Cellulose sulfonic acid as a green, efficient, and reusable catalyst for Nazarov cyclization of unactivated dienones and pyrazoline synthesis

Article abstract of DOI:10.1039/c5ra19773b

A high yielding, eco-friendly and simple procedure for the synthesis of five membered carbo- and heterocycles through cellulose sulfonic acid (CSA) mediated electrocyclization processes has been developed. Cellulose sulfonic acid (CSA) not only was able to induce the cyclization of "unactivated" dienones generating cyclopentenoids; it was also able to trigger the cyclization of α,β-unsaturated hydrazones giving rise to pyrazolines in excellent yields under green reaction conditions. The ease of catalyst recovery and reusability, short reaction time, simple experimental and work-up procedure; compared to the conventional methods, makes this protocol practical, environmentally friendly and economically desirable. The cellulose-SO₃H (CSA) was characterized by FT-IR spectroscopy, powder X-ray diffraction (XRD) and Scanning Electron Microscopy (SEM) analyses, and catalyst stability was judged by thermogravimetry/differential thermal analysis (TG/DTA). The catalyst can be recycled several times without significant loss of catalytic activity.

Full text of DOI:10.1039/c5ra19773b

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Page 1 of 27
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Cellulose sulfonic acid as a green, efficient, and reusable catalyst for Nazarov
cyclization of unactivated dienones and pyrazoline synthesis
Zahra Daneshfar, Ali Rostami*
Abstract
A high yielding, ecoꢀfriendly and simple procedure for the synthesis of five membered carboꢀ and
heterocycles through cellulose sulfonic acid (CSA) mediated electrocyclization processes has been
developed. Cellulose sulfonic acid (CSA) not only was able to induce the cyclization of “unactivated”
dienones generating cyclopentenoids; it was also able to trigger the cyclization of α,βꢀunsaturated
hydrazones giving rise to pyrazolines in excellent yields under green reaction conditions. The ease of
catalyst recovery and reusability, short reaction time, simple experimental and workꢀup procedure;
compared to the conventional methods, makes this protocol practical, environmentally friendly and
economically desirable. The celluloseꢀSO3H (CSA) was characterized by FTꢀIR spectroscopy, powder Xꢀ
ray Diffraction (XRD) and Scanning Electron Microscopy (SEM) analyses, and catalyst stability was
judged by Thermogravimetry/Differential Thermal Analysis (TG/DTA). The catalyst can be recycled
several times without significant loss of catalytic activity.
* Department of Polymer Chemistry, Faculty of Chemistry, Shahid Beheshti University, P. O. Box: 19839ꢀ4716, Tehran, I. R.
Iran. Email: a_rostami@sbu.ac.ir, Fax: +982122431671, Tel: +982129903106
† Electronic supplementary information (ESI) available. See DOI:

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Introduction:
Catalysis by homogeneous Brønsted acids is crucial for the manufacturing of important chemicals such as
alcohols, ethers, esters, and many starting materials for polymers and resins. However, their separation,
recycling and neutralization in chemical processes are costly and highly demanding. Sulfate wastes are
produced during the neutralization of the homogeneous acids, and further separation from the product
results in substantial energy consumption and material loss: more than 15 million tons of H2SO4, for
instance, is consumed as an unrecyclable catalyst each year. Consequently, the general criteria of a catalyst
as a reusable material that can constantly accelerate a chemical reaction would not meet.1
In recent years, a “green” strategy has been adapted in chemical processes, which requires the utilization of
recyclable solid acids as substituents for unrecyclable homogenous analogs. Their ease of separation from
liquid products by decantation or filtration and their multiple usages without neutralization could lead to
low cost and more efficient processes that will meet increasingly stringent environmental standards and are
economically viable.1f−1i A practical solid acid material for catalytic processes should maintain high
stability and possess numerous protonic acid sites. Therefore, a great amount of research has been devoted
to immobilization of sulfuric acid on solid supports that are comparable to their homogenous ones in terms
of activity, stability and cost: mesoporous and amorphous silica,2 mesoporous and amorphous carbon,3 and
magnetic nanoparticles (MNPs)4 are arguably the most extensively investigated and emerged as excellent
and ideal supports with significant industrial potentials. They owe extraordinary properties such as large
specific surface area, readily dispersion in reaction solution, simple functionalization with various groups,
and nonꢀtedious separation by centrifugation and filtration.
Among a diverse range of biodegradable materials, such as chitosan,5 gluconic acid,6 xanthan sulfuric acid,7
starch sulfuric acid,8 sulfuric acidꢀmodified PEG (PEGꢀOSO3H),9 eggshell,10 and Meglumine11 that have
been exploited as solidꢀsupport acid catalysts for acidꢀcatalyzed transformations, chlorosulfonic acid
supported on cellulose (CSA) is considered as one of the best candidates for the design and development of
green methods for the synthesis of biologically important compounds. Cellulose is viewed as one of the
most chemically uniform and abundant biopolymers made by nature, and one of the unlimited sources of

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raw materials for environmentally friendly processes.12 Given numerous reports utilizing cellulose sulfonic
acid as a solid Brønsted acid catalyst in a variety of acidꢀcatalyzed processes such as multicomponent
transformations and condensation reactions13 cycloaddition,14 diazotization,15 and dehydration reactions,16
application of this environmentally benign catalyst in other useful synthetic transformations is still missing.
Electrocyclization processes are considered a common protocol for rapid assembly of fiveꢀmembered
carboꢀ and heterocycles in medicinally important molecules and natural product synthesis. These reactions
that involve the concerted rearrangement of bonding electrons have the advantage of low activation barriers
resulting in mild reaction conditions.17 The Nazarov cyclization, discovered by Nazarov in 1941,18, 19 is an
important example of an 4π electrocyclic ring closure and a wellꢀestablished method for the generation of
cyclopentenone rings from divinyl (or arylvinyl) ketones in the presence of Lewis20 or Brønsted acids.21 In
the past, the harsh reaction conditions (strong acids, high temperatures, and high catalyst loading) and poor
regioisomeric control required for the Nazarov reaction delayed its synthetic utilities.19 Although Lewis
acids have been successfully utilized under catalytic conditions, some are only restricted to polarized or
alkoxy substituted Nazarov substrates and in need of rigorous anhydrous reaction conditions.20 However,
the ubiquitous presence of fiveꢀmembered carbocycles among natural products22 has stimulated massive
research effort to solve these problems and strategies such as “directed Nazarov cyclization”,23 the
“interrupted Nazarov reaction”,24 and employing a number of divinylketone equivalents or pentadienyl
cation precursors which undergo cyclization under milder conditions25 have been adopted. Despite these
developments, only a very few Nazarov reactions using a catalytic amount of Brønsted acid have been
conducted and they are mainly limited to oxygenꢀsubstituted or polarized dienones.26 To the best of our
knowledge there have not been any reports of using cellulose sulfonic acid as a recyclable biopolymeric
catalyst for the acidꢀcatalyzed Nazarov cyclization process and its synthetic utility has never been explored.
Another valuable eletrocyclization processes is 6π electrocyclization of α,βꢀunsaturated hydrazones into the
corresponding fiveꢀmembered heterocyclic pyrazolines.17,27 These molecules exhibit potent biological
activities, such as antidepressant, anticancer, antiꢀinflammatory, antibacterial, and antiviral activity.28
Initially, Fischer recognized this practical acidꢀmediated process, and Huisgen later noted the isoelectronic

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relationship between this transformation and the 6π electrocyclization of the pentadienyl anion.29,30 The
[2+3]ꢀdipolar cycloaddition of diazoalkanes and α,βꢀunsaturated carbonyl compounds is also another
pathway to such motifs.31 Yet, Fischer’s method is still considered as the most efficient approach for the
preparation of these heterocyclic compounds.32
The celluloseꢀSO3H catalytic system constitutes the following features: (1) It adds favorably well with
stateꢀofꢀtheꢀart results for the catalytic Nazarov cyclizations. (2) It was able to trigger the cyclization of
nonꢀoxygenꢀsubstituted or nonꢀpolarized dienones in excellent yields and short reaction time without resort
to anhydrous conditions and inert atmospheres. (3) An environmentally friendly protocol for different
electrocyclization processes avoiding harsh reaction conditions. (4) It is derived from celluloseꢀan unlimited
source of raw materials made by natureꢀ along with its ease of recovery and reusability make this catalytic
system practical and economically desirable. (5) The repeating structure of celluloseꢀSO3H could result in
spatial proximity of the acidic groups and greater acidic density enabling cooperative effect among acid
sites that give rise to enhanced acidic strength.
We report herein a high yielding and environmentally friendly protocol for 4π electrocyclization of
“unactivated” divinyl ketones and 6π electorcyclization of α,βꢀunsaturated hydrazones in the presence of
cellulose sulfonic acid furnishing fiveꢀmembered carboꢀ and heterocycles.
Experimental
General information
Reactions were carried out under airꢀconditioned environment. Solvents were distilled before use. Thin
layer chromatography was performed on glass plates precoated with 0.25 mm Kieselgel 60 F254 (Merck).
Flash chromatography column was packed with 230ꢀ400 mesh silica gel (Merck). Melting points were
measured on an Electrothermal 9200 apparatus. Mass spectra were recorded on a FinniganꢀMAT 8430 mass
spectrometer operating at an ionization potential of 70 eV. Infrared (IR) spectra were recorded on a
Shimadzu IRꢀ470 spectrometer. Proton nuclear magnetic resonance spectra (1H NMR) were recorded on a
Bruker DRXꢀ300 Avance spectrometer 300.13 MHz; chemical shifts (δ scale) are reported in parts per
million (ppm) downfield from tetramethylsilane and referenced to residual protium in the NMR solvent

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1
(DMSO: δ 2.50, CDCl3: δ 7.24). H NMR Spectra are reported in order: number of protons, multiplicity
and approximate coupling constant (J value) in hertz (Hz); signals were characterized as s (singlet), d
13
(doublet), t (triplet), m (multiplet) and br s (broad signal). The C NMR spectra were recorded at 75.47
MHz and 100 MHz; chemical shifts (δ scale) are reported in parts per million (ppm). The elemental
analyses were performed with an Elementar Analysen systeme GmbH VarioEL. Diffraction data were
collected on a STOE STADI P with scintillation detector, secondary monochromator and CuꢀKa1 radiation
(λ =1. 5406 Å). TG/DTA experiments were carried out by a BÄHR Thermo analysis with a temperature
program from 10 °C to 800 °C at a constant rate of 20 °C per min.
Preparation of cellulose sulfonic acid (CSA):
Cellulose sulfonic acid was prepared and characterized according to the known procedures.13c, 33 The
catalyst was prepared by adding chlorosulfonic acid (1.00 g, 9 mmol) to a stirred mixture of cellulose (5.00
g, DEAE for column chromatography, Merck) in nꢀHexanes (20 ml) at 0 °C for 2 h. After complete
addition, the mixture was stirred for additional 2 h. The mixture was filtered, washed with methanol and
dried at room temperature to afford cellulose–SO3H as white powder.
Titration analysis of cellulose–SO3H
In order to access the number of H+ site of cellulose sulfonic acids, acid–base titration was carried out. 0.2 g
of cellulose−SO3H was dissolved in deionized water (10 ml) and the titration experiment was carried out in
the presence of NaOH (0.1 N) and phenolphthalein as an indicator. Consequently the exact equivalence
point of titration was found 0.3 mmol g−1. A back titration strategy was also employed and no change in the
number of H+ sites in cellulose−SO3H was noticed (titration of other heterogenic acids was mentioned in
ESI †).
General procedure for the celluloseꢀSO3H catalyzed Nazarov cyclization
To a solution of divinyl ketone 1aꢀf (1 mmol) in EtOH (10 mL), celloluse sulfonic acid (0.4 g, 13 mol %)
was added and the reaction was stirred at 60 ºC for 12h. After completion of the reaction, the reaction
mixture was filtered to separate the catalyst. The solid catalyst was washed with EtOH (2 mL × 2), dried in

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oven at 60 °C and reused for further catalytic cycles. The filtrate was concentrated under reduced pressure,
and the crude compound was purified by thin layer chromatography performed on glass plates preꢀcoated
with silica (2:18, EtOAc/hexanes) to afford the desired Nazarov products 2aꢀf.
General procedure for the celluloseꢀSO3H catalyzed pyrazoline synthesis
To a suspension of (3aꢀf) (1 mmol) and cellulose sulfonic acid (0.3 g, 10 mol %) in EtOH (10 ml),
phenylhydrazine (0.21 g, 2 mmol) was added and stirred at 60°C. After completion of the reaction which
was monitored by TLC, the mixture was poured into cold water and the precipitate was filtered,
subsequently, ethyl acetate was added to the precipitate in order to dissolve the product and then was
filtered to separate the catalyst. The solid catalyst was washed with EtOH (2 mL × 2), dried in an oven at
60 °C and reused for further catalytic cycles. The filtrate was concentrated under reduced pressure and
purified by recrystallizing from ethanol and dried under high vacuum to afford the desired products (5aꢀf).
Results and discussion:
Preparation and characterization of cellulose–SO3H
The catalyst was prepared by adding chlorosulfonic acid to a stirred mixture of cellulose in nꢀHexanes.33
The number of H+ sites on cellulose sulfonic acid was determined by acid−base back titration experiment
and found to be 0.3 mmol g−1 while the sulfur content of the samples was 0.35 mmol g−1 as judged by
conventional elemental analysis. The similarity between these two values indicated that the most of the
sulfur species in the sample was part of the sulfonic acid groups.
The FT−IR spectrum of the catalyst showed a broad peak for an OH absorption band at the peaks at 3440
cm−1. Peaks at 1158, 1055, and 904 cm−1 indicated C−O stretching, C−C skeletal vibration, and C1−H ring
stretching of the glucose unit, respectively.34 The three new bands appeared in FTIR spectrum at 1163,
1048, and 674 cmꢀ1 corresponding to the O=S=O asymmetric and symmetric stretching vibrations and S–O
stretching vibration of the sulfonic acid groups (Fig.1, a). 35 The powder XRD pattern (Fig.1, b) of the
matrix showed characteristic diffraction peaks for the cellulose entity at 16.5, 22.5 and 34°.36 The SEM
micrographs (Fig.1, c) were used to study surface morphology of cellulose sulfonic acid and a
homogeneous fibrous surface was observed. To assess the thermal stability of cellulose sulfonic acid

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(CSA), TG/DTA experiments were carried out and the thermograms are illustrated in Fig.1, d. The weight
losses found by TGA measurements agreed well with those anticipated for the decomposition of cellulose
sulfonic acid to cellulose and the sulfonic acid group. As shown in Fig. 1d the TG curve seems to indicate a
threeꢀstage decomposition with a weight loss of 11.52 % between 73.17 °C and 123.28 °C which could be
assigned to the evaporation of surfaceꢀphysisorbed water. Another weight loss of 30.30 % between 291.37
°C−399.43 °C could be due to the decomposition of the loaded sulfuric acid along with the cellulose
polymer and the third weight loss of 26.70 % between 467.78 °C−534.71 °C could be attributed to the
decomposition of cellulose.37 The DTA measurements provide further evidence for the loss of physisorbed
water and loaded sulfonic acid moiety on the cellulose (see ESI †).
Fig. 1 (a) FT−IR spectra of (i) cellulose and (ii) cellulose−SO3H. (b) Powder XRD of (i) cellulose, (ii)
cellulose–SO3H. (c) SEM image of the fresh catalyst (cellulose−SO3H). (d) TG analysis of (i) cellulose and
(ii) cellulose–SO3H

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Catalytic activity of cellulose sulfonic acid
Except some few reports utilizing green strategies such as silica gel mediated Nazarov cyclization38 and
solventꢀfree Nazarov cyclization under microwave irradiation39, there have been only two examples of
Nazarov reaction utilizing solid acids as catalyst: Pale and coꢀworkers40 reported zeolite promoted
cyclization of arylvinyl ketones in good yields for less reactive substrates under harsh reaction conditions
that employs stoichiometric amount of solid acid while in another report, Chen and coꢀworkers41 described
heteropolyacids (HPAs) for the cyclization of mostly reactive and polarized dienones in acetonitrile at 40
°C. Since the development of mild acid promoters for nonꢀoxygenꢀsubstituted or nonꢀpolarized dienones
could play a significant role in the development of the Nazarov cyclization as an important synthetic
methodology; we envisioned that cellulose sulfonic acid, as a recyclable solid Brønsted acid might be able
to promote the Nazarov cyclization of simple unactivated dienones under mild reaction conditions.
Initial attempt was focused at Nazarov cyclization of dienone 1a as the model compound in the presence of
different Brønsted acids in ethanol at moderate heating (60 °C). We screened a variety of Brønsted acid
catalysts and solvents at different reaction times, temperatures, and catalyst loadings that are all
summarized in Table 1. As was expected the cyclization did not proceed in the presence of cellulose while
homogenous strong Brønsted acids such as hydrogen chloride, pꢀtoluene sulfuric acid, and camphor sulfuric
acid did not induce the Nazarov cyclization of the model compound either. A modest improvement in yield
and selectivity was obtained using mesoporous silica functionalized sulfonic acids (Table 1, entry 6 and 7)
while the best result was obtained in the presence of cellulose sulfonic acid and the substrate scope was
investigated using the latter catalyst. 42
Variation of the catalyst loading had a great effect on the catalytic activity (Table 1, entries 11−16). In the
absence of the catalyst the reaction did not proceed even after 24 hours. When the reaction was carried out
using 3.0, 6.0, and 9.0 mol %, both the rate of reaction and the chemical yields were evenly increased.
However, the best result was observed using 13 mol % catalyst at 60 °C providing the product in 97 % yield
in 45 minutes. A further increase in the catalyst loading slightly decreased the chemical yield of the desired
product while the rate of the reaction remained constant (see ESI †). From mechanistic viewpoint, all the

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acidic sites of the catalyst with the loading of 13 mol % are employed for the activation of the substrate.
Hence, increase in catalyst loading to 16 mol % does not have a significant effect on the activation of the
substrate.
The reaction did not proceed at room temperature even after 24 h, while heating the reaction to 70 °C
induced the cyclization furnishing the cyclopentenone 2a in 97 % yield. The best yield was observed when
the reaction was performed at 60 °C. Increasing or decreasing the temperature from 60 °C attenuated the
reaction yield (Table 1, entries 17, 19, 20 and 25). The impact of different solvents on the reaction yield
was also examined, and the best result was obtained in EtOH as an environmentally benign solvent (Table
1, entry 20).
We also detected a slight epimerization of the cis isomer to the thermodynamically more favored trans
isomer. Although the reaction was completed after 45 minutes with a trans/cis (60:40) diastereomeric ratio
favoring the trans isomer, increasing the reaction time to 12 h induced the cis to trans epimerization,
resulting a better diasteromeric ratio (66:34). Ultimately, the Nazarov cyclization proceeded very well in
EtOH at 60 °C and the desired cyclopentenone adduct 2a was obtained in 97 % yield in the presence of
chlorosulfonic acid supported on biomassꢀderived biopolymer. The efficiency of the cellulose−SO3H
catalyst could be related to the degree of substitution (DS) with OH groups, and multiple acidic sites on the
polymeric backbone and also to greater surface area and fine dispersion of the catalyst on the surface of
cellulose which was supported by the lack of efficiency in the case of galactose cellulose−SO3H (Table 1,
entry 8).
Table 1. Optimization for the synthesis of 2ꢀcyclopentenone 2aa
Entry
Catalyst
Time
(h) (°C)
T
Solvent
X
Yield
(%)
Trans/Cis
(%)d
(mol%)
Effect of catalyst
1
2
3
Cellulose sulfonic acid 0.75 60
EtOH
EtOH
EtOH
13
13
13
97b
no reaction
no reaction
60/40
PTSA
0.75 60
0.75 60
ꢀ
ꢀ
HCl

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4
5
6
7
8
Camphor sulfonic acid 0.75 60
EtOH
EtOH
EtOH
EtOH
EtOH
EtOH
EtOH
13
13
13
13
13
13
13
no reaction
ꢀ
ꢀ
LꢀProline
Silica sulfonic acid
0.75 60
0.75 60
no reaction
25b
80/20
61/39
56/34
45/55
ꢀ
MCMꢀ41 sulfonic acid 0.75 60
Galactose sulfonic acid 0.75 60
SBAꢀ15 sulfonic acid 0.75 60
26b
6b
9
10
7b
Cellulose
0.75 60
no reaction
Effect of catalyst loading
11
12
13
14
15
16
None
24
4
2
60
60
60
60
EtOH
EtOH
EtOH
EtOH
EtOH
EtOH
0
3
6
9
13
16
no reaction
40c
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
Cellulose sulfonic acid
Cellulose sulfonic acid
Cellulose sulfonic acid
Cellulose sulfonic acid 0.75 60
Cellulose sulfonic acid 0.75 60
51c
1.2
83c
97c
90c
Effect of solvent and temperature
17
18
19
20
21
22
23
24
25
26
27
28
Cellulose sulfonic acid
Cellulose sulfonic acid
Cellulose sulfonic acid 0.75 60
Cellulose sulfonic acid 0.75 70
Cellulose sulfonic acid
Cellulose sulfonic acid
Cellulose sulfonic acid
Cellulose sulfonic acid
24
6
RT
40
EtOH
EtOH
EtOH
EtOH
13
13
13
13
13
13
13
13
13
13
13
13
no reaction
no reaction
97c
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
97c
1
1
1
1
60 Toluene
40 CHCl3
40 CH2Cl2
40 Acetone
no reaction
no reaction
no reaction
no reaction
80c
no reaction
no reaction
60c
Cellulose sulfonic acid 0.75 60
MeOH
DMF
THF
Cellulose sulfonic acid
Cellulose sulfonic acid
Cellulose sulfonic acid
1
1
1
60
60
60
MeCN
a Reaction conditions: 1a (1 mmol), solvent (10 mL).
b Determined by 1H NMR spectroscopy, using anisol as internal standard.
c Isolated yield.
d The ratio of diastereomers was determined by 1H NMR spectroscopy.
Having optimized the conditions, we set to explore the reactivity of unreactive dienones for the Nazarov
cyclization prepared under a simple aldol condensation (see ESI †).
Dienone 1a−1f underwent a smooth cyclization under the conditions employed, providing cyclized products
2a−2f in excellent yields and a modest to excellent diastereomeric ratios (dr) depending on the substitution
pattern of the divenyl ketones. Installation of an electroꢀwithdrawing chloride group onto the orthoꢀposition
of the phenyl ring (1b) did not diminish the reaction yield, while it increased the diasteriomeric ratios (dr =
84:16) presumably due to the increasing steric demand of the chloroꢀphenyl substituent. Surprisingly, the
installation of the second chloride group onto the ortho position (1c) inverted the selectivity favoring the cis
isomer (dr = 21:79) suggesting the phenyl substituent might adopt an orthogonal orientation with respect to

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the methyl group. Cyclization of the sterically hindered substrate with αꢀphenyl substituent (1f) proceeded
smoothly with good induction, furnishing a single diastereiomer in high yield with complete
diasteroselectivity that was further confirmed via an NOE experiment (see ESI†). Divenyl ketones with
sensitive furan and thiophene substituents (1d−e) were stable under the present conditions providing
cyclopentenones 2d and 2e in 91 % and 92 % yields, respectively. The yield, reaction time, and conditions
in the presence of cellulose−SO3H are superior to those of other catalysts used for similar transformation.
Table 2. Nazarov cyclization of different divinyl ketones 1 in the presence of celluloseꢀSO3H
Entry
Substrate
Product a
Yield b,c Trans/Cisd
(%)
(%)
1
97
66/34
2
3
96
95
84/16
21/79
4
5
91
92
53/47
75/25

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6
95
100
a
b
c
Reaction conditions: substrates (1 mmol), catalyst (13 mol %), EtOH (10 ml).
Isolated yield.
All products were characterized by comparison of their H NMR and C NMR spectra
1
13
with those of authentic samples (see ESI†).
d Trans and cis isomers were identified by comparison with the literature data and their ratio
was determined by 1H NMR spectroscopy.
The plausible mechanism of a Nazarov cyclization is shown in Scheme 1. The reaction is initiated by the
reversible coordination of cellulose−SO3H as a solid Brønsted acid to the dienone substrate triggering the
electrocyclization of the pentadienyl cation I. The key step of the reaction mechanism involves a cationic 4
π electrocyclization process that proceeds through a conrotatory closure forming an oxyallyl cation II
having an anti relationship between R2 and R4 substituents. This step is usually followed by a loss of proton
from cation III, to give a single or a mixture of diastereiomeric cyclopentenone products. The trans
stereochemistry between R3 and R4 is due to the formation of the thermodynamically more stable product.
Scheme 1. Plausible mechanism for the Brønsted acid−catalyzed Nazarov reaction.
Encouraged by the remarkable results and having established that cellulose−SO3H constitutes an active
catalyst for the Brønsted acid catalyzed 4π electrocyclization process, we extended this protocol to another

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electrocyclization process catalyzed by a Brønstedꢀacid that involves a 6π electrocyclization of α,βꢀ
unsaturated hydrazones into the corresponding pyrazolines.
Recently, Holla and coꢀworkers reported a heterogeneous Amberlystꢀ15 promoted cyclization of α,βꢀ
unsaturated ketones in the presence of hydrazines under the reflux toluene conditions for two days affording
pyrazoline derivatives in moderate yield.43
Dibenzylideneacetone 3a in the presence of phenyl hydrazine 4 as the model compound has been used to
investigate the 6π electrocyclization process leading to pyrazoline 5a. We screened a variety of solid
Brønsted acid catalysts and solvents at different reaction times, temperatures, and catalyst loadings that are
all summarized in Table 3. As was anticipated the cyclization did not proceed in the presence of cellulose
Table 3, entry 1) while poor yields was obtained in the presence of galactose sulfonic acid, amorphous and
mesoporous silica functionalized sulfonic acids (Table 3, entries 2−4). The best result was obtained in the
presence of cellulose sulfonic acid (Table 3, entry 5) and the substrate scope was investigated using the
latter catalyst.
Variation of the catalyst loading had a great effect on the catalytic activity (Table 3, entries 6−10). In the
absence of the catalyst, the cyclization was accomplished only in 5% yield even after 48 hours. When the
reaction was carried out using 2.0, 5.0, 10.0 and 13.0 mol %, both the rate of reaction and the chemical
yields were evenly increased. However, the best result was observed using 10.0 mol % catalyst loading at
60 °C providing the product in 97 % yield in 2 hours.
The reaction proceed at room temperature providing the product in 45 % yield after 8 hours, while heating
the reaction to 40 °C induced the cyclization furnishing the pyrazoline 5a in 68 % yield. The best yield was
observed when the reaction was performed at 60 °C in ethanol (Table 3. entries 10−13). The impact of
different solvents on the reaction yield was also explored, dichloromethane as a chlorinated solvent and
toluene as an aromatic solvent were utilized resulting in poor yields of the product. The best results were
obtained in the presence of protic solvents and ethanol as an environmentally benign solvent was utilized to
investigate the generality of the reaction (Table 3, entries 14−16).

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Table 3. Optimization for the synthesis of pyrazoline 5aa
Entry
Catalyst
Time
T
Solvent
X
Yield b
(h) (°C)
(mol%)
(%)
Effect of catalyst
1
2
3
4
5
Cellulose
Galactose sulfonic acid
Silica sulfonic acid
MCMꢀ41 sulfonic acid
Cellulose sulfonic acid
24
2
2
2
2
60
60
60
60
60
EtOH
EtOH
EtOH
EtOH
EtOH
10
10
10
10
10
11
21
29
34
96
Effect of catalyst loading
6
7
8
9
10
None
48
4
3
2
2
60
60
60
60
60
EtOH
EtOH
EtOH
EtOH
EtOH
0
2
5
10
13
5
Cellulose sulfonic acid
Cellulose sulfonic acid
Cellulose sulfonic acid
Cellulose sulfonic acid
15
45
96
96
Effect of solvent and temperature
10
11
12
13
14
15
16
Cellulose sulfonic acid
Cellulose sulfonic acid
Cellulose sulfonic acid
Cellulose sulfonic acid
Cellulose sulfonic acid
Cellulose sulfonic acid
Cellulose sulfonic acid
8
4
2
2
2
2
2
RT
40
60
70
EtOH
EtOH
EtOH
EtOH
10
10
10
10
10
10
10
45
68
96
96
25
38
92
60 Toluene
40 CH2Cl2
60
MeOH
a Reaction conditions: 3a (1 mmol), solvent (10 mL).
bIsolated yield.
The optimized reaction conditions were then applied to several different substrates bearing both electronꢀ
donating and withdrawing groups: dibenzylideneacetones with halogen atom substituents 3bꢀd (Table 4,
entries 2−4) and methoxy substituent 3e (Table 4, entry 5) were well tolerated giving triꢀsubstituted
pyrazolines in high yields with an extra olefinic moiety for further manipulations. Finally, chalcone 3f in
the presence of cellulose−SO3H underwent cyclization to afford pyrazoline 5f in excellent yield (Table 4,
entry 6). The plausible mechanism of this reaction is shown in Scheme 2. First, condensation of an α,βꢀ
unsaturated ketone with a hydrazine furnishes the corresponding hydrazone I which subsequently
undergoes an electrocyclization process in the presence of Brønsted acid catalyst to afford the final
pyrazoline adduct IV after isomerization.

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Table 4. Reaction details of different α,βꢀunsaturated ketones 3 with phenyl hydrazine 4 in the presence of
cellulose−SO3H
Entry
Substrate
Producta
Timeb Yieldc, d
(h)
(%)
2
96
1
2
2
2
3
5
98
96
93
92
91
2
3
4
5
6

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a
Reaction conditions: substrates (1 mmol), catalyst (10 mol %), (10 ml EtOH), 60 °C.
b Reaction progress monitored by TLC.
c Isolated yield.
d
1
All products were characterized by comparison of their H NMR spectra with those of
authentic samples (see ESI†).
Scheme 2. Plausible mechanism for the Brønsted acidꢀcatalyzed 6π electrocyclization of α,β−unsaturated
hydrazones.
The catalyst reusability is an indispensable standard in heterogeneous catalysis fulfilling the green
chemistry principles. The recyclability of the catalyst in the Nazarov cyclization was examined using the
model reaction of dienone (1a) (1.00 mmol), in the presence of cellulose−SO3H (0.4 g, 13 mol %) in
ethanol (10 ml). After completion of the reaction, the catalyst was recovered by filtration, washed with
EtOH (2 mL × 2) and dried in the oven at 60 °C. The recovered catalyst was weighed each time and then
employed for further five additional consecutive runs under identical reaction conditions without any
significant loss of catalytic activity (Fig 2, c)
FT−IR analysis of the fresh and recovered catalyst (Fig 2, a) showed similar spectral patterns without any
loss in intensity and the SEM analyses were also employed to investigate the changes that occurred in
surface morphology of the recovered catalyst and a similar homogeneous fibrous morphology was revealed
(Fig.2, b).

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Fig 2. (a) FT−IR spectra of (i) cellulose−SO3H and (ii) cellulose−SO3H after three runs. (b) SEM image of
the recovered catalyst (cellulose−SO3H). (c) Recyclability of the catalyst (cellulose−SO3H) for the Nazarov
cyclization.
Conclusions
In conclusion, we have developed a high yielding, ecoꢀfriendly and simple procedure for the synthesis of
five membered carboꢀ and heterocycles through cellulose sulfonic acid mediated electrocyclization
processes. CelluloseꢀSO3H was able to trigger the cyclization of “unactivated” dienones generating
cyclopentenones in excellent yields under green reaction conditions. It was also easily recovered and reused
up to five additional runs without notable loss in the catalytic activity. This biopolymer based solid acid
was further employed for cyclization of α,βꢀunsaturated hydrazones generating pyrazolines in excellent
yields. Carbohydrate based polymeric acids constitute excellent candidates for heterogeneous catalysis due
to their biocompatibility, convenient manipulations and broad synthetic potentials. Their repeating
structures result in spatial proximity and greater acidic density enabling cooperative effect among acid sites

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that give rise to enhanced acidic strength.42 Efforts to develop other carbohydrate based catalytic systems
for applications in organic and polymer synthesis are underway in our laboratory.
Selected spectroscopic data for representative products:
3,4ꢀbis(2ꢀchlorophenyl)ꢀ2,5ꢀdimethylcyclopentꢀ2ꢀenone (2b):
Transꢀ3,4ꢀbis(2ꢀchlorophenyl)ꢀ2,5ꢀdimethylcyclopentꢀ2ꢀenone (2bʹ): white solid.; 96 % yield.; mp:109ꢀ
°
1
110 C.; TLC Rf = 0.46 (8:2; nꢀHexane: EtOAc).; H NMR (300 MHz, CDCl3): δH (ppm) 6.97ꢀ7.33 (m,
13
8H), 4.76 (q, 1H, J=7.2), 2.49 (q 1H, J=7.2), 1.76 (s, 3H), 1.39 (d, 3H, J=7.2).; C NMR(100 MHz,
CDCl3): 210.5, 165.7, 139.7, 135.8, 134.6, 134.2, 134.1, 132.1, 130.2, 129.9, 129.7, 129.5, 129.0, 128.1,
126.7, 52.6, 49.0, 15.5, 9.9.; IR(KBr, cmꢀ1): 2959, 2919, 2859, 1699, 1646, 1480, 1420, 1381, 1341, 1222,
1102, 1043, 837, 791, 751, 698, 645, 565, 453.; Ms m/z(%): 331(M+), 295, 267, 232, 202, 179, 152, 115,
75, 39. Anal. Calcd for C19H16Cl2O: C, 68.89; H, 4.87.; found C, 68.52; H, 5.38.
Cisꢀ3,4ꢀbis(2ꢀchlorophenyl)ꢀ2,5ꢀdimethylcyclopentꢀ2ꢀenone (2bʹʹ): white solid.; 96 % yield.; mp:109ꢀ
°
1
110 C.; TLC Rf = 0.46 (8:2; nꢀHexane: EtOAc).; H NMR (300 MHz, CDCl3): δH (ppm) 6.97ꢀ7.33 (m,
8H), 5.36 (d, 1H, J = 5.7), 3.05 (dd, 1H, J = 7.5, 5.7), 0.76 (d, 3H, J = 7.5).; 13C NMR(100 MHz, CDCl3):
211.0, 164.8, 140.7, 134.9, 134.0, 134.6, 132.3, 129.9, 129.7, 129.1, 128.1, 127.1, 126.7, 126.5, 126.3.; IR
(KBr, cmꢀ1): 2959, 2919, 2859, 1699, 1646, 1480, 1420, 1381, 1341, 1341, 1222, 1102, 1043, 837, 791,
751, 698, 645, 565, 453.; Ms m/z(%): 331(M+), 295, 267, 232, 202, 179, 152, 115, 75, 39.; Anal. Calcd for
C19H16Cl2O: C, 68.89; H, 4.87.; found C, 68.52; H, 5.38.
3,4ꢀbis(2,6ꢀdichlorophenyl)ꢀ2,5ꢀdimethylcyclopentꢀ2ꢀenone (2c):
Transꢀ3,4ꢀbis(2,6ꢀdichlorophenyl)ꢀ2,5ꢀdimethylcyclopentꢀ2ꢀenone (2cʹ): white solid.; 95 % yield.;
°
1
mp:130ꢀ131 C.; TLC Rf = 0.66 (9:1; nꢀHexane: EtOAc).; H NMR (300 MHz, CDCl3): δH (ppm) 7.07ꢀ
7.34 (m, 6H), 5.13 (d, 1H, J=3.4), 3.01 (qd, 1H, J=6.9, 3.4), 1.69 (s, 3H), 1.40 (d, 1H, J=6.9).; 13C
NMR(100 MHz, CDCl3): 211.5, 160.4, 136.9, 134.2, 134.0, 130.0, 129.9, 128.6, 128.2, 128.1, 128.0, 52.4,
45.2, 17.9, 9.0.; IR(KBr, cmꢀ1): 2965, 2925, 2846, 1712, 1646, 1560, 1427, 1374, 1328, 1182, 1082, 956,
771.; Ms m/z(%): 400(M+), 372, 335, 300, 236, 215, 186, 149, 115, 63, 43. Anal. Calcd for C19H14Cl4O: C,
57.03; H, 3.53.; found C, 57.09; H, 3.48.

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Cisꢀ3,4ꢀbis(2,6ꢀdichlorophenyl)ꢀ2,5ꢀdimethylcyclopentꢀ2ꢀenone (2cʹʹ): white solid.; 95 % yield.;
°
1
mp:130ꢀ131 C.; TLC Rf = 0.66 (9:1; nꢀHexane: EtOAc).; H NMR (300 MHz, CDCl3): δH (ppm) 7.07ꢀ
7.34 (m, 6H), 5.71 (d, 1H, J=3.4), 3.01 (qd, 1H, J=6.3, 3.4), 1.72 (s, 3H), 1.21 (d, 3H, J=6.3).; 13C
NMR(100 MHz, CDCl3): 209.6, 157.4, 142.4, 137.9, 137.2, 134.0, 131.1, 130.3, 128.7, 128.5, 128.0, 48.6,
45.1, 10.1, 9.3.; IR(KBr, cmꢀ1): 2965, 2925, 2846, 1712, 1646, 1560, 1427, 1374, 1328, 1182, 1082, 956,
771.; Ms m/z(%):400(M+), 372, 335, 300, 236, 215, 186, 149, 115, 63, 43 Anal. Calcd for C19H14Cl4O: C,
57.03; H, 3.53.; found C, 57.09; H, 3.48.
3,4ꢀdi(furanꢀ2ꢀyl)ꢀ2,5ꢀdimethylcyclopentꢀ2ꢀenone (2d):
Transꢀ3,4ꢀdi(furanꢀ2ꢀyl)ꢀ2,5ꢀdimethylcyclopentꢀ2ꢀenone (2dʹ): Orange solid.; 96 % yield.; mp:70ꢀ71
°C.; TLC Rf = 0.45 (8:2; nꢀHexane: EtOAc).; 1H NMR (300 MHz, CDCl3): δH (ppm) 6.10ꢀ7.55 (m, 8H),
3.95 (d, 1H, J=3), 2.55 (qd, 1H, J=7.5, 3), 2.16 (s, 3H), 1.30 (d, 3H, J=7.5).; 13C NMR(100 MHz, CDCl3):
209.5, 154.7, 150.8, 150.5, 144.8, 141.6, 133.3, 114.7, 112.0, 110.3, 106.1, 47.4, 46.9, 29.6, 16.0, 9.9.;
IR(KBr, cmꢀ1): 3124, 2972, 2925, 2866, 1798, 1692, 1626, 1460, 1374, 1341, 1222, 1142, 1069, 1003,
983, 910, 817, 744, 698, 585.; Ms m/z(%): 242(M+), 199, 171, 128, 108, 77, 39. Anal. Calcd for C15H14O3:
C, 74.36; H, 5.82.; found C, 74.28; H, 5.78.
°
Cisꢀ3,4ꢀdi(furanꢀ2ꢀyl)ꢀ2,5ꢀdimethylcyclopentꢀ2ꢀenone (2dʹʹ): Orange solid.; 96 % yield.; mp:70ꢀ71 C.;
TLC Rf = 0.46 (8:2; nꢀHexane: EtOAc).; 1H NMR (300 MHz, CDCl3): δH (ppm) 6.04ꢀ7.56 (m, 8H), 4.60
13
(d, 1H, J=7.2), 2.80 (qd, 1H, J=7.5, 7.2), 2.18 (s, 3H), 0.9 (d, 3H, J=7.5).; C NMR(100 MHz, CDCl3):
209.7, 153.3, 151.1, 150.4, 144.7, 141.6, 133.6, 114.3, 112.0, 110.2, 107.7, 44.7, 43.3, 29.7, 11.3, 9.9.;
IR(KBr, cmꢀ1): 3124, 2972, 2925, 2866, 1798, 1692, 1626, 1460, 1374, 1341, 1222, 1142, 1069, 1003,
983, 910, 817, 744, 698, 585.; Ms m/z(%): 242(M+), 199, 171, 128, 108, 77, 39. Anal. Calcd for C15H14O3:
C, 74.36; H, 5.82.; found C, 74.28; H, 5.78.
2,5ꢀdimethylꢀ3,4ꢀdi(thiophenꢀ2ꢀyl)cyclopentꢀ2ꢀenone (2e):
Transꢀ2,5ꢀdimethylꢀ3,4ꢀdi(thiophenꢀ2ꢀyl)cyclopentꢀ2ꢀenone (2eʹ): White solid.; 92 % yield.; mp:93ꢀ94
1
°C.; TLC Rf = 0.50 (8:2; nꢀHexane: EtOAc).; H NMR (300 MHz, CDCl3): δH (ppm) 6.80ꢀ7.51 (m, 8H),
13
4.26 (d, 1H, J=2.4), 2.50 (qd, 1H, J=7.5, 2.4), 2.17 (s, 3H), 1.35 (d, 3H, J=7.5).; C NMR(100 MHz,

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CDCl3): 209.2, 157.4, 146.5, 138.0, 133.7, 130.2, 126.9, 124.7, 124.2, 51.7, 51.1, 16.3, 10.5.; IR(KBr, cmꢀ
1): 3098, 2965, 2919, 2866, 1745, 1692, 1606, 1414, 1381, 1334, 1208, 1049, 996, 857, 698.; Ms m/z(%):
274(M+), 207, 185, 150, 115, 75, 57, 39.; Anal. Calcd for C15H14OS2: C, 65.66; H, 5.14; S, 23.37.; found C,
65.52; H, 5.38; S, 23.32.
Cisꢀ2,5ꢀdimethylꢀ3,4ꢀdi(thiophenꢀ2ꢀyl)cyclopentꢀ2ꢀenone (2eʹʹ): White solid.; 92 % yield.; mp:93ꢀ94
°C.; TLC Rf = 0.50 (8:2; nꢀHexane: EtOAc).; 1H NMR (300 MHz, CDCl3): δH (ppm) 6.79ꢀ7.25 (m, 8H),
13
4.86 (d, 1H, J=7.2), 2.90 (qd, 1H, J=7.5, 7.2), 2.20 (s, 3H), 0.90 (d, 3H, J=7.5).; C NMR(100 MHz,
CDCl3): 209.2, 157.5, 143.5, 138.5, 133.5, 129.7, 127.6, 127.0, 47.4, 45.9, 11.2, 10.4.; IR(KBr, cmꢀ1):
3098, 2965, 2919, 2866, 1745, 1692, 1606, 1414, 1381, 1334, 1208, 1049, 996, 857, 698.; Ms m/z(%):
274(M+), 207, 185, 150, 115, 75, 57, 39.; Anal. Calcd for C15H14OS2: C, 65.66; H, 5.14; S, 23.37.; found C,
65.52; H, 5.38; S, 23.32.
3,4ꢀbis(2,6ꢀdichlorophenyl)ꢀ2,5ꢀdiphenylcyclopentꢀ2ꢀenone (2f):
Cisꢀ3,4ꢀbis(2,6ꢀdichlorophenyl)ꢀ2,5ꢀdiphenylcyclopentꢀ2ꢀenone (2f): White solid.; 95 % yield.; mp:103ꢀ
°
104 C.; TLC Rf = 0.48 (8:2; nꢀHexane: EtOAc) .; 1H NMR (300 MHz, CDCl3): δH (ppm) 6.88ꢀ7.67 (m,
16H), 6.28 (d, 1H, J=7.5), 4.61 (d, 1H, J=7.5).; 13C NMR(100 MHz, CDCl3): 203.4, 156.8, 144. 2, 131.1,
130.6, 130.1, 130.0, 128.9, 128.4, 128.3, 128.2, 128.1, 128.0, 127.9, 127.8, 127.5, 126.4, 53.2, 48.8.;
IR(KBr, cmꢀ1): 2434, 1713, 1557, 1430, 1337, 1225, 1167, 1055, 884, 782, 684, 606, 563.; Ms m/z(%):
524(M+), 489, 335, 276, 246, 212, 176, 150, 105, 77, 39..; Anal. Calcd for C29H18Cl4O: C, 66.44; H, 3.46.;
found C, 66.42; H, 3.44.
Acknowledgements
We gratefully acknowledge funding from Shahid Beheshti university research council. The authors thank
Dr. Khosro Jadidi (Shahid Beheshti University) for providing us with some chemicals and Dr. Saadi
Samadi (University of Kurdistan) for his fruitful comments.

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Graphical and Textual Abstract
A high yielding and ecoꢀfriendly procedure for the preparation of cyclopentenoid and pyrazoline derivatives
via cellulose sulfonic acidꢀmediated electrocyclization processes.