Accelerated synthesis of 3,5-disubstituted 4-amino-1,2,4-triazoles under microwave irradiation

Article abstract of DOI:10.1016/S0040-4039(99)02350-3

A number of symmetrically 3,5-disubstituted 4-amino-1,2,4-triazoles are quickly prepared by the reaction of aromatic nitriles on hydrazine dihydrochloride in the presence of an excess of hydrazine hydrate in ethylene glycol under microwave irradiation. (C

Full text of DOI:10.1016/S0040-4039(99)02350-3

TETRAHEDRON
LETTERS
Pergamon
Tetrahedron Letters 41 (2000) 1539–1541
Accelerated synthesis of 3,5-disubstituted 4-amino-1,2,4-triazoles
under microwave irradiation
Fouad Bentiss,a Michel Lagrenée a and Didier Barbry b,∗
aLaboratoire de Cristallochimie et Physicochimie du Solide, CNRS UPRESA 8012, ENSCL, B.P. 108,
F-59652 Villeneuve d’Ascq Cedex, France
bLaboratoire d’Ingénierie Moléculaire, UPRES EA 2699, Université des Sciences et Technologies de Lille,
F-59655 Villeneuve d’Ascq Cedex, France
Received 1 October 1999; accepted 20 December 1999
Abstract
A number of symmetrically 3,5-disubstituted 4-amino-1,2,4-triazoles are quickly prepared by the reaction of
aromatic nitriles on hydrazine dihydrochloride in the presence of an excess of hydrazine hydrate in ethylene glycol
under microwave irradiation. © 2000 Elsevier Science Ltd. All rights reserved.
Keywords: 4-amino-1,2,4-triazoles; microwave irradiation.
4-Amino-1,2,4-triazoles 3 are potentially good corrosion inhibitors.1,2 These compounds can be
prepared by the nucleophilic attack of hydrazine derivatives on nitriles.3–9 The initial product, in each
case, is the 1,2-dihydro-1,2,4,5-tetrazine 2 which rearranges at elevated temperatures or on treatment with
acid to the corresponding 4-amino-1,2,4-triazole 3. One of these methods8 involves the reaction between
2-cyanopyridine 1h and hydrazine hydrate. The reaction product was 3,6-bis(2-pyridyl)-1,2-dihydro-
1,2,4,5-tetrazine 2h. This compound was rearranged by further treatment with hydrochloric acid to 3,5-
bis(2-pyridyl)-4-amino-1,2,4-triazole 3h. Recently, a one-step synthesis of 3,5-disubstituted 4-amino-
1,2,4-triazoles by direct reaction of hydrazine derivatives on nitriles bearing a variety of substituted
aromatic rings or heteroatoromatic has been reported.10
∗
Corresponding author. Fax: (33) 03 20 43 49 74; e-mail: didier.barbry@univ-lille1.fr (D. Barbry)
0040-4039/00/$ - see front matter © 2000 Elsevier Science Ltd. All rights reserved.
PII: S0040-4039(99)02350-3
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Table 1
Data for the synthesis of 3.5-diaryl-4-amino-1,2,4-triazoles 3a–i under microwave irradiation
This method allows the synthesis of the solely symmetrically 3,5-disubstituted 4-amino-1,2,4-
triazoles. We report that this reaction takes place in good yields and rapidly under microwave irradiation
(Table 1). This technique has been applied with success to a number of reactions proceeding with or
without solvent.11,12
Fig. 1. Yield versus time for 3,5-diphenyl-4-amino-triazole at 130°C
The initial product, in each synthesis of aminotriazoles, is the orange-coloured, dihydro-1,2,4,5-
tetrazine 2 which rearranges on treatment under acidic conditions into the corresponding 4-amino-1,2,4-
triazole 3. Addition of hydrazine dihydrochloride or sulfate was used to generate protons which promoted
the rearrangement of 2 into the triazole 3. Without using hydrazine dihydrochloride, the main reaction
product was 2. For example, using the same conditions, a mixture of benzonitrile 1a and hydrazine
hydrate, heated in ethylene glycol, leads to a mixture of 2 and 3 with about 70% of 2 (estimated by
integration of the nitrogen protons in 1H NMR). Compound 2 can be differentiated from 3 by oxidation
of the former to the red-coloured tetrazine. However, a further reliable basis of differentiaton is their 1H

1541
NMR spectra. The nitrogen protons of dihydrotetrazine appeared at a much lower field (δ=9.1 ppm) than
did those of 4-amino-1,2,4-triazoles (δ=6.4 ppm).
Under classical heating in a high boiling polar solvent such as ethylene or diethylene glycol obtention
of compounds 3 in good yield required much longer reaction times (45–60 min) at 130°C depending on
starting compounds 1 of the reaction.10 With microwave irradiation some reactions were complete after
just 4 min (compounds 3a and 3c) and did not exceed 10 min (compound 3d). The rates of formation of
3,5-diphenyl-4-aminotriazole at 130°C with classical heating and under microwave irradiation have been
compared (Fig. 1). Superheating of the solvent under microwave irradiation may lead to the observed
rate enhancement.14
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13. Typical procedure: A mixture of the corresponding aromatic nitrile (0.01 mol), hydrazine dihydrochloride (0.01 mol) and
hydrazine hydrate (0.03 mol) in ethylene glycol (5 ml) was introduced into a quartz cylindrical flask placed in a Synthewave
402 monomode microwave oven under a reflux condenser and irradiated for 4–10 min (60 W) at 130°C. After cooling, the
reaction mixture was diluted with water (10 ml). The precipitate thus obtained was filtered, washed with water, dried and
recrystallized from ethanol. Products were identified by 1H and 13C NMR, MS and IR spectroscopy: data were in agreement
with literature values.
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