22. Carboxylic Acid Derivatives: NAS

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

b. benzoic acid

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

Propose mechanisms for the following reactions.

(a)

(b)

Write a mechanism for each of the following reactions:

a. the uncatalyzed hydrolysis of methyl propionate.

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.

What reagents would you use to convert methyl propanoate to the following compounds?

c. N-ethylpropanamide

d. propanoic acid

Show how you would accomplish the following syntheses.

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

Using the mechanism for the acid-catalyzed hydrolysis of an ester as your guide, write the mechanism—showing all the curved arrows—for the acid-catalyzed reaction of acetic acid and methanol to form methyl acetate. Use HB⁺ and :B to represent the proton-donating and proton-removing species, respectively.

Propose mechanisms for the following reactions.

(d)

The Principle of Microscopic Reversibility states that a forward reaction and a reverse reaction taking place under the same conditions (as in an equilibrium) must follow the same reaction pathway in microscopic detail. The reverse of the Fischer esterification is the acid-catalyzed hydrolysis of an ester. Propose a mechanism for the acid-catalyzed hydrolysis of ethyl benzoate, PhCOOCH₂CH₃.

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.

Describe how the target molecule (butanone) can be synthesized in a high yield from butane.

Why do the nitro groups change the relative leaving tendencies of the carboxy and 2,4-dinitrophenoxy groups in the tetrahedral intermediate in Problem 11?

a. When a carboxylic acid is dissolved in isotopically labeled water (H₂O¹⁸) and an acid catalyst is added, the label is incorporated into both oxygens of the acid. Propose a mechanism to account for this.

c. If an ester is dissolved in isotopically labeled water (H₂O¹⁸) and an acid catalyst is added, where will the label reside in the product?

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