Dihydrocodeinone enol acetate

Dihydrocodeine [125-28-0] (33), introduced in Germany before 1930, and dihydrocodeinone enol acetate [466-90-0] (34) both have clinical activity and addiction potential comparable to codeine. 

Thebaine has been shown to react with lithium dimethylcuprate to give 7/j-methyldihydro- -thebaine (97),187,188 acid hydrolysis of which gives 7-methyl-thebainone-A (98) and its B/c-trans-isomer, which can be catalytically reduced to 7a- and 7/ -dihydrothebainone (99) and their B/c-trans-isomers. The la- and 7/j-dihydrothebainones are also obtained by the action of lithium dimethylcuprate on dihydrothebaine and on dihydrocodeinone enol acetate and subsequent hydrolysis of the products.187 The phenol (97) can be converted into the... 

Dihydrocodeinone [65, 69-70], 1-bromodihydrocodeinone [69], 14-hydroxydihydrocodeinone [38], and the alkyldihydrocodeinones [65] can be converted into esters of the enol form by heating the ketones with acid anhydrides and sodium salts. The enol esters and their salts are stable even in hot solution, but they are hydrolysed to the original ketones by boding with acids [69]. Dihydrocodeinone enol acetate [liv] is marketed as the drug acedicon. 

The preparation of a 7-substituted morphinan in high yield was first accomplished in 1980.(82) Thebaine (78) was reacted with lithium dimethyl-cuprate to yield (90%) 7/3-methyldihydrothebaine- > (79) together with 4% of the 7a-epimer. Previously, dihydrothebaine(83) and the enol acetate of dihydrocodeinone(84) had been shown to react with methyl Grignard reagents affording predominantly 5-methyldihydrothebainone with only a trace of the 7-methyl isomer.(85) The production of 79 gave entry into a new series of morphinans. 

Catalytic hydrogenation of dihydrothebaine methine [ix] with colloidal palladium in dilute acetic acid causes saturation of the 9 10 double bond, scission of the cyclic ether, and hydrolysis of the enol ether group giving dihydrothebainone dihydromethine [xvm] [3], and this is the most satisfactory method of preparing the latter. The dihydromethine [x] may be reduced to [xvm] under the same conditions [3]. [xvm] can also be prepared by hydrolysis of dihydrothebaine dihydromethine [x] to dihydrocodeinone dihydromethine [xix] (also accessible by the chromic acid oxidation of a-tetrahydrocodeimethine [xx] [3]) followed by aluminium amalgam reduction [3]. 

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