Csp2-O and C-C Bond Formation via Pd-Catalyzed Coupling Reaction of 2,4-Dichloroquinazoline

Article abstract of DOI:10.1002/jhet.2330

(Chemical Equation Presented) An efficient palladium-catalyzed C-O and subsequent C-C bond formation of 2,4-dichloroquinazoline have been described. The designed strategy results in the synthesis of novel 2-arylated quinazolin-4-ones framework with various aryl/heteroaryl boronic acids in moderate to good yields along with 2,4-diarylated quinazolines. This methodology offers a direct transformation of aryl halides to aryl alcohols/ketone as well as the straight forward application to generate a wide variety of monoaryl and diaryl quinazoline.

Full text of DOI:10.1002/jhet.2330

January 2016 Csp2–O and C–C Bond Formation via Pd-Catalyzed Coupling Reaction of
241
2,4-Dichloroquinazoline
*
Alka Sharma, Vijay Luxami, and Kamaldeep Paul
School of Chemistry and Biochemistry, Thapar University, Patiala 147004, India
*
E-mail: kpaul@thapar.edu
Additional Supporting Information may be found in the online version of this article.
Received May 8, 2014
DOI 10.1002/jhet.2330
Published online 23 March 2015 in Wiley Online Library (wileyonlinelibrary.com).
An efficient palladium-catalyzed C–O and subsequent C–C bond formation of 2,4-dichloroquinazoline
have been described. The designed strategy results in the synthesis of novel 2-arylated quinazolin-
4-ones framework with various aryl/heteroaryl boronic acids in moderate to good yields along with
2,4-diarylated quinazolines. This methodology offers a direct transformation of aryl halides to aryl
alcohols/ketone as well as the straight forward application to generate a wide variety of monoaryl
and diaryl quinazoline.
J. Heterocyclic Chem., 53, 241 (2016).
INTRODUCTION
antitubercular agents [44], and also components of several
approved drugs, such as erlotinib, gefitinib, canertinib,
vandetanib, and lapatinib [45]. Hence, the functionalization
of 2,4-dichloroquinazoline provides an interesting challenge
in medicinal/organic chemistry [46–49].
The formation of C–O bonds, e.g. hydroxylation and
alkoxylation, is one of the fundamental transformations in
organic synthesis. Recently, several research groups re-
ported palladium-catalyzed and copper catalyzed hydrox-
ylation of aryl halides under relatively mild conditions
[1–5], but many such reactions are limited to the couplings
of aromatic iodides and bromides because much higher
energy is required for the oxidative insertion of palladium
catalysts into the C–Cl bond of aryl chlorides [6–13]. The
different functionalizations of halogenated heteroaromatics
in such reactions has been extensively studied [14], for
example, Suzuki, Heck, Negishi reactions in the presence
of palladium catalysts including imidazopyridines [15],
pyridines [16,17], pyrazines [18–20], triazines [21,22],
quinazolines [23,24], cinnolines [25], α-carbolines [26],
imidazopyridazines [27–29], pyrazolopyrimidines [30–33],
triazolopyrimidines [34], pyrrolopyrimidines [35], purines
[36], and uridines [37].
The most widely used method is probably with
2-aminobenzamide or their derivatives under acidic or
basic conditions or in the presence of copper catalyst
(Scheme 1) [50,51]. Recently, Fu and coauthors devel-
oped novel cascade methods starting from 2-halobenzoic
acids or 2-halobenzamides [52–56]. Zhu and coauthors re-
ported alternative approaches via intramolecular C(sp2)-H
carboxamidation reaction of N-arylamidines involving
palladium catalyst [57]. Herein, we have reported the
palladium-catalyzed synthesis of 2-arylated-3H-quinazolin-
4-one and subsequently 2,4-diarylation quinazoline from
cheap and easily available starting material. This synthetic
strategy delivers palladium-catalyzed single-step oxida-
tion of 2,4-dichloroquinazoline at C4 position and
arylation at C2 position with aryl boronic acids (1a) along
with diarylation at C2 and C4 positions (1b) in the pres-
ence of water and mild base.
Quinazoline scaffold is present in a number of biologically
active drugs including potent kinase inhibitors [38,39], anti-
inflammatory [40], antiviral [41], anticancer [42,43],
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A. Sharma, V. Luxami, and K. Paul
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Scheme 1. Major approaches to quinazolin-4(3H)-ones.
RESULTS AND DISCUSSION
toluene and water (Table 1, entry 3) in a sealed tube at
110°C for 12 h to give 2-phenyl-3H-quinazolin-4-one
(1a) and 2,4-diphenylquinazoline (1b) in 75 and 16%
A variety of conditions and combinations of catalyst
systems, bases, and solvents were screened for optimal
reaction conditions for 2,4-dichloroquinazoline (derived
from anthranillic acids and urea followed by chlorination
with POCl3 [58]) with phenyl boronic acid (Table 1).
Interestingly, under most of the reaction conditions, C4
hydroxylated/C2 arylated was the major product, with
varying amounts of C2 and C4 diarylation product resulting
from different aryl/heteroaryl boronic acid. Csp2–O and
C–C coupling reactions between 2,4-dichloroquinazoline
and phenylboronic acid with palladium-based catalysts like
Pd(PPh3)4, Pd(PPh3)2Cl2, and Pd2(dba)3; Pd(PPh3)4 proved
as an effective catalyst for monoarylation (hydroxylated)
and diarylation (Table 1, entries 1–3). Among the variation
of bases such as K2CO3, Na2CO3, NaOtBu, and Cs2CO3,
with Pd(PPh3)4 catalyst (Table 1, entries 3–6), revealed
that K2CO3 turned out to be the most effective base to
give desired products (Table 1, entry 3). Further, catalytic
reactions using Pd(PPh3)2Cl2, better yields were obtained
with Na2CO3 (Table 1, entry 7) than K2CO3, Cs2CO3, or
NaOtBu (Table 1, entries 1, 8–9), but with Pd2(dba)3 and
different bases viz., K2CO3, Na2CO3, NaOtBu, or Cs2CO3,
a significant decrease in yields were observed (Table 1,
entries 2, 10–12). The effect of different solvents like tolu-
ene, acetonitrile, dioxane, and THF along with water as a
cosolvent were also studied, and toluene:H2O (9:1) proved
to be the best solvent system for the reactions (Table 1,
entries 3, 13–15). The arylation and hydroxylation failed
completely when the reaction was carried out in the absence
of palladium catalyst or base (Table 1, entries 16–17).
1
yields respectively. The H NMR spectrum of the 2-phe-
nyl-3H-quinazolin-4-one (1a) revealed the characteristic
broad 1H singlet of NH proton (exchangeable with D2O)
at downfield region of δ 11.20 ppm. Moreover, aromatic
region showed three triplet signals of six protons, one
doublet of one proton, and one multiplet of two protons.
Absence of NH singlet and appearance of 14 protons in
the aromatic region confirmed the formation of 2,
4-diphenylquinazoline (1b).
Thus, number of 2-aryl-3H-quinazolin-4-one and 2,
4-diarylquinazolines was prepared via coupling of 2,
4-dichloroquinazoline with variety of aryl boronic acids
under the optimized reaction conditions as shown in
Table 2. Both monosubstitution at C2 along with hydroxyl-
ation at C4 and disubstitution at C2 and C4 positions of
quinazoline participated well in C–O and C–C bond
forming reaction to afford the desired products.
We also examined the reactions of activated and
nonactivated substituted hetero (aryl) boronic acids
including electron-withdrawing and electron-donating
groups. Phenyl boronic acids with electron withdrawing
para-substituent such as fluoro, chloro, and bromo pro-
duced the corresponding hydroxylated monoaryl (major)
and diaryl (minor) products (Table 2, entries 2–4).
Compared with reaction of 4-bromophenyl boronic acids,
the yields in the case of corresponding 4-fluorophenyl
and 4-chlorophenyl boronic acids were lower indicating
that electron-withdrawing halogen substitution on the
phenyl boronic acid ring has major role for the reactivity.
4-Methoxyphenyl boronic acids with an electron
donating-methoxy group underwent smooth conversion
for monoarylation and diarylation of quinazoline to obtain
Having optimized the reaction conditions, we performed
a palladium-catalyzed reaction of 2,4-dichloroquinazoline
with 2.0 equivalent of phenylboronic acid, 10 mol% Pd
(PPh3)4, 2.0 equivalents of K2CO3 in 9:1 mixture of
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Csp2-O and C-C Bond Formation via Pd-Catalyzed Coupling Reaction of
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Table 1
Optimization of Pd-catalyzed hydroxylation and arylation of 2,4-dichloroquinazoline.
Yield (%)a
Entry
Catalyst
Base
Solvent
Time
1a
1b
1
2
3
4
5
6
7
8
Pd(PPh3)2Cl2
Pd2(dba)3
Pd(PPh3)4
Pd(PPh3)4
Pd(PPh3)4
Pd(PPh3)4
Pd(PPh3)2Cl2
Pd(PPh3)2Cl2
Pd(PPh3)2Cl2
Pd2(dba)3
Pd2(dba)3
Pd2(dba)3
Pd(PPh3)4
Pd(PPh3)4
Pd(PPh3)4
—
K2CO3
K2CO3
K2CO3
Na2CO3
Cs2CO3
NaOtBu
Na2CO3
Cs2CO3
NaOtBu
Na2CO3
Cs2CO3
NaOtBu
K2CO3
K2CO3
K2CO3
K2CO3
-
Toluene:H2O
Toluene:H2O
Toluene:H2O
Toluene:H2O
Toluene:H2O
Toluene:H2O
Toluene:H2O
Toluene:H2O
Toluene:H2O
Toluene:H2O
Toluene:H2O
Toluene:H2O
CH3CN: H2O
THF:H2O
10
14
12
8
8
8
10
10
10
14
14
14
8
10
10
9
42
40
75
60
65
62
44
42
40
40
35
38
68
65
68
-
10
11
16
12
10
10
11
9
9
5
10
5
10
11
12
13
14
15
16
17
8
13
15
10
-
Dioxane:H2O
Toluene:H2O
Toluene:H2O
Pd(PPh3)4
14
-
-
aIsolated yields, — indicates <5%.
Pd–X has accelerated the transmetalation step for hydrox-
ylation (Scheme 2).
75 and 20% yields respectively (Table 2, entry 5).
Selective hydroxylation/monoarylation products were
obtained with 3-methylphenyl boronic acids, thiophen-2-
boronic acids, and furan-2-boronic acids with 60–65%
yields (Table 2, entries 6–8). Finally, naphthalene-1-
boronic acids, hydroxylated/monosubstituted product was
predominant with 55% yield, and only 17% of disubsti-
tuted product was obtained (Table 2, entry 9 and Fig. 1).
CONCLUSION
We have developed an efficient, economical, and practical
method for the synthesis of palladium-catalyzed cross coupling
and subsequent hydroxylation of 2,4-dichloroquinazoline. A
variety of diarylated quinazoline have also been prepared from
activated and nonactivated heteroaryl substrates. Key to the
success is the use of water and boronic acids for unique simul-
taneous C–O and C–C bond formation in the presence of
palladium catalyst. Future work will be directed at further
optimization of this process and on the development of related
coupling reactions.
1
The, H and 13C-NMR as well as mass spectroscopic data
are in accordance with the proposed structures that were
confirmed also by elemental analyses (C, H, N).
The catalytic cycle of the palladium-catalyzed arylation
of quinazoline for C–C bond is thought to proceed via
Suzuki–Miyaura cross-coupling reactions. The process be-
gins with the oxidative addition of an aryl halide to Pd(0)
complex to form an aryl palladium(II)halide intermediate.
The transmetalation with a boronic acid and the reductive
elimination complete the catalytic cycle to form C2
monoarylation and C2/C4 diarylation products of
quinazoline. The cosolvent H2O has subsequently partici-
pated for the oxidation at C4 position for hydroxylation
product. Base is involved in the coordination sphere of
the palladium, and the formation of Ar–Pd–OH from Ar–
EXPERIMENTAL SECTION
General information. All commercially available compounds
were used without purification. Unless otherwise noted, reactions
were performed in oven-dried glassware. All reactions were run
under argon or nitrogen atmosphere. The reactions were carried out
in an oil bath using Microwave Vials (10–15 ml). Melting points
were determined in open capillaries and were uncorrected. 1H
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A. Sharma, V. Luxami, and K. Paul
Vol 53
Table 2
Hydroxylation/monoarylation and diarylation products with different arylboronic acidsa.
Entry
Ar
Products
Time
12
Products (%)
1
1a (75)
1b (16)
2
8
2a (64)
2b (25)
3
8
8
3a (68)
4a (70)
3b (19)
4
4b (trace)
5
8
5a (75)
5b (20)
6
8
6a (65)
6b (trace)
(Continued)
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Csp2-O and C-C Bond Formation via Pd-Catalyzed Coupling Reaction of
2,4-Dichloroquinazoline
245
January 2016
Table 2
(Continued)
Entry
7
Ar
Products
Time
Products (%)
8
7a (60)
8a (60)
9a (55)
7b (trace)
8
9
7
8
8b (trace)
9b (17)
aConditions: 2.0 mmol boronic acid, 10 mol% catalyst, 2.0 mmol base, solvent: cosolvent (9:1), reflux, 110°C, 8–12 h.
compounds were recorded at Waters Micromass Q-Tof Micro
(Milford, MA). The crystal structure was collected on Bruker AXS
KAPPA APEX II CCD diffractometer (Billerica, Massachusttes).
Reactions were monitored by thin layer chromatography (TLC)
with silica plate coated with silica gel HF-254, and column
chromatography was performed with silica gel 60–120/100–
200 mesh. Chloroform/methanol was adopted solvent systems.
General procedure. A vial equipped with stirring bar was
charged with 2,4-dichloroquinazoline (0.2 g, 1.0 mmol), K2CO3
(0.28 g, 2.0 mmol), and boronic acids (2.0 mmol), dissolved in
toluene:H2O (9:1) at 110°C under inert atmosphere. Then,
10 mol% of Pd(PPh3)4 was added, and vial was capped. The
reaction mixture was refluxed for 8–12 h. After the completion
of the reaction (monitored by TLC), the reaction mixture was
cooled and then extract with water and chloroform. Organic
layer was dried over sodium sulfate, filtered, and concentrated
under vacuo to get crude product. The residue was purified by
silica gel (60–120 mesh) column chromatography using hexane:
ethyl acetate (3:2) as eluents to give pure solid.
2-Phenyl-3H-quinazolin-4-one (1a).
This compound was
obtained as light yellow-colored solid (ethanol); mp 238–240°C
(Lit. [56] mp 235–237°C); 167mg, 75% yield; IR (KBr, cmÀ1
)
Figure 1. X-ray structure of compound 9b (CCDC No. 974588) [59].
[Color figure can be viewed in the online issue, which is available at
wileyonlinelibrary.com.]
1
ν: 3359, 3060, 1658, 1334, 1289; H NMR (400MHz, CDCl3): δ
11.20 (1H, s, NH), 8.33–8.31 (1H, d, J = 7.8 Hz), 8.21–8.19 (2H,
t, J = 6.0 Hz), 7.88–7.78 (2H, m), 7.59–7.57 (3H, t, J = 2.28 Hz),
7.52–7.48 (1H, t, J = 6.64 Hz); 13C NMR (100 MHz, CDCl3): δ
163.7, 151.7, 149.5, 135.0, 132.9, 131.8, 129.2, 128.1, 127.4,
126.9, 126.5, 120.8; MS-ESI, m/z: 223.1 (M+ 1)+.
2,4-Diphenyl-quinazoline (1b). This compound was obtained
as white-colored solid (ethanol); mp 118–119°C (Lit. [60] mp 116–
117°C); 45mg, 16% yield; IR (KBr, cmÀ1) ν: 3061, 1336, 1289; 1H
NMR and 13C NMR spectra were recorded on Jeol ECS-400 (1H,
400 MHz; 13C, 100 MHz) spectrometer (Tokyo, Japan) at ambient
temperature, using CDCl3 and DMSO-d6 as solvents. Chemical shifts
are reported in parts per million (ppm) with TMS as internal reference,
and J values are given in hertz. Mass spectra of the synthesized
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A. Sharma, V. Luxami, and K. Paul
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Scheme 2. Plausible reaction mechanism for hydroxylated monoarylation.
NMR (400 MHz, CDCl3): δ 8.70–8.68 (2H, d, J = 7.76 Hz), 8.17–
8.12 (2H, t, J = 8.72 Hz), 7.90–7.89 (3H, t, J = 4.60 Hz), 7.60–7.51
(7H, m); 13C NMR (100 MHz, CDCl3): δ 168.4, 160.3, 152.1,
138.3, 137.8, 133.7, 130.6, 130.3, 130.0, 129.3, 128.8, 128.7,
127.1, 121.8; MS-ESI, m/z: 283.1 (M + 1)+.
2-(4-Fluoro-phenyl)-3H-quinazolin-4-one (2a). This compound
was obtained as light yellow-colored solid (ethanol); mp 238–240°C
(Lit. [61] mp 251–253°C); 154 mg, 64% yield; IR (KBr, cmÀ1) ν:
3350, 3044, 1660, 1286, 1164; 1H NMR (400 MHz, CDCl3): δ 10.62
(1H, s, NH), 8.33–8.31 (1H, d, J= 7.76 Hz), 8.20–8.16 (2H, m),
7.83–7.82 (2H, d, J= 3.28 Hz), 7.54–7.50 (1H, m), 7.27–7.26 (2H, d,
J=5.04Hz); 13C NMR (100 MHz, CDCl3): δ 163.3, 162.4, 150.5,
149.4, 135.1, 131.8, 129.5, 129.4, 128.1, 127.1, 126.5, 126.3, 120.8,
116.5, 116.3; MS-ESI, m/z: 241.1 (M + 1)+.
(400 MHz, DMSO-d6): δ 12.55 (1H, s, NH), 8.17–8.15 (2H, d,
J = 8.24 Hz), 8.11–8.09 (1H, d, J = 7.80Hz), 7.79–7.75 (1H, t,
J = 7.56 Hz), 7.69–7.67 (1H, d, J = 8.28Hz), 7.54–7.52(2H, d,
J = 8.24 Hz), 7.48–7.44 (1H, t, J = 7.32 Hz); 13C NMR (100MHz,
DMSO-d6): δ 162.8, 151.7, 149.1, 136.9, 134.9, 132.0, 130.0,
129.1, 127.9, 127.0, 126.3, 121.5; MS-ESI, m/z: 257.5 (M+ 1)+.
2,4-bis(4-Chloro-phenyl)-quinazoline (3b). This compound
was obtained as white-colored solid (ethanol); mp 198–200°C;
67mg, 19% yield; IR (KBr, cmÀ1) ν: 3048, 1336, 1219, 1014; 1H
NMR (400 MHz, DMSO-d6): δ 8.57–8.55 (2H, d, J = 8.68 Hz),
8.19 (1H, s), 8.09–8.04 (2H, q, J = 8.28 Hz), 8.00–7.96 (1H, t,
J = 7.80 Hz), 7.87–7.85 (2H, d, J = 8.72Hz), 7.67–7.63 (2H, t,
J = 8.72 Hz), 7.55–7.53 (2H, d, J = 8.72Hz); 13C NMR (100MHz,
DMSO-d6): δ 167.4, 158.6, 151.7, 136.7, 136.4, 136.1, 135.8,
134.9, 132.2, 130.3, 129.2, 128.6, 127.1, 121.5; MS-ESI, m/z:
352.1 (M + 1)+; Anal. Calcd for C20H12Cl2N2: C, 68.39; H, 3.44;
N, 7.98. Found: C, 68.32; H, 3.81; N, 8.28.
2,4-bis(4-Fluoro-phenyl)-quinazoline (2b). This compound
was obtained as white-colored solid (ethanol); mp 170–172°C;
79 mg, 25% yield; IR (KBr, cmÀ1) ν: 3047, 1336, 1219, 1146;
2
1H NMR (400 MHz, CDCl3): δ 8.70–8.67 (2H, dd, J = 5.48 Hz,
2-(4-Bromo-phenyl)-3H-quinazolin-4-one (4a). This compound
was obtained as gray-colored solid (ethanol); mp 291–294°C
3J = 3.10 Hz), 8.15–8.08 (2H, dd, 2J = 8.28 Hz, 3J = 3.01 Hz),
7.91–7.87 (3H, m), 7.59–7.55 (1H, t, J = 7.32 Hz), 7.32–7.27
(2H, t, J = 10.08 Hz), 7.22–7.18 (2H, t, J = 8.72 Hz); 13C NMR
(100 MHz, CDCl3): δ 162.6, 161.2, 160.5, 158.7, 158.1, 154.6,
147.3, 129.6, 129.1, 129.0, 127.5, 127.4, 126.1, 126.0, 124.5,
122.5, 122.1, 116.8, 111.2, 110.9, 110.7; MS-ESI, m/z: 319.1
(M + 1)+; Anal. Calcd for C20H12F2N2: C, 75.46; H, 3.80; N,
8.80. Found: C, 75.30; H, 3.49; N, 9.03.
(Lit. [51] mp 295–296°C); 212 mg, 70% yield; IR (KBr, cmÀ1
)
ν: 3375, 3034, 1656, 1384, 1340, 504; 1H NMR (400 MHz,
DMSO-d6): δ 11.18 (1H, s, NH), 7.93–7.89 (2H, t, J = 8.24 Hz),
7.86 (1H, s), 7.73–7.71 (2H, dd, 2J = 6.88 Hz, 3J = 1.84 Hz),
7.60 (2H, s), 7.57–7.56 (1H, d, J = 4.60 Hz); 13C NMR
(100 MHz, DMSO-d6): δ 163.9, 161.8, 160.7, 135.8, 134.6,
134.5, 131.5, 131.4, 128.3, 128.2, 127.0, 126.8, 125.3, 120.9;
MS-ESI, m/z: 302.1 (M + 1)+.
2-(4-Chloro-phenyl)-3H-quinazolin-4-one (3a). This compound
was obtained as light yellow-colored solid (ethanol); mp 298–
300°C (Lit. [51] mp 299–300°C); 175 mg, 68% yield; IR (KBr,
cmÀ1) ν: 3341, 3046, 1671, 1342, 1281, 938; 1H NMR
2-(4-Methoxy-phenyl)-3H-quinazolin-4-one (5a).
This
compound was obtained as light yellow-colored solid (ethanol);
mp 245–247°C (Lit. [51] mp 247–248°C); 190 mg, 75% yield;
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247
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IR (KBr, cmÀ1) ν: 3350, 3061, 1672, 1298, 1242, 1026; 1H NMR
(400 MHz, CDCl3): δ 11.02 (1H, s, NH), 8.32–8.31 (1H, d,
J = 6.88 Hz), 8.19–8.16 (2H, t, J = 6.88 Hz ), 7.80–7.79 (2H, t,
J = 3.24 Hz), 7.50–7.48 (1H, m), 7.13–7.07(2H, m), 3.92 (3H, s,
OCH3); 13C NMR (100 MHz, CDCl3): δ 163.2, 162.5, 151.1,
149.6, 134.8, 131.8, 130.2, 128.8, 127.8, 126.4, 126.4, 125.0,
114.5, 113.9, 113.8, 55.5; GC-MS: 252.2 (M)+
Acknowledgment. We wish to thank UGC, New Delhi (41-322/
2012, SR) for providing funds. We wish to thank IISER, Mohali and
Punjab University, Chandigarh for carrying out crystallographic and
mass analysis respectively.
REFERENCES AND NOTES
2,4-bis(4-Methoxy-phenyl)-quinazoline (5b). This compound
was obtained as white-colored solid (ethanol) [60]; mp 115–117°C;
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2012, 14, 3688.
1
68 mg, 20% yield; IR (KBr, cmÀ1) ν: 3100, 1291, 1254, 1137; H
NMR (400 MHz, CDCl3): δ 8.17–8.15 (1H, d, J= 8.24 Hz), 8.02–
8.00 (2H, d, J= 8.28 Hz), 7.92–7.83 (2H, m), 7.80–7.77 (2H, d,
J= 8.68 Hz), 7.61–7.58 (2H, t, J = 7.32 Hz), 7.11–7.06 (3H, t,
J= 8.20 Hz), 3.90 (6H, s, OCH3); 13C NMR (100 MHz, CDCl3): δ
171.1, 161.9, 157.1, 153.1, 134.8, 132.1, 128.4, 128.1, 127.9,
127.6, 121.6, 114.3, 55.6; MS-ESI, m/z: 343.2 (M+1)+.
[2] Xiao, Y.; Xu, Y.; Cheon, H. S.; Chae, J. J Org Chem 2013, 78, 5804.
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2-m-Tolyl-3H-quinazolin-4-one (6a). This compound was
obtained as light yellow-colored solid (ethanol); mp 210–212°C
(Lit.[51] mp 210–211°C); 154 mg, 65% yield; IR (KBr, cmÀ1
)
1
ν: 3290, 3044, 1675, 1305, 1248; H NMR (400 MHz, CDCl3):
δ 10.96 (1H, s, NH), 8.34–8.32 (1H, d, J = 7.32 Hz), 8.03 (1H,
s), 7.97–7.95 (1H, d, J = 7.80 Hz), 7.84–7.81 (2H, m), 7.53–7.39
(3H, m), 2.51 (1H, s, CH3); 13C NMR (100 MHz, CDCl3): δ
163.5, 151.7, 149.4, 138.8, 134.7, 132.6, 132.4, 128.9, 127.8,
126.6, 126.2, 124.2, 120.7, 21.4; MS-ESI, m/z: 237.3 (M + 1)+.
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3047.
2-(Thiophen-2-yl)-3H-quinazolin-4-one (7a).
This compound
[12] Littke, A. F.; Fu, G. C. Angew Chem Int Ed 2002, 41, 4176.
[13] Roy, D.; Mom, S.; Beauperin, M.; Doucet, H.; Hierso, J. C.
Angew Chem Int Ed 2010, 49, 6650.
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Martinelli, M. J. J Org Chem 2007, 72, 5104.
was obtained as yellow-colored solid (ethanol); mp 277–280°C (Lit.
[56] mp 275–276°C); 137 mg, 60% yield; IR (KBr, cmÀ1) ν: 3365,
1
2991, 1681, 1375, 1252, 1057; H NMR (400 MHz, DMSO-d6): δ
2
3
10.96 (1H, s, NH), 7.71–7.70 (2H, dd, J=7.36Hz, J=2.76Hz),
7.56–7.38 (3H, m), 7.09–7.01 (2H, m); 13C NMR (100 MHz,
DMSO-d6): δ 162.9, 150.4, 140.7, 134.3, 131.4, 131.3, 128.3, 128.2,
126.7, 126.7, 121.9, 115.2, 114.3; MS-ESI, m/z: 229.2 (M + 1)+.
2-Furan-2-yl-3H-quinazolin-4-one (8a).
This compound
[17] Bianchini, C.; Giambastiani, G.; Luconi, L.; Meli, A. Coordin
Chem Rev 2010, 254, 431.
was obtained as light-yellow colored solid (ethanol); mp 217–
219°C (Lit. [50] mp 219–220°C); 127 mg, 60% yield; IR (KBr,
cmÀ1) ν: 3325, 3116, 1609, 1337, 1280, 1106; 1H NMR
(400 MHz, CDCl3): δ 11.43 (1H, s, NH), 8.95 (1H, d,
J = 8.68 Hz), 7.99–7.90 (2H, m), 7.83 (1H, s), 7.69 (2H, d,
J = 3.68 Hz), 6.72–6.70 (1H, m); 13C NMR (100 MHz, CDCl3);
δ 157.8, 157.0, 153.8, 152.5, 147.0, 139.4, 134.9, 128.3, 128.2,
127.2, 119.5, 118.3, 114.2, 112.9; GC-MS: 212.3 (M)+.
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2013, 11, 3583.
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Florent, J. C.; Bertounesque, E. Eur J Med Chem 2010, 45, 244.
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R. B.; Drew, L.; Ezhuthachan, J.; Gero, T. W.; Ogoe, C. A.; Omer, C. A.;
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2-Naphthalen-1-yl-3H-quinazolin-4-one (9a). This compound
was obtained as light yellow-colored solid (ethanol); mp 291–
293°C (Lit. [52] mp 289–292°C); 150 mg, 55% yield; IR (KBr,
1
cmÀ1) ν: 3433, 2981, 1669, 1284, 1252; H NMR (400 MHz,
DMSO-d6): δ 12.59 (1H, s, NH), 8.27–8.21 (2H, m), 8.06–8.04
(1H, d, J = 8.24 Hz), 7.98–7.90 (2H, dd, 2J = 5.48 Hz,
3J = 1.84 Hz), 7.83–7.74 (1H, m), 7.64–7.55 (4H, m); 13C NMR
(100 MHz, DMSO-d6): δ 162.5, 154.1, 149.2, 134.8, 133.6,
132.2, 130.8, 130.8, 128.7, 128.1, 127.9, 127.4, 127.1, 126.7,
126.3, 125.7, 125.4, 121.8; MS-ESI, m/z: 273.1 (M + 1)+.
2,4-Di-naphthalen-1-yl-quinazoline (9b).
This compound
was obtained as white-colored solid (ethanol) [60]; mp 160–
163°C; 65 mg, 17% yield; IR (KBr, cmÀ1) ν: 2977, 1335, 1249;
1H NMR (400 MHz, CDCl3): δ 8.84–8.82 (1H, d, J = 8.24 Hz),
8.28–8.23 (2H, dd, 2J = 7.32 Hz, 3J = 2.80 Hz), 8.05–8.03 (1H,
d, J = 8.24 Hz), 7.98–7.90 (4H, m), 7.71–7.49 (10H, m); 13C
NMR (100 MHz, CDCl3): δ 169.4, 163.0, 151.3, 134.8, 134.3,
133.8, 131.7, 131.4, 130.4, 130.0, 129.9, 129.1, 128.6, 128.0,
127.6, 127.5, 126.9, 126.9, 126.4, 126.1, 125.9, 125.8, 125.4,
125.2, 123.0; MS-ESI, m/z: 383.2 (M + 1)+.
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