An efficient catalyst- and solvent-free method for the synthesis of medicinally important dihydropyrano[2,3-c]pyrazole derivatives using ball milling technique

Article abstract of DOI:10.1007/s13738-015-0793-7

Dihydropyrano[2,3-c]pyrazole annulated heterocyclic compounds with diverse substituents on the 4H-pyran ring were efficiently prepared via a one-pot and four-component reaction of ethyl acetoacetate, hydrazine hydrate, aromatic aldehyde, and malononitrile

Full text of DOI:10.1007/s13738-015-0793-7

J IRAN CHEM SOC
DOI 10.1007/s13738-015-0793-7
ORIGINAL PAPER
An efficient catalyst‑ and solvent‑free method for the synthesis
of medicinally important dihydropyrano[2,3‑c]pyrazole
derivatives using ball milling technique
1
1
1
Mohammad G. Dekamin · Mohammad Alikhani · Atefeh Emami ·
1
1
Hossein Ghafuri · Shahrzad Javanshir
Received: 11 August 2015 / Accepted: 26 November 2015
Iranian Chemical Society 2015
©
Abstract Dihydropyrano[2,3-c]pyrazole annulated het-
erocyclic compounds with diverse substituents on the
predefined functionality especially in chemical biology
and drug discovery [11–14]. Indeed, one-pot MCRs often
shorten reaction times, giving higher overall chemical
yields and atom efficiency than multi-step synthesis, and
therefore can reduce waste and the use of energy and man-
power [1–14]. If such MCR reactions can be performed in
the absence of any catalyst and solvent, they can provide
the perfect platform for green synthesis without percolat-
ing anything to destroy the environment [15–20]. In this
context, reactions carried out using ball milling technique
are attractive from both environmental and economic points
of view, since reactions between solid reactants or melt
reaction mixtures are run in the absence of any organic
solvents. Indeed, ball milling refers to the use of friction,
collision, or other mechanical actions to provide required
energy of organic reactions in situ. Furthermore, near quan-
titative yields are often obtained using this technique, and
subsequent utilization of organic solvents for crystalliza-
tion or chromatography purification steps is substantially
reduced or no longer required. Therefore, synthetic proto-
cols under ball milling can be considered as genuine sol-
vent-free methods.
4
H-pyran ring were efficiently prepared via a one-pot and
four-component reaction of ethyl acetoacetate, hydrazine
hydrate, aromatic aldehyde, and malononitrile. The pro-
cedure proceeds without utilization of any catalyst or sol-
vent using ball milling technique at ambient temperature to
afford desired medicinally important dihydropyrano[2,3-c]
pyrazole derivatives. This protocol offers several advan-
tages such as avoiding the use of any toxic and hazardous
catalyst or solvent, mild reaction conditions, high to quan-
titative yields of products, low cost, and straightforward
work-up.
Keywords Catalyst-free conditions · Solvent-free
conditions · Ball milling technique · Green chemistry ·
Multicomponent reactions (MCRs) · Dihydropyrano[2,3-c]
pyrazole scaffold
Introduction
Multicomponent reactions (MCRs), defined as one-pot
reactions in which at least three different substrates join
through the covalent bonds, have steadily received con-
siderable attention in synthetic organic chemistry [1–10].
MCRs have emerged as an important tool for the rapid
generation of molecular complexity and diversity with
Ball milling technique, as an environmentally benign
method, has received increasing attention for organic syn-
thesis in recent years. Subsequently, some specific review
papers and book chapters have been published in the litera-
ture on the topic. Some typical examples include carbon–
carbon and carbon-heteroatom bond formation, oxidation
by solid oxidants, asymmetric organocatalytic reactions,
dehydrogenative coupling, and peptide or polymeric mate-
rials synthesis [15–22]. Hence, organic reactions run under
neat conditions by means of ball milling activation demon-
strate significant advantages including better energy bal-
ance, short reaction time, providing quantitative yields,
straightforward work-up, higher safety, and the potential
*
Mohammad G. Dekamin
mdekamin@iust.ac.ir
1
Pharmaceutical and Heterocyclic Compounds Research
Laboratory, Department of Chemistry, Iran University
of Science and Technology, Tehran 16846-13114, Iran
1
3

J IRAN CHEM SOC
A
B
C
Scheme 1 One-pot four-component synthesis of dihydropyrano[2,3-
c]pyrazole derivatives using ball milling technique at ambient tem-
perature
Fig. 1 Chemical structures of some dihydropyrano[2,3-c]pyrazole
derivatives with anticancer, antifungal, and antibacterial activities
for scale-up over other solvent-free conditions [13–22]. On
the other hand, a lot of attention has recently been paid to
the development of new methods for the synthesis of heter-
ocyclic compounds, due to their potential importance in the
pharmaceutical and agricultural fields [7, 13, 14, 23, 24].
Dihydropyrano[2,3-c]pyrazole derivatives are of high inter-
est because they generally show diverse biological proper-
ties such as fungicidal, bactericidal, and vasodilator activi-
ties as well as anticancer agents among others [25–30]. For
instance, dihydropyrano[2,3-c]pyrazole derivatives, such
as A, B, and C are valuable compounds as anticancer [26],
antifungal [26], and antibacterial agents [27], respectively
hydrate (2), malononitrile (3), and aromatic aldehydes (4a‑
q) by catalyst- and solvent-free methodology under ball
milling conditions at ambient temperature (Scheme 1).
Results and discussion
To find the optimized conditions, a systematic study with con-
sidering different variables affecting the reaction yield was
carried out for the reaction of ethyl acetoacetate (1), hydra-
zine hydrate (2), malononitrile (3), and 4-chlorobenzaldehyde
(4a) (molar ratio:1:1:1:1) as the model reaction. The results
are summarized in Table 1. Only a trace amount of the desired
6-amino-4-(4-chlorophenyl)-3-methyl-2,4-dihydropyrano[2,3-
c]pyrazole-5-carbonitrile (5a) was obtained under catalyst-
free and reflux conditions in water after 5 h (entry 1). Then,
the effect of catalyst loading on the completion of the reaction
was studied in the next step (entries 2–5). The use of potas-
sium phthalimide-N-oxyl (POPINO) and tetraethylammonium
2-(carbamoyl)benzoate (TEACB), as catalyst, in water under
reflux conditions improved the yield of the desired product
5a significantly (entries, 2–5). Interestingly, the yield of the
desired product 5a was improved more when it was run in
ball mill under catalyst-free conditions at ambient temperature
(entries, 6–8) compared to refluxing water (entries, 1–4). This
behavior can be attributed to the less solubility of the substrates
and reaction intermediates in water (Scheme 2). As shown in
Table 1, the best results in terms of the obtained yield of the
desired product 5a, required temperature and time of reaction
were obtained in ball mill under catalyst-free conditions.
In order to generalize the optimum conditions, different
derivatives of 6-amino-3-methyl-4-aryl-2,4-dihydropyrano[2,3-
c]pyrazole-5-carbonitrile (5a-q) were prepared from the
one-pot reaction mixture of ethyl acetoacetate (1), hydrazine
hydrate (2), malononitrile (3), and aromatic aldehydes (4a‑q)
under ball milling conditions in the absence of any catalyst at
ambient temperature. The results are summarized in Table 2.
As it is shown in Table 2, aromatic aldehydes with electron-
withdrawing groups (entries 1–7) accelerate the reaction
compared to the electron-donating groups (entries 9–15). In
(
Fig. 1).
Due to the important aforementioned properties of
pyranopyrazole derivatives, considerable attention has been
focused on the development of environmentally friendly
methodologies for the synthesis of dihydropyrano[2,3-c]
pyrazole scaffold by cyclization of aromatic aldehydes,
malononitrile, ethyl acetoacetate, and hydrazine hydrate
[
28]. A literature survey shows that several modified meth-
ods have been reported using different homogeneous or
heterogeneous catalysts such as tetrabutylammonium
hydrogen sulfate in acetonitrile or xylene [29], l-proline
[
[
30], N-methylmorpholine [31], lipase [32], γ-alumina
33], triethylamine [34], piperidine [35], triethylbenzylam-
monium chloride [36], and cetyltrimethylammonium
bromide (CTAB) [37]. However, many of the introduced
methods for synthesis of these compounds suffer from dis-
advantages including relying on the use of volatile organic
solvents under reflux conditions and expensive or odorous
catalysts, tedious work-up procedure, troublesome waste
discarding, long reaction times, and low yields. Therefore,
obviation of these limitations is necessary to develop a sim-
ple and green synthesis of dihydropyrano[2,3-c]pyrazole.
Thus, we decided to investigate a catalyst- and solvent-
free route for synthesis of dihydropyrano[2,3-c]pyrazole
scaffold with diverse substituents using ball milling tech-
nique. The reaction proceeded smoothly to afford different
derivatives of dihydropyrano[2,3-c]pyrazole (5a‑q) through
one-pot condensation of ethyl acetoacetate (1), hydrazine
1
3

J IRAN CHEM SOC
Table 1 Optimization of the reaction conditions for preparation 6-amino-4-(4-chlorophenyl)-3-methyl-2,4-dihydropyrano[2,3-c]pyrazole-5-car-
bonitrile (5a)
a
Entry
Catalyst loading (mol%)
–
Conditions
Temp.(°C)
Time (min)
Yield (%)
1
2
3
4
5
6
7
8
H O
Reflux
Reflux
Reflux
Reflux
50
5
2
Trace
25
2
b
POPINO (10)
H O
2
b
POPINO (20)
H O
2
45
2
c
TEACB (5)
H O
2
50
2
c
TEACB (5)
EtOH
90
40
45
60
80
–
–
–
Ball milling
Ball milling
Ball milling
Ambient
Ambient
Ambient
83
99d
99d
Reaction conditions: Ethyl acetoacetate (1, 1 mmol), hydrazine hydrate (2, 1 mmol), malononitrile (3, 1 mmol), and 4-chlorobenzaldehyde (4a,
1
mmol) under various conditions
a
The yields refer to the desired product 5a
Potassium phthalimide-N-oxyl
b
c
d
Tetraethylammonium 2-(carbamoyl)benzoate
The yields refers to isolated yield
addition to the aromatic aldehydes, the reaction was also pro-
ceeded smoothly using heterocyclic aldehydes in high to excel-
lent yields (entries 16 and 17).
The mechanism suggested in Scheme 2 seems to be rea-
sonable for the one-pot four-component reaction of ethyl
acetoacetate (1), hydrazine hydrate (2), malononitrile (3),
and aromatic aldehydes 4a‑q using ball milling technique.
The first step includes cyanocinnamonitriles (7) forma-
tion from the reaction between aldehydes 4a‑q and malo-
nonitrile (3). Then, Michael addition by the enol form of
range of dihydropyrano[2,3-c]pyrazole derivatives,
which are often encountered in biologically and pharma-
cologically actives compounds. The procedure proceeds
under catalyst- and solvent-free conditions at ambi-
ent temperature using ball milling technique. The most
important advantages of this method include the use of
catalyst- and solvent-free conditions, excellent yields,
and clean and simple work-up procedure that make this
method an instrumental alternative to the previous meth-
odologies for the scale-up of this one-pot four-compo-
nent reaction.
5
-methyl-2,4-dihydro-pyrazol-3-one intermediate (8E) on
the intermediate 7, cyclization and final tautomerization of
intermediate 9 affords the desired products 5a‑q.
Comparison of the present method with those reported
in the literature in respect to the catalyst loading, time,
required reaction conditions, yield, simplicity, and per-
formance reveals that the method presented here is
a simple and efficient method for the preparation of
dihydropyrano[2,3-c]pyrazole derivatives (Table 3).
Experimental section
General
All commercially available chemicals were obtained
from Merck and Aldrich, and used without further puri-
fications, except for benzaldehyde, which was used as
a fresh distilled sample. The ball mil was a Retsch MM
400 swing mill with its 3D driving of the balls. A 10-mL
stainless steel double-walled beaker was applied. Two
stainless steel balls with 12-mm diameter were used,
and the milling frequency was at 28 Hz and the ambient
Conclusion
In conclusion, we have developed a highly efficient and
green one-pot methodology for the synthesis of a wide
1
3

J IRAN CHEM SOC
Table 2 Catalyst- and solvent-free four-component synthesis of 6-amino-3-methyl-4-aryl-2,4-dihydropyrano[2,3-c]pyrazole-5-carbonitrile
derivatives (5a‑q) under ball milling conditions at ambient temperature
Product 5a
Yield (%)
b
References
Entry
Aldehyde 4
Time (min)
1
2
3
4
5
6
7
8
9
4-Chlorobenzaldehyde (4a)
4-Bromobenzaldehyde (4b)
4-Fluorobenzaldehyde (4c)
45
45
5a
5b
5c
5d
5e
5f
99
95
95
92
90
99
90
87
88
85
90
90
85
87
85
90
90
[38]
[39]
[36]
[34]
[40]
[38]
[40]
[38]
[38]
[38]
[39]
[39]
[38]
[40]
This work
[40]
[41]
45
2-Chlorobenzaldehyde (4d)
2,4-Dichlorobenzaldehyde (4e)
4-Nitrobenzaldehyde (4f)
60
60
30
3-Nitrobenzaldehyde (4g)
35
5g
5h
5i
Benzaldehyde (4h)
70
4-Hydroxybenzaldehyde (4i)
4-Methoxybenzaldehyde (4j)
2-Hydroxybenzaldehyde (4k)
4-Dimethylaminobenzaldehyde (4l)
4-Hydroxy-3-methoxybenzaldehyde (4 m)
2, 4-Dimethoxybenzaldehyde (4n)
3-Benzyloxy-4-hydroxybenzaldehyde (4o)
Furan-2-carbaldehyde (4p)
60
1
1
1
1
1
1
1
1
0
1
2
3
4
5
6
7
90
5j
90
5k
5l
90
105
105
120
70
5m
5n
5o
5p
5q
Thiophen-2-carbaldehyde (4q)
70
Reaction conditions: ethyl acetoacetate (1, 1 mmol), hydrazine hydrate (2, 1 mmol), malononitrile (3, 1 mmol), and aromatic aldehyde (4a-q,
1
mmol), under catalyst- and solvent-free conditions, at ambient temperature using ball mill technique
a
All compounds are known and their structures were established from their spectral data and melting points as compared with the authentic
samples or literature values [29–43]
b
The yields refers to isolated yield of 5a-q
temperatures. Analytical thin-layer chromatography
Typical procedure for the synthesis
(
TLC) for monitoring reactions was performed using
of dihydropyrano[2,3‑c]pyrazole derivatives (5a‑q)
Merck 0.2 mm silica gel 60 F-254 Al-plates. Melting
points were determined using an Electrothermal 9100
apparatus and are uncorrected. Microanalysis of the
products was carried out by a CHNS/O analyzer (Per-
A clean, dry, 10-mL ball mill vessel with two stainless steel
balls was charged with ethyl acetoacetate (1, 1 mmol) and
hydrazine hydrate (2, 1 mmol). The vessel was closed and
the milling was started at ambient temperatures at a speed of
28 Hz for 30 s. Then, malononitrile (3, 1 mmol) and aromatic
aldehyde (4a‑q, 1 mmol) were added to the vessel, and milling
was started under ambient temperature for the specific times as
indicated in Table 2. The reaction progress was monitored by
TLC. After completion of the reaction, the obtained solid was
suspended in water (60 °C, 5 mL) for 5 min, filtered through a
Buchner funnel, and dried in an oven at 60 °C for 1 h.
1
kin–Elmer Series II, 2400). H NMR (400 MHz) and
1
3
C NMR (100 MHz) spectra were recorded on Bruker
DRX-400 Avance spectrometers with DMSO as solvent
at room temperature. All yields refer to isolated products.
All compounds were well characterized using melting
points, IR and NMR spectral data as compared with those
obtained from authentic samples or reported in the litera-
ture [29–43].
1
3

J IRAN CHEM SOC
Scheme 2 A plausible
CN
mechanism for the one-pot
four-component reaction of
ethyl acetoacetate (1), hydrazine
hydrate (2), malononitrile (3),
and aromatic aldehydes (4a‑q)
under catalyst- and solvent-free
conditions using ball milling
technique at ambient tempera-
ture
O
O
+
CN
H
Ar
Ar
H
(3)
O
HO
(4a-q)
+
H
O
H2N NH2
N
O
(
1)
N
CN
H
NC
(2)
(
6)
(
8K)
Ar
H
CN
CN
H O + EtOH
2
H O
2
N
N
(
7)
H
O
H
N
O
H
H
N
Ar
:
(
8E)
CN
N
(
9)
Ar
Ar
O
CN
H
CN
HN
HN
N
N
O
(
NH
NH2
10)
(5a-q)
Table 3 Comparison of the
present method with other
methods for the synthesis of
dihydropyrano[2,3-c]pyrazole
derivative of 5a
Entry
Catalyst
TEBAa
Conditions
Temp. (°C)
Time (min)
Yield (%)
References
1
2
3
4
5
6
7
H O
90
360
35
99
90
97
88
90
80
99
[36]
2
γ-Alumina
l-Proline
Lipase
Imidazole
–
H O
Reflux
Reflux
30
[33]
2
H O
180
60
[27]
2
EtOH
[30]
H O
80
20
[42]
2
H O
Reflux
Ambient
240
45
[43]
2
–
Ball milling
This work
a
Triethylbenzylammonium chloride
Selected spectral data
CHaromatic), 12.15 (s, 1H, NH) ppm; 13C NMR (100 MHz,
DMSO-d ) δ 9.7, 35.5, 56.7, 97.2, 120.1, 131.2, 131.4,
6
6
‑Amino‑4‑(4‑chlorophenyl)‑3‑methyl‑2,4‑dihydropyrano
135.6, 143.5, 143.3, 154.7, 160.9 ppm [44].
[2,3‑c]pyrazole‑5‑carbonitrile (5a)
6‑Amino‑4‑(4‑hydroxy‑3‑phenoxymethyl‑phenyl)‑3‑me‑
White crystals, mp 235–236 °C, yield: 99 %, IR (KBr)
υ¯max 3439, 3246, 2193, 1639, 1599, 752 cm ; H NMR
thyl‑2,4‑dihydropyrano[2,3‑c]pyrazole‑5‑carbonitrile (5o)
−
1 1
(
1
400 MHz, DMSO-d ) δ 1.80 (s, 3H, CH ), 4.64 (s,
White crystals, mp 189–191 °C, yield: 85 %, Elemental
analysis for C H N O : C 67.37, H 4.85, N 14.96; found:
6
3
H, CHbenzylic), 6.95 (br s, 2H, NH ), 7.19–7.21 (d, 2H,
2
21 18
4
3
J = 8.4 Hz, CHaromatic), 7.38–7.40 (d, 2H, J = 8.4 Hz,
C 67.31, H 4.79, N 14.99; IR (KBr) υ¯max 3479, 3236,
1
3

J IRAN CHEM SOC
17. G. Kaupp, Cryst. Eng. Comm. 8, 794 (2006)
−
1 1
3
(
117, 2187, 1635, 1610, 1596, 1587, 756 cm ; H NMR
1
8. G. Kaupp, Cryst. Eng. Comm. 13, 3108 (2011)
400 MHz, DMSO-d ) δ 1.78 (s, 3H, CH ), 3.39 (s, 2H,
CH2benzylic), 4.45 (s, 1H, CHbenzylic), 6.82 (br s, 2H, NH2),
6
3
1
9. J. Mokhtari, M.R. Naimi-Jamal, H. Hamzeali, M.G. Dekamin,
G. Kaupp, Chemsuschem 2, 248 (2009)
20. M.R. Naimi-Jamal, J. Mokhtari, M.G. Dekamin, G. Kaupp, Eur.
6
5
.83-6.85 (m, 3H, J = 10.4 Hz, CH
), 7.37–7.40 (m,
), 12.06 (s, 1H, NH) ppm;
NMR (100 MHz, DMSO-d ) δ 9.7, 35.7, 55.5, 57.3, 97.6,
11.9, 113.2, 120.0, 120.9, 127.9, 128.3, 135.6, 136.8,
37.0, 147.3, 148.0, 154.7, 160.7 ppm.
aromatic
1
3
H, J = 6.8 Hz CH
C
J. Org. Chem. 2009, 3567 (2009)
aromatic
2
1. A. Stolle, T. Szuppa, S.E.S. Leonhardt, B. Ondruschka, Chem.
6
Soc. Rev. 40, 2317 (2011)
1
1
2
2. S. Mashkouri, M.R. Naimi-Jamal, Molecules 14, 474 (2009)
23. S.K. Khetan, T.J. Collins, Chem. Rev. 107, 2319 (2007)
4. M. Li, B.-X. Zhao, Eur. J. Med. Chem. 85, 311 (2014)
2
Acknowledgments We are grateful for the financial support from
The Research Council of Iran University of Science and Technology
25. S.R. Mandha, S. Siliveri, M. Alla, V.R. Bommena, M.R. Bom-
mineni, S. Balasubramanian, Bioorg. Med. Chem. Lett. 22, 5272
(2012)
(
IUST), Tehran, Iran (Grant No. 160/771).
2
2
2
6. D. Das, R. Banerjee, J. Chem. Pharm. Res. 6, 108 (2014)
7. J.R. Zgoda, J.R. Porter, Pharm. Biol. 39, 221 (2001)
8. Y. Zou, Y. Hu, H. Liu, D. Shi, ACS. Comb. Sci. 14, 38 (2012)
References
29. N.J. Parmar, S.B. Teraiya, R.A. Patel, N.P. Talpada, Tetrahedron
Lett. 52, 2853 (2011)
1
.
B.H. Rotstein, S. Zaretsky, V. Rai, A.K. Yudin, Chem. Rev. 114,
32 (2014)
30. P. Prasanna, S. Perumal, J.C. Menendez, Green Chem. 15, 1292
(2013)
8
2
3
.
.
M.M. Heravi, S. Moghimi, J. Iran. Chem. Soc. 8, 306 (2011)
H. Eshghi, M. Rahimizadeh, F. Eshkil, M. Hosseini, M. Baka-
voli, M. Sanei-Ahmadabad, J. Iran. Chem. Soc. 11, 685 (2014)
A.R. Moosavi-Zare, M.A. Zolfigol, O. Khaledian, V. Khakyza-
deh, M.D. Farahani, M.H. Beyzavi, H.G. Kruger, Chem. Eng. J.
31. F. Lehmann, M. Holm, S. Laufer, J. Comb. Chem. 10, 364
(2008)
32. N.J. Parmar, H.A. Barad, B.R. Pansuriya, N.P. Talpada, RSC
Adv. 3, 8064 (2013)
4
.
33. H. Mecadon, M. R. Rohman, M. Rajbangshi, B. Myrboh. Tetra-
2
48, 122 (2014)
hedron Lett. 52, 2523 (2011)
34. Litvinov YM, Shestopalov AA, Rodinovskaya LA, Shestopalov
AM, J. Comb. Chem. 914 (2009)
35. G. Vasuki, K. Kumaravel, Tetrahedron Lett. 49, 5636 (2008)
36. D. Shi, J. Mou, Q. Zhuang, L. Niu, N. Wu, X. Wang, Synth.
Commun. 34, 4557 (2004)
5
6
.
.
P.B. Oshiro, P.S. Lima, M.L. de Menezes, L.C. da Silva-Filho,
Tetrahedron Lett. 56, 4476 (2015)
M.A. Terzidis, V.G. Tsiaras, N.M. Drosos, P.M. Kasapidou, J.
Stephanidou-Stephanatou, C.A. Tsoleridis, G. Buth, G.E. Kosta-
kis, Tetrahedron Lett. 55, 5601 (2014)
L.G. Voskressensky, Chem. Heterocycl. Comp. 48, 535 (2012)
M.G. Dekamin, M. Eslami, Green Chem. 16, 4914 (2014)
M.G. Dekamin, M. Eslami, A. Maleki, Tetrahedron 69, 1074
7
8
9
.
.
.
37. T.S. Jin, A.Q. Wang, Z.L. Cheng, J.S. Zhang, T.S. Li, Synth.
Commun. 35, 137 (2005)
38. Y. Peng, G. Song, R. Dou, Green Chem. 8, 573 (2006)
39. K. Kanagaraj, K. Pitchumani, Tetrahedron Lett. 51, 3312 (2010)
40. H.V. Chavan, S.B. Babar, R.U. Hoval, B.P. Bandgar, Bull.
Korean Chem. Soc. 32, 3963 (2011)
41. S.R. Mandha, S. Siliveri, M. Alla, V.R. Bommena, M.R. Bom-
mineni, S. Balasubramanian, Bioorg. Med. Chem. Lett. 22, 5272
(2012)
42. A. Siddekha, A. Nizam, M.A. Pasha, Spectrochim. Acta. A. 81,
431 (2011)
43. M. Bihani, P. P. Bora, G. Bez, J. Chem. 2013, 8 (2013).
doi:10.1155/2013/920719
(
2013)
0. M.G. Dekamin, M. Azimoshan, L. Ramezani, Green Chem. 15,
11 (2013)
1. S. Shaaban, B. Abdel-Wahab, Mol. Divers. (2015). doi:10.1007/
s11030-015-9602-6
1
1
8
1
1
2. Y. Huang, A. Dömling, Mol. Divers. 15, 3 (2011)
3. C.C. Musonda, D. Taylor, J. Lehman, J. Gut, P.J. Rosenthal, K.
Chibale, Bioorg. Med. Chem. Lett. 14, 3901 (2004)
4. N. Sudhapriya, P.T. Perumal, C. Balachandran, S. Ignacimuthu,
M. Sangeetha, M. Doble, Eur. J. Med. Chem. 83, 190 (2014)
5. G. Mohammadi Ziarani, S. Faramarzi, N. Lashgari, A. Badiei, J.
Iran Chem. Soc. 11, 701 (2014)
1
1
1
44. S. Gogoi, C.G. Zhao, Tetrahedron Lett. 50, 2252 (2009)
6. O. Hosseinchi Qareaghaj, S. Mashkouri, M.R. Naimi-Jamal, G.
Kaupp, RSC Adv. 4, 48191 (2014)
1
3