Synthesis Of 1,3,4-Thiadiazole Derivatives And Nitrogen-Containing Heterocyclic Metal Complexes And Biological Activity Research

Heterocyclic compounds are a class of organic compounds that are ubiquitous in nature.Because of special chemical structures,they have unique biological activities,such as anti-inflammatory,anti-oxidation,anti-bacterial or anti-tumor,etc.which are widely used in medicine and agriculture.Taking a heterocyclic compound as a lead,it is an effective way to develop new drugs by structure modification of heterocyclic moleculestosynthesizenovelheterocycliccompounds.Amongthem,nitrogen-containing heterocycles have be widely used in agricultural fields,such as the insecticides?pymetrozine or thiamethoxam?,and the fungicide?carbendazim or propiconazole?.At the same time,the heterocyclic compound also has good coordination ability,and it can be complexed with metal ions to forms a structurally stable complex,so that the biological activity is more diverse,such as the fungicides currently used,copper thiabium and thidium copper.This topic is divided into two parts.The first part,using the principle of molecular splicing,a series of 1,3,4-thiadiazole derivative with excellent biological activity were synthesized by combination of some heterocyclic molecules and1,3,4-thiadiazole,and their biological activity was studied,such as in vitro inhibitive activity on plant fungal and antiproliferative activity on human tumor cells.In the second part,commercial nitrogen-containing heterocyclic pesticides with good activity were selected to form metal complexes by complexation of them with metal ions,and the obtained complex is studied for their bacteriostatic and insecticidal activity,hoping to discover new pesticides with dual efficacy of insecticidal and bacteriostatic activity.The main contents of this paper are as follows:1.Intermediate1?2-amino-5-substitutedphenyl-1,3,4-thiadiazole?was synthesized from thiocarbamide and substituted benzoic acid,and then 2(2-chloroacetylamino 5-substituted phenyl-1,3,4-thiadiazole was prepared by electrophilic reaction of the Intermediate with chloroacetyl chloride.Finally,11 new target products were obtained by connecting with sodium 3,5,6-Trichloropyridine.The products obtained were screened for the antimicrobial activity in vitro,and the antiproliferative activities against 4 kinds of human tumor cells were determined in vitro.2.The four compounds with selenazole ring was obtained by the reaction of the intermediate 2 with KSeCN,The products obtained were screened for the antimicrobial activity in vitro,and the antiproliferative activities against 2 kinds of human tumor cells were determined in vitro.3.Using pymetrozine as a ligand,two copper complexes were obtained by complexing copper acetate or copper sulfate.At the same time,their sustained release performance and in vitro antibacterial activity were investigated.The results showed that the copper complexes of pymetrozine had good sustained release performance and better antibacterial activity than the commercial thiamethoxam for the thin streak disease of rice.Further insecticidal activity tests showed that the complexes played distinct insecticidal activity against rice planthopper.4.Two zinc???complexes and two copper complexes were obtained by complexation of sodium 3,5,6-Trichloropyridine with zinc and copper salts,respectively.The antibacterial activity were studied.The results showed that the complexses had good antifungal activity against 6 plant fungal pathogens at the concentration of 50?g/mL,and they displayed certain antibacterial activity against the thin streak disease of rice at the concentration of 250 ppm.In summary,11 new trichloropyridine ring-containing 1,3,4-thiadiazole derivatives,4 selenazole ring-containing 1,3,4,-thiadiazole derivatives and 6nitrogen-containing metal complexes were synthesized in this paper.The biological activity of the compounds was assessed and it was found that all compounds have certain biological activities.The 1,3,4-thiadiazole derivatives has a high selective inhibitory effect on proliferation of SKOV3 tumor cells,with an IC₅₀0 between 2-10?M.The antibacterial effect of the obtained complexes was generally higher than that of the ligand,and the sustained release performance of the copper???complexes of pymetrozine was higher than that of the ligands.