Sinomenine hydrate

Goto and Mitsui then made an examination of the electrolytic reduction of numerous sinomenine derivatives, but in no case was the removal of the hydroxyl group at C-4 observed. The compounds reduced in this way were sinomenine, dihydrosinomenine, desmethoxydihydrosino-menine, desmethoxydihydrosinomeninol, sinomeninol, dihydrosino-meninol, sinomenine hydrate, and a- and /3-desmethoxysinomenine hydrate [30],... 

Hydrolysis of the enol ether may be achieved by 2N hydrochloric acid at 100° C., and if the solution is neutralized with sodium carbonate sinomenine hydrate [lxvh] is precipitated. This apparently exists in the hemiacetal form, but the 7-methoxyl group is readily lost and for all practical purposes sinomenine hydrate behaves as the a-diketone sino-meninone [Lxvm, R = H], and gives a dioxime and disemicarbazone [61]. 

When the base is liberated from the solution after hydrolysis with ammonia instead of sodium carbonate a dimolecular base bis-des-methylsinomenylidine is obtained instead of sinomenine hydrate [23], and this base is also obtained by the action of ammonia on the latter [61]. It is believed to arise from the self-condensation of the diketone, the carbonyl group at C-6 in each molecule condensing with the active methylene group at C-8 in the other, and the product is in fact a quinone. The structure of the product is shown in essence in [lxix]. The condensation of sinomeninone to bis-desmethylsinomenylidene is analogous to the self-condensation of diacetyl to p-xylene quinone [62],... 

Hydrolysis of the enol ether group of sinomenine is apparently not effected by concentrated sulphuric acid below 10° C., as sinomenine under these conditions gives sinomenine-1-sulphonic acid [lxxvii]. Sinomenine hydrate on treating in this way loses the 7-methoxyl group, the product being sinomeninone-1-sulphonic acid [Lxxvm]. Sinomenine derivatives with position 1 (i.e. para to the phenolic group) substituted, e.g. 1-bromosinomenine and disinomenine (see below) cannot be sulphonated in this way [67-68]. 

The bromination of sinomenine hydrate with three equivalents of bromine and of 1-bromosinomeninone with two equivalents of bromine yields 1 5 8-tribromosinomeninone, which is converted into 1-bromo-sinomeninone by catalytic reduction, and to 1-bromodesmethoxydesoxy-dihydrosinomenine on reduction by Clemmensen s method [69]. 

Diacetoxy-3-methoxyphenanthrene and triacetylisothebenine are obtained by the acetolysis of sinomenine hydrate and the 1-bromo-derivatives of these can be prepared in the same way from 1-bromosinomeninone. Catalytic reduction of both triacetylisothebenine and its 1-bromo-derivative affords triacetyl-9 10-dihydroisothebenine [55], believed by Schopf, Pfeiffer, and Hirsch [64] to be triacetylisothebenine when the same sequence of reactions was carried out on (—)-l-bromo-sinomeninone. /sothebenine is probably 4 6-dihydroxy-3-methoxy-5-(/3-methylaminoethyl)-phenanthrene [lxxxh], or the 4 7-dihydroxy-isomer [64], On heating with sodium hydroxide and methyl alcohol at 80° C., 1-bromotriacetyKsothebenine yields a compound C2oH2004NBr in 7 per cent, yield this is probably 1 -bromo-N-acetylisothebenine [55] (see also Chap. XXV). 

The exhaustive methylation of the free diketones has not been studied, but sinomenine hydrate on heating with ethyl sulphate and alkali gives 5 5 -diphenanthrene derivatives as does sinomenine under the same conditions [41]. 

Like other a-diketones and or o-quinones, e.g. dibenzoylsinomenol-quinone [15], sinomenine hydrate [lxvii behaving as lxvih, R = II] on heating with 30 per cent, hydrogen peroxide in glacial acetic acid is oxidized to a dibasic acid, sinomeninic acid [xo, R = H], This on bromination gives 1-bromosinomeninic acid [xc, R = Br], also obtainable by the oxidation of 1-bromosinomeninone [Lxvm, R = Br] [73]. (—)-1-bromosinomeninic acid can be prepared by the oxidation of (—)-1-bromosinomeninone it can be reduced catalytically to (—)-sinomeninic acid [74]. These acids exist as lactones. 

Methylsinomeninic acid [xci, R = H] and 1-bromomethylsinome-ninic acid [xci, R = Br] are formed when methylsinomeninone [73] and 1-bromomethylsinomeninone [44] respectively are oxidized with hydrogen peroxide. Similarly the oxidation of 1-bromosinomeneine ketone [lxxvi] affords 1-bromosinomeneinic acid [xcii] [73]. The ultraviolet absorption spectra of [xc, R = H], [xc, R = Br], and [xci, R = H] are very similar to that of sinomenine hydrate, which in turn is almost identical with that of sinomenine [73]. 

Bromosinomeneine ketone [lxxvi]. can be made to undergo the benzil —> benzilic acid transformation in hot alkali, the product being 1-bromosinomenilic acid [xcm]. This acid is also obtained when the amorphous product of bromination of 1-bromosinomeninone with one equivalent of bromine is treated with alkali, and from sinomenine hydrate and one equivalent of bromine [69]. 

Methoxy-4 6-diacetoxyphenanthrene [nr] is formed when codeinone [lii] [68] and sinomenine hydrate [un] [69] axe heated with acetic anhydride and sodium acetate a second product in the degradation of [lih] is triacetyh sothebenine [liv ]. The 1-bromo-derivative can be obtained in like manner from the antipodes of 1-bromosino-meninone [69-70] and reduced catalytically to [li]. Hydrolysis of [li] affords the corresponding 4 6-dihydroxy-compound, which results from heating codeinone methiodide with ethanol at 160° C. [71] both compounds have been identified by conversion to 3 4 6-trimethoxy-phenanthrene [68],... 

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