Reaction of hexahydropyirimidine-2,4,6-trione with naphthalen-2-amine and benzaldehydes

Article abstract of DOI:10.1134/S1070428007030190

Previously unknown 12-aryl-7,8,9,10,11,12-hexahydrobenzo[f]pyrimido[4,5-b] quinoline-9,11-diones were synthesized by three-component condensation of naphthalen-2-amine with substituted benzaldehydes and barbituric acid through intermediate 5-benzylidenebarbituric acids. Nauka/Interperiodica 2007.

Full text of DOI:10.1134/S1070428007030190

ISSN 1070-4280, Russian Journal of Organic Chemistry, 2007, Vol. 43, No. 3, pp. 432–438. © Pleiades Publishing, Ltd., 2007.
Original Russian Text © N.G. Kozlov, L.I. Basalaeva, 2007, published in Zhurnal Organicheskoi Khimii, 2007, Vol. 43, No. 3, pp. 433–438.
Reaction of Hexahydropyirimidine-2,4,6-trione
with Naphthalen-2-amine and Benzaldehydes
N. G. Kozlov and L. I. Basalaeva
Institute of Physical Organic Chemistry, National Academy of Sciences of Belarus,
ul. Surganova 13, Minsk, 220072 Belarus
e-mail: loc@ifoch.bas-net.by
Received February 22, 2006
Abstract—Previously unknown 12-aryl-7,8,9,10,11,12-hexahydrobenzo[f]pyrimido[4,5-b]quinoline-9,11-di-
ones were synthesized by three-component condensation of naphthalen-2-amine with substituted benzalde-
hydes and barbituric acid through intermediate 5-benzylidenebarbituric acids.
DOI: 10.1134/S1070428007030190
IIw and pyrimidinetrione III. The reactions were
carried out by heating equimolar amounts of the reac-
tants in boiling butanol for 30–40 min, and the prod-
ucts were 12-aryl-7,8,9,10,11,12-hexahydrobenzo[f]-
pyrimido[4,5-b]quinoline-9,11-diones VIa–VIu
(Scheme 1).
Hexahydropyrimidine-2,4,6-trione (barbituric acid)
constitutes a structural base of numerous medical
agents exhibiting antispasmodic, soporific, and narcot-
ic activity [1–3]. Apart from medical practice, deriva-
tives of barbituric acid are used as antioxidants and
lignin chromophores [4–6]. Therefore, syntheses of
new barbituric acid derivatives attract interest from
both theoretical and practical viewpoints. Barbituric
acid is highly reactive. Its hexahydropyrimidine pos-
sesses four labile hydrogen atoms, those attached to C5
being especially active. Barbituric acid readily under-
goes alkylation, and its condensations with ketones and
aldehydes are well known [7, 8].
Taking into account our previous data on the three-
component condensation involving naphthalen-2-
amine, benzaldehydes, and 1,3-diketones [11] and the
structure of final products VI, two possible reaction
pathways were presumed (Scheme 2). Both these are
equally probable, for the synthesis of Schiff bases IV
from naphthalen-2-amine, followed by their hetero-
cyclization with CH acids, and the condensation of
aldehydes with barbituric acid to form 5-benzylidene
derivatives V are well known [12, 13].
The present work continues our previous studies
[9, 10] on cascade heterocyclizations of naphthalen-2-
amine with substituted benzaldehydes and CH acids.
We examined three-component condensation of naph-
thalen-2-amine (I) with substituted benzaldehydes IIa–
The first reaction pathway includes formation of
unstable intermediate A which then decomposes into
Scheme 1.
R
2
1
3
4
O
O
12
11
NH2
CHO
HN
NH
NH
9
+
+
R
5
O
O
N
N
H
O
6
H
I
IIa–IIw
III
VIa–VIu
R = H (a), 4-Br (b), 4-O2N (c), 4-i-Pr (d), 4-Ph (e), 4-HO (f), 4-MeO (g), 3-Br (h), 3-O2N (i), 3-HO (j), 2-Cl (k), 2-O2N (l),
2-HO (m), 2-MeO (n), 2,4-Cl2 (o), 2-Cl-6-F (p), 3,4-(HO)2 (q), 2,4-(MeO)2 (r), 3,4-(MeO)2 (s), 3-MeO-4-HO (t), 3-EtO-4-HO (u),
4-Me2N (v), 4-Et2N (w).
432

REACTION OF HEXAHYDROPYIRIMIDINE-2,4,6-TRIONE
433
Scheme 1.
H
O
N
O
HN
R
R
III
I
+
IIa–IIw
O
N
NH
IV
A
H
N
O
O
H
N
HN
O
O
R
I
R
VIa–VIu
O
HN
–I
NH2
O
Va–Vw
B
I
II
+
III
V
B
VI
5-benzylidenebarbituric acid V and naphthalene-2-
amine (I). The highest electron density in molecule I is
localized on the carbon atom in the α-position with
respect to the amino group; addition at the double C=C
bond of V gives 5-[2-aminonaphthyl(aryl)methyl]-
hexahydropyrimidine-2,4,6-trione B, and hetero-
cyclization of the latter with elimination of water mol-
ecule yields the final product, 12-aryl-7,8,9,10,11,12-
hexahydrobenzo[f]pyrimido[4,5-b]quinoline-9,11-di-
one VI. According to the second pathway, condensa-
tion of substituted benzaldehyde with barbituric acid
gives 5-benzylidenebarbituric acid V having an elec-
trophilic carbon atom at the exocyclic double C=C
bond; intermediate V is capable of taking up naphtha-
len-2-amine at the α-carbon atom of the latter with
formation of structure B. Eventually, the examined
three-component condensation of naphthalen-2-amine
with benzaldehydes and barbituric acid may be regard-
ed as the reaction of compounds V with the amine.
ity on the exocyclic carbon atom at the double C=C
bond, thus favoring addition of naphthalene-2-amine,
and the yield of compounds VIb–VIe attains 55–70%.
The same substituents in the meta position do not
affect the reaction to an appreciable extent, so that the
yield of products VIh and VIi is smaller.
Electron-donor substituents in the benzene ring in-
crease the electron density on the electrophilic reaction
center of barbituric acid derivatives V as a result of
π-conjugation with the double bond, and the formation
of new C–C bond is hindered. Therefore, the yields of
compounds VIf and VIg are as poor as 30 and 37%,
respectively, while 5-benzylidenebarbituric acids Vv
and Vw fail to react with naphthalen-2-amine at all.
From the reaction mixtures obtained from naphthalen-
2-amine, barbituric acid, and aldehydes IIv and IIw,
only the corresponding barbituric acid derivatives Vv
and Vw were isolated. On the other hand, electron-
donor groups in the meta position of the benzene ring
in compounds V do not hamper the process so strong-
ly, and the yield of 12-(3-hydroxyphenyl)-7,8,9,10,-
11,12-hexahydrobenzo[f]pyrimido[4,5-b]quinoline-
9,11-dione (VIj) was greater by 12% than that of
12-(4-hydroxyphenyl)-7,8,9,10,11,12-hexahydro-
benzo[f]pyrimido[4,5-b]quinoline-9,11-dione (VIf).
Increase in the yield of final products was observed in
the three-component condensation with disubstituted
benzaldehydes containing two electron-donor substit-
uents in the meta and para positions. The yields of
In fact, 5-benzylidenebarbituric acids Va–Vw were
synthesized by reactions of aldehydes II with barbitur-
ic acid (III) in alcohol, and their subsequent treatment
with amine I under the same conditions gave 12-aryl-
7,8,9,10,11,12-hexahydrobenzo[f]pyrimido[4,5-b]-
quinoline-9,11-diones VIa–VIu.
Some general relations holding in the examined
condensation should be noted. Electron-withdrawing
groups in the para position of the benzene ring in
5-benzylidenebarbituric acids reduce the electron dens-
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KOZLOV, BASALAEVA
434
Chemical shifts of carbon nuclei in the 13C NMR spectrum
of compound VIb (10% solution in DMSO-d6)
1
structure was confirmed by the H NMR spectra. The
singlet at δ 5.60–6.20 ppm was assigned to 12-H, and
that at δ 8.80–9.29 ppm, to 7-H. A large difference in
the chemical shifts of these protons indicates that they
are separated by five bonds and that no spin–spin
coupling exists between them. The spectra also con-
tained singlets in the regions δ 10.08–10.38 and 10.35–
10.65 ppm due to NH protons in the pyrimidine ring of
compound VI.
Atom
δ, ppm
C1
122.65 d
127.08 d
123.93 d
128.68 d
130.43 s
128.53 d
117.49 d
133.83 s
145.00 s
150.18 s
162.83 s
086.21 s
035.85 d
114.92 s
130.80 s
145.89 s
129.82 d
130.97 d
119.10 s
C2
C3
C4
C4a
C5
C6
C6a
C7a
C9
C11
C11a
C12
C12a
C12b
C1'
C2'
C3'
C4'
Analysis of the H–1H and direct 13C–1H coupling
1
constants in the HMBC spectrum of compound VIb
allowed us to identify signals from carbon atoms in
its molecule (see table). The C12a signal appears at
δC 114.92 ppm; it showed cross peaks due to couplings
with protons resonating at δ 5.72 (12-H) and 9.18 ppm
(NH proton in the 1,4-dihydropyridine ring). The ab-
sence of correlation between 7-H, on the one hand, and
C12 bearing the aryl group and C1' of the phenyl sub-
stituent, on the other, provides an additional proof for
the assumed structure.
The IR spectra of VIa–VIu contained absorption
bands corresponding to stretching vibrations of the
N–H bonds (3520–3185 cm–1) and carbonyl groups
(1729–1701 cm–1). Compounds VIb and VIh charac-
teristically showed a strong absorption band at 581 and
578 cm–1, respectively, due to stretching vibrations of
the C–Br bond; strong bands belonging to symmetric
and antisymmetric stretching vibrations of the nitro
groups in VIc, VIi, and VIl were located at 1398–1396
and 1545–1542 cm–1, respectively.
12-(3,4-dihydroxyphenyl)-, 12-(3,4-dimethoxyphenyl)-,
12-(4-hydroxy-3-methoxyphenyl)-, and 12-(3-ethoxy-
4-hydroxyphenyl)-7,8,9,10,11,12-hexahydrobenzo[f]-
pyrimido[4,5-b]quinoline-9,11-diones VIq, VIs, VIt,
and VIu were 49, 53, 62, and 59%, respectively; i.e.,
they exceeded the yields of 12-(4-hydroxyphenyl)- and
12-(4-methoxyphenyl)-substituted analogs VIf and
VIg. Presumably, the meta-substituent in Vq, Vs, Vt,
and Vu partially eliminates electronic effect of the
para-hydroxy or para-alkoxy group due to distortion
of planar structure of molecule V [14].
The base peak in the mass spectra of VIa–VIu is
that with m/z 264 ([M – C6H4]+, Irel 100%); also, ion
peak with m/z 265 ([M – C6H4 +1]+, Irel 65–70%) is
present; the molecular ion peaks [M]+ had a relative
intensity of 28 to 35%. Positive fragment ions with
m/z 111 (Irel 28–33%), 134 (Irel 56–60%), 139 (Irel 90–
96%), 148 (Irel 72–78%), 153 (Irel 47–55%), 166
(Irel 32–39%), and 222 (Irel 18–23%) are formed from
the [M – C6H4]+ ion; they are observed in the mass
spectra of all compounds VIa–VIu and therefore are
not given in Experimental (except for [M]+).
Substituents in the ortho position are likely to exert
steric effect on the reaction center in 5-benzylidene-
barbituric acids V. Thus the yield of o-nitrophenyl
derivative VIl is slightly lower despite positive elec-
tronic effect of the nitro group. Steric effect of the
ortho-substituent is more distinct in 5-(2-methoxyben-
zylidene)hexahydropyrimidine-2,4,6-trione (Vn): the
yield of 12-(2-methoxyphenyl)-7,8,9,10,11,12-hexa-
hydrobenzo[f]pyrimido[4,5-b]quinoline-9,11-dione
(VIn) is as low as 14%.
EXPERIMENTAL
The IR spectra were recorded on a Nicolet Protege-
460 spectrometer with Fourier transform from samples
prepared as thin films of KBr pellets. The NMR spec-
tra were measured on a Bruker AC-500 spectrometer at
12-Aryl-7,8,9,10,11,12-hexahydrobenzo[f]pyrimido-
[4,5-b]quinoline-9,11-diones VIa–VIu were isolated as
crystalline substances melting above 320°C. Their
500 MHz for H and 125 MHz for 13C from 5% solu-
1
tions in DMSO-d6 using tetramethylsilane as internal
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REACTION OF HEXAHYDROPYIRIMIDINE-2,4,6-TRIONE
435
reference. The mass spectra were run on a Hewlett–
Packard HP 5890/5972 GC–MS system (electron
impact, 70 eV, HP-5MS column).
Yield 65%, yellow crystals. IR spectrum, ν, cm–1:
3388, 3196, 3075, 1707, 1645, 1591, 1545, 1471,
1
1396, 1349, 1236, 1111, 820, 749, 697, 579. H NMR
spectrum, δ, ppm: 5.90 s (1H, 12-H), 7.30–8.10 m
(10H, Harom), 8.96 s (1H, 7-H), 10.25 s (1H, NH),
10.50 s (1H, NH). Mass spectrum, m/z (Irel, %): 386
(30) [M]+. Found, %: C 65.24; H 3.63; N 14.47.
C21H14N4O4. Calculated, %: C 65.28; H 3.65; N 14.50.
5-Benzylidenehexahydropyrimidine-2,4,6-triones
Va–Vw were synthesized by heating equimolar
amounts of barbituric acid (III) and substituted benz-
aldehyde IIa–IIw in boiling alcohol for 20–30 min.
Their physical constants coincided with those reported
in [15–17].
12-(4-Isopropylphenyl)-7,8,9,10,11,12-hexa-
hydrobenzo[f]pyrimido[4,5-b]quinoline-9,11-dione
(VId). Yield 60%, colorless crystals. IR spectrum, ν,
cm–1: 3418, 3185, 3072, 2959, 2870, 1708, 1662, 1647,
1598, 1534, 1469, 1396, 1300, 1232, 814, 591. 1H NMR
spectrum, δ, ppm: 1.20 d [6H, CH(CH3)2, J = 7.0 Hz],
2.26 m [1H, CH(CH3)2], 5.70 s (1H, 12-H), 7.00 d
(1Harom, J = 6.9 Hz), 7.19 d (1Harom, J = 7.0 Hz.), 7.30–
7.50 m (5Harom), 7.80 and 7.96 m (3H, Harom), 8.90 s
(1H, 7-H), 10.28 s (1H, NH), 10.54 s (1H, NH). Mass
spectrum, m/z (Irel, %): 383 (33) [M]+. Found: %
C 75.21; H 5.51; N 11.00. C24H21N3O2. Calculated, %:
C 75.19; H 5.48; N 10.97.
12-Aryl-7,8,9,10,11,12-hexahydrobenzo[f]pyri-
mido[4,5-b]quinoline-9,11-diones VIa–VIu (general
procedure). a. A solution of 1.43 g (0.01 mol) of naph-
thalene-2-amine (I), 0.01 mol of substituted benzalde-
hyde IIa–IIw, and 1.3 g (0.01 mol) of barbituric acid
III in 20 ml of butanol was heated under reflux until
a solid product began to separate from the solution
(30–60 min). After cooling, te precipitate was filtered
off, washed with hot water and diethyl ether, and re-
crystallized from alcohol–benzene (1:1).
b. A solution of 0.01 mol of 5-benzylidenehexa-
hydropyrimidine-2,4,6-trione Va–Vw and 0.01 mol of
naphthalen-2-amine (I) in 20 ml of butanol was heated
under reflux until a solid product began to separate
from the solution. After cooling, the precipitate was
filtered off, and recrystallized from a 1:1 alcohol–ben-
zene mixture.
12-(Biphenyl-4-yl)-7,8,9,10,11,12-hexahydro-
benzo[f]pyrimido[4,5-b]quinoline-9,11-dione (VIe).
Yield 55%, colorless crystals. IR spectrum, ν, cm–1:
3412, 3176, 2945, 2876, 1714, 1667, 1640, 1591,
1538, 1471, 1396, 1322, 1236, 814, 591. 1H NMR spec-
trum, δ, ppm: 5.78 s (1H, 12-H); 6.90–7.10 m, 7.20–
7.50 m, and 7.60–7.80 m (13H, Harom); 7.80 d (1H,
12-Phenyl-7,8,9,10,11,12-hexahydrobenzo[f]pyri-
mido[4,5-b]quinoline-9,11-dione (VIa). Yield 60%,
colorless crystals. IR spectrum, ν, cm–1: 3191, 3073,
2957, 1705, 1642, 1590, 1541, 1470, 1449, 1390,
H
arom, J = 7.2 Hz.); 8.00 d (1H, Harom, J = 6.8 Hz);
9.10 s (1H, 7-H); 10.32 s (1H, NH); 10.60 s (1H, NH).
Mass spectrum, m/z (Irel, %): 417 (30) [M]+, 154 (43)
[C6H5C6H5]+. Found, %: C 77.65; H 4.54; N 10.10.
C27H19N3O2. Calculated, %: C 77.69; H 4.56; N 10.07.
1
1235, 813, 581. H NMR spectrum, δ, ppm: 5.70 s
(1H, 12-H), 6.80–7.30 m and 7.60–7.90 m (11H,
H
arom), 8.80 s (1H, 7-H), 10.08 s (1H, NH), 10.35 s
12-(4-Hydroxyphenyl)-7,8,9,10,11,12-hexahydro-
benzo[f]pyrimido[4,5-b]quinoline-9,11-dione (VIf).
Yield 30%, colorless crystals. IR spectrum, ν, cm–1:
3320, 3182, 3065, 2952, 2864, 1710, 1660, 1657, 1588,
1533, 1462, 1312, 1244, 816, 593. 1H NMR spectrum,
δ, ppm: 5.70 s (1H, 12-H); 6.50 d (1H, Harom, J =
6.7 Hz); 6.60–6.90 m, 7.50–7.70 m, and 8.10–8.30 m
(9H, Harom, and 1H, OH); 9.08 s (1H, 7-H); 10.28 s
(1H, NH); 10.37 s (1H, NH). Mass spectrum, m/z
(Irel, %): 357 (27) [M]+. Found, %: C 70.57; H 4.24;
N 11.79. C21H15N3O3. Calculated, %: C 70.58; H 4.23;
N 11.76.
(1H, NH). Mass spectrum, m/z (Irel, %): 341 (35) [M]+.
Found, %: C 73.87; H 4.35; N 12.33. C21H15N3O2. Cal-
culated, %: C 73.90; H 4.39; N 12.31.
12-(4-Bromophenyl)-7,8,9,10,11,12-hexahydro-
benzo[f]pyrimido[4,5-b]quinoline-9,11-dione (VIb).
Yield 70%, colorless crystals. IR spectrum, ν, cm–1:
3187, 3070, 2952, 1712, 1654, 1597, 1564, 1473,
1
1441, 1389, 1235, 815, 581. H NMR spectrum, δ,
ppm: 5.70 s (1H, 12-H); 7.20 m, 7.30–7.50 m, and
7.80–7.90 m (10H, Harom); 9.10 s (1H, 7-H); 10.30 s
(1H, NH); 10.60 s (1H, NH). Mass spectrum, m/z
(Irel, %): 420 (31) [M]+. Found, %: C 60.02; H 3.36;
Br 19.00; N 10.04. C21H14BrN3O2. Calculated, %:
C 60.00; H 3.33; Br 19.04; N 10.00.
12-(4-Methoxyphenyl)-7,8,9,10,11,12-hexahydro-
benzo[f]pyrimido[4,5-b]quinoline-9,11-dione (VIg).
Yield 37%, colorless crystals. IR spectrum, ν, cm–1:
3425, 3273, 3250, 3221, 3176, 3090, 2922, 2857, 1708,
1634, 1600, 1552, 1447, 1392, 1294, 1255, 1236, 1110,
12-(4-Nitrophenyl)-7,8,9,10,11,12-hexahydro-
benzo[f]pyrimido[4,5-b]quinoline-9,11-dione (VIc).
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KOZLOV, BASALAEVA
436
1
1045, 871, 821, 758, 581. H NMR spectrum, δ, ppm:
3.60 s (3H, OCH3), 5.69 s (1H, 12-H), 6.70 d (1H,
Harom, J = 6.9 Hz), 7.10–7.42 m and 7.80–7.85 m (8H,
Harom), 7.90 d (1H, Harom, J = 7.3 Hz), 8.98 s (1H, 7-H),
10.20 s (1H, NH), 10.50 s (1H, NH). Mass spectrum,
m/z (Irel, %): 371 (31) [M]+. Found, %: C 71.19;
H 4.53; N 11.56. C22H17N3O3. Calculated, %: C 71.15;
H 4.58; N 11.32.
Harom, J = 6.4 Hz); 9.10 s (1H, 7-H); 10.28 s (1H, NH);
10.50 s (1H, NH). Mass spectrum, m/z (Irel, %): 375
(29) [M]+. Found, %: C 67.16; H 3.77; Cl 9.38;
N 11.24. C21H14ClN3O2. Calculated, %: C 67.20;
H 3.73; Cl 9.33; N 11.20.
12-(2-Nitrophenyl)-7,8,9,10,11,12-hexahydro-
benzo[f]pyrimido[4,5-b]quinoline-9,11-dione (VIl).
Yield 53%, yellow crystals. IR spectrum, ν, cm–1:
3418, 3235, 3214, 3072, 2921, 1728, 1633, 1587, 1542,
1526, 1463, 1398, 1384, 1355, 1230, 821, 743, 690.
1H NMR spectrum, δ, ppm: 5.60 s (1H, 12-H), 7.10–
12-(3-Bromophenyl)-7,8,9,10,11,12-hexahydro-
benzo[f]pyrimido[4,5-b]quinoline-9,11-dione (VIh).
Yield 57%, colorless crystals. IR spectrum, ν, cm–1:
3185, 3064, 2953, 1712, 1656, 1600, 1561, 1478, 1437,
7.40 m and 7.60–7.90 m (9H, Harom), 8.38 d (1H, Harom
,
1
1392, 1235, 815, 578. H NMR spectrum, δ, ppm:
J = 7.0 Hz), 9.20 s (1H, 7-H), 10.30 s (1H, NH),
10.60 s (1H, NH). Mass spectrum, m/z (Irel, %): 386
(35) [M]+. Found, %: C 65.29; H 3.65; N 14.52.
C21H14N4O4. Calculated, %: C 65.28; H 3.65; N 14.50.
5.79 s (1H, 12-H); 7.10–7.18 m, 7.20–7.30 m, and
7.35–7.50 m (10H, Harom); 9.10 s (1H, 7-H); 10.40 s
(1H, NH); 10.60 (1H, NH). Mass spectrum, m/z
(Irel, %): 420 (34). Found, %: C 59.57; H 3.31;
Br 18.97; N 10.05. C21H14BrN3O2. Calculated, %:
C 60.00; H 3.33; Br 19.04; N 10.00.
12-(2-Hydroxyphenyl)-7,8,9,10,11,12-hexahydro-
benzo[f]pyrimido[4,5-b]quinoline-9,11-dione (VIm).
Yield 25%, colorless crystals. IR spectrum, ν, cm–1:
3318, 3190, 3068, 2954, 2873, 1716, 1660, 1653, 1587,
12-(3-Nitrophenyl)-7,8,9,10,11,12-hexahydro-
benzo[f]pyrimido[4,5-b]quinoline-9,11-dione (VIi).
Yield 43%, yellow crystals. IR spectrum, ν, cm–1:
3416, 3237, 3218, 3076, 2924, 1729, 1637, 1589,
1545, 1528, 1469, 1398, 1384, 1355, 1231, 822, 746,
1
1528, 1460, 1311, 1248, 815, 596. H NMR spectrum,
δ, ppm: 5.90 s (1H, 12-H); 6.65–6.90 m, 7.40–7.64 m,
and 8.00–8.20 m (10H, Harom); 9.24 s (1H, 7-H);
10.10 s (1H, NH); 10.60 s (1H, NH); 10.90 s (1H,
OH). Mass spectrum, m/z (Irel, %): 375 (29) [M]+.
Found, %: C 70.54; H 4.24; N 11.78. C21H15N3O3. Cal-
culated, %: C 70.58; H 4.23; N 11.76.
1
691. H NMR spectrum, δ, ppm: 5.90 s (1H, 12-H),
7.30–7.50 m (4H, Harom), 7.70 d (1H, Harom, J =
6.8 Hz), 7.82–7.94 m (4H, Harom), 8.10 s (1H, Harom),
9.29 s (1H, 7-H), 10.40 s (1H, NH), 10.65 s (1H, NH).
Mass spectrum, m/z (Irel, %): 386 (34) [M]+. Found, %:
C 65.21; H 3.67; N 14.54. C21H14N4O4. Calculated, %:
C 65.28; H 3.65; N 14.50.
12-(2-Methoxyphenyl)-7,8,9,10,11,12-hexahydro-
benzo[f]pyrimido[4,5-b]quinoline-9,11-dione (VIn).
Yield 14%, colorless crystals. IR spectrum, ν, cm–1:
3422, 3273, 3250, 3226, 3172, 3083, 2924, 2856, 1701,
1633, 1601, 1558, 1447, 1398, 1291, 1255, 1238, 1113,
12-(3-Hydroxyphenyl)-7,8,9,10,11,12-hexahydro-
benzo[f]pyrimido[4,5-b]quinoline-9,11-dione (VIj).
Yield 42%, colorless crystals. IR spectrum, ν, cm–1:
3320, 3182, 3071, 2954, 2864, 1710, 1665, 1652, 1583,
1531, 1462, 1310, 1248, 815, 591. 1H NMR spectrum,
δ, ppm: 5.76 s (1H, 12-H); 6.62–6.90 m, 7.60–7.75 m,
and 8.10–8.30 m (10H, Harom, and 1H, OH); 9.14 s
(1H, 7-H); 10.26 s (1H, NH); 10.34 s (1H, NH). Mass
spectrum, m/z (Irel, %): 357 (26) [M]+. Found, %:
C 70.59; H 4.21; N 11.75. C21H15N3O3. Calculated, %:
C 70.58; H 4.23; N 11.76.
1
1045, 873, 821, 753, 587. H NMR spectrum, δ, ppm:
3.90 s (3H, OMe); 6.00 s (1H, 12-H); 6.70–6.75 m,
6.80–6.84 m, 7.00–7.10 m, 7.20–7.25 m, 7.28–7.30 m,
7.40–7.45 m, and 7.70–7.80 m (9H, Harom); 8.19 d (1H,
Harom, J = 7.7 Hz); 8.91 s (1H, 7-H); 10.20 s (1H, NH);
10.40 s (1H, NH). Mass spectrum, m/z (Irel, %): 371
(28) [M]+. Found, %: C 71.11; H 4.56; N 11.34.
C22H17N3O3. Calculated, %: C 71.15; H 4.58; N 11.32.
12-(2,4-Dichlorophenyl)-7,8,9,10,11,12-hexa-
hydrobenzo[f]pyrimido[4,5-b]quinoline-9,11-dione
(VIo). Yield 61%, colorless crystals. IR spectrum, ν,
cm–1: 3185, 3079, 2953, 1728, 1670, 1601, 1567, 1472,
12-(2-Chlorophenyl)-7,8,9,10,11,12-hexahydro-
benzo[f]pyrimido[4,5-b]quinoline-9,11-dione (VIk).
Yield 49%, colorless crystals. IR spectrum, ν, cm–1:
3185, 3075, 2954, 1719, 1652, 1608, 1561, 1474, 1431,
1
1436, 1395, 1230, 823, 572. H NMR spectrum, δ,
ppm: 5.90 s (1H, 12-H); 7.22 d (1H, Harom, J =
7.00 Hz); 7.30–7.38 m, 7.40–7.47 m, and 7.80–7.85 m
(7H, Harom); 8.00 d (1H, Harom, J = 6.8 Hz); 9.24 s (1H,
7-H); 10.30 s (1H, NH); 10.51 s (1H, NH). Mass spec-
trum, m/z (Irel, %): 409 (33) [M]+. Found, %: C 61.58;
1
1392, 1230, 817, 572. H NMR spectrum, δ, ppm:
6.00 s (1H, 12-H); 7.00–7.09 m and 7.10–7.15 m (2H,
Harom); 7.28–7.30 m, 7.30–7.38 m, and 7.40–7.46 m
(5H, Harom); 7.80–7.86 m (2H, Harom); 8.09 d (1H,
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 43 No. 3 2007

REACTION OF HEXAHYDROPYIRIMIDINE-2,4,6-TRIONE
437
H 3.15; Cl 17.07; N 10.30. C21H13Cl2N3O2. Calculated,
%: C 61.61; H 3.18; Cl 17.11; N 10.27.
Harom), 7.80–7.85 m (2H, Harom), 7.96 d (1H, Harom, J =
6.5 Hz), 9.10 s (1H, 7-H), 10.40 s (1H, NH), 10.60 s
(1H, NH). Mass spectrum, m/z (Irel, %): 401 (17) [M]+.
Found, %: C 68.84; H 4.77; N 10.49. C23H19N3O4. Cal-
culated, %: C 68.82; H 4.74; N 10.47.
12-(2-Chloro-6-fluorophenyl)-7,8,9,10,11,12-
hexahydrobenzo[f]pyrimido[4,5-b]quinoline-9,11-
dione (VIp). Yield 64%, colorless crystals. IR spec-
trum, ν, cm–1: 3433, 3272, 3212, 3075, 1706, 1659,
1633, 1601, 1555, 1471, 1445, 1396, 1235, 784, 775.
1H NMR spectrum, δ, ppm: 6.20 s (1H, 12-H); 7.10–
7.20 m, 7.24–7.36 m, 7.40–7.48 m, and 7.80–7.85 m
(9H, Harom); 9.27 s (1H, 7-H); 10.31 s (1H, NH);
10.50 s (1H, NH). Mass spectrum, m/z (Irel, %): 393
(33) [M]+. Found, %: C 64.14; H 3.36; N 10.71.
C21H13ClFN3O2. Calculated, %: C 64.12; H 3.31;
N 10.68.
12-(4-Hydroxy-3-methoxyphenyl)-7,8,9,10,11,12-
hexahydrobenzo[f]pyrimido[4,5-b]quinolin-9,11-di-
one (VIt). Yield 62%, colorless crystals. IR spectrum,
ν, cm–1: 3510, 3210, 3078, 1709, 1642, 1590, 1547,
1512, 1473, 1446, 1393, 1289, 1224, 1113, 817.
1H NMR spectrum, δ, ppm: 3.64 s (3H, OCH3), 5.63 s
(1H, 12-H), 6.47 d (1H, Harom, J = 7.2 Hz), 6.52 d (1H,
Harom, J = 7.4 Hz), 7.00 s (1H, Harom), 7.30–7.38 m and
7.40–7.44 m (3H, Harom), 7.79–7.82 m (2H, Harom),
7.96 d (1H, Harom, J = 7.00 Hz), 8.20 s (1H, OH),
8.96 s (1H, 7-H), 10.28 s (1H, NH), 10.53 s (1H, NH).
Mass spectrum, m/z (Irel, %): 387 (29) [M]+. Found, %:
C 68.24; H 4.42; N 10.88. C22H17N3O4. Calculated, %:
C 68.20; H 4.39; N 10.85.
12-(3,4-Dihydroxyphenyl)-7,8,9,10,11,12-hexa-
hydrobenzo[f]pyrimido[4,5-b]quinoline-9,11-dione
(VIq). Yield 49%, colorless crystals. IR spectrum, ν,
cm–1: 3285, 3170, 2951, 2873, 1709, 1665, 1582, 1531,
1
1464, 1307, 1239, 810, 592. H NMR spectrum, δ,
ppm: 5.70 s (1H, 12-H); 7.00–7.08 m, 7.12–7.19 m,
7.22–7.30 m, and 7.30–7.48 m (6H, Harom, and 2H,
OH); 7.80–7.84 m (2H, Harom); 7.90 d (1H, Harom, J =
7.04 Hz); 9.00 s (1H, 7-H); 10.26 s (1H, NH); 10.54 s
(1H, NH). Mass spectrum, m/z (Irel, %): 373 (32) [M]+.
Found, %: C 68.59; H 4.00; N 11.30. C21H15N3O4. Cal-
culated, %: C 68.56; H 4.02; N 11.26.
12-(3-Ethoxy-4-hydroxyphenyl)-7,8,9,10,11,12-
hexahydrobenzo[f]pyrimido[4,5-b]quinoline-9,11-
dione (VIu). Yield 59%, colorless crystals. IR spec-
trum, ν, cm–1: 3520, 3206, 3079, 1707, 1641, 1592,
1514, 1472, 1444, 1397, 1275, 1237, 1114, 816.
1H NMR spectrum, δ, ppm: 1.25 t (3H, OCH2CH3),
3.86–3.94 m (2H, OCH2CH3), 5.60 s (1H, 12-H),
6.40 d (1H, Harom, J = 7.2 Hz), 6.50–6.54 m (1H,
12-(2,4-Dimethoxyphenyl)-7,8,9,10,11,12-hexa-
hydrobenzo[f]pyrimido[4,5-b]quinoline-9,11-dione
(VIr). Yield 40%, colorless crystals. IR spectrum, ν,
cm–1: 3410, 3200, 3080, 1705, 1647, 1611, 1587, 1540,
1508, 1471, 1397, 1294, 1228, 1210, 1117, 1036, 829,
H
arom), 6.90 s (1H, Harom), 7.30–7.42 m (3H, Harom),
7.80–7.84 m (2H, Harom), 7.93 d (1H, Harom, J =
6.9 Hz), 8.60 s (1H, OH), 9.08 s (1H, 7-H), 10.38 s
(1H, NH), 10.60 s (1H, NH). Mass spectrum, m/z
(Irel, %): 401 (27) [M]+. Found, %: C 68.87; H 4.76;
N 10.51. C23H19N3O4. Calculated, %: C 68.82; H 4.74;
N 10.48.
1
815, 573. H NMR spectrum, δ, ppm: 3.60 s (3H,
OCH3), 3.85 s (3H, OCH3), 5.90 s (1H, 12-H), 6.35 d
(1H, Harom, J = 7.2 Hz), 6.49 s (1H, Harom), 7.10 d (1H,
Harom, J = 6.5 Hz), 7.26–7.32 m and 7.35–7.42 m (3H,
The authors are thankful to Prof. Tkachev A.V. for
H
arom), 7.70 d (1H, Harom, J = 7.0 Hz), 7.78 d (1H,
recording the 13C NMR spectrum of compound VIb.
Harom, J = 7.0 Hz.), 8.19 d (1H, Harom, J = 7.2 Hz),
8.90 s (1H, 7-H), 10.15 s (1H, NH), 10.40 s (1H, NH).
Mass spectrum, m/z (Irel, %): 401 (29) [M]+. Found, %:
C 68.77; H 4.78; N 10.50. C23H19N3O4. Calculated, %:
C 68.82; H 4.74; N 10.47.
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12-(3,4-Dimethoxyphenyl)-7,8,9,10,11,12-hexa-
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