Green technology in pharmaceutical process development: Application in the synthesis of Acetaminophen, Ibuprofen and heterocycles

ORGN 401

Apurba Bhattacharya1, Victor H Suarez, ksvhs00@tamuk.edu2, Victoriano Tamez, ksvt002@tamuk.edu2, Nitinchandra Patel, ksndp02@tamuk.edu2, Frank Rinaldi, frank.rinaldi@bms.com3, and John A. Grosso, john.grosso@bms.com4. (1) Department of Chemistry, Texas A&M University Kingsville, MSC 161, 920 W Santa Gertrudes, Kingsville, TX 78363, (2) Department of CHemistry, Texas A&M University - Kingsville, 920 W Santa Gertrudes, Kingsville, TX 78363, (3) Brystol Myers Squibb Corporation, 1 Squibb Drive, New Brunswick, NJ 08903, (4) Process Research & Development, Bristol-Myers Squibb Co, NB 48, 1 Squibb Drive, New Brunswick, NJ 08903-0191
Over the past few years significant amount of research activities in the chemical community have been directed towards the development of new technologies for environmentally benign processes. Here in the chemistry department at Texas A&M University at Kingsville (TAMUK), we have established collaborative programs with several leading drug companies in which the BS/MS level research students are involved in developing processes for pharmaceutical intermediates that have little or no pollution potential or environmental risk and are both economically and technologically feasible. As part of this collaborative program a significant effort was directed towards development of efficient, economic and solvent free green technologies. Solvent free processes proceed under a novel, dual catalytic system whereby a co-catalyst (e.g. surfactant) in conjunction with the traditional catalyst is utilized to obtain superior kinetics, conversion and efficiency. The product could be separated from the catalyst by simple filtration without any exhaustive work-up, rendering the process simple and relatively waste free. Since no solvent is used, the space-time yield is higher, resulting in an efficient and economic process. The waste-free green technology has been applied to an efficient one-pot, one-step synthesis of a wide spectrum of heterocycles, acetaminophen (Tylenol„µ) as well as S-Ibuprofen that has important industrial significance. The scope and limitations of these methodologies in each of these vital synthetic areas will be discussed.