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M.A. Omar et al. / Tetrahedron 70 (2014) 3061e3072
4.2.12. 7-Methyl-2-phenylquinazoline (3l). According to the general
procedure, a mixture of CuI (9 mg, 0.05 mmol), K3PO4 (318 mg,
1.5 mmol), pivalic acid (20 mg, 0.2 mmol), 1-(2-bromo-4-
methylphenyl)methanamine (1e) (99 mg, 0.5 mmol), and benza-
midine hydrochloride (2a) (78 mg, 0.5 mmol) were reacted in dry
1,2-dichlorobenzene (3 mL) in a sealed vial at 110 ꢀC for 18 h. Flash
chromatography over silica gel (petroleum ether/EtOAc¼5:1) gave
3l as a colorless solid in 90% yield (164 mg, 0.74 mmol): mp
(4.46) nm; 1H NMR (300 MHz, CDCl3)
d 2.60 (br s, 3H, CH3), 7.44
(dd, 3J (5-H, 6-H)¼8.2 Hz, 4J (6-H, 8-H)¼1.3 Hz, 1H, 6-H), 7.48 (br dd,
3
3J (20-H, 30-H)¼6.8 Hz, J (50-H, 60-H)¼6.8 Hz, 2H, 30-H and 50-H),
7.80 (d, 3J (5-H, 6-H)¼8.2 Hz, 1H, 5-H), 7.84 (br s, 1H, 8-H), 8.55
(br dd, 3J (20-H, 30-H)¼6.8 Hz, 3J (50-H, 60-H)¼6.8 Hz, 2H, 20-H and 60-
H), 9.36 (s, 1H, 4-H); 13C NMR (75 MHz, CDCl3)
d 22.3 (CH3), 121.8
(C-4a), 126.7 (C-5), 127.4 (C-8), 128.7 (C-20 and C-60), 129.7 (C-6),
129.8 (C-30 and C-50), 136.6 (C-40), 136.7 (C-10), 145.3 (C-7), 150.9
(C-8a),159.8 (C-4), 160.0 (C-2); MS (ESI) m/z (%) 254 (100) [M]þ, 227
(30) [MꢂHCN]þ,192 (7),127 (13), 89 (36); HRMS (ESI) calculated for
ꢀ
~
107e109 C (dec); Rf 0.38 (petroleum ether/EtOAc¼2:1); IR (ATR)
n
3055, 2920, 1647, 1589, 1549, 1489, 1402, 1380, 882, 794, 764,
700 cmꢂ1; UV (MeCN) lmax (log
3
) 263 (4.62), 212 (4.45) nm; 1H
2.60 (br s, 3H, CH3), 7.41 (dd, 3J (5-H, 6-
C15H11ClN2 254.0611, found 254.0631.
NMR (300 MHz, CDCl3)
d
4
H)¼8.2 Hz, J (6-H, 8-H)¼1.3 Hz, 1H, 6-H), 7.46e7.57 (m, 3H, 30-H,
40-H and 50-H), 7.80 (d, 3J (5-H, 6-H)¼8.2 Hz, 1H, 5-H), 7.88 (br s, 1H,
8-H), 8.61 (br dd, 3J (20-H, 30-H)¼7.6 Hz, 3J (50-H, 60-H)¼7.6 Hz, 2H,
4.2.15. 7-Methyl-2-(pyridin-4-yl)quinazoline (3o). According to the
general procedure, a mixture of CuI (9 mg, 0.05 mmol), K3PO4
(318 mg, 1.5 mmol), pivalic acid (20 mg, 0.2 mmol), 1-(2-bromo-4-
methylphenyl)methanamine (1e) (99 mg, 0.5 mmol), and 4-
amidinopyridine hydrochloride (2e) (80 mg, 0.5 mmol) were
reacted in dry 1,2-dichlorobenzene (3 mL) in a sealed vial at 110 ꢀC
for 18 h. Flash chromatography over silica gel (petroleum ether/
EtOAc¼2:1) gave 3o as a yellow solid in 65% yield (71 mg,
0.32 mmol): mp 157e158 ꢀC (dec); Rf 0.33 (petroleum ether/
20-H and 60-H), 9.39 (s, 1H, 4-H); 13C NMR (75 MHz, CDCl3)
d 22.3
(CH3), 121.8 (C-4a), 126.7 (C-5), 127.4 (C-8), 128.5 (C-20, C-30, C-50,
and C-60),129.5 (C-6),130.5 (C-40),138.0 (C-10),145.2 (C-7),150.9 (C-
4a), 159.8 (C-4), 160.9 (C-2); MS (ESI) m/z (%) 220 (100) [M]þ, 193
(17) [MꢂHCN]þ, 165 (3), 110 (4), 89 (10), 84 (35); HRMS (ESI) cal-
culated for C15H12N2 220.1000, found 220.1005.
~
n
EtOAc¼1: 2); IR (ATR) 3010, 2112, 1621, 1578, 1538, 1490, 1403,
894, 848 cmꢂ1; UV (MeCN) lmax (log
) 267 (4.66), 209 (4.37) nm;
1H NMR (300 MHz, CDCl3) 2.62 (br s, 3H, CH3), 7.50 (dd, 3J (5-H, 6-
4.2.13. 7-Methyl-2-(4-methylphenyl)quinazoline (3m). Using ami-
dine 2b as the substrate: According to the general procedure,
a mixture of CuI (9 mg, 0.05 mmol), K3PO4 (318 mg, 1.5 mmol),
pivalic acid (20 mg, 0.2 mmol), 1-(2-bromo-4-methylphenyl)
methanamine (1e) (99 mg, 0.5 mmol), and 4-methylbenzamidine
hydrochloride (2b) (88 mg, 0.5 mmol) were reacted in dry 1,2-
dichlorobenzene (3 mL) in a sealed vial at 110 ꢀC for 18 h. Flash
chromatography over silica gel (petroleum ether/EtOAc¼10:1) gave
3m as a colorless solid in 57% yield (66 mg, 0.28 mmol). 7-Methyl-2-
(4-methylphenyl)quinazoline (3m) using imidate 4b as the sub-
strate: According to the general procedure, a mixture of CuI (9 mg,
0.05 mmol), K3PO4 (318 mg, 1.5 mmol), pivalic acid (20 mg,
0.2 mmol), 1-(2-bromo-4-methylphenyl)methanamine (1e)
(114 mg, 0.5 mmol), and ethyl-4-methylbenzimidate hydrochloride
(4b) (99 mg, 0.5 mmol) were reacted in dry 1,2-dichlorobenzene
(3 mL) in a sealed vial at 110 ꢀC for 18 h. Flash chromatography
over silica gel (petroleum ether/EtOAc¼5:1) gave 3m as a colorless
solid in 55% yield (63 mg, 0.26 mmol): mp 147e148 ꢀC (dec); Rf 0.49
~
n
2919, 2119, 1625, 1583,
3
d
H)¼8.4 Hz, 4J (6-H, 8-H)¼1.2 Hz, 1H, 6-H), 7.85 (d, 3J (5-H, 6-H)¼
8.4 Hz, 1H, 5-H), 7.89 (s, 1H, 8-H), 8.45 (br dd, 3J (20-H, 30-H)¼4.9 Hz,
3J (50-H, 60-H)¼4.9 Hz, 2H, 20-H and 60-H), 8.81 (br s, 2H, 30-H and 50-
H), 9.41 (s, 1H, 4-H); 13C NMR (75 MHz, CDCl3)
d 22.3 (CH3), 122.4
(C-20 and C-60), 122.6 (C-4a), 126.7 (C-5), 127.7 (C-8), 130.6 (C-6),
145.6 (C-7), 145.7 (C-10), 150.1 (C-30 and C-50), 150.0 (C-8a), 158.8 (C-
2), 160.0 (C-4); MS (ESI) m/z (%) 221 (100) [M]þ, 194 (9) [MꢂHCN]þ,
110 (3), 89 (10); HRMS (ESI) calculated for C14H11N3 221.0953, found
221.0951.
4.2.16. 6-Fluoro-2-phenylquinazoline (3p).16 According to the gen-
eral procedure, a mixture of CuI (9 mg, 0.05 mmol), K3PO4 (318 mg,
1.5 mmol), pivalic acid (20 mg, 0.2 mmol), 1-(2-bromo-5-
fluorophenyl)methanamine (1f) (101 mg, 0.5 mmol), and benza-
midine hydrochloride (2a) (78 mg, 0.5 mmol) were reacted in dry
1,2-dichlorobenzene (3 mL) in a sealed vial at 110 ꢀC for 18 h. Flash
chromatography over silica gel (petroleum ether/EtOAc¼10:1) gave
3p as a colorless solid in 58% yield (65 mg, 0.29 mmol): mp
150e151 ꢀC (dec) (lit.16 140e141 ꢀC).
(petroleum ether/EtOAc¼4:1); IR (ATR)
1543, 1490, 1402, 1376, 1174, 840, 794, 732, 697 cmꢂ1; UV (MeCN)
lmax (log
) 268 (4.36), 214 (4.24) nm; 1H NMR (300 MHz, CDCl3)
3
d
2.44 (br s, 3H, 100-H), 2.59 (br s, 3H, CH3), 7.33 (br dd, 3J (20-H, 30-
H)¼6.4 Hz, 3J (50-H, 60-H)¼6.4 Hz, 2H, 30-H and 50-H), 7.41 (dd, 3J (5-
4.2.17. 6-Fluoro-2-(4-methylphenyl)quinazoline (3q). According to
the general procedure, a mixture of CuI (9 mg, 0.05 mmol), K3PO4
(318 mg, 1.5 mmol), pivalic acid (20 mg, 0.2 mmol), 1-(2-bromo-5-
fluorophenyl)methanamine (1f) (101 mg, 0.5 mmol), and 4-
methylbenzamidine hydrochloride (2b) (88 mg, 0.5 mmol) were
reacted in dry 1,2-dichlorobenzene (3 mL) in a sealed vial at 110 ꢀC
for 18 h. Flash chromatography over silica gel (petroleum ether/
EtOAc¼10:1) gave 3q as a colorless solid in 62% yield (73 mg,
0.31 mmol): mp 139e141 ꢀC (dec); Rf 0.43 (petroleum ether/
~
H, 6-H)¼8.2 Hz, 4J (6-H, 8-H)¼1.3 Hz, 1H, 6-H), 7.79 (d, 3J (5-H, 6-
3
H)¼8.2 Hz, 1H, 5-H), 7.86 (br s, 1H, 8-H), 8.50 (br dd, J (20-H, 30-
H)¼6.4 Hz, 3J (50-H, 60-H)¼6.4 Hz, 2H, 20-H and 60-H), 9.36 (s, 1H, 4-
H); 13C NMR (75 MHz, CDCl3) 21.4 (C-100), 22.3 (CH3), 121.7 (C-4a),
d
126.7 (C-5), 127.3 (C-8), 128.4 (C-20 and C-60), 129.3 (C-30, C-50, and
C-6), 135.2 (C-40), 140.8 (C-10), 145.2 (C-7), 150.9 (C-8a), 159.7 (C-4),
161.0 (C-2); MS (ESI) m/z (%) 234 (100) [M]þ, 207 (10) [MꢂHCN]þ,
149 (12), 126 (10), 117 (11); HRMS (ESI) calculated for C16H14N2
234.1157, found 234.1147.
EtOAc¼5:1); IR (ATR)
n
3080, 2116, 1627, 1584, 1549, 1489, 1348,
1208, 1178, 1143, 828, 785, 726, 667 cmꢂ1; UV (MeCN) lmax (log
)
3
4.2.14. 7-Methyl-2-(4-chlorophenyl)quinazoline (3n). According to
the general procedure, a mixture of CuI (9 mg, 0.05 mmol), K3PO4
(318 mg, 1.5 mmol), pivalic acid (20 mg, 0.2 mmol), 1-(2-bromo-4-
methylphenyl)methanamine (1e) (99 mg, 0.5 mmol), and 4-
chlorobenzamidine hydroiodide (2c) (147 mg, 0.5 mmol) were
reacted in dry 1,2-dichlorobenzene (3 mL) in a sealed vial at 110 ꢀC
for 18 h. Flash chromatography over silica gel (petroleum ether/
EtOAc¼10:1) gave 3n as a pale yellow solid in 85% yield (107 mg,
0.42 mmol): mp 159e160 ꢀC (dec); Rf 0.40 (petroleum ether/
~
332 (3.50), 263 (4.34), 250 (4.33), 208 (4.45) nm; 1H NMR
3
(300 MHz, CDCl3)
d
2.44 (s, 3H, CH3), 7.34 (br dd, J (20-H, 30-H)¼
6.4 Hz, 3J (50-H, 60-H)¼6.4 Hz, 2H, 30-H and 50-H), 7.52 (dd, 3J (6-F, 5-
H)¼7.7 Hz, 4J (5-H, 7-H)¼2.7 Hz, 1H, 5-H), 7.66 (ddd, 3J (7-H, 8-H)¼
8.5 Hz, 3J (6-F, 7-H)¼8.5 Hz, 4J (5-H, 7-H)¼2.7 Hz, 1H, 7-H), 8.10 (br
dd, 3J (7-H, 8-H)¼8.5 Hz, 4J (6-F, 8-H)¼2.8 Hz, 1H, 8-H), 8.43 (br dd,
3
3J (20-H, 30-H)¼6.4 Hz, J (50-H, 60-H)¼6.4 Hz, 2H, 20-H and 60-H),
9.41 (s, 1H, 4-H); 13C NMR (75 MHz, CDCl3)
d
21.5 (CH3), 110.1 (d, 2J
(CeF)¼22.9 Hz, C-5), 123.7 (d, 3J (CeF)¼10.2 Hz, C-4a), 124.5 (d, 2J
(CeF)¼25.15 Hz, C-7), 128.4 (C-20 and C-60), 129.4 (C-30 and C-50),
131.1 (d, 3J (CeF)¼8.8 Hz, C-8),134.8 (C-10),141.0 (C-40), 147.8 (C-8a),
EtOAc¼5:1); IR (ATR)
n
2918, 2089, 1622, 1570, 1543, 1486, 1410,
) 263 (4.68), 214
888, 847, 787, 728, 688 cmꢂ1; UV (MeCN) lmax (log
3