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 7, 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 tert-butoxide in refluxing tert-butyl alcohol, yielding 1-aryl-3,5-bis­(het)­arylpyrazoles 9 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 9, 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 tert-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.