Studies On The Synthesis Of Benzimidazoles And Benzimidazolines Catalyzed By Hafnium(?)

Benzimidazole is the core structure of many drugs.Meanwhile,benzimidazoline has been used as a good reducing agent in many organic reactions and hydrogen storage materials.Benzimidazole and benzimidazoline compounds possess diverse biological activities,and have been utilized as photoelectric materials.However,e efficient synthetic methods for these compounds are still limited currently.Therefore,studies on the novel and efficient methods for the preparation of these compounds are of great importance.In this thesis,activated carbon-supported hafnium chloride(Hf Cl4/C)was investigated as a novel and highly efficient catalyst for parallel synthesis of substituted benzimidazoles.The catalytic activity of Hf Cl4,optimization of reaction conditions,solid support/catalyst recovery,microscopic surface morphology of Hf Cl4/C,and the application of Hf Cl4/C in parallel synthesis were systematically studied and achieved excellent results.The reaction conditions were optimized and the catalyst(Hf Cl4/C)was recovered.In addition,the current thesis also explored the synthesis of fluoro-substituted benzimidazolines,benzoxazolines,and benzothiazolines catalyzed by hafnium trifluoromethanesulfonate(Hf(OTf)4).The experimental results showed that Hf(OTf)4 has strong catalytic activity toward the cyclization of fluoroketone and phenylenediamine and is superior than other catalysts reported in literature.The detailed research is described as follow.1)Hf Cl4/C-catalyzed synthesis of benzimidazoles: First,we studied the catalytic effect of Hf Cl4 on the synthesis of benzimidazoles under homogeneous conditions.By comparison with other Lewis acid catalysts of Group IV B,it was determined that Hf Cl4 has the best catalytic performance in the synthesis of benzimidazoles.Subsequently,we optimized a series of reaction conditions such as the amount of catalyst,solvent,temperature,and extended the Hf Cl4-catalyzed method to the reactions of N-aryl-substituted o-phenylenediamine/aryl aldehyde,N-aryl-substituted o-phenylenediamine/alkyl aldehyde,N-alkyl-substituted o-phenylenediamine/aryl aldehyde,N-alkyl-substituted o-phenylenediamine/alkyl aldehyde.29 benzimidazole compounds were synthesized and characterized.These results showed the high efficiency and versatility of Hf Cl4 catalyst in homogeneous catalysis of benzimidazole synthesis.In order to recover the catalyst,we utilized a variety of solid support to load Hf Cl4 catalyst.The reactivity of the corresponding solid-supported catalysts were systematically studied.It was found that(5% w/w)activated carbon-supported hafnium tetrachloride(Hf Cl4/C)had the best catalytic activity and could be reused up to 10 times.Scanning electron microscopy(SEM)experiments showed that Hf Cl4 was absorbed on the surface of carbon as crystals.After repeated use,Hf(IV)catalyst was desorbed and readsorbed,appearing as amorphous solid on the surface of the activated carbon.Through a series of experiments,we elucidated that the reason why Hf Cl4/C catalyst could be efficiently recycled is mainly because the activated carbon has strong adsorption of the Hf(IV)salt.The heating and cooling of reaction could effectively desorb and redeposit Hf(IV)salt.Due the the high efficiency,versatility,and simple work-up procedure of Hf Cl4/C catalyst,we further applied this novel supported catalyst to the fast parallel synthesis of a small benzimidazole compound library.The yield and the purity(analyzed by HPLC method)of the products determined proved the value of Hf Cl4/C in rapid parallel synthesis of benzimidazoles.2)Hf(OTf)4-catalyzed synthesis of fluorobenzimidazolines: Benzimidazoline is unstable and prone to self-oxidation to produce benzimidazole.In contrast fluorinated benzimidazoline is much stable.However,due to the strong electron-withdrawing effect of the fluorine atoms,the reactivity of fluoroketone is very low.Therefore,its cyclization reaction with o-phenylenediamine and other related compounds is difficult to occur.Based on the recent report of gallium trifluoromethanesulfonatecatalyzed synthesis of fluorobenzimidazolines and progress the activation of carbonyl compounds with hafnium(IV)catalyst,the current thesis explored the possibility to catalyze the synthesize fluorobenzimidazolines with hafnium trifluoromethanesulfonate(Hf(OTf)4).Through the comparative experiments,we proved that the catalytic efficiency of Hf(OTf)4 is significantly higher than that of Ga(OTf)3.Hf(OTf)4 is superior to Ga(OTf)3 in terms of cost,reaction rate,and amount of catalyst needed.By using o-phenylenediamine and trifluoroacetophenone as model compounds,we optimized the cyclization reaction conditions such as the amount of catalyst,reaction solvent and successfully extended the method to the reactions of N-Aryl-substituted o-phenylenediamine/aryl fluoroketone,N-aryl-substituted o-phenylenediamine/alkyl fluoroketone,N-alkyl-substituted o-phenylenediamine/aryl fluoroketone.24 fluorobenzimidazoline derivatives were synthesized and characterized.In addition,Hf(OTf)4 also exhibited excellent catalytic activity in synthesis of fluorobenzoxazolines and fluorobenzothiazolines,and 8 corresponding derivatives were synthesized.