One-pot conversion of thebaine to hydrocodone and synthesis of neopinone ketal.
The ethylene glycol ketal of neopinone was prepared in a one-pot procedure by the reaction of thebaine with ethylene glyocol in the presence of p-toluenesulfonic acid. The ketal is also an intermediate in the conversion of thebaine to hydrocodone with ethylene glycol and Pd(OAc)(2), followed by hydrogenation. Additionally, a one-pot procedure for the conversion of thebaine to hydrocodone was achieved by employing palladium catalysis in aqueous medium. Palladium serves a dual purpose in this transformation, first for the activation of the dienol ether of thebaine and second as a hydrogenation catalyst. This procedure was found to be comparable to the two-step protocol which employs diimide reduction of thebaine followed by acid-catalyzed hydrolysis of the resulting 8,14-dihydrothebaine to hydrocodone. Experimental and spectral data are provided for all compounds.
Carroll
Robert J
RJ
Department of Chemistry and Centre for Biotechnology, Brock University, 500 Glenridge Avenue, St. Catharines, ON, Canada, L2S 3A1.
Leisch
Hannes
H
Rochon
Lena
L
Hudlicky
Tomas
T
Cox
D Phillip
DP
D006853:Hydrocodone / Q000737:chemistry*; D009019:Morphinans / Q000138:chemical synthesis*; D013797:Thebaine / Q000737:chemistry*
D009019:Morphinans; C538738:cyclic-1,2-ethanediyl acetal 8,14-didehydro-4,5-epoxy-3-methoxy-17-methylmorphinan-6-one; D013797:Thebaine; D006853:Hydrocodone