9.3 Nucleophilic Acyl Substitution Reactions

LEARNING GOALS

After   Chapter 9.3,    you will    be  able    to:

Describe    the mechanism   for transesterification reactions

Explain how strong  acid    and strong  base    conditions  would   impact  the mechanism   of

hydrolysis  of  an  amide

Identify    the nucleophile and electrophile    within  nucleophilic    acyl    substitution    reactions

such    as:

Although there are a seemingly infinite number of reactions in which carboxylic acid derivatives can
participate, a much smaller group of reactions will appear on the MCAT. As we will observe, these
reactions have much in common with those of carboxylic acids and other carbonyl-containing
compounds. Many of the properties we have already discussed determine the ways in which these
reactions proceed.

ANHYDRIDE CLEAVAGE

As with carboxylic acids, nucleophilic acyl substitution involves nucleophilic attack of the carbonyl
carbon with displacement of a leaving group. All carboxylic acid derivatives can participate in
nucleophilic substitution reactions at different relative rates. Specifically, anhydrides are most
reactive toward nucleophiles, followed by esters, and finally amides. One example of this is the
formation of amides from the nucleophilic substitution reaction between ammonia and any
carboxylic acid or derivative. The example shown in Figure 9.13 is not only a nucleophilic