Month 2019
Synthesis and Biological Evaluation of Novel 3-(4-Chlorophenyl)-2-(substituted)
quinazolin-4(3H)-one Derivatives
chloroform : methanol (9:1) as eluted to obtain the pure
product to give the product 4a–g.
added portion-wise while stirring. After complete addition,
the reaction mixture was refluxed with stirring for 8 h. Then
the reaction mixture was filtered off and quenched in
ice-cold water. The solid product obtained was filtered and
crystallized from benzene to give 5. Yield: (2.83 g, 74%),
mp 264°C. Anal. Calcd for C15H9ClN2O2: C, 63.28; H,
3-(4-Chlorophenyl)-2-styrylquinazolin-4(3H)-one (4a).
Yield: (87%), mp 186°C. Anal. Calcd for C22H15ClN2O:
C, 73.64; H, 4.21; N, 7.81. Found: C, 73.51; H, 4.13; N,
1
7.98. H NMR (300 MHz, CDCl3) δ: 6.35 (d, 1H, ─CH),
1
7.15–8.03 (m, 12H, Ar─H), 8.42 (d, 1H, ─CH). IR
(nujol, cmÀ1): 3053–2837 (Ar C─H), 1683 (C═O). MS,
m/z: 359 (M + 1).
3.19; N, 9.84. Found: C, 63.16; H, 3.11; N, 9.87. H NMR
(300 MHz, CDCl3) δ: 7.41–8.01 (m, 8H, Ar─H), 9.43
(s, 1H, ─CHO). IR (nujol, cmÀ1): 3051–2827 (Ar C─H),
1678 (C═O). MS, m/z: 285 (M + 1).
3-(4-Chlorophenyl)-2-(2-fluorostyryl)quinazolin-4(3H)-one
(4b).
Yield: (79%), mp 192°C. Anal. Calcd for
General procedure for the synthesis of 6a–g.
To a
C22H14ClFN2O: C, 70.12; H, 3.74; N, 7.43. Found: C,
solution of compound 5 (0.001 mol, 0.285 g) in EtOH
was added substituted phenyl amine (0.001 mol) and a
few drops of acetic acid was added. The resulting
mixture was refluxed 8 h. EtOH was removed under
reduced pressure, and the product was recrystallized from
absolute ethanol and gave the desired compounds 6a–g.
3-(4-Chlorophenyl)-2-((phenylimino)methyl)quinazolin-
4(3H)-one (6a). Yield: (90%), mp 206°C. Anal. Calcd for
1
70.03; H, 3.65; N, 7.58. H NMR (300 MHz, CDCl3)
δ: 6.31 (s, 1H, ─CH), 7.12–8.03 (m, 12H, Ar─H), 8.42
(d, 1H, ─CH). IR (nujol, cmÀ1): 3052–2832 (Ar C─H),
1682 (C═O). MS, m/z: 377 (M + 1).
3-(4-Chlorophenyl)-2-(3-fluorostyryl)quinazolin-4(3H)-one
(4c).
Yield: (82%), mp 190°C. Anal. Calcd for
C22H14ClFN2O: C, 70.12; H, 3.74; N, 7.43. Found: C,
1
70.05; H, 3.61; N, 7.61. H NMR (300 MHz, CDCl3) δ:
C21H14ClN3O: C, 70.10; H, 3.92; N, 11.68. Found: C,
1
6.33 (d, 1H, ─CH), 7.35–8.04 (m, 12H, Ar─H), 8.52 (d,
1H, ─CH). IR (nujol, cmÀ1): 3055–2832 (Ar C─H),
1680 (C═O). MS, m/z: 377 (M + 1).
70.01; H, 3.83; N, 11.79. H NMR (300 MHz, CDCl3) δ:
7.01–8.03 (m, 13H, Ar─H), 8.49 (s, 1H, ─CH). IR
(nujol, cmÀ1): 3053–2835 (Ar C─H), 1680 (C═O). MS,
3-(4-Chlorophenyl)-2-(4-fluorostyryl)quinazolin-4(3H)-one
m/z: 360 (M + 1).
3-(4-Chlorophenyl)-2-(((2-fluorophenyl)imino)methyl)
quinazolin-4(3H)-one (6b). Yield: (86%), mp 211°C. Anal.
(4d).
Yield: (83%), mp 193°C. Anal. Calcd for
C22H14ClFN2O: C, 70.12; H, 3.74; N, 7.43. Found: C,
1
70.01; H, 3.63; N, 7.55. H NMR (300 MHz, CDCl3) δ:
Calcd for C21H13ClFN3O: C, 66.76; H, 3.47; N, 11.12.
1
6.33 (d, 1H, ─CH), 7.17–8.05 (m, 12H, Ar─H), 8.53 (d,
Found: C, 66.61; H, 3.35; N, 11.29. H NMR (300 MHz,
1H, ─CH). IR (nujol, cmÀ1): 3053–2832 (Ar C─H),
CDCl3) δ: 7.01–8.01 (m, 12H, Ar─H), 8.52 (s, 1H,
─CH). IR (nujol, cmÀ1): 3053–2832 (Ar C─H), 1680
1682 (C═O). MS, m/z: 377 (M + 1).
3-(4-Chlorophenyl)-2-(2-(trifluoromethyl)styryl)quinazolin-
4(3H)-one (4e). Yield: (80%), mp 199°C. Anal. Calcd for
(C═O). MS, m/z: 378 (M + 1).
3-(4-Chlorophenyl)-2-(((3-fluorophenyl)imino)methyl)
quinazolin-4(3H)-one (6c). Yield: (82%), mp 210°C. Anal.
C23H14ClF3N2O: C, 64.72; H, 3.31; N, 6.56. Found: C,
1
64.61; H, 3.29; N, 6.65. H NMR (300 MHz, CDCl3) δ:
Calcd for C21H13ClFN3O: C, 66.76; H, 3.47; N, 11.12.
1
6.32 (d, 1H, ─CH), 7.13–8.04 (m, 12H, Ar─H), 8.41 (d,
Found: C, 66.67; H, 3.41; N, 11.29. H NMR (300 MHz,
1H, ─CH). IR (nujol, cmÀ1): 3052–2830 (Ar C─H),
CDCl3) δ: 7.05–8.03 (m, 12H, Ar─H), 8.50 (s, 1H,
─CH). IR (nujol, cmÀ1): 3052–2837 (Ar C─H), 1683
1682 (C═O). MS, m/z: 427 (M + 1).
3-(4-Chlorophenyl)-2-(3-(trifluoromethyl)styryl)quinazolin-
4(3H)-one (4f). Yield: (81%), mp 197°C. Anal. Calcd for
(C═O). MS, m/z: 378 (M + 1).
3-(4-Chlorophenyl)-2-(((4-fluorophenyl)imino)methyl)
quinazolin-4(3H)-one (6d). Yield: (91%), mp 214°C. Anal.
C23H14ClF3N2O: C, 64.72; H, 3.31; N, 6.56. Found: C,
1
64.60; H, 3.21; N, 6.73. H NMR (300 MHz, CDCl3) δ:
Calcd for C21H13ClFN3O: C, 66.76; H, 3.47; N, 11.12.
1
6.41 (d, 1H, ─CH), 7.19–8.04 (m, 12H, Ar─H), 8.49 (d,
Found: C, 66.63; H, 3.39; N, 11.25. H NMR (300 MHz,
1H, ─CH). IR (nujol, cmÀ1): 3051–2830 (Ar C─H),
CDCl3) δ: 7.08–7.93 (m, 12H, Ar─H), 8.50 (s, 1H,
─CH). IR (nujol, cmÀ1): 3051–2834 (Ar C─H), 1682
(C═O). MS, m/z: 378 (M + 1).
1682 (C═O). MS, m/z: 427 (M + 1).
3-(4-Chlorophenyl)-2-(4-(trifluoromethyl)styryl)quinazolin-
4(3H)-one (4g). Yield: (83%), mp 200°C. Anal. Calcd for
3-(4-Chlorophenyl)-2-(((3-(trifluoromethyl)phenyl)imino)
C23H14ClF3N2O: C, 64.72; H, 3.31; N, 6.56. Found: C,
methyl)quinazolin-4(3H)-one (6e).
Yield: (83%), mp
1
64.63; H, 3.24; N, 6.69. H NMR (300 MHz, CDCl3) δ:
218°C. Anal. Calcd for C22H13ClF3N3O: C, 61.77; H,
3.06; N, 9.82. Found: C, 61.63; H, 2.97; N, 9.91. 1H
NMR (300 MHz, CDCl3) δ: 7.01–8.01 (m, 12H, Ar─H),
8.51 (s, 1H, ─CH). IR (nujol, cmÀ1): 3055–2832 (Ar
C─H), 1682 (C═O). MS, m/z: 428 (M + 1).
6.33 (d, 1H, ─CH), 7.11–8.06 (m, 12H, Ar─H), 8.43 (d,
1H, ─CH). IR (nujol, cmÀ1): 3053–2832 (Ar C─H),
1680 (C═O). MS, m/z: 427 (M + 1).
Preparation
of
3-(4-chlorophenyl)-4-oxo-3,4-
dihydroquinazoline-2-carbaldehyde (5).
Compound
3
3-(4-Chlorophenyl)-2-(((3-(trifluoromethyl)phenyl)imino)
(0.01 mol, 2.85 g) was dissolved in hot dioxane (50 mL),
and then powdered selenium dioxide (0.02 mol, 1.2 g) was
methyl)quinazolin-4(3H)-one (6f).
216°C. Anal. Calcd for C22H13ClF3N3O: C, 61.77; H,
Yield: (81%), mp
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet