Microwave-assisted synthesis of substituted fluoroazines using KF*2H2O

ORGN 734

Anatoliy M. Shestopalov, shchem@dol.ru1, Alexander E. Fedorov1, Liudmila A. Rodinovskaya1, Alexander A. Shestopalov1, and Andrei A. Gakh, gakhaa@ornl.gov2. (1) N.D. Zelinsky Institute of Organic Chemistry, Leninsky Pr., 47, Moscow, 119991, Russia, (2) Oak Ridge National Laboratory, Oak Ridge, TN 37831-6242
Fluorinated azines are important class of organic compounds for cancer treatment. Nucleophilic substitution of good leaving groups (such as R2S+, R3N+, SO2R, NO2, Hal) is one of the most frequently used methods for the preparation of these compounds. Normally, these reactions are conducted in dry aprotic solvents (DMSO, DMF, THF), since it is known that attempted reactions of 2- and 4-halopyridines with fluoride anion sources in the presence of water were unsuccessful. We demonstrated that fluorinated azines can be prepared using hydrated potassium fluoride (KF*2H2O) under microwave irradiation. The highest yields were achieved with the ratio of starting materials to KF*2H2O equal to 1:2. Fluorinated azines can also be prepared in good yields from bromo- and chloroazines under microwave irradiation in aqueous DMSO. This research was supported by the Global IPP program through the International Science and Technology Center (ISTC). Oak Ridge National Laboratory is managed and operated by UT-Battelle, LLC, under U.S. Department of Energy contract DE-AC05-00OR22725. This paper is a contribution from the Discovery Chemistry Project.