The Preparation And Application Of 2-bromo-1-aryl-2-(1H-1,2,4-triazol-1-yl) Ethanone

2-Aminothiazole is a very important intermediate.Its derivatives are provided with a wide range of biological or physiological activity.Hydrophobic group contributes to the promotion of small molecule drugs to cancer cells required specific enzyme inhibition to a certain extent.In order to search for novel compounds with higher anticancer activity,we introduced the alkyl into the thiazole amine derivatives containing triazole ring.Many bromination methods can be applied to synthesize 2-bromo-1-aryl-2-（1H-1,2,4-triazol-1-yl）ethanone（C）.The NaBr/H₂O₂ bromination method can not only overcome some defects of NBS and Br₂ bromination methods,such as low conversion,complicated work-up etc.,but also has certain advantages,such as high efficiency,safety and simplified operation.Compounds C were designed and synthesized from with 1-aryl-2-（1H-1,2,4-triazol-1-yl）ethanone（B）by bromination under NaBr/H₂O₂ condition.The key factors influencing the reaction were studied,such as the mole ration of the aryl ketones,sodium bromide and hydrogen peroxide methyl,the amount of catalysts,the reaction temperature and the reaction time.Simplex optimization method was used to obtain the best synthesis conditions:n（B）:n（NaBr）:n（H₂O₂）:n（H₂SO₄）=1:1.4:3.0:0.53,70℃,t=3.0 h.Under this condition,the highest yields of C1 and C2 reached 88.0%and 85.0%,respectively.N-[4-Aryl-5-（1H-1,2,4-triazol-1-yl）thiazol-2-yl]alkyl amides（E）were designed and synthesized from B by cyclization with thiourea and N-acylation with anhydride/acyl chloride.The yield of the synthesized compounds was 31.3%to 97.8%and the structures of them were confirmed by ¹H NMR.The acylating agent and the structures of alkyl had a great impact on N-acylation.E3 and E10,which were synthesized with propionic anhydride,had higher yields of 93.2%and 97.8%.Compounds E were tested for the anticancer activity.The preliminary bioassays indicated that some compounds exhibited good inhibitory activities against Hela.The inhibitory rates of E5,E7,E9 and E12 against Hela（0.100 mmol/L）were 90.0%,90.7%,95.%and 95.4%,respectively.The IC₅₀ of E2,E4,E5,E7,E9,E11,E12,E14 were below0.061 mmol/L.E9（0.034 mmol/L）presented the best inhibitory activity,which was similar to cisplatin（0.036 mmol/L）,it could be used for further study.