Simple and efficient protocol for the synthesis of novel dihydro-1H-pyrano[2,3-c]pyrazol-6-ones via a one-pot four-component reaction

Article abstract of DOI:10.1016/j.tetlet.2012.10.025

Ba(OH)₂ catalyzed simple and efficient one-pot four-component reaction of Meldrums acid, ethyl acetoacetate, hydrazine hydrate, and aromatic aldehydes to give 3-methyl-4-aryl-4,5-dihydro-1H-pyrano[2,3-c]pyrazol-6-ones in refluxing water is reported. The yields are high and the reactions go to completion in 1-2 h.

Full text of DOI:10.1016/j.tetlet.2012.10.025

Tetrahedron Letters 53 (2012) 6834–6837
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Tetrahedron Letters
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Simple and efficient protocol for the synthesis of novel
dihydro-1H-pyrano[2,3-c]pyrazol-6-ones via a one-pot
four-component reaction
⇑
Sadeq Hamood Saleh Azzam, M. A. Pasha
Department of Studies in Chemistry, Central College Campus, Palace Road, Bangalore University, Bengaluru 560001, India
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 5 July 2012
Revised 3 October 2012
Accepted 5 October 2012
Available online 13 October 2012
Ba(OH)2 catalyzed simple and efficient one-pot four-component reaction of Meldrums acid, ethyl aceto-
acetate, hydrazine hydrate, and aromatic aldehydes to give 3-methyl-4-aryl-4,5-dihydro-1H-pyrano[2,3-
c]pyrazol-6-ones in refluxing water is reported. The yields are high and the reactions go to completion in
1–2 h.
Ó 2012 Elsevier Ltd. All rights reserved.
Keywords:
Pyranopyrazole-6-ones
Aromatic aldehydes
Meldrums acid
Ethyl acetoacetate
Hydrazine hydrate
Ba(OH)2
Water
Multicomponent reaction (MCR) is a process in which three or
more accessible components are combined together in one-pot to
produce a final product which shows the features of all the input
reactants and therefore, offers the greatest possibilities for molec-
ular diversity in one step with minimum synthetic time and effort.1
As MCRs are one-pot reactions, they are easier to carry out than the
multistep syntheses. This strategy is an important development in
the drug discovery in the context of rapid identification and opti-
mization of biologically active lead compounds.2 In addition, MCRs
are environmentally friendly, and often proceed with excellent
chemoselectivities.3 There are three wings (techniques) of green
chemistry which, if combined, would result in an excellent green
chemistry protocol.4 These techniques are: the efficient use of sol-
vent-free reactions,5 reusability of heterogeneous catalysts,6 and
use of multicomponent reactions.6a
One of the most challenging aspects in the medicinal chemistry
is the design and synthesis of biologically active compounds,7 and
dihydro-1H-pyrano[2,3-c]pyrazoles represent an interesting tem-
plate for medicinal chemistry and play an essential role as biolog-
ically active molecules.8 Many of the pyrano[2,3-c]pyrazoles are
known for their antimicrobial,9 insecticidal,10 anti-inflammatory,11
anticancer,12 and molluscicidal activities.13
are also used as pharmaceutical ingredients and biodegradable
agrochemicals.15 The first reported pyranopyrazole was synthe-
sized by the reaction between 3-methyl-1-phenyl-pyrazolin-5-
one and tetracyanoethylene.15
Another attractive area in green chemistry is designing organic
reactions in aqueous media.16 Water offers several benefits such as
control over exothermic reactions, salting out, and salting in, as
well as variation of pH.17 We have earlier reported the synthesis
of
6-amino-3-methyl-4aryl-1,4-dihydropyrano[2,3-c]pyrazol-5-
carbonitriles using glycine,18 iodine,19 and imidazole20 as catalysts
in water. In continuation of our efforts to develop methods for the
synthesis of novel heterocyclic compounds using readily available,
inexpensive, and environmentally friendly catalysts,21–27 herein,
we report a rapid and efficient one-pot four-component synthesis
of some novel 3-methyl-4-aryl-4,5-dihydro-1H-pyrano[2,3-c]pyra-
zol-6-ones28 by the reaction of aromatic aldehydes, Meldrums acid,
hydrazine hydrate, and ethyl acetoacetate in the presence of
readily available, inexpensive, mild, green, and common laboratory
chemical Ba(OH)2 as a basic catalyst in water (Scheme 1).
In order to optimize the reaction conditions, we carried out the
reaction between 3,4,5-trimethoxybenzaldehyde, ethyl acetoace-
tate, Meldrums acid, and hydrazine hydrate in the presence of
10 mol % of Ba(OH)2 at reflux in different solvents such as EtOH,
MeOH, H2O, and CH3CN; among all these solvents, H2O was found
to be the best in terms of the yield of the product and time of
completion compared to common organic solvents. The results of
this study are presented in Table 1.
During the last few years, synthesis of dihydropyrano
[2,3-c]pyrazoles has received great interest.14 Pyranopyrazoles
⇑
Corresponding author. Tel./fax: +91 80 22961337.
E-mail address: mafpasha@gmail.com (M.A. Pasha).
0040-4039/$ - see front matter Ó 2012 Elsevier Ltd. All rights reserved.
http://dx.doi.org/10.1016/j.tetlet.2012.10.025

S. H. S. Azzam, M. A. Pasha / Tetrahedron Letters 53 (2012) 6834–6837
6835
Table 3
Ar
Ar
Effect of the amount of Ba(OH)2 on the synthesis of (5a)a
O
O
O
2
H
O
O
Ba(OH)2
H2O /
3
Entry
Ba(OH)2 (mol %)
Yield (%)
O
N
O
+
+
N
H
O
5
O
1
2
3
4
5
7
10
12
50
65
93
93
NH2
O
Reflux, 1-2 h
H2N
4
1
Scheme 1. Synthesis of 3-methyl-4-aryl-4,5-dihydro-1H-pyrano[2,3-c]pyrazol-6-
ones
a
Reactions are performed on a 1 mmol scale of the reactants.
Table 1
Table 4
Synthesis of 3-methyl-4-aryl-4,5-dihydro-1H-pyrano[2,3-c]pyrazol-6-ones
Effect of solvent on the synthesis of 3-methyl-4-(30,40,50-trimethoxyphenyl)-4,5-
dihydro-1H-pyrano[2,3-c]pyrazol-6-one (5a)a
Entry Aldehyde (3)
Producta Time (h) Yieldb (%) MP (°C)
Entry
Solvent
Time (h)
Yield (%)
1
2
3
4
5
6
7
8
3,4,5-(MeO)3C6H2CHO 5a
1.5
1
1.5
2
2
2
93
93
93
90
92
90
91
ND
ND
ND
ND
205
1
2
3
4
Ethanol
Methanol
CH3CN
H2O
5
6
4
1.5
90
87
85
93
4-MeOC6H4CHO
3-MeOC6H4CHO
2-ClC6H4CHO
2-HOC6H4CHO
4-FC6H4CHO
3-NO2C6H4CHO
HCHO
5b
5c
5d
5e
5f
5g
5h
5i
157–160
133–135
142–145
235–237
178–180
212
—
—
—
—
a
Reactions are performed on a 1 mmol scale of the reactants.
2
10
10
10
10
9
10
11
CH3CHO
CH3CH2CHO
CH3CH2CH2CHO
5j
5k
Table 2
Influence of various catalysts on the synthesis of 3-methyl-4-(30,40,50-trimethoxy-
phenyl)-4,5-dihydro-1H-pyrano[2,3-c]pyrazol-6-one (5a)a
ND-not detected.
a
All isolated products are new and were characterized by IR, 1H NMR, and 13C
Entry
Catalyst (10 mol %)
Time (h)
Yield (%)
NMR spectral analyses and CHN analysis.
b
1
2
3
4
K2CO3
Piperidine
NaOH
8
7
3
1.5
30
40
65
93
Isolated yields.
Ba(OH)2
To select the best catalyst, we carried out the reaction between
3,4,5-trimethoxybenzaldehyde, ethyl acetoacetate, Meldrums acid,
a
Reactions are performed on a 1 mmol scale of the reactants.
O
O
O
A r
N H
2
O
H
N
2
+
+
O
O
H
1
O
_
3
O
2
_
4
O H
O
O H
O
_
A r
O
+
N
N
H
O
II
I
A r
O
O
O
A r
H
O
O
N
N
H
N
_
+
O
O
H
_
_
O
O
N
H
II I
O
O
O
A r
A r
A r
O
_
_
_
+
H
C O
2
O
N
N
N
N
H
N
H
O
O
O
O
N
H
O
O
5
Scheme 2. Mechanism of formation of 3-methyl-4-aryl-4,5-dihydro-1H-pyrano[2,3-c]pyrazol-6-ones.

6836
S. H. S. Azzam, M. A. Pasha / Tetrahedron Letters 53 (2012) 6834–6837
and hydrazine hydrate in the presence of 10 mol % of different ba-
sic catalysts such as Ba(OH)2, K2CO3, piperidine, and NaOH. We
found that, K2CO3 did not afford the product in good yield and
reaction time was very long, similar results were obtained with
piperidine. The yield of the desired product improved to a very less
extent when NaOH was used as a basic catalyst and the product
was a mixture and a sticky mass. When the same reaction was car-
ried out in the presence of Ba(OH)2, the product was obtained in
very high yield (93%) within 1.5 h (Table 2, entry 4). The results
of this study are presented in Table 2.
References and notes
1. (a) Ugi, I. Pure Appl. Chem. 2001, 73, 187; (b) Dömling, A.; Ugi, I. Angew. Chem.,
Int. Ed. 2000, 39, 3168.
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Raabe, G. Nature 2006, 861.
4. Sheldon, R. A. Green Chem. 2005, 7, 267.
We have also varied the amount of Ba(OH)2 from 5, 7, and 10
to 12 mol % and the results revealed that, 10 mol % gives
excellent yield of the product in a short duration as shown in
Table 3.
After optimizing the conditions, the generality of this method
was examined by the reaction of different substituted aldehydes
with ethyl acetoacetate, Meldrums acid, and hydrazine hydrate
in the presence of 10 mol % Ba(OH)2 in water under reflux. We also
examined the use of aliphatic aldehydes to get the corresponding
products (Table 4 entries 8–11) but there was no product forma-
tion even after 10 h under the optimized reaction conditions, and
the results of this study are shown in Table 4.
It is found that, various aromatic aldehydes containing electron-
donating or electron-withdrawing functional groups at different
positions did show a difference in the reaction time but the yields
of products were almost same (Table 4).
The formation of the product in the present reaction is expected
to involve the following tandem reaction mechanism:
Formation of pyrazolone I by the reaction between 1 and 2 and
Knoevenagel condensation between 3 and 4 to give II. Michael
addition of I with II followed by cyclization is expected to give a
tricyclic intermediate III which may lose a molecule of acetone
and a molecule of CO2 in subsequent steps to give the final product
5 as shown in Scheme 2. In order to establish the mechanism of the
reaction, the intermediates-pyrazolone29 and the Knoevenagel ad-
duct30 were prepared separately (characterized by the 1H NMR and
13C NMR spectral analysis) and were treated with each other to get
the product 5a under the standardized reaction condition, which
clearly indicates that the intermediates I and II are formed during
the course of the present reaction.
5. (a) Wang, G.-W.; Komatsu, K.; Murata, Y.; Shiro, M. Nature 1997, 387, 583; (b)
Varma, R. S.; Kumar, D.; Dahiya, R. J. Chem. Res. 1998, s, 324; (c) Nozoe, T.;
Tanimoto, K.; Takemitsu, T.; Kitamura, T.; Harada, T.; Osawa, T.; Takayasu, O.
Solid State Ionics 2001, 141, 695; (d) Lamartine, R.; Perrin, R. In Spill Over of
Adsorbed Species; Pajonk, G. M., Teichner, S. J., Germain, J. E., Eds.; Elsevier:
Amsterdam, 1983; p 251.
6. (a) Tsukinoki, T.; Nagashima, S.; Mitoma, Y.; Tashiro, M. Green Chem. 2000, 2,
117; (b) Ballini, R.; Bosica, G.; Maggi, R.; Ricciutelli, M.; Righi, P.; Sartori, G.;
Sartorio, R. Green Chem. 2001, 3, 178; (c) Amantini, D.; Fringuelli, F.; Piermatti,
O.; Pizzo, F.; Vaccaro, L. Green Chem. 2001, 3, 229.
7. Hailes, H. C. Org. Process Res. Dev. 2007, 11, 114.
8. Kuppusamy, K.; Kasi, P. Tetrahedron Lett. 2010, 51, 3312.
9. El-Tamany, E. S.; El-Shahed, F. A.; Mohamed, B. H. J. Serb. Chem. Soc. 1999, 64, 9.
10. Ismail, Z. H.; Aly, G. M.; El-Degwi, M. S.; Heiba, H. I.; Ghorab, M. M. J. Egypt Biot.
2003, 13, 73.
11. Zaki, M. E. A.; Soliman, H. A.; Hiekal, O. A.; Rashad, A. E. Z. Naturforsch., C. 2006,
61, 1.
12. Wang, J. L.; Liu, D.; Zhang, Z. J.; Shan, S.; Han, X.; Srini vasula, S. M.; Croce, C. M.;
Alnemri, E. S.; Huang, Z. Proc. Natl. Acad. Sci. U.S.A. 2000, 97, 7124.
13. (a) Abdelrazek, F. M.; Metz, P.; Metwally, N. H.; El-Mahrouky, S. F. Arch. Pharm.
2006, 339, 456; (b) Abdelrazek, F. M.; Metz, P.; Kataeva, O.; Jaeger, A.; El-
Mahrouky, S. F. Arch. Pharm. 2007, 340, 543.
14. (a) Sharanin, Y. A.; Sharanina, L. G.; Puzanova, V. V. Zh. Org. Khim. 1983, 19,
2609; (b) Rodinovskaya, L. A.; Gromova, A. V.; Shestopalov, A. M.; Nesterov, V.
N. Russ. Chem. Bull., Int. Ed. 2003, 52, 2207.
15. Junek, H.; Aigner, H. Chem. Ber. 1973, 106, 914.
16. (a) Herrerias, C. I.; Yao, X.; Li, Z.; Li, C. Chem. Rev. 2007, 107, 2546; (b) Li, C. J.;
Chan, T. H. Comprehensive Organic Reactions in Aqueous Media; John Wiley &
Sons, 2007; (c) Grieco, P. A. Organic Reactions in Water; Thomson R Science
Glasgow: Scotland, 1998.
17. Gnanasambandam, V.; Kandhasamy, K. Tetrahedron Lett. 2008, 49, 5636.
18. Madhusudana Reddy, M. B.; Pasha, M. A.; Jayashankara, V. P. Synth. Commun.
2010, 40, 2930.
19. Madhusudana Reddy, M. B.; Pasha, M. A. J. Indian Chem. 2012, 51B, 537.
20. Siddekha, A.; Nizam, A.; Pasha, M. A. Spectrochim. Acta, Part A 2011, 81, 431.
21. Madhusudana Reddy, M. B.; Pasha, M. A. Synth. Commun. 1895, 2010, 40.
22. Pasha, M. A.; Jayashankara, V. P. Bioorg. Med. Chem. Lett. 2007, 17, 621.
23. Pasha, M. A.; Jayashankara, V. P. J. Indian Chem. 2007, 46B, 1328.
24. Madhusudana Reddy, M. B.; Pasha, M. A. Chin. Chem. Lett. 2010, 21, 1025.
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In summary, we have demonstrated a simple, efficient, and a
novel one-pot four-component protocol for the synthesis of some
new pyranopyrazol-6-one derivatives in water using Ba(OH)2 as
27. Aatika, N.; Pasha, M. A. J. Saudi Chem. Soc. 2011, 15, 55.
28. General procedure for the synthesis of 3-methyl-4-aryl-4,5-dihydro-1H-
pyrano[2,3-c]pyrazol-6-ones: In
a 50 mL round bottom flask, a mixture of
a
readily available, inexpensive, and efficient catalyst. The
hydrazine hydrate (2 mmol), ethyl acetoacetate (2 mmol), and Ba(OH)2
(10 mol %) were taken, 10 mL water was added to the mixture and stirred in
an oil bath at reflux for 15 min; aromatic aldehyde (2 mmol) and Meldrums
acid (2 mmol) were then added and refluxing was continued for the remaining
time (Table 4). The crude product thus separated was filtered, washed with
water, the solid was dried, and subjected to silica gel column chromatography
[silica gel G; 100–200 mesh, using EtOAc–hexane (1: 9) as eluent] to get the
pure products. The structures of all the products were established by IR, 1H
NMR, 13C NMR spectral, and elemental analyses. Spectral data: 3-methyl-4-
advantages offered by this method are: simple reaction condition,
short reaction time, ease of product isolation, and excellent yields.
We wish to state that this method involves environmentally
friendly procedure, and is the first procedure for the synthesis of
novel
3-methyl-4-aryl-4,5-dihydro-1H-pyrano[2,3-c]pyrazol-6-
one derivatives.
(30,40,50-trimethoxyphenyl)-4,5-dihydro-1H-pyrano[2,3-c]pyrazol-6-one
Yellow crystalline solid (93%, 0.590 g); mp 205 °C: IR (KBr) : 3387 (br),
2968 (s), 1734 (vs), 1694 (s), 1622 (s), 1569 (vs), 1498 (s), 1448 (s), 1375 (s),
1236 (s), 1173 (vs), 1033 (s) cmꢀ1 1H NMR (400 MHz, DMSO-d6): d 2.88 (d,
J = 8.0 Hz, 2H, CH2), 3.43 (s, 3H, Me), 3.59 (s, 3H, OCH3), 3.62 (s, 3H, OCH3), 3.82
(s, 3H, OCH3), 4.81 (t, J = 8.0 Hz, 1H, CH), 6.61 (s, 2H, Ph), 10.85 (s, 1H, NH); 13
NMR (100 MHz, DMSO-d6): d 169.8 (O–C@O), 154.6, 147.3, 132.8, 128.8, 114.8,
108.1 (all ArCs), 145.0 (C–C@N pyrazole), 136.8 (O–C@C pyrazole), 117.8 (C@C
pyrazole), 60.1 (2 ꢁ OCH3), 56.5 (OCH3), 54.7 (CH2),29.7 (CH), 14.7 (CH3); Anal.
Calcd for C16H18 N2O5: C, 60.37; H, 5.70; N, 8.80%. Found: C, 60.36; H, 5.70; N,
8.80%. 3-methyl-4-(4’-methoxyphenyl)-4,5-dihydro-1H-pyrano[2,3-c]pyrazol-6-
(5a):
m
Acknowledgments
;
S.H.S.A. gratefully acknowledges the Sana University, Yemen for
a fellowship; and the authors thank the VGST, Dept. of Science &
Technology, Government of Karnataka for the CESEM Award Grant
No. 24 (2010-2011).
C
one (5b): Orange amorphous solid (93%, 0.474 g); mp 157–160 °C: IR (KBr)
3401 (br), 2939 (s), 1734 (vs), 1704 (s), 1663 (s), 1504 (vs), 1447 (s), 1373 (vs),
1249 (vs), 1173 (s), 1034 (vs) cmꢀ1 1H NMR (400 MHz, DMSO-d6): d 3.19 (d,
m:
Supplementary data
;
J = 8.4 Hz, 2H, CH2), 3.34 (s, 3H, CH3), 3.84 (s, 3H, OCH3), 4.29 (t, J = 8.0 Hz, 1H,
CH), 6.74 (m, 2H, Ph), 7.04–7.21(dd, J1 = 8.4 Hz, J2 = 8.8 Hz, 2H, Ph), 11.10 (s, 1H,
NH); 13C NMR (100 MHz, DMSO-d6): d 169.9 (O–C@O), 154.9, 142.9, 129.9,
127.0, 113.9 (all ArCs), 148.9 (C–C@N pyrazole), 138.8 O–C@C pyrazole), 114.3
(C@C pyrazole), 55.8 (OCH3), 52.0 (CH2), 29.9 (CH), 13.6 (CH3); Anal. Calcd for
Supplementary data associated with this article can be found, in
the online version, at http://dx.doi.org/10.1016/j.tetlet.2012.
10.025.

S. H. S. Azzam, M. A. Pasha / Tetrahedron Letters 53 (2012) 6834–6837
6837
C14H14 N2 O3: C, 65.11; H, 5.46; N, 10.85%. Found: C, 65.12; H, 5.47; N, 10.84%.
3-methyl-4-(3’-methoxyphenyl)-4,5-dihydro-1H-pyrano[2,3-c]pyrazol-6-one
J = 8.0 Hz, 2H, CH2), 3.64 (s, 3H, CH3), 4.29 (t, J = 6.0 Hz, 1H, CH), 7.00–7.03 (m,
2H, Ph), 7.11–7.28 (m, 2H, Ph), 11.23 (s, 1H, NH); 13C NMR (100 MHz, DMSO-
d6): d 171.8 (O–C@O), 152.5, 130.1, 130.0, 115.0, 105.0 (all ArCs), 160.1 (C–C@N
pyrazole), 140.2(O–C@C pyrazole), 115.2 (C@C pyrazole), 52.3 (CH2), 32.9 (CH),
11.2 (CH3); Anal. Calcd for C13H11FN2O2: C, 63.41; H, 4.50; N, 11.38%. Found: C,
63.39; H, 4.50; N, 11.39%. 3-methyl-4-(3’-nitrophenyl)-4,5-dihydro-1H-
pyrano[2,3-c]pyrazol-6-one (5g): Pale orange crystalline solid (90%, 0.486 g);
(5c): White amorphous solid (93%, 0.474 g); mp 133–135 °C: IR (KBr)
(br), 2968 (s), 1733 (vs), 1704 (s), 1668 (s), 1596 (vs), 1508 (s), 1448 (s), 1375
(s), 1283 (vs), 1152 (vs), 1060 (s) cmꢀ1 1H NMR (400 MHz, DMSO-d6): d 3.09
m: 3356
;
(d, J = 8.4 Hz, 2H, CH2), 3.54 (s, 3H, CH3), 3.84 (s, 3H, OCH3), 4.36 (t, J = 8.0 Hz,
1H, CH), 6.99 (s, 1H, Ph), 7.37–7.42 (m, 2H, Ph), 7.68 (d, J = 5.6 Hz, 1H, Ph),
11.13 (s, 1H, NH); 13C NMR (100 MHz, DMSO-d6): d 169.7 (O–C@O), 153.3,
141.6, 129.7, 122.2, 115.7, 112.6 (all ArCs), 144.5 (C–C@N pyrazole), 135.7 (O–
C@C pyrazole), 116.0 (C@C pyrazole), 55.7 (OCH3), 52.7 (CH2), 32.9 (CH), 12.6
(CH3); Anal. Calcd for C14H14 N2O3: C, 65.11; H, 5.46; N, 10.85%. Found: C,
65.12; H, 5.47; N, 10.84%. 3-methyl-4-(2’-cholorophenyl)-4,5-dihydro-1H-
pyrano[2,3-c]pyrazol-6-one (5d): Pale orange crystalline solid (90%, 0.4672 g);
mp 212 °C: IR (KBr)
m: 3389 (br), 2968 (s), 1733 (vs), 1704 (s), 1668 (w), 1596
(s), 1538 (vs), 1448 (s), 1375 (w), 1348 (s), 1256 (s), 1173 (s), 1033 (s) cm0ꢀ1
;
1H NMR (400 MHz, DMSO-d6): d 3.10 (d, J = 8.0 Hz, 2H, CH2), 3.50 (s, 3H, CH3),
4.29 (t, J = 8.0 Hz, 1H, CH), 7.54 (d, J = 8.0 Hz, 1H, Ph), 7.79 (d, J = 7.6 Hz, 1H, Ph),
8.01 (d, J = 8.0 Hz, 1H, Ph), 8.18 (d, J = 3.2 Hz, 1H,Ph), 10.99 (s, 1H, NH); 13C
NMR (100 MHz, DMSO-d6): d 172.6 (O–C@O), 148.6, 147.7, 130.6, 122.7, 122.0,
102.3 (all ArCs),, 152.8 (C–C@N pyrazole), 135.2 (O–C@C pyrazole), 112.3 (C@C
pyrazole), 52.2 (CH2), 36.6 (CH), 10.8 (CH3); Anal. Calcd for C13H11 N3O4: C,
57.14; H, 4.06; N, 15.38%. Found: C, 57.14; H, 4.06; N, 15.38%.
mp 142–145 °C: IR (KBr)
1615 (s), 1508 (s), 1447 (s), 1380 (s), 1276 (vs), 1173 (vs), 1034 (s), 746 (vs)
cmꢀ1 1H NMR (400 MHz, CDCl3): d 3.19 (d, J = 8.4 Hz, 2H, CH2), 3.54 (s, 3H,
m: 3394 (br), 2959 (s), 1734 (vs), 1704 (s), 1666 (vs),
;
CH3), 4.69 (t, J = 8 Hz, 1H, CH), 7.06–7.25 (dd, J1 = 6.4 Hz, J2 = 6.4 Hz, 2H, Ph),
7.29 (d, J = 7.6 Hz, 1H, Ph), 7.59 (d, J = 7.2 Hz, 2H, Ph), 11.15 (s, 1H, NH); 13C
NMR (100 MHz, CDCl3): d 170.1 (O–C@O), 141.1, 129.9, 128.9, 126.9, 122.1,
117.1 (all ArCs),, 149.9 (C–C@N pyrazole), 135.3 (O–C@C pyrazole), 114.1 (C@C
pyrazole), 52.1 (CH2), 32.1 (CH), 10.7 (CH3); Anal. Calcd for C13H11ClN2O2: C,
59.44; H, 4.22; N, 10.66%. Found: C, 59.12; H, 4.22; N, 10.65%. 3-methyl-4-(2’-
hydroxyphenyl)-4,5-dihydro-1H-pyrano[2,3-c]pyrazol-6-one (5e): Pale yellow
29. Synthesis of 5–methyl–2,4–dihydro-pyrazol–3–one (I): A mixture of hydrazine
hydrate (10 mmol), ethyl acetoacetate (10 mmol), and Ba(OH)2 (10 mol %)
were taken, 5 mL water was added to the mixture and stirred at 26 °C for
45 min (TLC), the crude solid thus separated was filtered, washed with water,
and dried to get 5-methyl-2,4-dihydro-pyrazol-3-one in quantitative yield
whose structure was established by 1H NMR and 13C NMR spectral analysis.
White solid, mp: 215–216 °C; 1H NMR (400 MHz, CDCl3): d 1.55 (s, 3H, CH2),
3.14 (s, 2H, CH2), 6.80 (s, 1H, NH); 13C NMR (100 MHz, CDCl3): d 168.1 (NH–
C@O), 153.9 (–C@N), 43.5 (CH2), 20.6 (CH3).
amorphous solid (92%, 0.444 g); mp 235–237 °C: IR (KBr)
(s), 2968 (s), 1733 (vs), 1694 (w), 1622 (s), 1508 (w), 1448 (s), 1375 (s), 1269
(s),1163 (s),1033 (s) cmꢀ1 1H NMR (400 MHz, DMSO-d6): d 2.99 (d, J = 6.8 Hz,
m: 3562 (br), 3362
;
30. Synthesis of 2,2-dimethyl-5-(30,40,50-trimethoxybenzylidene)-[1,3]-dioxane-4,6-
dione (II): A mixture of 3,4,5-trimethoxy benzaldehyde (2 mmol), Meldrum’s
acid (2 mmol), and Ba(OH)2 (10 mol %) were taken in 5 mL water and stirred at
reflux for 15 min (TLC), the solid thus separated was filtered, washed with
water, and dried to get 2,2-dimethyl-5-(30,40,50-trimethoxybenzylidene)-[1,3]-
dioxane-4,6-dione in almost pure form. The structure was confirmed by
1HNMR and 13CNMR spectral analysis. Pale green solid, mp: 118 °C; 1H NMR
(400 MHz, CDCl3): d 1.76 (s, 6H, 2 ꢁ CH3), 3.10 (s, 6H, OCH3), 3.98 (s, 3H, OCH3),
7.61 (s, 2H, AcH), 8.32 (s, 1H, @CH); 13C NMR (100 MHz, CDCl3): d 167.8
(2 ꢁ O–C@O), 148.8 (H–C@C), 144.9, 131.4, 129.9, 111.1, 108.2, 106.2 (all ArCs),
117.8 (CO–C@C), 103.3 (>C–O), 57.8, 55.8, 53.5 (3 ꢁ OCH3), 30.1, 27.8 (2 ꢁ CH3).
2H, CH2), 3.29 (s, 1H, OH), 3.69 (s, 3H, CH3), 4.29 (t, J = 6.8 Hz, 1H, CH), 6.94–
6.98 (m, 2H, Ph), 7.39 (d, J = 7.2 Hz, 1H, Ph), 7.67 (d, J = 8 Hz, 2H, Ph) 11.09 (s,
1H, NH); 13C NMR (100 MHz, DMSO-d6): d 169.7 (O–C@O), 159.5, 131.7, 120.5,
119.9, 117.4 (all ArCs), 144.7 (C–C@N pyrazole), 134.1(O–C@), 114.7 (C@C
pyrazole), 52.9 (CH2), 32.9 (CH), 12.3(CH3); Anal. Calcd for C13H12 N2O3: C,
63.93; H, 4.95; N, 11.47%. Found: C, 63.93; H, 4.95; N, 11.49%. 3-methyl-4-(4’-
fluorophenyl)-4,5-dihydro-1H-pyrano[2,3-c]pyrazol-6-one (5f): Pale orange
crystalline solid (91%, 0.442 g); mp 178–180 °C: IR (KBr)
(s), 1734 (vs), 1704 (s), 1681 (s), 1544 (vs), 1504 (s), 1448 (s), 1354 (vs), 1223
(vs), 1152 (vs), 1034 (s) cmꢀ1 1H NMR (400 MHz, DMSO-d6): d 3.17 (d,
m: 3398 (br), 2959
;