22. Carboxylic Acid Derivatives: NAS

Propose mechanisms for the nucleophilic acyl substitutions to form ethyl benzoate as shown on the previous page.

b. What is the product of the reaction of acetamide with HO⁻? The pK_a of NH₃ is 36; the pK_a of H₂O is 15.7.

Phosgene is the acid chloride of carbonic acid. Although phosgene was used as a war gas in World War I, it is now used as a reagent for the synthesis of many useful products. Phosgene reacts like other acid chlorides, but it can react twice.

(b) Predict the products formed when phosgene reacts with 1 equivalent of methanol, followed by 1 equivalent of aniline.

In each part, rank the compounds in order of increasing rate of nucleophilic attack at C=O by a strong nucleophile like methoxide.

(a)

What compounds are formed from the reaction of benzoyl chloride with the following reagents?

k. potassium formate

Show how you would use appropriate acyl chlorides and amines to synthesize the following amides.

(c) cyclohexanecarboxamide

(d)

Propose a mechanism for the reaction of acetic anhydride with water.

Which of the following proposed reactions would take place quickly under mild conditions?

(a)

(b)

(c)

(d)

(e)

Show how you would synthesize each compound, starting with an ester containing no more than eight carbon atoms. Any other necessary reagents may be used.

(a) Ph₃C–OH

(b) (PhCH₂)₂CHOH

(c) PhCONHCH₂CH₃

Using the pKa values listed in [TABLE 15.1], predict the products of the following reactions:

d.

Predict the products of the following reactions.

(a) phenol + acetic anhydride

(b) phenol + acetic formic anhydride

(c) aniline + phthalic anhydride

Show how you would synthesize the following esters from appropriate acyl chlorides and alcohols.

(c) benzyl benzoate

(d) cyclopropyl cyclohexanecarboxylate

Propose a mechanism for the reaction of aniline with acetic anhydride to give acetanilide.

There are many methods for activating a carboxylic acid in preparation for coupling with an amine. The following method converts the acid to an N-hydroxysuccinimide (NHS) ester.

(b) Propose a mechanism for the reaction shown.

Predict the products of the following reactions.

(e)

(f)