CHEM. RES.

CHINESE UNIVERSITIES 2010, 26(4), 554557

*Corresponding author. E-mail: [email protected]
Received September 23, 2009; accepted November 16, 2009.
Supported by the National Natural Science Foundation of China(Nos.20533010 and 20873041) and Shanghai Leading Aca-
demic Discipline Project, China(No.B409).

[Bmim]OAc Catalyzed Michael Addition of Active Methylene to
, -Unsaturated Carboxylic Esters and Nitriles
YANG Yu, WANG Li-bing, ZHANG Zhan, LI Cai-meng, FU Xian-lei and GAO Guo-hua
*

Shanghai Key Laboratory of Green Chemistry and Chemical Processes, Department of Chemistry,
East China Normal University, Shanghai 200062, P. R. China

Abstract Michael addition of active methylene compounds to ,-unsaturated carboxylic esters and nitriles was ef-
fectively catalyzed by a basic ionic liquid, 1-butyl-3-methylimidazolium acetate([Bmim]OAc). The bis-addition
products were selectively obtained in high yields under mild reaction conditions.
Keywords Michael addition; [Bmim]OAc; Bis-addition; Mild reaction condition
Article ID 1005-9040(2010)-04-554-04

1 Introduction
Michael addition is one of the most important
carbon-carbon bond formation reactions in organic
chemistry and is widely applied in organic synthe-
ses
[13]
. Conventionally, this type of addition reac-
tions of nucleophiles and unsaturated carbonyl com-
pounds is catalyzed by strong bases and Lewis acids,
leading to undesired by-products and environmentally
hazardous residues
[48]
. To solve these problems,
many catalysts
[912]
have been developed. However,
these catalysts were also suffered from a large amount
of catalyst used
[9]
, long reaction time
[10,11]
, high
temperature
[12]
and low yields
[9,11]
. Ionic liquids, as a
new kind of solvent and catalyst, have been applied in
many organic reactions
[1318]
. Recently, a task-
specific ionic liquid, [Bmim]OH, has been used as a
catalyst and a reaction medium in Michael addition of
active methylene compounds to conjugated ketones,
carboxylic esters and nitriles
[19]
. However, in this pro-
tocol, a large amount of [Bmim]OH was required in
order to achieve high yields. In this article, we would
like to report a basic ionic liquid, 1-butyl-3-methyli-
midazolium acetate([Bmim]OAc) to catalyze Michael
addition of active methylene to , -unsaturated car-
boxylic esters and nitriles under room temperature.
2 Experimental
2.1 General Procedure
N-Methylimidazolium was fractionally distilled.
The other reagents were commercial reagents of A. R.
grade and used without further purification. Quantita-
tive analysis of the reaction mixture was performed
with a gas chromatograph(Shimadzu GC-14B). Proton
magnetic resonance spectra(
1
H NMR) were recorded
on J EOL 400 MHz with tetramethylsilane as the
internal standard.
2.2 Synthesis of 1-Butyl-3-methylimidazolium
Acetate([Bmim]OAc)
AgOAc(0.67 g, 4 mmol) was added to a solution
of [Bmim]Cl(0.700 g, 4 mmol) in water(10 mL) and
stirred at room temperature for 4 h. The suspension
was filtered to remove silver chloride. The water was
removed in vacuo to afford 0.69 g(85%) of a colorless
oil.
1
H NMR(500 MHz, CDCl
3
), : 11.10(s, 1H),
7.28(s, 1H), 7.22(s, 1H), 4.29(t, J=8.0 Hz, 2H), 4.05(s,
3H), 1.97(s, 3H), 1.831.89(m, 2H), 1.351.39(m,
2H), 0.96(t, J=8.0 Hz, 3H).
2.3 Typical Experimental Procedure for Michael
Reaction
[Bmim]OAc(0.099 g, 0.05 mmol) was added to a
solution of ethyl cyanoacetate(0.227 g, 2 mmol) and
methyl acrylate(0.430 g, 5 mmol) in DMSO(2 mL).
The reaction mixture was stirred for 5 min. The reac-
tion was quenched by adding water(80 mL). The re-
sulting mixture was extracted with ethyl ether(30
mL3). The combined organic phase was dried with
anhydrous MgSO
4
, and evaporated. The crude product
No.4 YANG Yu et al. 555

was analyzed with a gas chromatograph and purified
by column chromatography over silica gel to afford
0.524 g(yield 92%) of the corresponding bis-addition
pro- duct(1c) as light yellow oil.
3 Results and Discussion
3.1 Effect of Various Solvents
The addition reaction of ethyl cyanoacetate with
methyl acrylate was carried out in various solvents in
the presence of a catalytic amount of [Bmim]OAc
(Scheme 1). As shown in Table 1, the catalytic activity
of [Bmim]OAc varied with different solvents. In
DMSO, DMF and THF, the same product was ob-
tained in the yields of 94%, 87%, and 78%, respec-
tively within 5 min at room temperature. However, the
catalytic activity of [Bmin]OAc was relatively low in
CHCl
3
, acetone and toluene and the same product was
obtained in the yields of 77%, 69% and 40% in 1 h,
respectively. The addition reaction hardly proceeded
in the protonic solvents such as ethanol and water un-
der the same reaction condition. It is worth mentio-
ning that only a bis-addition product was detected in
the reaction mixture.





Scheme 1 Michael addition reaction of ethyl
cyanacetate with methyl acrylate
Table 1 Effects of various solvents on Michael addition
*

Solvent Reaction time/min GC yield(%)
DMSO 5 94
DMF 5 87
THF 5 78
CHCl
3
60 77
CH
3
COCH
3
60 69
Toluene 60 40
Ethanol 60 <1
Water 60 5
* Reaction conditions: methyl acrylate: 5 mmol; ethyl cyanoacetate:
2 mmol; [Bmim]OAc: 0.2 mmol; solvent: 2 mL; temperature: 30 C.
3.2 Effects of Various Ionic Liquids
In order to check the catalytic species of ionic
liquids, ionic liquids with different cations and anions
were applied to catalyzing the addition reaction of
ethyl cyanoacetate with methyl acrylate. The results
are listed in Table 2. In the presence of molar fraction
of 2.5% [Bmim]OAc, ethyl cyanoacetate reacted
with methyl acrylate, affording the corresponding
Table 2 Effect of various ionic liquids on
Michael addition
*

Entry Ionic liquid(molar fraction) Time/min GC yield(%)
1 [Bmim]OAc (2.5%) 5 92
2 [Bmim]OH (2.5%) 5 10
3 [Bmim]Br (2.5%) 10 0
4 [Bmim]BF
4
(2.5%) 10 0
5 [Bmmim]OAc (2.5%) 5 46
6 [Bmim]OAc (1%) 10 66
7 [Bmmim]OAc (1%) 10 36
* Reaction conditions: methyl acrylate: 5 mmol; ethyl cyanoacetate:
2 mmol; DMSO: 2 mL; temperature: 30 C.
product in a yield of 92% within 5 min at room tem-
perature(Entry 1). In comparison, [Bmim]OH gave a
low yield of 10% under the same reaction condi-
tions(Entry 2), and [Bmim]Br and [Bmim]BF
4
did not
show any catalytic activity(Entries 3 and 4). These
results indicate that the anions of the ionic liquids play
a dominating role in the addition reaction. The anion
of OAc

showed the highest activity in the addition

reaction. However, when 1,2-dimethyl-3-butyl imida-
zolium acetate([Bmmim]OAc), in which the proton in
2-position of imidazolium is replaced by a methyl
group, was applied to catalyzing the reaction of ethyl
cyanoacetate with methyl acrylate, the activity
dropped to 46%(Entry 5). Similar results were also
observed in the less amount of ionic liquids(1%).
[Bmim]OAc afforded the desired product in a yield of
66%, while [Bmmim]OAc gave a yield of 36%
(Entries 6 and 7). The above results show that pro-
ton on 2-position in imidazolium cation also plays an
important role in catalyzing the reaction of ethyl cya-
noacetate and methyl acrylate. Others and we
[2022]
have found the proton on the 2-position of imidazo-
lium cation can activate carbonyl group through the
hydrogen bond interaction in the carbomethoxylation
and Diels-Alder reactions. The role of proton on the
2-position of imidazolium cation in the addition reac-
tion can be explained as the activation of the carbonyl
group of methyl acrylate through hydrogen bonding,
while the OAc

group acts as a base to form carbanion

by the deprotonation of cyanoacetate(Scheme 2).
[Bmim]OAc can activate both the reactants, exhibiting
the highest activity among the ionic liquids we ap-
plied.






Scheme 2 Deprotonation of cyanoacetate

556 CHEM. RES. CHINESE UNIVERSITIES Vol.26


3.3 Reaction of Various Active Methylene Com-
pounds and , -Unsaturated Carboxylic Esters
and Nitriles
In order to investigate the generalities of this
procedure, the reactions of various active methylene
compounds with ,-unsaturated carboxylic esters and
nitriles were carried out in the presence of
[Bmim]OAc(Scheme 3). The results are summarized
in Table 3. Ethyl cyanoacetate reacted with methyl
acrylate, ethyl acrylate and acrylonitrile, giving the
sole bis-addition products(1c, 2c and 3c) in the yields
of 92%, 95% and 91%, respectively(Entries 13).
The use of malononitrile furnished the corresponding




Scheme 3 Michael addition reaction of various active
methylene compounds with , -unsatu-
rated carboxylic esters and nitriles in the
presence [Bmim]OAc
Table 3 Michael addition catalyzed by ionic liquid [Bmim]OAc
a

Entry Active methylene compound R
3
Product Reaction time/min Yield(%)
b

1 CO
2
Me
(1c)
5 92
2 CO
2
Et
(2c)
30 95
3 CN

(3c)
45 91
4 CO
2
Me

(4c)
45 92
6 CO
2
Et
(5c)
45 97
6 CN

(6c)
45 83
7
c
CN

(7c)
180 71
8
d
CO
2
Me
(8c)
30 85
9
c
CN

(9c)
150 98
a. Reaction conditions: methyl acrylate: 5 mmol; ethyl cyanoacetate: 2 mmol; [Bmim]OAc: 0.05 mmol; solvent: 2 mL; temperature: 30 C; b. isolated
yield;

c. 60 C, [Bmim]OAc: 0.10 mmol; d. [Bmim]OAc: 0.10 mmol.
No.4 YANG Yu et al. 557



bis-addition products(4c, 5c and 6c) in high
yields(Entries 46). Diethyl malonate reacted with
acrylonitrile as well to afford the bis-addition pro-
duct(7c) in a good yield(71%) at a relative higher
temperature(60 C) in a longer reaction time in the
presence of 5% [Bmim]OAc(Entry 7). The reaction
of nitroethane with methyl acrylate proceeded well
and gave the bis-addition product in a yield of
85%(Entry 8). In terestingly, phthalimide also un-
derwent the addition reaction with acrylonitrile and
furnished the mono-addition product in a yield of
98%(Entry 9).
3.4
1
H NMR Spectra of Synthesized Compounds
Compound 1c: light yellow oil.
1
H NMR(400
MHz, CDCl
3
), : 4.29(q, J=8.0 Hz, 2H), 3.72(s, 6H),
2.562.64(m, 2H), 2.392.47(m, 2H), 2.272.34
(m, 2H), 2.132.21(m, 2H), 1.34(t, J=8.0 Hz, 3H).
Compound 2c: light yellow oil,
1
H NMR(500
MHz, CDCl
3
), : 4.28(q, J=7.0 Hz, 2H), 4.134.18
(m, 4H), 2.552.59(m, 2H), 2.412.44(m, 2H),
2.282.30(m, 2H), 2.172.20(m, 2H), 1.35(t, J=7.0
Hz, 3H), 1.27(t, J=7.2 Hz, 6H).
Compound 3c: light yellow oil,
1
H NMR(400
MHz, CDCl
3
), : 4.38(q, J=8.0 Hz, 2H), 2.622.71
(m, 2H), 2.502.58(m, 2H), 2.382.45(m, 2H),
2.172.24 (m, 2H), 1.39(t, J=8.0 Hz, 3H).
Compound 4c: white solid,
1
H NMR(500 Hz,
CDCl
3
), : 3.74(s, 6 H), 2.702.75(m, 4H),
2.312.35(m, 4H).
Compound 5c: light yellow oil,
1
H NMR(400 Hz,
CDCl
3
), : 4.20(q, J=8.0 Hz, 4H), 2.702.74(m, 4H),
2.322.36(m, 4H), 1.29(t, J=8.0 Hz, 6H).
Compound 6c: white solid,
1
H NMR(500 MHz,
CDCl
3
), : 2.802.83(m, 4H), 2.432.46(m, 4H).
Compound 7c: white solid,
1
H NMR(400 MHz,
CDCl
3
), : 4.28(q, J=8.0 Hz, 4H), 2.47(t, J=8.0 Hz,
4H), 2.26(t, J=8.0 Hz, 4H), 1.30(t, J=8.0 Hz, 6H).
Compound 8c: yellow oil,
1
H NMR(500 MHz,
CDCl
3
), : 3.69(s, 6H), 2.282.38(m, 6H), 2.15
2.19(m, 2H), 1.54(s, 3H).
Compound 9c: white solid,
1
H NMR(500 MHz,
CDCl
3
), : 7.757.77(m, 2H), 7.887.90(m, 2H),
4.01(t, J=6.9 Hz, 2H), 2.81(t, J=6.9 Hz, 2H).
4 Conclusions
In summary, basic ionic liquid, [Bmim]OAc, is
an effective catalyst for Michael addition of active
methylene compounds with ,-unsaturated carboxy-
lic esters and nitriles. The [Bmim]OAc catalyzed pro-
tocol has the advantages of mild reaction condition,
short reaction time and high selectivity for bis-
addition products.

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