The Journal of Organic Chemistry
Article
127.1, 126.8, 123.3, 114.0, 55.4. HRMS (ESI) m/z calcd for
C15H13N2O [M + H]+ 237.1022, found 237.1031.
120−121 °C); 1H NMR (CDCl3, 500 MHz) δ 9.60 (s, 1H), 8.70 (d, J
= 8.0 Hz, 1H), 8.17−8.19 (m, 2H), 7.93−8.03 (m, 4H), 7.70 (t, J = 7.5
Hz, 1H), 7.64 (t, J = 7.5 Hz, 1H), 7.52−7.58 (m, 2H); 13C NMR
(CDCl3, 125 MHz) δ 163.5, 160.4, 150.6, 136.3, 134.3, 134.2, 131.2,
130.4, 129.6, 128.7, 128.5, 127.7, 127.1, 126.8, 125.89, 125.87, 125.3,
123.1. HRMS (ESI) m/z calcd for C18H13N2 [M + H]+ 257.1073,
found 257.1070.
2-(3,4-Dimethoxyphenyl)quinazoline (3g).22 Rf = 0.41 (hexane/
ethyl acetate = 5:1), white solid (38.8 mg, 73% yield), mp 110−111 °C
(lit. 112−114 °C); 1H NMR (CDCl3, 500 MHz) δ 9.41 (s, 1H), 8.20
(d, J = 1.5 Hz, 1H), 8.05 (d, J = 8.5 Hz, 1H), 7.86−7.89 (m, 2H), 7.56
(t, J = 7.5 Hz, 1H), 7.01 (d, J = 8.5 Hz, 1H), 4.06 (s, 3H), 3.97 (s,
3H); 13C NMR (CDCl3, 125 MHz) δ 160.7, 160.3, 151.4, 150.8,
149.1, 134.0, 130.9, 128.4, 127.1, 126.8, 123.3, 122.0, 111.2, 110.9,
56.0, 55.9. HRMS (ESI) m/z calcd for C16H15N 2O2 [M + H]+
267.1128, found 267.1134.
2-(Furan-2-yl)quinazoline (3o).16b Rf = 0.3 (hexane/ethyl acetate =
10:1), brown solid (35.7 mg, 91% yield), mp 131−132 °C (lit. 131−
132 °C); 1H NMR (CDCl3, 500 MHz) δ 9.38 (s, 1H), 8.09 (d, J = 9.0
Hz, 1H), 7.88−7.91 (m, 2 H), 7.69 (s, 1H), 7.59 (t, J = 8.0 Hz, 1H),
7.45 (d, J = 3.5 Hz, 1H), 6.61−6.62 (m, 1H); 13C NMR (CDCl3, 125
MHz) δ 160.7, 154.1, 152.5, 150.5, 145.3, 134.5, 128.4, 127.3, 123.4,
114.1, 112.3. HRMS (ESI) m/z calcd for C12H9N2O [M + H]+
197.0709, found 197.0708.
2-(1,3-Dihydroisobenzofuran-5-yl)quinazoline (3h).15b Rf = 0.47
(hexane/ethyl acetate = 5:1), yellow solid (38 mg, 76% yield), mp
1
126−128 °C (lit. 123−125 °C); H NMR (DMSO-d6, 500 MHz) δ
9.63 (s, 1H), 8.12−8.19 (m, 2H), 7.99−8.00 (m, 3H), 7.68−7.71 (m,
1H), 7.08 (d, J = 8.0 Hz, 1H), 6.14 (s, 2H); 13C NMR (DMSO-d6, 125
MHz) δ 161.1, 159.3, 149.8, 149.7, 147.9, 134.7, 131.7, 127.74, 127.67,
127.3, 123.10, 123.07, 108.4, 107.6, 101.6. HRMS (ESI) m/z calcd for
C15H11N2O2 [M + H]+ 251.0815, found 251.0824.
2-(Thiophen-2-yl)quinazoline (3p).10a Rf = 0.47 (hexane/ethyl
acetate = 10:1), white solid (39.4 mg, 93% yield), mp 131−133 °C (lit.
1
132−134 °C); H NMR (CDCl3, 300 MHz) δ 9.35 (s, 1H), 8.14−
8.16 (m, 1H), 8.01 (d, J = 8.7 Hz, 1H), 7.85−7.90 (m, 2H), 7.51−7.59
(m, 2H), 7.18−7.21 (m, 1H); 13C NMR (CDCl3, 125 MHz) δ 160.5,
157.9, 150.7, 143.9, 134.3, 129.9, 129.2, 128.3, 128.2, 127.2, 127.0,
123.4. HRMS (ESI) m/z calcd for C12H9N2S [M + H]+ 213.0481,
found 213.0487.
2-(4-Fluorophenyl)quinazoline (3i).16a Rf = 0.3 (hexane/ethyl
acetate = 20:1), white solid (43.5 mg, 97% yield), mp 135−137 °C (lit.
1
135−137 °C); H NMR (CDCl3, 300 MHz) δ 9.44 (s, 1H), 8.60−
8.65 (m, 2H), 8.07 (d, J = 8.4 Hz, 1H), 7.91 (t, J = 7.8 Hz, 2H), 7.61
(t, J = 7.5 Hz, 1H), 7.21 (t, J = 8.7 Hz, 2H); 13C NMR (CDCl3, 125
MHz) δ 165.7, 163.7, 160.5, 160.1, 150.7, 134.2, 130.7, 130.6, 128.6,
127.3, 127.1, 123.5, 115.6, 115.5. HRMS (ESI) m/z calcd for
C14H10FN2 [M + H]+ 225.0823, found 225.0827.
6-Fluoro-2-phenylquinazoline (3q).14 Rf = 0.27 (hexane/ethyl
acetate = 10:1), white solid (39.4 mg, 88% yield), mp 120−121 °C (lit.
1
120−121 °C); H NMR (CDCl3, 300 MHz) δ 9.41 (s, 1H), 8.58−
8.60 (m, 2H), 8.07−8.12 (m, 1H), 7.64−7.69 (m, 1H), 7.52−7.54 (m,
4H); 13C NMR (CDCl3, 125 MHz) δ 161.4, 160.7, 159.8, 159.7,
159.4, 148.0, 137.7, 131.4, 131.3, 130.7, 128.6, 128.5, 124.6, 124.4,
124.0, 123.9, 110.2, 110.0. HRMS (ESI) m/z calcd for C14H10FN2 [M
+ H]+ 225.0823, found 225.0827.
2-(4-Bromophenyl)quinazoline (3j).15c Rf = 0.33 (hexane/ethyl
acetate = 20:1), white solid (49.4 mg, 87% yield), mp 120−121 °C (lit.
120−121 °C); 1H NMR (CDCl3, 500 MHz) δ 9.43 (s, 1H), 8.50 (d, J
= 8.5 Hz, 2H), 8.06 (d, J = 9.0 Hz, 1H), 7.89−7.92 (m, 2H), 7.60−
7.66 (m, 3H); 13C NMR (CDCl3, 125 MHz) δ 160.5, 160.1, 150.7,
137.0, 134.2, 131.8, 130.2, 128.6, 127.4, 127.1, 125.4, 123.6. HRMS
(ESI) m/z calcd for C14H10BrN2 [M + H]+ 285.0022, found 285.0034.
2-[4-(Trifluoromethyl)phenyl]quinazoline (3k).23 Rf = 0.43 (hex-
ane/ethyl acetate = 5:1), white solid (39.5 mg, 72% yield), mp 143−
144 °C (lit. not reported); 1H NMR (DMSO-d6, 500 MHz) δ 9.76 (s,
1H), 8.75 (d, J = 8.5 Hz, 2H), 8.21 (d, J = 8.0 Hz, 1H), 8.06−8.12 (m,
2H), 7.93 (d, J = 8.5 Hz, 2H), 7.78−7.81 (m, 1H); 13C NMR
(DMSO-d6, 125 MHz) δ 161.6, 158.4, 149.7, 141.2, 135.1, 130.7,
150.5, 128.7, 128.4, 128.0, 127.9, 125.8, 125.7, 125.3, 123.6, 123.1.
HRMS (ESI) m/z calcd for C15H10F3N2 [M + H]+ 275.0791, found
275.0798.
6-Chloro-2-phenylquinazoline (3r).12c Rf = 0.39 (hexane/ethyl
acetate = 20:1), pale yellow solid (41.8 mg, 87% yield), mp 157−159
1
°C (lit. 157−159 °C); H NMR (CDCl3, 300 MHz) δ 9.40 (s, 1H),
8.58−8.62 (m, 2H), 8.03 (d, J = 9.0 Hz, 1H), 7.91 (d, J = 2.1 Hz, 1H),
7.82−7.85 (m, 1H), 7.52−7.55 (m, 3H); 13C NMR (CDCl3, 125
MHz) δ 161.4, 159.5, 149.3, 137.6, 135.1, 132.8, 130.9, 130.4, 128.7,
128.6, 125.8, 124.0. HRMS (ESI) m/z calcd for C14H10ClN2 [M + H]+
241.0527, found 241.0535.
7-Nitro-2-phenylquinazoline (3s). Rf = 0.28 (hexane/ethyl acetate
= 10:1), white solid (31.1 mg, 62% yield), mp 140−143 °C; IR (KBr)
2925, 1687, 1567, 1526, 1421, 1326, 1291, 927, 823, 740, 706, 686,
668 cm−1; 1H NMR (CDCl3, 500 MHz) δ 9.61 (s, 1H), 8.96 (s, 1H),
8.65−8.66 (m, 2H), 8.36−8.37 (m, 1H), 8.11 (d, J = 8.5 Hz, 1H),
7.56−7.57 (m, 3H); 13C NMR (CDCl3, 125 MHz) δ 162.9, 160.8,
151.2, 150.5, 136.9, 131.6, 129.0, 128.9, 128.8, 125.7, 124.9, 120.7.
HRMS (ESI) m/z calcd for C14H10N3O2 [M + H]+ 252.0768, found
252.0772.
4-(Quinazolin-2-yl)benzaldehyde (3l). Rf = 0.37 (hexane/ethyl
acetate = 5:1), white solid (25.7 mg, 55% yield), mp 167−168 °C; IR
(KBr): 2924, 2856, 2360, 1693, 1626, 1551, 1207, 1055, 796, 729, 688
cm−1; 1H NMR (DMSO-d6, 500 MHz) δ 10.12 (s, 1H), 9.76 (s, 1H),
8.75 (d, J = 8.0 Hz, 2H), 8.21 (d, J = 8.0 Hz, 1H), 8.07−8.10 (m, 4H),
7.78−7.81 (m,, 1H); 13C NMR (DMSO-d6, 125 MHz) δ 193.0, 161.5,
158.7, 149.7, 142.6, 137.4, 135.1, 129.8, 128.6, 128.4, 128.0, 127.9,
123.5. HRMS (ESI) m/z calcd for C15H11N2O [M + H]+ 235.0866,
found 235.0879.
6-Methyl-2-phenylquinazoline (3t).24 Rf = 0.41 (hexane/ethyl
acetate = 10:1), pale yellow solid (36.1 mg, 82% yield), mp 130−132
1
°C (lit. 130−132 °C); H NMR (CDCl3, 500 MHz) δ 9.38 (s, 1H),
2-(4-Nitrophenyl)quinazoline (3m).16b Rf = 0.31 (hexane/ethyl
acetate = 10:1), yellow solid (28.1 mg, 56% yield), mp 218−220 °C
8.60 (d, J = 8.5 Hz, 2H), 7.98 (d, J = 8.5 Hz, 1H), 7.72−7.74 (m, 1H),
7.67 (s, 1H), 7.50−7.55 (m, 3H), 2.58 (s, 3H); 13C NMR (CDCl3,
125 MHz) δ 160.4, 159.7, 149.4, 138.2, 137.4, 136.4, 130.4, 128.6,
128.4, 128.3, 125.8, 123.6, 21.6. HRMS (ESI) m/z calcd for C15H13N2
[M + H]+ 221.1073, found 221.1068.
1
(lit. 218−219 °C); H NMR (DMSO-d6, 500 MHz) δ 9.80 (s, 1H),
8.80 (d, J = 9 Hz, 2H), 8.43 (d, J = 9.0 Hz, 2H), 8.24 (d, J = 9.0 Hz,
1H), 8.09−8.15 (m, 2H), 7.81−7.84 (m, 1H); 13C NMR (DMSO-d6,
125 MHz) δ 161.7, 157.9, 149.7, 148.8, 143.3, 135.3, 129.2, 128.7,
128.1, 128.0, 124.0, 123.6. HRMS (ESI) m/z calcd for C14H10N3O2
[M + H]+ 252.0768, found 252.0766.
8-Methyl-2-Phenylquinazoline (3u).25 Rf = 0.32 (hexane/ethyl
acetate = 20:1), pale yellow solid (28.6 mg, 65% yield), mp 59−61 °C
(lit. 59−61 °C); 1H NMR (DMSO-d6, 500 MHz) δ 9.64 (s, 1H), 8.60
(m, 2H), 7.96 (d, J = 8 Hz, 1H), 7.86 (d, J = 7 Hz, 1H), 7.75−7.62 (m,
4H), 2.78 (s, 3H); 13C NMR (DMSO-d6, 125 MHz) δ 161.3, 158.9,
148.7, 137.7, 135.9, 134.3, 130.7, 128.7, 128.1, 127.3, 125.4, 123.2,
16.4. HRMS (ESI) m/z calcd for C15H13N2 [M + H]+ 221.1073, found
221.1076.
2-(4-nitrophenyl)-4H-benzo[d]1,3-oxazine (4m).16b Rf = 0.34
(hexane/ethyl acetate = 10:1), white solid (15.8 mg, 31% yield), mp
93−94 °C (lit. 92−93 °C); 1H NMR (CDCl3, 300 MHz) δ 8.26−8.33
(m, 4H), 7.29−7.35 (m, 2H), 7.22−7.26 (m, 1H), 7.04 (d, J = 7.2 Hz,
1H), 5.46 (s, 2H); 13C NMR (CDCl3, 125 MHz) δ 155.3, 149.6,
139.0, 138.3, 129.2, 128.8, 127.5, 125.2, 123.8, 123.4, 122.0, 66.7.
HRMS (ESI) m/z calcd for C14H11N2O3 [M + H]+ 255.0764, found
255.0763.
2-Aminobenzaldehyde (5a).26 Rf = 0.24 (hexane/ethyl acetate =
10:1), colorless oil (21.1 mg, 87% yield); 1H NMR (CDCl3, 500
MHz) δ 9.87 (s, 1H), 7.47−7.49 (m, 1H), 7.29−7.33 (m, 1H), 6.73−
6.76 (m, 1H), 6.65 (d, J = 8.5 Hz, 1H), 6.12 (s, 2H); 13C NMR
(CDCl3, 125 MHz) δ 194.0, 149.8, 135.7, 135.1, 118.8, 116.3, 116.0.
2-(Naphthalen-1-yl)quinazoline (3n).21 Rf = 0.23 (hexane/ethyl
acetate = 10:1), white solid (38.4 mg, 75% yield), mp 120−121 °C (lit.
11347
dx.doi.org/10.1021/jo401908g | J. Org. Chem. 2013, 78, 11342−11348