Synthesis of N‐Benzylated Anilines from the Reaction of Anilines and Benzyl Chloroformate

Abstract

Reactions of benzyl chloroformate with a series of substituted anilines produced N‐carbobenzyloxy “CBZ” products along with the unexpected N‐benzylated “Bn” compounds. Reaction of aniline, 1a, gave the CBZ, or 2a, and Bn, or 3a, products in 29% and 14% yield, respectively. For 2‐nitro‐, 2‐bromo‐, and 2‐bromo‐5‐nitroanilines, the N‐benzylated compounds were produced exclusively. However, 2‐methoxy‐, 4‐bromo, 4‐iodo, and 4‐ethylanilines gave mainly CBZ products. Other compounds reported in this study gave mixtures of the two products. For 4‐chloro‐3‐nitroaniline, in addition to the Bn and CBZ products (53% and 14% yield, respectively), a N,N‐dibenzylated product was isolated in 27% yield. Collectively, the results indicated that electron‐withdrawing groups, particularly at the ortho position, directed the formation of Bn compounds, whilst electron‐donating groups, especially at the ortho and para positions, favored the synthesis of CBZ products.

Keywords:

• N‐Benzylated aniline
• CBZ
• Freidel–Crafts reaction
• Ortho and Para position

Acknowledgments

The authors thank the NSF‐REU, NIH (RR16461‐10) from the BRIN Program, and Furman University for support.