An attempt to prepare sulfonyl analogues of fotemustine: unexpected rearrangement to sulfamate during nitrosation step

This paper describes a flexible strategy to access diethyl ((((N-(2-chloroethyl)-N-nitrososulfamoyl)amino)arylmethyl) phosphonates, as aryl analogues of fotemustine. The new aryl sulfamidophosphonates prepared from 2-chloroethylamine were successfully obtained under eco-environmental conditions using ultrasound irradiation. These compounds did not produce the expected nitroso analogues of fotemustine after the nitrosation reaction but the corresponding sulfamates which were fully characterized. Some attempts to understand this rearrangement reaction were conducted, and particularly the corresponding nitrosoureas analogues could be isolated with good yield. The novel sulfonamidophosphonates as well as their sulfamate derivatives were evaluated for their cytotoxic effect on a panel of tumor cells. A flexible strategy to access to dialkyl (((N-(2-chloroethyl)-N-sulfamoyl) amino) arylmethyl) phosphonates, as sulfonamidophosphonates precursors of Fotemustine analogues was developed. The last nitrosation step proceeded as a rearrangement to the non expected sulfonate analogues.