Question

what is order of reactivity of subsitution acid derivatives towards nucleophilic reaction?

Answer 1

Reactivity trends. There are five main types of acyl derivatives. Acid halides are the mostreactive towards nucleophiles, followed by anhydrides, esters, and amides. Carboxylate ions are essentially unreactive towards nucleophilic substitution, since they possess no leaving group.

Answer 2

Generally, acid halides are the most reactive towards nucleophiles, followed by anhydrides, esters, and amides. The reactivity of these five classes of compounds covers a broad range; the relative reaction rates of acid chlorides and amides differ by a factor of 10^13.

Resonance is the another factor that plays an important role in determining the reactivity of acyl compounds is resonance. Esters exhibit less resonance stabilization than amides, so the formation of a tetrahedral intermediate and subsequent loss of resonance is not as energetically unfavorable. Anhydrides experience even weaker resonance stabilization, since the resonance is split between two carbonyl groups, and are more reactive than esters and amides. In acid halides, there is very little resonance, so the energetic penalty for forming a tetrahedral intermediate is small. This helps explain why acid halides are the most reactive acyl derivatives.

Reactivity order follows as:

acyl chloride > anhydride > thioester > ester = carboxylic acid > amide > carboxylate