Solid acid induced cyclocondensation: A facile, one-pot synthesis of 7H-[1,2,4]triazolo[3,4-b][1,3,4]thiadiazines

Article abstract of DOI:10.1080/10426500214303

7H-[1,2,4]Triazolo[3,4-b][1,3,4]thiadiazines are synthesized in good yields by the catalytic action of sulfuric acid adsorbed on sillica gel. Starting from 4-amino-5-substituted-1,2,4-triazole-3-thiones and employing cyclocondensation reaction with α-chlo

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Phosphorus, Sulfur, and Silicon and the Related
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Solid Acid Induced Cyclocondensation: A Facile,
One-Pot Synthesis of 7H-[1,2,4]triazolo[3,4-b]
[1,3,4]thiadiazines
M. M. Heravi a , M. Bakherad b , M. Rahimzadeh b & M. Bakavoli b
a Department of Chemistry, School of Sciences, Azzahra University, Vanak, Tehran, Iran
b Department of Chemistry, School of Sciences, Ferdowsi University, Mashhad, Iran
Version of record first published: 27 Oct 2010.
To cite this article: M. M. Heravi , M. Bakherad , M. Rahimzadeh & M. Bakavoli (2002): Solid Acid Induced Cyclocondensation:
A Facile, One-Pot Synthesis of 7H-[1,2,4]triazolo[3,4-b][1,3,4]thiadiazines, Phosphorus, Sulfur, and Silicon and the Related
Elements, 177:10, 2403-2407
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Phosphorus, Sulfur and Silicon, 2002, Vol. 177:2403–2407
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Copyright 2002 Taylor & Francis
1042-6507/02 $12.00 + .00
DOI: 10.1080/10426500290110432
SOLID ACID INDUCED CYCLOCONDENSATION:
A FACILE, ONE-POT SYNTHESIS OF
7H-[1,2,4]TRIAZOLO[3,4-b][1,3,4]THIADIAZINES
M. M. Heravi,a M. Bakherad,b M. Rahimzadeh,b
and M. Bakavolib
Department of Chemistry, School of Sciences, Azzahra
University, Vanak, Tehran, Irana and Department of Chemistry,
School of Sciences, Ferdowsi University, Mashhad, Iranb
(Received December 4, 2001; accepted January 29, 2002)
7H-[1,2,4]Triazolo[3,4-b][1,3,4]thiadiazines are synthesized in good
yields by the catalytic action of sulfuric acid adsorbed on sillica
gel. Starting from 4-amino-5-substituted-1,2,4-triazole-3-thiones and
employing cyclocondensation reaction with -chloroacetonitrile and
-haloketones, the desired triazolothiadiazines have been synthesized
satisfactorilly.
Keywords: -Haloketones; cyclocondensation; solid acid; triazolothia-
diazine
INTRODUCTION
7H-[1,2,4]Triazolo[3,4-b][1,3,4]thiadiazines are a class of hetero-
cycles with known antimicrobial1 and analgesic activities.2 The
routes to these fused heterocyclic compounds ideally involve cy-
clocondensation of 4-amino-5-substituted-1,2,4-triazole-3-thiones with
-chloroacetonitrile or -haloketones in neutral or basic media.3 An ex-
amination of the literature disclosed that acid catalyzed cyclocondensa-
tion of these compounds to their corresponding 7H-[1,2,4]triazolo[3,4-
b][1,3,4]thiadiazines have received relatively little attention and only
one article was found that showed the use of an acid catalyst for this
conversion.1
In connection with our work on the use of solid acids as pro-
moters for fine chemical preparations,4 and in the course of our
Address correspondence to M. Bakavoli, Department of Chemistry, School of Sciences,
Ferdowsi University, Mashhad, Iran. E-mail: mbakavoli@sciencel.um.ac.ir
2403

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M. M. Heravi et al.
investigations towards the synthesis of heterocyclic systems via het-
erocyclization reactions,5 we deemed it interesting to study the cyclo-
condensation of 4-amino-5-substituted-1,2,4-triazole-3-thiones 1 with
-chloroacetonitrile and -haloketones in the presence of a solid acid.
We have found that the one-pot cyclocondensation of the triazole 1
with either reagents can be carried out in good yield over sulfuric
acid adsorbed on silica gel to give the desired 7H-[1,2,4,]triazolo[3,4-
b][1,3,4]thiadiazines 2–4.
The catalyst is easily prepared by mixing chromatographic grade
silica (Merck, kieselgel 60,70–230 mesh) with 3% of its weight with
sulfuric acid dissolved in acetone following a reported procedure.6 This
catalyst, a yellow-brown powder, can be stored in a dessicator for a long
period of time without appreciable loss of activity.
The required 4-amino-5-substituted-1,2,4-triazole-3-thiones 1 were
prepared as previously reported.7
These compounds with -chloroacetonitrile and -haloketones un-
derwent cyclocondensation when treated with finely ground sulfuric
acid adsorbed on silica gel in boiling ethanol or isopropanol to yield
7H-[1,2,4]triazolo[3,4-b][1,3,4]thiadiazines 2–4 (Scheme 1).
SCHEME 1
The structure assigned to compounds 2–4 was on the basis of their
analytical and spectral data (Table I) and in the case of known com-
pounds by comparison with authentic samples.

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M. M. Heravi et al.
In summary, the 7H-[1,2,4]triazolo[3,4-b][1,3,4]thiadiazines have
been synthesized by a convenient method using sulfuric acid adsorbed
on silica gel as the catalyst.
EXPERIMENTAL SECTION
M.P.s were determined on a Reichert apparatus and are uncorrected.
IR spectra were recorded on a Schimadzu Spectrometer as KBr disk.
1H NMR spectra were recorded on a Bruker (100 MHZ) instrument.
Mass spectra were obtained from Varian CH-7 at 70 eV. Microanalysis
were performed by Tarbiat Modarres University, Tehran, Iran.
General Procedure for the Preparation of
7H-3-Substituted-6-phenyl-[1,2,4]triazolo-
[3,4-b][1,3,4]thiadiazines 2a--c
A mixture of 1 (1 mmol), phenacyl bromide (1 mmol), and finely ground
sulfuric acid adsorbed on silica gel (0.2 g) in isopropanol (5 ml) was
refluxed for 4 h and filtered. The filtrate was concentrated and the pre-
cipitate recrystallized from ethanol to give white to pale yellow crystals
(data in Table I).
General Procedure for the Preparation of
7H-3-Substituted-6-methyl-[1,2,4]triazolo-
[3,4-b][1,3,4]thiadiazines 3a--b
A mixture of 1 (1 mmol), chloroacetone (1 mmol), and finely ground
sulfuric acid adsorbed on silica gel (0.2 g) in ethanol (5 ml) was refluxed
for 5 h. The catalyst was filtered off and the filtrate was concentrated.
The precipitate was recrystallized from ethanol to give white to pale
yellow crystals (data in Table I).
General Procedure for the Preparation of
7H-3-Substituted-6-amino[1,2,4]triazolo-
[3,4-b][1,3,4]thiadiazines 4a--b
A mixture of 1 (1 mmol), -chloroacetonitrile (2 mmol), and finely
ground sulfuric acid adsorbed on silica gel (0.2 g) was refluxed for 6 h.
After removing the catalyst and concentrating the filtrate, the residue
was recrystallized from ethanol to give white to pale yellow crystals
(data in Table I).

Solid Acid Induced Cyclocondensation
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