An Efficient Method for the Synthesis of N-uracil-4-oxo-thiazolidines without Catalyst

Article abstract of DOI:10.1002/jhet.3589

We have developed highly efficient, one-pot three component reaction of 5-amino-uracil and aromatic aldehydes with thioglycolic acid for the synthesis of N-uracil-thiazolidinones in excellent yields. The same products were also prepared by the reaction of Schiff bases of 5-amino-uracil with thioglycolic acid. In addition, benzylation of thiazolidinone derivatives and Schiff bases by using benzyl chloride was investigated. The results obtained from elemental microanalysis and different spectral data are in agreement with the assigned structures.

Full text of DOI:10.1002/jhet.3589

Month 2019
An Efficient Method for the Synthesis of N-uracil-4-oxo-thiazolidines
without Catalyst
*
Asmaa H. Mohamed
and Raafat M. Shaker
Chemistry Department, Faculty of Science, Minia University, El-Minia, Egypt
*E-mail: asmaachemistry@yahoo.com
Received October 4, 2018
DOI 10.1002/jhet.3589
Published online 00 Month 2019 in Wiley Online Library (wileyonlinelibrary.com).
We have developed highly efficient, one-pot three component reaction of 5-amino-uracil and aromatic al-
dehydes with thioglycolic acid for the synthesis of N-uracil-thiazolidinones in excellent yields. The same
products were also prepared by the reaction of Schiff bases of 5-amino-uracil with thioglycolic acid. In ad-
dition, benzylation of thiazolidinone derivatives and Schiff bases by using benzyl chloride was investigated.
The results obtained from elemental microanalysis and different spectral data are in agreement with the
assigned structures.
J. Heterocyclic Chem., 00, 00 (2019).
INTRODUCTION
benzotriazole
tetramethyl
uronium
[18],
N,N0-
dicyclohexylcarbodiimide [19], silica gel [20], [bmim]
[PF6] [21], ZnCl2 [22], ferrite [23], Hunig’s base [24],
[BmIm]OH [25], molecular sieves [26], sodium sulfate
[27], montmorillonite K-10 [28], nano-Fe3O4@SiO2 [29],
[Et3NH][HSO4] [30], DBSA [31], and baker’s yeast [32].
In addition, the structure of uracil still attracts the
attendance of organic chemists and biologist [33–38],
because of wide array of biological activities, synthetic
accessibility, and ability to grant drug like properties to
the compound libraries suffixed on it at the N1, N3, C5,
and C6 positions [39].
In continuation of our interest in the development of
new and simple methods for the synthesis of
polyfunctionally substituted heterocyclic compounds
starting from 5-amino-uracil [40–44], we wish to report
an efficient one-pot method for the synthesis of N-
uracil-thiazolidinones.
In recent years, the chemistry of 4-thiazolidinone
derivatives has been the subject of intense research by
biologists and organic chemists because such
compounds represent substantial scaffolds in drug
discovery [1,2]. According to this approach, thiazolidin-
4-ones have been reported to own wide spectrum of
biological activity such as antimicrobial [3–7],
antitubercular [8,9], antitumoral [10], anticancer [11,12],
anti-inflammatory [13], antiglioma [14], anticonvulsant
[15], anti-HIV-1 [16], antioxidant [5,12], and analgesic
properties [17].
The most well-known and classical method for the
synthesis of these compounds includes two-component
and three-component reactions involving primary amines,
an oxo-compound and thiolic acids in the presence
of diverse catalysts, such as hexafluorophosphate
© 2019 Wiley Periodicals, Inc.

A. H. Mohamed and R. M. Shaker
Vol 000
Scheme 1. Synthesis of N-uracil-thiazolidinones 5a–d.
RESULTS AND DISCUSSION
It has been known that the uracil ring has a high
potential to form polar intermolecular and hydrogen bond
interactions [35]. The electrophilic attack at uracil ring
involves nitrogen’s (N1, N3), oxygen’s (O2 and O4), or
(C6), so the formation of compounds 6 and 7 was
possible when we studied the alkylation of 5a–d with
benzyl chloride in the presence of potassium carbonate as
a base. The benzylated derivatives 6a–d was formed in
75–78% yield. The support for the structure of 6 was
provided from spectral data and elemental analysis. For
example, the 13C NMR spectrum of compound 6a
showed three values for 3C═O at 171.59, 159.73, and
150.29 ppm that exhibited strong absorption bands at
1702, 1634, and 1600 cmꢀ1 in its IR spectrum, and
Scheme 1 outlines the synthesis of 5-(4-oxo-2-aryl
thiazolidin-3-yl)pyrimidine-2,4(1H,3H)-dione 5a–d via
one-pot three-component reaction of 5-aminouracil (1),
aromatic aldehydes 2a–d, and thioglycolic acid (3)
without catalyst in dioxane as a solvent. The structure of
the thiazolidinones 5a–d was further supported by an
alternative synthesis. Thus, cyclocondensation of Schiff
bases 4a–d with compound 3 in equimolar proportions in
dioxane gave the same products 5a–d. The formation of
compounds 5a–d was rationalized by initial formation
of an imine 4a–d, which undergoes attack by the sulfur
nucleophile, followed by intramolecular cyclization on
elimination of water. All products have been fully
characterized by analytical and spectroscopic data. For
example, compound 5a exhibited an IR spectrum with
1
these facts allowed us to discard the structure 7. The H
NMR spectrum of 6a revealed that the alkylation
occurs only at the N-1 and N-3 atoms, which showed
disappearance of two NH protons and showed signals
strong absorption bands at 3439 and 3292 cmꢀ1
,
belonging to stretching vibrations of the NH groups, in
addition to the absorption bands at 1718, 1685, and
for the N1CH2 (δ 4.75) and N3CH2 protons
=
(δ = 4.79 ppm). Furthermore, the fragmentation patterns
of the mass spectra of 6a showed the molecular ion
peak at m/z = 514 (M+1) and m/z 513 (M+), respectively.
Further confirmation of structures 6a–d was made via
the synthesis of alkylated Schiff base 8a–d, prepared
from the reaction of compounds 4a–d with benzyl
chloride. Subsequent refluxing of 8a–d with 2-
1
1659 cmꢀ1 for carbonyl groups. Its H NMR spectrum
revealed three sharp singlet signals at 11.50, 9.37, and
8.11 (two NH groups and CH for uracil ring, 3-NH,
1-NH, and 6-CH, respectively) and three singlet signals
at 6.00, 5.23, and 3.92 ppm (CH2 of pipronal, CH and
CH2 of thiazolidinone ring, respectively).
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

Month 2019
One-Pot Three-Component Reaction of 5-Aminouracil, Aromatic Aldehydes, and
Thioglycolic Acid To Give 4-Oxothiazolidin-3-yl-pyrimidine-2,4(1H,3H)-diones
Scheme 2. Benzylation of compounds 5a–d.
mercaptoacetic acid (3) in benzene smoothly converts it to
the final products 6a–d (Scheme 2).
filtered off. The products 4a–d were obtained in very
good yields.
(E)-5-((benzo[d][1,3]dioxol-5-ylmethylene)amino)pyrimidine
-2,4(1H,3H)-dione (4a).
Pale yellow solid; mp 358–
360°C; yield 89%; IR (KBr): νmax/cmꢀ1 = 3269 (NH),
CONCLUSION
1
1624 (CO), 1608 (C═N). H NMR (400 MHz, DMSO):
δH = 6.10 (s, 2H, CH2), 6.99–7.01 (d, 1H, J = 8.0 Hz,
Ar─H), 7.25–7.27 (d, 1H, J = 8.0 Hz, Ar─H), 7.38
(s, 1H, Ar─H), 7.53 (s, 1H, N═CH), 9.23 (s, 1H, C6H),
11.10 (s, 1H, NH), 11.31 (s, 1H, NH).13C NMR
(100 MHz, DMSO): δC = 102.05 (CH2), 105.87, 108.79,
122.74, 125.23, 132.19 (CH─Ar), 137.84, 148.45,
150.13 (C─Ar), 150.58 (C═N), 158.08 (CO), 161.89
(CO). MS, (m/z) (%): 259 (M+, 85). Anal. for C12H9N3O4
(259.22): calcd C, 55.60; H, 3.50; N, 16.21; found: C,
We have reported a simple method for the synthesis of
N-uracilthiazolidinones by using one-pot three-
component reaction of 5-amino uracil, thioglycolic
acid and some aromatic aldehydes. The alkylation of
thiazolidinones with benzyl chloride in the presence
of K2CO3 was studied. In addition, the definite
structures of the novel products have been confirmed
by spectral data.
55.78; H, 3.55; N, 16.37.
(E)-5-(((1H-indol-3-yl)methylene)amino)pyrimidine-
2,4(1H,3H)-dione (4b). Yellow crystals; mp 344–346°C;
EXPERIMENTAL
yield 85%, IR (KBr): νmax/cmꢀ1 = 3245, 3159 (NH),
General remarks. All reagents were purchased from
Alfa Aesar or Fluka and were used without further
purification. Melting points were measured in capillary
tubes using a Büchi 530 melting point apparatus and
are uncorrected. IR spectra were measured using a
Bruker Tensor 27 instrument. 1H NMR (300 or
400 MHz) and 13C NMR (75 or 101 MHz) spectra
were recorded in DMSO-d6 on BrukerAvance II-300
and Avance DRX-400 spectrometers with trimethylsilyl
(for 1H) or the solvent (for 13C, δC = 77.01 ppm) as
the internal standards. Mass spectral measurements (EI,
70 eV) were performed using a Finnigan MAT 8430
spectrometer.
1
1640 (CO), 1622 (C═N). H NMR (400 MHz, DMSO):
δ = 7.13–7.11 (t, 1H, J = 8.0 Hz, Ar─H), 7.20–7.18
(t, 2H, J = 2.0 Hz, Ar─H), 7.49–7.46 (m, 2H,
Ar─H + N═CH), 7.89–7.88 (d, 1H, J = 2.8 Hz, CH-
Indol), 8.36–8.34 (d, 1H, J = 8.0 Hz, Ar─H), 9.34
(s, 1H, CH-6), 10.91 (s, 1H, NH), 11.63 (s, 1H, NH),
11.21 (s, 1H, NH).13CNMR (100 MHz, DMSO):
δ = 112.22 (C-3-indol), 115.59 (C-5), 120.64, 122.50,
123.20, 124.98 (CH─Ar), 132.95 (C-6), 134.38, 137. 88
(C─Ar), 150.83 (C═N), 155.90 (CO), 162.49 (CO). MS,
(m/z) (%): 256.16 (M+2), 254 (M+, 100). Anal. for
C13H10N4O2 (254.24): calcd C, 61.41; H, 3.96; N, 22.04.
Found: C, 61.61; H, 4.03; N, 22.23.
Synthesis of compounds 4a–d.
To a mixture of
(E)-5-((4-chlorobenzylidene)amino)pyrimidine-2,4(1H,3H)-
dione (4c). Pale yellow solid; mp 346–348°C; yield 93%
(Gouvea et al. 13 345–346°C).
(E)-5-((4-(dimethylamino)benzylidene)amino)pyrimidine-2,4
compound 1 (2 mmol) and the aldehydes 2a–d (2 mmol)
in DMSO (10 mL), p-TSA (10 mg) was added. The
reaction mixture was stirred for 24
h at room
(1H,3H)-dione(4d).
322–324°C (Rawal et al. 18 322–324°C).
Pale yellow solid, yield 86%; mp
temperature. The precipitated solid was obtained by
pouring the reaction mixture onto cold water, and then
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

A. H. Mohamed and R. M. Shaker
Vol 000
General procedures for the synthesis of compounds
5a–d.
Method A.
1H, HC-6), 9.30 (s, 1H, NH), 11.40 (s, 1H, NH).13C
NMR (100 MHz, DMSO): δ = 32.25 (CH2), 62.29 (CH-
thiazolidinone), 108.51 (C-5), 129.02,129.13, 129.96
(CH─Ar), 132.07 (HC-6), 132.17, 133.48, 139.86
(C─Ar), 162.12 (CO), 167.47 (CO), 171.39 (CO). MS,
(m/z) (%): 325 (M+2, 25), 323 (M+, 60). Anal. for
C13H10ClN3O3S (323.75): calcd C, 48.23; H, 3.11;
N, 12.98; S, 9.90; found: C, 48.41; H, 3.16; N, 13.14,
(three-component reaction): Refluxing a
mixture of compound (1) (1 mmol), 2-mercaptoacetic
acid (3, 2 mmol), and the appropriate aldehyde (1 mmol)
in dioxane for 10 h. The collected water was removed by
using the Dean–Stark trap and then the reaction mixture
was neutralized by a solution of sodium carbonate after
cooling. The solvent was removed under reduced
pressure and then the oily residue was powdered by
S; 9.85.
5-(2-(4-(Dimethylamino)phenyl)-4-oxothiazolidin-3-yl)pyri
midine-2,4(1H,3H)-dione (5d). Pale yellow solid; mp 328–
330°C; yield (A) 79%, (B) 80%; IR (KBr): νmax/
cmꢀ1 = 3217 (NH), 1698 (CO), 1665 (CO), 1649 (CO).
1H NMR (400 MHz, DMSO): δ = 2.87 (s, 3H, CH3),
3.17 (s, 3H, CH3), 3.79 (s, 2H, CH2), 5.23 (s, 1H, CH-
thiazolidinone), 6.62–6.65 (d, 1H, J = 8.0 Hz, Ar─H),
7.17–7.19 (d, 1H, J = 8.0 Hz, Ar─H), 8.09–8.11 (m, 2H,
Ar─H), 9.37 (s, 1H, HC-6), 10.69 (s, 1H, NH), 11.50
(s, 1H, NH).13C NMR (100 MHz, DMSO): δ = 27.86
(2CH3), 42.33 (CH2), 69.60 (CH-thiazolidinone), 112.38
(C-5), 113.63, 113.70, 128.82, 129.28 (CH─Ar), 129.67
(HC-6), 138.90, 150.03 (C─Ar), 160.96 (CO), 167.62
(CO), 169.41 (CO). MS, (m/z) (%): 332 (M+, 12).
Anal. for C15H16N4O3S (332.38): calcd C, 54.20; H,
4.85; N, 16.86; S, 9.65; found: C, 54.40; H, 4.89; N,
17.01; S, 9.59.
treatment with diethyl ether to afford compounds 5a–d.
Method B. (two-component reaction): To a well-stirred
suspension of the appropriate 4a–d (1 mmol) in dioxane
(10 mL), 2-mercaptoacetic acid (3, 2 mmol) was added.
The reaction mixture was refluxed for 8 h and the
collected water was removed by using the Dean–Stark
trap. After cooling, the deposited solid was filtered off
and crystallized from dimethylformamide (DMF)/ethanol
to give the title compounds 5a–d.
5-(2-(Benzo[d][1,3]dioxol-5-yl)-4-oxothiazolidin-3-yl)pyrimi
dine-2,4(1H,3H)-dione (5a).
Yellow crystals; mp 328–
330°C; yield (A) 83%, (B) 83%; IR (KBr): νmax/
cmꢀ1 = 3439–3292 (NH), 1718 (CO), 1685 (CO), 1659
1
(CO). H NMR (400 MHz, DMSO): δ = 3.92 (s, 2H,
CH2), 5.23 (s, 1H, CH-thiazolidinone), 6.00 (s, 2H, CH2),
7.23 (s, 1H, Ar─H), 7.43–7.36 (m, 2H, Ar─H), 8.11
(s, 1H, HC-6), 9.37 (s, 1H, NH), 11.50 (s, 1H, NH).
13CNMR (100 MHz, DMSO): δ = 53.18 (CH2), 63.45
(CH-thiazolidinone), 101.56 (CH2), 108.18 (C-5), 113.52,
113.72, 114.15 (CH─Ar), 126.15 (HC-6), 130.07,
149.89, 150.13 (C─Ar), 161.00 (CO), 169.54 (CO),
171.57 (CO). MS, (m/z) (%): 333 (M+, 22). Anal. for
C14H11N3O5S (333.32): calcd C, 50.45; H, 3.33; N,
General procedures for the synthesis of compounds
6a–d.
Method A. The reaction mixture of 5a–d (1 mmol) and
solid K2CO3 (4 mmol) in 5-mL dry DMF was stirred for
30 min. The first fraction of benzyl chloride (3 mmol)
was added, and then the reaction mixture was stirred for
3–4 h at room temperature. The next fraction of benzyl
chloride (1 mmol) was added; the reaction mixture was
stirred for further 10 h and poured onto cold water.
The pale yellow precipitate was filtered, washed with
water, and crystallized from ethanol.
12.61; S, 9.62; found: C, 50.65; H, 3.38; N, 12.79; S, 9.54.
5-(2-(1H-indol-3-yl)-4-oxothiazolidin-3-yl)pyrimidine-
2,4(1H,3H)-dione (5b). Yellow crystals; mp 330–332°C;
yield (A) 78%, (B) 80%; IR (KBr): νmax/cmꢀ1 = 3269–
1
3166 (NH), 1680 (CO), 1666 (CO), 1640 (CO). H NMR
Method B.
To a well-stirred suspension of the
(400 MHz, DMSO): δ = 4.13 (s, 2H, CH2), 6.20 (s, 1H,
CH-thiazolidinone), 7.70–7.69 (m, 2H, Ar─H), 8.17 (m,
2H, Ar─H), 8.27 (s, 1H, CH), 8.29 (s, 1H, HC-6), 9.50
(s, 1H, NH), 9.92 (s, 1H, NH-indol), 11.50 (s, 1H, NH).
13CNMR (100 MHz, DMSO): δ = 49.06 (CH2), 94.80
(CH-thiazolidinone), 108.18 (C-5), 109.52, 115.88,
117.00, 120.25, 122.00, 125.00 (CH─Ar), 128.27 (HC-
6), 131.25, 146.96 (C─Ar), 162.00 (CO), 164.00 (CO),
166.00 (CO). MS, (m/z) (%): 328 (M+, 42). Anal. for
C15H12N4O3S (328.38): calcd C, 54.87; H, 3.68; N,
appropriate 8a–d (1 mmol) in dry benzene (20 mL), 2-
mercaptoacetic acid (3, 2 mmol) was added. The
reaction mixture was refluxed for 8 h. The collected
water was removed by using the Dean–Stark trap. After
cooling, the deposited solid was filtered off and
crystallized from ethanol to give the title compounds.
5-(2-(Benzo[d][1,3]dioxol-5-yl)-4-oxothiazolidin-3-yl)-1,3-di
benzylpyrimidine-2,4(1H,3H)-dione (6a).
White solid;
mp 168–170°C; yield (A) 75%, (B) 77%; IR (KBr):
νmax/cmꢀ1 = 1702 (CO), 1634 (CO), 1600 (CO), 1435
1
(CH2). H NMR (400 MHz, DMSO): δ = 3.95 (s, 2H,
17.06; S, 9.77; found: C, 55.09; H, 3.72; N, 17.21; S, 9.71.
5-(2-(4-Chlorophenyl)-4-oxothiazolidin-3-yl)pyrimidine-
2,4(1H,3H)-dione (5c). Pale yellow solid; mp 340–342°C;
CH2), 4.75 (s, 2H, CH2), 4.79 (s, 2H, CH2), 6.00 (s, 1H,
CH-thiazolidinone), 6.03 (s, 2H, CH2), 6.81–7.09 (m, 3H,
Ar─H), 7.23–7.29 (m, 10H, Ar─H), 8.04 (s, 1H, HC-6).
13C NMR (100 MHz, DMSO): δ = 32.51 (CH2), 44.43
(N─CH2), 52.36 (N─CH2), 63.32 (CH-thiazolidinone),
101.83 (CH2), 108.35 (C-5), 110.75, 122.73, 127.57,
yield (A) 80%, (B) 80%; IR (KBr): νmax/cmꢀ1 = 3206
(NH), 1705 (CO), 1654 (CO), 1645 (CO). 1H NMR
(400 MHz, DMSO): δ = 3.93 (s, 2H, CH2), 6.03 (s, 1H,
CH-thiazolidinone), 7.35–7.48 (m, 4H, Ar─H), 8.09 (s,
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

Month 2019
One-Pot Three-Component Reaction of 5-Aminouracil, Aromatic Aldehydes, and
Thioglycolic Acid To Give 4-Oxothiazolidin-3-yl-pyrimidine-2,4(1H,3H)-diones
127.69, 127.76, 128.28, 128.79 (CH─Ar), 128.97 (HC-6),
132.43, 136.47, 136.92, 148.19, 148.38 (C─Ar), 150.29
(CO), 159.73 (CO), 171.59 (CO). MS, (m/z) (%): 513
(M+, 12). Anal. for C28H23N3O5S (513.56): calcd C,
65.48; H, 4.51; N, 8.18; S, 6.24; found: C, 65.66; H,
4.56; N, 8.30; S, 6.19.
1,3-Dibenzyl-5-(2-(1-benzyl-1H-indol-3-yl)-4-oxothiazolidin-
3-yl)pyrimidine-2,4(1H,3H)-dione (6b). Pale yellow solid;
5.51; N, 10.93; S, 6.26; found: C, 68.11; H, 5.55; N,
11.11; S, 6.21.
General procedure for the synthesis of compounds 8a–d.
The reaction mixture of 4a–d (1 mmol) and solid K2CO3
(4 mmol) in 5-mL dry DMF was stirred for 30 min.
Then, the first fraction of benzyl chloride (3 mmol) was
added, and the reaction mixture was stirred for 3–4 h at
room temperature. Then, the next fraction of benzyl
chloride (1 mmol) was added; the reaction mixture was
stirred for further 10 h and poured onto cold water. The
pale yellow precipitate was filtered, washed with water,
mp 190–192°C; yield (A) 73%, (B) 73%; IR (KBr):
νmax/cmꢀ1 = 1701 (CO), 1675 (CO), 1650 (CO), 1440
1
(CH2). H NMR (400 MHz, DMSO): δ = 3.45 (s, 2H,
CH2), 4.13 (s, 4H, 2CH2), 4.74 (s, 2H, CH2), 5.00 (s, 1H,
CH-thiazolidinone), 6.80–6.82 (m, 2H, Ar─H + CH-
indol), 7.16–7.32 (m, 19H, Ar─H + HC-6).13C NMR
(100 MHz, DMSO): δ = 30.26 (CH2), 44.11 (N─CH2),
52.00 (N─CH2), 55.80 (N─CH2), 64.50 (CH-
thiazolidinone), 122.40, 126.22, 127.29, 127.54, 127.59,
127.65, 127.80, 128.02, 128.13, 128.68, 128.78, 128.88
(CH─Ar), 129.05 (HC-6), 136.97, 137.16, 137.53,
138.51 (C─Ar), 150.20 (CO), 161.27 (2CO). MS, (m/z)
(%): 598 (M+, 20). Anal. for C36H30N4O3S (598.71):
calcd C, 72.22; H, 5.05; N, 9.36; 5.36; found: C, 72.41;
H, 5.09; N, 9.52; S, 5.32.
and crystallized from ethanol.
(E)-5-((benzo[d][1,3]dioxol-5-ylmethylene)amino)-1,3-diben
zylpyrimidine-2,4(1H,3H)-dione (8a). Pale yellow solid; mp
156–158°C; yield 76%, IR (KBr): νmax/cmꢀ1 = 1633
1
(CO), 1618 (C═N), 1448 (CH2). H NMR (400 MHz,
DMSO): δ = 5.04 (s, 2H, N─CH2), 5.07 (s, 2H,
N─CH2), 6.10 (s, 2H, CH2), 7.00–7.02 (d, 1H,
J = 8.0 Hz, Ar─H), 7.23–7.38 (m, 12H, Ar─H), 8.13 (s,
1H, HC-6), 9.25 (s, 1H, HC═N).13C NMR (100 MHz,
DMSO): δ = 44.60 (N─CH2), 52.27 (N─CH2), 102.12
(CH2), 105.91 (CH─Ar), 108.86 (C-5), 122.88, 125.54,
127.67, 128.04, 128.13, 128.29, 128.82, 129.15, 129.30,
131.95, 132.19 (CH─Ar), 137.01, 137.44, 139.90,
148.50 (C─Ar), 150.40 (HC-6), 150.45 (C═N), 159.14
(CO), 160.19 (CO). MS, (m/z) (%): 439 (M+, 16). Anal.
for C26H21N3O4 (439.46): calcd C, 71.06; H, 4.82; N,
1,3-Dibenzyl-5-(2-(4-chlorophenyl)-4-oxothiazolidin-3-yl)
pyrimidine-2,4(1H,3H)-dione (6c). White crystal; mp 184–
186°C; yield (A) 75%, (B) 76%; IR (KBr): νmax/
cmꢀ1 = 1698 (CO), 1630 (CO), 1610 (CO), 1420 (CH2).
1H NMR (400 MHz, DMSO): δ = 3.94 (s, 2H, CH2),
4.71 (s, 2H, N─CH2), 4.76 (s, 2H, N─CH2), 6.05 (s,
1H, CH-thiazolidinone), 6.98–7.07 (m, 5H, Ar─H),
7.24–7.28 (m, 4H, Ar─H), 7.38–7.47 (m, 5H, Ar─H),
8.08 (s, 1H, HC-6). 13C NMR (100 MHz, DMSO):
δ = 31.90 (CH2), 43.92 (N─CH2), 51.86 (N─CH2),
62.02 (CH-thiazolidinone), 110.04 (C-5), 121.17, 127.13,
127.25, 127.76, 128.27, 128.46, 128.65 (CH─Ar),
129.99 (HC-6), 133.52, 135.91, 136.36, 137.52, 145.61,
149.68 (C─Ar), 159.15 (CO), 171.20 (2CO). MS, (m/z)
9.56; found: C, 71.25; H, 4.86; N, 9.60.
(E)-1,3-dibenzyl-5-(((1-benzyl-1H-indol-3-yl)methylene)ami
no)pyrimidine-2,4(1H,3H)-dione (8b). Pale yellow solid;
mp 98–100°C; yield 70%; IR (KBr): νmax/
cmꢀ1 = 1634 (CO), 1620 (C═N), 1450 (CH2). 1H
NMR (400 MHz, DMSO): δ = 4.75 (s, 2H, N─CH2),
5.00 (s, 2H, N─CH2), 5.55 (s, 2H, N─CH2), 6.81–
6.83 (m, 2H, Ar─H), 7.23–7.39 (m, 11H,
Ar─H + CHindol), 7.58–7.60 (d, 1H, J = 8.0 Hz,
Ar─H), 8.12–8.14 (d, 1H, J = 8.0 Hz, Ar─H), 8.48 (s,
1H, HC-6), 9.95 (s, 1H, HC═N). 13C NMR (100 MHz,
DMSO): δ = 50.29 (N─CH2), 52.00 (N─CH2), 55.88
(N─CH2), 111.88 (C-5), 117.89, 121.56, 122.40,
123.03, 124.10, 125.30, 127.32, 127.53, 127.58, 127.69,
127.79, 127.83, 127.92, 128.07, 128.15, 128.27, 128.68,
128.77, 128.88, 128.97, 129.06, 129.14, 129.21
(CH─Ar), 137.45 (HC-indol), 137.57, 138.54, 141.45
(C─Ar), 150.40 (C═N), 150.28 (CO), 161.26 (CO).
MS, (m/z) (%): 524 (M+, 10). Anal. for C34H28N4O2
(524.61): calcd C, 77.84; H, 5.38; N, 10.68; found: C,
,
(%): 503 (Mꢀ1 22), 505 (M+1, 10). Anal. for
C27H22ClN3O3S (504.00): calcd C, 64.34; H, 4.40; N,
8.34; S, 6.36; found: C, 64.51; H, 4.45; N, 8.54; S, 6.31.
1,3-Dibenzyl-5-(2-(4-(dimethylamino)phenyl)-4-oxothiazoli
din-3-yl)pyrimidine-2,4(1H,3H)-dione (6d).
Pale yellow
crystal; mp 190–192°C; yield (A) 73%, (B) 73%; IR
(KBr): νmax/cmꢀ1 = 1702 (CO), 1628 (CO), 1615 (CO),
1
1445 (CH2). H NMR (400 MHz, DMSO): δ = 3.69 (s,
3H, CH3), 3.74 (s, 3H, CH3), 3.95 (s, 2H, CH2), 5.00 (s,
2H, N─CH2), 5.07 (s, 2H, N─CH2), 6.10 (s, 1H, CH-
thiazolidinone), 7.36–7.24 (m, 14H, Ar─H), 8.14 (s, 1H,
HC-6).13C NMR (100 MHz, DMSO): δ = 31.24 (CH2),
44.20 (N─CH2), 51.90 (N─CH2), 67.52 (CH-
thiazolidinone), 109.49 (C-5), 120.96, 121.17, 127.13,
127.25, 127.44, 127.75, 128.20 (CH─Ar), 128.55 (HC-
6), 136.19, 136.65, 145.93, 150.45 (C─Ar), 159.94 (CO),
168.71 (CO), 170.85 (CO). MS, (m/z) (%): 512 (M+, 14).
Anal. for C29H28N4O3S (512.62): calcd C, 67.95; H,
77.99; H, 5.41; N, 10.87.
(E)-1,3-dibenzyl-5-((4-chlorobenzylidene)amino)pyrimidine-
2,4(1H,3H)-dione (8c). Pale yellow solid; mp 184–186°C;
yield 77%; IR (KBr): νmax/cmꢀ1 = 1645 (CO), 1625
(C═N), 1455 (CH2). 1H NMR (400 MHz, DMSO):
δ = 5.05 (s, 2H, CH2), 5.07 (s, 2H, CH2), 7.30–7.38 (m,
10H, Ar─H), 7.51–7.54 (d, J = 9.0 Hz, 2H, Ar─H),
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

A. H. Mohamed and R. M. Shaker
Vol 000
[17] Popiołeka, Ł.; Piątkowska-Chmielb, I.; Gawrońska-
Grzywaczb, M.; Biernasiukc, A.; Izdebskab, M.; Herbetb, M.; Sysab,
M.; Malmc, A.; Dudkab, J.; Wujeca, M. Biomed Pharmacother 2018,
103, 1337.
7.82–7.85 (d, J = 9.0 Hz, 2H, Ar─H), 8.21 (s, 1H, HC-6),
9.41 (s, 1H, CH═N). MS, (m/z) (%): 429 (M+, 20). Anal.
for C25H20ClN3O2 (429.90): calcd C, 69.85; H, 4.69; N,
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(E)-1,3-dibenzyl-5-((4-(dimethylamino)benzylidene)amino)
pyrimidine-2,4(1H,3H)-dione (8d). Pale yellow solid; mp
164–166°C; yield 76%; IR (KBr): νmax/cmꢀ1 = 1702
(CO), 1663 (C═N), 1567 (CH2). 1H NMR (400 MHz,
DMSO): δ = 2.98 (s, 6H, 2CH3), 5.01(s, 2H, CH2), 5.06
(s, 2H, CH2), 6.73–6.76 (d, 2H, J = 9.0 Hz, Ar─H),
7.26–7.37 (m, 10H, Ar─H), 7.61–7.64 (d, 2H,
J = 9.0 Hz, Ar─H), 7.92 (s, 1H, HC-6), 9.04 (s, 1H,
CH═N). MS, (m/z) (%): 438 (M+, 18). Anal. for
C27H26N4O2 (438.52): calcd C, 73.95; H, 5.98; N, 12.78;
found: C, 74.16; H, 6.02; N, 12.92.
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SUPPORTING INFORMATION
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Additional supporting information may be found online
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Journal of Heterocyclic Chemistry
DOI 10.1002/jhet