Silica-bonded N-propylpiperazine sodium n-propionate as an efficient recyclable catalyst for one-pot synthesis of 2-amino-4-aryl-4H,8H-6-methyl-8-oxo-pyrano[3,2-b]pyran derivatives

Article abstract of DOI:10.1007/s11164-014-1769-4

Abstract An efficient and convenient method for synthesis of a series of 2-amino-4-aryl-4H,8H-6-methyl-8-oxo-pyrano[3,2-b]pyran derivatives by one-pot, three-component reaction of an aromatic aldehyde, malononitrile or a cyanoacetate, and 5-hydroxy-2-meth

Full text of DOI:10.1007/s11164-014-1769-4

Res Chem Intermed
DOI 10.1007/s11164-014-1769-4
Silica-bonded N-propylpiperazine sodium n-propionate
as an efficient recyclable catalyst for one-pot synthesis
of 2-amino-4-aryl-4H,8H-6-methyl-8-oxo-
pyrano[3,2-b]pyran derivatives
•
Syed Sheik Mansoor Azhar Ariffin S. P. N. Sudhan
•
Received: 21 April 2014 / Accepted: 11 July 2014
Ó Springer Science+Business Media Dordrecht 2014
Abstract An efficient and convenient method for synthesis of a series of 2-amino-
4-aryl-4H,8H-6-methyl-8-oxo-pyrano[3,2-b]pyran derivatives by one-pot, three-
component reaction of an aromatic aldehyde, malononitrile or a cyanoacetate, and
5-hydroxy-2-methyl-4H-pyran-4-one (allomaltol) in the presence of a catalytic
amount of silica-bonded N-propylpiperazine sodium n-propionate (SBPPSP), in
aqueous ethanol, is described. The method has the advantages of short reaction time,
mild reaction conditions, high yields, and convenience.
Keywords 5-Hydroxy-2-methyl-4H-pyran-4-one (allomaltol) ꢀ Silica-bonded
N-propylpiperazine sodium n-propionate ꢀ Pyrano[3,2-b]pyran ꢀ Malononitrile ꢀ
Cyanoacetate
Introduction
Multicomponent reactions (MCRs) have attracted much attention in combinatorial
and medicinal chemistry. MCRs have significant advantages over conventional
linear-type syntheses by virtue of their convergence, productivity, facile execution,
and high yield [1]. MCRs are valuable and efficient synthetic methods for
construction of highly complex molecules and for introducing molecular diversity in
a single step by use of simple building blocks [2]. With a small set of starting
S. S. Mansoor (&) ꢀ S. P. N. Sudhan
Research Department of Chemistry, Bioactive Organic Molecule Synthetic Unit, C. Abdul Hakeem
College, Melvisharam 632 509, Tamil Nadu, India
e-mail: smansoors2000@yahoo.co.in
A. Ariffin
Department of Chemistry, Faculty of Science, University of Malaya, 50603 Kuala Lumpur,
Malaysia
123

S. S. Mansoor et al.
materials, very large compound libraries can be developed in a short time then used
in research on medicinal chemistry. Because of these advantages, development of
new, environmentally benign MCRs has been recognized as one of the most
important topics of green chemistry [3].
The 5-hydroxy-2-methyl-4H-pyran-4-one (allomaltol) structure is important in
many natural and synthetic compounds. A series of 3-hydroxy-6-methyl-2-((4-
substituted piperazin-1-yl)methyl)-4H-pyran-4-one derivatives has been synthesized
by reaction of allomaltol with suitable piperazine derivatives under Mannich
reaction conditions. The antibacterial activity of the compounds was assessed
in vitro by using broth dilution for determination of minimum inhibitory
concentration (MIC) [4]. Their inhibitory effects on the enzyme DNA gyrase were
evaluated by use of a DNA gyrase supercoiling assay. Allomaltol and its derivatives
also have a variety of other interesting bioactivity, for example anticancer [5],
anticonvulsant [6], antidiabetic [7], antimalarial [8], and antimicrobial [9].
Many pyrans and fused pyran derivatives also have a wide range of pharma-
cological and biological activity, for example antiviral [10], anti-tuberculosis [11],
anti-HIV [12], anti-Alzheimer [13], calcium channel antagonist [14], anti-fungal
[15], anti-leukemic [16], anticonvulsant [17], antiproliferative [18], and anti-
diabetic [19]. Pyranopyranones, also, are known for their biological properties,
including antioxidant and cytotoxic activity [20]. Synthesis of the pyranopyranone
structure is, thus, of great importance.
Methods have recently been developed for synthesis of pyrano[4,3-b]pyran
derivatives by one-pot reaction of aromatic aldehydes with malononitrile and
4-hydroxy-6-methylpyran-2-one using catalysts such as KF/Al2O3 [21], alum
(KAl(SO4)2ꢀ12H2O) [22], mesoporous NH2-MCM-41 [23], ammonium acetate
under solvent-free conditions using the grinding method [24], nano-CaO based on
eggshell waste [25], and [BMIm]BF4-LiCl [26]. We have synthesized a series of
pyrano[4,3-b]pyran derivatives by using thiourea dioxide (TUD) in water [27].
A survey of the literature revealed that few methods are available for synthesis of
pyrano[3,2-b]pyran derivatives [28–30]. Li et al. [28] reported the synthesis of a
series of 2-amino-4-aryl-4H,8H-6-methyl-8-oxo-pyrano[3,2-b]pyran derivatives
from an aromatic aldehyde, malononitrile or a cyanoacetate, and allomaltol via a
one-pot three-component reaction catalyzed by Et3N in the ionic liquid [bmim]BF4.
Rahmati et al. [29] synthesized 20-amino-60-(hydroxymethyl)-80H-spiro[indoline-
3,40-pyrano[3,2-b]pyran]-2,80-diones by one-pot, three-component reaction of isatin,
kojic acid, and an active methylene compound, for example ethyl cyanoacetate,
methyl cyanoacetate, or malononitrile, in methanol, with a catalytic amount of 1,4-
diazabicyclo[2.2.2]octane. Parthasarathy et al. [30] developed a Cu(OTf)2-catalyzed
efficient synthesis of spiropyrano[3,2-b]pyran-4(8H)-ones by one-pot, three com-
ponent reaction of isatin, kojic acid, and an active methylene compound. Although
these methods are useful, there is still a need to develop methods which proceed
under mild reaction conditions.
The development of heterogeneous catalysts for organic synthesis has become a
major topic of research. Economic and environmental concerns encourage use of
heterogeneous catalysts for organic transformations. These catalysts are convenient
to handle and easy to remove from the reaction mixture, making the experimental
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Silica-bonded N-propylpiperazine sodium n-propionate
procedure simple and eco-friendly [31]. Heterogeneous catalysts are known to
suppress side reactions, resulting in better selectivity and product yield. Moreover,
replacement of liquid acids and bases with the corresponding cleaner solid
alternatives with such desirable characteristics as being non-stoichiometric, non-
corrosive, and reusable is also attractive. Use of solid basic catalysts, for example
hydrotalcites and basic zeolites has been studied in numerous reactions [32, 33].
Their use also avoids complex neutralization and separation steps, and the recovered
catalysts can be readily regenerated for further use.
Silica-bonded N-propylpiperazine sodium n-propionate (SBPPSP) has recently
received substantial attention as an efficient catalyst for construction of carbon–
carbon and carbon–hetero atom bonds [34, 35], because of its eco-friendly nature,
ease of handling, high reactivity, and easy work-up procedures. SBPPSP has been
used as a recyclable heterogeneous solid-base catalyst for synthesis of 3,4-
dihydropyrano[c]chromenes [34] and 4H-pyran derivatives [35]. An efficient
heterogeneous palladium catalyst system has been developed by immobilization
of Pd nanoparticles on SBPPSP. SBPPSP effectively stabilizes the Pd nanoparticles,
improving their stability against aggregation. The catalytic activity of these catalysts
has been investigated in the Sonogashira reaction [36].
In a continuation of our studies on the use of solid catalysts in organic
transformations [37–41], we report an efficient method for synthesis of pyrano[3,2-
b]pyran derivatives with SBPPSP as catalyst, by three-component condensation of
an aromatic aldehyde, malononitrile or a cyanoacetate, and 5-hydroxy-2-methyl-
4H-pyran-4-one in EtOH–H2O (50:50 v/v) under reflux (Scheme 1).
R1
O
CHO
SBPPSP
(0.06 g)
OH
R
H3C
O
O
R
+
+
R1
EtOH-H2O
(50:50 v/v)
Reflux
CN
H3C
O
O
NH2
1
2
3
4
O
O
O
R = CN,
N
SiO2
COOMe,
COOEt
Si
SBPPSP
N
O Na
O
B Na
Scheme 1 Preparation of 2-amino-4-aryl-4H,8H-6-methyl-8-oxo-pyrano[3,2-b]pyran derivatives from
aromatic aldehydes, malononitrile/methyl cyanoacetate/ethyl cyanoacetate, and allomaltol, catalyzed by
SBPPSP in EtOH–H2O (50:50 v/v) under reflux
123

S. S. Mansoor et al.
Experimental
Apparatus and analysis
Chemicals were purchased from Merck, Fluka, and Aldrich. All yields refer to
isolated products unless otherwise stated. 1H NMR (500 MHz) and 13C NMR
(125 MHz) spectra were obtained by use of a Bruker DRX-500 Avance at ambient
temperature, with TMS as internal standard. FT-IR spectra were obtained as KBr
discs on Shimadzu spectrometer. Mass spectra were obtained by use of a Varian
Saturn 2000 GC–MS instrument. Elemental analysis were performed by use of a
Perkin Elmer 2400 CHN elemental analyzer.
General procedure for synthesis of pyrano[3,2-b]pyran derivatives
A dry 50-mL flask was charged with a mixture of aromatic aldehyde 1 (1 mmol),
malononitrile or cyanoacetate 2 (1 mmol), and allomaltol 3 (1 mmol) and the
mixture was heated under reflux in EtOH–H2O (50:50 v/v) containing SBPPSP
(0.06 g, 5.2 mol%). After completion of the reaction, as indicated by thin-layer
chromatography, the reaction mixture was filtered. The residue was washed with
warm ethanol (3 9 30 mL) to separate the heterogeneous catalyst. The crude
products precipitated on cooling of the filtrate and were purified by recrystallization
from ethanol (95 %). The recovered catalyst was dried and reused for subsequent
runs.
Spectral data for the synthesized compounds (4a–z)
2-Amino-6-methyl-8-oxo-4-(4-chlorophenyl)-4H,8H-pyrano[3,2-b]pyran-3-
carbonitrile (4a)
IR (KBr, cm-1): 3,450 and 3,370 (NH2), 3,274 (Ar–H), 2,208 (CN), 1,707 (C=O);
1H NMR (500 MHz, DMSO-d6) d: 2.09 (s, 3H, CH3), 4.67 (s, 1H, CH), 6.55 (s, 1H,
=CH), 6.97 (s, 2H, NH2), 7.22 (d, J = 8.0 Hz, 2H, Ar–H), 7.40 (d, J = 8.0 Hz, 2H,
Ar–H) ppm; 13C NMR (125 MHz, DMSO-d6) d: 21.3, 31.3, 54.9, 100.5, 111.1,
117.7, 126.2, 127.9, 129.1, 138.0, 143.9, 164.0, 168.5, 177.7 ppm; MS (ESI): m/
z 315 (M ? H)?. Anal. Calcd. for C16H11ClN2O3 (%): C, 61.06; H, 3.52; N, 8.90.
Found: C, 61.00; H, 3.47; N, 8.83.
2-Amino-6-methyl-8-oxo-4-(3-methylphenyl)-4H,8H-pyrano[3,2-b]pyran-3-
carbonitrile (4b)
IR (KBr, cm-1): 3,444 and 3,366 (NH2), 3,282 (Ar–H), 2,217 (CN), 1,712 (C=O);
1H NMR (500 MHz, DMSO-d6) d: 2.09 (s, 3H, CH3), 2.19 (s, 3H, CH3), 4.71 (s, 1H,
CH), 6.56 (s, 1H, =CH), 6.98 (s, 2H, NH2), 7.33 (t, J = 8.0 Hz, 1H, ArH), 7.57 (tt,
J = 8.2 Hz, J0 = 1.3 Hz, 1H, Ar–H), 7.72 (t, J = 2.2 Hz, 1H, Ar–H), 7.83 (dd, dd,
J = 8.2 Hz, J0 = 2.2 Hz, J00= 1.3 Hz, 1H, Ar–H) ppm; 13C NMR (125 MHz,
DMSO-d6) d: 20.4, 21.5, 31.4, 55.5, 101.3, 111.3, 117.5, 126.4, 127.7, 129.3, 138.2,
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Silica-bonded N-propylpiperazine sodium n-propionate
143.8, 164.1, 168.7, 177.9 ppm; MS (ESI): m/z 295 (M ? H)?. Anal. Calcd. for
C17H14N2O3 (%): C, 69.38; H, 4.79; N, 9.52. Found: C, 69.31; H, 4.73; N, 9.50.
2-Amino-6-methyl-8-oxo-4-(2-fluorophenyl)-4H,8H-pyrano[3,2-b]pyran-3-
carbonitrile (4c)
IR (KBr, cm-1): 3,439 and 3,384 (NH2), 3,280 (Ar–H), 2,219 (CN), 1,711 (C=O);
1H NMR (500 MHz, DMSO-d6) d: 2.10 (s, 3H, CH3), 4.63 (s, 1H, CH), 6.55 (s, 1H,
=CH), 6.93 (s, 2H, NH2), 7.26–7.45 (m, 4H, Ar–H) ppm; 13C NMR (125 MHz,
DMSO-d6) d: 20.7, 31.6, 55.7, 100.9, 110.6, 117.4, 126.2, 128.2, 129.7, 138.1,
144.2, 163.7, 168.5, 178.2 ppm; MS (ESI): m/z 299 (M ? H)?. Anal. Calcd. for
C16H11FN2O3 (%): C, 64.43; H, 3.72; N, 9.39. Found: C, 64.35; H, 3.70; N, 9.31.
2-Amino-6-methyl-8-oxo-4-(4-nitrophenyl)-4H,8H-pyrano[3,2-b]pyran-3-
carbonitrile (4d)
IR (KBr, cm-1): 3,452 and 3,382 (NH2), 3,284 (Ar–H), 2,220 (CN), 1,705 (C=O);
1H NMR (500 MHz, DMSO-d6) d: 2.12 (s, 3H, CH3), 4.65 (s, 1H, CH), 6.57 (s, 1H,
=CH), 6.88 (s, 2H, NH2), 7.19 (d, J = 8.2 Hz, 2H, Ar–H), 7.39 (d, J = 8.2 Hz, 2H,
Ar–H) ppm; 13C NMR (125 MHz, DMSO-d6) d: 20.5, 30.8, 56.0, 100.8, 110.7,
118.2, 125.7, 128.3, 129.5, 137.6, 144.0, 163.6, 168.6, 178.3 ppm; MS (ESI): m/
z 326 (M ? H)?. Anal. Calcd. for C16H11N3O5 (%): C, 59.08; H, 3.41; N, 12.92.
Found: C, 59.00; H, 3.37; N, 12.88.
2-Amino-6-methyl-8-oxo-4-(3-chlorophenyl)-4H,8H-pyrano[3,2-b]pyran-3-
carbonitrile (4e)
IR (KBr, cm-1): 3,440 and 3,374 (NH2), 3,283 (Ar–H), 2,210 (CN), 1,713 (C=O);
1H NMR (500 MHz, DMSO-d6) d: 2.16 (s, 3H, CH3), 4.64 (s, 1H, CH), 6.63 (s, 1H,
=CH), 6.94 (s, 2H, NH2), 7.20–7.38 (m, 4H, Ar–H) ppm; 13C NMR (125 MHz,
DMSO-d6) d: 21.0, 30.9, 56.3, 101.4, 110.6, 118.1, 125.9, 128.5, 129.2, 137.8,
144.1, 163.8, 169.3, 178.0 ppm; MS (ESI): m/z 315 (M ? H)?. Anal. Calcd. for
C16H11ClN2O3(%): C, 61.06; H, 3.52; N, 8.90. Found: C, 61.02; H, 3.44; N, 8.87.
2-Amino-6-methyl-8-oxo-4-(2-methoxyphenyl)-4H,8H-pyrano[3,2-b]pyran-3-
carbonitrile (4f)
IR (KBr, cm-1): 3,443 and 3,373 (NH2), 3,278 (Ar–H), 2,214 (CN), 1,710 (C=O);
1H NMR (500 MHz, DMSO-d6) d: 2.12 (s, 3H, CH3), 3.66 (s, 3H, OCH3), 4.63 (s,
1H, CH), 6.63 (s, 1H, =CH), 6.92 (s, 2H, NH2), 7.28–7.47 (m, 4H, Ar–H) ppm; 13
C
NMR (125 MHz, DMSO-d6) d: 21.2, 30.6, 55.4, 56.2, 101.2, 110.8, 117.8, 126.3,
127.8, 129.2, 137.9, 144.5, 163.9, 169.0, 177.9 ppm; MS (ESI): m/z 311 (M ? H)?.
Anal. Calcd. for C17H14N2O4 (%): C, 65.80; H, 4.55; N, 9.03. Found: C, 65.72; H,
4.50; N, 9.00.
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S. S. Mansoor et al.
2-Amino-6-methyl-8-oxo-4-(2-methylphenyl)-4H,8H-pyrano[3,2-b]pyran-3-
carbonitrile (4g)
IR (KBr, cm-1): 3,447 and 3,385 (NH2), 3,277 (Ar–H), 2,213 (CN), 1,709 (C=O);
1H NMR (500 MHz, DMSO-d6) d: 2.08 (s, 3H, CH3), (2.22 s, 3H, CH3), 4.65 (s,
1H, CH), 6.58 (s, 1H, =CH), 6.89 (s, 2H, NH2), 7.21–7.41 (m, 4H, Ar–H) ppm; 13
C
NMR (125 MHz, DMSO-d6) d: 20.2, 21.4, 31.3, 54.7, 101.4, 111.2, 117.7, 126.5,
128.4, 130.2, 137.6, 143.7, 163.7, 169.2, 177.9 ppm; MS (ESI): m/z 295 (M ? H)?.
Anal. Calcd. for C17H14N2O3 (%): C, 69.38; H, 4.79; N, 9.52. Found: C, 69.30; H,
4.77; N, 9.53.
2-Amino-6-methyl-8-oxo-4-(4-fluorophenyl)-4H,8H-pyrano[3,2-b]pyran-3-
carbonitrile (4h)
IR (KBr, cm-1): 3,441 and 3,384 (NH2), 3,281 (Ar–H), 2,209 (CN), 1,712 (C=O);
1H NMR (500 MHz, DMSO-d6) d: 2.13 (s, 3H, CH3), 4.64 (s, 1H, CH), 6.57 (s, 1H,
=CH), 6.91 (s, 2H, NH2), 7.23 (d, J = 8.0 Hz, 2H, Ar–H), 7.43 (d, J = 8.0 Hz, 2H,
Ar–H) ppm; 13C NMR (125 MHz, DMSO-d6) d: 20.8, 31.5, 55.3, 101.5, 110.4,
117.8, 125.7, 128.3, 130.3, 137.9, 143.8, 164.0, 169.0, 177.7 ppm; MS (ESI): m/
z 299 (M ? H)?. Anal. Calcd. for C16H11FN2O3 (%): C, 64.43; H, 3.72; N, 9.39.
Found: C, 64.32; H, 3.73; N, 9.35.
2-Amino-6-methyl-8-oxo-4-(3-bromophenyl)-4H,8H-pyrano[3,2-b]pyran-3-
carbonitrile (4i)
IR (KBr, cm-1): 3,449 and 3,373 (NH2), 3,280 (Ar–H), 2,210 (CN), 1,714 (C=O);
1H NMR (500 MHz, DMSO-d6) d: 2.12 (s, 3H, CH3), 4.67 (s, 1H, CH), 6.51 (s, 1H,
=CH), 6.88 (s, 2H, NH2), 7.23–7.45 (m, 4H, Ar–H) ppm; 13C NMR (125 MHz,
DMSO-d6) d: 21.3, 31.7, 55.7, 100.9, 111.0, 118.3, 125.8, 127.7, 130.4, 138.2,
143.9, 164.2, 168.7, 177.7 ppm; MS (ESI): m/z 361 (M ? H)?. Anal. Calcd. for
C16H11BrN2O3 (%): C, 53.50; H, 3.09; N, 7.80. Found: C, 53.42; H, 3.02; N, 7.77.
2-Amino-6-methyl-8-oxo-4-(3-nitrophenyl)-4H,8H-pyrano[3,2-b]pyran-3-
carbonitrile (4j)
IR (KBr, cm-1): 3,436 and 3,372 (NH2), 3,287 (Ar–H), 2,214 (CN), 1,708
(C=O); 1H NMR (500 MHz, DMSO-d6) d: 2.11 (s, 3H, CH3), 4.70 (s, 1H, CH), 6.60
(s, 1H, =CH), 6.91 (s, 2H, NH2), 7.32–7.50 (m, 4H, Ar–H) ppm; 13C NMR
(125 MHz, DMSO-d6) d: 20.7, 30.8, 56.0, 100.8, 111.2, 118.2, 126.3, 128.0, 130.0,
138.3, 143.8, 164.2, 168.9, 178.0 ppm; MS (ESI): m/z 326 (M ? H)?. Anal. Calcd.
for C16H11N3O5 (%): C, 59.08; H, 3.41; N, 12.92. Found: C, 59.04; H, 3.42; N,
12.86.
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Silica-bonded N-propylpiperazine sodium n-propionate
2-Amino-6-methyl-8-oxo-4-(3,4-dichlorophenyl)-4H,8H-pyrano[3,2-b]pyran-3-
carbonitrile (4k)
IR (KBr, cm-1): 3,442 and 3,381 (NH2), 3,284 (Ar–H), 2,216 (CN), 1,703 (C=O);
1H NMR (500 MHz, DMSO-d6) d: 2.15 (s, 3H, CH3), 4.68 (s, 1H, CH), 6.62 (s, 1H,
=CH), 6.92 (s, 2H, NH2), 7.17 (dd, 1H, J = 8.7 Hz, J0 = 2.0 Hz, Ar–H), 7.30 (d,
1H, J = 2.0 Hz, Ar–H), 7.55 (d, 1H, J = 8.7 Hz, Ar–H) ppm; 13C NMR (125 MHz,
DMSO-d6) d: 20.6, 31.0, 56.1, 100.9, 110.6, 117.9, 126.2, 128.0, 129.5, 138.0,
143.7, 163.7, 168.8, 178.2 ppm; MS (ESI): m/z 350 (M ? H)?. Anal. Calcd. for
C16H10Cl2N2O3 (%): C, 55.04; H, 2.89; N, 8.02. Found: C, 54.95; H, 2.85; N, 8.03.
2-Amino-6-methyl-8-oxo-4-(2,4-dichlorophenyl)-4H,8H-pyrano[3,2-b]pyran-3-
carbonitrile (4l)
IR (KBr, cm-1): 3,447 and 3,384 (NH2), 3,279 (Ar–H), 2,218 (CN), 1,711 (C=O);
1H NMR (500 MHz, DMSO-d6) d: 2.11 (s, 3H, CH3), 4.65 (s, 1H, CH), 6.55 (s, 1H,
=CH), 6.90 (s, 2H, NH2), 7.22 (d, 1H, J = 8.3 Hz, Ar–H), 7.41 (dd, 1H,
J = 8.3 Hz, J0 = 2.4 Hz, Ar–H), 7.58 (d, 1H, J = 2.4 Hz, Ar–H) ppm; 13C NMR
(125 MHz, DMSO-d6) d: 20.8, 31.1, 55.7, 100.7, 110.5, 117.6, 126.0, 128.4, 129.8,
138.1, 144.2, 163.7, 168.7, 178.1 ppm; MS (ESI): m/z 350 (M ? H)?. Anal. Calcd.
for C16H10Cl2N2O3 (%): C, 55.04; H, 2.89; N, 8.02. Found: C, 55.00; H, 2.87; N,
8.00.
2-Amino-6-methyl-8-oxo-4-(4-chloro-3-nitrophenyl)-4H,8H-pyrano[3,2-b]pyran-3-
carbonitrile (4m)
IR (KBr, cm-1): 3,453 and 3,378 (NH2), 3,273 (Ar–H), 2,215 (CN), 1,715 (C=O);
1H NMR (500 MHz, DMSO-d6) d: 2.13 (s, 3H, CH3), 4.64 (s, 1H, CH), 6.52 (s, 1H,
=CH), 6.93 (s, 2H, NH2), 7.40 (d, 1H, J = 2.0 Hz, Ar–H), 7.53 (dd, 1H,
J = 8.6 Hz, J0 = 2.0 Hz, Ar–H), 7.82 (d, 1H, J = 8.6 Hz, Ar–H) ppm; 13C NMR
(125 MHz, DMSO-d6) d: 21.4, 31.3, 55.8, 101.3, 110.7, 117.6, 125.9, 128.3, 129.9,
137.5, 144.3, 163.9, 169.2, 178.0 ppm; MS (ESI): m/z 360.5 (M ? H)?. Anal.
Calcd. for C16H10ClN3O5 (%): C, 53.42; H, 2.80; N, 11.68. Found: C, 53.35; H,
2.75; N, 11.64.
2-Amino-6-methyl-8-oxo-4-(3-fluorophenyl)-4H,8H-pyrano[3,2-b]pyran-3-
carbonitrile (4n)
IR (KBr, cm-1): 3,438 and 3,382 (NH2), 3,281 (Ar–H), 2,216 (CN), 1,708 (C=O);
1H NMR (500 MHz, DMSO-d6) d: 2.09 (s, 3H, CH3), 4.63 (s, 1H, CH), 6.55 (s, 1H,
=CH), 6.92 (s, 2H, NH2), 7.26–7.44 (m, 4H, Ar–H) ppm; 13C NMR (125 MHz,
DMSO-d6) d: 21.0, 30.7, 55.5, 101.4, 111.3, 118.3, 125.7, 127.8, 130.1, 137.9,
144.0, 164.1, 169.0, 177.8 ppm; MS (ESI): m/z 299 (M ? H)?. Anal. Calcd. for
C16H11FN2O3 (%): C, 64.43; H, 3.72; N, 9.39. Found: C, 64.41; H, 3.66; N, 9.38.
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Methyl 2-amino-6-methyl-8-oxo-4-(4-fluorophenyl)-4H,8H-pyrano[3,2-b]pyran-3-
carboxylate (4o)
IR (KBr, cm-1): 3,428 and 3,360 (NH2), 3,272 (Ar–H), 1,699 (C=O), 1,665 (C=O);
1H NMR (500 MHz, DMSO-d6) d: 2.21 (s, 3H, CH3), 3.69 (s, 3H, CH3), 4.72 (s, 1H,
CH), 6.59 (s, 1H, =CH), 6.95 (s, 2H, NH2), 7.32 (d, J = 8.0 Hz, 2H, Ar–H), 7.54 (d,
J = 8.0 Hz, 2H, Ar–H) ppm; 13C NMR (125 MHz, DMSO-d6) d: 19.5, 30.1, 53.3,
55.4, 102.6, 111.4, 126.0, 128.0, 128.5, 138.0, 143.4, 163.0, 166.6, 172.5,
176.2 ppm; MS (ESI): m/z 332 (M ? H)?. Anal. Calcd. for C17H14FNO5 (%): C,
61.63; H, 4.26; N, 4.23. Found: C, 61.55; H, 4.21; N, 4.19.
Methyl 2-amino-6-methyl-8-oxo-4-(3-nitrophenyl)-4H,8H-pyrano[3,2-b]pyran-3-
carboxylate (4p)
IR (KBr, cm-1): 3,431 and 3,366 (NH2), 3,277 (Ar–H), 1,707 (C=O), 1,671 (C=O);
1H NMR (500 MHz, DMSO-d6) d: 2.23 (s, 3H, CH3), 3.60 (s, 3H, CH3), 4.61 (s, 1H,
CH), 6.55 (s, 1H, =CH), 6.93 (s, 2H, NH2), 7.21-7.49 (m, 4H, Ar–H) ppm; 13C NMR
(125 MHz, DMSO-d6) d: 19.7, 30.6, 53.2, 55.5, 102.8, 111.5, 126.3, 127.8, 128.7,
138.1, 143.6, 163.5, 166.2, 172.6, 176.3 ppm; MS (ESI): m/z 359 (M ? H)?. Anal.
Calcd. for C17H14N2O7 (%): C, 56.99; H, 3.94; N, 7.82. Found: C, 56.90; H, 3.89; N,
7.80.
Methyl 2-amino-6-methyl-8-oxo-4-(2-chlorophenyl)-4H,8H-pyrano[3,2-b]pyran-3-
carboxylate (4q)
IR (KBr, cm-1): 3,439 and 3,361 (NH2), 3,273 (Ar–H), 1,701 (C=O), 1,673 (C=O);
1H NMR (500 MHz, DMSO-d6) d: 2.19 (s, 3H, CH3), 3.63 (s, 3H, CH3), 4.64 (s, 1H,
CH), 6.57 (s, 1H, =CH), 6.87 (s, 2H, NH2), 7.34-7.55 (m, 4H, Ar–H) ppm; 13C NMR
(125 MHz, DMSO-d6) d: 19.9, 30.3, 53.5, 55.3, 102.5, 111.0, 126.5, 127.7, 128.9,
137.5, 143.4, 163.3, 166.4, 172.7, 176.0 ppm; MS (ESI): m/z 348.5 (M ? H)?.
Anal. Calcd. for C17H14ClNO5 (%): C, 58.72; H, 4.06; N, 4.03. Found: C, 58.66; H,
4.02; N, 4.00.
Methyl 2-amino-6-methyl-8-oxo-4-(3-bromophenyl)-4H,8H-pyrano[3,2-b]pyran-3-
carboxylate (4r)
IR (KBr, cm-1): 3,444 and 3,372 (NH2), 3,280 (Ar–H), 1,695 (C=O), 1,677 (C=O);
1H NMR (500 MHz, DMSO-d6) d: 2.16 (s, 3H, CH3), 3.61 (s, 3H, CH3), 4.70 (s, 1H,
CH), 6.60 (s, 1H, =CH), 6.94 (s, 2H, NH2), 7.24 (t, J = 8.0 Hz, 1H, ArH), 7.47 (tt,
J = 8.2 Hz, J0 = 1.3 Hz, 1H, Ar–H), 7.66 (t, J = 2.2 Hz, 1H, Ar–H), 7.76 (dd, dd,
J = 8.2 Hz, J0 = 2.2 Hz, J00 = 1.3 Hz, 1H, Ar–H) ppm; 13C NMR (125 MHz,
DMSO-d6) d: 20.2, 31.0, 53.6, 55.3, 102.6, 111.3, 126.4, 128.1, 128.8, 137.6, 143.3,
163.6, 166.3, 172.7, 176.5 ppm; MS (ESI): m/z 393 (M ? H)?. Anal. Calcd. for
C17H14BrNO5 (%): C, 52.06; H, 3.60; N, 3.57. Found: C, 52.01; H, 3.56; N, 3.53.
123

Silica-bonded N-propylpiperazine sodium n-propionate
Methyl 2-amino-6-methyl-8-oxo-4-(4-methylphenyl)-4H,8H-pyrano[3,2-b]pyran-3-
carboxylate (4s)
IR (KBr, cm-1): 3,438 and 3,374 (NH2), 3,274 (Ar–H), 1,703 (C=O), 1,669 (C=O);
1H NMR (500 MHz, DMSO-d6) d: 2.07 (s, 3H, CH3), 2.15 (s, 3H, CH3), 3.66 (s, 3H,
CH3), 4.63 (s, 1H, CH), 6.61 (s, 1H, =CH), 6.92 (s, 2H, NH2), 7.23 (d, J = 8.0 Hz,
2H, Ar–H), 7.50 (d, J = 8.0 Hz, 2H, Ar–H) ppm; 13C NMR (125 MHz, DMSO-d6)
d: 20.0, 31.1, 53.3, 55.2, 102.7, 111.5, 126.2, 127.9, 128.7, 137.7, 143.4, 163.2,
166.7, 172.5, 176.4 ppm; MS (ESI): m/z 328 (M ? H)?. Anal. Calcd. for
C18H17NO5 (%): C, 66.05; H, 5.23; N, 4.28. Found: C, 65.97; H, 5.21; N, 4.24.
Methyl 2-amino-6-methyl-8-oxo-4-(2-fluorophenyl)-4H,8H-pyrano[3,2-b]pyran-3-
carboxylate (4t)
IR (KBr, cm-1): 3,442 and 3,370 (NH2), 3,267 (Ar–H), 1,706 (C=O), 1,673 (C=O);
1H NMR (500 MHz, DMSO-d6) d: 2.14 (s, 3H, CH3), 3.65 (s, 3H, CH3), 4.69 (s, 1H,
CH), 6.58 (s, 1H, =CH), 6.91 (s, 2H, NH2), 7.16-7.35 (m, 4H, Ar–H) ppm; 13C NMR
(125 MHz, DMSO-d6) d: 19.7, 30.7, 53.2, 55.6, 102.4, 111.3, 126.3, 127.8, 128.5,
137.8, 143.5, 163.1, 166.3, 172.4, 176.2 ppm; MS (ESI): m/z 332 (M ? H)?. Anal.
Calcd. for C17H14FNO5 (%): C, 61.63; H, 4.26; N, 4.23. Found: C, 61.59; H, 4.23;
N, 4.17.
Ethyl 2-amino-6-methyl-8-oxo-4-(2,4-dichlorophenyl)-4H,8H-pyrano[3,2-b]pyran-
3- carboxylate (4u)
IR (KBr, cm-1): 3,452 and 3,389 (NH2), 3,289 (Ar–H), 1,712 (C=O), 1,670 (C=O);
1H NMR (500 MHz, DMSO-d6) d: 1.01 (t, 3H, J = 7.0 Hz, CH3), 2.05 (s, 3H,
CH3), 3.77 (q, 2H, J = 7.0 Hz, CH2), 4.67 (s, 1H, CH), 6.55 (s, 1H, =CH), 6.91 (s,
2H, NH2), 7.16 (d, 1H, J = 8.2 Hz, Ar–H), 7.47 (dd, 1H, J = 8.2 Hz, J0 = 2.4 Hz,
Ar–H), 7.62 (d, 1H, J = 2.4 Hz, Ar–H) ppm; 13C NMR (125 MHz, DMSO-d6) d:
14.5, 21.4, 31.6, 55.3, 58.3, 100.4, 110.3, 125.6, 128.2, 129.5, 135.2, 144.0, 164.2,
166.4, 172.1, 178.0 ppm; MS (ESI): m/z 397 (M ? H)?. Anal. Calcd. for
C18H15Cl2NO5 (%): C, 54.56; H, 3.82; N, 3.54. Found: C, 54.50; H, 3.77; N, 3.50.
Ethyl 2-amino-6-methyl-8-oxo-4-(3,4-dichlorophenyl)-4H,8H-pyrano[3,2-b]pyran-
3-carboxylate (4v)
IR (KBr, cm-1): 3,449 and 3,390 (NH2), 3,295 (Ar–H), 1,709 (C=O), 1,672 (C=O);
1H NMR (500 MHz, DMSO-d6) d: 1.03 (t, 3H, J = 7.0 Hz, CH3), 2.11 (s, 3H,
CH3), 3.79 (q, 2H, J = 7.0 Hz, CH2), 4.65 (s, 1H, CH), 6.54 (s, 1H, =CH), 6.91 (s,
2H, NH2), 7.23 (dd, 1H, J = 8.4 Hz, J0 = 2.0 Hz, Ar–H), 7.41 (d, 1H, J = 2.0 Hz,
Ar–H), 7.57 (d, 1H, J = 8.4 Hz, Ar–H) ppm; 13C NMR (125 MHz, DMSO-d6) d:
14.6, 21.6, 31.8, 55.7, 58.4, 100.6, 110.2, 125.5, 128.4, 129.6, 135.3, 143.7, 164.0,
166.3, 172.3, 178.2 ppm; MS (ESI): m/z 397 (M ? H)?. Anal. Calcd. for
C18H15Cl2NO5 (%): C, 54.56; H, 3.82; N, 3.54. Found: C, 54.48; H, 3.79; N, 3.51.
123

S. S. Mansoor et al.
Ethyl 2-amino-6-methyl-8-oxo-4-(3-bromophenyl)-4H,8H-pyrano[3,2-b]pyran-3-
carboxylate (4w)
IR (KBr, cm-1): 3,450 and 3,392 (NH2), 3,293 (Ar–H), 1,710 (C=O), 1,675 (C=O);
1H NMR (500 MHz, DMSO-d6) d: 1.04 (t, 3H, J = 7.0 Hz, CH3), 2.15 (s, 3H,
CH3), 3.83 (q, 2H, J = 7.0 Hz, CH2), 4.63 (s, 1H, CH), 6.55 (s, 1H, =CH), 6.88 (s,
2H, NH2), 7.20–7.48 (m, 4H, Ar–H) ppm; 13C NMR (125 MHz, DMSO-d6) d: 14.7,
21.3, 31.5, 55.4, 58.6, 100.3, 110.3, 125.4, 128.2, 129.7, 135.4, 143.6, 164.4, 166.0,
172.5, 178.3 ppm; MS (ESI): m/z 407 (M ? H)?. Anal. Calcd. for C18H16BrNO5
(%): C, 53.22; H, 3.97; N, 3.45. Found: C, 53.17; H, 3.95; N, 3.43.
Ethyl 2-amino-6-methyl-8-oxo-4-(3-fluorophenyl)-4H,8H-pyrano[3,2-b]pyran-3-
carboxylate (4x)
IR (KBr, cm-1): 3,457 and 3,387 (NH2), 3,288 (Ar–H), 1,714 (C=O), 1,677 (C=O);
1H NMR (500 MHz, DMSO-d6) d: 1.07 (t, 3H, J = 7.0 Hz, CH3), 2.14 (s, 3H,
CH3), 3.80 (q, 2H, J = 7.0 Hz, CH2), 4.72 (s, 1H, CH), 6.53 (s, 1H, =CH), 6.93 (s,
2H, NH2), 7.27–7.46 (m, 4H, Ar–H) ppm; 13C NMR (125 MHz, DMSO-d6) d: 14.8,
21.5, 31.4, 55.6, 58.5, 100.5, 110.4, 125.3, 128.3, 129.8, 135.6, 143.5, 164.1, 166.2,
172.4, 178.4 ppm; MS (ESI): m/z 346 (M ? H)?. Anal. Calcd. for C18H16FNO5
(%): C, 62.61; H, 4.67; N, 4.06. Found: C, 62.55; H, 4.62; N, 4.02.
Ethyl 2-amino-6-methyl-8-oxo-4-(4-nitrophenyl)-4H,8H-pyrano[3,2-b]pyran-3-
carboxylate (4y)
IR (KBr, cm-1): 3,455 and 3,377 (NH2), 3,282 (Ar–H), 1,703 (C=O), 1,661 (C=O);
1H NMR (500 MHz, DMSO-d6) d: 1.00 (t, 3H, J = 7.0 Hz, CH3), 2.09 (s, 3H,
CH3), 3.82 (q, 2H, J = 7.0 Hz, CH2), 4.68 (s, 1H, CH), 6.52 (s, 1H, =CH), 6.92 (s,
2H, NH2), 7.17 (d, J = 8.2 Hz, 2H, Ar–H), 7.40 (d, J = 8.2 Hz, 2H, Ar–H) ppm;
13C NMR (125 MHz, DMSO-d6) d: 14.5, 21.4, 31.8, 55.7, 58.4, 100.7, 110.5, 125.4,
128.2, 129.5, 135.2, 143.8, 164.6, 166.6, 172.6, 178.3 ppm; MS (ESI): m/z 373
(M ? H)?. Anal. Calcd. for C18H16N2O7 (%): C, 58.06; H, 4.33; N, 7.52. Found: C,
58.00; H, 4.29; N, 7.48.
Ethyl 2-amino-6-methyl-8-oxo-4-(4-methoxyphenyl)-4H,8H-pyrano[3,2-b]pyran-3-
carboxylate (4z)
IR (KBr, cm-1): 3,446 and 3,380 (NH2), 3,289 (Ar–H), 1,707 (C=O), 1,660 (C=O);
1H NMR (500 MHz, DMSO-d6) d: 1.02 (t, 3H, J = 7.0 Hz, CH3), 2.06 (s, 3H,
CH3), 3.61 (s, 3H, OCH3), 3.87 (q, 2H, J = 7.0 Hz, CH2), 4.63 (s, 1H, CH), 6.58 (s,
1H, =CH), 6.93 (s, 2H, NH2), 7.25 (d, J = 8.1 Hz, 2H, Ar–H), 7.43 (d, J = 8.1 Hz,
2H, Ar–H) ppm; 13C NMR (125 MHz, DMSO-d6) d: 14.3, 21.5, 31.6, 55.6, 58.3,
100.9, 110.3, 125.6, 128.4, 129.7, 135.6, 143.5, 164.3, 166.2, 172.7, 178.7 ppm; MS
(ESI): m/z 358 (M ? H)?. Anal. Calcd. for C19H19NO6 (%): C, 63.86; H, 5.36; N,
3.92. Found: C, 63.78; H, 5.31; N, 3.88.
123

Silica-bonded N-propylpiperazine sodium n-propionate
Results and discussion
We report herein an efficient and environmentally benign procedure for synthesis of
2-amino-4-phenyl-4H,8H-6-methyl-8-oxo-pyrano[3,2-b]pyran derivatives by three-
component condensation of an aromatic aldehyde with malononitrile or a cyanoester
and 5-hydroxy-2-methyl-4H-pyran-4-one catalyzed by SBPPSP in EtOH–H2O
(50:50 v/v) under reflux. SBPPSP was prepared as reported in the literature [34].
To determine the optimum conditions, we initially investigated reaction of
4-chlorobenzaldehyde (1a) with malononitrile and 5-hydroxy-2-methyl-4H-pyran-
4-one in the solvents CH3CN, CHCl3, MeOH, EtOH, and H2O under reflux, with
SBPPSP (0.06 g) as catalyst, as model reaction. When an aprotic polar solvent, for
example CH3CN, was used the reaction afforded the corresponding pyrano[3,2-
b]pyran 4a in modest yield after reflux for 90 min (Table 1, entry 1). However,
reactions in protic solvents, for example EtOH or H2O, under reflux gave better
yields (Table 1, entries 4 and 5). The model reaction was also examined under
solvent-free conditions at 80 °C and gave 4a in 55 % yield after 70 min (Table 1,
entry 6). When the amount of catalyst was increased to 0.08 g and the temperature
Table 1 Optimization of reaction conditions for the synthesis of 4a
Entry
Catalyst
Amount of
catalyst
Solvent
Temperature
(°C)
Time
(min)
Yield (%)a
1
SBPPSP
SBPPSP
SBPPSP
SBPPSP
SBPPSP
SBPPSP
SBPPSP
SBPPSP
SBPPSP
SBPPSP
SBPPSP
SBPPSP
SBPPSP
SBPPSP
SBPPSP
PNPS
0.06 g
0.06 g
0.06 g
0.06 g
0.06 g
0.06 g
0.06 g
0.08 g
0.08 g
0.06 g
0.06 g
0.06 g
0.04 g
0.02 g
0.08 g
0.06 g
10 mol%
10 mol%
10 mol%
10 mol%
CH3CN
Reflux
Reflux
Reflux
Reflux
Reflux
80
90
90
30
30
30
70
70
70
70
25
15
25
20
30
15
90
60
60
40
60
43
55
81
84
77
55
81
77
84
77
94
79
80
62
94
77
61
55
73
74
2
CHCl3
3
MeOH
4
EtOH
5
H2O
6
Solvent-free
7
Solvent-free
100
8
Solvent-free
80
9
Solvent-free
100
10
11
12
13
14
15
16
17
18
19
20
EtOH–H2O (30:70 v/v)
EtOH–H2O (50:50 v/v)
EtOH–H2O (70:30 v/v)
EtOH–H2O (50:50 v/v)
EtOH–H2O (50:50 v/v)
EtOH–H2O (50:50 v/v)
EtOH–H2O (50:50 v/v)
EtOH–H2O (50:50 v/v)
EtOH–H2O (50:50 v/v)
EtOH–H2O (50:50 v/v)
EtOH–H2O (50:50 v/v)
Reflux
Reflux
Reflux
Reflux
Reflux
Reflux
Reflux
Reflux
Reflux
Reflux
Reflux
KH2PO4
NH4OAc
TBAF
HMTA
Reaction conditions: 4-chlorobenzaldehyde (1 mmol), allomaltol (1 mmol), and malononitrile (1 mmol),
solvent 5 mL, reflux
a
Isolated yields
123

S. S. Mansoor et al.
Table 2 Preparation of 2-amino-4-aryl-4H,8H-6-methyl-8-oxo-pyrano[3,2-b]pyran derivatives from
aromatic aldehydes, malononitrile/methyl cyanoacetate/ethyl cyanoacetate, and allomaltol catalyzed by
SBPPSP in EtOH–H2O (50:50 v/v)
Entry Aldehydes
R
Product
Time (min)
Yield (%)a
Cl
Cl
H C
3
O
CN
NH
O
2
4a
CHO
O
H C
3
1
CN
15
94
H C
3
H C
O
O
CN
NH
3
O
2
4b
CHO
2
3
CN
CN
30
12
89
95
F
H C
3
O
CN
F
O
NH
2
4c
NO
CHO
O
O
2
NO
2
H C
3
CN
NH
O
2
4d
CHO
O
Cl
4
5
6
CN
20
15
35
90
92
85
Cl
H C
O
O
CN
3
O
NH
2
4e
CHO
CN
CN
H CO
3
H C
3
O
CN
NH
H CO
3
O
2
4f
CHO
O
H C
3
H C
3
O
CN
NH
H C
3
O
2
4g
O
CHO
7
CN
30
86
123

Silica-bonded N-propylpiperazine sodium n-propionate
Table 2 continued
F
F
H C
3
O
O
CN
NH
O
2
4h
CHO
8
CN
CN
CN
20
20
20
85
88
91
Br
Br
H C
O
O
CN
NH
3
O
2
4i
CHO
9
O N
2
O N
2
H C
3
O
CN
NH
O
2
4j
O
CHO
Cl
10
Cl
Cl
Cl
H C
3
O
O
CN
O
4k
Cl
NH
2
CHO
11
12
CN
15
15
92
93
Cl
Cl
O
H C
3
CN
NH
Cl
O
2
4l
CHO
O
CN
Cl
O N
2
Cl
O N
2
H C
3
O
CN
NH
O
2
4m
CHO
O
F
13
14
CN
CN
20
18
84
F
H C
3
O
O
CN
O
NH
2
4n
CHO
93
123

S. S. Mansoor et al.
Table 2 continued
F
F
H
C
O
O
COOMe
3
O
NH
2
4o
CHO
15
COOMe
20
87
O N
2
O N
2
H C
3
O
COOMe
O
NH
2
4p
CHO
O
16
17
18
COOMe
COOMe
COOMe
20
15
20
86
92
91
Cl
H C
O
COOMe
3
Cl
O
NH
2
4q
O
Br
CHO
Br
H C
3
O
O
COOMe
O
NH
2
4r
CHO
CH
3
CH
3
H C
3
O
O
COOMe
O
NH
2
4s
CHO
19
20
COOMe
COOMe
30
15
85
93
F
H C
3
O
COOMe
F
O
4t
NH
2
CHO
Cl
O
Cl
Cl
H C
3
O
COOEt
Cl
O
NH
2
4u
CHO
O
21
COOEt
15
89
123

Silica-bonded N-propylpiperazine sodium n-propionate
Table 2 continued
Cl
Cl
Cl
Cl
H C
3
O
COOEt
O
NH
2
4v
CHO
CHO
CHO
O
22
23
24
COOEt
COOEt
COOEt
15
20
20
88
89
91
Br
Br
H C
O
COOEt
3
O
NH
2
4w
O
F
F
H C
3
O
O
COOEt
O
NH
2
4x
NO
2
NO
2
H C
3
O
COOEt
O
4y
NH
2
O
CHO
25
COOEt
20
89
85
OCH
3
OCH
3
H C
3
O
O
COOEt
O
4z
NH
2
CHO
26
COOEt
35
Reaction conditions: arylaldehyde (1 mmol), malononitrile/methyl cyanoacetate/ethyl cyanoacetate
(1 mmol), and allomaltol (1 mmol), EtOH–H2O (50:50 v/v) 5 mL, reflux
a
Isolated yields
to 100 °C, the yield of 4a increased to 84 % (Table 1, entry 9). The model reaction
was studied in different EtOH–H2O mixtures. When the reaction was performed in
EtOH–H2O (30:70 v/v) and EtOH–H2O (70:30 v/v) the yield was 77 and 79 %,
respectively (Table 1, entries 10 and 12). EtOH–H2O (50:50 v/v) was shown to be
the most suitable solvent for this condensation in terms of yield and reaction time
(Table 1, entry 11).
123

S. S. Mansoor et al.
NC
Ar
R
H
O
R
SBPPSP
-H2O
H2C
+
Ar
H
CN
(a)
1
2
NC
R
B
Ar
O
H
(a)
H3C
O
R
N
H3C
O
Ar
H
C
O
H
B
O
(b)
O
3
Ar
B
R
Ar
O
H
H3C
O
O
R
H3C
O
O
NH2
NH
4
O
Scheme 2 Possible mechanism for formation of the pyrano[3,2-b]pyran derivatives
We next investigated the optimum amount of SBPPSP by varying the amount of
catalyst. Maximum yield was obtained by use of 0.06 g (5.2 mol%) catalyst
(Table 1, entry 11). When the amount of catalyst was reduced from 0.06 to 0.04 g
and 0.02 g the yield decreased from 94 to 80 and 62 %, respectively (Table 1,
entries 13 and 14). Increasing the amount of SBPPSP above 0.06 g had no
significant effect on product yield (Table 1, entry 15).
When the model reaction was performed in the presence of silica-bonded N-
propylpiperazine (PNPS) (3-piperazine-N-propylsilica) [42] in EtOH–H2O (50:50 v/
v) under reflux conditions the yield was 77 % (Table 1, entry 16). To show SBPPSP
is an efficient catalyst, we performed the model reaction in the presence of other
catalysts—potassium dihydrogen phosphate (KH2PO4), ammonium acetate (NH4-
OAc), tetrabutylammonium fluoride (TBAF), and hexamethylenetetramine
(HMTA) (Table 1, entries 17–20). With these catalysts, yields were lower than
with SBPPSP (Table 1, entry 11). Thus, EtOH–H2O (50:50 v/v) and 0.06 g SBPPSP
were chosen as the optimum conditions for investigation of the scope of the
procedure.
Subsequent reaction of a variety of substituted aromatic aldehydes with
malononitrile and 5-hydroxy-2-methyl-4H-pyran-4-one were attempted under
similar conditions. The reactions proceeded smoothly, and equally well for
123

Silica-bonded N-propylpiperazine sodium n-propionate
96
Recycling of SBPPSP
94%
94
92%
92
90%
90
88
86
88%
1
2
3
4
Number of Runs
Fig. 1 Recycling of the SBPPSP catalyst in the preparation of 2-amino-6-methyl-8-oxo-4-(4-
chlorophenyl)-4H,8H-pyrano[3,2-b]pyran-3-carbonitrile (4a)
aldehydes with electron-withdrawing or electron-donating substituents, affording
the corresponding pyrano[3,2-b]pyrans in excellent yields (Scheme 1). We observed
delicate electronic effects: aldehydes with electron-withdrawing groups reacted
rapidly whereas electron-donating groups reduced the reactivity, so longer reaction
times were required. The results are summarized in Table 2 (entries 1–14).
Encouraged by these results, we tried to extend the scope of the catalytic activity
of SBPPSP to condensation of aromatic aldehydes and 5-hydroxy-2-methyl-4H-
pyran-4-one with methyl cyanoacetate or ethyl cyanoacetate. Substituted aromatic
aldehydes underwent condensation successfully under the same conditions and the
corresponding pyrano[3,2-b]pyran derivatives were obtained in high yields
1
(Table 2, entries 15–26). All the products were characterized by IR, H NMR,
13C NMR, and mass spectroscopy and elemental analysis.
On the basis of a previous report [35], a plausible mechanism for this reaction is
depicted in Scheme 2. The first step is Knoevenagel condensation between aromatic
aldehyde 1 and malononitrile or cyanoacetate 2 in the presence of the immobilized
base to form intermediate a. Michael addition of allomaltol 3 to intermediate a then
furnishes intermediate b. Finally, product 4 was obtained by intramolecular
cyclization and tautomerism.
Recovery and reuse of the SBPPSP was studied by using preparation of 4a as a
model. On completion of the reaction the mixture was filtered and the solid residue
was washed with hot ethanol, dried in air, and reused as the catalyst in the next
reaction. As shown in Fig. 1, the solid base SBPPSP can be recycled at least four
times without significant decrease in catalytic activity; yields ranged from 94 to
88 %.
123

S. S. Mansoor et al.
Conclusion
We have developed a simple method for synthesis of pyrano[3,2-b]pyran derivatives
by one-pot, three-component cyclocondensation of an aromatic aldehyde, malon-
onitrile or a cyanoacetate, and 5-hydroxy-2-methyl-4H-pyran-4-one, in aqueous
ethanol, in the presence of a catalytic amount of silica-bonded N-propylpiperazine
sodium n-propionate (SBPPSP) as efficient, reusable, and green heterogeneous basic
catalyst. Attractive features of the method are good yields, simple procedure, short
reaction times, easy work-up, high catalytic activity, and recyclability and
reusability of the catalyst. The catalyst can be used at least four times without
substantial reduction of its catalytic activity.
Acknowledgments The author Mansoor would like to express his gratitude to the management of C.
Abdul Hakeem College, Melvisharam 632 509, Tamil Nadu, India, for the use of their facilities and their
general support.
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