Regioselective synthesis of 2-substituted [1,2,4]Triazolo[5,1-b][1,3] thiazin-7-ones by heteropolyacids

Article abstract of DOI:10.1080/10426500903213548

2-Substituted [1,2,4]triazolo[5,1-b][1,3]thiazin-7-ones 3 were synthesized via regioselective cyclization of 4H-[1,2,4]triazol-3-ylsulfanyl-acrylic acids 2 in the presence of catalytic amounts of heteropolyacids at room temperature in very good yields and

Full text of DOI:10.1080/10426500903213548

Phosphorus, Sulfur, and Silicon, 185:1672–1675, 2010
Copyright ꢀC Taylor & Francis Group, LLC
ISSN: 1042-6507 print / 1563-5325 online
DOI: 10.1080/10426500903213548
REGIOSELECTIVE SYNTHESIS OF 2-SUBSTITUTED
[1,2,4]TRIAZOLO[5,1-b][1,3]THIAZIN-7-ONES
BY HETEROPOLYACIDS
Radineh Motamedi,1 Majid M. Heravi,2 Zahra Nazari,1
and Fatemeh F. Bamoharram3
1Department of Chemistry, School of Sciences, Payam Noor University,
Tehran, Iran
2Department of Chemistry, School of Sciences, Azzahra University,
Vanak, Tehran, Iran
3Department of Chemistry, Islamic Azad University, Mashhad Branch,
Mashhad, Iran
2-Substituted [1,2,4]triazolo[5,1-b][1,3]thiazin-7-ones 3 were synthesized via regioselective
cyclization of 4H-[1,2,4]triazol-3-ylsulfanyl-acrylic acids 2 in the presence of catalytic
amounts of heteropolyacids at room temperature in very good yields and rates.
Keywords Heteropolyacids; regioselective cyclization; [1,2,4]triazolo[5,1-b][1,3]thiazin
INTRODUCTION
[1,3]Thiazine-ones are important heterocyclic systems that are used in biologically
active compounds.1,2 A series of 2-substituted [1,2,4]triazolo[5,1-b][1,3]thiazin-7-ones 3
was synthesized by Peter et al. by cyclization of 1,2,4-triazol-3-thiols 1 with diethylethoxy-
methylene malonate in good yields.3 This heterocyclic system has also been afforded by
condensation of mercapto-1,2,4-triazole-4-amines 5 with methyl propionates and hydroly-
sis of the resulting S-acrylic esters to the corresponding S-acrylic acids 2 and subsequent
cyclization to 3 or 4.4 Cyclization of 2 to 3 or 4 using thionyl chloride has also been reported
as an independent synthesis.4 The regioselective cyclization of 2 to 3 in the presence of
conc. H2SO4 in good to high yield was reported by Heravi et al.5
The identification and use of better and milder conditions for the synthesis of these
heterocyclic systems using new catalysts have been the focus of recent attention. In this
context, the use of heteropolyacids (HPAs), which are low in toxicity, highly stable toward
humidity, recyclable, and air-stable, have attracted increasing attention.6 The use of HPAs
as green catalysts not only gave good yields in shorter reaction times at room temperature,
but also provided a procedure that did not use corrosive reagents or solvents. HPAs have
been used as industrial catalysts for several liquid-phase reactions7–10 such as alcohol
Received 5 March 2009; accepted 27 July 2009.
Address correspondence to Radineh Motamedi, Department of Chemistry, School of Sciences, Payam Noor
University, Tehran, Iran. E-mail: r motamedi@pnu.ac.ir
1672

REGIOSELECTIVE SYNTHESIS WITH HETEROPOLYACIDS
1673
dehydration,11 alkylation,12 and esterification.13 Therefore, in continuing our work using
HPA14–17 to synthesize heterocyclic systems, we investigated the use of this catalyst for the
synthesis of some triazolothiazines. Here we report a rapid and ecologically safe method
for the synthesis of triazolothiazines 3.
RESULTS AND DISCUSSION
First, triazoles 1a–c were prepared by a known reported method.18 Condensation
of equimolar quantities of triazoles 1a–c and propiolic acid in a Michael-type addition
afforded adducts identified as the S-substituted acrylic acids 2 in good yields (70–80%)
(Scheme 1). Physical and spectroscopic data of these compounds confirmed the formation
of adducts 2.5
Scheme 1
Regioselective cyclization of propynylmercapto heterocyclic compounds to con-
densed thiazoles 3 occurred in the presence of conc. H2SO4 after 2 h at 50◦C in 68–80%
yield.5 Fusion of triazole and triazine moieties can occur in two different ways, as rep-
resented by 3 and 4. The structures of 3 and 4 can be distinguished by differences in
chemical shift of the substituent (R group) on C-5 of the triazolo ring. The carbonyl group
in structure 4 is in the peri position to these substitutes; in the case of a methyl group at
this position, a considerable anisotropic effect would be expected.4 The 1H NMR spectrum
of 3b showed the ring signal at δ = 2.75 ppm, indicating almost no downfield shift.5 In
accordance to the cyclization product structure 3b, 3a and 3c are assigned to the cyclization
products of 2a and 2c. In a recent publication, we demonstrated the utility of HPAs (Keggin,
K3PW12O40, H3PMo12O40, K7PWMo11O39; Wells–Dawson, H6P2W18O62, H6P2Mo18O62;
Preyssler, H14[NaP5W29MoO110]) for regioselective cyclization of 2 to 3. Thus, compounds
2 were treated with catalytic amounts of HPAs in acetic acid as solvent at room temperature.
The yields and reaction times are reported in Table I.
Comparison of physical and spectroscopic data for the products confirmed the struc-
ture of 3.5 As shown in Table I, the rate was four to 12 times faster in the presence of HPAs
compared to the use of H2SO4.
Generally, the results demonstrate that a Preyssler HPA is the most efficient catalyst
for these reactions owing to a higher number of acidic protons. It seems that the presence
of molybdenum ions in mixed HPAs enhances the yield and cyclization rate. Accordingly,

1674
R. MOTAMEDI ET AL.
Table I Catalytic synthesis of 2-substituted [1,2,4]triazolo[5,1-b][1,3]thiazin-7-ones by heteropolyacids
Compd.
3A
3B
3C
R
H
Me
195–196
196–1973
Ph
264–265
264–2653
Mp (◦C)
232–233
230–2323
Lit.
Yield (%) and time using H14[NaP5W29MoO110
Yield (%) and time using H3PMo12O40
Yield (%) and time using K3PW12O40
Yield (%) and time using K7PWMo11O39
Yield (%) and time using H6P2Mo18O62
Yield (%) and time using H6P2W18O62
]
78%; 15 min
75%; 20 min
74%; 35 min
70%; 25 min
68%; 20 min
68%; 35 min
88%; 10 min
82%; 15 min
82%; 25 min
82%; 20 min
85%; 15 min
85%; 25 min
90%; 10 min
85%; 15 min
80%; 30 min
85%; 20 min
85%; 15 min
85%; 20 min
K7PWMo11O39 and H6P2Mo18O62 were more reactive than K3PW12O40 and H6P2W18O62,
which is in good agreement with the more oxidative effect reported for Mo compounds
compared to W.12
The catalyst is not soluble in acetic acid, which allows for easy separation and
recovery by filtration for immediate reuse. No significant decrease in catalyst reactivity
was observed after three uses.
In this article, we have developed a method using an ecofriendly and reusable hetero-
geneous inorganic catalyst for regioselective synthesis of 2-substituted [1,2,4]triazolo[5,1-
b][1,3]thiazin-7-ones. The reasonable reaction times, good yields, simple workup proce-
dure, and environmentally friendly conditions are the main advantages of this method.
EXPERIMENTAL
Most chemicals were purchased from Merck Chemical Company (Darmstadt, Ger-
many) and Fluka (Buchs, Switzerland). 1,2,4-Triazol-3-thiols 1 were prepared using a
previously published method.14–18
Preparation of 5-Substituted-3-(4H-[1,2,4]triazol-3-ylsulfanyl)-acrylic
Acids (2a–c): General Procedure
A solution of 1,2,4-triazol-3-thiol 1 (0.01 mol) and propiolic acid (0.01 mol) in
methanol (30 mL) was refluxed for 5 h. The solvent was evaporated to dryness under
reduced pressure, and the crude product was crystallized from H2O to afford 2a–c in
78–85% yield. The products are known compounds and were identified by their spectral
and physical data.5
Preparation of 2-Substituted [1,2,4]Triazolo[5,1-b][1,3]thiazin-7-ones
(3a–c): General Procedure
A mixture of 2 (0.9 mmol) and the appropriate heteropolyacid (0.04 mmol) in acetic
acid (20 mL) was stirred for the indicated time (Table I) at room temperature. Reaction
progress was monitored by TLC. After completion of the reaction, the catalyst was removed
by filtration and washed with acetic acid (the catalyst is not soluble in acetic acid) and then
diethyl ether. It could be reused and subjected to a second run of reaction; the yield of
product was almost identical to yield obtained by using fresh catalyst. The solvent was

REGIOSELECTIVE SYNTHESIS WITH HETEROPOLYACIDS
1675
evaporated to dryness under reduced pressure, and the crude product was crystallized from
H2O to afford 3a–c (Table I). The products are known compounds and were identified by
comparison of spectral and physical data.5
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