Ultrasound-promoted green approach for the synthesis of sulfonamides using natural, stable and reusable Natrolite nanozeolite catalyst at room temperature

Article abstract of DOI:10.1016/j.ultsonch.2013.07.012

Natural Natrolite nanozeolite has been investigated as an efficient and reusable catalyst for the N-sulfonylation of amines under ultrasound irradiation at room temperature. Compared with traditional methods, the significant advantages for method are green solvent, milder and cleaner conditions, higher purity and yields, shorter reaction time, easier work-up procedure and the lower generation of waste or pollutions. The catalyst can be recovered and reused several times without significant loss of its catalytic activity.

Full text of DOI:10.1016/j.ultsonch.2013.07.012

Accepted Manuscript
Ultrasound-promoted green approach for the synthesis of sulfonamides using
natural, stable and reusable Natrolite nanozeolite catalyst at room temperature
Mahmoud Nasrollahzadeh, Ali Ehsani, Akbar Rostami-Vartouni
PII:
S1350-4177(13)00165-X
DOI:
http://dx.doi.org/10.1016/j.ultsonch.2013.07.012
ULTSON 2351
Reference:
To appear in:
Ultrasonics Sonochemistry
Received Date:
Revised Date:
Accepted Date:
2 April 2013
20 June 2013
19 July 2013
Please cite this article as: M. Nasrollahzadeh, A. Ehsani, A. Rostami-Vartouni, Ultrasound-promoted green approach
for the synthesis of sulfonamides using natural, stable and reusable Natrolite nanozeolite catalyst at room
temperature, Ultrasonics Sonochemistry (2013), doi: http://dx.doi.org/10.1016/j.ultsonch.2013.07.012
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Ultrasound-promoted green approach for the synthesis of
sulfonamides using natural, stable and reusable Natrolite
nanozeolite catalyst at room temperature
Mahmoud Nasrollahzadeh*, Ali Ehsani, Akbar Rostami-Vartouni
Department of Chemistry, Faculty of Science, University of Qom, Qom 37185-359, Iran
Abstract: Natural Natrolite nanozeolite has been investigated as an efficient and
reusable catalyst for the N-sulfonylation of amines under ultrasound irradiation at
room temperature. Compared with traditional methods, the significant advantages for
method are green solvent, milder and cleaner conditions, higher purity and yields,
shorter reaction time, easier work-up procedure and the lower generation of waste or
pollutions. The catalyst can be recovered and reused several times without significant
loss of its catalytic activity.
Keyword: N-Sulfonylation; Tosyl chloride; Amine; Ultrasound irradiation; Natural
Natrolite nanozeolite
1. Introduction
Sulfonylation of amines is a well known reaction in the synthesis pharmaceutically
valuable compounds [1]. During the last few years, sulfonamides have been the focus
of much research interest related to their important role as antibacterial, diuretics,
anticonvulsants, hypoglycaemic, and HIV protease inhibitors in pharmaceuticals.
Moreover, sulfonamides have been employed as inhibitors of dihydropteroate
synthetase and as an important amine-protecting group [2,3].
One of the most promising methods of synthesis of the sulfonamides involves the
reaction between sulfonyl chlorides with excess ammonia [4a]. Classical methods for
the synthesis of sulfonamides have involved reaction of amines with sulfonyl
chlorides in the presence of base or different catalysts in organic solvents at high
temperature and pressure [4-7].
Earlier reported methods for the N-sulfonylation of amines suffer from certain
disadvantages such as the use of expensive catalysts, difficulty in availability or
preparing the starting materials or catalysts, the environmental pollution caused by
utilization of non-green solvents and homogeneous catalysts, low yields, long reaction
times, tedious work-up, waste control and formation of side products, especially bis-
sulfonylation for primary amines [5,6]. Therefore, the development of a catalytic
synthetic method for sulfonamides still remains as an active research area.
* Corresponding author. Tel.: +98 25 32103595; Fax: +98 25 32850953. E-mail address: mahmoudnasr81@gmail.com (M.
Nasrollahzadeh)
1

There is considerable interest in the applications of heterogeneous catalysts for the
organic synthesis [8]. Moreover, using inexpensive and non corrosive heterogeneous
catalysts, chemical transformations occur with better efficiency, higher purity of the
products, and simpler work-up, with evident economic and ecological advantages
especially for the industrial processes. Nanozeolites are crystalline hydrated
aluminosilicates of the earth alkalines. The application of inorganic solid acids,
especially nanozeolites, as effective heterogeneous catalysts for organic synthesis has
received considerable attention in the recent decades due to their microporosity, large
surface area, and thermal and chemical stability nanozeolites [9]. We recently
published synthesis of tetrazoles and formamides in high yields using Natural Iranian
Natrolite nanozeolite as a stable, reusable and heterogeneous catalyst [9b-9d].
In recent years, there has been a tremendous upsurge of interest in various chemical
transformations performed under ultrasound irradiation [10a]. In an irradiated liquid
with high-intensity ultrasound, the collapse of bubbles caused by cavitation produces
intense local heating and high pressures, with very short lifetimes; these transient,
localized hot spots drive high energy chemical reactions. The hot spot has an
equivalent temperature of roughly 5000 °C (9,000 °F), a pressure of about 2000
atmospheres, a lifetime considerably less than a microsecond, and heating and cooling
rates above 10 billion °C per second [10b-e]. Moreover, with using ultrasound
irradiation, chemical transformations occur, with higher yields and purity of the
products, shorter reaction times and milder conditions, that create economical
advantages [11]. We recently published synthesis of 1-aryl-5-amino-1H-tetrazoles, 1-
substituted 1H-1,2,3,4-tetrazoles, 2-iminooxazolidines and formamides in high yields
by ultrasound irradiation [11]
In continuation of our recent studies on application of Natrolite nanozeolite and
also sonochemistry [9b-9d,11], we hereby report a new protocol for the N-
sulfonylation of amines using Natural Iranian Natrolite nanozeolite as a stable
heterogeneous catalyst under ultrasound irradiation at room temperature (Scheme 1).
2. Result and discussion
As a part of our growing interest in sonochemistry, with the aim of improving the
synthesis of sulfonamide derivatives, we decided to carry out a systematic study on
the preparation of these compounds under significantly milder conditions.
2.1. Physico-chemical characterization of Natrolite zeolite
2

Zeolites are comprised of channels and cavities in molecular dimensions ranging
from 3 to 10 ꢀ in diameter. The structural formula of zeolite is Mx/n
[(AlO2)x(SiO2)y]•wH2O, where M is an alkali or alkaline earth cation, n is the valence
of the cation, w is the number of water molecules per unit cell, x and y are the total
number of tetrahedral atoms per unit cell and the y/x ratio (Si/Al ratio) usually ranges
from 1 to 5 or 10 to 100 for high silica zeolites [12]. The framework structure of
zeolite consists of a three dimensional network of SiO4 and AlO4 tetrahedra linked
together by oxygen (Figure 1) which the ordered Na+ ions and H2O molecules fill the
voids of the framework [13]. The extra framework cation compensates the negative
charge of the zeolite framework that is created due to substitution of a silicon atom by
an aluminium atom. The negative charge on alumina tetrahedra is neutralized by
monovalent or divalent cations such as sodium, calcium, etc which are located in the
structural channel cavities and resulting in an electrically neutral framework. The
Natrolite zeolite is one of zeolites with Al2Si3O10 main structural unit. The Natrolite
zeolite can be classified as fibrous zeolites with small pores (channels in the
framework structure) which mostly consist of 8 members of oxygen ring systems (the
diameter of their pores < 4.5 Å), and the Na+ cations occupy positions in the eight-
ring channels. Our recent study has shown that the Natrolite zeolite can be used as a
very active catalyst in the organic synthesis [9b-9d].
Figure 1
2.2. Characterization of Natrolite nanozeolite
Natural Iranian Natrolite nanozeolite as a new heterogeneous catalyst used in the
present reactions was characterized by powder XRD, XRF, SEM, TG-DTA analysis
and FT-IR spectra as explained below.
2.2.1. Powder X-ray Diffraction (XRD)
An X-ray diffraction study of nanozeolites can be used to identify their exact
structure, calculation of the unit cell parameters and to determine their degree of
crystallinity. Also, this technique can signify whether the solid sample is amorphous
or crystalline phase. The purity of the solid crystal will be measured by comparing the
X-ray diffractogram pattern of the sample with X-ray diffractogram pattern of the
standard sample. The XRD powder patterns of a sample show very good crystallinity
(Figure 2a). The X-ray powder diffraction was applied for its phase purity in which its
pattern was completely matched with that of the Natrolite zeolite (according to the
JCPDS file no. 20-759, Figure 2b). The actual phases for this catalyst were Silicon
Oxide cristabolite-SiO2 (cubic) and Aluminium Silicate nanozeolite.
Figure 2
2.2.2. XRF analysis
3

The chemical composition of silica and alumina was established by a wavelength
dispersive XRF spectrophotometer (Tables 1 and 2). Based on the XRF technique, the
mineral content of the zeolitic material from quarry face was Natrolite 99.95 % (w/w)
[12]. The composition of the Natrolite nanozeolite used in the present work is
(Na17.52K0.144Ca0.365Mg0.065) (Al20.44Si27.74O96) 19.16H2O and the SiO2/Al2O3 weight
ratio of the material is 1.62 [14].
Table 1
Table 2
2.2.3. Infrared spectroscopy
In the relevant FT-IR spectra, peaks 950-1200 cm-1 are probably related to the Si-
O-Si and Si-O-Al vibrations, peaks 3619, 3440 and 1640 cm-1 to the presence of the
zeolitic water and peaks 500-800 cm-1 to the pseudo-lattice vibrations. Above 1500
cm-1, the familiar bending HOH peak will appear at 1640 cm-1 while their asymmetric
and symmetric stretching peaks appear at 3440, and 3619 cm-1, respectively (Figure 3)
[9b].
Figure 3
The thermal stability of nanozeolite is increased with increasing the SiO2/Al2O3
ratio in the framework. In low amount of silica (SiO2/Al2O3 < 5) the crystalline
decomposition temperature is near 700 ºC, while for those nanozeolites contain the
high silica ratio the crystalline decomposition temperature is about 1300 ºC.
According to the IR spectra, the crystalline decomposition temperature of the
Natrolite nanozeolite is about 900 ºC [14].
2.2.4. Scanning electron microscopy (SEM) analysis
The shape and size of the Natrolite nanozeolite were determined by scanning
electron microscopy (SEM). The surface of the nanozeolite specimens is highly
heterogeneous due to the coexistence of different zeolite phases together with other
crystalline and amorphous materials.
2.2.5. Thermal analysis
Thermogravimetric analysis (TGA) and differential thermal analysis (DTA) were
carried out in flowing air (120 ml min-1) at a heating rate of 2 °C min-1 on an
autonomic TG/DTA. In the TG/DTA data a gradual weight decreasing was only
observed between 300 and 400 °C due to desorption of the surface waters (Figure 4).
The Natrolite nanozeolite gives off its water rapidly in a single temperature range,
though it has only one type of water molecule in its structure which is in good
agreement with the previous report [14]. Thus, the thermal reaction data have been
4

used for the purpose of identification and interpretation of the nanozeolite structure. In
general, the thermal stability of zeolitic framework structure increases with increasing
the silica to alumina ratio [15] and the method of thermal/acid treatment or ion-
exchange [16].
Figure 4
2.3. Optimization of the reaction conditions
In the initial experiment, we investigated various conditions in the model reaction
of p-anisidine with tosyl chloride in the presence of Natrolite nanozeolite under
ultrasound irradiation at room temperature (Table 3). The effect of various amounts of
catalyst and different solvents on the model reaction was conducted. Several organic
solvents such as THF, EtOAc, DMF and ethanol were examined. According to data
given in Table 3, ethanol was the most efficient solvent for this reaction. No reaction
was observed in the absence of catalyst without ultrasonic irradiation (Table 1, entry
1). When the reaction was carried out at room temperature using Natrolite nanozeolite
and in the absence of ultrasonic irradiation, the product was obtained in lower yield
and longer reaction time (Table 3, entry 5), while in the presence of ultrasonic
irradiation, the yield increased to 87-96% and the reaction time is reduced to 4 min
(Table 3, entry 7). It is a well-established fact that ultrasound irradiation accelerates
the reactions. In addition, the reaction was slow in the absence of catalyst (Table 3,
entry 6), it indicated that combination method (ultrasound irradiation and Natrolite
nanozeolite) played a significant role on the product yield and reaction time. Based on
these results, the best conversion was observed when the reaction was performed in
ethanol under ultrasound irradiation in the presence of amine (1.0 mmol), tosyl
chloride (1.0 mmol) and Natrolite nanozeolite (0.08 g) (Table 3, entry 7). No
significant improvement on the yield was observed using higher amounts of the
catalyst (Table 3, entries 8-9). Due to its shortcoming of difficult recovery,
homogeneous catalysts could not be considered as economic and green catalysts even
if displayed good catalytic capacity.
Table 3
The effect of irradiation frequency and reaction temperature on the reaction yield
was also examined. When the frequency was 40 kHz, the yield of reaction (96 %)
(Table 4, entry 2) was better than that with 25 kHz irradiation within 6 min (87 %,
Table 4, entry 1). The result showed that 40 kHz was the appropriate frequency for
this reaction. In order to further improvement of the reaction output, we tried to
perform the reaction in higher temperature under ultrasound irradiation. However, the
yield did not increase. Consequently, it was indicated that there was no remarkable
ultrasonic temperature effect on this reaction. Thus, we choose 25 °C as the
appropriate temperature.
5

Table 4
The first principle of green chemistry states that it is better to prevent waste
production than to treat waste or clean it up after it has been created [17]. Therefore,
in the reaction of p-anisidine with tosyl chloride (mole ratio 1.0:1.0), after completion
of the reaction, there is no tosyl chloride residue and no side product in the reaction
mixture and the method did not require any further purification.
Various sulfonamides were synthesized from aliphatic and heterocyclic amines and
aromatic amines containing both electron-donating and electron-withdrawing groups
in excellent yields under ultrasound irradiation at room temperature which the results
were indicated in Table 5. The present procedure did not show any remarkable
difference in the yield of desired products. In all cases, the experimental results show
that the reaction times are reduced and the yields increased under sonication
conditions. The nature of the substituent on the amine did not affect the reaction yield.
That is to say, electron-withdrawing groups played a key role in affecting the rate of
reaction and the reaction requires a longer time, probably due to the low basicity of
these amines. The reactions appeared to be insensitive to the steric hindrance around
the reaction site. For instance, dibenzylamine and diphenylamine gave a high yield
(Table 5, entries 12 and 13).
Table 4
As shown in Table 4, secondary amines effectively reacted with tosyl chloride in
the presence of 0.08 g Natrolite nanozeolite and afforded the corresponding
sulfonamides in excellent yields (Table 5, entries 9-10 and 12-13). The N-
sulfonylation of secondary amine needs longer reaction times than primary one; due
to higher steric hindrance on the nitrogen atom. Thus excellent chemoselectivity was
observed for the conversion of primary amines in the presence of secondary amines,
as shown in Scheme 2.
With molecules containing both the hydroxyl and amino groups, only the N-
sulfonylated products were formed. So the O-sulfonylation did not take place and the
present method shows an excellent chemoselectivity (Table 5, entry 14).
To show the advantages of proposed method in comparison with other reported
methods, we summarized some of results for N-sulfonylation of p-nitroaniline in
Table 6, which shows that Natrolite nanozeolite is an equally or more efficient
6

catalyst with respect to reaction time and yield than previously reported ones. The
present method offers several notable features, compared with the other literature
works on the N-sulfonylation of amines, i.e., (1) natural and highly efficient
heterogeneous catalyst activity, (2) ease of handling and cost efficiency of the
catalyst, (3) avoidance of the high reaction temperature, (4) avoidance of the non-
green solvents application and by-products preparation (5) wide substrate scope and
generality especially for amines containing electron-withdrawing groups, (6) higher
yields and purity, shorter reaction time and milder conditions, (7) less time consuming
and more environmentally friendly, (8) effective reusability and recycling of the
catalyst, making it a useful and attractive strategy for the synthesis of sulfonamide
compounds. It is important to mention that side product was not observed under the
reaction conditions, thus this method did not require any further purification. Zeolites
have definite advantages over conventional solid catalysts: less or no corrosion, no
waste or disposal problems, high thermostability, easy setup of continuous processes,
etc. Numerous potential applications of nanozeolites have been found in industry for
water purification, as catalysts, for the preparation of advanced materials and in
nuclear reprocessing. They are widely used in medicine and agriculture and also to
extract nitrogen from air to increase oxygen content for both industrial and medical
purposes.
Table 6
2.4. Acidity and basicity of zeolite
Natrolite zeolite catalytic properties are very much depending on both their
chemical and physical aspects. The activity of the zeolites increases with an increase
of the aluminium content in the framework and increase in the radius of the counter
cation. The presence of both acidic and basic sites in zeolites makes the material as
unique type of catalyst in various reactions [18]. The basicity of zeolites has received
much attention recently, because of their important roles in a variety of base-catalyzed
reactions [19]. The basicity of zeolites has been proved to play a specific role even in
some acid-catalyzed reactions [20].
Generally, the basic sites on the surface of the solid catalyst (zeolite) are of Lewis
type. The zeolite oxygen basicity arises from the presence of negatively charged AlO4
tetrahedra. The negative charge is borne by the four oxygens of such a tetrahedron
shared with the four neighboring SiO4. The exchangeable cations act as Lewis acid
sites, forming a conjugated acid-base pair which can interact with any molecule. On
the basis of experimental results in literature, mainly obtained on Natrolite zeolite the
following two rules were established: (1) the basicity increases with increasing Al
content of the framework; (2) for a given Al content basicity increases with the size of
the exchangeable cation. Among of various zeolite groups, Natrolite appears to be
more stable than the other zeolites such as ꢀ-zeolite and Natural zeolite Heulandite.
7

Natrolite has small pores with small Si/Al ratio of 1.36 (large Al/ (Al + Si) ratio),
while that ratio is 10.0 for ꢀ-zeolite and 5.0 for Natural zeolite Heulandite. Higher Al
content increases the basicity of the framework, which may cause stronger
electrostatic interaction with cations and result in more stable structure [21].
The strength of acid sites is found to vary with (i) zeolite structure framework, (ii)
Si/Al ratio, and (iii) metal ions exchanges in the zeolite structure framework [22]. The
XRF results show that the acidic sites on the surface of the Natrolite zeolite are Al2O3
which can catalyze this reaction. The activity of the Natrolite zeolite in acid catalyzed
N-sulfonylation of amines originates from the tetrahedral framework aluminium
atoms which induce a potentially active acid site. Silicates do not have acidic
character and there is one type of acid catalytic activity associated with the Natrolite
zeolite namely Lewis acidity which corresponds to an electron pair acceptor.
Natrolite zeolite is a small pore zeolite (i.e. Ø < 4.5 Å) with 8-membered ring
openings which belongs to the fibrous family. According to the literature results [14],
BET surface area of Natrolite zeolite is low. The role of Lewis basicity was found to
be more important than the changes in specific area or micropore volume of different
cation-exchanged samples in deciding the catalyst activity in the N-sulfonylation of
amines reaction. Unlike the general trend, the catalyst activity was found to increase
with decrease in BET surface area, indicating that Lewis basic sites of solid catalysts
are more important for N-sulfonylation of amines than the specific surface area.
2.5. Proposed mechanism
The possible mechanism for the N-sulfonylation of amines using Natrolite zeolite
as a natural and reusable catalyst under ultrasound irradiation conditions is shown in
Scheme 3. The Lewis acidity and Lewis basicity of the catalyst probably has an
important role in promotion of the sulfonylation process. It was proposed that the
coordination of the double bond of S=O of sulfonyl chloride in the presence of
nanozeolite allows to the formation of sulfonamide via nucleophilic attack of the
amino group. Due to the higher basicity, the reactivity of aromatic amines containing
electron-donating groups is increased in comparison with amines containing electron-
withdrawing groups.
Ar
δ+
NHR1R2
δ−
Cl
..
SO2Ar
Cl
R1
SO2Ar
S
R1R2NH
HCl
+
N
O
O
R2
Nat. Zeolite
Nat. Zeolite
Scheme 3. Mechanism of the N-sulfonylation of amines by ultrasound irradiation and Natrolite nanozeolite.
It was clear that the ultrasound irradiation could accelerate N-sulfonylation of
amines under mild conditions without formation of impurity. The following is
8

expected to be plausible reason for the higher yields and shorter reaction times during
ultrasonic irradiation. Once more, ultrasound enhanced the rate of a reaction and,
consequently, reduced energy consumption. It also facilitates reaction at ambient
conditions eliminating the use of high-pressure reactors, higher temperatures etc. In
general, US have chemical and mechanical effects. The chemical and physical effects
of ultrasonic irradiation originate from acoustic cavitations. Ultrasound provides an
unusual mechanism due to the immense temperatures and pressures and the
extraordinary heating rate generated by cavitation bubble collapse [23]. The
breakdown of SO2-Cl and N-H bonds in tosyl chloride and amines facilitates the
elimination of HCl and the final sulfonamides will be produced. Energy of these
cleavages and formation of sulfonamides are provided by the short-lived and localized
hot spots that generated during the cavitational collapse. Since this system is a
heterogeneous catalytic system, it seems that the main effect of US is due to its
mechanical effect. On the other hand, during the sonication, break-up of the surface
structure allows penetration of reactants and/or release of materials from surface and
accelerated motion of suspended particles leads to better mass transfer [10e].
2.6. Characterization of the reaction products
The structures of the products were in agreement with their IR and NMR spectra. In
the IR spectra of the products, the NH peak had disappeared and two strong
absorptions bands were detected. New absorption bands in the FT-IR spectra of the N-
tosylated products were attributed to the SO2 of the tosyl group.
2.7. Catalyst reuse and stability
Natrolite zeolite works under heterogeneous conditions. The catalyst was separated
from the reaction mixture with filtration, washed with ethyl acetate and dried. The
XRD patterns before and after the reaction revealed that the nanozeolite retained its
crystallinity throughout. As shown in Table 7, the catalyst can be reused for at least
five successive runs with no significant loss in its reactivity. The recovered catalyst
was purified by washing with ethyl acetate followed by drying in an oven. In every
experiment, more than 98% of the catalyst was easily recovered from the reaction
mixture. The catalyst was separated and was reused as such for subsequent
experiments under similar reaction conditions. Acids are well-known to act as proton-
exchangers with Na-zeolites. Since the reaction will produce one molecule of HCl, we
are more inclined to believe that the HCl proton able exchange with sodium cations.
Also, probably HCl promotes the dealumination of the framework alumination of the
Natrolite nanozeolite and change affect the catalytic efficiency after several reaction
cycles. Thus, yields of the product decreased only slightly after five time’s reuse of
catalyst.
9

Table 7
3. Experimental
3.1. Apparatus and analysis
All reagents were purchased from Merck and Aldrich and used without further
1
purification. H NMR spectra were recorded on Bruker Avance DRX 90 MHz
instruments, using TMS as internal standard. FT-IR spectra were recorded on a
Shimadzu 470 spectrophotometer. Melting points were determined with X-6 (Beijing
Fukai Co. Ltd.) melting point apparatus and are uncorrected. TLC was performed on
Merck-precoated silica gel 60-F254 plates. Natural Iranian Natrolite nanozeolite was
obtained from the Hormak area (city of Zahedan, province of Sistan & Baluchestan,
Iran). Ultrasonication was performed in a Shanghai Branson-BUG40-06 ultrasound
cleaner with a frequency of 40 kHz and an output power of 250 W. The temperature
of the water bath can be controlled by a controlled automatic constant temperature
cooling circulatory system. All spectroscopic data of the products were identical to
data from authentic samples.
3.2. Ultrasonic process equipment
Ultrasonic energy is transmitted to the reaction vessel through the liquid medium,
usually water in the tank. For safety purpose, the sonochemical reactor consisted of
two layers of stainless steel sheet. The sonochemical reactor configuration used in the
present work is basically an ultrasonic bath with liquid holding capacity of 5 L. The
internal dimension of the ultrasonic cleaner tank is 48 cm × 28 cm × 20 cm.
Sonication was performed in an ultrasound cleaner with a frequency of 25 and 40 kHz
through manual adjustment and an output power of 250 W. The reactions were carried
out in a round-bottomed flask of 25 mL capacity. The reaction flask was located at the
center of the cleaner, and the surface of the reactants was placed slightly lower than
the level of the water. The addition or removal of water controlled the temperature of
the water bath. The temperature of the water bath was controlled at 25-30 °C. All the
experimental parameters were done at 40 kHz with output power of 250 W.
3.3. General procedure for the N-sulfonylation of amines by Natrolite nanozeolite
under ultrasound irradiation
The reactions were carried out in a round-bottomed flask of 25 mL capacity
suspended at the center of the cleaning bath, 5 cm below the surface of the liquid. To
the mixture of amine (1.0 mmol) and tosyl chloride (1.0 mmol) in 4 mL of ethanol,
Natrolite nanozeolite (0.08 g) was added. The mixture was sonicated at 25-30 °C
(bath temperature, the temperature inside the reactor was also 25-30 °C) for the
appropriate time (Table 5) in an US bath having a frequency of 40 kHz and an input
power of 250 W. The addition or removal of water controlled the temperature of the
10

water bath. The water bath was controlled at 25-30 °C. The progress of the reaction
was monitored by TLC. After completion of the reaction, catalyst was filtrated. The
filtrated catalyst, which was washed with ethyl acetate and activated at 100 °C for 2 h,
could be reused in next cycle without considerable activity loss at least five successive
runs for the same reaction. The solvent was concentrated under reduced pressure to
afford the pure product as solid in good to excellent yields. All compounds were
compared with the corresponding compounds prepared by the reported procedure
[7,24-28]. All compounds were known and were characterized by spectral analysis.
Table 5, entry 2: 1H NMR (90 MHz, CDCl3): ꢁ = 2.36 (s, 3H), 6.98-7.68 (m, 9H).
Table 5, entry 4: 1H NMR (90 MHz, CDCl3): ꢁ = 2.35 (s, 3H), 6.73-7.68 (m, 9H).
Table 5, entry 5: 1H NMR (90 MHz, CDCl3): ꢁ = 2.35 (s, J = 3), 6.89-7.84 (m, 9H).
1
Table 5, entry 6: H NMR (90 MHz, CDCl3): ꢁ = 2.01 (s, 3H), 2.35 (s, 3H), 7.04-
7.77 (m, 9H).
1
Table 5, entry 7: H NMR (90 MHz, CDCl3): ꢁ = 2.36 (s, 3H), 3.73 (s, 3H), 6.66-
7.63 (m, 9H).
Table 5, entry 8: 1H NMR (90 MHz, CDCl3): ꢁ = 2.03 (s, 6H), 2.41 (s, 3H), 6.05 (s,
1H), 7.01-7.63 (m, 7H).
Table 5, entry 9: 1H NMR (90 MHz, CDCl3): ꢁ = 2.39 (s, 3H), 2.93 (s, 2H), 3.68 (s,
2H), 7.29 (d, J = 7.8, 2H), 7.59 (d, J = 7.7, 2H).
Table 5, entry 10: 1H NMR (90 MHz, CDCl3): ꢁ = 2.43 (s, 3H), 3.23 (s, 8H), 6.87-
7.17 (m, 9H).
Table 5, entry 11: (90 MHz, CDCl3): ꢁ = 2.42 (s, 3H), 4.06 (d, J = 11.9, 2H), 4.82
(s, 1H), 7.21-7.78 (m, 9H).
Table 5, entry 12: 1H NMR (90 MHz, CDCl3): ꢁ = 2.44 (s, 3H), 4.32 (s, 4H), 7.11-
7.78 (m, 14H).
Table 4, entry 14: 1H NMR (90 MHz, CDCl3): ꢁ = 1.15-1.38 (m, 4H), 2.44 (s, 3H),
3.48 (s, 1H), 3.98-4.22 (m, 2H), 7.16-7.84 (m, 9H).
11

4. Conclusions
In conclusion, we have developed a mild, clean, fast, novel and safe methodology
for the chemoselective N-sulfonylation of amines using Natrolite nanozeolite as a
natural and reusable catalyst under ultrasound irradiation at room temperature with
high yields, short reaction times and easy work-up in which the separation techniques
are not necessary to get the pure compounds. A comparison of different solvents
reveals that ethanol leads to slightly better yields. Further investigations on the
application of this catalyst on other catalytically synthetic reactions are in progress.
Acknowledgements
We gratefully acknowledge from the Iranian Nano Council and University of Qom
for the support of this work.
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14

Graphical Abstract
Ultrasound-promoted green approach for the synthesis of
sulfonamides using natural, stable and reusable Natrolite
nanozeolite catalyst at room temperature
Mahmoud Nasrollahzadeh*, Ali Ehsani, Akbar Rostami-Vartouni
Department of Chemistry, Faculty of Science, University of Qom, Qom 37185-359, Iran
15

Research highlights:
‹ Synthesis of sulfonamides under mild conditions and ultrasound irradiation.
‹ Reaction catalyzed by Natural and reusable heterogeneous catalyst.
‹ Catalyst can be easily recovered and reused.
‹ Better reaction times, higher yields and easier work-up.
‹ Side product was not observed under the reaction conditions.
16

Scheme captions
Scheme 1. N-sulfonylation of amines by ultrasound irradiation and Natrolite
nanozeolite.
Scheme 2. Chemoselective N-sulfonylation of amines.
Scheme 3. Mechanism of the N-sulfonylation of amines by ultrasound irradiation and
Natrolite nanozeolite.
17

18

19

Ar
S
δ+
NHR1R2
δ−
Cl
..
SO2Ar
Cl
R1
SO2Ar
R1R2NH
HCl
+
N
O
O
R2
Nat. Zeolite
Nat. Zeolite
Scheme 3. Mechanism of the N-sulfonylation of amines by ultrasound irradiation and Natrolite nanozeolite.
20

Figure captions
Figure 1. Aluminosilicate framework of zeolite.
Figure 2. (a) XRD diffraction pattern of the Natrolite nanozeolite and (b) comparison
of the XRD pattern of the Natrolite nanozeolite with the International zeolite
Association (IZA) standards.
Figure 3. FT-IR spectrum of the Natrolite nanozeolite.
Figure 4. TG-DTA data measured for the Natrolite nanozeolite.
21

Figure 1. Aluminosilicate framework of zeolite.
22

Figure 2. (a) XRD diffraction pattern of the Natrolite nanozeolite and (b) comparison of the XRD
pattern of the Natrolite nanozeolite with the International zeolite Association (IZA) standards.
23

Figure 3. FT-IR spectrum of the Natrolite nanozeolite.
24

Figure 4. TG-DTA data measured for the Natrolite nanozeolite.
25

Table captions
Table 1
The XRF data of the Natrolite nanozeolite.
Table 2
Elemental analysis of the Natrolite nanozeolite.
Table 3
Natrolite nanozeolite catalyzed ultrasound-assisted synthesis of sulfonamides using p-
anisidine (1.0 mmol) and tosyl chloride (1.0 mmol) at room temperature: optimization
of the reaction conditions.
Table 4
Effect of the ultrasonic temperature and the ultrasonic frequency.
Table 5
Green N-sulfonylation of amines by Natrolite nanozeolite under ultrasound
irradiation.
Table 6
Comparison present methodology with other reported catalysts in the N-sulfonylation
of p-nitroaniline.
Table 7
Recyclability of the Natrolite nanozeolite.
26

Table 1
The XRF data of the Natrolite nanozeolite.
Fragment
% Weight
SiO2
45.99
Al2O3
28.32
Na2O
15.01
K2O
0.185
MgO
0.071
CaO
0.917
H2O
9.46
27

Table 2
Elemental analysis of the Natrolite nanozeolite.
Element
Ba
ppm
794
43
Element
Pb
ppm
37
67058
Ce
Sr
Co
Cr
1
4
V
Y
18
8
Cu
1391
8
58
94
Zn
Nd
U
Th
W
29
0
0
0
Mo
Cl
Rb
Ni
10
0
Zr
1411
28

Table 3
Natrolite nanozeolite catalyzed ultrasound-assisted synthesis of sulfonamides using p-anisidine (1.0
mmol) and tosyl chloride (1.0 mmol) at room temperature: optimization of the reaction conditions.
Entry
Method
Without USa
Without USa
Without USa
Without USa
Without USa
With USb
Natrolite nanozeolite (g) Solvent (4 mL)
Time (min)
Yieldc %
1
2
3
4
5
6
7
8
9
0.0
0.08
0.08
0.08
0.08
0.0
EtOH
THF
15
15
20
15
15
60
4
0
65
68
80
87
85
96
95
96
EtOAc
DMF
EtOH
EtOH
EtOH
EtOH
EtOH
With USb
0.08
0.1
With USb
4
4
With USb
0.15
a Carrying out the reactions under conventional conditions.
b The ultrasonic power 250 W, irradiation frequency 40 kHz.
c Isolated yield.
29