Thebainone methyl enolate

Small and Browning agree with Schbpf and Winterhalder that thebainone methyl enolate (formed by 1 6 addition in which the oxygen bridge is ruptured and ethylenic linkages produced at C —C and C —C ) may be the primary intermediate in tWs reaction since it is hydrogenated... 

Thebainone methyl enolate. CuHjjOjN. This possible intermediate in the hydrogenation of thebaine to dihydrothebainone-J-5 6-methyl enolate (see above) has m.p. 154-6°, [a] ° -f 9-6° (EtOH). ... 

Most of the dihydrothebainone produced from thebaine is former under mild conditions of hydrogenation and probably not via dihydro thebaine, but by way of thebainone methyl enolate and dihydrothebainone A-5 6-methyl enolate as described above. 

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]. 

Codeine [i] on heating in alcohol with [319-23] or without [324] acid, with [319-21] or without [322-4] hydrogen, in the presence of noble metal catalysts, undergoes rearrangement to dihydrocodeinone [xiv]. The yields claimed for the transformation are up to 95 per cent. [323], but Rapoport [304] was unable to obtain yields in excess of 50 per cent. Thebadnone-A [xxxvn] is a by-product in this reaction, and can be made the main product by modifying the conditions [325] (cf. the conversion of codeine methyl ether to thebainone-A enol methyl ether by sodium ethoxide). 

Catalytic or sodium and alcohol reduction of thebainone-A enol methyl ether [vi] affords a substance initially allotted the structure [ix] as it is different from an isomeric substance obtained by the catalytic reduction of dihydrotbebaine- >, at that time believed to be [n] [3]. It is now clear that this base is in fact dihydrothebainone A°-enol methyl ether [x] and is formed from [vi] by 1 4-addition of hydrogen to the conjugated system. The product of catalytic reduction of dihydrothebaine- must therefore be the isomeric AB-enol methyl ether [ix] produced by saturation of the 8 14-double bond of [iv]. Bentley, Robinson, and Wain [5] have in this way obtained a base different from that obtained by Small and Browning [3], but believe their product is the true dihydrothebainone-A5-enol methyl ether [ix] as it can also be prepared in 98 per cent, yield by the sodium and liquid ammonia reduction of dihydrothebaine [xi] [5]. 

Dihydrothebainone [xn] or its A6-enol methyl ether [x] is produced in considerable quantity in all reductions of thebaine even under mild conditions, and cannot arise from further reduction of dihydrothebaine. It undoubtedly arises from 1 6-reduction of the conjugated system to give thebainone-A enol methyl ether [vi], which then suffers further 1 4-reduction to dihydrothebainone A6-enol methyl ether [x], the latter boing hydrolysed in acid solution to dihydrothebainone [xn]. This mechanism was suggested by SchOpf and Winterhalder [14], but Small... 

When thebaine [i] is reduced by sodium and boiling alcohol [1-3], or best by sodium in liquid ammonia [4-5], scission of the 4 5-oxygen bridge occurs with the addition of two atoms of hydrogen and production of a phenolic dihydrothebaine, for which the name dihydrothe-baine-< has now been adopted [5]. The sodium-ammonia reduction is rapid, simple, and results in excellent yields of product. Reduction of thebaine with lithium aluminium hydride also yields a phenolic base, /3-dihydrothebaine, which is isomeric with dihydrothebaine- [6], Dihydrothebaine- was first allotted the structure [n] on the basis of its reactions [3], and 3-dihydrothebaine the structure [m] with the abnormal configuration at C-14 on the basis of its hydrolysis to ]S-thebainone-A [iv] [6] thebainone-A enol methyl ether [m] with the normal configuration at C-14, which results from the isomerization of codeine methyl ether [v] under the influence of hot sodium ethoxide, is known to give thebainone-A [rv, C-14 epimer] on hydrolysis [3]. 

Thebainone-A enol methyl ether [m] can be reduced catalytically or with sodium and alcohol to dihydrothebainone A6-enol methyl ether [xi] [3, 12] (erroneously given the A5 structure [rx] at first [3]) and from the catalytic reduction dihydrothebainol-6-methyl ether, identical with the compound obtained from /3-dihydrothebaine, is also obtained [12]. The fact that tliebainono-A onol methyl other and /3-dihydrothebaine... 

Thebainone-A enol methyl ether gives thebainone-A on hydrolysis so readily that no salts of the enol ether can be prepared even in anhydrous media [3]. 

Thebainone-A can also be prepared by the catalytic rearrangement of codeine [vi] under the influence of palladized charcoal at 80° C. [2] by the hydrolysis of thebainone-A enol methyl ether [vn] (prepared by the rearrangement of codeine methyl ether on heating with sodium ethoxide) [3] by the hydrolysis of /j-ethylthiocodide [vm] (obtained by the action of sodium ethoxide on bromo- or /3-chlorocodide) [4-8] (see Chap. XVII) and, in small amount, by the hydrolysis of dihydrothe-baine- [iv] [3]. 

No enol ether of /3-thebainone-A epimeric with thebainone-A enol methyl ether [vn] has been prepared /3-dihydrothebaine was first thought to be such a compound [16] but subsequently was shown to have the structure [hi] [17]. 

This enol ether [xxxi] is the product of catalytic or sodium amalgam reduction of thebainone-A enol methyl ether [vn] [3], from which it arises by 1 4-addition of hydrogen to the conjugated system, and it can also be prepared by the hydrogenation of thebaine in neutral solution [3]. It is very readily hydrolysed to dihydrothebainone, which doubtless arises from this during the reduction of thebaine in acid solution. (Dihydrothebainone was prepared by Speyer and Ereunds [10] by the reduction of thebaine in neutral solution and no doubt arose from the enol ether by hydrolysis during the isolation of the product.)... 

Thebainone-A enol methyl ether 154-156 Eton granules + 9-6 22 3... 

The reduction of thebaine with lithium aluminium hydride has been reexamined, and in the presence of aluminium chloride conditions have been found to give either thebainone-A enol methyl ether or neodihydrothebaine as the main product. Also obtained was a new base, isometathebainone enol methyl ether (86), identified by hydrolysis to isometathebainone (87), which gives... 

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... 

Dihydrothebainone [ix], obtained by the catalytic reduction of thebainone-A [v] [1] and thebainone-B [xm] [13], can be most conveniently prepared by the catalytic reduction of thebaine in acid solution [9-12, 25], and it can also be obtained by the hydrolysis of its two enol ethers (see below). It is a phenolic, ketonic, base, that shows the diazo-reaction in dilutions up to 1 in 2,000,000 [26-27], gives a methyl ether [28], oxime [9], semicarbazone [29], and a benzylidene [30] and piperonylidene [25] derivative. The optical antipode is produced by the sodium amalgam reduction of sinomenine [xxvi] and is known as desmethoxydihydrosinomenine [31]. 

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