Synthesis And Fungicidal Activity Of Thienyl Pyrroline-2-one Derivatives

Heterocyclic compounds play an important role in the research and development of green pesticides.In the screening for novel and bioactive compounds,the design and synthesis of heterocyclic compounds is one of the effective ways.Pyrrolidone derivatives have a wide range of biological activities,such as antiviral,antitumor and antioxidation activity.In addition,thiophene derivatives also show good fungicidal,herbicidal and insecticidal activity.In this paper,thiophene ring was introduced to the 3-position of pyrroline-2-one to design and synthesize two series of sixty-nine novel thienyl pyrrolinone derivatives.Their preliminary fungicidal activities were also evaluated.The intermediates 3-(thiophen-2-yl)-4-hydroxy-pyrrolidin-2-one 4a-4e were prepared by the reaction of esterification,N-acetylation,Dieckmann cyclization and acidification starting from glycine,sarcosine,alanine,isoleucine and phenylalanine,respectively.Twenty-nine 3-(thiophen-2-yl)pyrroline-2-one derivatives A-F containing ester group at 3-position of pyrroline ring were synthesized by the reaction of intermediates 4a-4e with chloroformate or acid chloride.At the same time,forty 3-(thiophen-2-yl)pyrroline-2-one derivatives G-H containing phenylhydrazone groups were obtained by the successive reaction from intermediates 4a-4c with a-bromo-substituted acetophenone and substituted phenylhydrazine.The structures of the target compounds were confirmed by FT-IR,1H NMR,MS and elemental analysis.The antifungal activities of the target compounds and the control fungicide drazoxolon against Fusarium graminearum,Rhizoctorzia solani,Botrytis cinerea and Colletotrichum capsici were evaluated using a radial growth inhibition technique in vitro.At the concentration of 10 ?g/mL,the target compounds showed different levels of inhibition activity,and the compounds G-H had higher activity than the compounds A-F.Among them,the inhibitory rates of compounds G7 and H6 exceeded 80%against F.graminearum,R.solani and C.capsici.The EC50 values of some selected compounds were determined.The compounds G7 and I7 displayed notable activity against R.solani with EC50 values of 1.2584 ?g/mL and 0.6018?g/mL,respectively,lower than 1.7746 ?g/mL of the control drug drazoxolon.The compounds I4 and I7 exhibited good activity against C.capsici with EC50 values of 4.0790 ?g/mL and 4.4830 ?g/mL,respectively,also better than 19.4614?g/mL of drazoxolon.The preliminary structure and activity relationship of the target compounds was analyzed.The result about the compounds A-E indicated that the compounds with medium sized alkyl at the alcohol part of the ester showed higher activity.The introduction of methyl at 1-position or methyl,sec-butyl or benzyl group at 5-position of the pyrroline would be helpful for improving the fungicidal activity.When the proton of the thiophene ring was substituted by a bromine atom,the inhibitory rates of the compounds would increase about 10%-30%.For the compounds G-M,both type and position of the substituents on the two phenyl rings were important influencing factors on fungicidal activity.The antifungal activity was preferable when the substituent was 4-F,4-Cl or 4-Br at the phenyl ring of phenylhydrazone.When the substituent at the phenyl ring of the acetophenone was 4-OCH3,4-F or 4-Cl,better activity was expressed.