SYNTHESIS OF 3-PYRIDYL-SUBSTITUTED 5-AMINO-1,2,4-TRIAZOLES
1895
ized with a 20% HCl solution to pH 8–9, and cooled
to 3–5°C. The precipitate formed was filtered off, re-
crystallized from water, and dried at 130°C. Yield 5.0 g
(76%), mp 216–217°C (mp 220–221°C [10]). 1H NMR
spectrum, δ, ppm: 5.32 br.s (2H, NH2 of tautomer B),
6.07 br.s (2H, NH2 of tautomer A), 7.32–7.43 m (1H,
H-5'), 7.81–7.90 m (2H, H-3' and H-4'), 8.57 m (1H,
H-6'), 12.22 br.s (1H, NH of tautomer A), 13.44 br.s
(1H, NH of tautomer B). Mass-spectrum, m/z (Irel, %):
161 (45) [M]+, 105 (100), 78 (40), 51 (24). Found by
potentiometric titration: M = 161.3. Calculated: M =
161.16. Found (%): C 51.95, H 4.44, N 43.61. C7H7N5.
Calculated (%): C 52.17, H 4.38, N 43.45.
Mass-spectrum, m/z (Irel, %): 160 (100) [M-HCl]+, 118
(15), 104 (55), 77 (23), 57 (12). Found (%): C 49.05,
H 4.65, N 28.58. C8H9ClN4. Calculated (%): C 48.86,
H 4.61, N 28.49.
CONCLUSIONS
(1) 3-Pyridyl-substituted 5-amino-1,2,4-triazoles
should be synthesized without isolation of guanyl
hydrazides by heating a mixture of aminoguanidine
hydrocarbonate,
pyridinecarboxylic
acid,
and
hydrochloric acid in a 1 : 1.3 : 1 molar ratio in the
course of 5–6 h at a temperature of 180–185°C. When
obtaining free aminotriazoles, it is advisable to diminish
the duration of the acid-catalyzed stage of synthesis
to 3 h and to cyclize guanyl hydrazides by boiling an
aqueous-alkaline solution of the reaction mixture.
5-Amino-3-(pyridin-3-yl)-1,2,4-triazole
(II).
Obtained similarly to compound I. Yield 5.23 g (80%),
mp 226–227°C (mp 224–225°C [10]). 1H NMR
spectrum, δ, ppm: 6.15 br.s (2H, NH2), 7.41 d.d (1H,
H-5', 3J 7.8 and 4.8 Hz), 8.16 d.t (1H, H-4', 3J = 8.1 Hz,
(2) The N-4 atom of the triazole ring is protonated in
5-amino-3-(pyridin-2-yl)-1,2,4-triazole hydrochloride,
and the N-1' atom of the pyridine moiety, in 5-amino-
3-(pyridin-4-yl)-1,2,4-triazole. In 5-amino-3-(pyridin-
2-yl)-1,2,4-triazole hydrochloride solutions, both
tautomers are present in comparable concentrations.
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4J = 1.8 Hz), 8.53 d.d (1H, H-6', J = 5.1 Hz, J =
1.8 Hz), 9.03 d (1H, H-6', 4J = 1.2 Hz), 12.28 br.s (1H,
NH). Mass-spectrum, m/z (Irel, %): 161 (100) [M]+, 119
(20), 105 (32), 78 (14), 57 (11). Found by potentiometric
titration: M = 160.8. Calculated: M = 161.16. Found
(%): C 52.01, H 4.28, N 43.71. C7H7N5. Calculated (%):
C 52.17, H 4.38, N 43.45.
ACKNOWLEDGMENTS
5-Amino-3-(pyridin-4-yl)-1,2,4-triazole
(III).
Obtained similarly to compound I. Yield 4.62 g (70%),
mp 271–272°C (mp 272–274°C [10]). 1H NMR
spectrum, δ, ppm: 6.22 br.s (2H, NH2), 7.76 d.d (2H,
H-3' and H-5', J = 4.5 Hz, J = 1.5 Hz), 8.57 d (2H,
H-2' and H-6', 3J = 5.7 Hz), 12.35 br.s (1H, NH). Mass-
spectrum, m/z (Irel, %): 161 (100) [M]+, 119 (13), 105
(18), 78 (12), 57 (13), 51 (11). Found by potentiometric
titration: M = 161.4. Calculated: M = 161.16. Found
(%): C 52.26, H 4.35, N 43.39.
The study was financially supported by the RF
Ministry of Education and Science under the Federal
target program “Scientific and Scientific-Pedagogical
Personnel in the Innovative Russia), contract P1472,
project NK-186P/3.
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REFERENCES
1. Patent Appl. WO2008/117943A1.
2. Lipinski, C.A., J. Med. Chem., 1983, vol. 26, no. 1,
C7H7N5. Calculated (%): C 52.17, H 4.38, N 43.45.
pp. 1–6.
5-Amino-3-phenyl-1,2,4-triazole hydrochloride
(XVI). To a solution of 1 g (6.2 mmol) of 5-amino-3-
phenyl-1,2,4-triazole (XVII) in 5 ml of ethanol was
added under agitation and heating to boiling a 0.74-g
portion (6.8 mmol) of a 33.5% aqueous solution of HCl,
the mixture was cooled to 0–5°C, and the precipitate
formed was filtered off, recrystallized from ethanol, and
dried at 130°C. Yield 0.79 g (65%), mp 258–260°C.
1H NMR spectrum, δ, ppm: 7.50 m (3H, Ph), 7.95 m
(2H, Ph), 8.00 br.s (2H, NH2). 13C NMR spectrum, δ,
ppm: 124.99 (C-1'), 125.97 (C-2' and C-6'), 128.96 (C-
3' and C-5'), 130.97 (C-4'), 148.57 (C-3), 152.07 (C-5).
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