1,2,4-Tris(trifluoromethyl)benzene: Selective lithiation and subsequent electrophilic substitution

Article abstract of DOI:10.1016/S0040-4020(97)10335-0

1,2,4-Tris(trifluoromethyl)benzene quantitatively undergoes a hydrogen/metal exchange when treated with an ethereal solution of lithium 2,2,6,6-tetramethylpiperidide. Proton abstraction occurs concomitantly from positions 5 and 6, the ratios varying from 80 : 20 to 90 : 10, depending on the reaction conditions. Pure 5-iodo-1,2,4-tris(trifluoromethyl)benzene can be readily obtained by fractional crystallization of the regioisomeric mixture and allows one to prepare 5-substituted derivatives of 1,2,4- tris(trifluoromethyl)benzene by consecutive reaction with tert-butyllithium and an electrophile.