由3-氟-4-硝基甲苯两步合成1,2,6-三取代苯并咪唑

Two-step Synthesis of 1,2,6-Trisubstituted Benzimidazoles from 3-Fluoro-4-nitrotoluene

以3-氟-4-硝基甲苯为初始原料,先借助微波合成N-取代-2-硝基-4-甲基苯胺,其与不同的醛反应合成了1,2,6-三取代苯并咪唑。从反应温度、投料比两方面对第一步的取代反应进行了反应条件优化,确定了最佳反应条件：反应温度为83℃,投料比为n（3-氟-4-硝基甲苯）∶n（苯乙胺）∶n（K2CO3）=1.0∶1.5∶1.8,此时5-甲基-2-硝基-N-苯乙基苯胺（Ⅱa）产率为99.2%,5-甲基-2-硝基-N-（3-苯基丙基）苯胺（Ⅱb）产率为98.9%。从催化剂的用量、反应温度两方面对第二步反应进行了反应条件优化,确定了最佳反应条件：乙醇为溶剂、5-甲基-2-硝基-N-苯乙基苯胺（2 mmol）、醛（2 mmol）、1 mol/L的Na2S2O4水溶液18 m L,反应时间40-120 min,此时2-（4-氯苯基）-6-甲基-1-苯乙基-苯并咪唑（Ⅲb）收率为91.3%。与文献中报道的反应时间12 h相比,反应时间大大缩短。在该条件下合成10种1,2,6-三取代苯并咪唑,9种为新化合物,产物结构经IR、-1HNMR和-（13）CNMR进行了确证。

N-substituted 2-nitro-4-methyl-anilines were prepared from 3-fluoro-4-nitrotoluene under microwave irradiation,and then they reacted with different aldehydes to synthesize 1,2,6-substituted benzimidazole derivatives.The effect of reaction temperature and reactant feed ratio on the first step reaction was optimized.Under the optimum reaction conditions of temperature 83 ℃,n（3-fluoro-4-nitrotoluene） ∶ n（phenylethylamine） ∶ n（K2CO3） = 1.0 ∶ 1.5 ∶ 1.8,the yield of 5-methyl-2-nitro-Nphenylethylaniline（Ⅱa） and 5-methyl-2-nitro-N-（3-phenylpropyl） aniline（Ⅱ b） was 99.2% and98.9%,respectively.The reaction conditions were optimized for both amount of catalyst and reaction temperature in the second step reaction,and the optimum reaction conditions were determined as follows： the amount of aldehyde and N-substituted-2-nitro-4-methylaniline was 2 mmol,ethanol was used as solvent,18 m L Na2S2O4 aqueous solution（1 mol/L） was used as catalyst,and the reaction time was between 40 minutes and 2 hours,the yield of Ⅲb was 91.3%,which was shorter than that of the literature（12 hours）.Ten kinds of 1,2,6-trisubstituted benzimidazole derivatives were synthesized,and nine of them were new compounds.All compounds were identified by IR,1 HNMR and13 CNMR.