Insight into the mechanism of the Froehde test for morphine

Abstract

The Froehde reaction for morphine employs a solution of sodium molybdate in concentrated sulphuric acid. This test has been extended to other alkaloids giving different colours. In this communication we present an insight into the reaction with morphine. It has the particularity that it does not invoke the concept of electron back donation since this known point of view reverses the normal polarization of a functional group. This route is based on a novel theoretical finding: the activation of a mixed ester (organic-inorganic) by means of protonation and water loosening. This causes Umpolung (polarity inversion) at ortho position, favouring a nucleophilic attack instead of the electrophilic one due to the original phenol group in morphine. The final part of the route to morphine ortho-quinone goes smooth via a six member concerted mechanism.