Synthesis And Fungicidal Activity Of Pyrazolidinedione Derivatives Incorporating Substituted Phenylhydrazine And Ester Moieties

The pyrazole derivatives often show the characteristics of high efficiency,low toxicity and environmental friendly,have a wide range of applications in the field of pesticides.They are a very important compound type in new pesticide discovery research.A series of pyrazolidine-3,5-dione derivatives with phenylhydrazine moiety were found exhibitting high fungicidal activity.In this article,carboxylic ester groups were introduct at 1-position of hydrazine group of pyrazolidine-3,5-dione to design and synthesize of thirty-six novel pyrazolidine-3,5-dione derivatives incorporating substituted phenylhydrazine and ester moieties,and their fungicidal were activity preliminarily evaluated.Firstly diethyl malonate was used as the starting material to prepare 4-(1-hydroxy-ethylidene)-pyrazolidine-3,5-dione 4 by the reactions of hydrazinolysis,cyclization and acylation.Then,1-acyl-4-(1-hydroxy-ethylidene)-pyrazolidine-3,5-diones 5a and 5b were synthesized by the reaction of N-acylation with acetyl chloride and butyryl chloride,respectively.These intermediates 4,5a and 5b were reacted with substutited phenylhdyrazines respectively to give 5 kinds of pyrazolidine-3,5-dione derivatives with substutited phenylhdyrazine group 6a-6e.Then compounds 6 were reacted with 8 chloroformic ester respectively to give twenty-eight pyrazolidine-3,5-dione derivatives with substutited phenylhdyrazines and carboxylic ester groups A1-A8,B1-B8,C1-C8 and E1-E4.In addition,malonic acid was used as the starting material to prepare 1-phenyl-4-(1-hydroxy-ethylidene)-pyrazolidine-3,5-dione 4a by the reaction of cyclization with phenylhydrazine and acylation with acetyl chloride.This intermediate was reacted with substutited phenylhdyrazines respectively to give 1-phenyl-4-(1-(2-(4-chlorophenyl)hydrazino)-pyrazolidine-3,5-dione 6f.Then this intermediate was reacted with eight chloroformic esters respectively to give eight pyrazolidine-3,5-dione derivatives with substutited phenylhdyrazines and carboxylic ester groups D1-D8.The structures of these title compounds were comfirmed by IR,1H NMR and MS.The fungicidal activities of the title compounds against Fusarium graminearum,Botrytis cinerea,Rhizoctonia solani and Colletotrichum capsici were evaluated by mycelial growth rate method The results indicated that most compounds showed remarkable fungicidal activities at the concentration of 10 p.g/mL and 1 ?g/mL.The EC50 values of all the compounds from series A to C and E against R.solani were lower than 1.0 ?g/mL except the compound B8.Among them,the EC50 values of twenty-one compounds were lower than 0.2802 ?g/mL of carbendazol.Compounds A2 and B6 showed the most remarkable fungicidal activities with the EC50 values of 0.0053 ?g/mL and 0.0085?g/mL,respectiely.The EC50 values of the most compounds against F.graminearum were lower than 0.3631 ?g/mL of carbendazol.Among which,the compounds C1 and C5 showed highest activity with the EC50 values of 0.1879?g/mL and 0.1944 ?g/mL.The EC50 values of the most compounds against B.cinerea were lower than 0.8241 ?g/mL of penthiopyrad,among which,the compounds C5 and C6 showed highest activity with the EC50 values of 0.3504 ?g/mL and 0.3628?g/mL,respectiely.The compound C6 showed highest activity against C.capsici with the EC50 value of 0.1512?g/mL,lower than 0.2786 ?g/mL of penthiopyrad.Compounds A2,A6,B3,B6,C1,C4,C6 and E2-E4 gave EC50 values lower than 1.0?g/mL against all the four kinds of tested fungi.The analysis of the structure-activity relationship indicated an important rule.The group at 1-position of pyrazolidine-3,5-dione ring apparently affect the fungicidal activity.The C series of compounds with the 1-acetyl group showed best fungicidal activity,and the following were compounds of series A without substituent group and compounds of series B with the 1-butyryl group.The compounds of series D with the group 1-phenyl showed the weaker fungicidal activities than other compounds.It could be presumed that the fungicidal activity had some relationship with the ability of electron-withdrawing or electron-donating and the size of the group at the 1-position of pyrazolidine.The compounds with the electron-withdrawing group,such as acetyl group and butyryl group,at 1-position of pyrazolidine,showed higher fungicidal activity than the compounds with the electron-donating group,such as the phenyl group.And the compounds with the more little substituent group at the 1-position of pyrazolidine,such as acetyl group,the fungicidal activity was higher than the compounds with the bigger substituent group,such as the butyryl group.