Question

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

Answer 1

The compounds should be arranged from least reactive to most reactive towards nucleophilic acyl substitution as: Sodium acetate, Ethyl acetate, Acetamide, Ethyl thioacetate, Acetic anhydride, Acetyl chloride.

Step-by-step explanation:

In chemistry, particularly organic chemistry, the reactivity of compounds towards nucleophilic acyl substitution is dictated by the ability of different leaving groups to depart from the acyl group. A good leaving group will make a compound more reactive towards these reactions. According to established reactivity orders, the compounds provided by the student should be arranged as follows with respect to increasing reactivity:

1. Sodium acetate (C)
2. Ethyl acetate (D)
3. Acetamide (E)
4. Ethyl thioacetate (A)
5. Acetic anhydride (F)
6. Acetyl chloride (B)

This order highlights that a compound like sodium acetate is least reactive, largely due to its resonance stability as a carboxylate anion. Whereas ethyl acetate is slightly more reactive but still less than amides. Ethyl thioacetate is more reactive due to the sulfur atom's ability to stabilize the leaving group better than oxygen. Acetic anhydride is even more reactive due to the good leaving group ability of the acetate ion. Finally, acetyl chloride ranks as the most reactive due to the excellent leaving group ability of the chloride ion.

Answer 2

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

Step-by-step 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.