Nicotinic acid functionalized organomodified silica as an efficient heterogeneous catalyst for the synthesis of benzoyl fumarate

Article abstract of DOI:10.1016/j.tetlet.2013.09.057

A new hybrid catalyst has been developed by incorporating nicotinic acid onto an organomodified silica. The catalyst was applied as a heterogeneous catalyst for the synthesis of benzoyl fumarate. The reactions work well in the presence of 20 wt % of the catalyst at room temperature to produce the desired products in high yield. The catalyst could be recovered and reused without appreciable change in activity.

Full text of DOI:10.1016/j.tetlet.2013.09.057

Accepted Manuscript
Nicotinic acid functionalized organomodified silica as an efficient heterogene‐
ous catalyst for the synthesis of benzoyl fumarate
Rana Sanjay Kumar Singh, Bishwapran Kashyap, Prodeep Phukan
PII:
S0040-4039(13)01611-0
DOI:
http://dx.doi.org/10.1016/j.tetlet.2013.09.057
TETL 43557
Reference:
To appear in:
Tetrahedron Letters
Received Date:
Revised Date:
Accepted Date:
8 August 2013
10 September 2013
13 September 2013
Please cite this article as: Singh, R.S.K., Kashyap, B., Phukan, P., Nicotinic acid functionalized organomodified
silica as an efficient heterogeneous catalyst for the synthesis of benzoyl fumarate, Tetrahedron Letters (2013), doi:
http://dx.doi.org/10.1016/j.tetlet.2013.09.057
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Nicotinic acid functionalized organomodified silica as
an efficient heterogeneous catalyst for the synthesis
of benzoyl fumarate
Rana Sanjay Kumar Singh, Bishwapran Kashyap and Prodeep Phukan
O
O
COOMe
H
O
COOMe
S
H
N
+
DME, 0 oC - rt
COOMe
R
R
COOMe

1
Tetrahedron Letters
journal hom epage: www.elsevier.com
Nicotinic acid functionalized organomodified silica as an efficient heterogeneous catalyst
for the synthesis of benzoyl fumarate
Rana Sanjay Kumar Singh, Bishwapran Kashyapa, Prodeep Phukan a*
a Department of Chemistry, Gauhati University, Guwahati -781014, Assam, India; E-mail: pphukan@yahoo.com
ARTICLE INFO
ABSTRACT
Article history:
Received
Received in revised form
Accepted
A new hybrid catalyst has been developed by incorporating nicotinic acid onto an
organomodified silica. The catalyst was applied as a heterogeneous catalyst for the synthesis of
benzoylfumarate. The reactions work well in presence of 20 wt% of the catalyst at room
temperature to produce the desired products in high yield. The catalyst could be recovered and
reused without appreciable change in activity.
Available online
2009 Elsevier Ltd. All rights reserved.
Keywords:
Organomodified silica,
Heterogeneous catalyst,
Benzoylfumarate,
DMAD,
Aldehydes
The modification of silica and related materials by attachment
of organic functionalities onto their surfaces is an important area
of research in heterogeneous catalysis directed toward achieving
green chemistry goals.1 Surface functionalization of mesoporous
silica has been widely practiced in recent years for generating
active sites necessary for heterogeneous catalytic activity.
Numerous strategies have been described for immobilizing
inorganic and/or organic active species on or within the silica
matrices.1a Functionalization of mesoporous silica surface via
tethering of an active group generally can be done in two
different ways: through the so-called “post-synthesis” method,2
which involves grafting an organotrialkoxysilane onto the pore
surfaces after mesoporous material synthesis, and through the
“direct synthesis” method,3 in which the functional groups are
introduced during the synthesis of the mesoporous material. The
pore functionalization is achieved through the co-condensation
reaction occurring between the organotrialkoxysilane and the
silica source in the presence of a structure-directing agent. The
direct synthesis method is considered more predictable and hence
valuable, because it can avoid several shortcomings of the post-
grafting method, such as reduction in pore size, pore blocking at
the aperture and difficulties in controlling the loadings as well as
the distribution of active sites.4
homogeneous condition.10 In addition, there are a few more
examples for the synthesis of benzoyl fumarates from aldehyde
and DMAD.11 However, till date, heterogeneous approach has
not been applied for this transformation. We have developed a
new nicotinic acid functionalized organomodified mesoporous
silica catalyst, for the first time, which acts as heterogeneous
catalyst for the synthesis of benzoyl fumarates (Scheme 1). It has
been observed that the organomodified silica, which has been
characterized by various methods including spectroscopy and
electron microscopy, is suitable as heterogeneous catalysts for the
preparation of benzoyl fumarates from aldehydes and DMAD.
O
O
COOMe
H
O
COOMe
S
H
N
+
DME, 0 oC - rt
COOMe
R
R
COOMe
Scheme 1: Synthesis of benzoyl fumarates
To realize our goal, we have developed
a
new
organomodified mesoporous silica by incorporating nicotinic
acid to the thiol group of mercaptopropyl silica (MPMS).
Initially, MPMS was prepared by mixing tetraethylorthosilicate
and mercaptopropyl (triethoxy) silane with a solution of n-
dodecylamine in aqueous ethanol.3a,b The MPMS was
characterized by powder X ray diffraction, IR spectra, TGA,
SEM and EDX. The appearance of low-angle broad XRD peaks
at 2Ө = 0.5- 2 degree is the characteristic of mesoporous nature
of MPMS (Figure 1). The observed pattern does not show well
resolved diffraction peaks. The broad peaks seen for this material
suggest the lack of long-range order in the structure. In the IR
Benzoyl fumarates and its corresponding acids are known to
be important precursor for the synthesis of many agrochemicals,5
drugs6 and organic transformations.7 Nair et al. and latter Shi et
al. have prepared benzoyl fumarates by one pot reaction between
dimethylacetylenediacetate (DMAD) and aldehyde in presence of
Lewis base as homogeneous catalyst.8 Bayat et al. have prepared
this benzoyl fumarate by multicomponent reaction between
DMAD, aldehyde and PPh3.9 We have also developed a ferrocene
based pyridine catalyst for benzoyl furmarate synthesis under

2
Tetrahedron
spectrum (Figure S1 of SI), the presence of bands at 2950, 2560
with the MCM-41 class of silicates. Unlike MPMS, it shows a
sharp peak at around 2Ө = 7°. The IR spectra of nicotinic acid
functionalized MPMS shows bands at around 1360-1310 cm-1
and 1725-1700 cm-1 which indicates the presence of aromatic C-
N vibration of pyridine ring and carbonyl group respectively. The
SEM picture (Figure 4) indicates no significant change in
morphology after functionalization of MPMS with nicotinic acid.
cm-1 and a broad peak at around 3300-3400 cm-1 confirms the
presence of propyl, thiol(-S-H stretching) and Si-OH groups in
the MPMS. The TGA (Figure S3 of SI) study indicates that loss
in weight up to 100 °C is due to loss of water molecule from the
surface and one main weight loss in the range 340-680 °C is due
to loss of organic group from the surface. Morphology of MPMS
was also analyzed by using SEM (Figure 2) and it is obvious
from the picture that the major portion of the material is made up
of aggregates of smaller roughly spherical particles. A second
type of structure consists of single particles, again roughly
spherical, but of much larger size. Some of these are aggregated
into groups of two or three, but not into larger aggregates. The
spherical structures present are often seen in a range of
mesostructured materials. EDX data (Figure S2 of SI) confirms
the presence of thiol moiety in the MPMS.
Figure 3. XRD pattern of nicotinic acid functionalized MPMS
Figure 1: XRD pattern of MPMS
Figure 4: SEM image of nicotinic acid functionalized MPMS
Pore size distributions and surface areas were measured by N2
adsorption studies for both the MPMS and nicotinic acid
functionalized MPMS (Figure S7-S10, SI). In both cases the
materials displayed isotherms characteristic hysteresis loop of
type IV (according to the scheme of classification recommended
by IUPAC) of HMS materials with small pores and high surface
areas. The isotherms of MPMS and nicotinic acid functionalized
MPMS are of similar shape indicating that porous structure has
been retained after functionalization. Pore size distribution is
quite narrow with BJH adsorption pore average diameter between
Figure 2: SEM image of MPMS
Nicotinic acid functionalized MPMS was prepared by simple
esterification between MPMS and nicotinic acid in DCM
(Scheme 2). Functionalization was carried out by stirring a
mixture of MPMS, nicotinic acid, dicyclohexylcarbodiamide and
DMAP in dry DCM under N2 atmosphere at room temperature
for 48 h. The resulting white solid was separated by filtration,
washed several times with DCM and dried in vacuum.
2.17487
- 4.1727 nm. It has been observed that on
functionalization of thiol group with nicotinic acid, there is a
drop in surface area as well as in average pore size.
After the confirmation of the structure and morphology of the
prepared nicotinic acid functionalized MPMS we intend to test its
efficiency as heterogeneous catalysts for the preparation of
benzoyl fumarates from aldehydes and dimethylacetylene-
diacetate (DMAD). Initially, the reaction between 4-
nitrobenzaldehyde and DMAD was selected as a model reaction
to investigate the best reaction condition (Table 1). In a typical
reaction, 10 wt% of the catalyst was added to a mixture of 4-
nitrobenzaldehyde (1 mmol) and DMAD (1 mmol) in DME (5
O
COOH
DCC, DMAP
SH
S
+
CH2Cl2
N
N
Scheme 2: Synthesis of Nicotinic acid functionalized MPMS
The X-Ray diffraction patterns (Figure 3) were also measured
for nicotinic acid functionalized MPMS and as expected, these
materials do not display the degree of long range order associated

3
4a
5a
4b
ml) at 0 °C under N2 atmosphere. The reaction was continued at
room temperature for appropriate time and it was found that 12 h
of stirring gives the maximum yield. After usual work-up, the
crude product was purified using column chromatography to get
the pure product. It was observed that 20 wt% of the catalyst and
12 h of reaction time give the best result. Further reaction using
25 wt% of catalyst did not improve the reaction yield. The
reaction in other solvents such as THF and acetonitrile produced
lower yield. The reaction in DCM did not proceed at all. Finally,
20 wt% of catalyst was found to be the optimum amount for the
best yield.
O
COOMe
H
O
H
5
73
COOMe
F
F
5b
O
O
COOMe
H
H
6
7
66
69
70
64
60
COOMe
MeO
Cl
MeO
Cl
6b
O
6a
7a
O
COOMe
H
H
COOMe
Table 1 Reaction of p-nitrobenzaldehyde with DMAD catalyzed by
7b
O
nicotinic acid functionalized MPMS catalyst in different solvent.a
O
COOMe
H
O
COOMe
O
COOMe
Br
Br
H
H
Catalyst
8
H
DME, 00C-RT
COOMe
O2N
COOMe
O2N
COOMe
8b
O
8a
Entr
y
1
2
3
4
5
6
7
Catalyst
(wt%)
10
10
15
15
15
15
20
Solvent
Time (h)
Yield (%)b
O
COOMe
H
H
DME
DME
DME
THF
MeCN
DCM
DME
DME
DME
7
60
67
72
65
30
trace
78
79
0
9
COOMe
12
12
12
24
24
12
12
24
9b
O
9a
O
COOMe
H
H
10
COOMe
8
9
25
0
10b
O
10a
O
O
O
COOMe
aReaction condition: 4-nitrobenzaldehyde (1 mmol), DMAD (1 mmol),
solvent (4 mL), 0 °C-rt; bisolated yield
11
12
13
77c
76d
76e
H
H
H
H
COOMe
O2N
O2N
O2N
O2N
O2N
O2N
After establishing the optimum reaction condition, the scope
of the reaction was examined with various aldehydes under the
same reaction condition (Table 2).12 It has been observed that
various aldehydes undergo this reaction with good efficiency
under the reaction condition. It was observed that, presence of
electron withdrawing group in the benzene ring gives better yield
(Table 2, Entry 2-8) than electron donating groups (Table 2 Entry
10).
O
O
COOMe
H
COOMe
COOMe
H
COOMe
aReaction condition: aldehyde (1 mmol), DMAD (1 mmol), catalyst (20
wt%), DME (4 mL), 0 °C-rt. 12h; b. isolated yield; c. catalyst reused: 1st
run; d. catalyst reused: 2nd run; e. catalyst reused: 3rd run.
Table 2: Synthesis of benzoyl fumarates catalyzed by nicotinic acid
functionalized MPMS.a
Reusability of the catalyst was tested with 4-
nitrobenzaldehyde. To reuse, the catalyst was filtered after
completion of the reaction, washed with petroleum ether, dried
under vacuum and then kept in a desiccator overnight before
reuse. It was observed that the catalyst could be reused for three
times without appreciable loss in activity (Table 2, Entry 11-13).
Sl
No
Yield
(%)b
Reactant
Product
O
O
COOMe
H
H
1
2
72
COOMe
1b
O
1a
COOMe
H
O
The mechanism of the reaction has already been discussed in
detail by Shi.8b Accordingly, the pyridine moiety attached to the
MPMS core acts as a nucleophilic promoter to form a zwitter
ionic intermediate at the initial stage of the reaction.8b Subsequent
reaction with aldehyde followed by an intramolecular proton
transfer process leads to formation of the product.
H
75
COOMe
Cl
Cl
2a
3a
2b
O
O
COOMe
H
H
H
3
4
81
78
In conclusion, we have effectively prepared a nicotinic acid
functionalized organomodified silica catalyst from MPMS. The
catalyst was characterized using XRD, SEM, IR, TGA and EDX.
It was further demonstrated that the prepared functionalized silica
COOMe
Br
Br
3b
O
O
COOMe
H
acts as
a heterogeneous catalyst for the synthesis of
COOMe
O2N
O2N

4
Tetrahedron
temperature). After completion of the reaction (TLC),
the reaction mixture was filtered and the solvent from
the filtrate was removed and the residue was purified
with column chromatography using 20% ethyl
acetate/petroleum ether as eluent to get the product. The
recovered catalyst was washed with petroleum ether,
dried under vacuum and then kept in a desiccator
overnight before reuse.
benzoylfumarates from aldehydes and DMAD. The catalyst is
reusable with good yield
Acknowledgement: Financial support from UGC (grant No.
41-206/2012/SR) is gratefully acknowledged. RSKS thanks UGC
(NERO) and BK thanks CSIR for research fellowship.
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12. Typical procedure: The catalyst (20 wt % based on
aldehyde) was added to a mixture of aldehyde (1 mmol)
and DMAD (1 mmol) in DME (4 ml) at 0 °C under N2
atmosphere and the reaction mixture was stirred for
12h, (first two hours at 0 °C and then at room