Synthesis of Thiadiazine、Thiosemicarbazide、Thiadiazole Derivatives Containing Benzimidazole under Microwave Irradiation
The application of microwave irradiation in organic synthesis develope very fast, since 1969, the first time the microwave irradiation technology used in organic reactions by American scientist Vanderhoff. The characteristic of microwave irradiation is that it can heating reaction substrates in a very short time, this heating method can make these reactions which can not proceed on conventional heating processes taking place. Microwave technology has a wide application prospect in all branches of chemistry, biotechnology and environmental protection.Benzimidazole moiety displays a broad spectrum of biological activities including antiviral, antifungicide, anti-inflammatory effects, some benzimidazole compounds have found applications in diverse therapeutic areas for hypertension and ulcer. 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. 1,2,4-triazolo[3,4-b]-1′,3′,4′-thiadiazine, thiosemicarbazide, 1,3,4-thiadiazole heterocyclic compounds also exhibits high biological activities, such as anti-inflammatory, analgesic, antibacterial, inhibit microorganism, antiviral and regulation of plant growth.In order to realize combination of multiform active ingredients, we designed and have synthesized a series of novel thiadiazine, thiosemicarbazide and 1,3,4-thiadiazole derivatives which containing benzimidazole compounds in order to enhance their biological activities. It extended the research field of such compounds and provided abundant leading compounds for later selecting work of effective drugs.This thesis consists of two major parts:The first part is about literature review. The progress in application and synthesis of benzoimidazole, thiadiazine, thiosemicarbazide, thiadiazole derivatives and the principle of microwave irradiation and it’s application in organic reactions were systematic exposition.The second part is about experimental content. Major work as follows:1. A series of novel 1,2,4-triazolo[3,4-b]- 1′,3′,4′-thiadiazine derivatives were synthesized by the reaction of 3-(2-substituted benzoimidazole-1-methylene)-4-amino-5-mercapto-1,2, 4-triazole withα-bromoacetophenones under microwave irradiation and heating. Comparison of the conventional refluxing method and microwave irradiation accelerate means, discussed for the results; 2. A series of novel 1-(2-trifluoromethylbenzimidazol-1-acetyl)-4-aroylthiosemicarbazide were synthesized by the reaction of 1-(2-trifluoromethylbenzimidazole-1-yl)acetyl hydrazine with aroylisothiocyanate under microwave irradiation and heating.The preliminary biological activity of the target compounds have been tested;3. 1-(2-trifluoromethylbenzimidazol-1-acetyl)-4-aroylthiosemicarbazide were synthesized under microwave irradiation. Then compounds were cyclized in acetic acid to afford a series of novel 2-aroylamino-5-(2-trifluoromethylbenzimidazol-1-ylmethyl)-1,3,4-thiadi- azole in excellent yields under microwave irradiation. Comparison of the conventional refluxing method and microwave irradiation accelerate means, discussed for the results.The innovations of the paper are based on the follow:1. 3-(2-methyl benzoimidazole-1-methylene)-6-aryl-7H-1′,2′,4′-triazolo[3,4-b]-1″,3″,4″- thiadiazine and 3-(2-trifluoromethyl benzoimidazole-1-methylene)-6-aryl-7H-1′,2′,4′ -triazolo[3,4-b]-1″,3″,4″-thiadiazine were synthesized unreported in the literatures under microwave irradiation. The conditions of microwave irradiation were discussed;2. A series of novel 1-(2-trifluoromethylbenzimidazol-1-acetyl)-4-aroylthio-semicarbazide were synthesized under microwave irradiation. The preliminary biological activity of the target compounds have been tested, the result show that compound 2a have some anti-HIV-1 reverse transcriptase activity;3. Ten 2-aroylamino-5-(2-trifluoromethyl-benzimidazol-1-ylmethyl)-1,3,4-thiadiazole were synthesized under microwave irradiation, ten precursor compounds were synthesized under microwave irradiation too. After two steps of the microwave irradiation, high purity products were obtained.