Synthesis And Properties Of Novel Bisthienopyrimidinone Derivatives

The derivatives of thienopyrimidinones, one of the focuses in the research and development of agrochemicals, have been found to have widespread biological activities. Many of them have been used as pesticide, fungicide and medicine. On the other hand, the derivatives of bisthiophenes have been developed for different purposes in the pharmaceutical field and have been tested as potential antitumor, antiviral, antibiotic, analgesic and antipyretic drugs. Further more, some of them are of potential interest as organic electric materials. However, there is little report of a generally useful synthesis of bisthienopyrimidinones. In this paper, we studied the synthesis of novel bisthienopyrimidinones by utilizing aza-Wittig reaction. What the paper studied may be summarized as follows:1.One hundred and thirty six novel bisthienopyrimidinones, six novel heterocyclic system of 5H-2,3-dithia-5,7-diaza-cyclopenta[cd]indenes and ten unreported intermediate were synthesized.The structure of all these compounds were confirmed by IR,¹H NMR, EI-MS and elementalanalyses. Some of them were confirmed by ¹³C NMR and X-ray crystal diffraction.Thosecompounds are summarized as follows:(1) bisthienomonopyrimidinones (81)(2) bisthienobispyrimidindiones (55) (3) 5H-2,3-dithia-5,7-diaza-cyclopenta[cd]indenes (6)(4) intermediates(10) 2.The selective synthesis of iminophosphorane 1 from diethyl 3,4-diaminothieno[2,3-b]thiophene-2,5-dicarboxylate and further reaction of the isolated monoiminophosphorane 1 or bisthienomonopyrimidinones 4,6,8 with triphenylphosphine, hexachloroethane and triethylamine were studied. Novel bisthienomonopyrimidinones 4, 6, 8 were synthsizd from iminophosphorane 1 by utilizing aza-Wittig reaction. The method of preparation of diethyl 3,4-diaminothieno[2,3-b]thiophene-2,5-dicarboxylate was studied and improved.3.Novel diethyl 3,6-diaminothieno[3,2-b]thiophene-2,5-dicarboxylate 34 was designed and synthesized, and bisiminophosphorane 24 was easily prepared from 34. Bisthienobispyrimidindiones 27,29,31 were efficiently synthesized via aza-Wittig reactions from 24. The selective reactions of bisiminophosphorane 24 with aromatic isocyanates were also studied.4. Monoiminophosphorane 1 reacted with aryl or alkyl isocyanates to give stable monocarbodiimides.However, in the presence of catalytic amount of potassium carbonate, the monocarbodiimides were transferred into previously unreported 5H-2,3-dithia-5,7-diaza-cyclopenta[cd]indenes 9 via direct cyclization in high yields.5.Novel diazide 17 was designed and synthesized. Monoiminophosphorane 18 and bisiminophosphorane 15 were synthesized from bisazide 17 via Staudinger Reaction. The reactions of bisiminophosphorane 15 with aryl isocyanates were also studied.6. The antitumor activities of 13 compounds were also researched and some of them displayed strongantiproliferative and cytotoxicity effect on human lung cancer cell lines A549. The best of them was 6h which displayed comparable inhibition (78.6%) in 160μg·ml^-1 with standard Mitomycin (MMC) in 80μg·ml^-1.The IC₅₀ of 8a was less than 10μ·gm^-1.The antibacterial activities of 21 compounds were tested and some of them showed good fungicidal activities. For example, 5a exhibited 84% inhibition of Botrytis cinereapers in 100 ppm.