Green synthesis of tetrahydrobenzo[b] pyrans, pyrano[2,3-c] pyrazoles and spiro[indoline-3,4′-pyrano[2,3-c] pyrazoles catalyzed by nano-structured diphosphate in water

Article abstract of DOI:10.1039/c6ra15800e

A green and recoverable nano-structured diphosphate (Na₂CaP₂O₇) was synthesized and fully characterized using FT-IR spectra, X-ray diffraction patterns (XRD), scanning electron microscopy (SEM), and energy-dispersive X-ray

Full text of DOI:10.1039/c6ra15800e

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Green Synthesis of Tetrahydrobenzo[b]pyrans, Pyrano [2, 3-
c]pyrazoles and Spiro
[indoline-3,4'-pyrano[2,3-c]pyrazoles
Catalyzed by Nano-structured diphosphate in Water
Behrooz Maleki*1, Negar Nasiri1, Reza Tayebee1 Amir Khojastehnezhad*2 and Hossien Ali
Akhlaghi1
1Department of Chemistry, Hakim Sabzevari University, Sabzevar, 96179-76487, Iran
E-mail: malekibehrooz@gmail.com, Fax: +9844010300; Tel: +985144013324
2Young Researchers and Elite Club, Mashhad Branch, Islamic Azad University, Mashhad, Iran
E-mail: akhojastehnezhad@yahoo.com
Abstract
A green and recoverable nanoꢀstructured diphosphate (Na2CaP2O7) was synthesized and
fully characterized using FTꢀIR spectra, Xꢀray diffraction patterns (XRD), scanning electron
microscopy (SEM), and energyꢀdispersive Xꢀray spectroscopy (EDX) analysis. The
nanostructured catalyst has been successfully used as reusable nanostructured catalyst for green,
simple and efficient synthesis of tetrahydrobenzo[b]pyrans, pyrano[2,3ꢀc]pyrazoles and spiro
[indolineꢀ3,4'ꢀpyrano[2,3ꢀc]pyrazoles in aqueous media. The catalyst shows environmentally
benign character, which can be easily prepared, stored, and recovered several times without
obvious significant loss of catalytic activity.
Keywords: oneꢀpot multiꢀcomponent reactions, tetrahydrobenzo[b]pyrans and pyrano[2,3ꢀ
c]pyrazoles, nanoꢀstructured diphosphate (Na2CaP2O7), green chemistry.
Introduction
One important symbol of green chemistry is reducing the use of organic solvents because of
the economical and environmental concerns associated with them. Water plays an essential role
in life processes and also a medium for the organic synthesis.1,2 Water is clean, nonꢀtoxic, and
hazardꢀfree in handling, nonꢀinflammable, cheap and a readily available solvent. Furthermore,
because of its highly polarity, high surface tension, high specific heat capacity and network of
hydrogen bonds, water plays a significant role in many reactions.3 In 1980, Breslow discovered
that DielsꢀAlder reactions could be performed in water with a huge acceleration.4,5 This
discovery led to a considerable interest of synthetic organic chemists in the study of using water
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as a reaction solvent.6,7 To date, a great number of organic reactions have been carried out in
water successfully.8
The pyran ring system is present in numerous biologically active natural products as well as
many synthetic compounds.9 Tetrahydrobenzo[b]pyrans and pyrano[2,3ꢀc]pyrazoles have a
broad spectrum of biological and pharmacological activity, such as anticancer, antiꢀcoagulant,
antimicrobial, antiꢀinflammatory, antiꢀanaphylactic, and molluscicidal activity.10ꢀ13
Conventionally, the synthesis of tetrahydrobenzo[b]pyrans has been performed through a
oneꢀpot reaction of three components in the presence of various catalysts such as the
Fe3O4@SiO2–imid–PMA nanoparticle,14 choline hydroxide based ionic liquid [Ch][OH],15 red
sea sand under microwave or ultrasonic irradiation,16 hexadecyltrimethyl ammonium bromide
(HTMAB),17 sodium bromide (NaBr),18 ionic liquids,19ꢀ22 tetraꢀmethyl ammonium hydroxide,23
molecular iodine (I2),24 Nꢀmethylimidazole,25 sodium selenite,26 tetrabutylammonium bromide
(TBAB),27 amine or amino acid,28 potassium phosphate (K3PO4),29 magnetic core–shell titanium
dioxide nanoparticles (Fe3O4@SiO2@TiO2),30 Nano αꢀAl2O3 supported ammonium dihydrogen
phosphate (NH4H2PO4/Al2O3),31 phenylboronic acid [PhB(OH)2],32 cerium(III) chloride
(CeCl3.7H2O),33,34 nanosized TiO2,35 silica coated magnetiteꢀpolyoxometalate nanoparticles
(Fe3O4@SiO2@NHꢀNH2–H3PW12O40),36 meglumine,37 magnetic La0.7Sr0.3MnO3 nanoparticles,38
RuBr2(PPh3)4,39 lactose,40 and silica coated magnetic NiFe2O4 nanoparticles supported
H3PW12O40 (NFSꢀPWA).41
However, a number of these methods suffer from certain drawbacks such as poor yields,
difficult workups, long reaction times, high temperatures, the utilization of alternative energy
source (microwave or ultrasonic), and the use of volatile or hazardous organic solvents.
Therefore, it seemed desirable to develop a more efficient and a general method for the synthesis
of tetrahydrobenzo[b]pyrans and pyrano[2,3ꢀc]pyrazoles.
On the basis of the information obtained from the nanoꢀstructured diphosphate Na2CaP2O7
(DIPH), we predicted that the DIPH can be used as an efficient catalyst for the promotion of the
reactions which requires the use of a catalyst to speedꢀup. So, we were interested to investigate
the applicability of this reagent in the promotion of the synthesis tetrahydrobenzo[b]pyrans and
pyrano [2,3ꢀc]pyrazoles.
2

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For the present study, the synthesis of the DIPH has been carried out from Na2CO3, CaCO3
and NH4H2PO4 in 1:1:2 proportion, respectively, by following the literature procedure.42 In
recent years, the DIPH has been used as catalyst in organic synthesis43,44 as it has been shown to
be nonꢀtoxic, green and stable, inexpensive, safe, nonꢀvolatile, nonꢀcorrosive and reꢀusable.
In our progressive program to develop efficient and environmentally benign protocols for
the synthesis of various products,45ꢀ59 we tried to report a highly efficient method for the
synthesis of tetrahydrobenzo[b]pyrans and pyrano [2,3ꢀc]pyrazoles catalyzed by a DIPH in water
(Scheme 1).
H3C
N
N
O
O
Ar
O
Ar
H3C
N
CN
O
O
CN
5
3
+ CH2(CN)2
+ Na2CaP2O7
Ar
H
H2O/reflux
N
H2O/reflux
O
NH2
O
NH2
1
2
4a-k
6a-g
O
O
NH2NH2
H2O/reflux
H3C
CN
OCH2CH3
7
Ar
O
H3C
N
N
NH2
H
8a-h
Scheme. 1 Synthesis of tetrahydrobenzo[b]pyrans and pyrano [2,3ꢀc]pyrazoles catalyzed by a
DIPH in water
.
Nanostructured diphosphate (Na2CaP2O7) was characterized by several methods including
FTꢀIR, SEM, XRD and EDX. The existence of P2O7 units was confirmed by the symmetrical
vibration bands of P–O–P at 720 cm−1 as well as the antiꢀsymmetric vibration bands at 890 cm−1.
The related vibrations of the PO4 groups were shared between two fields: a field of symmetrical
vibrations at 990 cm−1 and 1030 cm−1 and another that ranged from 1130 to1280 cm−1 (Figure
S1).42ꢀ44 Scanning Electronic Microscopy (SEM) was used to study the morphology of the
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surface of Na2CaP2O7 (Figure S2). Also, to confirm the formation of Na2CaP2O7 nanostructure,
the XRD patterns of sample was studied (Figure S3). The XRD pattern of Na2CaP2O7
nanostructure indicates that these nanostructures have synthesized well and all of the major
peaks matching with the previous literatures.42ꢀ44 Moreover, the elemental analysis obtained from
the EDX spectra of catalyst (Figure S4), shows the existence of all of the elements in the
Na2CaP2O7 nanostructures and these results are in agreement with other results.
At first, we selected the benzaldehyde (1 mmol), dimedone (1 mmol), and malononitrile (2
mmol) as model substrates to establish optimum reaction conditions in the presence of DIPH
(Table 1). When the reaction was performed under solventꢀfree conditions, a low yield of target
product was obtained (Entry 1). To find the best solvent for this transformation, the present
threeꢀcomponent reaction was screened in methanol, ethanol, and water (Table 2, Entries 2ꢀ4).
Among these solvents, water was found to be the best one and afforded the highest yield (Entry
5). Then, the amount of the catalyst was evaluated in the model reaction in refluxing water
(Entries 6ꢀ7). The results showed that 20 mol% of DIPH was the best choice for completing the
reaction (Entry 5) and the use of excessive catalyst had no impact either on the rate of the
reaction or on the product yield (Entry 7). When the reaction was attempted without a catalyst, it
was found that no product was obtained even after 1 h (Entry 8).
Table 1 Optimization of reaction conditionsa
Entry
Catalyst (mol %)
Conditions
Solventꢀfree/100 0C
MOH/reflux
Time (min)
Yield (%)b
1
2
3
4
5
6
7
8
20
20
15
10
10
10
10
10
10
60
72
80
20
EtOH/reflux
82
20
EtOH:Water/reflux
Water/reflux
88
20
94
10
Water/reflux
84
30
Water/reflux
94
None
Water/reflux
None
a Benzaldehyde (1 mmol), dimedone (1mmol), malonitrile (1 mmol) in refluxing water.
b Isolated yields
Under These optimal conditions (Table 1, Entry 4), the scope and specificity of this protocol
was further investigated. At first, a broad range of structurally diverse aldehydes were treated
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with malononitrile and dimedone (see Table 2) in order to synthesis of tetrahydrobenzo[b]pyrans
derivatives 4a-k. As shown in Table 2, all reactions proceeded efficiently and the desired
products were obtained from high to excellent yields in relatively short times without any
formation of byꢀproducts. The reaction of aromatic aldehyde carrying electron donating or
electronꢀwithdrawing groups was also successfully carried out with this method (Table 2, Entries
1ꢀ11). The reactions showed corresponding compounds in excellent yields.
Encouraged by these results, we extended this study for three component synthesis of
pyrano[2,3ꢀc]pyrazoles (6a-g) in the presence of a catalytic amount of DIPH. Considering the
reaction time and the yield, the DIPH (20 mol%) was selected as the optimum catalyst used in
the refluxing water. Using the optimized reaction conditions, a range of substituted pyrano[2,3ꢀ
c]pyrazoles were synthesized (Table 2, Entries 12ꢀ18). Moreover, the oneꢀpot, fourꢀcomponent
synthesis of pyrano[2,3ꢀc]pyrazoles could be successfully used for the synthesis of
corresponding compounds (8a-h). This method was found to be effective for aromatic aldehydes
bearing either electron donating or electronꢀwithdrawing substituents (Entries 19ꢀ21, 24ꢀ26) as
well as for the heterocyclic aldehyde (Entries 22, 23).
Table 2 Green synthesis of tetrahydrobenzo[b]pyran and pyrano[2,3ꢀc]pyrazoles derivatives catalyzed by DIPH in
refluxing water
Entry
1
Ar
Product
4a
Time (min) Yield (%)a
Mp (°C)
231ꢀ233
207ꢀ209
212ꢀ214
230ꢀ232
192ꢀ194
212ꢀ214
226ꢀ228
177ꢀ179
210ꢀ212
202ꢀ204
183ꢀ185
164ꢀ166
180ꢀ182
187ꢀ188
Lit. Mp (°C) [ref]
231ꢀ233 [18]
203ꢀ206 [21]
210ꢀ213 [23]
230ꢀ232 [23]
188ꢀ190 [20]
211ꢀ212 [41]
225ꢀ228 [23]
177ꢀ179 [23]
211ꢀ214 [18]
203ꢀ205 [26]
180ꢀ182 [27]
169ꢀ171 [17]
175ꢀ177 [17]
185ꢀ186 [31]
Ph
10
10
10
10
10
15
10
10
10
10
10
10
15
15
94
90
89
92
90
86
95
95
94
91
90
93
86
90
2
4ꢀClC6H4
4ꢀCH3C6H4
3ꢀClC6H4
3ꢀMeOC6H4
2ꢀCH3C6H4
4ꢀCNC6H4
4ꢀNO2C6H4
3ꢀNO2C6H4
4ꢀBrC6H4
2,4ꢀClC6H4
Ph
4b
4c
3
4
4d
4e
5
6
4f
7
4g
8
4h
4i
9
10
11
12
13
14
4j
4k
6a
4ꢀClC6H4
4ꢀBrC6H4
6b
6c
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15
16
17
18
19
20
21
22
23
24
25
26
4ꢀCH3C6H4
4ꢀCH3OC6H4
3ꢀNO2C6H4
4ꢀNO2C6H4
Ph
20
20
15
20
10
15
15
10
20
15
10
15
80
174ꢀ177
171ꢀ173
189ꢀ191
195ꢀ197
244ꢀ245
213ꢀ215
246ꢀ248
225ꢀ226
215ꢀ217
224ꢀ226
250ꢀ252
228ꢀ230
176ꢀ178 [31]
6d
6e
6f
82
90
87
92
86
85
92
90
90
90
89
170ꢀ172 [31]
190ꢀ192 [31]
197ꢀ199 [31]
244ꢀ245 [19]
211ꢀ213 [19]
248ꢀ250 [19]
224ꢀ226 [37]
216ꢀ217 [37]
222ꢀ223 [19]
248ꢀ249 [37]
232ꢀ233 [22]
6g
8a
8b
8c
8d
8e
8f
4ꢀCH3OC6H4
4ꢀBrC6H4
2ꢀThienylC6H4
4ꢀPyridinC6H4
3ꢀBrC6H4
4ꢀNO2C6H4
8g
8h
3ꢀNO2C6H4
a Isolated yields
Spiro heterocycles, especially spirocyclic oxindole nucleus, are a substantial category of
natural alkaloids that possess various biological and pharmacological activities, such as
spirotryptostatin A, B, which are isolated from the fermentation broth of Aspergillus fumigates,
inhibits of cell cycle at G2/M phase and Koumine,60 which is one of the alkaloids isolated from
the Gelsemium sempervirens plant that has antitumor and analgesic activities.61 Chitosenine as a
Gardneria multiflora oxindole alkaloid has ganglioblocking action.62 These interesting properties
promoted us to widen the applicability of this procedure with isatins.63
To explore the scope of this reaction to form a spiroheterocyclic compound, we investigated
the use of acenaphtyleneꢀ1,2ꢀdione (9) or isatin (10) as a substrate to react with the hydrazine
hydrate, malononitrile, ethyl acetoacetate under the optimized conditions. As expected the
reaction proceeded well to afford spiro[acenaphthyleneꢀ1,4'ꢀpyrano[2,3ꢀc]pyrazole (11) in 60
min with 64% yield and spiro [indolineꢀ3,4'ꢀpyrano[2,3ꢀc]pyrazole] derivatives (12a-g) (Scheme
2, Table 3). These successful results clearly indicate that the present catalytic approach is
extendable to a wide variety of substrates.
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O
O
O
H3C
N
CN
N
H
O
NH2
R
O
O
11
9
Na2CaP2O7
CH2(CN)2
or
+
+
or
H3C
OC2H5
O
NH2NH2
7
2
HN
H2O/reflux
O
O
R
H3C
N
N
CN
H
N
H
10
O
NH2
12a-g
Scheme. 2 Synthesis of spiro-pyrano[2,3ꢀc]pyrazole derivative
Table 3. Green synthesis of spiro [indolineꢀ3,4'ꢀpyrano[2,3ꢀc]pyrazole] derivatives (12a-h) using DIPH in
refluxing water
Mp (oC)
Time
(min)
Entry
Products (12a-g)
Yielda (%)
Found
Reported [ref]
50
78
284ꢀ286
285ꢀ286 [37]
12a
70
74
278ꢀ280
279ꢀ281 [37]
12b
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40
85
274ꢀ276
296ꢀ298
274ꢀ275 [37]
12c
12d
12e
40
87
90
297ꢀ298 [37]
282ꢀ283 [37]
40
35
280ꢀ282
272ꢀ274
91
82
270ꢀ271 [37]
12f
40
>300
>300 [63]
12g
a Isolated yields
The reusability of the catalyst was also investigated. For this purpose, the same model
reaction was again studied under optimized conditions. After the completion of the reaction, the
acetone was added to the reaction mixture to dissolve the product. Then, the catalyst was
removed by filtration. It was reꢀused directly in the model reaction to give 4a in yields of 94%,
92%, 91%, 91%, 90% and 89% for six consecutive runs at 10 min.
In order to illustrate the efficiency of our procedure, results for the preparation of
tetrahydrobenzo[b]pyrans and pyrano[2, 3ꢀc]pyrazoles previously reported are compared with
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our data (Table 4). The present method using DIPH as catalyst offers several advantages such as
excellent yields, a simple procedure, short reaction times, facile workꢀup and greener conditions.
The green aspect of the DIPH catalyst has been discussed in terms of being nonꢀcorrosive,
presenting fewer disposals problem, facile isolation of the products, and recyclability.
Table 4 Comparison of the efficiencies of various catalysts used in the synthesis of tetrahydrobenzo[b]pyrans and
pyrano[2, 3ꢀc]pyrazoles
Product
Catalyst
Fe3O4@SiO2–imid–PMA
Red sea sand
[Ch][OH]
Reaction conditions
H2O/Reflux
Time (min)
Yield (%)a
[ref]
[14]
20
360
60
10
10
10
10
15
45
10
94
84
92
91
94
88
90
80
90
92
EtOH/Reflux
H2O/80 0C
[16]
[15]
4a
NaBr/MWI
solventꢀfree, 70 °C
H2O/Reflux
solventꢀfree/60 0C
solventꢀfree/50 0C
EtOH/Reflux
[18]
DIPH
This study
[19]
[bmim]OH
Lꢀproline/[Bmim]BF4
NH4H2PO4/Al2O3
NFSꢀPWA
[22]
[31]
8a
EtOH/Reflux
[41]
DIPH
H2O/Reflux
This study
a Isolated yields.
Conclusion
In conclusion, we have developed a green and simple protocol for the synthesis of
tetrahydrobenzo[b]pyran and pyrano[2,3ꢀc]pyrazole derivatives via a three or four component
condensation reaction in the presence of DIPH in water. This method was found not only to be
applied to aromatic and heteroaromatic aldehydes, but also to be useful for the synthesis of
ketoneꢀderived dihydroprano[2,3ꢀc]pyrazole, spiro[indolineꢀ3,4'ꢀpyrano[2,3ꢀc]pyrazole] and
spiro[acenaphthyleneꢀ1,4'ꢀpyrano[2,3ꢀc]pyrazole]. This procedure provides several advantages
such as high yields, wide scope of substrates, short reaction times, nonꢀvolatile, nonꢀcorrosive,
absence of sideꢀreactions, simple workꢀup procedure, nonꢀtoxic, evasion of hazardous catalysts
or solvents, and the minimization of cost and waste generation owing to the recycling of the
catalyst.
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Experimental Section
All reagents were obtained from commercial sources and were used without purification. IR
1
13
spectra were recorded as KBr pellets on a Shimadzu 435ꢀUꢀ04 spectrophotometer. H and C
NMR spectra were determined on a Bruker DRXꢀ300 Avance spectrometer in DMSOꢀd6 or
CDCl3, and shifts are given in δ downfield from tetramethylsilane (TMS) as an internal standard.
Melting points were determined using an Electrothermal 9200 apparatus and are uncorrected.
General Procedure for the Synthesis of Tetrahydrobenzo[b]pyrans (4a-k)
The catalyst, DIPH (20 mol %), was added to a mixture of the aldehydes (1 mmol), malononitrile
(1.2 mmol), and dimedone (1 mmol), and 1 ml of water in a 5 ml flask fitted with a reflux
condenser. The resulting mixture was heated to reflux (an oil bath) for the appropriate time (see
Table 2) with stirring (spin bar). After the completion of the reaction as determined by TLC
(hexaneꢀethyl acetate, 4:1), the acetone (2 ml) was added and the mixture stirred for 2 min. The
catalyst was removed by filtration and washed with acetone and calcined at 500 °C for 1 h before
reꢀuse. Then the resulting crude reaction mixture was poured onto crushed ice and the
precipitated solid was collected and recrystallized from ethanol (96%, 5 ml) to afford the pure
tetrahydrobenzo[b]pyrans derivatives 4a-k. The products were identified by their melting points,
1HꢀNMR, and IR spectroscopies.
General Procedure for the Synthesis of Pyrano[2,3-c]pyrazoles (6a-g)
The catalyst, DIPH (20 mol %), was added to a mixture of the aldehydes (1 mmol), malononitrile
(1.2 mmol), and 3ꢀmethylꢀ1ꢀphenylꢀ2ꢀpyrazolineꢀ5ꢀone (1 mmol), and 1 ml of water in a 5 ml
flask fitted with a reflux condenser. The resulting mixture was heated to reflux (an oil bath) for
the appropriate time (see Table 2) with stirring (spin bar). After the completion of the reaction as
determined by TLC (hexaneꢀethyl acetate, 4:1), the acetone (2 ml) was added and the mixture
stirred for 2 min. The products and catalyst were isolated as described above and recrystallized
from 96% ethanol (20 ml) to afford pyrano[2,3ꢀc]pyrazoles 6a-g.
General Procedure for the Synthesis of Pyrano[2,3-c]pyrazoles (8a-h)
The catalyst, DIPH (20 mol %), was added to a mixture of the aldehydes (1 mmol), malononitrile
(1.2 mmol), hydrazine hydrate (2 mmol), ethylacetoacetate (1 mmol), and 1 ml of water in a 5 ml
flask fitted with a reflux condenser. The resulting mixture was heated to reflux (an oil bath) for
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the appropriate time (see Table 2) with stirring (spin bar). After the completion of the reaction as
determined by TLC (hexaneꢀethyl acetate, 4:1), the acetone (2 ml) was added and the mixture
stirred for 2 min. The products and catalyst were isolated as described above and recrystallized
from 96% ethanol (20 ml) to afford pyrano[2,3ꢀc]pyrazoles 8a-h.
General Procedure for the Synthesis of Spiro [indoline-3,4'-pyrano[2,3-c]pyrazoles (12a-g)
The catalyst, DIPH (20 mol %), was added to a mixture of the isatins (1 mmol), malononitrile
(1.2 mmol), hydrazine hydrate (2 mmol), ethylacetoacetate (1 mmol), and 1 ml of water in a 5 ml
flask fitted with a reflux condenser. The resulting mixture was heated to reflux (an oil bath) for
the appropriate time (see Table 2) with stirring (spin bar). After the completion of the reaction as
determined by TLC (hexaneꢀethyl acetate, 4:1), the acetone (2 ml) was added and the mixture
stirred for 2 min. The products and catalyst were isolated as described above and recrystallized
from 96% ethanol (20 ml) to afford pyrano[2,3ꢀc]pyrazoles 12a-g.
Spectroscopic Data of Representative Compounds.
2-Amino-3-cyano-4-phenyl-7,7-dimethyl-5-oxo-4H-5,6,7,8-tetrahydrobenzo[b]pyran (4a),
1H NMR (300 MHz, CDCl3, ppm) δ 1.04 (s, 3H), 1.13 (s, 3H), 2.11ꢀ2.21 (m, 2H), 2.42 (s, 2H),
13
4.67 (s, 1H), 6.52 (brs, 2H, D2O exchangeable), 7.14ꢀ7.42 (m, 5H); C NMR (75 MHz, CDCl3,
ppm) δ 26.32, 27.65, 31.24, 35.09, 39.08, 49.98, 59.74, 113.09, 118.42, 125.86, 126.63, 127.54,
142.68, 158.54, 162.32, 194.24; IR (KBr disc, cmꢀ1): 3314, 3202, 2214, 1688, 1624, 1507, 1482,
1370.
2-Amino-3-cyano-4-(3-methoxyphenyl)-7,7-dimethyl-5-oxo-4H-5,6,7,8-
1
tetrahydrobenzo[b]pyran (4e). H NMR (300 MHz, DMSOꢀd6, ppm) δ 0.92 (s, 3H), 1.01 (s,
3H), 2.05 (d, 2H), 2.66 (d, 2H), 3.45 (s, 3H), 4.17 (s, 1H), 7.06 (brs, 2H, D2O exchangeable),
7.13ꢀ7.26 (m, 3H), 7.34 (s, 1H); 13C NMR (75 MHz, DMSOꢀd6, ppm) δ 27.30, 28.78, 32.33,
35.52, 35.58, 38.43, 50.44, 58.41, 112.74, 120.19, 128.91, 129.63, 131.80, 144.16, 158.98,
163.61, 197.00; IR (KBr disc, cmꢀ1): 3370, 3180, 2185, 1660, 1624, 1509, 1492, 1380.
1
6-Amino-3-methyl-5-cyano-4-(phenyl)-1-phenyl-1,4-dihydropyrano[2,3-c]pyrazole (6a), H
NMR (300 MHz, DMSOꢀd6): δ 1.77 (s, 3H), 5.16 (s, 1H), 7.28ꢀ7.48 (m, 10H), 7.78 (brs, 2H,
D2O exchangeable); 13C NMR (75 MHz, CDCl3, ppm) δ 25.02, 40.43, 50.45, 59.13, 113.24,
11

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DOI: 10.1039/C6RA15800E
118.67, 126.45, 126.06, 127.67, 128.03, 128.98, 129.14, 130.14, 140.05, 154.05, 162.34; IR
(KBr disc, cmꢀ1): 3425, 3332, 2200, 1620, 1590, 1484, 1386.
6-Amino-3-methyl-5-cyano-4-(4-methylphenyl)-1-phenyl-1,4-dihydropyrano[2,3-c]pyrazole
(6d). 1H NMR (300 MHz, DMSOꢀd6, ppm): δ 1.01 (s, 3H), 2.46 (s, 3H), 5.12 (s, 1H), 5.98 (brs,
2H, D2O exchangeable), 7.11ꢀ7.79 (m, 9H); 13C NMR (75 MHz, DMSOꢀd6, ppm) δ 25.18, 26.56,
41.04, 50.25, 60.63, 113.24, 118.04, 125.13, 126.45, 127.52, 128.18, 129.89, 130.68, 131.43,
141.67, 153.69, 160.11; IR (KBr disc, cmꢀ1): 3413, 3321, 2196, 1620, 1589, 1448, 1381.
6-Amino-3-methyl-5-cyano-4-(3-nitrophenyl)-1-phenyl-1,4-dihydropyrano[2,3-c]pyrazole
1
(6f). H NMR (300 MHz, DMSOꢀd6, ppm): δ 1.79 (s, 3H), 5.16 (s, 1H), 6.05 (brs, 2H, D2O
exchangeable), 7.19ꢀ7.68 (m, 8H), 8.01 (s, 1H); 13C NMR (75 MHz, DMSOꢀd6, ppm) δ 25.67,
41.12, 51.61, 61.05, 113.78, 119.14, 125.79, 126.54, 126.98, 127.32, 128.12, 128.67, 129.34,
130.78, 131.05, 140.67, 154.67, 159.89; IR (KBr disc, cmꢀ1): 3420, 3310, 2198, 1618, 1598,
1568, 1490, 1386.
6-Amino-3-methyl-4-(4-methoxyphenyl)-1,4-dihydro-pyrano[2,3-c]pyrazole-5-carbonitrile
(8b). 1H NMR (300 MHz, DMSOꢀd6, ppm): δ 1.79 (s, 3H), 3.45 (s, 3H), 4.56 (s, 1H), 6.88 (brs,
2H, D2O exchangeable), 7.10 (d, 2H), 7.19 (d, 2H), 12.01 (s, 1H, D2O exchangeable); 13C NMR
(75 MHz, DMSOꢀd6, ppm) δ) δ 10.22, 35.17, 36.01, 57.64, 97.82, 121.31, 126.04, 128.64,
136.19, 136.07, 141.64, 155.22, 161.35; IR (KBr disc, cmꢀ1): 3483, 3254, 2191, 1641, 1608,
1492, 1390.
6-Amino-3-methyl-4-(4-bromophenyl)-1,4-dihydro-pyrano[2,3-c]pyrazole-5-carbonitrile
1
(8c). H NMR (300 MHz, DMSOꢀd6, ppm): δ 1.75 (s, 3H), 4.81 (s, 1H), 6.48 (brs, 2H, D2O
exchangeable), 7.09 (d, 2H), 7.32 (d, 2H), 12.12 (s, 1H, D2O exchangeable); 13C NMR (75 MHz,
DMSOꢀd6, ppm) δ) δ 10.12, 33.62, 55.69, 96.23, 120.01, 128.45, 129.79, 132.54, 133.30, 135.21,
140.54, 155.89, 161.98; IR (KBr disc, cmꢀ1): 3444, 3238, 2195, 1637, 1600, 1491, 1394.
6'-Amino-3'-methyl-2-oxo-1'H-spiro[indoline-3,4'-pyrano[2,3-c]pyrazole]-5'-carbonitrile
(12a): 1H NMR (300 MHz, DMSOꢀd6, ppm): δ 1.54 (s, 3H), 6.91 (s, 1H), 7.02 (s, 2H), 7.17 (s,
2H, D2O exchangeable), 7.23 (s, 1H), 10.55 (s, 1H, D2O exchangeable), 12.25 (s, 1H, D2O
exchangeable); IR (KBr disc, cmꢀ1): 3420, 3390, 3330, 3130, 2680, 2180, 1710, 1640, 1580,
1520, 1420, 1320, 1210, 1160, 1050.
12

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DOI: 10.1039/C6RA15800E
Acknowledgements
The authors thank the Research Council of Hakim Sabzevari University for a partial support of
this work.
Supporting Information
Electronic Supplementary Information (ESI) available: [including the Figure S1ꢀS4 for
characterization of catalyst].
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DOI: 10.1039/C6RA15800E
Graphical Abstract
Green Synthesis of Tetrahydrobenzo[b]pyrans, Pyrano [2, 3-c] pyrazoles and Spiro [indoline-3,4'-pyrano[2,3-
c]pyrazoles Catalyzed by Nano-structured diphosphate in Water
Behrooz Maleki*1, Negar Nasiri1, Reza Tayebee1 Amir Khojastehnezhad*2 and Hossien Ali Akhlaghi1
R
HN
O
H3C
CN
N
N
H
O
NH2
N
a
O
n
o
P
N
a
O
O
O
a
C
C
a
a
N
P
o
O
n
a
H3C
OC2H5
N
NH2NH2
O
R
N
ArCHO
OC2H5
H
Ar
O
H3C
N
O
H3C
CN
Ar
O
CH3
CH2(CN)2
H2O/reflux
CN
O
N
N
NH2
N
N
CH3
O
N
H
NH2
NH2NH2
ArCHO
O
O
O
P
a
ArCHO
Ar
C
2
a
N
o
n
2
a
N
7
O
CN
NH2
O
► Preparation of nanostructured diphosphate Na2CaP2O7.
► Avoiding of any acid catalysts.
► The prepared catalyst is reusable and ecoꢀfriendly.
► The method is easy and contains simple experimental procedure.
17