Synthesis of dihydroisoindole derivatives

A series of isotryptamine and hydroxyisotryptamine derivatives were synthesized because of their potential pharmacological activities. The following results were achieved: (1) A new synthetic route was developed for the preparation of isotryptamine and its N-alkyl derivatives from isoindolin-1-one-3-ethanoic acid. (2) A modified synthetic route was developed first for the preparation of 1-nitrosodihydroxynaphthalenes, then for that of hydroxyisoindolin-1- one-3-ethanoic acids and finally, for hydroxyisotryptamines and their N-alkyl derivatives. (3) It was shown that isoindolin-1-one-3-ethanamide, hydroxyisoindolin-1-one-3-ethanamide and their Nalkylated derivatives can be synthesized in good yield from the corresponding acids and urea derivatives. (4) As standard reduction methods gave only very low yields of isotryptamine derivatives the requirements of reducing lactamamide groupings were reinvestigated. Contrary to published reports it was shown that boron trifluoride plays a catalytic role in the reaction and it was established that (a) the nature of the solvent used (b) the order in which the reagents are added and (c) the generation of diborane in situ determine the yield of the amine. (5) A new tricyclic compound, isocarboline, was synthesized by ring closure, via a methylene bridge, between the two nitrogen atoms of isotryptamine.