title: 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.
abstract: 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.
authors.affiliation: New Chemistry unit, Jawaharlal Nehru Centre for Advanced Scientific Research, Jakkur, Bangalore-560064, India.
authors.forename: S Vijay
authors.initials: SV
authors.lastname: Kumar
authors.forename: Santosh K
authors.initials: SK
authors.lastname: Yadav
authors.forename: B
authors.initials: B
authors.lastname: Raghava
authors.forename: B
authors.initials: B
authors.lastname: Saraiah
authors.forename: H
authors.initials: H
authors.lastname: Ila
authors.forename: K S
authors.initials: KS
authors.lastname: Rangappa
authors.forename: Arpan
authors.initials: A
authors.lastname: Hazra
mesh_terms: D003500:Cyclization; D006834:Hydrazines / Q000737:chemistry*; D007659:Ketones / Q000737:chemistry*; D015394:Molecular Structure; D011720:Pyrazoles / Q000138:chemical synthesis* / Q000737:chemistry; D013237:Stereoisomerism
chemical_list: D006834:Hydrazines; D007659:Ketones; D011720:Pyrazoles