Synthesis and in vitro antibacterial activities of 5-(2,3,4,5-Tetrahydro- 1H-chromeno[2,3-d]pyrimidin-5-yl)pyrimidione derivatives

Article abstract of DOI:10.1002/cjoc.201100112

A series of novel 5-(2,3,4,5-tetrahydro-1H-chromeno[2,3-d]pyrimidin-5-yl) pyrimidione derivatives have been synthesized from substituted salicylaldehydes and barbituric acid or 2-thiobarbituric acid in water catalyzed by phase transfer catalysis of triethylbenzyl ammonium chloride (TEBA). Elemental analysis, IR, ¹H NMR, and ¹³C NMR elucidated the structures of all the newly synthesized compounds. In vitro antimicrobial activities of synthesized compounds have been investigated against Escherichia coli, Bacillus subtilis, Staphylococcus aureus, and Pseudomonas aeruginosa. These newly synthesized derivatives exhibited significant in vitro antibacterial activity. A series of novel 5-(2,3,4,5-tetrahydro-1H-chromeno[2,3-d]pyrimidin- 5-yl)pyrimidione derivatives have been synthesized from substituted salicylaldehydes and barbituric acid or 2-thiobarbituric acid in water catalyzed by phase transfer catalysis of triethylbenzyl ammonium chloride (TEBA). Elemental analysis, IR, ¹H NMR, and ¹³C NMR elucidated the structures of all the newly synthesized compounds. In vitro antimicrobial activities of synthesized compounds have been investigated against Escherichia coli, Bacillus subtilis, Staphylococcus aureus, and Pseudomonas aeruginosa. Copyright

Full text of DOI:10.1002/cjoc.201100112

FULL PAPER
DOI: 10.1002/cjoc.201100112
Synthesis and in vitro Antibacterial Activities of 5-(2,3,4,5-
Tetrahydro-1H-chromeno[2,3-d]pyrimidin-5-yl)pyrimidione
Derivatives
Cheng, Qingfang*,a,b(程青芳)
Wang, Qifab(王启发)
Tan, Tinga(谈婷)
Wang, Mingxiaoa(王明逍)
Chen, Naa(陈娜)
a Department of Chemical Technology, Huaihai Institute of Technology, Lianyungang, Jiangsu 222005, China
b Jiangsu Key Laboratory of Marine Biotechnology, Huaihai Institute of Technology, Lianyungang,
Jiangsu 222005, China
A series of novel 5-(2,3,4,5-tetrahydro-1H-chromeno[2,3-d]pyrimidin-5-yl)pyrimidione derivatives have been
synthesized from substituted salicylaldehydes and barbituric acid or 2-thiobarbituric acid in water catalyzed by
1
phase transfer catalysis of triethylbenzyl ammonium chloride (TEBA). Elemental analysis, IR, HNMR, and 13
C
NMR elucidated the structures of all the newly synthesized compounds. In vitro antimicrobial activities of synthe-
sized compounds have been investigated against Escherichia coli, Bacillus subtilis, Staphylococcus aureus, and
Pseudomonas aeruginosa. These newly synthesized derivatives exhibited significant in vitro antibacterial activity.
Keywords 5-(2,3,4,5-tetrahydro-1H-chromeno[2,3-d]pyrimidin-5-yl)pyrimidione, antibacterial activity, phase
transfer catalysis, water
Introduction
good yields. The concept of reaction “on water” is now
well established.[16]
Chromene and derivatives are an important class of
heterocyclic compounds, which are found to possess
antiestrogenic activity,[1] and are evaluated for potas-
sium channel opening and hypotensive activies,[2,3] an-
timicrobial,[4,5] cytotoxicity,[6] antifungal,[7] and mollu-
scidials activies.[8] The primidine group possesses wide
range of biological and pharmacological activities.[9,10]
Because of intense interest in the biological activity of
these compounds, in recent years, several synthetic
procedures for preparing of chromene and pyrimidine
derivatives have been reported.[6,11] The fusion of
chromene to pyrimidine ring is known to increase the
biological activity.[5,6]
Water, represents the solvent par excellence because
of its potential advantages in terms of cost, safety,
work-up procedure and environmental concerns, and
presents different reactivity and selectivity patterns
compared with those observed in common organic sol-
vents. There are a number of chemical transformations
that are not only compatible with water but actually
benefit from its unique physical and chemical properties,
e.g., high cohesive energy density, high dielectric con-
stant and internal pressure, and hydrophobic effect.[12] A
large number of organic reactions such as Diels-Alder
reactions,[13] Claisen rearrangement reactions,[14] and
Mannich reactions[15] can be carried out in water with
By considering all above aspects, and continuing our
studies on the reaction in water,[17-19] we report for the
first time an efficient one-pot synthesis of 5-(2,3,4,5-
tetrahydro-1H-chromeno[2,3-d]pyrimidin-5-yl)pyrimi-
dione derivatives from substituted salicylaldehydes and
barbituric acid or thiobarbituric acid in water catalyzed
by phase transfer catalysis.
Results and Discussion
The effects of catalysts were first studied. At the first
stage, the reaction of salicylaldehyde with barbituric
acid was carried out at 50 ℃ in water without adding
any catalyst, the yield is low even though the reaction
time prolonged. On the other side, the principal limita-
tion of adding no catalysis at 50 ℃ is the concomitant
formation of 3a and 4 (Scheme 1). In the presence of
phase transfer catalysis (PTS), the high yield transfor-
mations were carried out without any significant
amounts of undesirable side product 4.
We have not established a detailed mechanism for
the formation of 3a, however, significant amounts of 4
have formed leading us to propose a possible reaction
mechanism to explain the formation of 3a. The forma-
tion of products 3a can be rationalized by initial forma-
tion of intermediate 4 via condensation of 1a and 2.
*
E-mail: cheng_qingfang@yahoo.com.cn
Received July 8, 2011; accepted August 19, 2011; published online January 19, 2012.
386
© 2012 SIOC, CAS, Shanghai, & WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
Chin. J. Chem. 2012, 30, 386—390

5-(2,3,4,5-Tetrahydro-1H-chromeno[2,3-d]pyrimidin-5-yl)pyrimidione Derivatives
Scheme 1 Scheme 2
R1
O
O
CHO
NH
NH
O
H2O
CHO
OH
O
NH
NH
O
+
OH
H2O
X
+
TEBA
HN
NH
O
R1
1a
2
O
1
N
H
OH
X
X
N
H
2
O
O
X = O or S
3a 3h
O
O
O
O
+
Table
2
Synthesis of 5-(2,3,4,5-tetrahydro-1H-chromeno-
HN
NH
[2,3-d]pyrimidin-5-yl)pyrimidiones 3a—3ha
HN
NH
O
N
H
O
N
H
O
O
O
4
Product
3a
R1
X
O
S
Time/min
Yieldb/%
m.p./℃
268—270
＞300
3a
H
45
50
55
60
55
65
60
65
90
H
86
3b
Subsequent Michael addition of 2 to the intermediate 4
followed by isomerization and dehydration afforded
product 3a (Scheme 1).
Cl
O
S
87
＞300
3c
Cl
84
252—254
240—242
245—246
250—251
265—266
3d
The efficiency of various phase transfer catalysts
(PTS) has also been compared (Table 1). Two types of
phase transfer catalysts including tetramethyl ammo-
nium chloride (TMAC), tetrabutyl ammonium chloride
(TBAC), triethylbenzyl ammoium chloride (TEBA),
tetrabutyl ammonium bromide (TBAB), and cetyl-
trimethyl ammonium bromide (CTAB) were selected as
the catalyst for this reaction. The results are presented in
Table 1.
Br
O
S
88
3e
Br
86
3f
NO2
O
S
81
3g
NO2
84
3h
a Reaction temperature is 50 ℃. b Isolated yield.
Antimicrobial screening
In vitro antibacterial activity was screened by con-
sidering zone of inhibition of growth. The synthesized
compounds 3a—3h were screened with their different
concentrations with standard antibiotics such as strep-
tomycin.
Table 1 Effect of catalyst on the synthesis of 3a
Entry
Catalyst
TMAC
TBAC
TEBA
TBAB
CTAB
Time/min
Yield/%
75
1
2
3
4
5
80
90
50
90
90
The results showed that most of our designed com-
pounds had moderate to good in vitro antibacterial ac-
tivities in between 0.6—5.0 mmol/L concentration as
shown in Table 3 with the increase of the concentration
of compounds 3a—3h, the antibacterial activity was
gradually increasing, but it was not affected so much.
Compounds 3a (R1＝H, X＝O), 3g (R1＝NO2, X＝O)
and 3h (R1＝NO2, X＝S) have the zone of inhibition
14.6, 15.9 and 15.1 mm respectively, comparable to that
of the standard streptomycin (15.1 mm) against Staphy-
lococcus aureus. Compounds 3e (R1＝Br, X＝O), 3g
(R1＝NO2, X＝O) and 3h (R1＝NO2, X＝S) have the
zone of inhibition 13.8, 14.1 and 13.9 mm, respectively,
comparable to that of the standard streptomycin (15.3
mm) against Bacillus subtilis. The data indicate that a
change in the substituent might also affect the antibacte-
rial activity of the title compounds 3a—3h. Comparison
of biological activities among 3a—3h shows functional
groups as R1＝NO2 to be potentially more active against
Staphylococcus aureus. Also antibacterial potency of
compounds among 3a—3h shows that functional groups
as R1＝Br/NO2 are more active against Bacillus subtilis.
So, these newly synthesized derivatives had the most
intense antibacterial activities against Gram positive
bacteria such as Staphylococcus aureu or Bacillus sub-
tilis.
79
90
80
84
The results showed that the reaction using TEBA as
the phase transfer catalyst gave the best result. Thus,
TEBA was chosen as the catalyst for all further reac-
tions.
In order to apply this reaction to a library synthesis,
we have extended the reaction of substituted salicylal-
dehydes with barbituric acid or thiobarbituric acid under
similar conditions (water/TEBA/50 ℃), furnishing the
respective 5-(2,3,4,5-tetrahydro-1H-chromeno[2,3-d]-
pyrimidin-5-yl)pyrimidione derivatives (Scheme 2). The
optimized results are summarized in Table 2.
The results presented in the Table 2 indicate the
scope and generality of the method, which is efficient,
not only for urea or thiourea but also for salicylaldehyde
as well as substituted salicylaldehydes. In most cases,
the reactions proceeded smoothly to produce the corre-
sponding 5-(2,3,4,5-tetrahydro-1H-chromeno[2,3-d]py-
rimidin-5-yl)pyrimidione derivatives with good yields.
Chin. J. Chem. 2012, 30, 386—390
© 2012 SIOC, CAS, Shanghai, & WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
www.cjc.wiley-vch.de
387

Cheng et al.
FULL PAPER
Table 3 The antibacterial activity of the compounds 3a—3h
DMSO-d6 solution. Elemental analysis was performed
on an Elementar Vario EL III analyzer. Melting points
were determined on an XT-5A digital melting-points
apparatus and are uncorrected.
Diameter inhibition zone/mm
Concentration/
Product
－
1
(mmol•L )
0.6
1.2
2.5
5.0
0.6
1.2
2.5
5.0
0.6
1.2
2.5
5.0
0.6
1.2
2.5
5.0
0.6
1.2
2.5
5.0
0.6
1.2
2.5
5.0
0.6
1.2
2.5
5.0
0.6
1.2
2.5
5.0
E. coli B. subtilis S. aureus P. aeruginosa
9.9
10.1
10.5
11.8
9.2
9.0
11.1
12.3
13.8
14.6
12.6
11.4
10.3
9.9
9.7
9.9
3a
3a
3a
3a
3b
3b
3b
3b
3c
3c
3c
3c
3d
3d
3d
3d
3e
3e
3e
3e
3f
Biological evaluation procedure
9.3
The compounds were diluted in dimethylformamide
(DMF) with required concentrations by serial dilution
method.[20] Antimicrobial activity was evaluated by
screening of the compounds by standard method, i.e.
agar cup plate method against a panel of human patho-
genic microorganisms: two Gram positive (Bacillus
subtilis CMCC(B) 63501; Staphylococcus aureu
CMCC(B) 26003), two Gram negative (Escherichia coli
CMCC(B) 44102; Pseudomonas aeruginosa CMCC(B)
10104) were used for the antibacterial studies. Microor-
ganisms were maintained at 37 ℃ on Mueller Hinton
(MH) agar slants. The plates containing bacterial organ-
isms were incubated at (37±0.5) ℃ for 24 h. The zone
of inhibition was calculated by measuring the diameter
zone of inhibition of bacterial growth around the disc.
An average of three independent determinations was
recorded.
10.2
10.7
11.3
11.1
10.6
9.9
10.3
11.2
9.0
9.5
9.3
10.1
10.6
9.8
9.8
10.4
9.6
10.0
11.3
11.6
12.9
10.5
10.9
11.8
12.5
10.6
11.7
12.9
13.8
10.2
10.7
11.9
13.2
12.2
12.8
13.2
14.1
11.8
12.2
12.9
13.9
9.7
10.1
10.7
11.5
8.9
10.3
10.8
11.3
9.3
10.2
10.5
11.3
8.7
9.8
9.9
9.5
10.6
11.1
9.9
10.3
10.8
10.9
11.3
12.1
12.7
8.7
10.4
11.2
9.8
Typical procedure for preparation of products 3a—
3h
10.5
11.0
11.4
9.7
10.3
10.9
11.3
9.5
Preparation of 5-(2,4-dioxo-2,3,4,5-tetrahydro-1H-
chromeno[2,3-d]pyrimidin-5-yl)pyrimidine-2,4,6(1H,
3H,5H)-trione (3a) is described as an example: To a
solution of salicylaldehyde (5 mmol) and barbituric acid
(10 mmol), TEBA (5 mg) in 15 mL of water was added
under 50 ℃. After the completion of the reaction (moni-
tored by TLC), the crude products collected by filtration
were washed respectively with ether and 90 ℃ water
and recrystallised from EtOH, to give the product 3a.
5-(2,4-Dioxo-2,3,4,5-tetrahydro-1H-chromeno[2,
3-d]pyrimidin-5-yl)pyrimidine-2,4,6(1H,3H,5H)-tri-
one (3a) m.p. 268—270 ℃; 1H NMR (DMSO-d6, 400
MHz) δ: 3.84 (d, J＝4.9 Hz, 1H), 4.70 (d, J＝4.9
Hz,1H), 7.01—7.23 (m, 2H), 7.31—7.36 (m, 2H), 11.01
(s, 1H), 11.20 (s, 1H), 11.31 (s, 1H), 12.0 (s, 1H); 13C
NMR (DMSO-d6, 100 MHz) δ: 34.0, 53.7, 85.6, 116.9,
121.2, 126.0, 128.4, 129.6, 149.5, 149.8, 150.9, 155.8,
163.8, 169.3, 170.0; IR (KBr) ν: 3464, 3278, 1701, 1657,
10.3
10.6
11.1
11.2
11.9
12.6
13.2
10.5
11.3
12.3
12.8
9.2
10.1
10.6
11.0
11.1
12.0
12.3
13.1
10.4
11.1
11.9
12.5
3f
9.9
3f
10.5
13.2
14.3
15.0
15.9
11.9
12.7
13.3
15.1
3f
3g
3g
3g
3g
3h
3h
3h
3h
－
1
1525, 1493, 1460, 1382, 1280, 1126 cm . Anal. calcd
for C15H10N4O6: C 52.63, H 2.94, N 16.37; found C
52.59, H 2.95, N 16.43.
Strepto-
mycin
5.0
16.1
15.3
15.1
15.7
5-(4-Oxo-2-thioxo-2,3,4,5-tetrahydro-1H-chrome-
no[2,3-d]pyrimidin-5-yl)-2-thioxopyrimidine-4,6(1H,
5H)-dione (3b) m.p.＞300 ℃; H NMR (DMSO-d6,
Experimental
1
Apparatus and materials
400 MHz) δ: 5.12 (s, 1H), 6.83—7.01 (m, 2H), 7.09—
7.22 (m, 2H), 11.84 (s, 1H), 12.14 (s, 1H), 12.28 (s, 1H),
12.36 (s, 1H), 13.31 (s, 1H); 13C NMR (DMSO-d6, 100
MHz) δ: 26.5, 91.1, 98.3, 116.0, 123.3, 125.5, 128.4,
129.1, 149.3, 155.7, 157.8, 158.7, 161.4, 173.6, 177.5;
IR (KBr) ν: 3460, 3238, 1692, 1657, 1562, 1544, 1485,
All reagents were purchased from commercial
sources and used without further purification. The pro-
gress of the reactions was monitored by TLC on silica
plates. IR spectra were recorded on a Varian F-1000
－
spectrometer in KBr with absorptions in cm . 1H NMR
and 13C NMR spectra were recorded on a Bruker DRX
400 MHz spectrometer at 400 and 100 MHz in
1
－
1
1460, 1269, 1132 cm . Anal. calcd for C15H10N4O4S2:
C 48.12, H 2.69, N 14.97; found C 48.16, H 2.64, N
388
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© 2012 SIOC, CAS, Shanghai, & WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
Chin. J. Chem. 2012, 30, 386—390

5-(2,3,4,5-Tetrahydro-1H-chromeno[2,3-d]pyrimidin-5-yl)pyrimidione Derivatives
14.94.
5-(2,4-Dioxo-7-chloro-2,3,4,5-tetrahydro-1H-
chromeno[2,3-d]pyrimidin-5-yl)pyrimidine-2,4,6(1H,
3H,5H)-trione (3c)
m.p. ＞ 300 ℃; 1H NMR
IR (KBr) ν: 3468, 3109, 1738, 1722, 1688, 1658, 1640,
－
1
1544, 1384, 1126 cm . Anal. calcd for C15H9N5O: C
46.52, H 2.34, N 18.09; found C 46.45, H 2.39, N 18.16.
5-(4-Oxo-2-thioxo-7-nitro-2,3,4,5-tetrahydro-1H-
chromeno[2,3-d]pyrimidin-5-yl)-2-thioxopyrimidine-
(DMSO-d6, 400 MHz) δ: 3.91 (d, J＝4.8 Hz, 1H), 4.73
(d, J＝4.8 Hz, 1H), 7.11—7.36 (m, 2H), 7.62 (s, 1H),
10.87 (s, 1H), 11.16 (s, 1H), 11.25 (s, 1H), 12.15 (s, 1H);
13C NMR (DMSO-d6, 100 MHz) δ: 34.6, 54.8, 87.6,
118.2, 127.3, 128.2, 128.7, 130.4, 147.5, 150.2, 151.3,
157.2, 164.8, 169.1, 170.4; IR (KBr) ν: 3478, 3218,
1
4,6(1H,5H)-dione (3h) m.p. 265—266 ℃; H NMR
(DMSO-d6, 400 MHz) δ: 5.95 (s, 1H), 6.85 (d, J＝7.2
Hz, 1H), 7.29 (d, J＝7.2 Hz, 1H), 7.91 (s, 1H), 10.31 (s,
1H), 11.44 (s, 1H, NH), 11.61 (s, 1H, NH), 12.41 (s, 1H,
NH), 12.51 (s, 1H, OH); 13C NMR (DMSO-d6, 100
MHz) δ: 28.2, 91.1, 97.5, 117.9, 123.8, 124.9, 127.6,
141.5, 156.8, 157.3, 160.2, 161.5, 163.3, 174.2, 178.8;
IR (KBr) ν: 3418, 3241, 1751, 1682, 1647, 1586, 1521,
－
1
1691,1640, 1599, 1475, 1436, 1347, 1245, 1137 cm .
Anal. calcd for C15H9N4O6Cl: C 47.82, H 2.41, N 14.88;
found C 47.89, H 2.36, N 14.81.
－
1
5-(4-Oxo-2-thioxo-7-chloro-2,3,4,5-tetrahydro-
1H-chromeno[2,3-d]pyrimidin-5-yl)-2-thioxopyrimi-
1436, 1342, 1154 cm . Anal. calcd for C15H9N5O6S2: C
42.96, H 2.16, N 16.70; found C 43.04, H 2.17, N 16.65.
1
dine-4,6(1H,5H)-dione (3d) m.p. 252—254 ℃; H
NMR (DMSO-d6, 400 MHz) δ: 5.08 (s, 1H), 7.03—7.28
(m, 2H), 7.53 (s, 1H), 10.21 (s, 1H), 11.84 (s, 1H),
12.25 (s, 1H), 12.39 (s, 1H), 13.38 (s, 1H); 13C NMR
(DMSO-d6, 100 MHz) δ: 27.1, 90.3, 97.1, 118.2, 126.4,
130.3, 131.1, 131.4, 150.3, 156.2, 158.1, 162.5, 159.2,
172.4, 179.2; IR (KBr) ν: 3502, 3384, 1657, 1640, 1629,
1580, 1471, 1352, 1258, 1143 cm . Anal. calcd for
C15H9N4O4ClS2: C 44.06, H 2.22, N 13.71; found C
44.01, H 2.31, N 13.79.
Conclusions
In conclusion, we have descried a one-pot and effi-
cient procedure for the preparation of 5-(2,3,4,5-tetra-
hydro-1H-chromeno[2,3-d]pyrimidin-5-yl)pyrimidione
derivatives from salicylaldehyde or substituted sali-
cylaldehydes with barbituric acid or 2-thiobarbituric
acid at 50 ℃ in water using TEBA as phase transfer
catalysis. The antimicrobial activities of these new syn-
thesized compounds have been evaluated. All com-
pounds demonstrated potent inhibition against all the
strains tested. The importance of such work lies in the
possibility that the new compounds might be more effi-
cacious drugs against bacteria, which could be helpful
in designing more potent antibacterial agents for thera-
peutic use.
－
1
5-(2,4-Dioxo-7-bromo-2,3,4,5-tetrahydro-1H-
chromeno[2,3-d]pyrimidin-5-yl)pyrimidine-2,4,6(1H,
1
3H,5H)-trione (3e) m.p. 240—242 ℃; H NMR
(DMSO-d6, 400 MHz) δ: 3.94 (d, J＝4.9 Hz, 1H), 4.71
(d, J＝4.9 Hz, 1H), 7.09 (d, J＝7.0 Hz, 1H), 7.29 (s,
1H), 7.52 (d, J＝7.0 Hz, 1H), 10.94 (s, 1H), 11.11 (s,
1H), 11.23 (s, 1H), 12.08 (s, 1H); 13C NMR (DMSO-d6,
100 MHz) δ: 35.2, 54.4, 88.3, 115.9, 118.5, 128.3, 131.4,
133.5, 147.2, 151.2, 151.9, 157.6, 164.7, 169.6, 171.8;
IR (KBr) ν: 3514, 3234, 1674, 1596, 1546, 1427, 1391,
Acknowledgment
－
1
We are grateful to the financial support from the
Foundation of Jiangsu Key Laboratory of Marine Bio-
technology (No. 2009HS04).
1341, 1299, 1175 cm . Anal. calcd for C15H9N4O6Br: C
42.77, H 2.15, N 13.31; found C 42.69, H 2.21, N 13.39.
5-(4-Oxo-2-thioxo-7-bromo-2,3,4,5-tetrahydro-
1H-chromeno[2,3-d]pyrimidin-5-yl)-2-thioxopyrimi-
1
dine-4,6(1H,5H)-dione (3f) m.p. 245—246 ℃; H
References
NMR (DMSO-d6, 400 MHz) δ: 5.09 (s, 1H), 6.95 (d,
J＝7.0 Hz, 1H), 7.22 (s, 1H), 7.39 (d, J＝7.0 Hz, 1H),
10.19 (s, 1H), 11.37 (s, 1H), 12.33 (s, 1H), 12.45 (s, 1H),
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13
13.39 (s, 1H); C NMR (DMSO-d6, 100 MHz) δ: 26.5,
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90.8, 97.9, 116.9, 118.3, 130.8, 131.2, 131.5, 148.7,
156.3, 159.7, 161.3, 162.7, 173.7, 177.9; IR (KBr) ν:
3517, 3234, 1658, 1641, 1624, 1545, 1477, 1369, 1321,
－
1
[5] Rai, U. S.; Isloor, A. M.; Shetty, P.; Vijesh, A. M.; Prabhu, N.; Isloor,
S.; Thiageeswaran, M.; Fun, H. K. Eur. J. Med. Chem. 2010, 45,
2695.
1278 cm . Anal. calcd for C15H9N4O4BrS2: C 39.74, H
2.01, N 12.36; found C 39.65, H 2.08, N 12.29.
5-(2,4-Dioxo-7-nitro-2,3,4,5-tetrahydro-1H-chro-
meno[2,3-d]pyrimidin-5-yl)pyrimidine-2,4,6(1H,3H,
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5H)-trione (3g)
m.p. 250 — 251 ℃; 1H NMR
(DMSO-d6, 400 MHz) δ: 3.99 (d, J＝4.5 Hz, 1H), 4.86
(d, J＝4.5 Hz, 1H), 7.04 (d, J＝7.2 Hz, 1H), 7.31 (d,
J＝7.2 Hz, 1H), 8.02 (s, 1H), 10.98 (s, 1H), 11.32 (s,
1H), 11.47 (s, 1H), 12.23 (s, 1H); 13C NMR (DMSO-d6,
100 MHz) δ: 36.8, 55.6, 89.8, 117.8, 123.7, 124.8, 127.4,
141.3, 156.2, 156.8, 161.3, 161.8, 164.2, 171.1, 173.6;
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