Synthesis of zwitterionic 4-hydroxy-2(1H)-quinolinone derivatives

Synthesis and SAR studies of novel 6,7,8‐substituted 4‐substituted benzyloxyquinolin‐2(1H)‐one derivatives for anticancer activity

“…A general synthetic approach to the key intermediate 4‐hydroxyquinolin‐2(1 H )‐one is the Knorr quinoline synthesis, which involves cyclization and dehydration of a transient β‐ketoanilide, formed by condensation of a β‐keto ester and aniline at relatively high temperature. More specific synthetic approaches include cyclization of N ‐acetylanthranilic acid derivatives (Buckle et al ., ), condensation of malonates/malonic acid with anilines using ZnCl 2 and POCl 3 (Zhang et al ., ; Priya et al ., ), Ph 2 O (Ahvale et al ., ) and cyclization of malonodianilides with PPA (Cai et al ., ; Park et al ., ; Moradi‐e‐Rufchahi, ), CH 3 SO 3 H/P 2 O 5 (Kappe et al ., ) and p ‐toluenesulfonic acid (Nadaraj et al ., ). In our study, 4‐hydroxyquinolin‐2(1 H )‐one derivatives ( 5a–i ) were synthesized by treatment of a substituted aniline ( 1a–i ) with diethylmalonate ( 2 ) in one flask (Mohamed, ; Arya and Agarwal, ), followed by cyclization of the formed monoanilide ( 3a–i ) or malondianilide ( 4a–i ) precursors in the presence of PPA.…”

“…Physical and spectroscopic data for 5a are given in the succeeding text; the data for the remaining compounds are provided as Supporting Information. (Mohamed, 1991;Nadaraj et al, 2006;Arya and Agarwal, 2007;Park et al, 2007;Zhang et al, 2008) Compound 5a (3.48 g, 21.59 mmol) was obtained from aniline (1a) (3.82 g, 41.01 mmol) and diethylmalonate (2) (7.88 g, 49.20 mmol); yield: 53%; light-yellow solid; mp: 276-278°C; IR (KBr) ν (cm −1 ): 1660 (C = O); 1 H NMR (200 MHz, DMSO-d6) δ (ppm): 5.77 (s, 1H, H-3), 7.12 (t, J = 7.5 Hz, 1H, H-6), 7.26 (d, J = 8.2 Hz, 1H, H-8), 7.47 (t, J = 7.8 Hz, 1H, H-7), 7.77 (d, J = 8.0 Hz, 1H, H-5), 11.28 (br. s, 1H, NH); 13 C NMR (50 MHz, DMSO-d6) δ (ppm): 98.…”

Novel heterocyclic derivatives of pyrano[3,2-c]quinolinone from 3-(1-ethy1-4-hydroxy-2-oxo-2(1H)-quinolin-3-yl)-3-oxopropanoic acid

“…For example, degradation of 1 in boiling 2N sodium hydroxide aqueous solution yielded 1-ethyl-3-acetyl-4-hydroxyquinolin-2(1H)-one through pyrone ring opening, followed by decarboxylation [11,12]. In continuation to previous research on 4-hydroxyquinolin-2(1H)-ones [13][14][15][16][17][18], the present paper reports the synthesis of the new 3-(1-ethy1-4-hydroxy-2-oxo-2(1H)-quinolin-3-yl)-3-oxo-propanoic acid (2) and the study of its chemical reactivity towards some ortho-hydroxyaldehydes and ortho-aminoaldehydes, in search of new quinolinone derivatives of potential biological activity.…”

“…1 H NMR spectra were measured on Gemini-200 (200 MHz) and/or Mercury-300BB (300MHz) spectrometers, using DMSO-d6 as solvent and TMS (δ) as internal standard. 13 C NMR spectra were measured on a Mercury-300BB (75MHz) spectrometer, using DMSO-d6 as solvent and TMS (δ) as internal standard. Mass spectra were obtained using a GC-2010 Shimadzu Gas chromatography-mass spectrometer (70 eV) instrument.…”

New cyclic zwitterionic building blocks for the synthesis of piperidine-2,4-dione and pyridine-2-one compounds

“…Beside the synthetic potential of such scaffolds, it is interesting to note that zwitterionic pyridin-2-one-type compounds have been little studied, 6,7 and might also exhibit interesting biological properties. 8…”