Fused [1]Benzazepines. Pentacyclic [1]Benzazepines by Reaction of 1H-[1]Benzazepine-2,5(3H,4H)-dione with Aldehydes

Condensation reaction of lH-[l]benzazepine-2.5(3H,4H)-dione (1) with the aromatic aldehydes (2a-e) in the presence of piperidine furnished 4-benzylidene-1H-[llbenzazepine-2,5(3H,W)-diones (3a-e), whereas in the presence of potassium hydroxide the 7a,8,15a,l5b-tetrahydro-l5b-hydroxy-5H-[1lbenzazepino[4'.5':4.51cyclopenta[l,Z-c][l]benzazep~ne-6.9.1 5(7H,8aHr1 4H-triones (4a-e) wereformed.The reaction of 1 with formaldehyde yielded the splro compound (7) as the product of a Diels-Alder dimerization.Like many natural occurring a-methylenesesquiterpene lactones, several synthetically prepared a-benzylidenecycloalkanones exhibit cytotoxic activity.'One possible mode of action of these agents is accounted to be enzyme inhibition due to alkylation of thiol groups.In the course of studies on the chemistry of [llbenzazepines, it was intended to prepare 4-alkyl~dene substituted [llbenzazepine-2,5-diones with a view to gain derivatives with antitumor activity.The 4-arylidene substituted compounds (3a-e) were synthesized by heating the lH-[l]benzazepine-2.5(3H,4Hdlone (1) with a sultable aromatic aldehyde (2a-e) without solvent in the presence of a catalytic amount of plperidine.accordlng to the method of L6vai and Szab6,"n all cases only one of the two possible diastereomers was isolated.Compound (3a) was shown to beE-configurated, because in an NOE experiment irradiation on the signal of the methyiene protons resulted In a significant enhancement of the ortho phenyl proton signals.whereas the vinylic proton signal was not affected.When 1 was reacted with the aromatic aldehydes (2a-e) in ethanolic solution containing potassium hydroxlde, the pentacycllc compounds (4a-el were isolated instead of the expected products (3a-e).The formation of 4