Cleavage Of The C-C Triple Bond Of The Ketoalkynes: Synthesis Of 4(3H)-Quinazolinones

Quinazolinones widely present in natural products and drugs, such as Rutaecarpine from a Chinese herbal drug named Wu-Chu-Yu was used to treat headache and cholera. Luotonin A from a Chinese plant(Peganumn nigellastrum) showed cytotoxicity to the murine leukemia P388 cell line. In addition, Raltitrexed(brandname: Tomudex) with a quinazoline core have played an effective role in clinical therapy. The 4(3H)-quinazolinone systems are also reported to have a wide range of other useful biological properties, such as anticonvulsant, antiviral, anti-inammatory, antifungal, antimicrobial, and antimalarial. As a result, tremendous synthetic efforts have been made for their synthesis. Most methods reported in literature exist some drawbacks, such as requirement of heavy metal as catalysts, excessive toxic oxidants and microwave radiation. Therefore, development of simple and environmentally benign protocol is still highly desired. Herein, we report a strategy for the synthesis of 2-arylquinazolin-4(3H)-one from ketoalkynes via C-C triple bond cleavage via selectively cleavage of the triple bond of ketoalkynes under oxidant-, metal-, and ligand-free conditions. Various 4(3H)-quinazolinones were obtained through fragmentation of full alkynes and formation of three C-N and C-H bonds. In addition, the scope of this reaction was successfully expanded to heteroaryl ketoalkyne and 2-aminothiophene-3-carboxamide.