The mechanism of Fleury test for morphine

Abstract

The test under study is due to M. Fleury. He used morphine dissolved, at room temperature, in 1/20 N sulphuric acid; added some lead superoxide (lead dioxide), stirred for 8 min., let stand 4 min; the water-clear liquid was separated, and a drop of ammonia was added. A brown colour occurs immediately. These experimental data indicate not a fast reaction, but a rather complex mechanism. In this communication a reaction mechanism is provided for the first time. Protonated lead dioxide is the reactive species which on interaction with the phenol group in morphine forms a mixed ortho-plumbate. Protonation of this ester does not favor further reaction. However, reaction with a second reactive species is favourable for a push-pull seven-member reaction mechanism. Enolization of the dienone formed restores aromaticity. Protonation of the Pb=O double bond in the obtained intermediate promotes a 7-atom concerted mechanism. 2,3-Dioxomorphine is formed along with an oxide hydrate that yields water and two molecules of plumbous oxide.