Synthesis of 1, 1-Difluoro-2-(o-Chlorophenyl)-2-(p-Chlorophenyl) ethane for Testing as a Possible Adrenal Cancer Drug

Abstract

Based on the high adrenacorticolytic activity and subsequent use of 1,1- dichloro-2-(o-chlorophenyl)-2-(p-chlorophenyl)ethane ( 0,p'-DDD ) as an adrenal cancer drug (trade name: Mitotane,) an organic synthesis of the o,pf- DDD analog l,l-difluoro-2-(o-chlorophenyl)-2-(p-chlorophenyl)ethane was attempted through two synthetic pathways: (1) a Darzen's Condensation of o,p'-dichlorobenzophenone to form 2-(o-chlorophenyl)-2-(p-chlorophenyl) ethanal, and (2) a three-step process consisting of a Wittig reaction, a hydroboration-oxidation, and an oxidation to the aforementioned aldehyde. The aldehyde would be treated with DAST (Diethylaminosulfur trifluoride) to obtain the desired difluorinated compound. The Darzen's Condensation was attempted unsuccessfully several times, and the first two steps of the alternate pathway were successfully carried out, with a maximum yield of 73% for the Wittig reaction and 75% for the hydroboration-oxidation.