22. Carboxylic Acid Derivatives: NAS

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

(e)

Show how you would use anhydrides to synthesize the following compounds. In each case, explain why an anhydride might be preferable to an acid chloride.

(c) phthalic acid monoamide 

(d) succinic acid monomethyl ester

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

(a) isopentyl alcohol → isopentyl acetate (banana oil)

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

(b) 3-ethylpentanoic acid → 3-ethylpentanenitrile

Show how you would accomplish the following synthetic conversions efficiently and in good yield. You may use any necessary additional reagents and solvents.

(g)

What are the products of the following reactions?

a.

What products would you expect to obtain from the following reactions?

b. methyl carbamate + methylamine

Starting with methyl acetate, what neutral nucleophile would you use to synthesize each of the following compounds? b. acetamide

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

(b)

Starting with acetyl chloride, what neutral nucleophile would you use to synthesize each of the following compounds?

e.

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.

How can the following compounds be prepared from the given starting materials?

a.

Write a mechanism for each of the following reactions:

b. the aminolysis of phenyl formate, using methylamine.

What is the product of an acyl substitution reaction—a new carboxylic acid derivative, a mixture of two ­carboxylic acid derivatives, or no reaction—if the new group in the tetrahedral intermediate is the following? a. a stronger base than the substituent that is attached to the acyl group

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.

(a) Explain why an NHS ester is much more reactive than a simple alkyl ester.