Novel Analgesics and Molecular Rearrangements in the Morphine-Thebaine Group. I. Ketones Derived from 6,14-endo-Ethenotetrahydrothebaine

Abstract

Several ketones I1 derived from 6,14-endo-ethenotetrahydrothebaine have been prepared by the Diels- Alder addition of certain a,P-unsaturated ketones to thebaine, by the action of cadmium alkyls on the corresponding acid chloride I1 (R = Cl), and, in some cases, by the action of Grignard reagents on the corresponding ester I1 (R =OEt) which is the adduct of thebaine and ethyl acrylate. Both 7a and 70 forms of the ketone I1 (R = Me), the ester I1 (R = OEt), and the nitrile 111 have been isolated. Attempts to convert the 7a ketone TI (R = Me) into the 7/3 isomer have resulted only in the formation of a keto1 X (R = H). Many of the bases prepared in this work are potent analgesics. The reaction product obtained from thebaine methiodide and p-benzoquinone has been shown to be a charge-transfer complex and not a true Diels-Alder adduct