γ-Oxo Carboxylic Acids in Heterocyclic Synthesis, III. Synthesis of Biologically Active 4-Benzylamino-6-(5,5-dioxodibenzothiophen- 2-yl)-2,3,4,5-tetrahydropyridazin-3-ones

Abstract

α-Benzylamino-β-(5,5-dioxodibenzothiophen-2-carbonyl)propionic acid (1) has been synthesized by treating the corresponding β-aroylacrylic acid with benzylamine in dry benzene. On treatment with hydrazine hydrate the keto acid 1 furnishes the corresponding pyridazinone derivative 2. The behaviour of 2 towards carbon electrophiles, namely, ethyl chloroacetate, acrylonitrile, formaldehyde and secondary amines (under Mannich reaction conditions), aromatic aldehydes and carbon nucleophiles, namely, POCl3/PCl3 and P2S5 has been investigated. The 3-chloropyridazine derivative 13 reacts with hydrazine hydrate to give the 3-hydrazino derivative 14. On treatment with ethyl acetoacetate and/or acetylacetone the hydrazine 14 undergoes cyclization to afford pyrazolone derivative 16 and 3-(3,5-dimethylpyrazol- 1-yl)pyridazine derivative 17, respectively. On reaction with acetylhydrazine in boiling butanol and/or sodium azide in DMF the 3-chloropyridazine derivative 13 affords the triazolo[4,3-b]pyridazine 18 and the tetrazolo[1,5-b]pyridazine 19, respectively. The anti-microbial activity of the synthesized derivatives has been investigated.