Microwave Assisted Synthesis of 6-Aryl-3-substituted-5H-[1,2,4]triazolo[4,3-b][1,2,4]triazoles: A Case for a Comparative Study

Article abstract of DOI:10.1080/10426500214890

A simple and fast synthesis of 6-aryl-3-substituted-5H-[1,2,4]triazolo[4,3-b][1,2,4]triazoles 4 in high yields has been developed by microwave assisted heterocyclization of N-(3-methylthio-5-substituted-4H-1,2,4-triazol-4-yl)benzenecarboximidamides 3. The effectiveness of the microwave irradiation and conventional heating for the formation of compounds 4 has been investigated.

Full text of DOI:10.1080/10426500214890

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Phosphorus, Sulfur, and Silicon and the Related
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Microwave Assisted Synthesis of 6-Aryl-3-
substituted-5H-[1,2,4]-triazolo[4,3-b][1,2,4]triazoles:
A Case for a Comparative Study
M. Rahimizadeh a , A. Davoodnia a , M. M. Heravi b & M. Bakavoli a
a Ferdowsi University of Mashhad, Iran
b Azzahra University, Vanak, Tehran, Iran
Published online: 27 Oct 2010.
To cite this article: M. Rahimizadeh , A. Davoodnia , M. M. Heravi & M. Bakavoli (2002) Microwave Assisted Synthesis of 6-
Aryl-3-substituted-5H-[1,2,4]-triazolo[4,3-b][1,2,4]triazoles: A Case for a Comparative Study, Phosphorus, Sulfur, and Silicon
and the Related Elements, 177:12, 2923-2929, DOI: 10.1080/10426500214890
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Phosphorus, Sulfur and Silicon, 2002, Vol. 177:2923–2929
C
Copyright 2002 Taylor & Francis
1042-6507/02 $12.00 + .00
DOI: 10.1080/10426500290146974
MICROWAVE ASSISTED SYNTHESIS OF
6-ARYL-3-SUBSTITUTED-5H-[1,2,4]-
TRIAZOLO[4,3-b][1,2,4]TRIAZOLES: A CASE
FOR A COMPARATIVE STUDY
M. Rahimizadeh,a A. Davoodnia,a M. M. Heravi,b
and M. Bakavolia
Ferdowsi University of Mashhad, Irana and Azzahra University,
Vanak, Tehran, Iranb
(Received May 10, 2002; accepted July 14, 2002)
A
simple and fast synthesis of 6-aryl-3-substituted-5H-[1,2,4]-
triazolo[4,3-b][1,2,4]triazoles 4 in high yields has been developed by
microwave assisted heterocyclization of N-(3-methylthio-5-substituted-
4H-1,2,4-triazol-4-yl)benzenecarboximidamides 3. The effectiveness of
the microwave irradiation and conventional heating for the formation
of compounds 4 has been investigated.
Keywords: 1,2,4-Triazolo[4,3-b][1,2,4]triazoles; conventional heating;
heterocyclization; methyl iodide; microwave irradiation; photographic
coupler
1,2,4-Triazolo[4,3-b][1,2,4]triazoles are very interesting compounds
with diverse properties. These compounds have been considered as
4
antifungal1 and photographic couplers.2 The routes to 1,2,4-triazolo-
[4,3-b][1,2,4]triazoles mainly involve heterocyclization of suitably
substituted-1,2,4-triazoles with appropriate reagents such as acid
chlorides, hydroximoyl chloride, halonitriles, isocyanates, carbon
disulfide, and diarylcarbodiimides in suitable solvents (see for example
references5–10). A literature survey disclosed that aryl nitriles have
been relatively little explored for the synthesis of 1,2,4-triazolo[4,3-
b][1,2,4]triazoles and there are only two references cited in the
literature dealing with this matter.11,12 Thus, it seemed of interest to ex-
amine the reaction of aryl nitriles with substituted 1,2,4-triazoles as a
Address correspondence to M. Bakavoli, Department of Chemistry, School of
Sciences, Ferdowsi University of Mashhad, Mashhad, 91779, Iran. E-mail: mbakavoli@
science1.um.ac.ir or mbakavoli@yahoo.com
2923

2924
M. Rahimizadeh et al.
convenient procedure for the synthesis of some 1,2,4-triazolo[4,3-
b][1,2,4]triazoles 4. In the present work we have investigated the
reaction of aryl halides with N-(3-methylthio-5-substituted-4H-1,2,4-
triazol-4-yl)benzenecarboximidamides 3 for the synthesis of some
6-aryl-3-substituted-5H-1,2,4-triazolo[4,3-b][1,2,4]triazoles
microwave irradiation.
4
using
Microwave irradiation is a nonconventional energy source whose
popularity and synthetic utility in organic chemistry has increased
16
considerably in recent years.13
The rapid heating induced by such
radiation avoids harsh classical conditions and the decomposition of
the reagents, leading to the formation of products under mild reaction
conditions, thus increasing the yield.
RESULTS AND DISCUSSIONS
Treatment of 4-amino-5-substituted-4H-[1,2,4]triazole-3-thiones
1
with aromatic nitriles in the presence of potassium t-butoxide in
t-butanol under reflux gave products identified as N-(3-substituted-
5-thioxo-1,5-dihydro-4H-1,2,4-triazol-4yl)benzenecarboximidamide
2
(Scheme 1 and Table I). Furthermore, methylation of compounds 2 with
methyl iodide in the presence of sodium hydroxide at room temperature
SCHEME 1

2925

2926

Microwave Assisted Synthesis of 6-Aryl-3-substituted
2927
TABLE II Fast Heterocyclisation Reaction of N-(3-methylthio-
5-substituted-4H-[1,2,4]triazol-4-yl)benzenecarboximidamides
(3a–e) under Microwave Irradiation
Products
R
Ar
Yield (%)
m.p.
C
Lit17
4a
4b
4c
4d
4e
CH3
CH3
CH3
CH3
H
C6H5
72
77
58
68
56
227–229
260–262
276–278
237–239
215–216
226–228
263–264
—
238–240
216–218
4-Cl-C6H4
4-Br-C6H4
4-Me-C6H4
C6H5
afforded the corresponding N-(3-methylthio-5-substituted-4H-1,2,4-
triazol-4-yl)benzenecarboximidamide 3. The structures of the products
were deduced from their spectra and elemental analysis (Table I). For
example, the 1H NMR spectrum of 3a in d6-DMSO shows two singlets
at 2.17 ppm (3H, Me) and 2.52 ppm (3H, SMe) and a multiplet at
7.30–8.0 ppm (7H, Ph, and NH2). The IR spectrum of this compound
1
shows two bands in the region 3350–3200 cm due to the NH2 group.
The spectral data for compounds 3 are given in Table I.
When compounds 3 in a little amount of N,N-dimethylacetamide
were subjected to microwave irradiation for the indicated time
(Table III), the cyclic products 4 were obtained (Table II). The structure
of the new product 4c was established from its analytical and spectral
data and for known compounds 4a, b, d, and e by comparison with
authentic samples.
It is noteworthy that reaction times required are longer in the ab-
sence of microwave irradiation. We investigated the effectiveness of
the microwave irradiation and conventional heating for the formation
of compounds 4a–e. The results are summarized in Table III. It can
be concluded that the synthesis of compounds 4a–e under microwave
irradiation were 36–72 times faster and the yields are higher than con-
ventional heating methods. This ratio between the reaction time using
TABLE III Comparison of Time and Yields on the Formation of
Compounds 4a–e Using Microwave and Conventional Heating
Conventional heating
Microwave heating
Product
t/min ( C)
Yield (%)
Power/W
t/min
Yield (%)
tc/tmw
4a
4b
4c
4d
4e
360(120)
360(110)
360(130)
360(120)
360(130)
21
25
19
23
14
700
700
1000
700
7
5
10
10
10
72
77
58
68
56
51
72
36
36
36
1000

2928
M. Rahimizadeh et al.
conventional heating and microwave irradiation (tc/tmw) shows the mi-
crowave heating effect.
In conclusion, we have developed a simple, efficient and fast practical
method for one-pot conversion of N-(3-methylthio-5-substituted-4H-
1,2,4-triazol-4-yl)benzencarboximidamides into 6-aryl-3-substituted-
5H-1,2,4-triazolo[4,3-b][1,2,4]triazoles by applying microwave irradia-
tion in solvent free conditions.
EXPERIMENTAL
Melting points were recorded on an Electrothermal type 9100 melting
point apparatus. The IR spectra were obtained on a 4300 Shimadzu
Spectrometer. The 1H NMR (100 MHz) spectra were recorded on a
Bruker AC 100 Spectrometer. Mass spectra were obtained from Varian
CH-7 instrument at 70 eV. Elemental analyses were performed by Tar-
biat Modarres University, Tehran, Iran.
Compounds 4a, b, d, e were known compounds and their physical
data, IR, and NMR spectra were essentially identical with those of au-
thentic samples.
N-(3-Substituted-5-thioxo-1,5-dihydro-4H-1,2,4-triazol-
4-yl)benzenecarboximidamide 2a--e
Typical Procedure
A mixture of 4-amino-3-methyl-4H-[1,2,4]triazole-5-thione 1 (1.30 g,
0.01 mol), benzonitrile (1.23 g, 0.012 mol) and Potassium t-butoxide
(2.24 g, 0.02 mol) in t-butanol (60 ml) was heated under reflux for
6 h. After the completion of the reaction, the precipitate was filtered
off dissolved in water, and subsequently neutralized by 1N HCl. The
crude product was collected and recrystallized from ethanol to give com-
pounds 2a in high yield (see Table I).
N-(3-Methylthio-5-substituted-4H-[1,2,4]triazol-4-yl)-
benzenecarboximidamides 3a--e
Typical Procedure
To a stirred solution of the foregoing compound 2a (1.17 g, 0.005 mol)
in sodium hydroxide (0.28 g, 0.007 mol) and water (30 ml), methyl io-
dide (0.71 g, 0.005 mol) was gradually added. The stirring was continued
for 0.5 h at room temperature. The crude product was filtered and re-
crystallized from acetonitrile to give compound 3a in good yield (see
Table I).

Microwave Assisted Synthesis of 6-Aryl-3-substituted
2929
6-Aryl-3-substituted-5H-1,2,4-triazolo[4,3-b][1,2,4]-
triazoles 4a--e
Typical Procedure
The foregoing compound 3a (0.49 g, 0.002 mol) in a little amount of
N,N-dimethylacetamide were subjected to microwave irradiation for 7
min. The crude product was recrystallized from benzene-ethanol to give
compound 4a in good yield (see Table III).
4c,6-(4-bromo-phenyl)-3-methyl-5H-[1,2,4]triazolo[4,3-b][1,2,4]tria-
zole, Anal. Calcd for C10H8BrN5:C, 43.19; H, 2.90; N, 25.18, Found:
1
C, 43.08; H, 2.98; N, 25.09. H NMR: (d6-DMSO), 2.56 (s, 3H, Me),
7.6–8.2 (m, 4H, p-Br-C6H4), 13.4 (broad, 1H, NH); IR (KBr disc):
,
3060, 2920, 1630 cm 1; MS: m/z, M+ 278.
REFERENCES
[1] M. T. M. El-Wassimy, M. Abdel-Rahman, A. B. A. G. Ghattas, and O. A. A. Abd Allah,
Phosphorous, Sulfur, Silicon Relat. Elem., 70(1–2), 99 (1992).
[2] D. Chapman, U.S. 3,598,602 (Cl. 96-109; C 07d, G 03C), 10 Aug 1971, Appl. 07 Oct
1969; C. A. 76: P106442e.
[3] F. Ishii, Jpn. Kokai Tokkyo Koho JP 07,120,896 [95,120,896] (Cl. G03C7/38), 12 May
1995; C. A. 123; P213018 g.
[4] H. Fukunaga, N. Furutachi, and G. Furusawa, Eur. Pat. Appl. EP342, 637 (Cl.
G03C7/38), 23 Nov 1989, JP Appl. 88/118,075, 17 May 1988; 125PP. C. A. 113:
P68234 m.
[5] T. A. F. O’Mahony, R. N. Butler, and F. L. Scott, J. Chem. Soc., Perkin Trans. 2, 10,
1319 (1972).
[6] C. Parkanyi, Abdou O. Abdelhamid, and J. C. S. Cheng, J. Heterocyclic Chem., 21,
1029 (1984).
[7] K. T. Potts and C. Hirsch, J. Org. Chem., 1, 143 (1968).
[8] P. Molina, A. Lorenzo, R. Ma Claramunt, and J. Elguero, Tetrahedron Lett., 25, 5427
(1984).
[9] P. Molina, M. Alajarin, A. Ferao, and M. J. Perez de Vega, J. Chem. Soc., Perkin
Trans. 1, 12, 2667 (1987).
[10] P. Molina, M. Alajarin, A. Ferao, A. Lorenzo, and M. J. Vilaplana, Heterocycles, 27,
161 (1988).
[11] P. Molina, M. Alajarin, and M. J. Perez de Vega, Heterocycles, 23, 2613 (1985).
[12] P. Molina, M. Alajarin, and M. J. Vilaplana, Synthesis, 415 (1983).
[13] S. Caddick, Tetrahedron, 52, 1403 (1995).
[14] C. R. Strauss and R. W. Trainor, Aust. J. Chem., 48, 1665 (1995).
[15] F. Langa, P. de la Cruz, A. de la hoz, A. Diaz-Ortiz, and E. Diez-Barra, Contemp.
Org. Synth., 4, 373 (1997).
[16] D. M. P. Mingos and A. G. Whittaker, Microwave Dielectric Heating Effects in Chem-
ical Synthesis under Extreme or non-Classical Conditions, edited by R. Van Eldik
and C. P. Hubbard (John Wiley and Sons, New York, 1997).
[17] H. H. Takimoto, G. C. Denault, and S. Hotta, J. Heterocyclic Chem., 3, 119 (1966).