

Describe how each of the following compounds can be prepared, using a Reformatsky reaction:

c.

Propose mechanisms for the following reactions.

(c)

Propose mechanisms for the following reactions.

(d)

The mechanism for acidic hydrolysis of a nitrile resembles the basic hydrolysis, except that the nitrile is first protonated, activating it toward attack by a weak nucleophile (water). Under acidic conditions, the proton transfer (tautomerism) involves protonation on nitrogen followed by deprotonation on oxygen. Propose a mechanism for the acid-catalyzed hydrolysis of benzonitrile to benzamide.

Compare each of the mechanisms listed here with the mechanism for each of the two parts of the acid-catalyzed hydrolysis of an ester, indicating a. similarities. b. differences.

4. acid-catalyzed hydrolysis of an amide

What products would you expect to obtain from the following reactions?

c. urea + water

d. β-ethylglutaric acid + acetyl chloride + Δ

Which ester hydrolyzes more rapidly? a. methyl acetate or phenyl acetate?

Which ester hydrolyzes more rapidly? b. phenyl acetate or benzyl acetate?

Compare each of the mechanisms listed here with the mechanism for each of the two parts of the acid-catalyzed hydrolysis of an ester, indicating a. similarities. b. differences.

1. acid-catalyzed formation of a hydrate

For each heterocyclic compound,

(ii) show what compounds would result from complete hydrolysis.

(a)

(b)

(c)

How could you convert N-methylbenzamide to the following compounds?

b. benzoic acid