Arrange the following compounds in the order of increasing reactivity toward nucleophilic acyl substitution, with least reactive at the top and most reactive at the bottom. (hint: for carboxylates, think of acid-base chemistry to infer the reactivity).
a. ethyl thioacetate
b. acetyl chloride
c. sodium acetate
d. ethyl acetate
e. acetamide
f. acetic anhydride

The correct order of increasing reactivity toward nucleophilic acyl substitution is E < D < C < A < F < B.

Explanation:

The stability of the leaving group best determines the manner of reactivity of carboxylates to nucleophilic substitution after the substitution of the nucleophile to the leaving group. The leaving group should, therefore, be protonated with hydrogen ion in the solution to form a stable molecule. From the given list: The leaving group for A, Ethyl thioacetate will be ethanethiol. For B, Acetyl chloride will be Hydrochloric acid. For C, Sodium acetate will be Sodium Hydroxide. For D, Ethyl acetate will be Ethanol. For E, Acetamide will be Ammonia, and for F, Acetic anhydride will be Ethanoic acid. The reactivity of the substitution reaction is dependent on the stability of these leaving groups. The stability of these leaving groups depends on their pKa, and the more the pKa, the lesser the acidity of the leaving group, and the lower the reactivity. Therefore, considering their pKa: A is 8.5, B is -7, C is 13.8, D is 15.9, E is 36, and F is 4.8. When we rearrange this pKa in descending order, we have E, D. C, A, F, B. Which is also the increased reactivity of the nucleophilic acyl substitution.