REGIOSELECTIVE SYNTHESIS OF ALKYL DERIVATIVES OF 3,5-DIAMINO-1,2,4-TRIAZOLE
629
5-Amino-1-phenyl-3-(3-phenylpropyl)amino-
1,2,4-triazole X. A solution of 0.74 g (0.0055 mol) of
3-phenylpropanal in 5 ml of ethanol was added drop-
wise over a period of 10 min with vigorous stirring
at 0 5 C to a solution of 1.05 g (0.006 mol) of III in
10 ml of ethanol. The mixture was stirred for 2 h,
after which 0.34 g (0.009 mol) of NaBH4 was added
in portions at 20 30 C. The mixture was stirred for
30 min, heated to boil, and refluxed for 30 min. The
solvent was distilled off, 10 ml of water was added to
the residue, the oil that separated out was extracted
with chloroform (3 5 ml), and the extract was fil-
tered through a bed of alumina (4 cm in diameter,
3 cm high). The solvent was distilled off, and com-
pound X was crystallized from acetonitrile.
(0.15 mol) of NaBH4 was added in small portions at
20 30 C. The mixture was stirred for 30 min, heated
to boil, and refluxed for 30 min. The solvent was dis-
tilled off, 300 ml of water was added to the residue,
and the precipitate (compound XXI) was filtered off,
washed with water, dried, and crystallized.
The filtrate and wash waters were evaporated to
a volume of 50 ml; the precipitate that formed on
cooling (compound XX) was filtered off and crystal-
lized.
3-Acetylamino-5-o-methoxybenzylidenamino-1-
phenyl-1,2,4-triazole XXIV. A mixture of 1 g
(0.0046 mol) of XXIII, 0.75 g (0.0055 mol) of
2-methoxybenzaldehyde, and 1 ml of DMF was re-
fluxed for 1 h, diluted with 10 ml of water, and ex-
tracted with chloroform (3 10 ml). The extract was
dried over CaCl2 and filtered through a bed of alumi-
na (4 cm in diameter, 3 cm high); the solvent was
distilled off, and the residue was crystallized.
3-Alkylamino-5-amino-1,2,4-triazoles XIII XIX.
a. A solution of 2.9 g (0.072 mol) of NaOH in 2 ml of
water was added to a suspension of 10 g (0.063 mol)
of nitrate XI in 20 ml of ethanol. The mixture was re-
fluxed for 5 min, after which a solution of 0.057 mol
of appropriate aldehyde in 10 ml of ethanol was
added, the mixture was refluxed for 1 h, and 3.3 g
(0.086 mol) of NaBH4 was added in portions. The mix-
ture was refluxed for an additional 30 min, the solvent
was evaporated to a small volume, and 40 ml of water
was added to the residue. The resulting solution was
cooled, and the precipitate thus formed was filtered
off, washed with water, and crystallized.
5-Alkylamino-3-acetylamino-1-R-1,2,4-triazoles
XXV XXIX. A mixture of 0.01 mol of XXII or
XXIII and 0.012 mol of appropriate aldehyde in 2 ml
of DMF was refluxed for 1 h and diluted with 20 ml of
ethanol. To the resulting solution, 0.68 g (0.018 mol)
of NaBH4 was added in small portions at 50 60 C,
after which the mixture was refluxed for 30 min.
The solvent was evaporated to a small volume, and
40 ml of water was added to the residue. The pre-
cipitate thus formed was filtered off, washed with
water, and crystallized.
b. A solution of 4.8 g (0.12 mol) of NaOH in
10 ml of H2O was added with stirring to a suspension
of 14.1 g (0.1 mol) of acetyl derivative XII in 50 ml
of ethanol. The mixture was refluxed until it became
fully homogeneous (10 15 min), after which it was
neutralized with acetic acid to pH 7 9, and 10.1 g
(0.09 mol) of appropriate aldehyde was added drop-
wise with stirring. The mixture was refluxed for
20 min, after which 5.13 g (0.135 mol) of NaBH4 was
added in portions over a period of 10 min. The mix-
ture was refluxed for an additional 20 min and evap-
orated to a small volume. The residue was diluted
with 100 ml of water, and the resulting solution was
evaporated by half and cooled. The precipitate thus
formed was filtered off, washed with water, and crys-
tallized.
5-Alkylamino-3-amino-1-R-1,2,4-triazoles XXX
XXXIV. A mixture of 0.005 mol of XXV XXIX,
10 ml of ethanol, and 3 ml of concentrated HCl was
refluxed for 2 h and then neutralized with a 10%
aqueous solution of sodium acetate. The precipitate
thus formed was filtered off, washed with water, and
crystallized.
CONCLUSIONS
(1) Condensation of 3,5-diamino-1-R-1,2,4-tri-
azoles (R = Alk, Ar) with aldehydes at an equimolar
ratio of the reactants, followed by hydrogenation of
the resulting Schiff bases, is a one-pot method for
regioselective synthesis of 3-alkylamino-5-amino-1-R-
1,2,4-triazoles.
5-Amino-3-(3-phenylpropyl)amino-1,2,4-triazole
XX and 3,5-di(3-phenylpropyl)amino-1,2,4-triazole
XXI. A solution of 12.06 g (0.09 mol) of 3-phenyl-
propanal in 10 ml of ethanol was added with vigorous
stirring over a period of 10 min at 0 5 C to the reac-
tion mixture obtained as described above by hydrol-
ysis of 14.1 g (0.1 mol) of acetyl derivative XII.
The mixture was stirred for 2 h, after which 5.7 g
(2) 3,5-Diamino-1,2,4-triazole (R = H) reacts se-
lectively only with aldehydes in which the carbonyl
group is conjugated with the aromatic ring. Condensa-
tion with aliphatic aldehydes followed by hydrogena-
tion yields a mixture of 3-alkylamino-5-amino-1,2,4-
triazoles and 3,5-dialkylamino-1,2,4-triazoles.
RUSSIAN JOURNAL OF APPLIED CHEMISTRY Vol. 79 No. 4 2006