Synthesis, Bioactivity And Quantitative Calculation Of Novel N - Containing Heterocyclic Compounds

The synthesis and properties research of nitrogen-containing heterocyclic derivatives have attracted widespread attention of chemists as well as biologists due to their diverse biological activities. With the aim to screening novel nitrogen-containing heterocyclic derivatives with potenial antimicrobial agents,501,2,4-triazoles and 4 isoxazol compounds were synthesized, and their properties were also reaearched.The synthesis of 5-substituted-4-amino-1,2,4-triazole-3-thione Schiff bases:starting from formic acid, acetic acid, propionic acid, n-butyric acid, phenylacetic acid,4-pyridine carboxylic acid,4-methyl benzoic acid and 2-methoxy benzoic acid, intermediate products 5-substituted-4-amino-1,2,4-triazole-3-thione were synthesized, then 501,2,4-triazole Schiff bases were synthesized by condensation reaction using intermediate with 2-chloro-6-fluorobenzene formaldehyde,3-phenoxy benzaldehyde,4-pyridine formaldehyde,4-methoxy-2,3,6-trimethyl benzaldehyde,4-(1H imidazole) benzaldehyde,5-bromo-2-hydroxy-3-methoxy benzaldehyde, furaldehyde and 4-methoxy acetophenone, among them, 48 compounds were novel. The crystal structure of compounds Ⅱ13, Ⅱ14, Ⅱ34, Ⅱ49 and II50 were obtained. All the target compounds were charcrationed by melting piont, elemental analysis, FI-IR and 1H NMR.The synthesis of (3-(2-chloro-6-fluorophenyl)-5-substituted-isoxazol-4-yl) (phenyl) methanone:starting from 2-chloro-6-fluorobenzene formaldehyde, intermediate 2-chloro-6-fluoro-N-hydroxybenzimidoyl chloride were synthesized, then 4 isoxazol derivatives were synthesized by 1,3-dipolar cycloaddition reaction using intermediate with 3-(3-phenyl)-1-phenylprop-2-en-1-one,3-(2-fluorophenyl)-1-phenylprop-2-en-1-one,3-(3-fluorophenyl)-1-phenylprop-2-en-1-one and 3-(3-fluorophenyl)-1-phenylprop-2-en-l-one respectively. The crystal structure of compounds 3 a was obtained. Their structure were charcrationed by melting piont, elemental analysis, FI-IR and H NMR.Use compound Ⅱ49 as sample, the structure and frequencies of compound Ⅱwere calculated by the DFT/B3LYP and HF methods with 6-311+G(d,p) and 6-311G basis sets, all the calculated frequencies were positive. Compared the calculated structure parameters, FI-IR and 1H NMR data with experimental data, DFT/B3LYP method is more suitable for this compound, and 6-311 G+ (d,p) and 6-311G basis sets just have a little difference.According to the calculated conclusion from compound Ⅱ49, the structure and frequencies of compounds Ⅱ, Ⅱ14, Ⅱand Ⅱ50 were calculated by DFT/B3LYP method with middle basis set(6-31G(d)). Their natural charge and frontier orbital energy were also calculated by the same method. The structure and frequencies of compound 3a were calculated by DFT/B3LYP method with 6-31G+(d,p) basis set. Its natural charge and frontier orbital energy were also calculated by the same method.The in vitro antifungal activities of compounds Ⅱ1-32, Ⅱ49, Ⅱ50 and 3a-d against four vegetable pathogens Gibberlla nicotiancola, Pythium solani, Gibberlla saubinetii and Fusarium oxysporium f.s.p. niveum have been tested using plate agar method. Use the same method, the antifungal activities of compounds Ⅱ33-48 against six vegetable pathogens Gibberlla saubinetii, Alternaria iycopersici, Phytophthora capsici, Fusarium oxysporium f.sp. cucumber, Cercospora arachidicola hori and Physalospora piricola have been tested at the concrentration of 50 ug·mL-1. The antifungal activities test indicated parts of the synthesized compounds showed excllent antifungal activities. The antibacterial acticities of compounds Ⅱ1-50 and 3a against Sacillus subtilis, Staphylococcus aureus and Escherichia coli have been tested using K-B disk diffusion method at the concrentration of 100 ug·mL-1. Antimicrobial activities test showed compounds with 3-phenoxy group and no subsititued at position-5 in the triazole ring appeared to increase the antimicrobial activities.