Catalyst-free anti-Markovnikov hydroamination and hydrothiolation of vinyl heteroarenes in aqueous medium: an improved process towards centhaquine.

ABSTRACT

Catalyst-free hydroamination and hydrothiolation of alkenes have been achieved in an aqueous medium. The anti-Markovnikov addition works efficiently in suspended water at room temperature and allows straightforward access to centhaquine, a drug used for the management of hypovolemic shocks in critically ill patients, and its derivatives. Various primary and secondary amines, thiols, and hydrazides were successfully reacted with a number of heteroaryl/aryl-alkenes. The scalability of the process has been demonstrated by synthesizing centhaquine at a 19.65 g scale. A comparative analysis of the present process with previous approaches has been provided on the basis of green chemistry metrics.