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There is considerable interest in quinolones as antibacterial agents: (a) Andriole, V. T. The Quinolones; Academic Press: London, 1988.
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4-Quinolones have two tautomeric forms: either the hydroxy tautomer as 4-hydroxyquinoline or the carbonyl tautomer as 4-quinolones, although these compounds exist favorably in the keto form. For more information, see: (a) Pfister-Guillouzo, G.; Guimon, C.; Frank, J.; Ellison, J.; Katritzky, A. R. Justus Liebigs Ann. Chem. 1981, 366.
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4-Quinolones have two tautomeric forms: either the hydroxy tautomer as 4-hydroxyquinoline or the carbonyl tautomer as 4-quinolones, although these compounds exist favorably in the keto form. For more information, see: (a) Pfister-Guillouzo, G.; Guimon, C.; Frank, J.; Ellison, J.; Katritzky, A. R. Justus Liebigs Ann. Chem. 1981, 366.
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During the process of this study, Buchwald et al. reported a mild, two-step synthesis of 4-quinolone via Cu-catalyzed amidation followed by the base-promoted cyclization. The substrate scope was limited to the preparation of 2-aryl-4-quinolones: (a) Jones, A. P.; Anderson, K. W.; Buchwald, S. L. J. Org. Chem. 2007, 72, 7968.
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During the process of this study, Buchwald et al. reported a mild, two-step synthesis of 4-quinolone via Cu-catalyzed amidation followed by the base-promoted cyclization. The substrate scope was limited to the preparation of 2-aryl-4-quinolones: (a) Jones, A. P.; Anderson, K. W.; Buchwald, S. L. J. Org. Chem. 2007, 72, 7968.
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Xantphos has been reported to be an excellent ligand for amidation: (a) ; Kamer, P. C.; Van Leeuwen, P. W. N.; Reek, J. N. H. Acc. Chem. Res. 2001, 34, 895.
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Addition of formamide to the reaction mixture in toluene led to formation of a gel which resulted in difficult stirring
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Addition of formamide to the reaction mixture in toluene led to formation of a gel which resulted in difficult stirring.
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However, the use of acetamide which has more than one α-protons led to lower yield of 4-quinolone due to formation of 2-quinolone. Also see ref 10
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However, the use of acetamide which has more than one α-protons led to lower yield of 4-quinolone due to formation of 2-quinolone. Also see ref 10.
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