Synthesis Of Heterocyclic Derivatives Containing 2-Trifluoromethyl Benzimidazole

As an active center functional group of some enzymes, benzimidazole scaffold takes part in many signficant biochemical processes and paly an important role in biological activities. Because they have one nitrogen atom with lone pair electrons, benzimidazole compounds are endowed with capability of complex and molecular recognition and they can analogue biological molecule. Benzimidazole moiety display a broad spectrum of biological activity including antiviral, antifungicide, anti-inflammatory effects, some benzimidazole compounds have found applications in diverse therapeutic areas for hypertension and ulcer. Therefore benzimidazole compounds have attracted considerable attention of the pharmaceutical industry. 1, 2, 4-triazole, 1,3, 4-thiadiazole and 1,3, 4-oxadiazole also have been broadly used as fungicide, insecticide, herbicide, growth hormone, and so on .In view of these observation and realizing the inforcement of many physilogical activities by means of combining these heterocycles, we designed and synthesized benzimidazole compounds incorporating with 1, 2, 4-triazole, 1, 3, 4-thiadiazole and 1, 3, 4-oxadiazole in effort to enhance their biological activity. A serise of desired benzimidazole derivatives were obtained and this supports a convenience for pharmaceuty studies. The strutures of all the synthesized compounds were confirmed by elemental analysis, IR and ¹H NMR spectroscopy.The major works of the paper:1. Synthesis of 1, 2, 4-triazole, 1, 3, 4-thiadiazole and 1, 3, 4-oxadiazole containing 2-trifluoromethyl benzimidazoleThe nucleophilic addition of 2-trifluoromethyl benzimidazole-1-acetyl hydrazine with aryl isothiocyanates gave the key intermediates, 1-N- (2-trifluoromethyl benzimidazole-1-acetyl)-4 -aryl-3-thiosemicarbazides. Then cyclization of the acylthiosemicarbazide in hydrazine hydrate, concentrated H₂SO₄, 5%KI-I₂ solution respectively generated 1, 2, 4-triazole, 1, 3, 4-thiadiazole and 1, 3, 4-oxadiazole.2. Synthesis of Mannich bases containing 2-trifluoromethyl benzimidazole and 1, 2, 4-triazole-5-thione under ultrasonic irradiationAcylthiosemicarbazides were cyclized in sodium hydroxide aqueous solution to afford 3-(2-trifluoromethyl benzimidazole-1- methylene)-4-aryl-1, 2, 4-triazole-5-thiones.The reaction of 1, 2, 4-triazoles with four amines gave sixteen new Mannich bases by means of ultrasonic...