Study On Insertion Cyclization Involved By Thiazole Compounds

Compounds containing thiazole rings have a wide range of pharmacological activities,and their research and synthesis methods and structures have become hot topics.The molecular synthesis library containing thiazole ring compounds has been screened out for physiologically active drugs,which has attracted the attention of chemists in recent years.A large number of literature reviews have reported the synthesis of thiazolone compounds and their derivatives,as well as the development of simple and effective methods for the synthesis of these thiazolone compounds and how to increase the substrate type of thiazolone derivatives has attracted wide attention of scientists.Thiazoles are widely used in organic chemistry and in the total synthesis of natural products.Natural products containing these structural units have a large amount of biological activity,such as anti-tumor,antibacterial,anti-viral,malaria and immunosuppressive activities,but these natural molecules are not substituted.A variety of compounds of thiazole/Oxazole-C₅-Holdning.der.This thiazolylpyrazole has a functionalized structural unit and a small molecule compound of C₅.Based on the characteristics of thiazole compounds,this paper studies the insertion and ring-forming reactions involved in thiazoles to expand the type of thiazolone substrate.It also attempts to use oxazole derivatives and pyrazole derivatives.Further looping reaction attempts.It mainly includes the following two parts:1.Synthesis of spiropropane thiazolone derivativesWe first synthesized more than 20 kinds of stable sulfur ylide and under the action of a base,the thiazolone-derived olefin can react with the stable sulfur ylide form[2+1]cycloaddition in a yield of 30-99%.The diastereoselectivity of 1:1-10:1 gives a spiropropane thiazolone derivative and more than 20 spiropropane thiazolone derivatives are obtained.The mechanism of the[2+1]ring formation reaction was further inferred by literature investigation and analysis of experimental results.2.Synthesis of stilbene spiropropane thiazolone derivativesIn this experiment,sulfonium ylide and different kinds of thiazolone derivatives were synthesized,and sulfur ylide and thiazolone were reacted under base catalysis.After[2+1]cycloaddition,ring opening,proton transfer,a new CC bond is formed.After a series of conditions optimization,22 lanthanide-spirocyclopropane ketazole derivatives are obtained in60%-90%yield.The reaction can be scaled up to a gram scale and the yield can reach 80%.And we also try to use other heterocyclic compounds such as pyrazole derivatives,oxazole derivatives and lanthanide sulfur ylide to react.Finally,by analyzing the literature and the analysis of the experimental results,we give the possible mechanism of the reaction..In summary,based on the insertion of a thiazole compound into a ring-forming reaction,a new method for synthesizing a spiropropane thiazolone derivative and a lanthanide-spirocyclopropthiazolone derivative has been developed,which broadens the substrate of the thiazolone derivative.Also promoted the application of heterocyclic compounds and thiazolone derivatives in medicine.