Synthesis of cyclopropylamine with phase transfer catalysis

Abstract

Cyclopropylamine is synthesized with γ-butyrolactone and isopropanol by five steps of ring-opening esterification, cyclization, hydrolysis, acylation and Hofmann degradation. Cyclization and hydrolysis are key steps in the process, and Phase Transfer Catalysis (PTC) is used in the two steps respectively. In the cyclization reaction, because solid-liquid PTC, sodium hydroxide is applied instead of expensive sodium alcoholate, the reaction can be carried out in mild conditions. The optimum reaction conditions are as follows: 0.03:1:1.5 mole ratio of BTEAC to ester to sodium hydroxide, reacting at 50 °C for 2 h with yield of 92%. Hydrolysis of isopropyl cyclopropanecarboxylate is accelerated by liquid-liquid PTC, and the order of catalytic activity is BTEC > BTMAC > CTMAB > TBAB. The results show that the new synthesis method is superior to those from literature and feasible for production with simple routes, mild reaction conditions, cheap materials and total yield of 52.6%.

Keywords

cyclopropylamine / synthesis / γ-butyrolactone / phase transfer catalysis

References

[1] Joseph T Blackwell, Denham S. Process for the manufacture of cyclopropylamine[P]. US Pat, No. 4590292. 1986

[2] Cahoy Roger P, Phillips L V. Cyclopropylamine from butyrolactone[P]. Ger Offen Pat, No. 1939759. 1970

[3] LiHe-ping, GeHong, ZhangFu-qiang. New technology for synthesis of cyclopropylamine[J]. Chemical World, 1997, 38(7): 358-360(in Chinese)

[4] ZhaoXue-qing, ZhangYuan. Synthesis of cyclopropylamine[J]. Chinese Journal of Pharmaceuticals, 1994, 25(5): 225-225(in Chinese)

[5] LiMei, GuoHui-yuan. Graphical synthetic routes of cyclopropylamine[J]. Chinese Journal of Pharmaceuticals, 1992, 23(3): 141-141(in Chinese)