BmimOAc Catalyzed Michael Addition of Active Methylene to Unsaturated Carboxylic Esters and Nitriles

8/10/2019 BmimOAc Catalyzed Michael Addition of Active Methylene to Unsaturated Carboxylic Esters and Nitriles

http://slidepdf.com/reader/full/bmimoac-catalyzed-michael-addition-of-active-methylene-to-unsaturated-carboxylic 1/4

CHEM. RES. CHINESE UNIVERSITIES 2010, 26(4), 554—557

———————————

*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

α, β -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 α, β -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[1—3]

. 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[4—8]

. To solve these problems,

many catalysts[9—12] 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[13—18]

. 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 inorder 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 α, β -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(1H NMR) were recorded

on JEOL 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.1H NMR(500 MHz, CDCl3), δ: 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), 1.83—1.89(m, 2H), 1.35—1.39(m,

2H), 0.96(t, J =8.0 Hz, 3H).

2.3 Typical Experimental Procedure for MichaelReaction

[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

mL×3). The combined organic phase was dried with

anhydrous MgSO4, 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

product(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

CHCl3, 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

CHCl3 60 77

CH3COCH3 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%) 5 103 [Bmim]Br (2.5%) 10 0

4 [Bmim]BF4 (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]BF4 did not

show any catalytic activity(Entries 3 and 4). Theseresults 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[20—22]

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 α, β -Unsaturated Carboxylic Esters

and Nitriles

In order to investigate the generalities of this

procedure, the reactions of various active methylene

compounds with α, β -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 1—3).

The use of malononitrile furnished the corresponding

Scheme 3 Michael addition reaction of various active

methylene compounds with α, β -unsatu-

rated carboxylic esters and nitriles in the

presence [Bmim]OAc

Table 3 Michael addition catalyzed by ionic liquid [Bmim]OAca

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

1 CO2Me

(1c)

5 92

2 CO2Et

(2c)

30 95

3 CN

(3c)

45 91

4 CO2Me

(4c)

45 92

6 CO2Et

(5c)

45 97

6 CN

(6c)

45 83

7c CN

(7c)

180 71

8d CO2Me

(8c)

30 85

9c 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 4—6). Diethyl malonate reacted with

acrylonitrile as well to afford the bis-addition pro-

duct(7c) in a good yield(71%) at a relative highertemperature(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).

3.41H NMR Spectra of Synthesized Compounds

Compound 1c: light yellow oil.1H NMR(400

MHz, CDCl3), δ: 4.29(q, J =8.0 Hz, 2H), 3.72(s, 6H),

2.56—2.64(m, 2H), 2.39—2.47(m, 2H), 2.27—2.34

(m, 2H), 2.13—2.21(m, 2H), 1.34(t, J =8.0 Hz, 3H).

Compound 2c: light yellow oil,1H NMR(500

MHz, CDCl3), δ: 4.28(q, J =7.0 Hz, 2H), 4.13—4.18

(m, 4H), 2.55—2.59(m, 2H), 2.41—2.44(m, 2H),

2.28—2.30(m, 2H), 2.17—2.20(m, 2H), 1.35(t, J =7.0

Hz, 3H), 1.27(t, J =7.2 Hz, 6H).

Compound 3c: light yellow oil,1H NMR(400

MHz, CDCl3), δ: 4.38(q, J =8.0 Hz, 2H), 2.62—2.71

(m, 2H), 2.50—2.58(m, 2H), 2.38—2.45(m, 2H),

2.17—2.24 (m, 2H), 1.39(t, J =8.0 Hz, 3H).

Compound 4c: white solid,1H NMR(500 Hz,

CDCl3), δ: 3.74(s, 6 H), 2.70—2.75(m, 4H),

2.31—2.35(m, 4H).

Compound 5c: light yellow oil,1H NMR(400 Hz,

CDCl3), δ: 4.20(q, J =8.0 Hz, 4H), 2.70—2.74(m, 4H),

2.32—2.36(m, 4H), 1.29(t, J =8.0 Hz, 6H).

Compound 6c: white solid,1H NMR(500 MHz,

CDCl3), δ: 2.80—2.83(m, 4H), 2.43—2.46(m, 4H).Compound 7c: white solid,

1H NMR(400 MHz,

CDCl3), δ: 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,1H NMR(500 MHz,

CDCl3), δ: 3.69(s, 6H), 2.28—2.38(m, 6H), 2.15—

2.19(m, 2H), 1.54(s, 3H).

Compound 9c: white solid,1H NMR(500 MHz,

CDCl3), δ: 7.75—7.77(m, 2H), 7.88—7.90(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 α, β -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.

References

[1] Myers J. K., Jacobsen E. N., J. Am. Chem. Soc., 1999, 121, 8959

[2]

Yadav J. S., Reddy B. V. S., Baishya G., J. Org. Chem., 2003, 68,

7098

[3] Azizi N., Saidi M. R., Tetrahedron, 2004, 60, 383

[4] Kobayashi S., Synlett ., 1994, 25, 689

[5] Ambhaikar N. B., Snyder J. P., Liotta D. C., J. Am. Chem. Soc., 2003,

125, 3690

[6] Sani M., Bruche L., Chiva G., Fustero S., Piera J., Volonterio A.,

Zanda M., Angew. Chem., Int. Ed., 2003, 42, 2060

[7] Fadini L., Togni A., Chem. Commun., 2003, 30

[8] Adrian J. C., Snapper M. L., J. Org. Chem., 2003, 68, 2143

[9] Martin-Aranda R. M., Ortega-Cantero E., Rojas-Cervantes M. L.,

Vicente-Rodriguez M. A., Banares-Munoz M. A., Catal. Lett., 2002,

84, 201[10] Yang L., Xu L. W., Xia C. G., Tetrahedron Lett., 2005, 46 , 3279

[11] Kim D. Y., Huh S. C., Kim S. M., Tetrahedron Lett., 2001, 42, 6299

[12] Horvath A., Tetrahedron Lett., 1996, 37 , 4423

[13] Chiappe C., Leandri E., Tebano M., Green Chem., 2006, 8, 742

[14] Xin X., Guo X., Duan H. F., Lin Y., Sun H., Catal. Commun., 2007, 8,

115

[15] Cole A. C., Jensen J. L., Ntai I., Traro K. L. T., Weaver K. J.,

Forbes D. C., Davis J. H., J. Am. Chem. Soc., 2002, 124, 5962

[16] Jiang N., Ragauskas A. J., Tetrahedron Lett., 2007, 48, 273

[17] Jiang T., Gao H. X., Han B. X., Zhao G., Chang Y., Wu W., Gao L.,

Yang G., Tetrahedron Lett., 2004, 45, 2699

[18] Xawkat A., Ablajan K., Hiraku S., Chem. Res. Chinese Universities,

2009, 25(2), 161

[19] Ranu B. C., Banerjee S., Org. Lett., 2005, 7 , 3049

[20] Fu X., Zhang Z., Li C., Wang L., Ji H., Yang Y., Zou T., Gao G., Ca-

tal. Commun., 2009, 10, 665

[21] Aggarwal A. A., Lancaster N. L., Sethi A. R., Weltoro T., Green

Chem., 2002, 4, 517

[22] Gholap A. R.,Venkatesan K., Daniel T., Lahoti R. J., Srinivasan K. V.,

Green Chem., 2003, 5, 693

Documents

BmimOAc Catalyzed Michael Addition of Active Methylene to Unsaturated Carboxylic Esters and Nitriles