An aqueous medium synthesis and tautomerism study of 3(5)-amino-1,2,4-triazoles

Article abstract of DOI:10.1016/j.tetlet.2009.02.172

A catalyst-free highly efficient synthesis of 3(5)-amino-5(3)-(het)aryl-1,2,4-triazoles in aqueous medium was performed using conventional heating and microwave irradiation. The tautomerism in the products was investigated using NMR spectroscopy and X-ray crystallography. The effects of the substitution, temperature, solvents, and concentration on the tautomerism were studied. The triazoles were found to exist in 1H-forms, the 4H-form was not observed either in solid state or in solution. In general, 5-amino-1,2,4-triazoles were electronically preferred in the tautomeric equilibrium, but some exceptions from the established relationship were also identified.

Full text of DOI:10.1016/j.tetlet.2009.02.172

Tetrahedron Letters 50 (2009) 2124–2128
Contents lists available at ScienceDirect
Tetrahedron Letters
journal homepage: www.elsevier.com/locate/tetlet
An aqueous medium synthesis and tautomerism study
of 3(5)-amino-1,2,4-triazoles
*
Anton V. Dolzhenko , Giorgia Pastorin, Anna V. Dolzhenko, Wai Keung Chui
Department of Pharmacy, Faculty of Science, National University of Singapore, 18 Science Drive 4, Singapore 117543, Singapore
a r t i c l e i n f o
a b s t r a c t
Article history:
A catalyst-free highly efficient synthesis of 3(5)-amino-5(3)-(het)aryl-1,2,4-triazoles in aqueous medium
was performed using conventional heating and microwave irradiation. The tautomerism in the products
was investigated using NMR spectroscopy and X-ray crystallography. The effects of the substitution, tem-
perature, solvents, and concentration on the tautomerism were studied. The triazoles were found to exist
in 1H-forms, the 4H-form was not observed either in solid state or in solution. In general, 5-amino-1,2,4-
triazoles were electronically preferred in the tautomeric equilibrium, but some exceptions from the
established relationship were also identified.
Received 12 January 2009
Revised 9 February 2009
Accepted 20 February 2009
Available online 26 February 2009
Ó 2009 Elsevier Ltd. All rights reserved.
1
,2,4-Triazoles represent a class of heterocyclic compounds of
have often ignored this phenomenon and some data were misin-
terpreted. In this Letter, we present a study on the tautomerism
in 3(5)-amino-5(3)-(het)aryl-1,2,4-triazoles using NMR spectros-
copy and X-ray crystallography.
1
significant importance in agriculture and medicine. They are also
used in metalloorganic chemistry as polyfunctional ligands.
Among 1,2,4-triazoles, 3(5)-amino-1,2,4-triazoles have been recog-
nized, primarily, as valuable synthons for the construction of more
complex structures, particularly biologically active fused heterocy-
cles (e.g., 1,2,4-triazolo[1,5-a]pyrimidines and 1,2,4-triazolo[1,5-
a][1,3,5]triazines ).
The most straightforward and commonly used method for the
preparation of 3(5)-amino-1,2,4-triazoles 2 involves the cyclocon-
densation of amidoguanidines 1 (Scheme 1). However, the use of a
2
Green chemistry, which is an essential part of process devel-
opment in modern chemistry, has also begun to influence medic-
3
9
inal chemistry significantly. The design of an environmentally
4
friendly synthesis includes elaboration of methods able to avoid
or minimize the formation of byproducts, the selection of a safe
solvent, and effective use of energy. Water is considered to be
1
0
the best solvent for sustainable chemistry.
We found that
5
high temperature (often above the melting point) or the presence
5
e
of a strong base in the reaction complicated the work-up and led
to decreased yields of the products. Herein we describe a method
which avoids these drawbacks and leads to 3(5)-amino-1,2,4-tria-
zoles via a simple and eco-friendly procedure.
Tautomerism in five-membered heterocyclic systems is an
intriguing phenomenon, which has been recognized for a long
HN N
N NH
R
NH2
R
NH2
N
O NH2
1
2
6
time. A knowledge of the tautomeric preferences and the factors
Scheme 1.
affecting the equilibrium are essential for understanding the reac-
tivity of compounds in chemical processes and their effects on
biological systems. Due to annular prototropic tautomerism,
1
,2,4-triazoles, particularly amino-1,2,4-triazoles without substit-
HN N
N NH
uents on the ring nitrogen atoms, a priori can exist in three forms,
namely, 3-amino-1H-1,2,4-triazoles (A), 5-amino-1H-1,2,4-tria-
R
NH2
R
NH2
N
N
zoles (B), and 3-amino-4H-1,2,4-triazoles (C) (Scheme 2).
number of theoretical reports have appeared in the area of
tautomerism in amino-1,2,4-triazoles, but experimental studies
A
A
B
7
N N
R
NH
2
N
H
C
*
Corresponding author. Tel.: +65 6516 2657; fax: +65 6779 1554.
E-mail address: phada@nus.edu.sg (A.V. Dolzhenko).
Scheme 2.
0
040-4039/$ - see front matter Ó 2009 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2009.02.172

A. V. Dolzhenko et al. / Tetrahedron Letters 50 (2009) 2124–2128
2125
Table 1
Synthesis of triazoles 2a–j via cyclocondensation of amidoguanidines 1 under conventional heating
HN N
N NH
R
NH2
R
NH2
N
O NH2
1
2
Triazole
R
Reaction time (h)
Volumea (ml)
Yield (%)
Mp (°C) (lit.)
5
e
2
2
2
2
2
2
2
2
2
2
a
b
c
d
e
f
g
h
i
Ph
4-MeC
4
4
8
3
6
6
8
4
6
6
20
20
40
20
97
98
96
95
94
95
97
92
98
98
186–187 (186–187)
8a
6
H
4
209 (207)
4-MeOC
4-FC
4-ClC
2-Furyl
2-Thienyl
2-Pyridyl
3-Pyridyl
4-Pyridyl
6
H
4
226 (224–226)5e
188–189
6
H
4
b
5e
6
H
4
60
229–230 (227–229)
20
30
20
20
20
211–212 (204–206)8b
214
220–221 (217)8
224–225 (223)
c
8c
d
j
272–274 (276–278)5
a
Volume of water per 1 g of 1.
b
4
0% ethanol was used as solvent.
Table 2
ing factor of the reaction and increasing the volume of water or
using a co-solvent (ethanol) was required for some less soluble
amidoguanidines 1. However, when ethanol was used as the sole
solvent instead of water, the conversion of 1a into 3(5)-amino-
5(3)-phenyl-1,2,4-triazole (2a) did not proceed to completion
even after 3 days of heating under reflux.
Optimization of the microwave-assisted synthesis of 2a
HN N
N NH
Ph
NH2
Ph
NH2
N
O NH2
1
a
2a
Microwave irradiation is an alternative source of energy,
which allows highly effective use of the heat produced, reduces
reaction times and often improves yields. Microwave-assisted
syntheses have found extensive applications in heterocyclic
Microwave power (W)
Reaction time (s)
Yield (%)
5
0
420
150
120
70
94
100
88
100
150
200
1
2
chemistry, and a number of methods for the preparation of
,2,4-triazoles using microwave irradiation have been reported.13
However, no data on microwave-based syntheses of 3(5)-amino-
,2,4-triazoles are available. Since water is an excellent solvent
1
82
1
1
4
for microwave-assisted reactions, and provided it is a suitable
medium for cyclocondensation of 1 under conventional heating,
we attempted to use it as a solvent in the microwave-initiated
synthesis. Four regimes with fixed microwave irradiation power
were applied using a CEM ‘Discover’ apparatus and 100 W was
(
het)arylamidoguanidines 1, upon heating in water, underwent
quantitative cyclocondensation with elimination of a water mol-
ecule affording 3(5)-amino-5(3)-(het)aryl-1,2,4-triazoles 2 (Table
1
1
1
). The reaction provided the products in excellent purity and
found to be optimal microwave power for the cyclization of 1a
did not require the presence of base or catalyst. The solubility of
the starting (het)arylamidoguanidines 1 was found to be a limit-
15
(
Table 2). These conditions were then applied successfully for
the preparation of other 3(5)-amino-5(3)-(het)aryl-1,2,4-triazoles
2) (Table 3). We attempted to prepare 2a by heating 1a in eth-
(
anol using similar irradiation conditions. However, a longer reac-
tion time (5 min) was required and the isolated yield was lower
(
86%).
The structures of the compounds prepared and in particular
Table 3
Microwave-assisted synthesis of triazoles 2a–j in water, 100 W
their tautomerism were investigated using both NMR spectros-
copy, which is considered to be the most informative and accu-
HN N
N NH
1
6
R
NH2
rate method for solutions, and X-ray crystallography, which
provides comprehensive structural information in the solid
R
NH2
N
O NH2
1
6b,c
1
2
state.
The 1,2,4-triazoles 2 were found to exist in amino forms; imino
1
7
Triazole
R
Reaction time (s)
Yield (%)
forms were disfavored according to literature data. Of the three
tautomeric forms theoretically possible due to annular tautomer-
ism (Scheme 2), forms A and B were found to be present in the
solutions of triazoles 2, while form C was not observed under the
experimental conditions.
2
2
2
2
2
2
2
2
2
2
a
b
c
d
e
f
g
h
i
Ph
150
165
165
150
180
165
180
150
150
150
100
100
100
90
100
100
100
84
4-MeC
4-MeOC
4-FC
4-ClC
2-Furyl
6 4
H
6
H
4
6
H
4
6
H
4
The equilibrium between the tautomers was established rap-
idly and the compositions did not change with time. Identical
spectra for the tautomeric system A–B were observed on dis-
solving the samples and after equilibration of the solution
overnight.
2-Thienyl
2-Pyridyl
3-Pyridyl
4-Pyridyl
100
88
j

2
126
A. V. Dolzhenko et al. / Tetrahedron Letters 50 (2009) 2124–2128
Table 4
Tautomerism in 3(5)-amino-1,2,4-triazoles in DMSO-d
6
solution
HN N
N NH
R
NH2
R
NH2
N
N
A
B
1H NMR signals of tautomeric forms A and B in DMSO-d
(0.1 M), ppm
K
ꢀ
D
G
298 (kJ mol
ꢀ1
)
Triazole
R
6
T
3
(5)-NH
2
N(1)-H
A
B
A
B
2
2
2
2
2
2
2
2
2
2
a
b
c
d
e
f
g
h
i
Ph
4-MeC
5.29
5.25
5.21
5.31
5.37
5.29
5.34
5.33
5.42
5.48
6.05
6.01
5.99
6.04
6.10
6.07
6.09
6.08
6.18
6.22
13.20
13.09
12.99
13.18
13.25
13.20
13.16
13.45
13.41
13.64
12.04
11.96
11.90
12.05
12.12
12.07
12.02
12.23
12.22
12.35
8.2
6.1
5.0
14.2
20.6
13.6
22.9
1.6
5.2
4.4
4.0
6.6
7.5
6.5
7.8
1.2
8.0
8.4
6
H
4
4-MeOC
4-FC
4-ClC
2-Furyl
2-Thienyl
2-Pyridyl
3-Pyridyl
4-Pyridyl
6
H
4
6
H
4
6
H
4
25.2
30.1
j
vation could be attributed to possible intramolecular hydrogen
bonding between N1–H and the nitrogen atom of the pyridyl
and the oxygen atom of the furyl moieties in form A. The intra-
molecular hydrogen bonding N1–HꢁꢁꢁX (X = O, N) would prevent
movement of the tautomeric equilibrium toward ‘electronically’
favored form B despite the strong electron-withdrawing effect
of the heterocycles. However, this explanation became wide
open to criticism by detailed analysis of further experiments.
HN N
N NH
NH2
NH2
N
N
R
R
A
B
8
7
6
5
4
3
Cl
1
The signals of N(1)–H in the H NMR spectra appeared at the
same range and had similar line widths for all triazoles 2.
Increasing the concentration of the samples from 0.1 to 1.0 M
F
caused a ꢂ0.2 ppm downfield shift of the signals (particularly
1
NH and NH
2
) in the H NMR spectra without affecting K
T
. Heat-
H
ing the sample should disfavor systems stabilized by intramolec-
ular hydrogen bonding and would shift the equilibrium to form
B. However, no significant changes in K were observed for 2f,h
T
Me
OMe
at elevated temperatures, similarly to triazoles 2 without poten-
tial intramolecular hydrogen bonding. The signals of the tautom-
1
ers A and B appeared clearly in the H NMR spectra in DMSO-d
6
solution and coalesced only on heating (Fig. 2). Interestingly,
addition of nonpolar CDCl to the DMSO-d solution of triazoles
f,h did not strengthen the intramolecular hydrogen bonding as
-0.2
-0.1
0.0
0.1
0.2
0.3
3
6
σ
2
Figure 1. Correlation of -
D
G for the tautomeric equilibrium of 3-amino-5-aryl- and
) of the R group.
expected. In contrast, the rate of the tautomeric exchange be-
came too fast to be observed on the NMR time-scale. Only one
set of signals appeared in the NMR spectra when a mixture of
5
-amino-3-aryl-1,2,4-triazoles with the Hammett constant (
r
6 3
DMSO-d and CDCl (1:1) was used as solvent for the experi-
The NH and NH
spectra in DMSO were quite distinct allowing calculation of K
values (Table 4). 5-Amino-1,2,4-triazoles B were identified to
be the predominant tautomers. The substituent showed signifi-
cant effects on the equilibrium between tautomeric forms A
and B. This effect was strongly dependent on the electronic
2
signals of tautomers A and B in the 1H NMR
ment, as exemplified in Figure 2. Therefore, the ‘‘anomalous”
thermodynamic stability of tautomeric forms A for 2f,h as well
as the effect of solvents on the rate of tautomeric exchange is
still to be revealed.
Unsymmetrical 3,5-disubstituted 1,2,4-triazoles have been
known to crystallize in the form of the tautomer bearing an elec-
T
properties of the substituents. It was found that the K
T
and
tron-acceptor substituent at position 3 and an electron-donor
1
8
19
D
G
298 values correlated well with the Hammett constants of
the substituents on the phenyl ring of 2a–e: ꢀ 298 = 8.086
5.265, R = 0.998 (Fig. 1). Therefore, the thermodynamic stabil-
substituent at position 5.
Surprisingly, we found that the
D
G
r
presence of forms A and B in the crystal was possible even for
compounds bearing substituents with considerably different
electronic properties. Thus, two compounds, that is, 5-amino-3-
phenyl-1,2,4-triazole and 3-amino-5-phenyl-1,2,4-triazole (2a)
crystallized together in the same crystal (Fig. 3) despite the fact
2
+
ity of form B in comparison with A increased together with the
electron-withdrawing properties of the substituents. This rela-
tionship could also be extended to some heterocyclic, that is,
3
1
2
-pyridyl, 4-pyridyl, and 2-thienyl substituents at C3(5) of the
,2,4-triazole ring. However, experimental results for compounds
f,h with 2-furyl and especially 2-pyridyl substituents at these
that the K
8.2. Conversely, 2h with a K
crystallized solely as 5-amino-3-(pyridin-2-yl)-1,2,4-triazole
T
value for their equilibrium in DMSO-d
6
solution was
T
in DMSO-d solution equal to 1.6,
6
positions were outside this correlation. At first glance, this obser-
(form B) (Fig. 4).

A. V. Dolzhenko et al. / Tetrahedron Letters 50 (2009) 2124–2128
2127
e
d
c
b
a
1
4.0
13.5
13.0
12.5
12.0
11.5
11.0
10.5
10.0
9.5
ppm)
9.0
8.5
8.0
7.5
7.0
6.5
6.0
5.5
5.0
(
Figure 2. 1H NMR spectra (300 MHz) of 3(5)-amino-5(3)-(pyridin-2-yl)-1,2,4-triazole (2h) 0.1 M solution in DMSO-d
solution in DMSO-d –CDCl (1:1), 27 °C (e).
6
, 27 °C (a); 50 °C (b); 100 °C (c); 150 °C (d); 0.1 M
6
3
In conclusion, an efficient and environmentally friendly method
for the preparation of 3(5)-amino-1,2,4-triazoles has been devel-
oped and some aspects of the tautomerism in these compounds
have been described.
Acknowledgments
This work is supported by the National Medical Research Coun-
cil, Singapore (NMRC/NIG/0019/2008 and NMRC/NIG/0020/2008).
The authors thank Koh Lip Lin and Tan Geok Kheng for the X-ray
crystallography studies.
References and notes
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Figure 3. X-ray structure of 2a, CCDC 717328.20
1
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2
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3
8
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0 0
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13
4
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0 0 0
6
C NMR (75 MHz, DMSO-d ): d 123.6 (C-5 ), 127.9 (C-3 ), 132.4 (C-4 ), 146.5
1
9
.
0
0
(C-2 ), 149.0 (C-6 ), 156.1 and 157.5 (C-3 and -5). Compound 2j: H NMR
), 7.78 (dd, J 4.5, 4
3
J
1
(300 MHz, DMSO-d
6
): d 5.48* and 6.22 (two s, 2H, NH
2
0
0
3
0
0
1.5 Hz, 2H, H-3 and -5 ), 8.60 (d, J 5.7 Hz, 2H, H-2 and -6 ), 12.35 and 13.64*
(two s, 1H, NH); C NMR (75 MHz, DMSO-d ): d 119.5 (C-3 and -5 ), 139.2 (C-
4 ), 149.9 (C-2 and -6 ), 156.4 and 157.6 (C-3 and -5). *—signals of minor
tautomers A.
13
0
0
6
0
0
0
1
1
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Commun. 2000, 30, 3031–3040; (k) Bentiss, F.; Lagrenee, M.; Barbry, D.
Tetrahedron Lett. 2000, 41, 1539–1541.
14. (a) Polshettiwar, V.; Varma, R. S. Chem. Soc. Rev. 2008, 37, 1546–1557; (b)
Polshettiwar, V.; Varma, R. S. Acc. Chem. Res. 2008, 41, 629–639; (c) Dallinger,
D.; Kappe, C. O. Chem. Rev. 2007, 107, 2563–2591.
15. General procedure for the microwave synthesis of 3(5)-amino-5(3)-het(aryl)-1,2,4-
triazoles (2): (Het)arylamidoguanidines (1, 1 mmol) were irradiated in 3 ml of
water using a CEM ‘Discover’ microwave apparatus, (see Tables 2 and 3 for
power and time). After cooling, the precipitated products 2 were filtered,
washed with ice-cold water and dried.
16. (a) Claramunt, R. M.; Lopez, C.; Santa Maria, M. D.; Sanz, D.; Elguero, J. Prog.
Nucl. Magn. Reson. Spectrosc. 2006, 49, 169–206; (b) Kleinpeter, E. Adv. Mol.
Struct. Res. 2000, 6, 97–129; (c) Elguero, J.; Katritzky, A. R.; Denisko, O. V. Adv.
Heterocycl. Chem. 2000, 76, 1–84.
1
significant changes in the yields. Compound 2a: H NMR (300 MHz, DMSO-
3
0
6 2
): d 5.29* and 6.05 (two s, 2H, NH
), 7.32 (t, J 7.2 Hz, 1H, H-4 ), 7.39 (t, J
3
3
d
7
(
0 0 0 0
.2 Hz, 2H, H-3 and -5 ), 7.89 (d, J 6.8 Hz, 2H, H-2 and -6 ), 12.04 and 13.20*
13
0
0
two s, 1H, NH); C NMR (75 MHz, DMSO-d
6
): d 125.4 (C-3 and -5 ), 128.1 (C-
0
0
0
0
4
5
6
), 128.3 (C-2 and -6 ), 132.3 (C-1 ), 152.4*, 157.3, 158.4 and 164.4* (C-3 and -
). Compound 2b: 1H NMR (300 MHz, DMSO-d
6
0
): d 2.32 (s, 3H, Me), 5.25* and
3
0
3
.01 (two s, 2H, NH
2
), 7.19 (d, J 7.9 Hz, 2H, H-3 and -5 ), 7.77 (d, J 7.9 Hz, 2H,
0
0
13
H-2 and -6 ), 11.96 and 13.09* (two s, 1H, NH); C NMR (75 MHz, DMSO-d
6
): d
0.8 (Me), 125.4 (C-3 and -5 ), 128.9 (C-2 and -6 ), 129.6 (C-1 ), 137.4 and
0
0
0
0
0
2
1
0
1
39.1* (C-4 ), 152.5*, 157.3, 158.5 and 164.2* (C-3 and -5). Compound 2c:
): d 3.78 (s, 3H, OMe), 5.21* and 5.99 (two s, 2H, NH
H
NMR (300 MHz, DMSO-d
6
6
2
),
.95 (d, 3J 8.7 Hz, 2H, H-3 and -5 ), 7.81 (d, J 8.7 Hz, 2H, H-2 and -6 ), 11.90
0
0
3
0
0
1
3
and 12.99* (two s, 1H, NH); C NMR (75 MHz, DMSO-d
): d 55.0 (OMe), 113.8
C-3 and -5 ), 125.0 (C-1 ), 126.8 (C-2 and -6 ), 152.3*, 157.2, 158.4 and 164.2*
6
0
0
0
0
0
(
(
0
1
C-3 and -5), 159.4 and 160.1* (C-4 ). Compound 2d: H NMR (300 MHz,
DMSO-d
3
6
): d 5.31* and 6.04 (two s, 2H, NH
2
), 7.22 (dd, J 8.7, 3
3
J
HF 8.7 Hz, 2H, H-
0
0
3
4
0
0
2
and -5 ), 7.91 (dd, J 8.7,
J
HF 5.7 Hz, 2H, H-2 and -6 ), 12.05 and 13.18* (two
13
0
0
s, 1H, NH); C NMR (75 MHz, DMSO-d
6
): d 115.2 (d,
J
CF 22.3 Hz, C-3 and -5 ),
1
27.2 (d, 3
C-3 and -5), 162.1 (d,
0 0 0
JCF 8.2 Hz, C-2 and -6 ), 128.9 (d, JCF 2.9 Hz, C-1 ), 157.3 and 157.5
1 1
4
0
JCF 244.6 Hz, C-4 ). Compound 2e: H NMR (300 MHz,
3
(
0
DMSO-d
5
6
): d 5.37* and 6.10 (two s, 2H, NH
2
), 7.46 (d, J 8.3 Hz, 2H, H-3 and -
0
3
0
0
13
), 7.88 (d, J 8.3 Hz, 2H, H-2 and -6 ), 12.12 and 13.25* (two s, 1H, NH);
C
0 0 0 0
6
NMR (75 MHz, DMSO-d ): d 126.9 (C-3 and -5 ), 128.4 (C-2 and -6 ), 131.2 (C-
1
0
0
), 132.6 (C-4 ), 157.4 (C-3 and -5). Compound 2f: H NMR (300 MHz, DMSO-
3
1
0
d
6
): d 5.29* and 6.07 (two s, 2H, NH
2
), 6.54 (dd, J 3.0 and 1.5 Hz, 1H, H-4 ), 6.67
3
0
3
0
(
d, J 3.0 Hz, 1H, H-3 ), 7.68 (d, J 1.5 Hz, 1H, H-5 ), 12.07 and 13.20* (two s, 1H,
13
0
0
0
NH); C NMR (75 MHz, DMSO-d
6
): d 107.4 (C-4 ), 111.2 (C-3 ), 142.5 (C-5 ),
47.6 (C-2 ), 152.1 and 156.9 (C-3 and -5). Compound 2g: H NMR (300 MHz,
), 7.07 (dd, J 4.9 and 3.4 Hz, 1H, H-
), 7.40 (d, J 3.0 Hz, 1H, H-3 ), 7.46 (d, J 4.9 Hz, 1H, H-5 ), 12.02 and 13.16*
): d 124.2 (C- 4 ), 125.4 (C-5 ),
27.4 (C-3 ), 135.5 (C-2 ), 154.7 and 157.1 (C-3 and -5). Compound 2h: H NMR
0
1
1
3
DMSO-d
6
): d 5.34* and 6.09 (two s, 2H, NH
2
0
3
0
3
0
4
17. Curtis, A. D. M. Sci. Synth. 2004, 13, 603–639.
18. We used the Hammett constant values from: Hansch, C.; Leo, A.; Taft, R. W.
Chem. Rev. 1991, 91, 165–195.
13
0
0
(
two s, 1H, NH); C NMR (75 MHz, DMSO-d
6
0
0
1
1
(
5
(
5
1
300 MHz, DMSO-d
6
): d 5.33* and 6.08 (two s, 2H, NH
2
), 7.25–7.51 (m, 1H, H-
19. Buzykin, B. I.; Mironova, E. V.; Nabiullin, V. N.; Gubaidullin, A. T.; Litvinov, I. A.
Russ. J. Gen. Chem. 2006, 76, 1471–1486.
20. Dolzhenko, A. V.; Tan, G. K.; Koh, L. L.; Dolzhenko, A. V.; Chui, W. K. Acta
Crystallogr., Sect. E 2009, 65, o126. doi:10.1107/S1600536808042165.
21. Dolzhenko, A. V.; Tan, G. K.; Koh, L. L.; Dolzhenko, A. V.; Chui, W. K. Acta
Crystallogr., Sect. E 2009, 65, o125. doi:10.1107/S1600536808042177.
0
0
0
0
), 7.74–8.00 (m, 2H, H-3 and -4 ), 8.52–8.69 (m, 1H, H-6 ), 12.23 and 13.45*
13
13
two s, 1H, NH); C NMR C NMR (75 MHz, DMSO-d
6
): d 120.7* and 120.9 (C-
0
0
0
0
), 123.0 and 124.3* (C-3 ), 136.5 and 137.5* (C-4 ), 146.5* and 150.7 (C-2 ),
0
1
49.2 (C-6 ), 151.6*, 157.2, 158.6 and 164.4* (C-3 and -5). Compound 2i:
H
NMR (300 MHz, DMSO-d
6
): d 5.42* and 6.18 (two s, 2H, NH
2
), 7.43 (dd, 3J 7.5