Suggested Improved Method for the Ing‐Manske and Related Reactions for the Second Step of Gabriel Synthesis of Primary Amines

Abstract

This work demonstrates an improvement in the Ing‐Manske and related procedures by the increase of pH of the reaction mixture after the complete disappearance of N‐substituted phthalimide. Hydrazinolysis of N‐phenylphthalimide (1a) gave 80% of the desired primary amines after 5.3 h in the absence of added NaOH. The reaction time was reduced to 1.6 h and 1.2 h when 1 eq. and 5 eq. of NaOH were added to the reaction mixture after the complete disappearance of 1a. Hydroxyaminolysis of N‐(4‐ethylphenyl)phthalimide (1b) gave 80% of the desired primary amines after 7.5 h of reaction time (at added [NaOH] = 0). When 10 eq. and 20 eq. of NaOH were added to the reaction mixture after the disappearance of 1b, the reaction time was reduced to 4 h and 2 h, respectively. Methylaminolysis of N‐(2‐ethylphenyl)phthalimide (1c) gave 80% of the desired primary amines after 1.7 h (at added [NaOH] = 0). The reaction time was reduced to 1 h and 0.7 h when 1 eq. and 25 eq. of NaOH were added to the reaction mixture after the complete disappearance of 1c.

Keywords:

• Gabriel synthesis
• Ing‐Manske procedure
• N‐substituted phthalimides
• Aminolysis

Acknowledgments

We wish to thank the University of Malaya for financial support (Vote F0718/2002B) and IRPA (Grant No. 09‐02‐03‐0147).