Tetrahydrothebaine

When addition of hydrogen takes place simultaneously at C —am C —C tetrahydrothebaine is formed and it is argued that formation of tb tetrahydro-base supports Gulland and Robinson s formula, since Wielanc and Kotake s —C bridge (XL) would not be reduced under the mih... 

Tetrahydropapaverine, 186 Tetrahydropapaverolines, 289 Tetrahydroriddelline, 605 Tetrahydroshobakunine, 329, 340 Tetrahydrostrychnine, 564 Tetrahydrothebaine, 243 Tetrahydroyobyrine, 504, 505 Tetrahydroyobyrinecarboxylic acid ... 

The Diels-Alder reaction of thebaine with various electrophiles yields compounds (Fig. 7.19) that have extremely high potencies, over 1000-fold higher than morphine in some cases (see Refs. 370, 371). X-ray (372) and NMR (373) analysis of 19-propylthevinol, the 3-methyl ether of etorphine (42 above), indicates that the 6,14-etheno bridge is held inside (endo) the tetrahydrothebaine ring system and below the plane (a) of the Cy-Cg bond (see Fig. 7.19 and Ref 283) the C ring is held in a boat conformation by the 6,14-endo etheno bridge. 

Catalytic hydrogenation [494-9] and electrolytic reduction [500] of morphine affords dihydromorphine [xi], which can also be obtained by the demethylation of dihydrocodeine the optical antipode can be prepared in the sinomenine series from (4-)-dihydrocodeine [502-3] (see Chap. XXVI], Dihydromorphine can be esterified [504], converted into ethers [371, 504], heteroethers [446-8], and di-ethers [505], Dihydromorphine dimethyl ether is identical with tetrahydrothebaine [505-7] it can be demethylated to dihydromorphine [506-7],... 

Catalytic hydrogenation of codeine proceeds rapidly with saturation of the 7 8 double bond and formation of dihydrocodeine [m, R = OH] [267-9], also obtainable by the electrolytic reduction of codeine [270], the catalytic reduction of neopine [xm] [271], the methylation of dihydromorphine [272], and the catalytic reduction of dihydro-codeinone [xiv] [273]. By the latter method the optical antipode of dihydrocodeine may be prepared from the sinomenine series [274-5] (see Chap. XXVII). Both enantiomorphs can be demethylated to the corresponding dihydromorphines [269, 274-5]. Dihydrocodeine methyl ether is identical with tetrahydrothebaine [276-8] (see Chap. XIII). 

Examination of the infra-red and ultra-violet absorption spectrum of /3-dihydrothebaine indicated that it has in fact the structure [n] initially allotted to dihydrothebaine- [6]. Such a conjugated diene would be expected to imdergo 1 4-addition of hydrogen with final production of [vm], a reduction parallel to the production of tetrahydrothebaine from thebaine (see below). 

The catalytic hydrogenation of thebaine was first investigated by Oldenberg [8-9], who isolated a crude, amorphous substance to which he gave the name tetrahydrothebaine and which was doubtless a complex mixture of bases. The non-phenolic dihydrothebaine [xi] may be prepared in only moderate yield by the hydrogenation of thebaine... 

Tetrahydrothebaine [xiv] was finally isolated by Schopf and Winter-halder [13] and shown to be identical with dihydromorphine dimethyl ether. It is obtained in good yield by hydrogenation of thebaine in acetic acid over platinum oxide [16-17] or in ethanol over highly active (W 6) Raney nickel [18],... 

Tetrahydrothebaine [xrv] arises as a result of 1 4-addition of hydrogen giving the intermediate [xvn], the isolated double bond of which is immediately further reduced. 

Mild catalytic reduction of thebaine hydrochloride in aqueous or dilute acetic acid solution using a platinum [1] or colloidal palladium catalyst [2-6] results in saturation of the 8 14-double bond and production of dihydrothebaine [i]. The yield is never high, as considerable amounts of dihydrothebainone [n] and tetrahydrothebaine [hi] are produced simultaneously, not by further reduction of dihydrothebaine, which is stable under these conditions. 

Further work on the reduction of thebaine by chemical means has been published since Chapter 8 of Volume II was written. This supports the conclusions outlined previously (Vol. II, pp. 199-203), (402, 403). A careful search of the mother liquors from the commercial hydrogenation of thebaine has led to the isolation of about 1 % of neopine methyl ether (CCCLIII) (404). It is, of course, possible that more of this substance is formed than can be isolated since most of it might well be reduced further to tetrahydrothebaine which is also produced in the reduction. 

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