The chemistry of Anderson’s test for codeine

The Anderson test for codeine entails the interaction of codeine with concentrated nitric acid and heating to dryness. These drastic conditions give rise to a long series of reactions that is provided for the first time. The initial steps are salt formation, codeine nitrate, followed by nitration of the aromatic ring at the activated position, C-2. Then occurs a molecular rearrangement analogue to the transformation of morphine to apomorphine. This implies a series of reactions that include dehydration of the allylic alcohol, double bond migration, 1,3-chain migration, cyclohexadiene formation, ring opening of the dihydro-furane ring followed by formation of a dihydro-phenanthrene structure. The last stage involves methylamine evolution after two C─N fissions and alkalinization of the reaction medium in order to obtain the free amine.