Role of in situ spectroscopy in developing a plug flow reactor and control system for the continuous production of cyclopropylamine

I&EC 153

Joseph R. Zoeller, jzoeller@eastman.com, Norma L. Buchanan, nlbuchan@eastman.com, Daniel L. Terrill, Steven P. Bellner, and Elizabeth C. Sharkey. Research Laboratories, Eastman Chemical Company, P.O. Box 1972, Kingsport, TN 37662-5150
Cyclopropylamine is becoming an increasingly important moiety in pharmaceutical formulations used as anti-viral agents and antibiotics for the treatment of drug resistant bacterial strains. As a consequence, market demand has become large enough to a continuous process. Eastman Chemical Company has developed a continuous process using a plug flow reactor to convert of cyclopropyl amide to cyclopropyl amine via the Hofmann rearrangement utilizing sodium hypochlorite and caustic. Critical to developing this process was the application of in situ infrared and UV-visible spectroscopy where these spectroscopic methods were used (1) to develop an understanding of competing pathways, (2) to measure kinetic parameters for the sequential rearrangement steps which ultimately determined the reactor design, (3) to monitor reactor performance during development, and (4) to develop a control strategy for the continuous process. We will discuss the role of these spectroscopic methods in the development of the continuous cyclopropylamine process.