Activity and behavior of imidazolium salts as a phase transfer catalyst for a liquid-liquid phase system

Article abstract of DOI:10.1016/j.tetlet.2006.09.060

The structure-activity relationship and behavior of N,N′-dialkylimidazolium salts as a phase transfer and/or ion-exchange catalyst in a liquid-liquid phase system were investigated for the reactions such as β-elimination reaction of alkyl halides, nucleophilic epoxidation of α,β-unsaturated carbonyl compounds, alkylation of active methylenes, and nucleophilic substitution reaction.

Full text of DOI:10.1016/j.tetlet.2006.09.060

Tetrahedron Letters 47 (2006) 8055–8058
Activity and behavior of imidazolium salts as a phase
transfer catalyst for a liquid–liquid phase system
*
Sentaro Okamoto, Kouichi Takano, Tomohiro Ishikawa,
Satoshi Ishigami and Akiko Tsuhako
Department of Material and Life Chemistry, Kanagawa University, 3-27-1 Rokkakubashi, Kanagawa-ku, Yokohama 221-8686, Japan
Received 22 August 2006; revised 11 September 2006; accepted 14 September 2006
Available online 2 October 2006
0
Abstract—The structure–activity relationship and behavior of N,N -dialkylimidazolium salts as a phase transfer and/or ion-exchange
catalyst in a liquid–liquid phase system were investigated for the reactions such as b-elimination reaction of alkyl halides, nucleophilic
epoxidation of a,b-unsaturated carbonyl compounds, alkylation of active methylenes, and nucleophilic substitution reaction.
Ó 2006 Elsevier Ltd. All rights reserved.
Imidazolium salts 1 are a well-known heterocycle but
workers also reported hydrolysis of 1-chloro-2,2,2-triflu-
have recently been recognized as versatile molecules
oroethane in DMF, DMSO, NMP or c-butyrolactone/
1
5b
for use as polar organic solvents (ionic liquids, when
H O but the solvent system seems homogeneous. In
2
ꢀ
X is a bulky counter ion) and a precursor of stable het-
these cases, only 1-n-butyl-3-methylimidazolium salt as
an imidazolium salt was used. Compared with nitrogen
and phosphorus quaternary cations 2 and 3, the salts of
which have widely been utilized as phase transfer cata-
erocyclic carbenes2 (when R = H), ligating to metal
atoms, and playing itself as a catalyst (Fig. 1). Recently,
2
3
the molecules have assumed a new aspect as a phase
transfer or anion exchange catalyst. The use of imidazo-
lium salts 1 as a phase transfer catalyst under solid–
liquid biphasic conditions has been reported, which
involves alkylation and Michael addition reactions of
6
lysts, the imidazolium cation has been reported to be
6
b
more stable and is unique because its positive charge
is highly delocalized to a five membered heterocyclic
ring, the nature of the planar cation of which with var-
iation of substituents might be useful for their design
and functionalization as catalysts. However, the struc-
tural requirement and relationship to activity and mech-
anistic behavior as a catalyst have been little explored.
Herein reported is the results of investigation on cata-
lytic activity of 1 having various substituents for several
reactions, which clarified the structural requirement for
the use of 1 as a catalyst and gave their mechanistic
aspects.
4
active methylene compounds and cross-aldol reaction.
Meanwhile, the use of 1 in organic/aqueous liquid–
liquid biphasic systems has recently been reported by
Lourenco and Afonso for nucleophilic alkylation and
5
a
substitution reactions in CH Cl /H O. Kim and co-
2
2
2
For the present study, imidazolium salts 1a–g were
prepared by the sequential alkylation of imidazole or
2-substituted imidazole, respectively, according to the
conventional reaction procedure. Thus, 1-substituted
1
or 1,2-disubstituted imidazole prepared from R X and
imidazole or 2-substituted imidazole was alkylated with
R X. The procedure afforded 1a–g in a 83–99% yield
through two steps.
3
Figure 1. Structure of imidazolium salts 1 and quaternary salts
2
and 3.
*
Corresponding author. Tel.: +81 45 481 5661; fax: +81 45 413
First, we investigated the nucleophilic epoxidation
9770; e-mail: okamos10@kanagawa-u.ac.jp
of a,b-unsaturated ketone 4 to 5 in the presence of a
0040-4039/$ - see front matter Ó 2006 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2006.09.060

8056
S. Okamoto et al. / Tetrahedron Letters 47 (2006) 8055–8058
catalytic amount (3 mol %) of imidazolium salts 1 in the
two-phase system of aqueous NaOCl solution and an
organic solvent, and evaluated the efficiency of various
1
having different substituents. The results are summa-
rized in Table 1, in which the relative efficiency value
was calculated based on the yields of 5 observed after
an appropriate reaction time. In the actual experiments,
the reactions were highly dependent on the stirring effi-
ciency. Therefore, to avoid errors arising from stirring
efficiency, the reactions were performed using the same
type and size of vessels and magnetic stirring bars with
the same stirring rate and the reaction with 1c was al-
ways carried out as the standard when the reactions with
other catalysts were performed. Values for efficiency
shown in Table 1 were calculated as a ratio of yield of
Figure 2. Possible mechanism of epoxidation of 4 to 5.
posed to give the corresponding urea derivative and un-
7
known compounds (Eq. 1).
5
with each catalyst toward that with 1c in toluene under
the same reaction conditions. As can be seen from Table
, imidazolium salts, except for 2-unsubstituted 1a,
ð1Þ
1
exhibited catalytic activity for the transformation. The
systematic structure–activity relationship was observed
among compounds 1d–g which have a phenyl group at
the 2-position of imidazolium ring and N-substituents
with different chain length at the 1- and 3-positions: In-
crease of the total carbon number of chains at the 1- and
Since an imidazolium salt 1c solved in toluene and acted
as an ion-exchange catalyst for the reaction of Table 1, a
1
c/toluene/H O system was utilized to nucleophilic sub-
2
stitution reaction (Eq. 2). As expected, the conversion of
alkyl bromide to the iodide proceeded in the presence of
an imidazolium salt 1c, and 1c was a better catalyst than
3
-positions increased catalytic activity, presumably due
+
ꢀ
to enhanced solubility of (imidazolium) X and/or
+
ꢀ
(
imidazolium) OCl in the organic solvent utilized.
TBAB (n-Bu NBr) under the given conditions.
4
Actually, 1d which is nearly insoluble in toluene could
not catalyze the reaction in a toluene–water system. As
illustrated in Figure 2, 1 may act as an ion-exchanging
agent in the reaction media, that is, an (imidazo-
+
ꢀ
ꢀ
lium) OCl generated catalytically from (imidazo-
ð2Þ
+
lium) X might be an active species.
To clarify the reason why 2-unsubstituted imidazolium
salt 1a could not catalyze the reaction of 4 to 5, 1a
was treated with aqueous NaOCl/CH Cl and it was
Next, we studied the behavior of imidazolium salts as
catalysts under the basic conditions required for basic
b-elimination reaction of alkyl halide to alkene (Eq. 3)
and nucleophilic alkylation of the compounds having a
acidic proton (Eq. 4). The b-elimination reaction of
alkyl halide was performed as follows: A mixture of
aqueous 50% NaOH (1 mL), toluene (1 mL), and
PhCH CH Br (1.5 mmol) was stirred at room tempera-
2
2
found that under oxidative conditions 1a was decom-
Table 1. Relative efficiency of catalysts for the nucleophilic epoxida-
tion of 4 to 5 with aqueous NaOCl
2
2
ture (22–24 °C) in the absence or presence of imidazo-
lium salt 1 or TBAB (5 mol %). It was found that
imidazolium salts 1a and 1c could effectively catalyze
the reaction as well as TBAB. It was noted that 2-unsub-
stituted imidazolium 1a as well as substituted 1c could
equally exhibit catalytic activity, while 1a could not cat-
alyze nucleophilic epoxidation of 4 to 5 and decomposed
under the oxidative conditions. The time course of the
reactions with 1c and TBAB was traced by GC analyses
and is shown in Figure 3. A control experiment without
catalyst did not afford the product styrene at all. Time
versus log(1 ꢀ x) plots (x = conversion, 0 6x 6 1) for
both reactions catalyzed by 1c and TBAB fit well to
simple lines when the conversion was less than 80%
a
b
Catalyst
Total C-number
Relative efficiency
Toluene
CH
2
Cl
2
No
TBAB
—
—
16
16
16
5
8
12
16
No reaction
No reaction
0.93
0.56
0
0.98
1
1
1
1
1
1
1
a
b
c
d
e
f
0
0.83
0.93
c
1.00 (Standard)
0
0.86
0.96
0.91
1.07
0.77
0.96
1.12
g
a
b
c
Total carbon-number of the substituents at the 1- and 3-positions of
the imidazolium ring.
The value is shown as the ratio of yield of 5 with each catalyst toward
that with 1c in toluene under the same reaction conditions.
Compound 5 was obtained in 92% isolated yield by the reaction with
(<ꢁ10 h), where the reaction could be considered as
an expected pseudo-first order under the conditions in
the presence of large excess of a base and a relatively
small amount of catalyst to the substrate halide. The re-
sults indicate that catalyst 1c was stable and did not
3
mol % of 1c for 24 h at room temperature.

S. Okamoto et al. / Tetrahedron Letters 47 (2006) 8055–8058
8057
Figure 3. Reaction time course (a) and time versus log(1 ꢀ x) plots (b) of elimination reaction of PhCH
2
CH
2
Br in aqueous NaOH–toluene.
(
x = conversion (0 6 x 6 1)).
change the structure of its cation counterpart during the
reaction.
the corresponding alkylated indene in good yield and
recovered 1c with 10% of deuterium incorporation at
the C4 (or C5) position. The deuterium incorporation
thus observed was apparently larger than the total D/
H ratio included in the mixture of the substrates,
reagents (1c and KOH), and solvent (H O). It is pointed
2
ð3Þ
out that the reaction under basic conditions at least
involves the C4- (or C5-) anion of 1c, which can act as
a base for deprotonation of indene.
Deprotonation and alkylation reaction of the com-
pounds having an acidic proton illustrated in Eq. 4
was investigated. Thus, 1c as well as TBAB were effec-
tive for the alkylation of indene in an aqueous KOH–
toluene system to give selectively mono-alkylated com-
pound in a good yield (Eq. 4).8
ð5Þ
ð6Þ
ð4Þ
To clarify an active species as a base and the structural
stability of 1 under the basic conditions, we carried out
1
the following experiments: The H NMR spectra of the
residue obtained by the reaction of 1c with an excess
amount of KOH in toluene/H O and the following con-
2
centration of the organic phase indicated an imidazo-
lium ring structure similar to 1c, peaks of which had
somewhat different chemical shifts from those of 1c.
As revealed from Eq. 5, protons at the 4- and 5-posi-
tions could be exchanged with the protons of solvent(s)
by a deprotonation/protonation pathway under the
Based on these results, a possible mechanism for the
elimination reaction of alkyl halides and alkylation of
indene is illustrated in Figure 4. The imidazolium
bromide 1 can react with MOH (M = K or Na) on the
surface between the organic and aqueous phases to give
imidazol-4-ylidene A, which may deprotonate an acidic
9
basic conditions. Meanwhile, as shown in Eq. 6, it
was found that the reaction of deuterated indene (totally
proton of the substrate to occur the elimination or
1
0
+ꢀ
7
6%D at 1- and 3-positions) and n-BuBr in toluene–
alkylation reaction and generate (imidazolium)
X
5
0% KOH in H O with 50 mol % of 1c, which gave
again. In addition, a catalytic cycle involving an
2

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S. Okamoto et al. / Tetrahedron Letters 47 (2006) 8055–8058
2
. Wanzlick, H. W.; Schonherr, H.-J. Angew. Chem., Int. Ed.
Engl. 1968, 7, 141; Ofele, K. J. Organomet. Chem. 1968, 12,
2; Arduengo, A. J., III; Diash, V. R.; Harlow, R. L.;
4
Kline, M. J. Am. Chem. Soc. 1992, 114, 5530; Arduengo,
A. J., III; Harlow, R. L.; Kline, M. J. Am. Chem. Soc. 1991,
1
13, 361; Herrmann, W. A.; K o¨ cher, C. Angew. Chem., Int.
Ed. 1997, 36, 2162; Arduengo, A. J., III. Acc. Chem. Res.
999, 32, 913; Bourissou, D.; Guerret, O.; Gabba ¨ı , F. P.;
1
Bertrand, G. Chem. Rev. 2000, 100, 39; Weskamp, T.;
B o¨ hm, V. P. W.; Herrmann, W. A. J. Organomet. Chem.
Figure 4. Possible mechanism of elimination reaction and proton-
exchange reaction of the imidazolium.
2000, 600, 12; Cowley, A. H. J. Organomet. Chem. 2001,
617, 105; Enders, D.; Gielen, H. J. Organomet. Chem. 2001,
617, 70; Herrmann, W. A.; Weskamp, T.; B o¨ hm, V. P. W.
+
ꢀ
Adv. Organomet. Chem. 2001, 48, 1; Jafarpour, L.; Nolan,
S. P. Adv. Organomet. Chem. 2001, 46, 181; Herrmann, W.
A. Angew. Chem., Int. Ed. 2002, 41, 1290; Cavell, K. J.;
McGuinness, D. S. Coord. Chem. Rev. 2004, 248, 671.
. Enders, D.; Balensiefer, T. Acc. Chem. Res. 2004, 37, 534;
Recent examples: Matsumoto, Y.; Tomioka, K. Tetra-
hedron Lett. 2006, 47, 5843; Kano, T.; Sasaki, K.;
Maruoka, K. Org. Lett. 2005, 7, 1347; Singh, R.; Kissling,
R. M.; Letellier, M. A.; Hedrick, J. L. J. Org. Chem. 2004,
69, 209; Sohn, S. S.; Rosen, E. L.; Bode, J. W. J. Am. Chem.
Soc. 2004, 126, 14370; Burstein, C.; Glorius, F. Angew.
Chem., Int. Ed. 2004, 43, 6205; Suzuki, Y.; Yamauchi, K.;
Muramatsu, K.; Sato, M. Chem. Commun. 2004, 2770;
Grasa, G. A.; Singh, R.; Nolan, S. P. Synthesis 2004, 971;
Suzuki, Y.; Toyota, T.; Imada, F.; Sato, M.; Miyashita, A.
(
imidazolium) OH (B), derived from 1 by an ion-ex-
change reaction, as an active base cannot be ruled out.
An anion A may also be generated through the forma-
tion of B.
3
In contrast to imidazolium 1a–g, the benzo derivative of
1
1
imidazolium salt 1h could not catalyze the b-elimina-
tion reaction shown in Eq. 2. It was found that the reac-
tion of 1h with KOH gave the corresponding ring-
opening product (Eq. 7).
˚
Chem. Commun. 2003, 1314; Grasa, G. A.; GuAN veli, T.;
Singh, R.; Nolan, S. P. J. Org. Chem. 2003, 68, 2812.
4
. (a) Muthusamy, S.; Gnanaprakasam, B. Tetrahedron Lett.
2
005, 46, 635; (b) G e´ nisson, Y.; Viguerie, N. L.; Andr e´ , C.;
Baltas, M.; Gorrichon, L. Tetrahedron: Asymmetry 2005,
6, 1017; (aa) Rivas, F. M.; Riaz, U.; Giessert, A.; Smulik,
J. A.; Diver, S. T. Org. Lett. 2001, 3, 2673; (c) Kryshtal, G.
V.; Zhdankina, G. M.; Zlotin, S. G. Eur. J. Org. Chem.
1
ð7Þ
In summary, we have reported the structural require-
ment and structure–activity relationship of 1,3-disubsti-
tuted and 1,2,3-trisubstituted imidazolium as a phase
transfer catalyst in a liquid–liquid phase system under
various reaction conditions. In addition to a similar
ion-exchanging mechanism to that for usual phase
transfer catalysts such as quaternary ammonium salts,
it was suggested that the reaction under the basic condi-
tions may involve an imidazol-4-ylidene compound as
an active species. These results might be useful for fur-
ther application and design of imidazolium salts as a
phase transfer catalyst.
2
005, 2822.
5. (a) Lourenco, N. M. T.; Afonso, A. M. Tetrahedron 2003,
59, 789; (b) Lee, H.; Kim, K. H.; Kim, H.; Lee, S. D.;
Kim, H. S. J. Fluorine Chem. 2004, 125, 95; Patents have
pointed out the possibility of imidazolium salts as a PTC:
Welz-Biermann, U.; Ignatjev, N.; Bernhardt, E.; Finze,
M.; Willner, H. Ger. Offen. 2004, DE 10306617 A1
2
3
0040826; Vorbrueggen, H. Ger. Offen. 1989, 14, DE
733471 A1 19890420.
6
. Lygo, B.; Andrews, B. I. Acc. Chem. Res. 2004, 37, 518;
Jones, R. A. Quaternary Ammonium Salts, 1st ed.;
Academic: London, 2001; O’Donnell, M. J. Asymmetric
phase transfer reactions. In Catalytic Asymmetric Synthe-
sis, 2nd ed.; Ojima, I., Ed., Verlag Chemie: New York,
2
000; Starks, C. M.; Liotta, C. L.; Halpern, M. Phase-
Transfer Catalysis; Chapman and Hall: New York, 1994;
Kellaer, W. E. Phase-Transfer Reactions. In Fluka-Com-
pendium; Georg Thieme: New York, 1986; Vol. 1; Dehm-
low, E. V.; Dehmlow, S. S. Phase Transfer Catalysis; Verlag
Chemie: Weinheim, 1980; Starks, C. M.; Liotta, C. Phase
Transfer Catalysis; Academic Press: New York, 1978.
. Weiss, R.; Reichel, S. Eur. J. Inorg. Chem. 2000, 1935; Shi,
Z.; Thummel, R. P. Tetrahedron Lett. 1995, 36, 2741;
Begtrup, M. J. Chem. Soc., Chem. Commun. 1975, 334.
. 3-Butyl-1H-indene might be produced by alkene-isomer-
ization of initially produced 1-butyl-1H-indene.
Acknowledgment
We thank the support by a Science Frontier Project
from The Ministry of Education, Culture, Sport, Science
and Technology (Japan).
7
References and notes
8
9
1
. Binnemans, K. Chem. Rev. 2005, 105, 4148; Hemeon, I.;
Dickson, S.; Singer, R. D. Recent Research Developments
in Organic Chemistry 2002, 6, 499; Dupont, J.; de Souza,
R. F.; Suarez, P. A. Z. Chem. Rev. 2002, 102, 3667;
Olivier-Bourbigou, H.; Magna, L. J. Mol. Catal. A: Chem.
002, 182–183, 419; Wasserscheid, P.; Keim, W. Angew.
Chem., Int. Ed. 2000, 39, 3772; Welton, T. Chem. Rev.
999, 99, 2071.
2
. Ring deuteration of imidazolium cations in D O under
basic conditions has been reported Giernoth, R.; Bank-
mann, D. Tetrahedron Lett. 2006, 47, 4293.
1
1
0. Prepared from indene by the reaction with 10% KOH in
O in the presence of n-Bu NBr (5 mol %).
D
2
4
2
1. Preparation of 1h: Rivas, F. M.; Riaz, U.; Giessert, A.;
Smulik, J. A.; Diver, S. T. 2001, 3, 2673.
1