Efficient access to benzochromeno[2,3-d ]pyrimidine derivatives from β-enamino nitriles by bis(trichloromethyl) carbonate and triphenylphosphine oxide

Article abstract of DOI:10.3184/174751914X13909344481573

A mild and efficient synthesis of novel benzochromeno[2,3-d ]pyrimidine derivatives is described. A number of 8,10-dichloro- 7-aryl-7H-benzo[7,8] chromeno[2,3-d ]pyrimidines and 9,11-dichloro-12-aryl-12H-benzo[5,6]chromeno[2, 3-d ]pyrimidines were synthes

Full text of DOI:10.3184/174751914X13909344481573

JOURNAL OF CHEMICAL RESEARCH 2014
VOL. 38 MARCH, 143–146
RESEARCH PAPER 143
Efficient access to benzochromeno[2,3-d]pyrimidine derivatives
from β-enamino nitriles by bis(trichloromethyl) carbonate and
triphenylphosphine oxide
Ye Zou, Zhenhua Li and Weike Su*
Key Laboratory for Green Pharmaceutical Technologies and Related Equipment of Ministry of Education, College of Pharmaceutical Sciences,
Zhejiang University of Technology, Hangzhou 310014, P.R. China
A mild and efficient synthesis of novel benzochromeno[2,3-d]pyrimidine derivatives is described. A number of 8,10-dichloro-
7-aryl-7H-benzo[7,8]chromeno[2,3-d]pyrimidines and 9,11-dichloro-12-aryl-12H-benzo[5,6]chromeno[2,3-d]pyrimidines
were synthesised by the cyclisation of 2-amino-4-aryl-4H-benzo[h]chromene-3-carbonitriles or 3-amino-1-aryl-1H-benzo[f]
chromene-2-carbonitriles with bis(trichloromethyl) carbonate and triphenylphosphine oxide in moderate to good yields.
Keywords: benzochromeno[2,3-d]pyrimidine, cyclisation, bis(trichloromethyl) carbonate, triphenylphosphine oxide
Pyrano[2,3-d]pyrimidine derivatives are an important class
of heterocycles that have received considerable attention due
to their pharmacological properties such as antimicrobial,1–3
anticancer,4,5 antifungal6 and antiviral7 activities. They possess
wide utility but the availability of synthetic methods is
limited, typically relying on two-component condensation of
2-benzylidenemalononitrile with barbituric acid.8,9
In recent years, improvement were made by the reaction
of benzylidenemalononitriles with barbituric acids in ionic
liquids,10 or under microwave irradiation11,12 to shorten the
reaction time and raise the yields. Some novel strategies13–17
have also been developed to prepare pyrano[2,3-d]pyrimidine
derivatives. Limitations of these methods, however, include
requirement for longer reaction times, use of expensive
reagents, complex synthetic pathways, and unsuitability for
industrialisation. So the development of new and convenient
synthetic approaches to these scaffolds is of great interest to the
medicinal chemistry community.
carbonitriles leading to 8,10-dichloro-7-aryl-7H-benzo[7,8]
chromeno[2,3-d]pyrimidines or 9,11-dichloro-12-aryl-12H-
benzo[5,6]chromeno[2,3-d]pyrimidines by bis(trichloromethyl)
carbonate (BTC) and Ph3PO.
Results and discussion
2-Amino-4-aryl-4H-benzo[h]chromene-3-carbonitriles 1a–j
and 3-amino-1-aryl-1H-benzo[f]chromene-2-carbonitriles3a–e
were synthesised by three-component solvent-free condensation
of α/β-naphthol, substituted arylaldehydes and malononitrile in
the presence of Na2CO3 as an efficient catalyst with excellent
yields.18 We subsequently carried out the reaction of compounds
1a–j and3a–ewithBTCandPh3POinchlorobenzeneat110 °Cto
produce the corresponding 8,10-dichloro-7-aryl-7H-benzo[7,8]
chromeno[2,3-d]pyrimidine 2a–j and the 9,11-dichloro-12-aryl-
12H-benzo[5,6]chromeno[2,3-d]pyrimidine 4a–e in moderate
to good yields (Schemes 1 and 2, Table 1).
The activity of this reaction was found to be solvent-
dependent. Various solvents were examined for the cyclisation
reaction, including dichloromethane, 1,2-dichlorethane,
acetonitrile, toluene and chlorobenzene. The best results were
obtained in chlorobenzene with good yield (84%) after a short
reaction time (60 min).
In the development of highly expedient methods for the
synthesisofpyrano[2,3-d]pyrimidinederivatives,wereporthere
a convenient and versatile method directly from the cyclisation
of widely available 2-amino-4-aryl-4H-benzo[h]chromene-3-
carbonitriles or 3-amino-1-aryl-1H-benzo[f]chromene-2-
R
R
Cl
OH
CN
N
CN
CN
Na2CO3
neat, 120 oC
BTC/Ph3PO
PhCl, 110 oC
+
R
CHO +
N
NH2
O
Cl
O
2(a-j)
1(a-j)
Scheme 1 Synthesis of 8,10-dichloro-7-aryl-7H-benzo[7,8]chromeno[2,3-d]pyrimidine.
R
R
Cl
OH
CN
CN
CN
Na2CO3
BTC/Ph3PO
+
R
CHO +
N
neat, 120 oC
PhCl,
o
110 C
NH2
O
N
O
Cl
3(a-e)
4(a-e)
Scheme 2 Synthesis of 9,11-dichloro-12-aryl-12H-benzo[5,6]chromeno[2,3-d]pyrimidine.
* Correspondent. E-mail: pharmlab@zjut.edu.cn
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144 JOURNAL OF CHEMICAL RESEARCH 2014
Table 1 Synthesis of benzo chromene[2,3-d]pyrimidine derivatives
Table 2 Synthesis of 2c under different conditions
Entrya
R
Time/min
Product
Yield/%b
OCH3
OCH3
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
C6H5
60
60
60
60
60
70
90
90
90
90
60
70
70
90
90
2a
2b
2c
2d
2e
2f
2g
2h
2i
80
81
84
82
79
74
73
71
73
70
78
83
84
73
74
2-OCH3C6H4
4-OCH3C6H4
4-CH3C6H4
1-Naphthalene
4-FC6H4
4-ClC6H4
4-BrC6H4
2-BrC6H4
2,4-Cl2C6H3
C6H5
Cl
N
7a
8
7
CN
BTC/Ph3PO
PhCl, 110 oC
N
NH2
O
O
Cl
10
11a
2c
1c
2j
4a
4b
4c
4d
4e
Ratio
1c:BTC:Ph3PO
Reaction
Entry
Yield/%a
temperature/oC
4-OCH3C6H4
4-CH3C6H4
2-BrC6H4
1
2
3
5
6
7
8
9
10
11
12
13
1:0.3:0
1:0.3:0.3
1:0.3:1
1:0.3:2
1:1:1
1:1:2
1:1:3
1:2:3
1:1:4
1:1:3
1:1:3
110
110
110
110
110
110
110
110
110
90
0
Trace
25
20
55
68
84
81
82
4-ClC6H4
aReaction condition: 2-amino-4-aryl-4H-chromene-3-carbonitrile (1 mmol),
BTC (1 mmol), Ph3PO (3 mmol), 110 °C.
bIsolated yields.
In order to determine the optimal conditions, we screened
various ratios of reactants at different temperatures for the above
reaction. The model reaction was carried out simply by reaction
53
70
77
100
120
1:1:3
aIsolated yields based on 1c.
of
2-amino-4-(4-methoxyphenyl)-4H-benzo[h]chromene-3-
carbonitrile 1c with BTC and Ph3PO in chlorobenzene (Table 2).
The absence of Ph3PO resulted in the failure of the reaction
to give the corresponding pyrano[2,3-d]pyrimidine derivative
(Table 2, entry 1). The use of catalytic amount of Ph3PO also
would not promote this cyclisation, only giving a trace of the
product (Table 2, entry 2). Note that the reaction proceeded by
smooth 1:1:3 addition in chlorobenzene to produce 2c in 84%
yield at 110°C (Table 2, entry 8). Furthermore, in an effort to
improve the yield, we increased the amount of BTC or Ph3PO
and observed no obvious change in the product yield (Table 2,
entries 9 and 10). A brief examination of reaction temperature
revealed that the reaction proceeded most efficiently in
chlorobenzene at 110 °C (Table 2, entry 8). When the reaction
temperature dropped, the corresponding yield also dropped.
(Table 2, entries 11 and 12). We also observed a decrease in
yield when the reaction temperature was >110 °C, coupled with
the formation of unidentified impurities (Table 2, entry 13).
The structure of all products 2a–j and 4a–e was confirmed by
IR, 1H NMR, 13C NMR, MS, and HRMS. From the IR spectrum
of the product (2c), the disappearance of characteristic bands at
3416, 3324 cm–1 for the NH2 and at 2194 cm–1 for the CN in
the starting material, meanwhile, the appearance of a strong
band at 1528 cm–1 for C=N of the pyrimidine ring indicated
The possible mechanism of the formation of
benzochromeno[2,3-d]pyrimidine is shown in Scheme 3.
Initially, the amino-group of 1 was reacted with BTC to form an
intermediate 5,19,20 which reacted with Ph3PCl2 generated in situ
from BTC and Ph3PO, formed the O–P bond and converted to 6.
The chlorination of C-8 position of 6 acquired the intermediate
7. Finally, the chlorination of C-10 position was accomplished
by the replacement of Ph3PO with chloride and afforded the
final product 2.
Conclusion
In conclusion, we have developed a new and efficient strategy
for convenient synthesis of 8,10-dichloro-7-aryl-7H-benzo[7,8]
chromeno[2,3-d]pyrimidine and 9,11-dichloro-12-aryl-12H-
benzo[5,6]chromeno[2,3-d]pyrimidines with moderate to good
yields in the BTC/Ph3PO system. This method has been applied
to a range of substrates. The yield of the reaction depends
on the substituents in the phenyl ring. The advantages of the
present procedure are experimental simplicity and easy work-
up. Further biological applications of these compounds are
currently in progress in our laboratory.
1
the formation of product. From the H NMR spectrum, the
Experimental
absence of two singlets at 4.75 ppm (two amine protons) and
4.80 ppm (proton attached to C-7) in the starting material and
the disappearance of signals at 61.8 ppm (C-7a), 117.4 ppm
(C-8) and 158.6 ppm (C-11a) and the appearance of signals
at 114.6 ppm (C-7a), 157.7 ppm (C-8), 158.9 ppm (C-10), and
165.0 ppm (C-11a) in the 13C NMR spectra confirm the structure
of compound 2c. Besides, MS, and HRMS also supported the
structural formation.
Utilising these optimal conditions (Table 2, entry 8), the
reaction was extended to other aryl substrate (2a–j and 4a–e)
in moderate to good yields (Table 1). Moreover, the structures
of aryl bearing electron-donating groups (Table 1, entries 2–4,
12 and 13) often led to higher yields than those with electron-
withdrawing groups (Table 1, entries 6–10, 14 and 15).
All reagents were purchased from commercial sources and used
without treatment, unless otherwise indicated. Melting points were
determined with a Büchi B-540 capillary melting point apparatus and
are uncorrected. IR spectra were measured in KBr on an AVATAR-370
spectrometer. 1H (400 MHz) NMR and 13C (100 Hz) NMR spectra were
recorded on a Varian spectrometer in CDCl3 using tetramethylsilane
(TMS) as internal standards, chemical shifts are expressed in ppm.
LRMS (lower resolution mass spectra) and HRMS (high resolution
mass spectra) were obtained on Finnigan Trace DSQ (ESI) and Bruker
Daltonics micrOTOF-Q II instrument, respectively.
Synthesis of 2a–j and 4a–e; general procedure
BTC (0.89 g, 3 mmol/8 mL PhCl) was added to a stirred solution
of Ph3PO (2.50 g, 9 mmol) in PhCl (15 mL) dropwise at 0–5 °C.
After complete addition the mixture was stirred for 30 min at room
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JOURNAL OF CHEMICAL RESEARCH 2014 145
BTC + Ph3PO
Ph
3P-Cl Cl
R
O
R
O
N
CN
C
N
Cl3CO
OCCl3
NH2
O
C O
5
Cl
R
O
1
N
N
O
PPh3
Cl
6
R
Cl
N
R
O
Cl
N
Cl
N
O
Cl
N
O
PPh3
Cl
7
2
Scheme 3 Possible reaction pathways of the formation of benzochromeno[2,3-d]pyrimidine.
temperature. Then 1a–j/ 3a–e (3 mmol) was added, and the mixture
was heated to 110 °C until completion of reaction (followed by TLC,
hexane: ethyl acetate=3:1). After the reaction mixture had been
washed with water and extracted with dichloromethane, the organic
layer was dried over anhydrous Na2SO4, concentrated and purified
over column chromatography to afford the pure product.
cm–1; 1H NMR (400 MHz, CDCl3, ppm) δ 8.42 (d, J=8.4 Hz, 1H), 7.75
(d, J=8.1 Hz, 1H), 7.56 (ddt, J=13.8, 9.5, 6.9 Hz, 3H), 7.10 (dt, J=20.3,
8.3 Hz, 5H), 5.31 (s, 1H), 2.26 (s, 3H); 13C NMR (100 Hz, CDCl3, ppm) δ
165.1, 162.4, 157.8, 143.4, 139.8, 137.3, 133.4, 129.6, 127.9, 127.5, 127.1,
126.9, 125.6, 125.4, 123.6, 121.3, 118.2, 114.5, 42.2, 21.1; MS (ESI): 393
([M + H]+); HRMS (ESI) calcd for C22H15Cl2N2O ([M+H]+): 393.0565;
found: 393.0559.
8,10-Dichloro-7-(naphthalen-1-yl)-7H-benzo[7,8]chromeno[2,3-d]
pyrimidine (2e): White solid, m.p. 241.8−242.7 °C; IR (KBr): 1529
(–C=N at pyrimidine ring), 1256 (C–O–C at pyran ring), 668 (C–Cl)
cm–1; 1H NMR (400 MHz, CDCl3, ppm) δ 8.46 (t, J=9.9 Hz, 2H), 7.88
(d, J=8.1 Hz, 1H), 7.68 (dd, J=19.6, 7.9 Hz, 3H), 7.63−7.48 (m, 3H),
7.39 (d, J=8.5 Hz, 1H), 7.30 (t, J=7.7 Hz, 1H), 7.11 (d, J=8.6 Hz, 2H),
6.24 (s, 1H); 13C NMR (100 Hz, CDCl3, ppm) δ 165.0, 162.8, 157.8,
142.5, 140.2, 133.6, 133.2, 130.6, 129.2, 128.1, 127.4, 127.1, 127.0,
127.0, 125.9, 125.7, 125.4, 124.7, 123.5, 122.3, 121.3, 118.2, 114.8; MS
(ESI): 429 ([M+H]+); HRMS (ESI) calcd for C25H15Cl2N2O ([M+H]+):
429.0567; found: 429.0578.
8,10-Dichloro-7-phenyl-7H-benzo[7,8]chromeno[2,3-d]pyrimidine
(2a): White solid, m.p. 217.0−219.3 °C; IR (KBr): 1529 (–C=N at
pyrimidine ring), 1260 (C–O–C at pyran ring), 666 (C–Cl) cm–1;
1H NMR (400 MHz, CDCl3, ppm) δ 8.44 (d, J=8.4 Hz, 1H), 7.77 (d,
J=8.1 Hz, 1H), 7.64−7.51 (m, 3H), 7.29−7.15 (m, 6H), 5.39 (s, 1H); 13
C
NMR (100 Hz, CDCl3, ppm) δ 165.1, 162.4, 157.9, 143.4, 142.7, 133.4,
128.9, 128.1, 127.6, 127.5, 127.1, 127.0, 125.6, 125.4, 123.6, 121.4,
117.9, 114.4, 42.6; MS (ESI): 379 ([M+H]+); HRMS (ESI) calcd for
C21H13Cl2N2O ([M+H]+): 379.0399; found: 379.0411.
8,10-Dichloro-7-(2-methoxyphenyl)-7H-benzo[7,8]chromeno[2,3-d]
pyrimidine (2b): White solid, m.p. 214.8−216.4 °C; IR (KBr): 2836
(–OCH3), 1530 (–C=N at pyrimidine ring), 1259 (C–O–C at pyran
1
ring), 666 (C–Cl) cm–1; H NMR (400 MHz, CDCl3, ppm) δ 8.43 (d,
8,10-Dichloro-7-(4-fluorophenyl)-7H-benzo[7,8]chromeno[2,3-d]
pyrimidine (2f): White solid, m.p. 175.9−178.2 °C; IR (KBr): 1529
(–C=N at pyrimidine ring), 1260 (C–O–C at pyran ring), 1226 (C–F),
J=8.3 Hz, 1H), 7.75 (d, J=8.1 Hz, 1H), 7.61−7.55 (m, 1H), 7.54−7.48 (m,
2H), 7.26 (dd, J=7.5, 1.5 Hz, 1H), 7.23−7.17 (m, 2H), 6.90 (td, J=7.5,
1.0 Hz, 1H), 6.78 (d, J=8.2 Hz, 1H), 5.59 (s, 1H), 3.63 (s, 3H); 13C NMR
(100 Hz, CDCl3, ppm) δ 165.8, 161.5, 157.5, 156.7, 143.7, 133.3, 131.4,
130.7, 130.3, 129.1, 127.4, 126.8, 125.5, 124.9, 123.4, 121.2, 120.7, 117.1,
114.1, 111.6, 55.5, 38.5; MS (ESI): 409 ([M+H]+); HRMS (ESI) calcd
for C22H15Cl2N2O2 ([M + H]+): 409.0505; found: 409.0511.
8,10-Dichloro-7-(4-methoxyphenyl)-7H-benzo[7,8]chromeno[2,3-d]
pyrimidine (2c): White solid, m.p. 146.4−147.5 °C; IR (KBr): 2835
(–OCH3), 1528 (–C=N at pyrimidine ring), 1257 (C–O–C at pyran
ring), 663 (C–Cl) cm–1; 1H NMR (400 MHz, CDCl3, ppm) δ 8.46–8.40
(m, 1H), 7.77 (d, J=8.1 Hz, 1H), 7.64−7.50 (m, 3H), 7.19−7.09 (m, 3H),
6.81−6.73 (m, 2H), 5.34 (s, 1H), 3.72 (s, 3H); 13C NMR (100 Hz, CDCl3,
ppm) δ 165.0, 162.4, 158.9, 157.8, 143.4, 135.1, 133.4, 129.2, 127.5, 127.1,
127.0, 125.6, 125.5, 123.7, 121.4, 118.3, 114.7, 114.4, 55.3, 41.8; MS
(ESI): 409 ([M+H]+); HRMS (ESI) calcd for C22H13Cl2N2O2 ([M–H]+):
407.0360; found: 407.0370.
1
664 (C–Cl) cm–1; H NMR (400 MHz, CDCl3, ppm) δ 8.43−8.39 (m,
1H), 7.76 (d, J=7.9 Hz, 1H), 7.63−7.51 (m, 3H), 7.22−7.15 (m, 2H), 7.12
(d, J=8.5 Hz, 1H), 6.98−6.90 (m, 2H), 5.35 (s, 1H); 13C NMR (100 Hz,
CDCl3, ppm) δ 164.9, 163.0, 162.4, 160.6, 157.9, 143.3, 138.5, 133.4,
129.8, 127.5, 127.2, 125.7, 125.2, 123.5, 121.3, 117.6, 115.9, 114.1, 41.8;
MS (ESI): 397 ([M+H]+); HRMS (ESI) calcd for C21H12Cl2FN2O
([M + H]+): 397.0315; found: 397.0322.
8,10-Dichloro-7-(4-chlorophenyl)-7H-benzo[7,8]chromeno[2,3-d]
pyrimidine (2g): White solid, m.p. 170.9−172.3 °C; IR (KBr):
1529 (–C=N at pyrimidine ring), 1257 (C–O–C at pyran ring), 664
1
(C–Cl) cm–1; H NMR (400 MHz, CDCl3, ppm) δ 8.43 (dd, J=8.4,
0.5 Hz, 1H), 7.78 (d, J=8.0 Hz, 1H), 7.64− 7.52 (m, 3H), 7.26−7.20 (m,
2H), 7.20−7.10 (m, 3H), 5.38 (s, 1H); 13C NMR (100 MHz, CDCl3, ppm)
δ 164.8, 162.4, 158.0, 143.2, 141.0, 133.5, 133.3, 129.5, 129.1, 127.5,
127.3, 127.1, 125.7, 125.1, 123.4, 121.3, 117.2, 113.8, 41.9; MS (ESI): 413
([M + H]+); HRMS (ESI) calcd for C21H12Cl3N2O ([M+H]+): 413.0010;
found: 413.0008.
8,10-Dichloro-7-(4-methylphenyl)-7H-benzo[7,8]chromeno[2,3-d]
pyrimidine (2d): White solid, m.p. 179.7−181.4 °C; IR (KBr): 1527
(–C=N at pyrimidine ring), 1258 (C–O–C at pyran ring), 661 (C–Cl)
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146 JOURNAL OF CHEMICAL RESEARCH 2014
7-(4-Bromophenyl)-8,10-dichloro-7H-benzo[7,8]chromeno[2,3-d]
pyrimidine (2h): White solid, m.p. 175.8−178.0 °C; IR (KBr): 1528
(–C=N at pyrimidine ring), 1258 (C–O–C at pyran ring) cm–1; 1H NMR
(400 MHz, CDCl3, ppm) δ 8.42 (d, J=8.4 Hz, 1H), 7.78 (d, J=8.0 Hz,
1H), 7.66−7.51 (m, 3H), 7.42 −7.35 (m, 2H), 7.16−7.06 (m, 3H), 5.36 (d,
J=9.8 Hz, 1H); 13C NMR (100 MHz, CDCl3, ppm) δ 164.9, 162.4, 158.2,
143.4, 141.6, 133.5, 132.1, 129.8, 127.5, 127.3, 127.2, 125.8, 125.1, 123.6,
121.7, 121.3, 117.3, 113.8, 42.1; MS (ESI): 457 ([M+H]+); HRMS (ESI)
calcd for C21H10BrCl2N2O ([M–H]+): 454.9359; found: 454.9352.
7-(2-Bromophenyl)-8,10-dichloro-7H-benzo[7,8]chromeno[2,3-d]
pyrimidine (2i): White solid, m.p. 258.4−259.6 °C; IR (KBr): 1529
(–C=N at pyrimidine ring), 1259 (C–O–C at pyran ring), 659 (C–Cl)
cm–1; 1H NMR (400 MHz, CDCl3, ppm) δ 8.40 (d, J=8.3 Hz, 1H), 7.75
(d, J=8.0 Hz, 1H), 7.62−7.50 (m, 4H), 7.33 (d, J=8.5 Hz, 1H), 7.18−6.94
(m, 3H), 6.01 (s, 1H); 13C NMR (100 MHz, CDCl3, ppm) δ 165.1, 162.8,
158.2, 142.8, 142.4, 133.4, 133.1, 131.0, 128.9, 128.4, 127.5, 127.2,
127.0, 125.6, 124.7, 123.4, 123.1, 121.3, 117.1, 113.8, 40.8; MS (ESI):
457 ([M+H]+); HRMS (ESI) calcd for C21H10BrCl2N2O ([M–H]+):
454.9359; found: 454.9350.
8,10-Dichloro-7-(2,4-dichlorophenyl)-7H-benzo[7,8]chromeno[2,3-d]
pyrimidine (2j): Yellow solid, m.p. 237.0−238.5 °C; IR (KBr): 1529
(–C=N at pyrimidine ring), 1259 (C–O–C at pyran ring), 663 (C–Cl)
cm–1; 1H NMR (400 MHz, CDCl3, ppm) δ 8.41 (d, J=8.3 Hz, 1H), 7.77
(d, J=8.0 Hz, 1H), 7.57 (tt, J=6.9, 5.4 Hz, 3H), 7.41 (d, J=2.0 Hz, 1H),
7.22 (d, J=8.5 Hz, 1H), 7.12 (dd, J=8.4, 2.0 Hz, 1H), 6.98 (d, J=8.4 Hz,
1H), 5.97 (s, 1H); 13C NMR (100 MHz, CDCl3, ppm) δ 165.3, 162.6,
158.5, 143.2, 139.2, 134.1, 133.6, 133.3, 131.7, 129.8, 128.2, 127.5, 127.4,
127.2, 125.8, 124.6, 123.5, 121.4, 116.4, 113.2, 38.4; MS (ESI): 447
([M + H]+); HRMS (ESI) calcd for C21H9Cl4N2O ([M–H]+): 444.9474;
found: 444.9467.
12-(2-Bromophenyl)-9,11-dichloro-12H-benzo[5,6]chromeno[2,3-d]
pyrimidine (4d): White solid, m.p. 285.6−287.4 °C; IR (KBr): 1530
(–C=N at pyrimidine ring), 1214 (C–O–C at pyran ring), 686 (C–Cl)
cm–1; 1H NMR (400 MHz, CDCl3, ppm) δ 8.45 (d, J=8.5 Hz, 1H), 7.81
(t, J=9.0 Hz, 2H), 7.59−7.48 (m, 2H), 7.47−7.40 (m, 2H), 7.28−7.24 (m,
1H), 7.13 (td, J=7.7, 1.3 Hz, 1H), 6.99 (ddd, J=8.0, 7.4, 1.7 Hz, 1H), 6.24
(s, 1H); 13C NMR (100 MHz, CDCl3, ppm) δ 181.5, 165.0, 162.3, 147.2,
141.0, 133.9, 131.9, 131.6, 130.7, 130.5, 129.1, 128.8, 128.3, 127.5, 125.6,
123.9, 122.5, 117.2, 114.4, 38.9; Mass: 457 ([M+H]+); HRMS (ESI)
calcd for C21H10BrCl2N2O ([M–H]+): 454.9359; found: 454.9350.
9, 11-Dichloro-12-(4-chlorophenyl)-12H-benzo[5,6]chromeno[2,3-d]
pyrimidine (4e): White solid, m.p. 208.7−210.2 °C; IR (KBr): 1533
(–C=N at pyrimidine ring), 1213 (C–O–C at pyran ring), 643 (C–Cl)
cm–1; 1H NMR (400 MHz, CDCl3, ppm) δ 7.94 (d, J=8.4 Hz, 1H), 7.83
(t, J=8.8 Hz, 2H), 7.51 (ddd, J=8.4, 7.0, 1.3 Hz, 1H), 7.48−7.40 (m, 2H),
7.34−7.26 (m, 2H), 7.22−7.15 (m, 2H), 5.90 (s, 1H); 13C NMR (100 MHz,
CDCl3, ppm) δ 164.7, 161.6, 157.7, 147.1, 139.6, 133.5, 131.7, 130.4,
130.1, 129.6, 129.0, 128.9, 127.7, 125.6, 122.6, 117.1, 115.8, 114.5, 38.6;
Mass: 413 ([M+H]+); HRMS (ESI) calcd for C21H12Cl3N2O ([M+H]+):
413.0010; found: 413.0013.
We gratefully acknowledge financial support from the
National Natural Science Foundation of China (No. 21176222)
and Natural Science Foundation of Zhejiang Province (No.
LY2B02020).
Received 12 December 2013; accepted 8 January 2014
Paper 1302335 doi: 10.3184/174751914X13909344481573
Published online: 7 March 2014
9,11-Dichloro-12-phenyl-12H-benzo[5,6]chromeno[2,3-d]pyrimidine
(4a): White solid, m.p. 188.4−189.2 °C; IR (KBr): 1529 (–C=N
References
1
at pyrimidine ring), 1286 (C–O–C at pyran ring) cm–1; H NMR
1
M.M. Ghorab and A.Y. Hassan, Phosphorus, Sulfur Silicon Relat. Elem.,
1998, 141, 251.
(400 MHz, CDCl3, ppm) δ 8.01 (d, J=8.5 Hz, 1H), 7.81 (t, J=8.4 Hz,
2H), 7.54−7.34 (m, 5H), 7.25−7.20 (m, 2H), 7.16−7.09 (m, 1H), 5.91 (s,
1H); 13C NMR (100 MHz, CDCl3, ppm) δ 170.6, 164.8, 161.6, 147.1,
141.2, 131.6, 130.3, 130.2, 128.8, 128.3, 127.5, 125.5, 122.8, 117.2,
116.4, 115.0, 39.2; MS (ESI): 379 ([M+H]+); HRMS (ESI) calcd for
C21H13Cl2N2O ([M+H]+): 379.0399; found: 379.0391.
2
A.H. Bedair, H.A. Emam, N.A. El-Hady, K.A.R. Ahmed and A.M.
El-Agrody, Farmaco, 2001, 56, 965.
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H.M. Alya and M.M. Kamal, Eur. J. Med. Chem., 2012, 47, 18.
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9,11-Dichloro-12-(4-methoxyphenyl)-12H-benzo[5,6]chromeno[2,3-d]
pyrimidine (4b): White solid, m.p. 221.5−223.9 °C; IR (KBr): 2837
(–OCH3), 1530 (–C=N at pyrimidine ring), 1255 (C–O–C at pyran
1
ring) cm–1; H NMR (400 MHz, CDCl3, ppm) δ 8.00 (d, J=8.4 Hz,
1H), 7.80 (dd, J=8.3, 4.6 Hz, 2H), 7.53−7.47 (m, 1H), 7.46−7.38 (m,
2H), 7.30−7.22 (m, 2H), 6.77−6.71 (m, 2H), 5.85 (s, 1H), 3.67 (s, 3H);
13C NMR (100 MHz, CDCl3, ppm) δ 164.6, 161.5, 158.6, 157.2, 146.9,
133.5, 131.6, 130.2, 130.0, 128.8, 127.5, 125.5, 122.8, 117.1, 116.5, 115.2,
114.1, 55.2, 38.3; MS (ESI): 409 ([M+H]+); HRMS (ESI) calcd for
C22H15Cl2N2O2 ([M + H]+): 409.0505; found: 409.0500.
9,11-Dichloro-12-(4-methylphenyl)-12H-benzo[5,6]chromeno[2,3-d]
pyrimidine (4c): White solid, m.p. 204.9−206.6 °C; IR (KBr): 1530
(–C=N at pyrimidine ring), 1286 (C–O–C at pyran ring) cm–1; 1H NMR
(400 MHz, CDCl3, ppm) δ 8.02 (d, J=8.4 Hz, 1H), 7.81 (t, J=7.4 Hz,
2H), 7.54−7.39 (m, 3H), 7.24 (d, J=2.9 Hz, 2H), 7.02 (d, J=8.0 Hz, 2H),
5.89 (s, 1H), 2.21 (s, 3H); 13C NMR (100 MHz, CDCl3, ppm) δ 164.7,
161.5, 157.3, 146.9, 138.3, 137.3, 131.6, 130.3, 130.0, 129.4, 128.7,
128.1, 127.5, 125.4, 122.8, 117.1, 116.5, 115.1, 38.8, 21.1; MS (ESI): 393
([M + H]+); HRMS (ESI) calcd for C22H15Cl2N2O ([M+H]+): 393.0565;
found: 393.0560.
8
9
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