Ionic liquid as catalytic and reusable media for cyanoethoxycarbonylation of aldehydes

Article abstract of DOI:10.1016/j.catcom.2010.04.005

Various ionic liquids (IL 1-9) based on N-methyl N'-alkyl imidazolium salts were explored as catalytic media in cyanoethoxycarbonylation of various aldehydes. The study revealed that the alkyl chain length and counter ion of the ionic liquid are critical

Full text of DOI:10.1016/j.catcom.2010.04.005

Catalysis Communications 11 (2010) 907–912
Contents lists available at ScienceDirect
Catalysis Communications
journal homepage: www.elsevier.com/locate/catcom
Ionic liquid as catalytic and reusable media for cyanoethoxycarbonylation
of aldehydes
⁎
Noor-ul H. Khan , Santosh Agrawal, Rukhsana I. Kureshy, Sayed H.R. Abdi, Arghya Sadhukhan,
Renjith S. Pillai, Hari C. Bajaj
Discipline of Inorganic Materials and Catalysis, Central Salt and Marine Chemicals Research Institute (CSMCRI), Council of Scientific & Industrial Research (CSIR), G. B. Marg,
Bhavnagar- 364 002, Gujarat, India
a r t i c l e i n f o
a b s t r a c t
Article history:
Various ionic liquids (IL 1–9) based on N-methyl N′-alkyl imidazolium salts were explored as catalytic media
in cyanoethoxycarbonylation of various aldehydes. The study revealed that the alkyl chain length and
counter ion of the ionic liquid are critical for the product yield. The highest product yield of cyanohydrin
carbonate (up to 96%) was obtained with C5 alkyl chain with Br− as counter ion (IL 3). On the other hand
PF−6 as counter ion failed to catalyze the cyanoethoxycarbonylation reaction.
Received 5 February 2010
Received in revised form 2 April 2010
Accepted 7 April 2010
Available online 14 April 2010
© 2010 Elsevier B.V. All rights reserved.
Keywords:
Cynoethoxycarbonylation
Aldehydes
Ionic liquid
Solvent free
Ethylcyanoformate
Catalysis
1. Introduction
environmentally benign synthetic protocol, previously we have
reported the synthesis of cyanosilylethers of aldehydes and ketones
Ionic liquids (ILs) are of current interest as eco-friendly
alternatives to the volatile organic solvents in organic synthesis
and catalysis [1]. ILs are essentially made up of organic cations and
inorganic anions [2–4] with unique chemical and physical properties
such as negligible vapor pressure and decent solubility for organic,
inorganic and organometallic compounds [5,6]. Notably, switching
over to an ionic liquid from a traditional organic solvent often results
in a significant improvement in reactivity and selectivity of a cata-
lytic system [1]. ILs also have the ability to support homogeneous
catalysts for their recyclability. Various ionic liquids are reported in
the literature, however 1,3-dialkylimidazolium salts as room tem-
perature ILs have emerged as leading media for various organic
transformations [7–10].
Cyanohydrin esters are useful intermediates for pharmaceuticals,
agrochemicals, and insecticides [11–15]. These cyanohydrin esters
[16–26] can readily be synthesized by cyanocarbonylation of
aldehydes in the presence of various catalysts [27–32]. However,
invariably this reaction uses environmentally hazardous solvents and
requires extreme reaction parameters such as prolonged reaction
time, very low reaction temperatures, tedious product isolation and
difficult catalyst recovery. In the quest of developing solvent-free and
[33], aminonitriles [34], β-amino carbonyl compounds [35] under
solvent-free condition. Herein we are reporting for the first time the
use of ionic liquids as reusable catalyst as well as reaction media for
cyanoethoxycarbonylation of aldehydes using ethylcyanoformate as
a cyanide source.
2. Experimental
2.1. General information
NMR spectra were obtained with a Bruker F113V spectrometer
(500 MHz and 125 MHz for 1H and 13C respectively) and are
referenced internally with TMS. High-resolution mass spectra were
obtained with a LC–MS (Q-TOF) LC (Waters), MS (Micromass)
instruments. For the product purification flash chromatography was
performed using silica gel 60–200 mesh purchased from s. d. Fine-
Chemicals Limited, Mumbai (India). Shimadzu GC with CHORMATO-
PAK (2 m, 4 mm) was used for the conversion of the substrates.
2.2. General procedure for the cyanoethoxycarbonylation
The cyanoethoxycarbonylation reaction was conducted in a
5 ml RBF sealed with a rubber septum. At first a mixture of 0.5 g of
ionic liquids (IL 1–9) and an appropriate aldehyde (0.625 mmol)
was stirred magnetically for 10 min. To this stirring solution,
⁎
Corresponding author. Fax: +91 0278 2566970.
E-mail address: khan251293@yahoo.in (N.H. Khan).
1566-7367/$ – see front matter © 2010 Elsevier B.V. All rights reserved.
doi:10.1016/j.catcom.2010.04.005

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N.H. Khan et al. / Catalysis Communications 11 (2010) 907–912
Calc. for C14H15NO3 C 68.56, H 6.16, N 5.71 found C 68.63, H 6.21, N
5.68 ppm.
2.2.8. 2-Ethoxycarbonyl-2-hydroxy-3,3-dimethylbutanenitrile (2k)
1H NMR δ=1.12 (s, 9H), 1.35 (t, J=7, 3H), 4.25–4.31 (m, 2H),
4.92 (s, 1H) ppm. 13C NMR δ=14.12, 25.10, 34.89, 65.37, 73.19,
115.96, 153.93 ppm. Anal. Calc. for C9H15NO3 C 58.36, H 8.16, N 7.56
found C 58.40, H 8.23, N 7.49.
2.2.9. 2-Ethoxycarbonyl-2-hydroxy-4-methylpentanenitrile (2l)
1H NMR δ=0.99 (d, J=5.5, 6H), 1.34 (t, J=7, 3H), 1.80–1.91 (m,
3H), 4.25–4.30 (m, 2H), 5.23 (t, J=7.5, 1H) ppm. 13C NMR δ=14.11,
22.03, 22.15, 24.36, 40.85, 63.47, 65.37, 116.76, 153.62 ppm. Anal. Calc.
for C9H15NO3 C 58.36, H 8.16, N 7.56 found C 58.31, H 8.18, N 7.52.
Fig. 1. Structure of various ionic liquids.
ethylcyanoformate (1.2 mmol, 0.098 ml) was added through a
syringe over a period of 5 min and the resulting reaction mass was
further stirred for 2 h. The progress of the reaction was monitored
by TLC. After the completion of the reaction, the product was
extracted with n-hexane (3×2 ml) and purified by column chro-
matography (hexane:ethylacetate 90:10). The recovered ionic
liquid was kept under vacuum for 8 h to remove volatiles and
stored in a desiccator for its reuse in subsequent catalytic runs.
Characterization data of some of the representative compounds
are discussed below.
3. Result and discussion
A series of ionic liquids (IL 1–9) (Fig. 1) based on N-methyl N′-
alkyl imidazole having different alkyl chain lengths and counter ions
was explored for their usefulness in cyanoethoxycarbonylation of
benzaldehyde as a model substrate at room temperature and the
results are presented in Table 1. Ionic liquids viz., 1-ethyl-3-methyl
imidazolium bromide (IL 1), 1-dodecyl-3-methyl imidazolium bro-
mide (IL 5) and 1-butyl-3-methyl imidazolium chloride (IL 6) were
solid at room temperature; hence dry dichloromethane was used as
co-solvent for carrying out cyanoethoxycarbonylation of benzalde-
hyde. These ILs in combination with dichloromethane gave 2-
ethoxycarbonyl-2-hydroxy-2-phenyl-acetonitrile in excellent yields
(80–98%) in 4–12 h (entries 1, 5 and 6). Room temperature ILs viz., IL
2 and IL 3 bearing C4 and C5 alkyl chain length with Br− as counter
ion (entries 2, 3) do not require the use of co-solvent to give the
desired product in excellent yield (∼98%) in 4 and 2 h respectively.
Liquid IL with C7 alkyl chain (IL 4) though gave high product yield
(86%) but took 12 h reaction time (entry 4). These results led us to
explore the role of counter anion with the ILs having alkyl chain C4
and C5 where desired products were obtained in excellent yields.
Besides, the results achieved with Cl− as counter ion (entries 6 and 7)
were as good as with Br− ion. Ironically, when PF−6 was used as
counter ion there was no product formation even after 24 h (entries 8,
9). Surprisingly in the absence of any of the above ILs (entry 11) or in
the presence of CH2Cl2 (a commonly preferred solvent for this system,
entry 12) there was no product formation in cyanoethoxycarbonylation
2.2.1. 2-Ethoxycarbonyl-2-hydroxy-2-phenyl-acetonitrile (2a)
Colorless liquid. 1H NMR δ=1.32 (t, J=7.5, 3H), 4.25–4.30 (m, 2H),
6.26 (s, 1H), 7.43–7.54 (m, 5H) ppm. 13C NMR 14.21, 65.73, 66.48,
115.93, 127.99, 129.38, 130.74, 131.37, 153.53 ppm.
2.2.2. 2-Ethoxycarbonyl-2-hydroxy-2-(2-methylphenyl)-acetonitrile
(2b)
1H NMR δ=1.33 (t, J=7.5, 3H), 2.44 (s, 3H), 4.25–4.31 (m, 2H),
6.38 (s, 1H), 7.23–7.37 (m, 3H), 7.55 (d, J=8, 1H) ppm. 13C NMR
δ=14.27, 19.06, 64.72, 65.75, 115.83, 126.93, 128.75, 129.55, 130.83,
131.48, 136.90, 153.61 ppm.
2.2.3. 2-Ethoxycarbonyl- 2-hydroxy-2-(4-methylphenyl)-acetonitrile
(2c)
1H NMR δ=1.33 (t, J=7, 3H), 2.38 (s, 3H), 4.28 (q, J=7, 2H), 6.22
(s, 1H), 7.24–7.26 (m, 2H), 7.42–7.43 (m, 2H) ppm. 13C NMR δ=14.32,
21.53, 66.48, 65.73, 116.10, 128.12, 130.10, 141.14, 153.65 ppm.
2.2.4. 2-Ethoxycarbonyl-2-hydroxy-2-(3-methylphenyl)-acetonitrile
(2d)
Table 1
1H NMR δ=1.33 (t, J=7, 3H), 2.38 (s, 3H), 4.24–4.30 (m, 2H), 6.22
(s, 1H), 7.26–7.34 (m, 4H) ppm. 13C NMR δ=14.24, 21.24, 65.70, 66.53,
116.02, 125.09, 128.57, 129.26, 131.26, 131.51, 139.40, 153.57 ppm.
Effect of carbon chain and counter ion on cyanoethoxycarbonylation of benzaldehyde.a
2.2.5. 2-Ethoxycarbonyl-2-hydroxy-2-(2-methoxylphenyl)-acetonitrile
(2e)
Entry
Ionic liquid
Time (h)
Conversion (%)b
1H NMR δ=1.32 (t, J=7, 3H), 3.86 (s, 3H), 4.26–4.29 (m, 2H), 6.58
(s, 1H), 6.94(d, J=8, 1H), 7.00–7.03 (m, 1H), 7.40–7.4(m, 1H), 7.55
(dd, J=2, 6, 1H) ppm. 13C NMR δ=14.28, 55.90, 61.85, 65.57, 111.25,
116.10, 119.60, 121.09, 128.09, 132.21, 153.66, 156.89 ppm.
1c
2
3
IL 1; [C2mim]+ Br−
IL 2; [C4mim]+ Br−
IL 3; [C5mim]+ Br
IL 4; [C7mim]+ Br−
IL 5; [C12mim]+ Br−
IL 6; [C4mim]+ Cl−
IL 7; [C5mim]+ Cl−
IL 8; [C4mim]+ PF−6
IL 9; [C5mim]+ PF−6
IL 3; [C5mim]+ Br−
–
4
4
2
93
98
N98
86
80
4
12
12
4
2.5
24
24
30
48
48
5c
6c
7
98
97
2.2.6. 2-Ethoxycarbonyl-2-hydroxy-2-(4-bromophenyl)-acetonitrile
(2h)
8
9
NR
NR
98
NR
NR
1H NMR δ=1.31 (t, J=7, 3H), 4.22–4.30 (m, 2H), 6.20 (s, 1H), 7.40
(d, J=8.5, 2H), 7.57 (d, J=8.5, 2H) ppm. 13C NMR δ=14.24, 65.78,
65.92, 115.52, 125.21, 129.60, 130.40, 132.63, 153.3 8 ppm.
10d
11
12e
–
a
0.5g ionic liquid (IL 1–9), benzaldehyde 63 μl, ethylcyanoformate 98 μl.
Conversion determined by GC Analysis SHIMADZU GC-14B, CHORMATO-PAK (2 m,
2.2.7. 2-Ethoxycarbonyl-2-hydroxy-3-methyl-4-phenyl-but-3-enonitrile
(2j)
b
4 mm) column.
1H NMR δ=1.37 (t, J=7, 3H), 2.06 (s, 3H), 4.31 (q, J=5, 2H), 5.79
(s, 1H), 6.85 (s, 1H), 7.29–7.39 (m, 5H) ppm. 13C NMR δ=13.68, 65.10,
69.73, 114.84, 127.53, 127.94, 128.56, 133.02, 134.72, 153.02 ppm. Anal.
c
Using 0.5 ml CH2Cl2.
10 mol% ionic liquid with respect to the benzaldehyde.
Reaction carried out in CH2Cl2 as a solvent (1 ml).
d
e

N.H. Khan et al. / Catalysis Communications 11 (2010) 907–912
909
Table 2
Cyanoethoxycarbonylation of various aldehydes.a
Entry
1
Substrate
Product
Conversion (%)b (yield) (%)c
N98 (94)
1a
1b
2a
N98 (95)
2
3
2b
N98 (93)
2c
1c
4
N99 (95)
1d
2d
5
6
N99 (96)
1e
2e
N98 (92)
1f
2f
7
N98 (93)
2g
1g
8
N99 (95)
2h
1h
(continued on next page)

910
N.H. Khan et al. / Catalysis Communications 11 (2010) 907–912
Table 2 (continued)
Entry
Substrate
Product
Conversion (%)b (yield) (%)c
9
N99 (93)
2i
2j
1i
1j
N98 (94)
10
11
12
N97 (91)
N97 (90)
N98 (92)
1k
2k
1l
2l
13
1m
2m
a
0.5 g (2.3 mmol) of ionic liquid IL 3, 0.625 mmol of respective aldehyde and 1.2 mmol of ethylcynoformate were stirred for 2 h at room temperature.
Conversion determined by SHIMADZU GC-14B, CHORMATO-PAK (2 m, 4 mm) column.
Isolated yield.
b
c
Fig. 2. 13C NMR spectrum of the mixture of ionic liquid IL 3 and ethylcyanoformate (ECF) in CDCl3 (only those peaks have been marked where changes were observed). Peaks marked
with A and B belong to the starting material and intermediate species respectively.

N.H. Khan et al. / Catalysis Communications 11 (2010) 907–912
911
Scheme 1. Proposed mechanism for cyanoethoxycarbonylation of benzaldehyde in IL 3.
of benzaldehyde. These results clearly demonstrate the role of ILs as
catalyst as well as reaction media.
first step) to give the product (ethylcyanohydrin carbonate) and
liberate the bromide ion (Step 2, Scheme 1). Since PF−6 ion is not basic
enough to produce such an intermediate species (B), it failed to
catalyze the cyanation reaction. Further, chloride ion is also basic
(though to a lesser extent than bromide), ILs having Cl− counter ion
also show fairly good catalytic activity (Table 1, entries 6, 7).
The recyclability experiments were carried out in IL 3 as rep-
resentative ionic liquid in the cyanoethoxycarbonylation of 2-MeO-
benzaldehyde as a representative substrate at room temperature.
After completion of the catalytic reaction the products were ex-
tracted with n-hexane and purified by column chromatography. The
recovered ionic liquid was dried in vacuum and was used as such for
the subsequent catalytic runs. The catalytic system worked well up to
eight catalytic runs (Fig. 3).
Among the various ILs used, IL 3 furnished best result in
cyanoethoxycarbonylation of benzaldehyde, hence this ionic liquid
was further employed as catalytic medium for the cyanoethoxycarbo-
nylation of various aromatic and aliphatic aldehydes (Table 2). Excellent
product yields (90–96%) achieved for all the aliphatic and aromatic
substrates used in the present study suggest that this protocol is quite
general in nature for cyanoethoxycarbonylation reaction.
It was rather intriguing to note that cyanoethoxycarbonylation
of benzaldehyde proceeded smoothly in IL 2 and IL 3 but failed to
proceed with IL 7 and IL 8. This led us to examine the role of counter
ions in these ILs. It was clearly evident from the results that ILs with
Br− and Cl− as counter ions worked well possibly due to the suf-
ficient basic nature to polarize ethylcyanoformate (ECF), which is
not the case with PF−6 as counter ion. In order to capture an
intermediate species during cyanoethoxycarbonylation reaction, we
have taken equimolar quantity of ECF and IL 3 in CDCl3 and recorded
its 13C NMR after 30 min (Fig. 2). The NMR spectrum clearly shows
the presence of two sets of peaks for methylene and methyl carbons.
While peaks marked with A in Fig. 2 belongs to ECF (compared with
pure ECF) peaks marked with B are from the intermediate species
B (Step 1, Scheme 1). Similarly along with CN from ECF (at δ
109.26 ppm) peak for −CN (at δ 111.45) possibly from intermediate
B can also been seen. Based on these observations it can be deduced
that a basic bromide ion polarize ECF and liberates −CN ion which
attacks the carbonyl carbon of aldehyde (polarized by the electron
deficient imidazole ring). Simultaneously, negatively charged oxy-
gen of aldehyde attacks the acylbromide intermediate (formed in the
4. Conclusion
In conclusion we have developed a green and straightforward
protocol for the synthesis of cyanohydrincarbonates of aldehydes
using various ionic liquids as catalytic medium. Among all the ionic
liquids used excellent product yield (up to 96%) was obtained with IL
3 in 2 h. Easy recyclability of ILs used in the present study with
virtually no evaporational losses makes this protocol environmentally
safe and scalable process for the synthesis of cyanohydrin carbonates
of aldehydes.
Acknowledgements
S. Agrawal is thankful to CSIR for awarding the Senior Research
Fellowship. N.H. Khan is thankful to DST and CSIR Network project on
Catalysis for financial assistance, and also to the Analytical Section of
the Institute for providing instrumentation facilities. Authors are
extremely grateful to Prof. Daniel A. Singleton (Department of
Chemistry, Texas A&M University) for their valuable suggestions in
bringing out the most plausible reaction mechanism.
Appendix A. Supplementary data
Supplementary data associated with this article can be found, in
the online version, at doi:10.1016/j.catcom.2010.04.005.
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