Synthesis of 6-Aryl-4H-imidazo[1,2-b][1,2,4]triazoles and 6-Aryl-thiazolo[3,2-b][1,2,4]triazoles

Article abstract of DOI:10.1002/jhet.2161

The cyclization of the derivatives of 3-aminotriazole, 2-(5-substituted 4H-1,2,4-triazol-3-ylamino)-1-arylethanones and 2-(4H-1,2,4-triazol-3-ylthio)-1-arylethanones to yield 6-aryl-4H-imidazo[1,2-b][1,2,4]triazoles and 6-aryl-thiazolo[3,2-b][1,2,4]triazoles has been described.

Full text of DOI:10.1002/jhet.2161

Month 2014 Synthesis of 6-Aryl-4H-imidazo[1,2-b][1,2,4]triazoles and 6-Aryl-thiazolo
[3,2-b][1,2,4]triazoles
*
T. Krishnaraj and S. Muthusubramanian
Department of Organic Chemistry, School of Chemistry, Madurai Kamaraj University, Madurai 625 021 India
*
E-mail: muthumanian2001@yahoo.com
Additional Supporting Information may be found in the online version of this article.
Received October 4, 2013
DOI 10.1002/jhet.2161
Published online 00 Month 2014 in Wiley Online Library (wileyonlinelibrary.com).
The cyclization of the derivatives of 3-aminotriazole, 2-(5-substituted 4H-1,2,4-triazol-3-ylamino)-
1-arylethanones and 2-(4H-1,2,4-triazol-3-ylthio)-1-arylethanones to yield 6-aryl-4H-imidazo[1,2-b]
[1,2,4]triazoles and 6-aryl-thiazolo[3,2-b][1,2,4]triazoles has been described.
J. Heterocyclic Chem., 00, 00 (2014).
INTRODUCTION
led to triazole ring fused with imidazole/thiazole ring, the
common nitrogen occupying the bridge head. A set of 15
The synthesis of heterocyclic compounds with more
nitrogen atoms in the ring has been attracting increasing
interest over the past decade because of their utility in
various applications, such as propellants, explosives,
pyrotechnics, and especially in chemotherapy. In recent
years, the chemistry of triazoles and their fused heterocyclic
derivatives has received considerable attention owing to their
synthetic and effective biological importance. The 1,2,4-
triazole nucleus has been incorporated in a wide variety of
therapeutically important agents displaying antimicrobial
activities [1]. Thiazolotriazoles, which contain two rings –
thiazole and triazole – fused together, can exist in both the
isomeric forms, thiazolo[3,2-b][1,2,4]triazole and thiazolo
[2,3-c][1,2,4]triazole. Thiazolo[3,2-b][1,2,4]triazoles pos-
sess a broad spectrum of biological activities – antimicrobial
[2], analgesic, anti-inflammatory [3], antipyretic [4], and
anticancer properties [5]. Barbuceanu et al. have synthesized
a set of thiazolo[3,2-b][1,2,4]triazoles and evaluated their
antibacterial activity [6]. A series of fluoro group containing
thiazolotriazoles have been synthesized and tested for their
anti-inflammatory, analgesic, and antimicrobial activities
[7]. Bakali et al. have synthesized large aromatic building
block-bearing cationic side chains of thiazolotriazoles and
investigated them as telomeric G-quadruplex stabilizers [8].
Roy et al. have reported a series of 5,6-diarylthiazolo[3,2-
b][1,2,4]triazoles and evaluated their potency and selectivity
against human COX-1 and COX-2 enzymes [9].
imidazo[1,2-b][1,2,4]triazoles
3 has been synthesized
(Scheme 1). The ester (1, R1 = COOEt) has been hydrolyzed
during the reaction, and thus in the case of 3b, 3e, 3h, 3k, and
3n, the corresponding carboxylic acids were obtained.
It should be mentioned that the reaction can take place
through either of the tautomeric forms 2A or 2B or both.
Thus 3A and/or 3B can be expected by ring tautomerized
form of the initial keto compound involving in the ring
closure (Scheme 2). The reaction has shown to give only
one product exclusively. Unfortunately, the one dimensional
NMR data are not useful enough to assign the correct struc-
ture between 3A and 3B. However, in 3m (Fig. 1), the signal
at 7.89ppm gives only one HMBC contour with the carbon
at 150.8 ppm. Had it been A, it is expected to give two
HMBC contours with carbons at 150.8 and 131.3 ppm, as
both can have three bond connectivity. Hence, structure B
is the correct one, and for all compounds, it is assigned that
way. In related systems also, such a cyclization has been
noticed (vide infra).
Other isomeric structures such as C and D (Fig. 2) can
be ruled out for this type of compounds. This is because
structures A and B of 3f alone can account for the two
dimensional NMR data, while structures C and D cannot.
NH of 3f gives HMBC contours with three carbons. This
can be the case only when A/B is the correct structure,
not with C/D.
In an attempt to prepare the sulfur analog of the imidazo
[1,2-b][1,2,4]triazoles 3, the same strategy of derivatizing
the third position by an acyl group followed by dehydra-
tion was effected, now on 3-mercapto-1,2,4-triazole. There
are already some reports regarding the self cyclization of
the ketone 4 by different dehydrating agents [4,11,12]. In
this work, we have employed sulfuric acid, and some
RESULTS AND DISCUSSION
In continuation of our search of possible fused heterocy-
cles from 3-aminotriazole [10], simple N-acyl derivatives
of 3-amino-1,2,4-triazole and 3-mercapto-1,2,4-triazole have
been subjected to intramolecular dehydration, and this has
© 2014 HeteroCorporation

T. Krishnaraj and S. Muthusubramanian
Vol 000
Scheme 1. Reagents and conditions: (i) R2COCH2Br, EtOH, K2CO3, RT,
halogen or CF3 group is present, the sulfonation is not
taking place. When the ring does not have any substitu-
ent or if methyl or methoxy group is in the ring, the
sulfonation takes place at the appropriate place. In the
case of 4h, the cyanide gets hydrolyzed to give amide
after cyclization.
stirring, 6 h, and (ii) aqueous ethanolic KOH, 95°C, 12 h.
As in the case of imidazoltriazole 3, in the case of
thiazolotriazole 5 also, there can be two possible structures:
A and B. The signal at 8.44 ppm gives only one HMBC
contour in 5c (Fig. 3), with 156.8 ppm, while the
structure A is expected to give two contours, not only with
156.8 ppm but also with 127.3 ppm. Hence, the correct
structure must be B and not A.
It has been shown that the cylcization of 4 by
polyphosphoric acid leads to thiazolotriazole B and not A
[11]. This is confirmed by X-ray studies also. However,
compounds of type 4 have shown to undergo cyclization
to structure A in anhydrous POCl3. But under acidic condi-
tions, 4 cyclizes to structure B [4]. This type of
thiazolotriazoles has been constructed by a different route
also. The triazole can be built over the thiazole ring as
reported [12].
Scheme 2
Triazoloimidazoles 3h and 3i have been tested for their
antibacterial activities. The microdilution method for
estimation of minimum inhibitory concentration (MIC)
values was applied to evaluate the antimicrobial activity
using agar diffusion method. They exhibited good activity
against both the gram negative bacteria, Escherichia coli
(MIC being 0.5 and 1.0 mg, respectively) and Paratyphi
A (MIC being 0.5 and 1.0 mg, respectively), but their
activities against the gram positive bacteria, Staphylococcus
aureus and Paratyphi A, are not encouraging.
Triazolothiazoles 5c and 5k are found to be active towards
E. coli (MIC being 1.0 and 2.0 mg, respectively), Paratyphi
A (MIC being 1.0 and 2.0 mg, respectively), S. aureus
(MIC being 2.0 and 2.0 mg, respectively), and Paratyphi A
(MIC being 2.0 and 2.0 mg, respectively).
EXPERIMENTAL
All chemicals used in this investigation were of reagent grade
quality and used without further purification. All melting points
were recorded in open capillaries and are uncorrected. The 1H
and 13C NMR spectra were recorded on a Bruker 400 MHz spec-
trometer at 400 MHz and 100 MHz, respectively, in CDCl3/
DMSO-d6 using TMS as internal standard. The chemical shifts
are presented in δ-scale. Microanalyses were carried out on a
PerkinElmer instrument (Lv Venlo, The Netherlands). All chro-
matographic separations were performed on 60–120 mesh silica
gel using petroleum ether–ethyl acetate as eluent, unless men-
tioned otherwise.
For antibacterial activity experiments, the compounds were
dissolved in DMSO to prepare chemical stock solution of
20 mg/mL. Gentamycin was used as the standard drug. Initially,
the stock cultures of bacteria were revived by inoculating in broth
media and grown at 37°C for 18 h. The agar plates of the
Figure 1. NMR data for 3m.
new compounds have been targeted at. The results are in-
teresting and presented in the succeeding texts.
Thirteen differently substituted thiazolo[3,2-b][1,2,4]
triazoles 5 have been synthesized by this protocol
(Scheme 3). In some cases, cyclization is followed by
sulfonation. Thus, 4a and 4g undergoes sulfonation at the
para position after cyclization. In 4i, the position ortho to
the methyl has been sulfonated after cyclization; while in
4m, the position para to methoxy has been sulfonated. 4f
does not undergo the cyclization at all. When nitro or
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

Month 2014
6-Aryl-4H-imidazo[1,2-b]/thiazolo[3,2-b][1,2,4]triazoles
Figure 2. Possible structures of 3f.
Scheme 3. Reagents and conditions: (i) R2COCH2Br, EtOH, K2CO3, RT, stirring, 6 h, and (ii) concentrated H2SO4, 40°C, 5 h.
aforementioned media were prepared, and wells were made in
the plate. Each plate was inoculated with 18-h-old cultures
(100 μL, 10À4 cfu) and spread evenly on the plate. After 20 min,
the wells were filled with compound at different concentrations.
The control wells with gentamycin were also prepared. All the
plates were incubated at 37°C for 24 h, and the diameter of inhi-
bition zone were noted. The derivatives of 2 and 4 were prepared
by known procedures, and the analytical data for unreported 2 and
4 are alone provided here.
Ethyl 5-((2-oxo-2-phenylethyl)amino)-4H-1,2,4-triazole-3-
carboxylate (2, R1 = COOEt, R2 = Ph). This compound was
obtained as white solid; yield 88%; mp 195–196°C; IR (KBr)
1
3401, 3129, 1723, 1636 cmÀ1; H NMR (400 MHz, DMSO-d6)
δ 1.25 (t, J = 7.2 Hz, 3H), 4.22 (q, J = 7.2 Hz, 2H), 5.69 (s, 2H),
6.53 (bs, 2H), 7.59 (t, J = 7.4 Hz, 2H), 7.71 (t, J = 7.4 Hz, 1H),
8.02 (d, J = 7.4 Hz, 2H); 13C NMR (100 MHz, DMSO-d6)
Figure 3. NMR data for 5c.
δ 14.1, 53.5, 60.4, 128.1, 128.9, 134.0, 134.4, 150.7, 157.4,
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DOI 10.1002/jhet

T. Krishnaraj and S. Muthusubramanian
Vol 000
160.0, 192.1; ESI mass (m/z) Calcd [C13H14N4O3 + H]+274.11,
found 275.2.
191.3; ESI mass (m/z) Calcd [C11H11FN4OS + H]+266.06,
found 267.1.
2-((5-(Methylthio)-4H-1,2,4-triazol-3-yl)amino)-1-phenylet-
hanone (2, R1 = SMe, R2 = Ph). This compound was obtained as
white solid; yield 92%; mp 194–195°C; IR (KBr) 3193, 2927, 1685,
2-((4H-1,2,4-Triazol-3-yl)amino)-1-(3-methoxyphenyl)ethanone
(2, R1 =H, R2 = 3-MeOPh).
This compound was obtained as
1
viscous liquid; yield 85%; H NMR (400 MHz, DMSO-d6) δ 3.83
(s, 3H), 5.53 (s, 2H), 6.19 (bs, 2H), 7.27 (d, J= 8.2 Hz, 1H), 7.32–
7.33 (m, 1H), 7.35 (s, 1H), 7.49 (t, J= 7.9 Hz, 1H), 7.61
(d, J= 7.9 Hz, 1H); 13C NMR (100 MHz, DMSO-d6) δ 53.4, 55.8,
113.0, 120.2, 120.9, 130.5, 136.3, 149.0, 156.7, 159.9, 162.9; ESI
mass (m/z) Calcd [C11H12N4O2]+232.10, found 232.8.
1
1564 cmÀ1; H NMR (400 MHz, DMSO-d6) δ 2.40 (s, 3H), 5.52 (s,
2H), 6.33 (bs, 2H), 7.59 (t, J= 7.4 Hz, 2H), 7.69 (t, J= 7.4 Hz, 1H),
8.02 (d, J= 7.4 Hz, 2H); 13C NMR (100 MHz, DMSO-d6) δ 13.4,
52.9, 128.0, 128.9, 133.9, 134.5, 156.3, 157.3, 192.6; ESI mass (m/
z) Calcd [C11H12N4OS + H]+248.07, found 249.2.
Ethyl 5-((2-oxo-2-(p-tolyl)ethyl)amino)-4H-1,2,4-triazole-3-
Ethyl 5-((2-(3-methoxyphenyl)-2-oxoethyl)amino)-4H-1,2,4-
triazole-3-carboxylate (2, R1 = COOEt, R2 = 3-MeOPh).
This compound was obtained as white solid; yield 87%; mp 197–
carboxylate (2, R1 = COOEt, R2 = p-tolyl).
was obtained as white solid; yield 86%; mp 210–211°C; IR (KBr)
3411, 3128, 1728, 1637 cmÀ1 1H NMR (400 MHz, DMSO-d6)
This compound
;
198°C; IR (KBr) 3389, 3133, 1726, 1640 cmÀ1 1H NMR
;
δ 1.25 (t, J = 7.2Hz, 3H), 2.40 (s, 3H), 4.21 (q, J = 7.2 Hz, 2H),
5.66 (s, 2H), 6.52 (bs, 2H), 7.39 (d, J = 7.9 Hz, 2H), 7.93
(d, J = 7.9 Hz, 2H); 13C NMR (100 MHz, DMSO-d6) δ 14.5, 21.7,
53.8, 60.8, 128.6, 129.8, 132.3, 144.9, 151.1, 157.8, 160.4, 192.0;
ESI mass (m/z) Calcd [C14H16N4O3]+288.12, found 288.9.
(400 MHz, DMSO-d6) δ 1.25 (t, J = 7.2 Hz, 3H), 3.83 (s, 3H),
4.20 (q, J = 7.2 Hz, 2H), 5.67 (s, 2H), 6.52 (bs, 2H), 7.29
(d, J = 8.1 Hz, 1H), 7.50–7.53 (m, 2H), 7.61 (d, J = 7.7 Hz, 1H);
13C NMR (100 MHz, DMSO-d6) δ 14.5, 54.1, 55.9, 60.9, 113.1,
120.3, 120.9, 130.5, 136.1, 151.1, 157.8, 159.9, 160.4, 192.4;
ESI mass (m/z) Calcd [C14H16N4O4]+304.12, found 304.8.
2-((5-(Methylthio)-4H-1,2,4-triazol-3-yl)amino)-1-(p-tolyl)
ethanone (2, R1 = SMe, R2 = p-tolyl).
obtained as white solid; yield 88%; mp 170–171°C; IR (KBr)
3382, 2925, 1679, 1562 cmÀ1 1H NMR (400 MHz, DMSO-d6)
δ 2.39 (s, 3H), 2.40 (s, 3H), 5.47 (s, 2H), 6.31 (bs, 2H), 7.39
(d, J = 8.0Hz, 2H), 7.91 (d, J = 8.0 Hz, 2H); 13C NMR (100 MHz,
DMSO-d6) δ 13.4, 21.3, 52.8, 128.2, 129.4, 132.1, 144.4, 156.2,
157.3, 192.1; ESI mass (m/z) Calcd [C12H14N4OS + H]+262.09,
found 263.2.
This compound was
1-(4-Bromophenyl)-2-((5-(methylthio)-4H-1,2,4-triazol-3-yl)
amino)ethanone (2, R1 = SMe, R2 = 4-BrPh). This compound
was obtained as white solid; yield 82%; mp 175–176°C; IR
;
(KBr) 3382, 2916, 1684, 1584 cmÀ1 1H NMR (400MHz,
;
DMSO-d6) δ 2.38 (s, 3H), 5.50 (s, 2H), 6.32 (bs, 2H), 7.79 (d,
J = 8.4Hz, 2H), 7.93 (d, J = 8.4 Hz, 2H); 13C NMR (100MHz,
DMSO-d6) δ 13.4, 53.0, 128.0, 130.1, 132.0, 133.6, 156.4, 157.3,
192.4; ESI mass (m/z) Calcd [C11H11BrN4OS + H]+325.98,
found 327.4.
Ethyl 5-((2-(4-chlorophenyl)-2-oxoethyl)amino)-4H-1,2,4-
triazole-3-carboxylate (2, R1 = COOEt, R2 = 4-ClPh).
This
General procedure for the synthesis of 6-aryl-4H-imidazo
compound was obtained as white solid; yield 86%; mp 252–253°
[1,2-b][1,2,4]triazole (3).
Compound 2 was treated with
1
C; IR (KBr) 3405, 3121, 1723, 1640cmÀ1; H NMR (400 MHz,
aqueous ethanolic potassium hydroxide, and the reaction mixture
was heated at 95°C for 12h. The resultant mass was acidified
with concentrated hydrochloric acid to give 3, which was purified
by crystallization in ethanol.
DMSO-d6) δ 1.25 (t, J = 7.2 Hz, 3H), 4.21 (q, J = 7.2 Hz, 2H),
5.68 (s, 2H), 6.53 (bs, 2H), 7.67 (d, J = 8.5 Hz, 2H), 8.05
(d, J = 8.5 Hz, 2H); 13C NMR (100 MHz, DMSO-d6) δ 14.1, 53.6,
60.4, 129.0, 130.0, 132.8, 138.9, 150.8, 157.3, 160.0, 191.5; ESI
mass (m/z) Calcd [C13H13ClN4O3]+308.07, found 308.8.
6-Phenyl-4H-imidazo[1,2-b][1,2,4]triazole (3a).
compound was obtained as white solid; yield 86%; mp 251–252°
C; IR (KBr) 1615, 1494, 1183 cmÀ1 1H NMR (400 MHz,
This
1-(4-Chlorophenyl)-2-((5-(methylthio)-4H-1,2,4-triazol-3-
;
yl)amino)ethanone (2, R1 = SMe, R2 = 4-ClPh).
This
DMSO-d6) δ 7.33 (t, J = 7.4 Hz, 1H), 7.45 (t, J = 7.4 Hz, 2H), 7.74
(d, J = 7.4 Hz, 2H), 7.89 (s, 1H), 8.22 (s, 1H), 12.48 (bs, 1H); 13C
NMR (100 MHz, DMSO-d6) δ 103.9, 124.8, 128.5, 129.4, 129.9,
131.8, 151.3, 154.2; Anal. Calcd for C10H8N4: C, 65.21; H, 4.38;
N, 30.42%. Found: C, 65.38; H, 4.26; N, 30.40%; ESI mass (m/z)
Calcd [C10H8N4 + H]+184.07, found 185.2.
compound was obtained as white solid; yield 84%; mp 179–180°
1
C; IR (KBr) 3383, 2914, 1683, 1589cmÀ1; H NMR (400 MHz,
DMSO-d6) δ 2.38 (s, 3H), 5.50 (s, 2H), 6.31 (bs, 2H), 7.65
(d, J = 8.4Hz, 2H), 8.01 (d, J = 8.4 Hz, 2H); 13C NMR (100 MHz,
DMSO-d6) δ 13.3, 52.9, 128.9, 129.9, 133.2, 138.7, 156.3, 157.2,
191.7; ESI mass (m/z) Calcd [C11H11ClN4OS + H]+282.03,
found 283.2.
6-Phenyl-4H-imidazo[1,2-b][1,2,4]triazole-2-carboxylic
acid (3b).
This compound was obtained as white solid; yield
90%; mp 222–223°C; IR (KBr) 3358, 2940, 1630, 1355cmÀ1; 1H
NMR (400 MHz, DMSO-d6) δ 7.38 (t, J = 7.3 Hz, 1H), 7.48 (t,
J = 7.6Hz, 2H), 7.79 (d, J = 7.6 Hz, 2H), 8.32 (s, 1H), 12.86 (bs,
2H); 13C NMR (100 MHz, DMSO-d6) δ 103.5, 124.8, 128.6,
129.0, 129.1, 133.4, 150.7, 156.1, 161.6; Anal. Calcd for
C11H8N4O2: C, 57.89; H, 3.53; N, 24.55%. Found: C, 57.63; H,
3.50; N, 24.68%; ESI mass (m/z) Calcd [C11H8N4O2]+228.06,
found 228.8.
Ethyl 5-((2-(4-fluorophenyl)-2-oxoethyl)amino)-4H-1,2,4-
triazole-3-carboxylate (2, R1 = COOEt, R2 = 4-FPh).
This
compound was obtained as white solid; yield 88%; mp 230–231°
1
C; IR (KBr) 3388, 3138, 1725, 1643cmÀ1; H NMR (400 MHz,
DMSO-d6) δ 1.25 (t, J = 7.2 Hz, 3H), 4.21 (q, J = 7.2 Hz, 2H),
5.68 (s, 2H), 6.53 (bs, 2H), 7.43 (t, J = 8.8 Hz, 2H), 8.08–8.12
(m, 2H); 13C NMR (100 MHz, DMSO-d6) δ 14.1, 53.2, 60.4,
116.0, 131.1, 131.2, 150.7, 157.4, 160.0, 165.2, 190.8; ESI mass
(m/z) Calcd [C13H13FN4O3-H]+292.10, found 290.8.
2-Methylthio-6-phenyl-4H-imidazo[1,2-b][1,2,4]triazole (3c).
This compound was obtained as white solid; yield 86%; mp 290–
1-(4-Fluorophenyl)-2-((5-(methylthio)-4H-1,2,4-triazol-3-
yl)amino)ethanone (2, R1 = SMe, R2 = 4-FPh).
This
291°C; IR (KBr) 3104, 2922, 1601, 1278 cmÀ1 1H NMR
;
compound was obtained as white solid; yield 86%; mp 166–167°
(400 MHz, DMSO-d6) δ 2.54 (s, 3H), 7.32 (t, J = 7.5 Hz, 1H),
7.44 (t, J = 7.5 Hz, 2H), 7.71 (d, J = 7.5Hz, 2H), 8.17 (s, 1H), NH
not seen; 13C NMR (100MHz, DMSO-d6) δ 13.9, 103.8, 124.3,
128.0, 129.0, 129.4, 129.9, 151.3, 162.8; Anal. Calcd for
C11H10N4S: C, 57.37; H, 4.38; N, 24.33%. Found: C, 57.19; H,
1
C; IR (KBr) 3390, 3130, 1684, 1572cmÀ1; H NMR (400 MHz,
DMSO-d6) δ 2.38 (s, 3H), 5.50 (s, 2H), 6.32 (bs, 2H), 7.41
(t, J = 8.2 Hz, 2H), 8.09 (d, J = 8.2 Hz, 2H); 13C NMR (100 MHz,
DMSO-d6) δ 13.4, 52.9, 115.9, 131.0, 131.1, 156.3, 157.2, 165.1,
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6-Aryl-4H-imidazo[1,2-b]/thiazolo[3,2-b][1,2,4]triazoles
4.43; N, 24.42%; ESI mass (m/z) Calcd [C11H10N4S + H]+230.06,
found 231.1.
(100 MHz, DMSO-d6) δ 103.4, 116.0, 126.5, 126.6, 130.6, 150.8,
153.6, 161.5; Anal. Calcd for C10H7FN4: C, 59.40; H, 3.49; N,
27.71%. Found: C, 59.37; H, 3.61; N, 27.70%; ESI mass (m/z)
Calcd [C10H7FN4]+202.07, found 202.7.
6-(p-Tolyl)-4H-imidazo[1,2-b][1,2,4]triazole (3d).
compound was obtained as white solid; yield 83%; mp 270–
271°C; IR (KBr) 3125, 2909, 1608, 1474cmÀ1 1H NMR
This
;
6-(4-Fluorophenyl)-4H-imidazo[1,2-b][1,2,4]triazole-2-
(400MHz, DMSO-d6) δ 2.33 (s, 3H), 7.28 (d, J = 8.0 Hz, 2H),
7.64 (d, J = 8.0 Hz, 2H), 7.88 (s, 1H), 8.16 (s, 1H), 12.41 (bs,
1H); 13C NMR (100 MHz, DMSO-d6) δ 20.8, 102.9, 124.3,
126.7, 129.5, 131.5, 137.5, 150.7, 153.6; Anal. Calcd for
C11H10N4: C, 66.65; H, 5.08; N, 28.26%. Found: C, 66.72; H,
5.36; N, 28.51%; ESI mass (m/z) Calcd [C11H10N4 + H]+198.09,
found 199.2.
carboxylic acid (3k).
This compound was obtained as white
solid; yield 96%; mp 256°C; IR (KBr) 3163, 1684, 1616 cm-1; 1H
NMR (400MHz, DMSO-d6) δ 7.37 (t, J = 8.8 Hz, 2H), 7.83–7.86
(m, 2H), 8.31 (s, 1H), 12.77 (bs, 1H), 13.09 (bs, 1H); 13C NMR
(100 MHz, DMSO-d6) δ 103.4, 116.0, 116.2, 125.6, 127.0, 127.1,
132.5, 150.6, 161.0; Anal. Calcd for C11H7FN4O2: C, 53.66; H,
2.87; N, 22.76%. Found: C, 53.83; H, 2.94; N, 22.48%; ESI mass
(m/z) Calcd [C11H7FN4O2]+246.06, found 246.8.
6-(p-Tolyl)-4H-imidazo[1,2-b][1,2,4]triazole-2-carboxylic
acid (3e).
This compound was obtained as white solid; yield
6-(4-Fluorophenyl)-2-(methylthio)-4H-imidazo[1,2-b][1,2,4]
triazole (3l). This compound was obtained as white solid; yield
87%; mp 301–302°C; IR (KBr) 2920, 1614, 1504cmÀ1; 1H NMR
(400 MHz, DMSO-d6) δ 2.48 (s, 3H), 7.30 (t, J = 8.8 Hz, 2H),
7.72–7.75 (m, 2H), 8.13 (s, 1H), 12.46 (bs, 1H); 13C NMR
(100 MHz, DMSO-d6) δ 13.9, 103.7, 116.1, 126.0, 126.3, 129.0,
151.2, 161.5, 162.8; Anal. Calcd for C11H9FN4S: C, 53.21; H,
3.65; N, 22.57%. Found: C, 53.47; H, 3.24; N, 22.38%; ESI mass
(m/z) Calcd [C11H9FN4S + H]+248.05, found 249.1.
6-(3-Methoxyphenyl)-4H-imidazo[1,2-b][1,2,4]triazole (3m).
This compound was obtained as white solid; yield 92%; mp 305°C;
IR (KBr) 3137, 1617, 1487 cmÀ1; 1H NMR (400MHz, DMSO-d6)
δ 3.81 (s, 3H), 6.91 (d, J = 7.2 Hz, 1H), 7.31–7.38 (m, 3H), 7.89 (s,
1H), 8.29 (s, 1H), 12.46 (bs, 1H); 13C NMR (100 MHz, DMSO-d6)
δ 55.3, 103.7, 109.9, 113.6, 116.7, 130.1, 130.8, 131.3, 150.8,
153.8, 159.8; Anal. Calcd for C11H10N4O: C, 61.67; H, 4.71; N,
26.15%. Found: C, 61.48; H, 4.82; N, 26.10%; ESI mass (m/z)
Calcd [C11H10N4O]+214.09, found 214.7.
6-(3-Methoxyphenyl)-4H-imidazo[1,2-b][1,2,4]triazole-
2-carboxylic acid (3n). This compound was obtained as white
solid; yield 96%; mp 205°C; IR (KBr) 3575, 1714, 1602 cmÀ1; 1H
NMR (400 MHz, DMSO-d6) δ 3.81 (s, 3H), 6.94–6.96 (m, 1H),
7.31–7.38 (m, 3H), 8.35 (s, 1H), 12.74 (bs, 1H), 13.09 (bs, 1H);
13C NMR (100 MHz, DMSO-d6) δ 55.3, 103.8, 110.2, 114.3,
117.0, 130.2,*133.3, 150.6, 156.1, 159.8, 161.6; Anal. Calcd for
C12H10N4O3: C, 55.81; H, 3.90; N, 21.70%. Found: C, 55.63; H,
4.21; N, 27.65%; ESI mass (m/z) Calcd [C12H10N4O3-H]+258.08,
found 256.8.*Two carbon signals merged here.
88%; mp 253–254°C; IR (KBr) 3130, 1699, 1604 cmÀ1; 1H NMR
(400MHz, DMSO-d6) δ 2.34 (s, 3H), 7.29 (d, J = 7.5 Hz, 2H),
7.69 (d, J = 7.5 Hz, 2H), 8.24 (s, 1H), 12.90 (bs, 2H); 13C NMR
(100MHz, DMSO-d6) δ 21.2, 103.3, 125.1, 125.3, 126.8, 128.6,
129.6, 138.5, 150.8, 162.0; Anal. Calcd for C12H10N4O2: C,
59.50; H, 4.16; N, 23.13%. Found: C, 60.01; H, 4.08; N, 23.26%;
ESI mass (m/z) Calcd [C12H10N4O2]+242.08, found 242.8.
2-(Methylthio)-6-(p-tolyl)-4H-imidazo[1,2-b][1,2,4]triazole
(3f). This compound was obtained as white solid; yield 82%; mp
289–290°C; IR (KBr) 3052, 1606, 1470, 1247 cmÀ1 1H NMR
;
(400 MHz, DMSO-d6) δ 2.32 (s, 3H), 2.55 (s, 3H), 7.26 (d,
J= 8.0 Hz, 2H), 7.61 (d, J= 8.0 Hz, 2H), 8.10 (s, 1H), 12.40 (bs, 1H);
13C NMR (100 MHz, DMSO-d6) δ 14.3, 21.2, 103.6, 124.7, 127.0,
130.0, 130.4, 137.9, 151.6, 162.9; Anal. Calcd for C12H12N4S: C,
58.99; H, 4.95; N, 22.93%. Found: C, 59.12; H, 4.78; N, 22.83%;
ESI mass (m/z) Calcd [C12H12N4S+H]+244.08, found 245.2.
6-(4-Chlorophenyl)-4H-imidazo[1,2-b][1,2,4]triazole (3g).
This compound was obtained as white solid; yield 90%; mp 317–
318°C; IR (KBr) 3115, 2853, 1617, 1490 cmÀ1 1H NMR
;
(400 MHz, DMSO-d6)
δ
7.53 (d, J= 8.5Hz, 2H), 7.76
(d, J= 8.5 Hz, 2H), 7.90 (s, 1H), 8.26 (s, 1H), 12.54 (bs, 1H); 13C
NMR (100 MHz, DMSO-d6) δ 103.9, 126.0, 128.6, 129.0, 130.6,
132.4, 151.0, 153.8; Anal. Calcd For C10H7ClN4: C, 54.93; H,
3.23; N, 25.62. Found: C, 54.46; H, 3.22; N, 25.39%; ESI mass (m/
z) Calcd [C10H7ClN4]+218.04, found 218.8.
6-(4-Chlorophenyl)-4H-imidazo[1,2-b][1,2,4]triazole-2-
carboxylic acid (3h). This compound was obtained as white
solid; yield 94%; mp 300–301°C; IR (KBr) 3150, 1685,
6-(4-Bromophenyl)-2-(methylthio)-4H-imidazo[1,2-b][1,2,4]
triazole (3o). This compound was obtained as white solid; yield
1609 cmÀ1; H NMR (400 MHz, DMSO-d6) δ 7.58 (d, J=8.4Hz,
1
2H), 7.83 (d, J= 8.4 Hz, 2H), 8.38 (s, 1H), 12.93 (bs, 2H); 13C
NMR (100 MHz, DMSO-d6) δ 104.0, 126.4, 129.1, 132.9, 150.6,
161.5, Not all carbons picked up; Anal. Calcd for C11H7ClN4O2: C,
50.30; H, 2.69; N, 21.33%. Found: C, 50.46; H, 2.78; N, 21.19%;
ESI mass (m/z) Calcd [C11H7ClN4O2]+262.03, found 262.8.
90%; mp 299–300°C; IR (KBr) 1609,1484, 1393 cmÀ1; H NMR
1
(400 MHz, DMSO-d6) δ 2.54 (s, 3H), 7.71 (s, 4H), 8.23 (s, 1H)
NH not seen; 13C NMR (100 MHz, DMSO-d6) δ 14.3, 104.7,
121.2, 126.6, 129.3, 131.7, 132.3, 151.8, 163.4; Anal. Calcd for
C11H9BrN4S: C, 42.73; H, 2.93; N, 18.12%. Found: C, 42.56; H,
3.14; N, 18.25%; ESI mass (m/z) Calcd [C11H9BrN4S+H]+307.97,
found 309.6.
6-(4-Chlorophenyl)-2-(methylthio)-4H-imidazo[1,2-b][1,2,4]
triazole (3i). This compound was obtained as white solid; yield
78%; mp 304–305°C; IR (KBr) 3048, 1610, 1488, 1248 cmÀ1; 1H
NMR (400 MHz, DMSO-d6) δ 2.54 (s, 3H), 7.52 (d, J = 8.5 Hz,
2H), 7.73 (d, J = 8.5 Hz, 2H), 8.21 (s, 1H), 12.50 (bs, 1H); 13C
NMR (100 MHz, DMSO-d6) δ 13.8, 104.3, 125.9, 128.4, 128.8,
129.1. 132.3, 151.4, 163.0; Anal. Calcd for C11H9ClN4S: C,
49.91; H, 3.43; N, 21.16%. Found: C, 50.23; H, 3.61; N, 21.07%;
ESI mass (m/z) Calcd [C11H9ClN4S + H]+264.02, found 265.3.
6-(4-Fluorophenyl)-4H-imidazo[1,2-b][1,2,4]triazole (3j).
This compound was obtained as white solid; yield 92%; mp 302–
2-((4H-1,2,4-Triazol-3-yl)thio)-1-(4-chlorophenyl)ethanone
(4b). This compound was obtained as white solid; yield 86%; mp
118–119°C; IR (KBr) 3079, 2853, 1692, 1583cmÀ1 1H NMR
;
(400 MHz, DMSO-d6) δ 4.79 (s, 2H), 7.63 (d, J = 8.5 Hz, 2H),
8.03 (d, J = 8.5 Hz, 2H), 8.40 (s, 1H), 14.02 (bs, 1H); 13C NMR
(100 MHz, DMSO-d6) δ 40.1, 128.9, 130.3, 134.3, 138.5, 146.2,
192.9. Not all carbons picked up; ESI mass (m/z) Calcd
[C10H8ClN3OS-H]+253.01, found 252.2.
2-((4H-1,2,4-Triazol-3-yl)thio)-1-(4-(trifluoromethyl)phenyl)
ethanone (4e). This compound was obtained as white solid;
yield 72%; mp 103–104°C; IR (KBr) 3116, 2860, 1676,
303°C; IR (KBr) 3121, 2858, 1619, 1508cmÀ1 1H NMR
;
(400MHz, DMSO-d6) δ 7.34 (t, J = 8.8 Hz, 2H), 7.77–7.81
(m, 2H), 7.90 (s, 1H), 8.21 (s, 1H), 12.49 (bs, 1H); 13C NMR
1321 cmÀ1 1H NMR (400 MHz, DMSO-d6) δ 4.85 (s, 2H),
;
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

T. Krishnaraj and S. Muthusubramanian
Vol 000
7.93 (d, J = 8.2 Hz, 2H), 8.21 (d, J = 8.2 Hz, 2H), 8.48 (s, 1H),
14.04 (bs, 1H); 13C NMR (100 MHz, DMSO-d6) δ 40.6, 124.8,
128.2,*129.6, 133.0, 133.3, 139.3, 193.8; ESI mass (m/z) Calcd
[C11H8F3N3OS + H]+287.03, found 288.2.*Two carbon signals
merged here.
2-((4H-1,2,4-Triazol-3-yl)thio)-1-(2-methoxyphenyl)ethanone
(4m). This compound was obtained as white solid; yield 74%;
mp 102–103°C; IR (KBr) 2833, 1681, 1594 cmÀ1 1H NMR
;
(400 MHz, DMSO-d6) δ 3.90 (s, 3H), 4.59 (s, 2H), 7.03
(t, J = 7.7 Hz, 1H), 7.19 (d, J = 7.7 Hz, 1H), 7.55–7.61 (m, 2H),
8.33 (s, 1H) NH not seen; 13C NMR (100MHz, DMSO-d6) δ
43.8, 56.4, 112.9, 121.0, 126.4, 130.5, 134.8, 146.8, 156.8, 159.0,
195.3; ESI mass (m/z) Calcd [C11H11N3O2S + H]+249.06, found
250.2.
2-((4H-1,2,4-Triazol-3-yl)thio)-1-(4-(diethylamino)phenyl)
ethanone (4f). This compound was obtained as viscous liquid;
1
yield 71%; H NMR (400 MHz, DMSO-d6) δ 1.22 (t, J = 7.2 Hz,
6H), 3.44 (q, J = 7.2 Hz, 4H), 4.40 (s, 2H), 6.67 (d, J = 8.6 Hz,
2H), 7.89 (d, J = 8.6 Hz, 2H), 8.03 (s, 1H) NH not seen; 13C
NMR (100 MHz, DMSO-d6) δ 12.4, 38.0, 44.6, 110.3, 121.7,
130.2, 131.5, 148.9, 152.0, 192.1. Not all the carbons picked up;
ESI mass (m/z) Calcd [C14H18N4OS+ H]+290.12, found 291.3.
2-((4H-1,2,4-Triazol-3-yl)thio)-1-([1,1′-biphenyl]-4-yl)ethanone
(4g). This compound was obtained as white solid; yield 86%; mp
General procedure for the synthesis of substituted thiazolo
[3,2-b][1,2,4]triazole (5).
Compound 4 was treated with
concentrated sulfuric acid, and the reaction mixture was heated
at 40°C for 5 h. The resultant mass was basified with aqueous
ammonia to give 5, which was purified by crystallization.
Compounds 5a–m were prepared by this method (5a, 5g, 5i,
and 5m were not basified with aqueous ammonia but were
added to water and filtered to give the sulfonated products).
4-(Thiazolo[3,2-b][1,2,4]triazol-6-yl)benzenesulfonic acid (5a).
This compound was obtained as white solid; yield 78%; high
148–149°C; IR (KBr) 3235, 1671, 1602, 1299 cmÀ1 1H NMR
;
(400MHz, DMSO-d6) δ 4.84 (s, 2H), 7.45 (t, J = 7.2 Hz, 1H),
7.52 (t, J = 7.2 Hz, 2H), 7.78 (d, J = 8.5 Hz, 2H), 7.85
(d, J = 8.4 Hz, 2H), 8.10 (d, J = 8.4 Hz, 2H), 8.39 (s, 1H), 14.02
(bs, 1H); 13C NMR (100MHz, DMSO-d6) δ 40.6, 127.4, 127.5,
128.9, 129.5, 134.8, 139.3, 145.3, 146.7, 156.8, 193.7. Not all the
carbons picked up; ESI mass (m/z) Calcd [C16H13N3OS-
H]+295.08, found 294.2.
;
melting: IR (KBr) 1413, 1172 cmÀ1 1H NMR (400 MHz,
DMSO-d6) δ 6.73 (s, 1H), 7.76 (d, J = 8.2 Hz, 2H), 7.99 (s, 1H),
8.19 (d, J = 8.2 Hz, 2H), 8.44 (s, 1H); 13C NMR (100MHz,
DMSO-d6) δ 112.0, 126.2, 126.5, 128.1, 131.5, 149.4, 156.6,
157.2; Anal. Calcd for C10H7N3O3S2: C, 42.70; H, 2.51; N,
14.94%. Found: C, 42.58; H, 2.62; N, 15.07%; ESI mass (m/z)
Calcd [C10H7N3O3S2]+280.99, found 280.2.
4-(2-((4H-1,2,4-Triazol-3-yl)thio)acetyl)benzonitrile (4h). This
compound was obtained as white solid; yield 78%; mp 143–144°
1
C; IR (KBr) 3089, 2234, 1705, 1405cmÀ1; H NMR (400 MHz,
DMSO-d6) δ 4.82 (s, 2H), 8.03 (d, J = 8.4Hz, 2H), 8.15 (d,
J = 8.4 Hz, 2H), 8.39 (s, 1H) NH not seen; 13C NMR (100 MHz,
DMSO-d6) δ 40.2, 115.8, 118.5, 129.4, 133.2, 139.3, 146.6,
156.7, 193.8; ESI mass (m/z) Calcd [C11H8N4OS-H]+244.04,
found 243.1.
2-((4H-1,2,4-Triazol-3-yl)thio)-1-(p-tolyl)ethanone (4i). This
compound was obtained as white solid; yield 84%; high melting;
1H NMR (400 MHz, DMSO-d6) δ 2.37 (s, 3H), 4.76 (s, 2H), 7.33
(d, J= 8.0 Hz, 2H), 7.89 (d, J=8.0Hz, 2H), 8.37 (s, 1H); 13C NMR
(100 MHz, DMSO-d6) δ 21.6, 128.9, 129.7, 133.5, 144.4, 145.0.
Not all carbons are picked up; ESI mass (m/z) Calcd [C11H11N3OS-
H]+233.06, found 232.6.
2-((4H-1,2,4-Triazol-3-yl)thio)-1-(3-chlorophenyl)ethanone
(4j). This compound was obtained as white solid; yield 72%; mp
133–134°C; IR (KBr) 2915, 1677, 1569 cmÀ1; 1H NMR (400 MHz,
DMSO-d6) δ 4.80 (s, 2H), 7.59 (t, J= 7.8Hz, 1H), 7.73–7.76 (m, 1H),
7.96–8.02 (m, 1H), 8.03 (s, 1H), 8.41 (s, 1H), 14.03 (bs, 1H); 13C
NMR (100 MHz, DMSO-d6) δ 40.6, 127.4, 128.4, 131.2, 133.6,
134.1, 137.9, 193.3. Not all the carbons picked up; ESI mass (m/z)
Calcd [C10H8ClN3OS + H]+253.01, found 254.3.
6-(4-Chlorophenyl)thiazolo[3,2-b][1,2,4]triazole (5b). This
compound was obtained as viscous liquid; yield 76%; H NMR
1
(400 MHz, DMSO-d6) δ 7.64 (d, J = 8.4 Hz, 2H), 8.04
(s,
1H), 8.26 (d, J = 8.4 Hz, 2H), 8.44 (s, 1H); 13C NMR
(100 MHz, DMSO-d6) δ 111.9, 126.5, 127.9, 129.0, 130.3,
134.2, 156.2, 156.7; Anal. Calcd for C10H6ClN3S: C, 50.96; H,
2.57; N, 17.83%. Found: C, 51.08; H, 2.34; N, 17.73%; ESI
mass (m/z) Calcd [C10H6ClN3S + H]+235.00, found 236.2.
6-(4-Bromophenyl)thiazolo[3,2-b][1,2,4]triazole (5c). This
compound was obtained as white solid; yield 76%; mp 180–
181°C; IR (KBr) 3063, 1491,1175 cmÀ1 1H NMR (400 MHz,
;
DMSO-d6) δ 7.79 (d, J = 8.5 Hz, 2H), 8.04 (s, 1H), 8.20 (d,
J = 8.6 Hz, 2H), 8.44 (s, 1H); 13C NMR (100 MHz, DMSO-d6) δ
112.4, 123.3, 127.3, 128.5, 130.8, 132.4, 156.6, 156.8; Anal.
Calcd for C10H6BrN3S: C, 42.87; H, 2.16; N, 15.00%. Found:
C, 42.78; H, 2.32; N, 15.38%; ESI mass (m/z) Calcd
[C10H6BrN3S + H]+278.95, found 280.3.
6-(4-Fluorophenyl)thiazolo[3,2-b][1,2,4]triazole (5d). This
1
compound was obtained as viscous liquid; yield 70%; H NMR
(400 MHz, DMSO-d6) δ 7.43 (t, J = 8.6 Hz, 2H), 7.97
(s,
2-((4H-1,2,4-Triazol-3-yl)thio)-1-(3-nitrophenyl)ethanone
(4k). This compound was obtained as yellow solid; yield 76%;
1H), 8.29 (d, J = 8.6 Hz, 2H), 8.45 (s, 1H); 13C NMR
(100 MHz, DMSO-d6) δ 111.4, 116.4, 124.8, 129.2, 131.0,
156.6, 157.2, 161.8; Anal. Calcd for C10H6FN3S: C, 54.78; H,
2.76; N, 19.17%. Found: C, 54.66; H, 2.82; N, 19.18%; ESI
mass (m/z) Calcd [C10H6FN3S + H]+219.03, found 220.2.
6-((4-Trifluoromethyl)phenyl)thiazolo[3,2-b][1,2,4]triazole
(5e). This compound was obtained as viscous liquid; yield 70%;
1H NMR (400 MHz, DMSO-d6) δ 7.96 (d, J= 8.2 Hz, 2H), 8.22
(s, 1H), 8.48 (d, J= 8.2 Hz, 3H), 8.49 (s, 1H); 13C NMR (100 MHz,
DMSO-d6) δ 113.8, 125.3, 125.8, 126.8, 129.5, 130.0, 131.3,
156.2, 156.8; Anal. Calcd for C11H6F3N3S: C, 49.07; H, 2.25; N,
15.61%. Found: C, 49.32; H, 2.18; N, 15.56%; ESI mass (m/z)
Calcd [C11H6F3N3S+H]+269.02, found 270.2.
mp 162–163°C; IR (KBr) 2916, 1696, 1522cmÀ1 1H NMR
;
(400MHz, DMSO-d6) δ 4.85 (s, 2H), 7.86 (t, J = 7.9 Hz, 1H),
8.44–8.53 (m, 3H), 8.70 (s, 1H), 14.05 (bs, 1H); 13C NMR
(100MHz, DMSO-d6) δ 40.6, 123.1, 128.1, 131.0, 135.0, 137.3,
145.2, 148.4, 193.2. Not all carbons picked up; ESI mass (m/z)
Calcd [C10H8N4O3S + H]+264.03, found 265.3.
2-((4H-1,2,4-Triazol-3-yl)thio)-1-(2-chlorophenyl)ethanone
(4l).
This compound was obtained as viscous liquid; yield
70%; 1H NMR (400 MHz, DMSO-d6) δ 4.56 (s, 2H), 7.32–
7.35 (m, 1H), 7.43–7.45 (m, 2H), 7.58 (d, J = 7.6 Hz, 1H), 8.13
(s, 1H) NH not seen; 13C NMR (100 MHz, DMSO-d6) δ 41.8,
126.6, 129.7, 130.1, 130.8, 132.1, 136.8, 196.9. Not all
carbons picked up; ESI mass (m/z) Calcd [C10H8ClN3OS-
H]+253.01, found 252.5.
4′-(Thiazolo[3,2-b][1,2,4]triazol-6-yl)-[1,1′-biphenyl]-4-sulfonic
acid (5g).
This compound was obtained as white solid; yield
1
82%; high melting; IR (KBr) 3183, 1428, 1180 cmÀ1; H NMR
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

Month 2014
6-Aryl-4H-imidazo[1,2-b]/thiazolo[3,2-b][1,2,4]triazoles
(400MHz, DMSO-d6) δ 7.71–7.75 (m, 4H), 7.90 (d, J = 8.3 Hz,
2H), 8.06 (s, 1H), 8.34 (d, J = 8.3 Hz, 2H), 8.47 (s, 1H); 13C NMR
(100MHz, DMSO-d6) δ 111.2, 126.1, 126.2, 126.7, 126.8, 127.1,
131.1, 139.1, 140.5, 147.6, 156.2. Not all carbons picked up;
Anal. Calcd for C16H11N3O3S2: C, 53.77; H, 3.10; N, 11.76%.
Found: C, 53.52; H, 3.38; N, 11.52%; ESI mass (m/z) Calcd
[C16H11N3O3S2 + H]+357.02, found 358.2.
131.8, 132.1, 132.8, 156.1. Not all carbon seen; Anal. Calcd for
C10H6ClN3S: C, 50.96; H, 2.57; N, 17.83%. Found: C, 51.06; H,
2.63;
N,
17.71%;
ESI
mass
(m/z)
Calcd
[C10H6ClN3S + H]+235.00, found 236.3.
4-Methoxy-3-(thiazolo[3,2-b][1,2,4]triazol-6-yl)benzenesulfonic
acid (5m). This compound was obtained as white solid; yield
72%; high melting; 1H NMR (400 MHz, DMSO-d6) δ 3.88
(s, 3H), 7.18 (d, J = 8.6 Hz, 1H), 7.71 (d, J = 8.6 Hz, 1H), 7.84
(s, 1H), 8.37 (s, 1H), 8.45 (s, 1H), the acidic hydrogen is not seen;
13C NMR (100 MHz, DMSO-d6) δ 56.5, 111.5, 114.6, 115.8,
127.2, 128.5, 128.8, 141.1, 156.0, 157.4. Not all carbons seen;
Anal. Calcd for C11H9N3O4S2: C, 42.44; H, 2.91; N, 13.50%.
Found: C, 42.29; H, 3.12; N, 13.49%; ESI mass (m/z) Calcd
[C11H9N3O4S2 + H]+311.00, found 312.1.
4-(Thiazolo[3,2-b][1,2,4]triazol-6-yl)benzamide (5h).
compound was obtained as white solid; yield 81%; mp 227–228°C;
1H NMR (400 MHz, DMSO-d6) δ 7.51 (s, 2H), 8.04
(d,
This
J= 7.9 Hz, 2H), 8.11 (s, 1H), 8.31 (d, J= 7.9 Hz, 2H), 8.46 (s,1H);
13C NMR (100 MHz, DMSO-d6) δ 113.0, 126.3, 128.5, 130.4,
131.2, 135.3, 156.6, 157.3, 167.6; Anal. Calcd for C11H8N4OS: C,
54.09; H, 3.30; N, 22.94%. Found: C, 54.28; H, 3.29; N, 22.84%;
ESI mass (m/z) Calcd [C11H8N4OS + H]+244.04, found 245.2.
2-Methyl-5-(Thiazolo[3,2-b][1,2,4]triazol-6-yl)benzenesulfonic
acid (5i). This compound was obtained as white solid; yield 74%;
Acknowledgments. The authors thank BioGenics, Hubli, for the
antibacterial activity studies and UGC, New Delhi, for the
financial support to S. M.
high melting; IR (KBr) 3335, 2900, 1026 cmÀ1 1H NMR
;
(400 MHz, DMSO-d6) δ 2.60 (s, 3H), 7.34–7.86 (m, 2H), 7.87
(s, 1H), 8.06 (d, J = 7.8 Hz, 1H), 8.44 (s, 1H), 8.52 (s, 1H); 13C
NMR (100 MHz, DMSO-d6) δ 20.1, 110.5, 124.4, 126.4,
131.4, 131.5, 137.5, 146.8, 156.0, 156.6. Not all carbon seen;
Anal. Calcd for C11H9N3O3S2: C, 44.73; H, 3.07; N, 14.23%.
Found: C, 44.56; H, 3.12; N, 14.38%; ESI mass (m/z) Calcd
[C11H9N3O3S2 + H]+295.01, found 296.2.
REFERENCES AND NOTES
[1] Demirbas, A.; Sahin, D.; Demirbas, N.; Karaoglu, S. A. Eur J
Med Chem 2009, 44, 2896.
[2] El-Sherif, H. A. H.; Mahmoud, A. M.; Sarhan, A. A. O.;
Hozien, Z. A.; Habib, O. M. A. J Sulfur Chem 2006, 27, 65.
[3] Berk, B.; Aktay, G.; Yesilada, E.; Ertan, M. Pharmazie 2001,
56, 613.
[4] Pignatello, R.; Mazzone, S.; Panico, A. M.; Mazzone, G.;
Pennisi, G.; Castana, R.; Matera, M.; Blandino, G. Eur J Med Chem
1991, 26, 929.
[5] Lesyk, R.; Vladzimirska, O.; Holota, S.; Zaprutko, L.; Gzella, A.
Eur J Med Chem 2007, 42, 641.
6-(3-Chlorophenyl)thiazolo[3,2-b][1,2,4]triazole (5j).
compound was obtained as white solid; yield 71%; mp 163–164°
C; IR (KBr) 3064, 1468,1170 cmÀ1 1H NMR (400 MHz,
This
;
DMSO-d6) δ 7.58–7.64 (m, 2H), 8.15 (s, 1H), 8.21 (d, J = 6.6 Hz,
1H), 8.37 (s, 1H), 8.47 (s, 1H); 13C NMR (100 MHz, DMSO-d6)
δ 112.8, 124.8, 125.7, 129.4, 129.5, 129.9, 130.9, 133.7, 156.2,
156.8; Anal. Calcd for C10H6ClN3S: C, 50.96; H, 2.57; N, 17.83.
Found: C, 51.03; H, 2.64; N, 17.58%; ESI mass (m/z) Calcd
[C10H6ClN3S + H]+235.00, found 236.3.
[6] Barbuceanu, S. F.; Almajan, G. L.; Sarametm, I.; Draghicim, C.;
Tarcomnicu, A. I.; Bancescu, G. Eur J Med Chem 2009, 44, 4752.
[7] Karthikeyan, M. S. Eur J Med Chem 2009, 44, 827.
[8] Bakali, J. E.; Klupsch, F.; Guedin, A.; Brassart, B.; Fontaine, G.;
Farce, A.; Roussel, P.; Houssin, R.; Bernier, J. L.; Chavatte, P.; Mergny, J.
L.; Riou, J. F.; Henichart, J. P. Bioorg Med Chem Lett 2009, 19, 3434.
[9] Roy, P.; Leblanc, Y.; Ball, R. G.; Brideau, C.; Chan, C. C.;
Chauret, N.; Cromlish, W.; Ethier, D.; Gauthier, J. Y.; Gordon, R.; Grieg, G.;
Guay, J.; Kargman, S.; Lau, C. K.; O’Neill, G.; Silva, J.; Therien, M.;
Van Staden, C.; Wong, E.; Xu, L.; Prasit, P. Bioorg Med Chem Lett
1997, 7, 57.
6-(3-Nitrophenyl)thiazolo[3,2-b][1,2,4]triazole (5k). This
compound was obtained as yellow solid; yield 73%; mp
231–232°C; 1H NMR (400 MHz, DMSO-d6) δ 7.88–8.37 (m,
3H), 8.52 (s, 1H), 8.64 (d, J = 7.8 Hz, 1H), 9.22 (s, 1H); 13C
NMR (100MHz, DMSO-d6) δ 114.5, 121.0, 124.5, 129.5, 129.7,
131.0, 132.8, 148.6, 156.8. Not all carbon seen; Anal. Calcd for
C10H6N4O2S: C, 48.78; H, 2.46; N, 22.75%. Found: C, 48.59; H,
2.63; N, 22.81%; ESI mass (m/z) Calcd [C10H6N4O2S+H]+246.02,
found 247.1.
6-(2-Chlorophenyl)thiazolo[3,2-b][1,2,4]triazole (5l).
This
[10] Krishnaraj, T.; Muthusubramanian, S. Accepted for publica-
tion in J Heterocyclic Chem.
[11] Henichart, J. P.; Houssin, R.; Bernier, J. L. J Heterocyclic
Chem 1986, 23, 1531.
compound was obtained as white solid; yield 70%; mp 139–140°
C; IR (KBr) 3061, 1463,1175 cmÀ1; 1H NMR (400MHz, DMSO-
d6) δ 7.53–7.62 (m, 2H), 7.70–7.80 (m, 3H), 8.34 (s, 1H); 13C
NMR (100MHz, DMSO-d6) δ 115.0, 126.8, 127.5, 128.9, 130.1,
[12] Potts, K. T.; Husain, S. J Org Chem 1971, 36, 10.
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet