Cu-grafted functionalized mesoporous SBA-15: A novel heterogeneous catalyst for facile one-pot three-component C-S cross-coupling reaction of aryl halides in water

Article abstract of DOI:10.1021/op4000994

A highly ordered 2D hexagonal Cu-grafted functionalized mesoporous SBA-15 (Cu-PIF-SBA-15) has been designed through postsynthetic modification of mesoporous SBA-15. Surface functionalization technique has been employed to synthesize-NH₂ functionalized mesoporous SBA-15 material. Schiff base condensation of this-NH₂ functionalized SBA-15 with phloroglucinol dialdehyde leads to the formation of PIF-SBA-15. Reaction of PIF-SBA-15 with Cu(OAc)₂·H₂O in ethanol under reflux leads to the formation of Cu-PIF-SBA-15 catalyst. This Cu-PIF-SBA-15 catalyst exhibits excellent catalytic activity in a one-pot three-component C-S coupling reaction for a diverse range of aryl halides (bromide and chloride) with thiourea and benzyl bromide in aqueous medium to offer aryl alkyl thioether in very good yields. Due to the strong binding ability of the imine-N and phenolic-OH functional groups present in the phloroglucinol diimine moiety of the framework, the anchored Cu(II) could not leach out from the surface of the mesoporous catalyst during the course of reaction, and it has been observed that six repetitive reaction cycles could not cause any appreciable loss in the catalytic activity of this material.

Full text of DOI:10.1021/op4000994

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Full Paper
Cu-grafted functionalized mesoporous SBA-15: a novel
heterogeneous catalyst for facile one-pot three component
C-S cross-coupling reaction of aryl halides in water
John Mondal, Parijat Borah, Arindam Modak, Yanli Zhao, and Asim Bhaumik
Org. Process Res. Dev., Just Accepted Manuscript • DOI: 10.1021/op4000994 • Publication Date (Web): 09 Sep 2013
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Cuꢀgrafted functionalized mesoporous SBAꢀ15: a novel heterogeneous
catalyst for facile oneꢀpot three component CꢀS crossꢀcoupling reaction
of aryl halides in water
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John Mondal,†,‡ Parijat Borah,‡ Arindam Modak,† Yanli Zhao*,‡,Ф and Asim Bhaumik*,†
†Department of Materials Science, Indian Association for the Cultivation of Science, Jadavpur
700 032, India
‡Division of Chemistry and Biological Chemistry, School of Physical and Mathematical Sciences
Nanyang Technological University, 21 Nanyang Link, 637371 (Singapore)
ФSchool of Materials Science and Engineering, Nanyang Technological University, 50 Nanyang
Avenue, 639798 (Singapore)
*Address for correspondence. Eꢀmail: msab@iacs.res.in and zhaoyanli@ntu.edu.sg
Abstract
A highly ordered 2Dꢀhexagonal Cuꢀgrafted functionalized mesoporous SBAꢀ15 (CuꢀPIFꢀSBAꢀ
15) has been designed through postꢀsynthetic modification of mesoporous SBAꢀ15. Surface
functionalization technique has been employed to synthesize –NH2 functionalized mesoporous
SBAꢀ15 material. Schiffꢀbase condensation of this –NH2 functionalized SBAꢀ15 with
phloroglucinolꢀdialdehyde leads to the formation of PIFꢀSBAꢀ15. Reaction of PIFꢀSBAꢀ15 with
Cu(OAc)2.H2O in ethanol under reflux leads to the formation of CuꢀPIFꢀSBAꢀ15 catalyst. This
CuꢀPIFꢀSBAꢀ15 catalyst exhibits excellent catalytic activity in oneꢀpot three component CꢀS
coupling reaction for a diverse range of aryl halides (bromide and chloride) with thiourea and
benzyl bromide in aqueous medium to offer aryl alkyl thioether in very good yields. Due to
strong binding ability of the imineꢀN and phenolicꢀOH functional groups present in the
phloroglucinolꢀdiimine moiety of the framework, the anchored Cu(II) could not leach out from
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the surface of the mesoporous catalyst during the course of reaction and it has been observed that
six repetitive reaction cycles not could cause any appreciable loss in the catalytic activity of this
material.
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Keywords: Aryl alkyl thioethers; Cuꢀcatalyzed CꢀS coupling reaction; oneꢀpot three component
couplings; thioetherification; functionalized mesoporous silica.
Introduction
Catalytic methods involving the CꢀS bond formation reactions have been emerged as most
versatile and powerful tool for the synthesis of value added thioethers.1,2 Among thioethers the
diaryl sulfides are of great significance due to their broad spectrum of therapeutic activities and
they can be employed for diverse clinical applications in the treatment of cancer,3 HIV,
Alzheimer’s4 and Parkinson’s diseases.5 CꢀC, CꢀO, CꢀN cross coupling reactions can be
effectively mediated by using various types of transition metal catalysts.6,7 However, metal
catalyzed Sꢀarylation has been comparatively less explored than Nꢀarylation and Oꢀarylation
because of the associated oxidative SꢀS homocoupling reaction and deactivation of metal
catalysts by sulfur containing compounds. Various transition metals including Pd,8 Fe,9 Co,10
Ni11 and Cu12 catalysts have been employed for Sꢀarylation reactions. Among them the copper
catalysts have been considered as the most effective and attractive in the Sꢀarylation of aryl
halides with thiols due to their high abundance and environmentally benign reaction conditions
with minimum waste and health hazard to the environment. Usually, CꢀS coupling reactions
suffers from the severe drawbacks including direct use of volatile and foulꢀsmelling thiols, which
could lead to strict environmental and safety problems, and thus place a ceiling on any scale up
operation. Moreover, most of the CꢀS bond formation reactions are performed in the presence of
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toxic, flammable, expensive, non recyclable organic solvents and their disposal has been
regarded as a key issue for the sustainable development of catalytic process in chemical industry.
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To make the catalytic processes green and sustainable considerable efforts have been
devoted to carry out the CꢀS coupling reactions under solventꢀfree conditions or in ionic liquid13
or by using water as a reaction medium.14ꢀ16 Water as a reaction medium also provides greater
chemoselectivity compared with the other organic solvents.17 In order to overcome the problems
of the handling of thiols, various novel odorless protocols for making the CꢀS bond have been
developed by the researchers. Oneꢀpot Michael addition reactions via an odorless process
involving inꢀsitu generation of Sꢀalkylisothiouronium salts in water18 and oneꢀpot
thioetherification of aryl halides using thiourea19 (free from the foul smell of thiols) are worthy
to mention here. The organic compounds such as 3ꢀ[bis(alkylthio)methylene]pentaneꢀ2,4ꢀ
diones,20 dialkyl disulfides,21 4,4ꢀbis(alkylthio)butꢀ3ꢀenꢀ2ꢀones22 have been rigorously employed
as thiol equivalent precursors for this purpose. But the shortcomings associated with these
odorless protocols include use of homogeneous catalysts, strong alkaline medium and long
reaction time. As a result these catalytic methods for CꢀS coupling or Sꢀarylation reaction lacks
in the recycling efficiency of the catalyst.
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Recently, heterogeneous catalysts are hugely acknowledged for the sustainable
development of any catalytic process due to their easy recovery, recycling as well as
minimization of undesired toxic wastes23 and Eꢀfactor.24 The problems usually connected with
the homogeneous catalysts can be easily overcome by heterogenisation of homogeneous
counterpart onto insoluble inorganic or organic solid support in which active components are
strongly immobilized.25 Among several approaches of immobilization on the insoluble solid
matrices organically functionalized mesoporous materials can be regarded as the most promising
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one in the catalysis research area due to their huge surface area, high adsorption capacity, tunable
pore size distribution, high hydrothermal and mechanical stability.26ꢀ28 The periodicity of
nanoscale pores in these organically functionalized mesoporous materials could favor the easy
accessibility of the catalytic sites and possible diffusion of the solvent and reactants within the
insoluble solid matrix.29 Mesoporous materials could be functionalized through several organic
reactions in such a way so that the organic functional groups offer a crucial role to anchor the
catalytic active sites (metal/metal oxide nanoparticles,30,31 metal complexes12) covalently at the
surface of the pores with the preservation of porous host structure. Recently, we have developed
Cu(II)ꢀanchored furfural imineꢀfunctionalized mesoporous silica, which exhibited excellent
catalytic activity for conducting oneꢀpot thioetherification in aqueous medium.32
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Herein, we design a new Cuꢀcontaining phloroglucinolꢀdiimine functionalized
mesoporous SBAꢀ15 catalyst via covalent grafting of Cu(II) at the surface of mesopores and the
material has been employed in the oneꢀpot, odorless CꢀS coupling reaction of aryl halides
(bromide and chloride) using thiourea and benzyl bromide in aqueous medium in the presence of
K2CO3 base at 100 OC. At first, amine functionalized mesoporous SBAꢀ15 has been synthesized
by the surface functionalization of calcined SBAꢀ15 with 3ꢀaminopropylꢀtriethoxysilane. This
amine functionalized SBAꢀ15 undergoes Schiffꢀbase condensation reaction with phloroglucinolꢀ
dialdehyde to offer PIFꢀSBAꢀ15 material, which on treatment of Cu(OAc)2.H2O in absolute
ethanol leads to the formation of novel CuꢀPIFꢀSBAꢀ15 mesoporous catalyst. This CuꢀPIFꢀSBAꢀ
15 catalyst has been thoroughly characterized by using powder XRD, HR TEM, FE SEM, N2
sorption, FT IR, ICPꢀAES, AAS and EXAFS experimental tools.
Experimental section
Synthesis of 3-aminopropyl functionalized SBA-15. Pure silica SBAꢀ15 was
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synthesized by following the reported procedure as described before.33 0.1 g calcined SBAꢀ15
was dispersed in 15 ml CHCl3. Then 0.18 g of 3ꢀaminopropyltriethoxysilane (3ꢀAPTES) was
added dropwise into the dispersed CHCl3 solution and the resulting mixture was allowed to stir
at room temperature under N2 atmosphere for about 12 h. The resulting white solid was isolated
by filtration followed by washing with chloroform and dichloromethane and finally dried in air.
The white colored solid was designated as ꢀNH2ꢀSBAꢀ15.
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Synthesis of phloroglucinol-diimine functionalized mesoporous SBA-15 (PIF-SBA-15).
Phloroglucinolꢀdialdehyde was prepared by following the procedure as described before.34 Light
red colored phloroglucinolꢀdialdehyde (0.0008 mol, 0.145g) was dissolved in 5 ml methanol by
simple stirring at room temperature. 3ꢀAPTES functionalized SBAꢀ15 material (ꢀNH2ꢀSBAꢀ15)
was also dispersed into 15 ml methanol under continuous stirring condition. Then previously
prepared phloroglucinolꢀdialdehyde solution was added dropwise into the amine functionalized
methanol solution. After complete addition of aldehyde solution the resulting reaction mixture
was kept under refluxing condition for about 10 h at 333 K. The color change of the reaction
mixture from colorless to deep red was observed and no further color change took place on
further reflux. The reaction mixture was cooled at room temperature and the final red product
was collected through filtration, washed repeatedly with hot methanol to remove the unreacted
dialdehyde. The red colored material was dried in air and was designated as PIFꢀSBAꢀ15.
Synthesis of Cu-PIF-SBA-15. 1 g of the light red colored PIFꢀSBAꢀ15 was suspended in
20 ml absolute ethanol under stirring condition. Then 0.2 g of Cu(OAc)2.H2O was added into the
ethanol solution and was refluxed for about 12 h at 363 K. The color of the mesoporous material
was changed into brown color. The reaction mixture was cooled at room temperature and the
resulting mesoporous material was filtered through suction with thoroughly washing with
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ethanol. The isolated brown colored mesoporous solid was designated as CuꢀPIFꢀSBAꢀ15
catalyst. The outline for the preparation of this CuꢀPIFꢀSBAꢀ15 catalyst is shown in Scheme 1.
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General procedure for one-pot three component C-S coupling reaction over Cu-PIF-
SBA-15. An ovenꢀdried round bottomed flask equipped with magnetic stirring bar was charged
with K2CO3 (552 mg, 4 mmol), thiourea (91 mg, 1.2 mmol), aryl halide (1 mmol), benzyl
bromide (188 mg, 1.1 mmol) and CuꢀPIFꢀSBAꢀ15 (25 mg) in 5 ml water. Then the resulting
mixture was refluxed in a preheated oil bath at 373 K under aerobic condition for the appropriate
reaction time. Progress of the reaction was monitored by TLC. After a period of time the reaction
was stopped and the reaction mixture was cooled at room temperature. Cuꢀcatalyst was collected
by filtration. Then the catalyst was washed repeatedly with water to remove the unreacted base
and thiourea. Then the filtrate was extracted with EtOAc. The combined organic layer was
washed with water and brine solution. Then the combined organic layer was dried over
anhydrous Na2SO4 and evaporated to dryness to deliver the desired aryl alkyl thioethers as
colorless oil. The isolated crude product was characterized by 1H and 13C NMR. The one pot CꢀS
coupling reaction of aryl halide by using thiourea and benzyl bromide catalyzed by CuꢀPIFꢀ
SBAꢀ15 catalyst using H2O as a solvent is depicted in the Scheme 2.
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Results and discussion
The small angle Xꢀray powder diffraction patterns for the PIFꢀSBAꢀ15 and CuꢀPIFꢀSBAꢀ
15 samples are shown in the plots a and b of Figure 1. As seen from the figure that PIFꢀSBAꢀ15
material displays three characteristic diffraction peaks in the 2θ region of 0.9 to 2.0 and these can
be attributed for the 100 (strong), 110 (weak) and 200 (weak) reflections corresponding to the
2Dꢀhexagonal mesostructure (Figure 1a). Decrease in the intensities of the peaks for the 110 and
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200 planes for CuꢀPIFꢀSBAꢀ15 could be attributed to the grafting of Cu(II) complexes at the
surface of the imine functionalized mesoporous SBAꢀ15 material, which causes the lowering of
local order (Figure 1b).35 Whereas an increase in the dꢀspacing associated with the grafting of
Cu(II) complexes in CuꢀPIFꢀSBAꢀ15 material (Figure 1b) could be responsible for the small shift
in the XRD pattern. N2 adsorption/desorption isotherms for the CuꢀPIFꢀSBAꢀ15 catalyst has
been given in the Figure 2. The material presents typical type IV isotherm with a very large H2
type hysteresis loop in the 0.5 to 0.8 relative pressure of N2. Mesopores with ordered
arrangement can be established from this isotherm and the large hysteresis loop, which is the
special feature for the large tubular pores of SBAꢀ15. The BET surface area for CuꢀPIFꢀSBAꢀ15
material is 208 m2gꢀ1. The pore size distribution of the material has been shown in the inset of
Figure 2. The pore size distribution has been calculated by employing nonꢀlocal density
functional theory (NLDFT) method, which suggests that large mesopores having dimensions ca.
6.3 nm are uniformly distributed throughout the material. Pore volume of this material is 0.209
ccgꢀ1. This pore volume is large enough to allow diffusion of bulky organic molecules
throughout the mesoporous channel and helps them to interact with each other for performing
this oneꢀpot three component coupling reaction.27
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TEM images of the CuꢀPIFꢀSBAꢀ15 catalyst are shown in the Figure 3. Figure 3A also
suggests that the large mesopores having dimensions ca. 6ꢀ7 nm are arranged regularly in a
honeyꢀcomb like hexagonal array throughout the material. Information regarding channel
directions, which are parallel to the thickness of the plate and the 110 reflection planes in the
sample is noticeable from the TEM image (Figure 3B, perpendicular to the pore axis). The Fast
Fourier Transform (FFT) pattern of a selected area of the sample (inset of the Figure 3B) reveals
the 2Dꢀhexagonal arrangement of the large mesopores.36 The black colored spots observed in the
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TEM images (Figures 3A and 3B) are the Cuꢀnanoclusters, which could be formed due to the
coordination of phenolic–OH group and imineꢀnitrogen atoms with Cu2+. The TEM image of the
blank mesoporous SBAꢀ15 without Cu has been shown in the Figure 3D. From this image it is
quite evident that the pores having dimension 6ꢀ7 nm are not blocked with the copper. No black
colored spots are found at the surface of the pores for this blank mesoporous SBAꢀ15 material
devoid of copper (Figure 3D). EPR spectra for the CuꢀPIFꢀSBAꢀ15 material (Figure 4)
displayed four splitting features (mI= ꢀ3/2, ꢀ1/2, +1/2, +3/2) in the lowꢀfield region for the
parallel component, which are generated due to the hyperfine coupling between the unpaired
electron and the nuclear spin of copper (I=3/2). But the signal for the perpendicular component
(g┴= 2.07) remains unꢀresolved. From this EPR spectrum we can conclude that Cu2+ cations
present in the sample assume axial symmetry. Another two important parameters g║= 2.26 and
A║= 165G can be calculated from this EPR spectrum, which suggests the significant tetrahedral
distortion of square planar complex around the Cu(II) ion.37 In a planar bonding g║ decreases and
A║ increases in the order of CuO4>CuO3N>CuO2N2>CuN4. Here in our EPR spectrum for Cuꢀ
PIFꢀSBAꢀ15 catalyst g║ and A║ values are 2.26 and 165G, respectively. Thus from the A║ and
g║ values it can be concluded that tetrahedrally distorted Cu(II) discrete units are present in Cuꢀ
PIFꢀSBAꢀ15.38
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FT IR spectrum for phloroglucinolꢀdiimine functionalized SBAꢀ15 (PIFꢀSBAꢀ15, Figure
5a) shows the peak at 1649 cmꢀ1, which can be attributed to the C=N bond stretching frequency
of the imine bond. IR spectrum of CuꢀPIFꢀSBAꢀ15 material (Figure 5b) displays the peak for the
C=N stretching frequency at ca.1631 cmꢀ1, which has been shifted to higher wavenumber,
indicating that C=N bond is coordinated to Cu(II) through the lone pair of electron of nitrogen of
Schiffꢀbase ligand. The two strong absorption bands centered at 1564 cmꢀ1 and 1456 cmꢀ1 is
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attributed to the asymmetric and symmetric vibrations, respectively, of the bridging acetate
ions.39 This result clearly signifies that Cu has been covalently grafted into the mesopores
channel of the PIFꢀSBAꢀ15 material via coordination with imine N and O donors of
phloroglucinolꢀdiimine Schiffꢀbase ligand. The two Cu atoms are linked together by bridging
acetate ions.
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Extended Xꢀray absorption fine structure (EXAFS spectrum) of CuꢀPIFꢀSBAꢀ15 (Figure
6A) catalyst illustrates very small preꢀedge peaks due to 1s→3d transition at 8999.2 eV,
corresponding to the oxidation state of Cu as ∼+2. To get a more quantitative insight, the
χ
(R)
experimentally obtained
with theoretically generated spectra (Figure 6B). To start with, the experimental spectrum the
(R)
versus R spectra of the CuꢀPIFꢀSBAꢀ15 sample has been fitted
χ
known crystallographic structure of CuO has been used to generate the theoretical
versus R
spectrum of the sample. Catalyst environment and the coꢀordination number of Cu in the Cuꢀ
PIFꢀSBAꢀ15 catalyst are given in Table 1. A CuꢀO first shell at a distance of 1.95 Å and having a
coordination number of 4, a second CuꢀO shell at a distance of 2.78 Å and having a coordination
number of 2 and a third CuꢀCu shell at distance of 2.90 Å and having coordination of 4 have
been considered as a reference to provide the theoretical spectrum of the sample upto a distance
χ
(R)
of 4 Å from the central Cu atom. Subsequently, the theoretically generated
versus R
R
spectrum has been fitted with the experimentally obtained spectrum with the bond distance ( ),
N
σ 2
coordination number ( ) and the DebyeꢀWaller factor ( , representing the thermal and
χ(R)
structural disorders) as fitting parameters. The experimentally obtained
versus R spectra of
the catalyst CuꢀPIFꢀSBAꢀ15 catalyst was subsequently been fitted the bestꢀfit curves in Figure
6B. Further, the best fit parameters have been given in Table 1. This EXAFS analysis data (Table
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1) of the CuꢀPIFꢀSBAꢀ15 catalyst clearly proves that the CuꢀO coordination takes places in the
Cuꢀcomplex grafted with the SBAꢀ15 material.
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FEꢀSEM images of CuꢀPIFꢀSBAꢀ15 are shown in the Figure 7. From the Figures 7A and
7B it is definitely observed that Cu nanoclusters (having dimensions ca 0.22ꢀ0.3 ꢁm) are formed
due to the coordination of imineꢀN atoms and O atoms of phenolic–OH groups and these are
dispersed homogeneously throughout the surface of the material. The SEM images reveal that
the Cuꢀnanoclusters are attached onto the surface of the functionalized silica and they form an
isolated irregular cluster island with a wide size distribution. The image further revealed that the
white contrasts observed throughout the specimen are the locally populated Cuꢀnanoclusters.
Actually these Cu nanoclusters are strongly anchored with the organic ligands which are viewed
from the upper surface of the catalyst. The physical phenomena involve for the generation and
stabilization of Cuꢀnanoclusters are the (i) interaction at the surface and (ii) diffusion of
nanoclusters at the surface. These Cuꢀnanoclusters are generated due to the interaction of the
surface functional groups with the metal ions. Now these already generated Cuꢀnanoclusters
along with the other Cuꢀcoordinated sites undergo diffusion to develop larger cluster island at the
surface.40 As a result catalytically active Cuꢀnanoclusters are more exposed at the surface of the
catalyst,41 which facilitates the interact with the organic reactants readily in the oneꢀpot three
component CꢀS coupling reaction.
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Catalysis:
CuꢀPIFꢀSBAꢀ15 mesoporous heterogeneous catalyst has been employed in a series of
oneꢀpot CꢀS coupling reaction of different aryl halides with thiourea and benzyl bromide in
aqueous medium under aerobic conditions (Scheme 2). We have performed a control experiment
to make sure that the catalytic activity originates from the grafted Cuꢀsites into the mesoporous
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channel of the CuꢀPIFꢀSBAꢀ15 catalyst (Table 2). The oneꢀpot CꢀS coupling reaction of 4ꢀ
bromoanisole, thiourea and benzyl bromide was taken as a representative case to carry out this
control experiment. At first the reaction was performed in absence of any catalyst (Table 2, entry
1) in aqueous medium at 100 oC. However, no product formation was observed in this case. We
have also carried out this threeꢀcomponent coupling reaction by using SBAꢀ15, SBAꢀ15ꢀNH2
and PIFꢀSBAꢀ15 (Table 2, entries 2, 3 and 4) as the catalysts at 100 oC in H2O. But in these cases
also no reaction takes place and the starting components remain unreacted. Triggered by these
unsatisfied results, the reaction was carried out by using homogeneous phase Cu(OAc)2.H2O as
catalyst (Table 2, entry 5). In this case product yield was 42%. This result clearly proves that the
catalytic activity generates from the Cuꢀsites. But due to homogenous nature of the
Cu(OAc)2.H2O it cannot be reused and recycled for further times. Homogeneous part of the
catalyst with a loading 0.14 mmol gꢀ1 takes 15 h to carry out the reaction with the corresponding
product yield 42%. But when this homogeneous part of the catalyst is grafted in the imine
functionalized mesoporous SBAꢀ15 material with a loading 0.164 mmol gꢀ1, then the rate of the
catalytic reaction is drastically increased. Loading is increased in about 0.02 mmol gꢀ1 in our
catalyst compared with the homogeneous counterpart. So from this result we can conclude that
the rate of the catalytic reaction has been increased with the increase of loading of copper by
little bit amount for our CuꢀPIFꢀSBAꢀ15 catalyst compared with the homogeneous counterpart of
the catalyst. Then the reaction was performed using Cuꢀnanoparticles grafted SBAꢀ15 (Table 2,
entry 6) under same reaction condition. In this case yield of the product has been increased a
little. But when this oneꢀpot coupling reaction was carried out in the presence of CuꢀPIFꢀSBAꢀ15
catalyst (Table 2, entry 7) then the yield significantly increased upto 79%. This experimental
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result proves that the surface area and mesoporocity offer a decisive role for performing oneꢀpot
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three component CꢀS coupling reaction for preparation of different substituted thioethers. Large
surface area allows the diffusion of organic molecules into the mesoporous channel of
functionalized SBAꢀ15 material and helps them to interact with the Cuꢀnanoclusters grafted at
the surface. That is why the rate of this CꢀS coupling reaction is quite high than the other
conventional catalysts.
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Effect of reaction temperature. Temperature plays a crucial role in the catalytic activity
of CuꢀPIFꢀSBAꢀ15 for this CꢀS coupling reaction in aqueous medium considering the reaction of
4ꢀbromoanisole, thiourea and benzyl bromide as a representative case (Table 3). Table 3 further
revealed that no reaction occurred at 25 °C while conversion increased steadily up to 100 °C
with no further benefit above this temperature.
Effect of solvent. In order to optimize the best solvent needed for this reaction, we have
carried out this oneꢀpot CꢀS coupling reaction in various solvent under aerobic condition over
CuꢀPIFꢀSBAꢀ15 as catalyst. The oneꢀpot aryl sulfur coupling reaction of 4ꢀbromoanisole,
thiourea and benzyl bromide in the presence of K2CO3 base has been considered as the
representative case. The results are listed in the Table 4. All the reactions have been performed
under refluxing condition considering the different solvents. Only reaction in DMF has been
o
conducted at 110 C. For the solvent like THF poor yield of product is obtained. But with the
addition of polar protic solvent in THF yield increased upto 10%. As the lack of solvation on the
nucleophile (here thiolate ion) increases the rate of substitution reaction. When EtOH (polar
protic) was used as solvent then the thiolate ion gets solvated through solvation and hence 40%
product yield was obtained. When polar aprotic solvents like DMF and CH3CN are used then
50% and 45% yield of products are obtained, respectively. Here yield has been increased a little
bit amount compared with the polar protic solvent EtOH due to presence of naked thiolate
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nucleophile. But surprisingly in water 79% yield of product was obtained, which may be due to
the good solubility of thiourea and potassium carbonate in water. Thus, for this oneꢀpot
thioetherification reaction by using CuꢀPIFꢀSBAꢀ15 catalyst water can be regarded as the best
solvent.
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Oneꢀpot three component CꢀS coupling reaction under optimized condition (water as
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reaction medium and 100 C reaction temperature) was performed by considering various
aromatic halides (bromide and chloride) with benzyl bromide and thiourea (Table 5). The times
(h) taken to carry out the reaction for different compounds are given in the Table 5. The results
of Table 5 suggest that reaction takes 10ꢀ12 h for completion for all bromoꢀ and chloroꢀarenes
and the respective turn over numbers (TONs) are moderately high ca 171ꢀ193. 1H and 13C NMR
results are listed in the supporting information (ESI). Cu content in the fresh CuꢀPIFꢀSBAꢀ15
catalyst was 0.164 mmol gꢀ1 as measured by ICPꢀAES analysis. Electron donating (Table 5,
entries 1, 5 and 9) and electron withdrawing (Table 5, entries 2, 4, 6, 7, 10, 11, 12, 13 and 14)
functional groups attached with the aryl chlorides and bromides underwent oneꢀpot Sꢀarylation
reaction very smoothly. The metaꢀsubstituted bromoꢀ and chloroꢀarenes (Table 5, entries 9 and
14) participated in the aryl sulfur coupling reaction without any complexity. Thus the nature and
position of the functional groups attached with the aryl bromides and chlorides do not play
significant role for this reaction. Heterocyclic bromide likes 4ꢀbromopyrazole (Table 5, entry 8)
became compatible for this reaction. Several sensitive functional groups such as ꢀCl, ꢀBr, ꢀNO2
attached with the aromatic ring took part in the reaction with equal efficiency (Table 5, entries 9ꢀ
14).
Reusability of the catalyst. In order to check reusability of the CuꢀPIFꢀSBAꢀ15 catalyst,
the oneꢀpot CꢀS coupling reaction of 4ꢀbromoanisole, thiourea and benzyl bromide under
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optimized reaction conditions was carried out. After the completion of the reaction, catalyst was
recovered from the reaction mixture by employing simple separation technique. Then the catalyst
was washed with copious amount of water to remove excess base and thiourea. Then catalyst
was again washed with ethyl acetate followed by with diethyl ether to remove excess organic
reactants. Then the recovered catalyst was dried in air and activated in an oven at 75 oC for about
6 h. The CuꢀPIFꢀSBAꢀ15 catalyst had the potential of efficient recycling for further six
additional reaction cycles without significant loss of catalytic activity establishing the recycling
and reusability of the catalyst. Only very little drop in the product yield in each catalytic cycle is
observed. It is quite evident from the Table 6 that the TON of the catalyst is retained from fresh
to the 6th reaction cycles, suggesting high catalytic efficiency of CuꢀPIFꢀSBAꢀ15.
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Leaching Test. Leaching test was performed to understand the nature of the CuꢀPIFꢀ
SBAꢀ15 catalyst. After the reaction was over, the catalyst was separated by filtration. Then 30
wt% of nitric acid was added to the filtrate, and the resulting solution was adjusted to 5 wt%
nitric acid solution. Now Cu content in the filtrate solution was determined by using Atomic
absorption spectrometric (AAS) analysis. Atomic absorption spectrometric analysis of the liquid
phase suggested absence of Cu in the filtrate and it remains completely colorless. Further, the
ICPꢀAES analysis for the reused catalyst confirms that no leaching of Cu takes place during the
course of reaction. Cu content has been marginally reduced to 0.159 mmol gꢀ1 after the sixth
catalytic reaction cycle (this decrease is within the experimental error of the ICPꢀAES chemical
analysis). These experimental results clearly signify that no leaching of Cu occurred during the
course of the reaction and Cuꢀnanoclusters are covalently grafted with the organic functional
groups in the mesoporous silica. Thus, CuꢀPIFꢀSBAꢀ15 catalyzed CꢀS coupling reactions are
purely heterogeneous in nature.
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Hot filtration Test. Hot filtration test was carried out under optimized condition
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considering 4ꢀbromo anisole as the representative case. After 6 h of the reaction it has been
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realized that only ca. 50% conversion was achieved, confirmed by GC and H NMR analysis.
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Then the CꢀS coupling reaction was again continued with this filtrate for another 6 h under the
similar reaction conditions. But no further increase in product conversion after another 6 h
reaction time was observed. This experimental result clearly proves that Cu complex
nanoclusters are covalently anchored with the organic functional groups in the mesopore surface
of functionalized SBAꢀ15 material. No further increase in product conversion beyond 50% has
been observed. This further suggested no leaching of Cu during the course of reaction and
heterogeneous nature of the catalyst. AAS analysis for the Cu content in used CuꢀPIFꢀSBAꢀ15
catalyst revealed 1.05 wt% Cu, which is a close agreement with the Cu loading of the fresh
catalyst estimated independently from the ICPꢀAES analysis.
Plausible reaction pathway. Oneꢀpot three component CꢀS coupling reaction proceeds
via in situ formation of S
ꢀalkylisothiouronium salt.19 The plausible reaction pathway catalyzed
by CuꢀPIFꢀSBAꢀ15 catalyst for the development of aryl alkyl thioether has been shown in the
Figure 8. At the first step, thiourea reacts with benzyl bromide in the presence of K2CO3 base to
produce Sꢀalkylisothiouronium salt. This Sꢀalkylisothiouronium salt has been hydrolyzed with
base to generate thiolate ions and urea. Pyrolysis of urea upon heat treatment of the reaction
mixture takes place to offer CO2 (g) and ammonia. Generated thiolate ions are the synthetic
equivalent of thiols. Aryl halide in undergoes oxidative addition reaction with the Cu(II)ꢀ
complex grafted into the mesoporous wall of phloroglucinolꢀdiimine functionalized SBAꢀ15
material to afford an intermediate (A). Then in situ generated thiol moiety takes part into the
nucleophilic addition reaction with the intermediate (A) to produce an aryl organocopper sulfide
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intermediate (B). This intermediate B on reductive elimination provided cross coupled aryl alkyl
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thioether.
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Characterization of the reused catalyst: Reused catalyst was further characterized by
small angle powder XRD pattern, TEM and SEM analyses in order to investigate any further
noticeable change occurs in the catalyst after the catalysis. Small angle powder Xꢀray diffraction
pattern of the reused catalyst (Figure 1c) displays the characteristic mesophase of the CuꢀPIFꢀ
SBAꢀ15 catalyst. Only a little decrease in the intensity of peak for the reused catalyst in the XRD
pattern is observed, which may be due to the blocking of some mesopores by organic molecules
during the course of reaction. From this XRD pattern we can conclude that the 2Dꢀhexagonal
mesophase of the CuꢀPIFꢀSBAꢀ15 catalyst has been preserved after the catalysis. A little shift in
the powder XRD pattern of reused catalyst occurs (Figure 1c). After several repetitive reaction
cycles the expansion in poreꢀwall for the reused catalyst could occur due to the hydrolysis of
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silica species present at the catalyst surface. As a result
dꢀspacing for the reused catalyst is
increased. This increase in the ꢀspacing is responsible for the shift in the peak position for the
d
reused catalyst. TEM image (Figure 3C) of the reused catalyst suggests that the 2Dꢀhexagonal
mesostructure of the CuꢀPIFꢀSBAꢀ15 material has been retained and there is no obvious change
in uniform distribution of Cuꢀnanoclusters throughout the material after the catalysis. SEM
images of the reused CuꢀPIFꢀSBAꢀ15 catalyst (Figures 7C and 7D) further suggest us that there
is no change in the morphology and size of the Cuꢀgrafted sites during the catalysis. The above
results imply that the catalyst was very stable during the catalysis and could sustain these
conditions.
Conclusions
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In conclusion, we have developed a novel Cu(II)ꢀgrafted phloroglucinolꢀdiimine
functionalized mesoporous SBAꢀ15 material by using post grafting technique. Surface
functionalization, Schiffꢀbase condensation followed by Cu(II) impregnation resulted this Cuꢀ
grafted phloroglucinolꢀdiimine functionalized mesoporous SBAꢀ15. This novel mesoporous
catalyst CuꢀPIFꢀSBAꢀ15 has been employed to carry out an efficient, oneꢀpot, odorless CꢀS
coupling reaction of aryl halides (bromides and chlorides) using thiourea and benzyl bromide in
aqueous medium in the presence of K2CO3 base at 100 oC. This novel protocol is free from foulꢀ
smelling thiols for preparation of CꢀS bond is easy, clean, inexpensive, practical and
environmentally benign. This catalyst showed negligible leaching of Cu, and can be reused for
six repetitive reaction cycles without significant loss of any catalytic activity. Thus, growing
demand of environmentally benign synthesis could be achieved over CuꢀPIFꢀSBAꢀ15 in this CꢀS
coupling reactions using water as the reaction medium.
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Supporting Information
Characterization techniques, Preparation of Cuꢀnanoparticles supported over SBAꢀ15, 1H
and 13C NMR chemical shifts for different coupling products are available in the Supporting
Information. This information is available free of charge via the Internet at http://pubs.acs.org/.
Acknowledgements
JM and AM thank CSIR, New Delhi for their respective senior research fellowships.
Prof. Asim Bhaumik wishes to thank DST Unit on Nanoscience for providing instrumental
facility at IACS. JM, PB and Prof. Zhao thank the Singapore National Research Foundation
Fellowship (NRF2009NRFꢀRF001ꢀ015), Singapore National Research Foundation CREATE
program—Singapore Peking University Research Centre for a Sustainable LowꢀCarbon Future,
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and Nanyang Technological University for financial support and to help for further
measurements.
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2011
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335, 236ꢀ241.
(30) Mondal, J.; Sen, T.; Bhaumik, A. Dalton Trans., 2012, 41, 6173–6181.
(31) Mondal, J.; Modak, A.; Bhaumik, A. J. Mol. Catal. A: Chem. 2011,
350, 40ꢀ48.
(32) Mondal, J.; Modak, A.; Dutta, A.; Basu, S.; Jha, S. N.; Bhattacharyya, D.; Bhaumik, A.
Chem. Commun. 2012 48, 8000–8002.
(33) Wang, JꢀQ.; Huang, L.; Xue, M.; Wang, Y.; Gao, L.; Zhu, J. H.; Zou, Z. J. Phys. Chem.
2008, 112, 5014ꢀ5022.
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Table 1 Bestꢀfit parameters of the bond distance, coordination number and the DebyeꢀWaller
5
6
factors for the CuꢀPIFꢀSBAꢀ15 catalyst.
7
8
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
Cu-O1
1.97
Cu-O2
2.71
Cu-Cu
3.37
R (Å)
N
2.5
0.9
1.5
σ 2
0.005
0.005
0.005
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Table 2 Screening of different catalysts for oneꢀpot three component CꢀS coupling reactiona
3
4
5
6
7
8
Entry
Catalyst
Time (h)
Yieldb(%)
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
1
2
3
4
5
No catalyst
SBAꢀ15
15
15
15
15
15
0.0
0.0
SBAꢀ15ꢀNH2
PIFꢀSBAꢀ15
Cu(OAc)2.H2Oc
0.0
0.0
42.0
Cu nanoparticles
supported over SBAꢀ15
6
7
15
12
50.0
79.0
CuꢀPIFꢀSBAꢀ15d
aReaction conditions: 4ꢀbromoanisole (1 mmol, 187 mg), benzyl bromide (1.1 mmol, 188 mg),
thiourea (1.2 mmol, 91 mg), K2CO3 (4 mmol, 552 mg), solvent (H2O, 5 ml), temperature (100
oC) CuꢀPIFꢀSBAꢀ15 Catalyst (25 mg). Isolated yield of product, Cu loading 0.14 mmol gꢀ1.
b
c
d
Cu loading in CuꢀPIFꢀSBAꢀ15 catalyst 0.164 mmol gꢀ1.
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Table 3 Effect of reaction temperature (oC) for oneꢀpot three component CꢀS coupling reactiona
3
4
5
6
7
8
9
Entry
Temperature (oC)
Yieldb (%)
No reaction
5
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
1
2
25
40
3
4
5
60
80
30
60
79
100
aReaction conditions same as that given in Table 2. All the reactions were performed for 12 h.
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Table 4 Variation of different solvents for oneꢀpot three component CꢀS copuling reactiona
3
4
5
6
7
8
9
Solvent
THFb
Yield (%)
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
5
THF: H2O (1:1)c
EtOHd
10
40
50
45
79
DMFe
CH3CNf
H2Og
aReaction conditions same as that given in Table 2, b65 oC, c65 oC, d90 oC, e110 oC, f80 oC, g100
oC. All the reactions were performed for 12 h; Cu loading in CuꢀPIFꢀSBAꢀ15 catalyst 0.164
mmol gꢀ1.
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Table 5 Oneꢀpot three component CꢀS coupling reaction of different haloarenes catalyzed by
CuꢀPIFꢀSBAꢀ15 catalyst under optimized reaction conditiona
Entry
Aryl Halides
Time
(h)
Product
Yield
(%)
TONb
193
191
183
183
8
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
H3CO
Br
12
10
12
10
79
78
75
75
1
2
3
4
H3CO
O2N
S
S
O2N
Br
Br
S
S
S
OHC
H3C
Br
Br
OHC
H3C
12
12
10
12
78
76
75
78
191
185
183
191
5
6
7
8
H3COC
NC
Br
H3COC
NC
S
Br
S
N
NH
N
S
Br
NH
HO
S
HO
Br
12
78
191
9
OHC
OHC
O2N
Cl
12
12
75
72
183
175
10
11
O2N
S
S
OHC
Cl
OHC
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9
NC
Cl
12
12
12
75
70
70
183
171
171
12
13
14
NC
S
H3COC
HO
Cl
H3COC
HO
S
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
S
Cl
aReaction conditions is same as that given in Table 2.; Turn over number (TON) = moles of
b
substrate converted per mole of active site; Cu loading in CuꢀPIFꢀSBAꢀ15 = 0.164 mmol gꢀ1.
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Table 6 Recycling potential of mesoporous CuꢀPIFꢀSBAꢀ15 catalyst in CꢀS coupling reactions
5
6
7
8
9
No. of cycles
Yield (%)
Time (h)
TON
Fresh
79
Run 1
79
Run 2
79
Run 3
77
Run 4
77
Run 5
75
Run 6
74
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
12
12
12
12
12
12
12
193
193
193
187
187
183
180
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