Synthesis Of Pyrazoles And Thiazoles Via Enaminone-Participated Aromatic Annulation

Heterocyclic compounds present prevalently in nature,they are also the most frequent structural fragment in functional molecules such as pharmaceuticals and materials.For example,more than 85% biologically active molecules contain heterocyclic structure.Therefore,heterocycle construction is one of the longstanding and fundamental research topics in organic synthesis.By employing enaminones as the major building blocks,the works in this thesis aim at environmentally begnin methods for the construction of pyrazole and thiazole heterocycles,conveying the systematic investigation on the synthesis of pyrazole and thiazole heterocyclic molecules and their derivatives.The thesis contains three parts.The first section,transition metal-free,three-component synthesis of pyrazoles with enaminones,hydrazine hydrochlorides and DMSO.Using DMSO as the carbon source to react with enaminones and phenyl hydrazine hydrochlorides,the efficient[2+2+1] annulation has been achieved for the synthesis of pyrazoles in the copromotion of molecular iodine and Selectfluor.The isotope labelling experiment confirms that one of the carbon atoms in the pyrazole comes from DMSO,and two reaction pathways exist to access the target products.In addition,by alternating DMSO with aldehydes,the synthesis of trisubstituted pyrazoles has been accomplished under catalyst-free conditions.The second section,tandem reactions of enaminones,phenyl hydrazines and halides for the synthesis of 4-halopyrazoles.By employing electrochemical synthesis,the tandem annulation and C-H halogenation reactions of enaminones,phenyl hydrazine hydrochlorides and halides affording 4-halopyrazoles have been established.When phenyl hydrazine hydrochlorides are used as substrates and hydrochloric acid as analyte,4-chloropyrazoles are obtained.When phenyl hydrazine hydrochlorides have been altered into the phenyl hydrazines,and in the presence of KBr,the products of 4-bromopyrazoles are selective produced.Control experiments suggest that the in situ generated pyrazole from enaminone and phenyl hydrazine is the key intermediate.The free radical reactions of pyrazoles with halo free radical give the corresponding halopyrazoles.The third section,electrochemical annulation of enaminones and thioureas for the thiazoles synthesis and the tunable dearomatization.Under electrochemical conditions,the aromatic annulation reactions providing thiazoles with enaminones and thioureas have been realized.The reactions proceed under mild room temperature,and display high efficiency even in the 10 mmol scale-up synthesis.Moreover,by means of modifying parameters such as current,analyte etc,the selective dearomatization of thiazole by dialkoxylation has been reached,offering synthetic route to thiazolines.