Heteropolyacides as green and reusable catalysts for the synthesis of [3,4-b][1,3,4] thiadiazines

Article abstract of DOI:10.4314/bcse.v28i1.8

Synthesis of [3,4-b][1,3,4]thiadiazines from the condensation of 4-amino-6-methyl-3-thioxo-1,2,4-triazine-5(2H)-one (AMTTO) or 4-amino-1,4-dihydro-5-methyle-1,2,4-triazole-5-thione (AMTT) with phenacyl bromide in the presence of a catalytic amount of vari

Full text of DOI:10.4314/bcse.v28i1.8

Bull. Chem. Soc. Ethiop. 2014, 28(1), 67-71.
Printed in Ethiopia
DOI: http://dx.doi.org/10.4314/bcse.v28i1.8
ISSN 1011-3924
 2014 Chemical Society of Ethiopia
HETEROPOLYACIDES AS GREEN AND REUSABLE CATALYSTS FOR THE
SYNTHESIS OF [3,4-b][1,3,4] THIADIAZINES
1
*
2
Fatemeh Hakimi , Alireza Hassanabadi , Masoumeh Tabatabaee and Majid M. Heravi
3
4
1
Department of Chemistry Payame Noor Univercity, P.O. Box 19395-3697, Tehran, Iran
Department of Chemistry, Zahedan Branch, Islamic Azad University, P.O. Box 98135-978,
Zahedan, Iran
2
3
Department of Chemistry, Yazd Branch, Islamic Azad University, P.O. Box 89195-155, Yazd,
Iran
4
Department of Chemistry, School of Sciences, Azzahra University, Tehran, Iran
(Received October 16, 2012; revised September 25, 2013)
ABSTRACT. Synthesis of [3,4-b][1,3,4]thiadiazines from the condensation of 4-amino-6-methyl-3-thioxo-
,2,4-triazine-5(2H)-one (AMTTO) or 4-amino-1,4-dihydro-5-methyle-1,2,4-triazole-5-thione (AMTT) with
1
phenacyl bromide in the presence of a catalytic amount of various heteropolyacids (HPAs) under refluxing
conditions is reported.
KEY WORDS: Heteropolyacids, Phenacyl bromide, Heterocyclization, Thiadiazines
INTRODUCTION
1
,2,4-Triazolo[3,4-b][1,3,4]thiadiazines and 1,2,4-triazino[3,4-b][1,3,4]thiadiazines constitute
two classes of compounds interesting from view points of chemical reactivity [1-4] and
biological activity. Antibacterial [5-7] and anti-inflammatory [8], antivirial [9, 10], antitumor
[
11, 12], and antifungal [13] activity, as well as interesting CNS depressing activity [14] has
been reported for certain of the derivatives. Due to their importance, the synthesis of these
compounds is interested for the discovery of improved protocols towards milder and high
yielding approaches.
It was shown that some heteropolyanions exhibited interesting catalytic properties as green
and eco-friendly catalysts for both redox and/or acid–base type reactions in industrial
applications [15, 16]. Examples of acid–base type catalysis are: cracking and alkylation of
hydrocarbons, dehydration of alcohols, electrophilic addition of alcohols to olefines, etc [17,
1
8]. Heteropolyacids, both solid and in solution, are compared with the strongest mineral acids
exhibiting even strength higher than mineral acids, and are comparable to that to the so-called
superacids [19]. Heteropolyacids (HPAs) are well defined molecular clusters that are remarkable
for their molecular and electronic structural diversity and their significance is quite diverse in
many areas, e.g., catalysis, medicine, and materials science [20, 21]. HPAs are complex proton
acid that incorporate polyoxometalate anions (heteropolyanions) having metal-oxygen octahedra
as the basic structural units and catalysis by them is a field of increasing importance [22-30].
Heteropolyacids as solid acid catalysts are green with respect to corrosiveness, safety, quantity
of waste, and separ ability and it is well known that the use of heteropolyacid catalysts for
organic synthesis reactions can give a lot of benefits. Heteropolyacids are widely used in variety
of acid catalyzed reactions [31-38]. As part of our current studies on the development of new
routes in organic synthesis [39-41], we report an efficient one-pot synthesis of the [1,3,4][3,4-
b]-thiadiazine derivatives, employing readily available starting materials.
_
*
_________
Corresponding author. E-mail: fatemeh.hakimi@yahoo.com

68
Fatemeh Hakimi et al.
EXPERIMENTAL
Materials and instruments
Melting points were determined with an Electrothermal 9100 apparatus. Elemental analysis
were performed using a Costech ECS 4010 CHNS-O analyzer at analytical laboratory of Islamic
Azad University Yazd branch. Mass spectra were recorded on a FINNIGAN-MAT 8430 mass
spectrometer operating at an ionization potential of 70 eV. IR spectra were recorded on a
1
13
Shimadzu IR-470 spectrometer. H and C NMR spectra were recorded on Bruker DRX-500
Avance spectrometer at solution in d -DMSO using TMS as internal standard. The chemicals
6
used in this work were purchased from Fluka (Buchs, Switzerland) and were used without
further purification. Heteroployacids (HPAs) were prepared as previously described in the
literature [41, 42] and also the compounds AMTTO and AMTT was prepared as previously
described in the literature[43-45].
General procedure for preparation of compounds 6
A mixture of AMTTO or AMTT (2 mmol) , Phenacyl bromide (2 mmol) and heteropolyacid
0
.04 g was added to a magnetically stirred solution of sodium( 0.046 g, 2 mmol) in ethanol (30
mL). The reaction mixture was stirred for 45min under refluxing conditions. The resulting
precipitate was collected by filtration on a Buchner funnel and washed with 10 mL of cold
ethanol to afford the pure title compounds 3 or 6.
Catalyst reusability
At the end of the reaction, the catalyst could be recovered by a simple filtration. The recycled
catalyst could be washed with dichloromethane and used in a second run of the reaction process.
The results of the first and subsequent experiments were almost consistent in yields.
The selected spectral data
3
-methyl-6-phenyl-7H-[1,2,4]triazolo[3,4-b][1,3,4]thiadiazin (6).Pale orange crystal, m.p. 195
o
-1
–
N, 24.33%. Found: C, 57.48; H, 4.25; N, 24.41. MS (m/z, %): 230 (5). H NMR (500 MHz, d -
10 4
197 C, IR (KBr) (νmax cm ): 1705, 1560. Analyses: calcd. for C11H N S: C, 57.37; H, 4.38;
1
6
1
3
DMSO): δ 2.49 (3H, s, CH
125.8 MHz, d -DMSO): δ 17.41 (CH
50.19 and 170.41 (7C) ppm.
3
), 4.38 (2H, s, SCH
2
), 7.56-8.02 (5H, m, C
6 5
H ) ppm. C NMR
(
6
3
), 33.09 (SCH
2
), 129.32, 130.84, 132.28, 134.72, 148.42,
1
RESULTS AND DISCUSSION
Herein, we wish to report the condensation of 4-amino-6-methyl-3-thioxo-1,2,4-triazine-5(2H)-
one (AMTTO) or 4-amino-1,4-dihydro-5-methyle-1,2,4-triazole-5-thione (AMTT) with
phenacyl bromide in the presence of sodium ethoxide under refluxing conditions and the use of
Keggin type heteroployacids (HPAs), including H [PW O ], H [SiW O ], K [PMo W O ]
3
12 40
4
12 40
7
2
9
40
3 2 2
and H [PW12O40].6H O-SiO (Scheme 1).
Bull. Chem. Soc. Ethiop. 2014, 28(1)

Heteropolyacides as green and reusable catalysts for synthesis of [3,4-b][1,3,4] thiadiazines 69
Ph
NH2
N
O
S
N
O
Heteropolyacids
+
C H ONa / EtOH , reflux, 45min
S
N
O
Br
+
Ph
_
HN
N
N
CH3
2
5
N
CH3
AMTTO
3
Ph
NH2
N
O
N
N
Heteropolyacids
+
C H O Na / EtOH , reflux, 45min
S
CH3
Br
+
_
S
CH3
Ph
N
N
2 5
H
N
N
6
AMTT
Scheme 1. Condensation of AMTTO or AMTT with phenacyl bromide in the presence of
heteroployacids (HPAs) as catalyst.
The compounds 3 was characterised by NMR, IR spectroscopy and elemental analysis [40].
Compounds 6 was new and its structure was deduced by elemental and spectral analysis. The
1
H-NMR spectrum of compound 6 exhibited one sharp singlet signal readily recognized for
protons of the methyl (δ = 2.49 ppm), and a single signal was observed at 4.38 ppm for
13
methylene group. The aromatic protons resonated between 7.56-8.02 ppm. The C-NMR
spectrum of compound 3 shows nine distinct signals, which is consistent with the proposed
structure. The mass spectrum of 6 displayed the molecular ion peak at m/z = 230. The IR
spectrum of compound 6 also supported the suggested structure.
It is reasonable to assume that compound 6 results from the initial addition of AMTT to
phenacyl bromide to intermediate 4. Heterocycization of 4 can lead to the formation of 6 not 5
1
according to the spectral data, H-NMR, it was identified as the structure 6. By elucidation of
the structure, it can be assumed that HPA catalyzed cyclization of 4 to 6 proceeds via direct
attack of the amino group to C=O phenyl bond activated by proton coordination of HPA, then
with elimination H
2
O can occurred 6 (Scheme 2).
Ph
N
N
O
Ph
HPA
S
CH3
NH2
N
_
NH2
O
N
N
+
Na / EtOH
S
CH3
C H O
2
5
S
N
6
Br
CH3
+
Ph
N
N
Ph
N
N
H
HPA
NH
N
AMTT
4
S
CH3
N
N
5
Scheme 2. Suggested mechanism for formation of compound 3.
In order to determine the optimum quantity of heteropolyacids, the condensation of
AMTTO) or (AMTT) with phenacyl bromide in the presence of sodium ethoxide under
(
Bull. Chem. Soc. Ethiop. 2014, 28(1)

70
Fatemeh Hakimi et al.
refluxing conditions (Table 1), heteropolyacids of 0.04 g gave an excellent yield in 45 min
Table 1, entry 12). To study the scope of the reaction, a series of heteropolyacids were applied.
(
As shown in Table 1, H
yields (Table 1, entry 12).
3 2 2
[PW12O40].6H O-SiO showed the highest activity and gave better
Table 1. Effect of different reaction time and amount of various heteropolyacids on synthesis of [3,4-
b][1,3,4]thiadiazines.
a
Yield (%)
Entry
Catalyst (g)
Time (min)
Product 3
Product 6
60
1
2
3
4
5
6
7
8
9
H
3
H
4
K
7
H
3
H
3
H
4
K
7
H
3
H
3
H
4
K
7
H
3
H
3
H
4
K
7
H
3
[PW12
[SiW12
[PMo
O
40] (0.01)
40] (0.01)
40] (0.01)
40].6H O-SiO
40] (0.02)
40] (0.02)
40] (0.02)
40].6H O-SiO
40] (0.04)
40] (0.04)
40] (0.04)
40].6H O-SiO
40] (0.08)
40] (0.08)
40] (0.08)
40].6H O-SiO
180
180
180
180
120
120
120
120
45
62
60
70
88
70
67
74
84
79
75
80
95
80
76
78
90
O
60
2
W
9
O
72
[PW12
[PW12
O
O
2
2
2
2
2
(0.01)
(0.02)
(0.04)
(0.08)
87
69
[SiW12
[PMo
O
64
2
W
9
O
73
[PW12
[PW12
O
O
2
82
76
1
1
1
1
1
1
1
0
1
2
3
4
5
6
[SiW12
[PMo
O
45
73
2
W
9
O
45
79
[PW12
[PW12
O
O
2
45
93
30
75
[SiW12
[PMo
O
30
74
2
W
9
O
30
76
[PW12
O
2
30
89
a
Isolated yield.
CONCLUSION
In summary, we have shown that heteroployacids (HPAs) as green and reusable catalysts for the
synthesis of [3,4-b][1,3,4]thiadiazines have advantages in condensation reaction of AMTTO or
AMTT with phenacyl bromide such as shorter reaction times, simple work-up, and affords good
yield. The present method does not involve any hazardous organic solvent. Therefore, this
procedure could be classified as green chemistry.
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