Study On The Synthesis Of Highly Substituted Thiophene Derivatives And Reactions Of Thioamide With Benzyne

Thiophene is an important privileged heterocyclic scaffold in numerousbiologically active pharmacophores and natural products. Over the years, thiophenederivatives have attracted considerable attention among medicinal and syntheticorganic chemists due to their utility as versatile intermediates in organic synthesis.Additionally, anthelmintic and insecticidal activities of some pharmacophores havebeen ascribed to building blocks involved thiophene structure. In view of shortcomingsof commonly used previous synthesis such as requiring extra sulfur source, the alkalicatalyst, the metal catalyst, needing high temperature and long reaction time, this paperfocused on a new method of constructing the novel multi-substituted thiopheneskeleton exhibiting potential biological activities with thioamides as synthons.In the first chapter, we generally described the extensive applications ofβ-ketothioamides (polar ketene N,S-acetal compounds) and arylglyoxals in organicsynthesis; different protocols of preparing thiophene derivatives; as well as theimportant utilities of multi-component reactions and benzyne in organic synthesis.In the second chapter, a one-pot three-component reaction method wasestablished to synthesize multi-substituted thiophene derivatives, and novel highlysubstituted thiophene derivative4was prepared starting with β-aroylthioamide,arylglyoxals, and5,5-dimethyl-1,3-cyclohexanedione, which had not been reported inliteratures. By comparing the impacts on reactions of different kinds of catalyst andsolvent along with various dosages of catalyst, proceeding in trifluoroethanol at60oCwas found the optimal condition. The present synthesis shows fascinating features suchas high regioselectivity, concise one-pot, short reaction time, easy purification,providing an alternative approach for easy access to highly substituted thiophenes. In addition, the effects of several different substituents on the reaction time and the yieldof products were also explored. Experimental results show that the method can achievea pretty high yield, and the reaction selectivity is excellent.In chapter three, we explored an approach to synthesize a new kind of thioamide.A relatively novel S-phenyl thioamide5was first generated via the reaction ofβ-aroylthioamide with benzyne. Besides, the best results were obtained when reactionswere carried out in acetonitrile at50oC in the presence of KF and18-crown-6.The structures of all the synthesized compounds were characterized by IR,1HNMR,13C NMR, and HRMS. Furthermore, single crystals of compound4c and5awere cultured and their precise spatial configurations were determined.