Allo-i/r-codeine

Isocodeine is one of the products of hydrolysis of a-chlorocodide [244-5], /3-chlorocodide [238, 243, 250], bromocodide [244, 252], and iodocodide [247], (The name was applied to the product of mineral acid hydrolysis of dihydrothebaine- by Freund [405], but this was a misnomer, see Chap. XIV.) It is also obtained by the methylation of a-isomorphine [245, 252], There was some initial confusion regarding the identity of isocodeine [245, 252, 406-7], which forms a molecular compound [m.p. 145-146° C.] with allo-i/r-codeine [244-5, 253], but this was clarified by Lees [245]. 

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 ]. 

Tetrahydrodesoxycodeine [xrv] is the end-product of reduction of desoxycodeine-A [4], desoxycodeine-C [3], and dihydrodesoxycodeines-B [21], -C [21], and -E [32]. It is also formed in varying amounts during the reduction of the halogenocodides [6-7, 21, 29] (see Chap. VIII) and during the catalytic hydrogenation of allo-i/r-codeine [25] it is identical with Mannich s dehydroxytetrahydrocodeine [7],... 

Two sulphonic acids result from the sulphonation of allo-i/ -codeine-N-oxide, and these on bromination and reduction of the per bromide are converted to bromoallo-i/r-codeine dibromide [295]. 

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]. 

The first product of hydrolysis of a-chlorocodide to be clearly recognized was i/r-codeine [n, R = Me] [36], and following the isolation of isocodeine [18, 37] and allo- -codeine [18] from the hydrolysis of bromocodide (q.v.) all three isomers were obtained by the hydrolysis of a- and /3-chlorocodide with acetic acid, the proportions varying with the two isomeric chloro compounds thus ... 

A base m.p. 130-132° C. obtained by the hydrogenation of dihydro-desoxycodeine-C, when pure has m.p. 144-145° C. and is in fact (/3-) tetrahydrodesoxycodeine [28]. Speyer and Krauss [35] also claimed to have prepared a-tetrahydrodesoxycodeine by the reduction of allo-i/r-chlorocodide, later shown to be /3-chlorocodide [36], but reinvestigation of the reduction revealed the production of only dihydrodesoxycodeine-D and (/3-) tetrahydrodesoxycodeine [21]. The desoxytetrahydro-iji-codeine obtained by the catalytic reduction of tetrahydro-i/<-chlorocodide and stated to be identical with a-tetrahydrodesoxycodeine [35] is too inadequately described to admit identification. 

Hydrogenation in neutral or weakly acid solution with a palladium catalyst affords tetrahydro-i/r-codeinone [xxix] [7, 28] which is further reduced by sodium and alcohol to tetrahydro-i/r-codeine [xxx], the latter being obtained directly from i/r-codeinone by sodium and alcohol reduction. In no case do derivatives of allo-[Pg.171]

Methoxy-4 8-diacetoxyphenanthrene [Lxxxm]. /3-Dimethyl-aminoethanol and [Lxxxm] are formed when i/r-codeinone [lxxxiv] is heated with acetic anhydride, but the main product of this reaction is triacetylthebenine [lxxxv, R = Ac] [89]. i/r-Codeinone methiodide and ethanol at 160° C. give 3-methoxy-4 8-dihydroxyphenanthrene [89-90], which on methylation affords 3 4 8-trimethoxyphenanthrene [90], identical with an authentic specimen prepared in the usual way from 2-nitroveratric aldehyde and 2-methoxyphenylacetic acid [67]. In this way the location of the hydroxyl group in i/r-codeine and allo- -codeine, at C-8, was proved. 

Allo- r-codeine is the third product of hydrolysis of a-chlorocodide [244-5, 250], /3-chlorocodide [238, 243, 250], bromocodide [243-4, 251, 253, 407], and iodocodide [247], It differs from -codeine only in the spatial arrangement of the —CH-OH— group, as is shown by the production of i/i-codeinone when it is oxidized [305, 407, 416]. It is related to /3-isomorphine, from which it can be prepared by methylation [ 245, 253]. Though it is formed by the hydrolysis of a-chlorocodide it yields /3-chlorocodide exclusively when treated with phosphorus penta-chloride [238, 305]. 

As in the if>- and allo- r-codeine series (Chap. IV), reduction of the double bonds of thebaine [i] without opening of the cyclic ether, giving [xi] and [xrv], is favoured by hydrogenation of the hydrochloride rather than of the base [10-14, 16-17],... 

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