Preparation And Application Of Several Five-membered Heterocyclic Compounds Containing Phenylhydrazine Group

Tetramic acid and tetronic acid compounds are often found in natural products,which have many biological activities,such as antitumor,antiviral,antibacterial,antifungal and herbicidal activity.Compounds containing phenylhydrazine group often show significant biological activities.The researchers modified the structures of tetramic acid or tetronic acid compounds and introduced substituted phenylhydrazine group to design and synthesize a variety of pyrrolidinedione,pyrrolinone and furanone derivatives containing substituted phenylhydrazine with good biological activity.Zhang and Bao synthesized isopropyl 2-(4-chlorophenyl)-1-(1-(4-((isoprop-oxycarbonyl)oxy)-2-oxo-2,5-dihydro-1H-pyrrol-3-yl)vinyl)hydrazine-l-carboxylate(the test code named NN-2215)and isopropyl 2-(4-chlorophenyl)-1-(1-(4-((isoprop-oxycarbonyl)oxy)-2-oxo-2,5-dihydrofuran-3-yl)vinyl)hydrazine-1-carboxylate(the test code named NN-301),respectively.These two compounds exhibited remarkable activity against plant pathogenic fungi.Hu and Wang replaced the pyrrolidone ring with pyrazolidone to synthesize 4-(1-(2-(2,4-dichlorophenyl)hydrazinyl)-ethylidene)pyrazolidine-3,5-dione(the test code named NN-400)and isopropyl 1-(1-(1-acetyl-3,5-dioxopyrazolidin-4-ylidene)ethyl)-2-(4-chlorophenyl)hydrazine-caroxyla te(the test code named NN-401),respectively.These compounds also showed significant inhibitory effect on plant pathogenic fungi,such as Fusarium graminearum.In this paper,the compounds NN-2215,NN-301,NN-400 and NN-401 were synthesized firstly.Subsequently,their green environment-friendly suspension concentrate were developed.Finally,their field efficacy trials were carried out.NN-2215 was synthesized with glycine as raw material.Firstly,3-(1-hydroxyl-ethylidene)pyrrolidine-2,4-dione was prepared by the reactions of esterification,amidation and cyclization.Then,it was sequentially reacted with substituted phenylhydrazine and isopropyl chloroformate to obtine the target cmpound pyrroliane-2,4-dione derivative containing phenylhydrazine and ester groups.NN-301 was synthesized with ethyl 4-chloroacetoacetate and potassium tert-butyl alcohol as raw material.By the substitution,cyclization and acylation reactions 3-(1-hydroxylethylidene)furan-2,4-dione was given.Then,it was sequentially reacted with substituted phenylhydrazine and isopropyl chloroformate to gain the target cmpound furan-2,4-dione derivative,which contains phenylhydrazine and ester groups.NN-400 was synthesized with diethyl malonate as raw material.By the hydrazinolysis,cyclization and acylation reactions 4-(1-hydroxylethylidene)-pyrazolidine-3,5-dione was synthesised.Next,it was reacted with 4-chlorophenylhydrazine to obtain the target compound.Finally,NN-401 was synthesized from 4-(1-hydroxyl-ethylidene)pyrazolidine-3,5-dione.By acylation reaction 1-acetyl-4-(1-hydroxy-lethylidene)pyrazolidine-3,5-dione was given.Which was sequentially reacted with 4-chlorophenylhydrazine and isopropyl chloroformate to obtain the target compound pyrazolidine-3,5-dione containing phenylhydrazine and ester groups.By screening the types and dosages of wetting and dispersant agents,thickeners,antifreezes and other components,the formula of four water suspension concentrats(20%NN-2215 SC,20%NN-301 SC,20%NN-400 SC and 20%NN-401 SC)were determined as follows:20%of active ingredient+5%emulsifier-A+5%ethoxy modified polytrisiloxane+1%water-soluble azone +0.1%xanthan gum + 1.5%magnesium aluminum silicate+2.5%ethanediol+90.1%silicone defoamer+1%tributyl phosphate+63.8%deionized water.Then,these four water suspension concentrats were prepared with horizontal sand mill.The performance parameters of the suspension concentrats were checked.The results showed that the viscosity were 544 mpa.s-555 mpa.s.,pH values were close to neutral,suspension rates were greater than 80%,dispersivity was good,and the heat storage stability and cold storage stability were qualified.The field efficacy and plant safety test against wheat scab(Fu.sarium graminearum)of above suspension concentrats were carried out.The results showed that:(1)20%NN-2215 SC at experimental doses of 187.5 g ai/hm2,375.0 g ai/hm2 and 562.5 g ai/hm2 had certain control effects.Among them,the effect of 74.74%at 562.5 g ai/hm2 was close to that of the control fungicide 80%carbendazim WP at 750.0 g ai/hm2.(2)20%NN-301 SC at the experimental dose of 375.0 g ai/hm2 showed the effect of 54.37%.(3)20%NN-400 SC at the experimental doses of 187.5 g ai/hm2 and 375.0 g ai/hm2 of had certain control effects.Among them,the effect of 75.24%at 375.0 g ai/hm2 treatment was higher than that of 80%carbendazim WP at 750.0 g ai/hm2.(4)20%NN-401 SC at the experimental doses of 187J5 g ai/hm2 and 375.0 g ai/hm2 also had certain control effects.Among them,the control effect of 70.52%at 375.0 g ai/hm2 was higher than that of the control agent 80%carbendazim WP at 750.0 g ai/hm2.(5)The above four suspension concentrats at the various tested doses did not cause phytotoxicity to wheat.