14.9:
Nucleophilic Acyl Substitution of Carboxylic Acid Derivatives
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All carboxylic acid derivatives undergo nucleophilic acyl substitution reactions. These are addition–elimination reactions in which a nucleophile displaces the leaving group of an acyl derivative to form a different acyl derivative. The mechanism depends on the nature of the nucleophile and the leaving group. Generally, they exist as neutral species under acidic conditions and as relatively stable anions under basic conditions. The acid-catalyzed mechanism begins with the protonation of the carbonyl oxygen, rendering the carbonyl carbon more electrophilic. This is followed by a nucleophilic attack at the carbonyl carbon to form a tetrahedral intermediate. Next, deprotonation of the tetrahedral intermediate, followed by protonation of the leaving group, leads to the departure of the leaving group as a neutral species. A final proton transfer step yields the substitution product. Under basic conditions, the nucleophile attacks the carbonyl carbon, forming a tetrahedral alkoxide intermediate. Here, the leaving group departs as a relatively stable anion, giving the substitution product.
14.9:
Nucleophilic Acyl Substitution of Carboxylic Acid Derivatives
Nucleophilic acyl substitution is an important class of substitution reactions involving a nucleophile and an acyl compound, such as carboxylic acids and their derivatives. In these reactions, the leaving group attached to the acyl group is substituted by a nucleophile. The general mechanism proceeds via two steps.
- Addition: Nucleophilic attack at the carbonyl carbon, forming a tetrahedral intermediate.
- Elimination: Departure of the leaving group.
The net outcome of the addition–elimination reaction is the conversion of one acyl derivative into another. The reaction can be carried out in the presence of an acid or a base catalyst depending on the reactivity of the acyl derivative.
