Study On The Cross Coupling Reactions Of Acrylamides With Ethers, Sulfonylhydrazine And Aldehyde

In recent years, oxidative cross-coupling reaction has attracted a lot of people’s attention. According to this process, different synthetic methods of generating five or six-membered ring to give natural-like products and pharmaceutical compounds with biological activity are developed. It is the main reason why people study this type of reaction. In recent years, many articles in this major have been reported, this shows the importance of this type of reaction.Small molecule compounds play an important role in drug discovery. At present,most of the drugs on the market are synthesized by small molecules and biological macromolecules, such as binding enzymes, proteins, DNA etc. For example, HIV-1integrase inhibitor, antitumor activity against a human pancreatic carcinoma cell line,selective inhibitors of cyclin-dependent kinase 4, and a potent caspase-3 inhibitor. Use a reasonable method to synthesis a large number of functional small molecules. By a method of high-throughput screening to obtain a pharmaceutical leading compounds with biological activity quickly and efficiently. Because of structure of Quinolinone derivatives are more similar to the structure of alkaloids, it is widely used in drug leading compounds discovering. Use this method to synthesize the nitrogen-containing heterocyclic compounds is widely reported. Because of its simple condition and cheap raw materials, this type of reaction is widely used to synthesis drug leading compounds. Is is both an opportunity and a challenge to synthesize functional molecules effectively.Oxidative cross-coupling reaction is often used in the synthesis of indole derivatives and quinolinone derivatives. Because of its conditions are not harsh, drugs are simple and widely used. According to previous reports and studies, in this article we mainly use TBHP as a oxidant. Under relatively inexpensive metal catalyst, we designed three different reactions. The first part is a reaction of ether and double bond.Maybe, the reaction mechanism is in the presence of FeCl3 and DBU, t-butyl hydroperoxide(TBHP) fission to t-BuO ? and ? OH radicals, after t-BuO ? radicalattacked ether and then formed a ether radical that attached the double bond of acrylamide and then the radical transferred elsewhere, cyclization reaction occurred,formed the isoquinolinone six-membered ring. The second part is a reaction of benzenesulfonohydrazide and double bond of acrylamide. Maybe, the reaction mechanism is in the presence of sodium iodide and TBAB, t-butyl hydroperoxide(TBHP) fission to t-BuO ? and ? OH radicals, after t-BuO ? radical attackde benzenesulfonohydrazides and then formed a benzenesulfonyl radical that attackde the double bond of acrylamide and then the radical transferred elsewhere, cyclization reaction occurred, formed the isoquinolinone six-membered ring. The third part is the cyclization reaction of aldehydes with a double bond of acrylamide. Maybe, the reaction mechanism is that,under the heating conditions,t-butyl hydroperoxide(TBHP)fission to t-BuO ? and ? OH radicals, after t-BuO ? attacked aromatic aldehyde and then formed a radical that attacked the double bond of acrylamide and then the radical transferred elsewhere, cyclization reaction occurred, formed the isoquinolinone six-membered ring.The conditions of these three reaction are very simple, inexpensive price catalyst used, good selectivity and high yield. I believe that these reactions will be found to play a greater role in the future of drug discovery, and also enrich isoquinoline derivatives synthetic methods, having academic and economic value.