Chloromethylated polystyrene immobilized ruthenium complex of 2-(2-pyridyl)benzimidazole catalyst for the synthesis of bioactive disubstituted ureas by carbonylation reaction

Article abstract of DOI:10.1039/c8nj00475g

Polymer supported transition metal complex catalysts have numerous applications as heterogeneous catalysts due to their ease of synthesis and commercial availability. Ru-Py-Merf was synthesized by anchoring 2-(2-pyridyl)benzimidazole to the polymer matrix, followed by loading of ruthenium salt. This Ru-Py-Merf material was thoroughly characterized by FTIR spectroscopy, UV-vis absorption spectroscopy, FE-SEM analysis, EDAX analysis, CHN analysis, AAS spectroscopy and TGA. Ru-Py-Merf showed excellent catalytic activity in the synthesis of symmetric and asymmetric disubstituted ureas by reductive carbonylation of nitrobenzenes and anilines. The as-synthesized Ru-Py-Merf catalyst is entirely heterogeneous in nature, thermally stable and can be easily reused up to six times.

Full text of DOI:10.1039/c8nj00475g

View Article Online
View Journal
NJC
Accepted Manuscript
This article can be cited before page numbers have been issued, to do this please use: S. Islam, T. K. Dey,
K. Ghosh, P. Basu and R. A. Molla, New J. Chem., 2018, DOI: 10.1039/C8NJ00475G.
This is an Accepted Manuscript, which has been through the
Volume 40 Number
1 January 2016 Pages 1–846
Royal Society of Chemistry peer review process and has been
accepted for publication.
NJC
Accepted Manuscripts are published online shortly after
New Journal of Chemistry
www.rsc.org/njc
A journal for new directions in chemistry
acceptance, before technical editing, formatting and proof reading.
Using this free service, authors can make their results available
to the community, in citable form, before we publish the edited
article. We will replace this Accepted Manuscript with the edited
and formatted Advance Article as soon as it is available.
You can find more information about Accepted Manuscripts in the
author guidelines.
Please note that technical editing may introduce minor changes
to the text and/or graphics, which may alter content. The journal’s
standard Terms & Conditions and the ethical guidelines, outlined
in our author and reviewer resource centre, still apply. In no
event shall the Royal Society of Chemistry be held responsible
for any errors or omissions in this Accepted Manuscript or any
consequences arising from the use of any information it contains.
ISSN 1144-0546
PAPER
Jason B. Benedict et al.
The role of atropisomers on the photo-reactivity and fatigue of
diarylethene-based metal–organic frameworks
rsc.li/njc

Please do not adjust margins
New Journal of Chemistry
Page 1 of 10
View Article Online
DOI: 10.1039/C8NJ00475G
Journal Name
ARTICLE
Chloromethylated polystyrene immobilized ruthenium complex of
2-(2-Pyridyl)benzimidazole catalyst for the synthesis of bioactive
disubstituted ureas by carbonylation reaction
Received 00th January 20xx,
Accepted 00th January 20xx
Tusar Kanto Dey,a Kajari Ghosh,b,¥ Priyanka Basu,a, ¥, Rostam Ali Molla,b and Sk. Manirul Islama*
DOI: 10.1039/x0xx0
www.rsc.org/
Abstract
Polymer supported transition metal complex catalysts has enormous applications as heterogeneous catalyst due to ease of
synthesis and commercial availability. Ru-Py-Merf was synthesized by anchoring 2-(2-Pyridyl)benzimidazole to the polymer
matrix and then loading ruthenium salt on it. This Ru-Py-Merf material was thoroughly characterized by FTIR spectroscopy,
UV-Vis absorption spectra, FE-SEM analysis, EDAX analysis, CHN analysis, AAS spectroscopy and TGA. Ru-Py-Merf showed
excellent catalytic activity in the synthesis of symmetric and asymmetric disubstituted ureas by reductive carbonylation of
nitrobenzenes and anilines. The synthesized Ru-Py-Merf catalyst is entirely heterogeneous in nature, thermally stable and
can be easily reused up to six times.
association of alkylating pharmacophores with high affinity DNA
binders. Additionally, presence of diaryl urea in many kinase
inhibitors, such as RAF, KDR and Aurora kinases made it a novel
Introduction
Carbonylation reaction using CO as a C1 source showed their
authority in chemical industries for conversion of organic substrate
to some new fine chemicals.1 Specifically, transition metal-catalyzed
carbonylation of nitro and amino compounds has been developed
as a promising synthetic pathway for the production of carbonyl
compounds. Use of Carbon monoxide as a reductant in the past
confined to some few reactions, its use in organic synthesis,
especially in the reductive carbonylation of nitro aromatics and the
oxidative carbonylation of aromatic amines, has increased
dramatically.2 Also use of CO in the industry has been increased in
the last decays due to synthesis of aryl carboxylic acids,3 amides,4
aldehydes5 etc. More specifically to say carbonylation of methanol
to acetic acids and nitro compounds to disubstituted ureas have
gained much more attention. The stunning aspect of fixing carbonyl
groups into organic products at the similar time forming new bonds
provides this class of transformations tremendously expensive
leading scheme for the production of a variety of urea derivatives.
organic intermediate.6 The derivatives of disubstituted urea are
widely used in the manufacture pharmaceutical composition for the
treatment of RET dependent tumor diseases. It is also used for the
treatment of protein kinase dependent diseases particularly
proliferative diseases, agricultural pesticides,7 treatment of diabetic
neuropathy and as herbicides.8
The common synthetic pathway for synthesis of ureas is the
reaction of amines with CO by using non metallic catalysts like tert-
amine.9 In this pathway the yield of urea can only be increased by
using excess sulfur which leads to the formation of toxic by-product
hydrogen sulfide. Shiwei Lu and his coworkers reported the
synthetic procedure for the synthesis of symmetrical disubstituted
ureas by sulfur-catalyzed carbonylation in ionic liquids.10 But this
methodology requires high CO pressure and high reaction
temperature. The other techniques require selenium-catalyst which
is toxic in nature and requires continuous oxygen flow in the
reaction medium.11 So, for the large scale synthesis of substituted
symmetric ureas and more challenging unsymmetrical ureas12
design of a new catalytic system is essential. Ru, Pd and Rh
incorporated metal complexes are very indispensable for the
synthesis of ureas by reductive carbonylation.13-15 Ru is very
Chemical fixation of carbon monoxide steadily has been a focus of
study among researchers for emergent environmentally benign
protocols for the production of different biologically active and
industrially crucial intermediates. The tremendous binding ability of
the disubstituted urea with assured acceptors is an imperative
pharmacophore in developing anticancer drugs. The NH functional
group present in the disubstituted urea is a supportive hydrogen
bond donor, while the oxygen atom is considered as a marvelous
acceptor. Furthermore, the structure of aryl urea is helpful for
18
promising material for activation of CO216,17 and CO subsequently
it converts them into many fine chemicals. Along with this, Ru may
also act as photo catalyst19 and nano reactors20. Nowadays, Ru is
widely used for the synthesis of methanol from CO221. But it is also
essential to design a suitable support which will influence the
catalytic activity of Ru in the disubstituted urea synthesis.
Chloromethylated polystyrene is one such true support which will
make the catalyst heterogeneous and tailoring of this polymer
This journal is © The Royal Society of Chemistry 20xx
J. Name., 2013, 00, 1-3 | 1
Please do not adjust margins

Please do not adjust margins
New Journal of Chemistry
Page 2 of 10
View Article Online
DOI: 10.1039/C8NJ00475G
ARTICLE
Journal Name
support by suitable ligand in a complexation manner will transform Preparation of 2-(2-Pyridyl)benzimidazole:
it as an excellent catalytic support.
2-(2-Pyridyl)benzimidazole was synthesized by following the
procedure mentioned in correlation of previous reported
literatures27. In a 50 ml round bottomed flask 20 mL of ethanol, o-
phenylenediamine (20 mmol) and picolinaldehyde (20 mmol) were
added under constant stirring. Then p-toluenesulfonic acid (20
mmol) added drop by drop for 20 minutes. The reaction mixture
was refluxed for 24 hour under N2 atmosphere. The reaction
mixture was extracted with DCM in presence of water for at least
three times. After complete removal of water the product was
purified by column chromatography and analyzed by 1H NMR
spectroscopy (supporting information).
Transition metals containing Chloromethylated polystyrene
supported heterogeneous catalysts are very imperative and gaining
huge attention owing to their admirable catalytic activity and easily
recoverability. Designing of
a catalytic system by loading of
ruthenium metal ion on the surface of functionalized
chloromethylated polystyrene make it an extremely primitive
catalyst for the reductive carbonyltion of disubstituted ureas under
mild conditions. Chloromethylated polystyrene can be easily
functionalized by imidazole type ligands. Imidazole type ligands are
well known due to their superior cross linking with polymers22,23
and they can easily bind with Ru with their electron enriched Preparation of merrifield anchored 2-(2-Pyridyl) benzimidazole
nitrogen site. Such type of many chloromethylated polystyrene ligand (Py-Merf):
supported polymer catalyst are reported earlier and they are highly
At first 3 g of chloromethylated polystyrene was well swelled in 20
thermal stable and heterogeneous in nature so that they can be
mL DMF and stirred in room temperature for 2 hour. Then 1.625 g
reused easily up to 5 times.18,24-26
of 2-(2-Pyridyl)benzimidazole was dissolved in 15 mL DMF and it
was added little by little to the previous suspension. The color of
In this context we have reported chloromethylated polystyrene
the final solution immediately changed to yellow. After it 4.5 mL
supported Ru-polymer complex for the synthesis of symmetrical
triethyl amine and 30 mL ethyl acetate were added and refluxed at
and unsymmetrical ureas by carbonylation of nitro and amino
80 0C for 24 hour. Then it was cooled to room temperature and
compounds under 4 atm pressure and 90 0C temperature without
filtered through a gouch funnel under high vacuum. It was washed
production of any toxic by-products. The two nitrogen atoms
with copious amount of DMF and hot ethanol for several times and
present in the polymer supports facilitates it to bind with
finally dried in hot air oven at 60 0C temperature.
ruthenium very strongly so that it cannot get leached to the
reaction medium. So choice of ruthenium in this tailoring practice is Preparation of merrifield anchored 2-(2-Pyridyl) benzimidazole
an appropriate one. Ruthenium is very promising metal in the supported ruthenium catalyst (Ru-Py-Merf):
disubstituted urea synthesis by chemical fixation of carbon
At first RuCl3.3H2O (2 mmol) was dissolved in 10 mL DMSO and
monoxide. To get maximum efficiency from the catalyst many
placed in a magnetic stirrer. Then 1 g of polymeric ligand was added
parameters are varied. And it is important to say that our prepared
to it and refluxed for 24 h with vigorous stirring. After cooling at
catalyst is recyclable up to 6 times without any significant loss of its
room temperature the residue was filtered under vacuum and
catalytic activities.
washed with methanol for three times. Then it was dried in hot
oven at 80 0C for 4 hour.
Experimental
Materials and reagents
Chloromethylated polystyrene
(5.5%
crosslinking),
o-
phenylenediamine, picolinaldehyde were purchased from Sigma-
Aldrich and used without any additional purification. Solvents used
like DMF, methanol, ethyl acetate, DCM were purchased from
Merck India and used after distillation by standard distillation
process and dried by molecular sieve. The derivatives of anilines,
nitrobenzenes, p-toluenesulfonic acid were purchased from Alfa-
Aesar and used after recrystallization process.
Physical measurements
The FT-IR spectra of the samples were recorded from 450 to 4000
cm-1 on a Perkin Elmer FTIR 783 spectrophotometer using KBr
pellets. UV-Vis spectra were taken using a Shimadzu UV- 2401PC
doubled beam spectrophotometer having an integrating sphere
attachment for solid samples. Thermogravimetric analysis (TGA)
was carried out using a Mettler Toledo TGA/DTA 851. Surface
morphology of the samples was measured using a scanning electron
microscope (SEM) (ZEISS EVO40, England) equipped with EDAX
facility. Ruthenium content in the catalyst was determined using a
Varian AA240 atomic absorption spectrophotometer (AAS). High
pressure reactor assembled magnetic stirrer attached with
autoclave (AmAr Equipment, model no.SE-1TAP-II) was used to
perform the reaction of nitrobenzene and amine derivatives.
Scheme 1: Synthesis of merrifield anchored 2-(2-
Pyridyl)benzimidazole supported ruthenium catalyst (Ru-Py-Merf).
General procedure for the synthesis of disubstituted ureas
In a stainless steel high pressure autoclave reactor 4 mL DMF, 4 mL
Preparation of Catalyst:
methanol,
5
mmol nitrobenzene and 10 mmol aniline were
The synthesis of Ru-Py-Merf is outlined in Scheme 1.
2 | J. Name., 2012, 00, 1-3
This journal is © The Royal Society of Chemistry 20xx
Please do not adjust margins

Please do not adjust margins
New Journal of Chemistry
Page 3 of 10
View Article Online
DOI: 10.1039/C8NJ00475G
Journal Name
ARTICLE
introduced. Then 25 mg of catalyst was added to the mixture and transfer at around 120 and 163 nm. The high resolution bands of
stirred for 10 minutes. Then FeCl3 (300 mg) was added to the Ru-Py-Merf catalyst from 300 to 800 nm are shown in the inset. This
reaction mixture. The reactor was then closed and CO was purged image suggests that there are many weak absorption peaks in this
in the reactor maintaining the pressure 4 atm and temperature 90 above mentioned which are attributed due to the d-d transition
0C. Then the reaction was carried out for 5 hour. The reactor was (spin allowed) of ruthenium present in the Ru-Py-Merf complex
cooled to room temperature and the reaction mixture was filtered catalyst.
by a whatman 42 filter paper. The filtrate was then extracted with
ethyl acetate for three times and concentrated to get the crude
product. A white crystal appeared after cooling which was then
washed with diethyl ether and dried in vacuum. The product was
characterized by 1H NMR spectroscopy (supporting information).
Results and discussion
Characterization:
Fig.3 UV-Vis spectra of Py-Merf and Ru-Py-Merf (Inset picture
represents high resolution UV-Vis spectra of Ru-Py-Merf)
From FTIR spectroscopy the functional groups present in the
Fig.1 FE-SEM image of (A) Py-Merf, (B) Ru-Py-Merf.
merrifield
anchored
2-(2-Pyridyl)benzimidazole
supported
ruthenium catalyst complex can be identified precisely. In Fig. 4 the
FTIR spectrum of Py-Merf and Ru-Py-Merf are represented.
Spectrum (A) shows two sharp band at 2995 and 2924 cm-1 due to
the presence of aromatic C-H bonds and CH2 bond respectively. The
band at 1613 cm-1 is due to the stretching mode of vibration of C=N
bond. The stretching mode of vibration of C-N bond shows a small
intense peak at 1397 cm-1. Spectrum (b) represents the FTIR spectra
of Ru-Py-Merf. The stretching frequency of aromatic C-H bonds and
CH2 bond are now slightly shifted to 3022 and 2918 cm-1 in the
desired catalyst. The stretching frequency of C=N bond and C-N
bond are also shifted to 1606 and 1421 cm-1.29,30 The presence of
The change in morphology throughout the preparation of catalyst
was determined by field emission scanning electron microscope as
shown in the Fig. 1. Fig. 1A represents the FESEM image of 2-(2-
Pyridyl)benzimidazole bound chloromethylated polystyrene
material. It shows the cross linking polymeric nature of Py-Merf
material. Fig. 1B shows Ru bound Py-Merf material (Ru-Py-Merf)
where change in morphology is clearly observed. The
agglomeration of polymeric particles of Ru-Py-Merf is more than
that of Py-Merf due to complexation.
The EDAX spectrum of Py-Merf and Ru-Py-Merf are shown in the
following Fig. 2 A and 2 B respectively. The spectrum of Py-Merf Ru-N bond is confirmed by the presence of a band at 544 cm-1. Also
there is Ru-O bond which is confirmed by the band at 470 cm-1.
confirms the presence of carbon, oxygen and chlorine. The peak of
chlorine arises probably due to the presence of some unreacted
chloromethylated polystyrene. The EDAX spectra of Ru-Py-Merf
confirm the presence of ruthenium in the polymeric complex. SEM
image and EDAX analysis assured that the attachment of the
ruthenium metal onto the merrifield anchored 2-(2-
Pyridyl)benzimidazole supported ruthenium catalyst (Ru-Py-Merf).
Fig.4 FTIR spectra of (A) Py-Merf and (B) Ru-Py-Merf
Thermogravimetric analysis was executed to ascertain the stability
Fig.2 EDAX spectrum of (A) Py-Merf, (B) Ru-Py-Merf
of Py-Merf and Ru-Py-Merf maintaining a heating rate 10 0C/minute
0
0
The UV-Vis spectra of Py-Merf and Ru-Py-Merf are represented in
the following Fig. 3. The band of Py-Merf showed one major
absorption peak at 115 nm and one shoulder at 154 nm. These
peaks are due to the intra-ligand charge transfer.28 The electronic
spectrum of Ru-Py-Merf is shown by the red line. It mainly showed
two major absorption peaks due to the ligand to metal charge
in an air oven from 30 C to 600 C. Py-Merf started to decompose
from 175 0C and then decomposition continues till it completely
diminishes. It is also important to say that a small weight loss of Py-
Merf also observed in the around 100 0C due to presence of
moisture. But a dramatical change was observed when Ru was
incorporated in the polymeric support. The Ru-Py-Merf catalyst was
This journal is © The Royal Society of Chemistry 20xx
J. Name., 2013, 00, 1-3 | 3
Please do not adjust margins

Please do not adjust margins
New Journal of Chemistry
Page 4 of 10
View Article Online
DOI: 10.1039/C8NJ00475G
ARTICLE
Journal Name
0
thermally stable upto 330 C after which it started to degrade (Fig.
5). So, our prepared catalyst is more stable than the supported
ligand.
Fig.6 Effect of pressure and temperature on 1-phenyl-3-p-tolylurea
synthesis
Reaction conditions: Nitrobenzene (5 mmol), p-toluidine (10
mmol), DMF (4 mL), MeOH (4 mL), FeCl3 (300 mg), catalyst (25 mg),
time (5 h).
Fig.5 TGA plot of (A) Py-Merf and (B) Ru-Py-Merf
The metal content of the Ru-Py-Merf was measured by atomic
absorption spectroscopy and the percentage of carbon, hydrogen
and nitrogen was measured by CHN analyzer. The data of the
mentioned analysis are represented in Table 1.
Table 2: Effect of solvent and co-solvent in the synthesis of
disubstituted urea
Entry
Solvent
Co solvent
Solvent : Co
Yield
(%)b
38
solvent
1:1
1:1
1:1
1:1
1:1
1:2
2:1
-
Table 1: Elemental analysis
1.
2.
3.
4.
5.
6.
7.
8.
Benzene
DMSO
Acetonitrile
DMF
MeOH
MeOH
MeOH
MeOH
EtOH
MeOH
MeOH
-
Compound
C %
H %
N %
Ru %
92
Py-Merf
74.31
4.42
13.51
-
79
Ru-Py-Merf
66.13
5.34
11.92
6.42
97
The emergence of new FTIR bands and shift in other FTIR bands of
Ru-Py-Merf catalyst has been used as additional evidence for
grafting of the metal in Py-Merf. In addition the polymer supported
ruthenium complex was also characterized by UV, FTIR, AAS, CHN
and analysis to forecast the complexation of metal ions as well as to
establish the structures of the complex.
DMF
89
DMF
96
DMF
94
DMF
22
Reaction conditions: Nitrobenzene (5 mmol), p-toluidine (10
Catalytic Activity
0
mmol), FeCl3 (300 mg), catalyst (25 mg), 4 atm pressure, 90 C, 5 h.
bisolated yield of product.
Effect of solvent is also an important parameter for this experiment.
Choice of appropriate solvent and co solvent promotes the yield of
this reaction. We have performed this reaction by varying different
solvents and co-solvents taking p-toluidine and nitrobenzene as a
model reaction and the results are tabulated in Table 2.
Interestingly we have found that using DMF as a solvent and
methanol as a co solvent maximum yield was obtained. When we
used non polar solvent like benzene the yield was extremely low.
Also we performed this reaction without co-solvent and it was
found that without co solvent the yield of the product was poor.
The role of co-solvent is vital for this reaction and choice of best co-
solvent is also crucial part to get maximum yield of product.
Alcohols are subjected as best co-solvent and their presence in the
reaction medium can leap the yield of product massively. In this
reaction methanol acts as best co-solvent because of its highly polar
nature. The yield of product in presence of ethanol as a co-solvent
slightly lowers down due to polarity change from methanol to
ethanol. Also, the DMF: MeOH molar ratio controls the yield of the
Scheme 2: Synthesis of 1-phenyl-3-p-tolylurea catalysed by Ru-Py-
Merf
In the 1-phenyl-3-p-tolylurea urea synthesis effect CO pressure and
reaction temperature are the very important parameters. To find
out the best optimized pressure and temperature a series of
experiments were performed varying pressure from 2 atm to 6 atm
and temperature from 80 0C to 95 0C. The data of these
0
experiments are summarized in the Figure 6. It is clear that at 90 C
temperature and 4 atm CO pressures are the optimum condition for
1-phenyl-3-p-tolylurea synthesis. Bellow this temperature and
pressure a lower yield was observed. But above 90 0C and 4 atm the
yields are almost remained unaltered. All the reactions were
performed in this experiment temperature and pressure are strictly
maintained.
4 | J. Name., 2012, 00, 1-3
This journal is © The Royal Society of Chemistry 20xx
Please do not adjust margins

Please do not adjust margins
New Journal of Chemistry
Page 5 of 10
View Article Online
DOI: 10.1039/C8NJ00475G
Journal Name
ARTICLE
reaction as on increasing the molar ratio from 1:1 to 1:2, the yield maximum yield and there was no increase in yield of product when
slightly lowers down. This may be due to dilution of the reaction the reaction time was elaborated. So prolonging of reaction time
medium or increasing of polarity than the optimum value. So, the has not any influence on the disubstituted urea synthesis. Also
above data establish that use of DMF as solvent and MeOH as co- when the reaction time decreases from 5 hour to 4 hour the yield of
solvent in 1:1 proportion is the best choice for significant yield of the product lowers down.
product.
Table 3: Optimization for amount of Catalyst and Co-catalyst
Entry
Amount of
catalyst (g)
0.05
Amount of co-
Yield
(%)b
97
catalyst (g)
0.4
1.
2.
3.
4.
5.
6.
Table 4: Synthesis of di-substituted ureas in the presence of Ru-
Py-Merf catalyst
0.04
0.4
97
0.03
0.4
97
0.025
0.3
97
Entry
Amines
Nitros
Product
Yield
(%)b
0.025
0.25
0.3
82
0.02
79
Reaction conditions: Nitrobenzene (5 mmol), p-toluidine (10
mmol), DMF (4 mL), MeOH (4 mL), 4 atm CO pressure, 90 0C, 5 h.
bisolated yield of product.
1.
93
The effect of amount catalyst and co catalyst has great influence in
the 1-phenyl-3-p-tolylurea urea synthesis. Here FeCl3 is chosen to
perform the role of co-catalyst. Lewis acidic nature of FeCl3 makes
the reaction condition milder and promotes the yield of product
exceptionally. As FeCl3 is easily commercially available and very
cheap than the other Lewis acids, it is used as co-catalyst to
perform this reaction. The reaction was also performed in absence
of FeCl3 maintaining the same reaction conditions but the yield of
product was very low. So to expose the accurate amount of co-
catalyst and catalyst for this reaction a set of reactions were
performed varying different amount of catalyst and co-catalyst. The
results are represented in the Table 3. It was experimentally
observed that only 25 mg of catalyst and 300 mg of co catalyst
(FeCl3) is sufficient to carry out the reaction. When the amount of
co-catalyst decreased from 300 mg to 250 mg maintaining same
amount of catalyst the yield of the reaction also decreased from
97% to 82%. So, FeCl3 plays a crucial role in the disubstituted urea
synthesis.
2.
3.
4.
96
99
98
5.
97
6.
7.
trace
92
Fig.7 Effect of reaction time on 1-phenyl-3-p-tolylurea synthesis
Reaction conditions: Nitrobenzenes (5 mmol), p-toluidine (10
mmol), FeCl3 (300 mg), catalyst (25 mg), DMF (4 mL), MeOH (4 mL),
4 atm CO pressure, temperature (90 0C).
8.
9.
trace
93
The influence of reaction time for the synthesis of 1-phenyl-3-p-
tolylurea a representative bar diagram is shown in the Fig. 7 from
the experimental observation by varying the reaction time from 3
to 6 hour. It is clearly observed that only at 5 hour the reaction gave
This journal is © The Royal Society of Chemistry 20xx
J. Name., 2013, 00, 1-3 | 5
Please do not adjust margins

Please do not adjust margins
New Journal of Chemistry
Page 6 of 10
View Article Online
DOI: 10.1039/C8NJ00475G
ARTICLE
Journal Name
electron density decreases from the -NO2 group the possibility of
the reduction of nitro to amine group increases. So, higher yield
was observed for electron withdrawing groups present in the nitro
derivatives than the electron donating groups. In addition it is
essential to mention that when the reaction was performed
without any addition of FeCl3, the yield of isolated product lowers
down to 48 % from 97 % . But in presence of FeCl3 when no catalyst
was added during the course of reaction only trace amount of
product was found. So FeCl3 only promotes the yield of reaction but
if there is no catalyst in reaction medium there will be no product
formation. In this reaction FeCl3 act as a co-catalyst during
reformation of urea from carbamate it may facilitate the
reaction.
10.
95
28
11.
12.
trace
13.
14.
48c
Plausible mechanism
The plausible mechanism for the synthesis of disubstituted ureas
are proposed in Fig. 8. Mechanism of any catalytic reaction is
important for better understanding of chemistry behind every
explanation. Our proposed mechanism explains the role of Ru-Py-
Merf in the reductive carbonylation pathway for the synthesis of
disubstituted ureas. The reaction initiates by the complex formation
of nitrobenzene with Ru-Py-Merf complex catalyst. In this process
carbon monoxide is converted to carbon dioxide. This only happens
in presence of Ru-Py-Merf. After it the formed complex further get
carbonylated by insertation of CO moiety and the carbon monoxide
group get attached with the nitrogen atom of nitrobenzene. Further
an aniline molecule reacts with the carbonylated complex
compound and produces disubstituted urea by removing catalyst
from its moiety. But the reaction does not seize here because the
co-solvent methanol takes a major role in the mechanism. Presence
of MeOH seriously increases the yield of product by forming an
ester compound. This ester compound is formed when some
amount of disubstituted urea reacts with methanol by releasing an
aniline moiety. Finally the ester compound then again reacts with
aniline releasing the desired product in large scale. So this path i.e.
the involvement of methanol in the reaction pathway increases the
rate of the reaction and acts as a finest co-solvent.31-33 So, the
proposed reaction mechanism is in good agreement with the results
discussed earlier.
traced
Reaction conditions: Nitrobenzenes (5 mmol), amines (10
mmol), FeCl3 (300 mg), Ru-Py-Merf catalyst (25 mg), DMF (4 mL),
MeOH (4 mL), 4 atm CO pressure, temperature (90 0C), time (5
h). bisolated yield of product. isolated yield of product without
c
FeCl3. disolated yield of product without Ru-Py-Merf but in
presence of FeCl3.
To discover the scope of this reaction several derivatives of
amines and nitrobenzenes were used including aliphatic and
aromatic amines. The isolated yields of the respective products are
represented in Table 4. All the reactions were performed under
optimized conditions. Primarily different amines were used (Table
4, Entries 1-6, 9-10) to find out the effect of electron withdrawing,
electron donating functional groups, aliphatic and aromatic amines
in the disubstituted ureas synthesis catalyzed by Ru-Py-Merf. It was
established that aliphatic amines give elevated yield than aniline
and among them cyclohexyl amine (Table 4, Entry 3) gave the
maximum yield. On increasing the chain length from methyl amine
to butyl amine (Table 4, Entries 9,10) the yield of product gradually
increases. The reason behind this consequence is inductive effect,
as inductive effect increases on nitrogen atom of amine the yield of
respective product increases gradually. The presence of electron
withdrawing nitro group in the ortho position (Table 4, Entry 6)
highly deactivates the aniline group, as a result very trace amount
of product was found. So electron withdrawing groups present in
the amine lowers down the yield of product but electron donating
groups present in the amine highly elevates the yield of product for
example 4-methoxyaniline, p-toluidine (Table 4, Entries 4,5).
Benzylamine also gives higher yield than aniline (Table 4, Entry 3)
due to the more active -NH2 group. When the functional group of
nitrobenzene was varied we found an interesting result that
electron donating group present in nitrobenzene extremely
decreases the yield of product (Table 4, Entry 8). But electron
withdrawing group moderately gave better yield (Table 4, Entry 7)
with respect to the others. When non aromatic nitro compound like
nitromethane was used the yield of product was found to be
extremely low (Table 4, Entry 11). In addition to this when hetero
amine and hetero nitro compounds were used it was found that
they are extremely inert for this reaction (Table 4, Entry 12). As the
Fig.8 Plausible mechanism of disubstituted urea synthesis catalysed
by Ru-Py-Merf complex
6 | J. Name., 2012, 00, 1-3
This journal is © The Royal Society of Chemistry 20xx
Please do not adjust margins

Please do not adjust margins
New Journal of Chemistry
Page 7 of 10
View Article Online
DOI: 10.1039/C8NJ00475G
Journal Name
ARTICLE
Recyclability of catalyst
Comparison of catalytic effectiveness of polymer supported
ruthenium catalyst with the other reported systems
Table 5 represent the efficiency for the synthesized Ru-Py-Merf
catalyst with the other reported catalyst performed for the
synthesis of diphenyl urea. It is obvious from the following table
that the present merrifield anchored 2-(2-Pyridyl)benzimidazole
supported ruthenium catalyst is more mesmerizing and well
proficient one than previous catalysts.
Table 5: Comparison with other reported systems for diphenyl urea
synthesis
Sl.
No.
1.
Catalyst
Reaction condition
Yield
(%)
90
Ref.
0
PdI2
Aniline, DME, 100 C,
16 atm of CO, 4 atm
of air, and 40 atm of
CO2, 10 h.
34
Fig.9 Recycling diagram of Ru-Py-Merf complex catalyst
Recyclability is also an important parameter to prove the novelty of
any catalyst. Our prepared catalyst is also highly reusable (up to 6
times) without any large change of its efficiency. The catalyst can be
easily recovered by centrifugation of the reaction mixture. Then
after washing with hot methanol and followed by drying in hot air
oven at 60 0C for 3 hour the catalyst is ready to use for next
reaction. The recyclability curve of Ru-Py-Merf in 1-phenyl-3-p-
tolylurea synthesis is shown Fig. 9.
2.
3.
K2PdI4
Aniline, 110 0C, 170
atm of CO and O2, 60
h.
96
98
35
36
Pd(OAc)2
Aniline,
Nitrobenzene,
Xylene, 110 0C, 40
atm of CO, 2 h.
4.
1-n-butyl-3- n-butylamine, 170 0C,
55.1
37
methyl
9.86 atm of CO2, 19
imidazolium h.
hydroxide
[Bmim]OH
5.
6.
BMImCl
/CsOH
Aniline,
room
temperature, CO2, 36
h.
27
92
38
18
[Ru(PSimd)( Nitrobenzene,
CO)2Cl2]
aniline, CH3OH FeCl3,
DMF, 120 0C, 5 h, 60
atm CO pressure.
Nitrobenzene,
7.
Ru-Py-Merf
93
In this
study
Fig.10 FESEM image of Ru-Py-Merf after sixth recycle
Aniline, FeCl3, DMF,
The FE-EM image of Ru-Py-Merf catalyst after 6 recycles is shown in
Fig. 10. So it can be concluded that no appreciable change in
morphology of Ru-Py-Merf was found after 6 recycle which prove
that the heterogeneous catalyst is adequately done the reaction for
several times.
MeOH,
4 atm CO
pressure, 90 0C, 5 h.
Heterogeneity test
Whether the synthesized catalyst completely works as
heterogeneous manner or not, a heterogeneity test was performed
for 1-phenyl-3-p-tolylurea synthesis from p-toluidine and
nitrobenzene in the presence of ruthenium catalyst. At first the
catalyst was carried out for 2 h then removed from the reaction
mixture and the yield of the product was found to be 68 %. Then
the reaction was again continued for 3 hour without catalyst. After
5 h the yield of the product was determined and no alteration of
yield. So it can be concluded that there was no leaching of metal
from the polymer support. This was also confirmed by AAS that
there is no significance amount of ruthenium metal in the reaction
mixture.
Fig.11 FTIR spectra of Ru-Py-Merf after sixth recycle
This journal is © The Royal Society of Chemistry 20xx
J. Name., 2013, 00, 1-3 | 7
Please do not adjust margins

Please do not adjust margins
New Journal of Chemistry
Page 8 of 10
View Article Online
DOI: 10.1039/C8NJ00475G
ARTICLE
Journal Name
After sixth recycle the FTIR spectra of Ru-Py-Merf was measured
and represented in Fig. 11. It was clearly observed that there is no
change in bonding framework of synthesized Ru-Py-Merf catalyst
after sixth recycle.
3.
4.
5.
6.
V. P. Boyarskii, T. E. Zhesko, and S. A. Lanina, Russ. J.
Appl. Chem., 2005, 78, 1844-1848.
M. V. Khedkar, T. Sasaki, and B. M. Bhanage, ACS Catal.,
2013, 3, 287-293.
Conclusion
In summary, it can be concluded that Ru-Py-Merf is an outstanding
polymeric transition metal complex which show excellent catalytic
activity for the synthesis of symmetric and asymmetric
disubstituted ureas by reductive carbonylation under mild pressure
and temperature (4 atm of CO pressure and 90 0C temperature).
Fixation of carbon monoxide in organic substrate for the production
of fine chemicals is very challenging and our synthesized catalyst is
appropriate contender for the disubstituted urea synthesis. In this
reaction FeCl3 acts as co-catalyst and methanol acts as co-solvent
which promotes the yield of the reaction. The effect of electron
donating and electron withdrawing groups present in the amines
and nitrobenzenes are well studied and the reason behind them are
well explained. The synthesized catalyst is stable up to 330 0C and
can be reused up to 6 times without any significant loss of its
catalytic activity due to its heterogeneous nature. Also it is
imperative to state that no leaching of metal ion occurs from the
functionalized polymeric support. So our synthesized Ru-Py-Merf
catalyst opened a new strategic method of reductive carbonylation
near the researchers and industries.
T. Ueda, H. Konishi, and K. Manabe, Angew. Chem. Int.
Ed., 2013, 52, 8611-8615.
L. Garuti, M. Roberti, G. Bottegoni, and M. Ferraro ,
Curr Med Chem., 2016, 23, 1528- 1548.
7.
8.
9.
G. Groszek, Org. Process Res. Dev., 2002, 6, 759-761.
B. Thavonekham, Synthesis, 1997, 10, 1189-1194.
R. A. Franz, F. Applegath, F.V. Morriss, and F. Baiocchi, J.
Org. Chem., 1961, 26, 3309-3312.
X. Wang, P. Li, X. Yuan, and S. Lu, J. Mol. Catal. A:
Chem., 2006, 255, 25-27.
10.
11.
N. Sonoda, T. Yasuhara, K. Kondo, and T. Ikeda, J. Am.
Chem. Soc., 1971, 93, 6344-6344.
Acknowledgments
12.
13.
A. M. Tafesh, and J. Weiguny, Chem. Rev., 1996, 96,
S.M.I. acknowledges the Department of Science and Technology,
DST-SERB, (Project No EMR/2016/004956), New Delhi, Govt. of
India, Council of Scientific & Industrial Research, CSIR, (Project No
02(0284)/16/EMR-II), Date: 06-12-2016; and Technology, West
Bengal (DST-WB, Sanction No. 811(sanc.)/ST/P/S&T/4G-8/2014
Dated: 04.01.2016) for funding. PB is thankful to the NFOBC for
UGC, New Delhi for her JRF. KG and RAM acknowledges The
2035-2052.
N. D Ca, P. Bottarelli, A. Dibenedetto, M. Aresta, B.
Gabriele, G. Salerno, and M. Costa, J. Catal., 2011, 282,
120-127.
Department of Science
& Technology (DST) for their NPDF
14.
15.
D. K. Mukherjee, and C. R. Saha, J. Mol. Catal. A: Chem.,
2003, 193, 41-50.
(PDF/2016/000160) and (PDF/2017/000218). We sincerely thank
Department of Chemistry of the University of Burdwan for
infrastructural facilities. We acknowledge Department of Science
and Technology (DST) and University Grant Commission (UGC) New
Delhi, India for providing support to the Department of Chemistry,
University of Kalyani under PURSE, FIST and SAP program
F. Shi, Q. Zhang, Y. Gu, and Y. Deng, Adv. Synth. Catal.,
2005, 347, 225-230.
16.
17.
18.
Z. Yang, H. Wang, G. Ji, X. Yu , Y. Chen, X. Liu, C. Wu,
and Z. Liu, New J. Chem., 2017, 41, 2869-2872.
* Author to whom correspondence should be addressed.
Dr. Sk. Manirul Islam, Department of Chemistry, University of
Kalyani, Kalyani, Nadia, 741235, W.B., India. Phone: + 91- 33-2582-
8750, Fax: 91-33-2582-8282, E-mail: manir65@rediffmail.com
S. Bontemps, L. Vendier, and S. Etienne, J. Am. Chem.
Soc., 2014, 136, 4419-4425.
Notes and references
S. M. Islam, K. Ghosh, A. S. Roy, R. A. Molla N. Salam, T.
Chatterjee , and M. A. Iqubal, J. Organomet. Chem.,
2014, 772-773, 152-160.
1.
(a) S. Sumino, A. Fusano, T. Fukuyama, and I. Ryu, Acc.
Chem. Res., 2014, 47, 1563-1574.
A. Jana, J. Mondal, P. Borah, S. Mondal, A. Bhaumik,
and Y.Zhao, Chem. Commun., 2015, 51, 10746-10749.
19.
20.
(b) X. F. Wu, H. Neumann, and M. Beller, Chem. Rev.,
2013, 113, 1-35.
J. Mondal, S. K. Kundu, H. Ng, W. Kwok, R. Singuru, P.
Borah, H. Hirao, Y. Zhao, and A. Bhaumik, Chem. Eur.j.,
2015, 21, 19016-19027.
2.
A. M. Tafesh, and J. Weiguny, Chem. Rev., 1996, 96,
N. M. Rezayee, C. A. Huff, and M. S. Sanford, J. Am.
Chem. Soc., 2015, 137, 1028-1031.
21.
22.
2035-2052.
J. F. Soulé, H. Miyamura, and S. Kobayashi, J. Am. Chem.
8 | J. Name., 2012, 00, 1-3
This journal is © The Royal Society of Chemistry 20xx
Please do not adjust margins

Please do not adjust margins
New Journal of Chemistry
Page 9 of 10
View Article Online
DOI: 10.1039/C8NJ00475G
Journal Name
Soc., 2013, 135, 10602-10605.
X. Mu, J. Meng, Z. Li, and Y. Kou, J. Am. Chem. Soc.,
ARTICLE
23.
24.
25.
26.
27.
28.
2005, 127, 9694-9695.
R. A. Molla, K. Ghosh, K. Tuhina, and S. M. Islam, New J.
Chem., 2015, 39, 921-930.
M. Halder, M. M. Islam, S. Ahammed, and S. M. Islam,
RSC Adv., 2016, 6, 8282-8289.
S. M. Islam, K. Ghosh, A. S. Roy, and, R. A. Molla, Appl.
Organometal. Chem. 2014, 28, 900-907.
G. Xiang, W. Cui, S. Lin, L. Wang, H. Meier, L. Li, and D.
Cao, Sens. Actuators, B, 2013, 186, 741-749.
P. Anitha, R. Manikandan, A. Endo, T. Hashimoto, and P.
Viswanathamurthi, Spectrochim. Acta Part A Mol.
Biomol. Spectro., 2012, 99, 174-182.
29.
30.
V. V. Raju, K. P. Balasubramanian, C. Jayabalakrishnan,
and V. Chinnusamy, Nat. Sci., 2011, 3, 542-591.
B. Prabhakaran, N. Santhi, and M. Emayavaramban,
Phys. Astronomy, 2013, 3, 53-66.
31.
32.
C. W. Lee, and J. S. Lee, J. Mol. Catal., 1993, 81, 17-25.
J. H. Kim, D. W. Kim, M. Cheong, H. K. Kim, and D. K.
Mukherjee, Bull. Korean Chem. Soc., 2010, 31, 1621 -
1627.
33.
34.
35.
D. K. Mukherjee, and C. R. Saha, J. Catal., 2002, 210,
255-262.
B. Gabriele, G. Salerno, R. Mancuso, and M. Costa, J.
Org. Chem., 2004, 69, 4741-4750.
N. Della, P. Bottarelli , A. Dibenedetto , M. Aresta , B.
Gabriele, G.Salerno, and M. Costa, J. Catal., 2011, 282,
120-127.
36.
37.
38.
J. S. Oh, S. M. Lee, and J. K. Yeo, Ind. Eng. Chem. Res.,
1991, 30.
T. Jiang, X. Ma, Y. Zhou, S. Liang, J. Zhang, and B. Han,
Green Chem., 2008, 10, 465-469.
F. Shi, Y. Deng, T. Sima, J. Peng, Y. Gu, and B. Qiao,
Angew. Chem. Int. Ed., 2003, 42, 3257-3260.
This journal is © The Royal Society of Chemistry 20xx
J. Name., 2013, 00, 1-3 | 9
Please do not adjust margins

New Journal of Chemistry
Page 10 of 10
View Article Online
DOI: 10.1039/C8NJ00475G
Graphical Abstract
Chloromethylated polystyrene immobilized ruthenium complex of 2-(2-
Pyridyl)benzimidazole catalyst for the synthesis of bioactive disubstituted
ureas by carbonylation reaction
Tusar Kanto Dey,a Kajari Ghosh,b,¥ Priyanka Basu,a, ¥, Rostam Ali Molla,b and Sk. Manirul
Islama*
aDepartment of Chemistry, University of Kalyani, Kalyani, Nadia, 741235, W.B., India
bDepartment of Chemistry, University of Burdwan, Burdwan 713104, W.B., India
¥ These Authors contributed equally
Ru-Py-Merf complex heterogeneous catalyst is synthesized by three step process. At first 2-
(2-Pyridyl)benzimidazole is synthesized from o-phenylenediamine and picolinaldehyde then
it is tailored with chloromethylated polystyrene to get Py-Merf. Finally ruthenium ion is
loaded in Py-Merf to get Ru-Py-Merf complex. The synthesized Ru-Py-Merf exhibited
maximum catalytic efficiency for the synthesis of symmetric and asymmetric disubstituted
ureas by reductive carbonylation of nitrobenzenes and amines under 4 atm CO pressure and
90 0C temperature using FeCl3 as co-catalyst and MeOH as co-solvent.