Synthesis And Fungicidal Structure Activity Relationship Of 2-substituted Aminocycloalkylsulfonamides

The intermediate 2-aminocycloalkylsulfonamides were prepared by reductive amination with chesulfamide as a lead compound with good fungicidal activity,and then reacted with halogenated alkanes,substituted benzyl bromide,2-chloroethylbenzene,3-chloropropylbenzene,2-haloacetate,5-chloromethylpyridine,5-chloromethylthiazole,N-substituted 2-chloroacetamide were used to synthesize eight different types(?-1 to ?-59)of the 2-substituted aminocycloalkylsulfonamides.The structures of all 59 compounds were confirmed by 1H NMR,13C NMR,HRMS,elemental analysis,IR.In addition,the three compounds of ?-8,IV-16 and IV-47 also were confirmed by X-ray single crystal diffraction.The fungicidal spectrum screening test of all compounds was screened by mycelial growth inhibition method.The main contents of the experiment were as follows:(1)Botrytis cinerea,Pyricularia grisea,Rhizoctonia solani Kiihn,Bipolari sorokiniana,Phytophthora capsici,Fusarium graminearum Schw,Exserohilum turcicum(Pass.)Leonard et Suggs.The results showed that the compounds had high control effect on the gray mold and the rice blast.At 50?g/mL,the inhibitory rate of 28 compounds against gray mold was more than 70%and the inhibitory rate of five compounds against rice blast was 100%.In order to further verify the activity of target compounds against Botrytis cinerea and Magnaporthe grisea,the fungicidal toxicity was determined.Three strains of Botrytis cinerea CY-09,HLD-15,DL-11 collected from different areas of Liaoning Provinceand and Magnaporthe grisea were selected.The results of fungicidal toxicity test showed that substituted benzyl,substituted phenethyl,substituted methyl thiazole and N-substituted-2-chloroacetamide expressed higher activity,especially 5-chloromethylthiazole.In the case of compound IV-24,The EC50 values of compound IV-24 aganist CY-09,HLD-15 and DL-11 were 3.17 ?g/mL,1.41 ?g/mL,2.37 ?g/mL,respectively,less than procymidone(10.3 ?g/mL,6.03 ?g/mL,4.04 ?g/mL)and pyrimethamine(-,3.88 ?g/mL,2.79 ?g/mL).Compared with the other two kinds of control agents boscalid and cyprodinil,?-24 also had a good inhibitory effect.In addition,its EC50 value aganist Magnaporthe grisea was 4.62?g/mL lower than that of the control agent isoprothiolane(EC50 = 6.11 ?g/mL).The compounds were subjected to in vivo experiments using live potting method.The results showed that the inhibitory rate of the six compounds was over 90%better than carbendazim(59.6%),procymidone(83.5%),pyrimethamine(82.0%),cyprodinil(88.6%)in the cucumber living pot experiment.The effects of compounds ?-38(88.1%),IV-39(79.0%)and ?-41(87.8%)were higher than those of the control drugs boscalid(78.2%),pyrimethamine(50.4%),and procymidone(65.7%)in the tomato pot experiment.Considering the fungicidal activity in vitro and in vivo,the compound ?-24 with high activity was selected to carry out the indoor phytotoxicity test.The results of the initial phytotoxicity test showed that compound IV-24 did not produce any damage to the plant height and leaf volume of tomato seedlings and cucumber seedlings at high concentration of 700 ?g/mL.The relationship between the fungicidal activity and the structures showed that the activity of the compounds with substituted alkanes(R3)and substituted carboxylate were not good.The length of carbon chain between the amino group and the benzene ring was different,the fungicidal activity was very different,substituted phenylethyl>substituted benzyl>substituted phenylpropyl.The activity of compounds connected with fluorine atoms,bromine atoms on benzene ring was significantly improved.Substituted thiazole and substituted pyridine as two kinds of substituted heterocyclic,the activity of substituted pyridine compounds was obviously lower than that of substituted thiazole.The fungicidal activity of most 2-chloro-N-substitued phenylacetamides compounds was high,but when the substituents are in the 3-and 5-positions,the compounds are nearly inactive and the substituents in the 2-and 4-positions had higher activity,especially,when the fluorine atoms at the 2-and 4-positions.When the structure of the cycloalkyl group(R1)changed,the activity also changed greatly.The activity of the six-membered ring was higher than that of the five-membered ring and the seven-membered ring,and the greater the substituent groups attached to the cycloalkyl group,the worse the activity.In this paper,two kinds of active substituents were selected by derivatization synthesis and activity evaluation of 2-aminocycloalkylsulfonamides,which were substituted methyl thiazoles and N-substituted-2-chloroacetamides.This study laid the foundation for the follow-up research and development.