Bromination-dehydrobromination of 4-aryl-5-nitro-6-phenyl-3,4- dihydropyrimidin-2(1H)-ones

Article abstract of DOI:10.1007/s11178-005-0180-4

Depending on the conditions, bromination of 4-aryl-5-nitro-6-phenyl-3,4- dihydropyrimidine-2(1H)-ones and subsequent dehydrobromination gives either 4-aryl-5-nitro-6-phenylpyrimidin-2(1H)-ones or their mixtures with the corresponding 4-aryl-5-bromo-6-meth

Full text of DOI:10.1007/s11178-005-0180-4

Russian Journal of Organic Chemistry, Vol. 41, No. 3, 2005, pp. 417–422. Translated from Zhurnal Organicheskoi Khimii, Vol. 41, No. 3, 2005,
pp. 425–430.
Original Russian Text Copyright © 2005 by Sedova, Gatilov, Shkurko.
Bromination–Dehydrobromination
of 4-Aryl-5-nitro-6-phenyl-3,4-dihydropyrimidin-2(1H)-ones
V. F. Sedova, Yu. V. Gatilov, and O. P. Shkurko
Vorozhtsov Novosibirsk Institute of Organic Chemistry, Siberian Division, Russian Academy of Sciences,
pr. Akademika Lavrent’eva 9, Novosibirsk, 630090 Russia
e-mail: oshk@nioch.nsc.ru
Received July 17, 2004
Abstract—Depending on the conditions, bromination of 4-aryl-5-nitro-6-phenyl-3,4-dihydropyrimidine-2(1H)-
ones and subsequent dehydrobromination gives either 4-aryl-5-nitro-6-phenylpyrimidin-2(1H)-ones or their
mixtures with the corresponding 4-aryl-5-bromo-6-methoxy-5-nitro-6-phenyltetrahydropyrimidin-2-ones which
are formed as two diastereoisomers.
Some 4-aryl-5-nitro-3,4-dihydropyrimidin-2(1H)-
ones exhibit an appreciable biological activity, specif-
ically as calcium channel modulators [1]. We recently
found that several 4-aryl-5-nitro-6-phenyl-3,4-dihydro-
pyrimidin-2(1H)-one derivatives show a high anti-
arrhythmic activity [2]. According to the data of [3],
the stability of the heterocyclic fragment in 1,4(or 3,4)-
dihydropyrimidines and structurally related 1,4-dihy-
dropyridines to aromatization is important for their
biological activity. Therefore, it seemed to be reason-
able to examine the behavior of 4-aryl-5-nitro-6-
phenyl-3,4-dihydropyrimidin-2(1H)-ones I in dehydro-
genation and oxidation reactions which could result in
aromatization of the heteroring.
The present communication reports on the bromina-
tion and subsequent dehydrobromination of dihydro-
pyrimidinones Ia–Ic. This two-step technique is
widely used for aromatization of dihydropyrimidi-
nones [4]. Here, the first step (i.e., bromination) is
usually determining. It was shown that the ease of
bromination of 4,6-diphenyldihydropyrimidin-2-ones
depends on the substituent in position 5 of the hetero-
ring. The bromination of 4,6-diphenyldihydropyrimi-
din-2-ones having such substituent in position 5 as
ethoxycarbonyl, aroxy, or nitro group requires more
severe conditions as compared to the corresponding
5-unsubstituted and 5-alkyl derivatives [4–6]. For
example, compound Ia undergoes bromination with
bromine in boiling acetic acid, and the subsequent
dehydrobromination yields pyrimidinone IIa [5].
heating in acetic acid, and the bromination product was
isolated and treated with pyridine in boiling methanol.
As a result, we obtained 4-(3-chlorophenyl)-5-nitro-
6-phenylpyrimidin-2(1H)-one (IIb) in good yield
(Scheme 1). Unlike compounds Ia and Ib, 4-(4-meth-
oxyphenyl)-5-nitro-6-phenyl-3,4-dihydropyrimidin-
2(1H)-one (Ic) readily reacted with an equimolar
amount of bromine both in acetic acid and in chloro-
form at room temperature. However, the reaction
involved only the methoxyphenyl group to give 4-(3-
bromo-4-methoxyphenyl)-5-nitro-6-phenyl-3,4-di-
hydropyrimidin-2(1H)-one (Id). This is consistent with
published data on ready bromination of para-substi-
tuted anisoles [7]. The subsequent bromination of com-
pound Id with an equimolar amount of bromine in
acetic acid on heating, followed by dehydrobromina-
tion, afforded a mixture of products containing
4-(3-bromo-4-methoxyphenyl)-5-nitro-6-phenylpyri-
midin-2(1H)-one (IId) and dibromo derivatives
(according to the data of elemental analysis and mass
spectrometry). We succeeded in isolating compound
IId and a mixture of dibromo derivatives, but we failed
to separate the latter into inidividual components. The
absence in that mixture of compounds like I and II
with a dibromomethoxyphenyl group ([M]+ 481 and
479, respectively) suggests that the addition of
bromine occurred at the double C5=C6 bond in the
heteroring.
We also made an attempt to effect bromination
under milder conditions, in chloroform at room tem-
perature. There are no published data on the behavior
of diarylpyrimidinones I under these conditions, while
Taking into account these findings, we performed
bromination of 3-chlorophenyl derivative Ib on
1070-4280/05/4103-0417 © 2005 Pleiades Publishing, Inc.

SEDOVA et al.
418
Scheme 1.
O
HN
N
O
Cl
Ib
Ph
2
HN1 3 NH
18
15
12
9
6
4
NO2
(1) Br2/AcOH
(2) Py/MeOH
7
11
10
17
16
13
14
5
IIb
8
NO2
O
O
R
(1) Br2/AcOH
(2) Py/MeOH
Ib, Ic
HN
NH
HN
N
Br
Br
Ic
Ph
O
Ph
NO2
NO2
OMe
OMe
Id
IId
HN
NH
(1) Br2/AcOH
(2) Py/MeOH
MeO
H
∆
Ia, Id
IIa, IId
+
IIIa, IIId
IIa, IId
Ph
Br
NO2
R
IIIa, IIId
R = H (a), m-Cl (b), p-OMe (c), 3-Br-4-OMe (d).
structurally related 4-aryl-6-methyl-5-nitro-3,4-di-
hydropyrimidin-2(1H)-ones are known to undergo
bromination mainly at the 6-methyl group [8]. The
bromination of compounds Ia and Id in chloroform,
followed by dehydrobromination, afforded in each
case two products, pyrimidinone IIa or IId and
bromine-containing tetrahydropyrimidinone IIIa or
IIId. Compound Ib failed to react under the same
conditions.
uracils [11]. The presence of bromine and methoxy
group in positions 5 and 6, respectively, of the hexa-
hydropyrimidine ring in compounds III was confirmed
by the 13C NMR spectra and by the calculation of the
chemical shifts of C5 and C6 according to the additivity
1
scheme. Analysis of the H and 13C NMR spectra
of IIIa and IIId showed that these compounds are
approximately equimolar mixtures of two diastereo-
isomers.
In the IR spectra of IIIa and IIId, stretching
vibrations of the carbonyl groups appear at 1689 and
1676 cm–1. The molecular ion peak in the mass
spectrum of IIIa is a doublet with m/z 405/407
(C17H16BrN3O4), while compound IIId shows a triplet
with m/z 513/515/517 (C18H17Br2N3O5). The presence
of bromine atoms and methoxy group in molecules
IIIa and IIId also follows from the analytical data and
1H and 13C NMR spectra. Compound IIIa is converted
into pyrimidinone IIa on heating to 230°C; first, the
initial compound changes its color (presumably due to
elimination of hydrogen bromide), and methanol is
then released.
By analogy with 4-(o-nitrophenyl)- and 4-(m-fluoro-
phenyl)-5-nitro-6-phenyl-3,4-dihydropyrimidin-2(1H)-
ones [12], compounds Ia and Id are likely to exist
mainly in a flattened boat conformation with pseudo-
axial 4-aryl group which declines over the C2N3C5C6
plane (conformer A; Scheme 2). Taking into account
the high conformational mobility of the heteroring
(according to the PM3 calculations, the activation
enthalpy ∆H≠ for ring inversion in isolated molecule
Ia is 1.67 kJ/mol; for the solvated molecule, the
corresponding value should be slightly greater), some
equilibrium amount of the second conformer (B)
should be present in solution. Conformer B also has
a flattened boat structure, but the 4-aryl group therein
is oriented equatorially. Analysis of the steric models
of conformers A and B showed that, under conditions
of kinetic control, attack by bromine molecule on the
The formation of substituted 5-bromo-6-alkoxy(or
hydroxy)-5,6-dihydropyrimidines in the bromination is
well known for pyrimidin-2-ones [9], 1,2-dihydropyri-
midin-2-ylmethylene(cyano)acetic acid esters [10], and
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BROMINATION–DEHYDROBROMINATION OF 4-ARYL-5-NITRO-6-PHENYL-...
419
Scheme 2.
Ar
NO2
NO2
H
H
Ar
Ar
4
4
O
H
H
Br
Br
4
5
5
5
N
N
N
O
· · ·
N
N
O
N
H
6
6
6H
H
Ph
O2N
Ph
Ph
H
H
MeO
Br
Br
Ia-A, Id-A
IIIa-A, IIId-A
Br
Br
Br
Br
Ar
H
Ar
4
4
H
H
O
O2N
O2N
5
5
6
N
N
N
O
· · ·
N
O
N
Ar
N
H
4
H
6
6H
5
Ph
MeO
Ph
Ph
H
H
NO2
H
Ia-B, Id-B
IIIa-B, IIId-B
double bond can occur only from the spatially acces-
sible exo side of the heteroring. Rehybridization of the
C5 atom from sp2 to sp3 leads to distortion of the
heteroring, so that the bromine atom and 4-aryl group
in conformer A occupy equatorial positions while the
nitro group and 4-H become axial. Conformer B is
characterized by the opposite orientation of substit-
uents at C5. Both structures are then stabilized via
addition of bromide ion at position 6 of the heteroring.
and δ 5.55 and 5.98 ppm for IIId (3J3,4 ≈ 0 Hz); there-
fore, the 4-H atom in both diastereoisomers is axial
[13] and the 4-aryl group occupies equatorial position.
Such orientation of the aryl group is typical of phenyl-
substituted cyclohexanes, cyclohexanones [17], and
tetrahydropyrimidin-2-ones (thiones) [13–15].
In keeping with the above stated, the most probable
structures of compounds IIIa and IIId are diastereo-
isomeric configurations A and B. We calculated by the
AM1, PM3, and HF/3-21G methods the thermo-
dynamic stabilities ∆Hf of four diastereoisomers A–D
of IIIa with axial hydrogen atom and equatorial phenyl
group on C4. The following ∆Hf values were obtained
for diastereoisomers A–D, respectively, kJ/mol: AM1:
66.94, 67.15, 73.47, 84.85; PM3: –56.07, –50.92,
–47.61, –49.50; HF/3-21G: 0.00, 0.79, 28.49, 31.17
(E = –3669.576144 a.u.). These data are consistent
with the greater thermodynamic stability of diastereo-
isomers A and B, as compared to diastereoisomers C
and D in which the 6-methoxy group is equatorial
while the 6-Ph group is axial.
6-Methoxytetrahydropyrimidin-2-one III is formed
by heating of intermediate 5,6-dibromo derivative in
boiling methanol in the presence of pyridine. Presum-
ably, in the two cases derivatives with axial methoxy
group on C6 are mainly formed. The orientation of the
methoxy and phenyl groups on C6 can be judged on
the basis of the data reported for hydrogenated pyri-
midinones; in keeping with these data, phenyl group
tends to occupy equatorial position while hydroxy or
alkoxy group is usually oriented axially due to its
anomeric effect [13–16].
While elucidating the structure of diastereoisomers
III, we also considered published data for tetrahydro-
pyrimidin-2-ones which were found to exist in a dis-
torted boat conformation with the base formed by the
N1N3C4C6 atoms of the pyrimidine ring [13, 14]. The
orientation of substituents in position 4 of the pyri-
midine ring in compounds IIIa and IIId follows from
Thus the bromination of compounds Ia, Ib, and Id
with bromine in acetic acid on heating and the sub-
NO2
Br
Ar
Ar
4
4
H
H
Br
MeO
O2N
MeO
5
5
N
N
O
N
N
O
6
6
H
H
H
H
1
Ph
Ph
the H NMR spectra. The spectra contain two singlets
from 4-H at δ 5.57 and 6.03 ppm for compound IIIa
IIIa-C, IIId-C
IIIa-D, IIId-D
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 41 No. 3 2005

SEDOVA et al.
420
sequent dehydrobromination occurs selectively to give
pyrimidinones IIa, IIb, and IId. When the bromination
of compounds Ia and Id is carried out under milder
conditions (in chloroform at room temperature), the
subsequent dehydrobromination involves only a part of
the products while the others are converted into stable
bromine-containing tetrahydropyrimidin-2-ones IIIa
and IIId. Stable 5-bromo-5-nitrotetrahydropyrimidin-
2-ones were isolated for the first time as mixtures of
two diastereoisomers.
and ethanol. Yield 1.4 g (70%), mp 226–228°C (from
EtOH). UV spectrum, λmax, nm (logε): 249 (4.17), 297
(3.99). IR spectrum, ν, cm–1: 1656 (C=O), 1528 (NO2,
asym.), 1328 (NO2, sym.). Mass spectrum, m/z (Irel, %):
329 (24.2) and 327 (69.8) [M]+, 312 (1.5) and 310
(4.3) [M – OH], 301 (6.9) and 299 (28.6) [M – CO],
292 (24.0), 140 (20.1), 138 (63.1), 115 (26.2), 113
(11.0), 111 (28.3), 104 (100.0), 81 (43.3), 77 (60.3).
Found, %: C 58.78; H 3.05; Cl 10.20; N 12.83.
[M]+ 327.0401. C16H10ClN3O3. Calculated, %: C 58.63;
H 3.08; Cl 10.82; N 12.82. M 327.0410.
4-(3-Bromo-4-methoxyphenyl)-5-nitro-6-phenyl-
3,4-dihydropyrimidin-2(1H)-one (Id). A solution of
2.15 g (13 mmol) of bromine in 5 ml of chloroform
was added dropwise with stirring at room temperature
to a suspension of 3.25 g (10 mmol) of compound Ic in
25 ml of chloroform. The mixture was stirred for 12 h,
and the precipitate was filtered off and washed with
chloroform. Methanol, 15 ml, and pyridine, 2.5 ml,
were added to the product, the mixture was heated for
1.5 h under reflux, and the precipitate was filtered off
and washed with water and methanol. Yield 2.2 g
(55%), mp 208–210°C (from EtOH). UV spectrum,
EXPERIMENTAL
The IR spectra were recorded in KBr on a Bruker
Vector-22 spectrometer. The UV spectra of solutions
in ethanol were measured on a Specord M-40 spectro-
photometer. The 1H and 13C NMR spectra were obtain-
ed on Bruker AC-200 and AM-400 spectrometers
using DMSO-d6 as solvent and reference. The mass
spectra (electron impact, 70 eV) were run on a Fin-
nigan MAT 8200 instrument with direct sample admis-
sion into the ion source. The purity of the products was
checked by TLC on Silufol UV-254 plates using
CHCl3 as eluent; spots were visualized under UV light.
λ
max, nm (logε): 228 (4.31), 346 (3.89). IR spectrum, ν,
cm–1: 1693 (C=O), 1496 (NO2, asym.), 1303 (NO2,
5-Nitro-4,6-diphenyl-3,4-dihydropyrimidin-
2(1H)-one (Ia) was synthesized according to the pro-
cedure reported in [5]. 13C NMR spectrum (100 MHz),
δC, ppm: 54.31 (C4), 122.54 (C5), 126.50 (Ph), 127.79
(C9, C11), 128.17 (C10), 128.49 (Ph), 128.94 (Ph),
129.93 (Ph), 132.56 (C13), 142.29 (C7), 149.71 (C6),
150.43 (C2).
1
sym.). H NMR spectrum (400 MHz), δ, ppm: 3.86 s
(3H, OMe), 5.62 d (1H, 4-H, 3J = 3.5 Hz), 7.18 d (1H,
m-H, J = 8.5 Hz), 7.42 d.d (1H, o-H, J = 8.5, 4J =
3
3
4
2 Hz), 7.43–7.60 m (5H, Ph), 7.62 d (1H, o-H, J =
2 Hz), 8.38 d (1H, 3-H, J = 3.5 Hz), 10.14 s (1H,
3
1-H). 13C NMR spectrum (100 MHz), δC, ppm: 53.19
(C4); 56.32 (OMe); 110.67 (C9); 113.02 (C11); 122.23
(C5); 126.85, 127.74, 128.47, 129.96 (Carom); 131.18
(C8); 132.39 (C13); 135.93 (C7); 149.66 (C6); 150.25
(C10); 155.18 (C2). Mass spectrum, m/z (Irel, %): 405
(7.8) and 403 (8.5) [M]+, 388 (86.4) and 386 (86.7)
[M – OH], 357 (100), 355 (81.9), 308 (8.8), 277 (15.3),
218 (38.3), 171 (42.9), 117 (7.8), 104 (20.4), 103 (5.8),
102 (5.1), 77 (15.4). Found, %: C 51.03; H 3.54;
Br 19.80; N 10.43. [M]+ 403.0185. C17H14BrN3O4. Cal-
culated, %: C 50.51; H 3.49; Br 19.77; N 10.40.
M 403.0168.
4-(3-Chlorophenyl)-5-nitro-6-phenyl-3,4-di-
hydropyrimidin-2(1H)-one (Ib) and 4-(4-methoxy-
phenyl)-5-nitro-6-phenyl-3,4-dihydropyrimidin-
2(1H)-one (Ic) were prepared as described in [2].
13C NMR spectrum of Ic (50 MHz), δ, ppm: 53.62
(C4); 55.06 (OMe); 114.10 (C9, C11); 122.86 (C5);
127.53, 127.58, 128.23, 129.64 (Carom); 132.49 (C13);
134.29 (C7); 148.99 (C6); 150.26 (C10); 158.99 (C2).
4-(3-Chlorophenyl)-5-nitro-6-phenylpyrimidin-
2(1H)-one (IIb). A solution of 1.1 g (7 mmol) of
bromine in 5 ml of acetic acid was added to a solution
of 2.0 g (6 mmol) of compound Ib in 20 ml of acetic
acid, and the mixture was heated for 1 h under reflux.
The mixture was poured into 200 ml of water, and the
yellow precipitate was filtered off and washed with
water and methanol. Methanol, 20 ml, and pyridine,
3 ml, were added to the product, the mixture was
heated for 4 h under reflux, poured into 100 ml of
water, and acidified with 10% hydrochloric acid, and
the precipitate was filtered off and washed with water
4-(3-Bromo-4-methoxyphenyl)-5-nitro-6-phenyl-
pyrimidin-2(1H)-one (IId). A solution of 1.0 g
(6 mmol) of bromine in 7 ml of acetic acid was added
dropwise with stirring at room temperature to a sus-
pension of 2.0 g (5 mmol) of compound Id in 20 ml of
acetic acid. The mixture was stirred for 12 h at room
temperature, heated for 0.5 h under reflux, cooled, and
poured into 300 ml of water. The yellow precipitate
was filtered off, washed with water, and dried on
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 41 No. 3 2005

BROMINATION–DEHYDROBROMINATION OF 4-ARYL-5-NITRO-6-PHENYL-...
421
a filter. Methanol, 15 ml, and pyridine, 2.2 ml, were
added to the product, the mixture was heated for 0.5 h
under reflux and cooled, and the precipitate was
filtered off and washed in succession with ethanol,
10% hydrochloric acid, water, and ethanol again. Yield
1.6 g, mp 195–260°C; recrystallization from dioxane
gave 1.0 g (50%) of compound IId with mp 270–
272°C. UV spectrum, λmax, nm (logε): 207 (4.51),
240 sh (4.18), 316 (4.08). IR spectrum, ν, cm–1: 1654
(C=O), 1519 (NO2, asym.), 1356 (NO2, sym.). 1H NMR
spectrum (200 MHz), δ, ppm: 3.93 s (3H, OMe), 7.25 d
7.35–7.51 m (20H, Ph), 7.66 s and 7.72 s (1H, 3-H),
8.43 s and 8.62 s (1H, 1-H). 13C NMR spectrum
(100 MHz), δC, ppm: 49.90 and 51.22 (OMe); 58.40
and 62.34 (C4); 89.16 and 90.87 (C6); 105.76 and
106.67 (C5); 127.58, 127.78, 127.88, 128.06, 128.82,
128.91, 128.97, 129.15, 129.19, 129.42, 129.75, 129.92
(Carom); 132.11 and 132.39 (C13); 134.21 and 134.59
(C7); 153.75 and 154.15 (C2). Mass spectrum, m/z
(Irel, %): 407 (4.9) and 405 (4.1) [M]+, 375 (2.0) and
373 (1.6) [M – MeOH], 329 (34.6) and 327 (35.9) [M –
MeOH – NO2], 294 (23.2) [M – MeOH – Br], 278
(14.5), 253 (6.9), 251 (7.9), 249 (10.4), 247 (20.1), 218
(12.5), 171 (10.5), 162 (59.9), 136 (100), 134 (11.8),
132 (19.7), 105 (32.6), 104 (49.9), 103 (7.8), 102
(14.4), 77 (37.9). Found, %: C 50.20; H 3.85; Br 19.35;
N 10.25. [M]+ 405.0321. C17H16BrN3O4. Calculated,
%: C 50.26; H 3.97; Br 19.67; N 10.34. M 405.0324.
3
(1H, 11-H, J = 8.7 Hz), 7.51–7.62 m (6H, 12-H,
4
C6H5), 7.85 d (1H, 8-H, J = 2.1 Hz), 11.17 br.s (1H,
NH). 13C NMR spectrum (50 MHz), δC, ppm: 56.66
(OMe); 110.72 (C9); 112.62 (C11); 127.23 (C5); 127.40,
128.27, 128.58, 128.66 (Carom); 131.02 (C13); 132.33
(C7); 132.67 (C8); 152.29 (C6); 156.17 (C4); 157.64
(C10); 169.20 (C2). Mass spectrum, m/z (Irel, %): 403
(26.8) and 401 (24.8) [M]+, 388 (7.2) and 386 (7.5)
[M – Me], 375 (7.1) and 373 (9.0) [M – CO], 357
(13.5) and 355 (11.2) [M – NO2], 242 (11.0), 240
(12.0), 214 (14.8), 212 (13.8), 122 (13.8), 105 (100),
104 (39.1), 77 (80.9). Found, %: C 50.52; H 3.19;
Br 20.10; N 10.17. [M]+ 401.0017. C17H12BrN3O4.
Calculated, %: C 50.76; H 3.01; Br 19.87; N 10.45.
M 401.0011.
The methanol–pyridine filtrate was poured into
150 ml of water, and the precipitate was filtered off,
washed in succession with water, 10% hydrochloric
acid, water again, and methanol, and dried in air to
isolate 1.6 g (36%) of compound IIa, mp 249–250°C
(from EtOH); published data [5]: mp 248–251°C.
5-Bromo-4-(3-bromo-4-methoxyphenyl)-6-
methoxy-5-nitro-6-phenyl-3,4,5,6-tetrahydropyri-
midin-2(1H)-one (IIId) (a mixture of stereoisomers
A and B) was synthesized as described above for com-
pound IIIa. A mixture of 1.0 g (2.5 mmol) of com-
pound Id and 0.5 g (3 mmol) of bromine in 8 ml of
chloroform was stirred for 3 days at room temperature.
Treatment of the mixture afforded 0.2 g (15%) of
a mixture of diastereoisomers IIId-A and IIId-B with
mp 205–206°C (from EtOH–dioxane). IR spectrum, ν,
cm–1: 1689, 1675 sh (C=O); 1560 (NO2, asym.); 1330
By diluting the dioxane mother liquor with water
we isolated a mixture of mono- and dibromo-substi-
tuted compounds (according to the mass spectral data).
5-Bromo-6-methoxy-5-nitro-4,6-diphenyl-3,4,5,6-
tetrahydropyrimidin-2(1H)-one (IIIa) (a mixture of
stereoisomers A and B). A solution of 2.7 g
(17 mmol) of bromine in 10 ml of chloroform was
added to a suspension of 4.4 g (15 mmol) of compound
Ia in 40 ml of chloroform. The mixture was stirred for
10 h at room temperature and was left to stand for
10 days. A solid gradually separated from the solution;
it was filtered off, washed with chloroform, and dis-
persed in 50 ml of methanol, 4 ml of pyridine was
added, and the mixture was kept for 24 h and was then
heated for 5 h under reflux. The precipitate was filtered
off, washed in succession with 10% hydrochloric acid,
water, and methanol, and dissolved in hot methanol,
the solution was cooled, and the product was precip-
itated with water, filtered off, and dried in air. Yield of
diastereoisomer mixture IIIa-A/IIIa-B 2.4 g (40%),
mp 214–216°C (from MeOH). IR spectrum, ν, cm–1:
1689, 1676 sh (C=O); 1560 (NO2, asym.); 1339 (NO2,
1
(NO2, sym.). H NMR spectrum (200 MHz), δ, ppm:
3.18 s and 3.23 s (3H, OMe), 3.84 s (6H, OMe), 5.55 s
and 5.98 s (1H, 4-H), 7.07 d and 7.12 d (1H, 11-H,
3J11,12 = 4.3 Hz), 7.30–7.48 m (6H, 12-H, C6H5), 7.57 d
4
and 7.68 d (1H, 8-H, J8,12 = 2 Hz), 7.75 s and 7.81 s
(1H, 3-H), 8.50 s and 8.68 s (1H, 1-H). 13C NMR spec-
trum (50 MHz), δC, ppm: 49.87 and 51.19 (6-OMe);
56.26 (10-OMe); 57.36 and 61.21 (C4); 89.11 and
90.80 (C6); 105.81 and 106.43 (C5); 109.65 and 109.90
(C9); 111.78 and 112.00 (C11); 127.53, 127.83, 128.83,
128.85, 129.72, 130.26, and 130.65 (Carom); 132.03 and
132.31 (C13); 133.51 and 134.20 (C7); 153.66 and
154.09 (C2); 155.99 (C10). Mass spectrum, m/z (Irel, %):
517 (2.1), 515 (3.9), 513 (2.3) [M]+, 439 (8.2), 437
(15.6) i 435 (9.2) [M – MeOH – NO2], 404 (6.5) and
402 (5.7) [M – MeOH – Br], 359 (6.0), 357 (12.0) and
1
sym.). H NMR spectrum (400 MHz), δ, ppm: 3.20 s
and 3.25 s (3H, OMe), 5.57 s and 6.03 s (1H, 4-H),
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SEDOVA et al.
422
7. Roedig, A., Methoden der organischen Chemie
(Houben–Weyl), Müller, E., Bayer, O., Meerwein, H.,
and Ziegler, K., Eds., Stuttgart: Georg Thieme, 1960,
4th ed., vol. 5, part 4, p. 269.
355 (5.3), 242 (12.7) and 240 (11.7), 215 (6.1) and 213
(7.4), 214 (11.2) and 212 (10.7), 162 (64.0), 136 (100),
134 (9.4), 132 (4.0), 105 (43.0), 104 (46.0), 103 (9.3),
102 (8.1), 77 (44.6). Found, %: C 42.58; H 3.53;
Br 29.70; N 7.73. [M]+ 512.9532. C18H17Br2N3O5·
0.25C4H8O2. Calculated, %: C 42.47; H 3.57; Br 29.75;
N 7.82. M 512.9536.
8. Remennikov, G.Ya., Kravchenko, S.A., Kapran, N.A.,
and Pirozhenko, V.V., Ukr. Khim. Zh., 2000, vol. 66,
p. 111.
9. Tee, O.S. and Paventi, M., J. Org. Chem., 1980, vol. 45,
From the methanol–pyridine filtrate we isolated
0.65 g (64%) of compound IId, mp 269–271°C (from
dioxane).
p. 2072.
10. Oleinik, I.V., Zagulyaeva, O.A., Grigorkina, O.A., and
Mamaev, V.P., Khim. Geterotsikl. Soedin., 1991, p. 1110.
Thermal decomposition of compound IIIa.
A 30-mg portion of compound IIIa was heated for
5 min at 230°C. The resulting melt was recrystallized
from ethanol. The product was identical to IIa in the
melting point (248–251°C) and IR spectrum [5].
11. Tee, O.S. and Berks, C.G., J. Org. Chem., 1980, vol. 45,
p. 830; Miyashita, O., Kasahara, T., and Matsumura, K.,
Chem. Pharm. Bull., 1982, vol. 30, p. 2333; Brown, D.J.,
The Pyrimidines. Supplement II, New York: Wiley,
1985, pp. 438, 441.
12. Rybalova, T.V., Sedova, V.F., Gatilov, Yu.V., and
Shkurko, O.P., Zh. Strukt. Khim., 2002, vol. 43, p. 580;
Rybalova, T.V., Sedova, V.F., Gatilov, Yu.V., and Shkur-
ko, O.P., Zh. Strukt. Khim., 2004, vol. 45, p. 302.
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