Sulfuric acid-modified PEG-6000 (PEG-OSO3H): A biodegradable, reusable solid acid catalyst for highly efficient and eco-friendly synthesis of novel bis-Knoevenagel products under solvent-free conditions

Article abstract of DOI:10.1016/j.tetlet.2013.05.012

Sulfuric acid-modified PEG-6000 (PEG-OSO₃H) is used as a highly efficient, biodegradable, and reusable acid catalyst for the synthesis of novel acyclic and heterocyclic bis-Knoevenagel products under thermal solvent-free conditions. The remarkable features of this green, new methodology are high conversions, cleaner reaction profile, simple experimental and work-up procedure, and economic viability. The catalyst is characterized for the first time by SEM-EDX and powder XRD. The catalyst can be reused several times without significant loss of its catalytic activity.

Full text of DOI:10.1016/j.tetlet.2013.05.012

Accepted Manuscript
Sulfuric acid-modified PEG-6000 (PEG-OSO H): A biodegradable, reusable
3
solid acid catalyst for highly efficient and eco-friendly synthesis of novel bis-
Knoevenagel products under solvent-free conditions
Zeba N. Siddiqui, Tabassum Khan
PII:
S0040-4039(13)00760-0
DOI:
http://dx.doi.org/10.1016/j.tetlet.2013.05.012
TETL 42912
Reference:
To appear in:
Tetrahedron Letters
Received Date:
Revised Date:
Accepted Date:
1 January 2013
30 April 2013
3 May 2013
Please cite this article as: Siddiqui, Z.N., Khan, T., Sulfuric acid-modified PEG-6000 (PEG-OSO H): A
3
biodegradable, reusable solid acid catalyst for highly efficient and eco-friendly synthesis of novel bis-Knoevenagel
products under solvent-free conditions, Tetrahedron Letters (2013), doi: http://dx.doi.org/10.1016/j.tetlet.
2013.05.012
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Sulfuric acid-modified PEG-6000 (PEG-OSO3H): A biodegradable, reusable
solid acid catalyst for highly efficient and eco-friendly synthesis of novel bis-
Knoevenagel products under solvent-free conditions
Zeba N. Siddiqui,* Tabassum Khan
E-mail address of Corresponding author*: siddiqui_zeba@yahoo.co.in
Phone no: Tel. +91 9412653054
Address for correspondence: Dr.Zeba N. Siddiqui
Associate Professor
Department of Chemistry,
Aligarh Muslim University,
Aligarh-202002, India.
1

Graphical abstract
2

Sulfuric acid-modified PEG-6000 (PEG-OSO3H): A biodegradable, reusable
solid acid catalyst for highly efficient and eco-friendly synthesis of novel bis-
Knoevenagel products under solvent-free conditions
Zeba N. Siddiqui* and Tabassum Khan
Department of Chemistry, Aligarh Muslim University, Aligarh, 202002, India.
Corresponding author. Email: siddiqui_zeba@yahoo.co.in
Abstract
Sulfuric acid-modified PEG-6000 (PEG-OSO3H) is used as a highly efficient, biodegradable
and reusable acid catalyst for the synthesis of novel acyclic and heterocyclic bis-Knoevenagel
products under thermal solvent-free conditions. The remarkable features of this green, new
methodology are high conversions, cleaner reaction profile, simple experimental and work-up
procedure and economic viability. The catalyst is characterized for the first time by SEM-EDX
and powder XRD. The catalyst can be reused several times without significant loss of its
catalytic activity.
Keywords:PEG-OSO3H, bis-Knoevenagel products, solvent-free condition.
3

Organic catalytic reactions have emerged as powerful synthetic tool for the synthesis of highly
functionalized compounds.The eco-friendly and economically viable catalysts to make the
organic transformations useful and are highly demanded by academic laboratories and
industries.1 In this respect, development of immobilized catalysts that allow simple work-up
procedure and easy separation of products from reaction mixture is challenging and important.2
Knoevenagel condensation is a facile and versatile method for the formation of carbon-
carbon bond,3 with numerous applications in the synthesis of fine chemicals,4 hetero-Diels–
Alder reactions5 and in the synthesis of carbocyclic as well as heterocycliccompoundsof
biological significance.6Generally, the reaction is catalysed by bases,7 ionic liquids,8 amino
12
acids,9 basic MCM-41 silica,10 Na-SBA-1,11 Ni–SiO2 and nanocrytalline ceria-zirconia.13
Many of the reported methods involve refluxing in hazardous organic solvents for prolonged
time, use of expensive and toxic catalysts, high temperature, low product yields and harsh
conditions with non-recyclable catalysts.
Recently, much attention has been directed towards the use of polymer-supported
catalysts from the economical point of view and in applications to industrial processes due to
their unique properties such as low cost, high catalytic activity, easy work-up and separation of
products and catalysts.14Among the different polymeric matrices employed in solid-phase
chemistry, polyethylene glycol has emerged as a very convenient support for the synthesis of a
variety of small organic molecules, ligands, and catalysts.15Sulfuric acid-modified PEG-6000
(PEG-OSO3H) is an example of polyethylene glycol-supported catalyst which is functionalized
by sulfonic acid groups. Itismild, biodegradable, recyclable, non-volatile and non-corrosive
organic acid which has been used for the synthesis of several heterocyclic molecules.15b,16
Thus, based on the above findings and in continuation of our interest in the developmentof
efficient, economical and new methodologies,17 we herein report, for the first time, theuse of
PEG-sulfuric acid (PEG-OSO3H) as a biodegradable, environmentally benignand recyclable
4

solid acid catalyst, for the synthesis of novel acyclic and heterocyclic bis-Knoevenagel
condensation products under solvent-free conditions in excellent yields.18The catalyst was
recycled up to seven runs.The formation of PEG-OSO3H system was detected by FT-IR,
powder XRD and SEM-EDX analysis (Fig. 1, Fig. 2, Fig. 3 and Fig. 4,SI).
In our initial investigation to establish the optimum reaction conditions
terephthaldehyde (1) (1.00 mmol, 0.134 g),diethyl malonate (2a)(2.00 mmol, 0.32 g) and PEG-
OSO3H (0.013 mmol, 0.08 g) under solvent-free conditions at 70 °C was chosen as a model
reaction (Scheme 1). The controlled experiment demonstrated need of a catalyst, since the
substrates did not react in the absence of the catalyst even after prolonged heating. Only 19%
yield of the corresponding product was obtained in the presence of PEG-OSO3H at room
temperature (Table 1, entry 1), whereas by increasing the temperature to 60 °C and then 70 °C,
a significant improvement was observed and yield of the product increased remarkably after 2
min (Table 1, entry 2, 3). Thus, 70 °C was chosen as reaction temperature in further
investigations. Further, increase in temperature to 80 °C had no significant change in the yield
of the product (Entry 4).
Scheme 1.Synthesis of 3(a-r) under solvent-free conditions.
To compare the efficiency as well as capacity of the solvent-free conditions in comparison with
solvent conditions, the model reaction was examined in the presence of PEG-OSO3H in
5

different solvents (Table 1). When the reaction was performed in EtOH, MeOH,
(CH3)2CHOHlower yield of the product (3a) was obtained after a longer time period
(Table 1, entry 5,6, 7) whereas in H2O, THF and CH3CN, only trace amounts of the
product was obtained (Table 1, entry 8, 9, 10). In AcOH relatively high yield of the product
was obtained but reaction took longer time period for completion (Table 1, entry 11).
When the reaction was carried out under solvent-free condition, it was completed within 2 min
with considerable increase in yield of product 3a (99%) (Table1, entry 3). Further in a
comparative study using other green solvents, the model reaction was also performed in PEG-
400, PEG-600 and CH2OH.CHOHCH2OHand was observed that the reaction completed
relatively in shorter time but with mixture of products (entry 12-14). Thus, our study revealed
that solvent-free condition is the best condition for PEG-OSO3H catalyzed formation of bis-
Knoevenagel products in terms of reduced reaction time and excellent yield of the products.
Table 1 Effect of various solvents versus the solvent-free on the model reaction.a
Entry
Solvent
Temperature
Timeb
Yield (%)c
1
2
3
4
5
6
7
8
9
Solvent-free
Solvent-free
Solvent-free
Solvent-free
EtOH
MeOH
(CH3)2CHOH
H2O
25 °C
60 °C
70 °C
1.1 h
10 min
2 min
2 min
4.5 h
5 h
7 h
6 h
25 h
21 h
19
86
99
97
67
64
46
Trace
Trace
Trace
80 °C
Reflux
Reflux
Reflux
Reflux
Reflux
Reflux
THF
CH3CN
10
11
12
13
14
Acetic acid
PEG-400
PEG-600
Reflux
Reflux
Reflux
Reflux
5.2 h
3.2 h
4 h
75
61(mixture)
47(mixture)
63(mixture)
CH2OH.CHOHC
H2OH
3
a
Reaction conditions: terephthaldehyde (1, 1.00mmol, 0.134 g), diethyl malonate (2a,
2.00mmol, 0.32 g), catalyst (0.013 mmol, 0.08 g), thermal solvent-free condition, T=70°C.
bReaction progress monitored by TLC.
cIsolated yields.
6

In order to establish superiority of the PEG-OSO3H over other catalysts the model
reaction was carried out under various sulfur analog acidic catalysts (Table 2). When the model
reaction was examined inH2SO4-AcOH, p-toluene sulfonic acid (PTS), SiO2-NH2SO3H,
Xanthan-H2SO4, NaHSO4-SiO2,SiO2-H2SO4and camphor-sulfonic acid (CSA), the reaction
took longer time period for completion with lower to moderate yield of the product (entry 2-8).
With NH2SO3Hand NH2C6H4SO3H the reaction was not successful (entry 9-10). Thus, PEG-
OSO3H is a more efficient and superior catalyst over other acidic catalysts in terms of time,
yield and reaction conditions.
Table 2Comparison of catalytic activity of different catalysts on the model reaction.a
Entry
Catalyst
Timeb
Yield (%)c
PEG-OSO3H
H2SO4-AcOH
PTS
SiO2-NH2SO3H
Xanthan- H2SO4
NaHSO4- SiO2
SiO2- H2SO4
CSA
2 min
2.6 h
1.5 h
2.2 h
1.4 h
1.3 h
1.8 h
20 min
-
99
59
68
69
70
71
70
1
2
3
4
5
6
7
8
9
81
NH2SO3H
NH2C6H4SO3H
Incomplete
Incomplete
-
10
a
Reaction conditions: terephthaldehyde (1, 1.00 mmol, 0.134 g), diethyl malonate (2a, 2.00
mmol, 0.32 g), catalyst (0.013 mmol, 0.08 g), thermal solvent-free conditions, T=70°C.
bReaction progress monitored by TLC.
cIsolated yields.
In order to establish the best reaction conditions, we performed an optimization study
using model substrates (terephthaldehyde 1, 1.00 mmol (0.134 g) and diethyl malonate 2a, 2.00
mmol (0.32 g) in the presence of varying amounts of catalyst (Fig. 5). It was found that the
optimum amount of catalyst turned out to be 0.013 mmol (0.08 g) in order to obtain best
results.No significant improvement in the yield was observed on increasing the loading to
7

0.016 mmol (0.10 g), whereas the yield decreased due to decreasing the amount of catalyst to
0.01 mmol (0.06 g).
100
90
80
70
60
50
0.01
0.02
0.03
0.04
0.05
0.06
0.07
0.08
0.09
0.10
0.11
Catalyst amount (g)
Fig 5.Effect of catalyst loading on the model reaction.
Recyclability of the catalyst was checked out under solvent-free conditions using model
reaction of terephthaldehyde (1) with diethyl malonate(2a) in the presence of PEG-OSO3H
(0.013 mmol, 0.08 g). After completion of the reaction, the catalyst was recovered.The catalyst
was then reused for sevenruns adopting the identical protocol without significant loss in
product yield(Table 4)as can also be seen from XRD and SEM spectra (Fig. 2b and Fig. 6, SI).
It is worth mentioning here that for every cycle the catalyst was tested for the reaction at
microscale.
Under these optimized reaction conditions the scope and generality of the current
protocol was further demonstrated by reaction of terephthaldehyde/isophthalaldehyde (1a-b)
with different acyclic and cyclic active methylene compounds (2a-n) under solvent-free
conditions. All the reactions proceeded smoothly and were completed within 2-8 min to afford
the products in excellent yield (95-99%)(3a-r) (Table 5).
8

Table 5Synthesis of bis-Knoevenagel condensation products (3a-r) under thermal solvent-free
conditions.a
Timeb (min)
Yieldc (%)
Entry
3a
2a-n
Product
2
99
3
5
97
98
3b
3c
3d
3e
3f
7
2
4
4
96
99
95
96
3g
3h
3
8
99
97
3i
9

5
2
95
99
3j
3k
2
3
6
98
97
95
3l
3m
3n
2
99
3o
4
95
3p
10

6
96
3q
4
98
3r
aReaction conditions: terephthaldehyde/isophthalaldehyde(1a-b, 1.00 mmol, 0.134 g), different
acyclic and cyclic active methylene compounds (2a-n, 2.00 mmol) andPEG-OSO3H (0.013
mmol, 0.08 g), thermal solvent-free condition, T=70°C.
bReaction progress monitored by TLC.
c Isolated yields.
The structure of compounds (3a-n)was deduced on the basis of their spectral analysis.
The IR spectrum of the newly synthesised compound3a showed sharp and strong absorption
bands at 1628 and 1726 cm-1 for C=C and C=O of ester group. The proton nuclear magnetic
resonance spectroscopy (1H NMR) exhibitedmultiplets from δ 1.23-1.35 and δ 4.28-4.36 for
CH3 and CH2 groups of diethyl malonate moiety. Four aromatic protons appeared as singlet at
δ 7.46. The two olefinic protons were discernible as a singlet at δ 7.69. The 13C NMR spectrum
showed signals at δ 14.10 and δ 61.84 for CH3 and CH2 groups of diethyl malonate moieties
whereas the aromatic carbons appeared in the range of δ 129.70-134.80. The olefinic carbons
C-1′ and C-2 were present at δ 127.61 and δ 140.65 whereascarbonyl carbons of ester groups
appeared at δ 163.6 and δ 166.29 respectively (SI). Further confirmation of the structure was
provided by mass spectrometry which showed M+at m/z 419.2 (M++1 peak). The reaction of
11

terephthaldehyde/isophthalaldehyde1a-b with dimedone 2l,triacetic acid lactone 2mand 4-
hydroxycoumarin 2n did not give the expected Knoevenagel condensation products; instead, it
afforded 3o,3p,3q and 3r in a very short period of time (Table 5). The IR spectrum of 3o
showed sharp and strong absorption bands at 1599 cm-1 and 3325 cm-1 for carbonyl and
1
hydroxyl groups of dimedone moiety respectively. The H NMR exhibited sharp singlets at δ
1.10 and δ 1.21 for CH3 groups and a multiplet at δ 2.26-2.46for CH2groups of dimedone
moiety respectively. Another singlet integrating for two protons at δ 5.48 was assigned to
methine proton. Four aromatic protons appeared as singlet at δ 7.01. The four hydroxyl protons
were discernible as singlets at δ 11.35 and δ 11.83 respectively. The 13C NMR spectrum
showed signals at δ 27.95, 31.06 for CH3 groups and C-5 carbons of dimedone moieties
whereas methine, CH2and C-2 carbons appeared at δ 46.40, 59.11 and 114.65 respectively. The
aromatic carbons appeared in the range of δ 126.04-136.11 andsignals at δ 187.96 and δ
162.19were for hydroxyl and carbonyl group of dimedone moiety respectively. Further
confirmation of the structure was provided by mass spectrometry which showed at m/z 659.3
(M++1 peak). A plausible mechanism for the formation of 3o is depicted in Scheme 2.
12

Scheme 2.Plausible mechanism for the synthesis of 3o.
In conclusion, we have reported a highly efficient andeco-friendly method for the
synthesis of novel bis-Knoevenagel condensation products in excellent yieldusing PEG-
OSO3H as inexpensive, biodegradable and recyclable catalyst. Prominent advantages of this
method are broad scope, operational simplicity, practicability, economic viability, excellent
yield of the products in shorter reaction time, easy work-up, reusability of the catalyst.
Moreover, the direct heating of the reaction mixture at lower temperature and solvent-free
conditions have marked our work as a green and economically benign methodology. We
believe that this method will be a more practical alternative to the other existing methods.
Acknowledgments
The authors are thankful to the SAP scheme (DRS-I) from the University GrantsCommission
(UGC), New Delhi. The authors are also thankful to the Centre of Nanotechnology,
Department of Applied Physics, University Sophisticated Instrument Facility (USIF), AMU,
Aligarh for providing powder X-Ray diffractometer, SEM-EDXfacilities andSAIF, CDRI,
13

Lucknow, Punjab University, Chandigarhfor providing spectral data.One of the authors (T.K.)
would like to acknowledge the UGC, New Delhi, for the financial assistance in the form of
Junior Research Fellowship [F. 17-43/08 (SA-I) ].
References
1.Corma, A. Chem. Rev.1995, 95, 559.
2.Anastas, P.T.; Warner, J.C. Green Chemistry: Theory and Practice, Oxford University
Press, Oxford, 1998.
3.Ryabukhin, S.V.; Plaskon, A.S.; Volochnyuk, D.M.; Pipko, S.E.; Shivanyuk, A.N.;
Tolmachev, A.A. J. Comb. Chem.2007, 9, 1073.
4.Tietze, L.F.; Saling, P. Synlett1992, 281.
5.Majumdar, K.C.; Taher, A.; Nandi, R.K. Tetrahedron2012, 68, 5693.
6.Tietze, L.F. Chem. Rev.1996,96, 115.
7. Han, J.; Xu, Y.; Su, Y.; She, X.; Pan, X. Catal. Commun.2008,9, 2077.
8. Parvin, M.N.; Jin, H.; Ansari, M.B.; Oh, S.M.; Park, S.E. Appl. Catal. A: Gen.2012,205,
413.
9. Hu, Y.; He, Y.H.; Guan, Z. Catal. Commun.2010, 11, 656.
10. Martins, L.; H¨olderich, W.; Hammer, P.; Cardoso, D. J. Catalysis2010,271, 220.
11. Gracia, M.D.; Jurado, M.J.; Luque, R.; Campelo, J.M.; Luna, D.; Marinas, J.M.;
Romero, A.A. MicroporousMesoporous Mater2009,118, 87.
12. Pullabhotla, V.S.R.R.; Rahman, A.; Jonnalagadda, S.B.; Catal. Commun.2009, 10, 365.
13. Postole, G.; Chowdhury, B.; Karmakar, B.; Pinki, K.; Banerji, J.; Auroux, A. J.
Catalysis2010, 269, 110.
14. Fournier, D.; Hoogenboom, R.; Schubert, U.S. Chem. Soc. Rev.2007,36, 1369.
15. (a) Jain, S.L.; Singhal, S.; Sain, B. Green Chem.2007, 9, 740; (b) Hasaninejad, A.;
Shekouhy, M.; Zare, A.; Ghattali,S.M.S. H.; Golzar, N.; J. Iran.Chem. Soc.2011, 2,
14

411; (c) Quan, Z.J.; Da, Y.X.; Zhang, Z.; Wang, X.C. Catal.Commun.2009, 10, 1146.
16. (a) Reddy,C.B.;Kumar, K.S.; Kumar,M.A.; Reddy, M.V.N.; Krishna, B.S.; Naveen,
M.; Arunasree, M. K.; Reddy, C.S.; NagaRaju, C.; Reddy,C.D. Eur. J. Med.Chem.
2012,47, 553; (b)Kumar,R.; Nandi,G.C.; Verma, R.K.; Singh,M.S. Tetrahedron
Lett.2012, 51, 442; (c)Nazeruddin,G.M.; Pandharpatte, M.S.; Mulani,K.B. C.R.
Chim.2012, 15, 91.
17.(a) Siddiqui, Z.N. Tetrahedron Lett.2012, 53, 4974; (b) Siddiqui, Z.N.; Farooq, F. J.
Mol. Catal. A: Chem.2012, 363, 451;(c) Siddiqui, Z.N.; Musthafa, T.N.M. Tetrahedron
Lett.2011,52, 4008.
18.General procedure for the synthesis of novel bis-Knoevenagel products under solvent-
free conditions
A mixture of terephthaldehyde/isophthalaldehyde1a-b(1.00mmol, 0.134 g), acyclic and cyclic
active methylene compounds 2a–n (2.00 mmol) and PEG-OSO3H (0.013 mmol, 0.08 g) were
mixed thoroughly using a mortar and pestle. The reaction mixture was then transferred to an
open Pyrex 100 mL beaker and heated at 70 ˚C for the given time (Table 5).After completion
of the reaction (monitored by TLC), the reaction mixture was cooled to room temperature and
H2O (5 mL) was added to it, and shaken for 3 min to dissolve PEG-OSO3H. The crude product
(insoluble in water) was filtered and recrystallized from hot ethanol (3 mL) to afford the pure
product (3a-r). Inorder to recover the catalyst, the filtrate was dried under reduced pressure
and recovered catalyst was washed with diethyl ether (2 mL) twice andreused after drying
under reduced pressure.
15

Sulfuric acid-modified PEG-6000 (PEG-OSO3H): A biodegradable,
reusable solid acid catalyst for highly efficient and eco-friendly synthesis of
novel bis-Knoevenagel products under thermal solvent-free conditions
Zeba N. Siddiqui* and Tabassum Khan
Department of Chemistry, Aligarh Muslim University, Aligarh, 202002, India.
Corresponding author. Email: siddiqui_zeba@yahoo.co.in
Supporting Information
Contents
General Information…………………………………………………………..…….......1-2
Experimental….................................................................................................................2
Synthesis of the PEG-OSO3H catalyst............................................................................2
FT-IR analysis of PEG-OSO3H.......................................................................................2-3
Powder X-ray diffraction (XRD) analysis of PEG-OSO3H..........................................3
SEM-EDX analysis of PEG-OSO3H...............................................................................3-4
Table 3……………………………………………………………………………………4-5
Recycling study of PEG-OSO3H....................................................................................5-6
General procedure for the synthesis of bis-Knoevenagel products............................6-7
Spectroscopy data of compounds..........................………………………………….....7-12
References………………………………………………………………………………..12
General Information:
Melting points of all synthesized compounds were taken in a Riechert Thermover instrument
and are uncorrected. The IR spectra (KBr) were recorded on Perkin Elmer RXI spectrometer.
1

1H NMR and 13C NMR spectra were recorded on a Bruker Avance II 400 spectrometer using
tetramethylsilane (TMS) as an internal standard and DMSO-d6/CDCl3 as solvent. ESI-MS
were recorded on a THERMO Finnigan LCQ Advantage max ion trap mass spectrometer
having a ESI source. Elemental analyses (C, H and N) were conducted using the Elemental
vario EL III elemental analyzer and their results were found to be in agreement with the
calculated values. Chemicals were of commercial grade and used without further purification.
The homogeneity of the compounds was checked by thin layer chromatography (TLC) on
glass plates coated with silica gel G254 (E. Merck) using chloroform-methanol (3:1) mixture
as mobile phase and visualized using iodine vapours. X-ray diffractograms (XRD) of the
catalyst were recorded in the 2θ range of 10-70° with scan rate of 4°/ min on a Rigaku
Minifax X- ray diffractometer with Ni-filtered Cu Kα radiation at a wavelength of
1.54060°A. The SEM-EDX characterization of the catalyst was performed on a JEOL JSM-
6510 scanning electron microscope equipped with energy dispersive X-ray spectrometer
operating at 20 kV.
Experimental:
Preparation of catalyst
At 0 °C, chlorosulfonic acid (10 mmol, 1.16 g) was added to a solution of PEG-6000 (1
mmol, 6.0 g) in CH2Cl2 (10 mL). Then the resulting solution was stirred at room temperature
overnight, and the solution was concentrated under vacuum. Appropriate ether (50 mL) was
added, and the precipitate filtered and washed with ether (30 mL) three times to afford the
PEG-OSO3H, according to the reported procedure.1
FT-IR spectrum of the catalyst
The FT-IR spectrum of the catalyst is shown in Fig. 1. A broad peak for OH absorption band
was present at 3100-3600 cm-1. The peaks at 2917, 2877 and at 1111 cm-1 represented CH3,
CH2 stretching, and C-O-C symmetric stretching of the PEG unit, respectively.2 The presence
2

of sulfonic acid functional group was established on the basis of a broad peak centred at
1162-1022 cm-1 as a result of merger of peaks at 1162, 1022 and 1111 cm-1 (C-O of PEG
moiety), whereas the peak for S–O stretching mode is present at 662 cm-1.
Fig. 1. FT-IR spectra of PEG-OSO3H
Powder X-ray diffraction (XRD) analysis of the catalyst
The structure of the prepared catalyst (PEG-OSO3H) was identified by powder XRD. The
XRD pattern of the matrix showed characteristic diffraction peaks for PEG moiety at 19.5,
23.6 and 24.5°.2 The other characteristic peaks were due to SO3 group.
Fig. 2. Powder XRD of (a) fresh PEG-OSO3H and (b) PEG-OSO3H after seventh runs.
SEM-EDX analysis of the catalyst
To study the surface morphology of the catalyst, SEM micrographs of the catalyst was
employed. The SEM images of the catalyst (Fig. 3) showed smooth, compact and
homogeneous uniform surface.
3

Fig. 3. SEM images of the catalyst (PEG-OSO3H) at different magnifications.
EDX analysis (Fig. 4) of the catalyst showed the presence of C, O and S elements suggesting
the formation of expected catalytic system.
Fig. 4. EDX analysis of the catalyst (PEG-OSO3H).
To the best of our knowledge there is no report on the characterization of the catalyst
PEG-OSO3H using XRD and SEM–EDX study.
The activity of different loadings of chlorosulfonic acid on PEG support was also
investigated for the synthesis of (3a), by using 5 mmol (0.58 g), 10 mmol (1.16 g) and 15
mmol (1.74 g) of chlorosulfonic acid supported on PEG 1 mmol (6.0 g) (Table 3). With 5
mmol PEG-OSO3H lower yield of the product was obtained in longer time period possibly
due to the lower ratio of chlorosulfonic acid to PEG (Table 3, entry 1) whereas with 15 mmol
PEG-OSO3H again yield was not satisfactory (Table 3, entry 3). The excellent yield of the
product was obtained with 10 mmol PEG-OSO3H (Table 3, entry 2).
4

Table 3 Effect of acid loading on the support for the synthesis of 3a in thermal solvent-free
conditionsa.
Entry
PEG-OSO3H
5 mmol
Time (min)b
Yield (%)c
8
2
2
76
99
84
1
2
3
10 mmol
15 mmol
a
Reaction conditions: terephthaldehyde (1, 1.00 mmol, 0.134 g), diethyl malonate (2a, 2.00
mmol, 0.32 g), catalyst (0.013 mmol, 0.08 g), thermal solvent-free condition, T=70°C.
b Reaction progress monitored by TLC.
c Isolated yields.
The reusability of the catalyst was checked out under solvent-free condition using
model reaction of terephthaldehyde (1) with diethyl malonate (2a) in the presence of PEG-
OSO3H (0.013 mmol, 0.08 g). After completion of the reaction (monitored by TLC), the
reaction mixture was cooled to room temperature, added H2O (5 mL) and shaken for 3 min to
dissolve PEG-OSO3H. The crude product (insoluble in water) was filtered and recrystallized
from hot ethanol (3 mL) to afford the pure product (3a). In order to recover the catalyst, the
filtrate was evaporated under reduced pressure and recovered catalyst was washed with
diethyl ether twice and dried. The recovered catalyst was reused for seven runs adopting the
identical protocol without significant loss in product yield (Table 4). It is worth mentioning
here that for every cycle the catalyst was tested for the reaction at microscale.
Table 4 Recycling data of the catalyst for the model reaction.a
Runs
Catalyst recycles
Timeb
Yieldc
1
2
0
1
2 min
2 min
99
99
5

3
4
5
6
7
2
3
4
5
6
2 min
2 min
4 min
4 min
4 min
99
98
96
96
95
a
Reaction conditions: terephthaldehyde (1, 1.00 mmol, 0.134 g), Diethyl malonate (2a, 2.00
mmol, 0.32 g), catalyst (0.013 mmol, 0.08 g), thermal solvent-free condition, T=70°C.
b Reaction progress monitored by TLC.
c Isolated yields.
Identity of the recovered catalyst was checked by powder XRD (Fig. 2 b) and SEM
(Fig. 6) analysis. It was found that peaks remained the same and there was no change in the
morphology of the catalyst as compared to the fresh catalyst. These data established that
PEG-OSO3H is not damaged upon its reuse as a homogeneous catalyst.
Fig. 6. SEM images of the recovered catalyst (PEG-OSO3H) at different magnifications.
General procedure for the synthesis of bis-Knoevenagel products under solvent-free
conditions
A mixture of terephthaldehyde/isophthalaldehyde 1a-b (1.00 mmol, 0.134 g), acyclic and
cyclic active methylene compounds 2a–n (2.00 mmol) and PEG-OSO3H (0.013 mmol, 0.08
g) were mixed thoroughly using a mortar and pestle. The reaction mixture was then
transferred to an open Pyrex 100 mL beaker and heated at 70 ˚C for the given time (Table 5).
6

After completion of the reaction (monitored by TLC), the reaction mixture was cooled to
room temperature, added H2O (5 mL) and shaken for 3 min to dissolve PEG-OSO3H. The
crude product (insoluble in water) was filtered and recrystallized from hot ethanol (3 mL) to
afford the pure product (3a-r). In order to recover the catalyst, the filtrate was evaporated
under reduced pressure and recovered catalyst was washed with diethyl ether twice (2 mL)
and reused after drying under reduced pressure.
Spectroscopy data of compounds:
Tetraethyl 2,2'-(1,4-phenylenebis(methanylylidene))dimalonate (3a)
1
Yellow solid; m.p. 125-127 °C; IR (KBr) cm-1: 1628 (C=C), 1726 (COO). H NMR (400
MHz, CDCl3): δ = 1.26-1.36 (12H, m, 4 x CH3), 4.28-4.36 (8H, m, 4 x CH2), 7.46 (4H, s,
13
C6H4), 7.69 (2H, s, -CH=C). C NMR (100 MHz, CDCl3): δ = 14.10 (2 x CH3), 61.84 (2 x
CH2), 127.61 (2 x =C), 129.70, 134.80 (Ar-C), 140.65(2 x CH=), 163.62, 166.29 (4 x COO).
ESI-MS: (m/z) 419.2 (M+). Anal. Calcd. For C22H26O8: C, 63.21; H, 6.22; found: C, 63.18; H,
6.26.
Tetraethyl 2,2'-(1,3-phenylenebis(methanylylidene))dimalonate (3b)
1
White solid; m.p. 121-123 °C; IR (KBr) cm-1: 1611 (C=C), 1721 (COO). H NMR (400
MHz, CDCl3): δ = 1.23-1.38 (12H, m, 4 x CH3), 4.26-4.34 (8H, m, 4 x CH2), 7.21-7.43 (3H,
13
m, C6H4), 7.62 (1H, s, C6H4), 8.12 (2H, s, -CH=C). C NMR (100 MHz, CDCl3): δ = 13.98
(2 x CH3), 61.14 (2 x CH2), 125.13 (2 x =C), 128.20, 133.0, 134.03 (Ar-C), 142.16(2 x CH=),
164.02, 165.19 (4 x COO). ESI-MS: (m/z) 419.1 (M+). Anal. Calcd. For C22H26O8: C, 63.21;
H, 6.22; found: C, 63.18; H, 6.26.
(2E,2'E)-diethyl 2,2'-(1,4-phenylenebis(methanylylidene))bis(3-oxobutanoate) (3c)
Shining red solid; m.p. 131-133 °C; IR (KBr) cm-1: 1603 (C=C), 1662 (CO), 1726 (COO). 1H
NMR (400 MHz, CDCl3): δ = 1.26 (6H, m, 2 x CH3), 4.32 (4H, m, 2 x CH2), 7.49 (4H, s,
C6H4), 10.04 (2H, s, -CH=C). 13C NMR (100 MHz, CDCl3): δ = 14.15 (2 x CH3), 31.23 (2 x
7

CH3), 61.91(2 x CH2), 127.84, 130.0(Ar-C), 135.59 (2 x =C), 139.67(2 x CH=), 191.87 (2 x
CO), 194.30 (2 x COO). ESI-MS: (m/z) 359.1 (M+). Anal. Calcd. For C20H22O6: C, 67.10; H,
6.15; found: C, 67.07; H, 6.12.
3,3'-(1,4-phenylenebis(methanylylidene))bis(pentane-2,4-dione) (3d)
1
Dark red crystals; m.p. >300 °C; IR (KBr) cm-1: 1603 (C=C), 1698 (CO). H NMR (400
13
MHz, CDCl3): δ = 2.39 (12H, s, 4 x CH3), 7.47 (4H, s, C6H4), 10.02 (2H, s, -CH=C). C
NMR (100 MHz, CDCl3): δ = 15.21 (4 x CH3), 126.3, 128.0(Ar-C), 133.19 (2 x =C),
138.29(2 x CH=), 165.81 (4 x CO). ESI-MS: (m/z) 299.1 (M+). Anal. Calcd. For C18H18O4: C,
72.54; H, 6.04; found: C, 72.57; H, 6.07.
2.3.4. 2,2'-(1,4-phenylenebis(methanylylidene))dimalononitrile (3e)
White solid; m.p. 205-207 °C (lit. 206-208 °C)3; IR (KBr) cm-1: 1635 (C=C), 2235 (CN). 1H
NMR (400 MHz, CDCl3): δ = 8.19 (4H, s, C6H4), 10.12 (2H, s, -CH=C). 13C NMR (100
MHz, DMSO-d6): δ = 110.21 (2 x =C), 114.6 (4 x CN), 129.83, 130.10 (Ar-C), 139.65 (2 x
CH=). ESI-MS: (m/z) 231.1 (M+). Anal. Calcd. For C14H6N4: C, 73.11; H, 2.61; N, 24.34;
found: C, 73.07; H, 2.64; N, 24.30.
2,2'-(1,4-phenylenebis(methanylylidene))bis(1H-indane-1,3(2H)-dione) (3f)
Green solid; m.p. 257–259 °C; IR (KBr) cm-1: 1602 (C=C), 1693 (CO). 1H NMR (400 MHz,
DMSO-d6): δ = 7.07-7.38 (8H, m, Ar-C), 7.45 (4H, s, C6H4), 8.10 (2H, s, -CH=C). 13C NMR
(100 MHz, DMSO-d6): δ = 104.71 (2 x =C), 123.10, 126.72, 127.5, 131.91 (Ar-C), 137.91 (2
x CH=), 190.13 (4 x CO). ESI-MS: (m/z) 391.6 (M+). Anal. Calcd. For C26H14O4: C, 80.07;
H, 3.59; found: C, 80.10; H, 3.57.
2,2'-(1,3-phenylenebis(methanylylidene))bis(1H-indane-1,3(2H)-dione) (3g)
Greenish yellow solid; m.p. >300 °C; IR (KBr) cm-1: 1587 (C=C), 1690 (CO). 1H NMR (400
13
MHz, CDCl3): δ = 7.32-7.67 (3H, m, C6H4), 7.94 (1H, s, C6H4), 8.18 (2H, s, -CH=C). C
NMR (100 MHz, CDCl3): δ = 103.27 (2 x =C), 124.15, 125.17, 127.5, 133.01 (Ar-C), 139.21
8

(2 x CH=), 191.23 (4 x CO). ESI-MS: (m/z) 391.1 (M+). Anal. Calcd. For C26H14O4: C,
80.07; H, 3.59; found: C, 80.10; H, 3.57.
4,4'-(1,4-phenylenebis(methanylylidene))bis(3-methyl-1-phenyl-1H-pyrazol-5(4H)-one (3h)
1
Reddish brown solid; m.p. >300 °C; IR (KBr) cm-1: 1604 (C=C), 1684 (CO). H NMR (400
MHz, CDCl3): δ = 2.38 (6H, s, 2 x CH3), 7.18-7.96 (14H, m, Ar-C, C6H4), 8.59 (2H, s, -
CH=C). 13C NMR (100 MHz, CDCl3): δ = 30.92 (2 x CH3), 119.14 (2 x =C), 128.83, 129.0,
132.1, 133.50 (Ar-C), 139.10 (2 x CH=), 176.23 (2 x CO). ESI-MS: (m/z) 447.5 (M+). Anal.
Calcd. For C28H22N4O2: C, 75.40; H, 4.93; N, 12.55; found: C, 75.37; H, 4.96; N, 12.51.
2,2'-(1,4-phenylenebis(methanylylidene))bis(2H-benzo[b][1,4]thiazin-3(4H)-one) (3i)
1
Light yellow solid; m.p. 151 °C; IR (KBr) cm-1: 1583 (C=C), 1662 (CO), 3202 (NH). H
NMR (400 MHz, DMSO-d6): δ = 7.40 (4H, s, C6H4), 7.58-7.98 (8H, m, Ar-H,), 10.04 (2H, s,
13
-CH=C), 10.57 (2H, s, NH). C NMR (100 MHz, DMSO-d6): δ = 116.67 (2 x =C), 124.70,
129.33, 130.02, 132.50 (Ar-C), 139.31 (2 x CH=), 191.38 (2 x CO). ESI-MS: (m/z) 429.2
(M+). Anal. Calcd. For C24H16N2O4S2: C, 67.35; H, 3.74; N, 6.54; found: C, 67.37; H, 3.77;
N, 6.57.
5,5'-(1,4-phenylenebis(methanylylidene))bis(2,2-dimethyl-1,3-dioxane-4,6-dione) (3j)
White soild ; m.p. 183–185 °C; IR (KBr) cm-1: 1607 (C=C), 1722 (CO). 1H NMR (400 MHz,
13
DMSO-d6): δ = 2.68 (12H, s, 4 x CH3), 7.46 (4H, s, C6H4), 9.98 (2H, s, -CH=C). C NMR
(100 MHz, DMSO-d6): δ = 27.94 (4 x CH3), 101.78 (2 x C2), 105.89 (2 x =C), 127.07,
129.87 (Ar-C), 137.09 (2 x CH=), 191.47 (4 x CO). ESI-MS: (m/z) 387.1 (M+). Anal. Calcd.
For C20H18O8: C, 62.23; H, 4.66; found: C, 62.25; H, 4.64.
5,5'-(1,4-phenylenebis(methanylylidene))bis(1,3-dimethylpyrimidine-2,4,6(1H,3H,5H)-
trione) (3k)
1
Light yellow powder; m.p. >300 °C; IR (KBr) cm-1: 1578 (C=C), 1729 (CO). H NMR (400
MHz, DMSO-d6): δ = 1.24 (6H, s, 2 x CH3), 2.11 (6H, s, 2 x CH3), 7.48 (4H, s, C6H4), 8.11
(2H, s, -CH=C). 13C NMR (100 MHz, DMSO-d6): δ = 29.4 (4 x CH3), 119.40 (2 x =C),
9

129.5, 132.1 (Ar-C), 141.6 (2 x CH=), 150.7 (2 x C2), 172.3 (2 x C4, C6). ESI-MS: (m/z)
411.5 (M+). Anal. Calcd. For C20H18N4O6: C, 58.59; H, 4.39; N, 13.65; found: C, 58.57; H,
4.34; N, 13.61.
5,5'-(1,3-phenylenebis(methanylylidene))bis(1,3-dimethylpyrimidine-2,4,6(1H,3H,5H)-
trione) (3l)
Yellow powder; m.p. >300 °C; IR (KBr) cm-1: 1579 (C=C), 1734 (CO). 1H NMR (400 MHz,
DMSO-d6): δ = 2.10 (6H, s, 2 x CH3), 3.14 (6H, s, 2 x CH3), 8.15-8.17 (3H, m, C6H4), 8.41
13
(1H, s, C6H4), 8.48 (2H, s, -CH=C). C NMR (100 MHz, DMSO-d6): δ = 30.1 (4 x CH3),
120.24 (2 x =C), 128.1, 132.1, 133.6, 135.0 (Ar-C), 143.1 (2 x CH=), 149.3 (2 x C2), 174.2
(2 x C4, C6). ESI-MS: (m/z) 411.8 (M+). Anal. Calcd. For C20H18N4O6: C, 58.59; H, 4.39; N,
13.65; found: C, 58.57; H, 4.34; N, 13.61.
5,5'-(1,4-phenylenebis(methanylylidene))bis(pyrimidine-2,4,6(1H,3H,5H)-trione)) (3m)
Light yellow powder; m.p. >300 °C; IR (KBr) cm-1: 1570 (C=C), 1745 (CO), 3212 (NH). 1H
NMR (400 MHz, DMSO-d6): δ = 8.06 (4H, s, C6H4), 8.32 (2H, s, -CH=C), 11.31 (2 x NH),
11.45 (2 x NH). 13C NMR (100 MHz, DMSO-d6): δ = 121.10 (2 x CH=), 128.49, 135.64 (Ar-
C), 137.16 (2 x =C), 153.4 (2 x C2), 164.3 (2 x C4, C6). ESI-MS: (m/z) 355.1 (M+). Anal.
Calcd. For C16H10N4O6: C, 54.28; H, 2.82; N, 15.82; found: C, 54.26; H, 2.84; N, 15.85.
5,5'-(1,4-phenylenebis(methanylylidene))bis(2-thioxodihydropyrimidine-4,6(1H,5H)-dione)
(3n)
Orange powder; m.p. >300 °C; IR (KBr) cm-1: 1574 (C=C), 1702 (CO), 3196 (NH). 1H NMR
(400 MHz, DMSO-d6): δ = 8.12 (4H, s, C6H4), 8.33 (2H, s, -CH=C), 11.69 (2 x NH), 12.50 (2
x NH). 13C NMR (100 MHz, DMSO-d6): δ = 122.2 (2 x CH=), 127.14, 133.16 (Ar-C), 138.13
(2 x =C), 166.9 (2 x C4, C6), 175.2 (2 x C2). ESI-MS: (m/z) 387.3 (M+). Anal. Calcd. For
C16H10N4O4S2: C, 49.78; H, 2.59; N, 14.50; found: C, 49.75; H, 2.54; N, 14.53.
2,2',2'',2'''-(1,4-phenylenebis(methanetriyl))tetrakis(3-hydroxy-5,5-dimethylcyclohex-2-
enone) (3o)
10

1
Shining white powder; m.p. 265 °C; IR (KBr) cm-1: 1599 (CO), 3326 (OH). H NMR (400
MHz, CDCl3): δ = 1.10 (12H, s, 4 x CH3), 1.21 (12H, s, 4 x CH3), 2.26-2.46 (16H, m, 8 x
CH2), 5.48 (2H, s, 2 x CH), 7.01 (4H, s, C6H4), 11.35 (2H, s, 2 x OH), 11.83 (2H, s, 2 x OH).
13C NMR (100 MHz, DMSO-d6): δ = 27.95 (8 x CH3), 31.06 (4 x C5), 46.40 (2 x CH),
59.11(8 x CH2), 114.65 (4 x C2), 126.04, 136.11(Ar-C), 162.19 (4 x C3), 187.96 (4 x C1).
ESI-MS: (m/z) 659.3 (M+). Anal. Calcd. For C40H50O8: C, 73.01; H, 7.60; found: C, 73.04; H,
7.64.
2,2',2'',2'''-(1,3-phenylenebis(methanetriyl))tetrakis(3-hydroxy-5,5-dimethylcyclohex-2-
enone) (3p)
White powder; m.p. 278 °C; IR (KBr) cm-1: 1595 (CO), 3315 (OH). 1H NMR (400 MHz,
CDCl3): δ = 1.11 (12H, s, 4 x CH3), 1.26 (12H, s, 4 x CH3), 2.30-2.51 (16H, m, 8 x CH2),
5.54 (2H, s, 2 x CH), 7.34-7.69 (3H, m, C6H4), 7.62 (1H, s, C6H4), 9.93 (2H, s, 2 x OH),
11.87 (2H, s, 2 x OH). 13C NMR (100 MHz, DMSO-d6): δ = 26.99 (8 x CH3), 30.45 (4 x C5),
45.35 (2 x CH), 58.98 (8 x CH2), 114.15 (4 x C2), 125.2, 126.04, 134.2, 136.11(Ar-C),
163.52 (4 x C3), 188.21 (4 x C1). ESI-MS: (m/z) 659.1 (M+). Anal. Calcd. For C40H50O8: C,
73.01; H, 7.60; found: C, 73.04; H, 7.64.
3,3′,3″,3‴ -(1,4-phenylenebis(methanetriyl))tetrakis(4-hydroxy-6-methyl-2H-pyran-2-one)
(3q)
1
White powder; m.p. 253 °C; IR (KBr) cm-1: 1705 (CO), 3421 (OH). H NMR (400 MHz,
DMSO-d6): δ = 2.20 (12H, s, 4 x CH3), 6.05 (4H, s, 4 x CH5), 6.90 (2H, s, 2 x CH), 8.09 (4H,
13
s, C6H4), 11.71 (4H, s, br, 4 x OH). C NMR (100 MHz, DMSO-d6): δ = 19.10 (4 x CH3),
33.18 (2 x CH), 101.75 (4 x C3), 126.16, 129.79 (Ar-C), 160.66 (4 x C5), 166.59 (4 x C6),
168.18 (4 x C2), 192.20 (4 x C4). ESI-MS: (m/z) 603.6 (M+). Anal. Calcd. For C32H26O12: C,
63.84; H, 4.32; found: C, 63.87; H, 4.29.
11

3,3’-(1,4-phenylenebis((2-hydroxy-4-oxo-4H-chromen-3-yl)methylene))bis(4-hydroxy-2H-
chromen-2-one) (3r)
1
Shining white powder; m.p. >300 °C; IR (KBr) cm-1: 1719 (CO), 3380 (OH). H NMR (400
MHz, DMSO-d6): δ = 6.44 (2H, s, 2 x CH), 7.15 (4H, s, C6H4), 7.34-7.96 (16H, m, Ar-H).
13C NMR (100 MHz, DMSO-d6): δ = 35.18 (2 x CH), 99.48 (4 x C3), 123.74, 125.4, 128.3,
128.9, 132.13 (Ar-C), 167.23 (4 x C2), 183.12 (4 x C4). ESI-MS: (m/z) 747.2 (M+). Anal.
Calcd. For C44H26O122: C, 70.84; H, 3.48; found: C, 70.87; H, 3.45.
References:
1. Kiasat, A. R.; Mehrjardi, M. F. Catal. Commun. 2008, 9, 1497.
2. Tang, B.; Qiu, M.; Zhang, S.; Solar Energy Mater. Solar Cells 2012, 105, 242.
3. Mukhopadhyay, C.; Ray, S. Catal. Commun. 2011, 12, 1496.
12