Trihalogenomethylsulphenylation of tetraisopropyl methylenebisphosphonates

Abstract

Trihalogenomethylthiomethylenebisphosphonates, [(PrⁱO)₂PO]₂CRSCCl_nF_3-n(n= O–2; R = H,Me), are formed by the reaction of salts of tetraisopropyl methylenebisphosphonates, [(PrⁱO)₂PO]₂CRM (M = Li,Na; R = H,Me), with trihalogenomethanesulphenyl chlorides, CCl_nF_3-nSCl (n= 0–2). The ester products are transesterified with bromotrimethylsilane and hydrolysed with aqueous methanolic sodium hydroxide to give the corresponding tetrasodium salts of the bisphosphonic acids. The sulphenylation reactions are complex and are facilitated by the use of Lewis acids. Sulphenylations using chlorodifluoro-and dichloro-methanesulphenyl chlorides afford unexpected additional products arising from chlorine replacement by fluorine.