22. Carboxylic Acid Derivatives: NAS

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 a-bromo ester with zinc.

<IMAGE>

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

c. <IMAGE>

Propose mechanisms for the following reactions.

(c) <IMAGE>

Propose mechanisms for the following reactions.

(d) <IMAGE>

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.

(c) 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.

<IMAGE> (Solved Problem 20-1)

(b) Finish the solution for Solved Problem 20-1 by providing a mechanism for the acid-catalyzed hydrolysis of ethyl formate.