14.8:
Relative Reactivity of Carboxylic Acid Derivatives
Like carboxylic acids, the derivatives also undergo nucleophilic acyl substitution reactions. The relative reactivity depends on the basicity of the leaving group and the resonance stabilization of the derivative.
Recall that the weaker the base, the better the leaving group.
In this series, the halide ion is the weakest base and the best leaving group making acid halides the most reactive.
The reactivity decreases with an increase in the basicity of the leaving group.
Since amide ions are strong bases and poor leaving groups, amides are the least reactive.
Another competing factor is the resonance stabilization of the derivatives.
The electron-donating ability of the substituents increases the electron density on the carbonyl carbon, stabilizing the positive charge. This renders the carbonyl carbon less electrophilic, thereby decreasing the reactivity.
Since resonance stabilization increases with the electron-donating ability of the substituents, acid halides are the most reactive and amides the least reactive.
14.8:
Relative Reactivity of Carboxylic Acid Derivatives
Carboxylic acid derivatives such as acid halides, anhydrides, esters, and amides undergo nucleophilic acyl substitution reactions with varying degrees of reactivity.
A key factor in assessing the reactivity of the acid derivatives is the basicity of the substituent or the leaving group. The lower the basicity of the leaving group, the higher the reactivity of the derivative. The basicity of the leaving group follows this order:
Halide ions < Acyloxy ions < Alkoxy ions < Amine ions
Consequently, acid halides are the most reactive, while amides are the least reactive.
Another factor that determines the relative reactivity arises from a combination of resonance and inductive effects. In acid derivatives, the electronegativity of the substituent influences the electrophilicity of the carbonyl carbon. A highly electronegative substituent will exhibit a stronger electron-withdrawing inductive effect, making the carbonyl carbon more electrophilic and more susceptible to a nucleophilic attack. The electron-withdrawing ability of the substituents follows this order:
Halide ions > Acyloxy ions > Alkoxy ions > Amine ions
Accordingly, the reactivity trend from the most reactive to the least reactive acid derivative is:
Acid halides > Acid anhydrides > Esters > Amides