Nickel-catalyzed Kumada Cross-coupling Reaction for the Synthesis of 2,4-Diarylquinazolines

Article abstract of DOI:10.1002/jhet.2513

A series of 2,4-diarylquinazolines have been successfully synthesized via the Ni-catalyzed cross-coupling reaction of quinazoline-4-tosylates and aryl Grignard reagents, which provided alternative straightforward approaches for the introduction of aryl groups to quinazolines at C-4 position.

Full text of DOI:10.1002/jhet.2513

Month 2015
Nickel-catalyzed Kumada Cross-coupling Reaction for the Synthesis of
2,4-Diarylquinazolines
Xinglin Ye,a,b Zhihan Yuan, Yirong Zhou, Qin Yang, Yepeng Xie, Zhihong Deng, and Yiyuan Peng
a
a
a
a
a
a
*
aKey Laboratory of Small Functional Organic Molecule, Ministry of Education and Key Laboratory of Green Chemistry,
Jiangxi Normal University, Jiangxi Province, Nanchang, Jiangxi 330022, China
bDepartment of Chemistry and Environmental Engineering, Jiujiang University, Jiujiang, Jiangxi 332005, People’s Republic of China
*
E-mail: yypeng@jxnu.edu.cn; yiyuanpeng@yahoo.com
Additional Supporting Information may be found in the online version of this article.
Received April 2, 2015
DOI 10.1002/jhet.2513
Published online 00 Month 2015 in Wiley Online Library (wileyonlinelibrary.com).
A series of 2,4-diarylquinazolines have been successfully synthesized via the Ni-catalyzed cross-coupling
reaction of quinazoline-4-tosylates and aryl Grignard reagents, which provided alternative straightforward
approaches for the introduction of aryl groups to quinazolines at C-4 position.
J. Heterocyclic Chem., 00, 00 (2015).
INTRODUCTION
is no reported on the quinazoline-4-tosylates as electrophile
substrates in Kumada coupling for synthesis of
diarylquinazolines. We here report the results of nickel-
catalyzed Kumada cross-coupling reaction between
quinazoline-4-tosylates and Grignard reagents to access 2,4-
diarylquinazolines in good yields under mild conditions.
Quinazolines have attracted immense interest because
of their potential bioactivities [1–3]. Particularly,
4-functionalized quinazolines have been demonstrated
as effective fungicides, anti-inflammatory, anti-cancer,
anti-microbial, and anti-hypertensive agents [4,5]. During
the past decade, considerable progress has been made for
the synthesis of quinazoline derivatives [6,7]. However,
most of these examples usually require harsh reaction
conditions. Therefore, there is great room to develop
novel and efficient catalytic systems for accessing
4-functionalized quinazolines under mild conditions. In
light of our interest in quinazoline chemistry, our group
has recently made great progress on the synthesis of
4-functionalized quinazolines [8]. In those reports, we
have developed several alternative routes for the synthe-
sis of functionalized quinazolines by using quinazoline-
4-tosylates as starting material to react with aryl
mercaptan[8b] and organoboron reagents [8c]. These pre-
vious results showed that the toluene-4-sulfonic (TS)
group at the 4-position of quinazoline can act as an effective
leaving group. In continuation of our studies toward the
preparation of 4-functionalized quinazolines, we are
searching for other simple and efficient approaches to en-
rich the quinazolines chemistry. On the other hand,
nickel-catalyzed Kumada coupling reaction is regarded as
one of the most excellent methods for the formation of a
carbon–carbon bond [9]. Activated aryl tosylates and
heteroaromatic tosylates have been reported, which were
suitable substrates for the cross-coupling reaction with
Grignard reagents [10]. To the best of our knowledge, there
RESULTS AND DISCUSSION
At the outset, the reaction of 2-(p-methyl phenyl)qui-
nazoline-4-tosylate (1a) and phenyl magnesium bromide
(2a, 1.1 equiv) was selected as the model reaction in
THF for optimizing the reaction conditions. A variety of
catalysts were screened in this cross-coupling reaction.
The desired product 3a was obtained in 79, 71, and 65%
yields at 60°C in the presence of Ni(DPPF)Cl2, Ni(DPPE)Cl2,
and Ni(DPPP)Cl2, respectively (Table 1, entries 1–3). It was
found that Ni(DPPF)Cl2 in combination with PPh3 ligand is
the best catalyst, which finished the reaction within only
45 min and giving the highest yield of 80% (Table 1, entry
8). Other N or P ligand only gave slightly low yields (entries
9 and 10). The reaction gave 76% yield when it was carried
out at 30°C(entry 11). Reduction of the catalyst load
amounted to 1–2 mol % only slightly decreased the yield to
72–70% (Table 1, entries 12 and 13). The control experiments
show that the reaction efficiency decreased in the absence of
PPh3 ligand (entry 14) and no product was obtained without
adding the Ni(DPPF)Cl2 catalyst (entry 15). Fe(acac)3, FeCl3,
and FeCl2 were also tested as the coupling catalyst; the prod-
uct 3a were isolated only in unsatisfactory yields (Table 1,
entries 16–21). Then, the impact of counterion in Grignard
© 2015 HeteroCorporation

X. Ye, Z. Yuan, Y. Zhou, Q. Yang, Y. Xie, Z. Deng, and Y. Peng
Vol 000
Table 1
the corresponding 2-aryl-4-phenyl quinazolines 3a–i in
good yields. Moreover, when R1 is phenyl, it was found
that whatever electron-donating or electron-withdrawing
group on the R1 is, substrates were given the corresponding
product in good to excellent yields (entries 3a–h). It is
Reaction parameters optimization.a
Table 2
Substrate scope.a
Entry
Catalyst
Ligand
DPPF
DPPE
DPPP
PPh3
DPPF
PPh3
PPh3
PPh3
1.10-Phen
PCy3
PPh3
PPh3
PPh3
—
PPh3
NMP
TMEDA
NMP
TMEDA
NMP
TMEDA
PPh3
2
Yield (%)b
79
71
65
73
76
66
66
80
72
74
76
72
70
62
1
2
3
4
5
6
7
8
Ni(DPPF)Cl2
Ni(DPPE)Cl2
Ni(DPPP)Cl2
Ni(PPh3)2Br2
NiCl2
2a
2a
2a
2a
2a
2a
2a
2a
2a
2a
2a
2a
2a
2a
2a
2a
2a
2a
2a
2a
2a
2b
2c
NiCl2
Ni(PPh3)2Cl2
Ni(DPPF)Cl2
Ni(DPPF)Cl2
Ni(DPPF)Cl2
Ni(DPPF)Cl2
Ni(DPPF)Cl2
Ni(DPPF)Cl2
Ni(DPPF)Cl2
—
Fe(acac)3
Fe(acac)3
Fe(acac)2
FeCl3
9
10
11c
12d
13e
14
15
16
17
18
19
20
21
22
23
No reaction
22
Trace
Trace
No reaction
No reaction
No reaction
73
FeCl3
FeCl2
Ni(DPPF)Cl2
Ni(DPPF)Cl2
PPh3
No reaction
aAll reactions were performed in 0.2-mmol scale, standard conditions: 1a
(0.2 mol), 2a (0.22 mmol), 5 mol % catalyst, 10 mol % ligand, and solvent
(2 mL), in air atmosphere, at 60°C.
bIsolated yield.
cThe reaction was carried out at 30°C.
d2 mol % catalyst was added.
e1 mol % catalyst was added.
reagent on the reaction was investigated. The reaction of 1a
and phenyl magnesium chloride (2b) gave 3a in a yield of
73%. However, when the reagent 2b was replaced by phenyl
magnesium iodide (2c), no product was detected. Finally, the
optimized conditions for the coupling reaction were
established by using Ni(DPPF)Cl2 (5 mol %) and PPh3
(10mol %) as the catalyst at 60°C in THF.
With the optimized conditions in hand, we next explored the
generality of this Kumada cross-coupling reaction by employing
a variety of 4-OTs-quinazolines and Grignard reagents.
In order to understand the influence of the structural and
functional motifs on the reaction of phenyl magnesium
bromide 2a, a range of quinazoline-4-tosylates 1 were then
tested. The results were depicted in Table 2. For all cases,
2-arylquinazoline-4-tosylates 1 reacted 2a well, leading to
(Continued)
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DOI 10.1002/jhet

Month 2015
Coupling Reaction for the Synthesis of 2,4-Diarylquinazolines
Table 2
(Continued)
amyl magnesium bromide, was used, the reaction became
complex (3k). As expected, the reaction of aryl Grignard
reagents gave the corresponding products in good yields.
Electron-donating substituted aryl Grignard reagents had
more reactivity and gave higher yields than those with
the electron-withdrawing substituted (entries 3l–o vs 3p).
The reactions of o-methyl phenyl magnesium bromide
afforded lower yields probably due to its steric hindrance
(entries 3q and r). Moderate yields were obtained as well,
when heterocyclic Grignard reagent was utilized. For
example, the reactions of 2-thienyl magnesium bromide
with 1a and b provided the corresponding products 3 s
and t in the yields of 69 and 66%.
In order to obtain more information about this unique
Kumada cross-coupling reaction, substrates 1y, contain-
ing both OTs and aryl chloride 1y(Cl) or bromide
1y(Br) moiety, were utilized under the identical condi-
tions (Table 3). When Grignard 2a reacted with 2-(4-Br-
phenyl)quinazoline-4-OTs 1y(Br), both of the OTs group
and the Br group can be coupled in a one-pot reaction,
affording the product 3y2 as the sole product. As can be
seen from Table 3, a poor yield (30%) of 3y2 was obtained
when equal molecular ratio of 2a:1y(Br) was used; how-
ever, the yield of compound 3y2 can be improved to 67%
when 4.0 equiv of Grignard 2a was added. For the
reaction of Grignard 2a with 2-(4-Cl-phenyl)quinazoline-4-
OTs 1y(Cl), the chloride-substituted product 3y1(Cl) and
compound 3y2 can be isolated in 57 and 14% yield when
equal molecular ratio of 2a:1y(Cl) was used, respectively.
However, this situation can be changed when increasing
Table 3
The reaction of substrates containing both OTs and aryl chloride
or bromide.a
aIsolated yield.
X=Br
Yield of
X=Cl
Yield of
noteworthy that the 2-heterocyclic substrate 1i could also
be well tolerated in the reaction, leading to the expected
product 3i in 76% yield. However, when R1 is H or alkyl
(such as c-C6H11), the reactions did not take place, and
no product was obtained (3j).
Yield of
3y2
Yield of
3y2
2a:1y
3y1
3y1
1:1
2:1
4:1
0
0
0
30
49
67
57
37
0
14
40
65
Then we examined the reactivity of different kinds of
Grignard reagents. When alkyl Grignard reagent, such as
aIsolated yield.
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X. Ye, Z. Yuan, Y. Zhou, Q. Yang, Y. Xie, Z. Deng, and Y. Peng
Vol 000
the amount of the Grignard reagent 2a, because the yield of
compound 3y1(Cl) decreased gradually and eventually, no
product 3y1(Cl) can be detected when the amount of
Grignard 2a was increased to 4.0 equiv; the product 3y2
was isolated in 65% yield.
129.9, 130.0, 130.2, 130.8, 131.3, 133.6, 137.4, 137.5,
138.8, 151.7, 163.4, 168.1; HRMS (ESI): m/z [M+Na]+.
Anal. Calcd. for C21H16N2Na: 319.1211. Found: 319.1207.
4-Phenyl-2-m-tolyl quinazoline (3d) [12].
This com-
pound was obtained as a white solid, yield 48.0 mg (81%),
1
mp 115–117°C; H NMR (400 MHz, CDCl3): δ 2.49 (s,
3H CH3), 7.31–7.33 (m, 1H), 7.41–7.44 (m, 1H),
7.53–7.60 (m, 4H), 7.87–7.89 (m, 3H), 8.11–8.17 (m, 2H),
8.48 (d, J = 7.6 Hz, 2H); 13C NMR (100MHz, CDCl3): δ 21.7,
121.8, 126.0, 127.1, 127.2, 128.6, 128.7, 129.2, 129.3, 130.0,
130.3, 131.5, 133.7, 137.8, 138.3, 152.1, 160.5, 168.4; HRMS
(ESI): m/z [M + Na]+. Anal. Calcd for C21H16N2Na: 319.1211.
Found: 319.1232.
CONCLUSION
In conclusion, we have developed an efficient approach to
4-functionalized quinazolines via the Kumada cross-coupling.
A wide range of 4-functionalized-quinazolines were obtained
in moderate to good yields under mild reaction conditions.
These Ni-catalyzed coupling reactions of quinazoline-4-
tosylates with Grignard reagents provided one of the most
straightforward approaches for the introduction of aryl groups
to quinazolines at C-4 position.
2-(4-Methoxyphenyl)-4-phenyl-quinazoline (3e) [11]. This
compound was obtained as a white solid, yield 48.1 mg
1
(77%), mp 158–160°C; H NMR (400 MHz, CDCl3): δ
3.90 (s, 3H, OCH3), 7.03 (d, J = 8.8 Hz, 2H), 7.49 (t,
J = 8.0 Hz, 1H), 7.57–7.60 (m, 3H), 7.85–7.89 (m, 3H),
8.11 (t, J = 7.6 Hz, 2H), 8.65 (d, J = 8.8 Hz, 2H); 13C
NMR (100 MHz, CDCl3): δ 55.4, 113.8, 121.4, 126.5,
127.0, 128.5, 128.9, 129.9, 130.2, 130.4, 130.9, 133.4,
137.8, 152.1, 160.1, 161.8, 168.2.
EXPERIMENTAL
General procedure for synthesis of 3. To a mixture of
quinazoline-4-tosylates
1 (0.20 mmol) and Grignard
reagent 2 (1.1 equiv) in THF (2.0 mL), Ni(DPPF)Cl2
(5 mol %) and PPh3 (10 mol %) were added subsequently.
The mixture was stirred at 60°C for 45 min. After
completion of the reaction as indicated by TLC, a
saturated aqueous solution of NH4Cl (10 mL) was added,
and the product was extracted with ethyl acetate (10 mL).
The organic layer was dried over MgSO4 and evaporated
the solvent, followed by purification by chromatography
on silica gel to provide the corresponding product 3
(eluent: PE–EtOAc, 50:1 to 20:1).
2-(4-N,N-di-methylaminophenyl)-4-phenyl-quinazoline
(3f).This compound was obtained as a brown solid, yield
48.1 mg (74%), mp 177–179°C; IR (KBr): 3052, 2954,
1
1602, 1529, 1482, 1370, 1173, 946, 777, 702 cmÀ1; H
NMR (400 MHz, CDCl3): δ 3.05 (s, 6H, ÀN(CH3)2), 6.81
(d, J =8.8Hz, 2H), 7.43 (t, J=7.6Hz, 1H), 7.54–7.57 (m,
3H), 7.79–7.82 (m, 1H), 7.86–7.88 (m, 2H), 8.03–8.09 (m,
2H), 8.59 (d, J = 8.8 Hz, 2H); 13C NMR (100MHz, CDCl3):
δ 40.3, 111.7, 121.2, 125.8, 125.9, 127.0, 128.4, 128.5,
128.7, 129.7, 130.0, 130.2, 133.3, 138.0, 152.2, 160.7, 168.0;
HRMS (ESI): m/z [M + H]+. Anal. Calcd. for C22H20N3:
326.1657. Found: 326.1663.
4-Phenyl-2-p-tolyl-quinazoline (3a) [11].
This com-
pound was obtained as a white solid, yield 47.4 mg
1
(80%), mp 189–190°C; H NMR (400 MHz, CDCl3): δ
2.44 (s, 3H, CH3), 7.33 (d, J = 8.0 Hz, 2H, ArH), 7.51
(t, J = 8.0 Hz, 1H, ArH), 7.58–7.60 (m, 3H, ArH),
7.84–7.89 (m, 3H, ArH), 8.11 (t, J = 8.0 Hz, 2H, ArH),
8.58 (d, J = 8.0 Hz, 2H, ArH); 13C NMR (100 MHz,
CDCl3): δ 21.6, 121.6, 126.7, 127.0, 128.5, 128.7, 129.1,
129.3, 129.9, 130.2, 133.5, 135.5, 137.8, 140.7, 152.0,
160.4, 168.2.
2-(4-Fluorophenyl)-4-phenyl quinazoline (3g) [12].
This
compound was obtained as a white solid, yield 50.4 mg
(84%), mp 153–157°C; 1H NMR (400MHz, CDCl3): δ
7.17–7.21 (m, 2H), 7.52–7.62 (m, 4H), 7.86–7.90 (m, 3H),
8.12 (d, J= 4.0 Hz, 2H), 8.70 (dd, J=5.6, 8.4 Hz, 2H); 13C
2
NMR (100MHz, CDCl3): δ 115.4 (d, JC–F =20.0 Hz),
121.6, 126.9 (d, 3JC–F =12.0 Hz), 128.6, 129.1, 130.0, 130.2,
130.7, 130.9, 133.6, 134.4, 137.6, 152.0, 159.3, 163.4 (d, JC–
F = 248.0Hz), 168.4; HRMS (ESI): m/z [M +Na]+. Anal.
Calcd. for C20H13FN2Na: 323.0960. Found: 323.0983.
2,4-Diphenyl quinazoline (3b) [12].
This compound
was obtained as a white solid, yield 45.7 mg (81%), mp
1
122–123°C; H NMR (400 MHz, CDCl3): δ 7.52–7.61
2-(4-Trifluoromethylphenyl)-4-phenylquinazoline
[12]. This compound was obtained as a white solid,
(3h)
(m, 7H), 7.87–7.91 (m, 3H), 8.15 (t, J = 8.4 Hz, 2H),
8.69 (d, J = 8.4 Hz, 2H); 13C NMR (100 MHz, CDCl3): δ
121.7, 126.9, 127.1, 128.4, 128.6, 128.7, 129.2, 129.9,
130.2, 130.5, 133.6, 137.7, 138.2, 152.0, 160.3, 168.3.
4-phenyl-2-o-tolyl quinazoline (3c) [12]. This com-
pound was obtained as a white solid, yield 46.8 mg
yield 61.6 mg (88%), mp 123–126°C; 1H NMR
(400 MHz, CDCl3): δ 7.60–7.62 (m, 4H), 7.76–7.78 (m,
2H), 7.88–7.94 (m, 3H), 8.17 (t, J = 7.6 Hz, 2H), 8.81 (d,
J = 8.0 Hz, 2H); 13C NMR (100MHz, CDCl3): δ 120.9,
121.9, 124.4, 126.1, 126.6, 127.6, 127.9, 128.2, 129.1,
131.5 (q, JC–F = 32.0Hz), 132.8, 136.3, 140.5, 150.8,
157.7, 167.5; HRMS (ESI): m/z [M +Na]+. Anal. Calcd.
for C21H13F3N2Na: 373.0929. Found: 373.0957.
1
(79%), mp 72–74°C; H NMR (400 MHz, CDCl3): δ 2.67
(s, 3H, CH3), 7.34–7.57 (m, 3H), 7.58–7.62 (m, 4H), 7.86–
7.99 (m, 4H), 8.16 (d, J=8.8Hz, 2H); 13C NMR (100MHz,
CDCl3): δ 21.3, 121.0, 126.1, 127.0, 127.3, 128.6, 129.2,
Journal of Heterocyclic Chemistry
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Coupling Reaction for the Synthesis of 2,4-Diarylquinazolines
3
4
2-(Furan-2-yl)-4-phenyl quinazoline (3i) [13].
This
(d, JC–F = 9.0 Hz), 133.6, 133.8 (d, JC–F = 3.0 Hz),
138.1, 152.1, 160.2, 162.7 (d, 1J = 250 Hz), 167.2; HRMS
(ESI): m/z [M + Na]+. Anal. Calcd. for C20H13FN2Na:
323.0960. Found: 323.0957.
2-Phenyl-4-(o-tolyl)quinazoline (3q).
pound was obtained as a white solid, yield 37.9 mg
compound was obtained as a brown solid, yield 41.4 mg
(76%), mp 168–170°C; 1H NMR (400MHz, CDCl3): δ 6.61 (s,
1H, furan H), 7.51–7.59 (m, 5H), 7.70 (s, 1H, furan H),
7.82–7.87 (m, 3H), 8.07 (d, J= 8.0 Hz, 1H), 8.18 (d, J= 8.0 Hz,
1H, Furan H); 13C NMR (100MHz, CDCl3): δ 112.3, 114.4,
121.6, 127.1, 127.2, 128.5, 128.6, 128.9, 130.1, 133.9, 137.2,
145.4, 151.5, 152.8, 153.5, 168.9; HRMS (ESI): m/z [M + Na]+.
Anal. Calcd. for C18H12N2ONa: 295.0847. Found: 295.0847.
This com-
(64%), mp 143–145°C; IR (KBr): 3061, 2957, 1605, 1567,
1540, 1385, 1337, 1258, 1025, 776 cmÀ1
;
1H NMR
(400MHz, CDCl3): δ 2.24 (s, 3H, CH3), 7.39–7.53 (m, 8H),
7.69 (d, J= 8.4 Hz, 1H), 7.88 (t, J= 7.6 Hz, 1H), 8.16 (d,
J= 8.4Hz, 1H), 8.66 (d, J=8.0 Hz, 2H); 13C NMR (100MHz,
CDCl3): δ 19.0 (CH3), 121.6, 124.6, 126.0, 126.1, 127.5,
127.7, 128.0, 128.2, 128.6, 129.5, 129.7, 132.7, 135.4, 135.9,
137.2, 150.4, 159.3, 168.8; HRMS (ESI): m/z [M +Na]+. Anal.
Calcd. for C21H16N2Na: 319.1211. Found: 319.1224.
2-Phenyl-4-(p-tolyl)quinazoline (3l) [12].
This com-
pound was obtained as a white solid, yield 49.7mg (84%),
1
mp 123–124°C; H NMR (400MHz, CDCl3): δ 2.49 (s,
3H, CH3), 7.40 (d, J= 7.6Hz, 2H), 7.49–7.55 (m, 4H), 7.80
(d, J=8.0Hz, 2H), 7.84–7.88 (m, 1H), 8.14 (d, J= 8.8Hz,
2H), 8.69 (d, J=7.6Hz, 2H); 13C NMR (100 MHz, CDCl3):
δ 20.4, 120.6, 125.8, 126.0, 127.5, 127.7, 128.1, 128.2,
129.2, 129.4, 132.4, 133.8, 137.2, 139.1, 150.9, 159.2, 167.2.
4-(4-Methoxyphenyl)-2-phenyl quinazoline (3m) [11]. This
compound was obtained as a white solid, yield 52.4 mg
4-(o-Tolyl)-2-(p-tolyl)quinazoline (3r).
pound was obtained as a white solid, yield 42.1 mg
This com-
(68%), mp 165–167°C; IR (KBr): 3061, 2955, 1537,
1453, 1337, 773, 738cmÀ1; H NMR (400MHz, CDCl3): δ
1
1
(84%), mp 141–142°C; H NMR (400 MHz, CDCl3): δ
2.23 (s, 3H, CH3), 2.44 (s, 3H, CH3), 7.32 (d, J= 8.0 Hz,
2H), 7.37–7.49 (m, 5H), 7.67 (d, J =8.4 Hz, 1H), 7.86
(t, J=7.8Hz, 1H), 8.13 (d, J=8.4Hz, 1H), 8.55
(d, J=8.0Hz, 2H); 13C NMR (100MHz, CDCl3): δ 19.0,
20.5, 121.5, 124.6, 125.8, 126.0, 127.7, 127.9, 128.1, 128.3,
128.6, 129.7, 132.6, 134.5, 135.5, 135.9, 139.7, 150.5, 159.3,
168.7; HRMS (ESI): m/z [M+H]+. Anal. Calcd. for
C22H19N2: 311.1548. Found: 311.1559.
3.86 (s, 3H, OCH3), 7.05 (d, J = 8.0 Hz, 2H), 7.42–7.50
(m, 4H), 7.78–7.84 (m, 3H), 8.06–8.12 (m, 2H), 8.62 (d,
J = 8.0 Hz, 2H); 13C NMR (100 MHz, CDCl3): δ 55.5,
114.0, 121.7, 126.8, 127.1, 128.5, 128.7, 129.2, 130.2,
130.4, 131.9, 133.4, 138.3, 152.1, 160.2, 161.3, 167.7.
2,4-Di-p-tolyl-quinazoline (3n) [8c].
This com-
pound was obtained as a white solid, yield 49.7 mg
1
4-(Thiophen-2-yl)-2-(p-tolyl)quinazoline (3s).
This
(80%), mp 139–140°C; H NMR (400 MHz, CDCl3): δ
compound was obtained as a white solid, yield 41.7 mg
2.44 (s, 3H, CH3), 2.50 (s, 3H, CH3), 7.32 (d, J= 8.0Hz,
2H), 7.40 (d, J=8.0Hz, 2H), 7.51 (t, J= 7.6 Hz, 1H), 7.80
(d, J= 7.6Hz, 2H), 7.86 (t, J= 7.6 Hz, 1H), 8.11–8.14
(m, 2H), 8.58 (d, J = 8.0 Hz, 2H); 13C NMR (100MHz,
CDCl3): δ 21.5, 21.6, 121.7, 126.7, 127.1, 128.7, 129.1,
129.3, 129.4, 130.2, 133.4, 134.9, 135.6, 140.1, 140.7,
152.0, 160.3, 168.2; HRMS (ESI): m/z [M + Na]+. Anal.
Calcd. for C22H18N2Na: 333.1368. Found: 333.1367.
(69%), mp 162–164°C; IR (KBr): 3066, 2955, 1534,
1
1428, 1337, 733, 672cmÀ1; H NMR (400MHz, CDCl3):
δ 2.45 (s, 3H, CH3), 7.28 (t, J=8.8Hz, 1H), 7.34
(d, J=7.2Hz, 2H), 7.57–7.67 (m, 2H), 7.86–7.91
(m, 2H), 8.11 (d, J=8.4Hz, 1H), 8.48 (d, J=8.4Hz, 1H),
8.57 (d, J=8.0Hz, 2H); 13C NMR (100MHz, CDCl3): δ
21.6, 120.5, 126.0, 127.2, 128.1, 128.2, 128.5, 129.4,
130.4, 131.0, 133.5, 135.2, 140.8, 142.1, 152.5, 160.1,
160.3; HRMS (ESI): m/z [M+H]+. Anal. Calcd. for
C19H15N2S: 303.0956. Found: 303.0966.
4-(4-Methoxyphenyl)-2-p-tolyl quinazoline (3o) [8c].
This
compound was obtained as a white solid, yield 55.4 mg
(85%), mp 153–154°C; 1H NMR (400MHz, CDCl3): δ 2.37
(s, 3H, CH3), 3.86 (s, 3H, OCH3), 7.05 (d, J= 8.4 Hz, 2H),
7.26 (d, J=8.0Hz, 2H), 7.45 (t, J= 7.6 Hz, 1H), 7.78–7.83
(m, 3H), 8.02 (d, J=8.0Hz, 1H), 8.08 (d, J= 8.0 Hz, 1H),
8.51 (d, J= 8.0 Hz, 2H); 13C NMR (100 MHz, CDCl3): δ
21.5, 55.5, 114.0, 121.6, 126.6, 127.1, 128.6, 129.1, 129.3,
130.3, 131.9, 133.3, 135.6, 140.6, 152.1, 160.3, 161.2,
167.6; HRMS (ESI): m/z [M+ Na]+. Anal. Calcd. for
C22H18N2NaO: 349.1317. Found: 349.1297.
2-Phenyl-4-(thiophen-2-yl)quinazoline
(3t).
This
compound was obtained as a white solid, yield 38.1 mg
(66%), mp 112–114°C; IR (KBr): 3069, 2956, 1560,
1
1488, 1337, 1260, 1028, 953, 731, 700 cmÀ1; H NMR
(400 MHz, CDCl3): δ 7.27–7.29 (m, 1H), 7.51–7.67
(m, 5H), 7.87–7.93 (m, 2H), 8.13 (d, J = 8.4 Hz, 1H),
8.50 (d, J = 8.4 Hz, 1H), 8.69 (d, J = 7.6 Hz, 2H); 13C
NMR (100 MHz, CDCl3): δ 120.6, 126.0, 127.4, 128.2,
128.6, 129.4, 130.4, 130.5, 130.6, 131.1, 133.6, 137.9,
142.0, 152.5, 160.0, 160.4; HRMS (ESI): m/z [M + H]+.
Anal. Calcd. for C18H13N2S: 289.0799. Found: 289.0812.
4-(4-Fluorophenyl)-2-phenyl quinazoline (3p) [12].
This
compound was obtained as a white solid, yield 46.9 mg
(78%), mp 144–146°C; 1H NMR (400MHz, CDCl3): δ
7.28–7.32 (m, 2H), 7.52–7.57 (m, 4H), 7.89–7.93 (m, 3H), 8.10
(d, J=8.4Hz, 1H), 8.17 (d, J=8.4Hz, 1H), 8.68 (d, J=8.0Hz,
7-Methyl-2,4-diphenyl quinazoline (3u).
This com-
pound was obtained as a white solid, yield 48.0mg (81%),
2
2H); 13C NMR (75MHz, CDCl3): δ 115.5 (d, JC–F=20.0Hz),
mp 176–178°C; IR (KBr): 3065, 2959, 1536, 1486, 1397,
1
1343, 702 cmÀ1; H NMR (400 MHz, CDCl3): δ 2.59
121.6, 126.7, 127.1, 128.6, 128.8, 129.3, 130.6, 132.2
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

X. Ye, Z. Yuan, Y. Zhou, Q. Yang, Y. Xie, Z. Deng, and Y. Peng
Vol 000
(s, 3H, CH3), 7.36 (d, J=8.4Hz, 1H), 7.50–7.58 (m, 6H), 7.88
(t, J=7.2Hz, 2H), 7.93 (s, 1H), 8.00 (d, J=8.4Hz, 1H), 8.68
(d, J=7.6Hz, 2H); 13C NMR (100MHz, CDCl3): δ 22.1,
119.9, 126.7, 128.1, 128.2, 128.5, 128.7, 129.2, 129.3, 129.9,
130.2, 137.9, 138.4, 144.5, 152.3, 160.4, 167.8; HRMS
(ESI): m/z [M+Na]+. Anal. Calcd. for C21H16N2Na:
319.1211. Found: 319.1195.
7-Methyl-4-phenyl-2-(p-tolyl)quinazoline (3v). This com-
pound was obtained as a white solid, yield 49.7 mg (80%),
mp 202–204°C; IR (KBr): 3062, 2959, 1622, 1535, 1488,
1342, 1171, 795, 774, 694cmÀ1; 1H NMR (400 MHz, CDCl3):
δ 2.44 (s, 3H, CH3), 2.60 (s, 3H, CH3), 7.31–7.36 (m, 3H),
7.58–7.59 (m, 3H), 7.87–7.89 (m, 2H), 7.92 (s, 1H), 8.00
(d, J = 7.6 Hz, 1H), 8.57 (d, J = 8.4 Hz, 2H); 13C NMR
(100 MHz, CDCl3): δ 20.5, 21.1, 118.7, 125.7, 126.9,
127.4, 127.5, 128.0, 128.2, 128.8, 129.1, 134.5, 136.8,
139.6, 143.4, 151.2, 159.4, 166.7; HRMS (ESI): m/z
[M + H]+. Anal. Calcd. for C22H19N2: 311.1548. Found:
311.1549.
2-(4′-Methyl-[1,1′-biphenyl]-4-yl)-4-(p-tolyl)quinazoline
(3y2).
This compound was obtained as a yellow solid,
mp 135–137°C; IR (KBr): 3023, 2921, 1487, 1384, 978,
;
761,703cmÀ1 1H NMR (400 MHz, CDCl3): δ 2.40
(s, 3H, CH3), 2.48 (s, 3H, CH3), 7.26 (d, J= 7.2 Hz, 2H),
7.39 (d, J =7.2Hz, 2H), 7.50 (t, J= 7.2 Hz, 1H), 7.58
(d, J=7.6Hz, 2H), 7.73–7.85 (m, 5H), 8.14 (t, J=6.4Hz,
2H), 8.75 (d, J= 8.0 Hz, 2H); 13C NMR (100MHz, CDCl3):
δ 21.2, 21.5, 121.7, 126.8, 127.0, 127.1, 127.2, 129.1,
129.2, 129.3, 129.6, 130.3, 133.5, 135.0, 137.0, 137.5,
137.9, 140.2, 143.1, 152.0, 160.1, 168.3; HRMS (ESI):
m/z [M +Na]+. Anal. Calcd. for C28H22N2Na: 409.1681.
Found: 409.1701.
Acknowledgments. We are grateful to the National Natural Science
Foundation of China (grant no. 21162012 and 21362014), Jiangxi
Provincial Department of Science and Technoloy (for Jiangxi’s
Key Laboratory of Green Chemistry, and no. 20122BAB203007),
and the Science Foundation of Education Department of Jiangxi
province (grant no. GJJ10386 and GJJ12616) for their financial
support.
7-Methyl-2,4-di-p-tolylquinazoline (3w). This com-
pound was obtained as a white solid, yield 52.4mg (81%),
mp 160–162°C; IR (KBr): 3062, 2955, 1610, 1532, 1342,
1
1170, 787, 726cmÀ1; H NMR (400 MHz, CDCl3): δ 2.43
REFERENCES AND NOTES
(s, 3H, CH3), 2.49 (s, 3H, CH3), 2.59 (s, 3H, CH3), 7.31 (d,
J= 8.0 Hz, 3H), 7.39 (d, J= 8.0 Hz, 2H), 7.78 (d, J= 8.0Hz,
2H), 7.90 (s, 1H), 8.01 (d, J= 8.4Hz, 1H), 8.57 (d, J=
8.0Hz, 2H); 13C NMR (100MHz, CDCl3): δ 20.4, 20.5,
21.1, 118.7, 125.7, 126.9, 127.5, 127.8, 128.1, 128.2, 129.1,
134.1, 134.6, 138.9, 139.5, 143.2, 151.2, 159.3, 166.6; HRMS
(ESI): m/z [M +H]+. Anal. Calcd. for C23H21N2: 325.1705.
Found: 325.1713.
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(82%), mp 149–150°C; H NMR (400MHz, CDCl3): δ
7.17–7.20 (m, 1H), 7.52–7.55 (m, 6H), 7.76–7.78
(m, 2H), 7.81–7.86 (m, 1H), 7.98 (d, J=8.4Hz, 1H),
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1
2
2
112.2 (d, JC–F = 22.0Hz), 112.6 (d, JC–F =12.0Hz), 125.4
(d,5JC–F = 2.0 Hz), 127.9, 128.6, 128.8 (d, JC–F =11.0Hz),
3
3
3
129.3 (d, JC–F= 3.0Hz), 129.7, 130.9, 133.6 (d, JC–F=9.0Hz),
4
1
137.5, 140.2 (d, JC–F= 3.0Hz), 153.4, 156.7 (d, JC–F=259.0Hz),
4
160.3, 166.0 (d, JC–F = 4.0 Hz); HRMS (ESI): m/z
[M + Na]+. Anal. Calcd. for C20H13FN2Na: 323.0960.
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2-(4-Chlorophenyl)-4-(p-tolyl)quinazoline (3y1) [8c].
This
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compound was obtained as a yellow solid, mp 156–157°C;
1H NMR (400MHz, CDCl3): δ 2.50 (s, 3H, CH3), 7.39
(d, J=8.0Hz, 1H), 7.45–7.49 (m, 3H), 7.54 (t, J=8.0Hz,
1H), 7.63 (d, J= 8.0 Hz, 1H), 7.67 (s, 1H), 7.87 (t,
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Found: 353.0839.
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

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Journal of Heterocyclic Chemistry
DOI 10.1002/jhet