Efficient One-Pot Synthesis of Quinazoline and Benzopyrano[2,3-d]pyrimidine Derivatives Catalyzed by N-Bromosulfonamides

Article abstract of DOI:10.1002/jhet.2570

N,N,N',N'-tetrabromobenzene-1,3-disulfonamide and poly(N,N’-dibromo-N-ethyl-benzene-1,3-disulfonamide) were used as efficient catalysts for one-pot synthesis of new quinazoline derivatives from various aldehydes, 2-amino-benzophenone, and ammonium acetate

Full text of DOI:10.1002/jhet.2570

Month 2015
Efficient One-Pot Synthesis of Quinazoline and Benzopyrano[2,3-d]
pyrimidine Derivatives Catalyzed by N-Bromosulfonamides
*
Ramin Ghorbani-Vaghei, Mina Shirzadi-Ahodashti, Fattemeh Eslami, Seyedeh Mina Malaekehpoor, Zahra Salimi,
Zahra Toghraei-Semiromi, and Samira Noori
Department of Organic Chemistry, Faculty of Chemistry, Bu-Ali Sina University, 65174 Hamedan, Iran
*
E-mail: rgvaghei@yahoo.com
Additional Supporting Information may be found in the online version of this article.
Received August 4, 2015
DOI 10.1002/jhet.2570
Published online 00 Month 2015 in Wiley Online Library (wileyonlinelibrary.com).
N,N,N’,N’-tetrabromobenzene-1,3-disulfonamide and poly(N,N’-dibromo-N-ethyl-benzene-1,3-disulfonamide)
were used as efficient catalysts for one-pot synthesis of new quinazoline derivatives from various aldehydes, 2-
amino-benzophenone, and ammonium acetate in good to excellent yields and new benzopyrano[2,3-d]pyrimidine
derivatives from salicylic aldehydes, various cyclic amines, and malononitrile in good to high yields.
J. Heterocyclic Chem., 00, 00 (2015).
INTRODUCTION
as, anti-histaminic [1], anti-hypertensive [2], antiplas
modial [3], anti-diabetes [4], antibacterial [5], antiviral
[6], anticarcinogen [7], and antimalarial [8]. Also, soporific
and sedative actions of some of quinazoline derivatives
have been reported [9]. Pyrimidines and their derivatives
are well-known heterocyclic compounds, which have been
studied for over a century because of a variety of chemical
and biological properties. Particularly, benzopyranopyrim-
idines are important pharmacophores that exhibit anti-
inflammatory, anti-aggregating, anti-platelet, analgesic,
and anti-thrombotic activities [10–13]. In vivo activity by
benzopyranopyrimidines have been shown in mice with
One of the most important and pliable routes for the
preparation of heterocyclic compounds with significant bi-
ological activities is multicomponent reactions (MCRs).
High selectivity, high atom-economy, rapid, and facility
are central issues in MCRs. Quinazoline and their fused-
ring derivatives, which belong to the N-containing hetero-
cyclic compounds, are one of the most prevalent class of
compounds in medicinal chemistry. A large number of
quinazolines and their condensed derivatives possess broad
spectrum of biological and pharmacological activities such
© 2015 HeteroCorporation

R. Ghorbani-Vaghei, M. Shirzadi-Ahodashti, F. Eslami, S. M. Malaekehpoor,
Z. Salimi, Z. Toghraei-Semiromi, and S. Noori
Vol 000
Figure 1. Bioactive compounds with quinazoline and benzopyranopyrimidine core skeleton.
Scheme 1. Synthesis of quinazoline and benzopyrano[2,3-d]pyrimidine derivatives.
Table 1
Reaction times and yields in various conditions.
Entry
Solvent
Amount of catalyst [TBBDA (g)]
Temperature (°C)
Time (h)
Yield (%)b
1
2
3
4
5
6
7
8
Solvent-free
Solvent-free
Solvent-free
CH3CN
0.08
0.08
0.08
0.08
0.08
0.05
0.08
0.1
0.03
0.05
0.08
0.1
rt
45
100
45
45
45
45
45
45
45
45
45
24
20
15
3
5
7
5
3
6
5
0
11
23
0
H2O
0.9
Ethanol/ H2O
Ethanol/ H2O
Ethanol/ H2O
Ethanol
Ethanol
Ethanol
17
33
27
10
48
85
73
9
10
11
12
3
4
Ethanol
aExperimental conditions: 4-chlorobenzaldehyde (1 mM), ammonium acetate (2.5 mM) and 2-amino-benzophenone (1 mM).
bIsolated yield.
TBBDA, tetrabromobenzene-1,3-disulfonamide.
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Synthesis of Quinazolines and Benzopyrano[2,3-d]pyrimidines
Table 2
Synthesis of quinazoline derivatives using TBBDA or PBBS as catalysts.
TBBDA
PBBS
Entry
1
Aldehyde
Producta
Time (h)/yield (%)b
Time (h)/yield (%)b
Ref.
[11]
3/85
5/65
2
3/85
5/58
[11]
3
3/90
5/53
[18]
4
3/65
5/42
[18]
5
3/85
5/65
—
6
3/95
5/45
—
(Continued)
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

R. Ghorbani-Vaghei, M. Shirzadi-Ahodashti, F. Eslami, S. M. Malaekehpoor,
Z. Salimi, Z. Toghraei-Semiromi, and S. Noori
Vol 000
Table 2
(Continued)
TBBDA
PBBS
Entry
7
Aldehyde
Producta
Time (h)/yield (%)b
Time (h)/yield (%)b
Ref.
4/82
3/75
3/93
7/69
—
8
5/45
[11]
9
5/72
—
10
7/72
9/55
—
11
7/93
9/75
—
12
3/94
5/70
—
(Continued)
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Synthesis of Quinazolines and Benzopyrano[2,3-d]pyrimidines
Table 2
(Continued)
TBBDA
PBBS
Entry
13
Aldehyde
Producta
Time (h)/yield (%)b
Time (h)/yield (%)b
Ref.
3/75
5/40
—
14
3/77
5/52
—
aThe known compounds were characterized from their physical properties, by comparing them with authentic samples, and using spectroscopic methods
bIsolated yield.
TBBDA, tetrabromobenzene-1,3-disulfonamide; PBBS, poly(N,N’-dibromo-N-ethyl-benzene-1,3-disulfonamide).
P388 lymphocytic leukemia [14]. In recent years, LiClO4,
ionic liquid, and microwave irradiation have been utilized
for synthesis of these compounds [15–17]. Because of very
diverse pharmacological significance exhibited by the
quinazoline and pyrimidine systems (Fig. 1), we hereby re-
port one-pot synthesis of some new quinazoline and
benzopyrano[2,3-d]pyrimidine derivatives via MCRs un-
der various conditions.
ketones, various aldehydes and ammonium acetate in ethanol
and synthesis of benzopyrano[2,3-d]pyrimidine derivatives
from salicylic aldehydes, malononitrile, and various cyclic
amines via one-pot and pseudo four-component reaction in
the presence of TBBDA or PBBS as catalysts under mild con-
ditions (Scheme 1).
Initial efforts focused on optimizing conditions for
synthesis of 2-(4-chlorophenyl)-4-phenylquinazoline from
4-chlorobenzaldehyde, ammonium acetate, and 2-amino-
benzophenone as a model reaction under various conditions.
We examined various solvents and solvent-free conditions
with different temperatures and variety amount of catalyst
for this model reaction and behold that TBBDA (0.08g)
with ethanol under 45°C can be increased rate of reaction
and yield of product (3h, 85%, Table 1, entry 11). The re-
sults are summarized in Table 1.
RESULTS AND DISCUSSION
As a part of our research in organic synthesis catalyzed by
N,N,N’,N’-tetrabromobenzene-1,3-disulfonamide (TBBDA)
and poly(N,N’-dibromo-N-ethyl-benzene-1,3-disulfonamide)
(PBBS) [18–27], hereby, we report simple, green, and effi-
cient method for synthesis of quinazoline derivatives via
one-pot, three-component reaction of substituted o-aminoaryl
To establish the scope and generality of this protocol,
we examined variety of aldehydes containing either
Scheme 2. Synthesis of bis-quinazoline.
Journal of Heterocyclic Chemistry
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R. Ghorbani-Vaghei, M. Shirzadi-Ahodashti, F. Eslami, S. M. Malaekehpoor,
Z. Salimi, Z. Toghraei-Semiromi, and S. Noori
Vol 000
Scheme 3. Suggested mechanism for the synthesis of quinazoline derivatives.
Table 3
Optimization of reaction in various conditions
Entry
Solvent
Catalyst amount [TBBDA (g)]
Time (h)
Yield (%)b
1
2
3
4
5
6
7
8
9
Ethylacetate
Dichloromethane
Acetonitrile
H2O
EtOH/H2O
EtOH
EtOH
EtOH
EtOH
0.06
0.06
0.06
0.06
0.06
24
24
24
10
24
24
24
24
24
39
27
32
-
25
29
67
78
85
No catalyst
0.01
0.03
0.06
aExperimental conditions: 2-hydroxybenzaldehyde (2.3 mM), morpholine (1 mM) and malononitrile (1 mM).
bIsolated yield.
TBBDA, tetrabromobenzene-1,3-disulfonamide.
Table 4
Synthesis of benzopyrano[2,3-d]pyrimidine derivatives in the presence of TBBDA or PBBS
Yield (%)b
Entry
1
Aldehyde
Amine
Product
TBBDA
87
PBBS
54
Ref.
-
2
82
51
-
(Continued)
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Synthesis of Quinazolines and Benzopyrano[2,3-d]pyrimidines
Table 4
(Continued)
Yield (%)b
PBBS
Entry
3
Aldehyde
Amine
Product
TBBDA
90
Ref.
[15]
58
50
52
4
5
85
83
[15]
-
6
82
48
-
7
92
53
[15]
8
81
53
[15]
(Continued)
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

R. Ghorbani-Vaghei, M. Shirzadi-Ahodashti, F. Eslami, S. M. Malaekehpoor,
Z. Salimi, Z. Toghraei-Semiromi, and S. Noori
Vol 000
Table 4
(Continued)
Yield (%)b
Entry
9
Aldehyde
Amine
Product
TBBDA
78
PBBS
45
Ref.
-
aProducts were characterized from their physical properties, by comparison with authentic samples, and by spectroscopic methods.
bIsolated yield.
TBBDA, tetrabromobenzene-1,3-disulfonamide; PBBS, poly(N,N’-dibromo-N-ethyl-benzene-1,3-disulfonamide).
Scheme 4. Suggested mechanism for the synthesis of benzopyrano[2,3-d]pyrimidine derivatives.
electron-withdrawing or electron-donating substituents,
which successfully reacted with o-aminoarylketone and
ammonium acetate and gave corresponding products
with good to high yields. The results are shown in
Table 2.
Also, we synthesized bis-quinazoline with good yield via
one-pot reaction between 4,4’-(propane-1,3-diylbis(oxy))
dibenzaldehyde, o-aminoarylketone (2 mM), and ammo-
nium acetate (2 mM) under optimal reaction condition
(Scheme 2).
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Month 2015
Synthesis of Quinazolines and Benzopyrano[2,3-d]pyrimidines
In the Scheme 3, we suggested a mechanism for the con-
version of the o-aminoaryl ketones, various aldehydes, and
ammonium acetate to quinazoline derivatives. According
to this mechanism, TBBDA can be releases Br+ as electro-
philic species and the carbonyl groups activated by this cat-
alyst and gave products [24,28].
Also, in another study, we synthesized benzopyrano
[2,3-d]pyrimidine derivatives via one-pot, pseudo four-
component reaction with good to high yield. So, for
optimization of reaction conditions, we applied 2-
hydroxybenzaldehyde, morpholine, and malononitrile as a
model reaction. Various solvents and amounts of TBBDA
were used, and the best result was achieved by ethanol and
TBBDA (0.06 g, 85%, Table 3, entry 9). Also, this model
reaction was carried out by HBr (48%) and the yield of
product (24 h, 50%) less because TBBDA was used. The
results are summarized in Table 3.
In order to study the scope and generality of these catalysts
in MCR, we carried out the efficacy of TBBDA and PBBS in
the synthesis of benzopyrano[2,3-d]pyrimidine derivatives.
Various cyclic amines and salicylic aldehydes were used,
and the corresponding products were obtained with good to
high yields. The results are presented in Table 4.
Mechanistically, it is likely that TBBDA or PBBS releases
Br+ in situ, which acts as an electrophilic species [18]. The
mechanism shown in (Scheme 4) is proposed for the synthe-
sis of benzopyrano[2,3-d]pyrimidine derivatives [16].
Typical procedure for the preparation of 2-(4-chlorophenyl)-
4-phenylquinazoline (Table 2, entry 1).
A mixture of 4-
chlorobenzaldehyde (1mM), 2-aminobenzophenone (1mM),
ammonium acetate (2.5mM), and TBBDA (0.08g,
0.16mM) or PBBS (0.1g) was stirred under 45°C for
appropriate time. After completion of the reaction, which
was monitored by thin-layer chromatography [acetone/n-
hexane (4:14)], the mixture was cooled to room
temperature. Then, ethanol (5 mL) was added to the
mixture. The solid product was collected by filtration,
washed with ethanol, and purified by recrystallization from
ethanol. After evaporation of the ethanol, cool methylene
dichloride (2 mL) was added, and catalyst was recovered.
Typical procedure for the synthesis of 2-(2-hydroxyphenyl)
-4-(4-methylpiperidine-1-yl)-5H-benzopyrano[2,3-d]pyrimidine
(Table 4, entry 1). A mixture of salicylaldehyde (2.3mM),
malononitrile (1mM), 4-methylpiperidine (1mM), ethanol
(5mL), and TBBDA (0.11mM, 0.06g) were stirred at
room temperature for 24h. The progress of reaction was
monitored by thin-layer chromatography [n-hexane/
acetone (10:3)]. After completion of the reaction, the
precipitate product was collected, washed with ethanol.
Removal of the solvent under reduced pressure gave the
catalyst. The crude product was recrystallized from ethyl
acetate to afford the pure product.
Physical and spectroscopic data. 6-Chloro-2-(4-(dimethy
lamino)phenyl)-4-phenylquinazoline: Yellow solid, mp:
159–161°C. IR (KBr, νmax, cmÀ1): 1162, 1184, 1364,
1389, 1418, 1528, 1559, 1601. 1H NMR (400MHz,
CDCl3): δH (ppm) 3.092 (s, CH3, 6H), 6.81–8.59 (m, Ar-
H, 12H). 13C NMR (100 MHz, CDCl3): δC (ppm) 40.2
(2CH3), 111.6, 121.6, 125.4, 125.7 (C Ar), 128.6, 129.9,
130.03, 130.06, 131.4, 134.1, 137.4, 150.7, 152.2, 160.9,
167.1. MS: m/z 359.2. Anal. Calcd for C22H18ClN3: C,
77.74; H, 5.04; N, 11.68. Found: C, 77.00; H, 4.68; N,
11.33 (Table 2, entry 5).
CONCLUSION
In summary, we have developed efficient, green, simple,
and one-pot procedure for synthesis of remarkable biolog-
ically substituted quinazoline and benzopyrano[2,3-d]py-
rimidine derivatives using TBBDA and PBBS as
catalysts. Inexpensive catalysts, simple method, high
yields, and easy work up are advantages of this method.
6-Chloro-2-(3-methoxyphenol)-4-phenylquinazoline: Yel-
low solid, mp: 249–250°C. IR (KBr, νmax, cmÀ1): 800,
1
1381, 1479, 1534, 1558. H NMR (400MHz, CDCl3): δH
(ppm) 3.9 (s, CH3, 3H), 6.9–8.3 (m, Ar-H, 11H), 14.04 (s,
OH, 1H). 13C NMR (100MHz, CDCl3): δC (ppm) 56.1
(OCH3), 114.5, 118.2, 119.1, 121.3 (C Ar), 121.6, 126.1,
128.9, 129.4, 130.0, 130.7, 133.0, 135.3, 136.2, 148.2,
148.9, 151.2, 161.1, 167.4. MS: m/z 362. Anal. Calcd for
C21H15ClN2O2: C, 69.52; H, 4.17; N, 7.72. Found: C,
69.09; H, 4.01; N, 7.69 (Table 2, entry 6).
EXPERIMENTAL
All commercially available chemicals were
purchased from Merck (Kenilworth, NJ,) and Fluka
(Buchs, Switzerland) companies and used without
further purification unless otherwise stated. Infrared
(IR) spectroscopy was conducted on a Perkin Elmer
GX FT-IR spectrometer. Nuclear magnetic resonance
(NMR) spectra were recorded in DMSO-d6 and CDCl3
on Bruker Avance 400 MHz FT spectrometers using
tetramethylsilane (TMS) as an internal standard. Chem-
ical shifts were expressed in parts per million (ppm).
Mass spectra were recorded on a Shimadzu QP 1100
BX Mass Spectrometer. Elemental analyses (C, H, N)
were performed with a 4010 CHNS-O Analyzer.
6-Chloro-4-phenyl-2-(3-bromophenyl)quinazoline: White
solid, mp: 190–191°C. IR (KBr, νmax, cmÀ1): 800, 1382,
1
1480, 1534, 1557. H NMR (400MHz, CDCl3): δH (ppm)
7.3–8.8 (m, Ar-H, 12H). 13C NMR (100 MHz, CDCl3): δC
(ppm) 122.3 (C Ar), 122.9, 125.8, 127.2, 128.8, 130.0,
130.1, 130.3, 130.9, 131.6, 133.0, 133.6, 134.7, 136.8,
139.8, 150.3, 158.9, 167.7. MS: m/z 395. Anal. Calcd for
C20H12BrClN2: C, 60.71; H, 3.06; N, 7.08. Found: C,
60.44; H, 2.89; N, 6.66 (Table 2, entry 7).
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

R. Ghorbani-Vaghei, M. Shirzadi-Ahodashti, F. Eslami, S. M. Malaekehpoor,
Z. Salimi, Z. Toghraei-Semiromi, and S. Noori
Vol 000
6-Chloro-4-phenyl-2-(3,4,5-trimethoxyphenyl)quinazoline:
Pale-yellow solid, mp: 164–165°C. IR (KBr, νmax, cmÀ1):
1123, 1386, 1413, 1506, 1536, 1555, 1590. 1H NMR
(400 MHz, CDCl3): δH (ppm) 3.96–4.03 (m, 3OCH3,
9H), 7.28–8.10 (m, Ar-H, 10H). 13C NMR (100 MHz,
CDCl3): δC (ppm) 40.9 (OCH3), 56.2 (OCH3), 60.9
(OCH3), 105.8, 122.0 (C Ar), 125.8, 128.7, 130.0, 130.2,
130.7, 132.4, 133.2, 134.5, 137.0, 140.5, 150.4, 153.3,
159.9, 167.4. MS: m/z 406.2. Anal. Calcd for
C23H19ClN2O3: C, 67.9; H, 4.71; N, 6.89. Found: C,
67.16; H, 4.53; N, 6.69 (Table 2, entry 9).
2-(2-Hydroxyphenyl)-4-(4-methylpiperidin-1-yl)-5H-
benzopyrano[2,3-d]pyrimidine: Yellow solid, mp: 158–
159°C. IR (KBr, vmax, cmÀ1): 3059, 2950, 2808, 1599,
1
1183. H NMR (400MHz, CDCl3): δH (ppm) 1.02–1.04
(d, J = 8.0 Hz, 3H, CH3), 1.34–1.44 (m, 2H, CH2),
1.64–1.74 (m, 1H, CH2), 1.80–1.82 (m, 1H, CH2),
1.84–1.86 (m, 1H, CH), 2.98–3.05 (m, 2H, CH2), 3.85–
3.87 (m, 2H, CH2), 3.88–3.90 (m, 1H, CH2), 3.92 (s,
2H, CH2), 6.89–6.98 (m, 2H, Ar H), 7.08–7.12 (m, 1H,
Ar H), 7.17–7.26 (m, 3H, Ar H), 7.36–7.32 (m, 1H, Ar
H), 8.42 (dd, Ja = 7.0 Hz , Jb = 2.0 Hz, 1H, Ar H), 13.45
(s, 1H, OH). 13C NMR (100 MHz, CDCl3): δC (ppm)
21.8 (CH3), 25.6 (CH2CH2), 30.9 (CH), 34.1 (2CH2),
48.8 (CH2), 97.4 (C6’), 117.1, 117.5, 118.6, 118.8,
119.5, 124.3 (C Ar), 128.2 , 128.5, 129.2, 132.8, 150.6,
160.4, 162.0, 164.4, 165.0. MS: m/z 373. Anal. Calcd
for C23H23N3O2: C, 73.95; H, 6.21; N, 11.25. Found:
C, 73.49; H, 6.18; N, 11.11 (Table 4, entry 1).
6-Chloro-4-phenyl-2-(thiophen-2-yl)quinazoline: White
solid, mp: 219–220°C. IR (KBr, νmax, cmÀ1): 703, 844,
1
1384, 1436, 1477, 1540. H NMR (400MHz, CDCl3): δH
(ppm) 7.19–8.21 (m, Ar-H, 11H). 13C NMR (100MHz,
CDCl3): δC (ppm) 122.0, 125.9, 128.3, 128.7, 129.6,
130.0, 130.2, 130.3, 130.4, 132.3, 134.6, 136.7, 143.7,
150.3, 157.4, 167.6. MS: m/z 322 (Table 2, entry 10).
6-Chloro-2-(furan-2-yl)-4-phenylquinazoline:
Pale-
2-(2-Hydroxyphenyl)-4-(4-methylpiperazin-1-yl)-5H-
benzopyrano[2,3-d]pyrimidine: Yellow solid, mp: 179–
181°C. IR (KBr, vmax, cmÀ1): 3057, 2963, 2842,1598,
brown solid, mp: 198–199°C. IR (KBr, νmax, cmÀ1):
1
1379, 1470, 1536, 1586. H NMR (400 MHz, CDCl3): δH
(ppm) 6.6 (q, Ar-O, 1H), 7.50–8.11 (m, Ar-H, 10H). 13C
NMR (100 MHz, CDCl3): δC (ppm) 112.3, 114.7, 122.0,
125.9, 128.7, 129.9, 130.3, 132.6, 134.8, 136.2, 145.5,
150.0, 152.4, 153.6, 168.0. MS: m/z 306. Anal. Calcd for
C18H11ClN2O: C, 70.48; H, 3.61; N, 9.13. Found: C,
70.23; H, 3.20; N, 9.09 (Table 2, entry 11).
1
1186. H NMR (400 MHz, CDCl3): δH (ppm) 2.39 (s,
3H, CH3), 2.61–2.64 (t, J = 4.8 Hz, 4H, 2CH2), 3.54–3.56
(t, J = 4.8 Hz, 4H, 2CH2), 3.90 (s, 2H, CH2), 6.90–6.99
(m, 2H, Ar-H), 7.09–7.13 (m, 1H, Ar-H), 7.18–7.28 (m,
3H, Ar-H), 7.33–7.38 (m, 1H, Ar-H), 8.40–8.42 (dd,
Ja =8.0Hz, Jb =2.0Hz, 1H, Ar-H), 13.24 (s, 1H, OH).13C
NMR (100MHz, CDCl3): δC (ppm) 25.7 (CH2), 46.1 (N-
CH3), 48.1 (2CH2), 54.8 (2CH2), 97.4, 117.1, 117.6,
118.5, 118.8, 119.3, 124.4, 128.3, 128.5, 129.2, 132.9,
150.5, 160.3, 162, 164.6, 164.6. MS: m/z 374. Anal. Calcd
for C22H22N4O2: C, 70.57; H, 5.92; N, 14.96. Found:
C,70.41; H, 5.93; N, 15.08 (Table 4, entry 2).
7-Bromo-2-(5-bromo-2-hydroxyphenyl)-4-(4-methylpi-
peridin-1-yl)-5H-benzopyrano[2,3 d]pyrimidine: Yellow
solid, mp: 233–235°C. IR (KBr, vmax, cmÀ1): 2949,
2838, 1596, 1221. 1H NMR (400 MHz, CDCl3): δH
(ppm) 1.03–1.05 (d, J = 6.4 Hz, 3H, CH3), 1.33–1.43 (m,
2H, CH2), 1.64–1.77 (m, 1H, CH2), 1.81–1.83 (m, 1H,
CH2), 1.83–1.86 (m, 1H, CH), 3–3.07 (m, 2H, CH2),
3.85 (m, 1H, CH2), 3.88 (m, 1H, CH2), 3.90 (s, 2H,
CH2), 6.85–6.88 (d, J = 8.8 Hz, 1H, Ar-H), 7.06–7.08 (d,
J = 8.4 Hz, 1H, Ar--H), 7.35–7.38 (m, 2H, Ar-H), 7.40–
7.43 (dd, J = 2.8 Hz, 1H, ArH), 8.51 (d, J = 2.4 Hz, 1H,
Ar-H), 13.16 (s,1H, OH).13C NMR (100 MHz, CDCl3):
δC (ppm) 21.8 (CH3), 25.5 (CH2), 30.8 (CH2), 34.1
(2CH2), 48.8 (2CH2), 112.4, 116.8, 118.8, 119.5, 121.5
(C Ar), 131.3, 131.4, 131.5, 134.3, 134.5, 134.9, 135.5,
159.5. MS: m/z 531. Anal. Calcd for C23H21Br2N3O2: C,
52.00; H, 3.98; N, 7.91. Found: C, 51.71; H, 4; N, 7.86
(Table 4, entry 5).
6-Chloro-4-phenyl-2-(pyridine-4-yl)quinazoline: White
solid, mp: 194–195°C. IR (KBr, νmax, cmÀ1): 695, 833,
1413, 1478, 1529, 1555, 1595. 1H NMR (400MHz,
CDCl3): δH (ppm) 7.40–8.19 (m, Ar-H, 11H). 13C NMR
(100 MHz, CDCl3): δC (ppm) 122.3, 122.7, 125.8, 128.8,
130.0, 130.5, 131.0, 133.8, 134.9, 136.6, 145.0, 150.2,
150.4, 158.3, 167.9. MS: m/z 318. Anal. Calcd for
C19H12ClN3: C, 71.81; H, 3.81; N, 13.22. Found: C,
71.51; H, 3.61; N, 13.20 (Table 2, entry 12).
6-Chloro-2-(2,4-dichlorophenyl)-4-phenylquinazoline:
Pale-yellow solid, mp: 149–150°C. IR (KBr, νmax
,
cmÀ1): 697, 824, 1384, 1481, 1527, 1555, 1586. 1H
NMR (400 MHz, CDCl3): δH (ppm) 8.81–7.84 (m, Ar-
H, 12H). 13C NMR (100 MHz, CDCl3): δC (ppm)
127.2, 128.4, 128.9, 129.0, 130.0, 130.1, 130.5,
130.6, 130.8, 132.8, 133.7, 134.0, 134.9, 135.0,
135.8, 136.4, 136.5, 150.0, 160.5, 167.6. MS: m/z
385 (Table 2, entry 13).
6-Chloro-2-(3-methylphenyl)-4-phenylquinazoline: Milky
solid, mp: 181–182°C. IR (KBr, νmax, cmÀ1): 1HNMR
(400MHz, CDCl3): δH (ppm) 2.5 (s, CH3, 3H), 7.3–8.5 (m,
Ar-H, 12H). 13C NMR (100 MHz, CDCl3): δC (ppm) 21.5
(CH3), 122.1, 125.8, 125.7, 129.1, 130.0, 130.2, 130.8,
131.6, 132.5, 134.5, 137.1, 137.7, 138.2, 150.5, 160.6,
167.5. MS: m/z 330. Anal. Calcd for C19H12ClN3: C,
76.24; H, 4.57; N, 8.47. Found: C, 75.70; H, 4.31; N, 8.07
(Table 2, entry 14).
7-Bromo-2-(5-bromo-2-hydroxyphenyl)-4-(4-methylpi-
perazin-1-yl)-5H-benzopyrano[2,3-d]pyrimidine: Yellow
solid, mp: 229–231°C. IR (KBr, vmax, cmÀ1): 3074,
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

Month 2015
Synthesis of Quinazolines and Benzopyrano[2,3-d]pyrimidines
2936, 2843, 1596, 1150. 1H NMR (400 MHz, CDCl3): δH
(ppm) 2.39 (s, 3H, CH3), 2.60–2.63 (t, J = 4.8 Hz, 4H,
2CH2), 3.53–3.55 (t, J = 4.8 Hz, 4H, 2CH2), 3.90 (s, 2H,
CH2), 6.85–6.87 (d, J = 8.8 Hz, 1H, ArH), 7.07–7.09 (d,
J=8.4Hz, 1H, ArH), 7.35–7.37 (m, 2H, ArH), 7.40–7.43
(dd, J=6.0Hz, 1H, ArH), 8.50 (d, J=2.4Hz, 1H, ArH),
13.36 (s, 1H, OH). 13C NMR (100 MHz, CDCl3): δC
(ppm) 25.5 (CH), 46.1 (CH3), 48.1 (2CH2), 54.8 (2CH2),
116.9, 118.8, 119.6, 119.9, 121.2 (C Ar), 131.2, 131.3,
131.4, 135.6, 149.5, 159.4. MS: m/z 532. Anal. Calcd
for C22H20Br2N4O2: C, 49.65; H, 3.79; N, 10.53. Found:
C, 49.64; H, 3.81; N, 10.55 (Table 4, entry 6).
2-(2-Hydroxy-3-methoxyphenyl)-9-methoxy-4-(4-methyl-
piperazin-1-yl)-5H-benzopyrano[2,3-d]pyrimidine: Yellow
solid, mp: 179–181°C. IR (KBr, vmax, cmÀ1): 3052,
2928, 2840, 1581. 1H NMR (400 MHz, CDCl3): δH
(ppm) 2.37 (s, 3H, CH3), 2.60–2.62 (t, J = 4.4 Hz, 4H,
2CH2), 3.53–3.55 (t, J = 4.8 Hz, 4H, 2CH2), 3.92 (s, 2H,
CH2), 3.93 (s, 3H, OMe), 3.94 (s, 3H, OMe), 6.70–6.80
(m, 3H, Ar-H), 6.95–7.05 (m, 2H, Ar-H), 8.09–8.11 (dd,
Ja =8.0sHz, Jb =1.6Hz, 1H, Ar-H), 13.76 (s, 1H, OH).
13C NMR (100MHz, CDCl3): δC (ppm) 25.8 (CH), 46.1
(CH3), 48.1 (2CH2), 54.8 (2CH2), 56.05 (OCH3), 56.06
(OCH3), 97.3, 110.6, 113.9, 117.8, 118.6, 119.7, 120.1
(C Ar), 121.1, 124.2, 140.1, 148.2, 148.6, 150.6, 162.2,
164.2, 164.5. MS: m/z 434. Anal. Calcd for
C22H20Br2N4O2: C, 66.34; H, 6.03; N, 12.89. Found: C,
65.80; H, 6.01; N; 12.90 (Table 4, entry 9).
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Journal of Heterocyclic Chemistry
DOI 10.1002/jhet