Dihydrothebainone bromination

Codeine has also been prepared in 70% overall yield, again without purification of intermediate compounds, from dihydrothebainone (132) by the route (132) — (137) shown in Scheme 4. The initial product of the action of bromine and then alkali on dihydrothebainone is the 1,7-dibromo-derivative of dihydro-codeinone, which can be reduced to dihydrocodeinone (133). This may be converted into 7-bromodihydrocodeinone dimethyl ketal (136), which on treatment with potassium t-butoxide in DMSO at 120 °C is converted exclusively into thebaine, but at 60 °C the product is codeinone dimethyl ketal (137), which can be hydrolysed to codeinone (131).154 The process has obvious value in the possible synthesis of codeine via dihydrothebainone, for which a patent has been filed covering a process that proceeds from the reduced isoquinoline (138) 155 the conversion of A-formylnordihydrothebainone into dihydrothebainone by hydrolysis and reductive methylation and by ketalization, reduction, and hydrolysis has been reported.156... 

For many years it was assumed that bromination occurred at C-5 as well as at C-l, and this assumption appeared to be endorsed by the ease of cyclization of B/C cis compounds relative to their B/C trans isomers. In the former the alicyclic bromine was ideally located for displacement by the phenoxide anion. However, Bentley 54 had suggested, without experimental evidence, that C-7 appeared to be the more likely site of C-ring bromination. Once isolation of B/C cis and B/C fraas-dihydrothebainone and dihy-... 

Bromination of dihydrothebainone proceeds with the formation of 1-bromodihydrothebainone with one mole of bromine, 1 5-dibromodi-hydrothebainone [xxxix] with two moles of bromine [45], and 1 5 7-tribromodihydrothebainone [xl] with three moles of bromine [46]. Treatment of the 1 5-dibromo-oompound [xxxix] with alkali results in loss of hydrogen bromide and closure of the 4 5 ether bridge, the product being 1-bromodihydrocodoinone, reductive dobromination of which affords dihydrooodoinono [xxxiti] [45, 47] the lattor oan bo converted... 

The nature of this substance was first elucidated by Schopf and Pfeiffer [54], who, following the conversion of dihydrothebainone [xi/vm], through 1 5-dibromodihydrothebainone [xlix] to 1-bromodihydroco-deinone [l] by bromination and treatment with alkali, and the similar conversion of 14-hydroxydihydrothebainone [li] to 1-bromo-l 4-hydroxy -dihydrocodeinone [lit], showed that 1-bromosinomeneine results in 80 per cent, yield from treating sinomenine with bromine and then with alkali [54], The intermediate 1 5-dibromosinomenine [un] has boon isolated and converted to 1-bromosinomeneine by warming... 

The optical antipode of 1-bromosinomeninone, viz. (—)-1-bromosinomeninone, is produced in small amounts during the conversion of dihydrothebainone to 1-bromodihydrocodeinone [l] by bromination and subsequent treatment with alkali. That it arises from the 7-bromo-derivative is confirmed by its production when dihydrothebainone is brominated with three equivalents of bromine and the resulting 1 5 7-tribromodihydrothebainone [lxxi] treated with alkali, and when 1-bromodihydrocodeinone [l] is treated with one equivalent of bromine in the presence of potassium carbonate and methanol [64]. The formation of (-)-1-bromosinomeninone [lxvih, R = Br] from 1 5 7-tribro-modihydrothebainone [lxxi] is analogous to the production of buchucamphor [lxxii] from dibromomenthone [lxxih] and from... 

The course of the closure of the 4,5-oxide bridge of dihydrothebainone by bromination and treatment with alkali has been studied. The sequence of products is 1-bromo-, l,7a-dibromo-, and l,5/S,7a-tribromodihydrothebainone the last of these, on boiling with ethanol, is converted into an equilibrium mixture of 1,7a- and l,7/3-dibromo-dihydrocodeinones. Cyclodehydration of 5-benzyldihydromorphinone to the base (146) with hydrobromic acid has been achieved. 

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