8000 Chem. Commun., 2012, 48, 8000–8002 This journal is c The Royal Society of Chemistry 2012

Cite this: Chem. Commun., 2012, 48, 8000–8002

One-pot thioetherification of aryl halides with thiourea and benzyl

bromide in water catalyzed by Cu-grafted furfural imine-functionalized

mesoporous SBA-15w

John Mondal,a Arindam Modak,a Arghya Dutta,a Sohini Basu,b Shambhu Nath Jha,b

Dibyendu Bhattacharyyaband Asim Bhaumik*

a

Received 8th February 2012, Accepted 26th June 2012

DOI: 10.1039/c2cc32676k

Surface functionalization of SBA-15 followed by its reaction

with Cu(OAc)2 has been carried out to develop a new Cu-grafted

functionalized mesoporous material, which catalyzes one-pot

three component coupling of different aryl halides with thiourea

and benzyl bromide in aqueous medium to produce aryl thioethers

in very good yields (80–88%).

The construction of carbon–sulphur bonds represents an

indispensable tool for the synthesis of many target molecules

that have significant pharmaceutical impact. These compounds

are also used as molecular precursors for the design of new

functionalized materials.1 A number of drugs, which are applied

for the treatment of Alzheimer’s disease, Parkinson’s disease

and diabetes, as well as immune and inflammatory diseases,

carry aryl sulfide moieties at their backbone unit.2 In recent

years, a great deal of attention has been paid to the new, green

and efficient synthetic protocols for C–S bond construction,

especially under eco-friendly and safe reaction conditions.3

Cross-coupling reactions mediated by transition metal catalysts4

become a valuable tool in organic synthesis and material science

for the generation of new carbon–heteroatom bonds.5 Preparation

of thioethers via aryl sulfur coupling reaction of aryl halides and

thiols has been conducted in the presence of various catalysts, such

as Pd,6 Cu,7 Ni,8 Co and Fe salts.9 The problems traditionally

associated with these C–S coupling reactions include direct use of

volatile and foul-smelling thiols, which leads to environmental and

safety problems and limits the use of this method for large scale

operation. Moreover, these C–S coupling reactions are mostly

carried out in the presence of expensive, toxic, flammable

organic solvents and their disposal becomes a serious problem

for the chemical industry.10 Thus, designing an efficient and

environmentally friendly catalytic process for C–S coupling

reactions is highly desirable.

To eliminate these problems, new catalytic methods under

solvent-free conditions,11 using ionic liquids12 and water13 as the

reaction medium have been developed. Being a cheap, abundant,

non-toxic, non-flammable and relatively green solvent, replacement

of the organic solvents by water becomes an essential achievement

to address the industrial and environmental concerns.14

Two novel protocols for C–S bond forming reactions, including

one-pot Michael addition reactions via an odourless process

involving in situ generation of S-alkylisothiouronium salts in

water15 and one-pot thioetherification of aryl halides using

thiourea16 (free from the foul smell of thiols), have been

developed in recent years. But these newly developed protocols

are carried out in the presence of metal complexes as a

homogeneous catalyst, which has disadvantages of difficult

product separation from reaction mixture, recovery of catalyst

and problems associated with the recycling of the catalyst. One

of the simplest approaches is to immobilize the homogeneous

catalyst at the surface of an insoluble high surface area solid

support.17 Functionalized silica materials containing surface

donor sites can bind the metal cations at the surface of the

catalyst strongly and, as a result, the possibility of the leaching

of active metal sites from the catalyst surface would be low

during the liquid phase reaction. Organically functionalized

mesoporous materials have gained increasing attention as

adsorbents,18 catalysts,19 gas storage,20 conducting materials21

etc. due to their high surface area and tunability of the surface

functionality. Metal sites are grafted inside the pores, thus

becoming an alternative inexpensive, non-air sensitive, recycl-

able and easily separable heterogeneous catalyst, which could

address industrial and environmental concerns.

In this communication, we first report the synthesis of a new

furfural imine-functionalized mesoporous SBA-15 catalyst

grafted with Cu(II) (Scheme 1) and its excellent catalytic

activity in an efficient, one-pot, odourless process for

thioetherification reaction of aryl halides with benzyl bromide

and thiourea in aqueous medium in the presence of K2CO3

base at 100 1C. This heterogeneous catalyst was developed via

surface functionalization with 3-aminopropyl-triethoxysilane,

followed by Schiff-base condensation of the surface –NH2

groups with furfural. Cu(OAc)2 in absolute ethanol is allowed

to react with the Schiff-base anchored mesoporous SBA-15 to

aDepartment of Materials Science, Indian Association for theCultivation of Science, Jadavpur, Kolkata-700 032, India.E-mail: msab@iacs.res.in; Fax: +91 33 2473 2805;Tel: +91 33 2473 4971

bApplied Spectroscopy Division, Bhabha Atomic Research Centre,Mumbai-400085, India

w Electronic supplementary information (ESI) available: XRD, EXAFS,N2 sorption, MASNMR, EPR, FT IR, UV of Cu-F-SBA-15, recycling ofcatalyst, 1H and 13C NMR of thioethers. See DOI: 10.1039/c2cc32676k

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This journal is c The Royal Society of Chemistry 2012 Chem. Commun., 2012, 48, 8000–8002 8001

produce novel Cu(II) grafted mesoporous SBA-15 catalyst

Cu-F-SBA-15 (Scheme 1).

The small angle X-ray powder diffraction pattern for 3-amino-

propyl functionalized SBA-15 (A) (Fig. S1a, ESIw) shows three

characteristic diffraction peaks in the 0.9 to 2.0 degrees of 2y and

these can be attributed to the 100 (strong), 110 (weak) and

200 (weak) reflections, respectively, corresponding to the

2D-hexagonal mesophase.When this 3-aminopropyl-functionalized

SBA-15 (A) was subjected to Schiff-base condensation (B) and

subsequent reaction with Cu(OAc)2 (C), then a considerable

decrease in the intensities of the peaks are observed (Fig. S1b

and c, ESIw), however a single intense peak is present in the

both samples, suggesting the preservation of the mesophase.

This decrease in the peak intensities on grafting of Cu at the

surface could be attributed to the lowering of local order.22 The

wide angle XRD pattern of Cu-F-SBA-15 suggested a new

orthorhombic phase of the pore wall and this has been retained

after catalytic recycling (Fig. S2–S3, Table S1, ESIw).N2 sorption analysis suggested Cu-F-SBA-15 (Fig. S4, ESIw)

has a BET surface area and pore volume of 117 m2g�1 and

0.126 ccg�1, respectively. SEM analysis suggested that the

material has a rod-shaped particle morphology (Fig. S5, ESIw).Furthermore, FTIR spectra indicate the coordination of Cu

with the imine CQN bond and bridging acetate ions as shown

for species C in Scheme 1 (Fig. S6, ESIw). UV-vis spectra

(Fig. S7, ESIw) suggested the charge transfer and d–d transitions of

Cu+2. Furthermore, solid state 13C and 29Si MAS NMR results

suggested the presence of organic species and Si environments

in Cu-F-SBA-15 (Fig. S8, ESIw). The HR TEM image of

Cu-F-SBA-15 (Fig. 1A) clearly suggests a uniform honeycomb-

like hexagonal array of ordered pores (dimension ca. 4.0–4.6 nm).

The FFT diffractogram (inset) suggested 2D-hexagonal pore

channels.23 Furthermore, in this TEM image the black colour

spots could be attributed to the presence of grafted Cu-sites

formed due to the coordination of imine-N and furfural-O atom

with Cu(II) at the surface. The TEM image of used Cu-F-SBA-15

catalyst suggested the retention of the hexagonal pores after the

reaction (Fig. 1B). EPR spectra for the Cu-F-SBA-15 (Fig. 1Ca)

showed four splitting features (mI = �3/2, �1/2, +1/2, +3/2)

in the low-field region for the parallel component due to

the hyperfine interaction between the unpaired electron and

the nuclear spin of copper (I= 3/2), whereas the signal for the

perpendicular component (g> = 2.06) remains un-resolved.

These characteristics are typical for isolated Cu2+ cations in

axial symmetry.24 Also, the EPR spectrum of Cu-F-SBA-15

revealed the following parameters: gJ = 2.26 and AJ = 172G,

which is strong evidence for the presence of discrete CuON3 units.

These g andA values resemble those for Cu(II) ions in the distorted

square planar symmetry.24 For the reused catalyst (Fig. 1Cb) the

four splitting patterns and the g>, gJ and AJ values remain

unchanged, suggesting that the geometry and the environment

of the catalyst remain unaltered after reuse. The EPR spectrum of

Cu(OAc)2 on the other hand showed dimeric Cu species with a

much shorter Cu–Cu distance (Fig. S9, ESIw). Furthermore, the

EXAFS spectra of Cu-F-SBA-15 (Fig. 1D) of the fresh and the

used catalyst show very small pre-edge peaks due to 1s-3d

transition at 8977.9 eV, corresponding to the oxidation state of

Cu asB+2.25 Their edge structures are very similar to each other.

This implies that the local structures around the Cu atom in the

reused catalyst remain unchanged after the catalytic reaction.

The catalyst environment and the co-ordination number of Cu

in the fresh and the reused catalyst are obtained from the radial

distribution curve (Fig. S10 and Table S2, ESIw).One-pot thioetherification (Scheme 2) of different aryl halides

using thiourea and benzyl bromide in aqueous medium at 100 1C

over Cu-F-SBA-15 resulted in different aryl alkyl thioethers

(Table 1) in good yields. All of the products are characterized

by 1H and 13CNMR, respectively (ESIw, S12). The Cu content of

the fresh catalyst was 0.986 mmol g�1, as measured by ICP-AES

analysis. The reaction takes 10–12 h for completion for

all bromo- and chloro-arenes and the respective turnover

frequencies (TOFs) are moderately high at ca 85–112

(Table 1). In order to check the heterogeneous nature of the

catalyst, a hot filtration test, leaching test and three phase test

were performed (ESIw, S1). After separation from the reaction

mixture, the recovered catalyst was successively washed with

copious amounts of water to remove excess base, followed by ethyl

Scheme 1 The synthesis of Cu-anchored mesoporous SBA-15

catalyst (Cu-F-SBA-15).

Fig. 1 HR TEM images of fresh (A) and reused (B) catalyst; EPR (C)

and EXAFS (D) of Cu-F-SBA-15 catalyst: fresh (a) and reused (b).

Scheme 2 Cu-anchored mesoporous SBA-15 catalyst mediated one-pot

thioetherification of aryl halides.

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8002 Chem. Commun., 2012, 48, 8000–8002 This journal is c The Royal Society of Chemistry 2012

acetate and then finally with acetone. It was then dried under air

overnight and used in the next cycle. It was observed that the

catalyst can be recycled for six consecutive cycles (ESIw, S13)without significant loss in catalytic activity. On the other hand,

a control experiment with homogeneous phase catalysts

Cu(OAc)2�H2O, SBA-15-supported Cu nanocatalyst, pure

SBA-15 and furfural-SBA-15 (Table S3, ESIw), showed very poor

yields under these conditions. The plausible reaction pathway

could be the same as that suggested by Firouzabadi et al.16 Thus,

our experimental results suggest that Cu-F-SBA-15 is an efficient

and recyclable heterogeneous catalyst for one-pot thioetherification

reaction in aqueous medium for the synthesis of aryl thioethers.

In conclusion, we have developed a novel protocol for one-pot

thioetherification of different aryl halides with thiourea and benzyl

bromide in the presence of K2CO3 base in water medium at 100 1C

over a furfural imine-functionalized Cu-grafted mesoporous

SBA-15 heterogeneous catalyst. This procedure is free from

foul-smelling thiols and work-up becomes easy, practical and

eco-compatible, diminishing environmental concerns. Commercially

available aryl halides make this procedure much easier than using

corresponding thiols via in situ generation of thiolate ions. The

high catalytic efficiency of the Cu-anchored SBA-15 catalyst

suggests the future potential application of this catalytic system

for the synthesis of different unsymmetrical aryl alkyl thioethers.

Notes and references

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Table 1 Thioetherification of different aryl halides (Br, Cl) in aqueousmedium over Cu-F-SBA-15 using thiourea

Entry Aryl HalidesTime(h) Product Yield(%) TOF(h�1)

1 12 82 87.2

2 10 88 112.3

3 12 86 91.5

4 12 85 90.4

5 11 85 98.6

6 12 82 87.2

7 10 84 107.2

8 12 81 86.2

9 10 80 102.1

10 12 86 91.5

11 12 84 89.3

12 12 83 88.3

13 12 80 85.1

14 12 82 87.2

15 10 81 103.4

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