Synthesis of 1-Aminocodeine as a Synthon for Other Codeine Derivatives

The first nitration of codeine by using bismuth nitrate pentahydrate under mild reaction conditions is described. The resulting 1-nitrocodeine was reduced to 1-aminocodeine, a key precursor for the synthesis of the azo derivative and several hydrazones. Structures of both 1-nitrocodeine and 1-aminocodeine were unequivocally determined by single-crystal X-ray analysis. The reported preliminary synthetic study lays the groundwork for the synthesis of modified codeine derivatives with potential biological activity.