Highly regioselective, base-catalyzed, biginelli-type reaction of aldehyde, phenylacetone and urea/thiourea kinetic vs. thermodynamic control

Article abstract of DOI:10.1080/17415993.2017.1402332

An efficient one-pot regioselective synthesis of various novel 3,4-dihydropyrimidin-2(1H)-one (DHPMs) via a three-component Biginelli-type condensation of aldehyde, phenylacetone and urea/thiourea under two different based-catalyzed conditions is described. In kinetic control path, lithium N, N-diisopropylamide (LDA-20 mol % generated in situ from n-BuLi and diisopropylamine) was used as the base, in tetrahydroforane (THF) as the solvent at 0°C. Thermodynamic control path was run with NaH as the base, in EtOH as the solvent under reflux status. The simple procedure, mild base-catalytic reaction conditions, no column chromatography and good to high yields are important features of this protocol.

Full text of DOI:10.1080/17415993.2017.1402332

Journal of Sulfur Chemistry
ISSN: 1741-5993 (Print) 1741-6000 (Online) Journal homepage: http://www.tandfonline.com/loi/gsrp20
Highly regioselective, base-catalyzed, biginelli-type
reaction of aldehyde, phenylacetone and urea/
thiourea kinetic vs. thermodynamic control
Manijeh Nematpour, Elham Rezaee, Mehdi Jahani & Sayyed Abbas Tabatabai
To cite this article: Manijeh Nematpour, Elham Rezaee, Mehdi Jahani & Sayyed Abbas
Tabatabai (2017): Highly regioselective, base-catalyzed, biginelli-type reaction of aldehyde,
phenylacetone and urea/thiourea kinetic vs. thermodynamic control, Journal of Sulfur Chemistry,
DOI: 10.1080/17415993.2017.1402332
To link to this article: https://doi.org/10.1080/17415993.2017.1402332
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Date: 27 November 2017, At: 01:04

JOURNAL OF SULFUR CHEMISTRY, 2017
https://doi.org/10.1080/17415993.2017.1402332
Highly regioselective, base-catalyzed, biginelli-type reaction
of aldehyde, phenylacetone and urea/thiourea kinetic vs.
thermodynamic control
Manijeh Nematpoura, Elham Rezaeea, Mehdi Jahanib and Sayyed Abbas Tabatabaia
aDepartment of Pharmaceutical Chemistry, School of Pharmacy, Shahid Beheshti University of Medical
Sciences, Tehran, Iran; bDepartment of Chemistry, Sharif University of Technology, Tehran, Iran
ABSTRACT
ARTICLE HISTORY
Received 19 July 2017
Accepted 4 November 2017
An efficient one-pot regioselective synthesis of various novel
3,4-dihydropyrimidin-2(1H)-one (DHPMs) via a three-component
Biginelli-type condensation of aldehyde, phenylacetone and urea/
thioureaundertwodifferentbased-catalyzedconditionsisdescribed.
In kinetic control path, lithium N, N-diisopropylamide (LDA-20 mol %
generated in situ from n-BuLi and diisopropylamine) was used as the
base, intetrahydroforane (THF) as thesolventat 0°C. Thermodynamic
control path was run with NaH as the base, in EtOH as the solvent
under reflux status. The simple procedure, mild base-catalytic reac-
tion conditions, no column chromatography and good to high yields
are important features of this protocol.
KEYWORDS
3,4-Dihydropyrimidin-2(1H)-
one; lithium
N,N-diisopropylamide;
biginelli- type;
phenylacetone;
urea/thiourea;
kinetic-thermodynamic
1. Introduction
Biginelli reaction is an acid(base)-catalyzed one-pot synthesis of 3,4-dihydropyrimidin-
2(1H)-ones (DHPMs) using multicomponent condensation of easily-accessible starting
materials, including (thio)urea, active methylene compound and aldehyde [1–5]. DHPMs
are an interesting pharmacophore in the medicinal chemistry and fascinating target for
combinatorial chemistry of biologically active heterocycles with novel properties in the
past two decades [6–8]. Also, DHPM was applied as a key core in the synthesis of wide
variety pharmaceutical compounds, significant biomolecules, diverse natural products and
interesting alkaloids with special properties [9] and functional materials such as adhesive
[10], polymers and fabric dyes [11]. Furthermore, some of the DHPMs show many attrac-
tive properties such as antiviral, antibacterial, antitumour, antimalarial, anti-inflammatory,
CONTACT Sayyed Abbas Tabatabai
sa_tabatabai@sbmu.ac.ir
This article makes reference to supplementary material available on the publisher’s website at https://doi.org/10.1080/
17415993.2017.1402332
© 2017 Informa UK Limited, trading as Taylor & Francis Group

2
M. NEMATPOUR ET AL.
Scheme 1. Regioselective synthesis of novel 3,4-dihydropyrimidin-2(1H)-one (DHPMs) under two dif-
ferent conditions: kinetic and thermodynamic control.
antidiabetic, antitubercular, antileishmanial, anti-epileptic, antiproliferative activities, etc.
[12–16]. A number of polysubstituted DHPMs have been found to be antihypertensive
agents, potent calcium channel blockers [17], A2B receptor antagonists [18] and mPGES-
1 inhibitors [19]. Presently, the Biginelli reaction is exploited in solid-phase synthesis for
heterocyclic compound [20] and asymmetric synthesis for bioactive chiral DHPMs [21].
Despite extensive studies on the Biginelli-type reactions, achieving to new approaches
in synthesis of DHPMs with various substitutions in mild reaction conditions is a great
deal of attention. The standard protocol for the Biginelli reaction generally involves the
use of a Lewis or protic acid [22–25] and few methods are available under basic condi-
tions. In addition, most reported Biginelli-type protocl led to formation of thermodynamic
compunds.
Herein, we report a novel simple and efficient protocol for regioselective synthesis of
various novel 3,4-dihydropyrimidin-2(1H)-one (DHPMs) via a three-component conden-
sation of aldehyde, phenylacetone and urea/thiourea with good to high yields under two
different conditions (Scheme 1). In the kinetic control reaction (Path A), the base LDA (in
situ generated from n-BuLi and diisopropylamine) in tetrahydroforane (THF) at 0°C was
used while the thermodynamic control pathway (Path B) [3,26–28] was run with NaH as
the base in EtOH under the terms of reflux.
2. Results and discussion
At first, urea 1a, benzaldehyde 2a and phenylacetone 3 were selected as a model reaction
and then the reaction was optimized under two different conditions separately. In Path A
(kinetic control reaction), changing the solvent and amount of catalyst are checked out.
It is proved that THF is the most optimal solvent compared to MeOH, EtOH, CH2Cl2,
MeCN, DMF and acetone. Finally, the reaction was optimized by 20 mol% of LDA as the
base-catalyst, 1.5 mmol of urea, 1.2 mmol of benzaldehyde and 1.5 mmol of phenylacetone
in THF at 0°C (Table 1).
Using the optimized conditions described above, various 6-benzyl-4-phenyl-3,4-
dihydropyrimidin-2(1H)-one were synthesized from urea, phenylacetone and benzalde-
hyde with various electron-withdrawing or electron-donating substituents on the aromatic
rings (Table 2).
1
Structures of compounds 4a-m were assigned by H NMR, 13C NMR, IR and mass
spectral data (http://dx.doi.org/10.1080/17415993.2017.1402332). The 1H NMR spectrum
of 4a exhibited two singlet for two NH group (δ = 6.04 and 8.61 ppm), three doublet in

JOURNAL OF SULFUR CHEMISTRY
3
Table 1. Formation of product 4a under different reac-
tions conditions.
Entry
Solventa
Time/h
Yield 4a (%)
1
2
MeOH
EtOH
CH2Cl2
THF
MeCN
DMF
Acetone
6
6
5
1
4
5
6
32
38
33
81
52
59
49
3
4b
5
6
7
aReactions were performed using 1a (1.5 mmol), 2a (1.2 mmol), 3
(1.5 mmol) and LDA as the base-catalyst (20 mol %) under different
solvent (2 mL) at 0°C.
b10 mol% LDA as the base-catalyst, reaction time was 5 h.
Table 2. Synthesis of 3,4-dihydropyrimidin-2(1H)-one derivatives under kinetic control condition
(Path A).
Entry
1–4
X
R
Ar
Yield of 4 (%)
1
2
3
4
5
6
7
8
a
b
c
d
e
f
g
h
i
O
O
O
O
O
O
S
S
S
S
S
H
H
H
H
H
H
H
H
H
Ph
81
83
79
73
77
88
85
87
79
91
78
79
83
4-Cl-C6H4
2-Cl-C6H4
2-OH-C6H4
4-OMe-C6H4
4-NO2-C6H4
Ph
4-Cl-C6H4
4-OMe-C6H4
4-NO2-C6H4
4-Br-C6H4
4-Cl-C6H4
4-NO2-C6H4
9
10
11
12
13
j
k
l
H
Et
Me
Me
S
S
m
aliphatic range for CH2 benzyli group (δ = 3.62 ppm, J = 6.3 Hz) protons and two CH
group (δ = 5.26 and 5.67 ppm, J = 4.8 Hz) protons together with multiplication charac-
teristic aromatic protons. The 13C NMR spectrum of 4a exhibits 13 signals in agreement
with the proposed structure. The mass spectrum of 4a defined the molecular ion peak
at m/z = 264. The NMR spectra of compounds 4b-m are like that of 4a, except for the
substituents, which showed signals in the appropriate regions of the spectrum.
To extend our work of this field, we performed this reaction in the presence of sodium
hydride as base in EtOH under the terms of reflux, thermodynamic control condition (Path
B). These reactions led to 6-methyl-4,5-diphenyl-3,4-dihydropyrimidin-2(1H)-one 5a in
high yields (Scheme 2). Formation of this heterocyclic product can be attributable to the
reaction has progressed from thermodynamic path. Structures of compounds 5a-k were
confirme by 1H-NMR, 13C-NMR, Mass and IR spectrum.

4
M. NEMATPOUR ET AL.
Scheme 2. Synthesis of 6-methyl-4,5-diphenyl-3,4-dihydropyrimidin-2(1H)-one derivatives under ther-
modynamic control condition (Path B).
Table 3. Optimization of reaction conditions for the formation of product 5a from 1.5 mmol of urea,
1.2 mmol of benzaldehyde and 1.5 mmol of phenylacetone under the terms of reflux.
Base-catalysta
Solvent
Yield (%)b
Base-catalysta
Solvent
Yield (%)b
NaHc
NaH
NaH
KOt-Bu
KOt-Bu
KOt-Bu
K2CO3
K2CO3
K2CO3
EtOH
MeOH
DMF
EtOH
DMF
MeCN
EtOH
DMF
88
82
34
80
30
26
47
28
22
KOH
KOH
EtOH
DMF
34
23
30
21
38
21
–
NaOH
NaOH
NaOEt
NaOEt
LiOH
EtOH
MeCN
EtOH
MeCN
EtOH
DMF
LiOH
n-BuLi
–
–
MeCN
EtOH
a20 mol% catalyst unless stated otherwise.
bReaction time 3 h.
c10 mol% catalyst, reaction time was 7 h.
We optimize the reaction conditions by changing the solvent and base. Several base such
as NaH, KOt-Bu, K2CO3, KOH, NaOH, NaOEt, LiOH and n-BuLi were tested. EtOH and
NaH show the best results among various solvents and bases in this reaction. Eventually,
this reaction was performed using 20 mol% of NaH as the base-catalyst, 1.5 mmol of urea,
1.2 mmol of benzaldehyde and 1.5 mmol of phenylacetone in EtOH under the terms of
reflux (Table 3).
Various 6-methyl-4,5-diphenyl-3,4-dihydropyrimidin-2(1H)-one were synthesized
from urea, phenylacetone and various benzaldehyde under the optimized conditions
described above (Table 4). We have used aliphatic aldehyde instead of aromatic aldehyde
under thermodynamic and kinetic control condition but we were unable to isolate the
various dihydropyrimidin derivatives 4 and 5.
A possible reaction mechanism is shown in Scheme 3. It is proposed that phenylacetone
3, an unsymmetrical dialkyl ketone, can form two regioisomeric enolates on deprotona-
tion. The formation of an enolate mixture can be governed by kinetic or thermodynamic
factors. Under two different conditions, LDA as the base, in THF as the solvent at 0°C,
kinetic enol (A) is formed. When NaH was used as the base and EtOH as solvent, under
the terms of reflux, thermodynamic enol (B) is formed. Aldol condensation of aldehyde 2
with enol (A or B), followed by elimination of the resulting hydroxyl group gives one 7.
Subsequent aza-Michael addition of urea 1 to enone 7 leads to the formation of Michael
adduct 8. Compunds 4 or 5 were formed from intermediate 8 undergo cyclization reaction
and subsequent loss of water [29].

JOURNAL OF SULFUR CHEMISTRY
5
Table 4. Synthesis of 6-methyl-4,5-diphenyl-3,4-dihydropyrimidin-2(1H)-one
derivatives.
Entry
1–5
X
R
Ar
Yield of 5 (%)
1
2
3
4
5
6
7
8
a
b
c
d
e
f
g
h
i
O
O
O
O
S
S
S
S
S
H
H
H
H
H
H
H
Me
Me
Me
Et
Ph
88
92
90
79
93
75
89
85
77
87
86
4-NO2-C6H4
4-Cl-C6H4
4-OMe-C6H4
4-NO2-C6H4
4-OMe-C6H4
Ph
Ph
9
10
11
4-OMe-C6H4
4-Br-C6H4
4-Cl-C6H4
j
k
S
S
Scheme 3. A plausible mechanism the formation of compounds 4, 5.
3. Conclusion
In conclusion, a novel protocol, one-pot regioselective synthesis of various 3,4-
dihydropyrimidin-2(1H)-one (DHPMs) via a three-component Biginelli-type condensa-
tion of aldehyde, phenylacetone and urea/thiourea under two different conditions, kinetic
control; LDA-20 mol % as the base in THF at 0°C and thermodynamic control; NaH as the
base, in EtOH, under the terms of reflux, affording good to high yields was described. The
generally available substrates, mild conditions, high yields and ease purification procedure
make this reaction suitable for the synthesis of various 3,4-dihydropyrimidin-2(1H)-one.

6
M. NEMATPOUR ET AL.
4. Experimental
4.1. General
All chemicals were obtained commercially and used without further purification. IR
1
Spectra: Shimadzu-IR-460 spectrometer; bond positions in cm−1. H- and 13C-NMR
Spectra: Bruker DRX-500 Avance instrument using TMS as internal standard and CDCl3
as applied solvent at 500.1 and 125.7 MHz, resp.; the abbreviations used for NMR sig-
nals: s = singlet, d = doublet, t = triplet, m = multiplet and δ in ppm, J in Hz. MS:
Finnigan-MAT-8430EI-MS mass spectrometer; at 70 eV; in m/z (rel. %). mp: melting points
(uncorrected) Electrothermal-9100 apparatus. Elemental analyses: Vario EL III CHNOS
elemental analyzer.
4.2. General procedure for preparation of compounds 4
A solution of n-BuLi (20 mol %) in THF (2 mL) was slowly added to diisopropylamine
(20 mol%) and the mixture was stirred at at 0°C for 1 min. Then, a mixture of urea 1a
(1.5 mmol), benzaldehyde 2a (1.2 mmol) and phenylacetone 3 (1.5 mmol) in THF (3 mL)
was slowly added to the first solution and the mixture was stirred at 0°C for 1 h. After
completion of the reaction [about 1 h; TLC (AcOEt/ hexane 1:4) monitoring], the resulting
solid was isolated by filtration and washed with acetone.
4.2.1. 6-Benzyl-4-phenyl-3,4-dihydropyrimidin-2(1H)-one (4a)
White powder, mp: 223–225°C; yield: 0.21 g (81%). IR (KBr) (νmax, cm−1): 3114, 1620,
1237, 1178, 1090. 1H-NMR (500 MHz, CDCl3): δ = 3.62 (2 H, d, J = 6.3, CH2), 5.26 (1
H
H, d, 3J = 4.8, CH), 5.67 (1 H, d, 3J = 4.8, CH), 6.04 (1 H, s, NH), 7.13 (2 H, d, 3J = 7.5,
Ar), 7.19 (1 H, t, 3J = 7.5, Ar), 7.24 (2 H, t, 3J = 7.5, Ar), 7.40 (2 H, d, 3J = 7.7, Ar), 7.48
(1 H, t, 3J = 7.7, Ar), 7.60 (2 H, t, 3J = 7.7, Ar), 8.61 (1 H, s, NH). 13C-NMR (125.7 MHz,
CDCl3): δ = 41.8 (CH2), 56.3 (CH), 100.0 (CH), 125.9 (CH), 126.1 (2 CH), 127.7 (2 CH),
C
128.7 (2 CH), 129.9 (2 CH), 131.5 (C), 133.7 (CH), 135.4 (C), 143.4 (C), 153.3 (C=O). EI-
MS: 264 (M+, 8), 207 (15), 187 (86), 173 (34), 91 (100), 77 (19), 57 (23). Anal. Calc. for
C17H16N2O (264.32): C, 77.25; H, 6.10; N, 10.60%. Found: C, 77.27; H, 6.13; N, 10.58%.
4.2.2. 6-Benzyl-4-(4-chlorophenyl)-3,4-dihydropyrimidin-2(1H)-one (4b)
White powder, mp: 260–262°C; yield: 0.25 g (83%). IR (KBr) (νmax, cm−1): 3122, 1658,
1241, 1182, 1095. 1H-NMR (500 MHz, CDCl3): δ = 3.73 (2 H, d, J = 6.5, CH2), 5.10 (1
H
H, d, 3J = 4.8, CH), 5.66 (1 H, d, 3J = 4.8, CH), 6.02 (1 H, s, NH), 7.06 (2 H, d, 3J = 7.4,
Ar), 7.18 (1 H, t, 3J = 7.4, Ar), 7.27 (2 H, t, 3J = 7.4, Ar), 7.38 (2 H, d, 3J = 7.9, Ar), 7.90 (2
H, d, 3J = 7.9, Ar), 8.00 (1 H, s, NH). 13C-NMR (125.7 MHz, CDCl3): δ = 43.1 (CH2),
C
57.6 (CH), 100.0 (CH), 126.6 (2 CH), 127.4 (2 CH), 128.7 (CH), 129.9 (2 CH), 130.6 (2
CH), 132.4 (C), 134.4 (C), 142.1 (C), 147.4 (C), 153.8 (C=O). EI-MS: 298 (M+, 2), 240
(18), 207 (29), 111 (67), 91 (100), 77 (45), 58 (14). Anal. Calc. for C17H15ClN2O (298.77):
C, 68.34; H, 5.06; N, 9.38%. Found: C, 68.38; H, 5.10; N, 9.33%.
4.2.3. 6-Benzyl-4-(2-chlorophenyl)-3,4-dihydropyrimidin-2(1H)-one (4c)
White powder, mp: 231–233°C; yield: 0.24 g (79%). IR (KBr) (νmax, cm−1): 3116, 1660,
1244, 1184, 1097. 1H-NMR (500 MHz, CDCl3): δ = 3.80 (2 H, d, J = 6.7, CH2), 5.24 (1
H

JOURNAL OF SULFUR CHEMISTRY
7
H, d, 3J = 4.7, CH), 5.80 (1 H, d, 3J = 4.7, CH), 6.52 (1 H, s, NH), 7.19 (1 H, d, 3J = 7.8,
Ar), 7.28 (1 H, t, 3J = 7.8, Ar), 7.31–7.36 (3 H, m, Ph), 7.59 (2 H, t, 3J = 7.5, Ar), 7.78 (1
H, t, 3J = 7.8, Ar), 7.98 (1 H, d, 3J = 7.8, Ar), 8.22 (1 H, s, NH). 13C-NMR (125.7 MHz,
CDCl3): δ = 41.7 (CH2), 56.8 (CH), 104.5 (CH), 126.9 (CH), 127.4 (CH), 127.8 (C), 128.8
C
(2 CH), 129.9 (CH), 130.2 (2 CH), 130.9 (CH), 131.7 (CH), 132.9 (C), 135.8 (C), 144.7 (C),
153.0 (C=O). EI-MS: 298 (M+, 4), 207 (77), 187 (84), 111 (85), 91 (100), 77 (79). Anal.
Calc. for C17H15ClN2O (298.77): C, 68.34; H, 5.06; N, 9.38%. Found: C, 68.31; H, 5.11; N,
9.40%.
4.2.4. 6-Benzyl-4-(2-hydroxyphenyl)-3,4-dihydropyrimidin-2(1H)-one (4d)
White powder, mp: 253–255°C; yield: 0.20 g (73%). IR (KBr) (νmax, cm−1): 3446, 3332,
1626, 1240, 1151, 1094. 1H-NMR (500 MHz, CDCl3): δ = 3.76 (2 H, d, J = 6.8, CH2),
H
4.99 (1 H, d, 3J = 4.8, CH), 5.36 (1 H, d, 3J = 4.8, CH), 6.00 (1 H, s, OH), 6.24 (1 H, s,
NH), 7.18 (2 H, d, 3J = 7.4, Ar), 7.22 (1 H, t, 3J = 7.6, Ar), 7.26–7.33 (3 H, m, Ph), 7.38
(1 H, t, 3J = 7.6, Ar), 7.46 (1 H, d, 3J = 7.6, Ar), 7.88 (1 H, d, 3J = 7.6, Ar), 8.18 (1 H,
s, NH). 13C-NMR (125.7 MHz, CDCl3): δ = 42.0 (CH2), 55.6 (CH), 101.5 (CH), 120.0
C
(CH), 124.4 (CH), 125.8 (CH), 125.9 (CH), 128.7 (2 CH), 129.2 (2 CH), 130.6 (CH), 132.5
(C), 134.9 (C), 135.5 (C), 142.1 (C), 151.3 (C=O). EI-MS: 280 (M+, 5), 222 (18), 189 (25),
91 (100), 58 (88). Anal. Calc. for C17H16N2O2 (280.32): C, 72.84; H, 5.75; N, 9.99%. Found:
C, 72.80; H, 5.78; N, 10.02%.
4.2.5. 6-Benzyl-4-(4-methoxyphenyl)-3,4-dihydropyrimidin-2(1H)-one (4e)
Cream powder, mp: 239–241°C; yield: 0.23 g (77%). IR (KBr) (νmax, cm−1): 3455, 1680,
1242, 1153, 1095. 1H-NMR (500 MHz, CDCl3): δ = 3.54 (2 H, d, J = 6.7, CH2), 3.72 (3
H
H, s, OMe), 5.34 (1 H, d, 3J = 4.8, CH), 5.89 (1 H, d, 3J = 4.8, CH), 6.37 (1 H, s, NH),
7.23 (2 H, d, 3J = 7.2, Ar), 7.25-7.34 (5 H, m, Ph), 7.48 (2 H, d, 3J = 7.2, Ar), 8.13 (1 H,
s, NH). 13C-NMR (125.7 MHz, CDCl3): δ = 42.5 (CH2), 52.2 (CH), 55.2 (OMe), 100.2
C
(CH), 120.0 (2 CH), 126.1 (2 CH), 127.8 (CH), 129.0 (2 CH), 131.4 (2 CH), 132.8 (C),
134.8 (C), 145.0 (C), 148.2 (C), 152.5 (C=O). EI-MS: 294 (M+, 15), 236 (16), 203 (52),
187 (79), 107 (51), 91 (100), 77 (54). Anal. Calc. for C18H18N2O2 (294.35): C, 73.45; H,
6.16; N, 9.52%. Found: C, 73.47; H, 6.19; N, 9.48%.
4.2.6. 6-Benzyl-4-(4-nitrophenyl)-3,4-dihydropyrimidin-2(1H)-one (4f)
Pale yellow powder, mp: 269–271°C; yield: 0.27 g (88%). IR (KBr) (νmax, cm−1): 3291, 1622,
1554, 1360, 1095. 1H-NMR (500 MHz, CDCl3): δ = 3.61 (2 H, d, J = 6.7, CH2), 4.98 (1
H
H, d, 3J = 4.8, CH), 5.26 (1 H, d, 3J = 4.8, CH), 6.25 (1 H, s, NH), 7.30 (2 H, d, 3J = 7.5,
Ar), 7.44 (2 H, d, 3J = 8.0, Ar), 7.59 (2 H, t, 3J = 7.5, Ar), 7.71 (1 H, t, 3J = 7.5, Ar), 8.01 (2
H, d, 3J = 8.0, Ar), 8.71 (1 H, s, NH). 13C-NMR (125.7 MHz, CDCl3): δ = 41.0 (CH2),
C
56.0 (CH), 103.3 (CH), 127.4 (2 CH), 128.7 (2 CH), 129.2 (2 CH), 130.2 (CH), 132.5 (2
CH), 135.7 (C), 136.0 (C), 144.8 (C), 148.9 (C), 152.1 (C=O). EI-MS: 309 (M+, 15), 252
(31), 187 (35), 122 (18), 91 (100), 77 (15), 58 (24). Anal. Calc. for C17H15N3O3 (309.32):
C, 66.01; H, 4.89; N, 13.58%. Found: C, 66.00; H, 4.90; N, 13.53%.
4.2.7. 6-Benzyl-4-phenyl-3,4-dihydropyrimidine-2(1H)-thione (4g)
White powder, mp: 240–242°C; yield: 0.24 g (85%). IR (KBr) (νmax, cm−1): 3466, 1643,
1158, 1105. 1H-NMR (500 MHz, CDCl3): δ = 3.77 (2 H, d, J = 6.4, CH2), 5.25 (1 H, d,
H

8
M. NEMATPOUR ET AL.
3J = 4.8, CH), 5.70 (1 H, d, 3J = 4.8, CH), 6.34 (1 H, s, NH), 7.19 (2 H, d, 3J = 7.5, Ar),
7.26 (1 H, t, 3J = 7.5, Ar), 7.33 (2 H, t, 3J = 7.5, Ar), 7.60 (2 H, t, 3J = 7.7, Ar), 7.72 (1
H, t, 3J = 7.7, Ar), 7.87 (2 H, d, 3J = 7.7, Ar), 9.11 (1 H, s, NH). 13C-NMR (125.7 MHz,
CDCl3): δ = 42.8 (CH2), 58.0 (CH), 102.1 (CH), 126.1 (2 CH), 127.3 (2 CH), 127.8 (CH),
C
129.0 (2 CH), 130.0 (CH), 131.2 (2 CH), 131.9 (C), 135.8 (C), 141.9 (C), 175.0 (C=S). EI-
MS: 280 (M+, 10), 204 (29), 189 (38), 91 (100), 77 (49), 73 (10). Anal. Calc. for C17H16N2S
(280.39): C,72.82; H, 5.75; N, 9.99%. Found: C, 72.80; H, 5.77; N, 9.95%.
4.2.8. 6-Benzyl-4-(4-chlorophenyl)-3,4-dihydropyrimidine-2(1H)-thione (4h)
White powder, mp: 255–257°C; yield: 0.27 g (87%). IR (KBr) (νmax, cm−1): 3366, 1679,
1162, 1117. 1H-NMR (500 MHz, CDCl3): δ = 3.40 (2 H, d, J = 6.8, CH2), 5.38 (1 H, d,
H
3J = 4.8, CH), 5.95 (1 H, d, 3J = 4.8, CH), 6.45 (1 H, s, NH), 7.21 (2 H, d, 3J = 7.6, Ar),
7.25 (1 H, t, 3J = 7.6, Ar), 7.32 (2 H, t, 3J = 7.6, Ar), 7.61 (2 H, d, 3J = 7.9, Ar), 8.00 (2 H,
d, 3J = 7.9, Ar), 9.11 (1 H, s, NH). 13C-NMR (125.7 MHz, CDCl3): δ = 41.9 (CH2), 58.4
C
(CH), 101.1 (CH), 125.3 (2 CH), 125.5 (2 CH), 127.5 (2 CH), 128.9 (CH), 130.0 (2 CH),
130.2 (C), 131.8 (C), 135.7 (C), 144.9 (C), 175.0 (C=S). EI-MS: 314 (M+, 4), 240 (90),
203 (59), 111 (100), 91 (62), 73 (72). Anal. Calc. for C17H15ClN2O2S (314.83): C, 64.85; H,
4.80; N, 8.90%. Found: C, 64.85; H, 4.76; N, 8.93%.
4.2.9. 6-Benzyl-4-(4-methoxyphenyl)-3,4-dihydropyrimidine-2(1H)-thione (4i)
Cream powder, mp: 244–246°C; yield: 0.24 g (79%). IR (KBr) (νmax, cm−1): 3368, 1638,
1252, 1106. 1H-NMR (500 MHz, CDCl3): δ = 3.55 (2 H, d, J = 6.8, CH2), 3.67 (3 H, s,
H
OMe), 5.05 (1 H, d, 3J = 4.6, CH), 5.55 (1 H, d, 3J = 4.6, CH), 6.25 (1 H, s, NH), 7.25 (2 H,
d, 3J = 7.4, Ar), 7.33 (1 H, t, 3J = 7.4, Ar), 7.40–7.48 (4 H, m, Ph), 7.50 (2 H, d, 3J = 7.6,
Ar), 9.01 (1 H, s, NH). 13C-NMR (125.7 MHz, CDCl3): δ = 41.1 (CH2), 58.6 (CH), 60.1
C
(OMe), 102.5 (CH), 118.6 (2 CH), 126.7 (2 CH), 127.9 (CH), 128.6 (2 CH), 129.4 (2 CH),
130.1 (C), 131.9 (C), 135.6 (C), 143.9 (C), 175.5 (C=S). EI-MS: 310 (M+, 19), 237 (24),
219 (25), 107 (36), 91 (100). Anal. Calc. for C18H18N2OS (310.41): C, 69.65; H, 5.84; N,
9.02%. Found: C, 69.67; H, 5.90; N, 9.07%.
4.2.10. 6-Benzyl-4-(4-nitrophenyl)-3,4-dihydropyrimidine-2(1H)-thione (4j)
Pale yellow powder, mp: 275–277°C; yield: 0.30 g (91%). IR (KBr) (νmax, cm−1): 3363, 1682,
1551, 1345, 1160, 1109. 1H-NMR (500 MHz, CDCl3): δ = 3.68 (2 H, d, J = 6.8, CH2),
H
4.73 (1 H, d, 3J = 4.8, CH), 5.59 (1 H, d, 3J = 4.8, CH), 6.15 (1 H, s, NH), 7.09 (2 H, d,
3J = 7.4, Ar), 7.28-7.33 (3 H, m, Ph), 7.49 (2 H, d, 3J = 7.9, Ar), 7.89 (2 H, d, 3J = 7.9,
Ar), 9.05 (1 H, s, NH). 13C-NMR (125.7 MHz, CDCl3): δ = 41.2 (CH2), 60.7 (CH), 102.1
C
(CH), 126.8 (CH), 126.9 (2 CH), 127.5 (2 CH), 128.7 (2 CH), 129.9 (2 CH), 130.1 (C), 131.6
(C), 135.8 (C), 142.9 (C), 174.4 (C=S). EI-MS: 325 (M+, 15), 251 (44), 234 (48), 203 (40),
122 (66), 91 (60), 77 (100). Anal. Calc. for C17H15N3O2S (325.38): C, 62.75; H, 4.65; N,
12.91%. Found: C, 62.77; H, 4.62; N, 12.95%.
4.2.11. 6-Benzyl-4-(4-bromophenyl)-1,3-diethyl-3,4-dihydropyrimidine-2(1H)-thione
(4k)
White powder, mp: 250–252°C; yield: 0.26 g (78%). IR (KBr) (νmax, cm−1): 1675, 1160,
1107. 1H-NMR (500 MHz, CDCl3): δ = 0.99 (3 H, t, J = 6.8, Me), 1.19 (3 H, t, J = 6.8,
H
Me), 3.22 (2 H, q, J = 6.8, NCH2), 3.35 (2 H, q, J = 6.8, NCH2), 3.54 (2 H, d, J = 6.8,

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CH2), 5.29 (1 H, d, 3J = 4.8, CH), 5.98 (1 H, d, 3J = 4.8, CH), 7.63 (2 H, t, 3J = 7.6, Ar),
7.68 (1 H, t, 3J = 7.6, Ar), 8.05 (2 H, d, 3J = 7.6, Ar), 8.09 (2 H, d, 3J = 7.9, Ar), 8.40 (2 H,
d, 3J = 7.9, Ar). 13C-NMR (125.7 MHz, CDCl3): δ = 16.9 (Me), 18.6 (Me), 40.9 (CH2),
C
41.3 (NCH2), 43.4 (NCH2), 60.0 (CH), 100.1 (CH), 126.9 (2 CH), 127.2 (2 CH), 128.1 (C),
130.3 (4 CH), 131.7 (CH), 132.5 (C), 135.9 (C), 147.8 (C), 177.7 (C=S). EI-MS: 415 (M+,
5), 385 (24), 259 (44), 154 (100), 91 (61), 77 (70). Anal. Calc. for C21H23BrN2S (415.39):
C, 60.72; H, 5.58; N, 6.74%. Found: C, 60.70; H, 5.60; N, 6.77%.
4.2.12. 6-Benzyl-4-(4-chlorophenyl)-1,3-dimethyl-3,4-dihydropyrimidine-2(1H)-
thione (4l)
Cream powder, mp: 264–266°C; yield: 0.27 g (79%). IR (KBr) (νmax, cm−1): 1630, 1251,
1100. 1H-NMR (500 MHz, CDCl3): δ = 2.95 (3 H, s, NMe), 3.10 (3 H, s, NMe), 3.63 (2
H
H, d, J = 6.3, CH2), 5.27 (1 H, d, 3J = 4.6, CH), 5.68 (1 H, d, 3J = 4.6, CH), 7.05 (1 H, t,
3J = 7.6, Ar), 7.38–7.43 (4 H, m, Ph), 7.76 (2 H, d, 3J = 7.9, Ar), 7.92 (2 H, d, 3J = 7.9, Ar).
13C-NMR (125.7 MHz, CDCl3): δ = 41.4 (CH2), 42.3 (NMe), 42.9 (NMe), 56.4 (CH),
C
102.0 (CH), 127.8 (2 CH), 128.2 (C), 129.3 (2 CH), 129.8 (CH), 130.1 (C), 130.7 (2 CH),
131.9 (2 CH), 140.1 (C), 147.2 (C), 173.2 (C=S). EI-MS: 344 (M+2, 14), 342 (7), 327 (20),
265 (33), 251 (31), 91 (100), 77 (77). Anal. Calc. for C19H19ClN2S (342.89): C, 66.55; H,
5.59; N, 8.17%. Found: C, 66.57; H, 5.61; N, 8.21%.
4.2.13. 6-Benzyl-1,3-dimethyl-4-(4-nitrophenyl)-3,4-dihydropyrimidine-2(1H)-thione
(4m)
Pale yellow powder, mp: 289–291°C; yield: 0.29 g (83%). IR (KBr) (νmax, cm−1): 1689, 1557,
1
1342, 1155, 1100. H-NMR (500 MHz, CDCl3): δ = 2.92 (3 H, s, NMe), 3.01 (3 H, s,
H
NMe), 3.88 (2 H, d, J = 6.8, CH2), 5.26 (1 H, d, 3J = 4.6, CH), 5.64 (1 H, d, 3J = 4.6, CH),
7.27 (1 H, t, 3J = 7.6, Ar), 7.30-7.35 (4 H, m, Ph), 7.50 (2 H, d, 3J = 7.9, Ar), 8.04 (2 H, d,
3J = 7.9, Ar). 13C-NMR (125.7 MHz, CDCl3): δ = 41.1 (CH2), 42.0 (NMe), 42.7 (NMe),
C
57.1 (CH), 100.5 (CH), 126.2 (2 CH), 127.4 (2 CH), 127.8 (CH), 128.7 (2 C), 129.2 (2 CH),
132.5 (2 CH), 135.7 (C), 144.9 (C), 175.1 (C=S). EI-MS: 353 (M+, 7), 338 (25), 234 (28),
231 (32), 122 (82), 91 (64), 77 (100). Anal. Calc. for C19H19N3O2S (353.44): C, 64.57; H,
5.42; N, 11.89%. Found: C, 64.50; H, 5.40; N, 11.88%.
4.3. General procedure for preparation of compounds 5
Amixture of urea 1a (1.5 mmol), benzaldehyde 2 (1.2 mmol) and phenylacetone 3
(1.5 mmol) in EtOH (3 mL) was slowly added to NaH (20 mol %) and the mixture was
stirred at 75°C for 3 h. After completion of the reaction [about 3 h; TLC (AcOEt/hexane 1:3)
monitoring], the resulting solid was isolated by filtration and washed with diethyl ether.
4.3.1. 6-Methyl-4,5-diphenyl-3,4-dihydropyrimidin-2(1H)-one (5a)
White powder, mp: 220–222°C; yield: 0.23 g (88%). IR (KBr) (νmax, cm−1): 3209, 1636,
1397, 1103. 1H-NMR (500 MHz, CDCl3): δ = 2.61 (3 H, s, Me), 5.28 (1 H, s, CH), 6.25
H
3
(1 H, s, NH), 7.26–7.30 (3 H, m, Ph), 7.44 (2 H, d, J = 7.3, Ar), 7.60 (2 H, t, 3J = 7.7,
Ar), 7.71 (1 H, t, 3J = 7.7, Ar), 7.87 (2 H, d, 3J = 7.7, Ar), 8.06 (1 H, s,NH). 13C-NMR
(125.7 MHz, CDCl3): δ = 18.8 (Me), 57.6 (CH), 112.4 (C), 123.5 (2 CH), 127.4 (2 CH),
C
128.8 (CH), 129.3 (2 CH), 130.2 (2 CH), 132.5 (CH), 133.1 (C), 135.7 (C), 144.7 (C), 152.0

10
M. NEMATPOUR ET AL.
(C=O). EI-MS: 264 (M+, 11), 250 (21), 206 (26), 187 (84), 110 (80), 77 (100), 58 (31).
Anal. Calc. for C17H16N2O (264.32): C, 77.25; H, 6.10; N, 10.60%. Found: C, 77.21; H,
6.08; N, 10.56%.
4.3.2. 6-Methyl-4-(4-nitrophenyl)-5-phenyl-3,4-dihydropyrimidin-2(1H)-one (5b)
Pale yellow powder, mp: 266–268°C; yield: 0.28 g (92%). IR (KBr) (νmax, cm−1): 3192, 1636,
1527, 1350, 1256, 1102, 1049. 1H-NMR (500 MHz, CDCl3): δ = 2.45 (3 H, s, Me), 5.63
H
(1 H, s, CH), 6.33 (1 H, s, NH), 7.29–7.35 (3 H, m, Ph), 7.40 (2 H, d, 3J = 7.5, Ar), 7.50 (2
H, d, 3J = 7.9, Ar), 7.91 (2 H, d, 3J = 7.9, Ar), 8.86 (1 H, s, NH). 13C-NMR (125.7 MHz,
CDCl3): δ = 18.2 (Me), 57.2 (CH), 113.4 (C), 122.6 (C), 127.5 (2 CH), 128.8 (2 CH),
C
129.2 (CH), 130.7 (2 CH), 132.6 (2 CH), 142.1 (C), 144.5 (C), 147.3 (C), 152.2 (C=O).
EI-MS: 309 (M+, 15), 251 (23), 232 (31), 187 (57), 122 (48), 110 (42), 77 (100), 58 (27).
Anal. Calc. for C17H15N3O3 (309.32): C, 66.01; H, 4.89; N, 13.58%. Found: C, 66.09; H,
4.91; N, 13.55%.
4.3.3. 4-(4-Chlorophenyl)-6-methyl-5-phenyl-3,4-dihydropyrimidin-2(1H)-one (5c)
White powder, mp: 233–235°C; yield: 0.27 g (90%). IR (KBr) (νmax, cm−1): 3193, 1637,
1
1257, 1141, 1036. H-NMR (500 MHz, CDCl3): δ = 2.46 (3 H, s, Me), 5.50 (1 H, s,
H
CH), 6.29 (1 H, s, NH), 7.30-7.36 (3 H, m, Ph), 7.41 (2 H, d, 3J = 7.4, Ar), 7.48 (2 H, d,
3J = 8.0, Ar), 7.93 (2 H, d, 3J = 8.0, Ar), 8.11 (1 H, s, NH). 13C-NMR (125.7 MHz, CDCl3):
δ = 17.7 (Me), 58.6 (CH), 112.9 (C), 126.7 (2 CH), 127.3 (2 CH), 128.7 (CH), 129.7 (2
C
CH), 130.7 (2 CH), 132.5 (C), 136.7 (C), 140.0 (C), 142.4 (C), 152.7 (C=O). EI-MS: 298
(M+, 7), 240 (51), 221 (100), 187 (65), 111 (89), 77 (89). Anal. Calc. for C17H15ClN2O
(298.77): C, 68.34; H, 5.06; N, 9.38%. Found: C, 68.30; H, 5.10; N, 9.40%.
4.3.4. 4-(4-Methoxyphenyl)-6-methyl-5-phenyl-3,4-dihydropyrimidin-2(1H)-one (5d)
Cream powder, mp: 243–245°C; yield: 0.23 g (79%). IR (KBr) (νmax, cm−1): 3377, 1689,
1168, 1109. 1H-NMR (500 MHz, CDCl3): δ = 2.67 (3 H, s, Me), 3.76 (3 H, s, OMe), 5.47
H
(1 H, s, CH), 6.05 (1 H, s, NH), 7.28–7.33 (4 H, m, Ph), 7.44 (2 H, d, 3J = 7.5, Ar), 7.47 (1
H, t, 3J = 7.3, Ar), 7.89 (2 H, d, 3J = 7.5, Ar), 8.31 (1 H, s, NH). 13C-NMR (125.7 MHz,
CDCl3): δ = 18.9 (Me), 56.2 (CH), 60.6 (OMe), 112.5 (C), 120.0 (2 CH), 128.7 (2 CH),
C
129.3 (CH), 129.7 (2 CH), 130.0 (2 CH), 130.7 (C), 132.7 (C), 132.9 (C), 141.9 (C), 153.6
(C=O). EI-MS: 294 (M+, 16), 236 (48), 217 (40), 187 (100), 110 (89), 77 (78). Anal. Calc.
for C18H18N2O2 (294.35): C, 73.45; H, 6.16; N, 9.52%. Found: C, 73.49; H, 6.18; N, 9.55%.
4.3.5. 6-Methyl-4-(4-nitrophenyl)-5-phenyl-3,4-dihydropyrimidine-2(1H)-thione (5e)
Pale yellow powder, mp: 259–261°C; yield: 0.30 g (93%). IR (KBr) (νmax, cm−1): 3190, 1643,
1531, 1350, 1259, 1178. 1H-NMR (500 MHz, CDCl3): δ = 2.66 (3 H, s, Me), 5.57 (1 H,
H
s, CH), 6.15 (1 H, s, NH), 7.22 (2 H, d, 3J = 7.3, Ar), 7.28 (1 H, t, 3J = 7.3, Ar), 7.36 (2 H,
t, 3J = 7.3, Ar), 7.41 (2 H, d, 3J = 7.9, Ar), 7.92 (2 H, d, 3J = 7.9, Ar), 10.05 (1 H, s, NH).
13C-NMR (125.7 MHz, CDCl3): δ = 18.8 (Me), 61.7 (CH), 116.3 (C), 126.2 (2 CH), 127.5
C
(CH), 127.7 (2 CH), 130.0 (2 CH), 130.6 (2 CH), 138.8 (C), 140.7 (C), 142.1 (C), 143.4 (C),
171.2 (C=S). EI-MS: 325 (M+, 8), 251 (39), 248 (32), 203 (35), 122 (77), 77 (80), 73 (100).
Anal. Calc. For C17H15N3O2S (325.38): C, 62.75; H, 4.65; N, 12.91%. Found: C, 62.77; H,
4.67; N, 12.90%.

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4.3.6. 4-(4-Methoxyphenyl)-6-methyl-5-phenyl-3,4-dihydropyrimidine-2(1H)-thione
(5f)
Cream powder, mp: 251–253°C; yield: 0.23 g (75%). IR (KBr) (νmax, cm−1): 3201, 1652,
1264, 1117, 1040. 1H-NMR (500 MHz, CDCl3): δ = 2.47 (3 H, s, Me), 3.84 (3 H, s, OMe),
H
5.48 (1 H, s, CH), 6.18 (1 H, s, NH), 7.29–7.35 (3 H, m, Ph), 7.48 (2 H, d, 3J = 7.3, Ar), 7.84
(2 H, d, 3J = 7.5, Ar), 7.92 (2 H, d, 3J = 7.5, Ar), 10.11 (1 H, s, NH). 13C-NMR (125.7 MHz,
CDCl3): δ = 17.7 (Me), 56.3 (OMe), 63.6 (CH), 113.6 (C), 120.6 (2 CH), 127.4 (2 CH),
C
128.7 (2 CH), 129.2 (2 CH), 130.1 (CH), 132.6 (C), 135.7 (C), 144.8 (C), 151.5 (C), 171.6
(C=S). EI-MS: 310 (M+, 12), 236 (50), 203 (49), 107 (68), 77 (100), 73 (41). Anal. Calc.
for C18H18N2OS (310.41): C, 69.65; H, 5.84; N, 9.02%. Found: C, 69.68; H, 5.88; N, 9.10%.
4.3.7. 6-Methyl-4,5-diphenyl-3,4-dihydropyrimidine-2(1H)-thione (5g)
White powder, mp: 229–231°C; yield: 0.25 g (89%). IR (KBr) (νmax, cm−1): 3173, 1650,
1264, 1117, 1005. 1H-NMR (500 MHz, CDCl3): δ = 2.41 (3 H, s, Me), 5.45 (1 H, s, CH),
H
6.21 (1 H, s, NH), 7.30-7.36 (3 H, m, Ph), 7.47 (2 H, d, 3J = 7.3, Ar), 7.62 (2 H, t, 3J = 7.7,
Ar), 7.74 (1 H, t, 3J = 7.7, Ar), 8.05 (2 H, d, 3J = 7.7, Ar), 10.01 (1 H, s, NH). 13C-NMR
(125.7 MHz, CDCl3): δ = 18.0 (Me), 60.2 (CH), 112.5 (C), 127.5 (CH), 128.8 (2 CH),
C
129.0 (2 CH), 129.2 (2 CH), 130.2 (2 CH), 132.5 (C), 135.7 (CH), 140.0 (C), 144.8 (C),
170.2 (C=S). EI-MS: 280 (M+, 12), 206 (49), 126 (52), 77 (100). Anal. Calc. for C17H16N2S
(280.39): C, 72.82; H, 5.75; N, 9.99%. Found: C, 72.85; H, 5.77; N, 10.03%.
4.3.8. 1,3,6-Trimethyl-4,5-diphenyl-3,4-dihydropyrimidine-2(1H)-thione (5h)
White powder, mp: 225–227°C; yield: 0.26 g (85%). IR (KBr) (νmax, cm−1): 1632, 1390,
1121. 1H-NMR (500 MHz, CDCl3): δ = 2.47 (3 H, s, Me), 2.91 (3 H, s, NMe), 3.01 (3 H,
H
s, NMe), 5.66 (1 H, s, CH), 7.47-7.59 (5 H, m, Ph), 7.61 (1 H, t, 3J = 7.6, Ar), 7.92 (2 H, d,
3J = 7.6, Ar), 7.98 (2 H, d, 3J = 7.8, Ar). 13C-NMR (125.7 MHz, CDCl3): δ = 18.4 (Me),
C
40.2 (NMe), 44.4 (NMe), 56.6 (CH), 111.9 (C), 127.4 (2 CH), 128.7 (2 CH), 129.0 (CH),
129.3 (CH), 130.7 (2 CH), 131.6 (2 CH), 132.3 (C), 134.4 (C), 145.4 (C), 172.7 (C=S).
EI-MS: 308 (M+, 10), 293 (20), 231 (29), 154 (66), 77 (100). Anal. Calc. for C19H20N2S
(308.44): C, 73.99; H, 6.54; N, 9.08%. Found: C, 73.90; H, 6.57; N, 9.00%.
4.3.9. 4-(4-Methoxyphenyl)-1,3,6-trimethyl-5-phenyl-3,4-dihydropyrimidine-2(1H)-
thione (5i)
Pale yellow powder, mp: 275–277°C; yield: 0.26 g (77%). IR (KBr) (νmax, cm−1): 1622, 1251,
1100, 1041. 1H-NMR (500 MHz, CDCl3): δ = 2.45 (3 H, s, Me), 2.92 (3 H, s, NMe), 3.02
H
(3 H, s, NMe), 4.02 (3 H, s, OMe), 5.89 (1 H, s, CH), 7.31-7.36 (3 H, m, Ph), 7.41 (2 H, d,
3J = 7.8, Ar), 7.78 (2 H, d, 3J = 7.6, Ar), 7.93 (2 H, d, 3J = 7.8, Ar). 13C-NMR (125.7 MHz,
CDCl3): δ = 19.9 (Me), 40.5 (NMe), 44.5 (NMe), 52.2 (CH), 56.0 (OMe), 111.4 (C), 122.6
C
(2 CH), 127.4 (2 CH), 128.7 (2 CH), 129.2 (2 CH), 130.1 (C), 132.5 (C), 134.6 (CH), 142.1
(C), 145.0 (C), 176.0 (C=S). EI-MS: 338 (M+, 12), 323 (23), 231 (24), 261 (51), 107 (25), 77
(100). Anal. Calc. for C20H22N2OS (338.47): C, 70.97; H, 6.55; N, 8.28%. Found: C, 70.93;
H, 6.50; N, 8.30%.
4.3.10. 4-(4-Bromophenyl)-1,3,6-trimethyl-5-phenyl-3,4-dihydropyrimidine-2(1H)-
thione (5j)
White powder, mp: 288–290°C; yield: 0.34 g (87%). IR (KBr) (νmax, cm−1): 1621, 1252,
1140, 1032. 1H-NMR (500 MHz, CDCl3): δ = 2.66 (3 H, s, Me), 2.98 (3 H, s, NMe), 3.03
H

12
M. NEMATPOUR ET AL.
(3 H, s, NMe), 5.60 (1 H, s, CH), 6.92 (1 H, t, 3J = 7.5, Ar), 7.14 (2 H, d, 3J = 7.5, Ar),
3
3
3
7.21 (2 H, d, J = 7.8, Ar), 7.31 (2 H, t, J = 7.5, Ar), 7.57 (2 H, d, J = 7.8, Ar). 13C-
NMR (125.7 MHz, CDCl3): δ = 18.6 (Me), 40.0 (NMe), 42.3 (NMe), 57.7 (CH), 114.4
C
(C), 126.7 (C), 129.8 (2 CH), 130.1 (2 CH), 133.1 (CH), 134.0 (2 CH), 138.3 (C), 138.9
(2 CH), 142.9 (C), 145.3 (C), 176.0 (C=S). EI-MS: 387 (M+, 7), 371 (50), 309 (24), 231
(33), 154 (100), 77 (81). Anal. Calc. for C19H19BrN2S (387.34): C, 58.92; H, 4.94; N, 7.23%.
Found: C, 58.90; H, 4.96; N, 7.28%.
4.3.11. 4-(4-Chlorophenyl)-1,3-diethyl-6-methyl-5-phenyl-3,4-dihydropyrimidine-
2(1H)-thione (5k)
Cream powder, mp: 279–281°C; yield: 0.32 g (86%). IR (KBr) (νmax, cm−1): 1655, 1161,
1021. 1H-NMR (500 MHz, CDCl3): δ = 0.95 (3 H, t, J = 6.8, Me), 1.14 (3 H, t, J = 6.8,
H
Me), 2.55 (3 H, s, Me), 3.09 (2 H, q, J = 6.8, NCH2), 3.22 (2 H, q, J = 6.8, NCH2), 5.62 (1
H, s, CH), 7.29–7.33 (4 H, m, Ph), 7.49 (2 H, d, 3J = 7.9, Ar), 7.73 (1 H, t, 3J = 7.6, Ar),
3
8.04 (2 H, d, J = 7.9, Ar). 13C-NMR (125.7 MHz, CDCl3): δ = 14.5 (Me), 15.6 (Me),
C
17.9 (Me), 41.9 (NCH2), 47.5 (NCH2), 57.6 (CH), 114.9 (C), 127.4 (2 CH), 128.7 (2 CH),
129.2 (CH), 130.1 (C), 132.5 (2 CH), 135.7 (2 CH), 136.9 (C), 144.8 (C), 145.9 (C), 176.8
(C=S). EI-MS: 370 (M+, 11), 355 (49), 341 (48), 259 (54), 111 (100), 77 (78). Anal. Calc.
for C21H23ClN2S (370.94): C, 68.00; H, 6.25; N, 7.55%. Found: C, 68.09; H, 6.19; N, 7.58%.
Disclosure statement
No potential conflict of interest was reported by the authors.
Funding
This work was supported by a grant from the Research Council of Shahid Beheshti University of
Medical Sciences [grant no. 10445].
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