SYNTHESIS AND STEREOCHEMICAL ASSIGNMENT OF 7-ARYLIDENE AND 7-HETEROARYLIDENE MORPHINAN-6-ONES

A number of (E)-7-arylidenenaltrexones were synthesized by azeotropic distillation of water from a benzene solution of naltrexone and an aro matic aldehyde (benzaldehyde, 4-chloro- and 4-fluorobenzaldehyde, 3-an d 4-pyridinecarboxaldehyde and 1-methyl-2-imidazolecarboxaldehyde) usi ng piperidine as a catalyst. In addition, (E)-7-benzylidenenaloxone wa s prepared by the previously published Claisen-Schmidt condensation us ing sodium hydroxide in methanol. The stereochemistry of these arylide ne derivatives 3-9 was determined to be (E) by means of nuclear Overha user enhancement experiments. The C-13 nmr spectra of (E)-3-9 are reco rded in deuteriochloroform and those of the hydrochlorides in deuterio dimethyl sulfoxide.