Generation And Trapping Of An Active 2-Methylene 1,3-Dicarbonyl Intermediate

The study of multicomponent reactions (MCRs) is a promising, hot field of chemistry, since they allow complex molecules to be created by using one reaction in a fast, efficient and time-saving manner. So developing new MCRs with environmentally benign methods has been recognized as one of the most important topics of green chemistry.In this theme, many multicomponent reactions of 1,3-disubstituted 5-pyrazolones and formaldehyde were developed in environmentally benign solvent systems. Styrenes, vinylferrocene and 2-phenylindoles could easily react, under solvent-free conditions or in glycerol solvent, with 1,3-disubstituted 5-pyrazolones and paraformaldehyde in the absence of any catalyst to afford a variety of complex molecules in moderate to excellent yields. Particularly, these MCRs are proved to be combinable with the synthesis of 1,3-disubstituted 5-pyrazolones from phenylhydrazines andβ-ketone esters in glycerol or a carboxylic acid-functionalized ionic liquid, [MIm-CO2H]BF4. Therefore, some two-step sequential reactions of phenylhydrazines,β-ketone esters, formaldehyde and styrenes or indoles were developed for the first time. All these MCRs were conducted in environmentally benign solvent systems that not only minimize generation of wastes but also simplify the work-up procedure.A cascade domino reaction was also developed in water. Water proved to be an efficient solvent for oxidation of a Baylis-Hillman adduct with IBX. The generated product, a methylene intermediate, could be trapped in situ by many nucleophiles in water, such as styrenes,β-dicarbonyl compounds, benzamide and less reactive indoles. This strategy offers an alternative way to Knoevenagel methylenylation ofβ-dicarbonyl compounds with formaldehyde for the formation of a methylene intermediate, thus allows the use of some nucleophiles that are chemically unstable to formaldehyde. The use of water as solvent, good recycling ability of IBX oxidant and wide substrate scopes make these reactions very attractive from the viewpoint of green chemistry.