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.