Synthesis And Activity Study Of Thiazole Salt Compounds Containing 1,3,4-oxa(thia)diazolyl

As one member of quaternary ammonium compounds,the thiazolium salts with broad spectrum of bioactivities,including antibacterial,antifungal,antimalarial and insecticidal activities,have been widely used in agriculture,industry and other fields.Meanwhile,1,3,4-oxadiazoles were viewed as a hotspot in research to develop novel pesticides,because of their extensive biological activities,such as antibacterial,antifungal,anti-inflammatory,anti-tuberculosis and so on.To develop new antimicrobial,this paper introduce the thiazole ring into 1,3,4-oxadiazole structure by the long-chain alkane,to synthesis a series of thiazolium salts bearing the 1,3,4-oxadiazole moiety.The starting material substituted benzoic or benzyl acid was treated with three steps,containing esterification,hydrazinolysis and cyclisation,to obtain one of the most important intermediate 5-substituted-1,3,4-oxadiazole-2-thiol.Then the important intermediate 5-substituted-1,3,4-oxadiazole-2-thiol reacted with dibromo-substituted alkanes and got the other intermediate 5-substituted-1,3,4-oxadiazole-2-substituted thioether.After that,the intermediate thioether reacted with thiazole ring under the condition of reflux and obtained our target compounds.According to the synthetic route,48 target compounds have been synthesized and all of the compounds were confirmed by 1HNMR,13 CNMR,MS.The biological activities of all the title compounds against three pathogenic bacteria were examined using the turbidimeter test in vitro.The results suggested that all compounds exhibited excellent inhibition effects against the three bacteria at the concentration of 200 ?g/mL and 100 ?g/mL.Futher research found that these compounds exhibited the best inhibition activities against Xoo,with the EC₅₀ values ranging from 0.10¹0.56 ?g/m L,which was much better than the control agent Bismerthiazol(EC₅₀ value was 92.61 ?g/mL).Secondly,these compounds showed good inhibition effect against Xac,with the EC₅₀ values ranging from 2.34¹7.58 ?g/mL,which was also better than the control agent Thiodiazole copper(EC₅₀ value was 216.70 ?g/m L).Compared with the former two bacterium,these compounds displayed slightly less inhibition rates against R.solanacearum ranging from 3.27⁸5.27 ?g/mL,but the EC₅₀ values were still much better than the control agent Bismerthiazol.As a whole,the compounds A12,A16,A30,A32,A36,A40,A46,A47 and A48 possessed excellent antibacterial activities against the three pathogenic bacterium with EC₅₀ values ranging from 0.10¹4.59 ?g/mL.