Solvent-free multicomponent reactions using the novel N-sulfonic acid modified poly(styrene-maleic anhydride) as a solid acid catalyst

Article abstract of DOI:10.1016/j.molcata.2014.04.024

A new N-sulfonic acid based on the polymer-support as a solid acid catalyst is prepared by the reaction of the modified poly(styrene-alt-maleic anhydride) with neat chlorosulfonic acid. 4H-Pyrimido[2,1-b]benzothiazole derivatives, tetrasubstituted imidazoles and benzoxanthenones as selected solvent-free multicomponent reactions were successfully synthesized using this catalyst. These eco-friendly protocols offer several advantages such as green and cost-effective procedures with excellent yield, shorter reaction time, simpler work-up, recovery, and reusability of metal-free solid acid heterogeneous catalyst along with tolerance of a wide range of functional groups.

Full text of DOI:10.1016/j.molcata.2014.04.024

Accepted Manuscript
Title: Solvent-free multicomponent reactions using the novel
N-sulfonic acid modified poly(styrene-maleic anhydride) as a
solid acid catalyst
Author: Majid. M. Heravi Elaheh Hashemi Yahya Shirazi
beheshtiha Khadijeh Kamjou Maryam Toolabia Nastaran
Hosseintash
PII:
S1381-1169(14)00162-9
DOI:
Reference:
http://dx.doi.org/doi:10.1016/j.molcata.2014.04.024
MOLCAA 9086
To appear in:
Journal of Molecular Catalysis A: Chemical
Received date:
Revised date:
Accepted date:
8-3-2014
19-4-2014
19-4-2014
Please cite this article as: Md.M. Heravi, E. Hashemi, Y.S. beheshtiha, K.
Kamjou, M. Toolabia, N. Hosseintash, Solvent-free multicomponent reactions
using the novel N-sulfonic acid modified poly(styrene-maleic anhydride) as
a solid acid catalyst, Journal of Molecular Catalysis A: Chemical (2014),
http://dx.doi.org/10.1016/j.molcata.2014.04.024
This is a PDF file of an unedited manuscript that has been accepted for publication.
As a service to our customers we are providing this early version of the manuscript.
The manuscript will undergo copyediting, typesetting, and review of the resulting proof
before it is published in its final form. Please note that during the production process
errors may be discovered which could affect the content, and all legal disclaimers that
apply to the journal pertain.

Revised
Solvent-free multicomponent reactions using the novel N-sulfonic acid
modified poly(styrene-maleic anhydride) as a solid acid catalyst
Majid. M. Heravi,*,a Elaheh Hashemi,a Yahya Shirazi beheshtiha,a Khadijeh Kamjou,a Maryam
Toolabia and Nastaran Hosseintasha
a Department of Chemistry, School of Science, Alzahra University, Vanak, Tehran, Iran
Corresponding author. Fax: + 98 21 88041344; e-mail: mmh1331@yahoo.com (M. M. Heravi)
Highlights
► Poly(styrene-co-maleic anhydride) was reacted with 4-aminopyridine and used as a polymeric support.
► This support was reacted with chlorosulfonic acid for the preparation of solid acid catalyst.
► A facile methodology for the solvent-free multicomponent reactions for the synthesis of 4H-Pyrimido[2,1-
b]benzothiazole derivatives, tetrasubstituted imidazoles and benzoxanthenones were successfully reported.
► This catalyst can promote the yields and reaction times and at least, can be loaded without pre-activation and reused
over several repeated runs.
Abstract:
A new N-sulfonic acid based on the polymer-support as a solid acid catalyst is prepared by the
reaction of the modified poly(styrene-alt-maleic anhydride) with neat chlorosulfonic acid. 4H-
Pyrimido[2,1-b]benzothiazole derivatives, tetrasubstituted imidazoles and benzoxanthenones as
selected solvent-free multicomponent reactions were successfully synthesized using this catalyst.
1
Page 1 of 30

These eco-friendly protocols offer several advantages such as green and cost-effective
procedures with excellent yield, shorter reaction time, simpler work-up, recovery, and reusability
of metal-free solid acid heterogeneous catalyst along with tolerance of a wide range of functional
groups.
Keywords: Polymer-supported catalyst, Poly(styrene-co-maleic anhydride), Acid catalyst,
Solvent-free multicomponent reaction
1. Introduction
Assembling several molecules into the product in one reaction step is as a result of the
convergent character of multi-component reactions (MCRs) which often give excellent chemo-
and regioselective products. These simple, atom economy and time-saving methods make that an
important procedure in the synthesis of biologically active compounds such as drugs and
agricultural chemicals [1,2].
Increasing the importance of heterocyclic compounds in the field of pharmaceuticals and
industrial chemicals has increased the development of simple, elegant and facile methodologies
for their synthesis. MCRs reactions remain the most efficient synthetic transformation to produce
heterocyclic compounds [3, 4].
Using the eco-friendly reusable heterogeneous catalysts such as solid acids instead of
conventional, toxic and polluting traditional homogeneous Brönsted and Lewis acid catalysts is
currently in much demand. Solid acids have many advantages over liquid acids in organic
reaction catalysis such as their efficiency, easy recyclability and recoverability, operational
simplicity, non-corrosive and environmental friendly nature. These benefits make them efficient
2
Page 2 of 30

catalysts in industry and there are more than 100 industrial transformations using over 103 solid
acids at the end of the last century [5-11]. Although, among various supports that can be used for
the preparation of the above mentioned catalysts [12-15], silica and zeolite are the more
extensively used [16-21], ‘leaching’ in these supported catalysts leads to loss of activity and they
º
are also thermally unstable above 120 C in their acid form. Consequently, the synthesis of new
support like polymers for the preparation of solid acid catalysts that addresses these drawbacks is
enviable [22-25].
Poly(styrene-co-maleic anhydride) (SMA) as a commercially available copolymer with reactive
anhydride groups, which are susceptible to be modified with different nucleophilic reagents, is
an attractive candidate support for design of different reagents [26-31] and catalyst [32]. In the
course of our studies on the modification and use of heterogeneous solid acid catalyst in organic
transformations [33-38], and in continuation of our interest in synthesis of biologically
heterocyclic systems via MCR [39-42] herein we attempted the reaction SMA with
4-aminopyridine and discovered the capability of new modified support in synthesis of new
N-sulfamic acid modified poly(styrene-maleic anhydride) catalyst. In addition, for the
development of environmentally benign chemical methods in which heterogeneous recyclable
catalysts are used under solvent-free conditions, we examined the efficiency of this heterogonous
catalyst in some solvent-free multicomponent reactions.
2. Experimental
2.1. Materials
3
Page 3 of 30

N,N-Dimethylformamide (DMF) and triethylamine (TEA) were distilled and kept in 4 Å
molecular sieve before use. The other reagents were not purified before use and were purchased
from Aldrich and Merck with high-grade quality (except SMA). SMA used in this study is
KARABOND SAM and its general formula is [(C8H8)0.6 (C4H2O3)0.4]n with Anhydride/imide
content = 40%, Mn = 86666 (g/mol), Mw = 182000 and Mw/Mn = 2.1.
2.2. Equipments
1
The H NMR and 13C NMR spectra were recorded by using Bruker Ultrashield 400 and 100
MHz respectively Advance instrument, with DMSO-d6 used as solvent. Proton resonances are
designated as singlet (s), doublet (d), triplet (t) and multiplet (m). FTIR spectra were recorded
using KBr disks on FT-IR Bruker Tensor 27 instrument in the 500-4000cm-1 region. The
vibrational transition frequencies are reported in wave numbers (cm-1). Band intensities are
assigned as weak (w), medium (m), and strong (s). The scanning electron micrographs of the
catalyst surface were recorded using Lecia Cambridge S 360 SEM instrument.
Thermogravimetric analysis (TGA/DTG) data were recorded on a Setaram instrument (Caluire,
France) at a heating rate of 10 °C/min under nitrogen atmosphere. All yields refer to isolated
products.
2.3. Catalyst synthesis
The chemical modification of SMA (1) was performed in two steps according to Lee et al.
optimized reactive condition [43]. 1.00 g SMA, 1.54 g 4-aminopyridine (2) and 15 ml dry DMF
4
Page 4 of 30

were added into a 100-ml glass reactor and then N2 gas was charged into the reactor and sealed.
The reactor was placed into a thermostatic oil-bath on the oscillator and the reactive mixture was
oscillated until the reagents dissolved in DMF and kept oscillating at 35 ºC for 3.5 h. After that,
0.6 ml acetic anhydride, 0.33 g sodium acetate and 0.3 ml triethylamine were added into the
reactor by syringe (Scheme 1). The temperature was continuously raised to 75 ºC and oscillating
for another continued for 3.5 h. The reaction mixture was cooled to room temperature, and was
poured slowly into 300 ml of vigorously stirring methanol. A fiber-like precipitated polymer was
repeatedly washed with methanol, collected by filtration and dried under reduced pressure at 70
ºC to constant weight. For further purification, the SMI polymer (3) was re-precipitated twice.
Chlorosulfonic acid (0.23 mL as a >97% standard solution) was added to a suspension of
powdered (0.5 g) SMI in 10 mL dry CH2Cl2 over a period of 5 min. The mixture was stirred at
room temperature for 6 h then dichloromethane was removed under reduced pressure. The solid
powder was dried under vacuum at 65 ºC for 4 h to afford SMI-SO3H (0.719 g) as a light-yellow
powder (Scheme 1).
IR spectrum of SMI (υmax: cm-1): 3209.61 (br), 2928.77 (br), 1783-1705 (s), 1665.01 (s), 1564.80
(s), 1415.83 (s), 1252.92 (w), 1192.59 (w), 1102.29 (w), 763.60 (s).
IR spectrum of SMI-SO3H (υmax: cm-1): 3208.56 (br), 1721.25 (s), 1655.39 (s), 1531.21 (m),
1288.53 (s), 1175.34 (s), 1069.94 (s), 1007.23 (s), 884.56 (s), 850.87 (s), 578.35 (s).
5
Page 5 of 30

CH CH2
O
CH CH2
O
n
CH CH2
O
n
O
o
Dry CH2Cl2, ClSO3H
n
2
O
i) , dry DMF, 35 C, 3 h
N
N
O
N
N
O
ii) Ac2O, Et3N, AcONa
75 oC, 3h
N
1
3
4
Cl
SO3H
Polymer-support
Cat. SMI-SO3H
NH2
2
Scheme 1. Preparation of SMI-SO3H catalyst.
2.4. Catalytic reactions
2.4.1 General procedure for the synthesis of 4H-pyrimido[2,1-b]benzothiazole derivatives
(8a-g)
A
mixture of the ethyl acetoacetate (1 mmol), benzaldehyde (1 mmol), and
2-aminobenzothiazole (1 mmol) in the presence of SMI-SO3H (0.08g) was stirred at 100 °C in an
oil bath. Completion of the reaction was monitored by TLC. After that, the mixture was cooled
to room temperature, then hot ethanol was added and the solid heterogeneous catalyst was easily
filtrated. The obtained catalyst was washed with acetone and dried under reduced pressured in 70
ºC for 3 h and stored for another consecutive reaction run. The filtrate was concentrated to
solidify and the crude product 8a was purified by re-crystallization from aqueous ethanol in 72%
yield. The selected benzothiazole derivatives (8b-g) were similarly synthesized and their
physical data were determined (Scheme 2).
6
Page 6 of 30

O
O
H3C
R2
R1
6a: R2 = OMe
SMI-SO3H
solvent-free, 100 °C
6b:
R
2 = OEt
O
CHO
+
N
R2
S
N
R1
NH2
S
N
CH3
8a: R1 = H, R2 = OEt
8b: R1 = 4-Cl, R2 = OEt
8c:
7
5a:
R
1 = H
5b: R1 = 4-Cl
5c: R1 = 3-NO2
5d: R1 = 4-OH
5e:
R
R
1 = 3-NO2, R2 = OEt
1 = 4-OH, R2 = OEt
8d:
8e: R1 = H, R2 = OMe
R
1 = 4-OMe
8f: R1 = 4-OMe, R2 = OMe
8g: R1 = 4-NO2, R2 = OMe
1
5f:
R = 4-NO2
Scheme 2. Synthesis of 4H-pyrimido[2,1-b]benzothiazole derivatives (8a-g)
1
The physical and spectral (melting point (Mp), IR, H NMR, and Mass) data for the new
derivatives 8b and 8c are as follow:
Ethyl-2-methyl-4-(4-chlorophenyl)-4H-pyrimido[2,1-b][1,3]benzothiazole-3-carboxylate
1
(8b, C20H17ClN2SO2): Mp 86-88 °C; IR (υmax, cm-1): 3390, 1699, 1670, 1588, 1496, 744; H
NMR: δH 1.21 (t, 3H, CH2CH3), 2.32 (s, 3H, CH3), 4-4.09 (m, 2H, OCH2), 6.48 (s, 1H, CH),
7.17-7.20 (t, 1H, ArH), 7.28-7.48 (m, 6H, ArH), 7.73-7.75 (d, 1H, Ar-H) ppm; MS (m/z): 384
(M+), 355, 311, 273, 245, 199, 175, 134.
Ethyl-2-methyl-4-(3-nitrophenyl)-4H-pyrimido[2,1-b][1,3]benzothiazole-3-carboxylate (8c,
C20H17N3SO4): Mp 222-224 °C; IR (υmax, cm-1): 3073,2981, 1656, 1581, 1505, 748; 1H NMR: δH
1.21 (t, J = 7 Hz, 3H, CH3), 2.34 (s, 3H, CH3), 3.99-4.13 (m, 2H, OCH2), 6.7 (s, 1H, CH), 7.18-
8.10 (m, 7H, ArH), 8.36 (s, 1H, ArH) ppm; MS (m/z,%): 395 (M+), 366, 322, 273, 245, 199, 175,
134.
7
Page 7 of 30

2.4.2 General procedure for the synthesis of 1,2,4,5-tetrasubstituted imidazoles (12a-m)
A mixture of benzil (1 mmol), benzaldehyde (1 mmol), aniline (1 mmol), ammonium acetate (1
mmol) and 0.03 g of SMI-SO3H was stirred in an oil-bath (90 ºC). After the completion of the
reaction, as monitored by TLC, the reaction mixture was cooled to room temperature. The
reaction mixture was soluble in warm absolute ethanol and separated from the catalyst which
was insoluble in Ethanol. The recovered catalyst was washed with acetone and dried under
reduced pressured in 70 ºC for 3 h and stored for another consecutive reaction run. The pure
product 12a was obtained by re-crystallization of the reaction mixture from ethanol (85% yield).
By the application of this reaction condition, other imidazole derivatives (12b-m) were
synthesized and their physical data were determined (Scheme 3).
3
1
3
11a:
R = Ph
12a:
12b:
12c:
R = H, R = Ph
11b: 4-Meo- C6H4
11c: R3 = 4-Me-C6H4
1
3
R3-NH3
+
R = H, R = 4-Meo- C6H4
1
3
R3
R = 4-Cl, R = Ph
OHC
12d: R1 = 4-Me, R3 = Ph
Ph
Ph
O
Ph
Ph
N
SMI-SO3H
solvent-free, 90 °C
12e: R1 = 4-Me, R3 = 4-Me-C6H4
1
3
12f:
12g:
12h:
R = 4-OH, R = Ph
R1
R1
N
1
3
OH
R = 4-OH, R = 4-Me-C6H4
5a: R1 = H
5b: R1 = 4-Cl
5c:
5d:
5e: R1 = 4-OMe
5g: R1 = 4-Me
5h: R1 = 2-NO2
R = 2-OH, R = Ph
1
3
9
NH4OAc
12i: R1 = 2-OH, R3 = 4-Me-C6H4
12j: R1 = 4-OMe, R3 = Ph
10
1
R = 3-NO2
1
3
1
12k:
12l:
12m:
R = 4-OH
R = 2-OMe, R = Ph
1
3
R = 3-NO2, R = Ph
1
3
R = 3-NO2, R = 4-Me-C6H4
Scheme 3. Synthesis of imidazoles derivatives (12a-m)
2.4.3 General procedure for the synthesis of benzoxanthenones (15a-g)
A heterogeneous mixture of β-naphthol (1.0 mmol), benzaldehyde (1.0 mmol), dimedone (1.0
mmol) and SMI-SO3H (0.07 g) is heated at 80 ºC in an oil bath under solvent-free condition. The
progress of the reaction was monitored by TLC. After the completion of the reaction, the product
8
Page 8 of 30

was extracted with hot ethanol and the catalyst was easily filtered. The filtered catalyst is washed
with acetone, dried under reduced pressure, and reused for successive runs. The filtrate is
concentrated and the crude product 15a is re-crystalized from ethanol to give 78% yield. Some
selected benzoxanthenones (15b-g) were prepared in the similar way and their physical data
were compared with those of authentic samples (Scheme 4).
1
5a:
5d:
5i:
R
R
R
= H
1 = 4-OH
1 = 2-OMe
5e: R1 = 4-OMe
R1
5j: R1 = 2-OMe,4-OH
CHO
1 = H
15a:
R
5k:
5l:
=
=
H
15b: R1 = 4-OH
15c: R1 = 2-OMe
15d: R1 = 4-OMe
15e:
isobutyl
R1
OH
O
O
SMI-SO3H
solvent-free, 80 °C
R
1 = 2-OH,3-OMe
=
H
+
15f:
15g:
= isobutyl
13
O
O
14
Scheme 4. Synthesis of benzoxanthenones derivatives (15a-g)
3. Results and discussion
3.1. Preparation and characterization of the SMI-SO3H catalyst
The high concentration and reactivity of the cyclic anhydride groups of SMA make this polymer
as an ideal support in organic synthesis [26-31]. In continuation of Nàjera and co-workers
achievements in using the modified SMA polymer for the synthesis of recoverable palladium
catalyst [32], we tried to examine the modification of SMA with 4-aminopyridine as a simpler
amine and investigated its ability as a support for the synthesis of solid acid catalysts. The
modification of SMA (1) with 4-aminopyridine (2) was successfully performed in two steps
following Lee et al. condition [43]. The conversion of maleic anhydride moiety in SMA to
maleimide was monitored by FT-IR spectrometer. After the reaction of SMA with 4-
aminopyridine, imide peaks were appeared at 1705-1738 cm-1 and no peak was observed at
9
Page 9 of 30

3300-3500 cm-1 for amino groups. That is to say, the imidization of SMA was completed and no
1
residual 4-aminopyridine was observed in the resulting SMI. Moreover, the H NMR spectrum
of this SMI has been attempted for emphasizing to absolute value of conversion and showed a
pattern similar to SMA [43] but aromatic protons of pyridine of residual 4-aminopyridine are
1
observed. In the H NMR spectra of this polymer, appearance of symmetric pseudoquartet C-H
proton of pyridine group around 7.99 ppm and absence of N-H peaks of amino group in 4-
aminopyridine group indicates the presence of amide groups in the polymer side chain.
IR spectrum of SMI (υmax, cm-1): 3209.61 (s), 2928.77 (s), 1783-1705 (s), 1665.01 (s), 1564.80
(s), 1415.83 (s), 1252.92 (w), 1192.59 (w), 1102.29 (w), 763.60 (s).
1H NMR of SMI (υmax, cm-1): 1.10 (m, 2H), 1.90 (s, 1H), 2.60 (s, 1H), 2.90 (m, 1H), 6.59 (1H,
Ar-H), 6.88 (1H, Ar-H), 6.88-7.36 (5H, Ar-H), 7.99 (2H, Ar-H).
The SMI prepared support was treated with neat chlorosulfonic acid at room temperature under a
facile and clean reaction conditions, thus the reaction needed no special work-up (Scheme 1).
FTIR spectrum of catalyst is completely different with that of SMI. This may be attributed to the
presence of an extra sulfonic acid group on the pyridine nitrogen of SMI-SO3H which caused the
increasing of the number of vibrational in FTIR spectrum of catalyst [22, 44]. The broad band
that centered at 3208.56 cm−1 in SMI-SO3H can be assigned to OH stretching of the SO3H group.
In addition, bands at 1288.53, 1175.34, 1069.94, 884.56 and 850.87 cm-1 are assigned to the
asymmetric and symmetric SO2 stretching, S-OH bending and symmetric S-N stretching
vibrations, respectively in SMI-SO3H spectrum [45]. On the other hand, “some changes in
aromatic ring” as a consequence of the sulfonated pyridine ion formation by the sulfonation
reaction, were observed. The bands at 1564.80 and 1415.83 cm-1 in SMI spectrum are completely
10
Page 10 of 30

changed and converted to weaker bands at 1531.21 and 1453.78 cm-1 in catalyst spectrum which
is related to the sulfonated pyridine ion ring.
IR spectrum of SMI-SO3H: 3208.56 (br), 1721.25 (s), 1655.39 (s), 1531.21 (m), 1288.53 (m),
1175.34 (s), 1069.94 (s), 1007.23 (s), 884.56 (s), 850.87 (s), 578.35 (s).
As it is clear from the SEM micrographs of SMI and SMI-SO3H, the primary structure of SMI
was completely changed after chemical modifications and the aggregation of particles was
retarded in SMI-SO3H catalyst (Fig. 1a and 1b). Fig. 1c with magnifying 21,000, clearly
illustrated the pendant sulfonic groups of the catalyst. Consequently, the surface area of the
catalyst was increased with size reductions and retardation of aggregation, which increased the
catalytic activity of the catalyst in the organic transformations.
Fig. 1. SEM image of SMI support and SMI-SO3H catalyst.
11
Page 11 of 30

TGA and DTGA (differential thermogravimetry) curves of SMI and SMI-SO3H catalyst under
nitrogen were illustrated in Fig 2. and Fig 3., and were used to study the thermal stability of the
acid catalyst. A weight loss below 100 ºC in TGA curves is corresponding to the loss of the
physically adsorbed solvent or trapped water from SMI and SMI-SO3H. SMI is thermally stable
up to 304 ºC, and could be used as a thermally stable support in the synthesis of various organic
catalysts. SMI-SO3H catalyst was mainly degraded by a four-stage process. The first weight loss
in the range of 30-110 ºC, with Tmax = 62, attributed to the loss of moisture contents. Thermal
decomposition of the pendant groups of catalyst caused to other weight loss, Tmax = 223, 272 and
333 ºC. The 48% weight loss of catalyst in Tmax = 333 ºC can also be attributed to the thermal
decomposition of sulfonic groups. High temperature for the decomposition of the catalyst can be
explained as intermolecular bonding interactions of the sulfonated SMI moiety in the solid state,
leading to the formation of a rigid network structure [22]. Since ,this catalyst is stable up to 226
ºC it could be considered and selected as a suitable and versatile catalyst in organic
transformations requires temperature range of 80-140 °C.
12
Page 12 of 30

Fig. 2. TGA of SMI support and SMI-SO3H catalyst.
Fig. 3. DTG of SMI support and SMI-SO3H catalyst.
Anthraquinone (H0 = -8.2), p-nitrotoluene (H0 = -11.35) and 4-chloronitrobenzene (H0 = -12.70)
were used as Hammett indicators [46] in benzene as the solvent for the evaluation of the acid
strength of SMI-SO3H (Table 1). After evacuating the catalyst at 125 °C for 2 h, it was cooled to
room temperature and allowed to contact with the vapor of the Hammett indicator. For
13
Page 13 of 30

determination of acid contents of SMI-SO3H through acid-base titration, a standard solution of
NaOH was added to a suspension of the catalyst in H2O-EtOH (1:1). The resulting mixture was
stirred for 2 h, and then a 0.01% solution of phenolphthalein in EtOH was added to the
suspension as an indicator [22]. The solution was titrated with a standard HCl solution and the
acid loading of SMI-SO3H was found to be in the range of 1.7 and 1.9 mmol g-1 by several
parallel experiments.
Table 1
Acid strength of SMI-SO3H
Indicator and H0
p-Nitrotoluene
Catalyst
Anthraquinone
4-Chloronitrobenzene
-8.2
+
−11.35
−12.70
SMI-SO3H
±
-
+, color changed clearly; −, color unchanged; ±, color changed unclearly.
3.2. Solvent-free multicomponent reaction using SMI-SO3H catalyst
The structural determination of SMI-SO3H encouraged us to try this catalyst in multi-component
reactions as part of our current studies on the development of new catalysts for the synthesis of
heterocyclic systems [33-38]. We initially investigated the efficiency of the catalyst for the
synthesis of 4H-pyrimido[2,1-b]benzothiazole derivatives (8a-g) by the condensation reaction of
2-aminobenzothiazole (7) with substituted benzaldehyde (5a-f) and β-dicarbonyl derivatives (6a
and 6b) (Scheme 2). For the optimization of the reaction condition, the condensation of
benzaldehde (5a), ethylacetoacetate (6b) and 2-aminobenzothiazole (7) as a model reaction was
selected. Firstly, we investigated the effectiveness of the catalyst by comparing the reaction in
0.07 g of different catalysts. From the result in Table 2, it is clear that the activity of our new
catalyst was similar to the Silica Perchloric Acid as an excellent acidic catalyst [47] and also
comparable with commercially available Amberlyst-15 catalyst which has many applications in
14
Page 14 of 30

organic transformations [48]. In addition, the effect of different solvents on the reaction time and
yields of the product was examined (Table 3) and we concluded that solvent-free conditions is
the condition of choice. Higher yield of solvent-free condition may be attributed to the higher
concentration of the reactants in reaction media ,which often facilitate these reactions to be
completed in shorter reaction times along with offering an easier workup [49 ]. The optimization
of the amount of the catalyst and reaction temperature indicated that the best result is achievable
in the presence of 0.08 g of catalyst at 100 ºC (Table 4). To evaluate the scope and limitations of
this methodology, we extended this optimized condition for the preparation of 4H-pyrimido[2,1-
b]benzothiazole derivatives. The results are illustrated in Table 5. It is noteworthy that the use of
this catalyst led to the preparation of different 4H-pyrimido[2,1-b]benzothiazole derivatives in
good yield. The selected benzothiazole derivatives (8a, 8d-g) were known and their physical data
were compared with those of authentic samples and found to be identical (Table 5) [50, 51]. In
addition, the structure of 8b and 8c as new compounds were confirmed from their spectral data
1
included infrared (FT-IR), H NMR, and mass spectroscopic analyses. The formation of
compound 8a and 8c were evident from the appearance of [M+] peak at m/z = 384 and 395
respectively in mass spectrum (ESI)+ and the appearance of characteristic methine proton as
singlet at δ = 6.48 and 6.7 ppm respectively in their 1H NMR spectrum.
Table 2
Solvent-free synthesis of 8a in presence of different catalysts at 100 °C.a
Entry
Catalyst
Time (h)
Yieldb (%)
1
2
3
6
Silica Perchloric Acid
Al2O3/KF
3
5
3
3
65
40
40
50
Nano-ZnO
AlCl3-HSO4
15
Page 15 of 30

7
8
9
SMI-SO3H
Dawson
Amberlyst-15
-
3
3
3
5
69
53
71
-
10
a 1 mmol (5a), 1 mmol (6b) and 1 mmol (7) in presence of 0.07 g of catalyst
b refers to the isolated yield
Table 3
Synthesis of 8a in presence of different solvents.a
Entry
Solvent
Time (h)
Temperature (°C)
Yieldb (%)
1
2
3
4
5
H2O
CH3CH2OH
CH3CN
DMF
3
3
3
3
3
Reflux
Reflux
Reflux
Reflux
100
45
30
35
60
69
-
a 1 mmol (5a), 1 mmol (6b) and 1 mmol (7) in presence of 0.07 g of catalyst and 5 mL of solvent
b refers to the isolated yield.
Table 4
Synthesis of 8a in presence of different amount of catalyst and temperature.a
Entry
Catalyst (g)
Temperature (°C)
Yieldb (%)
1
2
3
4
5
6
7
0.06
0.07
0.08
0.09
0.08
0.08
0.08
100
100
100
100
60
60
69
72
72
55
63
71
80
120
a 1 mmol (5a), 1 mmol (6b) and 1 mmol (7)
b refers to the isolated yield.
Table 5
Synthesis of 4H-pyrimido[2,1-b]benzothiazole derivatives (8a-g) under optimized conditions.a
Entry
Product
Time (h)
Yieldb(%)
Mp (°C)/Lit. Mp[ref]
8a
8b
3
3
178-180/175-176 [44]
86-88
1
2
72
71
16
Page 16 of 30

8c
4
222-224
3
4
5
69
73
74
8d
8e
3
3
210-212/205-207 [45]
143-145/144-145 [44]
8f
4
150-153/154-157 [44]
78-81/86-88 [44]
6
66
8g
3
7
76
a 1 mmol (5), 1 mmol (6) and 1 mmol (7) in presence of 0.08 g of catalyst at 100 ºC
b refers to the isolated yield.
Encouraged by these results, we were enough confident to examine the catalytic power of SMI-
SO3H catalyst in another multi-component reaction. Preliminary optimization of synthesis
reaction conditions of 1,2,4,5-tetrasubstituted imidazoles was performed using the pair benzyl
(9), benzaldehyde (5a) and aniline (11a). The comparison of two solvents and solvent-free
conditions (Table 6) showed that the solvent-free condition was the most suitable for the
synthesis of 12a, and therefore it was used in all subsequent experiments. The amount of the
catalyst was also optimized and 0.03 g was selected as the best amount (Table 6). The effect of
temperature was studied by carrying out both reactions at different temperatures (60, 80, 90, 100
and 120 ºC). It was also observed (Table 6) that yield depends on temperature and it was
increased as the reaction temperature was raised. However from 90, 100 to120 ºC there is no
appreciable increase in the yields observed. Thus, in the subsequent studies all reactions were
carried out at 90 ºC. The optimal conditions were then applied for the preparation of a series of
1,2,4,5-substituted imidazoles (12a-m). The product yields are shown in Table 7.
In summary, using this new catalyst provides an efficient route to access diverse and highly
functionalized imidazoles. The selected synthesized imidazole derivatives (12a-m) were known
and their physical data were compared with those of authentic compounds and found to be
identical (Table 6) [52-57].
17
Page 17 of 30

Table 6
Optimization conditions for the synthesis of 12a in presence of SMI-SO3H catalyst.a
Entry
Product
Solvent
Catalyst (g) Temperature (°C) Time (min)
Yieldb (%)
12a
12a
12a
12a
12a
12a
12a
12a
12a
12a
12a
0.05
0.05
0.05
0.05
Reflux
Reflux
Reflux
100
30
35
45
12
65
60
60
80
1
2
H2O
CH3CH2OH
CH3CN
3
4
-
-
100
5
0.02
0.03
0.04
0.03
0.03
0.03
0.03
20
12
12
15
12
12
12
76
-
-
-
-
-
-
100
6
80
80
100
7
60
69
78
80
80
7
80
8
90
9
120
10
a 1 mmol (9), 1 mmol (5a), 1 mmol (10), and 1 mmol (11a) in 5 mL of solvent (in solution experiments)
b refers to the isolated yield.
Table 7
Synthesis of imidazoles derivatives (12a-m) under optimized conditions.a
Entry
Product
Time (min)
Yieldb (%)
Mp (°C)/Lit. Mp[ref]
1
2
3
12a
12b
12c
12
10
15
80
82
88
216-218/216-218 [52]
171-173/171-173 [52]
148-151/148-151 [52]
18
Page 18 of 30

5
6
12d
12e
12f
10
10
10
15
15
20
10
10
15
20
79
80
93
90
92
89
76
80
79
76
184-185/183-185 [53]
192-193/192-194 [54]
287-289/285-286 [54]
234-236/233-235 [55]
250-252/253-255 [55]
227-230/227-230 [54]
184-186/183-185 [53]
150-152/149-152 [56]
>300/308-309 [57]
7
8
12g
12h
12i
9
10
11
13
15
16
12j
12k
12l
12m
150-151/149-151 [54]
a 1 mmol (9), 1 mmol (5a), 1 mmol (10), and 1 mmol (11a) in presence of 0.03 g catalyst at 90 ºC.
b refers to the isolated yield.
Further, three component reaction of β-naphthol (13), benzaldehyde (5a), and dimedone (14) was
investigated to synthesize benzoxanthenone 15a by using the aforementioned catalyst. After the
finding of the suitable amount of the catalyst, and temperature (Table 8) and examining of
different solvents the best condition including the solvent free condition, 0.07 g of catalyst, and
80 °C is reported as a condition of choice. Other derivatives of benzoxanthenones (15a-g) as an
important group of biologically active heterocycles were synthesized through these optimum
conditions. It is worthwhile to mention that aliphatic aldehyde, such as formaldehyde and
isobutyraldehyde, was successfully applied for the synthesis of benzoxanthenone 15f and 15g
respectively. The selected benzoxanthenones derivatives (15a-g) were known and their physical
data were compared with those of authentic compounds and found to be identical (Table 9) [58].
Table 8
Optimization conditions for the synthesis of 15a in presence of SMI-SO3H catalyst.a
Entry
Product
15a
Solvent
Catalyst (g)
Temperature (°C) Time (h)
Reflux
Yieldb (%)
0.05
3
Trace
1
H2O
19
Page 19 of 30

15a
CH3CH2
OH
0.05
Reflux
3
Trace
2
15a
15a
15a
15a
15a
15a
15a
15a
15a
0.05
0.05
Reflux
100
100
100
100
100
120
60
3
45
62
3
4
CH3CN
1.5
-
-
5
0.04
0.07
0.08
0.09
2
58
-
-
6
0.8
0.8
0.8
0.8
1.4
0.8
71
71
7
70
70
66
78
8
-
-
-
9
0.07
0.07
10
0.07
80
11
a 1 mmol (13), 1 mmol (5a), and 1 mmol (14) in 5 mL of solvent (in solution experiments)
b refers to the isolated yield.
Table 9
Synthesis of benzoxanthenones derivatives (15a-g) under optimized conditions.a
Entry
Product
Time (h)
Yieldb (%)
Mp (°C)/Lit. Mp[ref]
15a
15b
15c
15d
15e
0.8
0.8
149-151/152-154 [58]
220-222/223-224 [58]
205-208/204-206 [58]
208-210/203-205 [58]
181-183/185-187 [58]
1
2
3
4
5
78
80
81
80
74
0.75
0.8
0.8
20
Page 20 of 30

15f
3
3
177-179/173-175 [58]
186-189/190-192 [58]
6
7
66
76
15g
a 1 mmol (13), 1 mmol (5a), and 1 mmol (14) in presence of 0.07 g catalyst at 80 ºC.
b refers to the isolated yield.
To justify the efficiency of the SMI-SO3H catalyst in the synthesis of various heterocycles, the
possible mechanism for the preparation of benzoxanthenones 15a-g is proposed (Scheme 5). The
reaction proceeds via the ortho-quinone methides intermediate, formed by the nucleophilic
addition of 2-naphthol to protonated aldehydes catalyzed by the Brönsted acidic sites of SMI-
SO3H. Subsequent Michael addition of this in situ formed ortho-quinone methides to 1,3-
dicarbonyl compound followed by addition of the phenolic hydroxyl moiety to the carbonyl
groups of ketone provides cyclic hemiketal which on dehydration affords the product.
HO
H
CH CH2
O
CH CH2
O
n
n
R1
O
O
+
N
N
N
R1
+
OH
O
H
N
Cl
Cl
SMI-SO3H
SO3H
SO3
O
R1
CH
Continue the catalytic cycles
OH
HO
SMI-SO3H
+
H
O
O
OH
H
O
O
-H2O
O
O
O
R1
R1
R1
Scheme 5. Mechanism of the synthesis of 15a-g.
21
Page 21 of 30

From the green chemistry perspective, experiments concerning the recycling and reuse of the
catalyst was carried out. Upon completion of the reaction, the catalyst was simply recovered by
simple filtration, washing with acetone and drying at 70 ºC for 3 h. The recovered catalyst was
then added to a fresh reaction mixture for the synthesis of 8a, 12a and 15a compounds in each
selected multi-component reaction. The catalyst could be efficiently recovered and recycled even
after 6 cycles without suffering any significant drop in its catalytic activity or the yield of
reaction (Fig 4).
Fig. 4. The recyclability of the SMI-SO3H in the preparation of 8a, 12a, and 15a.
Conclusions
In summary, the synthesis of novel, thermally stable, green, inexpensive, and easy to prepare
solid acid that contain sulfonic acid group, in good yield, is reported. SMI-SO3H served as an
efficient and reusable catalyst in the green synthesis of benzothiazole, 1,2,4,5-tetrasubstituted
22
Page 22 of 30

imidazole, and benzoxanthenone derivatives. The catalyst plays a crucial role in progress of the
reactions in terms of the rate and yield of the products. Also, the use of this catalyst for these
transformations avoids the common problems in the recovery of the catalysts. This catalyst
system could be easily separated from the reaction mixture with high yields and purity and
directly reused after simple extraction. These successful ability of the SMI-SO3H in the various
multi-component reaction may be justified its application in other either known or novel multi-
component reactions.
Acknowledgment
M.M.H is thankful to Alzahra Research Council for the partial payment from his allocated grant
to this article.
References:
[1] J. Zhu, H. Bienyame, Multicomponent Reactions, Wiley-VCH: Weinheim, 2005.
[2] I. Nakamura, Y. Yamamoto, Chem. Rev. 104 (2004) 2127-2198.
[3] C. Hulme, S. Chappeta, C. Griffith, Y.-S. Lee, J. Dietrich, Tetrahedron Lett. 50 (2009) 1939-
1942.
[4] B. Jiang, T. Rajale, W. Wever, S. J. Tu, G. Li, Chem. Asian. J. 5 (2010) 2318-35.
[5] Y. M. Sania, W. M. Dauda A. W., A. R. A. Aziz, Appl. Catal. A-General. 470 (2014) 140-
161.
23
Page 23 of 30

[6] G. A. Benson, W. J. Spillane, Chem. Rev. 80 (1980) 151-186.
[7] X. Li, W. Eli, J. Mol. Catal. A-Chem. 279 (2008) 159-164.
[8] G. Chehardoli, M. A. Zolfigol, T. Faal-Rastgar, S. Mallakpour, A. Ghorbani-Choghamarani,
J. Chem. Sci. 121 (2009) 441-447.
[9] K. Pirkanniemi, M. Sillanpää, Chemosphere 48 (2002) 1047-1060.
[10] R. Dalpozzo, G. Bartoli, L. Sambri, P. Melchiorre, Chem. Rev. 110 (2010) 3501-3551.
[11] A.K. Chakraborti, B. Singh, S.V. Chankeshwara, A.R. Patel, J. Org. Chem. 74 (2009) 5967-
5974.
[12] M. Hara, T. Yoshida, A. Takagaki, T. Takata, J. N. Kondo, S. Hayashi, K. Domen, Angew.
Chem. Int. Ed. 43 (2004) 2955-2958.
[13] A. Shaabani, A. Maleki, Appl. Catal. A-General. 331 (2007) 149-151.
[14] B. L. A. Prabhavathi D., K. N. Gangadhar, P. S. S. Prasad, B. Jagannadh, R. B. N. Prasad,
Chem. Sus. Chem. 2 (2009) 617-620.
[15] A. Takagaki, M. Toda, M. Okamura, J. N. Kondo, S. Hayashi, K. Domen, M. Hara, Catal.
Today. 116 (2006) 157-161.
[16] F. Shirini, M. Mamaghani, M. Seddighi, Catal. Commun. 36 (2013) 31-37.
[17] E. M. Usai, M. F. Sini, D. Meloni, V. Solinas, A. Salis, Micropor. Mesopor. Mat. 179
(2013) 54-62.
[18] Z. Lin, L. Huang, Q. Ling, H. Chen, C. Zhao, J. Mol. Catal. A-Chem. 365 (2012) 73-79.
[19] M. M. Heravi, N. Tavakoli-Hoseini, F. Bamoharram, Green chemistry letters and reviews
(2010) 263-267.
24
Page 24 of 30

[20] M. Tajbakhsh, M. M. Heravi, B. Mohajerani, A. N. Ahmadi, J. Mol. Catal. A-Chem. 247
(2006) 213-215.
[21] D. Choudhary, S Paul, R. Guptaa, J. H. Clarkb, Green Chem. 8 (2006) 479-482.
[22] F. Shirini, O. G. Jolodar, J. Mol. Catal. A-Chem. 356 (2012) 61-69.
[23] F. Shirini, N. Ghaffari-Khaligh, O. Goli Jolodar, Dyes and Pigments 98 (2013) 290-296.
[24] F. Shirini, M. Abedini, R. Pourhasan, Dyes and Pigments 99 (2013) 250-255.
[25] H. Juan, Y. Xue-Yan, Y. Jiu-Yang, G. Ming-Lin, Mater. Lett. 117 (2014) 112-115.
[26] R. Chinchilla, D. J. Dodsworth, C. Nàjera, J. M. Soriano, Tetrahedron Lett. 42 (2001) 4487-
4489.
[27] R. Chinchilla, D. J. Dodsworth, C. Nàjera, J. M. Soriano, Tetrahedron Lett. 42 (2001) 7579-
7581.
[28] R. Chinchilla, D. J. Dodsworth, C. Nàjera, J. M. Soriano, Bioorg. Med. Chem. Lett. 12
(2002) 1817-1820.
[29] R. Chinchilla, D. J. Dodsworth, C. Nàjera, J. M. Soriano, Synlett (2003) 809.
[30] R. Chinchilla, D. J. Dodsworth, C. Nàjera, J. M. Soriano, Tetrahedron Lett. 44 (2002) 463-
466.
[31] R. Chinchilla, D. J. Dodsworth, C. Nàjera, J. M. Soriano, M. Yus, ARKIVOC (2003) 41-47.
[32] J. Gil-Molto´, S. Karlström, C. Nàjera, Tetrahedron 61 (2005) 12168-12176.
[33] M. M. Heravi, M. Tajbakhsh, A. N. Ahmadi, B. Mohajerani, Monatsh. Chem. 137 (2006)
175-179.
[34] M. M. Heravi, K. Bakhtiari, Z. Daroogheha, F. F. Bamoharram, Catal. Commun. 8 (2007)
1991-1994.
25
Page 25 of 30

[35] F. F. Bamoharram, M. M. Heravi, M. Roshani, M. Jahangir, A. Gharib Appl. Catal. A-
General. 302 (2006) 42-47.
[36] M. M. Heravi, M. Khorasani, F. Derikvand, H. A. Oskoole, F. F. Bamoharram, Catal.
Commun. 8 (2007) 1886-1890.
[37] M. M. Heravi, G. Rajabzadeh, F. F. Bamoharram, N. Seifi, J. Mol. Catal. A-Chem. 256
(2006) 238-241.
[38] M. M. Heravi, F. F. Bamoharram, G.Rajabzadeh, N. Seifi, M. Khatami, J. Mol. Catal. A-
Chem. 259 (2006) 213-217.
[39] M. M. Heravi, K. Bakhtiari, Z. Daroоgheha, F. F. Bamoharram, J. Mol. Catal. A-Chem. 273
(2007) 99-101.
[40] M. M. Heravi, B. Baghernejad, H. A. Oskooie, Tetrahedron let. 50 (2009) 767-769.
[41] M. M. Heravi, Z. Faghihi, J. Iran. Chem. Soc. 11 (2014) 209-224.
[42] M. M. Heravi, B. Baghernejad, H. A. Oskooie, R. Hekmatshoar, Tetrahedron Lett. 49
(2008) 6101-6103.
[43] S. -S. Lee, T. O. Ahn, J Appl. Polym. Sci. 71 (1999) 1187-1191
[44] B. Grzyb, J. Machnikowski, J.V. Weber, J. Anal. Appl. Pyrolysis 72 (2004) 121-130.
[45] N. P. G. Roeges, A Guide to the Complete Interpretation of Infrared Spectra of Organic
Structures, Wiley, New York, 1994.
[46] Y. X. Jiang, X. M. Chen, Y. F. Mo, Z. F. Tong, J. Mol. Catal. A: Chem. 213 (2004) 231-
234.
[47] R. Kumar, D. Kumar, A. K. Chakraborti, Synthesis 2007, 299-303.
[48] R. Pal, T. Sarkar, S. Khasnobis, ARKIVOC 2012, 570-609.
[49] J.O. Metzger, Angew. Chem. Int. Ed. 37 (1998) 2975-2978.
26
Page 26 of 30

[50] A. Shaabani, A. Rahmati, S. Naderi, Bioorg. Med. Chem. Lett. 15 (2005) 5553-5557.
[51] P. K. Sahu, P. K. Sahu, R. Jain, R. Yadav, D. D. Agarwal, Catal. Sci. Technol. 2 (2012)
2465-2475.
[52] B. Sadeghi, F. Mirjalili, M. M. Hashemi Tetrahedron Lett. 49 (2008) 2575-2577.
[53] X. B. Wang, L. He, T. Y. Jian, S. Ye, Chinese Chem. Lett. 23 (2012) 13-16.
[54] H. R. Shaterian, M. Ranjbar, K. Azizi, Chin. J. Chem. 29 (2011) 1635-1645.
[55] J. Safari, Z. Akbari, S. Naseh, Journal of Saudi Chemical Society (2012) in press.
[56] M. M. Heravi, F. Derikvand, M. Haghighi, Monatsh. Chem. 139 (2008) 31-33.
[57] B. Karami, F. Mohammadpour-Dehghani, K. Eskandari, Croat. Chem. Acta. 85 (2) (2012)
147-153.
[58] V. Rama, K. Kanagaraj, K. Pitchumani, Tetrahedron Lett. 53 (2012) 1018-1024.
27
Page 27 of 30

Figure captions
Scheme 1. Preparation of SMI-SO3H catalyst.
Scheme 2. Synthesis of 4H-pyrimido[2,1-b]benzothiazole derivatives (8a-g)
Scheme 3. Synthesis of imidazoles derivatives (12a-m)
Scheme 4. Synthesis of benzoxanthenones derivatives (15a-g)
Fig. 1. SEM image of SMI support and SMI-SO3H catalyst.
Fig. 2. TGA of SMI support and SMI-SO3H catalyst.
Fig. 3. DTG of SMI support and SMI-SO3H catalyst.
Scheme 5. Mechanism of the synthesis of 15a-g.
Fig. 4. The recyclability of the SMI-SO3H in the preparation of 8a, 12a, and 15a.
28
Page 28 of 30

Table Captions
Table 1. Acid strength of SMI-SO3H
Table 2. Solvent-free synthesis of 8a in presence of different catalysts at 100 °C.
Table 3. Synthesis of 8a in presence of different solvents.
Table 4. Synthesis of 8a in presence of different amount of catalyst and temperature.
Table 5. Synthesis of 4H-pyrimido[2,1-b]benzothiazole derivatives (8a-g) under optimized
conditions.
Table 6. Optimization conditions for the synthesis of 12a in presence of SMI-SO3H catalyst.
Table 7. Synthesis of imidazoles derivatives (12a-m) under optimized conditions.
Table 8. Optimization conditions for the synthesis of 15a in presence of SMI-SO3H catalyst.
Table 9. Synthesis of benzoxanthenones derivatives (15a-g) under optimized conditions.
29
Page 29 of 30