Expeditious Synthesis and Spectroscopic Characterization of 2-Methyl-3-substituted-quinazolin-4(3H)-one Derivatives

Abstract

Quinazoline and quinazolinone derivatives are well-known bioactive heterocycles owing to their therapeutic diversity and extensive medicinal application in drug design and pharmaceutics. A series of 2-methyl-3-substituted quinazolin-4(3H)-one derivatives 8a-q was herein synthesized from synthetic conversion of anthranilic acid to 2-methyl-4H-3,1-benzoxazi-4-one, 7 which was subsequently transformed to the targeted 2,3-disubstituted quinazolin-4(3H)-one derivatives 8a-q by reacting with some notable amino-containing moieties via an ameliorable pathway. The catalystfree synthesis was successful achieved by careful reaction optimization study using solvent choice and reaction temperature variability as key parameters. The chemical structures of the synthesized compounds were confirmed by IR, UV, 1 H-NMR, 13 C-NMR and DEPT-135 as well as analytical data.

Deep eutectic solvent for an expeditious sono-synthesis of novel series of bis -quinazolin-4-one derivatives as potential anti-cancer agents

“…The steric impact of the utilized diamines had an obvious effect on the effectiveness of these reactions. For instance, when the present method was put in an application for o- phenylene diamine ( 2f ), however, bis -quinazolinone derivative ( 9 , 67%) was isolated along with the mono-quinazolinone derivative [23,24] ( 8 , 33%). Whereas, by increasing the reaction time to 25 min and molar ratio of 1a to 2.5 mmol, the reaction yield was improved to 88% with the complete consumption of the mono-quinazolinone derivative 8 (monitored by TLC).…”

“…At the outset, the present study was commenced with optimization of the reaction conditions using 2-methyl-4 H -benzo[ d ][1,3]oxazin-4-one ( 1a ) and trans -cyclohexane-1,4-diamine ( 2a ) as model substrates (table 1). The initial endeavour utilizing conventional refluxing conditions in CH 3 CN and in the presence of K 2 CO 3 as the basic catalyst [23,24] afforded the hitherto unreported 3,3′-((1 R ,4 R )-cyclohexane-1,4-diyl) bis (2-methylquinazolin-4(3 H )-one) ( 3a ) but in a poor yield; instead, a considerable amount of starting materials remain unchanged (table 1, entry 1). Next, on performing the above reaction under ultrasonic irradiation (60 W) at 50°C for 20 min, furnished 40% of the product (table 1, entry 2).…”

“…White crystals, yield 98%, m.p. 190–192°C; IR (KBr): ν /cm −1 1679 (C = O), 1612, 1590 (C = N, C = C); 1 H NMR (400 MHz, DMSO- d 6 ): δ 8.29–8.26 (d, J = 7.1 Hz, 2H, Ar-H), 7.78 (s, 2H, Ar-H), 7.59–7.48 (t, J = 7.4 Hz, 2H, Ar-H), 7.25–7.21 (d, J = 7.1 Hz, 2H, Ar-H), 3.78 (s, 4H, C H 2 ), 2.30 ppm (s, 6H, C H 3 ); 13 C NMR (100 MHz, DMSO- d 6 ): δ 171.0 ( C = O), 144.9 ( C = N), 143.9, 132.7, 127.4, 126.4, 126.0, 121.3 (Ar-C), 42.5 ( C H 2 ), 20.4 ppm ( C H 3 ); MS (EI): m/z (%) 347 (M + +1, 1.8), 346 (M + , 100) [23,24].…”

“…White crystals, yield 33%, m.p. 109–111°C; IR (KBr): ν /cm −1 3324–2984 (NH 2 ), 1694 (C=O), 1611, 1594 (C=N, C=C); 1 H NMR (400 MHz, DMSO- d 6 ): δ 8.208–8.205 (d, J = 5.7 Hz, 1H, Ar-H), 7.93–7.91 (d, J = 7.8 Hz, 1H, Ar-H), 7.73–7.70 (d, J = 5.7 Hz, 1H, Ar-H), 7.66–7.63 (m, 2H, Ar-H), 7.48–7.44 (m, 2H, Ar-H), 7.28–7.24 (m, 1H, Ar-H), 6.50 (br, 2H, N H 2 ), 2.29 ppm (s, 3H, C H 3 ); 13 C NMR (100 MHz, DMSO- d 6 ): δ 171.1 ( C =O), 154.3 ( C =N), 141.7, 137.8, 135.0, 130.9, 130.1, 128.9, 127.7, 127.4, 126.7, 121.9, 117.4, 115.0 (Ar-C), 21.0 ppm ( C H 3 ); MS (EI): m/z (%) 252 (M + +1, 100), 251 (M + , 2.6) [23,24].…”

“…Latterly, many endeavours have been reported to demonstrate easy-to-handle, cost-effective and eco-friendly protocols for the preparation of quinazolinones [20][21][22]. Notwithstanding, to the best of our knowledge there have been restricted articles to date on the assembly of bis-quinazolinones [23,24]. Subsequently, the development of an effective and greener methodology for the construction of bis-quinazolinones is extremely in demand.…”