Ionic liquid as catalyst and reaction medium. The dramatic influence of a task-specific ionic liquid, [bmIm]OH, in Michael addition of active methylene compounds to conjugated ketones, carboxylic esters, and nitriles

Article abstract of DOI:10.1021/ol051004h

(Chemical Equation Presented) A task-specific ionic liquid, [bmIm]OH, has been introduced as a catalyst and as a reaction medium in Michael addition. Very interestingly, although the addition to α,β-unsaturated ketones proceeds in the usual way, giving the monoaddition products, this ionic liquid always drives the reaction of open-chain 1,3-dicarbonyl compounds with α,β-unsaturated esters and nitriles toward bis-addition to produce exclusively bis-adducts in one stroke.

Full text of DOI:10.1021/ol051004h

ORGANIC
LETTERS
2
005
Vol. 7, No. 14
049-3052
Ionic Liquid as Catalyst and Reaction
Medium. The Dramatic Influence of a
Task-Specific Ionic Liquid, [bmIm]OH, in
Michael Addition of Active Methylene
Compounds to Conjugated Ketones,
Carboxylic Esters, and Nitriles
3
Brindaban C. Ranu* and Subhash Banerjee
Department of Organic Chemistry, Indian Association for the CultiVation of Science,
JadaVpur, Kolkata 700 032, India
ocbcr@iacs.res.in
Received May 3, 2005
ABSTRACT
A task-specific ionic liquid, [bmIm]OH, has been introduced as a catalyst and as a reaction medium in Michael addition. Very interestingly,
although the addition to -unsaturated ketones proceeds in the usual way, giving the monoaddition products, this ionic liquid always drives
r,â
the reaction of open-chain 1,3-dicarbonyl compounds with
bis-adducts in one stroke.
r,
â
-unsaturated esters and nitriles toward bis-addition to produce exclusively
Ionic liquids have attracted increasing interest in the context
of green synthesis in recent times. Although ionic liquids
were initially introduced as alternative green reaction media
because of their unique chemical and physical properties of
nonvolatility, nonflammability, thermal stability, and con-
moisture sensitivity and decomposition of this chloroalumi-
nate salt under normal atmospheric conditions are two major
drawbacks to its practical use. Thus, a number of similar
ionic liquids have been developed subsequently by replace-
ment of chloroaluminate with anionic species such as
1
1c
trolled miscibility, today they have marched far beyond this
tetrafluoroborate and hexafluorophosphate. As a part of our
border, showing their significant role in controlling the
reaction as catalysts.1 The first successful use of an ionic
liquid, dialkylimidazolium chloroaluminate, as a catalyst in
program to explore the full potential of ionic liquids in
chemical transformations, we have already demonstrated the
very efficient role of ionic liquids as catalysts and reagents
c,2
3
4
2a
Friedel-Crafts acylations was reported in 1986. However,
in various reactions. In this letter, we report the dramatic
(
1) (a) Welton, T. Chem. ReV. 1999, 99, 2071. (b) Wasserscheid, P.;
(2) (a) Boon, J. A.; Levinsky, J. A.; Pflug, J. I.; Wilkes, J. S. J. Org.
Chem. 1986, 51, 480. (b) Harjani, J. R.; Nara, S. J.; Salunkhe, M. M.
Tetrahedron Lett. 2002, 43, 1127. (c) Namboodiri, V. V.; Varma, R. S.
Chem. Commun. 2002, 342. (d) Sun, W.; Xia, C.-G.; Wang, H.-W.;
Tetrahedron Lett. 2003, 44, 2409. (e) Qiao, K.; Yakoyama, C. Chem. Lett.
2004, 33, 472. (f) Akaiyama, T.; Suzuki, A.; Fuchibe, K. Synlett. 2005,
1024.
Keim, W. Angew. Chem., Int. Ed. 2000, 39, 3773. (c) Sheldon, R. Chem.
Commun. 2001, 2399. (d) Wilkes, J. S. Green Chem. 2002, 4, 73. (e) Yao,
Q. Org. Lett. 2002, 4, 2197. (f) Zerth, H. M.; Leonard, N. M.; Mohan, R.
S. Org. Lett. 2003, 5, 55. (g) Kumar, A.; Pawar, S. S. J. Org. Chem. 2004,
9, 1419. (h) Gu, D.-G.; Ji, S.-J.; Jiang, Z.-Q.; Zhou, M.-F.; Loh, T.-P.
Synlett 2005, 959.
6
1
0.1021/ol051004h CCC: $30.25
© 2005 American Chemical Society
Published on Web 06/11/2005

influence of a new tailor-made, task-specific, and stable ionic
liquid, [bmIm]OH, in Michael addition.
procedure11 to provide the corresponding adducts in high
yields. The results are summarized in Table 1. Very
interestingly, all open-chain 1,3-dicarbonyl compounds such
as acetylacetone, ethyl acetoacetate, diethyl malonate, and
ethyl cyanoacetate reacted with methyl vinyl ketone (entries
1, 4, 7, 15, 19, 22, 24) and chalcone (entries 9-12, 18) to
give the usual monoaddition products, whereas the same
reactions with methyl acrylate (entries 2, 6, 13, 16) or
acrylonitrile (entries 3, 14, 17) provided exclusively bis-
addition products. The use of 0.5 equiv or less of methyl
acrylate or acrylonitrile in these reactions also did not
produce any monoaddition product; only the bis-adducts were
isolated in proportionate yields. On the other hand, use of
excess methyl vinyl ketone did not furnish any bis-addition
product under identical reaction conditions. Surprisingly, the
reaction of nitroethane with methyl vinyl ketone, methyl
acrylate, or acrylonitrile proceeded in the normal way,
providing the monoadduct (entries 24-26). Although all the
conventional reagents produce the monoadduct in Michael
additions with these conjugated alkenes, the formation of
bis-adducts in one stroke with methyl acrylate and acryloni-
trile is not unprecedented and was reported in one procedure
using trans-hydrido(n′-o-enolato)ruthenium(II) complex.8d
But, the serious drawbacks of using this ruthenium catalyst
are a long reaction time (48-96 h) at 50-70 °C and
relatively low yields (60-89%). However, in general, the
great significance of this rather unusual bis-addition is the
formation of two C-C bonds in one step; moreover, these
adducts (entries 2, 3, 6, 13, 14, 16, 17) have great synthetic
potential, as they contain several important functional groups.
This ionic liquid, [bmIm]OH, is very successful in catalyzing
The Michael addition is one of the most useful carbon-
carbon bond-forming reactions and has wide synthetic
5
applications in organic synthesis. This reaction is tradition-
ally catalyzed by strong bases that often lead to undesirable
6
side reactions. A variety of Lewis acids are found to catalyze
this reaction, and these procedures are also not free from
7
disadvantages. Thus, a number of milder reagents such as
8
a
8b
8c
8d
2 3 2 3
Al O , K CO , rhodium complex, ruthenium complex,
8e
8f
clay-supported nickel bromide, quaternary ammonium salt,
and N-phenyltris(dimethylamino)iminophosphorane immo-
8g
bilized on polystyrene resin have been developed over the
past few years. Recently, room-temperature ionic liquids,
particularly [bmIm]BF
4
, have been used as alternative green
9
a
solvents to carry out the Michael addition using Ni(acac)
2
9
b
and Cu(II) triflate as catalysts. However, we have discov-
10
ered that a task-specific ionic liquid [bmIm]OH efficiently
promotes the Michael addition of 1,3-dicarbonyl compounds,
cyano esters, and nitro alkanes to a variety of conjugated
ketones, carboxylic esters, and nitriles without requiring any
other catalyst and solvent. The dramatic influence of this
catalyst in additions to certain conjugated alkenes is observed
6-9
(Scheme 1).
Scheme 1
(9) (a) Dell’Anna, M. M.; Gallo, V.; Mastrorilli, P.; Nobile, C. F.;
Romanazzi, G.; Suranna, G. P. Chem. Commun. 2002, 434. (b) Yadav, J.
S.; Reddy, B. V. S.; Baishya, G.; Narsaiah, A. V. Chem. Lett. 2005, 34,
1
02.
(10) Preparation of 1-Butyl-3-methylimidazolium Hydroxide [bmIm]-
1
3
OH. This was prepared by modification of a reported related procedure.
A variety of structurally diverse active methylene com-
pounds underwent Michael additions with several R,â-
unsaturated ketones, carboxylic esters, and nitriles by this
Solid potassium hydroxide (2.3 g, 40 mmol) was added to a solution of
[bmIm]Br (8.8 g, 40 mmol) in dry methylene chloride (20 mL), and the
mixture was stirred vigorously at room temperature for 10 h. The precipitated
KBr was filtered off, and the filtrate was evaporated to leave the crude
[
bmIm]OH as a viscous liquid that was washed with ether (2 × 20 mL)
(
3) (a) Ranu, B. C.; Das, A.; Samanta, S. J. Chem. Soc., Perkin Trans.
2002, 1520. (b) Ranu, B. C.; Dey, S. S. Tetrahedron Lett. 2003, 44, 2865.
c) Ranu, B. C.; Dey, S. S.; Hajra, A. Tetrahedron 2003, 59, 2417. (d)
and dried at 90 °C for 10 h to prepare the pure ionic liquid for use. This
was characterized by spectroscopic data: IR (neat) 3435, 3060, 1569, 1168
1
(
-
1 1
cm ; H NMR (300 MHz, CDCl3) δ 0.83 (t, J ) 7.2 Hz, 3H), 1.15-1.32
(m, 2H), 1.76-1.86 (m, 2H), 3.18-3.25 (bs, 1H), 4.00 (s, 3H), 4.23 (t, J
) 7.2 Hz, 2H), 7.46 (d, J ) 1.5 Hz, 1H), 7.59 (d, J ) 1.5 Hz, 1H), 10.15
(s, 1H); 13C NMR (75 MHz) δ 13.1, 19.0, 31.8, 36.4, 49.3, 122.0, 123.5,
Ranu, B. C.; Dey, S. S. Tetrahedron 2004, 60, 4183. (e) Ranu, B. C.; Das,
A. Aust. J. Chem. 2004, 57, 605. (f) Ranu, B. C.; Jana, R.; Dey, S. S. Chem.
Lett. 2004, 33, 274. (g) Ranu, B. C.; Jana, R. Eur. J. Org. Chem. 2005,
+
7
75.
136.5; HRMS calcd for C8H16N2O (M - OH) 139.2182, found 139.2355.
(4) Ranu, B. C.; Banerjee, S. J. Org. Chem. 2005, 70, 4517.
5) (a) Perlmutter, P. Conjugate Addition Reactions in Organic Synthesis;
(11) Representative Experimental Procedure for Michael Addition
of Methyl Vinyl Ketone with Ethyl 2-Oxo-cyclopentane Carboxylate
(Entry 19). Methyl vinyl ketone (420 mg, 6 mmol) was added dropwise to
a well stirred mixture of ethyl 2-oxo-cyclopentane carboxylate (755 mg, 5
mmol) in [bmIm]OH (468 mg, 3 mmol), and the reaction mixture was stirred
for 0.5 h until completion of the reaction (TLC). The product was then
distilled off directly from the reaction mixture to provide pure Michael
adduct (1.08 g, 96%) as a colorless oil. If the reaction was carried out in a
relatively smaller scale (1-2 mmol), the reaction mixture was extracted
with ethyl acetate. The extract was washed with brine, dried (Na2SO4), and
evaporated, leaving the crude product, which was purified by column
chromatography over silica gel to provide the pure product. The compound
(
Pergamon: Oxford, 1992. (b) Jung, M. E. In ComprehensiVe Organic
Synthesis; Trost, B. M., Fleming, I., Semmelhack, M. F., Eds.; Pergamon:
Oxford, 1991; Vol. 4.
(
6) (a) Bergmann, E. D.; Ginsburg, D.; Pappo, R. Org. React. 1959, 10,
79. (b) Kobayashi, S. Synlett 1994, 689.
7) (a) Christoffers, J. Eur. J. Org. Chem. 1998, 1259. (b) Srivastava,
1
(
N.; Banik, B. K. J. Org. Chem. 2003, 68, 2109. (c) Shimizu, K. I.; Miyagi,
M.; Kan-No, T.; Kodama, T.; Kitayama, Y. Tetrahedron Lett. 2003, 44,
7
421.
(8) (a) Ranu, B. C.; Bhar, S.; Sarkar, D. C. Tetrahedron Lett. 1991, 32,
1
13
2
811. Ranu, B. C.; Bhar, S. Tetrahedron 1992, 48, 1327. (b) Zhang, Z.;
was identified by comparison of its IR and H and C NMR spectroscopic
data with those reported.9b The ionic liquid left in the reaction vessel was
rinsed with ether (2 mL) and dried under vacuum at 90 °C for 2 h to
eliminate any water trapped from moisture and reused for subsequent
reactions. To compensate for the loss of some ionic liquid during washing,
an amount (200 mg) of fresh ionic liquid was added after five runs. This
procedure was followed for all the reactions listed in Table 1. However, in
bis-additions, 2 equiv of methyl acrylate and acrylonitrile was used.
Dong, Y.-W.; Wang, G.-W.; Komatsu, K. Synlett 2004, 61. (c) Paganelli,
S.; Schionato, A.; Botteghi, C. Tetrahedron Lett. 1991, 32, 2807. (d) Alvarez,
S. G.; Hasegawa, S.; Hirano, M.; Komiya, S. Tetrahedron Lett. 1998, 39,
209. (e) Laszlo, P.; Montaufier, M.-T.; Randriamahefa, S. L. Tetrahedron
Lett. 1990, 31, 4867. (f) Kim, D. Y.; Huh, S. C.; Kim, S. M. Tetrahedron
Lett. 2001, 42, 6299. (g) Bensa, D.; Constantieux, T.; Rodriguez, J. Synthesis
5
2
004, 923.
3050
Org. Lett., Vol. 7, No. 14, 2005

Table 1. Michael Addition Catalyzed by [bmIm]OH
a
Yields refer to those of pure isolated products characterized by IR and H and 13C NMR spectroscopic data. b Reaction was carried out at 110 °C.
1
this process making it feasible within a reasonable time
period (1.5-2.5 h) at room temperature with very high yields
of products (85-95%). We must admit that the reason for
this unusual behavior of this ionic liquid toward reaction with
methyl acrylate and acrylonitrile is not known at this stage.
However, the dramatic influence of ionic liquids on the
outcome of chemical reaction has also been observed in the
ketone by a tandem reaction of Michael addition followed
by aldol condensation. Certainly, this is of much synthetic
importance.
In general, all the reactions are very clean and reasonably
fast. The reaction conditions are mild (room temperature),
accepting several functional groups present in the molecules.
In relatively larger scale (3 mmol and greater) reactions, the
products are distilled directly from the reaction vessel, thus
avoiding organic solvents totally. The ionic liquid has been
1
2
reaction of toluene with nitric acid as reported recently.
The cyclic â-keto esters underwent smooth additions by
this procedure (entries 19-23). However, reaction of ethyl
cyclopentanone carboxylate (entry 27) with methyl vinyl
ketone at 110 °C furnished the annulated bicyclic conjugated
11
reused in up to six runs without loss of activity.
In conclusion, the present procedure using a basic (pH
9
.3 at 30 °C) and easily available ionic liquid [bmIm]OH
provides an efficient and convenient procedure for Michael
addition of active methylene compounds with conjugated
alkenes without requirement of any other catalyst and organic
solvent. This method offers marked improvements with
regard to operational simplicity, reaction time, reaction
conditions, general applicability, high isolated yields of
products, and greenness of procedure, avoiding hazardous
organic solvents and toxic catalysts, and thus it provides a
(
(
12) Earle, M. J.; Katdare, S. P.; Seddon, K. R. Org. Lett. 2004, 6, 707.
13) Mehnert, C. P.; Dispenziere, N. C.; Cook, R. A. Chem. Commun.
2
002, 1610.
(
(
(
(
(
14) Chong, R.; Clezy, P. S. Aust. J. Chem. 1967, 20, 123.
15) Zellars, G. R.; Levine, R. J. Org. Chem. 1948, 13, 911.
16) Kocovsky, P.; Dvarak, D. Tetrahedron Lett. 1986, 27, 5015.
17) Albertson, N. F. J. Am. Chem. Soc. 1950, 72, 2594.
18) Ono, N.; Kamimura, A.; Miyake, H.; Hamamoto, I.; Kaji, A. J.
Org. Chem. 1985, 50, 3691.
19) Heath, C. H.; Ellis, J. E. Tetrahedron Lett. 1971, 12, 4995.
(
Org. Lett., Vol. 7, No. 14, 2005
3051

better and practical alternative to the existing procedures.6-8
However, most significantly, this procedure demonstrates the
dramatic influence of the ionic liquid [bmIm]OH in directing
Michael addition of open-chain 1,3-dicarbonyl compounds
with methyl acrylate and acrylonitrile to bis-addition prod-
ucts, which are difficult to achieve by conventional methods
in one step. Certainly, this observation provides great promise
toward additional useful applications.
01(1936)/04], for this investigation. S.B. is thankful to CSIR
for his fellowship.
Supporting Information Available: Experimental pro-
1
13
cedures and characterization (IR and H and C NMR
spectroscopic data and elemental analysis) for the new
compounds reported in Table 1 (listed in entries 6, 16, 17,
20, 22, 23). This material is available free of charge via the
Internet at http://pubs.acs.org.
Acknowledgment. We are pleased to acknowledge the
financial support from CSIR, New Delhi [Grant No.
OL051004H
3052
Org. Lett., Vol. 7, No. 14, 2005