Synthesis of pyranopyrazoles using magnetic Fe3O4 nanoparticles as efficient and reusable catalyst

Article abstract of DOI:10.1016/j.tet.2014.03.024

Magnetic Fe₃O₄ nanoparticles as a heterogeneous catalyst, were found to be efficient for the synthesis of a series of pyranopyrazoles by a four component reaction of a mixture of hydrazine hydrate, ethyl acetoacetate, aldehydes/keton

Full text of DOI:10.1016/j.tet.2014.03.024

Tetrahedron 70 (2014) 2971e2975
Contents lists available at ScienceDirect
Tetrahedron
journal homepage: www.elsevier.com/locate/tet
Synthesis of pyranopyrazoles using magnetic Fe3O4 nanoparticles
as efficient and reusable catalyst
*
Mahmoud. Abd El Aleem. Ali. Ali. El-Remaily
Department of Chemistry, Faculty of Science, Sohag University, Sohag 82524, Egypt
a r t i c l e i n f o
a b s t r a c t
Article history:
Magnetic Fe3O4 nanoparticles as a heterogeneous catalyst, were found to be efficient for the synthesis of
a series of pyranopyrazoles by a four component reaction of a mixture of hydrazine hydrate, ethyl
acetoacetate, aldehydes/ketones and malononitrile in water at room temperature. The products were
attributed to the nanosize of about 16 nm in which the catalyst could act as a nanoreactor. The present
protocol offers the advantages of clean reaction, short reaction time, high yield, easy purification and
economic availability of the catalyst.
Received 7 January 2014
Received in revised form 5 March 2014
Accepted 8 March 2014
Available online 13 March 2014
Keywords:
Ó 2014 Elsevier Ltd. All rights reserved.
One-pot reactions
Magnetic Fe3O4 nanoparticles
Pyranopyrazoles
1. Introduction
excellent catalysts for organic reactions.8,15e17 Moreover, the mag-
netic properties make the complete recovery of the catalyst by
Green chemistry techniques continue to grow in importance
and alternative processes aim to conserve resources and reduce
costs. The replacement of conventional solvents with water, which
is harmless to health and is available in large quantities, is an in-
teresting basic approach along this line.1e3 In recent years, the focus
on green chemistry using environmentally benign reagents and
conditions is one of the most fascinating developments in the
synthesis of widely used organic compounds. The use of water as
a promising solvent for organic reactions has received considerable
attention in the arena of organic synthesis owing to its green
credentials.4e6 In addition, organic synthesis in aqueous media
offers key advantages, such as rate enhancement and insolubility of
the final products, which facilitates their isolation by simple fil-
tration. Due to increasing environmental concerns, the de-
velopment of clean synthetic procedures has become crucial and
demanding research. In this sense, heterogeneous organic reactions
have many advantages, such as ease of handling separation, recy-
cling and environmentally safe disposal.7,8 However, magnetic
nanoparticles (MNPs) have received a great deal of attention be-
cause of their potential biomedical applications in fields, such as
drug delivery,9,10 magnetic resonance imaging,11 bio-molecular
sensors,12 bio-separation13 and magneto-thermal therapy.14 Addi-
tionally, recent studies showed that magnetic nanoparticles are
means of an external magnetic field. These advantages become
greater if such reactions can be conducted in aqueous media.
Multi-component reactions (MCRs) have emerged as a powerful
tool for the construction of novel and complex molecular structures
due to their advantages over conventional multi-step synthesis. The
major advantages of MCRs include lower costs, shorter reaction
times, high atom-economy and energy savings from the avoidance
of time consuming and expensive purification processes. It is
established that MCRs are generally much more environmentally
friendly and offer rapid access to large compound libraries with
diverse functionalities.18e20 Pyrano[2,3-c]pyrazole molecule is an
emerging class of heterocycles,21aee which is widely explored as an
important core of the emerging drugs with numerous medicinal
activities including potential inhibitor of human Chk1 kinase,22a
anti-inflammatory,22b anticancer, analgesic, molluscicidal23 and
antimicrobial.24 The synthesis of substituted pyrano[2,3-c]pyrazole
can be accomplished in several ways including the use of 3-methyl-
1-phenylpyrazolin-5-one and tetracyanoethylene in the presence
of triethylamine.25 Literature shows that methods employing
piperazine,26
b g-alumina as catalysts have
-cyclodextrin27 and
been developed for the synthesis of 6-amino-4-alkyl/aryl-3-methyl-
2,4-dihydropyrano[2,3-c]pyrazole-5-carbonitriles. Although the
methods reported are effective, they are limited due to the levels of
toxicity arising by the use of piperazine and piperidine.25 In addi-
tion, these methods require expensive catalysts for the reaction.27
The solvent required for the reaction,27,28 makes the work up pro-
cedure tedious and cumbersome. Reported here is a simple,
* Tel.: þ201008036348; fax:þ20 93601159; e-mail address: msremaily@yahoo.com.
0040-4020/$ e see front matter Ó 2014 Elsevier Ltd. All rights reserved.
http://dx.doi.org/10.1016/j.tet.2014.03.024

2972
Mahmoud.A.ElAleem.Ali.Ali. El-Remaily / Tetrahedron 70 (2014) 2971e2975
a simple, rapid and high yielding one pot four component reaction
protocol for the synthesis of pyranopyrazole derivatives in water
using magnetically recoverable Fe3O4 nanoparticles as heteroge-
neous catalyst at room temperature.
product in the shortest time was obtained using Fe3O4 nano-
particles, which may be due to greater diffusion of Fe3O4 nano-
particles in the reaction mixture. The recovered catalyst was found
to be similar to the fresh Fe3O4 nanoparticles as shown in (Table 2).
The results represented in (Table 3) reports that the reaction in
magnetically recoverable Fe3O4 nanoparticles produced the highest
yield. Interestingly, when the reaction was carried out in the
presence of 1 mol % Fe3O4-MNPs, it generated a 70% yield of
product. Subsequent efforts were focused on optimizing conditions
for formation of pyranopyrazoles by using different amounts of
Fe3O4-MNPs to determine their effects on the reaction. As in-
dicated, the best result was obtained with 6 mol % Fe3O4-MNPs. The
reaction yield with increasing amount of Fe3O4-MNPs was not
substantially increased.
2. Results and discussion
Designing organic reactions in aqueous media is another pro-
gressing area in green chemistry. Water is an abundant and envi-
ronmentally benign solvent. This protocol offers flexibility in tuning
the molecular complexity and diversity. The reactions proceeded to
completion almost instantaneously and pure product was obtained
simply by recrystallization from ethanol without using any chro-
matographic techniques. The reaction between hydrazine hydrate
1, ethyl acetoacetate 2, ketones/aldehyde 3 and malononitrile 4,
stirred at room temperature for 1e5 min resulted in pyranopyr-
azoles 5aep (Table 1) in magnetically recoverable Fe3O4 nano-
particles as heterogeneous catalyst, but formed ketones after
stirring for 5e15 min (Scheme 1).
Table 3
Amount of catalyst
Entry
Catalysts
(mol %)
Yield (%)
Entry
Catalysts
(mol %)
Yield (%)
1
2
3
4
1
2
3
4
70
78
82
90
5
6
7
8
5
6
7
8
95
97
97
97
Table 1
Synthesis of pyranopyrazoles 5aep
No
R
R1
Time
(min)
No
R
R1
Time
(min)
5a
5b
5c
5d
5e
5f
Ph
H
H
H
H
H
H
H
H
1
2
3
3
4
4
3
5
5i
5j
4-OHePh
2-OHePh
4-BrePh
4-FePh
4-(CH3)2NePh
Ph
H
H
H
H
4
5
3
3
5
5
12
15
4-MeOePh
2,5-MeOePh
3,4,5-MeOePh
4-NO2ePh
3-NO2ePh
4-ClePh
The stability of magnetically recoverable Fe3O4 nanoparticles
and its activity were investigated in recycling experiments for the
reaction between hydrazine hydrate, ethyl acetoacetate, benzal-
dehyde and malononitrile under the optimized conditions. After
each cycle, the catalyst was separated magnetically, washed with
ethanol, dried at 50 ꢀC under vacuum to remove residual solvents
5k
5l
5m
5n
5o
5p
H
CH3
CH3
Ph
5g
5h
4-BrePh
Ph
3-ClePh
Scheme 1. Four component synthesis of pyranopyrazoles 5aep.
Table 2
The effect of different types of Fe3O4
No
Fe3O4
Fe3O4 NPs
Recovered Fe3O4 NPs
No
Fe3O4
Fe3O4 NPs
Recovered Fe3O4 NPs
Time (h)
Yield (%)
Time (min)
Yield (%)
Time (min)
Yield (%)
Time (h)
Yield (%)
Time (min)
Yield (%)
Time (min)
Yield (%)
5a
5b
5c
5d
5e
5f
1
3
2
2
2
3
2
2
73
71
65
68
70
63
74
66
1
2
3
3
4
4
3
5
97
95
97
93
94
96
93
94
1
2
3
3
4
4
3
5
97
95
97
93
94
96
93
94
5i
5j
3
4
2
2
4
5
8
6
69
58
73
72
68
69
49
67
4
5
3
3
5
5
15
13
96
93
97
96
91
90
88
91
4
5
3
3
5
5
15
13
96
93
97
96
91
90
88
91
5k
5l
5m
5n
5o
5p
5g
5h
In the absence of a catalyst, the reaction mixture produced no
product in water at room temperature but compound 5a produced
product after 8 h.29a Also, the reaction mixture worked up by using
three types of catalysts were examined, i.e., Fe3O4, Fe3O4 nano-
particles and recovered Fe3O4 nanoparticles.29b The highest yield of
and used for the following cycle. Fe3O4 MNPs could be reused up to
fourteen times without any significant loss of the initial catalytic
activity. A very small loss in the amount of catalyst accompanied
with a non-effective reduction in the initial catalytic activity from
the 8th to 14th times has been recorded.

Mahmoud.A.ElAleem.Ali.Ali. El-Remaily / Tetrahedron 70 (2014) 2971e2975
2973
In order to investigate the effect of the solvent, the process
above was also repeated in conventional organic solvents. Water, as
the solvent, provided the best yields compared to common organic
solvents.29a The use of ultra pure (milli-Q) water yielded more
product than using the double distilled (DD) water. All the syn-
thesized compounds were characterized by IR, NMR and elemental
analysis. The reaction mechanism29a,b of the product is proposed to
involve the following tandem reactions: pyrazolone 6 formation by
reaction between 1 and 2, Knoevenagel condensation between 3
and 4 (7), Michael addition of 6e7, followed by cyclization and
tautomerization, (Scheme 2).
Typically, 20 mmol of FeCl3$6H2O and 10 mmol of FeCl2$4H2O were
dissolved in 75 ml of distilled water in a three-necked bottom
(250 ml) under Air atmosphere for 1 h. Thereafter, under rapid
mechanical stirring, 10 ml of NaOH (10 M) was added into the so-
lution within 30 min with vigorous mechanical stirring and ultra-
sound treatment under continuous Ar atmosphere bubbling. After
being rapidly stirred for 1 h, the resultant black dispersion was
heated to 85 ꢀC for 1 h. The black precipitate formed was isolated by
magnetic decantation, exhaustively washed with double-distilled
water until neutrality, and further washed twice with ethanol
and dried at 60 ꢀC in vacuum.
Scheme 2. The reaction mechanism of synthesized pyranopyrazoles 5aep.
In an aqueous medium, the four component reaction protocol
developed in the present study offers a fast and eco-friendly
method for the synthesis of pyranopyrazoles. The protocol also
offers flexibility in tuning the molecular complexity and diversity in
a single step.
3.3. General procedure for pyranopyrazoles (5aep)
To a stirred aqueous mixture of hydrazine hydrate, 96% 1
(1 mmol) and ethyl acetoacetate 2 (1 mmol), ketones/aldehyde 3
(1 mmol), malononitrile 4 (1 mmol) and Fe3O4 nanoparticles
(6 mol %) as catalyst were added successively at room temperature
under an open atmosphere with vigorous stirring. After completion
of the reaction, the reaction mixture was dissolved in ethanol and
then the catalyst was separated magnetically. The magnetic Fe3O4
nanoparticles were washed three to four times with ethanol and
then dried at 50 ꢀC for 5 h. The product obtained was pure by TLC
and NMR spectroscopy. However, the products were further puri-
fied by recrystallization from ethanol.
3. Experimental
3.1. General
All melting points are uncorrected and were recorded on Melt-
Temp II melting point apparatus. IR spectra were measured as KBr
pellets on a Shimadzu DR-8001 spectrometer. 1H NMR spectra were
recorded on a Varian Gemini at 300 or 400 MHz using TMS as an
internal reference and CDCl3, (CD3)2CO or DMSO-d6 as a solvent.
Mass spectra were performed on a Shimadzu GCMS-QP 1000 mass
spectrometer at 70 eV. The elemental analyses were carried out on
a PerkineElmer 240C Microanalyzer. All compounds were checked
for their purity on TLC plates.
3.3.1. 6-Amino-2,4-dihydro-3-methyl-4-phenylpyrano[2,3-c]pyrazole-
5-carbonitrile 5a.28a Yield 97%, mp 167e196 ꢀC; IR (KBr):
n
3372
2.08 (s, 3H); 4.44 (s,
1H); 6.94 (s br, 2H); 7.17e7.44 (m, 5H); 13C NMR:
11.4; 24.8; 70.4;
(groups of NH, NH2), 2190.74 (CN) cmꢁ1;1H NMR:
d
d
112.2; 126.3; 127.2; 129.3; 130.9; 140.2; 143.9; 152.3; 160.0; MS, m/z
calcd for C14H12N4O[MþH]þ: 253.1089; found, 253.1092 (Rel Int.100%).
3.2. Preparation of the magnetic Fe3O4 nanoparticles
(MNPs)
3.3.2. 6-Amino-4-(4-methoxyphenyl)-3-methyl-2,4-dihydropyrano
[2,3-c]pyrazole-5-carbonitrile (5b).28a Yield 95%, mp 170e172 ꢀC; IR
Fe3O4-MNPs were prepared using simple chemical coprecipi-
(KBr):
2.07 (s, 3H); 3.70 (s, 3H); 4.61 (s, 1H); 7.16 (d, J¼8.7 Hz, 2H); 7.95 (d,
n ;
3483.78 (NH2), 3255.25 (NH), 2191.7 (CN) cmꢁ1 1H NMR:
tation described in the literature30 with little modification.
d

2974
Mahmoud.A.ElAleem.Ali.Ali. El-Remaily / Tetrahedron 70 (2014) 2971e2975
J¼8.4 Hz, 2H); 8.61 (s br, 2H); 13C NMR:
d
11.5; 24.5; 55.4; 70.4; 114.7;
(KBr): cmꢁ1, 1580, 1640, 2221, 3054, 3355, 3404; 1H NMR: 2.05 (s,
115.2; 127.8; 129.2; 140.5; 143.8; 153.3; 159.9; 160.0; MS, m/z calcd
3H); 4.73 (s,1H); 5.60 (br, 2H); 6.94e7.18 (m, 2H); 7.72e7.95 (m, 2H);
13C NMR: 11.4; 19.0; 71.4; 112.3; 119.1; 119.6; 122.3; 124.5; 126.7;
129.4; 130.2; 142.0; 154.8; 155.6; 159.8; MS (ESI): m/z calcd for
for C15H14N4O2 [MþH]þ: 283.1195; found, 283.1196 (Rel Int. 100%).
3.3.3. 6-Amino-4-(2,5-dimethoxyphenyl)-2,4-dihydropyrano-[2,3-c]
C
14H12N4O2 [MþH]þ: 269.1038; found, 269.1058.
pyrazole-5-carbonitrile (5c).28b Yield 97%; mp 222e224 ꢀC; IR (KBr):
n
3382, 3240, 2168, 1608, 1450 cmꢁ1; 1H NMR (400 MHz, (CD3)2CO):
3.3.11. 6-Amino-4-(4-bromophenyl)-2,4-dihydro-3-methylpyrano
[2,3-c]pyrazole-5-carbonitrile (5k).28a Yield 97%, mp 180e183 ꢀC; IR
(KBr): cmꢁ1, 1644, 2220, 3054, 3287, 3391; 1H NMR: 1.91 (s, 3H);
4.55 (s, 1H); 6.45 (br, 2H); 7.06 (d, J¼8.4 Hz, 2H); 7.43 (d, J¼8.1 Hz,
2H), 13C NMR: 11.15; 24.16; 70.76; 112.12; 119.12; 128.37; 130.19;
134.99; 141.98; 143.92; 153.72; 159.11; MS (ESI): m/z calcd for
dH 1.80 (s, 3H, CH3), 3.73 (s, 3H, OCH3), 3.74 (s, 3H, OCH3), 5.00 (s,1H,
4H), 5.59 (s, 2H, NH2), 6.51e6.52 (m, 1H, AreH), 6.60e6.69 (m, 1H,
AreH), 6.74 (s,1H, AreH) (ppm); 13C NMR (100 MHz, CDCl3þDMSO-
d6): dC 9.9, 28.6, 55.0, 55.8, 58.5, 97.3, 111.5, 113.9, 114.7, 120.5, 132.5,
135.6, 150.5, 153.3, 155.0, 160.8 (ppm); MS (ESþ) calcd for
C
16H16N4O3 312.1; found m/z 313.0 (MþH)þ, 335.0 (MþNa)þ.
C
14H11BrN4O [MþH]þ: 331.0194; found, 331.0198.
3.3.4. 6-Amino-4-(3,4,5-trimethoxyphenyl)-2,4-dihydropyrano-[2,3-
3.3.12. 6-Amino-4-(4-fluorophenyl)-2,4-dihydro-3-methylpyrano
[2,3-c]pyrazole-5-carbonitrile (5l).28a Yield 96%, mp 170e171 ꢀC; IR
(KBr): cmꢁ1, 1640, 2222, 3055, 3280, 3388; 1H NMR: 1.97 (s, 3H);
4.58 (s, 1H); 6.47 (br, 2H); 7.01 (d, J¼8.1 Hz, 2H); 7.18 (d, J¼8.1 Hz,
2H); 13C NMR: 12.0; 24.9; 70.9; 112.2; 126.4; 127.6; 130.5; 134.2;
141.4; 142.5; 154.5; 159.1; MS (ESI): m/z calcd for C14H11FN4O
[MþH]þ: 272. 0995; found, 272.0998.
c]pyrazole-5-carbonitrile (5d).28b Yield 93%, mp 230e232 ꢀC; IR
(KBr):
n ;
3381, 3246, 2170, 1610, 1455 cmꢁ1 1H NMR (DMSO-
d6þCDCl3, 400 MHz): dH 1.85 (s, 3H, CH3), 3.69 (s, 3H, OCH3), 3.73 (s,
3H, OCH3), 3.80 (s, 3H, OCH3), 4.48 (s, 1H, 4H), 6.03 (s, 2H, NH2), 6.37
(s, 2H, AreH) ppm. 13C NMR (DMSO-d6þCDCl3, 100 MHz): dC 9.6,
36.8, 54.5, 60.3, 96.9, 104.1, 105.4, 106.6, 120.5, 135.8, 139.2, 152.5,
154.8, 160.6 ppm. I MS (EIþ): calcd for C17H18N4O4 342.13; found
342.90 (MþH)þ, 365.10 (MþNa)þ.
3.3.13. 6-Amino-4-(4-(dimethylamino)phenyl)-2,4-dihydro-3-
methylpyrano[2,3-c]pyrazole-5-carbonitrile
(5m).28a Yield
91%,
3.3.5. 6-Amino-3-methyl-4-(4-nitrophenyl)-2,4-dihydropyrano[2,3-c]
mp 162e165 ꢀC; IR (KBr): cmꢁ1, 1641, 2199, 3050, 3284, 3408; 1H
NMR: 2.05 (s, 3H); 2.45 (s, 6H); 4.55 (s, 1H); 6.49 (s br, 2H); 6.72 (d,
J¼8.1 Hz, 2H); 7.71 (d, J¼8.1 Hz, 2H); 13C NMR: 11.5; 25.6; 40.8; 71.6;
111.1; 114.8; 126.9; 130.0; 137.5; 141.0; 153.0; 157.1; 159.4; MS (ESI):
m/z calcd for C16H17N5O [MþH]þ: 296.1511; found, 296.1521.
pyrazole-5-carbonitrile (5e).28a Yield 94%, mp 192e194 ꢀC; IR (KBr):
n
3383, 3272, 2198, 1620, 1451 cmꢁ1; 1H NMR: 2.04 (s, 3H); 4.73 (s,
1H); 6.22 (s br, 2H); 7.48 (d, J¼8.1 Hz, 2H); 8.17 (d, J¼8.1 Hz, 2H); 13
C
NMR: 11.4; 23.3; 70.7; 112.8; 127.9; 126.0; 130.0; 135.5; 141.9; 150.4;
154.2; 160.4 MS (ESI): m/z calcd for C14H11N5O3 [MþH]þ: 298.0940;
found, 298.0989.
3.3.14. 2-[1-(3-Methyl-5-oxo-4,5-dihydro-1H-pyrazol-4-yl)-1-phenyl-
ethyl]-malononitrile (5n).28a Yield 90%, mp 200e202 ꢀC; IR (KBr):
3.3.6. 6-Amino-3-methyl-4-(3-nitrophenyl)-2,4,dihydropyrano-[2,3-
n
3380, 3320, 3190 (NH and NH2), 2199 (CN) cmꢁ1; 1H NMR:
d
1.72 (s,
3H); 2.12 (s, 3H); 6.33 (s br, 2H); 7.18e7.23 (m, 1H); 7.28e7.35 (m, 2H);
7.37e7.48 (m, 2H); 13C NMR:
13.4; 27.8; 36.9; 75.4; 115.8; 122.6;
c]pyrazole-5-carbonitrile (5f).28a Yield 96%, mp 214e216 ꢀC; IR (KBr):
n
3385, 3278, 2189, 1622, 1456 cmꢁ1; 1H NMR:
d
2.03 (s, 3H); 4.75 (s,
1H); 6.38 (s br, 2H); 7.54e7.65 (m, 2H); 8.02e8.12 (m, 1H); 8.12 (s,
1H); 13C NMR:
11.9; 26.3; 71.4; 112.4; 121.3; 127.6; 129.6; 133.1;
d
125.2; 129.6; 130.8; 140.4; 146.5; 152.3; 155.8; MS, m/z calcd for
d
C
15H14N4O [MþH]þ: 267.1245; found, 267.1248.
135.2; 141.6; 147.2; 151.4; 154.0; 160.1; MS (ESI): m/z calcd for
C
14H11N5O3 [MþH]þ: 298.0940; found, 298.0989.
3.3.15. 6-Amino-4-(4-bromophenyl)-2,4-dihydro-3,4-dimethylpyrano
[2,3-c]pyrazole-5-carbonitrile (5o).28a Yield 88%, mp 180e181 ꢀC; IR
3.3.7. 6-Amino-4-(4-chlorophenyl)-2,4-dihydro-3-methylpyrano[2,3-
(KBr): n d 1.78
3472.2 (NH), 3240 (NH2), 2185.9 (CN) cmꢁ1; 1H NMR:
c]pyrazole-5-carbonitrile (5g).28a Yield 93%, mp 174e175 ꢀC; IR
(s, 3H); 2.15 (s, 3H); 6.58 (s br, 2H); 7.36 (d, J¼8.4 Hz, 2H); 7.64 (d,
1
(KBr):
n
3380, 3281, 2193, 1622, 1454 cmꢁ1; H NMR: 11.82 (s, 3H);
J¼8.7 Hz, 2H); 13C NMR:
d 12.2; 26.7; 37.0; 75.4; 116.8; 120.2; 128.5;
130.8; 133.1; 140.5; 145.6; 152.5; 155.8; m/z calcd for C15H13BrN4O
4.58 (s, 1H); 6.69 (s br, 2H); 7.18 (d, J¼8.1 Hz, 2H); 7.31 (d, J¼8.1 Hz,
2H); 13C NMR: 111.7; 24.4; 70.4; 112.1; 126.7; 127.6; 130.1; 134.2;
141.4; 142.1; 153.6; 159.3; MS (ESI): m/z calcd for C14H11ClN4O
[MþH]þ: 287.0699; found, 287.0699.
[MþH]þ: 345.0351; found, 345.0355 (Rel Int. 100%).
3.3.16. 6-Amino-2,4-dihydro-3-methyl-4,4-diphenylpyrano[2,3-c]pyr-
azole-5-carbonitrile (5p).28a Yield 91%, mp 210e211 ꢀC; IR (KBr):
n
3.3.8. 6-Amino-4-(3-chlorophenyl)-2,4-dihydro-3-methylpyrano[2,3-
3402 (NH), 3240 (NH2), 2222 (CN) cmꢁ1; 1H NMR: 2.25 (s, 3H); 6.33
(br, 2H); 6.82 (m, 2H); 7.20 (m, 4H); 7.61 (m, 4H); 13C NMR: 12.2;
49.4; 69.2; 115.7; 123.4; 127.3; 128.6; 131.2; 142.0; 147.4; 151.2;
159.9; MS, m/z (%), calcd for C20H16N4O [MþH]þ: 329.1402; found,
329.1403.
c]pyrazole-5-carbonitrile (5h).28a Yield 94%, mp 158e160 ꢀC; IR
(KBr):
n ;
3387, 3289, 2199, 1622, 1454 cmꢁ1 1H NMR: 2.05 (s, 3H);
4.46 (s, 1H); 6.56 (br, 2H); 7.04e7.14 (m, 2H); 8.52 (s, 1H); 8.59e8.61
(m, 1H): 13C NMR: 11.5; 24.4; 70.4; 101.4; 126.9; 127.9; 129.7; 130.6;
133.0; 134.2; 142.2; 148.8; 153.4; 159.1; MS (ESI): m/z calcd for
C
14H11ClN4O [MþH]þ: 287.0699; found, 287.0699.
Acknowledgements
3.3.9. 6-Amino-4-(4-hydroxyphenyl)-3-methyl-2,4-dihydropyrano
[2,3-c]pyrazole-5-carbonitrile (5i).28a Yield 96%, mp 222e224 ꢀC; IR
(KBr): cmꢁ1, 878, 1271, 1368, 1583, 1645, 2222, 3056, 3350, 3410; 1H
NMR: 2.00 (s, 3H); 4.46 (s, 1H); 6.44 (s br, 2H); 7.01 (d, J¼8.4 Hz, 2H);
6.07 (d, J¼8.1 Hz, 2H); 13C NMR: 12.0; 25.0; 71.0; 113.6; 119.5; 127.0;
130.2; 141.5; 143.8; 153.4; 154.5; 159.1; MS m/z (%): m/z calcd for
The author is deeply grateful to both of University of Granada,
Spain and Sohag University, Egypt for supporting and facilitating
this study.
References and notes
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14H12N4O2 [MþH]þ: 269.1038; found, 269.1052.
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[2,3-c]pyrazole-5-carbonitrile (5j).28a Yield 93%, mp 208e210 ꢀC; IR

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