A rapid and facile synthesis of new spiropyrimidines from 5-(2-arylethylidene-2-oxo)-1,3-dimethylpyrimidine-2,4,6-triones

Article abstract of DOI:10.1016/j.tet.2008.06.097

A series of new tetraazaspiro[5,5]-undec-4-ene-2,7,9,11-tetraones have been obtained by reaction of 5-(2-arylethylidene-2-oxo)-1,3-dimethylpyrimidine-2,4,6-triones with ureas. A three-component one-pot procedure to the spiranes synthesis was also developed. One-pot reaction of arylglyoxals, 1,3-dimethylbarbituric acid, and dimethylurea led to imidazolyl-1,3-dimethylbarbituric acids. Mechanisms of studied reactions were discussed.

Full text of DOI:10.1016/j.tet.2008.06.097

Tetrahedron 64 (2008) 8759–8765
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Tetrahedron
journal homepage: www.elsevier.com/locate/tet
A rapid and facile synthesis of new spiropyrimidines from
5-(2-arylethylidene-2-oxo)-1,3-dimethylpyrimidine-2,4,6-triones
Lali L. Gozalishvili a, Tetyana V. Beryozkina a, Irina V. Omelchenko b, Roman I. Zubatyuk b,
,
Oleg V. Shishkin b, Nadezhda N. Kolos a
*
a Organic Chemistry Department, V.N. Karazin Kharkiv National University, Svoboda sq. 4, 61077 Kharkiv, Ukraine
b STC ‘Institute of Single Crystals’, Lenina ave. 60, 61001 Kharkiv, Ukraine
a r t i c l e i n f o
a b s t r a c t
Article history:
A series of new tetraazaspiro[5,5]-undec-4-ene-2,7,9,11-tetraones have been obtained by reaction of
5-(2-arylethylidene-2-oxo)-1,3-dimethylpyrimidine-2,4,6-triones with ureas. A three-component one-
pot procedure to the spiranes synthesis was also developed. One-pot reaction of arylglyoxals, 1,3-di-
methylbarbituric acid, and dimethylurea led to imidazolyl-1,3-dimethylbarbituric acids. Mechanisms of
studied reactions were discussed.
Received 26 February 2008
Received in revised form 12 June 2008
Accepted 26 June 2008
Available online 28 June 2008
Ó 2008 Elsevier Ltd. All rights reserved.
Keywords:
Knoevenagel reaction
Spiropyrimidines
One-pot synthesis
a,b-Unsaturated ketones
Arylglyoxals
Ureas
1. Introduction
Moreover, spirocompounds based on barbituric acid show a high
hypnotic and sedative activity.14 Earlier we reported the synthesis of
It is well-known that enone systems are convenient and readily
available synthetic fragments in the preparation of various bio-
logically important heterocycles, especially nitrogen-containing
compounds, and also analogues of natural compounds.1–4 The vinyl
spiropyrolines15 obtained from 5,6-diamino-1,3-dimethyluracil and
a,b
-unsaturated ketones, and spirotetrahydropyridines16 produced
from 1,3-dimethylbarbituric acid, chalcones, and NH4OAc. In addi-
tion, the importance of pyrimidines with interesting pharmacolog-
ical activities has prompted many workers to synthesize a number of
pyrimidine derivatives.17,18
and carbonyl groups of a,b-unsaturated ketones form the common
system, and the reactions with nucleophilic reagents can proceed
either in the position 2 or 4 depending on polar influence of the
carbonyl group over the vinyl one.5
2. Results and discussions
Earlier, we found that the 1,2-nucleophilic addition to aromatic
a
,
b
-unsaturated ketones is typical for reactions with vicinal di-
amines, the nucleophilicity of which is considerably suppressed.6,7
At the same time, increase in the -deficiency of the vinylene bond
The targets of our research were 5-(2-arylethylidene-2-oxo)-
1,3-dimethylpyrimidine-2,4,6-triones 3a–g obtained by Knoeve-
nagel reaction of 1,3-dimethylbarbituric acid (1) and arylglyoxals
2a–g (Scheme 1). The reaction was accomplished in glacial acetic
acid at room temperature overnight. The structure of products 3a–g
was proved by 1H NMR and 13C NMR spectra and elemental analysis
data. The typical characteristic signal in their 1H NMR spectra is
a singlet corresponding to the vinylene protons at 8.00–8.50 ppm.
In the IR spectra, sharp bands were observed due to the stretching
vibration of all carbonyl groups (at 1663, 1676, and 1690 cmꢀ1) and
bands of C]C group (at 1630 cmꢀ1).
p
or utilization of more nucleophilic amino groups leads exclusively
to 1,4-addition.8,9 The mutual influence of the ethylene and car-
bonyl fragments on an enone reactivity is especially pronounced
in cyclic
condensation pathways for cyclic
their acyclic analogues may differ considerably, this is determined
not only by s-cis-configuration, but also by the stereochemistry of
the cyclic fragment.12,13
a,b
-unsaturated ketones with fixed geometry.10,11 The
a,b-unsaturated ketones and
We also examined the behavior of enones 3a–g in the reactions
with typical 1,4-binucleophilesddiamines 4a,b, and also with
ureas 5a–e (Scheme 2). Heating of the compound 3a with
* Corresponding author.
E-mail address: kolos@univer.kharkov.ua (N.N. Kolos).
0040-4020/$ – see front matter Ó 2008 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2008.06.097

8760
L.L. Gozalishvili et al. / Tetrahedron 64 (2008) 8759–8765
O
O
a signal of the NH proton of an enamine type in the low field. It
O
Me
O
Me
O
Ar
proves that at the stage of addition on the carbonyl group, more
basic and sterically less hindered amino group participates. The
further addition of the amino group on the exocyclic double bond
leads to spiropyrimidines 7 in the more thermodynamically stable
enamine form.
Spiropyrimidinones 7 were also obtained by a one-pot pro-
cedure (for compounds 7a,d,f) using the corresponding arylglyox-
als 2, acid 1, and ureas 5a,b.
HOAc
Ar
N
N
H
O
O
N
Me
O
N
Me
O
1
2a-g
3a-g
3a: Ar = Ph; 3b: Ar = 4-CH3-C6H4
3c: Ar = 4-Cl-C6H4; 3d: Ar = 4-Br-C6H4
3e: Ar = 4-I-C6H4; 3f: Ar = 2-thienyl
3g: Ar = 4-NO2-C6H4
The molecular ions of the spiropyrimidines 7 are of maximal in-
tensity in the mass spectra. The main fragmentations include elimi-
nation of 1,3-dimethyl-1,3-diazetidin-2,4-dione, an isocyanate
radical, an arylnitrile cation, and also regrouping with dimethylurea
elimination. Asatypical example, Scheme3 illustratesdecomposition
processes of compound 7d.
Spirocompounds 7 without substituents at N1 were easily
acylated (for pyrimidinones 7a,b,d) by acetic anhydride in the
indicated position.
Interaction of acid 1, glyoxals 2c,e and dimethylurea 5f in
methanol with catalytic amounts of glacial acetic acid leads to
hydantoins 9c,e (Scheme 4). The 1H NMR spectra (DMSO-d6) of
compounds 9c,e exhibited clear doublets of the substituted
aromatic nuclei, singlets of four methyl groups, and a singlet of the
methyne proton at 3.70 ppm. There are the signals of C-5 of
pyrimidine cycle at 80 ppm and the absence of spiroatom at
63–68 ppm in the 13C NMR spectra of products 9b,c,e.
The molecular ions of compound 9c,e are observed in their mass
spectra. Fragmentation includes elimination of diazetidine,
whereas the elimination of methylisocyanate molecule does not
take place.
Scheme 1.
o-phenylenediamines 4a,b in methanol at reflux resulted in the
well-known quinoxalines 6a,b,19 and 1,3-dimethylbarbituric acid
(1) (the last was isolated from the filtrate). The reaction of enones
3a–g with ureas 5a–e led to new spiropyrimidines 7a–m in good
yields (63–74%).
The structure of spiropyrimidines 7 was confirmed by 1H NMR
spectroscopy. The following signals were detected (DMSO-d6):
proton singlets of the methyl groups of the initial pyrimidine
fragment at 2.92–3.33 ppm, multiplets of the aromatic substituents
in positions N1 and C4 at 6.96–8.17 ppm, a vinylene singlet proton
at 6.12–7.25 ppm, and also broad NH-protons of the spirocycle
(compounds 7a–e) at 9.05–9.20 ppm and 11.5–12.0 ppm that refer
to amide (N1) and enamine (N3) protons, respectively. There is
a signal of spiroatom C-6 at 62.7–63.5 ppm in the 13C NMR spectra
of spiroproducts 7a–e (at 65.9–68.2 ppm for N-substituted spiranes
7f–l). There are intensive bands of carbonyl groups of spirocycle of
compounds 7a–l (at 1750–1765 cmꢀ1), and their acetyl derivatives
8a–c (at 1770 cmꢀ1) in the IR spectra. It is proved the steric tensity
of these systems.
It is also interesting that compounds 9b,e were synthesized
from enones 3b,e and urea 5f under similar experimental
conditions.
The physicochemical characteristics of product 9e obtaining by
one-pot procedure and from enone 3e are identical.
The use of arylsubstituted ureas 5b–d in the synthesis hardly
influences the yield of spiranes 7f,g,i,j,l,m, unlike the similar
reactions of chalcones with arylureas, where the yields of pyrimi-
dines decrease.20 The signal of the proton of the amide group is
absent in the 1H NMR spectra of compounds 7f–m and there is
NH2
N
Ph
MeOH
1
3a
R
NH2
H2N
R
N
4,6 a: R = H
4,6 b: R = Br
4a,b
6a,b
O
O
Me
O
Ar
Me
O
Ar
O
NHR
N
MeOH
N
O
N
NHR
O
N
O
N
Me
O
3a-g
5a-e
Me
5a: R = H; 5b: R = 4-CH3-C6H4
5c: R = 2-F-C6H4; 5d: R = 3-Cl-C6H4
5e: R = CH2CH2OCH3
Ar
Ar
Ar
O
O
O
NH
NH
N
Ac2O
Me
O
Me
O
Me
O
O
O
N
N
O
N
N
N
N
R
O
COMe
R
O
N
O
N
N
Me
Me
Me
8a-c
7a-m
8a: Ar = Ph
8b: Ar = 4-CH3-C6H4
8c: Ar = 4-I-C6H4
7a: Ar = Ph, R = H; 7b: Ar = 4-CH3-C6H4, R = H
7c: Ar = 4-Br-C6H4, R = H; 7d: Ar = 4-I-C6H4, R = H
7e: Ar = 4-NO2-C6H4, R = H; 7f: Ar = Ph, R = 4-CH3-C6H4
7g: Ar = Ph, R = 2-F-C6H4; 7h: Ar = Ph, R = CH2CH2OCH3
7i: Ar = 4-CH3-C6H4, R = 2-F-C6H4; 7j: Ar = 4-CH3-C6H4, R = 3-Cl-C6H4
7k: Ar = 4-Cl-C6H4, R = CH2CH2OCH3
7l: Ar = 4-Br-C6H4, R = 4-CH3-C6H4; 7m: Ar = 2-thienyl, R = 4-CH3-C6H4
Scheme 2.

L.L. Gozalishvili et al. / Tetrahedron 64 (2008) 8759–8765
8761
I
I
.
+
.
+
O
N
CH2
O
+
.
.
N
(CO)2[N(CH3)2]2
-I-C6H4-C=NH
-NC=O
m/z 42
O
N
-I
m/z 398
NH
NH
m/z 199
m/z 114
O
N
N
H
O
m/z 440
C
N
H
O
m/z 326
O
m/z 168
O
O
+
-HN=C=O
-[NH(CH3)]2CO
-I-C6H4-C=NH
m/z 210
-CO
m/z 255
m/z 283
m/z 352
.
-I
m/z 225
Scheme 3.
O
Ar
O
NMe
Me
O
O
N
H
MeHN
NHMe
O
O
Me
O
Ar
HOAc
MeOH
N
N
Me
N
Me
O
O
N
O
2c,e
1
9c,e
5f
Me
HOAc
MeOH
9b,e
5f
3b,e +
9c: Ar = 4-Cl-C6H4; 9e: Ar = 4-I-C6H4; 9b: Ar =4-CH3-C6H4
Scheme 4.
The molecular structure of hydantoin 9e was determined by X-
ray diffraction study (Fig. 1).
Retrosynthetic analysis (Scheme 5) shows two possibilities for
the one-pot synthesis of compounds 9c,e. The first way (path 1)
involves the formation of hydantoin from arylglyoxals 2 and
dimethylurea (5f) and then it condenses with dimethylbarbituric
acid (1) through Knoevenagel reaction.
The alternative way (path 2) assumes the formation of enone 3
or aldol 10, which undergoes nucleophilic addition (or substitution)
reaction with urea 5f and further cyclization into products 9.
However, hydantoin 11 obtained by well-known method23 does
not react with acid 1 to form compound 9 (Scheme 6). Therefore,
the way 2 seems to be more probable. It is also confirmed by the
formation of products 9b,e from unsaturated ketones 3b,e and urea
5f (Scheme 4).
The five-membered heterocycle is planar, while the six-mem-
bered rings are rotated with respect to this plane (the angles C(2)–
C(3)–C(5)–N(3) and C(5)–C(6)–C(8)–C(9) are 73.6(2)ꢁ and 58.4(3)ꢁ,
respectively). The molecules are linked into centrosymmetric di-
mers due to formation of strong intermolecular hydrogen bonds
O(3)–H(3O)/O(4)i [i: ꢀx,ꢀyþ2,ꢀzþ1] (H/O 1.73 Å, O–H/O 150ꢁ).
Shortening of the hydroxyl C(4)–O(3) bond up to 1.308(3) Å and
elongation of the carbonyl C(7)–O(4) bond up to 1.257(3) Å (mean
values are 1.22 and 1.33 Å, respectively21) most probably indicate
substantial charge transfer due to formation of the H-bond. Also, it
is interesting to note short intermolecular I(1)/C(1) contact 3.54 Å
(Van der Waals radii sum is 3.86 Å22), which very likely can be
Thus, we propose that hydantoins 9 and quinoxalines 6 form in
the reactions of enones 3 with dimethylurea (5f) and o-phenyl-
classified as I/p interaction.
enediamines 4 correspondingly via the addition to the p-deficient
C]C bond (1,4-addition). In the case of poor nucleophiles (for ex-
ample, urea) the first step of the reaction is the attack of carbonyl
group (1,2-addition) with further formation of spiranes 7. This ar-
gument was confirmed by formation of 2-aminothiazole derivative
13 in the reaction of enone 3a with thiourea (12) (Scheme 7).
At the same time, it is well-accepted in the literature that the
1,4-addition of ureas to
step.23–27 Enones 3 investigated in this work are characterized by
a higher -deficiency of the vinylene bond in comparison with
a,b-unsaturated ketones is the first reaction
p
chalcones. This leads to regioselective 1,2- or 1,4-nucleophilic ad-
dition to the enones 3, depending on the nucleophilicity of ureas.
Similar results were obtained by Al-Hajjar et al.24 For the one-pot
reaction of ethyl acetoacetate, arylglyoxals, and urea or N,N-dime-
thylurea in the presence of Lewis acids, 3,4-dihydropyrimidine
derivatives were obtained in the reaction with urea whereas
hydantoines were formed in the reaction with N,N-dimethylurea. A
weak nucleophile (unsubstituted urea) reacts in a 1,2-addition
fashion with the more active acetyl group, whereas N,N-dimethyl-
urea reacts with the C]C bond (1,4-addition). Further cyclization
with participation of the C]C bond or aroyl group leads to dihy-
dropyrimidines or hydantoines, respectively.
Figure 1.

8762
L.L. Gozalishvili et al. / Tetrahedron 64 (2008) 8759–8765
O
MeHN
NHMe
5f
H
2
Ar
O
O
O
O
Ar
O
NMe
O MeN
NHMe
Ar
O
Ar
Path 1
Path 2
Me
Me
O
Me
O
N
O
NMe
O
N
N
N
Me
O
O
N
Me
O
N
N
O
N
Me
O
Me
9
Me
O
O
O
OH
Me
Me
Ar
Me
O
Ar
N
N
N
5f
2
or
O
O
O
N
Me
O
O
N
Me
O
N
Me
O
10
3
Scheme 5.
4.2. Preparation of 5-(2-arylethylidene-2-oxo)-1,3-
dimethylpyrimidine-2,4,6-triones (3a–g)
Ph
O
N
N
O
HOAc
MeOH
N
HOAc
N
General procedure. A mixture of acid 1 (1.0 mmol) and aryl-
glyoxals 2a–g (1.0 mmol) in glacial acetic acid (10–12 mL) was
stirred at rt overnight. The products 3 were filtered off and washed
with water twice.
+
2a
5f
+
O
1
N
O
N
O
9
O
11
Scheme 6.
4.2.1. 1,3-Dimethyl-5-(2-oxo-2-phenylethylidene)-
pyrimidine-2,4,6(1H,3H,5H)-trione (3a)
3. Conclusions
The title compound was obtained as a colorless solid in 81%
yield (0.22 g), mp 199–200 ꢁC. [Found: C, 61.67; H, 4.39; N, 10.34.
C
It was shown that the mode of interaction of 5-(2-oxo-2-aryl-
ethyliden)-1,3-dimethylbarbituric acids with 1,3- or 1,4-binucleo-
phile is determined by their nucleophilic ability. The reaction may
proceed either at the double bond or at the carbonyl group of the
exocyclic fragment. Facile and efficient methods of new spiropyr-
imidinones 7 and imidazolylpyrimidinones 9 synthesis, including
a one-pot variant, starting from dimethylbarbituric acid (1), aryl-
glyoxals 2, and appropriately substituted ureas were developed.
14H12N2O4 requires C, 61.76; H, 4.44; N, 10.29%.] nmax (KBr, cmꢀ1
)
1630, 1662, 1675, 1690; dH (200 MHz, DMSO-d6) 3.03 (3H, s, Me),
3.22 (3H, s, Me), 7.48 (1H, m, p-Ph), 7.63 (2H, d, J 8.0 Hz, m-Ph), 7.87
(2H, d, J 8.0 Hz, o-Ph), 8.15 (1H, s, ]CHCO); dC (100 MHz, DMSO-d6)
28.5, 29.0, 125.3, 129.1, 129.6, 134.7, 135.4, 151.9, 152.1, 160.6, 161.1,
ꢂ
194.8; MS, m/z (I, %): 272 (Mþ , 100).
4.2.2. 1,3-Dimethyl-5-(2-oxo-2-p-tolylethylidene)-
pyrimidine-2,4,6-trione (3b)
The title compound was obtained as a colorless solid in 92%
yield (0.26 g), mp 213–214 ꢁC. [Found: C, 62.85; H, 4.88; N, 9.71.
C
4. Experimental
4.1. General
15H14N2O4 requires C, 62.93; H, 4.93; N, 9.79%.] nmax (KBr, cmꢀ1
)
1629, 1665, 1678, 1692; dH (200 MHz, DMSO-d6) 2.37 (3H, s, MeAr),
3.03 (3H, s, Me), 3.21 (3H, s, Me), 7.31 (2H, d, J 7.9 Hz, m-Ar), 7.75
(2H, d, J 7.9 Hz, o-Ar), 8.07 (1H, s, ]CHCO); dC (100 MHz, DMSO-d6)
21.8, 28.4, 29.0, 125.2, 129.2, 130.1, 133.0, 145.3, 151.9, 152.2, 160.6,
Starting materials were obtained from commercial suppliers.
Melting points were determined on a Kofler apparatus. The IR
spectra were recorded on a Specord-75 IR spectrometer in KBr. The
1H NMR spectra were recorded at 200 MHz on a Varian Mercury VX-
200 spectrometer and 13C NMR spectra were recorded at 100 MHz
on a Bruker AM-400 spectrometer with SiMe4 internal reference in
DMSO-d6. Mass spectra were taken on a Hewlett-Packard LC/MSD
1100 series instrument at atmospheric pressure by chemical ioni-
zation (positive APCI) mode. Reactions were monitored by TLC
(Silufol UV-254) in MeOH/toluene (1:1), toluene/EtOAc (1:1), and
toluene/EtOAc (1:4), and visualized under UV light or iodine fume.
Imidazolidine-2,4-dione 11 was synthesized by known
procedure.23
ꢂ
161.1, 194.4; MS, m/z (I, %): 286 (Mþ , 100).
4.2.3. 5-(2-(4-Chlorophenyl)-2-oxoethylidene)-
1,3-dimethylpyrimidine-2,4,6-trione (3c)
The title compound was obtained as a colorless solid in 68%
yield (0.205 g), mp 221–222 ꢁC. [Found: C, 54.89; H, 3.68; N, 9.19.
C
14H11ClN2O4 requires C, 54.83; H, 3.62; N, 9.13%.] nmax (KBr, cmꢀ1
)
1630, 1665, 1677, 1694; dH (200 MHz, DMSO-d6) 3.00 (3H, s, Me),
3.20 (3H, s, Me), 7.54 (2H, d, J 8.4 Hz, m-Ar), 7.81 (2H, d, J 8.4 Hz, o-
Ar), 8.11 (1H, s, ]CHCO); dC (100 MHz, DMSO-d6) 28.4, 29.0, 125.3,
HN
Ph
NH2
O
N
O
O
Me
S
H2N
NH
Ph
Me
O
2 MeOH
Me
O
N
NH2
N
S
Ph
N
O
S
O
N
Me
O
O
N
Me
OH
13
N
Me
O
3a
12
Scheme 7.

L.L. Gozalishvili et al. / Tetrahedron 64 (2008) 8759–8765
8763
129.9, 130.3, 135.0, 141.9, 151.9, 152.1, 160.7, 161.0, 194.8; MS, m/z (I,
4.4.1. 8,10-Dimethyl-4-phenyl-1,3,8,10-tetraazaspiro[5,5]-undec-
4-ene-2,7,9,11-tetraone (7a)
ꢂ
%): 306 (100), 308 (Mþ , 33).
The title compound was obtained as a colorless solid in 69%
yield (0.21 g), mp 230–231 ꢁC. [Found: C, 57.37; H, 4.51; N, 17.77.
4.2.4. 5-(2-(4-Bromophenyl)-2-oxoethylidene)-
1,3-dimethylpyrimidine-2,4,6-trione (3d)
C )
15H14N4O4 requires C, 57.32; H, 4.49; N, 17.83%.] nmax (KBr, cmꢀ1
The title compound was obtained as a colorless solid in 72%
yield (0.25 g), mp 230–231 ꢁC. [Found: C, 47.97; H, 3.10; N, 7.86.
C
1635, 1675, 1722, 1740, 1755, 3230; dH (200 MHz, DMSO-d6) 2.97
(3H, s, Me), 3.15 (3H, s, Me), 6.21 (1H, s, ]CH–), 7.26–7.35 (5H, m,
Ph), 9.08 (1H, s, NH), 11.66 (1H, s, NH); dC (100 MHz, DMSO-d6) 28.0,
28.1, 63.5, 91.4, 128.3, 128.7, 129.3, 138.4, 151.6, 155.4, 160.6, 164.3,
14H11BrN2O4 requires C, 47.89; H, 3.16; N, 7.98%.] nmax (KBr, cmꢀ1
)
1628, 1663, 1676, 1690; dH (200 MHz, DMSO-d6) 3.02 (3H, s, Me),
3.22 (3H, s, Me), 7.50 (2H, d, J 8.4 Hz, m-Ar), 7.71 (2H, d, J 8.4 Hz, o-
Ar), 8.11 (1H, s, ]CHCO); dC (100 MHz, DMSO-d6) 28.5, 29.0, 125.2,
129.7, 131.3, 133.0, 134.4, 151.9, 152.2, 160.6, 161.1, 194.7; MS, m/z (I,
ꢂ
171.9; MS, m/z (I, %): 314 (Mþ , 100).
4.4.2. 8,10-Dimethyl-4-(p-tolyl)-1,3,8,10-tetraazaspiro[5,5]-undec-
4-ene-2,7,9,11-tetraone (7b)
ꢂ
%): 350 (100), 352 (Mþ , 98).
The title compound was obtained as a colorless solid in 64%
yield (0.21 g), mp 226–227 ꢁC. [Found: C, 58.48; H, 4.95; N, 17.09.
C
4.2.5. 5-(2-(4-Iodophenyl)-2-oxoethylidene)-
1,3-dimethylpyrimidine-2,4,6-trione (3e)
16H16N4O4 requires C, 58.53; H, 4.91; N, 17.06%.] nmax (KBr, cmꢀ1
)
The title compound was obtained as a colorless solid in 89%
yield (0.35 g), mp 228–230 ꢁC. [Found: C, 42.17; H, 2.71; N, 7.08.
1628, 1676, 1719, 1743, 1762, 3253; dH (200 MHz, DMSO-d6) 2.24
(3H, s, MeAr), 2.97 (3H, s, Me), 3.15 (3H, s, Me), 6.17 (1H, s, ]CH–),
7.05–7.12 (4H, m, Ar), 9.04 (1H, s, NH), 11.54 (1H, s, NH); dC
(100 MHz, DMSO-d6) 21.2, 28.0, 28.1, 63.0, 91.3, 128.5, 129.9, 136.9,
C14H11IN2O4 requires C, 42.23; H, 2.78; N, 7.04%.] nmax (KBr, cmꢀ1
)
1631, 1664, 1673, 1692; dH (200 MHz, DMSO-d6) 3.03 (3H, s, Me),
3.22 (3H, s, Me), 7.60 (2H, d, J 8.2 Hz, o-Ar), 7.89 (2H, d, J 8.2 Hz, m-
Ar), 8.09 (1H, s, ]CHCO); dC (100 MHz, DMSO-d6) 28.5, 29.0, 125.2,
97.4, 131.5, 135.0, 139.7, 151.9, 152.2, 160.6, 161.1, 194.6; MS, m/z (I,
ꢂ
138.2, 151.5, 155.2, 160.5, 164.0, 171.7; MS, m/z (I, %): 328 (Mþ , 100).
4.4.3. 4-(4-Bromophenyl)-8,10-dimethyl-1,3,8,10-tetraazaspiro-
[5,5]-undec-4-ene-2,7,9,11-tetraone (7c)
ꢂ
%): 398 (Mþ , 100).
The title compound was obtained as a colorless solid in 66% yield
(0.26 g), mp 228–229 ꢁC. [Found: C, 45.86; H, 3.28; N, 14.20.
C
4.2.6. 1,3-Dimethyl-5-(2-oxo-2-(thiophen-2-yl)ethylidene)-
pyrimidine-2,4,6-trione (3f)
15H13BrN4O4 requires C, 45.82; H, 3.33; N, 14.25%.] nmax (KBr, cmꢀ1
)
The title compound was obtained as a colorless solid in 76% yield
(0.21 g), mp 228–230 ꢁC. [Found: C, 51.85; H, 3.58; N, 10.11; S, 11.49.
1625,1670,1715,1755, 3245;dH (200 MHz, DMSO-d6)2.96(3H, s, Me),
3.15 (3H, s, Me), 6.20 (1H, s, ]CH–), 7.20 (2H, d, J 8.5 Hz, o-Ar), 7.50
(2H, d, J 8.5 Hz, m-Ar), 9.11 (1H, s, NH),11.56 (1H, s, NH); dC (100 MHz,
DMSO-d6) 28.0, 28.1, 62.8, 91.4, 121.8, 130.5, 132.2, 137.8, 151.6, 154.4,
C
12H10N2O4S requires C, 51.79; H, 3.62; N, 10.07; S, 11.52%.] nmax
(KBr, cmꢀ1) 1630, 1663, 1675, 1691; dH (200 MHz, DMSO-d6) 3.01
(3H, s, Me), 3.21 (3H, s, Me), 7.02–7.10 (1H, m, -thienyl), 7.61 (1H, d,
J 2.8 Hz, -thienyl), 7.65 (1H, d, J 4.6 Hz, -thienyl), 8.00 (1H, s,
ꢂ
160.7, 164.2, 171.3; MS, m/z (I, %): 392 (100), 394 (Mþ , 98).
b
b
a
]CHCO); dC (100 MHz, DMSO-d6) 28.5, 29.0, 125.4, 129.1, 131.5,
4.4.4. 8,10-Dimethyl-4-(4-iodophenyl)-1,3,8,10-tetraazaspiro[5,5]-
undec-4-ene-2,7,9,11-tetraone (7d)
ꢂ
133.0, 138.1, 151.7, 152.1, 160.3, 161.1, 190.0; MS, m/z (I, %): 278 (Mþ
,
100).
The title compound was obtained as a colorless solid in 68%
yield (0.30 g), mp 249–250 ꢁC. [Found: C, 40.89; H, 3.03; N, 12.78.
C
15H13IN4O4 requires C, 40.93; H, 2.98; N, 12.73%.] nmax (KBr, cmꢀ1
)
4.2.7. 1,3-Dimethyl-5-(2-(4-nitrophenyl)-2-oxoethylidene)-
pyrimidine-2,4,6-trione (3g)
1632, 1677, 1722, 1760, 3235; dH (200 MHz, DMSO-d6) 2.97 (3H, s,
Me), 3.15 (3H, s, Me), 6.17 (1H, s, ]CH–), 7.05 (2H, d, J 8.2 Hz, o-Ar),
7.68 (2H, d, J 8.2 Hz, m-Ar), 9.08 (1H, s, NH), 11.66 (1H, s, NH); dC
(100 MHz, DMSO-d6) 28.0, 28.1, 62.9, 91.3, 96.0, 131.2, 138.0, 139.2,
The title compound was obtained as a colorless solid in 67%
yield (0.21 g), mp 209–210 ꢁC. [Found: C, 53.09; H, 3.55; N, 13.22.
C
14H11N3O6 requires C, 53.00; H, 3.49; N, 13.245%.] nmax (KBr, cmꢀ1
)
ꢂ
151.5, 155.4, 160.6, 164.3, 171.3; MS, m/z (I, %): 440 (Mþ , 100).
1632, 1669, 1675, 1693; dH (200 MHz, DMSO-d6) 3.07 (3H, s, Me),
3.26 (3H, s, Me), 8.07 (2H, d, J 8.0 Hz, o-Ar), 8.38 (2H, d, J 8.0 Hz, m-
Ar), 8.50 (1H, s, ]CHCO); dC (100 MHz, DMSO-d6) 28.6, 29.1, 125.5,
124.3, 130.2, 143.4, 152.3, 152.0, 152.7, 160.6, 161.9, 195.7; MS, m/z (I,
4.4.5. 8,10-Dimethyl-4-(4-nitrophenyl)-1,3,8,10-tetraazaspiro[5,5]-
undec-4-ene-2,7,9,11-tetraone (7e)
ꢂ
%): 317 (Mþ , 100).
The title compound was obtained as a colorless solid in 72%
yield (0.26 g), mp 242–243 ꢁC. [Found: C, 50.25; H, 3.59; N, 19.37.
C
15H13N5O6 requires C, 50.14; H, 3.65; N, 19.49%.] nmax (KBr, cmꢀ1
)
4.3. Preparation of 2-arylquinoxalines 6a,b
1633, 1679, 1722, 1757, 3245; dH (200 MHz, DMSO-d6) 2.92 (3H, s,
Me), 3.17 (3H, s, Me), 6.36 (1H, s, ]CH–), 7.53 (2H, d, J 8.1 Hz, o-Ar),
8.17 (2H, d, J 8.1 Hz, m-Ar), 9.19 (1H, s, NH), 11.59 (1H, s, NH); dC
(100 MHz, DMSO-d6) 28.0, 28.1, 62.7, 91.7, 124.8, 129.6, 145.6, 147.7,
A mixture of enone 3a (1.0 mmol) and o-phenylenediamines
4a,b (1.0 mmol) in methanol (8 mL) was heated at reflux for 1 h.
The resulting product was filtered off and washed with water and
hot methanol.
Compound 6a. Yellow solid. Yield: 64%, mp 76–77 ꢁC (77–
78 ꢁC).19 Compound 6b. Yellow solid. Yield: 68%, mp 124–125 ꢁC
(124–125 ꢁC).19
ꢂ
151.6, 155.4, 160.8, 164.0, 170.4; MS, m/z (I, %): 359 (Mþ , 100).
4.4.6. 8,10-Dimethyl-4-phenyl-1-(p-tolyl)-1,3,8,10-tetraazaspiro-
[5,5]-undec-4-ene-2,7,9,11-tetraone (7f)
The title compound was obtained as a colorless solid in 74% yield
(0.30 g), mp 217–218 ꢁC. [Found: C, 65.26; H, 4.90; N, 13.96.
4.4. Preparation of 4-aryl-8,10-dimethyl-1,3,8,10-
tetraazaspiro[5,5]-undec-4-ene-2,7,9,11-tetraones (7a–m)
C )
22H20N4O4 requires C, 65.34; H, 4.98; N, 13.85%.] nmax (KBr, cmꢀ1
1627, 1675, 1719, 1755, 3235; dH (200 MHz, DMSO-d6) 2.26 (3H, s,
Me–NAr), 3.06 (3H, s, Me), 3.33 (3H, s, Me), 6.85 (1H, s, ]CH–), 7.07
(2H, d, J 7.9 Hz, m-NAr), 7.18 (2H, d, J 7.9 Hz, o-NAr), 7.23–7.34 (5H,
m, Ph), 11.96 (1H, s, NH); dC (100 MHz, DMSO-d6) 20.9, 28.1, 66.6,
91.4, 128.7, 129.8, 131.8, 132.9, 123.6, 128.8, 129.0, 135.4, 151.2, 152.3,
General procedure A. A mixture of appropriate enones 3a–g
(2.0 mmol) and the corresponding urea derivatives 5a–e
(2.0 mmol) was heated at reflux in methanol (5–7 mL) for 0.5–1.5 h.
The resulting products were filtered off, washed with cold metha-
nol or recrystallized.
ꢂ
160.2 163.8, 168.9; MS, m/z (I, %): 404 (Mþ , 100).

8764
L.L. Gozalishvili et al. / Tetrahedron 64 (2008) 8759–8765
4.4.7. 8,10-Dimethyl-1-(2-fluorophenyl)-4-phenyl-1,3,8,10-
tetraazaspiro[5,5]-undec-4-ene-2,7,9,11-tetraone (7g)
1630, 1675, 1722, 1765, 3245; dH (200 MHz, DMSO-d6) 2.19 (3H, s,
Me–NAr), 3.01 (3H, s, Me), 3.16 (3H, s, Me), 6.90 (1H, s, ]CH–), 7.09
(2H, d, J 8.0 Hz, m-NAr), 7.26 (2H, d, J 8.2 Hz, o-Ar), 7.33 (2H, d, J
8.4 Hz, m-Ar), 7.41 (2H, d, J 8.0 Hz, o-NAr), 11.97 (1H, s, NH); dC
(100 MHz, DMSO-d6) 20.9, 28.1, 66.6, 91.4, 123.6, 130.1, 131.4, 132.9,
122.0, 131.7, 135.6, 136.6, 151.2, 152.3, 160.3, 163.7, 168.4; MS, m/z (I,
The title compound was obtained as a colorless solid in 39% yield
(0.16 g), mp 192–194 ꢁC. [Found: C, 61.69; H, 4.27; N, 13.76.
C
21H17FN4O4 requires C, 61.76; H, 4.20; N, 13.72%.] nmax (KBr, cmꢀ1
)
1635,1676,1721,1759, 3249; dH (200 MHz, DMSO-d6) 2.97 (3H, s, Me),
3.18 (3H, s, Me), 6.72 (1H, s, ]CH–), 7.16–7.26 (8H, m, PhþNAr), 7.42
(1H, t, J 7.6 Hz, NAr), 12.05 (1H, s, NH); dC (100 MHz, DMSO-d6) 28.1,
28.2,68.1,92.2,128.9,129.9,130.5,138.3,117.0,122.7,125.7,130.3,132.0,
ꢂ
%): 482 (100), 484 (Mþ , 99).
4.4.13. 8,10-Dimethyl-1-(p-tolyl)-4-(thiophen-2-yl)-1,3,8,10-
tetraazaspiro[5,5]-undec-4-ene-2,7,9,11-tetraone (7m)
ꢂ
156.6, 151.4, 159.9, 160.4, 163.9, 169.4; MS, m/z (I, %): 408 (Mþ , 100).
The title compound was obtained as a colorless solid in 62% yield
(0.25 g), mp 232–233 ꢁC. [Found: C, 58.62; H, 4.37; N, 13.52; S, 7.70.
4.4.8. 8,10-Dimethyl-1-(2-methoxyethyl)-4-phenyl-1,3,8,10-
tetraazaspiro[5,5]-undec-4-ene-2,7,9,11-tetraone (7h)
C
20H18N4O4S requires C, 58.53; H, 4.42; N, 13.65; S, 7.80%.] nmax (KBr,
cmꢀ1) 1627,1675,1720,1760, 3240; dH (200 MHz, DMSO-d6) 2.22 (3H,
s, MeAr), 3.09 (3H, s, Me), 3.17 (3H, s, Me), 6.84 (1H, t, J 4.6 Hz,
thienyl), 7.11–7.16(3H, m,m-NArþ -thienyl), 7.25(1H, s,]CH–), 7.36–
-thienyl),11.87 (1H, s, NH); dC (100 MHz, DMSO-
The title compound was obtained as a colorless solid in 63%
yield (0.23 g), mp 117–118 ꢁC. [Found: C, 57.98; H, 5.35; N, 15.47.
b-
C
18H20N4O5 requires C, 58.06; H, 5.41; N, 15.05%.] nmax (KBr, cmꢀ1
)
b
1629, 1675, 1722, 1740, 1755, 3230; dH (200 MHz, DMSO-d6) 2.96
(3H, s, Me), 3.13 (3H, s, Me), 3.18 (3H, s, OMe), 3.28–3.40 (2H, m,
CH2CH2OMe), 3.54–3.66 (2H, m, CH2CH2OMe), 6.26 (1H, s, ]CH–),
7.29–7.34 (5H, m, Ph), 11.75 (1H, s, NH); dC (100 MHz, DMSO-d6)
27.9, 40.0, 58.5, 66.0, 70.2, 91.3, 128.2, 128.6, 130.0, 137.5, 151.3,
7.40 (3H, m, o-NArþ
a
d6) 21.1, 28.3, 62.8, 92.9, 129.4, 133.2, 135.6, 137.5, 123.0, 127.2, 127.3,
ꢂ
130.1, 151.4, 152.1, 160.6, 163.7, 168.4; MS, m/z (I, %): 410 (Mþ , 100).
General procedure B: one-pot procedure. A mixture of 1,3-dime-
thylbarbituric acid (1) (1 mmol), the appropriate arylglyoxals 2a,d
(1 mmol), and ureas 5a,b (1 mmol) was heated at reflux in methanol
for 1–1.5 h. The resulting product was filtered off, washed with cold
methanol or recrystallized. Spiranes 7a,d,f were prepared in this way.
ꢂ
153.6, 160.4, 163.5, 167.0; MS, m/z (I, %): 372 (Mþ , 100).
4.4.9. 8,10-Dimethyl-1-(2-fluorophenyl)-4-(p-tolyl)-1,3,8,10-
tetraazaspiro[5,5]-undec-4-ene-2,7,9,11-tetraone (7i)
The title compound was obtained as a colorless solid in 62%
yield (0.26 g), mp 203–204 ꢁC. [Found: C, 62.51; H, 4.58; N, 13.22.
C
4.5. Preparation of 1-acetyl-4-aryl-8,10-dimethyl-1,3,8,10-
tetraazaspiro[5,5]-undec-4-ene-2,7,9,11-tetraones (8a–c)
22H19FN4O4 requires C, 62.56; H, 4.50; N, 13.27%.] nmax (KBr, cmꢀ1
)
1633, 1675, 1721, 1757, 3240; dH (200 MHz, DMSO-d6) 2.14 (3H, s,
MeAr), 3.00 (3H, s, Me), 3.17 (3H, s, Me), 6.69 (1H, s, ]CH–), 6.96–
7.02 (4H, m, m-ArþNAr), 7.15–7.27 (3H, m, o-ArþNAr), 7.43 (1H, t, J
7.6 Hz,NAr),12.08(1H, s, NH);dC (100 MHz, DMSO-d6) 21.2, 28.1, 28.2,
68.2, 92.1, 125.6, 129.6, 137.2, 138.5, 117.0, 122.7, 125.7, 130.3, 132.0,
General procedure. Spiroproducts 7a,b,d (1 mmol) were heated
at reflux in acetic anhydride (10 mmol) containing catalytic
amounts of sulfuric acid for 5–10 min. The precipitates of com-
pounds 8a–c were filtered off and washed with water twice.
ꢂ
156.6, 151.5, 159.9, 160.5, 164.0, 169.5; MS, m/z (I, %): 422 (Mþ , 100).
4.5.1. 1-Acetyl-8,10-dimethyl-4-phenyl-1,3,8,10-tetraazaspiro[5,5]-
undec-4-ene-2,7,9,11-tetraone (8a)
4.4.10. 1-(3-Chlorophenyl)-8,10-dimethyl-4-(p-tolyl)-1,3,8,10-
tetraazaspiro[5,5]-undec-4-ene-2,7,9,11-tetraone (7j)
The title compound was obtained as a colorless solid in 77%
yield (0.27 g), mp 222–223 ꢁC. [Found: C, 57.44; H, 4.45; N, 15.81.
The title compound was obtained as a colorless solid in 64%
yield (0.28 g), mp 205–206 ꢁC. [Found: C, 60.24; H, 4.41; N, 12.71.
C )
17H16N4O5 requires C, 57.30; H, 4.53; N, 15.72%.] nmax (KBr, cmꢀ1
1632, 1668, 1679, 1722, 1770, 3235; dH (200 MHz, DMSO-d6) 2.32
(3H, s, Me), 3.03 (6H, s, 2NMe), 6.62 (1H, s, ]CH–), 7.18–7.29 (5H, m,
Ph), 12.02 (1H, s, NH); dC (100 MHz, DMSO-d6) 24.5, 28.2, 63.3, 92.6,
128.3, 129.2, 129.8, 137.5, 151.4, 152.7, 160.5, 163.8, 168.0, 168.4; MS,
C
22H19ClN4O4 requires C, 60.21; H, 4.36; N,12.77%.] nmax (KBr, cmꢀ1
)
1627, 1676, 1721, 1760, 3242; dH (200 MHz, DMSO-d6) 2.15 (3H, s,
MeAr), 3.05 (3H, s, Me), 3.20 (3H, s, Me), 6.98 (1H, s, ]CH–), 7.03
(2H, d, J 8.2 Hz, m-Ar), 7.12–7.36 (3H, m, NAr), 7.43 (2H, d, J 8.2 Hz, o-
Ar), 7.68 (1H, s, NAr), 12.03 (1H, s, NH); dC (100 MHz, DMSO-d6) 21.1,
28.1, 28.2, 66.8, 91.3, 128.6, 129.9, 137.1, 138.2, 126.0, 127.8, 131.0,
133.7, 136.2, 139.5, 151.3, 158.9, 160.1, 163.9, 168.5; MS, m/z (I, %):
ꢂ
m/z (I, %): 356 (Mþ , 100).
4.5.2. 1-Acetyl-8,10-dimethyl-4-(p-tolyl)-1,3,8,10-
tetraazaspiro[5,5]-undec-4-ene-2,7,9,11-tetraone (8b)
ꢂ
438 (100), 440 (Mþ , 30).
The title compound was obtained as a colorless solid in 72%
yield (0.27 g), mp 226–227 ꢁC. [Found: C, 58.43; H, 4.93; N, 15.23.
4.4.11. 4-(4-Chlorophenyl)-8,10-dimethyl-1-(2-methoxyethyl)-
1,3,8,10-tetraazaspiro[5,5]-undec-4-ene-2,7,9,11-tetraone (7k)
The title compound was obtained as a colorless solid in 67%
yield (0.27 g), mp 140–141 ꢁC. [Found: C, 53.19; H, 4.75; N, 13.69.
C )
18H18N4O5 requires C, 58.37; H, 4.90; N, 15.13%.] nmax (KBr, cmꢀ1
1631, 1650, 1672, 1729, 1773, 3230; dH (200 MHz, DMSO-d6) 2.23
(3H, s, MeAr), 2.33 (3H, s, Me), 3.02 (3H, s, NMe), 3.16 (3H, s, NMe),
6.63 (1H, s, ]CH–), 7.08 (2H, d, J 7.9 Hz, m-Ar), 7.23 (2H, d, J 7.9 Hz,
o-Ar), 11.90 (1H, s, NH); dC (100 MHz, DMSO-d6) 21.2, 24.5, 28.2,
63.5, 92.7, 129.3, 129.4, 133.6, 138.4, 151.4, 152.7, 160.5, 163.8, 167.9,
C
18H19ClN4O5 requires C, 53.14; H, 4.71; N, 13.77%.] nmax (KBr, cmꢀ1
)
1625, 1670, 1720, 1758, 3235; dH (200 MHz, DMSO-d6) 3.00 (3H, s,
Me), 3.15 (3H, s, Me), 3.20 (3H, s, OMe), 3.26–3.36 (2H, m,
CH2CH2OMe), 3.50–3.60 (2H, m, CH2CH2OMe), 6.25 (1H, s, ]CH–),
7.29 (2H, d, J 8.5 Hz, m-Ar), 7.40 (2H, d, J 8.5 Hz, o-Ar), 11.76 (1H, s,
NH); dC (100 MHz, DMSO-d6) 27.9, 40.1, 58.5, 65.9, 70.2, 91.4, 128.9,
131.0, 134.6, 135.5, 151.3, 153.8, 160.4, 163.8, 167.4; MS, m/z (I, %):
ꢂ
168.3; MS, m/z (I, %): 370 (Mþ , 100).
4.5.3. 1-Acetyl-8,10-dimethyl-4-(4-iodophenyl)-1,3,8,10-
tetraazaspiro[5,5]-undec-4-ene-2,7,9,11-tetraone (8c)
The title compound was obtained as a colorless solid in 74% yield
(0.36 g), mp 230–232 ꢁC. [Found: C, 42.42; H, 3.20; N, 11.57.
ꢂ
406 (100), 408 (Mþ , 30).
C
17H15IN4O5 requires C, 42.34; H, 3.14; N, 11.62%.] nmax (KBr, cmꢀ1
)
4.4.12. 4-(4-Bromophenyl)-8,10-dimethyl-1-(p-tolyl)-1,3,8,10-
tetrazaspiro[5,5]-undec-4-ene-2,7,9,11-tetraone (7l)
1632,1660,1675,1725,1771, 3240; dH (200 MHz, DMSO-d6) 2.32 (3H,
s, Me), 2.99 (3H, s, NMe), 3.14 (3H, s, NMe), 6.55 (1H, s, ]CH–), 7.13
(2H, d, J 8.2 Hz, o-Ar), 7.65 (2H, d, J 8.2 Hz, m-Ar),12.04 (1H, s, NH); dC
(100 MHz, DMSO-d6) 24.5, 28.2, 63.9, 92.9, 95.5, 131.8, 136.3, 137.5,
The title compound was obtained as a colorless solid in 69%
yield (0.33 g), mp 206–207 ꢁC. [Found: C, 54.61; H, 3.80; N, 11.48.
ꢂ
C
22H19BrN4O4 requires C, 54.67; H, 3.96; N,11.59%.] nmax (KBr, cmꢀ1
)
151.4, 152.6, 160.6, 163.7, 167.0, 168.5; MS, m/z (I, %): 482 (Mþ , 100).

L.L. Gozalishvili et al. / Tetrahedron 64 (2008) 8759–8765
8765
4.6. Synthesis of 5-(5-aryl-1,3-dimethyl-2-oxo-2,3-dihydro-
1H-imidazol-4-yl)-1,3-dimethylpyrimidine-2,4,6-triones
(9b,c,e)
triclinic, P1, a¼9.7565(4), b¼9.7935(4), c¼11.4876(4) Å,
a
¼
112.298(4)ꢁ,
b
¼94.054(3)ꢁ,
g
¼98.715(3)ꢁ, V¼993.93(7) Å3, Z¼2,
dcalcd¼1.565 g cmꢀ1
,
m
¼1.639, 26,491 reflections measured up to
2
qmax¼30.0ꢁ, 5780 were independent (Rint¼0.021). Structure was
General procedure A: (one-pot synthesis). Equimolar amounts of
1, 2c,e, and 5f (1.0 mmol) were dissolved in methanol (5–7 mL) and
heated at reflux for 25–40 min. Crystals of 9c,e were filtered off,
washed with water and hot methanol.
solved by direct method and refined of F2 within anisotropic ap-
proximation for all non-hydrogen atoms using SHELXTL28 package.
All H atoms were placed in idealized positions (C–H¼0.93–0.98 Å,
O–H¼0.82 Å) and constrained to ride on their parent atoms, with
Uiso¼1.2 Ueq (except Uiso¼1.5 Ueq for methyl and hydroxy groups).
During the refinement, three isolated electron density peaks were
located, which were believed to be a solvent molecule (possibly
4.6.1. 5-(5-(4-Chlorophenyl)-1,3-dimethyl-2-oxo-2,3-dihydro-1H-
imidazol-4-yl)-1,3-dimethylpyrimidine-2,4,6-trione (9c)
The title compound was obtained as a colorless solid in 87%
yield (0.33 g), mp 254–255 ꢁC. [Found: C, 54.24; H, 4.63; N, 14.92.
ethanol or water). Satisfactory results (R1[F2>2
s
(F2)]¼0.046) were
obtained modeling the disordered C and O atoms, but large dis-
placement parameters for themwere observed. SQUEEZE procedure
implemented in PLATON29 indicated a solvent cavity of volume
135 Å3 centered at (0.5, 0, 0), containing approximately 14 electrons.
In the final refinement, this contribution was removed from the
intensity data that produced better refinement results. Final
refinement converged to wR2¼0.120 (all data), R1¼0.035 (for 4311
C
17H17ClN4O4 requires C, 54.19; H, 4.55; N, 14.87%.] nmax (KBr, cmꢀ1
)
1630, 1674, 1702; dH (200 MHz, DMSO-d6) 2.91 (3H, s, Me), 3.10 (3H,
s, Me), 3.13 (6H, s, 2NMe), 3.49 (1H, s, CH), 7.25 (2H, d, J 8.0 Hz, m-
Ar), 7.40 (2H, d, J 8.0 Hz, o-Ar); dC (100 MHz, DMSO-d6) 27.9, 28.9,
29.2, 80.0, 112.8, 132.9, 122.9, 129.1, 129.3, 130.8, 151.7, 154.0, 162.1;
ꢂ
MS, m/z (I, %): 376 (100), 378 (Mþ , 33).
reflections with F2>2
supplementary crystallographic data for this paper. These data can
be obtained free of charge from The Cambridge Crystallographic
Data Centre via www.ccdc.cam.ac.uk/data_request/cif.
s
(F2)), GOF¼1.06. CCDC 670178 contains the
4.6.2. 5-(5-(4-Iodophenyl)-1,3-dimethyl-2-oxo-2,3-dihydro-1H-
imidazol-4-yl)-1,3-dimethylpyrimidine-2,4,6-trione (9e)
The title compound was obtained as a colorless solid in 67%
yield (0.31 g), mp 198–200 ꢁC. [Found: C, 43.70; H, 3.71; N, 12.05.
C
17H17IN4O4 requires C, 43.61; H, 3.66; N, 11.97%.] nmax (KBr, cmꢀ1
)
Acknowledgement
1632,1670,1705; dH (200 MHz, DMSO-d6) 2.89 (3H, s, Me), 3.08 (3H,
s, Me), 3.12 (6H, s, 2NMe), 3.67 (1H, s, CH), 7.03 (2H, d, J 7.9 Hz, o-Ar),
7.67 (2H, d, J 7.9 Hz, m-Ar); dC (100 MHz, DMSO-d6) 27.8, 28.8, 29.3,
79.8,113.1,131.1, 94.4,129.9,123.0,138.0,151.9,154.0,162.3; MS, m/z
The authors wish to thank the Fund of fundamental researches
of Ukraine (grant F 25.3/032 of 03.09.07) for financial support.
ꢂ
(I, %): 468 (Mþ , 100).
General procedure B. A mixture of enones 3b,e (1.0 mmol) and 5f
(1.0 mmol) were heated at reflux in methanol (5–7 mL) for 1–1.5 h.
The products 9b,e were filtered off, washed with cold methanol or
recrystallized.
References and notes
1. Tietze, L. F. Chem. Rev. 1996, 96, 115.
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3. Ishmuratov, G. Yu.; Kharisov, R. Ya.; Latypova, E. R.; Talipov, R. F. Chem. Nat.
Compd. 2006, 42, 367.
4. Dhar, N. D. The Chemistry of Chalcones and Related Compounds; Wiley-Inter-
science: New York, NY, 1981; 285.
5. March, J.; Smith, M. B. Advanced Organic Chemistry: Reactions, Mechanisms, and
Structure; Wiley-Interscience: New York, NY, 2007; 2357.
6. Kolos, N. N.; Orlov, V. D.; Chebanov, V. A.; Shishkin, O. V.; Kulikov, A. Yu Chem.
Heterocycl. Compd. 1999, 9, 1230.
7. Kolos, N. N.; Orlov, V. D.; Arisa, D. Chem. Heterocycl. Compd. 1996, 1, 87.
8. Kolos, N.; Beryozkina, T.; Orlov, V. Heterocycles 2003, 60, 2115.
9. Kolos, N. N.; Beryozkina, T. V.; Orlov, V. D. Mendeleev Commun. 2002, 91.
10. Desenko, S. M. Chem. Heterocycl. Compd. 1994, 30, 125.
11. Toth, G.; Levai, A.; Szollosy, A. Liebigs Ann. Chem. 1992, 803.
12. Krause, N.; Hoffmann-Roder, A. Synthesis 2001, 2, 171.
13. Hakiki, A.; Mossadak, M.; Mokhles, M.; Duddeck, H.; Nikhlova, B. Tetrahedron
1995, 51, 2293.
4.6.3. 5-(1,3-Dimethyl-2-oxo-5-(p-tolyl)-2,3-dihydro-1H-imidazol-
4-yl)-1,3-dimethylpyrimidine-2,4,6-trione (9b)
The title compound was obtained as a colorless solid in 62%
yield (0.22 g), mp 220–221 ꢁC. [Found: C, 60.59; H, 5.72; N, 15.64.
C
18H20N4O4 requires C, 60.66; H, 5.66; N, 15.72%.] nmax (KBr, cmꢀ1
)
1629, 1667, 1702; dH (200 MHz, DMSO-d6) 2.26 (3H, s, MeAr), 2.89
(3H, s, Me), 3.07 (3H, s, Me), 3.12 (6H, s, 2 NMe), 3.47 (1H, s, CH),
7.10–7.16 (4H, m, Ar); dC (100 MHz, DMSO-d6) 21.2, 27.8, 28.8, 29.3,
80.0, 112.9, 131.5, 128.3, 129.0, 131.0, 137.8, 151.8, 154.0, 162.2; MS,
ꢂ
m/z (I, %): 356 (Mþ , 100).
14. Negwer, M. Organic-Chemical Drugs and their Synonyms, 7th revised and en-
larged ed.; Akademie: Berlin, 1994; Vol. 4, pp 2873, 2957.
15. Kolos, N. N.; Orlov, V. D.; Chebanov, V. A.; Shishkin, O. V.; Kuznetsov, V. P.;
Kulikov, A. Yu. Chem. Heterocycl. Compd. 1996, 978.
4.7. 5-(2-Amino-4-phenylthiazol-5-yl)-6-hydroxy-1,3-
dimethylpyrimidine-2,4-dione (13)
16. Kolos, N. N.; Beryozkina, T. V.; Yaremenko, F. G.; Enina, L. S.; Musatov, V. I. Funct.
Mater. 2005, 12, 569.
17. Ramasamy, K.; Imamura, N.; Hanna, N. B.; Finch, R. A.; Avery, T. L.; Robins, R. K.;
Revankar, G. K. J. Med. Chem. 1990, 33, 1220.
18. Bhattachary, B. K.; Ojwang, J. O.; Rando, R. F.; Huffman, J. H.; Rewankar, G. R.
J. Med. Chem. 1995, 38, 3957.
19. Figueras, J. J. Org. Chem. 1966, 31, 803.
20. Sabri, S. S.; Hussein, A. Q.; Al-Hajjar, F. H. J. Chem. Eng. Data 1985, 30, 512.
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741.
22. Zefirov, Yu. V.; Zorkii, P. M. Russ. Chem. Rev. 1989, 58, 421.
23. Balalai, S.; Soleiman, M.; Rominger, F. J. Iran. Chem. Soc. 2005, 2, 319.
24. Al-Hajjar, F. H.; Al-Farkh, Y. A.; Hamoud, H. S. Can. J. Chem. 1979, 57, 2734.
25. Mamaev, V. P.; Weis, A. L. Khim. Geterotsikl. Soedin. 1975, 1555.
26. Weis, A. L.; Mamaev, V. P. Khim. Geterotsikl. Soedin. 1977, 674.
27. Butler, A. R.; Hussain, J.; Leitch, E. J. Chem. Soc., Perkin Trans. 2 1980, 106.
28. Sheldrick, G. M. SHELXTL PLUS. PC Version. A System of Computer Programs for the
Determination of Crystal Structure from X-ray Diffraction Data; Bruker AXS:
Madison, Wisconsin, USA, 1998; Rev. 5.1.
A mixture of enone 3a (1.0 mmol) and thiourea (12) (1.0 mmol)
was heated at reflux in ethanol (8–10 mL) for 10 min. Product 13 as
colorless solid was filtered off and washed with ethanol in 62% yield
(0.20 g), mp >300 ꢁC. [Found: C, 54.60; H, 4.36; N, 17.05; S, 9.73.
C
15H14N4O3S requires C, 54.53; H, 4.27; N,16.96; S, 9.71%.] nmax (KBr,
cmꢀ1) 1622, 1665, 1676, 3220, 3326; dH (200 MHz, DMSO-d6) 3.01
(6H, s, 2Me), 7.23–7.43 (5H, m, Ph), 8.55 (2H, br s, NH2),12.75 (1H, br
s, OH); dC (100 MHz, DMSO-d6) 27.8, 78.0, 119.3, 132.0, 127.6, 128.6,
ꢂ
128.8, 131.6, 153.1, 161.8, 168.5, 167.0; MS, m/z (I, %): 330 (Mþ , 100).
4.8. X-ray diffraction study of 9e
X-ray diffraction study of 9e was performed on an ‘Xcalibur 3’
diffractometer at 300 K (graphite-monochromated Mo K
a radiation,
CCD detector,
u-scans). Crystal data: C17H17N6O6I (Mr¼468.25),
29. Spek, A. L. PLATON; University of Utrecht: The Netherlands, 2001.