Y-Codeimethine

Hofmann degradation of isocodeine follows the same course as the degradation of codeine, giving in the first step y-codeimethine the C-6 epimer of [xxi], which can be isomerized to S-codeimethine, the C-6 epimer of [xxn], and in the second step methylmorphenol [xxrv] [252, 410] (see Chap. VI). Dihydroisocodeine can be degraded to a methine base and a nitrogen-free substance [295]. 

Isocodeine methyl ether, prepared from the methyl ether methiodide [411] or by methylating isocodeine-N-oxide and reducing the product [265], cannot be isomerized to thebainone methyl enolate by heating with sodium ethoxide [265]. On degradation it yields y-codeimethine methyl ether [411]. 

Isocodeine can be degraded to y-codeimethine, the C-6 epimer of a-oodeimethine [15], and like the latter this undergoes isomerization in hot alcoholic alkali, S-codeimethine, epimeric with the /3-isomer, being formed [16]. -Codeine [xm] can be degraded to e-codeimethine [xiv]... 

In the same way that hydrolysis of a-chlorocodide gives isomers of codeine with no trace of codeine (see Chap. VIII) hydrolysis of a-chlorocodeimethine gives a mixture of y-, S-, and e-codeimethines, but no a-codeimethine. If the hydrolysis is carried out above 100° C., an additional product is a dihydrate of the e-isomer in which one molecule of water forms part of the molecular structure this is also formed from e-codeimethine by heating a solution of the acetate, and can be converted back to the normal form by heating above 80° C. in vacuo [72], a-chlorocodeimethine is regenerated by the action of phosphorus penta-chloride on y-codeimethine [63]. 

Cyanogen bromide converts acetyl-a-codeimethine to cyanonoracetyl-a-codeimethine [lvii, R = Ac] [33, 78] acetyl-)3- and y-codeimethines behave likewise, [lvh, R = Ac] is saponified to a-cyanonorcodei-mothine [lvh, R = H], whilst the -derivative gives the urea [nvm]... 

In the same way that hydrolysis of a-chlorocodide gives a mixture of isomers of codeine but no codeine, so hydrolysis of a-chlorocodeimethine gives a mixture of y-, S-, and e-codeimethines but no a-codeimethine [67], y-Codeimethine also gives a-chlorocodeimethine on treatment with phosphorus pentachloride [68],... 

Methylmorphenol is also obtained as the final product of exhaustive methylation of codeine ethiodide [10], y-codeimethine (the C-6 epimer of [m]) [11] and e-codeimethine methyl ether [vn, R = CH3] (obtained by the degradation of (/(-codeine methyl ether [vi, R = CH3]) [12-13] the other substances produced during the degradation of [vn, R = CH3] are trimethylamine, ethylene, and methyl alcohol [12], 1-Bromomethyl-morphenol [vin] arises in like manner by the degradation of 1-bromo-codeine [10, 14-16] and ethylmorphenol from morphine-3-ethyl ether [17]. 

The codeimethines can be esterified [5, 32-34, 14, 16-17, 20, 35-37] and methylated. Methylation can be accomplished by methyl sulphate or methyl iodide and cold 1 N. alkali, when quaternary salts of the methyl ethers are obtained [38-39]. The methyl ethers, however, are best prepared by degradation of the corresponding codeine methyl ethers. In this way a- [39-40], y- [41], and e- [41-42] codeimethine methyl ethers have been prepared, and the first two named can be converted to the /3- and 8-isomers respectively on heating with alcoholic alkali [39, 41]. Emde degradation of codeine methyl ether metho-chloride affords exclusively a-codeimethine methyl ether [43]. Hofmann degradation of the methiodides of /3- [38] and e- [42] codeimethine methyl ethers affords methylmorphenol [xvi, R = Me], ethylene, trimethylamine, and methanol. 

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