Synthesi Of The Multi-halobenzne Nitrile-substituted Quinazolinones And Research On Antibacterial Activity

The pathogenic bacteria showed multi-drug resistant to a variety of antibiotics, which has been widely used, resulting in the fact that infection treatment was not only difficult, mortality increased, and a rising trend which has caused high attention. Therefore, it is extremely urgent to looking for effective antimicrobial drugs which inhibit the growth of pathogenic bacteria. Quinazoline compounds were a kind of nitrogen-containing compounds with good biological activity, and have been widely applied in the fields of medicine and pesticides, such as sterilization, insecticide, anti-viral, anti-inflammatory, anti-tumor, anti-hypertensive, anti-tuberculosis, antimalarial. The application prospect of the quinazoline compounds was wide. Its molecular design, synthesis and biological activity have become a hot research of organic chemistry.This paper used5-chloro-8-nitroquinazolin-4(3H)-one compound (1) as a starting material, reflexing with amine compounds (2) in THF/DMF mixed solvent, resulting in the nucleophilic substitution reaction to obtain the quinazoline morpholine derivatives (3). The nitro was restored into amino group in the hydrogen (Pd/C) using tetrahydrofuran (THF) as solvent. At last, using K2CO3as the catalyst and THF/DMF (7:1) as the solvent, the selective single substitution reaction with polyhalogenated the phthalonitrile compounds (5) occured, Which18novel the multi-halobenzene nitrile-substituted quinazolinone compounds (6) was synthesized that have the polyhalogenated Isophthalonitrile, and have not been reported. The method had high reaction rate, was easy to operate, and had simple post-treatment. The obtained target compound and intermediate structures were confirmed by1H NMR,13C NMR, HRMS, and IR spectral datas.The antibacterial activity test for the synthesised8-aminoquinazoline ketones and the multi-halobenzene nitrile-substituted quinazolinone compounds have been conducted. The four pathogenic bacterias (BC, SA, EC, PA) and a fungus (CA) were selected in the drug sensitivity test, and the test results showed that the antibacterial activity of the compounds was selective, and the antibacterial activity of8-aminoquinazoline ketones to the4kinds of test bacteria are generally weak, while the antibacterial activity of the multi-halobenzene nitrile-substituted quinazolinone compounds were good. Rescreening determination of minimum inhibitory concentration (MIC) of the compound, which showed that most compounds antibacterial activity against Gram-positive bacteria (BC, SA) is better than Gram-negative bacteria (EC, PA). Where in the compound6f,6g,6i,6j,6k best antibacterial activity, fairly active control pharmaceutical norfloxacin. Determinity the minimum bactericidal concentration (MBC) of the five compounds further, the results showed that the effect of antimicrobial of bacteria greater than that of fungi. Morever, the compounds of6k,6j were better in killing bacteria like Gram-positive bacteria (BC, SA) than the control Connqught sparfloxacin, and the compound6k (MBC=7.8μg/mL) was better in controlling fungus (CA) than fluconazole (MBC=15.6μg/mL).