1952 Volume 72 Issue 12 Pages 1539-1541
In order to increase the yield of dihydroisoquinoline derivatives obtained by the condensation of safrol or methyleugenol with various acid amides, several kinds of condensation agents were tried but phosphoryl chloride seemed to be the most effective. In the preparation of 3, 4-dihydroneupaverine, i.e. 1-(3′, 4′-methylenedioxyphenyl)-3-methyl-6, 7-methylenedioxy-3, 4-dihydroisoquinoline, 3, 4-methylenedioxybenzonitrile is formed as a by-product, and therefore, p-nitrobenzonitrile or p-nitrobenzamide was applied to safrol by which the objective isoquinoline derivative was obtained in either case but it required a long period of time in the case of the former with a very poor yield. It is assumed, from this result, that nitrile itself does not directly react with safrol in this reaction but the amide adds to the double bond in safrol and then undergoes isoquinoline cyclization by the action of phosphoryl benzamide. It can also be assumed that the initially formed nitrile by the dehydration of acid amide also takes part in the reaction.
