Abstract
Brossi and Teitel have recently reported a synthesis of so-called corpaverine (I), mp 115-117°, whose IR and NMR spectra were identical with those of our sample, but the melting points of both specimens were not identical. Therefore, we have re-examined the synthesis of so-called corpaverine. Cyclization of N-(3-benzyloxy-4, 5-dimethoxy-phenethyl)-4-methoxyphenylacetamide with phosphoryl chloride afforded two isomers, one of which was isolated as its crystals, mp 84-86°, identical with our sample (I) reported previously. Furthermore, the synthesis of 7, 8-dimethoxy-1-(4-methoxybenzyl)-2-methyl-3, 4-dihydroisoquinolin-6-ol (IV) by Grignard reaction was carried out in order to compare our sample with Brossi's sample. At first the cyclization of the formyl derivative (VI) with phosphoryl chloride afforded a mixture of VII and VIII, which was separated by recrystallization of its perchlorates. After reduction with sodium borohydride, 8-benzyloxy-derivative (IX) was obtained as its hydrochloride, mp 188-190°, whose debenzylation gave the anhalamine hydrochloride. Secondly Grignard reaction of the methobromide (XIII) with 4-methoxybenzylmagnesium chloride afforded the benzyl-derivative (XV), whose debenzylation with acid gave a phenolic base, mp 84-86°. The IR (in CHCl3) and NMR (in CDCl3) spectra of this sample were not only identical with those of our authentic sample reported by us previously, but also with those of Brossi's sample, mp 115-117°. Accordingly we have concluded to confirm the identity between both specimens and suggesting polymorphism.
