Direct Synthesis Of 2-aminothiazole Derivatives Via Br(?)nsted Acid Promoted The Cleavage Of C-C Bond ? To Carbonyl Group

In recent decades,carbon-carbon bond cleavage has achieved rapid development and become a novel organic synthesis method,which has provide tremendous opportunities to discovery innovative reaction types and realize high efficient conversion of inert substrates.In the process of coping with the continuous difficulties and challenges that exist in the carbon-carbon bond cleavage reactions,a variety of disconnect strategies has gradually developed.The carbonyl group,which is characterized as an important functional group and reaction site of reaction substrates,has provided favourable support to achieve carbon-carbon bond cleavage process.With the emergence of a growing number of new methods and strategies,the reaction based on the cleavage of C-C bond a to carbonyl group has increasingly become the hot topics of organic chemistry.In this paper,we applied Bronsted acid to facilitate the cleavage of C-C bond a to carbonyl group to construct 2-aminothiazole derivatives,which display potential drug activity due to its important structure.Furthermore,we also explored the reaction mechanism of transformation process,and derivatized the products to access PLTP?CETP inhibitor and novel biheterocycles.The main content is as follows:In chapter 1,we first summarized the carbon-carbon bond cleavage strategy involving carbonyl in recent years.Combining with the understanding of C-C bond cleavage strategy,our group's in-depth study to 2-ene-1,4-diones and the potential pharmaceutically activity owing to 2-aminothiazole derivatives,we next proposed the research topic of this thesis.In chapter 2,based on our previous study on 2-ene-1,4-diones and the awareness of the importance of 2-aminothiazole derivatives,We studied the reaction of 2-ene-1,4-diones with thioureas with the promotion of concentrated hydrochloric acid in ethanol at reflux,which efficiently lead to the formation of 2-aminothiazole derivatives.In accordance with the control experiments and the experimental results,this domino process would integrate the following distinct transformations to obtain the final products:thio-Michael-addition,intramolecular cyclization,dehydration/aromatization and C-C bond cleavage reactions.Interestingly,water served as an important participant to promote the carbon-carbon bond cleavage.In addition,the products were further derivatized to important compounds.The treatment of reaction products with o-phenylenediamines or thioureas in methanol with CuO and I2 as catalysts can led to two novel kinds of biheterocycles;with the promotion of trifluoroacetic acid and triethylsilane,product ?-3ad can be successfully converted to reduction product,which is PLTP and CETP inhibitor.At last,all the obtained 2-aminothiazole compounds were characterized by 1H NMR,13C NMR,IR and MS.Among them,compound ?-3ah was further confirmed by X-ray single crystal diffraction.