Abstract
Synthetic routes of 3-methyl-2, 3, 4, 5, 6, 7-hexahydro-2, 7-methano-1H-3-benzazonine (X-A), 4-methyl-2, 3, 4, 5, 6, 7-hexahydro-1, 6-methano-1H-4-benzazonine (X-B) and 2-methyl-2, 3, 4, 5, 6, 7-hexahydro-1, 6-methano-1H-2-benzazonine (XX) having a new ring system were described.
4-Phenylcyclohexanone (I) was condensed with diethyl oxalate followed by decarbonylation to give ethyl 2-oxo-5-phenylcyclohexanecarboxylate (II), which was hydrolyzed to afford 4-phenylpimelic acid (III). 5, 9-Methanobenzocycloocten-8, 10-dione (IV) obtained by cyclization of III with PPA was reduced to 10-hydroxy-5, 9-methanobenzocycloocten-8- one (V), which in turn was derived to 8-acetoxy-5, 9- methanobenzocyclooctene (VI) by catalytic reduction over Adams catalyst in acetic acid containing a small amount of perchloric acid. VI was hydrolyzed, followed by a Jones oxidation to give 5, 9-methanobenzocycloocten-8-one (VII). The oxime (VIII) of VII was submitted to a Beckmann rearrangement with PPA to afford a mixture of 2, 3, 6, 7-tetrahydro-2, 7-methano-1H-3-benzazonin-4 (5H)-one (IX-A) and 2, 3, 6, 7-tetrahydro-1, 6-methano-1H-4-benzazonin-5 (4H)-one (I X -B)(ratio: ca. 10: 1), which were separated by fractional recrystallization. Both IX-A and IX-B were reduced with lithium aluminum hydride, followed by Clarke-Eschweiler methylation to give X-A and X-B, respectively.
4-Benzylcyclohexanone (XIV) obtained by catalytic reduction of p-benzylphenol (XIII) and the subsequent oxidation with chromic acid was derived to 3-benzyladipic acid (XV) by nitric acid oxidation, which was then cyclized to 4-oxo-1, 2, 3, 4-tetrahydronaphthalene-2-propionic acid (XVI). The ethyl ester (XVII) of XVI was derived to the oxime (XVIII), which was reduced to an amino-ester followed by cyclization to give 4, 5, 6, 7-tetrahydro-1, 6- methano-1H-2-benzazonin-3 (2H) one (XIX). Reduction of XIX with lithium aluminum hydride and the subsequent methylation afforded XX.
