Sustainable synthesis of sulfonamides using supported ionic liquid phase catalyst containing Keggin-type anion

Article abstract of DOI:10.1002/aoc.3407

A silica-supported ionic liquid phase catalyst containing Keggin-type anion has been prepared by covalent grafting of ferrocene-tagged ionic liquid in a matrix of silica followed by anion metathesis reaction. This novel catalyst served as a robust heterogeneous catalyst for the synthesis of biologically active sulfonamides from 4-toluenesulfonyl chloride and amines. Additionally, recycling experiments showed that the catalyst could be reused five times.

Full text of DOI:10.1002/aoc.3407

Full paper
Received: 3 July 2015
Revised: 3 September 2015
Accepted: 20 October 2015
Published online in Wiley Online Library: 22 December 2015
(wileyonlinelibrary.com) DOI 10.1002/aoc.3407
Sustainable synthesis of sulfonamides using
supported ionic liquid phase catalyst
containing Keggin-type anion
Megha Jagadalea, Sharanabasappa Khanapurea, Rajashri Salunkhea,
Mohan Rajmaneb and Gajanan Rashinkara*
A silica-supported ionic liquid phase catalyst containing Keggin-type anion has been prepared by covalent grafting of ferrocene-
tagged ionic liquid in a matrix of silica followed by anion metathesis reaction. This novel catalyst served as a robust heteroge-
neous catalyst for the synthesis of biologically active sulfonamides from 4-toluenesulfonyl chloride and amines. Additionally,
recycling experiments showed that the catalyst could be reused five times. Copyright © 2015 John Wiley & Sons, Ltd.
Additional supporting information may be found in the online version of this article at the publisher’s web-site.
Keywords: ferrocene; supported ionic liquid phase; Keggin-type anion; sulfonamides; reusability
features of SILP catalysts include high activity along with the ease
of separation from the reaction mixture by simple filtration. In addi-
Introduction
The prerequisite of sustainable chemistry is the design, manufacture
and use of efficient, effective, safe and more environmentally benign
chemical products and processes.[1] Within the broad framework of
sustainable development, synthetic chemists are striving to maxi-
mize resource efficiency through activities such as energy and non-
renewable resource conservation, risk minimization, pollution
prevention and minimization of waste at all stages. The frontier in
the architecture of sustainable chemistry is the use of alternative re-
action media that circumvent the problems associated with many of
the traditional volatile organic solvents that are detrimental to the
environment.[2] In this regard, ionic liquids (ILs) have attracted exten-
sive attention due to their extraordinary physical properties superior
to those of volatile organic solvents.[3] Owing to their unique proper-
ties such as negligible vapour pressure, relatively wide electrochem-
ically stable window, high chemical and thermal stability and
selective dissolvability for many organic and inorganic compounds,
ILs have received significant attention as alternative media in organic
synthesis.[4] A unique attribute of ILs is their modularity that allows for
tuning the properties by alterations in cation/anion combinations.[5]
Although the use of alternative reaction media can eliminate waste
and reduce hazard, these changes must be carefully implemented
to avoid unacceptable sacrifices in cost of performance. The applica-
tions of ILs into a business model is extremely challenging as they are
much more costly than traditional solvents, which are currently used
in industries. In addition, their low biodegradability, (eco)toxicological
properties and recovery by distillation have been major obstacles in
their applications at an industrial scale.[6] These drawbacks have
driven the quest for the new concept of supported ionic liquid phase
(SILP) catalysts involving immobilization of ILs onto a surface of a po-
rous high-area support material which provides a highly attractive
strategy to circumvent the drawbacks associated with ILs.[7] This
novel class of advanced materials dramatically reduces the amount
of ILs used without altering their properties. The other attractive
tion, chemical reactions using SILP catalysts can be conducted under
unusual conditions using fixed-bed reactor designs.[8] These interest-
ing properties associated with SILP catalysis have stimulated enor-
mous interest in the development of novel SILP catalysts for
various organic transformations in recent years.[9]
Sulfonamides represent a prominent class of bioactive com-
pounds with diverse therapeutic and pharmacological properties.[10]
In addition to their antibacterial, antifungal, anticonvulsant and anti-
inflammatory activities, various sulfonamides are also known to
inhibit several enzymes including carbonic anhydrase, glycogen
phosphorylase, cholestrolacyl transferase, serine protease, matrix
metalloproteinase and cyclooxygenase.[11] The widespread potential
value of sulfonamides has led to the discovery of commercially
available drugs such as Sildenafil (phosphodiesterase-5 inhibitor),
Amprenavir, Tipranavir (HIV protease inhibitor), Nimesulide (selec-
tive inhibitor of cyclooxygenase 2), Argatroban (thrombin inhibi-
tor), Udenafil (PDE5 inhibitor) and Sumatriptan (5-HT agonist)
(Fig. 1).[12] Recently, it has been reported that they act as transition
state mimetics of peptide hydrolysis and irreversible inhibitors of
cysteine protease.[13] In addition, many of their derivatives have
been used as herbicides and plaguicides.[14] Due to their intriguing
structural features and promising biological activities, sulfonamide
motifs have received significant attention as synthetic targets.
Consequently, large numbers of classical and non-classical methods
have developed for construction of sulfonamide frameworks.[15] The
*
Correspondence to: Gajanan Rashinkar, Department of Chemistry, Shivaji
University, Kolhapur, 416004, MS, India. E-mail: gsr_chem@unishivaji.ac.in
a Department of Chemistry, Shivaji University, Kolhapur, 416004, MS, India
b Sadguru Gadge Maharaj College, Karad, 415110, MS, India
Appl. Organometal. Chem. 2016, 30, 125–131
Copyright © 2015 John Wiley & Sons, Ltd.

M. Jagadale et al.
Figure 1. Bioactive sulfonamide drugs.
base-induced nucleophilic reaction between sulfonyl chlorides with
amines represents the most straightforward and practical way to
construct the sulfonamide core. A variety of synthetic strategies
have been reported for efficient synthesis of sulfonamides from sul-
fonyl chlorides with amines employing various catalysts as well as
microwave and ultrasonication techniques.[16] However, despite the
impressive progress, there remains a need for the development
of efficient methods for the synthesis of sulfonamides especially
using highly robust heterogeneous catalysts. In our continued
interest in the development of highly expedient methodologies for
biologically important scaffolds,[17] we report herein the synthesis
of bioactive sulfonamides from 4-toluenesulfonyl chloride and
amines using silica-supported ionic liquid phase catalyst containing
Keggin-type anion.
Results and discussion
Scheme 1. Synthesis of silica-supported ionic liquid phase catalyst
containing Keggin-type anion, [SilFemImi]3PW12O40
.
SILP catalysts are prepared either by simple adsorption or by cova-
lent attachment of ILs on the surface of high-area porous supports
like silica or polymer-based materials. The covalent binding ap-
proach offers robust SILP catalysts as it avoids the serious drawback
of leaching of ILs under vigorous reaction conditions that is often
encountered with the adsorption approach. The majority of novel
heterogeneous catalysts are primarily based on silica supports since
they display advantageous properties such as excellent chemical
and thermal stability, high porosity, and the fact that organic
groups can be robustly anchored to the surface to provide catalytic
centres. This prompted us to synthesize a silica-based SILP catalyst
using the covalent binding approach. The synthesis of the SILP cat-
alyst is summarized in Scheme 1. The activated silica was function-
alized with 3-chloropropyltriethoxysilane (1) to give 3-chloropropyl
silica following a literature procedure.[18] The IL-like unit was then
grafted on organofunctionalized silica by reacting 3-chloropropyl
silica with ferrocenyl imidazole (2)[19] to give SILP catalyst precursor
[SilFemImi]Cl (3). The anion metathesis reaction of 3 with phospho-
tungstic acid resulted in the desired SILP catalyst containing
Keggin-type anion, [SilFemImi]3PW12O40 (4).
Fourier transform (FT) Raman and FT-IR spectroscopies were
used as diagnostic tools to monitor the progress of the reaction in-
volved in the synthesis of the SILP catalyst. The FT Raman spectrum
of 3 displays peaks at 465 cmÀ1 (Fe–Cp stretching band), 3124,
3185 cmÀ1 (C–H stretching of Cp rings), 1328, 1410 and
1504 cmÀ1 (ring stretching modes of imidazolium ring) confirming
the grafting of ferrocenyl imidazolium units in the matrix of silica.
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Appl. Organometal. Chem. 2016, 30, 125–131

Sustainable synthesis of sulfonamides
The anion metathesis reaction was monitored using FT-IR spectros-
copy. The FT-IR spectrum of 4 displays characteristic peaks of the
Keggin anion at 1064 cmÀ1 (P–O stretching), 900 cmÀ1 (stretching
of W–O–W intra-bridges between corner-sharing WO6 octahedra),
802 cmÀ1 (stretching of W–O–W intra-bridges between corner
edge WO6 octahedra) and 597 cmÀ1 (P–O bending) supporting
the formation of [SilFemImi]3PW12O40. The FT-IR analysis reveals
that the Keggin-type anion is present in the single molecular form.
Elemental analysis of [SilFemImi]Cl reveals grafting of 0.18 mmol of
ferrocenylmethyl imidazolium units per gram. The quantification of
the Keggin-type anion in [SilFemImi]3PW12O40 was done using
energy-dispersive X-ray (EDX) spectroscopy. EDX element mapping
indicates the presence of 0.007 mmol of Keggin-type anion per
gram of SILP catalyst.
The thermogravimetric analysis of the SILP catalyst is shown in
Fig. 2. The thermogram of 4 shows an initial weight loss due to
physisorbed water below 100°C followed by a second small weight
loss centred up to 250 °C owing to the loss of water molecules in-
side the cavity of the Keggin-type anion. The further weight loss
in the range 250–530 °C is attributed to loss of surface-bound or-
ganic scaffolds and decomposition of polyoxometallate anion.
The large residual weight loss is due to formation of silica and me-
tallic oxides.
The morphology of SILP catalyst and pristine silica was studied
using scanning electron microscopy (SEM). From SEM images
(Figs. 3(A) and (B)), it is clear that catalyst particles in 4 are obtained
in a micrometric size with irregular morphology and shape mimick-
ing pristine silica. The X-ray diffraction (XRD) patterns of pristine sil-
ica and SILP catalyst are shown in Fig. 4. The XRD pattern of the
silica support exhibits a characteristic hump of amorphous silica
at a 2θ value of 22.09°. The XRD pattern of 4 reveals an amorphous
nature of the catalyst although there is slight shift in the position of
the hump. The absence of any characteristic reflection of Keggin-
type anion in the XRD pattern of 4 suggests uniform distribution
of anions in the SILP catalyst.
Our next task was to evaluate catalytic activity of the SILP catalyst
in the synthesis of sulfonamides. Initial studies to examine the effect
of solvent and catalyst loading were carried out using a model reac-
tion between 4-toluenesulfonyl chloride (5) and morpholine (6a).
The reaction of 5 (1 mmol) and 6a (1 mmol) in dichloromethane
(5 ml) was performed using various amounts of 4. We observe that
catalyst loading has a decisive influence on the reaction course.
For instance, when the amount of 4 is increased from 50 mg
Figure 3. SEM images of (A) silica, (B) [SilFemImi]3PW12O40 and (C)
recovered [SilFemImi]3PW12O40 catalyst after fourth run.
(0.00035 mol%) to 200 mg (0.0014 mol%) the yield of corresponding
product 4-[(4-methylphenyl)sulfonyl]morpholine (7a) increased con-
siderably (from 50 to 95%; Table 1, entries 1–4). However, a further
increase in catalyst amount does not substantially improve the yield
of product (Table 1, entry 5).
The influence of various solvents was the next variable studied.
To this end, we carried out the model reaction in a number of
Figure 2. Thermogravimetric analysis curve of [SilFemImi]3PW12O40
.
Appl. Organometal. Chem. 2016, 30, 125–131
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M. Jagadale et al.
Table 2. Solvent optimization for the synthesis of sulfonamidesa
Entry
Solvent
DMF
Time (min)
Yield (%)b
1
2
3
4
5
6
7
46
85
75
120
60
40
10
55
30
48
70
60
75
95
CHCl3
Methanol
1,4-Dioxane
Ethanol
CH3CN
CH2Cl2
aReaction conditions morpholine (1 mmol), 4-toluenesulfonyl chloride
(1 mmol), solvent (5 ml), [SilFemImi]3PW12O40 (200 mg).
bIsolated yields after chromatography.
Figure 4. XRD patterns of (1) silica and (2) [SilFemImi]3PW12O40
.
Table 1. Optimization of catalyst loading in synthesis of sulfonamidesa
Scheme 2. Synthesis of sulfonamides from 4-toluenesulfonyl chloride and
amines using [SilFemImi]3PW12O40
.
Entry
Catalyst (mg)
Time (min)
Yield (%)b
1
2
3
4
5
50 (0.00035 mmol)
100 (0.0007 mmol)
150 (0.00105 mmol)
200 (0.0014 mmol)
250 (0.00175 mmol)
35
30
25
10
10
50
60
65
95
96
Table 3. [SilFemImi]3PW12O40-catalysed synthesis of sulfonamidesa
aReaction conditions: morpholine (1 mmol), 4-toluenesulfonyl chloride
(1 mmol), dichloromethane (5 ml).
Reactant
R
R′
Product
Time (min) Yield (%)b
bIsolated yields after chromatography.
6a
6b
6c
6d
6e
6f
Morpholine
Ph
H
7a
7b
7c
10
5
95
94
87
80
81
80
87
84
82
70
77
76
H
H
H
H
H
H
H
H
Ph
Et
H
p-OMePh
p-NO2Ph
p-BrPh
p-MePh
o-MePh
o-OMePh
Cyclohexane
Ph
35
65
50
20
70
35
60
65
20
65
common organic solvents employing optimal amount of catalyst
(Table 2). The reaction gives lower yields in solvents such as
dimethylformamide (DMF), chloroform, methanol and 1,4-dioxane
(Table 2, entries 1–4) while moderate yields are observed in ethanol
and acetonitrile (Table 2, entries 5 and 6). Dichloromethane proves
to be the most efficient solvent as it leads to a shortened reaction
time and maximum yield of desired product 7a (Table 2, entry 7).
With optimal conditions in hand, we decided to explore the versa-
tility and generality of this method by reacting structurally diverse
arylamines with 4-toluenesulfonyl chloride under optimized reac-
tion conditions (Scheme 2). The reactions proceed efficiently
forming the desired sulfonamides in high yields within short times
(Table 3). In all cases, the desired sulfonamides are obtained in good
to excellent yields without any anomalies, highlighting the general
applicability of the protocol. The primary arylamines bearing
electron-donating groups, as well as electron-withdrawing substitu-
ents react efficiently forming the anticipated products in high yield
(Table 3, 6 c–f). Sterically hindered amines such as o-toluidine and
o-anisidine also perform well and yield the corresponding products
in high yields (Table 3, 6 g and 6h). In addition, aliphatic amines
such as cyclohexylamine also react effectively furnishing desired
product in good yield (Table 3, 6i). More significantly, secondary
amines such as diphenylamine and diethylamine can also serve as
7d
7e
7f
6 g
6 h
6i
7 g
7 h
7i
6j
7j
6 k
6 l
Et
7 k
7 l
H
aReaction conditions: 4-toluenesulfonyl chloride (1 mmol), amine
(1 mmol), dichloromethane (5 ml), [SilFemImi]3PW12O40 (200 mg).
bIsolated yields after chromatography.
reactants in this reaction, albeit giving the corresponding products
in slightly lower yields (Table 3, 6j and 6k). With the intention of im-
proving our synthetic methodology, we explored the reaction of
ammonia to synthesize primary sulfonamide. The successful out-
come of this reaction would be milestone for this protocol as
primary sulfonamide moiety is present in many clinically used drugs,
such as diuretics (furosemide, indapamide, chlorthalidone, thiazides),
carbonic anhydrase inhibitors (acetazolamide, dichlorophenamide,
dorzolamide and brinzolamide), antiepileptics (zonisamide and
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Appl. Organometal. Chem. 2016, 30, 125–131

Sustainable synthesis of sulfonamides
sulthiame), the antipsychotic sulpiride and the cyclooxygenase 2 in-
hibitors celecoxib and valdecoxib. We were delighted to find that
p-toluenesulfonyl chloride reacts efficiently with ammonia yielding
corresponding 4-methylphenylsulfonamide with a moderate yield
of 76% with a slightly longer reaction time (Table 3, 6 l). It is worth
noting that there is no formation of bis-sulfonated product during
the reaction.
Given the operational simplicity and broad generality of this
protocol, we sought to demonstrate the preparative utility of the
process. We performed the reaction of 5 and 6a on a 40 mmol
scale to generate 94% yield of the desired sulfonamide (7a). The
successful preparative-scale utility makes this protocol amenable
to large-scale synthesis of sulfonamides at an industrial level.
In the control experiments, desired sulfonamides are formed
only in trace quantities without using the SILP catalyst. Also, a very
low yield (21%) is observed for the model reaction in the presence
of 3 (200 mg) in dichloromethane after a prolonged reaction time
(2 h) indicating that the Keggin-type anion plays a vital role in the re-
action. The identity of all the compounds was ascertained on the ba-
sis of IR, 1H NMR, 13C NMR and mass spectroscopic data. The physical
and spectroscopic data are in accord with the proposed structures
and are in good agreement with the literature data.[16]
The tentative mechanistic rationale for the synthesis of sulfon-
amides using SILP catalyst is presented in Scheme 3. It is well
established that the bridging oxygens (Ob) in Keggin anions are less
acidic and their nucleophilic character can lead to covalent interac-
tions with electrophilic groups bearing hydrocarbons.[20] Based on
this fact, we envisaged the initial nucleophilic attack of the oxygen
lone pair of the bridging oxygen on the sulfonyl group of
4-toluenesulfonyl chloride to furnish intermediate II as the key step
of the mechanism. The further nucleophilic attack of amine on II re-
sults in the formation of III which is followed by a dissociative chem-
isorption involving transfer of a proton and two electrons from the
N–H bond to the bridging oxygen leading to the formation of IV that
subsequently loses the proton on bridging oxygen by elimination of
HCl to form desired sulfonamide as shown in Scheme 3.[21]
To determine whether the SILP catalyst is really heterogeneous
or whether it is merely a reservoir for catalytically active Keggin-
type anion species, we performed a hot filtration test with a model
reaction. While performing such a test, [SilFemImi]3PW12O40 was fil-
tered off after 50% of the reaction was completed and the liquid
phase of the reaction mixture was stirred at room temperature for
an additional 1 h. interestingly, no significant progress (GC-MS anal-
ysis) is observed. Moreover, using inductively coupled plasma
atomic emission spectrometry of the same reaction solution at the
midpoint of completion, we detect no metallic species associated
with the Keggin-type anion. These investigations are sufficient to
conclude that the observed catalysis is truly heterogeneous in nature.
The higher yields observed during reactions can be rationalized on
the basis of greater micro-polarity of 4. It has been well established
that the advanced properties of SILP catalysts are, in part, directly
related to the polarity change that the support matrix undergoes
when immobilized with an IL-like unit. A semi-quantitative assess-
ment to quantify the degree of polarity change has been successfully
attempted by means of steady-state fluorescence spectroscopy,
using pyrene as a probe.[22] The first band in the fluorescence spec-
trum of pyrene corresponds to the transition S1v=0 →S0v=0, and its in-
tensity (I1) is dependent on the polarity of the medium, provided the
existence of vibronic coupling between S1 and S2 states, while the
third band corresponds to the transition S1v=0 → S0v=2, and its
intensity (I3) is independent of the polarity. Thus, the ratio of
I1/I3 which is referred as the py value that can be converted into
dielectric constant (ε) provides an empirical polarity scale which
assesses the micro-polarity of SILP catalysts. The fluorescence
spectra of pyrene adsorbed onto silica and 4 were recorded
(Fig. 5). The spectrum of the silica shows an ε value of 3.39 while
that of 4 shows an ε value of 3.73 (Table 4). The substantially
higher ε value of 4 (ca 10%) as compared to silica can be attrib-
uted to the presence of ferrocene tether that leads to
unsymmetric charge distribution on the imidazole ring resulting
in the significant enhancement of overall polarity of 4. This factor
Figure 5. Fluorescence spectra of pyrene with [SilFemImi]3PW12O40 (1) and
silica (2).
Table 4. Fluorescence data for pyrene in silica and [SilFeImi]3PW12O40
Entry
Material
λ1
λ3
py (I1/I3)
εa
1
2
Silica
[SilFemImi]3PW12O40
450
450
469
467
0.88
0.97
3.39
3.73
aCalculated using ε = 0.238 × e[2.78 × py]
.
Scheme 3. Plausible mechanism for the synthesis of sulfonamides using
[SilFemImi]3PW12O40
.
Appl. Organometal. Chem. 2016, 30, 125–131
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M. Jagadale et al.
using a novel silica-supported ionic liquid phase catalyst containing
Keggin-type anion. Further applications of this catalyst in combi-
natorial synthesis are currently under investigation in our
laboratory.
Experimental
All reactions were carried out under air atmosphere in dried glass-
ware. FT-IR spectra were measured with a PerkinElmer One FT-IR
spectrophotometer. The samples were examined as KBr discs (ca
5% w/w). Raman spectroscopy was done using a Bruker FT-Raman
(MultiRAM) spectrometer. The elemental compositions of material
were analysed using EDX capability attached to a field emission
scanning electron microscope (Hitachi S 4800, Japan). 1H NMR
and 13C NMR spectra were recorded with a Bruker AC (300 MHz
1
for H NMR and 75 MHz for 13C NMR) spectrometer using CDCl3
as solvent and tetramethylsilane (TMS) as an internal standard.
Chemical shifts are expressed in parts per million (ppm) with TMS
as the internal reference and coupling constants are expressed in
hertz (Hz). Mass spectra were recorded with a Shimadzu QP2010
GCMS. The materials were analysed using SEM with a JEOL model
JSM with 5 kV and 20kV accelerating voltages. Elemental analyses
were performed with a EURO EA3000 vector model. Melting points
were determined using MEL-TEMP capillary melting point appara-
tus and were uncorrected. For fluorescence studies, samples of sil-
ica and [SilFemImi]3PW12O40 were suspended in a methanolic
solution of pyrene (0.01 mollÀ1) and stirred for 6 h. After filtration
and washing with MeOH, the solid was vacuum dried at 60 °C. The fluo-
rescence was measured using a PC-based JASCO FP-750 spectrofluo-
rometer, equipped with a 450 W xenon lamp. 1-N-(ferrocenylmethyl)
imidazole was synthesized following a literature procedure.[19]
Figure 6. Reusability of [SilFemImi]3PW12O40 in sulfonamide synthesis.
Table 5. Comparison of various catalysts for synthesis of N-(phenyl)-p-
toluenesulfonamide (7b)
Entry
Catalyst
Conditions
Time Yield
(min) (%)
Ref.
1
2
3
4
5
6
Natrolite zeolite
Nano ZnO
Ultrasound
50 °C
15 95
60 94
10 95
[16h]
[16e]
[16d]
[16a]
[16j]
Zn–Al hydrotalcite Ultrasound
CuO
Room temperature 120 88
Reflux 10 95
CdO nanopowder
[SilFemImi]3PW12O40 Room temperature
5
94 This work
coupled with the bulk of the ferrocenyl group that might well
change the permeability of the substrates into the matrix lead-
ing to maximum accessibility of the reactive functional group
in the silica lead to the superior catalytic performance.
Preparation of chloropropyl silica
A mixture of activated silica (3.0 g) and 3-chloropropyltriethoxysilane
(3.0 ml, 25.5 mmol) in 25 ml of toluene was refluxed at 100 °C in an
oil bath. After 24 h, reaction mixture was cooled, and the product
was filtered and repeatedly washed with toluene (3 × 5 ml) and dried
under reduced pressure at 100 °C for 8 h to produce chloropropyl
silica (2.8 g).
The recyclability of the SILP catalyst for the synthesis of sulfon-
amides was assessed by repeating the synthesis of 7a. In brief, upon
completion of the reaction, 4 was filtered, washed several times
with small amounts of dichloromethane and dried at 70°C. Follow-
ing this procedure, the recovered catalyst was reused for the syn-
thesis of sulfonamides five times. The results are shown in Fig. 6.
The reduction in conversion observed on successive recycles is as-
cribed to attrition during filtration and recovery of the catalyst.
The FT-IR spectrum of reused catalyst displays the characteristic IR
bands of Keggin-type anion at 1029, 912, 828 and 602 cmÀ1 which
is convincing evidence for the fact that the basic structure of the
catalyst is preserved even after the fifth catalytic cycle. In addition,
SEM analysis of reused catalyst shows no significant changes in
the morphology in comparison with fresh catalyst (Fig. 3(C)).
In order to show the merits of the SILP catalyst in comparison
with other catalysts used for similar reactions, we summarize sev-
eral results for the preparation of N-(phenyl)-p-toluenesulfonamide
(7b) in Table 5. It is evident from these results that 4 is more effec-
tive as compared to other reported catalysts.
Preparation of [SilFemImi]Cl (3)
A mixture of chloropropyl silica (4 g) and 1-N-ferrocenylmethyl im-
idazole 2 (2.12 g, 8 mmol) in 25 ml of DMF was heated at 80 °C in
an oil bath. After 72 h, the insoluble product was filtered, washed
with DMF (3× 50 ml), MeOH (3× 50ml) and CH2Cl2 (3 × 50 ml) and
dried under vacuum at 50 °C for 24 h to afford 3. Raman (ν, cmÀ1):
3185, 3124, 1504, 1406, 1328, 1169, 1084, 848, 740, 465. Elemental
analysis found (%): C, 9.01; H, 1.31; N, 0.51. Loading: 0.18mmol func-
tional group per gram.
Preparation of [SilFemImi]3PW12O40 (4)
A mixture of 3 (3g) and phosphotungstic acid (3.5g, 1.21 mmol) in
15ml of water was vigorously stirred at ambient temperature. After
72h, the insoluble product was filtered, washed with a copious
amount of water and dried under vacuum at 50 °C for 24 h to afford
4. FT-IR (neat, thin film, ν, cmÀ1): 575, 597, 802, 900, 1065, 2956,
3091, 3155. EDX (%): C, 8.31; O, 10.65; N, 1.62; W, 0.60; P, 0.24; Fe,
0.22. Loading of Keggin-type anion: 0.007 mmol functional group
per gram.
Conclusions
We have reported an operationally simple, economical and envi-
ronmentally friendly synthesis of biologically active sulfonamides
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Sustainable synthesis of sulfonamides
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General procedure for synthesis of sulfonamides
A mixture of amine (1mmol), p-toluenesulfonyl chloride (1mmol)
and [SilFemImi]3PW12O40 (200 mg) in dichloromethane (5ml) was
stirred at ambient temperature. After completion of the reaction
as monitored by TLC, the reaction mixture was filtered to remove
insoluble catalyst. Evaporation of solvent under vacuum followed
by column chromatography over silica gel using petroleum
ether–ethyl acetate (95:5 v/v) afforded pure sulfonamides.
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