22. Carboxylic Acid Derivatives: NAS

What are the products of the following reactions?

a.

b.

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

c.

Show how you would accomplish the following syntheses. Some of these conversions may require more than one step.

(e) cyclohexylamine → N-cyclohexylacetamide

(f) bromocyclohexane → dicyclohexylmethanol

How does acetic anhydride make it easier to form the anhydride?

Suggest the most appropriate reagent for each synthesis, and explain your choice.

(a)

How would you make the following compounds from N-benzylbenzamide?

c. benzyl alcohol

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

(e) tert-butyl acetate

(f) diallyl succinate

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.

(c) Propose a mechanism for the reaction of the NHS ester with an amine, R–NH₂.

What acyl chloride and amine are required to synthesize the following amides?

a. N-ethylbutanamide

b. N,N-dimethylbenzamide

Show how to synthesize the following compounds, using appropriate carboxylic acids and amines.

(c)

Predict the products of the following reactions.

(l)

We saw that acid anhydrides react with alcohols, water, and amines. In which of these reactions can the tetrahedral intermediate eliminate the carboxylate ion even if it does not lose a proton before the elimination step? Explain.

The reaction of a nitrile with an alcohol in the presence of a strong acid forms an N-substituted amide. This reaction, known as the Ritter reaction, does not work with primary alcohols.

b. Why does the Ritter reaction not work with primary alcohols?

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

f. cyclohexanol