Study On The Synthesis And Biological Activity Of 2-Oxocycloalkylsulfonamides And 2-Oxocycloalkylsulfonylureas

A few years earlier, we had been working with the research of N-substituted-2-Oxocyclododecyl-sulphonamides for fungicidal activity , and they had active activity against Gibberella zeae. Based on it novel 2-oxocycloalkylsulfonamides (22 compounds) were contrived and synthesized (Scheme 1.). Their structures were proved by IR, 1H NMR and elementary analysis.The bioassay indicated that some of them possess certain fungicidal activity against Botrytis cinerea Pers. and Sclerotinia sclerotiorum (Lib.) de Bary. The EC50 and EC90 of Compounds IVA-14 against Botrytis cinerea Pers. were 2 ug/ml and 16 ug/ml. The EC50 and EC90 of Compounds IVB-4 against Sclerotinia sclerotiorum (Lib.) de Bary. were 8 ug/ml and 38 ug/ml. They are more active than comparison pesticide chlorothalonil. In general, compounds containing a 6-membered ring (IVA) and 7-membered ring (IVB) are more active than those containing a 12-membered ring (IVC). In the series IV, the compounds in which R1 are the disubstituted phenyK R1=2,5-dichlorophenyl, 3,4-dichlorophenyl, 2,5-difluoroformphenyl, 3,5-difiuoroformphenyl) showed better activity than those in which R1 are the monosubstituted phenyl.QSAR study (CoMFA) 2-Oxocyclododecylsulphonamides showed that 2-Oxocyclododecylsulpho-nylureas (V) may have higher predicted activity. Meanwhile, to study the relationship between the size of the ring and their activity, a series of 2-oxocycloalkylsulfonylureas (32 compounds) have been contrived and synthesized derive from IV (Scheme 2.) . Their structures were proved by IR, 1H NMR and elementary analysis.The bioassay indicated that VC-15 showed active fungicidal activity against Botrytis cinerea Pers., Colletotrichum orbiculare (Berk. Et Mont.) Arx and Pythium aphanidermatum (Eds.) Fitzp .Their separate EC50 was 7μg/ml, 13μg/ml, 16ng/ml. They are more active than comparison pesticide Carbendazim and N-4-chlorophenyl-2-OxocyclododecylsuIphonamide against Colletotrichum orbiculare ( Berk. Et Mont.) Arx and Pythium aphanidermatum (Eds.) Fitzp. The result of biological assay was consistent with forecast of CoMFA. The antifungal activity of large ring compounds(VC)was better than normal ring compounds(VA and VB), and this result indicated that 12-membered ring was likely to be functional group with antifungal activity.The reaction of 2-oxoalkylsulfonic acid or 2-oxoalkylsulfonate with phosphorus trichloride or phosphorus pentachloride to afford corresponding 2-oxoalkylsulfonyl chloride had been reported in the literature, but the yield was low. We across-the-aboard research the reaction of potassium 2-oxoalkylsulfonates (II) with phosphorus pentachloride, phosphoryl chloride and oxalyl chloride. II reacted with phosphorus pentachloride to afford 1-chlorocycloalkene (VI) . A/I forms by loss of POCl3 and SO2C12 from the adduct (a) of the 2-oxoalkylsulfonyl chloride and PC15 (Scheme 3.).Here we report a new approach to synthesis of 2-chlorocycloalkanones (VII), which involves the treatment of potassium 2-oxocycloalkylsulfonates (II) with phosphoryl chloride in chloride/sulfolane in refluxing acetonitrile (Scheme 4.).We explored the use of oxalyl chloride as chlorinating agent for the preparation of 2-oxocycloalkylsulfonyl chloride (HI) and discovered that oxalyl chloride plus DMF as a catalyst gave a higher yield of III, which was converted into 2-oxocycloalkylsulfonamides (IV) by ammoniation. The 2-oxocycloalkylsulfonylureas (V) were obtained in acceptable yield by the reaction IV with phenyl chloroformate and amines successively (Scheme 2.).