Synthesis and Antimicrobial Activity of Some New Pyrimidinone and Oxazinone Derivatives Fused with Thiophene Rings Using 2-Chloro-6-ethoxy-4-acetylpyridine as Starting Material

摘要

A series of pyridines, pyrimidinones, oxazinones and their derivatives were synthesized as antimicrobial agents using citrazinic acid (2,6-dihydroxyisonicotinic acid) as a starting material. α,β-Unsaturated ketones >3a–>c were condensed with cyanothio-acetamide in the presence of ammonium acetate to give 2-cyanopyridinethiones >4a–>c, which were reacted with ethyl chloroacetate to yield the corresponding cyano esters >5a–>c. The esters >5a–>c were cyclized by action of sodium methoxide to aminoesters >6a–>c, which were aminolyzed with ammonia to corresponding aminoamide derivatives >7a-c. Also, the esters >6a–>c were hydrolyzed with NaOH to the corresponding sodium salt >8a–>c, which were treated with acetic anhydride to afford 2-methyloxazinones >9a–>c. The latter compounds were treated with ammonium acetate to afford 2-methylpyrimidinones >10a–>c, followed by methylation with methyl iodide to yield 2,3-dimethyl-pyrimidinones >11a–>c. The antimicrobial screening showed that many of these compounds have good antibacterial and antifungal activities comparable to streptomycin and fusidic acid used as reference drugs.