Solid phase synthesis of 1,2,4-triazoles under microwave irradiation

Article abstract of DOI:10.1081/SCC-120015566

1,2,4-Triazoles (3a-g) have been prepared from three component condensation reaction of acid hydrazide (1), S-methyl isothioamide hydroiodide (2), and ammonium acetate on the surface of silica gel under microwave irradiation.

Full text of DOI:10.1081/SCC-120015566

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Solid Phase Synthesis of 1,2,4-Triazoles Under
Microwave Irradiation
Shahnaz Rostamizadeh a c , Hasan Tajik b & Soheila Yazdanfarahi b
a Department of Chemistry , K. N. Toosi University of Technology , Tehran, Iran
b Department of Chemistry , Guilan University , Kashi, Guilan, Iran
c Department of Chemistry , K. N. Toosi University of Technology , P.O. Box 15875-4416,
Tehran, Iran
Published online: 20 Aug 2006.
To cite this article: Shahnaz Rostamizadeh , Hasan Tajik & Soheila Yazdanfarahi (2003) Solid Phase Synthesis of 1,2,4-Triazoles
Under Microwave Irradiation, Synthetic Communications: An International Journal for Rapid Communication of Synthetic
Organic Chemistry, 33:1, 113-117, DOI: 10.1081/SCC-120015566
To link to this article: http://dx.doi.org/10.1081/SCC-120015566
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SYNTHETIC COMMUNICATIONSÕ
Vol. 33, No. 1, pp. 113–117, 2003
Solid Phase Synthesis of 1,2,4-Triazoles
Under Microwave Irradiation
;1
Shahnaz Rostamizadeh, Hasan Tajik,2 and Soheila Yazdanfarahi2
*
1Department of Chemistry, K. N. Toosi University
of Technology, Tehran, Iran
2Department of Chemistry, Guilan University, Kashi, Guilan, Iran
ABSTRACT
1,2,4-Triazoles (3a–g) have been prepared from three component
condensation reaction of acid hydrazide (1), S-methyl isothioamide
hydroiodide (2), and ammonium acetate on the surface of silica gel
under microwave irradiation.
Key Words: Microwave; Solid phase; 1,2,4-triazoles.
*Correspondence: Shahnaz Rostamizadeh, Department of Chemistry, K. N.
Toosi University of Technology, P.O. Box 15875-4416 Tehran, Iran. E-mail:
rostamizadeh@hotmail.com.
113
DOI: 10.1081/SCC-120015566
Copyright & 2003 by Marcel Dekker, Inc.
0039-7911 (Print); 1532-2432 (Online)
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114
Rostamizadeh, Tajik, and Yazdanfarahi
Scheme 1.
Recently, much attention has been focused on the synthesis of 1,2,4-
triazoles because of their wide spectrum of biological properties.[1] They
can be used as antifungal,[2] antibacterial,[3] antiinflammatory,[4,5] tuber-
culo-therapeutic,[6,7] and antiasthmatic[8] activities. These compounds
[1,5,9,10]
have beenprepared by different methods.
Inrecent years the use of solid acidic catalysts,
[11]
such as clays,
zeolites, alumina, and silica gel have received considerable attention
in different areas of organic synthesis because of their environmental
compatibility, reusability, high selectivity, operational simplicity, low
cost, and ease of isolation of the products.
In continuation of our interest in the use of solid supports as non-
conventional reaction medium together with the method of rapidly heat-
ing by microwave oven,[12] hereinwe report a highly efficient procedure
for the synthesis of 1,2,4-triazoles. In this method three- component
condensation reaction of acid hydrazides (1), S-methyl isothioamide
hydroiodides (2), and ammonium acetate on the surface of silica gel
under microwave irradiation gave the corresponding 3,5-disubstituted-
1,2,4-triazoles (Sch. 1).
High yield, short reactiontime, pure products, and easy work up are
advantages of this procedure in comparison to other methods. The data
for the synthesis of 1,2,4-triazoles are shown in Table 1.
EXPERIMENTAL
Melting points were taken on an Electrothermal 9100 apparatus. IR
spectra were recorded with a Shimadzu IR-480 spectrometer (KBr). The
1H NMR spectra were determined in chloroform-d ona FT-NMR
Bruker AC-80 (80 MHz). Microwave irradiationwas carried out using
commercial microwave ovenMoulienx (2735 A). Merck silica gel
60GF254 was used for analytical and preparative TLC and for the

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1,2,4-Triazoles
115
Table 1. Cyclizationof acid hydrazides with S-methyl isothioamide hydroiodides.
Product
R1
C6H5
4-Me-C6H4
4-MeO-C6H4
Me
C6H5
4-NO2-C6H4
C6H5
R2
C6H5
C6H5
C6H5
C6H5
Me
Yield (%)
Time (min)
3a
3b
3c
3d
3e
3f
91
79
85
66
68
77
83
2
6
10
8
8
6
C6H5
4-Cl-C6H4
3g
8
solid phase microwave irradiations. Acid hydrazides were prepared
according to the literature method.[13,14]
General Procedure for Synthesis of
3,5-Di-substituted 1,2,4-Triazoles
A mixture of benzoic acid hydrazide (2 mmol), S-methyl isothioben-
zamide hydroiodide (2 mmol), and silica gel (1.2 g) was well ground with
a pestle and introduced to microwave irradiation at 900 W in an open
pyrex beaker for appropriate time (Table 1).
After complete conversion as indicated by TLC, the mixture was
extracted with dichloromethane (3 Â 30 mL) and washed with water
(3 Â 50 mL). The solvent was then evaporated in vacuo and the product
was purified by recrystallizationfrom appropriate solvetn to give
compounds (3a–f ).
3,5-Diphenyl-1,2,4-triazole (3a): Obtained from benzoic acid hydra-
zide and S-methyl isothiobenzamide hydroiodide; m.p. 189–191ꢀC (lit.[15]
190–192ꢀC); yield 91%; recrystallized from ether and light petroleum;
1H NMR (CDCl3): ꢀ 7.3–7.4 (m, 6H, Ar-H), 7.8–7.9 (m, 4H, Ar-H), 8.6
(s, 1H, NH) (D2O-labile).
3-(4-Methylphenyl)-5-phenyl-1H-1,2,4-triazole (3b): Obtained from
4-methyl benzoic acid hydrazide and S-methyl isothiobenzamide hydro-
iodide; m.p. 156–158ꢀC; yield 79%; recrystallized from ether and light
petroleum; 1H NMR (CDCl3): ꢀ 2.3 (s, 3H, CH3), 7.2 (m, 3H, Ar-H), 7.4
(m, 2H, Ar-H), 8.1 (m, 2H, Ar-H), 8.2 (m, 2H, Ar-H), 8.3 (s, 1H, NH)
(D2O-labile). Anal: calcd. for C15H13N3: C, 69.52; H, 5.87; N, 15.54;
found: C, 69.55; H, 5.88; N, 15.49%.

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Rostamizadeh, Tajik, and Yazdanfarahi
3-(4-Methoxyphenyl)-5-phenyl-1H-1,2,4-triazole (3c): Obtained from
4-methoxy benzoic acid hydrazide and S-methyl isothiobenzamide hydro-
iodide; m.p. 206–209ꢀC; yield 85%; recrystallized from ether and light
petroleum; 1H NMR (CDCl3): ꢀ 4 (s, 3H, O-Me), 7.5–7.7 (m, 5H,
Ar-H), 7.8–7.9 (4H, Ar-H), 8.1 (s, 1H, NH) (D2O-labile); Anal: calcd.
for C15H13N3O: C, 58.46; H, 5.18; N, 8.97; found: C, 58.39; H, 5.19; N,
8.99.
3-Methyl-5-phenyl-1H-1,2,4-triazole (3d): Obtained from acetic acid
hydrazide and S-methyl isothiobenzamide hydroiodide; m.p. 162–164ꢀC
(lit.[15] 163–164ꢀC); yield 66%; recrystallized from ethanol. 1H NMR
(CDCl3): ꢀ 2.6 (s, 3H, CH3-H), 7.5 (m, 3H, Ar-H), 8.0 (m, 2H, Ar-H),
8.1 (s, 1H, NH); (D2O-labile).
3-Phenyl-5-methyl-1H-1,2,4-triazole (3e): Obtained from benzoic acid
hydrazide and S-methyl isothiobenzamide hydroiodide; m.p. 161–163ꢀC
(lit.[15] 163–164ꢀC); yield 68%; recrystallized from ethanol. 1H NMR
(CDCl3): ꢀ 2.6 (s, 3H, CH3-H), 7.5 (m, 3H, Ar-H), 8.0 (m, 2H, Ar-H),
8.1 (s, 1H, NH); (D2O-labile).
3-(4-Nitrophenyl)-5-phenyl-1H-1,2,4-triazole (3f): Obtained from
4-nitro benzoic acid hydrazide and S-methyl isothiobenzamide hydroio-
dide; m.p. 231–234ꢀC (Lit.[15] 234–236); yield 77%; recrystallized from
1
ether and light petroleum. H NMR (CDCl3): ꢀ 7.4–7.5 (m, 3H, Ar-H),
7.3 (m, 2H, Ar-H), 7.8–7.9 (m, 2H, Ar-H), 8–8.9 (m, 2H, Ar-H), 8.6 (1H,
NH) (D2O-labile).
3-Phenyl-5-(4-chlorophenyl)-1H-1,2,4-triazole (3f): Obtained from
benzoic acid hydrazide and S-methyl isothio-4-chloro benzamide hydro-
iodide; m.p. 213–216ꢀC (Lit.[15] 212–214ꢀC); yield 77%; recrystallized
1
from ether and light petroleum. H NMR (CDCl3): ꢀ 7.3–7.4 (m, 3H,
Ar-H), 7.5 (m, 2H, Ar-H), 7.7 (m, 2H, Ar-H), 7.8 (m, 2H, Ar-H), 8.6
(1H, NH) (D2O-labile).
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Received inJapanSeptember 11, 2001

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