Chemical fixation of CO2: efficient synthesis of quinazoline-2,4(1H, 3H)-diones catalyzed by guanidines under solvent-free conditions

Article abstract of DOI:10.1016/j.tet.2010.04.011

Guanidines were proved to be efficient catalysts for the chemical fixation of carbon dioxide with 2-aminobenzonitriles under solvent-free conditions. Notably, the catalysts with low loading worked well for a variety of 2-aminobenzonitriles. As a result, quinazoline-2,4(1H, 3H)-diones by employing present protocol were obtained in good yields under mild conditions. This process represents an alternative approach for the greener chemical fixation of CO₂ to afford valuable compounds.

Full text of DOI:10.1016/j.tet.2010.04.011

Tetrahedron 66 (2010) 4063–4067
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Tetrahedron
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Chemical fixation of CO2: efficient synthesis of quinazoline-2,4(1H, 3H)-diones
catalyzed by guanidines under solvent-free conditions
*
´
Jian Gao, Liang-Nian He , Cheng-Xia Miao, Sebastien Chanfreau
State Key Laboratory and Institute of Elemento-Organic Chemistry, Nankai University, Tianjin 300071, People’s Republic of China
a r t i c l e i n f o
a b s t r a c t
Article history:
Guanidines were proved to be efficient catalysts for the chemical fixation of carbon dioxide with 2-
aminobenzonitriles under solvent-free conditions. Notably, the catalysts with low loading worked well
for a variety of 2-aminobenzonitriles. As a result, quinazoline-2,4(1H, 3H)-diones by employing present
protocol were obtained in good yields under mild conditions. This process represents an alternative
approach for the greener chemical fixation of CO2 to afford valuable compounds.
Ó 2010 Elsevier Ltd. All rights reserved.
Received 14 January 2010
Received in revised form 30 March 2010
Accepted 2 April 2010
Available online 8 April 2010
Keywords:
Quinazolinedione
Aminobenzonitrile
Guanidine
Carbon dioxide
Solvent-free process
1. Introduction
Recently, a promising strategy for the synthesis of quinazoline-2,4-
(1H, 3H)-diones starting from CO2 was proposed by Mizuno et al.,15
In recent years, quinazoline-2,4(1H, 3H)-diones and their de-
rivatives, such as 7-chloroquinazoline-2,4(1H, 3H)-dione and 6,7-
dimethoxy-quinazoline-2,4(1H, 3H)-dione, have drawn much attention
and interest due to their wide range of biological and pharmacological
activities.1–6 Reactions of anthranilic acid with urea,7 anthranilamide
with phosgene8 or anthranilic acid with potassium cyanate9 or chlor-
osulfonyl isocyanate10 are considered as conventional synthetic routes
to quinazoline-2,4(1H, 3H)-diones. Recently, alternative methods were
also developed to minimize the use of high toxic reagents and/or to
avoid harsh reaction conditions. In this context, greener synthetic
methodologies covering solid phase synthetic approachs,11 microwave-
assisted synthesis12 or metal involved methods13 have been available in
the literature. Nevertheless, the cyanate reagent is still needed for the
preparation of quinazoline-2,4(1H, 3H)-diones derivatives by utilizing
those improved processes. Therefore, the development of efficient and
greener synthetic strategy remains challenging.
in which stoichiometric organic base DBU (1,8-diazabicyclo [5.4.0]
undec-7-ene) is required. In this context, substantial progress was
achieved by developing catalytic process,16a solvent-free proto-
col,16b,c or heterogeneous catalysis for easy separation.16d,e De-
velopment of more efficient catalysts could be desirable and
challenging in order to decrease catalyst loading and shorten re-
action time as well as facilitate product separation.
Organic guanidines, which are categorized as organic super-
bases with ease of structural modification,17 are efficient organic
catalysts for the types of base induced reactions in organic syn-
thesis.18 Particularly, guanidines could interact with CO2 through
a kinetically reversible way, leading to CO2 fixation.19
As our continuous interest in chemical fixation of CO2,20 we de-
veloped an efficient approach for the synthesis quinazoline-2,4(1H,
3H)-diones from CO2 and 2-aminobenzonitriles catalyzed by low
amounts of organic guanidines without the need of any additional
solvent. In this regard, several guanidines were proved to be effective
for this process. Among the tested catalysts, the simplest guanidine, i.e.,
1,1,3,3-tetramethylguanidine (TMG) exhibited high catalytic activity.
Naturally abundant, inexpensive, non-flammable and non-toxic
carbon dioxide is regarded as an attractive and economical C1
building block in organic synthesis to produce useful compounds
and material.14 On the other hand, chemical fixation of CO2 would
be of great significance from the viewpoint of both utilization of
carbon resources and the increasing concern of the environment.
2. Results and discussion
The exploratory experiments were started by testing this pro-
tocol and screening the reaction conditions using 2-amino-
benzonitrile (1a) as the benchmark substrate, as depicted in
Scheme 1. Various organic bases were initially tested for the
* Corresponding author. Tel./fax: þ86 22 2350 4216; e-mail address: heln@
nankai.edu.cn (L.-N. He).
0040-4020/$ – see front matter Ó 2010 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2010.04.011

4064
J. Gao et al. / Tetrahedron 66 (2010) 4063–4067
reaction of incorporating CO2 into 2-aminobenzonitrile. As easily
seen from Table 1, the coupling reaction of 1a/CO2 did not occur at
all in the absence of any catalyst (entry 1). Moreover, several ex-
amined organic bases, such as hexamethylenetetramine (HMT) and
diethylenetriamine (DETA), were also found to be inactive at 80 ꢀC
(entry 2), presumably being ascribed to lack of enough basicity. To
our delight, the organic guanidine, e.g., N-(1,3-dimethylimidazoli-
din-2-ylidene) butan-1-amine (G1, Scheme 2) was effective for the
reaction and a 25% isolated yield of quinazoline-2,4(1H, 3H)-dione
(2a) was attained (entry 3). As anticipated, the reaction was further
facilitated by increasing in the reaction temperature (entries 3–5).
Excellent 2a yield was obtained at 120 ꢀC under solvent-free con-
ditions. It is also worth mentioning that the organic guanidines,
e.g., TMG, G1–G3 and 1,5,7-triazabicyclo [4.4.0] dec-1-ene (TBD)
used in this study (Scheme 2) gave excellent catalytic activity under
the identical reaction conditions (entries 5–9). More interestingly,
TMG showed the highest catalytic performance at the catalyst
amount as low as 2 mmol % relative to 1a (entries 10–14), being
presumably attributed to influence of basicity and steric effect. As
a consequence, the simplest and easily available guanidine, viz.
TMG was chosen as the catalyst for further investigation.
Subsequently, the effects of several reaction parameters were
investigated as listed in Table 2. Interestingly, good yield of 2a could
be reached even with low catalyst loading (entry 4, Table 2). On the
other hand, influence of the reaction time was examined. Satis-
factory result could be also achieved within 1 h (entry 6), which is
quite shorter in comparison with values in the literatures.15,16
Whereas, more than 3 h is needed for almost full completion of
the reaction (entries 3,7–9).
Table 2
Effect of reaction parameters on the reactiona
H
TMG
NH2
CN
N
O
NH
CO2
solvent-free
O
1a
2a
Entry
TMG (equiv.)
PCO2 (MPa)
Time (h)
Isolated yield (%)
1
2
3
4
5
6
7
8
9
0.2
0.1
10
10
10
10
10
10
10
10
10
4
4
4
4
0.5
1
3
5
6
87
87
87
82
21
69
88
87
88
0.05
0.02
0.05
0.05
0.05
0.05
0.05
H
NH2
CN
N
O
Guanidine
CO2
NH
solvent-free, 10 MPa
O
a
1a
Reaction conditions: 1a (0.591 g, 5 mmol), 120 ꢀC.
2a
Scheme 1. Guanidine-catalyzed reaction of 2-aminobenzonitrile 1a and CO2.
Shown in Figure 1 is the yield of the desired product as a function
of CO2 pressure in the reaction of CO2 and 1a. Obviously, 2a yield is
sensitive to CO2 pressure. Although CO2 pressure as low as 0.5 MPa
also worked well, 10 MPa gave the maximum value. However, fur-
ther increasing CO2 pressure up to 16 MPa led to a decrease in yield.
This is because excessive CO2 may cause low concentration of the
substrate and the catalyst, thus resulting in a low yield. Therefore,
10 MPa would be an appropriate operating pressure.
Table 1
Screening basesa
Entry
Cat.
Amount of Cat. (equiv.)
T (ꢀC)
Isolated yield (%)
1b
2b,c
3
0
HMT
G1
0
0.1
0.1
0.1
0.1
0.1
0.1
0.1
80
80
80
0
0
25
32
88
89
86
87
81
34
36
27
82
26
4
G1
100
120
120
120
120
120
120
120
120
120
120
5
G1
6
G2
90
80
70
60
50
7
G3
8
9
TMG
TBD
G1
G2
G3
0.1
10
11
12
13
14
0.02
0.02
0.02
0.02
0.02
TMG
TBD
a
Reaction conditions: 1a (0.591 g, 5 mmol), CO2 10 MPa, 4 h.
1a (0.1182 g, 1 mmol), 2 mL of DMF (dimethyl formamide), 12 h.
HMT: hexamethylenetetramine and other organic bases such as D301R (a kind
b
c
of ion exchange resin, i.e., polystyrene with N(CH3)2 as a functional group, supplied
from the Chemical Plant of Nankai University), PTA (1,3,5-triaza-7-phosphaada-
mantane), DETA (diethylenetriamine) also showed no catalytic activity under the
identical reaction conditions (see the Supplementary data).
0
2
4
6
8
10
12
14
16
18
Pressure (MPa)
R
N
N
N
N
N
N
Figure 1. Plot of yield as a function of CO2 pressure for the reaction of CO2 and 1a.
Reaction conditions: 1a (0.591 g, 5 mmol), TMG (29 mg, 0.25 mmol), 120 ꢀC, 4 h.
G1: R=n-Bu
G2: R=c-Hex
G3
To demonstrate the utility and generality of this approach to
the synthesis of quinazoline-2,4(1H, 3H)-diones, we examined the
reactions of various 2-aminobenzonitriles and CO2 by performing
the reaction under the identical conditions. A variety of 2-ami-
nobenzonitriles bearing electron-withdrawing or electron-
donating substituents were tested by employing TMG as the
catalyst (Table 3). It was found that the catalyst worked well for
NH
N
N
N
N
N
H
TMG
TBD
Scheme 2. Guanidines used in this study.

J. Gao et al. / Tetrahedron 66 (2010) 4063–4067
4065
Table 3
the formation of the intermediate 5a assisted by the o-cyano group
appears to be of great importance in the whole catalytic cycle. In
summary, TMG as a catalyst might play a dual role in this reaction:
(1) activating the substrate 1a by deprotonation to facilitate the
attack of CO2; (2) also activating the CO2 molecule via forming
a CO2–TMG complex.19 Therefore, the basicity of organic guanidine
is considered to be significant for this reaction.
Synthesis of various quinazoline-2,4(1H, 3H)-diones 2a–fa
Entry
Substrate
Product
Isolated yield (%)
89
H
N
O
NH
NH2
CN
1
O
1a
2a
H
N
MeO
MeO
O
NH
MeO
MeO
NH2
CN
TMG H
NHCOO
H
N
O
NH2
CN
2
88
TMG
O
CO2
O
1b
C N
N
2b
TMG H
-TMG
4a
1a
3a
H
Cl
N
O
Cl
NH2
H
N
N C O
OH
N
TMG H
O
NH
N
O
3
4
NH
60
95
CN
N
OH
6a
O
1c
O
TMG H
2c
5a
2a
H
N
Scheme 3. A plausible mechanism.
O
NH2
CN
NH
Cl
Br
Cl
Br
O
1d
3. Conclusions
2d
In conclusion, TMG was developed as an efficient catalyst for the
synthesis of several quinazoline-2,4(1H, 3H)-diones via a chemical
fixation of CO2 to 2-aminobenzonitriles in high isolated yield under
solvent-free conditions. Notably, the reaction could work well even
at 2 mmol % of catalyst loading or under CO2 pressure as low as
0.5 MPa. This approach would be more promising from the view-
point of Green Chemistry and Sustainable Society.
H
N
O
NH2
CN
5
NH
81
O
1e
2e
H
N
O
NH
NH2
CN
4. Experimental
4.1. Caution
6
91
F
F
O
1f
Cl
1g
2f
Experiments using compressed CO2 are potentially hazardous
and must only be carried out using the appropriate equipment and
under rigorous safety precautions.
Cl
H
N
O
NH
NH2
CN
7
0
O2N
O2N
O
4.2. Materials
2g
a
Reaction conditions: subtrate (2 mmol), TMG (11.6 mg, 5 mmol %), CO2 10 MPa,
120 ꢀC, 4 h. Reactions were performed in a 25 mL stainless steel autoclave.
Guanidines G1–G3 were synthesized according to the published
methods,21,17a which were given in Supplementary data. All other
guanidines and reagents were obtained commercially without
further purification. Carbon dioxide with a purity of 99.99% was
commercially available. Toluene and diethyl ether were freshly
distilled over sodium under nitrogen. Dichloromethane was dis-
tilled from calcium hydride.
most of 2-aminobenzonitriles (1a–f) tested in this study to give
the corresponding quinazoline-2,4(1H, 3H)-diones (2a–f) in ex-
cellent isolated yields (entries 1–6). The presence of electron-
donating group has likely no influence on the reaction (entry 2).
On the other hand, reactivity of meta-halogen substituted 2-ami-
nobenzonitriles is found to follow the trend of Cl>F>Br (entries 4–
6). Particularly, para-substituent 1c showed less active compared
with its meta counterpart 1d, probably due to electron-
withdrawing effect on the basicity. Indeed, 2-aminobenzonitrile
1g bearing both an m-nitro and an m-halogen group failed to react
with CO2 forming the product 2g even at reaction temperature as
high as 140 ꢀC.
4.3. Characterization
1H NMR spectra was recorded at Bruck 300 and 400 or Varian
Mercury-Plus 400 spectrometer in CDCl3 or DMSO-d6 and TMS
(0 ppm) was used as internal reference, 13C NMR was recorded at
75 MHz or 100.6 MHz in CDCl3 (or DMSO-d6) and CDCl3 (77.0 ppm)
(or DMSO-d6, 39.4 ppm) was used as internal reference. High-
resolution mass spectrometry was conducted using a Varian 7.0 T
FTICR-MS by ESI technique. ESI-MS were recorded on a Thermo
Finnigan LCQ Advantage spectrometer in ESI mode with a spray
voltage of 4.8 kV. Melting points were measured on an X4 appa-
ratus and uncorrected. Infrared (IR) spectra were recorded on
a Bruker Tensor27 FT-IR spectrophotometer with KBr pellets. The
characterization data (1H NMR, 13C NMR, IR, and ESI-MS) and
physical properties are reported below.
On the basis of previous studies15,16 and experimental results,
a plausible mechanism for the TMG-catalyzed reaction of 2-ami-
nobenzonitrile (1a) and CO2 is proposed as depicted in Scheme 3.
First of all, the carbonylation of 1a with CO2 generates the in-
termediate carbamate salt 3a promoted by TMG. Then, 4a is formed
via an intramolecular nucleophilic cyclization of 3a. After that,
followed by rearrangement of 4a through the intermediate iso-
cyanate 5a, 6a and the final product 2a were afforded. Additionally,

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J. Gao et al. / Tetrahedron 66 (2010) 4063–4067
4.4. General procedure for the TMG-catalyzed reaction of CO2
and 2-aminobenzonitrile
128.9, 139.2, 141.8, 150.0, 162.0; ESI-MS calcd for C8H5ClN2O2
196.59, found 195.21(MꢁH)ꢁ.
In a typical experiment, to a 50 mL stainless steel autoclave
with an inner glass tube were charged with 2-amino-
benzonitriles (5 mmol) and guanidine base (0.25 mmol). A cer-
tain amount of CO2 was introduced into the autoclave and then
the autoclave was heated to the reaction temperature. Then CO2
pressure was adjusted to the desired value and the reaction was
run under stirring for desired time. After completion of reaction,
the autoclave was allowed to be cooled in an ice bath and CO2
was slowly vented. The residue was treated with 1 N HCl (30 mL),
washed with tert-butyl methyl ether (20 mL) and dried under
vacuum at 60 ꢀC for 4 h to afford the desired product. The
products were further identified by NMR and MS (see the
Supplementary data), which are consistent with those reported
in the literature13c,16c and in good agreement with the assigned
structures. The NMR charts for the products and guanidines
G1–G3 were given in Supplementary data.
4.6.3. 6-Chloroquinazoline-2, 4(1H,3H)-dione (2d). White solid.
Mp>300 ꢀC (lit.16c >300 ꢀC). IR (KBr) 3198, 3058, 1711, 1668, 1483,
1428, 1284, 877 cmꢁ1 1H NMR (400 MHz, DMSO-d6):
; d 7.17 (d,
3J¼8.8 Hz, 1H), 7.68 (d, 3J¼8.8 Hz, 1H), 7.81 (s, 1H), 11.32 (s, 2H); 13
C
NMR (100.6 MHz, DMSO-d6) d 115.7, 117.5, 125.8, 126.1, 134.6, 139.7,
150.0, 161.7; ESIMS calcd for C8H5ClN2O2 196.59, found 195.17
(MꢁH)ꢁ.
4.6.4. 6-Bromoquinazoline-2,4(1H,3H)-dione (2e). White solid.
Mp>300 ꢀC (lit.13c >300 ꢀC). IR (KBr) 3193, 3066, 1742, 1701, 1613,
1480, 1433,1286, 836 cmꢁ1; 1H NMR (400 MHz, DMSO-d6)
d 7.71 (d,
3J¼8.7 Hz, 1H), 7.78 (dd, 2J¼8.8 Hz, 3J¼2.3 Hz, 1H), 7.93 (d,
3J¼2.3 Hz, 1H), 11.26 (s, 1H), 11.43 (s, 1H); 13C NMR (100.6 MHz,
DMSO-d6)
d 113.7, 116.1, 117.6, 128.8, 137.4, 139.9, 149.9, 161.6;
HRMS: calcd for C8H5BrN2O2 (MꢁH)ꢁ 238.9462, found 238.9455.
4.6.5. 6-Fluoroquinazoline-2,4(1H,3H)-dione
(2f). White solid.
Mp>300 ꢀC. IR (KBr) 3199, 3059, 1714, 1675, 1635, 1500, 1439, 1288,
4.5. Characterization data
884 cmꢁ1
;
1H NMR (400 MHz, DMSO-d6)
d
7.19 (q, 4J¼8.8 Hz, 1H),
7.52–7.60 (m, 2H), 11.20 (s, 1H), 11.41 (s, 1H); 13C NMR (100.6 MHz,
4.5.1. N-(1,3-Dimethylimidazolidin-2-ylidene) butan-1-amine
DMSO-d6) d (111.7, 112.0), (115.2, 115.3), (117.4, 117.5), (122.7, 122.9),
(G1). Colorless liquid. 1H NMR (400 MHz, CDCl3)
d
0.90 (t,
137.4, 150.0, (156.0, 158.4), (162.05, 162.07); HRMS calcd for
3J¼7.2 Hz, 3H), 1.31–1.40 (m, 2H), 1.47–1.55 (m, 2H), 2.77 (s, 6H),
C8H5FN2O2 (MꢁH)ꢁ 179.0262, found 179.0255.
3.12 (s, 4H), 3.32 (t, 3J¼7.2 Hz, 2H); 13C NMR (75 MHz, CDCl3)
d
13.96, 20.32, 35.58, 36.40, 47.20, 49.40, 156.88; ESI-MS calcd for
Acknowledgements
C9H19N3 169.27, found 170.39 (MþH)þ.
Financial support by the National Natural Science Foundation of
China (Grants Nos. 20672054, 20872073), and Research Fellowship
for International Young Scientists from NSFC (20950110325), the
111 project (B06005), and the Committee of Science and Technol-
ogy of Tianjin is gratefully acknowledged.
4.5.2. N-(1,3-Dimethylimidazolidin-2-ylidene)
cyclohexanamine
1.15–1.72 (m,
(G2). Colorless liquid. 1H NMR (400 MHz, CDCl3)
d
10H), 2.76 (s, 6H), 3.11 (s, 4H), 3.38–3.43 (m, 1H); 13C NMR
(100.6 MHz, CDCl3) d 25.2, 25.8, 31.3, 36.5, 44.9, 54.0, 155.4; ESI-MS
calcd for C11H21N3 195.30, found 196.26 (MþH)þ; HRMS: calcd for
C11H21N3 (MþH)þ 196.1808, found 196.1804.
Supplementary data
4.5.3. 2-Butyl-1,1,3,3-tetramethylguanidine (G3). Colorless liquid.
1H NMR (400 MHz, CDCl3)
d
0.89 (t, 3J¼7.4 Hz, 3H), 1.28–1.37 (m,
Supplementary data associated with this article can be found in
the online version, at doi:10.1016/j.tet.2010.04.011. These data in-
clude MOL files and InChIKeys of the most important compounds
described in this article.
2H), 1.46–1.53 (m, 2H), 2.64 (s, 6H), 2.73 (s, 6H), 3.09 (t, 3J¼7.4 Hz,
2H); 13C NMR (75 MHz, CDCl3)
d 13.7, 20.3, 34.6, 38.6, 39.0, 39.4,
48.8, 159.7; ESI-MS calcd for C9H21N3 171.28, found 172.27 (MþH)þ.
References and notes
4.6. Quinazoline-2,4(1H, 3H)-dione (2a)
1. Tran, T. P.; Ellsworth, E. L.; Stier, M. A.; Domagala, J. M.; Showalter, H. D. H.;
Gracheck, S. J.; Shapiro, M. A.; Joannides, T. E.; Singh, R. Bioorg. Med. Chem. Lett.
2004, 14, 4405–4409.
2. Hayao, S.; Havera, H. J.; Strycker, W. G.; Leipzig, T. J.; Kulp, R. A.; Hartzler, H. E.
J. Med. Chem. 1965, 8, 807–815.
3. (a) Kakuta, H.; Tanatani, A.; Nagasawa, K.; Hashimoto, Y. Chem. Pharm. Bull.
2003, 51, 1273–1282; (b) Boyles, D. C.; Curran, T. T.; Parlett, R. V. Org. Process Res.
Dev. 2002, 6, 230–233.
4. Meuldermans, W.; Hendrickx, J.; Woestenborghs, R.; van Peer, A.; Lauwers, W.;
De Cree, J.; Heykants, J. Arzneim. -Forsch. 1988, 38, 789–794.
White solid. Mp>300 ꢀC (lit.16c >300 ꢀC). IR (KBr) 3253, 3054,
2846, 1702, 1670, 1618, 1443, 755 cmꢁ1; 1H NMR (300 MHz, DMSO-
d6)
d
7.14–7.19 (m, 2H), 7.63 (t, 3J¼7.7 Hz, 1H), 7.88 (d, 3J¼7.7 Hz,1H),
11.13 (s, 1H), 11.27 (s, 1H); 13C NMR (100.6 MHz, DMSO-d6)
d
114.2,
115.2, 122.2, 126.9, 134.8, 140.8, 150.2, 162.7; ESI-MS calcd for
C8H6N2O2 162.15, found 161.17(MꢁH)ꢁ.
5. (a) Imagawa, J.; Sakai, K. Eur. J. Pharmacol. 1986, 131, 257–264; (b) Russell, R. K.;
Press, J. B.; Rampulla, R. A.; McNally, J. J.; Falotico, R.; Keiser, J. A.; Bright, D. A.;
Tobia, A. J. Med. Chem. 1988, 31, 1786–1793; (c) Russo, F.; Romeo, G.; Guccione,
S.; De Blasi, A. J. Med. Chem. 1991, 34, 1850–1854.
4.6.1. 6,7-Dimethoxyquinazoline-2,4(1H, 3H)-dione (2b). Light yel-
low solid. Mp>300 ꢀC (lit.16c >300 ꢀC). IR (KBr) 3471, 3379, 3294,
1708, 1653, 1625, 1467, 1436, 1265, 1099 cmꢁ1 1H NMR (400 MHz,
;
6. (a) Mounetou, E.; Legault, J.; Lacroix, J.; C-Gaudreault, R. J. Med. Chem. 2001, 44,
694–702; (b) Chao, Q.; Deng, L.; Shih, H.; Leoni, L. M.; Genini, D.; Carson, D. A.;
Cottam, H. B. J. Med. Chem. 1999, 42, 3860–3873.
7. (a) Pastor, G.; Blanchard, C.; Montginoul, C.; Torreilles, E.; Giral, L.; Texier, A.
Bull. Soc. Chim. Fr. 1975, 1331–1338; (b) Khalifa, M.; Osman, A. N.; Ibrahim, M.
G.; Ossman, A. R. E.; Ismail, M. A. Pharmazie 1982, 37, 115–117.
DMSO-d6)
d
3.74 (s, 3H), 3.78 (s, 3H), 6.63 (s, 1H), 7.22 (s, 1H), 10.90
55.6, 55.7,
(s, 1H), 11.08 (s, 1H); 13C NMR (100.6 MHz, DMSO-d6)
d
97.6, 106.1, 107.3, 136.4, 144.9, 150.3, 154.8, 162.3; ESI-MS calcd for
C10H10N2O4 222.2, found 221.07(MꢁH)ꢁ.
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