Perchloric acid modified-cellulose: A versatile, novel and biodegradable heterogeneous solid acid catalyst for single-pot synthesis of novel bis-pyran annulated heterocyclic scaffolds under solvent-free conditions

Article abstract of DOI:10.1039/c4nj00529e

A one-pot multi-component, green, and highly efficient protocol has been developed for the synthesis of novel bis-pyran annulated heterocyclic scaffolds (4a-r) using cellulose-perchloric acid (CPA) as an eco-friendly, biodegradable and recyclable catalyst

Full text of DOI:10.1039/c4nj00529e

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Perchloric acid modified-cellulose: a versatile,
novel and biodegradable heterogeneous solid
acid catalyst for single-pot synthesis of novel
bis-pyran annulated heterocyclic scaffolds under
solvent-free conditions†
Cite this:DOI: 10.1039/c4nj00529e
Tabassum Khan and Zeba N. Siddiqui*
A one-pot multi-component, green, and highly efficient protocol has been developed for the synthesis
of novel bis-pyran annulated heterocyclic scaffolds (4a–r) using cellulose–perchloric acid (CPA) as an
eco-friendly, biodegradable and recyclable catalyst in excellent yields under solvent-free conditions.
Other remarkable features of this environmentally benign protocol are short reaction time, a wide range
of functional group tolerance, use of inexpensive heterogeneous catalyst, and high yield of products via
a simple experimental and work-up procedure as compared to the conventional methods. The
cellulose–HClO4 (CPA) catalyst is characterized by using FTIR, powder XRD and SEM–EDX analyses. The
stability of the catalyst was evaluated by TG/DTA characterization techniques. The catalyst can be
recycled several times with a slight loss of its catalytic activity.
Received (in Porto Alegre, Brazil)
7th April 2014,
Accepted 9th July 2014
DOI: 10.1039/c4nj00529e
www.rsc.org/njc
however, suffer from their own limitations, such as complicated
multi-step reactions, low yield due to formation of side products,
Introduction
2-Amino-4H-pyran annulated heterocyclic derivatives are excel- prolonged reaction times, use of harmful organic solvents,
lent building blocks of naturally occurring products,1 posses- expensive catalysts, and harsh reaction conditions with non-
sing numerous biological and pharmacological properties like reusable catalysts.
anti-HIV,2 anti-tumor,3 anti-leishmanial,4 antioxidant,5 central
Herein, we report synthesis of a series of 2-amino-4H-pyran
nervous system (CNS) activities and effects,6 used for treatment annulated heterocyclic scaffolds using cellulose–perchloric acid
of Alzheimer’s disease7 and schizophrenia disorder.8 Some (CPA) under solvent-free conditions. The catalyst is novel, inexpen-
2-amino-4H-pyran derivatives have also been utilized for the sive and easily preparable. The catalyst is characterized by FTIR,
synthesis of laser dyes,9 photochromic materials,10 cosmetics, powder XRD, scanning electron microscopy (SEM) and energy
pigments,11 agrochemicals.12 They also serve as intermediates dispersive X-ray (EDX) spectrometry techniques. The stability
for the synthesis of organic compounds including pyridin-2- of the catalyst is evaluated by thermogravimetric/differential
ones,13 pyrano[2]pyrimidines,14 lactones,15 imidoesters,15 pyra- thermal analyses (TG/DTA). It is pertinent to mention that cellulose
nopyridine derivatives16 and polyazanaphthalenes.17
is a biodegradable polymer and serves as a unique support for
Due to the wide synthetic utility and potential applications of the synthesis of solid acid catalysts including cellulose–sulfuric
2-amino-4H-pyran annulated heterocyclic scaffolds, various acid which has been utilized in various organic transformations
methods for their syntheses have been reported which include viz. synthesis of 1,4-dihydropyridines,28 quinazolin-4(1H)-ones,29
the use of homogeneous (piperidine,18 (S)-proline,19 K3PO4,20 bis-chalcones30 and bis-pyrazolines30etc.
DBU under microwave irradiation,16 and amino functionalized
Thus, in continuation of our interest in the development of
ionic liquids21) as well as heterogeneous catalysts (chitosan,22 heterogeneous, recyclable solid catalysts and novel methodo-
KSF,23 cetyltrimethyl ammonium bromide,24 Mg–La mixed metal logies,31,32 we wish to report the synthesis of a series of 2-amino-
oxides,25 KF–alumina,26 and heteropolyacids27). These methods, 4H-pyran derivatives in excellent yields in a very short time
period via a one-pot, three-component reaction of dialdehydes/
substituted aldehydes, ethyl cyanoacetate/malononitrile and a
variety of C–H activated acids in the presence of cellulose–HClO4
Department of Chemistry, Aligarh Muslim University, Aligarh, 202002, India.
E-mail: siddiqui_zeba@yahoo.co.in
under solvent-free conditions (Scheme 1). The catalyst was
recycled up to several runs.
† Electronic supplementary information (ESI) available. See DOI: 10.1039/
c4nj00529e
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Scheme 1 Cellulose–HClO4 catalyzed synthesis of bis-pyran annulated heterocyclic scaffolds (4a–r).
compounds was checked by thin layer chromatography (TLC)
on glass plates coated with silica gel G254 (E. Merck) using a
chloroform–methanol (3 : 1) mixture as the mobile phase and
visualized using iodine vapors. X-ray diffractograms (XRD) of
the catalyst were recorded in the 2y range of 101–701 at a scan
rate of 41 per min on a Rigaku Minifax X-ray diffractometer with
Ni-filtered Cu Ka radiation at a wavelength of 1.54060 Å. The
SEM-EDX characterization of the catalyst was performed using
a JEOL JSM-6510 scanning electron microscope equipped with
an energy dispersive X-ray spectrometer operating at 20 kV. TG/
DTA results were obtained using DTG-60H, at a heating rate of
20 1C per min from 0 to 500 1C under a N2 atmosphere.
Experimental
General information
Melting points of all synthesized compounds were measured
using a Riechert Thermover instrument and are uncorrected.
The IR spectra (KBr) were recorded on a Perkin Elmer RXI
1
spectrometer. H NMR and 13C NMR spectra were recorded on
Bruker DRX-300 and Bruker Avance II 400 spectrometers, using
tetramethylsilane (TMS) as an internal standard and DMSO-d6/
CDCl3 as a solvent. ESI-MS were recorded on a THERMO
Finnigan LCQ Advantage max ion trap mass spectrometer
having an 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
Preparation of cellulose–perchloric acid (CPA)
calculated values. Chemicals were of commercial grade and Cellulose–HClO4 was prepared by the dropwise addition of
used without further purification. The homogeneity of the perchloric acid (1.0 g, 10 mmol) to a magnetically stirred
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mixture of cellulose (5.0 g) in n-hexane (20 mL) at 0 1C for 2 h.
After complete addition, the mixture was stirred for another 2 h.
The mixture was filtered, washed with acetone (30 mL) and
dried at room temperature to afford cellulose–HClO4 as white
powder (5.25 g).
Back titration analysis of cellulose–HClO4
NaOH solution (20 mL, 0.1 N) was added to cellulose–HClO4
(100 mg) in an Erlenmeyer flask. This solution was stirred for
10 min. The excess amount of base was neutralized by addition
of HCl solution (1 N) to the equivalence point of titration.
NaOH solution (20 mL, 0.1 N) when added to cellulose (100 mg)
without HClO4 and subjected to back titration under similar
conditions, no change in the strength of NaOH was observed.
This ruled out the possible reaction of NaOH with cellulosic-OH
groups.
Fig. 1 FT-IR spectra of (a) cellulose and (b) cellulose–HClO4.
General procedure for the synthesis of 2-amino-4H-pyran
annulated heterocyclic scaffolds (4a–u) under solvent-free
conditions
Terephthaldehyde/isophthaldehyde/substituted aldehydes (1a–e)
(1.00 mmol), ethyl cyanoacetate/malononitrile (2a–b) (2.00/
1.00 mmol), C–H activated acids (3) (2.00/1.00 mmol) and CPA
(0.08 g) were mixed in a 25 mL round bottom flask and heated for
a specific period of time at 70 1C (Tables 4–7). After completion of
the reaction (monitored by TLC), the reaction mixture was cooled
to room temperature and EtOAc (5 mL) added to it. The catalyst
in the form of solid was filtered off from the reaction mixture,
washed with EtOAc (2 mL Â 2), dried in an oven at 70 1C and
reused for further catalytic cycles. The filtrate was concentrated
under reduced pressure to afford the products (4a–u). The pure
products were obtained after recrystallization from ethanol (spec-
tral data in the ESI†).
Results and discussion
Preparation and characterization of cellulose–HClO4
The catalyst was prepared by adding perchloric acid to stirred
Fig. 2 Powder XRD of (a) cellulose, (b) fresh cellulose–HClO4 and (c)
solution of cellulose in n-hexane. The number of H+ sites on cellulose–HClO4 after eight runs.
cellulose–HClO4 was determined by back titration and found to
be 1 meq gÀ1
.
The FT-IR spectrum of the catalyst exhibited a broad peak
EDX analysis (Fig. 4) confirmed the presence of C, O and Cl
for an OH absorption band at 3440 cmÀ1. The peaks at 1158, elements in the synthesized CPA.
1055 and 904 cmÀ1 represented C–O stretching, C–C skeletal
To assess the thermal stability of cellulose–HClO4 (CPA),
vibrations, and C1–H ring stretching of the glucose unit, TG/DTA experiments were carried out and the thermograms are
respectively.33 The bands at 1158 and 1111 cmÀ1 were attri- illustrated in Fig. 5. For TG/DT analyses the sample was heated
buted to the asymmetric stretching whereas bands at 1055, 904 up to 500 1C at a constant rate of 20 1C per min in the nitrogen
and 623, 551 cmÀ1 were due to the symmetric stretching and atmosphere. The weight losses found from TGA measurements
rocking vibrations of HClO4 (Fig. 1).34
agreed fairly well with those expected for the decomposition
The powder XRD pattern (Fig. 2) of the matrix showed of cellulose–perchloric acid to cellulose and the perchloric
characteristic diffraction peaks for the cellulose moiety at acid group. As shown in Fig. 5(a) the TG curve seems to indicate
16.5, 22.5 and 341.35
two-stage decomposition with a weight loss of 52.56% between
The SEM micrographs (Fig. 3) were used to study surface 77.70 1C and 147.79 1C, which can be attributed to the evaporation
morphology of CPA and a homogeneous fibrous surface was of surface-physisorbed water. Another weight loss of 38.159%
revealed.
between 367.38–417.31 1C can be due to the decomposition of
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Fig. 3 SEM images (a and b) of the fresh catalyst (cellulose–HClO4) at
different magnifications.
Fig. 4 EDX analysis of cellulose–HClO4.
Fig. 5 (a) TG analysis of cellulose–HClO4. (b) DT analysis of cellulose–
HClO4.
the loaded perchloric acid along with the cellulose polymer.
Further evidence for the loss of physisorbed water and loaded
perchloric acid on cellulose was provided by DTA measurements product (4a) was obtained after a longer time period (Table 1,
(Fig. 5b).
entries 3–5). In aprotic solvents such as acetonitrile, chloro-
form, and dichloromethane product 4a was obtained in a trace
amount after a longer time period, whereas in dichloroethane
Catalytic activity of cellulose–HClO4
The catalytic activity of cellulose–HClO4 (CPA) was explored by 4a was obtained in low yield (Table 1, entries 6–9). Solvents
facile synthesis of highly functionalized bis-pyran annulated such as water, THF and dioxane again did not give satisfactory
heterocyclic scaffolds. In order to optimize reaction conditions, results (Table 1, entries 10–12). In environmentally benign
the reaction was studied by employing different solvents and solvents such as PEG-200, PEG-400, PEG-600, ethylene glycol,
solvent-free conditions at altered temperatures with the expec- and glycerol, the reaction again did not yield fruitful results in
tation to maximize product yield in short reaction time terms of time and yield of the product (entries 13–17). However,
(Table 1). For this purpose, the condensation reaction between the reaction performance was drastically enhanced under
terephthaldehyde (1a) (1.00 mmol), ethyl cyanoacetate (2a) solvent-free conditions when the temperature was increased
(2.00 mmol) and 4-hydroxycoumarin (3a) (2.00 mmol) was from 25 1C to 50 1C and then 70 1C and gave product 4a in
selected as a model reaction for the synthesis of compound excellent yield (98%) within a few min (4 min) (Table 1, entries
4a and the results are summarized in Table 1. It was observed 18–20). Therefore, 70 1C was chosen as the optimum tempera-
that when the model reaction was carried out in ethanol in the ture in further investigations. Further, an increase in tempera-
absence of any catalyst under reflux conditions, a trace amount ture to 80 1C did not show any significant enhancement in the
of the product was obtained after 1260 min (Table 1, entry 1), yield of the desired product. Thus, our study revealed that
and indicated the need of a catalyst. Then, the reaction was solvent-free conditions are the best conditions for cellulose–
conducted in the presence of cellulose–HClO4 under the same HClO4 catalyzed formation of bis-pyran annulated heterocyclic
conditions as above and yielded the product (63%) in 288 min. scaffolds (Scheme 1) and dihydropyrano[c]chromene scaffolds
In acetic acid the reaction completed comparatively in lesser in terms of enhanced yield of the products and reduced
time but addition of water to obtain the product yielded a reaction times. The highest catalytic activity under solvent-
mixture of products whereas in other polar protic solvents free conditions may be due to the good dispersion of active
such as methanol and iso-propanol, less yield of the desired reagent sites which facilitates better contact between reactant
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Table 1 Effect of various solvents versus the solvent-free on the model reactiona
Entry
Solvent
Temperature
Timeb (min)
Yieldc (%)
1
2
3
4
5
6
7
8
Ethanold
Ethanol
Reflux
Reflux
Reflux
Reflux
Reflux
Reflux
Reflux
Reflux
Reflux
Reflux
Reflux
Reflux
Reflux
Reflux
Reflux
Reflux
Reflux
25 1C
1260
288
120
360
444
780
600
480
294
1440
1440
1440
288
264
240
420
318
108
19
Trace
63
49 (Mixture)
42
Acetic acid
Methanol
Iso-propanol
Acetonitrile
Chloroform
Dichloromethane
Dichloroethane
Water
THF
Dioxane
PEG-200
PEG-400
PEG-600
Ethylene glycol
Glycerol
Solvent-free
Solvent-free
Solvent-free
Solvent-free
45
Trace
Trace
Trace
48
—
—
—
34
39
42
30
32
15
79
98
98
9
10
11
12
13
14
15
16
17
18
19
20
21
50 1C
70 1C
80 1C
4
4
a
Reaction conditions: terephthaldehyde (1a) (1.00 mmol), ethyl cyanoacetate (2a) (2.00 mmol) and 4-hydroxycoumarin (3a) (2.00 mmol), catalyst
b
c
d
(0.08 g). Reaction progress monitored by TLC. Isolated yields. No catalyst.
Table 2 Comparison of catalytic activity of different catalysts on the model reactiona
Entry
Catalyst
Conc. of H+
Timeb (min)
Yieldc (%)
1
Cellulose–HClO4
Perchloric-SiO2
PEG–OSO3H
Zn(L-proline)2
Sulfuric acid–SiO2
P2O5/SiO2
NaHSO4–SiO2
P2O5
PTS
Xanthan–OSO3H
Sulfamic acid–SiO2
Camphor–sulfonic acid
L-Proline
Chlorosulfonic acid
Amberlite IRC 50
Sulfamic acid
Sulfanilic acid
HClO4
(1 meq gÀ1
)
4
31
28
45
114
43
96
132
84
186
228
78
126
90
98
86
83
78
76
75
71
69
67
66
61
60
57
49
37
237
338
439
540
631
741
8
(1.2 meq gÀ1
(0.8 meq gÀ1
)
)
— (10 mol%)
(1.3 meq gÀ1
(0.08 g)
)
(0.08 g)
— (10 mol%)
— (10 mol%)
9
1042
1143
12
13
14
15
16
17
18
(0.8 meq gÀ1
(0.9 meq gÀ1
)
)
— (10 mol%)
— (10 mol%)
— (10 mol%)
— (10 mol%)
— (10 mol%)
— (10 mol%)
— (10 mol%)
258
1440
1440
21
Trace
Trace
77
a
Reaction conditions: terephthaldehyde (1a) (1.00 mmol), ethyl cyanoacetate (2a) (2.00 mmol) and 4-hydroxycoumarin (3a) (2.00 mmol), solvent-
b
c
free conditions, T = 70 1C. Reaction progress monitored by TLC. Isolated yields.
molecules and the catalyst.36 Moreover, due to the absence of needed for energy of activation is directly available to the
any solvent (as medium), there is no dilution effect and the heat reactant molecules.
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Table 3 Effect of the acid loading on the support for the model reactiona
Entry
Cellulose–HClO4
Timeb (min)
Yieldc (%)
1
2
3
5 mmol
10 mmol
15 mmol
12
4
4
72
98
86
a
Reaction conditions: terephthaldehyde (1a) (1.00 mmol), ethyl cyanoacetate (2a) (2.00 mmol) and 4-hydroxycoumarin (3a) (2.00 mmol), catalyst
b
c
(0.08 g), solvent-free conditions, T = 70 1C. Reaction progress monitored by TLC. Isolated yields.
conditions at 70 1C. The order of reactivity of various catalysts
was cellulose–HClO4 4 perchloric acid–SiO2 4 PEG–OSO3H 4
Zn(L-proline)2 4 HClO4 4 sulfuric acid–SiO2 4 P2O5/SiO2 4
NaHSO4–SiO2 4 P2O5 4 PTS 4 xanthan–OSO3H 4 sulfamic
acid–SiO2 4 camphor–sulfonic acid 4 L-proline 4 chlorosul-
fonic acid 4 amberlite IRC 50 4 sulfamic acid = sulfanilic acid
in terms of yield of the product (Table 2). Since HClO4 is the
strongest acid among the other acids/acid catalysts, the reac-
tion was also conducted in HClO4 alone and surprisingly
provided product 4a in 77% yield only. The product yield,
however, increased to a greater extent (98%) when cellulose–
HClO4 was used as a catalyst. The highest catalytic activity
shown by cellulose–HClO4 in comparison to HClO4 may be due
Fig. 6 Effect of catalyst loading on the model reaction.
A comparative study was also carried out using a variety of to greater surface area and fine dispersion of the catalyst on the
catalysts for obtaining the best yield of 4a under solvent-free surface of cellulose.
Scheme 2 Plausible mechanism for the synthesis of (4a).
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The effect of different amounts of perchloric acid on the
Paper
cellulose support was also investigated when synthesizing 4a,
by using 5 mmol, 10 mmol and 15 mmol of perchloric acid
supported on cellulose (5 g) (Table 3). Using 5 mmol cellulose–
HClO4 (lower ratio), unsatisfactory results were obtained in
terms of yield and time possibly due to less available H+ sites of
the catalyst (entry 1). Using 15 mmol cellulose–HClO4, the
reaction completed in a shorter time period but yield was not
satisfactory possibly due to formation of some side products
(entry 3). However, the excellent yield of the product was
obtained using 10 mmol cellulose–HClO4 (entry 2).
Variation of the catalyst loading also had a profound effect on
the catalytic activity (Fig. 6). When the reaction was carried out
using 0.02 g, 0.04 g and 0.06 g of the catalysts, the rate of the
reaction progressed steadily with lower to moderate yields.
However, the best performance was observed using 0.08 g of
CPA under solvent-free conditions at 70 1C. A further increase in
the catalyst loading had no significant enhancement in the yield
of the desired product and the rate of the condensation reaction.
Mechanistically (Scheme 2) all the H+ sites of the catalyst with an
optimum amount (0.08 g) are utilized for the activation of the
substrate. Therefore, the catalyst with an amount greater than
0.08 g does not have an effect on the activation of the substrate.
The recyclability of the catalyst is an important norm for
heterogeneous catalysis in order to satisfy the green chemistry
criteria. The recyclability of the catalyst was examined using the
model reaction of terephthaldehyde (1a) (1.00 mmol), ethyl cyanoa-
cetate (2a) (2.00 mmol) and 4-hydroxycoumarin (3a) (2.00 mmol) in
the presence of CPA as a catalyst under solvent-free conditions
(Fig. 7). After completion of the reaction, the catalyst was recovered
by filtration, washed with EtOAc (2 mL Â 2) and dried in oven at
70 1C. The recovered catalyst was then employed for further eight
additional repetitive runs adopting the identical protocol. After eight
runs the catalyst showed some decrease in the product yield (Fig. 7).
Similar patterns of powder XRD (Fig. 2b) and SEM-EDX
analyses (Fig. 8a, b and 9) were observed for the recovered
catalyst with some low intensity and extra peaks which may be
due to the catalyst deactivation or some changes in the morpho-
logy of the catalyst after eight runs. This fact was also checked by
measuring the concentration of the residual H+ on the recovered
catalyst through the titration method and showed marginal loss
of H+ sites (0.85 meq gÀ1).
Fig. 8 SEM images (a and b) of the recovered catalyst (cellulose–HClO4)
at different magnifications.
Encouraged by the remarkable results, we explored the
scope and generality of this novel protocol by the reaction of
terephthaldehyde/isophthaldehyde (1a–b), ethyl cyanoacetate/
malononitrile (2a–b) and 4-hydroxycoumarin (3a) in the
presence of CPA as a catalyst under solvent-free conditions.
All the reactions proceeded smoothly and were completed
within 4–7 min to afford the products (4a–c) in excellent yields
(97–98%) (Table 4). By replacing 4-hydroxycoumarin with
4-hydroxy-6-methyl-2H-pyran-2-one (3b), all the reactions
proceeded efficiently to produce the desired products (4d–f)
in higher yields (95–96%) within a short time period using the
same procedure (Table 4).
To further explore the scope of the reaction for construction
of bis-pyran annulated heterocyclic scaffolds, the reaction was
conducted using 1,3-dimethyl barbituric acid (3c) and indane-
1,3-dione (3d) as C–H-activated acids by adopting the identical
protocol. The reactions went on well affording the products
(4g–i) and (4j–l) in very good yields (95–98%) in a short span of
time (Table 5).
Extending the present study to other C–H-activated acids
such as dimedone (3e) and 3-methyl-1-phenyl-1H-pyrazol-5(4H)-
one (3f), the corresponding products (4m–o) and (4p–r) were
isolated in excellent yields (94–96%) under the optimized
reaction conditions (Table 6).
In addition, the reaction of 4-hydroxycoumarin (3a) and
malononitrile (2a) with substituted aldehydes (1c–e) was
also investigated to obtain dihydropyrano[c]chromene scaffolds
Fig. 7 Recycling data of cellulose–HClO4 for the model reaction.
Fig. 9 EDX analysis of the recovered cellulose–HClO4.
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Table 4 Cellulose–HClO4 catalyzed synthesis of bis-dihydropyrano[c]chromene (4a–c) and bis-dihydropyrano[b]pyran (4d–f) scaffoldsa
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Entry
Aldehyde
Activated C–H-acids
Alkyl nitrile
Product
Timeb (min)
Yieldc (%)
4a
1a
4
98
4bd
1a
1b
4
7
98
97
4cd
4d
1a
4
96
4ed
1a
1b
4
5
96
95
4f
a
Reaction conditions: terephthaldehyde/isophthaldehyde, (1a–b, 1.00 mmol), alkyl nitrile (2a–b, 2.00 mmol), activated C–H-acids (3a–b)
b
c
d
(2.00 mmol), catalyst (0.08 g), solvent-free conditions, T = 70 1C. Reaction progress monitored by TLC. Isolated yields. The products were
confirmed by melting points and compared with the reported literature.44,45
(4s–u) under similar reaction conditions with higher yields (95– for CH3 and CH2 groups of the ethyl cyanoacetate moiety,
98%) in a shorter time period.
respectively. Another singlet integrating for two protons at d
The structure of compounds (4a–u) was deduced on the 4.44 was assigned to the methine proton. The four NH2 protons
basis of their spectral analyses. The IR spectrum of the newly were discernible as singlets at d 6.77. Four aromatic protons
synthesized compound 4a showed broad bands for NH2 appeared as a singlet at d 7.16. Other aromatic protons
groups at 3198, 3321 and 3396 cmÀ1 and a sharp strong band appeared as a multiplet in the region d 7.29–7.75. The 13C
at 1710 cmÀ1 for CQO of the ester group. Other strong and NMR spectrum showed signals at d 13.94 and 61.20 for CH3 and
sharp bands at 1674 and 1603 cmÀ1 were assigned to the CH2 groups of the ethyl cyanoacetate moiety, respectively,
carbonyl group of the coumarin moiety and CQC (vinylamine), whereas methine (C-4) and C-3 carbons appeared at d 37.12
respectively. The proton nuclear magnetic resonance (1H NMR) and 74.72, respectively. The aromatic carbons appeared in the
spectra exhibited multiplets from d 1.21–1.31 and d 3.98–4.14 range of d 121.10–138.20 and the signal at d 161.21 was for C-2
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Table 5 Cellulose–HClO4 catalyzed synthesis of bis-tetrahydropyrano[d]pyrimidine (4g–i) and bis-dihydroindeno[b]pyran (4j–l) scaffoldsa
Paper
Entry
Aldehyde
Activated C–H-acids
Alkyl nitrile
Product
Timeb (min)
Yieldc (%)
4g
1a
4
98
4h
1a
4
5
98
98
4i
1b
4j
1a
7
96
4k
1a
1b
7
8
96
95
4l
a
Reaction conditions: terephthaldehyde/isophthaldehyde, (1a–b, 1.00 mmol), alkyl nitrile (2a–b, 2.00 mmol), activated C–H-acids (3c–d)
b
c
(2.00 mmol), catalyst (0.08 g), solvent-free conditions, T = 70 1C. Reaction progress monitored by TLC. Isolated yields.
carbon. Signals at d 169.30 and 174.71 were for carbonyl bis-pyran annulated heterocyclic scaffolds is depicted in
carbons of ester and coumarin moieties, respectively. Further Scheme 2. The initial step of the catalytic cycle involved the
confirmation for 4a was provided by the ESI mass spectrum, in situ formation of bis-Knoevenagel condensation product (5a)
which showed the molecular ion peak as the base peak at m/z by the reaction of dialdehyde (1a), ethyl cyanoacetate (2a) in the
649.2 (M+ + 1). A plausible mechanism for the formation of presence of CPA. The Knoevenagel condensation product (5a)
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Table 6 Cellulose–HClO4 catalyzed synthesis of bis-dihydropyrano[c]pyrazole (4p–r) and bis-benzo[b]pyrans (4m–o) scaffoldsa
Entry
Aldehyde
Activated C–H-acids
Alkyl nitrile
Product
Timeb (min)
Yieldc (%)
4md
1a
7
96
4nd
1a
7
96
4od
1b
1a
10
94
95
4p
6
4qd
1a
1b
6
95
94
4rd
10
a
Reaction conditions: terephthaldehyde/isophthaldehyde, (1a–b, 1.00 mmol), alkyl nitrile (2a–b, 2.00 mmol), activated C–H-acids (3e–f)
b
c
d
(2.00 mmol), catalyst (0.08 g), solvent-free conditions, T = 70 1C. Reaction progress monitored by TLC. Isolated yields. The products were
confirmed by melting points and compared with the reported literature.46,47
undergoes Michael addition with C–H-activated acid (3a) fol- solvent and a catalytic amount of cellulose–HClO4. The reaction
lowed by intramolecular cyclization to give final product 4a.
was refluxed for 30 min after which the catalyst was filtered
under hot conditions. The reaction was then continued under
same conditions without the catalyst for further 6 hours and it
Heterogeneity test
The leaching and heterogeneity of cellulose–HClO4 was was observed that the reaction could not proceed further.
checked by the hot filtration test employing terephthaldehyde, Therefore, it can be concluded that the catalyst is heteroge-
ethyl cyanoacetate and 4-hydroxycoumarin in ethanol as a neous in nature.
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Table 7 Cellulose–HClO4 catalyzed synthesis of dihydropyrano[c]chromene scaffoldsa (4s–u)
Entry
Aldehyde
Activated C–H-acid
Alkyl nitrile
Product
Timeb (min)
Yieldc (%)
98
4sd
6
4td
10
7
95
97
4ud
a
Reaction conditions: substituted aldehydes (1c–e, 1.00 mmol), alkyl nitrile (2b, 1.00 mmol), activated C–H-acid (3a, 1.00 mmol), catalyst (0.08 g),
b
c
d
solvent-free conditions, T = 70 1C. Reaction progress monitored by TLC. Isolated yields. The products were confirmed by melting points and
compared with the reported literature.44
2 K. Asres, A. Seyoum, C. Veeresham, F. Bucar and S. Gibbons,
Conclusion
Phytother. Res., 2005, 19, 557–558.
In conclusion, we have developed an eco-efficient and simple
3 H. Quan-Bin, Y. Nian-Yun, T. Hong-Lei, Q. Chun-Feng,
procedure for the expedient synthesis of novel bis-pyran annu-
S. Jing-Zheng, C. C. Donald, C. Shi-Lin, Q. L. Kathy and
lated heterocyclic scaffolds using cellulose–HClO4 as an environ-
mentally benign and heterogeneous biopolymer-based solid acid
catalyst under solvent-free conditions. The novel catalyst was
X. Hong-Xi, Phytochemistry, 2008, 69, 2187–2192.
4 T. Narender, Shweta and S. Gupta, Bioorg. Med. Chem. Lett.,
2004, 14, 3913–3916.
efficiently applicable to a wide variety of C–H activated acids,
5 A. J. Johnson, R. A. Kumar, S. A. Rasheed, S. P. Chandrika,
affording the corresponding bis-pyran annulated heterocyclic
A. Chandrasekhar, S. Baby and A. Subramoniam,
scaffolds in excellent yields. The catalyst was easily recoverable
J. Ethnopharmacol., 2010, 130, 267–274.
and recycled for eight runs. These features will facilitate this
6 J. Skommer, D. Wlodkowic, M. Matto and M. Eray,
procedure to find extensive applications in the field of organic
synthesis.
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F. Leonetti, C. Altomare and A. Carotti, J. Med. Chem., 2001,
44, 3195–3198.
8 S. R. Kesten, T. G. Heffner, S. J. Johnson, T. A. Pugsley,
Acknowledgements
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11 G. P. Ellis, in The Chemistry of Heterocyclic of Compounds.
The authors are thankful to the Centre of Nanotechnology,
Department of Applied Physics, University Sophisticated Instru-
ment Facility (USIF), AMU, Aligarh for providing the powder
X-Ray diffractometer, SEM–EDX facilities and SAIF, CDRI,
Lucknow, Punjab University, Chandigarh for providing spectral
data. One of the authors (T.K.) would like to acknowledge
University Grants Commission, New Delhi, for the financial
Chromenes, Chromanes and Chromones, ed. A. Weissberger
and E. C. Taylor, John Wiley, New York, NY, 1977, ch. II,
assistance in the form of Senior Research Fellowship [F.17-43/
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