Efficient dehydration of aldoximes to nitriles catalyzed by a Lewis acid ionic liquid

Article abstract of DOI:10.1246/cl.2011.396

A Lewis acid ionic liquid, 1-[4-(chlorosulfonyl)butyl]-3-methylimidazolium chlorosulfate ([CBMIm]SO₃Cl), with Lewis acid sites in both the anion and cation was synthesized. This was demonstrated to be an efficient catalyst for dehydration of aldoximes to nitriles. An unexpected self-induced phase separation of the reaction mixture was observed when the reaction was carried out in acetonitrile. This could be attributed to the hydrolysis of [CBMIm]SO₃Cl to regenerate 1-(4-sulfobutyl)-3-methylimidazolium hydrogensulfate ([SBMIm]HSO₄), which was the Bronsted precursor of [CBMIm]SO₃Cl.

Full text of DOI:10.1246/cl.2011.396

doi:10.1246/cl.2011.396
396
Published on the web March 12, 2011
Efficient Dehydration of Aldoximes to Nitriles Catalyzed by a Lewis Acid Ionic Liquid
Mizuki Nakajima, Kun Qiao,* Nobuhisa Kobayashi, Quanxi Bao, Daisuke Tomida, and Chiaki Yokoyama
Institute of Multidisciplinary Research for Advanced Materials, Tohoku University,
2-1-1 Katahira, Aoba-ku, Sendai, Miyagi 980-8577
(Received December 24, 2010; CL-101088; E-mail: kunqiao@tagen.tohoku.ac.jp)
(CH2)4
(CH2)4
A Lewis acid ionic liquid, 1-[4-(chlorosulfonyl)butyl]-3-
Me
Me
SOCl2
SO3H
SO2Cl
HSO4-
SO3Cl-
N
N
N
N
+
+
methylimidazolium chlorosulfate ([CBMIm]SO3Cl), with Lewis
acid sites in both the anion and cation was synthesized. This
was demonstrated to be an efficient catalyst for dehydration of
aldoximes to nitriles. An unexpected self-induced phase
separation of the reaction mixture was observed when the
reaction was carried out in acetonitrile. This could be attributed
to the hydrolysis of [CBMIm]SO3Cl to regenerate 1-(4-sulfo-
butyl)-3-methylimidazolium hydrogensulfate ([SBMIm]HSO4),
which was the Brønsted precursor of [CBMIm]SO3Cl.
Scheme 1. Synthesis of [CBMIm]SO3Cl from [SBMIm]HSO4.
Table 1. Catalytic conversion of benzaldehyde oxime in the
presence of acidic ionic liquidsa
O
N OH
N
Acidic IL
Solvent
H
H
+
[SBMIm]HSO4 [CBMIm]SO3Cl
Temp
/°C
Conv. Sel.b
Conv.
/%
Sel.b
/%
Run
Solvent
Acidic ionic liquids are an important subset of functional
ionic liquids that have many important applications in synthetic
chemistry.1 In comparison with conventional catalysts such as
AlCl3, H2SO4, HNO3, or HCl, acidic ionic liquids usually
improve catalytic performance, including enhancing the reaction
rate, increasing the yield, and simplifying product separation/
catalyst recycling.2
Sulfonyl chlorides are usually known as Lobe-LUMO
Lewis acids. Recently, we reported the synthesis of some
sulfonyl chloride-based Lewis acid ionic liquids and their use as
catalysts in synthetic chemistry.3 These Lewis acid ionic liquids
had only one Lewis acid site, which was located in either the
cation or the anion. As a continuation of this study, we herein
report synthesis of a novel sulfonyl chloride-based ionic liquid,
1-[4-(chlorosulfonyl)butyl]-3-methylimidazolium chlorosulfate
([CBMIm]SO3Cl), which features Lewis acid sites in both the
cation and anion. Our primary results showed that [CBMIm]-
SO3Cl was a very efficient catalyst for dehydration of aldoximes
to nitriles. Moreover, an unexpected self-induced phase separa-
tion was observed when the dehydration reaction was carried out
in acetonitrile.
[CBMIm]SO3Cl was easily synthesized by reaction of the
common Brønsted acid ionic liquid 1-(4-sulfobutyl)-3-methyl-
imidazolium hydrogensulfate ([SBMIm]HSO4), with SOCl2
(Scheme 1). To prepare [CBMIm]SO3Cl, 6 g of SOCl2 was
added dropwise to 10 g of [SBMIm]HSO4 in a 50 mL flask in an
ice water bath. Then the reaction mixture was stirred for 12 h at
room temperature. After another 2 h of reaction at 80 °C, excess
SOCl2 was removed from the reaction mixture via vacuum
distillation. The remaining yellow liquid was washed with
diethyl ether three times, and dried under vacuum at room
temperature. The structure of [CBMIm]SO3Cl was confirmed by
high-resolution mass spectrometry (HRMS), 1H NMR, FT-IR,
and element analysis (see Supporting Information; SI8).
Dehydration of aldoximes to nitriles is an important reaction
in synthetic chemistry. A variety of catalysts, such as diethyl
chlorophosphate, palladium, chlorosulfonic acid, and chloral,
have been applied to this reaction.4 However, only a few
examples of ionic liquid-based catalysts have been reported.5
/%
/%
1
2
3
4
Toulene
THF
Acetonitrile
80
80
80
7
10
26
48
51
77
82
90
91
42
79
99
81
95
94
97
Acetonitrile 100
aReaction conditions: ionic liquid, 0.57 mmol; solvent, 3 g;
oxime, 2.85 mmol; reaction time, 1 h. bSelectivity of benzo-
nitrile.
Therefore, we investigated the catalytic activity of [CBMIm]-
SO3Cl in dehydration of aldoximes. Benzaldehyde oxime was
used as the probe substrate in these experiments. For compar-
ison, the catalytic activity of [SBMIm]HSO4 was also examined,
and the results are summarized in Table 1.6
Benzaldehyde oxime in an acidic medium commonly reacts
via three different pathways, including dehydration to benzoni-
trile, hydrolysis to benzaldehyde, or the Beckmann rearrange-
ment to benzamide.7 Only benzonitrile and benzaldehyde were
detected as products when benzaldehyde oxime was treated with
the acidic ionic liquids [CBMIm]SO3Cl and [SBMIm]-
HSO4 in different solvents, including toluene, THF, and aceto-
nitrile. Benzamide, the product of the Beckmann rearrangement
of benzaldehyde oxime, was not detected in our experiments.
The results showed dehydration of benzaldehyde oxime to
benzonitrile depended largely on the catalyst, solvent, and
reaction temperature. The Lewis acid [CBMIm]SO3Cl provided
better catalysis of the reaction than the Brønsted acid
[SBMIm]HSO4 in terms of both conversion and selectivity
when the reaction was carried out under the same reaction
conditions. This enhanced catalytic activity was apparent in all
the different solvents tested (Runs 1-4). Increasing the reaction
temperature from 80 (Run 3) to 100 °C (Run 4) also enhanced
the catalytic activity.
The solvent, especially acetonitrile, played an important
role in this reaction. [SBMIm]HSO4 was immiscible with all of
the three solvents, and when it was used as the catalyst the
dehydration reaction proceeded in a biphasic manner with a very
Chem. Lett. 2011, 40, 396-397
© 2011 The Chemical Society of Japan
www.csj.jp/journals/chem-lett/

397
Table 2. Dehydration of aldoximes to nitriles in acetonitrile
catalyzed by [CBMIm]SO3Cla
observed. These results suggest that the acetonitrile/[CBMIm]-
SO3Cl system can be used as a recyclable catalytic system for
dehydration of aldoximes to nitriles with high catalytic perform-
ance and simple product separation.
Run
1
Aldoxime
Product
Time/h Conv./% Sel./%
Br
Br
NOH
In conclusion, we synthesized a novel ionic liquid,
[CBMIm]SO3Cl, that had Lewis acid sites in both its cation
and anion. This ionic liquid was an efficient catalyst for
dehydration of aldoximes to nitriles, and had higher catalytic
activity than its Brønsted acid precursor. Moreover, the aceto-
nitrile/[CBMIm]SO3Cl system resulted in self-induced phase
separation of the reaction mixture after dehydration of aldoximes
to nitriles. We believe this will lead to further applications in
acid-catalyzed dehydration reactions, and additional studies are
underway.
1.5
1
93
96
96
97
H
N
N
NOH
H
Br
Br
2
Cl
Cl
NOH
H
N
3
4
3
1
99
97
98
96
NOH
H
N
N
NOH
H
NO
NO
2
2
5
6
1
2
97
93
96
99
OH
OH
This work was supported in part by the Management
Expenses Grants for National Universities Corporations from the
Ministry of Education, Culture, Sports, Science and Technology
of Japan (MEXT).
N
NOH
aReaction conditions: ionic liquid, 0.57 mmol; acetonitrile, 3 g;
aldoxime, 2.85 mmol; reaction temp, 100 °C.
low reaction efficiency. Although [CBMIm]SO3Cl was also
immiscible with toluene and THF, it can show better catalytic
performance than [SBMIm]HSO4, which suggests that the Lewis
acid ionic liquid is more favorable for the reaction.
In contrast to [SBMIm]HSO4, [CBMIm]SO3Cl was miscible
with acetonitrile, and acetonitrile/[CBMIm]SO3Cl was the most
efficient catalytic system for dehydration of benzaldehyde
oxime to benzonitrile (Run 4). Interestingly, an unexpected
self-induced phase separation was observed when the aceto-
nitrile/[CBMIm]SO3Cl system was used for dehydration of
benzaldehyde oxime to benzonitrile (see SI8). The homogeneous
solution of acetonitrile/[CBMIm]SO3Cl/benzaldehyde oxime
became biphasic after the reaction finished.
Because [SBMIm]HSO4 is immiscible with acetonitrile, the
biphasic reaction mixture suggested that [CBMIm]SO3Cl might
be converted to [SBMIm]HSO4 via hydrolysis with water, which
is a by-product of the dehydration reaction. To confirm this, the
lower phase of the reaction solution was separated and analyzed
by HRMS. The results showed that the lower phase was a
mixture of [SBMIm]HSO4 (33%) and [CBMIm]SO3Cl (67%)
(see SI8). These results indicate that [CBMIm]SO3Cl is
converted to [SBMIm]HSO4, and that the acetonitrile/
[CBMIm]SO3Cl system can provide a simple way to separate
the product and catalyst.
The acetonitrile/[CBMIm]SO3Cl system was then applied
to dehydration of other aldoximes with high conversion and
selectivity (Table 2). The reaction resulted in self-induced phase
separation of [CBMIm]SO3Cl from acetonitrile in all the
experiments.
References and Notes
1
2
For the latest review on ionic liquids, see: H. Olivier-
Bourbigou, L. Magna, D. Morvan, Appl. Catal., A 2010,
373, 1, and references cited therein.
For examples of reactions catalyzed by acidic ionic liquids,
see: a) D. Fang, H. Zhang, Z. Liu, J. Heterocycl. Chem.
2010, 47, 63. b) J. Akbari, A. Heydari, H. R. Kalhor, S. A.
Kohan, J. Comb. Chem. 2010, 12, 137. c) S. Tang, A. M.
Scurto, B. Subramaniam, J. Catal. 2009, 268, 243. d) M. P.
Atkins, M. J. Earle, K. R. Seddon, M. Swadźba-Kwaśny, L.
Vanoye, Chem. Commun. 2010, 46, 1745, and references
cited therein.
3
4
a) K. Qiao, C. Yokoyama, Chem. Lett. 2004, 33, 472. b) Q.
Bao, K. Qiao, D. Tomida, C. Yokoyama, Chem. Lett. 2010,
39, 728.
For examples of dehydration of oximes to nitriles, see: a)
A. R. Sardarian, Z. Shahsavari-Fard, H. R. Shahsavari, Z.
Ebrahimi, Tetrahedron Lett. 2007, 48, 2639. b) H. S. Kim,
S. H. Kim, J. N. Kim, Tetrahedron Lett. 2009, 50, 1717. c)
D. Li, F. Shi, S. Guo, Y. Deng, Tetrahedron Lett. 2005, 46,
671. d) S. Chandrasekhar, K. Gopalaiah, Tetrahedron Lett.
2003, 44, 755.
5
6
D. Saha, A. Saha, B. C. Ranu, Tetrahedron Lett. 2009, 50,
6088.
The typical experimental procedure for dehydration of
aldoximes to nitriles in the presence of acidic ionic liquid
was as follows: aldoxime (2.85 mmol), solvent (3.0 g), and
ionic liquid (20% equiv) were placed in a 10 mL glass test
tube. Then the reaction was allowed to proceed at 100 °C for
the desired time. After the reaction was finished, the upper
phase was analyzed by a gas chromatograph (Shimadzu GC-
2014) equipped with a flame ionization detector and an
ULBON HR-52 capillary column (25 m © 0.32 mm i.d.,
Shinwa Chemical Industries Ltd., Japan). Toluene was used
as an internal standard.
Because [SBMIm]HSO4 was used as the precursor of
[CBMIm]SO3Cl, the lower phase could be converted into pure
[CBMIm]SO3Cl again by reacting the lower phase with SOCl2.
Our primary results showed that about 96% [CBMIm]SO3Cl can
be recovered (see SI8). Then the regenerated [CBMIm]SO3Cl
was reused for dehydration of benzaldehyde oxime to benzo-
nitrile. The catalytic activity for the regenerated [CBMIm]SO3Cl
was almost the same as that for the original catalyst, offering
97% conversion of benzaldehyde and 97% selectivity for
benzonitrile. The self-induced phase separation was also
7
8
A. Loupy, S. Régnier, Tetrahedron Lett. 1999, 40, 6221.
Supporting Information is available electronically on the
CSJ-Journal Web site, http://www.csj.jp/journals/chem-lett/
index.html.
Chem. Lett. 2011, 40, 396-397
© 2011 The Chemical Society of Japan
www.csj.jp/journals/chem-lett/