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

Vinay Kumar, S. and Yadav, S. K. and Raghava, B. and Saraiah, B. and Ila, H. and Rangappa, K. S. and Hazra, A. (2013) 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. Journal of Organic Chemistry, 78 (10). pp. 4960-4973. ISSN 0022-3263

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Official URL: http://doi.org/10.1021/jo400599e

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.

Item Type: Article
Uncontrolled Keywords: 1, 1 (4 bromophenyl) 3 (3, 1 (4 bromophenyl) 5 (3, 1 (4 chlorophenyl) 3 (4 methoxyphenyl) 5 phenyl 1h pyrazole, 1 (4 chlorophenyl) 3 (furan 2 yl) 5 (thiophen 2 yl) 1h pyrazole, 1 (4 chlorophenyl) 5 (4 methoxyphenyl) 3 phenyl 1h pyrazole, 1 (4 chlorophenyl) 5 (furan 2 yl) 3 (thiophen 2 yl) 1h pyrazole, 1 (4 fluorophenyl) 3 (4 methoxyphenyl) 5 methyl 1h pyrazole, 1 (4 fluorophenyl) 5 (4 methoxyphenyl) 3 methyl 1h pyrazole, 1 (4 methoxyphenyl) 5 (1 methyl 1h pyrrol 2 yl) 3 4 tolyl 1h pyrazole, 1 phenyl 3 (1 methyl 1h indol 3 yl) 5 (pyridin 3 yl) 1h pyrazole, 1 phenyl 3 (pyridin 3 yl) 5 (1 methyl 1h indol 3 yl) 1h pyrazole, 1 phenyl 3 (pyridin 3 yl) 5 (thiophen 2 yl) 1h pyrazole, 1 phenyl 3 (thiophen 2 yl) 5 (pyridin 3 yl) 1h pyrazole, 2, 3 (2, 3 (3 bromophenyl) 5 (4 methoxyphenyl) 1 phenyl 1h pyrazole, 3 (3 methylthiophen 2 yl) 1 phenyl 5 (3, 3 (4 chlorophenyl) 1, 3 Diphenyl 1, 3 diphenyl 1h pyrazole, 3 diphenyl 2, 3 diphenyl 5 (pyridin 4 yl) 1h pyrazole, 4, 4 dimethoxyphenyl) 3 (pyridin 4 yl) 1h pyrazole, 4 dimethoxyphenyl) 5 (pyridine 4 yl) 1h pyrazole, 4 ethyl 3 (4 methoxyphenyl) 1, 5, 5 (1 methyl 1h indol 3 yl) 3 (furan 2 yl) 1 (4 chlorophenyl) 1h pyrazole, 5 (3 bromophenyl) 3 (4 methoxyphenyl) 1 phenyl 1h pyrazole, 5 (3 methylthiophen 2 yl) 1 phenyl 3 (3, 5 (4 chlorophenyl) 1, 5 (furan 2 yl) 3 (1 methyl 1h indol 3 yl) 1 (4 chlorophenyl) 1h pyrazole, 5 dimethylphenyl) 1 (4 methoxyphenyl) 5 (thiophen 2 yl) 1h pyrazole, 5 diphenyl 1h pyrazole, 5 diphenyl 3 (pyridin 4 yl) 1h pyrazole, 5 trimethoxyphenyl) 1h pyrazole, 6 tetrahydrocyclopentacpyrazole, Alcohols, alkylation, article, Crystallographic data, Cyclization, Cyclocondensation, drug structure, drug synthesis, hydrazine derivative, Hydrazines, Hydrides, Ketones, Molecular Structure, Neutral conditions, Potassium, Potassium tert-butoxide, pyrazole derivative, Pyrazoles, Refluxing ethanols, Regioselective routes, Regioselectivity, Sodium compounds, Stereoisomerism, Tert-butyl alcohols, Three-component, unclassified drug, unindexed drug, X ray crystallography
Subjects: C Chemical Science > Chemistry
Divisions: Department of > Chemistry
Depositing User: Arshiya Kousar
Date Deposited: 15 Oct 2019 07:16
Last Modified: 15 Oct 2019 07:16
URI: http://eprints.uni-mysore.ac.in/id/eprint/8972

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