8-Codeimethine

Acetyl-i3-codcimethine. — methiodide rormyl-0-codcimethine. 0-codeimethine methyl ether 82... 

Alkaline degradation of codeine methiodide affords a-codeimethine [xxi] [185, 285], which can be isomerized by alcoholic alkali to /3-codeimethine [xxn] [187, 286-7], also obtainable by the degradation of neopine [xm] methiodide [271]. The degradation of codeine ethiodide follows a similar course [288]. These bases suffer dehydration and loss of the basic side-chain when heated with acetic anhydride and sodium acetate (when acetylmethylmorphol [xxm] is formed [187, 289-90]), and when subjected to further Hofmann degradation (which leads to methylmorphenol [xxiv] [290-2]). The resulting aromatic phenan-threne derivatives are of considerable importance in the elucidation of the basic structure of the morphine alkaloids and are discussed in detail in Chapter XXVII. 

Codeine methyl ether affords a-codeimethine methyl ether on Hofmann [262-3] or Emde [294] degradation. 

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]. 

Alkaline degradation of -codeine methiodide affords e-codeimethine [lxxxih], which resists isomerization [415, 428-9], and this on further degradation gives morphenol and acetylmethylmorphenol [428] (see Chap. VIII). Methine bases have also been prepared from i/r-codeine methyl ether [411, 419], dihydro-i/j-codeine-A [421] and its methyl ether [426], dihydro-i/j-codeine-B [421, 423], dihydro-i/f-codeine-C [295, 423] and its methyl ether [426], tetrahydro- -codeine [295] and its methyl ether [426]. 

Degradation of the quaternary salts of allo-i/r-codeine affords -codeimethine (the epimer of Lxxxm) [407] which cannot be isomerized [428], and methine bases have also been prepared from dihydroallo-i/r-codeine-A [431] and tetrahydroallo- -codeine [295, 431 ]. 

The quaternary salts of codeine and its isomers can be degraded to unsaturated bases to which the general term methylmorphimethine has hitherto been applied, but here the less cumbersome and more systematic term codeimethine [1] will be used, the term methylmorphimethine being reserved for the derivatives obtained from nuclear methylated morphines. The term dihydromethine will be applied to bases in which the double bond introduced by degradation has been saturated. In this way a convenient and unambiguous system of nomenclature is available. 

The reaction between silver oxide and the quaternary salts of morphine and codeine was first investigated, inconclusively, by How [2]. Grimaux, by heating codeine [i] methiodide with silver oxide or potassium hydroxide, obtained a-codeimethine [n] dionin methine likewise could be prepared from dionin (ethyl morphine) methiodide [3-4]. The reaction presumably proceeds by elimination of water from the methohydroxide, and Hesse found that evaporation of codeine methohydroxide solutions over concentrated sulphuric acid affords a-codeimethine [5]. 

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]... 

Heating with sodium ethoxide at 150° C. converts a-codeimethine to methylmorphol [xv, R = H] and /3 dimethylaminoethyl ethyl ether [24]. 

Zinc-dust distillation of a-codeimethine affords 10 per cent, of phenanthrene [14]. 

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. 

Halogenated Codeimethines 1-Bromocodeine can be degraded to 1-bromo-a-codeimethine [44-45], which can be converted to the /3-isomer [46] and degraded to 1-bromo-methylmorphenol [32] and 1-bromoacetylmethylmorphol [44-45]. The latter has been converted to l-bromo-3 4-dimethoxyphenanthrene, identical with an authentic specimen [45],... 

Bromination of a-codeimethine methyl ether in chloroform leads to bromohydroxydihydro-a-codeimethine methyl ether, which affords 3 6-dimethoxy-4-acetoxyphenanthrene on acetolysis [48], and in like manner the e-isomer can be degraded to 3 8-dimethoxy-4-acetoxy-phenanthrene [48]. 

Hydrogenation of -codeine in dilute acetic acid [65] or electrolytic reduction [55] affords dihydro- -codeine-B [xxv] obtained together with dihydro-i/r-codeine-C [xxvm] by reduction with sodium and alcohol [66]. These two compounds suffer Hofmann degradation in the usual way giving, respectively, dihydro-e-codeimethine-B [xxvi] [55, 60] and dihydro-e-codoimothine-C [xxix] [00], the latter also being... 

Hydrogenation of i/r-codeine in neutral solution affords tetrahydro-i/r-codeine [xxx] which yields tetrahydro-e-codeimethine-C [xxxi] on degradation, the latter being reducible to hexahydro-e-codeimethine [55, 65]. 

The methyl ethers of [xiv], [xxiv], [xxrx], and [xxxi] have been obtained by degradation of the corresponding (/(-codeine derivatives, [xiv], [xxix], and [xxxi] methyl ethers are reduced to hexahydro-e-codeimethine methyl ether, whilst the ether of [xxiv] is reduced to tetrahydro-e-codeimethine-A methyl ether [67]. 

Though the reduction of allo-i/ -codeine shows certain differences from that of i/r-codeine (see Chap. IV), reduced -codeimethines corresponding to [xxiv], [xxn], [xxvn], and [xxxi] have been prepared [55, 63, 68]. 

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