The reaction of Codeine with ammonium peroxodisulphate in acidic medium

The analytical chemistry of medicinal products is very important. In this communication the reactions occurring between the analyte codeine with ammonium persulphate in sulphuric acid are provided, as well the reaction mechanism. This colour reaction was devised by Orlow and Horst, codeine giving orange colour in this assay. The analytical procedure is interesting since it is a double variant of the Elbs persulphate oxidation which employs monophenols in alkaline medium that are oxidised to hydroxy phenols. The Orlow-Horst test uses a phenolic methyl ether instead of the free phenol, and the reaction medium is acid, not alkaline. There is sulfation at C-2, hydrion removal and aromatization, followed by protonation of the oxygen at C-2. This oxonium ion produces a δ+ on the sulphur atom plus a similar effect due to the sulphonyl group, facilitating addition of water and separation of 2-hydroxy-codeine. This compound forms a hydrogen bond in a five-member ring. Finally, a hydrion transfer in the inorganic intermediate gives sulphuric acid.