Synthesis of purines and adenines containing the hexafluoroisopropyl group

Viacheslav Petrov; Rebecca J Dooley; Alexander A Marchione; Elizabeth L Diaz; Brittany S Clem; William Marshall

doi:10.3762/bjoc.16.224

Synthesis of purines and adenines containing the hexafluoroisopropyl group

Beilstein J Org Chem. 2020 Nov 11:16:2739-2748. doi: 10.3762/bjoc.16.224. eCollection 2020.

Authors

Viacheslav Petrov^#¹, Rebecca J Dooley^#², Alexander A Marchione^#², Elizabeth L Diaz³, Brittany S Clem^#², William Marshall^#³

Affiliations

¹ Chemours Co. Fluoroproducts, Chemours Discovery Hub N2-136S, 201 Discovery Blvd, Newark, DE 19713, USA.
² Chemours Co. Fluoroproducts, Chemours Discovery Hub, 201 Discovery Blvd, Newark, DE 19713, USA.
³ DuPont Corporate Center for Analytical Sciences, Experimental Station, P.O. Box 80500, Wilmington, DE 19880-0500, USA.

^# Contributed equally.

Abstract

Several new derivatives of adenine, purine, and theophylline containing the (CF₃)₂CH group connected to a nitrogen atom of the imidazole ring were prepared by the reaction of 2,2,4,4-tetrakis(trifluoromethyl)-1,3-dithietane (1) with the corresponding substrates, resulting in the selective alkylation of one of the nitrogen atoms of the imidazole ring. The reaction proceeds under mild conditions in a polar solvent, giving the alkylated products in 47-78% yield. While for purine and 4- and 5-azabenzimidazole, the reaction led to a mixture of two isomers, the reaction of adenine and the corresponding 2-fluoro derivative was regioselective, resulting in the formation of only one isomer in each case. The alkylation of theophylline led to the formation of a new derivative of caffeine.

Keywords: 2,2,4,4-tetrakis(trifluoromethyl)-1,3-dithietane; adenine; caffeine; cyclic dimer of hexafluorothioacetone; hexafluoroisopropyl group; purine; theophylline.