One-pot conversion of thebaine to hydrocodone and synthesis of neopinone ketal.

Robert J Carroll, Hannes Leisch, Lena Rochon, Tomas Hudlicky, D Phillip Cox

Department of Chemistry and Centre for Biotechnology, Brock University, 500 Glenridge Avenue, St. Catharines, ON, Canada, L2S 3A1.

The Journal of organic chemistry 2009 Jan 16

filter terms:

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.

Citation

Robert J Carroll, Hannes Leisch, Lena Rochon, Tomas Hudlicky, D Phillip Cox. One-pot conversion of thebaine to hydrocodone and synthesis of neopinone ketal. The Journal of organic chemistry. 2009 Jan 16;74(2):747-52