Synthesis of 1-Iodo-substituted Codeine Derivatives

We have synthesized new N-demethyl-N-substituted derivatives (n-propyl, allyl) of 1- iodocodeine and their 7,8-dihydro analogues starting from codeine. Key intermediates, 1-iodonorcodeine and 1-iododihydronorcodeine were prepared from the corresponding 6-O-acetylated compounds using alpha- chloroethyl chloroformate. 3-O-Demethylation of 1-iodocodeine and 1-iododihydrocodeine with boron tribromide resulted in 1-iodomorphine and 1-iododihydromorphine, respectively. The latter compounds were transformed to their 3,6-di-O-acetyl derivatives. 8-Iodoapocodeine was prepared from 1-iodocodeine by acid-catalyzed rearrangement.