Study On The Synthesis And Bactericidal Activities Of 5-amino-thiazole-2-formylarylmines

2-aminothiazole derivatives are a kind of five-members heterocyclic compounds containing sulfur and nitrogen atoms,they have attracted wide attention of pesticide developers due to their excellent biological activities,high efficiency and low toxicity,much pesticides and pharmaceutical products of which have been commercialized.The structure of 5-aminothiazole compound was similar to 2-aminothiazole compound.However,they lacked common synthesis method and the biological activity development was relatively lagging behind owing to their special structure and complicated construction method.And till now,none pesticides and medicines of them have been commercialized.In order to find efficient and green new 5-aminothiazole fungicides,in the previous period of our work,more than 30 novel 5-aminothiazole amide derivatives have been designed and synthesized by using seedavax as the leading compound.Their preliminary screening results in vitro showed that the bactericidal activities of most target compounds were much higher than that of the control seedavax,and the structure-activity relationship of them deserved to be further studied.In this paper,based on the previous period of work,23 new 5-aminothiazole amide compounds were designed and synthesized by replacing the methyl at the4-position of the high activity 5-aminothiazole compounds with trifluoromethyl.Expecting to find new pesticide leading compounds withhigh activity by further study on their structural modification and the structure-activity relationship.Firstly,2-amino-3,3,3-trifluoromethylpropanitrile(intermediate 1)was synthesized through strecker reaction in room temperature by using75% trifluoroacetaldehyde,methanol-ammonia solutions and trimethylcyanosilane(TMSCN)as raw materials.Secondly,N-phenyl-2-chloroacetamides(intermediate 2)were synthesized by the reaction of substituted aniline with chloroacetyl chloride.Then,intermediate 3 were synthesized with the reaction of intermediate 2 and sulfur powder.Finally,the target compounds 5-aminothiazole aromatic amine were synthesized by the cyclization of 2-amino-3,3,3-trifluoromethylpropanitrile and intermediate 3 with triethylamine as catalyst.The effects of reaction temperature,time and solvent on the yield of intermediate 1,intermediate 3 and target compounds 4a-w have been investigated.And all the structure of target compounds were confirmed by NMR,IR and ESI-MS.The bioassay results of bactericidal activities showed that all target compounds have certain inhibitory effect on the six tested strains at a concentration of 50 μg/mL.Among them,the inhibitory activities of seven compounds(4a,4c,4g,4h,4k,4l and 4u)were better than that of the seedavax.Especially,the inhibition rate of compound 4u against Cucumber fusarium wilt,Rhizoctonia cerealis,Watermelon anthracis,Fusarium fujikuroi,and Alternaria solani were more than 4 times of that of seedavax,and its inhibition rate of apple ringworm was also more than2 times of the seedavax.