Synthesis And Antibacterial Activities Of N-(5-Alky-1,3,4-Thiadiazole-2-Yl)-s-(5-Substituted-4-N-o-Hydroplenylimino-1,2,4-Triazole-3-Yl)-α-Thioacetamide

1,2,4-triazole-compounds have the effect that they could inhibit pathaogen’s growth ormake them dead. When the condensation between the 4-amino of 1,2,4-triazole compoundsand carbonyl take place which could generates Schiff base derivatives, the antimicrobial andbactericidal activity of 1,2,4-triazole-compounds will higher. Moreover, the 2,5-substituted-1,3,4-thiadiazole compounds which is a significant medicinal and pesticide intermediate havea variety of functions, including weeding, antiviral, lowering blood pressure, sterilization,plant growth regulation and so on. At the same time,in many biologically active substancesthe amide and sulfide are also effective structure fragments which have good insecticidalactivity. Therefore, according to the principles of antivity superimposed, in the paper we usethe electrophilic reaction to splice the 5-substituteed-4-N-o-hydropehylimino-1,2,4-triazole-3-thime and N-（5-substituted-1,3,4- thiadiazole）-α-chloroacetylamine into the same one targetcompound molecule which generate a series of dual heterocyclic compounds including1,3,4 - thiadiazole, 1,2,4-triazole and bridge base -SCH₂CONH-.First, the cyclization reaction between substituted carboxylic acid and symmetricaldiamino-thiourea take place which generates 5-substituted-4-amino-1,2,4-trazole-3-thione.Then the intermediates reacte with salicylaldehyde through addition reaction and eliminationreaction to gain 5-substituted-4-N-o-hydropehylimino-1,2,4-triazole-3-thime; on the otherhand, Alkyl carboxylic acid reacts with thiosemicarbazide to generate 2-substituted-5-amino-1,3,4–thiadiazol. Then the products react with chloroacetyl chloride to generateN-（5-substituted-1,3,4–thiadiazole）-α-chloroacetylamine. Finally, the electrophilicsubstitution reaction between the above intermediates take place in the alkaline conditionwich generates N-（5-substituted-1,3,4-thiadiazole-2-yl）-S-（5-substituted-4-o-hydropehylimino-1,2,4-triazole-3-yl）-α-thioacetamide. The structures of compounds have been confirmed bythe¹H NMR and IR and the test of preliminary bioassary have been completed.The results of preliminary bioassay show that when the mass concentration is 0.01%, theintermediates and target compounds have the broad-spectrum antibacterial activity onEscherichia coli, Monilia albicans and Staphylococcus aureus. Among that the intermediates2a ²d，3a ³d，6a ⁶d have higher antibacterial activities that are more than 65%, andcomparisonly the antibacterial activity on Escherichia coli and Monilia albicans is a littlehigher than that of Staphylococcus aureus. Especially, the compound 3a ³d’s antibacterialactivity on these three fungis are as higher as 80%, 85% and 75%. The target compounds 7a⁷p’s antibacterial activities on these three fungis are all more than 85%, simultaneously theantibacterial activity on Staphylococcus aureus is more than 90% which is actually higherthan that of Escherichia coli and Monilia albican.Structure-activity analysis showed that the antibacterial activity on these three fungis of intermediates 3a³d are universally higher than that of 2a-2d which indicates that theintroduction of o-hydroxyphenyl or schiff base imine structure is important to promote theantibacterial activity of compounds. The antibacterial activity of 7a⁷p on these three fungisare universally higher than that of 3a³d and 6a⁶d. The result showed that the targetcompounds make the intermediates spliced through bridge base -SCH₂CONH- whichsignificantly improve the integral antibacterial activity. This result is in line withbiological principles of activity superimposed. Additionally the antibacterial activity is relatedto the substituted base of thiadiazole and the result showed that the smaller the substitutedbase, the higher antibacterial activity. With analysis we have the idea the reason may be due tothat the groups of macromolecules enlarge the overall volume of the compounds and the sterichindrance of the specific space with the targets might be increased which lower thecompounds’affinity to the targets leading to the reduction of antibaterial activity of thecompounds.