Green synthesis of a nano salt and its application as multifunctional organocatalyst for Knoevenagel condensation

Article abstract of DOI:10.1007/s11164-017-2998-0

1,2-Ethanediammonium 3-hydroxypropane-1-sulfonate [(EDA)(HPS)] as a novel nano multifunctional organosalt was synthesized via a simple and green chemical route and characterized using various techniques such as proton nuclear magnetic resonance (¹

Full text of DOI:10.1007/s11164-017-2998-0

Res Chem Intermed
DOI 10.1007/s11164-017-2998-0
Green synthesis of a nano salt and its application
as multifunctional organocatalyst for Knoevenagel
condensation
Moones Honarmand1
Received: 7 August 2016 / Accepted: 6 June 2017
Ó Springer Science+Business Media B.V. 2017
Abstract 1,2-Ethanediammonium 3-hydroxypropane-1-sulfonate [(EDA)(HPS)] as
a novel nano multifunctional organosalt was synthesized via a simple and green
chemical route and characterized using various techniques such as proton nuclear
magnetic resonance (1H NMR), thermogravimetric analysis (TGA), scanning
electron microscopy (SEM), transmission electron microscopy (TEM), and ele-
mental analysis. [(EDA)(HPS)] was successfully applied as a multifunctional
organocatalyst in Knoevenagel reaction of aryl/heteroaryl/alkyl aldehydes or
ketones with active methylene compounds. The hydroxyl and ammonium groups in
the structure of [(EDA)(HPS)] showed interesting effects on its catalytic efficiency.
[(EDA)(HPS)] was also recovered and reused five times without significant decrease
in activity. TEM and elemental analysis of the recovered catalyst after five reaction
cycles confirmed its durability and high stability under the applied reaction
conditions.
Keywords Nano Á Multifunctional Á Organocatalyst Á Knoevenagel
condensation
Introduction
Over the past decade, much research has focused on nanostructured materials,
because of their unique structural and textural properties [1, 2]. Different
synthetic techniques have been applied for preparation of nanostructured
materials, including sonochemical, sol–gel, precipitation, solid-state reaction,
&
Moones Honarmand
honarmand@birjandut.ac.ir; honarmand.moones@yahoo.com
1
Department of Chemical Engineering, Faculty of Mining, Civil and Chemical Engineering,
Birjand University of Technology, Birjand 97175/569, Iran
123

M. Honarmand
microwave irradiation, alcohothermal, and electrochemical methods [3, 4].
Although these protocols are valuable, most of them suffer from one or more
disadvantage such as long reaction time, high temperature, harsh reaction
conditions, low yield, or use of expensive, toxic, and hazardous stabilizers or
solvents. To overcome these drawbacks, much attention has been paid to
development of green and ecofriendly methods for synthesis of nanostructured
materials. Green synthetic protocols are generally simple and use nontoxic and
safe solvents.
Ammonium salts are well known as nerve-blocking agents in brain surgery,
disinfectants, sterilants, and surfactants [5]. In recent years, ammonium salts have
attracted considerable attention as organocatalysts owing to their negligible vapor
pressure, good solvating capability, tunable polarity, excellent thermal stability, and
ease of recyclability [6, 7]. Recently, Kumari et al. [8] synthesized nano ammonium
perchlorate, albeit by a harsh and time-consuming chemical route. Thus, it would be
preferable to introduce a green and simple method (not using expensive and
hazardous solvents, stabilizers, or high-temperature calcination) for synthesis of
nano ammonium salts.
Knoevenagel condensation is one of the most important reactions for synthesis
of valuable compounds that are widely used to prepare fine chemical
intermediates, herbicides, insecticides, cosmetics, perfumes, polymers, and
therapeutic drugs [9–11]. In Knoevenagel condensation, carbon–carbon double
bonds form through the reaction of carbonyl compounds with activated
methylenes in presence of different catalysts [12–15]. However, most reported
protocols suffer from inherent drawbacks related to use of organic solvents and
expensive catalysts, laborious and complex reaction workup, difficult catalyst
recovery, and environmental pollution. Therefore, the search for new catalysts
for Knoevenagel condensation reaction remains a topic of interest in synthetic
organic chemistry.
In continuation of our research work on use of new catalysts for organic reactions
[16–19], we present herein, for the first time, synthesis of 1,2-ethanediammonium
3-hydroxypropane-1-sulfonate [(EDA)(HPS)] as a nano organosalt via a simple and
green chemical route (Scheme 1). To explore the catalytic activity of
[(EDA)(HPS)], we used it as a novel, green, and reusable nanocatalyst for
Knoevenagel condensation. [(EDA)(HPS)] is a suitable catalyzing agent due to the
hydroxyl groups on the anionic moieties and ammonium groups on the cationic
moiety and can act as a multifunctional organocatalyst.
Scheme 1 Synthesis of [(EDA)(HPS)]
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Green synthesis of a nano salt and its application as…
Experimental
General information
Chemicals were purchased from Merck Chemical Company and used as received.
NMR spectra were recorded on a Bruker Avance DPX-400 using deuterated
dimethylsulfoxide (DMSO)-d6 and D2O as solvent and tetramethylsilane (TMS) as
internal standard. Melting points were determined using a Bu¨chi 510 apparatus and
are uncorrected. Product purity and reaction progress were assessed by thin-layer
chromatography (TLC) on silica gel POLYGRAM SIL G/UV254 plates. Elemental
analysis was carried out using an ECS4010 CHNSO analyzer. A Shimadzu
thermogravimetric analyzer (TG-50) was applied to characterize the gravimetric
(TG) behavior of the [(EDA)(HPS)] nano salt. TEM analysis was performed using a
Philips CM30. Product morphology was investigated by scanning electron
microscopy (SEM, model s4160; Hitachi, Japan) at accelerating voltage of 15 kV.
Large-scale synthesis of [(EDA)(HPS)]
Solution of 3-hydroxypropyl sulfonic acid (100 mmol, 14.00 g) in water (60 mL)
was added dropwise to aqueous solution of ethylenediamine (100 mmol, 7.412 g) at
room temperature. Stirring of the resultant solution was continued for another 20 h
at the same condition, then water was removed by distillation under reduced
pressure and the residue was dried at room temperature to obtain [(EDA)(HPS)] as
white solid (m.p. 298 °C).
Knoevenagel condensation reaction using [(EDA)(HPS)] organocatalyst
[(EDA)(HPS)] (10 mol%, 0.0340 g) was added to stirred mixture of aldehyde
(1 mmol) and active methylene compounds (1.2 mmol) at 60 °C under solvent-free
condition. The reaction mixture was stirred for appropriate time (Table 2). Reaction
progress was monitored by TLC. After reaction completion, warm ethanol (5 mL)
was added to the reaction mixture. The organocatalyst was filtered and completely
washed with warm ethanol (2 9 10 mL), then dried at room temperature. Solvent in
the remaining solution was evaporated under reduced pressure to give crude
products. Pure products were obtained by recrystallization in aqueous ethanol.
2-(Phenylmethylene)malononitrile M.p. 83–84 °C; 1H NMR (400 MHz, CDCl3):
d 7.54 (2H, t, J = 8.0 Hz, Ar), 7.64 (1H, t, J = 7.6 Hz, Ar), 7.79 (1H, s, CH=), 7.92
(2H, d, J = 7.6 Hz, Ar).
Recovery of [(EDA)(HPS)] organocatalyst after Knoevenagel condensation
reaction
[(EDA)(HPS)] (10 mol%, 0.170 g) was added to a stirred mixture of benzaldehyde
(5 mmol) and malononitrile (5.2 mmol) at 60 °C under solvent-free condition. The
reaction mixture was stirred for 50 min. After reaction completion, warm ethanol
123

M. Honarmand
(5 mL) was added to the reaction mixture. The organocatalyst was filtered and
completely washed with ethanol (2 9 10 mL), then dried at room temperature.
[(EDA)(HPS)] organocatalyst was then reused in the same condition as above for at
least five reaction runs, delivering the corresponding Knoevenagel product in high
yield.
Results and discussion
Synthesis and characterization of 1,2-ethanediammonium
3-hydroxypropane-1-sulfonate [(EDA)(HPS)] as nano multifunctional
organosalt
1,2-Ethanediammonium 3-hydroxypropane-1-sulfonate [(EDA)(HPS)] was synthe-
sized as novel nano multifunctional organosalt from cheap and readily available
starting materials. An important advantage of this nanocatalyst is the safe and
simple procedure for its preparation. The synthesized [(EDA)(HPS)] was charac-
1
terized by H NMR, elemental analysis, TGA, SEM, and TEM.
1
The H NMR spectra of [(EDA)(HPS)] in DMSO-d6 and D2O are shown in
Fig. 1. Hydrogens of methylene groups in anionic moieties appeared at
d = 1.77–1.84, 2.51–2.57, and 3.37–3.45 ppm. Presence of a singlet peak at
d = 3.08 ppm was attributed to C–H hydrogens of cationic moiety. Two broad
singlets at d = 3.37 and 8.01 ppm were assigned to OH and NH3 protons,
respectively. The latter assignment was confirmed by D2O exchange, which showed
a missing peak due to NH3 protons. Peaks were exchanged at 3.37 and 3.54 ppm,
related to exchange of OH protons in presence of D2O (Fig. 2b). These results are in
good agreement with the elemental analysis data (anal. calcd. for C8H24N2O8S2:
N = 8.23, C = 28.23, H = 7.11, S = 18.84 %; found: N = 8.27, C = 28.20,
H = 7.15, S = 18.89 %).
Thermogravimetric (TG) analysis was applied to determine the thermal stability
of [(EDA)(HPS)] (Fig. 2). According to the TGA results, [(EDA)(HPS)] was very
stable and showed no evident weight loss below 301 °C.
The size, shape, and morphology of [(EDA)(HPS)] nano organosalt were studied
by scanning electron microscopy (SEM) and transmission electron microscopy
(TEM).
SEM of [(EDA)(HPS)] revealed the morphology of the organosalt (Fig. 3).
Considering the TEM image (Fig. 4), [(EDA)(HPS)] had spherical morphology with
relatively good monodispersity. The particle size of [(EDA)(HPS)] was evaluated
based on the TEM results and found to be about 10 nm.
Catalytic activity of [(EDA)(HPS)] nano multifunctional organosalt
in Knoevenagel condensation reaction
After characterization, we studied application of [(EDA)(HPS)] nano multifunc-
tional organosalt as catalyst for Knoevenagel condensation reaction of benzalde-
hyde and malononitrile as model reaction under different conditions. Systematic
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Green synthesis of a nano salt and its application as…
Fig. 1 1H NMR spectra of [(EDA)(HPS)] in a DMSO-d6 and b D2O
investigation of temperature was performed in the range of 25–70 °C in presence of
10 mol% [(EDA)(HPS)] under solvent-free condition. The results are presented in
Table 1. As can be seen from Table 1, the best yield and conversion rate were
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M. Honarmand
100
80
60
40
20
0
Fig. 2 Thermogravimetric
(TG) analysis of [(EDA)(HPS)]
0
100
200
300
400
500
600
Temperature (°C)
Fig. 3 SEM of [(EDA)(HPS)]
(b)
20
(a)
10
0
6
10
14
20
24
Particle size (nm)
Fig. 4 a TEM and b particle size distribution of [(EDA)(HPS)]
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Green synthesis of a nano salt and its application as…
Table 1 Knoevenagel condensation reaction of benzaldehyde and malononitrile under different
condition
Entry
Catalyst
Amount of catalyst (mol%)
Temperature (°C)
Time (h)
Yield (%)a
1
2
3
4
5
6
7
[(EDA)(HPS)]
[(EDA)(HPS)]
[(EDA)(HPS)]
[(EDA)(HPS)]
[(EDA)(HPS)]
[(EDA)(HPS)]
–
10
10
10
10
5
25
50
60
70
60
60
60
6
82
87
95
95
91
90
19
4
50 min
50 min
3
2.5
–
4
12
Reaction conditions: molar ratio of benzaldehyde:malononitrile: 1:1.2
a
Isolated yield
obtained at 60 °C (Table 1, entry 3). Increasing the reaction temperature to 70 °C
had no effect on the product yield or reaction time (Table 1, entry 4). The impact of
the amount of catalyst was also investigated (Table 1, entries 5, 6), revealing that
the best result was obtained in presence of 10 mol% [(EDA)(HPS)] organosalt
(Table 1, entry 3). To demonstrate the role of the catalyst, Knoevenagel conden-
sation reaction of benzaldehyde and malononitrile was also examined in absence of
catalyst at 60 °C. Under these conditions, the reaction led to formation of the
desired product in low yield (19 %) after 12 h (Table 1, entry 7). The obtained
results show that presence of catalyst and appropriate temperature together
improved this reaction.
With the optimized conditions in hand (10 mol% catalyst at 60 °C under solvent-
free condition), the scope of this novel organocatalyst was examined in Knoeve-
nagel reaction of various aldehydes or ketones with active methylene compounds.
The results of these studies are summarized in Table 2. Generally, all reactions were
clean and the desired products were produced in excellent yields. Reaction of
benzaldehyde with activated methylene compounds such as malononitrile, ethyl
cyanoacetate, and cyanoacetamide proceeded well and produced the desired
products in 91–95 % yields (Table 2, entries 1–3). [(EDA)(HPS)] was equally
effective with substituted benzaldehydes bearing electron-releasing and electron-
withdrawing groups, and the Knoevenagel reaction proceeded with excellent yield
of the desired products (Table 2, entries 4–10). Interestingly, [(EDA)(HPS)]
organosalt efficiently promoted Knoevenagel condensation reaction when using
acid-sensitive aldehydes such as thiophene-2-carbaldehyde and furfural without
polymerization or decomposition (Table 2, entries 11, 12). [(EDA)(HPS)] organos-
alt was also successfully applied for Knoevenagel reaction of malononitrile with t-
butyraldehyde and 3-phenylpropionaldehyde as aliphatic aldehydes (Table 2,
entries 13, 14). It is noteworthy that benzophenone and acetophenone reacted with
malononitrile to produce the desired products in high yields (Table 2, entries 15,
16).
To investigate the effect of hydroxyl and amine functional groups in the structure
of [(EDA)(HPS)] on the catalytic process, different organosalts with OH-free
123

M. Honarmand
Table 2 Knoevenagel condensation reaction of various aldehydes or ketones with activated methylene
compounds in presence of [(EDA)(HPS)] organocatalyst
Entry
R
R0
X
Time (h) Yield (%)a M.p. (°C)/m.p. (°C) [References]
1
C6H5
H
H
H
H
H
H
H
H
H
H
H
H
H
H
CN
50 min
2
95
92
91
96
92
91
91
93
94
91
93
92
90
93
90
92
83–84/82–83 [21]
52–53/49–50 [23]
121–122/123–124 [24]
142–143/140.2 [22]
115–116/114–115 [23]
187/190 [22]
2
C6H5
CO2Et
3
C6H5
CONH2 2.5
4
2-NO2C6H4
4-MeOC6H4
4-OHC6H4
4-ClC6H4
2-ClC6H4
4-BrC6H4
2-MeOC6H4
2-Thienyl
2-Furyl
CN
CN
CN
CN
CN
CN
CN
CN
CN
CN
CN
20 min
5
2.5
6
1.5
7
2.5
161/162.5–163.5 [24]
95–96/94–94.5 [24]
168/165–166 [25]
84/79–80 [26]
8
1
9
30 min
3
10
11
12
13
14
15
16
30 min
30 min
3
91–92/91–92 [23]
61–62/67–68 [23]
63/64–65 [25]
t-C4H9
C6H5(CH2)2
C6H5
45 min
2.5
129–130/127–129 [27]
141/143–144 [25]
91–92/94–96 [25]
C6H5 CN
CH3 CN
C6H5
3
Reaction conditions: molar ratio of carbonyl compound:malononitrile:catalyst = 1:1.2:0.1, 60 °C, sol-
vent-free condition
a
Isolated yield
anionic moieties and only a NH3 group on the cationic moiety were synthesized.
The catalytic activity of the synthesized organosalts was checked in Knoevenagel
condensation reaction of benzaldehyde and malononitrile under the optimized
reaction conditions. 1,2-Ethanediammonium methanesulfonate [(EDA)(MS)] and
1-ammonium 2-aminoethane methanesulfonate [(AAE)(MS)] as OH-free organos-
alts gave the desired product in 41 and 24 % yield after 12 h and 10 min,
respectively (Table 3, entries 1, 2). These results indicate that the hydroxyl
functional groups could affect the catalytic activity of the catalyst. On the other
hand, the catalytic activity of butan-1-ammonium 3-hydroxypropane-1-sulfonate
[(BA)(HPS)] and 2-aminoethane-1-ammonium 3-hydroxypropane-1-sulfonate
[(AEA)(HPS)] as organosalts with only one NH3 group was also studied, with the
desired product being obtained in 41 and 55 % yield after 12 h and 10 min,
respectively (Table 3, entries 3, 4). This low product yield in presence of
[(AAE)(MS)] and [(AEA)(HPS)] is due to formation of byproduct. These results
indicate that the catalytic activity of [(EDA)(HPS)] was affected by both ammonium
functional groups in the structure of the organosalt. For further investigation, butan-
1-aminium methanesulfonate [(BA)(MS)] as OH- and NH2-free organosalt was
synthesized and its catalytic activity examined. The Knoevenagel product was
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Green synthesis of a nano salt and its application as…
Table 3 Knoevenagel condensation reaction of benzaldehyde and malononitrile in the presence of
different organosalts
Entry
1b
Time
12 h
Yield (%)a
35
2c
3d
10 min
12 h
24
41
4e
10 min
12 h
55
23
5f
Reaction conditions: molar ratio of benzaldehyde:malononitrile:catalyst = 1:1.2:0.1, 60 °C, solvent-free
condition
a
Isolated yield
b
[(EDA)(MS)] as white solid
c
[(AAE)(MS)] as white solid
d
[(BA)(HPS)] as white semisolid
e
[(AEA)(HPS)] as pale-yellow semisolid
f
[(BA)(MS)] as white solid
synthesized in 23 % yield after 12 h (Table 3, entry 5). This result shows that the
hydroxyl functional groups on the anionic moieties and both NH3 groups on the
cationic moiety in the organosalt have significant effects on the Knoevenagel
reaction. Together, these results show that [(EDA)(HPS)] could act as a
multifunctional organocatalyst in this reaction.
Based on these observations, a mechanism (supported by literature [20]) for the
Knoevenagel reaction is outlined in Scheme 2. H-acidic malononitrile is activated
by the hydroxyl groups of the catalyst, and the carbonyl group of aldehyde is
activated by the ammonium groups of the catalyst. Then, malononitrile attacks the
carbonyl group of benzaldehyde to gave intermediate I, which after appropriate
rearrangements followed by dehydration gives the desired product.
In addition to green nature, catalyst recovery is an important factor in green
synthetic processes. Catalyst recovery was investigated using the reaction of
benzaldehyde with malononitrile under standard reaction conditions. The reaction
was very clean with no side-product formation, and the desired product was
obtained in excellent yield. After reaction completion, warm ethanol was added to
the reaction mixture and the organocatalyst was filtered, washed with ethanol, and
dried at room temperature. It was then used in the above-mentioned reaction under
123

M. Honarmand
Scheme 2 Suggested
mechanism for Knoevenagel
reaction in presence of
[(EDA)(HPS)]
Fig. 5 Reusability of
[(EDA)(HPS)] for synthesis of
2-benzylidenemalononitrile
100
80
60
40
20
0
Yield (%)
Time (min)
1
2
3
4
5
Run number
the same conditions as before. The results illustrated that [(EDA)(HPS)]
organocatalyst could be recovered and reused at least five times without significant
loss of the initial catalytic activity (Fig. 5).
According to TEM analysis combined with elemental analysis of the recovered
catalyst (Fig. 6) and comparison with the results obtained from fresh catalyst, it is
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Green synthesis of a nano salt and its application as…
Fig. 6 TEM of [(EDA)(HPS)]
after five recovery times
apparent that the [(EDA)(HPS)] organocatalyst exhibited remarkable morphological
and structural stability during the reaction and the recycling experiments.
Conclusions
For the first time, 1,2-ethanediammonium 3-hydroxypropane-1-sulfonate
[(EDA)(HPS)] was synthesized as a green and environmentally friendly nano
organosalt from readily available starting materials. [(EDA)(HPS)] was character-
ized by various techniques. Spectral and analysis data confirmed successful
formation of [(EDA)(HPS)]. TG analysis of [(EDA)(HPS)] showed that the
synthesized organosalt had high thermal stability up to 301 °C. TEM revealed that
[(EDA)(HPS)] had unique spherical morphology with size of 6–24 nm. Application
of [(EDA)(HPS)] as catalyst for Knoevenagel condensation reaction was studied.
The most important advantages of the presented approach are high yield, cleaner
reaction profile, and easy workup, as well as excellent recyclability of this
environmentally benign and cost-effective catalyst. Hence, our methodology
exhibits high generality, making it appropriate for industrial application.
Acknowledgements The author is profoundly grateful to Birjand University of Technology and Iran’s
National Elites Foundation for their support of this work.
References
1. B. Soghomon, F. Rasmus, in Catalysis in Molten Ionic Media, ed. by F. Lantelme, H. Groult
(Elsevier, Amsterdam, 2013), p. 131
2. S. Ravina, N.H. Singh, J. Biomed. Nanotechnol. 7, 489 (2011)
3. M.M. Khalaf, H.G. Ibrahimov, E.H. Ismailov, Chem. J. 2, 118 (2012)
4. M. Atarod, M. Nasrollahzadeh, S.M. Sajadi, J. Colloid Interface Sci. 465, 249 (2016)
5. H. Q. Smith, US Patent, US3148214 A (1964)
6. J.Q. Wang, K. Dong, W.G. Cheng, J. Sun, S. Zhang, J. Catal. Sci. Technol. 2, 1480 (2012)
7. M. Uyanik, H. Okamoto, T. Yasui, K. Ishihara, Science 328, 1376 (2010)
8. M.A. Kumari, S. Jain, M.K. Jain, B. Bhattacharya, J. Energ. Mater. 31, 192 (2013)
123

M. Honarmand
9. F. Freeman, Chem. Rev. 80, 329 (1980)
10. M.S. Volkova, K.C. Jensen, N.A. Lozinskaya, S.E. Sosonyuk, M.V. Proskurnina, A.D. Meseca, N.S.
Zefirov, Bioorg. Med. Chem. Lett. 22, 7578 (2012)
11. F.M. Moghaddam, Z. Mirjafary, M.J. Javan, S. Motamen, H. Saeidian, Tetrahedron Lett. 55, 2908
(2014)
12. L.F. Tietze, U. Beifuss, The Knoevenagel reaction, in Comprehensive Organic Synthesis, ed. by B.M.
Trost (Pergamon, Oxford, 1991)
´
´
´
13. A. Franconetti, P. Domınguez-Rodrıguez, D. Lara-Garcıa, R. Prado-Gotor, F. Cabrera-Escribano,
Appl. Catal. A Gen. 517, 176 (2016)
14. X. Dong, Y. Hui, S. Xie, P. Zhang, G. Zhou, Z. Xie, RSC Adv. 3, 3222 (2013)
´ˇ
ˇ ´
´
ˇ
´
15. M. Almasi, V. Zelenak, M. Opanasenko, I. Cısarova, Catal. Today 243, 184 (2015)
16. S. Sobhani, M. Honarmand, Synlett 24, 236 (2013)
17. S. Sobhani, Z. Mesbah Falatooni, M. Honarmand, RSC Adv. 4, 15797 (2014)
18. S. Sobhani, M. Honarmand, C. R. Chimie 16, 279 (2013)
19. S. Sobhani, M.S. Ghasemzadeh, M. Honarmand, Catal. Lett. 144, 1515 (2014)
20. C. Yue, A. Mao, Y. Wei, M. Lu, Catal. Commun. 9, 1517 (2008)
21. H. Sheibani, M. Babaie, Synth. Commun. 40, 257 (2010)
22. S.K. Panja, N. Dwivedi, S. Saha, RSC Adv. 5, 65526 (2015)
23. J.S. Yadav, B.V.S. Reddy, A.K. Basa, B. Visali, A.V. Narsaiah, K. Nagaiah, Eur. J. Org. Chem. 2004,
546 (2004)
24. D.Y. Wang, G.H. Xi, J.J. Ma, C. Wang, X.C. Zhang, Q.Q. Wang, Synth. Commun. 41, 3060 (2011)
25. K. Yamashita, T. Tanaka, M. Hayashi, Tetrahedron 61, 7981 (2005)
26. X. Gao, C. Gao, R. Gao, Asian J. Chem. 27, 2145 (2015)
27. A. Zhuo, D. Xian, W. Jian-wei, X. Hui, ISRN Org. Chem. 2011, 676789 (2011)
123