Metal-organic framework Cu3 (BTC)2(H 2O)3 catalyzed Aldol synthesis of pyrimidine-chalcone hybrids

Article abstract of DOI:10.1016/j.catcom.2011.03.040

A typical metal organic framework, [Cu₃ (BTC)₂(H ₂O)₃, BTC = 1,3,5-benzene tricarboxylate] has been used for the synthesis of pyrimidine-chalcones. We have explored a green synthesis of pyrimidine chalcones unde

Full text of DOI:10.1016/j.catcom.2011.03.040

Catalysis Communications 12 (2011) 1170–1176
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Catalysis Communications
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Short Communication
Metal-organic framework Cu3 (BTC)2(H2O)3 catalyzed Aldol synthesis of
pyrimidine-chalcone hybrids
b
Naziyanaz B. Pathan a, Anjali M. Rahatgaonkar a, , Mukund S. Chorghade
⁎
a
Chemistry Department, Institute of Science, Civil Lines, R.T. Road, Nagpur 440001, India
Chorghade Enterprises, 14 Carlson, Circle, Natick, Massachusetts, 01760-4205, USA
b
a r t i c l e i n f o
a b s t r a c t
Article history:
A typical metal organic framework, [Cu3 (BTC)2(H2O)3, BTC=1,3,5-benzene tricarboxylate] has been used for
the synthesis of pyrimidine-chalcones. We have explored a green synthesis of pyrimidine chalcones under Cu3
(BTC)2 catalysis by Aldol condensation. Easy isolation of product, excellent yield, and recyclable catalyst
makes this reaction eco-friendly. The technology was demonstrated to be applicable to the synthesis of a host
of chemical hybrids.
Received 23 February 2011
Received in revised form 23 March 2011
Accepted 25 March 2011
Available online 9 April 2011
© 2011 Elsevier B.V. All rights reserved.
Keywords:
Metal organic framework (MOF)
Aldol condensation
Green synthesis
Cu3 (BTC)2(H2O)3
Pyrimidine chalcones
1. Introduction
antifilarial activity [3]. Our research encompasses the synthesis of
pyrimidine-chalcone hybrids.
Extensive research on diverse biological activities of heterocycles
has confirmed their immense significance in pathophysiology of
diseases. The amalgamation of two pharmacologically important
structural scaffolds leads to a new library of heterocycles, possessing
broad spectrum of activities against numerous pathogenic strains
and also striking activities against cancer. We have developed an
extensive research program on the synthesis and biological evalua-
tions of Chemical Hybrids (as “Molecular Lego Sets”) incorporating
diverse architecture of nuclei within their molecular framework and
to explore synergistic therapeutic relevance as thrombin inhibitors,
prostate specific antigen inhibitors, and anticancer drugs. We have
exemplified synthesis of an array of hybrid molecules: We combined
substituted pyrimidines with isoxazoline residues in hybrid scaffolds
in a single molecular framework to secure enhanced and systemat-
ically attenuated and accentuated biological activity. Synthesis of
hybrid molecules is of interest as a way of synergistically increasing
drug discovery portfolios.
The pioneering papers and reports of the yesteryears that described
base catalyzed synthesis of chalcones by the Claisen Schmidt conden-
sation were fraught with several limitations, such sub-optimal purity
and inefficiency of the methods for purification and evaluation of
synthesized compounds, undesirable side products, long reaction times
and low yields. In the Claisen Schmidt chalcone synthesis, various bases
like NaOH [4,5], KOH [6], solid base KF-Al2O3 under ultrasound irra-
diation [7] have been used. In addition, acid catalyzed reactions involves
the use of AlCl3 [8], BF3 [9] and dry HCl [10], extended reaction times,
difficulty in the catalyst preparation, high temperatures, use of special
apparatus, costly reagents and formation of side products. Development
of catalytic green chemical processes with organometalic complexes is
of growing interest because of the need to obviate use of corrosive and
hazardous liquid acids. Recently, use and utility of a wide range of
catalysts such as acidic alumina [11], acidic clays [12], organometallic
compounds [13], zeolites [14], ionic liquids [15], ion exchange resins
[16] and metal oxides [17] have been reported.
Because of their biological and therapeutic significance, chalcones
have been versatile key precursors of many heterocyclic compounds of
pharmaceutical relevance [1,2]. Pyrimidines, exhibit diverse pharma-
cological properties as effective bactericides, fungicides, viricides, in-
secticides, certain pyrimidine and annulated pyrimidine derivatives
are also known to display anticancer, antimalarial, antileshmaniel and
MOFs are crystalline solids wherein the structure is built by metal
ions or clusters of metal ions held in place by organic di- or multitopical
linkers [18,19]. In MOF, the transition metals have free coordination
positions that are not compromised in the construction of MOFs. These
materials are expected to have similarities with zeolites & related
microporous solids. Cu3(BTC)2(BTC=1,3,5-benzene tricarboxylate),
MOF combined with TEMPO [(2,2,6,6-Tetramethylpiperidin-1-yl)oxyl,
(CH2)3(CMe2)2NO] as cocatalyst has been used as an effective and
reusable heterogeneous catalyst for the aerobic oxidation of benzylic
alcohol [19]. Metal organic framework Fe (BTC) (BTC=1,3,5-benzene
⁎ Corresponding author. Tel.: +91 7122457644.
E-mail address: anjali_rahatgaonkar@yahoo.com (A.M. Rahatgaonkar).
1566-7367/$ – see front matter © 2011 Elsevier B.V. All rights reserved.
doi:10.1016/j.catcom.2011.03.040

N.B. Pathan et al. / Catalysis Communications 12 (2011) 1170–1176
1171
tricarboxylate), heterogeneous catalyst has been used for chalcone
synthesis in high yield and reduced reaction times via Claisen Schmidt
condensation [20].
but less reactive. Enroute to our goals of developing green processes,
we explored a pathway of synthesis of biologically active pyrimidine
chalcone hybrids under catalysis of Cu3(BTC)2(H2O)3 (MOF) in toluene
at 40 °C with constant stirring for 12 h. We optimized the reaction
conditions in order to check the authenticity of the reaction which was
carried out under catalysis of Cu3(BTC)2(H2O)3
TiO2–SO24−[21] was used for the synthesis of chalcones under
microwave irradiation in which sulphate loading by H2SO4 increased
the Lewis acidity of TiO2. Cu3(BTC)2(H2O)3 exhibit hard Lewis acid
character [22,23] and is found to be the first MOF catalyst deployed for the
Friedlander reaction between 2-aminobenzophenones and acetylacetone
under mild reaction conditions, leading to the corresponding quinolines
with excellent yield. Cu3(BTC)2 has attracted lavish attention because of
its interesting structural diversity, geometrical control and flexibility
arising from an axial Cu2+ and 1,3,5-benzene tricarboxylate (H3BTC)
(Crystal structure [24] in Scheme 1). Herein, we report use of a recyclable,
easily separable, eco-friendly and highly effective solid acid catalyst, Cu3
(BTC)2 for the synthesis of pyrimidine chalcones at 40 °C. When
conducted with solid acids this leads to better selectivity, increased
productivity and high yield of pyrimidine-chalcones.
2. Experimental
2.1. Materials and methods
Substituted acetophenone viz., 4-chloro-2-hydroxy acetophenone,
2-hydroxy-4-methyl acetophenone, differently substituted formyl
pyrimidine were made using analytical grade benzaldehyde, chlor-
obenzaldehyde, anisaldehyde, nitrobenzaldehyde (S. D. Fine Chem.
98.0%), urea/thiourea, absolute alcohol (99%), H2SO4 (Fischer 98%),
DMF, POCl3 (Thomas baker, 98%), hydrated form of cupric acetate,
benzene-1,3,5-tricarboxylic acid.
We embarked on the synthesis of pyrimidine chalcones by
conventional and non-conventional methods and synthesized a library
of new pyrimidine chalcones under base and acid catalysis. The Claisen
Schmidt condensation and Aldol condensation were our methods of
choice. The formyl pyrimidine constitutes an electron rich nucleus;
2.2. Apparatus
Thin layer chromatography was performed on silica gel G. Melting
points were determined by open-capillary method. IR spectra were
⁎
with a deactivated N- CHO centre, making the molecule more stable
Scheme 1. Proposed mechanism of Aldol condensation of acetophenone with formylpyrimidine under Cu-BTC catalysis.

1172
N.B. Pathan et al. / Catalysis Communications 12 (2011) 1170–1176
recorded using Shimadzu FT-IR spectrometer using KBr pellets. GC/
MS analysis was carried out using GC model: Shimadzu gas chro-
matograph coupled with QP5050 spectrometer at 1–1.5 ev. Proton
and carbon NMR spectra were recorded on a Brucker AVII FT-NMR
spectrometer operating at 400 MHz for the entire sample.
All synthesized compounds were structurally characterized by FT-
IR, 1HNMR, 13CNMR and GC–MS analyses (Table 3).
2.4.1.1. Ethyl 1,2,3,6-tetrahydro-1-(3-(2-hydroxy-5-methylphenyl)-3-
oxoprop-1-enyl)-4-methyl-2-oxo-6-phenylpyrimidin-5-carboxylate
(2a). Light Yellow crystal mp140 °C [C24H24N2O5],; IR (KBr disc) λ cm−1
3460, 3190, 1720, 1695, 1450; 1HNMR (CDCl3+CCl4, 400 MHz) δ 1.14
(t, 3 H, J=8.4), 1.6 (s, 3 H), 2.35 (s, 3 H), 4.0 (q, 2 H,J=4.6), 5.4 (d, 1 H,
J=4.1), 5.5 (s, 1 H), 7.3–7.5 (m, 8 H), 8.2 (d, 1 H, J=4.2); DI-MS: m/z
2.3. Claisen–Schmidt condensation: base catalyzed synthesis of substituted
ethyl 1,2,3,6-tetrahydro-1-(3-(2-hydroxyphenyl)-3-oxoprop-1-enyl)-4-
methyl-2-oxo/thioxo-6-phenyl pyrimidin-5-carboxylates
420 [M+H] +
.
Substituted 2′-hydroxy acetophenone (0.11 mmol) and ethyl 1-
formyl-1, 2, 3, 6-tetrahydro-4-methyl-2-oxo/thioxo-6-phenylpyrimi-
dine-5-carboxylate (1a–g) (0.1 mmol) were dissolved in ethanol
20 mL and the mixture was heated up to 60 °C. Then a solution of
0.3 mmol of NaOH (40%) was added till a red mass obtained and the
reaction mixture was kept for 24 h. It was subsequently decomposed
by ice cold 1:1 HCl till the reaction mixture became acidic. It was
further filtered, washed with dil. NaHCO3. The product was recrys-
tallized from ethanol: acetic acid (8:2) (2a–k). The purity of the
synthesized compounds was evaluated by using hexane: ethyl acetate
(7:3) as eluent.
2.4.1.2. Ethyl 6-(4-chlorophenyl)-1,2,3,6-tetrahydro-1-(3-(2-hydroxy-
5-methyl phenyl)-3-oxoprop-1-enyl)-4-methyl-2-oxopyrimidin-5-
carboxylate (2b). Yellow crystal mp125 °C [C24H23N2O5Cl]; IR (KBr
disc) λ cm−1 3465, 3185, 1715, 1690, 1455, 800; 1HNMR (CDCl3+CCl4,
400 MHz) δ 1.12 (t, 3 H, J=8.6), 1.7 (s, 3 H), 2.32 (s, 3 H), 4.1 (q, 2 H, J=
4.6), 5.2 (d, 1 H, J=4.1), 5.3 (s, 1 H), 7.2–7.5 (m, 8 H), 8.2 (d, 1 H, J=
4.2), 8.4 (s, 1 H); DI-MS: m/z 454 [M+H] +
.
2.4.1.3. Ethyl 1,2,3,6-tetrahydro-1-(3-(2-hydroxy-5-methylphenyl)-3-
oxoprop-1-enyl)-6-(4-methoxyphenyl)-4-methyl-2-oxopyrimidin-5-
carboxylate (2c). Brown crystal mp145 °C [C25H26N2O6]; IR (KBr disc)
λ cm−1 3416, 3155, 1715, 1670, 1455; 1HNMR (CDCl3+CCl4, 400 MHz)
δ 1.14 (t, 3 H, J=8.3), 2.3 (s, 3 H), 3.73 (s, 3 H), 3.8 (s, 3 H), 4.0 (q, 2 H,
J=4.4), 5.2 (s, 1 H), 6.5 (m, 8 H), 6.8 (d, 1 H, J=4.1), 7.8 (d, 1 H, J=4.2),
2.4. Aldol condensation: Cu3(BTC)2 catalyzed synthesis of substituted
ethyl 1,2,3,6-tetrahydro-1-(3-(2-hydroxyphenyl)-3-oxoprop-1-enyl)-4-
methyl-2-oxo/thioxo-6-phenylpyrimidin-5-carboxylates
8.9 (s, 1 H), 10.8 (s, 1 H); DI-MS: m/z 450 [M+H] +
.
Cu3(BTC)2 was prepared by known method [22] and was ground by
mortar & pestle. To a mixture of substituted acetophenone (1 mmol)
and substituted ethyl 1-formyl-1,2,3,6-tetrahydro-4-methyl-2-oxo/
thioxo-6-phenyl pyrimidin-5-carboxylate (1a–g) (1.1 mmol) in tolu-
ene, 0.075 g of Cu3(BTC)2 was added with one-two drops of conc. H2SO4
in order to accelerate the reaction in a forward direction. The mixture
was stirred at 40 °C for 10–12 h (Scheme 1). Completion of the reaction
was monitored by TLC. Ethyl acetate was added to the solid mass and
the insoluble catalyst was separated by filtration. The filtrate was dried
over anhydrous Na2SO4. The solvent was evaporated and the product
was obtained. The crude product was purified by column chromatog-
raphy using hexane: ethyl acetate (7:3) as mobile phase. The catalyst
recovered from the reaction mixture was reused for the 2nd cycle of
Aldol condensation. All compounds (2a–k) were synthesized by using
Cu3(BTC)2 up to 11th cycle.
2.4.1.4. Ethyl 1,2,3,6-tetrahydro-1-(3-(2-hydroxy-5-methylphenyl)-3-
oxoprop-1-enyl)-4-methyl-6-phenyl-2-thioxopyrimidin-5-carboxylate
(2 d). Yellow crystal mp135 °C[C24H24N2O4S]; IR (KBr disc) λ cm−1
3450, 3155, 1710, 1695, 1450; 1HNMR (CDCl3 +CCl4, 400 MHz) δ 1.12
(t, 3 H, J=8.3), 1.5 (s, 3 H), 2.2 (s, 3 H), 4.1(q, 2 H, J=4.6), 5.2 (d, 1 H,
J=4.0), 5.4 (s, 1 H), 7.2–7.6 (m, 8 H), 8.6 (d, 1 H, J=4.2), 8.9 (s, 1 H);
+
DI-MS: m/z 436 [M+H]
.
2.4.1.5. Ethyl 6-(4-chlorophenyl)-1,2,3,6-tetrahydro-1-(3-(2-hydroxy-
5-methyl phenyl)-3-oxoprop-1-enyl)-4-methyl-2-thioxopyrimidin-5-
carboxylate (2e). Yellow crystal mp115 °C [C24H23N2O4SCl]; IR (KBr
disc) λ cm−1 3315, 3145, 1715, 1695, 1455; 1HNMR (CDCl3+CCl4,
400 MHz) δ 1.1 (t, 3 H, J=8.4), 1.6 (s, 3 H), 2.1 (s, 3 H), 4.1(q, 2 H, J=
4.6), 5.1(d, 1 H, J=4.1), 5.4 (s, 1 H), 7.2–7.5(m, 8 H), 8.3 (d, 1 H, J=4.2),
The impact of variation of the quantity of Cu3(BTC)2 on Aldol syn-
thesis was investigated. The experiments were repeated by varying
the quantities of the catalyst for optimization of reaction conditions.
The results are depicted in Table 1.
8.4 (s, 1 H); DI-MS: m/z 470 [M+H] +
.
2.4.1.6. Ethyl 1-(3-(5-chloro-2-hydroxyphenyl)-3-oxoprop-1-enyl)-
1,2,3,6-tetrahydro-4-methyl-2-oxo-6-phenylpyrimidin-5-carboxylate
(2f). Yellow crystal mp180 °C [C23H21N2O5Cl]; IR (KBr disc) λ cm−1
3420, 3130, 1720, 1650, 1435; 1HNMR (CDCl3+CCl4, 400 MHz) δ 1.1
(t, 3 H, J=8.4), 1.63 (s, 3 H), 4.0 (q, 2 H, J=4.5),5.2 (d, 1 H, J=4.0), 5.5
2.4.1. Reusability of Cu3(BTC)2
The reusability of Cu3(BTC)2 was tested by recovering the catalyst
from every cycle. The insoluble catalyst was filtered out, dried and
reused with two drops of conc. H2SO4 without further purification for
second run. The procedure was repeated and the efficiency of the
catalyst was checked up to the 11th cycle. The results are depicted in
Table 2.
Table 2
Recycling of Cu3(BTC)2 in Aldol Synthesis of Ethyl 1,2,3,6-tetrahydro-1-(3-(2-hydroxy-
5-methylphenyl)-3-oxoprop-1-enyl)-4-methyl-2-oxo-6-phenylpyrimidin-5-carboxylate
(2a).
Entry
No. of cycles
Isolated yield (%)
Table 1
Variation of quantities of Cu3(BTC)2 on Aldol Synthesis of Ethyl 1,2,3,6-tetrahydro-1-(3-
(2-hydroxy-5-methylphenyl)-3-oxoprop-1-enyl)-4-methyl-2-oxo-6-phenylpyrimidin-
5-carboxylate (2a).
1
2
3
4
5
6
7
8
1st
87
87
85
85
85
83
83
80
80
78
78
64
2nd
3 rd
4th
5th
6th
7th
8th
9th
Entry
Cu3(BTC)2 in mg
Cu3(BTC)2 in mmol
Isolated yield (%)
1
2
3
4
5
6
7
20
40
50
60
75
0.0976
0.1952
0.244
0.292
0.366
0.488
0.732
No reaction
No reaction
30
60
87
87
87
7
10
11
12
10th
11th
12th
100
150

N.B. Pathan et al. / Catalysis Communications 12 (2011) 1170–1176
1173
Table 3
Physical Characteristic data of the Substituted ethyl 1,2,3,6-tetrahydro-1-(3-(2-hydroxyphenyl)-3-oxoprop-1-enyl)-4-methyl-2-oxo/thioxo-6-phenylpyrimidin-5-carboxylates
(2a-k).
°
Entry
2a
Ketone
Formylpyrimidine
Pyrimidine chalcone
Mp. ( C)
Isolated yield (%) a/b
87/76
140
2b
80/72
125
2c
145
72/69
135
82/74
2d
115
76/69
2e
180
84/68
2f
(continued on next page)

1174
N.B. Pathan et al. / Catalysis Communications 12 (2011) 1170–1176
Table 3 (continued)
°
Entry
2g
Ketone
Formylpyrimidine
Pyrimidine chalcone
Mp. ( C)
Isolated yield (%) a/b
85/68
120
2h
120
80/70
2i
155
115
105
70/62
84/71
71/66
2j
2k
a=Cu-BTC catalyzed Aldol condensation.
b=Base catalyzed Claisen Schmidt condensation.
(s, 1 H), 7.37.5 (m, 8 H), 8.4 (d, 1 H, J=4.2), 8.6 (s, 1 H); DI-MS: m/z 440
1 H, J=4.1), 5.3 (s, 1 H), 7.2–7.4 (m, 8 H), 8.2 (d, 1 H, J=4.2), 8.4 (s,
1 H); DI-MS: m/z 475 [M+H] +
[M+H] +
.
.
2.4.1.7. Ethyl 1-((E)-3-(5-chloro-2-hydroxyphenyl)-3-oxoprop-1-enyl)-
6-(4-chloro-phenyl)-1,2,3,6-tetrahydro-4-methyl-2-oxopyrimidin-5-
carboxylate (2 g). Yellow crystal mp120 °C [C23H20N2O5Cl2] ; IR (KBr
disc) λ cm−1 3416, 3135, 1720, 1665, 1445; 1HNMR (CDCl3+CCl4,
400 MHz) δ 1.13 (t, 3 H, J=8.4), 1.45 (s, 3 H), 4.1 (q, 2 H, J=4.6), 5.1 (d,
2.4.1.8. Ethyl 1-(3-(5-chloro-2-hydroxyphenyl)-3-oxoprop-1-enyl)-
1,2,3,6-tetrahydro-6-(4-methoxyphenyl)-4-methyl-2-oxopyrimidin-5-
carboxylate (2 h). Dark yellow crystal mp120 °C[C24H23N2O6Cl]; IR (KBr
disc) λ cm−1 3415, 3145, 1720, 1665, 1440; 1HNMR (CDCl3+CCl4,
400 MHz) δ 1.1 (t, 3 H, J=8.4), 2.3 (s, 3 H), 3.7 (s, 3 H), 4.0 (q, 2 H,

N.B. Pathan et al. / Catalysis Communications 12 (2011) 1170–1176
1175
J=4.6), 5.5 (s, 1 H), 7.3–7.5 (m, 8 H), 6.8 (d, 1 H, J=4.1), 7.8 (d, 1 H, J=
4.2), 8.8 (s, 1 H), 11.8 (s, 1 H); DI-MS: m/z 470 [M+H] +
The reusability of Cu3(BTC)2 was investigated for Aldol conden-
sation. The XRD pattern of used Cu3(BTC)2 when compared with fresh
Cu3(BTC)2 displayed no structural variations. In the second cycle,
the Cu3(BTC)2 showed deactivation in the absence of added H2SO4.
After addition of conc. H2SO4, there was considerable enhancement
in the efficiency of the reaction. These observations suggested that the
activity of Lewis acidity center in Cu3(BTC)2 diminished after every
use but that its activity could be modulated and regenerated by add-
ing conc. H2SO4.
In Cu3(BTC)2 catalyzed Aldol condensation, the reaction was
terminated by the removal of water molecule and desired α, β unsat-
urated product was achieved. No side reactions were observed, al-
though the yield was highly dependent on the substituents. Fig. 1
shows the time conversion plot for formyl pyrimidine 1 to pyrimidine
chalcone 2 under catalysis of Cu3(BTC)2 for Aldol condensation.
Therefore, Cu3(BTC)2 is the MOF showing best catalytic activity
for Aldol condensation in the presence of conc. H2SO4. Electron with-
drawing substituents like –Cl formyl pyrimidines, o-nitro formyl
pyrimidines gave much better yields than p-nitro formyl pyrimidine
under identical conditions: the reaction for the p-nitro substituent
proceeded in negligible yield. Aldol condensation of chloro substitut-
ed substrates resulted in excellent product formation in high yields.
Electron withdrawing groups at the phenyl ring of substituted formyl
pyrimidines favored formation of product whereas electron donating
groups lowered the yields.
.
2.4.1.9. Ethyl1-((E)-3-(5-chloro-2-hydroxyphenyl)-3-oxoprop-1-enyl)-
1,2,3,6-tetrahydro-4-methyl-6-(2-nitrophenyl)-2-oxopyrimidin-5-
carboxylate (2i). Yellow crystal mp155 °C [C23H20N3O7Cl]; IR (KBr disc)
λ cm−1 3450, 3155, 1715, 1695, 1465; 1HNMR (CDCl3+CCl4, 400 MHz)
δ 1.1 (t, 3 H, J=8.4), 1.5 (s, 3 H), 4.1 (q, 2 H, J =4.7), 5.2 (d, 1 H, J=4.3),
5.4 (s, 1 H), 7.3–7.8 (m, 8 H), 8.2 (d, 1 H, J=4.2), 8.8 (s, 1 H), 10.8
(s, 1 H); DI-MS: m/z 485 [M+H] +
.
2.4.1.10. Ethyl1-(3-(5-chloro-2-hydroxyphenyl)-3-oxoprop-1-enyl)-
1,2,3,6-tetrahydro-4-methyl-6-phenyl-2-thioxopyrimidin-5-carboxylate
(2j). Yellow crystal mp115 °C [C23H21N2O4SCl]; IR (KBr disc) λ cm−1
3460, 3190, 1720, 1695, 1450; 1HNMR (CDCl3+CCl4, 400 MHz) δ 1.14
(t, 3 H, J=8.4), 1.6 (s, 3 H), 4.0 (q, 2 H, J =4.6), 5.4 (d, 1 H, J=4.1), 5.5
(s, 1 H), 7.3–7.5 (m, 8 H), 8.2 (d, 1 H, J=4.2); DI-MS: m/z 456 [M+H] +
.
2.4.1.11. Ethyl 1-((E)-3-(5-chloro-2-hydroxyphenyl)-3-oxoprop-1-
enyl)-6-(4-chloro-phenyl)-1,2,3,6-tetrahydro-4-methyl-2-thioxopyrimidin-
5-carboxylate (2 k). Yellow crystal mp105 °C [C23H20N2O4SCl2]; IR (KBr
disc) λ cm−1 3465, 3185, 1720, 1690, 1455; 1HNMR (CDCl3+CCl4,
400 MHz) δ 1.1 (t, 3 H, J=8.4), 1.5 (s, 3 H), 4.1 (q, 2 H, J=4.6), 5.2 (d, 1 H,
J=4.1), 5.4 (s, 1 H), 7.2–7.6 (m, 8 H), 8.6 (d, 1 H, J=4.2), 8.9 (s, 1 H);
DI-MS: m/z 491 [M+H] +
.
3. Result and discussion
A novel, efficient methodology of synthesis of pyrimidine chalcone
has been developed by using acetophenone and substituted ethyl
1-formyl-1,2,3,6-tetrahydro-4-methyl-2-oxo/thioxo-6-phenyl
pyrimidin-5-carboxylate (1a–g) in Aldol condensation under catalysis
of Cu3(BTC)2(H2O)3 .The results are presented in Table 3. Initially no
reaction was observed when a base catalyzed reaction was carried out
at ambient temperature. Generally Claisen Schmidt condensation is
initiated via nucleophilic addition reaction. We observed that formyl
pyrimidines did not undergo nucleophilic addition reaction very
easily. To progress the reaction in forward direction, we increased the
reaction time and temperature. The desired products were obtained by
the conventional method with poor to moderate yield. This observa-
tion prompted us to explore new, efficient method of the synthesis of
chalcones. Surprisingly, addition of a catalytic amount of Cu3(BTC)2 to
the mixture of acetophenone & formylpyrimidine in toluene at 40 °C
with constant stirring for 12 h produced corresponding pyrimidine-
chalcones. Condensation was initiated with the formation of an
enolate ion. The mechanistic pathway appears to involve acidic
media which activates the carbonyl function, thereby making the
carbonyl group of formyl pyrimidine readily enolisable in the presence
of Cu3(BTC)2. Cu3(BTC)2 is a strong Lewis acid & functions as a
heterogeneous catalyst; we however observed negligible conversion
of 2 in absence of conc. H2SO4. The Lewis acidity of Cu3(BTC)2 was
modulated by adding 2 drops of conc. H2SO4 in order to accelerate the
reaction. Presumably the Lewis acid sites within the micropores of Cu3
(BTC)2 were activated. This addition facilitated protonation leading to
formation of enolates: the enolic form of acetophenone easily
approached the carbocation of the enolate of formyl pyrimidine and
attached itself to the centre (Scheme 1).
The desired structure of synthesized ethyl 1,2,3,6-tetrahydro-1-(3-
(2-hydroxy-5-methyl phenyl)-3-oxoprop-1-enyl)-4-methyl-2-oxo-6-
phenylpyrimidin-5-carboxylate 2a has been elucidated by the IR
spectrum showing the presence of O–H stretching and N–H absorp-
tion band at 3320 cm−1 and 3190 cm−1 respectively. A strong band at
1670 cm−1 showed the presence of conjugated carbonyl group
(NC=O). In 1HNMR spectrum of 2a the two different signals appeared
at δ 1.1 & triplet at δ 2.1 confirming the presence of two methyl groups A
singlet at δ 2.31 indicated the presence of –CH3 that derived from ring B.
Disappearance of a singlet of –CHO at δ 9.9 and appearance of two new
doublets at δ 6.8 (J=4.1 Hz) and δ 8.2 (J=4.2 Hz) integrating C2′–Hα
and C1′–Hβ protons from olefinic region. A characteristic singlet at δ 11.8
indicated the presence of Ar–OH. 13CNMR spectrum displayed two
different peaks for carbon carbon double bond [C2′–Hα and C1′–Hβ] at δ
109.6 and δ 144.4 also the presence of two signals at δ 189.6 for C3′=O
and at δ 145.6 for carbonyl group of pyrimidine that confirmed the
The heterogeneous catalytic activity of Cu3(BTC)2 was investigated
for the Aldol condensation. The reaction was carried out under opti-
mized conditions described in Table 1; the reaction mixture was filtered
after 2 h to remove Cu3(BTC)2. The acidic filtrate was kept for 24 h
without catalyst, complete recovery of initial substrate 1 with no con-
version of 2 confirmed that conc. H2SO4 only enhanced the performance
of Cu3(BTC)2 and did not catalyze the reaction in the absence of Cu3
(BTC)2.
Fig. 1. Time conversion plot for the Aldol Condensation of formyl pyrimidine 1a to
pyrimidine chalcone 2a under catalysis of Cu3(BTC)2 (reaction condition: substituted
formyl pyrimidine (0.1 mmol), substituted hydroxyphenone (0.11 mmol), catalyst
(0.075 g), toluene, 12 h, 40 °C).

1176
N.B. Pathan et al. / Catalysis Communications 12 (2011) 1170–1176
assigned structure. The product 2a was analyzed for C24H24N2O5 which
exhibited molecular ion at m/e 420 [M+1].
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Supplementary data to this article can be found online at
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