22. Carboxylic Acid Derivatives: NAS

Predict the esterification products of the following acid/alcohol pairs.

(d)

(e)

Propose a mechanism for the acid-catalyzed reaction of acetic acid with ethanol to give ethyl acetate.

Show how Fischer esterification might be used to form the following esters. In each case, suggest a method for driving the reaction to completion.

(c) ethyl phenylacetate

Propose a mechanism for the following reaction. (Hint: Number the carbons to help you see where they end up in the product.)

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

(b)

The mechanism of the Fischer esterification was controversial until 1938, when Irving Roberts and Harold Urey of Columbia University used isotopic labeling to follow the alcohol oxygen atom through the reaction. A catalytic amount of sulfuric acid was added to a mixture of 1 mole of acetic acid and 1 mole of special methanol containing the heavy ¹⁸O isotope of oxygen. After a short period, the acid was neutralized to stop the reaction, and the components of the mixture were separated.

(a) Propose a mechanism for this reaction.

(b) Follow the labeled ¹⁸O atom through your mechanism, and show where it is found in the products.

Show how Fischer esterification might be used to form the following esters. In each case, suggest a method for driving the reaction to completion.

(a) methyl salicylate

Show how each of the following compounds can be prepared, using the given starting material:

a.

Show how each of the following esters could be prepared using a carboxylic acid as one of the starting materials:

a. methyl butyrate (odor of apples)

Predict the esterification products of the following acid/alcohol pairs.

(a) CH₃CH₂CH₂COOH + CH₃OH

(b) CH₃OH + HNO₃

(c) 2 CH₃CH₂OH + H₃PO₄

Show how you would accomplish the following syntheses in good yields.

(c)

(d)

a. A student did not obtain any ester when he added 2,4,6-trimethylbenzoic acid to an acidic solution of ethanol. Why? (HINT: Build models.)

b. Would he have encountered the same problem if he had tried to synthesize the methyl ester of 4-methylbenzoic acid in the same way?

Show the alcohol and the acid chloride that combine to make the following esters.

(c)

(d)

Show how you would convert alanine to the following derivatives. Show the structure of the product in each case.

(a) alanine isopropyl ester

(b) N-benzoylalanine

Show how you would accomplish the following multistep syntheses. You may use any additional reagents and solvents you need.

(f)