Synthesis of Imidazole, Coumarin and Isoxazole Containing New Triheterocyclic Compounds and Their Derivatives.

Abstract

Reaction of substituted 4-amino-3-methyl-5-styrylisoxazoles 1 with 3-(2-bromoacetyl)coumarin 2 in abs. ethanol leads to the formation of 3-[2-(3-methyl-5-styryl-4-ylamino)acetyl]chromen-2-ones 3, which are subsequently cyclised by treatment with KSCN to 3-[1-(3-methyl-5-styryl-isoxazol-4-yl)-2-mercapto-1H-imidazol-4-yl]-1-benzopyran-2H-ones 4. 2Mercaptoimidazoles 4 on treatment with ClCH2COCl in DMF / abs. ethanol give unexpected product esters 5. The reaction of 4 with phenacyl bromides results in the formation of thioethers 6. IPC: Int.Cl. 7 C 07 D 261/00, 233/54, 311/10 The synthesis of imidazole, coumarin and isoxazole containing compounds and their derivatives attracted considerable attention from organic and medicinal chemists due to their considerable bioactivity. The imidazole ring bearing compounds, particularly 2mercaptoimidazoles have been reported to possess anti-inflammatory activity 1 . Various biological applications have been reported for isoxazoles such as antitumor 2 , CNS-active 3 , analgesic 4 , antimicrobial 5 and chemotherapy 6 . Coumarins and their derivatives are widely used as fragrances, pharmaceuticals and as agrochemicals 7 . We earlier reported the synthesis and biological activity of bi-heterocyclic compounds consisting of isoxazole and coumarin moieties 8 . The wide range of therapeutic value of isoxazole, imidazole and coumarin ring systems prompted us to plan the synthesis of new triheterocyclic compounds containing isoxazole, imidazole and coumarin ring systems. We herein report the synthesis of the title compounds, which may be useful as bioactive compounds. The reaction of substituted 4-amino-3-methyl-5styrylisoxazoles 9 1, obtained from the corresponding substituted 3-methyl-4-nitro-5-styryl isoxazoles 10 , with 3-(2-bromoacetyl)coumarin in absolute ethanol led to the formation of 3-[2-(3-methyl-5-styrylisoxazol-4-ylamino)acetyl]chormen-2-ones 3 in 6070% yields (Scheme I). IR spectrum of 3 showed the strong absorptions at 3378, 1720 and 1685 cm -1 due to NH, coumarin carbonyl and –CH2CO- functionalities,