Copper-Catalyzed Synthesis of 2-Arylquinazolinones from 2-Arylindoles with Amines or Ammoniums

Article abstract of DOI:10.1021/acs.joc.5b00957

A novel copper-catalyzed synthesis of quinazolinones from easily available 2-arylindoles and amines or ammoniums has been developed, which provided various quinazolinones in up to 99% yields for 43 examples. This strategy features tolerance of a wide range of functional groups, easily available starting materials, simple operation, mild reaction conditions, and environmental friendliness.

Full text of DOI:10.1021/acs.joc.5b00957

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Article
Copper-Catalyzed Synthesis of 2-Arylquinazolinones
from 2-Arylindoles with Amines or Ammoniums
Yadong Feng, Yudong Li, Guolin Cheng, Lianhui Wang, and Xiuling Cui
J. Org. Chem., Just Accepted Manuscript • DOI: 10.1021/acs.joc.5b00957 • Publication Date (Web): 22 Jun 2015
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Copper-Catalyzed Synthesis of 2-Arylquinazolinones from
2-Arylindoles with Amines or Ammoniums
8
9
Yadong Feng, Yudong Li, Guolin Cheng, Lianhui Wang, and Xiuling Cui*
Key Laboratory of Xiamen Marine and Gene Drugs, Institutes of Molecular Medicine
and School of Biomedical Sciences, Huaqiao University & Engineering Research
Center of Molecular Medicine, Ministry of Education, Xiamen 361021, China
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A novel copper-catalyzed synthesis of quinazolinones from easily available
2-arylindoles and amines or ammoniums has been developed, which provided various
quinazolinones in up to 99% yields for 43 examples. This strategy features tolerance
of a wide range of functional groups, easily available starting materials, simple
operation, mild reaction conditions and environmental friendliness.
■ INTRODUCTION
Quinazolinone is a ubiquitous and significant heterocycle and widely exists in
natural alkaloids and pharmaceuticals.[1] Various quinazolinones have been found to
be with bioactivities,[1-9] such as antibacterial,[2] antifungal,[3] antimalarial,[4]
anticancer,[5] antihypertensive,[6] antitubercular,[7] and anticonvulsant.[8]
As a result, numerous methods for synthesis of quinazolinone derivatives have
been developed.[10] Conventionally, such a structure was synthesized from the
condensation of halobenzoic acids, halobenzamides, aminobenzamides,
nitrobenzamides with amidines, benzyl alcohols, benzylamine, acid amides or amino
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acids. Metal-catalyzed insertion of carbon monoxide (CO) or isocyanide has provided
an alternative pathway to quinazolinones in moderate yields.[11] Although efficient as
documented in the literature, development of a straightforward, mild, economic and
environmentally friendly method for the preparation of quinazolinones from easily
available substrates is still highly desirable.
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Herein, we present a copper-catalyzed expansion reaction of 2-arylindoles with
amines or ammoniums, affording both of 2-substituted and 2,3-disubstituted
quinazolinones, simultaneously. In this catalytic process, molecular oxygen has been
significantly used as an oxidant. The corresponding products were obtained in good to
excellent yields with H2O as the sole by-product. In comparison with the existing
methods in the literature, this approach features with easy operation, cheap and easily
available starting material, high efficiency, environmentally friendliness and tolerance
of broad range of substrates. Moreover, it is applied to synthsize both of 2-substituted
and 2,3-disubstituted quinazolinones. To the best of our knowledge, this is the first
example of constructing quinazolinones from easily available 2-arylindoles and
amines or ammoniums via Baeyer-Villiger oxidation expansion using O2 as a clean
oxidant, followed by dehydration condensation ingeniously.
■ RESULTS AND DISCUSSION
At the outset of our studies, 2-phenyl-1H-indole (1a) and phenethylamine (2a)
were chosen as model substrates to optimize the reaction conditions. Initially, the
o
reaction was carried out in the presence of CuBr2 (5 mol%) in NMP at 80 C, and
afforded a 77% isolated yield of 3aa (Table 1, entry 1). In the absence of catalysts, the
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desired product 3aa could not be detected (Table 1, entry 2). Only trace amount of the
target product 3aa was observed in the absence of O2 or using t-BuOOH, H2O2 or
m-CPBA as an oxidant under air (Table 1, entries 3-6). Copper salts, such as
Cu(OAc)2, CuBr, CuCl and CuI were further screened and showed that CuBr favored
this transformation, probably due to its stronger electronegativity as well as better
ionization power, and the catalytic effect of freshly generated Cu2+ is better (Table 1,
entries 7-10 vs entry 1). Moreover, 1-methyl-2-pyrrolidinone (NMP) was proved to be
the best solvent and gave the desired product 3aa in 96% (Table 1,entry 8 vs entries
11-13). However, only 58% isolated yield of 3aa could be afforded using dried NMP.
Addition of 10 equiv of H2O resulted in 85% yield, which indicated that water in this
reaction system play an important role (Table 1, entries 14-15). The yield of 3aa
decreased with increasing or decreasing the reaction temperature (Table 1, entries
16-19 vs entry 8) as well as reducing the reaction time (Table 1, entries 20−21).
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Table 1. Optimization of the reaction of 1a with 2aa
O
NH2
catalyst,
N
+
solvent, T, O2
N
H
N
2a
3aa
1a
Entry
1
Catalyst
Solvent Temp (oC) Time (h) Yieldb (%)
CuBr2
-
NMP
NMP
NMP
NMP
NMP
80
80
80
80
80
24
24
24
24
24
77
2
No
3c
CuBr2
CuBr2
CuBr2
trace
trace
trace
4d
5e
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6f
7
CuBr2
Cu(OAc)2
CuBr
CuCl
CuI
NMP
NMP
NMP
NMP
NMP
DMSO
THF
80
80
80
80
80
80
80
80
80
80
60
70
90
100
80
80
24
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24
24
24
24
24
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18
12
trace
69
8
96
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9
91
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14g
15h
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20
21
73
CuBr
CuBr
CuBr
CuBr
CuBr
CuBr
CuBr
CuBr
CuBr
CuBr
CuBr
47
trace
trace
58
toluene
NMP
NMP
NMP
NMP
NMP
NMP
NMP
NMP
85
62
78
84
76
83
55
a Reaction conditions: 1a (0.25 mmol), 2a (0.5 mmol), catalyst (5 mol %), solvent
(2.0 mL), under O2 atmosphere (1 atm); b Isolated yield; c Under air; d Under air with
t-BuOOH (3 eq); e Under air with H2O2 (3 eq); f Under air with m-CPBA (3 eq); g
Using dried NMP; h Using dried NMP with H2O (10 eq).
With the optimized condition in hand, the scope of indoles was first investigated.
As shown in Scheme 1, Methyl group at ortho-, meta- and para-position of 2-phenyl
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in 2-aryl-1H-indole provided the corresponding products 3ab-3ad in 76%, 85% and
84% yields, respectively, which indicated that steric effect of 2-aryl groups did not
impact on this transformation obviously. Halogen groups, such as F, Cl, and Br, were
well-tolerated (3ae-3ag, and 3aj), which made this reaction particularly attractive for
increasing the molecular complexity by various transition-metal-catalyzed
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cross-coupling
reactions.
Both
of
2-(4-methoxyphenyl)-1H-indole
and
2-(4-trifluoromethylphenyl)-1H-indole proceeded well to give the corresponding
products 3ah and 3ai in 98% and 90% yields, respectively, which suggested electron
density in 2-aryl moieties also did not affect on this transformation significantly.
Furthermore, 2-naphthylindole was a suitable substrate as well, and provided the
corresponding product in 51% yield (3ak). Moreover, various substituents at C5 or C6
position of indoles, such as methyl, halo and isopropyl groups, could give the
corresponding products in satisfactory yields (74%-90%) (3al-3ar).
Scheme1. Scope of Indolea
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O
N
O
N
O
N
O
N
N
N
N
N
8
9
3ad
(84%)
3aa
3ac
(96%)
N
3ab
(85%)
N
(76%)
N
O
O
O
O
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N
N
N
N
N
OCH3
Cl
Br
F
3ae
3af
3ag
3ah
(98%)
(86%)
(93%)
N
(84%)
N
O
O
O
O
N
N
N
N
N
N
CF3
Cl
(65%)
Cl
3ak
3al
(87%)
3ai
(51%)
(90%)
O
3aj
O
N
O
F
Cl
N
N
N
N
N
3am
3an
3ao
(82%)
(74%)
(90%)
O
O
O
Br
N
N
N
F
N
N
N
3ap
(81%)
3ar
(84%)
3aq
(80%)
a Reaction conditions: 1 (0.25 mmol), 2a (0.5 mmol), CuBr (5 mol %), NMP (2 mL),
under O2 atmosphere (1 atm), 80 oC, 24 h.
Thereafter, we investigated a range of differently decorated amines (2b-2i)
(Scheme 2). Benzylamine, benzedrine, ethylamine, n-propylamine and n-butylamine
could be smoothly converted into the corresponding products in moderate to good
yields (60%-89%) (3bb and 3be-3bh). The electron density in phenyl of benzylamine
had a slight effect on this conversion. For instance, 4-tert-butyl benzylamine and
4-trifluoromethyl benzylamine provided the desired products 3bc and 3bd in 82% and
72% yields, respectively. Notably, long-chain dodecylamine could also be converted
into corresponding product in 60% yield (3bi). However, aniline and amines with
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large steric hindrance at N atom, such as tert-butylamine, could not be suitable
substrate for this transformation.
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Scheme 2. Scope of Aminea
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O
N
O
N
O
N
N
N
N
CF3
3bb (78%)
3bc (82%)
3bd (72%)
O
O
O
N
N
N
N
N
N
3bg (71%)
3be (80%)
3bf (89%)
O
O
N
N
N
N
3bh (85%)
3bi (60%)
a Reaction conditions: 1a (0.25 mmol), 2b-2i (0.5 mmol), CuBr (5 mol %), NMP (2
mL), under O2 atmosphere (1 atm), 80 oC, 24 h.
To further demonstrate the potential application of this protocol in organic
synthesis,
we
explored
this
strategy
for
the
preparation
of
2-phenylquinazolin-4(3H)-ones from indoles and ammoniums (Scheme 3). Various
indoles were well-tolerated in this reaction, affording the corresponding products in
good to excellent yields. In addition, ammoniums, such as NH4Cl and NH4HCO3,
could be used as efficient nitrogen source as well, and give the corresponding product
3ca in 55% and 78% yield, respectively (Scheme 4). To prove the practicality of this
ingenious
reaction
system,
a
gram-scale
synthesis
of
the
2-phenylquinazolin-4(3H)-one 3ca was performed. When 0.93 g 2-phenyl-1H-indole
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(1a) and 2.0 g NH3 (aq) (4) were loaded, 0.95 g of the corresponding product (3ca)
was obtained in 86% yield. Easy operation and high efficiency made this reaction
possess extensive applications in organic synthesis as well as in pharmaceutical
industry.
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Scheme 3. Reaction of Indoles with Ammoniuma
O
CuBr (5 mol%)
NH
R1
R1
+ NH3(aq)
NMP, O2, 80 o
C
R2
N
H
N
R2
3ca-3cq
1
4
a Reaction conditions: 1 (0.25 mmol), 4 (0.10 g), CuBr (5 mol %), NMP (2 mL), under
O2 atmosphere (1 atm), 80 oC, 24 h.
Scheme 4. Reaction of 2-Phenyl-1H-Indole (1a) with Ammoniums.
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Yamashita and Guan’s group has reported that 2-arylindole 1 could be converted
into lactone via Baeyer-Villiger oxidation reaction.[12a, 12b] To gain insight into the
reaction mechanism, several control experiments were conducted (Scheme 5). Firstly,
lactone 5a was synthesized from 2-arylindole catalysed by CuCl under O2 atmosphere.
Then, 5a reacted with NH3(aq) under the standard condition, product 3ca was
obtained in almost quantitative yield. On the other hand, when amine 2j was
introduced into the reaction, compound 6j was afforded as a main product and could
not be converted into the desired product 3bj, possibly due to the large steric
hindrance. The parallel experiments were performed using CuBr2 and CuBr as
catalyst for the model reaction under the standard reaction conditions. The reactions
were followed by GC. These results revealed that the catalytic activity of CuBr was
higher than CuBr2 and both exhibited an induction period (25 min) (see Fig 1 in
supporting information). CuBr showed higher activity than CuBr2. Based on above
results and literature,[12] a possible reaction mechanism was proposed and shown in
Scheme 6. Initially, compound 5 was formed via copper-catalyzed aerobic
Baeyer-Villiger oxidation reaction of 1 mediated by Cu, which was followed by
hydrolysis to give carboxylic acid 7. Subsequently, amination reaction of carboxylic
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acid 7 with amine 2 efficiently provided the amide 8, followed by dehydration
condensation to generate corresponding products 3.
7
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9
Scheme 5. Control Experiments.
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Scheme 6. A Plausible Reaction Mechanism.
O
O
CuBr (5 mol%), O2
hydrolysis
R2
R1
R2
O
OH
R1
R1
N
H
Beayer-Villiger
Oxidation
NH
R2
N
1
7
5
O
NH2-R3
-H2O
2
O
O
N
R3
NH R3
R1
-H2O
N
R1
NH
R2
R2
8
3
O
■ CONCLUSION
In summary, we have developed a simple and efficient copper-catalyzed reaction
for the construction of quinazolinones starting from 2-arylindoles. Cheap and easily
available CuBr, 2-arylindoles and amines or ammoniums were used as the catalyst
and starting materials, respectively. Moreover, both of 2-substituted and
2,3-disubstituted could afforded, economically and environmentally friendly O2 was
employed as an oxidant in this strategy. In comparison with the existing methods in
the literature, the present approach features high efficiency, environmentally
friendliness, tolerance of broad range of substrates, high atomic economy, and easy
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operation. To the best of our knowledge, there is first example of constructing
quinazolinones from easily available 2-arylindoles and amines or ammoniums via
sequential Baeyer-Villiger oxidation expansion under O2 together with continuous
dehydration condensation ingeniously.
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■ EXPERIMENTAL SECTION
General Methods. All commercial materials and solvents were used directly
without further purification. Melting points were determined on a melting point
1
apparatus and were uncorrected. H and 13C{1H} NMR spectra were measured on a
400 MHz spectrometer (1H 400 MHz, 13C 100 MHz) using CDCl3 or DMSO-d6 as the
solvent with tetramethylsilane (TMS) as the internal standard at room temperature.
HRMS ESI spectra were obtained on Q-TOF Spectrometer.
Preparation of Quinazolinones 3. A mixture of 2-arylindoles 1 (0.25 mmol),
amine 2 (0.5 mmol) or ammonium 4 (0.10 g), and CuBr (5 mol %) in NMP (2 mL)
o
was stirred at 80 C under oxygen for 24 h. After cooling to room temperature, the
reaction mixture was poured into water and extracted with EtOAc. The organic layer
was washed with brine, dried over MgSO4. purification by column chromatography
on silica gel using petroleum ether/ethyl acetate (10:1 to 5:1) as the eluent delivered
the desired products 3..
3-Phenethyl-2-phenylquinazolin-4(3H)-one (3aa).10w Eluent: petroleum ether/
ethyl acetate (10:1). White solid. Yield: 96% (78 mg): mp 198-200 oC. 1H NMR (400
MHz, DMSO - d6): δ 8.24 (d, J = 8.0 Hz, 1H), 7.94 – 7.80 (m, 1H), 7.68 (d, J = 8.1
Hz, 1H), 7.63 – 7.48 (m, 6H), 7.25 – 7.12 (m, 3H), 6.92 – 6.72 (m, 2H), 4.1(t, J = 7.8
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Hz, 2H), 2.83 (t, J = 7.8 Hz, 2H); 13C NMR (100 MHz, DMSO-d6) δ 161.1, 155.9,
146.8, 137.8, 135.2, 134.5, 129.6, 128.5, 128.3(overlapped), 127.9, 127.2, 127.0,
126.5, 126.1, 120.4, 46.9, 33.7.
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3-Phenethyl-2-(o-tolyl)quinazolin-4(3H)-one (3ab).10x Eluent: petroleum ether/
ethyl acetate (10:1). Colorless oil. Yield: 76% (65 mg). 1H NMR (400 MHz, CDCl3) δ
8.39 (d, J = 8.0 Hz, 1H), 7.83 – 7.72 (m, 2H), 7.59 – 7.52 (m, 1H), 7.44 (t, J = 7.2 Hz,
1H), 7.33 (t, J = 7.6 Hz, 2H), 7.24 – 7.15 (m, 4H), 6.86 (dd, J = 7.2, 2.0 Hz, 2H),
4.47 – 4.35 (m, 1H), 3.73 – 3.59 (m,1H), 3.00 – 2.89 (m, 1H), 2.85 – 2.74 (m, 1H),
2.21 (s, 3H); 13C NMR (100 MHz, CDCl3) δ 162.0, 155.7, 147.2, 137.7, 135.3, 134.7,
134.4, 130.6, 129.9, 128.7, 128.5, 127.8, 127.5, 127.1, 126.7, 126.6, 126.2, 121.0,
47.2, 34.5, 19.2.
3-Phenethyl-2-(m-tolyl)quinazolin-4(3H)-one (3ac).10x Eluent: petroleum ether
/ethyl acetate (10:1). White solid. Yield: 85% (72 mg): mp 128-130 oC. 1H NMR (400
MHz, CDCl3) δ 8.37 (d, J = 8.0 Hz, 1H), 7.83 – 7.70 (m, 2H), 7.57 – 7.49 (m, 1H),
7.38 (t, J = 7.5 Hz, 1H), 7.32 (d, J = 7.7 Hz, 1H), 7.19 (dd, J = 6.8, 3.8 Hz, 4H), 7.13
(s, 1H), 6.89 (dd, J = 6.5, 2.8 Hz, 2H), 4.19 (t, J = 7.8 Hz, 2H), 2.94 (t, J = 7.8 Hz,
2H), 2.40 (s, 3H);13C NMR (100 MHz, CDCl3) δ 162.2, 156.4, 147.2, 138.7, 137.8,
135.2, 134.4, 130.5, 128.8, 128.5(overlapped), 128.3, 127.5, 127.0, 126.7, 126.6,
124.7, 120.9, 47.6, 34.7, 21.4.
3-Phenethyl-2-(p-tolyl)quinazolin-4(3H)-one (3ad).10x Eluent: petroleum ether/
ethyl acetate (10:1). White solid. Yield: 84% (71 mg): mp 168-170 oC. 1H NMR (400
MHz, CDCl3) δ 8.36 (d, J = 8.0 Hz, 1H), 7.84 – 7.69 (m, 2H), 7.55 – 7.49 (m, 1H),
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7.33 – 7.27 (m, 4H), 7.23 – 7.14 (m, 3H), 6.91 (dd, J = 7.1, 2.1 Hz, 2H), 4.21 (t, J =
7.8 Hz, 2H), 2.92 (t, J = 7.8 Hz, 2H), 2.45 (s, 3H);13C NMR (100 MHz, CDCl3) δ
162.2, 156.3, 147.2, 139.9, 137.8, 134.3, 132.5, 129.3, 128.8, 128.5, 127.7, 127.5,
126.9, 126.7, 126.6, 120.9, 47.5, 34.7, 21.4.
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2-(4-Fluorophenyl)-3-phenethylquinazolin-4(3H)-one (3ae).10x Eluent:
petroleum ether/ ethyl acetate (10:1). White solid. Yield: 86% (74 mg): mp 177-178
oC. 1H NMR (400 MHz, CDCl3) δ 8.37 (d, J = 8.0 Hz, 1H), 7.83 – 7.75 (m, 1H), 7.72
(d, J = 7.9 Hz, 1H), 7.55 (t, J = 7.5 Hz, 1H), 7.35 – 7.28 (m, 2H), 7.24 – 7.11 (m, 5H),
6.88 (dd, J = 6.4, 2.8 Hz, 2H), 4.21 (t, J = 7.8 Hz, 2H), 2.92 (t, J = 7.8 Hz, 2H);13C
NMR (100 MHz, CDCl3) δ 163.3 (d, JC-F = 250.0 Hz), 162.1, 155.2, 147.0, 137.6,
134.5, 131.5 (d, JC-F= 3.6 Hz), 130.0(d, JC-F= 8.5 Hz), 128.8, 128.7, 127.5, 127.2,
126.8, 126.7, 120.9, 115.9 (d, JC-F= 22.0 Hz), 47.6, 34.6.
2-(4-Chlorophenyl)-3-phenethylquinazolin-4(3H)-one (3af).10x Eluent:
petroleum ether/ethyl acetate (10:1). White solid. Yield: 93% (84 mg): mp 156-157 oC.
1H NMR (400 MHz, CDCl3) δ 8.37 (d, J = 8.0 Hz, 1H), 7.82 – 7.75 (m, 1H), 7.71 (d,
J = 7.9 Hz, 1H), 7.55 (t, J = 7.5 Hz, 1H), 7.44 (t, J = 5.3 Hz, 2H), 7.26 – 7.16 (m, 5H),
6.89 (dd, J = 6.4, 2.9 Hz, 2H), 4.21 (t, J = 7.8 Hz, 2H), 2.93 (t, J = 7.8 Hz, 2H); 13C
NMR (100 MHz, CDCl3) δ 162.1, 155.1, 147.0, 137.6, 136.0, 134.5, 133.7, 129.3,
129.0, 128.8, 128.7, 127.5, 127.3, 126.8(overlapped), 120.9, 47.6, 34.6.
2-(4-Bromophenyl)-3-phenethylquinazolin-4(3H)-one (3ag). Eluent:
petroleum ether/ethyl acetate (10:1). White solid. Yield: 84% (84 mg): mp 133-134 oC.
1H NMR (400 MHz, CDCl3) δ 8.37 (d, J = 7.9 Hz, 1H), 7.78 (t, J = 7.6 Hz, 1H), 7.71
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(d, J = 8.0 Hz, 1H), 7.60 (d, J = 8.2 Hz, 2H), 7.54 (t, J = 7.5 Hz, 1H), 7.24 – 7.13 (m,
5H), 6.89 (dd, J = 6.2, 2.7 Hz, 2H), 4.25 – 4.13 (m, 2H), 2.97 – 2.87 (m, 2H); 13C
NMR (100 MHz, CDCl3) δ 162.0, 155.1, 147.0, 137.6, 134.5, 134.2, 131.9, 129.5,
128.8, 128.7, 127.5, 127.3, 126.8(overlapped), 124.2, 120.9, 47.6, 34.5; HRMS (ESI)
m/z calcd for C22H17BrN2O [M + H]+ 405.0603, found 405.0597.
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2-(4-Methoxyphenyl)-3-phenethylquinazolin-4(3H)-one (3ah).10x Eluent:
petroleum ether/ethyl acetate (5:1). White solid. Yield: 98% (88 mg): mp 129-130 oC.
1H NMR (400 MHz, CDCl3) δ 8.36 (dd, J = 8.0, 0.8 Hz, 1H), 7.80 – 7.70 (m, 2H),
7.55 – 7.48 (m, 1H), 7.35 – 7.31 (m, 2H), 7.19 (dd, J = 5.7, 4.2 Hz, 3H), 7.00 (d, J =
8.7 Hz, 2H), 6.93 (dd, J = 7.1, 2.1 Hz, 2H), 4.33 – 4.19 (m, 2H), 3.89 (s, 3H), 2.95 –
2.88 (m, 2H); 13C NMR (100 MHz, CDCl3) δ 162.3, 160.6 156.1, 147.2, 137.8, 134.3,
129.4, 128.8, 128.6, 127.8, 127.5, 126.9, 126.7, 126.6, 120.8, 114.1, 55.5, 47.6, 34.7.
3-Phenethyl-2-(4-(trifluoromethyl)phenyl)quinazolin-4(3H)-one (3ai). Eluent:
petroleum ether/ethyl acetate (10:1). White solid. Yield: 90% (89 mg): mp 164-165 oC.
1H NMR (400 MHz, DMSO-d6) δ 8.25 (d, J = 7.9 Hz, 1H), 7.87 (t, J = 8.0 Hz, 3H),
7.69 (t, J = 8.5 Hz, 3H), 7.61 (t, J = 7.5 Hz, 1H), 7.25 – 7.07 (m, 3H), 6.86 – 6.73 (m,
2H), 4.12 – 3.97 (m, 2H), 2.90 – 2.77 (m, 2H); 13C NMR (100 MHz, DMSO - d6) δ
161.0, 154.7, 146.7, 139.0, 137.8, 134.6, 130.0, 129.6, 129.0, 128.5, 128.4, 127.3,
127.2, 126.5, 126.2, 125.3, 122.6, 120.6, 47.0, 33.6; HRMS (ESI) m/z calcd for
C23H17F3N2O [M + H]+ 395.1371, found 395.1370.
2-(2,4-Dichlorophenyl)-3-phenethylquinazolin-4(3H)-one (3aj).10x Eluent:
petroleumether/ethyl acetate (10:1). Colorless oil. Yield: 65% (64 mg). 1H NMR (400
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MHz, CDCl3) δ 8.40 (d, J = 8.0 Hz, 1H), 7.82 – 7.66 (m, 2H), 7.62 – 7.45 (m, 2H),
7.28 (dd, J = 8.2, 1.9 Hz, 1H), 7.23 – 7.16 (m, 3H), 6.93 – 6.77 (m, 3H), 4.53 (dt, J =
13.5, 6.7 Hz, 1H), 3.63 (dt, J = 13.5, 8.2 Hz, 1H), 2.94 (q, J = 7.0 Hz, 2H); 13C NMR
(100 MHz, CDCl3) δ 161.6, 152.5, 147.0, 137.6, 136.4, 134.6, 133.2, 132.7, 130.6,
129.4, 128.8, 128.7, 127.5(overlapped), 127.5, 126.8, 126.7, 121.1, 47.4, 34.2.
2-(Naphthalen-2-yl)-3-phenethylquinazolin-4(3H)-one (3ak). Eluent:
petroleum ether/ethyl acetate (10:1). White solid. Yield: 51% (48 mg): mp 146-147 oC.
1H NMR (400 MHz, CDCl3) δ 8.40 (d, J = 8.0 Hz, 1H), 7.93 (t, J = 9.5 Hz, 2H), 7.88
– 7.83 (m, 1H), 7.82 – 7.71 (m, 3H), 7.65 – 7.52 (m, 3H), 7.43 (dd, J = 8.4, 1.3 Hz,
1H), 7.20 – 7.05 (m, 3H), 6.81 (d, J = 7.1 Hz, 2H), 4.34 – 4.20 (m, 2H), 3.03 – 2.92
(m, 2H); 13C NMR (100 MHz, CDCl3) δ 162.3, 156.2, 147.2, 137.7, 134.5, 133.5,
132.8, 132.6, 128.8, 128.6, 128.5(overlapped), 127.9, 127.8, 127.6, 127.3, 127.1,
127.0, 126.8, 126.6, 124.5, 121.0, 47.7, 34.6; HRMS (ESI) m/z calcd for C26H20N2O
[M + H]+ 377.1654, found 377.1650.
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6-Methyl-3-phenethyl-2-phenylquinazolin-4(3H)-one (3al). Eluent: petroleum
ether/ethyl acetate (10:1). White solid. Yield: 87% (74 mg): mp 178-179 oC. 1H NMR
(400 MHz, CDCl3) δ 8.16 (s, 1H), 7.61 (dt, J = 8.3, 5.0 Hz, 2H), 7.55 – 7.45 (m, 3H),
7.37 (dd, J = 7.6, 1.2 Hz, 2H), 7.18 (dd, J = 4.8, 1.5 Hz, 3H), 6.87 (dd, J = 6.4, 2.7 Hz,
2H), 4.23 – 4.11 (m, 2H), 2.96 – 2.85 (m, 2H), 2.53 (s, 3H); 13C NMR (100 MHz,
CDCl3) δ 162.1, 155.3, 145.2, 137.8, 137.3, 135.9, 135.4, 129.7, 128.8, 128.7, 128.6,
127.8, 127.4, 126.6, 126.1, 120.6, 47.5, 34.7, 21.4; HRMS (ESI) m/z calcd for
C23H20N2O [M + H]+ 341.1654, found 341.1649.
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7-Methyl-3-phenethyl-2-phenylquinazolin-4(3H)-one (3am). Eluent:
petroleum ether/ethyl acetate (10:1). White solid. Yield: 74% (63 mg): mp 171-172 oC.
1H NMR (400 MHz, CDCl3) δ 8.25 (d, J = 8.1 Hz, 1H), 7.59 – 7.45 (m, 4H), 7.37 (dd,
J = 10.7, 4.6 Hz, 3H), 7.23 – 7.13 (m, 3H), 6.87 (dd, J = 6.5, 2.7 Hz, 2H), 4.24 – 4.10
(m, 2H), 2.96 – 2.85 (m, 2H), 2.51 (s, 3H); 13C NMR (100 MHz, CDCl3) δ 162.1,
156.2, 147.3, 145.4, 137.8, 135.5, 129.7, 128.8, 128.7, 128.7, 128.6, 127.8, 127.2,
126.6, 126.5, 118.5, 47.4, 34.7, 21.9; HRMS (ESI) m/z calcd for C23H20N2O [M + H]+
341.1654, found 341.1651.
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6-Fluoro-3-phenethyl-2-phenylquinazolin-4(3H)-one (3an). Eluent: petroleum
ether/ethyl acetate (10:1). White solid. Yield: 90% (78 mg): mp 189-190 oC. 1H NMR
(400 MHz, CDCl3) δ 7.99 (dd, J = 8.5, 3.0 Hz, 1H), 7.74 (dd, J = 8.9, 4.9 Hz, 1H),
7.55 – 7.45 (m, 4H), 7.38 (dt, J = 3.7, 2.1 Hz, 2H), 7.22 – 7.15 (m, 3H), 6.87 (dd, J =
6.6, 2.9 Hz, 2H), 4.24 – 4.14 (m, 2H), 2.94 – 2.86 (m, 2H); 13C NMR (100 MHz,
CDCl3) δ 162.3, 161.5, 159.8, 155.4, 143.9, 137.6, 135.1, 130.0, 130.0, 129.9, 128.8,
128.7, 128.6, 127.8, 126.7, 123.2, 122.9, 122.2, 122.1, 111.7, 111.4, 47.6, 34.6;
HRMS (ESI) m/z calcd for C22H17FN2O [M + H]+ 345.1403, found 345.1400.
6-Chloro-3-phenethyl-2-phenylquinazolin-4(3H)-one (3ao). Eluent: petroleum
ether/ethyl acetate (10:1). White solid. Yield: 82% (74 mg): mp 170-171 oC. 1H NMR
(400 MHz, CDCl3) δ 8.33 (d, J = 2.0 Hz, 1H), 7.73 – 7.64 (m, 2H), 7.57 – 7.46 (m,
3H), 7.36 (d, J = 7.4 Hz, 2H), 7.23 – 7.11 (m, 3H), 6.93 – 6.79 (m, 2H), 4.26 – 4.13
(m, 2H), 2.94 – 2.84 (m, 2H); 13C NMR (100 MHz, CDCl3) δ 161.1, 156.4, 145.7,
137.5, 135.0, 134.8, 132.8, 130.0, 129.2, 128.8, 128.7, 128.6, 127.7, 126.7, 126.1,
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121.9, 47.7, 34.6; HRMS (ESI) m/z calcd for C22H17ClN2O [M + H]+ 361.1108, found
361.1104.
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ether/ethyl acetate (10:1). White solid. Yield: 81% (81 mg): mp 189-190 oC. 1H NMR
(400 MHz, CDCl3) δ 8.49 (d, J = 2.1 Hz, 1H), 7.84 (dd, J = 8.6, 2.1 Hz, 1H), 7.60 (d,
J = 8.7 Hz, 1H), 7.57 – 7.45 (m, 3H), 7.35 (d, J = 7.4 Hz, 2H), 7.24 – 7.09 (m, 3H),
6.94 – 6.81 (m, 2H), 4.27 – 4.14 (m, 2H), 2.96 – 2.84 (m, 2H); 13C NMR (100 MHz,
CDCl3) δ 161.0, 156.5, 146.0, 137.6, 137.5, 135.1, 130.0, 129.4, 129.3, 128.8, 128.7,
128.6, 127.7, 126.7, 122.3, 120.6, 47.7, 34.5; HRMS (ESI) m/z calcd for
C22H17BrN2O [M + H]+ 405.0603, found 405.0598.
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6-Isopropyl-3-phenethyl-2-phenylquinazolin-4(3H)-one (3aq). Eluent:
petroleum ether/ ethyl acetate (10:1). White solid. Yield: 80% (73 mg): mp 168-169
oC. 1H NMR (400 MHz, CDCl3) δ 8.22 (s, 1H), 7.71 – 7.64 (m, 2H), 7.54 – 7.45 (m,
3H), 7.38 (dd, J = 7.5, 1.4 Hz, 2H), 7.22 – 7.15 (m, 3H), 6.89 (dd, J = 6.8, 2.4 Hz, 2H),
4.23 – 4.13 (m, 2H), 3.10 (dt, J = 13.8, 6.9 Hz, 1H), 2.96 – 2.84 (m, 2H), 1.35 (d, J =
6.9 Hz, 6H); 13C NMR (100 MHz, CDCl3) δ 162.3, 155.3, 148.2, 145.5, 137.8, 135.4,
133.6, 129.7, 128.8, 128.7, 128.6, 127.8, 127.5, 126.6, 123.4, 120.7, 47.5, 34.7, 34.1,
23.9; HRMS (ESI) m/z calcd for C25H24N2O [M + H]+ 369.1967, found 369.1960.
7-Fluoro-3-phenethyl-2-phenylquinazolin-4(3H)-one (3ar). Eluent: petroleum
ether/ethyl acetate (10:1). White solid. Yield: 84% (72 mg): mp 150-151 oC. 1H NMR
(400 MHz, CDCl3) δ 8.37 (dd, J = 8.9, 6.1 Hz, 1H), 7.59 – 7.46 (m, 3H), 7.45 – 7.32
(m, 3H), 7.26 – 7.22 (m, 1H), 7.22 – 7.15 (m, 3H), 6.87 (dd, J = 6.4, 2.8 Hz, 2H), 4.26
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– 4.13 (m, 2H), 2.97 – 2.86 (m, 2H); 13C NMR (100MHz, CDCl3) δ 167.8, 165.3,
161.4, 157.4, 149.3, 149.2, 137.6, 135.1, 130.0, 129.6, 129.5, 128.8, 128.7, 128.6,
127.7, 126.7, 117.7, 117.7, 116.0, 115.8, 112.9, 112.6, 47.6, 34.6; HRMS (ESI) m/z
calcd for C22H17FN2O [M + H]+ 345.1403, found 345.1401.
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3-Benzyl-2-phenylquinazolin-4(3H)-one (3bb).10w Eluent: petroleum ether/
ethyl acetate (10:1). White solid. Yield: 78% (61 mg): mp 152-153 oC. 1H NMR (400
MHz, CDCl3) δ 8.38 (d, J = 8.2 Hz, 1H), 7.82 – 7.73 (m, 2H), 7.53 (ddd, J = 8.2, 6.3,
2.0 Hz, 1H), 7.47 (dd, J = 8.4, 6.1 Hz, 1H), 7.40 (t, J = 7.5 Hz, 2H), 7.34 (d, J = 7.7
Hz, 2H), 7.20 (dd, J = 6.5, 3.7 Hz, 3H), 6.97 – 6.86 (m, 2H), 5.28 (s, 2H); 13C NMR
(100 MHz, CDCl3) δ 162.5, 156.4, 147.3, 136.6, 135.3, 134.5, 129.9, 128.6, 128.5,
128.0, 127.6, 127.4, 127.1, 127.1, 127.0, 120.9, 48.8.
3-(4-(Tert-butyl)benzyl)-2-phenylquinazolin-4(3H)-one (3bc). Eluent:
petroleum ether/ ethyl acetate (10:1). White solid. Yield: 82% (76 mg): mp 166-167
oC. 1H NMR (400 MHz, CDCl3) δ 8.36 (d, J = 8.1 Hz, 1H), 7.81 – 7.73 (m, 2H), 7.54
– 7.37 (m, 6H), 7.22 (d, J = 8.3 Hz, 2H), 6.88 (d, J = 8.2 Hz, 2H), 5.25 (s, 2H), 1.26 (s,
9H); 13C NMR (100 MHz, CDCl3) δ 162.4, 156.4, 150.4, 147.3, 135.4, 134.5, 133.5,
129.8, 128.6, 128.1, 127.5, 127.1, 126.8(overlapped), 125.4, 120.9, 48.6, 34.4, 31.3;
HRMS (ESI) m/z calcd for C25H24N2O [M + H]+ 369.1967, found 369.1959.
2-Phenyl-3-(4-(trifluoromethyl)benzyl)quinazolin-4(3H)-one (3bd). Eluent:
petroleum ether/ethyl acetate (10:1). White solid. Yield: 72% (66 mg): mp 148-149 oC.
1H NMR (400 MHz, CDCl3) δ 8.37 (d, J = 8.1 Hz, 1H), 7.87 – 7.73 (m, 2H), 7.59 –
7.52 (m, 1H), 7.49 (t, J = 7.8 Hz, 3H), 7.42 (t, J = 7.5 Hz, 2H), 7.35 (d, J = 7.4 Hz,
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2H), 7.07 (d, J = 8.0 Hz, 2H), 5.31 (s, 2H); 13C NMR (100 MHz, CDCl3) δ 162.4,
156.0, 147.2, 140.6, 135.0, 134.8, 130.1, 128.8, 127.9, 127.7, 127.4, 127.3, 127.1,
125.5, 125.5, 120.7, 48.5; HRMS (ESI) m/z calcd for C22H15F3N2O [M + H]+
381.1215, found 381.1209.
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2-Phenyl-3-(3-phenylpropyl)quinazolin-4(3H)-one (3be).11a Eluent: petroleum
ether/ethyl acetate (10:1). White solid. Yield: 80% (68 mg): mp 135-136 oC. 1H NMR
(400 MHz, CDCl3) δ 8.33 (d, J = 8.0 Hz, 1H), 7.79 – 7.69 (m, 2H), 7.54 – 7.45 (m,
6H), 7.18 (t, J = 7.2 Hz, 2H), 7.12 (dd, J = 8.5, 5.8 Hz, 1H), 6.98 (d, J = 7.2 Hz, 2H),
4.05 – 3.96 (m, 2H), 2.51 (t, J = 7.6 Hz, 2H), 1.95 (dt, J = 15.5, 7.7 Hz, 2H); 13C
NMR (100 MHz, CDCl3) δ 162.2, 156.1, 147.2, 140.4, 135.3, 134.3, 129.8, 128.8,
128.3, 128.0, 127.6, 127.5, 127.0, 126.7, 125.9, 120.9, 45.5, 32.9, 29.7.
3-Ethyl-2-phenylquinazolin-4(3H)-one (3bf).10y Eluent: petroleum ether/ethyl
acetate (10:1). White solid. Yield: 89% (56 mg): mp 155-156 oC. 1H NMR (400 MHz,
CDCl3) δ 8.39 – 8.30 (m, 1H), 7.79 – 7.71 (m, 2H), 7.57 – 7.47 (m, 6H), 4.04 (q, J =
7.0 Hz, 2H), 1.22 (t, J = 7.1 Hz, 3H); 13C NMR (101 MHz, CDCl3) δ 162.0, 156.2,
147.2, 135.6, 134.3, 129.8, 128.8, 127.7, 127.5, 126.9, 126.7, 121.0, 41.2, 14.1.
2-Phenyl-3-propylquinazolin-4(3H)-one (3bg).10z Eluent: petroleum ether/ethyl
acetate (10:1). White solid. Yield: 71% (47 mg): mp 139-140 oC. 1H NMR (400 MHz,
CDCl3) δ 8.33 (d, J = 7.8 Hz, 1H), 7.79 – 7.70 (m, 2H), 7.57 – 7.47 (m, 6H), 3.94 (dd,
J = 8.8, 6.7 Hz, 2H), 1.64 (dd, J = 15.3, 7.6 Hz, 2H), 0.77 (t, J = 7.4 Hz, 3H); 13C
NMR (100 MHz, CDCl3) δ 162.1, 156.2, 147.2, 135.6, 134.3, 129.8, 128.7, 127.7,
127.4, 126.9, 126.7, 120.9, 47.4, 22.1, 11.1.
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3-Butyl-2-phenylquinazolin-4(3H)-one (3bh).11d Eluent: petroleum ether/ethyl
acetate (10:1). White solid. Yield: 85% (59 mg): mp 169-170 oC. 1H NMR (400 MHz,
CDCl3) δ 8.36 – 8.30 (m, 1H), 7.79 – 7.71 (m, 2H), 7.54 – 7.48 (m, 6H), 4.02 – 3.95
(m, 2H), 1.63 – 1.55 (m, 2H), 1.17 (dt, J = 14.8, 7.4 Hz, 2H), 0.76 (t, J = 7.4 Hz, 3H);
13C NMR (100 MHz, CDCl3) δ 162.2, 156.2, 147.2, 135.6, 134.3, 129.8, 128.7, 127.8,
127.4, 126.9, 126.7, 120.9, 45.7, 30.7, 19.9, 13.4.
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3-Dodecyl-2-phenylquinazolin-4(3H)-one (3bi). Eluent: petroleum ether/ethyl
acetate (10:1). Colorless oil. Yield: 60% (59 mg). 1H NMR (400 MHz, CDCl3) δ 8.34
(dd, J = 4.5, 4.0 Hz, 1H), 7.79 – 7.70 (m, 2H), 7.55 – 7.48 (m, 6H), 4.02 – 3.90 (m,
2H), 1.64 – 1.55 (m, 2H), 1.26 – 1.09 (m, 18H), 0.88 (t, J = 6.9 Hz, 3H); 13C NMR
(101 MHz, CDCl3) δ 162.1, 156.2, 147.2, 135.6, 134.2, 129.7, 128.7, 127.8, 127.4,
126.9, 126.7, 120.9, 45.9, 31.9, 29.6, 29.5, 29.4, 29.3, 29.3, 28.8, 28.6, 26.6, 22.7,
14.1; HRMS (ESI) m/z calcd for C26H34N2O [M + H]+ 391.2749, found 391.2744.
2-Phenylquinazolin-4(3H)-one (3ca).11c Eluent: petroleum ether/ethyl acetate
(10:1). White solid. Yield: 99% (55 mg): mp 245-246 oC. 1H NMR (400 MHz, CDCl3)
δ 11.75 (s, 1H), 8.36 – 8.24 (m, 3H), 7.88 – 7.76 (m, 2H), 7.65 – 7.56 (m, 3H), 7.54 –
7.45 (m, 1H); 13C NMR (100 MHz, CDCl3): 13C NMR (100 MHz, CDCl3) δ 163.9,
151.8, 149.5, 134.9, 132.8, 131.6, 129.0, 128.0, 127.4, 126.8, 126.4, 120.9.
2-(-Tolyl)quinazolin-4(3H)-one (3cb).11c Eluent: petroleum ether/ethyl acetate
(10:1). White solid. Yield: 80% (47 mg): mp 223-224 oC. 1H NMR (400 MHz, CDCl3)
δ 10.80 (s, 1H), 8.24 (d, J = 7.8 Hz, 1H), 7.80 (d, J = 3.3 Hz, 2H), 7.64 – 7.30 (m, 5H),
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2.53 (s, 3H); 13C NMR (100 MHz, CDCl3) δ 163.1, 153.5, 149.1, 136.9, 134.9, 133.6,
131.4, 130.6, 128.8, 127.9, 127.0, 126.4, 126.3, 120.8, 20.1.
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2-(M-tolyl)quinazolin-4(3H)-one (3cc).10j Eluent: petroleum ether/ethyl acetate
(10:1). White solid. Yield: 92% (54 mg): mp 211-212 oC. 1H NMR (400 MHz, CDCl3)
δ 11.81 (s, 1H), 8.33 (d, J = 7.8 Hz, 1H), 8.18 – 7.95 (m, 2H), 7.91 – 7.71 (m, 2H),
7.59 – 7.31 (m, 3H), 2.52 (s, 3H); 13C NMR (100 MHz, CDCl3) δ 163.9, 152.0, 149.6,
138.8, 134.8, 132.7, 132.4, 128.9, 128.1, 128.0, 126.7, 126.3, 124.5, 120.8, 21.5.
2-(P-tolyl)quinazolin-4(3H)-one (3cd).11c Eluent: petroleum ether/ethyl acetate
(10:1). White solid. Yield: 95% (56 mg): mp 237-238 oC. 1H NMR (400 MHz,
DMSO-d6) δ 12.46 (s, 1H), 8.15 (dd, J = 7.9, 1.2 Hz, 1H), 8.11 (d, J = 8.2 Hz, 2H),
7.86 – 7.80 (m, 1H), 7.73 (d, J = 8.0 Hz, 1H), 7.52 (dd, J = 11.1, 3.9 Hz, 1H), 7.36 (d,
J = 8.1 Hz, 2H), 2.40 (s, 3H);13C NMR (100 MHz, DMSO-d6) δ 162.2, 152.2, 148.8,
141.4, 134.5, 129.7, 129.1, 127.6,127.3, 126.3, 125.8, 120.9, 20.9.
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2-(4-Fluorophenyl)quinazolin-4(3H)-one (3ce).11c Eluent: petroleum ether/
ethyl acetate (10:1). White solid. Yield: 85% (51 mg): mp 292-293 oC. 1H NMR (400
MHz, DMSO-d6) δ 12.57 (s, 1H), 8.30 – 8.21 (m, 2H), 8.15 (dd, J = 7.9, 1.3 Hz, 1H),
7.89 – 7.80 (m, 1H), 7.73 (d, J = 7.9 Hz, 1H), 7.59 – 7.45 (m, 1H), 7.47 – 7.32 (m,
2H); 13C NMR (100 MHz, DMSO-d6) δ 165.3, 162.8, 162.2, 151.4, 148.6, 134.6,
130.4, 130.3, 129.2, 129.2, 127.5, 126.6, 125.9, 120.9, 115.7, 115.5.
2-(4-Chlorophenyl)quinazolin-4(3H)-one (3cf).11c Eluent: petroleum ether/
ethyl acetate (10:1). White solid. Yield: 91% (58 mg): mp 280-281 oC. 1H NMR (400
MHz, DMSO-d6) δ 12.58 (s, 1H), 8.17 (dd, J = 17.5, 8.2 Hz, 3H), 7.88 – 7.79 (m, 1H),
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7.74 (d, J = 8.1 Hz, 1H), 7.62 (d, J = 8.6 Hz, 2H), 7.53 (t, J = 7.5 Hz, 1H);13C NMR
(100 MHz, DMSO-d6) δ 162.2, 151.4, 148.6, 136.3, 134.7, 131.6, 129.6, 128.7, 127.5,
126.8, 125.9, 121.0.
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2-(4-Bromophenyl)quinazolin-4(3H)-one (3cg).10j Eluent: petroleum ether/
ethyl acetate (10:1). White solid. Yield: 76% (57 mg): mp 297-298 oC. 1H NMR (400
MHz, DMSO-d6) δ 12.61 (s, 1H), 8.22 – 8.07 (m, 3H), 7.90 – 7.69 (m, 4H), 7.58 –
7.48 (m, 1H); 13C NMR (100 MHz, DMSO-d6) δ 162.2, 151.5, 148.5, 134.7, 131.9,
131.6, 129.8, 127.5, 126.8, 125.9, 125.2, 121.0.
2-(4-Methoxyphenyl)quinazolin-4(3H)-one (3ch).10j Eluent: petroleum ether/
ethyl acetate (10:1). White solid. Yield: 99% (63 mg): mp 246-247 oC. 1H NMR (400
MHz, CDCl3) δ 10.77 (s, 1H), 8.36 – 8.25 (m, 1H), 8.20 – 8.05 (m, 2H), 7.84 – 7.70
(m, 2H), 7.48 (ddd, J = 8.1, 5.6, 2.7 Hz, 1H), 7.15 – 6.99 (m, 2H), 3.92 (s, 3H);13C
NMR (100 MHz, CDCl3) δ 163.3, 162.5, 151.2, 149.6, 134.9, 128.8, 127.8, 126.4,
126.4, 125.0, 120.6, 114.5, 55.5.
2-(4-(Trifluoromethyl)phenyl)quinazolin-4(3H)-one (3ci).11c Eluent:
petroleum ether/ethyl acetate (10:1). White solid. Yield: 69% (50 mg): mp 229-230 oC.
1H NMR (400 MHz, DMSO - d6) δ 12.74 (s, 1H), 8.38 (d, J = 8.2 Hz, 2H), 8.18 (dd, J
= 7.9, 1.1 Hz, 1H), 7.93 (d, J = 8.4 Hz, 2H), 7.90 – 7.83 (m, 1H), 7.78 (d, J = 7.9 Hz,
1H), 7.60 – 7.52 (m, 1H); 13C NMR (100 MHz, DMSO - d6) δ 162.1, 151.2, 148.4,
136.6, 134.7, 131.3, 130.9, 128.7, 127.7, 127.1, 125.9, 125.5, 125.5, 125.4, 125.3,
122.3, 121.2.
2-(2,4-Dichlorophenyl)quinazolin-4(3H)-one (3cj).10j Eluent: petroleum ether/
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ethyl acetate (10:1). White solid. Yield: 63% (46 mg): mp 225-226 oC. 1H NMR (400
MHz, DMSO-d6) δ 12.65 (s, 1H), 8.18 (dd, J = 8.0, 1.3 Hz, 1H), 7.90 – 7.80 (m, 2H),
7.72 (d, J = 8.3 Hz, 2H), 7.63 – 7.54 (m, 2H); 13C NMR (100 MHz, DMSO-d6) δ
161.4, 151.4, 148.4, 135.4, 134.6, 132.7(overlapped), 132.2, 129.1, 127.5(overlapped),
127.2, 125.8, 121.2.
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2-(Naphthalen-2-yl)quinazolin-4(3H)-one (3ck).11c Eluent: petroleum ether/
ethyl acetate (10:1). White solid. Yield: 82% (56 mg): mp 287-288 oC. 1H NMR (400
MHz, DMSO-d6) δ 12.67 (s, 1H), 8.83 (s, 1H), 8.32 (d, J = 8.6 Hz, 1H), 8.19 (d, J =
7.8 Hz, 1H), 8.11 – 8.05 (m, 2H), 8.02 (d, J = 8.4 Hz, 1H), 7.87 (t, J = 7.5 Hz, 1H),
7.81 (d, J = 8.0 Hz, 1H), 7.69 – 7.60 (m, 2H), 7.55 (t, J = 7.4 Hz, 1H);13C NMR (100
MHz, DMSO-d6) δ 162.2, 152.2, 148.8, 134.6, 134.1, 132.3, 129.9, 128.9, 128.1,
128.1, 127.9, 127.6, 127.5, 126.9, 126.6, 125.9, 124.5, 121.0.
6-Methyl-2-phenylquinazolin-4(3H)-one (3cl).10a Eluent: petroleum ether/ethyl
acetate (10:1). White solid. Yield: 97% (57 mg): mp 240-241 oC. 1H NMR (400 MHz,
DMSO-d6) δ 12.46 (s, 1H), 8.17 (d, J = 7.2 Hz, 2H), 7.95 (s, 1H), 7.68 – 7.62 (m, 2H),
7.61 – 7.50 (m, 3H), 2.46 (s, 3H);13C NMR (100 MHz, DMSO-d6) δ 162.2, 151.5,
146.7, 136.3, 135.9, 132.8, 131.2, 128.6, 127.6, 127.4, 125.2, 120.7, 20.8.
7-Methyl-2-phenylquinazolin-4(3H)-one (3cm).10m Eluent: petroleum ether/
ethyl acetate (10:1). White solid. Yield: 97% (57 mg): mp 229-230 oC. 1H NMR (400
MHz, DMSO-d6) δ 12.44 (s, 1H), 8.18 (dd, J = 8.0, 1.4 Hz, 2H), 8.05 (d, J = 8.1 Hz,
1H), 7.66 – 7.50 (m, 4H), 7.35 (dd, J = 8.1, 1.2 Hz, 1H), 2.48 (s, 3H);13C NMR (101
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MHz, DMSO-d6) δ 162.1, 152.3, 148.8, 145.0, 132.8, 131.3, 128.5, 128.0, 127.7,
127.1, 125.7, 118.6, 21.3.
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6-Fluoro-2-phenylquinazolin-4(3H)-one (3cn).10m Eluent: petroleum ether/
ethyl acetate (10:1). White solid. Yield: 97% (58 mg): mp 232-233 oC. 1H NMR (400
MHz, DMSO-d6) δ 12.67 (s, 1H), 8.20 – 8.13 (m, 2H), 7.85 – 7.79 (m, 2H), 7.72 (td, J
= 8.7, 3.0 Hz, 1H), 7.61 – 7.50 (m, 3H); 13C NMR (101 MHz, DMSO-d6) δ 161.7,
161.2, 158.8, 151.9, 145.6, 132.5, 131.4, 130.3, 128.9, 128.6, 127.7, 123.2, 122.9,
122.1, 110.6, 110.4.
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6-Bromo-2-phenylquinazolin-4(3H)-one (3co).10a Eluent: petroleum ether/ethyl
acetate (10:1). White solid. Yield: 68% (51 mg): mp 285-286 oC. 1H NMR (400 MHz,
DMSO-d6) δ 12.70 (s, 1H), 8.30 – 8.11 (m, 3H), 7.97 (dd, J = 8.7, 2.4 Hz, 1H), 7.71 (t,
J = 15.6 Hz, 1H), 7.63 – 7.49 (m, 3H); 13C NMR (100 MHz, DMSO-d6) δ 161.3,
153.1, 147.7, 137.3, 132.6, 131.6, 129.8, 128.6, 128.0, 127.8, 122.6, 118.8.
6-Isopropyl-2-phenylquinazolin-4(3H)-one (3cp).11c Eluent: petroleum ether/
ethyl acetate (10:1). White solid. Yield: 90% (59 mg): mp 225-226 oC. 1H NMR (400
MHz, DMSO-d6) δ 12.47 (s, 1H), 8.18 (d, J = 6.7 Hz, 2H), 7.99 (d, J = 1.8 Hz, 1H),
7.80 – 7.64 (m, 2H), 7.62 – 7.45 (m, 3H), 3.07 (dt, J = 13.8, 6.9 Hz, 1H), 1.28 (d, J =
6.9 Hz, 6H); 13C NMR (100 MHz, DMSO-d6) δ 162.3, 151.5, 147.0, 133.5, 132.7,
131.2, 128.5, 127.7, 127.6, 127.5, 122.3, 120.7, 33.1, 23.7.
7-Fluoro-2-phenylquinazolin-4(3H)-one (3cq).11c Eluent: petroleum ether/ethyl
acetate (10:1). White solid. Yield: 95% (57 mg): mp >300 oC. 1H NMR (400 MHz,
DMSO-d6) δ 12.63 (s, 1H), 8.27 – 8.14 (m, 3H), 7.63 – 7.47 (m, 4H), 7.37 (td, J = 8.7,
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2.5 Hz, 1H); 13C NMR (101 MHz, DMSO-d6) δ 167.1, 164.6, 161.6, 153.7, 150.9,
150.8, 132.4, 131.7, 129.0, 128.9, 128.6, 127.9, 118.0, 1152, 115.0, 112.5, 112.3.
■ ASSOCIATED CONTENT
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Supporting Information. NMR spectra of the compounds. This material is available
free of charge via the Internet at http://pubs.acs.org.
■ AUTHOR INFORMATION
Corresponding Author
*E-mail: cuixl@hqu.edu.cn.
Notes
The authors declare no competing financial interest.
■ ACKNOWLEDGMENT
This work was supported by Minjiang Scholar Program (10BS216), Xiamen Southern
Oceanographic Center (13GYY003NF16) and Huaqiao University.
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