Facile synthesis of pyrano[2,3-c]pyrazol-6-one derivatives under microwave irradiation in solvent-free conditions

Article abstract of DOI:10.1080/00397910500328886

A series of substituted 1H,6H-pyrano[2,3-c]pyrazol-6-one derivatives were synthesized from one-pot cyclocondensation of hydrazine derivatives or 1H-pyrazol-5-one derivatives with various β-keto esters under solvent-free conditions using microwave irradiation in short time with good to excellent yields. Copyright Taylor & Francis LLC.

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Facile Synthesis of
Pyrano[2,3‐c]pyrazol‐6‐one Derivatives
Under Microwave Irradiation in Solvent‐Free
Conditions
a
a
Mohammad M. Mojtahedi , Mohammad R. Jalali & Mohammad
a
Bolourtchian
a
Chemistry and Chemical Engineering Research Center of Iran, Tehran, Iran
Published online: 21 Aug 2006.
To cite this article: Mohammad M. Mojtahedi , Mohammad R. Jalali & Mohammad Bolourtchian (2006) Facile
Synthesis of Pyrano[2,3‐c]pyrazol‐6‐one Derivatives Under Microwave Irradiation in Solvent‐Free Conditions,
Synthetic Communications: An International Journal for Rapid Communication of Synthetic Organic Chemistry,
36:1, 51-57, DOI: 10.1080/00397910500328886
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Synthetic Communications , 36: 51–57, 2006
Copyright # Taylor & Francis LLC
ISSN 0039-7911 print/1532-2432 online
DOI: 10.1080/00397910500328886
Facile Synthesis of Pyrano[2,3-c]pyrazol-
6-one Derivatives Under Microwave
Irradiation in Solvent-Free Conditions
Mohammad M. Mojtahedi, Mohammad R. Jalali,
and Mohammad Bolourtchian
Chemistry and Chemical Engineering Research Center of Iran,
Tehran, Iran
Abstract: A series of substituted 1H,6H-pyrano[2,3-c]pyrazol-6-one derivatives were
synthesized from one-pot cyclocondensation of hydrazine derivatives or 1H-pyrazol-
5-one derivatives with various b-keto esters under solvent-free conditions using
microwave irradiation in short time with good to excellent yields.
Keywords: Cyclocondensation, microwave irradiation, pyrano[2,3-c]pyrazol-6-one,
solvent-free conditions
Pyranopyrazolone and their derivatives are a group of compounds possessing
a wide spectrum of biological activity. They exhibit analgesic, antiinflamma-
tory activities and act as vasodilators and hypotensive and hypoglycemic
[
1–3]
agents.
most of these methods are based on the reaction of hydrazine derivatives or
There are few general routes to obtain pyranopyrazolone, and
[
H-pyrazol-5-one with malononitrile, dimethyl acetylenedicarboxylate,
4]
[3]
1
[5–9]
or a b-keto ester in an oil bath at high temperature (130–1708C).
Recently, Stanovnik et al. reported the preparation of this heterocyclic ring
from the reaction of 1H-pyrazol-5-one with substituted 3-dimethylaminopro-
[10–12]
penoate in a solvent under reflux conditions for a long reaction time.
Received in the UK December 15, 2004
Address correspondence to Mohammad M. Mojtahedi, Chemistry and Chemical
Engineering Research Center of Iran, P.O. Box 14335-186, Tehran, Iran. E-mail:
mojtahedi@ccerci.ac.ir
51

52
M. M. Mojtahedi, M. R. Jalali, and M. Bolourtchian
There have been growing interest in applying microwave irradiation to
[
13,14]
enhancement of organic synthesis in solvent-free systems.
usually observed are decreasing reaction time and in some cases cleaner
The effects
[
15]
reactions with easier workup.
In view of these findings and as a further stage of our work on the
[
16]
synthesis of 1H-pyrazol-5-one,
here we describe the synthesis of 1H,6H-
pyrano[2,3-c]pyrazol-6-one derivatives from condensation of hydrazine
derivatives or 1H-pyrazol-5-one derivatives with various b-keto esters
under solvent-free conditions using microwave irradiation in short time with
good to excellent yields. When 1H-pyrazol-5-one 1 was treated with 1.0
equivalent of b-keto ester 2 under microwave irradiation, without any
solvent, the coupling reaction was completed after 3–5 min with the elimin-
ation of water and ethanol molecules and led to 1H,6H-pyrano[2,3-
c]pyrazol-6-one 3(a–f) (Scheme 1).
In another method, derivatives of 1H,6H-pyrano[2,3-c]pyrazol-6-one 5
were prepared from the reaction of a mixture of hydrazine derivative 4 with
2.0 equivalents of b-keto ester 2 by microwave irradiation after 3–4:30 min
(
Scheme 2). Water was added to the reaction mixture, the solid product was
removed by filtration, and the product was recrystallized from an ethanol–
water mixture.
In contrast, condensation of phenyl hydrazine and 2 equivalents of ethyl
acetoacetate by the use of classical heating in an oil bath (1408C) gave a
low yield (62%) of 3,4-dimethyl-1-phenyl-1H,6H-pyrano[2,3-c]pyrazol-
6-one after 4 h. The reaction of phenyl hydrazine with 2 equivalents of
ethyl benzoylacetate or ethy b-oxo-2-furanpropionate, however, did not
give the desired products. To examine relatively large-scale synthesis, we
irradiated 100 mmol of phenyl hydrazine and ethyl acetoacetate in a
conventional microwave oven for 6 min; 5a was obtained in 80% isolated
yield.
In conclusion, we report a rapid and efficient method for the preparation
of substituted pyrano[2,3-c]pyrazol-6-one from condensation of hydrazine
derivatives or 1H-pyrazol-5-one derivatives with various b-keto esters
under microwave irradiation in a short time with high yields without any
solvent.
Scheme 1.

Pyrano[2,3-c]pyrazol-6-one Derivatives
53
Scheme 2.
EXPERIMENTAL
A conventional microwave oven (900 W) was used for the irradiation of the
reaction mixture. All reported yields are isolated yields. Melting points
were determined with a Buchi melting-point apparatus without any correction.
IR spectra were recorded on a FT-IR Bruker model Vector 22 spectro-
1
photometer in KBr pellets; H NMR spectra were recorded on FT-NMR
Bruker Ac 80 (80 MHz) in DMSO-d and CDCl with TMS as internal
6
3
reference. Mass spectra were recorded on Fisons 8000 Trio instrument at an
ionization potential of 70 eV.
General Procedure for the Preparation of Pyranopyrazolone
Derivatives
Method A
A mixture of phenyl hydrazine (2 mmol, 0.22 g) and ethyl butyrylacetate
(4 mmol, 0.63 g) were placed in a Pyrex test tube, which was placed into a
microwave oven (900 W). The mixture was irradiated for the length of time
indicated in Table 1 by the pulsed irradiation technique (1 min with 29-s
intervals). After completion of the reaction, which was monitored by TLC
using hexane/ethyl acetate (8 : 2), the reaction mixture was poured into ice
water (10 mL). The precipitate was collected by filtration and recrystallized
using EtOH/H O, affording the pure product.
2
Method B
A mixture of 1-phenyl-3-propyl-5-pyrazolone (2 mmol, 0.22 g) and ethyl
butyrylacetate (2 mmol, 0.32 g) were placed in a Pyrex test tube. The
mixture was exposed to microwave irradiatied for the time given in
Table 2, using the pulsed irradiation technique (1 min with 29-s intervals).
After cooling, the reaction mixture was poured into ice water (10 mL). The
precipitate was collected by filtration and recrystallized using EtOH/H O,
2
affording the pure product.

54
M. M. Mojtahedi, M. R. Jalali, and M. Bolourtchian
Table 1. Preparation of substituted pyrano[2,3-c]pyrazol-6-one under microwave
irradiation (method A)
Time
(min)
Yield
(%)
Starting materials
Products
3
a
4
5
3
4
3
95
88
90
90
86
3
b
3
c
3
d
3
e
3
f
3:40
92
The structure of the products was approved by the comparison of their IR,
13
H NMR, C NMR, and MS spectra and their melting points with those
1
reported in the literature.
a: Yellow solid, mp 808C; H NMR (DMSO-d ): d 1.10 (t, 3H,
1
3
6
J ¼ 7.2 Hz), 1.70–2.00 (m, 2H), 2.60 (d, 3H, J ¼ 1.2 Hz), 2.95 (t, 2H,
1
3
J ¼ 8.0 Hz), 6.05 (d, 1H, J ¼ 1.2 Hz), 7.50–8.00 (m, 5H) ppm; C NMR
(
DMSO-d ): d 18.1, 24.3, 27.2, 35.5, 106.2, 110.1, 125.6, 131.2, 133.5,
6
1
34.4, 142.2, 153.1, 159.8, 165.5 ppm; IR (KBr): y 1747, 1546, 1455, 829,
þ
2
1
7
65 cm ; MS (70 eV): m/z ¼ 268 (M ), 240, 77.
[6]
1
3
b: Yellow solid, mp 2108C (2118C lit. ); H NMR (DMSO-d ): d 2.25
6
13
(
(
d, 3H, 1.2 Hz), 6.12 (q, 1H, 1.2 Hz), 7.50–8.10 (m, 10H) ppm; C NMR
DMSO-d ): d 25.4, 111.6, 118.5, 120.2, 127.2, 127.6, 129.4, 133.0, 133.3,
6

Pyrano[2,3-c]pyrazol-6-one Derivatives
55
Table 2. Preparation of substituted pyrano[2,3-c]pyrazol-6-one under microwave
irradiation (method B)
Time
(min)
Yield
(%)
Starting materials
Products
PhNHNH
PhNHNH
2
2
5a
4
:30
4
83
86
5
b
NH NH
2
2
5c
3
88
1
33.4, 133.7, 134.5, 150.2, 152.7, 161.1 ppm; IR (KBr): y 1734, 1595, 1534,
2
1
þ
1
179, 760, 690 cm ; MS (70 eV): m/z ¼ 302 (M ), 139, 115, 77.
13
[
6]
1
3
s, 3H), 5.90 (s, 1H), 7.30–7.95 (m, 10H) ppm; C NMR (CDCl ): d 15.2,
c: Yellow solid, mp 1358C (1408C lit. ); H NMR (CDCl ): d 2.08
3
(
3
1
1
7
05.3, 110.9, 121.5, 126.7, 126.8, 127.0, 127.5, 128.4, 128.5, 129.1, 129.6,
48.1, 155.4, 162.1 ppm; IR (KBr): y 1734, 1534, 1164, 1074, 843, 775,
2
1
þ
07 cm ; MS (70 eV): m/z ¼ 302 (M ), 115, 77.
1
3
.10–1.50 (m, 2H), 2.30–2.50 (t, 2H, 7.2 Hz), 5.87 (s, 1H), 7.30–7.95
d: Yellow solid, mp 1108C; H NMR (CDCl ): d 0.62 (t, 3H, 7.2 Hz),
3
1
1
m, 10H) ppm; C NMR (CDCl ): d 14.1, 21.3, 31.2, 106.7, 118.7, 120.6,
3
(
3
1
1
26.6, 126.8, 127.0, 127.1, 128.4, 128.5, 129.1, 129.6, 151.6, 155.4,
2
1
60.8 ppm; IR (KBr): y 1734, 1595, 1572, 1164, 1074, 775 cm ; MS
þ
(
70 eV): m/z ¼ 330 (M ), 301, 77.
1
3
s, 1H), 6.51–6.65 (m, 1H), 7.05–7.92 (m, 7H) ppm; C NMR (CDCl3):
e: Brown solid, mp 1648C; H NMR (CDCl ): d 2.53 (s, 3H), 6.14
3
13
(
d 16.4, 100.2, 112.4, 114.1, 120.8, 126.1, 126.8, 127.1, 127.5, 129.0, 145.9,
2
55.3, 158.1, 160.2 ppm; IR (KBr): y 1739, 1547, 1488, 791, 751 cm ; MS
1
1
þ
(70 eV): m/z ¼ 292 (M ), 187, 159, 77.
1
3
f: Red solid, mp 808C; H NMR (CDCl ): d 1.00 (t, 3H, J ¼ 7.2 Hz),
3
1
7
1
.50–1.90 (m, 2H), 2.49 (s, 3H), 2.40–2.80 (m, 2H), 5.76 (t, 1H, J ¼ 1 Hz),
1
.20–7.92 (m, 5H) ppm; C NMR (CDCl ): d 13.5, 14.6, 21.5, 34.6, 103.9,
3
3
20.4, 122.1, 126.6, 129.1, 129.5, 145.1, 152.6, 154.8, 160.0 ppm; IR (KBr):
2
1
þ
y 1751, 1548, 823, 763 cm ; MS (70 eV): m/z ¼ 268 (M ), 225, 77.
[
6]
1
5
a: Yellow solid, mp 1438C (1458C lit. ); H NMR (CDCl ): d 2.32
3
(
d, 3H, J ¼ 1.2 Hz), 2.40 (s, 3H), 5.75 (q, 1H, 1.2 Hz), 7.25–7.90 (m, 5H)
1
ppm; C NMR (CDCl ): d 14.2, 20.5, 105.3, 118.5, 120.2, 126.1, 128.1,
3
3
1
29.0, 145.3, 152.1, 154.5, 160.7 ppm; IR (KBr): y 1760, 1614, 1550, 1513,
2
1
þ
1
430, 1381, 1100, 830, 748 cm ; MS (70 eV): m/z ¼ 240 (M ), 77.
1
5
b: Yellow solid, mp 958C; H NMR (CDCl ): d 1.10 (t, 6H, J ¼ 7.2 Hz),
3
1
.50–1.90 (m, 4H), 2.55–2.90 (m, 4H), 5.80 (t, 1H, J ¼ 1 Hz), 7.25–7.90

56
M. M. Mojtahedi, M. R. Jalali, and M. Bolourtchian
1
m, 5H) ppm; C NMR (CDCl ): d 13.5, 14.4, 21.2, 21.5, 31.8, 34.6, 103.6,
3
(
3
1
1
2
10.8, 121.2, 122.0, 126.1, 129.7, 145.2, 152.1, 154.5, 160.2 ppm; IR (KBr): y
2
1
þ
742, 1605, 1542, 1457, 822, 681 cm ; MS (70 eV): m/z ¼ 296 (M ), 253,
40, 225, 91, 77.
[6]
1
5c: Yellow solid, mp 2398C (2458C lit. ); H NMR (DMSO): d 2.42
(
d, 3H, J ¼ 1.2 Hz), 2.53 (s, 3H), 5.90 (d, 1H), 12.50–13.50 (br, 1H) ppm;
1
3
C NMR (DMSO): d 14.4, 20.8, 106.2, 118.4, 129.7, 152.9, 154.5,
61.2 ppm; IR (KBr): y 3250, 1720, 1610, 1520, 1200, 1120, 1100, 930,
1
7
2
1
þ
60 cm ; MS (70 eV): m/z ¼ 164 (M ), 136, 107, 77.
ACKNOWLEDGMENT
We thank the Iranian Ministry of Science, Research, and Technology for
partial financial support of this work.
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