Recyclable, Graphite-Catalyzed, Four-Component Synthesis of Functionalized Pyrroles

<div><p></p><p>A facile, convenient, and multicomponent coupling strategy for the synthesis of highly functionalized pyrroles is developed using graphite as a catalyst, but devoid of moisture-sensitive metal catalysts and corrosive acidic reagents. This method involves four-component coupling reactions of ethyl acetoacetate compound or diethyl acetylene dicarboxylate, amines, aromatic aldehydes, and nitromethane without an inert atmosphere. This approach provides easy access to highly substituted pyrroles in good yields via one-pot tandem reaction. The method is very simple, straightforward, and environmentally friendly compared to the existing methods.</p> <p>[Supplementary materials are available for this article. Go to the publisher's online edition of <i>Synthetic Communications</i>® for the following free supplemental resource(s): Full experimental and spectral details.]</p> </div

Cyclocondensation of Arylhydrazines with 1,3-Bis(het)arylmonothio-1,3-diketones and 1,3-Bis(het)aryl-3-(methylthio)-2-propenones: Synthesis of 1‑Aryl-3,5-bis(het)arylpyrazoles with Complementary Regioselectivity

Two efficient highly regioselective routes for the synthesis of unsymmetrically substituted 1-aryl-3,5-bis­(het)­arylpyrazoles with complementary regioselectivity starting from active methylene ketones have been reported. In the first protocol, the newly synthesized 1,3-bis­(het)­aryl-monothio-1,3-diketone precursors (prepared by condensation of active methylene ketones with het­(aryl) dithioesters in the presence of sodium hydride) were reacted with arylhydrazines in refluxing ethanol under neutral conditions, furnishing 1-aryl-3,5-bis­(het)­arylpyrazoles <b>7</b>, in which the het­(aryl) moiety attached to the thiocarbonyl group of monothio-1,3-diketones is installed at the 3-position. In the second method, the corresponding 3-(methylthio)-1,3-bis­(het)­aryl-2-propenones (prepared in situ by base-induced alkylation of 1,3-monothiodiketones) were condensed with arylhydrazines in the presence of potassium <i>tert</i>-butoxide in refluxing <i>tert</i>-butyl alcohol, yielding 1-aryl-3,5-bis­(het)­arylpyrazoles <b>9</b> with complementary regioselectivity (method A). The efficiency of this protocol was further improved by developing a one-pot, three-component procedure for the synthesis of pyrazoles <b>9</b>, directly from active methylene ketones, by reacting in situ generated 3-(methylthio)-1,3-bis­(het)­aryl-2-propenones with arylhydrazines in the presence of sodium hydride (instead of potassium <i>tert-</i>butoxide as base). The structures and regiochemistry of newly synthesized pyrazoles were confirmed from their spectral and analytical data along with X-ray crystallographic data of three pairs of regioisomers