Acetylation of 3 Aminomethylbenzamide with Acetic Anhydride

To determine the major product formed in the reaction, we analyze the functional groups present in the starting material, 3-(aminomethyl)benzamide:

1. Aliphatic Primary Amine group ($-\text{CH}_2\text{NH}_2$): The lone pair of electrons on the nitrogen atom of the primary aliphatic amine is localized on the nitrogen atom. This makes it a strong nucleophile and readily available to attack electrophilic centers.

2. Primary Amide group ($-\text{CONH}_2$): The lone pair of electrons on the nitrogen of the amide group is delocalized via resonance with the adjacent carbonyl group: $\text{R}-\overset{\overset{\text{O}}{\parallel}}{\text{C}}-\ddot{\text{N}}\text{H}_2 \longleftrightarrow \text{R}-\overset{\overset{:\text{O}:^-}{\mid}}{\text{C}}=\overset{+}{\text{N}}\text{H}_2$ Due to this resonance stabilization, the electron density on the amide nitrogen is significantly reduced, rendering it extremely weakly nucleophilic compared to an amine.

When reacted with acetic anhydride ($(\text{CH}_3\text{CO})_2\text{O}$) in dichloromethane ($\text{CH}_2\text{Cl}_2$) under mild conditions:

• The nucleophilic acyl substitution selectively occurs at the more nucleophilic aliphatic amine ($-\text{CH}_2\text{NH}_2$) rather than the amide group ($-\text{CONH}_2$).
• The amino group attacks the carbonyl carbon of acetic anhydride, eliminating a molecule of acetic acid ($\text{CH}_3\text{COOH}$) and yielding the acetylated amine ($-\text{CH}_2\text{NHCOCH}_3$), while the amide group remains intact.

$\text{H}_2\text{NOC}-\text{C}_6\text{H}_4-\text{CH}_2\text{NH}_2 + (\text{CH}_3\text{CO})_2\text{O} \xrightarrow{\text{CH}_2\text{Cl}_2} \text{H}_2\text{NOC}-\text{C}_6\text{H}_4-\text{CH}_2\text{NHCOCH}_3 + \text{CH}_3\text{COOH}$

Therefore, the major product is represented by Option (A).

Correct Option: (A)