ORGANIC SYNTHESIS AND INDUSTRIAL
Russian Journal of Applied Chemistry, 2011, Vol. 84, No. 11, pp. 1890−1896.
Pleiades Publishing, Ltd., 2011.
Original Russian Text © V.M. Chernyshev, E.V. Tarasova, A.V. Chernysheva, V.A. Taranushich, 2011, published in Zhurnal Prikladnoi Khimii, 2011, Vol. 84,
No. 11, pp. 1804−1810.
Synthesis of 3-Pyridyl-substituted 5-Amino-1,2,4-triazoles
from Aminoguanidine and Pyridinecarboxylic Acids
V. M. Chernyshev, E. V. Tarasova, A. V. Chernysheva, and V. A. Taranushich
South-Russian State Technical University (Novocherkassk Polytechnic Institute),
Novocherkassk, Rostov-on-Don oblast, Russia
Received April 28, 2011
Abstract—Effect of the molar ratio between reagents, temperature, and synthesis duration on the yield of 3-pyridyl-
substituted 5-amino-1,2,4-triazoles in the reaction of aminoguanidine hydrochloride with pyridinecarboxylic
acids under acid catalysis conditions was studied. A single-reactor method for synthesis of 3-pyridyl-substituted
5-amino-1,2,4-triazoles and their hydrochlorides was developed.
3-Pyridyl-substituted 5-amino-1,2,4-triazoles (I)–
(III) and their derivatives are used as reagents for
synthesis of various biologically active and medicinal
substances [1–3] and coordination compounds [4–6].
Triazoles (I)–(III) are commonly produced by cycli-
zation of 2-guanyl hydrazides (IV)–(VI) of the corre-
sponding pyridinecarboxylic acids under their heating
in the crystalline state [2, 7, 8], boiling in an aqueous
solution , or under microwave heating :
where R is 2-pyridyl (I), (IV); 3-pyridyl (II), (V); or
4-pyridyl (III), (VI).
The main disadvantage of this method is that the
synthesis of the starting guanyl hydrazides (IV)–(VI)
by the reaction of pyridinecarboxylic acid hydrazides
with methylisothiourea sulfate is prolonged (3–4 days)
and is accompanied by release of the toxic gaseous
methyl mercaptan. An alternative way to synthesize
guanyl hydrazides by fusion of pyridinecarboxylic
acid chloroanhydrides with an excess amount of
aminoguanidine hydrochloride  is also poorly efﬁ cient
because of the high cost of the starting substances and
loss of aminoguanidine in isolation of the product.
Attempts have been made to synthesize compounds I–
III in a single stage by reacting pyridinecarboxylic acids
with aminoguanidine salts [2, 8, 11]. A rather high yield
(90%) was observed in fusion of aminoguanidine sulfate
(2 mol) with isonicotinic acid (1 mol) at 210°C . Even
though 1 mol of aminoguanidine is lost in isolation of the
product, this example demonstrates that a single-stage
synthesis of compounds I–III from aminoguanidine and
pyridinecarboxylic acids can be developed.
In this communication, we describe a single-
reactor method for synthesis of compounds I–III and
their hydrochlorides VII–IX from aminoguanidine
hydrocarbonate (AGH), hydrochloric acid, and
pyridinecarboxylic acids X–XII by the scheme.
It has been shown previously [12–15] that the key
stage in synthesis of 3-substituted 5-amino-1,2,4-
triazoles from aminoguanidine and carboxylic acids is
that in which guanyl hydrazides are formed. Because this
reaction is acid-catalyzed, it is advisable to synthesize
guanyl hydrazides at pH ≤ 1 and, for providing a high
equilibrium conversion, to use concentrated solution
with the minimum content of water, produced by mixing
of AGH with a minor excess of HCl
acid [13–15]. However, our attempt to synthesize
guanyl hydrazides hydrochlorides XIII–XV under the
conditions suggested in [13–15] failed.