A novel L-asparaginyl Amido ethyl methyl imidazolium bromide catalyst for heterogeneous epoxidation of α, β-unsaturated ketones

Article abstract of DOI:10.1016/j.molliq.2012.05.016

In the present work, a class of imidazolium based ionic liquid coupled with asparagine system was employed for asymmetric epoxidation. The heterogeneous catalyst exhibited excellent activity for epoxidation of α, β-unsaturated ketones, affording the corre

Full text of DOI:10.1016/j.molliq.2012.05.016

Journal of Molecular Liquids 172 (2012) 136–139
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Journal of Molecular Liquids
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Short Communication
A novel L-asparaginyl Amido ethyl methyl imidazolium bromide catalyst for
heterogeneous epoxidation of α, β-unsaturated ketones
Parasuraman Karthikeyan, Aswar Sachin Arunrao, Muskawar Prashant Narayan, Sythana Suresh Kumar,
⁎
S. Senthil Kumar, Pundlik Rambhau Bhagat
Organic Chemistry Division, School of Advanced Sciences, VIT University, Vellore,-632 014, India
a r t i c l e i n f o
a b s t r a c t
Article history:
In the present work, a class of imidazolium based ionic liquid coupled with asparagine system was employed
for asymmetric epoxidation. The heterogeneous catalyst exhibited excellent activity for epoxidation of α,
β-unsaturated ketones, affording the corresponding epoxy ketones in the presence of hydrogen peroxide. The
catalyst was easily recovered from the reaction mixture and reused for five consecutive runs.
© 2012 Elsevier B.V. All rights reserved.
Received 23 September 2011
Received in revised form 26 March 2012
Accepted 21 May 2012
Available online 2 June 2012
Keywords:
Epoxidation
Ionic liquid
Amino acid
Room temperature
1. Introduction
of α, β-unsaturated ketones using L-asparaginyl amido ethyl methyl
imidazolium bromide [L-Aaemim] Br (Scheme 1).
The development of efficient methods for the asymmetric epoxida-
tion of α, β-unsaturated ketones is an important goal in organic
synthesis, since optically active epoxy ketones are among the most
versatile building block and intermediate for the synthesis of many
natural products or biologically active compounds [1]. Over several
decades of development, a number of valuable catalytic methodologies
have been established for efficient asymmetric epoxidation induction
[2], mainly involving the use of chiral metal peroxides [3], asymmetric
phase transfer catalysts [4], poly amino acid catalysts [5], chiral
dioxiranes [6] or other organo catalysts [7].
Ionic liquid coupled with amino acid has been extensively studied due
to its many advantages including operational simplicity, highly effective
catalytic and recyclability [8]. However many types of ionic liquid have
been applied to the asymmetric epoxidation and fine tuning of the reac-
tion conditions with various oxidants has been performed. To date,
imidazolium based ionic liquids have been most widely used for synthesis
of epoxides by several groups including S. Chandrasekhar [9], C. Freire
[10], S. Tangestaninejad [11], W. A. Herrmann [12], D. Yin [13], Anil
Kumar [14], P. A.Z. Suareza, [15], C-G Xia [16] and S. Liu [17]. From the
above open literature, there was no report of ionic liquid coupled with as-
paragine amino acid in the asymmetric epoxidation of α, β-unsaturated
ketones (Fig. 1). Herein, we have reported the asymmetric epoxidation
2. Experimental section
2.1. Materials and methods
The 1H-NMR spectrum was recorded on a Bruker 500 using CDCl3/
DMSO-d6 as the solvent. Enantiomeric excesses were determined by
HPLC analysis on an Agilent 1100 using Chiralpak® OD-H or OJ-H
columns with racemic epoxides as standards. Column chromatography
was performed on silica gel (200–300 mesh). Analytical thin-layer
chromatography (TLC) was carried out on precoated silica gel GF-254
plates. All solvents and chemicals were commercially available and
used without further purification unless otherwise stated.
2.2. Preparation of [L-Aaemim] Br ionic liquid
A mixture of Boc-Asparagine (2.42 g, 11.0 mmol) and triethyl
amine (2.23 g, 22.0 mmol) in DMF was cooled in an ice-bath. The 1-
(2-aminoethyl)-3-methylimidazolium bromide [Aemim] Br (2.05 g,
10.0 mmol) was added and agitation continued at ambient temperature
for 24 h. After, the completion of the reaction, the mixture was exacted
with ether and poured to water. The unreacted Boc-asparagine was
removed by centrifugation. The aq. layer was concentrated using rotary
evaporator and ionic liquid was dried under vacuum 70 °C 6 h [18].
The BOC-[L-Aaemim] Br was deprotected using 50% TFA in dic-
hloromethane (5 mL) for 1 h at ambient temperature. After evaporation
of solvent from the mixture, TFA salts were removed by triturating the
⁎
Corresponding author. Tel.: +91 9047289073; fax: +91 416 2240411.
E-mail address: drprbhagat111@gmail.com (P.R. Bhagat).
0167-7322/$ – see front matter © 2012 Elsevier B.V. All rights reserved.
doi:10.1016/j.molliq.2012.05.016

P. Karthikeyan et al. / Journal of Molecular Liquids 172 (2012) 136–139
137
Table 1
Optimization of (3-(4-chlorophenyl) oxiran-2-yl)(phenyl) methanone using [L-Aaemim] Br.
S. No
Catalyst
Base
Time (h)
Yield (%)
1
2
3
4
5
6
7
8
NIL
NIL
NIL
NIL
NIL
NIL
Na2CO3
Na2CO3
NaHCO3
NaHCO3
NaOH
12
24
12
24
12
24
12
24
12
24
12
14
18
24
–
–
–
–
Fig. 1. L-asparaginyl amido ethyl methyl imidazolium bromide [L-Aaemim] Br.
–
NaOH
–
[L-Aaemim] Br
[L-Aaemim] Br
[L-Aaemim] Br
[L-Aaemim] Br
[L-Aaemim] Br
[L-Aaemim] Br
[L-Aaemim] Br
[L-Aaemim] Br
Na2CO3
Na2CO3
NaHCO3
NaHCO3
NaOH
NaOH
NaOH
NaOH
–
residue with 5 mL of methanol (saturated with ammonia). The
resulting mixture was concentrated using rotary evaporator and ionic
liquid was dried under vacuum 80 °C 3 h.
–
9
–
10
11
12
13
14
–
90
90
91
92
General procedure for epoxidation of α, β-unsaturated ketones
using [L-Aaemim] Br: A 25 mL flask was charged with L-asparaginyl
amido ethyl methyl imidazolium bromide (0.05 mmol), unsaturated
ketones (0.04 mol), DMF (5 ml), hydrogen peroxide (30%, 11 ml,
0.1 mol) and NaOH (0.01 mmol) was stirred for 12 h at ambient tem-
perature. After completion of the reaction, the product was extracted
with ether (3×5 mL). The combined ether extracts were concentrated
on a rotary evaporator and the crude product was purified by column
chromatography on silica gel to get the desired product.
Reaction condition: 0.04 mole (3-(4-chlorophenyl) oxiran-2-yl)(phenyl) methanone,
30% H2O2 (11 ml, 0. 1 mol), DMF (5 ml), [L-Aaemim] Br (0.05 mmol), ambient
temperature.
drying under vacuum for 3 h. As shown in Table 3, the [L-Aaemim] Br
ionic liquid could be reused at least five successive runs for the synthesis
of epoxide without significant loss of activity. The yields that remained
around 84–90% clearly illustrate the reusability of the catalyst.
The spectroscopic data for [L-Aaemim] Br; 1H-NMR (500 MHz,
DMSO-d6): δ 3.8(s, 3 H), 7.9(d, 1 H), 7.6(d, 1 H), 8.4(s,1 H), 4.9(t, 2 H),
3.2(t, 2 H) ,8.2(s, 1 H), 4.1(t, 1 H), 7.3(s,2 H), 2.3(t, 2 H), 5.4(s,2 H).
13C-NMR: 36.53, 130.28, 131.77, 136.39, 56.82, 21.28, 176.89, 54.98,
23.61, 177.32.
3. Result and discussion
Initially epoxidation reaction was carried out in the presence of
different bases without using any catalyst and solvent. It was found
that no product formed even after 24 h [Table 1, entry 1–6]. Next,
epoxidation was carried out in the presence of Na2CO3, NaHCO3 using
[L-Aaemim] Br as a catalyst, in DMF for different intervals. It was
noted that no product formation in the presence of weak bases
[Table 1, entry 7–10]. There was appreciable yield of epoxide when
the reaction was conceded in the presence of [L-Aaemim] Br and
NaOH at room temperature for 12 h [Table 1, entry 11]. Finally, effect
of reaction time to the yield of the product was studied at room temper-
ature for the same concentration of [L-Aaemim] Br ionic liquid. Almost
similar yield was obtained when increasing the catalyst loading and
duration [Table 1, entries 12 and 14].
To understand the capacity of this catalyst, we studied the epoxi-
dation of various α, β-unsaturated ketones under the optimized
condition and the results are summarized in Table 2.
As is obvious from Table 2, besides E-chalcone (Table 2, entry 1),
substituted E-chalcones are also good substrates for this reaction. For
example, E-4-methoxychalcone yielded the desired product in a 90%
yield (Table 2, entry 2). Similarly, the epoxide of E-2-hydroxychalcone
and E-2-chorochalocone was obtained in 88 and 87% yield (Table 2,
entry 3 and 4). An excellent yield (90%) was also obtained for the
product of E-4-chlorochalcone (Table 2, entry 5).
The spectroscopic data were consistent with those reported in the
literature [18–21].
2a: White solid, 1H NMR (500 MHz, CDCl3): δ 4.08 (d, 1 H), 4.30
(d, 1 H), 7.44–7.37 (m, 5 H), 7.51–7.47 (m, 2 H), 7.64–7.60
(m, 1 H), 8.01 (dd, 2 H).
2b: White solid, 1H-NMR (500 MHz, CDCl3): δ 3.87(s, 3 H), 4.07(d,
1 H), 4.26–4.25(d, 1 H), 6.96–6.94 (m, 2 H), 7.41–7.36(m, 5 H),
8.02–8.00(d, 2 H).
2c: White solid, 1H-NMR (500 MHz, CDCl3): δ 4.20 (d, 1 H), 4.42
(d, 1 H), 5.42 (s, 1 H), 7.32 (m, 2 H), 7.40–7.42 (m, 2 H),
7.55–7.58 (m, 2 H), 7.63 (m, 1 H), 8.05–8.02 (m, 2 H).
2d: White solid, 1H-NMR (500 MHz, CDCl3): δ 4.17 (d, 1 H), 4.41
(d, 1 H), 7.34–7.31 (m, 2 H), 7.41–7.39 (m, 2 H), 7.53–7.49
(m, 2 H), 7.63 (m, 1 H), 8.07–8.05 (m, 2 H).
2e: White solid, 1H-NMR (500 MHz, CDCl3): δ 4.04 (s, 1 H), 4.25
(d, 1 H), 7.28 (d, 2 H), 7.34 (d, 2 H), 7.47 (t, 2 H), 7.60 (dd, 1 H),
7.97 (d, 2 H).
2f: Yellow solid, 1H-NMR (500 MHz, CDCl3): δ 3.72 (d, 1 H), 5.75
(d, 1 H), 7.20–7.14 (m, 2 H), 7.54–7.50 (m, 1 H), 7.83 (dd, 1 H).
2g: Yellow solid, 1H-NMR (500 MHz, CDCl3): δ 3.70 (d, 1 H), 5.64
(d, 1 H), 7.07 (d, 1 H), 7.50–7.48 (m, 1 H), 7.80 (d, 1 H).
2h: Yellow solid, 1H-NMR (500 MHz, CDCl3): δ 2.33 (s, 3 H), 3.70
(d, 1 H), 5.60 (d, 1 H), 6.92 (d, 1 H), 7.35–7.32 (m, 1 H), 7.65
(d, 1 H).
Further, potential of catalyst was studied for epoxidation of chro-
mones (Table 2, entry 6). The electron repelling and electron donating
groups of chromone was also successfully epoxidized, and the product
was obtained in an excellent yield (Table 2, entries 7 and 8). A good
yield was also obtained for the product of isoflavone and substituted
isoflavones (Table 2, entry 9 and 10). The formation of all the products
was confirmed by 1HNMR spectra. The melting points were comparable
with the reported compounds.
2i: White solid, 1H-NMR (500 MHz, CDCl3): δ 3.85 (s, 3 H), 5.49
(s, 1 H), 6.50 (d, 1 H), 6.75 (dd, 1 H), 7.45–7.40 (m, 5 H), 7.92
(d, 1 H).
Reusability of the catalyst was investigated by the model reaction
under optimized condition. The catalyst [L-Aaemim] Br was recovered
from aq. layer by removing the water using rotary evaporator and
2j: Colorless oil, 1H-NMR (500 MHz, CDCl3): δ 3.80 (s, 3 H), 5.45
(s, 1 H), 7.06 (d, 1 H), 7.40–7.37 (m, 7 H).
4. Conclusion
We have developed a simple and efficient protocol for the epoxi-
dation of α, β-unsaturated ketones in the presence of [L-Aaemim]
Br catalyst. The method merits attention due to the simplicity of the
experimental procedure, the reduced waste production and the
Scheme 1. Synthesis of epoxide from α, β-unsaturated ketone using [L-Aaemim] Br.

138
P. Karthikeyan et al. / Journal of Molecular Liquids 172 (2012) 136–139
Table 2
Epoxidation of various α, β-unsaturated ketones using [L-Aaemim] Br.
Entry
1
Reactant
Product
Yielda (%)
93
eeb (%)
89
Melting point (°C)
Found
Literature value
88–90
88–90 [19]
2
95
90
55–57
55–58 [19]
3
4
5
92
88
90
88
87
90
90–93
65–67
48–49
90–91 [20]
65–68 [20]
49–51 [21]
6
7
94
90
90
85
63–65
90–92
65–66 [22]
92–94 [22]
8
9
87
82
80
78–80
80–82 [22]
c
122–124
121–123 [22]
c
10
89
Oil
Oil
Reaction condition: 0.04 mole α, β-unsaturated ketones, 30% H2O2 (11 ml, 0.1 mol), DMF (5 ml), 0.05 mmol of [L-Aaemim] Br, room temperature.
a
The yield of isolated epoxide.
Determined by chiral HPLC.
Not determined by chiral HPLC.
b
c
good yields in short reaction time. The present methodology utilizes
chalcones of aldehyde with both electron repelling and electron
donating groups with moderate to good yields of the epoxides
obtained under very mild reaction condition. The procedure is
operationally simple and the [L-Aaemim] Br could be easily recovered
and reused for the next cycle. Further exploration on the potential
application of other unsaturated compound is on underway in this
laboratory.
Acknowledgments
We gratefully acknowledge the management of VIT University for
providing required facilities and SAIF (IITM) for providing the spectral
data.
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