Bulbocapnine methyl ether

The reaction of ( + )-bulbocapnine methyl ether (42) with excess boron trichloride in methylene chloride containing 0.3% ethanol produces the catechol (43) together with the monophenol (44). However, with boron tribromide, it is the diphenol (45) which is produced. Both compounds (44) and (45) can be O-methylated with diazomethane to the dimethyl ether (46), and hydrolysis of (46) with dilute hydrochloric acid leads to (+)-corytuberine (47).43 Alternatively, methylation of (43), using diazomethane, affords (+)-corydine methyl ether (48). 

It was shown that the oxidation product obtained by treatment of bulbocapnine methyl ether (25f) with iodine in ethanol/water is not the tetradehydroaporphinium salt, as reported by Gadamer and Kuntze (443), but a dimer of the structure 37 (441, 441a) (Scheme 9). Reduction of this compound with zinc in dilute sulfuric acid gives racemic bulbocapnine methyl ether (25f), whereas reduction with complex hydrides affords the dimers 38 and 39. 

Scheme 9. Oxidation and dehydrogenation products of bulbocapnine methyl ether (25f)...

In ethanol-free methylene chloride, bulbocapnine methyl ether (30) with boron tribromide affords a mixture of diphenol 33 and phenanthrene 35. 

The presence of a little ethanol in the solvent leads, upon the addition of boron tribromide, to some hydrobromic acid resulting in formation of the hydrobromide salt of the initial aporphine. No phenanthrene is ultimately obtained under these conditions. Bonding of boron tribromide to the basic nitrogen seems to be the initial step in the opening of ring B. This is supported by the observation that reaction of (-f-)-bulbocapnine methyl ether (30) with boron tribromide in the presence of a strong base such as l,8-bis(dimethylamino)-naphthalene furnishes mainly the phenanthrene derivative 35. On the other hand, the hydrobromide salt of 30 when treated with boron tribromide produces only the diphenol 33. ... 

In the first authenticated dimerization of an aporphine, oxidation of (+)> bulbocapnine methyl ether (30) with iodine provided the dimer 36. Reduction of 36 with zinc in dilute sulfuric acid led to racemic 30, whereas reduction with lithium aluminum hydride supplied a pair of diastereomeric dimers 37. ... 

O-demethylation of aryl methyl ethers of nonphenolic aporphine alkaloids. Regioselective demethylation by this method occurs at positions 1,8, and 11 of the aporphine nucleus methylenedioxy functions survive the reaction (447). Selective cleavage of the methylenedioxy group in O-methyl-bulbocapnine with boron trichloride is discussed in Section III,C (448). The ether cleavage of methoxy- and methylenedioxy-substituted isoquinoline has been reviewed (346). 

It was possible to racemize bulbocapnine 0-methyl ether and 0-benzoyl-bulbocapnine by first oxidizing with iodine and subsequently reducing with zinc in dilute acid. The dZ-O-methyl ether melted at 136° and was resolvable into the I- and d-derivatives ([a] d 247° in chloroform) by means of d- and Z-tartaric acid, respectively. Hydrolysis of the dZ-O-benzoylbulbo-capnine (m.p. 201-202°) with sodium methylate yielded dZ-bulbocapnine (m.p. 209-210°). As in other aporphines, it was possible to effect scission of the nitrogen ring in bulbocapnine by treatment with benzoyl chloride at its boiling point. 

When it is methylated with nitrosomethylurethan in alcohol in the presence of potassium hydroxide there is formed an 0,0-dimethyl ether (m.p. 134° [a] b —314° (chloroform), —211° (ethanol)) which is not identical with bulbocapnine 0-methyl ether (78). Since all of the possible aporphines with methoxy or methylenedioxy groups in positions 2, 3, 5, 6 and 3, 4, 5, and 6 are known with the exception of 3,4-methylenedioxy-... 

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