【作者】 时天昊；

【导师】 李燕萍；

【作者基本信息】 新疆大学 ， 有机化学， 2006， 硕士

【摘要】 在自然界中，苯并咪唑作为许多酶的活性中心功能基，参与了许多重要的生物化学反应，对生命活动起着十分重要的作用。苯并咪唑具有一个含孤对电子的氮原子，从而使苯并咪唑类化合物具有很强的配位能力及分子识别能力，可以用于生物分子的模拟。苯并咪唑类化合物具有杀菌、杀虫、抗病毒、抗肿瘤等生物活性，有些治疗苯并咪唑类化合物可以治疗高血压和溃疡，因此它受到医药行业的关注。1，2，4-三唑、1，3，4-噻二唑、1，3，4-噁二唑等杂环也表现出明显的药物活性，如抗菌、消炎、驱虫、除草、调节植物生长等。 鉴于不同活性的杂环核在同一分子中聚集能明显改善化合物的生物活性的这一活性叠加原理，本论文将苯并咪唑分别与1，2，4-三唑、1，3，4噻二唑、1，3，4-噁二唑等杂环组合于同一分子中，合成出未见文献报道的一系列结构新颖的苯并咪唑类衍生物，以期实现多种生物活性的叠加，为苯并咪唑新药物的合成及研究工作提供应用基础。所有新化合物的结构均经过元素分析，IR和¹H NMR进行了确证。 本论文的主要工作： 1．合成含2-三氟甲基苯并咪唑的1，2，4-三唑、1，3，4-噻二唑和1，3，4-噁二唑衍生物2-三氟甲基苯并咪唑-1-乙酰肼与芳基异硫氰酸酯发生亲核取代反应得到相应的酰氨基硫脲，然后分别在水合肼、浓硫酸、5％KI-I₂的饱和溶液中合环，合成了系列含2-三氟甲基苯并咪唑的1，2，4-三唑、1，3，4-噻二唑、1，3，4-噁二唑。 2．超声辐射法合成含2-三氟甲基苯并咪唑的1，2，4-三唑硫酮类Mannich碱含2-三氟甲基苯并咪唑的酰氨基硫脲在氢氧化钠溶液中反应得到3-（2-三氟甲基苯并咪唑-1-亚甲基）-4-芳基-1，2，4-三唑-5-硫酮，然后采用超声辐射法与胺反应合成了16个Mannich碱。 3．合成含2-三氟甲基苯并咪唑的双噁二唑硫醚及亚砜更多还原

【Abstract】 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更多还原