REDUCTION OF 2-AMINO-3- AND -5-NITROPYRIDINE DERIVATIVES
117
Scheme 3.
Me
NO2
NH2
Me
NH2
Me
NO2
N H
N H
2 4
2
4
–
NH3
–NH3
N
N
H N
2
N
XIII
XIV
XV
Pyridin-3-amine (III). a. A mixture of 1.5 g
10.8 mmol) of 5-nitropyridin-2-amine (I) and 5 ml
~100 mmol) of hydrazine hydrate was heated for 7–
scribed above for pyridin-3-amine (method a). When
the reaction was complete, excess hydrazine-d was
distilled off in a stream of argon. The tarry residue was
extracted with diethyl ether, and the solvent was dis-
(
(
4
1
0 h at 110–120°C. The reaction was accompanied by
evolution of ammonia. When the reaction was com-
plete, excess hydrazine hydrate was distilled off in
a stream of argon. The tarry residue was extracted with
diethyl ether, and the extract was evaporated to obtain
a light lilac material which was purified by recrystal-
tilled off from the extract. Yield 0.3 g (30%), mp 52°C.
1
H NMR spectrum (CDCl ), δ, ppm: 4.45 br.s (2D,
3
ND ), 6.95 d (1H, 4-H, J = 6.0 Hz), 7.03 d (1H, 5-H,
2
J = 6.0 Hz), 8.00 m (1D, 6-D), 8.09 m (1H, 2-H).
Found, %: C 61.62; H (D) 9.26; N 28.74. C H D N .
5
3
3
2
lization from hexane. Yield 0.32 g (35%), mp 64°C.
Calculated, %: C 61.82; H (D) 9.34; N 28.84.
1
H NMR spectrum (CF COOH), δ, ppm: 4.18 s (2H,
2
2
3
(
2- H)-Pyridin-3-( H )amine (IX) was obtained
2
NH ), 6.87 d (1H, 4-H, J = 6.0 Hz), 6.97 d (1H, 5-H,
2
in a similar way from 1.5 g (10.8 mmol) of 3-nitro-
J = 6.0 Hz), 7.98 m (1H, 6-H), 8.03 m (1H, 2-H).
pyridin-2-amine (II) and 5 ml (~100 mmol) of hydra-
Found, %: C 63.62; H 6.38; N 29.58. C H N . Calcu-
1
5
6
2
zine-d . Yield 0.2 g (20%), mp 57°C. H NMR spec-
4
lated, %: C 63.81; H 6.43; N 29.76.
trum (CDCl ), δ, ppm: 3.95 br.s (2D, ND ), 6.89 m
3
2
b. A mixture of 1.5 g (10.8 mmol) of 3-nitropyridin-
-amine (II) and 5 ml (~100 mmol) of hydrazine hy-
(1H, 4-H), 6.95 m (1H, 5-H), 7.96 m (1H, 6-H), 8.01 m
(1D, 2-D). Found, %: C 61.72; H (D) 9.24; N 28.83.
2
drate was heated for 7–10 h at 110–120°C. Ammonia
evolved during the process. When the reaction was
complete, the product was isolated as described above
C H D N . Calculated, %: C 61.82; H (D) 9.34;
5 3 3 2
N 28.84.
-Methylpyridin-3-amine (XI). a. A mixture of
.53 g (10 mmol) of 4-methyl-3-nitropyridin-2-amine
X) and 10 ml (~200 mmol) of hydrazine hydrate was
4
1
in a. Yield 0.25 g (25%), mp 64°C. H NMR spectrum
1
(
(
CF COOH), δ, ppm: 4.15 s (2H, NH ), 6.89 d (1H,
3
2
4
-H, J = 6.0 Hz), 6.98 d (1H, 5-H, J = 6.0 Hz), 7.96 m
heated for 3–5 h at 110–120°C. When the reaction was
complete (ammonia no longer evolved), excess hydra-
zine hydrate was distilled off under reduced pressure in
a stream of argon, the tarry residue was extracted with
benzene or diethyl ether, and the extract was evaporat-
ed. Yield 0.53 g (49%), mp 105–106°C (from ben-
zene–petroleum ether); published data [11]: mp 106–
(
1H, 6-H), 8.01 m (1H, 2-H). Found, %: C 63.67;
H 6.39; N 29.62. C H N . Calculated, %: C 63.81;
5
6
2
H 6.43; N 29.76.
c. A solution of 1.65 g (10.7 mmol) of 5-nitropyri-
din-2-ylhydrazine (VI) in 5 ml (~100 mmol) of hydra-
zine hydrate was heated for 7–10 h at 110–120°C. The
product was isolated as described above in a. Yield
108°C. Found, %: C 66.42; H 7.40; N 25.81. C
Calculated, %: C 66.64; H 7.46; N 25.90.
H N .
8 2
6
0
.35 g (35%), mp 64°C. It showed no depression of the
melting point on mixing with an authentic sample of
pyridin-3-amine.
b. A mixture of 1.53 g (10 mmol) of 4-methyl-5-
nitropyridin-2-amine (XII) and 10 ml (~200 mmol) of
hydrazine hydrate was heated for 3–5 h at 110–120°C.
The mixture was then treated as described above in a.
Yield 0.62 g (57%), mp 106–107°C (from benzene–
d. 3-Nitropyridin-2-ylhydrazine (VII), 1.65 g
(
10.7 mmol), was dissolved in 5 ml (~100 mmol) of
hydrazine hydrate, and the solution was heated and
then treated as described above in a. Yield 0.25 g
hexane). Found, %: C 66.51; H 7.42; N 25.83. C
H N .
6 8 2
(
25%), mp 64°C. The product showed no depression of
Calculated, %: C 66.64; H 7.46; N 25.90.
the melting point on mixing with an authentic sample
of pyridin-3-amine.
5
-Methylpyridin-3-amine (XIV). a. Compound
XIV was synthesized from 1.53 g (10 mmol) of
5-methyl-3-nitropyridin-2-amine (XIII) and 10 ml
(~200 mmol) of hydrazine hydrate as described above
for compound XI (method a). Yield 0.44 g (41%),
2
2
(
6- H)-Pyridin-3-( H )amine (VIII) was obtained
2
from 1.5 g (10.8 mmol) of 5-nitropyridin-2-amine (I)
and 5 ml (~100 mmol) of hydrazine-d (N D ) as de-
4
2
4
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 45 No. 1 2009