由3-氟-4硝基甲苯两步合成1,2,6-三取代苯并咪唑

Synthesis of Benzimidazoles from 3-fluoro-4-nitrotoluene by a two-step procedure

摘要:

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，一步关环、脱水合成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）=1:1.5:1.8，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：71℃下，乙醇做溶剂，5-甲基-2-硝基-N-苯乙基苯胺(0.52g,2mmol)、不同的醛（0.28g,2mmol）、1mol/L的Na2S2O4水溶液18mL，在40min～2h反应完全，与文献中报道的12h相比，时间大大缩短。在此条件下合成10种1,2,6-取代苯并咪唑，9种为新化合物，产物结构经IR、1HNMR、13CNMR进行了表征。

Abstract:

Using 3-fluoro-4-nitrotoluene as the starting material, N-substituted 2-nitro-4-methyl-anilines were prepared under microwave irradition, then N-substituted 2-nitro-4-methyl-anilines reacted with different aldehydes to synthesize 1,2,6-substituted benzimidazole derivatives. The first step reaction conditions were optimized from the reaction temperature and the feed ratio and the optimum reaction conditions were determined as follows: the temperature was 83℃, the feed ratio was n(3-fluoro-4-nitrotoluene):n(Phenylethylamine): n(K2CO3) = 1: 1.5: 1.8, the yield of 5-methyl-2-nitro-N-phenylethylaniline (IIa) and 2-nitro-N- (3-phenylpropyl) aniline (IIb) was 99.2% and 98.9% respectively. The reaction conditions were optimized for both the amount of catalyst and the reaction temperature in the second step, and the optimum reaction conditions were determined as follows : the amount of aldehyde and N-substituted-2-nitro-4-methylaniline was 2mmol, ethanol was 30mL and 1mol/L Na2S2O4 aqueous solution was 18mL. Under reflux, the reaction time could be shorten from 12h to 40min-2h compared to the literature. 10 kinds of 1,2,6-trisubstituted benzimidazole derivatives were synthesized, nine of them were new compounds. All the structure of compounds were identified by IR, 1HNMR,13CNMR, respectively.