Potassium Fluoride-Modified Clay as a Reusable Heterogeneous Catalyst for One-Pot Synthesis of 3,4-Dihydropyrimidin-2(1H)-ones

Article abstract of DOI:10.1134/S1070428019090240

Potassium fluoride-modified clay collected from the region of Agadir (Morocco) was used as a hetaerogeneous catalyst in the one-pot synthesis of 3,4-dihydropyrimidine-2(1H)-one derivatives via the Biginelli reaction. The products were obtained with excell

Full text of DOI:10.1134/S1070428019090240

ISSN 1070-4280, Russian Journal of Organic Chemistry, 2019, Vol. 55, No. 9, pp. 1423–1431. © Pleiades Publishing, Ltd., 2019.
Potassium Fluoride-Modified Clay as a Reusable
Heterogeneous Catalyst for One-Pot Synthesis
of 3,4-Dihydropyrimidin-2(1H)-ones
S. Bentahara,* M. Ait Talebb, A. Saboura, A. Dbika, M. El Khomria, N. El Messaoudia,
A. Lacheraia, and R. Mamounib
a Laboratory of Applied Chemistry and Environment, Department of Chemistry,
Faculty of Science, Ibn Zohr University, Agadir, Morocco
*e-mail: safae.bentahar@edu.uiz.ac.ma
b Team of Materials, Catalysis, and Valorization of Natural Resources, Department of Chemistry,
Faculty of Science, Ibn Zohr University, Agadir, Morocco
Received November 28, 2018; revised July 1, 2019; accepted July 2, 2019
Abstract—Potassium fluoride-modified clay collected from the region of Agadir (Morocco) was used as a het-
erogeneous catalyst in the one-pot synthesis of 3,4-dihydropyrimidine-2(1H)-one derivatives via the Biginelli
reaction. The products were obtained with excellent yields (88–98%). The catalyst was characterized X-ray
powder diffraction, Fourier-transform IR spectroscopy, scanning electron microscopy, differential thermal
analysis, thermogravimetry, and Brunauer–Emmett–Teller (BET) analysis. Plausible reaction mechanisms for
both reactions have been proposed. The catalyst can be recycled five times without loss of catalytic activity.
Keywords: KF-modified clay, heterogeneous catalysts, Biginelli reaction, substituted pyrimidines, 3,4-dihy-
dropyrimidin-2(1H)-ones.
DOI: 10.1134/S1070428019090240
Multi-component reactions (MCRs) have become
more and more important in organic synthesis [1].
They play a central role in the development of modern
synthetic methodologies advocated by the pharma-
ceutical and biological sector. In addition, this type of
approach has several advantages such as atom econ-
omy and higher overall yield than in sequential syn-
thesis (notably due to the fact that the synthesis takes
place in one step, ensuring that the number of purifica-
tion steps is necessarily less) [2]. The Biginelli syn-
thesis of 3,4-dihydropyrimidin-2(1H)-ones [3] is a one-
pot multicomponent condensation of an aldehyde,
β-keto ester, and urea. This condensation is one of the
most studied reactions because it leads to products
with a wide range of biological and biomedical activ-
ities such as antibacterial [4], antifungal [5], antiviral
[6], as well as anti-inflammatory and antioxidant prop-
erties [7]. In addition, 3,4-dihydropyrimidin-2(1H)-one
derivatives behave as calcium channel blockers [8],
exert antihypertensive effect [9], and act as coronary
dilators. On the other hand, substituted pyrimidines
can be prepared by condensation of aromatic alde-
hydes with urea and ethyl cyanoacetate. It should be
noted that pyrimidines constitute an important class of
compounds having widespread applications in the
pharmaceutical field [10].
Several homogeneous catalysts (H2SO4 [11],
LiClO4 [12], H3BO3 [13], trifluoroacetic acid [14],
boric acid [13]) and heterogeneous catalysts (meso-
porous NH4H2PO4/MCM-41 [15], zeolite-supported
heteropolyacid [16], silica-bonded S-sulfonic acid [17],
ion exchange resins [18], silica-bonded N-propyl
sulfamic acid [8], and MCM-41-anchored sulfonic acid
[19]) have been employed to catalyze the Biginelli
reaction. The majority of these catalysts have disad-
vantages such as long reaction time, low yield, expen-
sive reagents, formation of toxic by-products, tedious
work-up, and strongly acidic conditions.
In this work, we used KF-modified clay as a low-
cost eco-friendly heterogeneous catalyst for the synthe-
sis of 3,4-dihydropyrimidin-2(1H)-ones (Scheme 1).
We studied the effect of the amount of catalyst, sol-
1423

BENTAHAR et al.
1424
Scheme 1.
R
CHO
KF-modified clay
MeCN, 40°C
O
O
O
O
+
+
H2N
NH2
Me
OEt
EtO
NH
R
Me
R
N
H
O
1a–1d
2
3a
4a–4d
KF-modified clay
MeCN, 40°C
O
NC
O
1a–1e
+
2
+
NC
NH
OEt
N
O
Et
3b
5a–5e
1, 4, 5, R = H (a), 4-MeO (b), 4-Me (c), 4-Cl (d), 3-O2N (e).
vent, temperature, and aromatic aldehyde nature on the
yield of the desired products for both reactions.
(–411), (013), (411), (020), (213), (–511), (511), (122),
(–204), and (222), respectively, in accordance with
JCPDS card no. 00-035-0591. The second phase was
attributed to silica due to coincidence with the standard
JCPDS card no. 01-087-2275. This phase is confirmed
by peaks located at 2θ = 16.14, 17.43, 18.81, 20.55,
25.43, 25.89, 26.26, 28.20, 32.24, 33.34, 35.65, 36.93,
37.57, 41.44° and characterized by Miller indices
(310), (301), (12–2), (400), (203), (402), (150), (033),
(61–1), (450), (153), (253), (07–1), and (154),
respectively.
The modified clay was characterized by X-ray
powder diffraction (XPD) using a Bruker Phaser dif-
fractometer with a copper anticathode bombarded by
accelerated electrons, which generated radiation wave-
length λα1 = 1.54060 Å and λα2 = 1.54439 Å at a tube
voltage of 30 kV and a tube current of 10 mA. The
X-ray powder pattern is shown in Fig. 1. According to
the obtained data, the modified clay contains two
phases: the first phase corresponds to merwinite which
is represented by peaks at 2θ = 23.22, 23.59, 29.57,
38.50, 38.86, 39.24, 39.61, 42.64, 45.31, 46.05, 46.69,
47.06, 48.90, of Miller indices (–111), (111), (012),
The FTIR spectrum of KF-modified clay (Burker
Vertex 70) is shown in Fig. 2. The spectrum indicated
the presence of silica which is represented by an in-
600
500
400
300
200
100
0
100
80
60
40
20
0
20
30
40
2θ, deg
4000
3000
3000
1000 ν, cm–1
Fig. 1. X-Ray powder pattern of the KF-modified clay.
Fig. 2. IR spectrum of the KF-modified clay.
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 55 No. 9 2019

POTASSIUM FLUORIDE-MODIFIED CLAY
1425
160
140
120
100
80
60
40
20
0
0.0
0.2
0.4
0.6
0.8
1.0
P/P0
Fig. 3. SEM microphotograph of the KF-modified clay.
Fig. 4. Nitrogen adsorption–desorption isotherms for the KF-
modified clay.
110
105
TG
50
DTA
40
30
20
10
0
100
5.085%
95
3.545%
2.552%
90
85
80
100 200 300 400 500 600 700 800 900 1000
Temperature, °C
Fig. 5. TG and DTA curves for KF-modified clay.
tense peak at 1099.78 cm–1 due to Si–O–Si stretchings
ent shapes with irregular morphologies and dimensions
of tens of microns. These agglomerates are formed by
aggregation of smaller particles of different sizes (from
1 to 10 μm). Magnification of a part of the SEM image
showed that the surface formed by all these particles is
characterized by the presence of pores and cavities of
heterogeneous shape and morphology (dimensions
ranging from 1 to 5 μm). These cavities and pores may
be useful for heterogeneous catalysis in organic
synthesis.
and Si–O stretching vibration bands appearing at
817.34–753.24 and 473.62 cm–1 [20]. Carbonates are
represented by a weak characteristic band of the CO32–
group located at 1419.32 cm–1 [21]. All these bands
already exist in the spectrum of the natural untreated
clay [22]. The only remarkable difference is the shape
of the broad band around 3400 cm–1, probably corre-
sponding to OH vibrations.
The morphology of the modified clay was inves-
tigated by scanning electron microscopy with a Supra
40 VP Colonne Gemini Zeiss instrument (Fig. 3). The
SEM photograph showed large agglomerates of differ-
The nitrogen adsorption–desorption isotherms of
the modified clay at 77 K are shown in Fig. 4. The
isotherm obtained is of type IV according to the
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 55 No. 9 2019

BENTAHAR et al.
1426
IUPAC classification [23]. This type of isotherm is
characterized by the presence of mesopores [24]. The
specific surface area of the clay treated by KF was
determined by the Brunauer–Emmett–Teller (BET)
method using a Quantachrome AsiQuin automated gas
sorption analyzer version 2.02. According to the nu-
merical data deduced from this isotherm, the modified
clay has a specific surface of 63.842 m²/g with a pore
diameter of 1.69 nm.
The thermal analysis of the modified clay was
carried out on a Shimadzu D 60 instrument. A 9.381-
mg sample of the modified clay was heated from 15.58
to 1100°C under dry air at a heating rate of
10 deg/min. The results obtained are shown in Fig. 5.
Three weight losses were observed. The first loss
(5.08%, 0.477 mg) between 22 and 300°C corresponds
to endothermic removal of surface water and bound
water. The second loss (3.545%, 0.332 mg) between
300 and 659°C is likely due to exothermic decomposi-
tion of organic matter which can be mixed with the
clay or bound to the surface. The third exothermic loss
(2.552%, 0.239 mg) is localized between 659 and
867°C, which can be attributed to the crystallization of
merwinite [25].
Table 1. Effect of the amount of KF-modified clay on the
yield of 3,4-dihydropyrimidin-2(1H)-ones 4a and 5aa
Amount of
the catalyst, mg
Reaction time, Product no.
Entry no.
min
(yield,b %)
01
02
03
04
05
06
07
08
09
10
10
20
30
40
50
10
20
30
40
50
90
60
35
35
35
90
60
25
25
25
4a (51)
4a (75)
4a (94)
4a (93)
4a (80)
5a (69)
5a (80)
5a (98)
5a (98)
5a (93)
To optimize the condensation conditions, the reac-
tion of benzaldehyde (1a, 1 mmol) with urea (2,
1.5 mmol) and ethyl acetoacetate (3a, 1 mmol), as well
as ethyl cyanoacetate (3b, 1 mmol), was carried out by
varying the amount of the catalyst (Table 1) and
solvent (Table 2) at different temperatures (Table 3).
As follows from the data in Table 1, the yield of 4a
increased from 51 to 94% (entry nos. 1–3), and the
yield of 5a increased from 69 to 98% (entry nos. 6–9),
as the amount of the catalyst was raised from 10 to
30 mg. Thus, 30 mg can be considered the optimal
amount of the KF-modified clay for these reactions.
a
Reaction conditions: benzaldehyde (1 mmol), urea (1.5 mmol),
ethyl acetoacetate or ethyl cyanoacetate (1 mmol), temperature
40°C, solvent acetonitrile.
b
Isolated yield.
Table 2. Influence of solvent on the yield of 3,4-dihydro-
pyrimidin-2(1H)-ones 4a and 5aa
According to Table 2, good yields of 4a were ob-
tained using acetonitrile (94%), methanol (75%), and
ethanol (71%) as solvents (entry nos. 1–3) after
35 min. In the synthesis of 5a, the yields were 98, 81,
and 76% in acetonitrile, methanol, and ethanol, respec-
tively (entry nos. 7–9), after 25 min. The lowest yields
were obtained using chloroform, water, and methylene
chloride for both reactions. Therefore, acetonitrile was
selected as the best solvent for the two condensations.
Similar results were reported previously [16, 26].
Reaction time, Product no.
Entry no.
Solvent
min
(yield,b %)
01
02
03
04
05
06
07
08
09
10
11
12
MeCN
MeOH
EtOH
CHCl3
H2O
35
35
35
35
35
35
25
25
25
25
25
25
4a (94)
4a (75)
4a (71)
4a (30)
4a (21)
4a (18)
5a (98)
5a (81)
5a (76)
5a (41)
5a (25)
5a (21)
CH2Cl2
MeCN
MeOH
EtOH
CHCl3
H2O
Raising the temperature from 22 to 40°C improved
the yield of 4a from 57 to 94% (Table 3, entry nos. 1,
2) and the yield of 5a from 61 to 98% (entry nos. 5, 6).
Further raising the temperature to 70°C either had no
effect or reduced the yield. This may be explained by
increased disagreement between the catalytic sites on
the clay surface at elevated temperature, so that the
reactants no longer adsorbed on the clay surface.
CH2Cl2
a
Reaction conditions: benzaldehyde (1 mmol), urea (1.5 mmol),
ethyl acetoacetate or ethyl cyanoacetate (1 mmol), temperature
40°C, catalyst amount 30 mg.
Having optimized the conditions of both reactions,
various aromatic aldehydes 1a–1e bearing electron-
donor and electron-withdrawing groups were involved
b
Isolated yield.
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 55 No. 9 2019

POTASSIUM FLUORIDE-MODIFIED CLAY
1427
Table 3. Temperature effect on the yield of 3,4-dihydro-
pyrimidin-2(1H)-ones 4a and 5aa
therein. The results are presented in Table 4. Both
reactions were relatively fast and were complete on the
average in 30 min, and the products were obtained in
excellent yields. No appreciable effect of the substit-
uent in the benzene ring on the reaction rate was ob-
served, but the substituent nature influenced extraction
and purification features of the product. Thus, the KF-
modified clay tolerates various substrates and thus
allows extension of the series of available new prod-
ucts certainly possessing new properties.
Temperature,
°C
Reaction
time, min
Product no.
(yield,b %)
Entry no.
1
2
3
4
5
6
7
8
22
40
60
70
22
40
60
70
35
35
35
35
25
25
25
25
4a (57)
4a (94)
4a (93)
4a (89)
5a (61)
5a (98)
5a (98)
5a (86)
To propose a plausible mechanism for the two
reactions, we tested three supports, namely raw clay,
clay treated with HCl, and KF-modified clay, in the
condensation of benzaldehyde (1a) with urea (2) and
ethyl acetoacetate (3a) or ethyl cyanoacetate (3b). No
condensation took place in the presence of HCl-treated
clay consisting essentially of silica, aluminum phos-
phate, and potassium chloride [28]. In the case of the
raw clay, which consists of dolomite (major phase) and
silica (minor phase) [22], we observed the formation of
a small amount of the product which we failed to
isolate. In contrast, the KF-modified clay (consisting
of silica and merwinite) afforded the desired products
with very good yields. Therefore, it was concluded that
merwinite is likely to be responsible for the catalytic
activity of KF-modified clay in the condensations
under study. Scheme 2 outlines a probable two-step
mechanism for the formation of 3,4-dihydropyrimidin-
2(1H)-one 4a. The first step is the formation of N-acyl-
imine intermediate via nucleophilic attack of urea on
the aldehyde. In fact, Merwinite calcium plays the role
of Lewis acid and makes the carbonyl carbon atom
a
Reaction conditions: benzaldehyde (1 mmol), urea (1.5 mmol),
ethyl acetoacetate or ethyl cyanoacetate (1 mmol), catalyst
amount 30 mg, solvent acetonitrile.
b
Isolated yield.
more electron-deficient [29]. This carbon atom is then
attacked by the lone electron pair of the urea nitrogen
atom, which leads to N-(1-hydroxybenzyl)urea. The
latter undergoes dehydration to give N-acylimine
which is activated by coordination of the lone electron
pair of the oxygen atom to the vacant orbital of cal-
cium metal [5]. The second step begins with enoliza-
tion of ethyl acetoacetate, and the enol attacks the
imine [29]. The subsequent intramolecular cyclization
and dehydration yield the final product.
Scheme 3 shows a probable mechanism of the con-
densation of benzaldehyde with urea and ethyl cyano-
acetate to give pyrimidine 5a. This mechanism in-
Table 4. Condensation of substituted benzaldehydes with urea and ethyl acetoacetate or ethyl cyanoacetate under the
optimized conditions (Scheme 1)a
mp, °C
Reaction time,
Entry no.
R
Product no.
Yield,b %
min
this work
published data
1
2
3
4
5
6
7
8
9
H
35
40
30
30
25
30
25
25
25
4a
4b
4c
4d
5a
5b
5c
5d
5e
94
88
91
96
98
91
95
97
91
203–205
206–208
213–215
211–213
55–57
200–202 [5]
4-MeO
4-Me
4-Cl
209–210 [27]
215.4–216.4 [2]
209.4–211.4 [2]
H
_
_
_
_
_
4-MeO
4-Me
4-Cl
82–84
098–100
92–94
3-O2N
137–139
a
Reaction conditions: aldehyde (1 mmol), urea (1.5 mmol), ethyl acetoacetate or ethyl cyanoacetate (1 mmol), catalyst amount 30 mg,
solvent acetonitrile, temperature 40°C.
Isolated yield.
b
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 55 No. 9 2019

BENTAHAR et al.
1428
Scheme 2.
Si
O
Ca
O
O
O
H
OH2
NH2
N
O
2
N-Acylimine
H
–
H
O
N-(1-Hydroxybenzyl)-urea
EtO
Me
H2N
HO
O
Ca
H
Si
O
Ca
N
NH
Ca
H
O
O
H
Si
O
NH2
O
Si
Ca
H
OEt
Me
KF-modified
clay
H
O
O
Ca
NH2
NH2
EtO
O
O
Ca
O
Si
O
O
H2N
O
O
O
Si
O
Me
Ca
Ca
Si
Ca
N
H
H
O
Si
O
O
H
Ca
Me
O
H
OEt
O
HN
O
O
HN
–H2O
EtO
NH
Me
N
O
H
cludes several steps. The first step is Knoevenagel
condensation between benzaldehyde and ethyl cyano-
acetate, which is preceded by deprotonation of ethyl
cyanoacetate by the negatively charged site at the
catalyst surface to give a very stable anion due to con-
jugation with the cyano group. The carbonyl carbon
atom of benzaldehyde is activated by the positively
charged site on the catalyst surface bonded to carbonyl
oxygen. The aldol undergoes dehydration to give
substituted alkene [30]. The second step is initiated by
nucleophilic attack of the lone electron pair of the urea
nitrogen atom on the ester carbonyl function, leading
to the departure of the ethoxy group as reported in the
case of homogeneous catalysis [31]. Next follows
cyclization via intramolecular attack of the second urea
nitrogen atom on the previously formed C=C double
bond to give the enol form [31] which tautomerizes to
the oxo structure. Finally, in situ N-alkylation affords
the final product, dioxopyrimidine 5a. In keeping with
published data, compound 5a was synthesized by
alkylation of preliminarily isolated and purified 2,4-di-
oxo-6-phenyl-1,2,3,4-tetrahydropyrimidine-5-carbo-
nitrile [32, 33].
The possibility of recycling the KF-modified clay
was studied in the synthesis of 5a under the optimal
conditions. For this purpose, the catalyst was succes-
sively washed with acetone and ether for 30 min and
then dried in an oven at 80°C for 8 h after each cycle.
The results showed that the KF-modified clay can be
recycled five times with no appreciable loss of its
catalytic activity (the total loss was equal to 5% after
five cycles).
In summary, we have reported the use of KF-
modified clay as a heterogeneous catalyst for the syn-
thesis of 3,4-dihydropyrimidin-2(1H)-ones via one-pot
three-component condensation of aromatic aldehydes
with urea and ethyl acetoacetate or ethyl cyanoacetate.
The products attract interest as potential biologically
and therapeutically active compounds. The described
reactions are complete in a shorter time than those
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 55 No. 9 2019

POTASSIUM FLUORIDE-MODIFIED CLAY
1429
Scheme 3.
O
H2N
NH2
Dehydration
CN
C
O
CN
H
O
OEt
H
H
H
O
OEt
NH2
O
O
O
Si
Ca
O
CN
OEt
O
Si
HN
Ca
Ca
O
O
H
Si
O
Ca
O
Ca
H
O
Si
O
C
OEt
H
NH2
O
Ca
O
Si
H
KF-modified
clay
C
HN
O
N
CN
HO
Et
OEt
O
C
+
C
N
Ca
H
O
Si
O
O
O
Si
HN
O
C
Et
NH
OEt
H
Si
HO
C
O
Ca
O
O
N
O
NC
Et
H
tra-
le
,4-te
onitri
,2,3
yl-1
hen
-6-p
ioxo
H
2
,4-d
O
N
O
H
carb
e-5-
idin
yrim
rop
hyd
NH
NC
CN
O
H
HN
OH
O
–H2
O
Ca Si
O
N
Et
catalyzed by other supports reported in the literature
and afford the target products in excellent yields and
with high purity under mild conditions.
Commercial reagents were purchased from Aldrich.
All solvents were distilled before used by standard
procedures. The 1H and 13C NMR spectra were record-
ed on a Bruker Avance DMX 300 spectrometer at
300 and 75 MHz, respectively; the chemical shifts are
given relative to tetramethylsilane. The IR spectra
were recorded with a Jasco 4100 spectrometer equipped
with an ATR accessory. The progress of reaction was
monitored by thin-layer chromatography (TLC) using
20×20-cm silica gel UV 254 plates (0.2 mm thick)
(ALBET). Spots were detected using an ultraviolet
lamp (λ 254 and 365 nm). The melting points were
measured with a Kofler bench (Wagner & Munz).
EXPERIMENTAL
The modified clay was prepared by adding 2 g of
KF to 10 g of the natural clay collected from the
Agadir region in 30 mL of distilled water. The mixture
was stirred at room temperature for 24 h. The resulting
material was washed several times with distilled water
and then centrifuged, dried in an oven at 70°C, and
finally crushed.
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 55 No. 9 2019

BENTAHAR et al.
1430
General procedure for the synthesis of 3,4-dihy-
solid, mp 55–57°C. IR spectrum, ν, cm–1: 3408 (N–H),
3018–2976 (C–Harom, CH3), 2879 (CH2), 2267–2136
(C≡N), 1700 (C=O), 1572 (C=O), 1440 (C=Carom),
1197 (C–N), 1072 (C–N). 1H NMR spectrum (CDCl3),
δ, ppm: 8.25 s (1H, NH), 8.02 d (2H, Harom), 7.58 m
(3H, Harom), 4.4 q (2H, CH2), 1.41 t (3H, CH3).
13C NMR spectrum (DMSO-d6), δC, ppm: 162.55,
155.53, 133.85, 131.82, 131.26, 129.77, 116.03,
103.08, 62, 39.39, 14.43.
dropyrimidin-2(1H)-ones 4a–4d and 5a–5e. A mix-
ture of 1 mmol of aldehyde 1a–1e, 1 mmol of ethyl
acetoacetate (3a) or ethyl cyanoacetate (3b), 1.5 mmol
of urea, and 30 mg of the KF-modified clay in 5 mL of
acetonitrile was stirred at 40°C until the reaction was
complete (TLC). The catalyst was filtered off, the
solvent was removed, the residue was extracted with
methylene chloride, the extract was evaporated, and
the residue was recrystallized from ethanol.
3-Ethyl-6-(4-methoxyphenyl)-2,4-dioxo-1,2,3,4-
tetrahydropyrimidine-5-carbonitrile (5b). Yield
91%, pale yellow solid, mp 82–84°C. IR spectrum, ν,
cm–1: 3498 (N–H), 3088–2893 (C–Harom, C–Haliph),
2191 (C≡N), 1711 (C=O), 1551 (C=O), 1509
(C=Carom) 1204 (C–N), 1155 (C–N), 1009 (C–O,
ether). 1H NMR spectrum (CDCl3), δ, ppm: 8.19 s (1H,
NH), 8.03 d (2H, Harom), 7.02 d (2H, Harom), 4.39 q
(2H, CH2), 3.9 s (3H, CH3), 1.41 t (3H, CH3).
13C NMR spectrum (DMSO-d6), δC, ppm: 164.02,
162.83, 154.89, 133.98, 124.42, 116.69, 115.42, 99.01,
62.53, 56.22, 39.36, 14.48.
Ethyl 6-methyl-2-oxo-4-phenyl-1,2,3,4-tetrahy-
dropyrimidine-5-carboxylate (4a). Yield 94%,
yellow solid, mp 203–205°C. IR spectrum, ν, cm–1:
3450 (N–H), 3102 (C–Harom), 3018–2886 (C–Haliph),
1634 (C=O), 1450 (C=Carom), 1210 (C–O, ester), 1141,
1
1057 (C–N). H NMR spectrum (CDCl3), δ, ppm:
7.63 s (1H, NH), 7.37 m (5H, Harom), 5.62 s (1H, NH),
5.42 s (1H, CH), 4.1 q (2H, CH2), 2.39 s (3H, CH3),
1.19 t (3H, CH3).
Ethyl 4-(4-methoxyphenyl)-6-methyl-2-oxo-
1,2,3,4-tetrahydropyrimidine-5-carboxylate (4b).
Yield 88%, yellow solid, mp 206–208°C. IR spectrum,
ν, cm–1: 3435 (N–H), 3095 (C–Harom), 2970–2865
(C–Haliph), 1684 (C=O, ester), 1621 (C2=O), 1467
3-Ethyl-6-(4-methylphenyl)-2,4-dioxo-1,2,3,4-
tetrahydropyrimidine-5-carbonitrile (5c). Yield
95%, white solid, mp 98–100°C. IR spectrum, ν, cm–1:
3470 (N–H), 3053–2831 (C–Harom, C–Haliph), 2204
(C≡N), 1704 (C=O), 1544 (C=O), 1447 (C=Carom),
1204 (C–N), 1001 (C–N). 1H NMR spectrum (CDCl3),
δ, ppm: 8.21 s (1H, NH), 7.85 d (2H, Harom), 7.35 d
(2H, Harom), 4.39 q (2H, CH2), 2.4 s (3H, CH3), 1.41 t
(3H, CH3). 13C NMR spectrum (DMSO-d6), δC, ppm:
162.47, 155.41, 144.88, 131.45, 130.34, 129.17,
116.26, 101.60, 62.73, 39.38, 21.82, 14.46.
1
(C=Carom), 1210 (C–O, ester), 1044 (C–N). H NMR
spectrum (CDCl3), δ, ppm: 7.14 d (2H, Harom), 7.1 s
(1H, NH), 6.88 d (2H, Harom), 5.41 s (1H, NH), 5.39 s
(1H, CH), 4.05 q (2H, CH2), 3.8 s (3H, CH3), 2.38 s
(3H, CH3), 1.19 t (3H, CH3).
Ethyl 6-methyl-4-(4-methylphenyl)-2-oxo-
1,2,3,4-tetrahydropyrimidine-5-carboxylate (4c).
Yield 92%, yellow solid, mp: 213–215°C. IR spec-
trum, ν, cm–1: 3484 (N–H), 3095 (C–Harom), 2991–
2850 (C–Haliph), 1684 (C=O, ester), 1614 (C2=O), 1454
(C=Carom), 1259 (C-Oester), 1065 (C-N). 1H NMR spec-
trum (CDCl3), δ, ppm: 7.22 d (2H, Harom), 7.18 d (2H,
Harom), 7.11 s (1H, NH), 5.39 s (1H, CH), 5.37 s (1H,
NH), 4.05 q (2H, CH2), 2.39 s (3H, CH3), 1.59 s (3H,
CH3), 1.19 t (3H, CH3).
6-(4-Chlorophenyl)-3-ethyl-2,4-dioxo-1,2,3,4-
tetrahydropyrimidine-5-carbonitrile (5d). Yield
97%, white solid, mp 92–94°C. IR spectrum, ν, cm–1:
3345 (N–H), 3067 (C–Harom), 2970 (CH3), 2914 (CH2),
2233 (CN), 1711 (C=O), 1565 (C=O), 1454 (C=Carom),
1182 (C–N), 1050 (C–N). 1H NMR spectrum (CDCl3),
δ, ppm: 8.21 s (1H, NH), 7.99 d (2H, Harom), 7.5 d (2H,
H
arom), 4.4 q (2H, CH2), 1.41 t (3H, CH3). 13C NMR
Ethyl 4-(4-chlorophenyl)-6-methyl-2-oxo-1,2,3,4-
tetrahydropyrimidine-5-carboxylate (4d). Yield
96%, yellow solid, mp 211–213°C. IR spectrum, ν,
cm–1: 3331 (N–H), 3102 (C–Harom), 3005–2873
(C–Haliph), 1669 (C=O, ester), 1593 (C2=O), 1461
spectrum (DMSO-d6), δC, ppm: 162.10, 154.16,
138.48, 132.92, 130.72, 129.96, 115.89, 103.73, 62.94,
39.38, 14.44.
3-Ethyl-6-(3-nitrophenyl)-2,4-dioxo-1,2,3,4-
tetrahydropyrimidine-5-carbonitrile (5e). Yield
91%, white solid, mp 137–139°C. IR spectrum, ν,
cm–1: 3317 (N–H), 3080 (C–Harom), 3005 (CH3), 2949
(CH2), 2204 (C≡N), 1704 (C=O), 1504 (C=O), 1475
1
(C=Carom), 1412, 1190 (C–O, ester), 1057 (C–N). H
NMR spectrum (CDCl3), δ, ppm: 7.22 m (4H, Harom),
5.25 s (1H, CH), 4.03 q (2H, CH2), 3.2 s (1H, NH),
3.2 s (1H, NH), 2.37 s (3H, CH3), 1.18 t (3H, CH3).
1
3-Ethyl-2,4-dioxo-6-phenyl-1,2,3,4-tetrahydro-
(C=Carom), 1204 (C–N), 1072 (C–N). H NMR spec-
pyrimidine-5-carbonitrile (5a). Yield 98%, white
trum (CDCl3), δ, ppm: 8.61 s (1H, NH), 8.35 d (2H,
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 55 No. 9 2019

POTASSIUM FLUORIDE-MODIFIED CLAY
1431
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ACKNOWLEDGMENTS
The authors thank Prof. A. Khallaayoun and
Prof. M. Ezahri for their valuable assistance.
CONFLICT OF INTEREST
The authors declare no conflict of interest.
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