N,N′-Dialkyl-4-Aryl-3,4-Dihydropyrimidinones and Thiones: Ceric Ammonium Nitrate Catalyzed Synthesis and Molecular Structure Determination by X-ray Crystallography

Article abstract of DOI:10.1002/jhet.2735

This work presents a microwave assisted solvent-free synthesis of N,N′-dialkyl-4-aryl-3,4-dihydropyrimidinones/thiones in the presence of Ceric Ammonium Nitrate (CAN) via direct condensation of aromatic aldehydes, β-keto ester, and N,N′-dialkylurea/thiour

Full text of DOI:10.1002/jhet.2735

Month 2016
N,N′-Dialkyl-4-Aryl-3,4-Dihydropyrimidinones and Thiones: Ceric
Ammonium Nitrate Catalyzed Synthesis and Molecular Structure
Determination by X-ray Crystallography
Chingrishon Kathing,a Sushil Kumar,b Shokip Tumtin,c Nongthombam Geetmani Singh,a Jims World Star Rani,a
a
a
*
Ridaphun Nongrum, and Rishanlang Nongkhlaw
aCentre for Advanced Studies in Chemistry, North-Eastern Hill University, Shillong, Meghalaya 793022, India
bDepartment of Chemistry, University of Delhi, Delhi 110007, India
cDepartment of Chemistry, Kirori Mal College, University of Delhi, Delhi 110007, India
E-mail: rlnongkhlaw@nehu.ac.in
Additional Supporting Information may be found in the online version of this article.
Received June 3, 2015
DOI 10.1002/jhet.2735
Published online 00 Month 2016 in Wiley Online Library (wileyonlinelibrary.com).
This work presents
a microwave assisted solvent-free synthesis of N,N′-dialkyl-4-aryl-3,4-
dihydropyrimidinones/thiones in the presence of Ceric Ammonium Nitrate (CAN) via direct condensation
of aromatic aldehydes, β-keto ester, and N,N′-dialkylurea/thiourea. The highlights of the methodology
adopted are (i) facile condensation of the reactants into product without any side-products, and (ii) short re-
action time with high yield and good purity. All the compounds synthesized were characterized and
1
established by spectroscopic techniques such as FTIR, H NMR, 13C NMR, and Mass. The structure of
the compound is further corroborated by single crystal X-ray diffraction analysis.
J. Heterocyclic Chem., 00, 00 (2016).
INTRODUCTION
Despite extensive research on this area, direct synthesis
of N,N′-dialkyl DHPM through “a classical Biginelli con-
densation” of aromatic aldehyde, β-keto ester, and N,N′-
dialkylurea/thiourea has not been well documented.
Exhaustive literature survey revealed that, Singh et al.
[12] have reported the synthesis of N,N′-dialkyl-4-aryl-
3,4-dihydropyrimidinones using Dowex-50 W ion
exchange resin. Sangran and co-workers [13] have also
carried out the work using low melting tartaric acid urea
mixtures. In addition, Biginelli reaction for the preparation
of N-substituted ureas and thioureas promoted by
Chlorotrimethylsilane has also been achieved by
Ryabukhin [14]. C. Mukhopadhya et al. [15] have also
employed alkaline metal (II) sulfates as a catalyst to
synthesize N,N′-dimethyl substituted and unsubstituted
4-aryl-3,4-dihydropyrimidones (thiones). Direct condensa-
tion for the preparation of N1 monoalkyl DHPM using
monoalkylated ureas has also been studied by Kappe and
Co-workers [16]. Furthermore, the use of high pressure
technique for the synthesis of DHPM has also been
reported by G. Jenner [17]. Even though there have been
extensive work on the synthesis of DHPM, their methodol-
ogies have been rendered ineffective despite the
“Multicomponent reaction” (MCR) plays a vital role in
the field of medicinal chemistry [1] for the rapid synthesis
of diverse classes of biologically potent organic molecules
for modern drug discovery [2]. Operational simplicity in
one pot is one of the key features of MCR, apart from being
cost effective, atom-economy, and minimization of waste
generation [3–5]. As far as the activation of any synthetic
reaction is concerned, environmentally benign microwave
induced reactions provide spectacular accelerations on the
reactions with a clean reaction profile [6]. Therefore, com-
bination of MCR and microwave irradiation (multicompo-
nent microwave synthesis) [7] has emerged as a powerful
technique, for the construction of complex heterocyclic
scaffolds [8].
The so-called “Biginelli compound”, i.e. 3,4-
dihydropyrimidin-2(1H)-one (DHPM) has prompted a wide-
spread research because of its multifaceted pharmacological
profiles [9]. The importance of DHPMs has also been inten-
sified because of their apparent structure–activity similarities
with the well-known Hantzsch-type dihydropyridines (DHP)
(e.g. nifedipine) [10,11].
© 2016 Wiley Periodicals, Inc.

C. Kathing, S. Kumar, S. Tumtin, N. G. Singh, J. W. S. Rani, R. Nongrum, and R. Nongkhlaw
Vol 000
satisfactory results because of prolonged reaction time, low
yield, and multitude of side-products [18].
5 mol% of catalyst loading and further increase in temper-
ature from 80°C to120°C resulted in the formation of side
products with low product yield. Similarly, no significant
impacts on the yield of the reactions were observed upon
increasing the amount of catalyst from 5 mol% up to
25mol%.
With an aim to develop an efficient methodology, we
have synthesized N,N′-dialkyl DHPM under solvent-free
condition in the presence of Ceric Ammonium Nitrate
(CAN) in catalytic amount of 5mol% as an activator under
microwave irradiation. The involvement of CAN in cata-
lytic amount gives an edge to the synthetic method as it
has emerged as a versatile reagent for various organic
transformations in modern chemical synthesis because of
its various characteristic features such as electron transfer
capacity, Lewis acid property, higher solubility in organic
solvents, low toxicity, and ease of handling [19,20].
Furthermore, the activation of MCR by environmentally
benign microwave irradiation is expected to provide a
clean synthetic route.
In order to generalize the scope of this methodology, a
series of reactions were carried out to synthesize N,N′-
dialkyl-4-aryl-3,4-dihydropyrimidinones (4a–4n) as shown
in Table 1 and the products were isolated by recrystalliza-
tion without column chromatography in good yield
(>80%) along with enhanced purity as determined from
the spectra. The reaction was also extended to thiourea
and their derivatives (4o–4t, Table 1) using N,N′-
dimethylthiourea, which are immensely important with re-
gard to their biological activities such as monastrol, [21]
which act as mitotic kinesin Eg5 inhibitors; notable results
similar to N,N′-dimethylurea derivatives were observed.
Upon further analysis, it was found that various aromatic
aldehydes bearing electron donating and electron with-
drawing groups undergo smooth transformation with no
major effect on the yield of the products. Apart from sim-
plicity in operation, the efficacy of our methodology is fur-
thermore validated by the survivals of varieties of
functional groups such as NO2, OH, Cl, OMe, etc.
The mechanistic pathway for the formation of N,N′-
dialkyl-4-aryl-3,4-dihydropyrimidinones is shown in
Scheme 2. The reaction is proposed to proceed through
the formation of carbonium ion (6) via an aldol condensa-
tion between aldehyde (1) and enolate of 1,3-dicarbonyl
compound (2) activated by Ce4+. The carbonium ion (6)
in turn reacts with N,N′-dimethylurea/thiourea (3) to gener-
ate an open chain intermediate uriede (7) which then un-
dergoes intramolecular cyclization to afford N,N′-dialkyl-
4-aryl-3,4-dihydropyrimidinones/thiones (4).
In order to compare the efficacy of our methodology
with the conventional method, the reaction was investi-
gated under reflux condition, using ethanol as a best
candidature as the reaction medium because ethanol has
been considered as a green solvent [22]. The products 4
(b,c,f,o,t) with yields of 60–70% could be achieved at
80°C in 1–3 h (Table 3). The satisfactory result provides
the scope of employing CAN as catalyst not only under
microwave irradiation but under conventional heating as
well. However, in spite of satisfactory results in conven-
tional method, the microwave induced method under dry
media is still preferable over conventional method as it is
more economical and meet the fundamental challenges to
conserve the environment.
RESULTS AND DISCUSSION
As a preliminary investigation, different quantities of re-
actants were explored and the best results were obtained
using 1:1:1.5 mol ratios of aromatic aldehydes, β-keto ester
and N,N′-dimethylurea/thiourea respectively. As a model
reaction (Scheme 1), benzaldehyde, ethyl acetoacetate,
and N,N′-dimethylurea (1:1:1.5) with catalytic amount of
CAN (5mol%) under solvent-free conditions were sub-
jected to microwave irradiation at 80°C for 90 s which
resulted the product 4b with an excellent yield of 96%
(Table 1).
Under normal room temperature stirring, product 4b was
formed in 12h with a mere 40% yield and no product for-
mation was observed in the absence of catalyst. The cata-
lytic efficiency of CAN for the synthesis of N,N′-dialkyl
DHPM is compared with various catalysts such as PTSA,
NaHSO4, AlCl3, and SnCl2·2H2O (Table 2). The compara-
tive study shows that CAN exhibits superior catalytic
efficiency over the other catalysts.
Furthermore, various operational parameters such as
temperature and catalyst loading which affects the product
formation was investigated and optimized. It was found
that the highest yield could be achieved at 80°C with
Scheme 1. Synthesis of N,N′-dialkyl-4-aryl-3,4-dihydropyrimidinones/
thiones. [Color figure can be viewed in the online issue, which is
available at wileyonlinelibrary.com.]
All the compounds synthesized were characterized by
spectroscopic techniques such as FTIR, 1H NMR, 13C
NMR, and Mass. The various analytic results for all
the compounds prepared were found to be in accordance
with the expected structure. As a representative, the
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DOI 10.1002/jhet

Month 2016
Synthesis of N,N′-Dialkyl-4-Aryl-3,4-Dihydropyrimidinones and Thiones
Table 1
CAN catalyzed synthesis of N,N′-dimethyl-4-aryl-3,4-dihydropyrimidinones and thiones (4a–4t).
Entry
R1
R2
R3
R4
X
Time (s)
Yielda (%)
Mp°C
4a
4b
4c
4d
4e
4f
4g
4h
4i
C6H5
C6H5
OMe
OEt
OMe
OMe
OMe
OEt
OMe
OMe
OEt
OMe
OMe
OEt
OMe
OMe
OMe
OEt
OMe
OMe
OEt
Me
Me
O
110
90
100
90
93
96
92
94
90
89
90
92
90
85
91
93
84
81
85
83
87
87
90
86
121–123
69–70
97–103
93–95
145–147
102–104
137–140
155–157
121–123
186–188
80–82
50–52
135–137
59–61
133–135
70–72
125–127
149–151
88–90
Me
Me
Me
Me
Me
Me
Me
Me
Me
Me
Me
Me
Me
Me
Me
Me
Me
Me
Me
Me
Me
Me
Me
Me
Me
Me
Me
Me
Me
Me
Me
Me
Me
Me
Me
Me
Me
Me
O
O
O
O
O
O
O
O
O
O
O
O
O
S
4-MeO-C6H4
4-Me-C6H4
4-NO2-C6H4
4-NO2-C6H4
3-NO2-C6H4
4-OH,3-MeO-C6H3
4-OH,3-MeO-C6H3
4-OH-C6H4
4-Cl-C6H4
4-Cl-C6H4
2-Cl-C6H4
2-Furyl
C6H5
120
120
115
100
115
120
110
110
100
145
155
146
140
135
120
125
4j
4k
4l
4m
4n
4o
4p
4q
4r
4s
4t
C6H5
4-Cl-C6H4
4-OH-C6H4
4-Me-C6H4
4-OH,3-MeO-C6H3
S
S
S
S
OMe
S
130–132
aIsolated yield.
Table 2
Effect of catalyst for the synthesis of 4b.
Table 3
Comparative study under microwave and reflux condition.
Sl. no
Catalyst
NaHSO4
PTSA
AlCl3
Time (min)
Yield (%)
MWI
RC
1
2
3
4
5
45
30
55
60
1.5
55
75
40
30
96
Compound
Time
(s)
Yield
(%)
Time
(min)
Yield
(%)
Entry
(4)
SnCl2.2H2O
CAN
1
2
3
4
5
4b
4c
4f
4o
4t
90
96
92
89
85
86
60
90
130
180
150
70
68
64
60
62
100
120
155
125
Scheme 2. Plausible mechanism for the formation of N,N′-dialkyl-4-aryl-
3,4-dihydropyrimidinones/thiones. [Color figure can be viewed in the
online issue, which is available at wileyonlinelibrary.com.]
MWI = microwave irradiation; RC = reflux condition.
Figure 1. Selected 1H and 13C NMR data of 4b. [Color figure can be
viewed in the online issue, which is available at wileyonlinelibrary.com.]
stretching frequency of the two carbonyl (C¼O) groups.
1
In H NMR spectrum, the methine (CH) proton appears
as a singlet at δ 5.24 and the singlet observed at δ 2.48 cor-
responds to the methyl group of ethyl acetoacetate moiety
on dihydropyrimidine ring. The two methyl groups of N,
N′-dimethylurea resonate at different fields as two singlets
compound 4b (Fig. 1) was selected whose spectral data is
interpreted as follows. The occurrence of absorption bands
at 1719 cmꢀ1 and 1690 cmꢀ1 in IR spectrum depicts the
Journal of Heterocyclic Chemistry
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C. Kathing, S. Kumar, S. Tumtin, N. G. Singh, J. W. S. Rani, R. Nongrum, and R. Nongkhlaw
Vol 000
Table 4
Crystal data of the compound 4b.
Empirical formula
C16H20N2O3
Formula weight
288.34
Temperature
Wavelength
293(2) K
0.71073 Å
Crystal system
Space group
Monoclinic
P 21/c
a
8.7884(7) Å
b
c
α
11.3956(11) Å
15.3417(14) Å
90°
β
γ
92.255(7)°
90°
Volume
Z
1535.3(2) Å3
4
Density (calculated)
Absorption coefficient
F(000)
Crystal size
Theta range for data
collection
1.247 Mg/m3
0.087 mmꢀ1
616
0.24 × 0.22 × 0.21 mm3
3.20 to 25.00°
Figure 2. Molecular structure of 4b; thermal ellipsoids are drawn at 30%
probability level. [Color figure can be viewed in the online issue, which is
available at wileyonlinelibrary.com.]
Index ranges
ꢀ10 ≤ h ≤ 10, ꢀ11 ≤ k ≤ 13, ꢀ
18 ≤ l ≤ 18
5450
Reflections collected
Independent reflections
Completeness to
2696 [R(int) = 0.0230]
99.8%
in the shielded region at δ 3.27 and δ 2.91 for N1-methyl
and N3-methyl respectively. In addition to the IR informa-
tion, the two carbonyl (C¼O) groups are also confirmed
from the 13C NMR spectrum by the chemical shift values
at δ 165.98 and δ 153.83.
The structure is further being elucidated from a single
crystal X-ray analysis of 4b; the crystal was obtained by
slow evaporation method from hexane. The molecular
structure of 4b is shown in Figure 2 and its crystallographic
data are listed in Table 4.
theta = 25.00°
Absorption correction
Max. and min. transmission
Refinement method
Data/restraints/parameters
Goodness-of-fit on F2
Final R indices [I > 2sigma
(I)]a, b
Multi-scan
0.9820 and 0.9795
Full-matrix least-squares on F2
2696/0/195
1.061
R1 = 0.0560, wR2 = 0.1584
R indices (all data)
Largest diff. peak and hole
R1 = 0.0757, wR2 = 0.1704
0.246 and ꢀ0.175 e.Åꢀ3
aR = Σ(‖Fo∣ –∣ Fc‖)/Σ∣ Fo∣.
bwR = {Σ[w(Fo2 – Fc2)2]/Σ[w(Fo2)2]}1/2
CONCLUSIONS
NMR, and Mass. Convenient experimental work up and
product isolation procedures without any tedious column
chromatography for purification of the compounds further
augment the efficacy of the methodology.
In summary, a novel and efficient methodology with an
excellent yield and short time of reaction has been devised
for the direct synthesis of N,N′-dialkyl DHPM and its
derivatives. The process involves the microwave assisted
reactions under solvent-free condition which have ensued
the rapid generation of a library of compounds as well as
minimization of waste production thereby making the pro-
cess more economical and environment friendly. The effi-
cacy of the synthetic process is evident from the fact that
the complete product formation could be accomplished
within 90–155s of reaction time with 81–96% of product
yield. The preparation of the compounds, which were
presumed to be complicated because of bulky nature of
N,N′-dimethylurea/thiourea compared to unsubstituted
urea/thiourea, was found to be rather facile and efficient
which is substantiated by X-ray crystallography as well
EXPERIMENTAL SECTION
Microwave reactions were carried out in a CEM Dis-
cover Benchmate microwave digester. Melting points were
determined in open capillary tubes and are uncorrected. In-
frared spectra were recorded on a Perkin Elmer Spectrum
400 FTIR instrument using KBr pellets and the frequencies
are expressed in cmꢀ1. 1H and 13C NMR (400MHz) spec-
tra were recorded on a Bruker Avance II-400 spectrometer
using CDCl3 as the solvent. Chemical shifts are reported in
ppm downfield from internal tetramethyl silane and are
given on the δ scale. Mass spectral data were obtained with
a JEOL D-300 (ESI) mass spectrometer. All reactions were
as spectroscopic techniques such as FTIR, H NMR, 13C
1
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Month 2016
Synthesis of N,N′-Dialkyl-4-Aryl-3,4-Dihydropyrimidinones and Thiones
monitored by TLC using precoated aluminum sheets (silica
gel 60F 254 0.2-mm thickness) and developed in an iodine
chamber or under UVGL-15 mineral light 254-nm lamp.
31.02, 34.43, 60.14, 60.84, 103.60, 126.62, 127.84,
128.59, 140.99, 149.24, 153.83, 165.98; MS (ESI): m/z
289 [M + 1]; Anal. cald. for C16H20N2O3: C, 66.65; H,
6.99; N, 9.72; O, 16.65; Found: C, 66.90; H, 6.85; N, 9.55.
General procedure for microwave assisted synthesis.
A
mixture of aromatic aldehyde (1 mmol), β-keto ester
(1 mmol), and N,N′-dimethylurea/thiourea (1.5 mmol) in
the presence of a catalytic amount of CAN (5 mol%) was
taken in a microwave reaction vial and irradiated in
microwave digester at 80°C, 15–20 bar, 80–120W for
90–155s. After the completion of the reaction (monitored
by TLC), the reaction mixture was extracted with ethyl
acetate and wash with brine (1× 10 mL) followed by
water (3× 10 mL). The combine extract was evaporated in
rotavapor and finally a solid was obtained. The solid
obtained was almost a pure product; however, in some
cases the products were further purified by
recrystallization from hexane or ethanol.
General procedure for conventional method of synthesis.
In a round bottom flask, the reactants aromatic aldehyde
(1 mmol), β-keto ester (1 mmol), and N,N′-dimethylurea/
thiourea (1.5 mmol) were taken with a catalytic amount
of CAN (5 mol%) in the presence of ethanol and refluxed
at 80°C for 1–3h. After the completion of the reaction
(monitored by TLC), the resultant reaction mixture was
extracted and purified to afford the compounds following
the same procedure as microwave method.
Methyl
1,2,3,4-tetrahydro-4-(4-methoxyphenyl)-1,3,6-
trimethyl-2-oxopyrimidine-5-carboxylate (4c). Light yellow
solid, yield 92%, mp 97–103°C; IR (KBr): 3049
(Ar―CH), 2945 (Alkyl–CH), 1702 (C¼O), 1667 (C¼O),
1214 (O―CO), 1031 (O―CH3) cmꢀ1
;
1H NMR
(400 MHz, CDCl3): δ 2.47 (s, 3H, CH3), 2.90 (s, 3H,
N3―CH3), 3.26 (s, 3H, N1―CH3), 3.67 (s, 3H, OCH3),
3.78 (s, 3H, COOCH3), 5.18 (s, 1H, CH), 6.81 (d,
J = 8.4 Hz, 2H, Ar), 7.13 (d, J= 8.4 Hz, 2H, Ar); 13C
NMR (100MHz, CDCl3): δ 16.63, 31.02, 34.33, 51.23,
55.21, 60.21, 103.63, 113.95, 127.75, 133.08, 149.20,
153.79, 159.19, 166.46; MS (ESI): m/z 305 [M + 1]; Anal.
cald. for C16H20N2O4: C, 63.14; H, 6.62; N, 9.20; O,
21.03; Found: C, 63.35; H, 6.52; N, 9.38.
Methyl 1,2,3,4-tetrahydro-1,3,6-trimethyl-4-(4-nitrophenyl)-
2-oxopyrimidine-5-carboxylate (4e).
Light yellow solid,
yield 90%, mp 145–147°C; IR (KBr): 3078 (Ar―CH),
2959 (Alkyl–CH), 1681 (C¼O), 1667 (C¼O), 1219
(O―CO), 1029 (O―CH3) cmꢀ1 1H NMR (400MHz,
;
CDCl3): δ 2.42 (s, 3H, CH3), 2.87 (s, 3H, N3―CH3),
3.21 (s, 3H, N1―CH3), 3.64 (s, 3H, OCH3), 5.30 (s, 1H,
CH), 7.33 (d, J =8.0 Hz, 2H, Ar), 8.10 (d, J = 8.0Hz, 2H,
Ar); 13C NMR (100MHz, CDCl3): δ 15.78, 30.22, 33.69,
50.48, 59.26, 101.32, 123.02, 126.38, 146.53, 147.13,
149.61, 152.47, 165.00; MS (ESI): m/z 320 [M + 1]; Anal.
cald. for C15H17N3O5: C, 56.42; H, 5.37; N, 13.16; O,
25.05; Found: C, 56.60; H, 5.52; N, 13.05.
X-ray structure analysis.
The intensity data was
collected on an Oxford Xcalibur CCD diffractometer
equipped with graphite monochromatic Mo-Kα radiation
(λ = 0.71073 Ǻ) at 293(2) K [23]. A multi-scan correction
was applied. The structure was solved by the direct
methods using SIR-92 and refined by full-matrix least-
squares refinement techniques on F2 using SHELXL97
[24]. The hydrogen atoms were placed into the calculated
positions and included in the last cycles of the
refinement. All calculations were done using Wingx
software package [25].
Crystallographic data for the structure of the compound
4b have been deposited with the Cambridge Crystallo-
graphic Data Centre as supplementary publication no.
CCDC 1008429. Copies of the data can be obtained, free
of charge, on an application to CCDC, 12 Union Road,
Cambridge CB2 1EZ, UK, (fax: +44-(0)1223-336033 or
e-mail:deposit@ccdc.cam.ac.Uk).
Ethyl 1,2,3,4-tetrahydro-1,3,6-trimethyl-4-(4-nitrophenyl)-2-
oxopyrimidine-5-carboxylate (4f).
Yellow solid, yield
89%, mp 102–104°C; IR (KBr): 3038 (Ar―CH), 2991
(Alkyl–CH), 1678 (C¼O), 1661 (C¼O), 1214 (O―CO),
1028 (O―CH2CH3) cmꢀ1; H NMR (400MHz, CDCl3):
1
δ 1.26 (t, J = 6.9 Hz, CH2CH3), 2.50 (s, 3H, CH3), 2.94
(s, 3H, N3―CH3), 3.28 (s, 3H, N1―CH3), 4.16 (q,
J = 6.9 Hz, CH2CH3), 5.37 (s, 1H, CH), 7.41 (d,
J = 8.4 Hz, 2H, Ar), 8.17 (d, J= 8.4 Hz, 2H, Ar); 13C
NMR (100MHz, CDCl3): δ 14.27, 16.74, 31.19, 34.64,
60.48, 60.37, 102.52, 123.97, 127.48, 147.53, 148.24,
150.31, 153.47, 165.56; MS (ESI): m/z 334 [M + 1]; Anal.
cald. for C16H19N3O5: C, 57.65; H, 5.75; N, 12.61; O,
24.00; Found: C, 57.80; H, 5.89; N, 12.45.
Characterization data of selected compounds are listed below
Ethyl 1,2,3,4-tetrahydro-1,3,6-trimethyl-2-oxo-4-phenylpy-
Methyl 1,2,3,4-tetrahydro-1,3,6-trimethyl-4-(3-nitrophenyl)-
rimidine-5-carboxylate (4b).
Colorless solid, yield 96%,
2-oxopyrimidine-5-carboxylate (4g).
Yellow solid, yield
mp 69–70°C; IR (KBr): 3029 (Ar―CH), 2977 (Alkyl–
CH), 1701 (C¼O), 1674 (C¼O), 1208 (O―CO), 1032
90%, mp 137–140°C; IR (KBr): 3094 (Ar―CH), 2947
(Alkyl–CH), 1703 (C¼O), 1678 (C¼O), 1205 (O―CO),
1
(O―CH2CH3) cmꢀ1
;
1H NMR (400 MHz, CDCl3): δ
1032 (O―CH3) cmꢀ1; H NMR (400MHz, CDCl3): δ
1.25 (t, J = 7.0Hz, CH2CH3), 2.48 (s, 3H, CH3), 2.91 (s,
3H, N3―CH3), 3.27 (s, 3H, N1―CH3), 4.13 (q,
J =7.0 Hz, CH2CH3), 5.24 (s, 1H, CH), 7.21–7.31 (m,
5H, Ar); 13C NMR (100 MHz, CDCl3): δ 14.23, 16.59,
2.52 (s, 3H, CH3), 2.94 (s, 3H, N3―CH3), 3.30 (s, 3H,
N1―CH3), 3.70 (s, 3H, OCH3), 5.35 (s, 1H, CH), 7.48–
8.15 (m, 4H, Ar); 13C NMR (100MHz, CDCl3): δ 16.71,
31.19, 34.59, 51.47, 60.42, 102.36, 121.81, 123.00,
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

C. Kathing, S. Kumar, S. Tumtin, N. G. Singh, J. W. S. Rani, R. Nongrum, and R. Nongkhlaw
Vol 000
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129.78, 132.51, 143.14, 148.47, 150.64, 153.32, 165.93;
MS (ESI): m/z 320 [M + 1]; Anal. cald. for C15H17N3O5:
C, 56.42; H, 5.37; N, 13.16; O, 25.05; Found: C, 56.59;
H, 5.22; N, 13.25.
Methyl
1,2,3,4-tetrahydro-1,3,6-trimethyl-4-phenyl-2-
thioxopyrimidine-5-carboxylate (4o). Offwhite solid, yield
85%, mp 133–135°C; IR (KBr): 3018 (Ar―CH), 2948
(Alkyl–CH), 1702 (C¼O), 1691 (C¼S), 1211 (O―CO),
1
1068 (O―CH3) cmꢀ1; H NMR (400 MHz, CDCl3): δ
2.47 (s, 3H, CH3), 3.48 (s, 3H, N3―CH3), 3.57 (s, 3H,
N1―CH3), 3.78 (s, 3H, OCH3), 5.59 (s, 1H, CH), 7.12–
7.32 (m, 5H, Ar); 13C NMR (100 MHz, CDCl3): δ 16.93,
38.11, 43.02, 51.70, 61.26, 105.72, 125.81, 128.01,
128.87, 139.47, 147.79, 166.10, 179.64; MS (ESI): m/z
291 [M+ 1]; Anal. cald. for C15H18N2O2S: C, 62.04; H,
6.25; N, 9.65; O, 11.02; S, 11.04; Found: C, 62.26; H,
6.15; N, 9.48.
Acknowledgments. The authors gratefully acknowledge SAIF,
NEHU, Shillong, for the spectral analyses and Department of
Chemistry, NEHU, Shillong, for the X-ray diffraction analysis.
C. Kathing acknowledges the financial assistance provided by
UGC (F1-17.1/2011-12/RGNF-ST-MAN-616).
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Journal of Heterocyclic Chemistry
DOI 10.1002/jhet