Unexpected Result of Imidazo[4,5-b]pyridine Bromination

Full text of DOI:10.1023/A:1025564908743

Russian Journal of Organic Chemistry, Vol. 39, No. 2, 2003, pp. 280 281. Translated from Zhurnal Organicheskoi Khimii, Vol. 39, No. 2, 2003,
pp. 302 303.
Original Russian Text Copyright
,
2003 by Yutilov, Lopatinskaya, Smolyar, Korol .
SHORT
COMMUNICATIONS
Unexpected Result of Imidazo[4,5-b]pyridine Bromination
Yu. M. Yutilov, Kh. Ya. Lopatinskaya, N. N. Smolyar, and I. V. Korol,
Litvinenko Institute of Physical Organic Chemistry, Ukrainian Academy of Sciences, Donetsk, 83114 Ukraine
Received April 10, 2002
On heating imidazo[4,5-b]pyridine (Ia) [1] with
excess bromine in the glacial acetic acid we un-
expectedly obtained a compound containing two
bromine atoms in a molecule and having in the IR
spectrum absorption corresponding to an amido
group. We assumed that the compound was 5,6-di-
bromoimidazo[3,5-b]pyridin-2-one (IIa) and con-
firmed by establishing its identity with an authentic
sample of IIa prepared by treating with bromine
imidazo[4,5-b]pyridine-2-one (III) [1] as we had
described in [2] for 1,3-dimethylimidazo[4,5-b]-
pyridine-2-one.
The bromination of base Ia in acetic acid in the
presence of sodium acetate provided the same result.
But the treating of compound Ia with bromine at the
molar ratio 1: 1 gave rise to 6-bromoimidazo[4,5-
b]pyridin-2-one (IV) corresponding to compound
described in [1]. It should be noted however that
bromination of base Ia in 50% aqueous acetic acid
furnished 6-bromoimidazo[4,5-b]pyridine (V) [3]:
Thus here the reaction proceeded similarly to
bromination of 1,2-dimethylimidazo[4,5-b]pyridine in
the same medium [4]. In the same way as base Ia
reacted with bromine 3-methylimidazo[4,5-b]pyridine
I III, R = H (a), CH3 (b).
(Ib) giving rise to dibromide IIb obtained also by
bromination of imidazolone IIIb.
5,6-Dibromoimidazo[4,5-b]pyridin-2-one
(IIa).
(a). To a solution of 0.6 g (5 mmol) of imidazo[4,5-
b]pyridine (Ia) and 0.82 g (10 mmol) of CH3COONa
in 20 ml of acetic acid was added by portions at stir-
ring a solution of 0.51 ml(10 mmol) of bromine in
3 ml of acetic acid. The reaction occurred with
precipitate formation. The suspension obtained was
heated at stirring for 5 h on a boiling water bath. The
acetic acid was distilled off in a vacuum to dryness,
and to residue was poured 15 ml of water, and the
solution was neutralized with 25% water solution of
ammonia. The separated precipitate was filtered off
The formation mechanism of compounds IIa, b is
yet unclear, but apparently first occurs covalent addi-
tion of acetic acid elements across the C=N bond of
the imidazole fragment of substrate I followed by
oxidation with bromine of the arising 1,2-dihydroimid-
azole into 2-acetoxyimidazole that further is cleaved
by the generated hydrogen bromide giving-2-oxy-
(oxo)imidazo[4,5-b]pyridine (III). The latter should
readily take up bromine affording dibromideII.
1070-4280/03/3902-0280$25.00 2003 MAIK Nauka/Interperiodica

UNEXPECTED RESULT OF IMIDAZO[4,5-b]PYRIDINE BROMINATION
281
and recrystallized from a mixture DMF water, 4: 1,
with addition of activated carbon. The obtained
colorless crystalline compound was washed with hot
ethanol and dried Yield 45 g (31%), mp > 360 C. IR
spectrum, , cm : 1695 (C=O). H NMR spectrum,
, ppm: 7.48 s (1H, H7); 11.11 s (1H, H1); 11.67 s
(1H, H3). Found, %: C 24.38; H 1.00; N 14.21.
C6H3Br2N3O. Calculated, %: C 24.60; H 1.03;
N 14.35.
5 h on a boiling water bath. Then the acetic acid was
distilled off in a vacuum. The oily residue was dis-
solved in 15 ml of water, and the solution was
neutralized with 25% water solution of ammonia. The
separated gray-brown precipitate was filtered off and
purified by recrystallization from 85% acetic acid.
Off-white compound IV was obtained in 0.27 g (25%)
1
1
1
yield, mp 361 363 C. IR spectrum, , cm : 1710
1
(C=O). H NMR spectrum, , ppm: 7.44 d (1H, H7,
J 1.96 Hz); 7.99 d (1H, H5, J 1.96 Hz); 11.28 s (1H,
H1); 11.74 s (1H, H3). Found, %: C 33.49; H 1.83;
N 19.48. C6H4BrN3O. Calculated, %: C 33.67;
H 1.88; N 19.63.
(b) To a solution of 4.05 g (30 mmol) of imidazo-
[4,5-b]pyridin-2-one (IIIa) and 5.1 g (62 mmol) of
CH3COONa in 80 ml of acetic acid was added drop-
wise a solution of 3.2 ml (62 mmol) of bromine in
10 ml of acetic acid. The mixture was heated with
stirring on a water bath for 5 h. The precipitate was
filtered off, washed with water, and dried. Yield
6.75 g (78%). mp > 360 C (from DMF). IR spec-
6-Bromoimidazo[4,5-b]pyridine (V). To a solu-
tion of 0.6 g (5 mmol) of imidazo [4,5-b]pyridine (Ia)
[1] in 27 ml of 50% acetic acid was added by portions
at stirring while heating to 70 C 0.51 ml (10 mmol)
of bromine. The reaction mixture was stirred at this
temperature for 5 h, the solvent was evaporated to
dryness, and the solid residue was dissolved in 20 ml
of water and neutralized with 25% aqueous ammonia.
The precipitate was filtered off, washed with a small
portion of cold water and with ethanol water mixture,
1: 1, and dried. Yield 0.65 g (61%), mp 225 226 C
1
1
trum, , cm : 1695 (C=O). H NMR spectrum, ,
ppm: 7.49 s (1H, H7); 11.12 s (1H, H1); 11.68 s (1H,
H3). Found, %: C 24.45; H 1.01; N 14.23.
C6H3Br2N3O. Calculated, %: C 24.60; H 1.03;
N 14.35.
5,6-Dibromo-3-methylimidazo[4,5-b]pyridin-2-
one (IIb). (a) Compound IIb was prepared under
conditions described above under procedure (a) for
compound IIa. From 0.66 g (5 mmol) of 3-methyl-
imidazo[4,5-b]pyridine (Ib) [5], 0.82 g (10 mmol) of
CCH3COONa, 20 ml of acetic acid, and 0.51 ml
(10 mmol) of bromine was obtained compound IIb in
0.57 g (38%) yield, mp 325 326 C (from DMF). IR
1
(from ethanol), (publ. mp 227 228 C [3]). H NMR
spectrum, , ppm: 8.19 s (1H, H2); 8.37 d (1H, H7, J
1.98 Hz); 8.39 d (1H, H5, J 1.98 Hz). Found, %:
C 36.20; H 2. 00; N 21.05. C6H4BrN3. Calculated,
%: C 36.39; H 2.04; N 21.22.
1H NMR spectra of compounds IIa, b, IV, V were
registered on spectrometer Gemini-200 (operating
frequency 200 MHz) from solutions in DMSO-d6 ,
internal reference HMDS. IR spectra were recorded
on spectrophotometer UR-20 from mulls in mineral
oil. The purity and homogeneity of compounds syn-
thesized was proved by TLC on Silufol UV-254
plates, eluent ethanol, development under UV irradia-
tion or in iodine vapor.
1
1
spectrum, , cm : 1695 (C=O). H NMR spectrum,
, ppm: 3.29 s (3H, N3 CH3); 7.64 s (1H, H7); 11.40
(1H, br. signal, H1). Found, %: C 27.24; H 1.61; N
13.55. C7H5Br2N3O. Calculated, %: C 27.39; H 1.64;
N 13.69.
(b) Synthesis was carried out as in procedure (b)
for compound IIa. From 0.6 g (4 mmol) of 3-methyl-
imidazo[4,5-b]pyridin-2-one (IIIb) [6], 0.66
g
REFERENCES
(8 mmol) of CH3COONa, 15 ml of acetic acid, and
0.42 ml (8 mmol) of bromine was obtained compound
IIb in 0.82 g (67%) yield, mp 324 326 C (from
1. Petrow, V. and Saper, J., J. Chem. Soc., 1948, no. 9,
1
1
p. 1389.
2. Yutilov,
DMF). IR spectrum, , cm : 1695 (C=O). H NMR
spectrum, , ppm: 3.28 s (3H, N3 CH3); 7.64 s (1H,
H7); 11.41 (1H, br. signal, H1). Found, %: C 27.27;
H 1.62; N 13.65. C7H5Br2N3O. Calculated %:
C 27.39; H 1.64; N 13.69.
Yu.M.,
Malyutina, V.F.,
Lopatin-
skaya, Kh.Ya., and Svertilova, I.A., Zh. Org. Khim.,
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3. Graboyes, H. and Day, A.R., J. Am. Chem. Soc., 1957,
vol. 79, p. 6421.
6-Bromoimidazo[4,5-b]pyridin-2-one (IV). To a
solution of 0.6 g (5 mmol) of imidazo [4,5-b]pyridine
(Ia) [1] in 15 ml of acetic acid was added by portions
at stirring 0.26 ml (5 mmol) of bromine in 7 ml of
acetic acid. The reaction occurred with precipitate
formation. The suspension obtained was heated for
4. Kazymov, A.V., Shchelkina, L.P., and Kabirova, N.G.,
Khim. Geterotsikl. Soed., 1971, p. 279.
5. Mizuno, Y., Ikehara, M., Iton, T., and Saito, K.,
J. Org., Chem., 1963, vol. 28, p. 1837.
6. Yutilov, Yu.M. and Svertilova, I.A., Khim. Getero-
tsikl. Soed., 1976, p. 1277.
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 39 No. 2 2003