Dihydrothebainone methyl enolate

Dihydrothebainone-A-5 6-methyl enolate, CjaHjjOjN, m.p. 164-165-5°, [a] ° — 115-7° (EtOH). Cold N/HCl converts it into dihydrothebainone hydrochloride. The isomeric dihydrothebainone-J-6 7-methyl enolate is formed on catalytic hydrogenation of phenolic dihydrothebaine. It has m.p. 127-8°, [a] ° — 8° (EtOH) and yields dihydrothebainone on acid hydrolysis. ... 

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. 

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... 

Dihydro thebaine-< absorbs only one mole of hydrogen on catalytic reduction, yielding dihydrothebainone AB-enol methyl ether [ix], which is identical with the product of sodium and liquid ammonia reduction of the non-phenolic dihydrothebaine [x] [5]. (A compound of different melting-point and specific rotation was prepared by Small and Brown-ing [3] by the catalytic reduction of dihydrothebaine-< and allotted the structure [xi] owing to a misconception of the structure of the latter. It is probably a mixture [5].) Dihydrothebainone [xn] is produced by the hydrolysis of [ix] showing that no rearrangement of the thebaine skeleton occurs during sodium and alcohol reduction [5]. 

S-Dihydrothebaine [n] absorbs two moles of hydrogen on reduction over platinum oxide, the product being dihydrothebainol-6-methyl ether [xm] [6], identical with the compound obtained in the reduction of thebaine in neutral solution [3]. The configuration at C-14 in [xm] is not known. A dihydro-derivative, dihydrothebainone A6-enol methyl ether [xi], can also be isolated from the products of reduction [12]. 

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... 

Dihydrothebainone-A-5 6-methyl enolate, CjgHggOgN, m.p. 164-165-5°, [ ]d ° 115-7° (EtOH). Cold N/HCl converts it into dihydrothebainone... 

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... 

Hydrolysis of dihydrothebaine methine [ix] affords dihydrocodeinone methine [xxi], which can be reduced catalytically to the dihydromethine [xix] or with aluminium amalgam to dihydrothebainone methine [xxn]. The nitrogen-free product of degradation of dihydrocodeinone methine [xxi] has not been isolated [3]. It was hoped to prepare the AB-enol methyl ether [xxm] of dihydrothebainone dihydromethine by the sodium and liquid ammonia reduction of dihydrothebaine methiodide, but only a complex mixture of products was obtained in this way. Sodium ammonia reduction of the methiodide of [vn] yielded only the original base, but [xxm] was finally obtained by the catalytic reduction of dihydrothebaine- dihydromethine [xxiv] [18]. 

The reduction of thebaine methiodide with sodium in liquid ammonia leads to dihydrothebaine- dihydromethine [xxx], also accessible by the reduction of dihydrothebaine- methiodide the methyl ether can be prepared in the same way from dihydrothebaine methyl ether methiodide. [xxx] can be hydrolysed by mineral acids to the-bainone-B dihydromethine [xxxi], and reduced with difficulty to dihydrothebainone dihydromethine AB-enol methyl ether. Its methiodide on reduction with sodium and ammonia yields 4-hydroxy-3 6-dimethoxy-13-ethyl-7 13 9 10-tetrahydrophenanthrene [Xxxii] and on alkaline degradation gives A6,8-6-methoxythebendiene [xxxm] [11],... 

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]. 

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.)... 

Dihydrothebainone dihydromethine A5-enol methyl ether [lvi] results from the hydrogenation of dihydrothebaine- dihydromethine [XXIV] [23]. 

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