Synthesis And Fungicidal Activity Of 2-acylamino-2-Substituted Penyl Ehylsulfonamides

Sulfonyl group,which exhibited a broad spectrum of biological activities,played a variety of roles in organism.So it was widely applied in the field of functional organic molecule design to make molecules own good biological activities.Especially for sulfonamides,comprised a substantial proportion and played a vital role not only in the medicines but also in the agrochemicals.As we all know,sulfonamides were the first drugs with a selective effect on bacteria,which could be used systemically against bacterial infections.Hence,sulfonamide antibiotics developed rapidly and were introduced into the agrochemicals to be against pests.Recently,great attention had increasingly been paid to developing compounds containing sulfonyl group as fungicides.Sulfonamide fungicides,such as tolnifanide,cyazofamid and amisulbrom,had been of commercialization and took some share in fungicide market.On the basis of the previous research,we made a deep research on sulfonamides with fungicidal activity.Based on the research of 2-substituted phenyl-2-oxo ethylsulfonamides and use for reference on the experiences of structure optimization of 2-oxocycloalkylsulfonamides,2-substituted phenyl-2-amide ethylsulfonamides were designed and synthesized.N-(2-trifluoromethyl-4-chlorophenyl)-2-(3,5-difluorophenyl)-2-aminoethylsulfonamide(WML-1)was synthesized from the lead compound N-(2-trifluoromethyl-4-chlorophenyl)-2-(3,5-difluorophenyl)-2-oxoethylsulfonamide by reductive amination.Then,we further synthesized N-(2-trifluoromethyl-4-chlorophenyl)-2-(3,5-difluorophenyl)-2-amide ethylsulfonamides(WML-2-WML-64)by the reaction of WML-1 with such acyl chlorides as substituted pyridine formyl chlorides,octanoyl chlorides,halogenated octanoyl chlorides,alkoxy octanoyl chlorides,alkylthio octanoyl chlorides and substituted benzoyl chlorides.Finally,a total of 64 new compounds were synthesized and their structures were identified by IR,1H NMR and HRMS.Forthermore,the primary bioassay of fungicidal activities of all the target compounds against Botrytis cinerea were tested by in vitro mycelium growth inhibition assay and in vivo greenhouse pot experiments.The results that all the compounds showed fungicidal activity against Botrytis cinerea.In the primary bioassay in vitro,the inhibition rate of some compounds were more than 90%.And in the primary bioassay in vivo,the results showed that there are 10 new compounds with the control efficiency of more than 60%,especially for compounds WML-36,WML-32,WML-2 and WML-58 with the control efficiency of 88.20%,84.01%,82.02%and 80.15%,respectively.6 compounds exhibited better control efficiency than the positive control procymidone(with the control efficiency of 72.32%).The other positive control pyrimethanil showed the 50,55%control efficiency against Botrytis cinerea in vivo,and 15 compounds showed better activity than that of pyrimethanil.With the objective of identifying the funficidal activity of the WML compounds against Botrytis cinerea,the EC50 values were also evaluated in vitro.Generally,compounds WML showed good activity,and the EC50 values of 33 compounds were lower than 10.0 mg/L,among them 27 compounds exhibited better activity than that of pyrimethanil(with the EC50 values of 7.71 mg/L),The compounds WML-27,WML-29,WML-12,WML-31,WML-25 and WML-33 showed excellent control efficiency against Botrytis cinerea,which were with the EC50 values of 0.66,1.26,1.51,1.52,1.67 and 1.89 mg/L,respectively,especially WML-27,which showed better activity than that of the positive control procymidone(with the EC50 values of 1.06 mg/L).Finally,the structure-activity relationship(SAR)of N-(2-trifluoromethyl-4-chlorophenyl)-2-(3,5-difluorophenyl)-2-amide ethylsulfonamides was analyzed.In the whole,substituted pyridine amido ethylsulfonamides showed better fungicidal acticvity than that of substituted octanoyl amide ethylsulfonamides,and substituted benzamido ethylsulfonamides the worst activity.It was need to be noticed that the introduction of substituted octanoyl amide group might make the compound showed excellent activity,such as compound WML-27 with the EC50 values of 0.66 mg/L and compound WML-29 with the EC50 values of 1.26 mg/L.From the steucture of introduced amide group,the compound with 6-fluoro-3-pyridine amido or 2,6-dichloro-5-fluoro-3-pyridine amido showed good activity when substituted pyridine amido chlorides were used in the reaction,the compound with ethoxy acetamido,2-bromo propionamido,trichloro acetamido,heptamido or ethylthio acetamido showing good activity when substituted octanoyl chlorides were used,and compound with 2-methyl,2,4-dichloro,2-fluoro or 4-chloro on the benzene ring of amide group exhibiting good activity when substituted benzoyl chlorides were used.At last but not the least,some compounds with high fungicidal activity were screened out by the evaluation of fungicidal activity of the synthetic compounds against Botrytis cinerea.The structure-activity relationship were also analyzed,whch could be used to direct the further development.Therefore,we could enrich the structures and kinds of sulfonamides.