Nano-MoO3 as a highly efficient heterogeneous catalyst for a one-pot synthesis of tetrahydropyrimidine derivatives in water

Article abstract of DOI:10.3184/174751914X14115772243815

A green and highly efficient one-pot synthesis of 16 1,3,4,5-tetrasubstituted 1,2,3,6-tetrahydropyrimidines, four of which are new, using a three-component reaction involving an aniline, formaldehyde and a dialkyl acetylenedicarboxylate in aqueous media at room temperature catalysed by nano-MoO3 has been achieved.

Full text of DOI:10.3184/174751914X14115772243815

JOURNAL OF CHEMICAL RESEARCH 2014
VOL. 38 OCTOBER, 607–610
RESEARCH PAPER 607
Nano-MoO3 as a highly efficient heterogeneous catalyst for a one-pot
synthesis of tetrahydropyrimidine derivatives in water
Elham Zarenezhada*, Mohammad Navid Soltani Radb, Mohammad Hossein Mosslemina,
Masoumeh Tabatabaeea and Somayeh Behrouzb
aDepartment of Chemistry, Yazd Branch, Islamic Azad University, PO Box 89195-155, Yazd, Iran
bDepartment of Chemistry, Shiraz University of Technology, 71555-313 Shiraz, Iran
A green and highly efficient one-pot synthesis of 16 1,3,4,5-tetrasubstituted 1,2,3,6-tetrahydropyrimidines, four of which are
new, using a three-component reaction involving an aniline, formaldehyde and a dialkyl acetylenedicarboxylate in aqueous
media at room temperature catalysed by nano-MoO3 has been achieved.
Keywords: three-component reaction, tetrahydropyrimidines, green synthesis, MoO3-nanoparticle
The synthesis of polyfunctionalised heterocyclic compounds
has received considerable attention in recent years owing to their
known potential as drugs.1 Although pyrimidine derivatives
are a well-known, diverse and interesting group of heterocyclic
drugs, largely owing to the presence of the heterocycle in the
DNA and/or RNA scaffold,2 dihydropyrimidine derivatives
have also attracted increasing interest owing to their activities
as antifungal,3 anti-hypertensive,4 and anti-tumour agents.5
Since multicomponent reactions (MCRs) yield complex
products from readily available starting materials giving good
yields in a single step process, they have emerged as green and
powerful tools in organic synthesis and drug discovery.6 Also,
since MCRs can employ a large range of starting materials,
many new classes of compounds can be synthesised which may
show novel pharmaceutical properties.7
already reported the synthesis of some tetrahydropyrimidine
derivatives in multi-step processes using organic media, but
in low yields.13 Recently, Darandale and coworkers reported
a three-component reaction between formaldehydes, anilines
and dialkyl acetylenedicarboxylate derivatives in boiling
water using ZrOCl2 as a catalyst to produce the corresponding
1,3,4,5-tetrasubstituted 1,2,3,6-tetrahydropyrimidine derivatives
in moderate to good yields.14 We have now found that the
same reaction can be carried out more rapidly in good to
excellent yields using MoO3-nanoparticles as a catalyst at
room temperature in H2O (Scheme 1) and we now describe
our successful synthesis of 16 1,3,4,5-tetrasubstituted
1,2,3,6-tetrahydropyrimidines, four of which are new.
Since MoO3-nanoparticles possess a high oxidation state of
Mo (Mo+6), they exhibit superior acid strength compared to
ZrOCl2 which we believe explains why they readily catalyse
the highly efficient synthesis of the title products under very
mild reaction conditions in a shorter reaction time.
Metal oxide nanoparticles are known as useful heterogeneous
catalysts which traditionally can catalyse MCRs. Development
of such catalysts has resulted in more economical and
environmentally friendly chemistry through replacing
nonselective, unstable, or toxic catalysts.8
Results and discussion
MoO3-nanoparticles were previously synthesised15 and their
nano structures have been characterised and confirmed by the
use of powder X-ray diffraction (PXRD) and scanning electron
microscopy (SEM). Figure 1 shows the XRD pattern of nano-
MoO3 and Fig. 2 refers to the SEM micrograph. The crystal size
structure was calculated from the Debye–Scherrer formula,
Dꢀ=ꢀkλꢀ/ꢀβcosθ,ꢀwhereꢀDꢀisꢀtheꢀcrystalliteꢀsize,ꢀkꢀisꢀaꢀconstantꢀ
(=ꢀ0.9ꢀ assumingꢀ thatꢀ theꢀ particlesꢀ areꢀ spherical),ꢀ λꢀ isꢀ theꢀ
wavelengthꢀofꢀtheꢀX‑rayꢀradiation,ꢀβꢀisꢀtheꢀlineꢀwidthꢀ(obtainedꢀ
afterꢀcorrectionꢀforꢀtheꢀinstrumentalꢀbroadening)ꢀandꢀθꢀisꢀtheꢀ
angle of diffraction. The average particle size obtained from
XRD data was ~50 nm.
MoO3-nanoparticles have received considerable attention
as an inexpensive, eco-friendly and highly reactive catalyst.
Furthermore, this catalyst is non-toxic and can be easily
handled for various organic transformations, affording the
corresponding products with high selectivity in excellent
yields.9 MoO3 exhibits remarkable Lewis acid properties
for various organic transformations in the liquid phase.10
This catalyst can be recycled many times and in most cases
its reactivity remains essentially intact; moreover, MoO3-
nanoparticles as a catalyst are quite active over a wide range
of temperatures being resistant to thermal breakdown.11 It
Tetrahydropyrimidine derivatives can be synthesised using
hazardous and toxic solvents,12 as but the requirement for high
temperatures, expensive organic solvents and long reaction
times limits the use of these methods. Sun and coworkers have
Initially, to obtain the optimised reaction conditions, we
selected the reaction of 4-methylaniline (1; X=H, Y=4-Me),
dimethyl acetylenedicarboxylates 2, and formaldehyde 3
O
NH2
COOR
O
RO
N
Nano-MoO3
C
+
X
+
X
2
H2O (10 mL), r.t., 5 min
H
H
RO
N
COOR
4
X
O
3
2
1
X : NO2, OH, CH3,Cl ,....
R: Me,Et
* Correspondent. E-mail: elham.zarenezhad2014@gmail.com
JCR1402797_FINAL.indd 607
17/10/2014 14:34:33

608 JOURNAL OF CHEMICAL RESEARCH 2014
O
O
Y
NH2
RO
RO
COOR
N
O
X
Nano-MoO3
H2O, r.t.,5 min
C
+
N
Y
+
2
H
H
X
COOR
2
Y
1
4
3
X
OMe
S
O
O
O
O
MeO
MeO
N
S
N
4n:
MeO
MeO
N
N
4a
: X=H , Y=Me , R=Me
4g
4h
: X=NO2 , Y=H , R=Et
: X=H , Y=Me, R=Et
4m:
4o:
N
N
4b
4c
: X=H , Y=NO2 , R=Me
N
N
4i
4j
: X=H , Y=Cl , R=Me
: X=H , Y=OH , R=Et
OMe
4d
4e
: X=H , Y=H , R=Me
: X=H , Y=OH , R=Me
: X=NO2, Y=H , R=Me
: X=H , Y=H , R=Et
OMe
N
O
S
4k
: X=H , Y=NO2 , R=Et
4l
: X=H , Y=Cl , R=Et
O
EtO
EtO
N
N
N
4f
EtO
EtO
N
4p:
N
O
N
O
S
N
OMe
Scheme 1 Synthesis of 1,3,4,5-tetrasubstituted 1,2,3,6-tetrahydropyrimidines catalysed by nano-MoO3.
(Scheme 1) in a molar ratio of 2:1:4 as a sample reaction,
respectively. To this end, we tested the influence of different
catalysts, solvents and temperatures on the reaction and the
results are shown in Table 1.
filtration and washing with EtOAc. The catalytic activity of the
nano-MoO3 remained intact after two runs and even after 10
successive runs had decreased only to 87%.
Under the optimised reaction conditions,
a
series
of
1,3,4,5-tetrasubstituted 1,2,3,6-tetrahydropyrimidines
When the reaction was carried out in the absence of catalyst,
a longer reaction time was required (40 min) and in this case a
low yield of product was attained (<35%) even if the reaction
time was prolonged (entry 1).
derivatives (4b–p) (Scheme 1) were synthesised in high yield
(89–95%) and characterised by appropriate spectroscopic and
physical methods (Table 2).
As can be seen in Table 2, this multi component approach
can be used for the synthesis of such products (4a–l) from
both aromatic amines with electron-withdrawing and electron-
donating groups. Furthermore, several heteroaromatic amines
were successfully used in this reaction producing products
4m–p with excellent results. In this procedure, the products
were easily separated from the reaction mixture by simple
filtration, as they were virtually insoluble in water. Also for
separating the catalyst from the crude product, the solid mixture
was washed with excess of EtOAc to remove the product from
the catalyst. We also attempted to use an aromatic aldehyde
instead of formaldehyde in this method; but no product was
obtained.
To obtain the desired product (4a), we tested the reaction using
seven different homogeneous and heterogeneous Bronsted and/
or Lewis acids (Table 1, entries 2–8). Among the tested acids,
10 mol% nano-MoO3 gave the best yield of 95% in 5 min
(entry 8) and was the catalyst of choice. We also investigated
the effect of using a greater amount of MoO3-nanoparticles.
However, by increasing the molar percentage of catalyst to 11
or 12% no further improvement was observed for the model
reaction (entries 9 and 10). A decrease in the amount of catalyst
to less than 10% resulted in decreased yields (entries 11 and
12). Also for nano-MoO3, it was demonstrated that H2O was the
best solvent in comparison with other solvents including EtOH,
CH3CN, MeOH and CH2Cl2 (entries 8 and 13–16). Therefore,
H2O was selected as the solvent of choice.
The heterogeneous nano-MoO3 catalyst used in this
experiment was recycled and reused several times by a simple
2000
0
5
10
20
30
40
50
60
70
80
Fig. 1 PXRD patterns of the synthesised MoO3 nano-crystal.
Fig. 2 Scanning electron micrographs for prepared nano-MoO3.
JCR1402797_FINAL.indd 608
17/10/2014 14:34:35

JOURNAL OF CHEMICAL RESEARCH 2014 609
Table 1 Optimisation of the three-component coupling reaction between
4-methylaniline 1 (X=4-Me) dimethyl acetylenedicarboxylate 1 (R=Me) and
formaldehyde 3 in water (Scheme 1)a
Table 2 Synthesis of 1,3,4,5-tetrasubstituted 1,2,3,6-tetrahydro-
pyrimidines derivatives (4a–p) using nano-MoO3 in water (Scheme 1)a
Yield/%b
Time/min
Product
Entry ref.
Entry
1
2
3
4
5
6
7
8
Catalyst/mol%
–
SiO2 (15)
Solvent
H2O
H2O
H2O
H2O
H2O
H2O
H2O
H2O
Time/min
40
20
50
50
50
50
50
5
Yield/%b
35
30
35
35
50
40
55
95
95
95
75
95
92
90
92
90
93
91
90
90
92
92
90
91
93
90
89
5
7
8
7
7
10
10
7
8
5
5
7
9
10
10
8
4a
4b
4c
4d
4e
4f
4g
4h
4i
4j
4k
4l
4m
4n
4o
4p
1
2
314
H3PO4 (15)
CF3CO2H (10)
CCl3CO2H (10)
PTSA (10)
ZrOCl2 (10)
MoO3 (10)
MoO3 (11)
MoO3 (12)
MoO3 (8)
414
514
614
714
8
914
9
H2O
H2O
H2O
5
10
10
1014
1114
1214
1314
1414
1514
1614
10
11
12
13
14
15
16
MoO3 (4)
H2O
15
70
MoO3 (10)
MoO3 (10)
MoO3 (10)
MoO3 (10)
EtOH
CH3CN
MeOH
CH2Cl2
20
20
20
20
53
62
62
50
aReaction conditions: arylamine or heteroarylamine (2 mmol), dialkyl
acetylenedicarboxylate (1 mmol), and formaldehyde (4 mmol) were left in
contact with catalyst in water at room temperature for various times.
bIsolated yield.
aReaction
conditions:
4-methylaniline
(2 mmol),
dimethyl
acetylenedicarboxylate (1 mmol), and formaldehyde (4 mmol) were left in
contact with catalyst in water or an organic solvent at room temperature
for various times.
bIsolated yield.
Dimethyl 1,3-bis(4-nitrophenyl)-1,2,3,6-tetrahydropyrimidine-4,5-
dicarboxylate (4b):ꢀYellowꢀsolid;ꢀyieldꢀ92%;ꢀm.p.ꢀ222–224ꢀ°C;ꢀIRꢀ(νmax):
3280, 2865, 1729, 1692, 1367 cm–1; 1H (DMSO-d6)ꢀδꢀ3.63ꢀ(s,ꢀ6H,ꢀ2CH3)
4.75 (s, 2 H, CH2) 5.70 (s, 2 H, CH2) 6.57–6.68 (m, 4 H, arom.), 6.81–7.24
(m, 4 H, arom.); 13C NMR (DMSO-d6)ꢀδꢀ52.8,ꢀ53.1,ꢀ80.0,ꢀ112.8,ꢀ116.9,ꢀ
122.5, 123.6, 124.2, 136.7, 137.5, 143.3, 150.5, 155.0, 165.0, 167.8;
ES-MS m/z: 353 (M+H). Anal. calcd for C20H18N4O8: C, 54.30; H, 4.10;
N, 12.66; found: C, 54.28; H, 4.13; N, 12.65%.
Dimethylꢁꢁꢁꢁ1,3-bis(4-chlorophenyl)-1,2,3,6-tetrahydropyrimidine-
4,5-dicarboxylate (4c): Red solid; yield 90%; 260–263 °C (lit.14
262–264ꢀ°C);ꢀIRꢀ(νmax): 3012, 2985, 1710, 1710 cm–1; 1 H NMR (CDCl3)
δꢀ3.72ꢀ(s,ꢀ6H,ꢀ2CH3), 4.39 (s, 2H, CH2), 5.40 (s, 2H, CH2), 7.01–7.19 (m,
4H, arom.), 7.31–7.52 (m, 4H, arom.);13C NMR (CDCl3)ꢀδꢀ54.0,ꢀ55.9,ꢀ
86.9, 115.2, 117. 0, 118.5, 126.5, 128.1, 131.0, 145.1, 146.3, 151.9, 168.1,
170.1;.ES-MS m/z: 422 (M+H). Anal. calcd for C20H18Cl2N2O4: C,
57.02; H, 4.31, N, 6.65; found: C, 56.92; H, 4.55; N, 7.01%.
Dimethylꢁꢁꢁꢁ1,3-diphenyl-1,2,3,6-tetrahydropyrimidine-4,5-di-
carboxylate (4d): Red-orange solid; yield 92%; (lit.14 197–199 °C);
IRꢀ (νmax): 3002, 2995, 1717, 1701 cm–1; 1H NMR (CDCl3)ꢀ δꢀ 3.61ꢀ
(s, 6H, 2CH3), 4.11 (s, 2H, CH2), 5.10 (s, 2H, CH2), 7.01–7.17 (m, 4H,
arom.), 7.40–7.57 (m, 4H, arom.), 7.75–7.91 (m, 2H, arom.); 13C NMR
(CDCl3)ꢀ δꢀ 53.0,ꢀ 56.1,ꢀ 86.2,ꢀ 113.0,ꢀ 115.2,ꢀ 118.7,ꢀ 120.9,ꢀ 123.1,ꢀ 130.9,ꢀ
144.1, 142.2, 150.1, 161.9, 167.9;ES-MS m/z: 352 (M+H). Anal. calcd
for C20H20N2O4:C, 68.17; H, 5.72; N, 7.95; found: C, 67.87; H, 6.02; N,
7.56%.
A plausible mechanism has been suggested for the formation
of 1,3,4,5-tetrasubstituted 1,2,3,6-tetrahydropyrimidines from
similar reactants to the ones we used catalysed by ZrOCl2
and we assume that our procedure using MoO3-nanoparticles
proceeds similarly.
14
Experimental
Solvents were purified by standard procedures, and stored over 3Å
molecular sieves. Reactions were followed by TLC using SILG/
UV 254 silica-gel plates. Melting points were determined with
an Electrothermal 9100 apparatus in open capillary tubes and are
uncorrected. Elemental analyses were performed using a Heraeus
CHN–O-Rapid analyser. IR spectra were recorded on a Shimadzu
IR-470 spectrometer. NMR spectra were obtained on a Bruker DRX-
400 Avance spectrometer (1H NMR at 400 Hz, 13C NMR at 100 Hz)
in CDCl3 or DMSO-d6 using tetramethylsilane as internal standard.
Chemicalꢀshiftsꢀ(δ)ꢀareꢀgivenꢀinꢀppmꢀandꢀcouplingꢀconstantsꢀ(J) in Hz.
1
Abbreviations used for H NMR signals are: s=singlet, d=doublet,
t=triplet, q=quartet, m=multiplet, b=broad. The chemicals used in
this work were purchased from Fluka or Merck and were used without
further purification.
Synthesis of tetrahydropyrimidine derivatives; general procedure
In a round-bottomed flask (10 mL), a mixture of aromatic amine
(2 mmol), dialkyl acetylenedicarboxylate (1 mmol), formaldehyde
(4 mmol), MoO3 (10 mol%) and H2O (5 mL) was stirred for the
appropriate times (Table 2). Progress of reactions was monitored by
TLC. On completion, the reaction mixture was washed with H2O
(10 mL) and EtOAc (10 mL) to afford a crude product which was
purified by recrystallisation in hot EtOH.
Dimethylꢁꢁꢁꢁ1,3-di-p-tolyl-1,2,3,6-tetrahydropyrimidine-4,5-di-
carboxylate (4a): Creamy solid; yield 92%; m.p. 194–198 °C; IR
(νmax): 3365, 2929, 1722, 1603, 1615 cm–1; 1H NMR (DMSO-d6)ꢀ δꢀ
2.50 (s, 6H, 2CH3) 3.33 (s, 3H, OCH3) 4.71 (s, 2 H, CH2) 5.35 (s, 2 H,
CH2) 6.58–6.81 (m, 4 H, arom.), 7.93–8.04 (m, 4 H, arom); 13C NMR
(DMSO-d6)ꢀδꢀ23.4,ꢀ52.2,ꢀ53.4,ꢀ57.8,ꢀ85.8,ꢀ112.5,ꢀ117.5,ꢀ126.6,ꢀ128.9,ꢀ
129.4, 129.9, 130.8, 141.6, 144.4, 147.2, 164.2, 166.4; ES-MS m/z: 380
(M+H). Anal. calcd for C22H24N2O4: C, 69.46; H, 6.36; N, 7.36; found:
C, 69.47; H, 6.40; N, 7.34%.
Dimethylꢁꢁꢁꢁ1,3-bis(4-hydroxyphenyl)-1,2,3,6-tetrahydropyrimidine-
4,5-dicarboxylate (4e): Red solid; yield 90%; (lit.14 240–242 °C); IR
1
(νmax): 3012, 2995, 1713, 1705 cm–1; H NMR (CDCl3)ꢀδꢀ3.49ꢀ(s,ꢀ6H,ꢀ
2CH3), 4.43 (s, 2H, CH2), 5.18 (s, 2H, CH2), 5.49 (s, 2H, OH), 6.93–7.09
(m, 4H, arom.), 7.14–7.32 (m, 4H, arom.); 13C NMR (CDCl3)ꢀδꢀ51.8,ꢀ55.9,ꢀ
87.9, 113.1, 113.8, 114.2, 115.1, 117.1, 118.2, 139.7, 142.9, 147.0, 167.1,
169.3. ES-MS m/z: 385 (M+H). Anal. calcd for C20H20N2O6: C, 62.49;
H, 5.24; N, 7.29; found: C, 61.99; H, 5.90; N, 7.39%.
Dimethyl 1,3-bis(3-nitrophenyl)-1,2,3,6-tetrahydropyrimidine-4,5-
dicarboxylate (4f): Red-orange solid; yield 93%; (lit.14 251–253 °C);
IRꢀ(νmax): 3011, 2989, 1711, 1702 cm–1; 1H NMR (CDCl3)ꢀδꢀ3.78ꢀ(s,ꢀ6H,ꢀ
2CH3), 4.10 (s, 2H, CH2), 5.54 (s, 2H, CH2), 7.10–7.12 (m, 4H, arom.),
7.45–7.61 (m, 4H, arom.); 13C NMR (CDCl3)ꢀδꢀ52.2,ꢀ54.1,ꢀ86.4,ꢀ104.9,ꢀ
112.1, 114.1, 116.9, 118.8, 120.9, 125.0, 130.0, 132.1, 142.1, 145.5,
148.4, 149.1, 168.2, 169.2. ES-MS m/z: 443 (M+H). Anal. calcd for
JCR1402797_FINAL.indd 609
17/10/2014 14:34:35

610 JOURNAL OF CHEMICAL RESEARCH 2014
C20H18N4O8: C, 54.30; H, 4.10; N, 12.66; found C, 54.33; H, 4.15; N,
12.68%.
355 (M+H). Anal. calcd for C18H18N4O4: C, 61.01; H, 5.132; N, 15.98;
found C, 60.98; H, 5.34; N, 16.01%.
Diethylꢁꢁꢁꢁ1,3-bis(3-nitrophenyl)-1,2,3,6-tetrahydropyrimidine-4,5-
dicarboxylate (4g): Red-orange solid; yield 91%; (lit.14 235–238 °C); IR
Dimethylꢁꢁꢁꢁ1,3-bis(6-methoxybenzo(d)thiazol-2-yl)-1,2,3,6-
tetrahydropyrimidine-4,5-dicarboxylate (4n): Red solid; yield 93%;
1
(νmax): 3022, 2980, 1716, 1703, 1500.9, 1328.1 cm–1; H NMR (CDCl3)
1
(lit.14ꢀ 242–244ꢀ°C);ꢀ IRꢀ (νmax): 3017, 2975, 1713, 1710 cm–1; H NMR
δ1.48ꢀ(t,ꢀ6H,ꢀ2CH3), 4.20 (s, 2H, CH2), 4.70 (q, J=7.1 Hz, 4H, 2CH2),
5.23 (s, 2H, CH2),7.31–7.50 (m, 4H, arom.), 7.81–7.99 (m, 4H, arom.);
13C NMR (CDCl3)ꢀδ19.8,ꢀ54.4,ꢀ64.9,ꢀ83.2,ꢀ108.1,ꢀ112.2,ꢀ114.9,ꢀ115.8,ꢀ
116.9, 120.9, 125.1, 136.9, 146.2 150.0, 164.9, 168.5; ES-MS m/z: 470
(M+H). Anal. calcd for C22H22N4O8: C, 56.17; H, 4.71; N, 11.91; found:
C, 56.40; H, 5.01; N, 12.06%.
(CDCl3)ꢀδꢀ3.65ꢀ(s,ꢀ6H,ꢀ2CH3), 3.85 (s, 6H, 2CH3), 3.98 (s, 2H, CH2),
4.91 (s, 2H, CH2), 6.92–7.07 (m, 4H, arom.), 7.40–7.60 (m, 4H, arom.);
13C NMR (CDCl3)ꢀδꢀ52.9,ꢀ57.5,ꢀ61.2,ꢀ86.1,ꢀ104.9,ꢀ114.9,ꢀ116.9,ꢀ119.1,ꢀ
131.3, 147.4, 151.0, 158.1, 165.1, 164.9, 167.2, 170.4.ES-MS m/z: 527
(M+H). Anal. calcd for C24H22N4O6S2: C, 54.74; H, 4.21; N, 10.64; S,
12.18. Found C, 55.09; H, 4.65; N, 10.32; S, 12.42%.
Diethylꢁꢁꢁꢁ1,3-di-p-tolyl-1,2,3,6-tetrahydropyrimidine-4,5-di-
carboxylate (4h):ꢀCreamyꢀsolid;ꢀyieldꢀ90%;ꢀm.p.ꢀ201–203ꢀ°C.ꢀIRꢀ(νmax):
3038, 2960, 1726, 1692 cm–1; 1H NMR (DMSO-d6)ꢀδꢀ1.23ꢀ(t,ꢀJ=8.0 Hz,
6H, 2CH3), 3.35 (s, 6H, 2CH3), 4.24 (q, J=8.0 Hz,4H, 2CH2) 4.70 (s,
2 H, CH2) 5.73 (s, 2 H, CH2) 6.58–6.81 (m, 4 H, arom.), 7.93–8.04 (m,
4 H, arom.); 13C NMR (DMSO-d6)ꢀδ15.4,ꢀ23.3,ꢀ55.6,ꢀ62.2,ꢀ85.2,ꢀ112.2,ꢀ
117.2, 126.2, 128.5, 129.3, 130.1, 131.2, 142.3, 143.9, 146.2, 162.9,
165.6. Anal. calcd for C24H28N2O4: C, 70.57; H, 6.91; N, 6.86; found: C,
70.60; H, 6.94; N, 6.83%.
Diethylꢁꢁꢁꢁ1,3-di(pyridin-2-yl)-1,2,3,6-tetrahydropyrimidine-4,5-
dicarboxylate (4o): Red-orange solid; yield 90%; (lit.14 255–259 °C);
1
IRꢀ (νmax): 3022, 2981, 1716, 1703 cm–1; H NMR (CDCl3)ꢀ δꢀ 1.60ꢀ (t,
J=7.9 Hz, 6H, 2CH3), 3.89 (s, 2H, CH2), 4.30 (q, J=7.9 Hz, 4H, 2CH2),
4.69 (s, 2H, CH2),7.50–7.72 (m, 4H, arom.), 7.88–8.19 (m, 4H, arom.);
13C NMR (CDCl3)ꢀδꢀ19.9,ꢀ54.0,ꢀ62.5,ꢀ83.0,ꢀ108.2,ꢀ116.8,ꢀ117.96,ꢀ121.9,ꢀ
137.2, 150.7 151.9, 156.9, 166.1, 169.0; ES-MS m/z: 383 (M+H). Anal.
calcd for C20H22N4O4: C, 62.82; H, 5.80; N, 14.65; found: 63.02; H,
5.38; N, 14.97%.
Diethyl 1,3-bis(4-hydroxyphenyl)-1,2,3,6-tetrahydropyrimidine-4,5-
dicarboxylate (4i): Red-orange solid; yield 90%;(lit.14 219–221 °C);
Diethyl 1,3-bis(6-methoxybenzo(d)thiazol-2-yl)-1,2,3,6-tetrahydro-
pyrimidine-4,5-dicarboxylate (4p): Red-orange solid; yield 89%;(lit.14
273–275ꢀ°C);ꢀIRꢀ(νmax): 3021, 2984, 1712, 1710 cm–1; 1H NMR (CDCl3)
δꢀ1.22ꢀ(t, J=7.6 Hz 6H, 2CH3), 3.70 (s, 2H, CH2), 3.93 (s, 6H, 2CH3),
4.42 (s, 2H, CH2), 4.55 (q, J=7.7 Hz, 4H, 2CH2), 7.02–7.11 (m, 2H,
arom.), 7.41–7.56 (m, 4H, arom.); 13C NMR (CDCl3)ꢀδꢀ21.0,ꢀ54.1,ꢀ58.1,ꢀ
64.2, 83.1, 107.1, 116.3, 118.1, 119.9, 134.1, 148.0, 158.4, 165.7, 167.0,
167.9, 169.2; ES-MS m/z: 555 (M+H). Anal. calcd for C26H26N4O6S2:
C, 56.30; H, 4.72; N, 10.10; S, 11.56; found: C, 57.00; H, 4.31; N, 10.12;
S, 12.08%.
1
IRꢀ (νmax): 3010, 2998, 1719, 1706 cm–1; H NMR (CDCl3)ꢀ δꢀ 1.54ꢀ (t,ꢀ
J=7.5 Hz, 6H, 2CH3), 4.20 (s, 2H, CH2), 4.90 (q, J=7.5 Hz, 4H, 2CH2),
5.20 (s, 2H, CH2), 5.56 (s, 2H, CH2), 6.88–7.15 (m, 4H, arom), 7.33–7.65
(m, 4H, arom.); 13C NMR (CDCl3)ꢀδꢀ21.1,ꢀ55.4,ꢀ70.0,ꢀ87.1,ꢀ115.2,ꢀ119.2,ꢀ
122.1, 123.1, 137.1, 140.7, 145.0, 146.0, 149.8, 166.1, 168.9.ES-MS m/z:
413 (M+H). Anal. calcd for C22H24N2O6: C, 64.07; H, 5.87; N, 6.79;
found: C, 65.01; H, 5.57; N, 6.38%.
Diethyl 1,3-diphenyl-1,2,3,6-tetrahydropyrimidine-4,5-dicarboxylate
(4j): Yellow solid; yield 92%; (lit.14ꢀ 84–86ꢀ°C);ꢀ IRꢀ (νmax): 3030,
2980.0, 1716.0, 1700.2 cm–1; 1H NMR (CDCl3)ꢀδꢀ1.02ꢀ(t,ꢀJ=7.4 Hz, 3H,
CH3),1.42 (t, J=7.4 Hz, 3H, CH3), 3.40 (s, 2H, CH2), 4.00 (q, J=7.4 Hz,
2H, CH2) 4.22 (q, J=7.4 Hz, 2H, CH2), 5.36 (s, 2H, CH2), 7.19–7.30 (m,
5H, arom.), 7.51–7.79 (m, 5H, arom.); 13C NMR (CDCl3)ꢀδꢀ21.0,ꢀ59.1,ꢀ
70.2, 75.9, 88.2, 113.2, 119.1, 122.0, 124.9, 128.2, 128.6, 143.1, 150.5,
166.2, 170.1; ES-MS m/z: 381 (M+H). Anal. calcd for C22H24N2O4: C,
69.46; H, 6.36; N, 7.36; found: C, 70.06; H, 6.01; N, 7.01%.
Diethylꢁꢁꢁꢁ1,3-bis(4-nitrophenyl)-1,2,3,6-tetrahydropyrimidine-4,5-
dicarboxylate (4k): Yellow solid; yield 92%; m.p. 189–192 °C; IR
(νmax): 3055, 2965, 1722, 1603, 1366 cm–1; 1H NMR (DMSO-d6)ꢀδꢀ1.29ꢀ
(t, J=8.0 Hz, 6H, 2CH3), 4.14–4.24 (m, 4H, 2CH2), 4.85 (s, 2 H, CH2),
5.34 (s, 2 H, CH2), 6.83–7.28 (m, 8 H, arom.); 13C NMR (DMSO-d6)
δꢀ14.8,ꢀ55.3,ꢀ63.1,ꢀ63.4,ꢀ85.0,ꢀ112.8,ꢀ116.9,ꢀ123.1,ꢀ124.7,ꢀ125.0,ꢀ136.1,ꢀ
137.2, 143.3, 150.5, 156.4, 164.4, 166.4; ES-MS m/z: 471 (M+H). Anal.
calcd for C22H22N4O8: C, 56.17; H, 4.71; N, 11.91; found: C, 56.19; H,
4.74; N, 11.90%.
Received 31 July 2014; accepted 13 September 2014
Paper 1402797 doi: 10.3184/174751914X14115772243815
Published online: 17 October 2014
References
1
2
A. Dömling, W. Wang and K. Wang, Chem. Rev., 2012, 112, 3083.
K.K. Pasunooti, H. Chai, C.N. Jensen, B.K. Gorityala, S. Wang and X.W.
Liu, Tetrahedron Lett., 2011, 52, 80.
3
4
5
6
7
G. Regnier, L. Canevar, R.J. Le, J.C. Douarec, S. Halstop and J. Daussy, J.
Med. Chem., 1972, 15, 295.
Y. Kotaiah, K.N. Hari, K. Naga Raju, C.V. Rao, S.B. Jonnalagadda and M.
Suresh, J. Korean Chem. Soc., 2012, 56, 1.
M.B. Deshmukh, S.M. Salunkhe, D.R. Patil and P.V. Anbhule, Eur. J. Med.
Chem., 2009, 44, 2651.
J. Zhu and H. Bienaymé, Multicomponent reactions, Wiley-VCH:
Weinheim., 2005.
Diethylꢁꢁꢁꢁ1,3-bis(4-chlorophenyl)-1,2,3,6-tetrahydropyrimidine-4,5-
dicarboxylate (4l): Red-orange solid; yield 90%; (lit.14 263–265 °C);
Z.I. Akritopoulou and S.W. Djuric, Synthesis of heterocycles via
multicomponent reactions II, R.V.A. Orru and E. Ruijter, eds.; Springer:
New York, 2010, pp. 231–287.
1
IRꢀ (νmax): 3030, 2994, 1722, 1701 cm–1; H NMR (CDCl3)ꢀ δꢀ 1.40ꢀ (t,
8
9
F.M. Matloubi and H. Saeidian, Mater. Sci. Eng. B, 2007, 139, 265.
Z. Peng Nanofibers – production, properties and functional applications,
T. Lin, ed. 2011; Vol. 1, pp. 135–151.
J=7.8 Hz, 6H, 2CH3), 4.09 (s, 2H, CH2), 4.50 (q, J=7.7 Hz, 4H, 2CH2),
5.60 (s, 2H, CH2), 7.19–7.30 (m, 4H, arom.), 7.68–7.99 (m, 4H, arom.);
13C NMR (CDCl3)ꢀδꢀ21.7,ꢀ56.2,ꢀ69.1,ꢀ86.5,ꢀ113.1,ꢀ120.1,ꢀ123.1,ꢀ125.5,ꢀ
128.1, 129.1, 144.2, 151.9, 166.2, 169.0. ES-MS m/z (%): 450 (M+H).
Anal. calcd for C22H22Cl2N2O4: C, 58.81; H, 4.94; N, 6.23; found: C,
59.01; H, 4.82; N, 6.32%.
Dimethylꢁꢁꢁꢁ1,3-di(pyridin-2-yl)-1,2,3,6-tetrahydropyrimidine-4,5-
dicarboxylate (4m): Red-orange solid; yield 91%; (lit.14 235–237 °C);
IRꢀ(νmax): 3018, 2978, 1715, 1712 cm–1; 1H NMR (CDCl3)ꢀδꢀ3.70ꢀ(s,ꢀ6H,ꢀ
2CH3), 3.98 (s, 2H, CH2), 4.90 (s, 2H, CH2), 6.81–7.15 (m, 4H, arom),
7.56–7.83 (m, 4H, arom); 13C NMR (CDCl3)ꢀδꢀ53.7,ꢀ56.0,ꢀ84.1,ꢀ108.1,ꢀ
117.1, 117.9, 122.0, 137.1, 149.2 151.1, 150.8, 165.2, 167.1; ES-MS m/z:
10 B.M. Reddy and V.R. Reddy. J. Mater. Sci. Lett., 2000, 19, 763.
11 M. Liqiang, H. Bin, C. Wen, Q. Yanyuan, L. Changshi, Y. Rusen, D. Ying
and L.W. Zhong, Adv. Mater., 2007, 19, 3712.
12 Q. Zhu, H. Jiang, J. Li, M. Zhang, X. Wang and C. Qi, Tetrahedron, 2009,
65, 4604.
13 C.W. Sun, T. Fang, J. Wang, Z. Hao and S. Nan J. Agric. Food Chem., 2012,
60, 9553.
14 S.N. Darandale, N.D. Pansare, A.N. Mulla and B.D. Shinde, Bioorg. Med.
Chem, Lett., 2013, 23, 2632.
15 X. Tian, Qin, L.; L. Xiangdong, M. Jian and C. Xueqiang J. Phys. Chem.,
B, 2006, 110, 2006.
JCR1402797_FINAL.indd 610
17/10/2014 14:34:35

Copyright of Journal of Chemical Research is the property of Science Reviews 2000 Ltd. and
its content may not be copied or emailed to multiple sites or posted to a listserv without the
copyright holder's express written permission. However, users may print, download, or email
articles for individual use.