Aza-Michael-type addition reaction catalysed by a supported ionic liquid phase incorporating an anionic heteropoly acid

Article abstract of DOI:10.1016/j.tetlet.2016.01.107

In this work, we have obtained substituted amines under mild conditions in good yields using the Aza-Michael-type addition of various amines to vinyl compounds catalysed by a supported ionic liquid incorporating an anionic heteropoly acid. Different catalysts, including Lewis acids, Br?nsted acids and heteropoly acids were investigated in which heteropoly acids having dual Br?nsted and Lewis acid characteristics were excellent catalysts. The ionic liquid incorporating a polytungstate anion supported on magnetic diatomaceous earth as a magnetically separable heterogeneous catalyst offered the best results in terms of yield. The solid nanocatalyst was easily removed with a magnet.

Full text of DOI:10.1016/j.tetlet.2016.01.107

Tetrahedron Letters 57 (2016) 1150–1153
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Tetrahedron Letters
journal homepage: www.elsevier.com/locate/tetlet
Aza-Michael-type addition reaction catalysed by a supported ionic
liquid phase incorporating an anionic heteropoly acid
b
Mohammad Hadi Ghasemi a, Elaheh Kowsari a, , Abbas Shafiee
⇑
a Department of Chemistry, Amirkabir University of Technology, Hafez Avenue, No. 424, PO Box: 159163-4413, Tehran, Iran
b Department of Medicinal Chemistry and Pharmaceutical Sciences Research Center, Tehran University of Medical Sciences, PO Box: 14155-6451, Tehran 14176, Iran
a r t i c l e i n f o
a b s t r a c t
Article history:
In this work, we have obtained substituted amines under mild conditions in good yields using the Aza-
Michael-type addition of various amines to vinyl compounds catalysed by a supported ionic liquid incor-
porating an anionic heteropoly acid. Different catalysts, including Lewis acids, Brønsted acids and hetero-
poly acids were investigated in which heteropoly acids having dual Brønsted and Lewis acid
characteristics were excellent catalysts. The ionic liquid incorporating a polytungstate anion supported
on magnetic diatomaceous earth as a magnetically separable heterogeneous catalyst offered the best
results in terms of yield. The solid nanocatalyst was easily removed with a magnet.
Received 26 November 2015
Revised 23 January 2016
Accepted 29 January 2016
Available online 4 February 2016
Keywords:
Aza-Michael-type addition
Supported ionic liquid
Magnetic support
Diatomaceous earth
Heteropoly acid
Ó 2016 Elsevier Ltd. All rights reserved.
The Aza-Michael-type addition has been catalysed by many
different acids and bases; however side reactions often occur.1
Therefore, efficient approaches are needed for the development
of mild catalysts for the Aza-Michael-type addition. A number of
alternative methodologies using catalysts such as metallic oxides,2
transition metals,3 lanthanides,4 perchloric acid,5 silica gel,6
cyclodextrin,7 organometallics,8 ionic liquids,9 solvent free condi-
tions10 and water as a solvent without any catalyst11 have been
reported. Recently, immobilization of homogeneous catalysts to
develop heterogeneous catalysts has seen increased importance.
Despite the fact that immobilized catalysts have various benefits
over typical catalysts, the recovery and separation of these cata-
lysts are quite difficult. In order to deal with this challenge, the
use of magnetic nanocatalysts is one of the most attractive and
applicable alternatives. These nanocatalysts can be recovered from
the reaction mixture by employing an external magnetic field.
Polytungstic acid, a heteropoly acid (HPA), is an active catalyst
for various reactions.12 It is an excellent catalyst due to its high
acidic power and thermal stability.13 More recently, ionic liquids
(IL) incorporating anionic heteropoly acid derivatives have been
studied as catalysts.14 Herein, a supported IL strategy has been
applied for the immobilization of a Keggin phosphotungstate
tally-friendly catalyst for the Aza-Michael-type addition of amines
to vinyl compounds at ambient temperature is reported
(Scheme 1).
Experiments were performed to find the best conditions for the
Aza-Michael-type addition of 2-vinyl pyridine and aniline as a
model reaction. In the absence of catalyst the reaction did not
occur (Table 1, entry 1). Different catalysts including Lewis acids
(Table 1, entries 2–4), Brønsted acids (Table 1, entries 5–7) and
heteropoly acids (Table 1, entries 8–11) were then examined.
Among the various acids, heteropoly acids (HPAs) were excellent
catalysts in the reaction of 2-vinyl pyridine and aniline. These
catalysts have dual Brønsted and Lewis acid characteristics and
promote the reaction of 2-vinyl pyridine. The activity of HPAs as
a catalyst is controlled by the amount of Lewis-acid sites on the
surface. Among the examined heteropoly acids, the best results
were obtained using phosphotungstic acid (Table 1, entries 10
and 11). It seems that the addition of phosphotungstic acid could
provide more active Lewis acid sites for the activation of 2-vinyl
pyridine in the Aza-Michael-type reaction. Higher reaction rates
were also observed with ILs possessing high dielectric constants.
In order to immobilize the polytungstate anion (PW),
a
supported IL strategy was applied. For this purpose, an IL
anion on magnetic diatomaceous earth (DE) as
a support
Fe3O4@DE@bmim3PW and its use as an efficient and environmen-
H
N
N
N
NPs-Fe3O4@DE@bmim3PW
R
+
R-NH2
⇑
Corresponding author. Tel.: +98 21 64543295; fax: +98 21 64543296.
E-mail address: kowsarie@aut.ac.ir (E. Kowsari).
Scheme 1. Addition of amines to 2-vinyl pyridine using Fe3O4@DE@bmim3PW.
http://dx.doi.org/10.1016/j.tetlet.2016.01.107
0040-4039/Ó 2016 Elsevier Ltd. All rights reserved.

M. H. Ghasemi et al. / Tetrahedron Letters 57 (2016) 1150–1153
1151
Table 1
incorporating the anionic polytungstate (bmim3PW) was prepared
in which the polytungstate anion (PW) was exchanged with ClÀ in
1-butyl-3-methylimidazolium chloride ([bmim]ClÀ).15 In the next
step, the IL was supported on magnetic diatomaceous earth (DE)
to produce NPs-Fe3O4@DE@bmim3PW (1).16 The catalytic perfor-
mance of the supported catalyst 1 for the direct addition of alky-
lamines to 2-vinyl pyridine was more remarkable than the ionic
liquid or NPs-Fe3O4@DE individually (Table 2). The best results
were obtained when equimolar amounts of amines and 2-vinyl
pyridine were used in the presence of 1 as the catalyst (Table 2,
entries 6 and 7). The synthesized alkylamine was easily isolated
in good yield and purity by filtration of the precipitated solid after
evaporation. The paramagnetic nanoparticles could be easily
removed with a magnet before evaporation of the solvent.
The presented method was shown to be applicable for the
Aza-Michael-type addition using a wide range of amines, such as
highly nucleophilic primary alkylamines and deactivated anilines,
to vinyl compounds such as 4-vinyl pyridine, 2-vinyl imidazole
and 2-vinyl pyridine (Scheme 2, Table 3).17 As shown in Table 3,
the Aza-Michael-type addition of amines provided the products
with high yields. Presumably, this is due to vinyl activation by
the vicinal nitrogen.
The reusability of catalyst 1 was investigated in the reaction of
2-vinylpyridine with aniline. In order to evaluate the stability and
recyclability, the catalyst was recovered by applying a magnetic
field and the collected solid was washed with THF, dried at 50 °C
for 6 h and reused in the next reaction. The catalyst was used for
5 reactions without any significant decrease in activity. Although
there is a possibility of IL leakage into the liquid phase, due to
the relatively strong interactions between the polar ionic liquid
phase and outer surfaces of the solid support this leakage is
minimized. Therefore, the catalyst activity remains without any
significant reduction in activity.
Reaction of 2-vinylpyridine with aniline using various catalystsa
Entry
Catalyst
Time (h)
Yieldb (%)
1
2
3
4
5
6
7
8
—
24
4
4
4
4
4
4
4
4
4
2
—
FeCl3Á6H2O
FeCl2Á4H2O
NPs-Fe3O4
H2SO4
43
35
45
55
32
35
65
72
90
85
H3PO4
CH3COOH
H3PMo12O40
H4SiW12O40
H3PW12O40
H3PW12O40
9
10
11
a
Reaction conditions: 2-vinylpyridine (0.54 mL, 5 mmol, 1 equiv), aniline
(0.46 mL, 5 mmol, 1 equiv), catalyst (3 mol %), CH2Cl2 (5 mL), rt.
b
Isolated yield.
Table 2
IL catalysed reaction of 2-vinylpyridine (A) with aniline (B)a
Entry Catalyst
Mole ratio (A/
B)
Time
(h)
Yieldb
(%)
1
2
3
4
5
6
[bmim]ClÀ
1:2
1:2
1:1
1:2
1:1
1:1
4
4
4
4
4
4
Trace
65
50
81
75
NPs-Fe3O4@DE@[bmim]ClÀ
NPs-Fe3O4@DE@[bmim]ClÀ
bmim3PW
bmim3PW
NPs-Fe3O4@DE@bmim3PW
(1)
93
7
NPs-Fe3O4@DE@bmim3PW
(1)
1:1
2
90
a
Reactions conditions: CH2Cl2 (5 mL), catalyst (3 mol %), rt.
Isolated yield.
b
In this Letter, the effect of different catalysts on the
Aza-Michael-type addition reaction was investigated. Among the
various catalysts used, the best results were achieved using
the IL bmim3PW which was physically supported on magnetic
diatomaceous earth furnishing a magnetically separable catalyst.
The activity may be due to a synergistic effect of the ionic liquid
incorporating the polytungstate anion and the magnetic solid
support. In conclusion, a simple and mild procedure for the
Aza-Michael-type addition of various amines to activated vinyl
NPs-Fe3O4@DE@bmim3PW
CH2Cl2, RT, 2 h
R2
N
R2R3NH
R1
R1
R3
+
N
R1
=
N
N
N
Scheme 2. Aza-Michael-type addition of various amines to vinyl compounds.
Table 3
Catalytic Aza-Michael-type addition of various amines to vinyl compounds
Entry
Amine
Producta
Yieldb (%)
NH2
H
N
N
1a
1b
1c
95
95
95
H
N
1
N
H
N
N
NH
H
N
N
2a
2b
2c
91
94
H
N
2
MeNH2 (40% aq)
N
H
N
N
N
83
(continued on next page)

1152
M. H. Ghasemi et al. / Tetrahedron Letters 57 (2016) 1150–1153
Table 3 (continued)
Entry
Amine
Me2NH
H2N
Producta
Yieldb (%)
85
N
N
3a
3b
3c
N
3
90
89
N
N
N
N
H
N
N
SO2NH2
4a
4b
93
95
SO2NH2
4
5
H
N
N
SO2NH2
O
N
N
N
H2N
SO2NHAc
5a
71
S
NHAc
O
N
H
N
H2N
N
N
6a
6b
75
83
S
S
S
6
7
H
N
N
H2N
N
N
H
N
N
N
N
7a
8a
8b
80
92
88
N
N
N
HN
8
N
NH2
H
N
N
9a
9b
75
78
9
H
N
N
N
NH2
NH2
H
N
COOH
10
11
10b
95
COOH
H
N
N
11a
11b
83
94
N
N

M. H. Ghasemi et al. / Tetrahedron Letters 57 (2016) 1150–1153
1153
Table 3 (continued)
Entry
Amine
Producta
Yieldb (%)
H
N
N
N
12a
12b
90
95
12
N
N
O
O
O
HN
N
N
N
13a
13b
85
79
13
N
a
Reaction conditions: vinyl compound (5 mmol, 1 equiv), amine (5 mmol, 1 equiv), catalyst (3 mol %), CH2Cl2 (5 mL), rt, 2 h.
Isolated yield.
b
7. Surendra, K.; Krishnaveni, N. S.; Sridhar, R.; Rao, K. R. Tetrahedron Lett. 2006, 47,
2125–2127.
8. Pettersen, D.; Piana, F.; Bernardi, L.; Fini, F.; Fochi, M.; Sgarzani, V.; Ricci, A.
Tetrahedron Lett. 2007, 48, 7805–7808.
9. (a) Chen, X.; Li, X.; Song, H.; Qian, Y.; Wang, F. Tetrahedron Lett. 2011, 52, 3588–
3591; (b) Chelghoum, M.; Bahnous, M.; Bouraiou, A.; Bouacida, S.; Belfaitah, A.
Tetrahedron Lett. 2012, 53, 4059–4061; (c) Yang, L.; Xu, L. W.; Zhou, W.; Li, L.;
Xia, C. G. Tetrahedron Lett. 2006, 47, 7723–7726.
compounds containing a nitrogen in the aromatic ring is reported.
This method is applicable to a wide variety of amines, and is a use-
ful alternative to other methods in the literature. Moreover, the
absence of side products such as polymers is an advantage of this
approach as polymerization is usually found with Brønsted acid
catalysts.18
10. (a) Ying, A. G.; Liu, L.; Wu, G. F.; Chen, G.; Chen, X. Z.; Ye, W. D. Tetrahedron Lett.
2009, 50, 1653–1657; (b) Huang, C.; Yin, Y.; Guo, J.; Wang, J.; Fan, B.; Yang, L.
RSC Adv. 2014, 4, 10188–10195.
Acknowledgments
11. (a) Matveeva, E. V.; Shipov, A. E.; Petrovskii, P. V.; Odinets, I. L. Tetrahedron Lett.
2011, 52, 6562–6565; (b) Ranu, B. C.; Banerjee, S. Tetrahedron Lett. 2007, 48,
141–143; Gawande, M. B.; Bonifácio, V. D. B.; Luque, R.; Branco, P. S.; R. Varma,
S. Chem. Soc. Rev. 2013, 42, 5522–5551.
The authors wish to gratefully thank the Research Affairs
Division at Amirkabir University of Technology (AUT), Tehran, for
financial support.
12. Kozhevnikov, I. V. Chem. Rev. 1998, 98, 171–198.
13. (a) Jafarzadeh, M.; Amani, K.; Nikpour, F. Tetrahedron Lett. 2005, 46, 7567–
7569; (b) Nikbakht, F.; Heydari, A.; Saberi, D.; Azizi, K. Tetrahedron Lett. 2013,
54, 6520–6523; (c) Narkhede, N.; Singh, S.; Patel, A. Green Chem. 2015, 17, 89–
107; (c) Drago, R. S.; Dias, J. A.; Maier, T. J. Am. Chem. Soc. 1997, 119, 7702–
7710.
14. (a) Fu, R.; Yang, Y.; Ma, Y.; Yang, F.; Li, J.; Chai, W.; Wang, Q.; Yuan, R.
Tetrahedron Lett. 2015, 56, 4527–4531; (b) Doherty, S.; Knight, J. G.; Ellison, J.
R.; Weekes, D.; Harrington, R. W.; Hardacre, C.; Manyar, H. Green Chem. 2012,
14, 925–929; (c) Alvim, H. G. O.; Bataglion, G. A.; Ramos, L. M.; de Oliveira, A. L.;
de Oliveira, H. C. B.; Eberlin, M. N.; de Macedo, J. L.; da Silva, W. A.; Neto, B. A. D.
Tetrahedron 2014, 70, 3306–3313; (d) Leng, Y.; Wang, J.; Zhu, D.; Ren, X.; Ge, H.;
Shen, L. Angew. Chem., Int. Ed. 2009, 48, 168–171.
Supplementary data
Supplementary data associated with this article can be found, in
the online version, at http://dx.doi.org/10.1016/j.tetlet.2016.01.
107.
References and notes
1. Ying, A. G.; Wang, L. M.; Deng, H. X.; Chen, J. H.; Chen, X. Z.; Ye, W. D. ARKIVOC
2009, xi, 288–298.
15. Yamaguchi, K.; Yoshida, C.; Uchida, S.; Mizuno, N. J. Am. Chem. Soc. 2005, 127,
530–531.
2. (a) Kantam, M. L.; Laha, S.; Yadav, J.; Jha, S. Tetrahedron Lett. 2009, 50, 4467–
4469; (b) Cheng, T.; Zhang, D.; Li, H.; Liu, G. Green Chem. 2014, 16, 3401–3427;
(c) Zare, A.; Hasaninejad, A.; Khalafi-Nezhad, A.; Zare, A. R. M.; Parhami, A.;
Nejabat, G. R. ARKIVOC 2007, i, 58–59; (d) Zare, A.; Hasaninejad, A.; Khalafi-
Nezhad, A.; Zare, A. R. M.; Parhami, A. ARKIVOC 2007, xiii, 105–115.
3. (a) Ferraccioli, R.; Carenzi, D.; Catellani, M. Tetrahedron Lett. 2004, 45, 6903–
6907; (b) Kobayashi, S.; Kakumoto, K.; Sugiura, M. Org. Lett. 2002, 4, 1319–
1322; (c) Xu, L. W.; Li, J. W.; Xia, C. G.; Zhou, S. L.; Hu, X. X. Synlett 2003,
2425–2427.
4. (a) Duan, Z.; Xuan, X.; Li, T.; Yang, C.; Wu, Y. Tetrahedron Lett. 2006, 47, 5433–
5436; (b) Reboule, I.; Gil, R.; Collin, J. Tetrahedron Lett. 2005, 45, 7761–7764; (c)
Matsubara, S.; Yoshiyoka, M.; Utimoto, K. Chem. Lett. 1994, 23, 827–830; (d)
Bartoli, G.; Bosco, M.; Marcantoni, E.; Petrini, M.; Sanbri, L.; Torregiani, E. J. Org.
Chem. 2001, 66, 9052–9055.
16. Preparation method and characterization of the immobilized ionic liquid on
magnetic diatomaceous earth (NPs-Fe3O4@DE@bmim3PW, 1) are provided in
the ESI.
17. General procedure for the Aza-Michael-type addition: 2-vinyl pyridine (0.53 g,
0.54 mL, 5 mmol, 1 equiv) and aniline (0.47 g, 0.46 mL, 5 mmol, 1 equiv) were
added to a solution of catalyst 1 (3 mol %) in dichloromethane (5 mL) and
stirred at room temperature for 2 h. The progress of the reaction was
monitored by TLC. After reaction completion, the catalyst was separated
using a magnet and the solvent removed by evaporation. The residue was
added to a toluene/aqueous NaOH (33%) (1:1) biphasic system to remove
impurities. The organic layer was separated and evaporated. The precipitate
was filtered off, washed with acetone (5 mL) and dried to afford phenyl-(2-
pyridin-2-yl-ethyl)-amine as a light brown solid. No further purification was
required (1.35 g, 90%). All new compounds were characterized using mp, 1H
NMR, 13C NMR, IR and MS analysis (see ESI).
5. (a) Azizi, N.; Saidi, M. R. Tetrahedron 2004, 60, 383–387; (b) Mukherjee, C.;
Misra, A. K. Lett. Org. Chem. 2007, 4, 54–59.
6. You, L. S.; Feng, S.; An, R.; Wang, X. H.; Bai, D. L. Tetrahedron Lett. 2008, 49,
5147–5149.
18. Susan, M. A. B. H.; Kaneko, T.; Noda, A.; Watanabe, M. J. Am. Chem. Soc. 2005,
127, 4976–4983.