Bronsted-acidic ionic liquid [HO3S(CH2) 4MIM][HSO4] as efficient and reusable catalyst for one-pot synthesis of β-acetamido ketones

Article abstract of DOI:10.1007/s00706-009-0193-8

Efficient and convenient synthesis of β-acetamido ketones has been achieved by one-pot reaction of acetophenone, aryl aldehydes, acetyl chloride, and acetonitrile in the presence of 3-methyl-1-(4-sulfonylbutyl)imidazolium hydrogensulfate [HO₃S(CH₂)₄MIM][HSO ₄], a Bronsted-acidic ionic liquid, as a green and reusable catalyst in solvent-free media at room temperature. The catalyst could be recycled and reused without noticeable decrease in catalytic activity.

Full text of DOI:10.1007/s00706-009-0193-8

Monatsh Chem (2009) 140:1499–1502
DOI 10.1007/s00706-009-0193-8
ORIGINAL PAPER
Brønsted-acidic ionic liquid [HO3S(CH2)4MIM][HSO4] as efficient
and reusable catalyst for one-pot synthesis of b-acetamido ketones
•
Abolghasem Davoodnia Majid M. Heravi
•
•
Leila Rezaei-Daghigh Niloofar Tavakoli-Hoseini
Received: 5 June 2009 / Accepted: 17 September 2009 / Published online: 7 November 2009
Ó Springer-Verlag 2009
Abstract Efficient and convenient synthesis of b-acet-
amido ketones has been achieved by one-pot reaction of
acetophenone, aryl aldehydes, acetyl chloride, and aceto-
nitrile in the presence of 3-methyl-1-(4-sulfonylbutyl)
imidazolium hydrogensulfate [HO3S(CH2)4MIM][HSO4],
a Brønsted-acidic ionic liquid, as a green and reusable
catalyst in solvent-free media at room temperature. The
catalyst could be recycled and reused without noticeable
decrease in catalytic activity.
drug-discovery processes [6, 7]. For this reason, the dis-
covery of novel MCRs and improving known MCRs are
popular areas of research in current organic chemistry.
b-Acetamido ketones are versatile intermediates because
their skeletons exist in a number of biologically important
compounds [8, 9]. They are usually prepared by acylation of
b-amino ketones [10], Michael addition to a,b-unsaturated
ketones [11], or photoisomerization of phthalimides [12].
The best known route for the synthesis of acetamido ketones
is the Dakin–West reaction [13], which involves the con-
densation of an amino acid with acetic anhydride in the
presence of a base via an azalactone intermediate [14]. Iqbal
et al. proposed another procedure for the formation of these
compounds through the MCR of an aryl aldehyde, aceto-
phenone, and acetyl chloride in acetonitrile in the presence
of CoCl2 [15] or montmorillonite K-10 clay [16].
Keywords Brønsted-acidic ionic liquids Á
Multi-component reactions Á One-pot synthesis Á
b-Acetamido ketones Á Solvent-free conditions
Introduction
b-Acetamido ketones have also been synthesized using
Cu(OTf)2 [17], silica-supported sulfuric acid [18], BiOCl
[19], ZrOCl2Á8H2O [20], NH2SO3H [21], H3PW12O40 [22],
FeCl3Á6H2O [23], and SnCl2Á2H2O [24] as catalysts.
Although these methods are quite useful, most have limi-
tations, for example requirement of expensive catalysts,
long reaction time, and harsh reaction conditions. There-
fore, the development of simple, efficient, clean, high-
yielding, and environmentally friendly approaches using
new catalysts for synthesis of these compounds is an
important task for organic chemists.
Multicomponent reactions (MCRs) are among the most
important procedures in organic synthesis and medicinal
chemistry [1–3]. These processes consist of two or more
synthetic steps, which are performed without isolation of
any intermediates [4, 5]. The diversity, efficiency, and
rapid access to small and highly functionalized organic
molecules make this approach of central interest in the
construction of combinatorial libraries and optimization of
Ionic liquids (ILs), recognized as environmentally benign
media, have been widely applied in many reactions as cata-
lysts or as dual catalyst–solvent because of their low vapor
pressure, reusability, and high thermal and chemical stability
[25, 26]. The introduction of Brønsted-acidic functional
groups into cations or anions of the ILs, especially the SO3H
functional group, obviously enhanced their acidities and
water solubilities [27–30]. Therefore, Brønsted-acidic ILs
A. Davoodnia (&) Á L. Rezaei-Daghigh Á N. Tavakoli-Hoseini
Department of Chemistry, Faculty of Sciences,
Islamic Azad University, Mashhad Branch,
91735-413 Mashhad, Iran
e-mail: adavoodnia@yahoo.com; adavoodnia@mshdiau.ac.ir
M. M. Heravi
Department of Chemistry, School of Sciences,
Azzahra University, Vanak, Tehran, Iran
123

1500
A. Davoodnia et al.
can be used as highly efficient acid catalysts. Moreover their
polar nature makes them useful for use under solvent-free
conditions. In fact, use of Brønsted-acidic ILs as catalysts is
an area of ongoing activity. However, development and
exploration of these catalysts are currently in the preliminary
stage.
Table 2, in comparison with conventional methods the
yields of the reaction under solvent-free conditions are
higher and the reaction time is shorter. Subsequently,
therefore, all reactions were carried out at room tempera-
ture in the presence of 65 mol% HO3S(CH2)4MIM][HSO4]
under solvent-free conditions.
In continuation of our previous work on the applications
of reusable acid catalysts in the synthesis of heterocyclic
compounds [31–33] here we wish to report the green
synthesis of b-acetamido ketones 3a–3l by use of 3-methyl-
1-(4-sulfonylbutyl)imidazolium hydrogensulfate [HO3S
(CH2)4MIM][HSO4] (Scheme 1), a Brønsted-acidic IL,
using one-pot condensation of acetophenone (1), aryl
aldehydes 2a–2l, acetyl chloride, and acetonitrile under
solvent-free conditions (Scheme 2).
To extend the preparative utility and generality of this
multicomponent reaction, a variety of aromatic aldehydes
containing both electron-donating and withdrawing sub-
stituents were used to obtain the corresponding
b-acetamido ketones in good yields under the optimized
reaction conditions (Table 3).
In conclusion, we have developed a mild and simple
method for synthesis of b-acetamido ketones using
[HO3S(CH2)4MIM][HSO4], a Brønsted-acidic IL. The
catalyst can be reused after simple work-up, with a gradual
decline of its activity being observed. Good yields, short
reaction times, simplicity of operation, and easy work-up
are some advantages of this procedure.
Results and discussion
To find the optimum conditions, synthesis of b-acetamido-
b-phenylpropiophenone (3a) was used as model reaction.
A mixture of acetophenone (4 mmol), benzaldehyde
(4 mmol), acetyl chloride (1.2 cm3), and acetonitrile
(12 cm3) was stirred under various reaction conditions
(Table 1). In the absence of the catalyst, b-acetamido-b-
phenylpropiophenone (3a) was obtained in trace amounts
after 180 min, whereas good results were obtained in the
presence of [HO3S(CH2)4MIM][HSO4] after 25–120 min
(entries 2–7). The optimum amount of [HO3S(CH2)4
MIM][HSO4] was 65 mol% (entry 6). A greater amount of
the catalyst was found to have an inhibitory effect on
formation of the product (entry 7).
Experimental
All chemicals were commercially available and used
without further purification. The Brønsted-acidic ionic
liquid [HO3S(CH2)4MIM][HSO4] was synthesized
according to Ref. [34]. Melting points were recorded on an
electrothermal type 9,100 melting point apparatus. The IR
spectra were obtained on a Shimadzu 4300 spectropho-
1
tometer as KBr disks. The H NMR (100 MHz) spectra
were recorded on a Bruker AC 100 spectrometer.
Also, the reaction was carried out in various solvents
and also under solvent-free conditions. As shown in
General procedure for the synthesis of b-acetamido
ketones 3a–3l
To a solution of 4 mmol acetophenone, 4 mmol aryl
aldehyde 2a–2l, 1.2 cm3 acetyl chloride, 12 cm3 acetoni-
trile, and 0.83 g [HO3S(CH2)4MIM][HSO4] (2.6 mmol,
65 mol%) were added. The reaction mixture was stirred at
room temperature for the appropriate time. The progress of
the reaction was monitored by TLC. After completion of
SO3H
Me
N
N
HSO4
[HO3S(CH2)4MIM][HSO4]
Scheme 1
Scheme 2
O
O
O
NHCOCH3
[HO3S(CH2)4MIM][HSO4]
H
+
CH3COCl
CH3CN
R
R
1
2a-2l
3a-3l
a: R = H
g: R = 4-NO2
h: R = 3-Me
i: R = 4-Me
j: R = 3-OH
k: R = 4-OH
l: R = 4-OMe
b: R = 3-Cl
c: R = 4-Cl
d: R = 3-Br
e: R = 2-NO2
f: R = 3-NO2
123

Brønsted-acidic ionic liquid as efficient and reusable catalyst
1501
ethyl acetate–n-hexane. The structure of the products was
1
confirmed by H NMR and IR spectroscopy, and compar-
Table 1 Effect of the amounts of [HO3S(CH2)4MIM][HSO4] on the
reaction
ison with authentic samples prepared by reported methods
[17–24].
Entry
Catalyst (mol%)
Time (min)
Yield (%)a
1
2
3
4
5
6
7
None
25
180
120
90
Trace
51
Recycling and reuse of the catalyst
30
55
40
45
57
The catalyst is soluble in water and could therefore be
recycled as the filtrate. The catalyst was recovered by
evaporation of the water, washed with diethyl ether, dried
at 50 °C under vacuum for 1 h and reused in another
reaction without appreciable reduction in the catalytic
activity. This procedure applied for 3a in a second run
resulted in 74% yield.
55
25
63
65
25
76
70
45
58
4 mmol acetophenone, 4 mmol benzaldehyde, 1.2 cm3 acetyl chlo-
ride, and 12 cm3 acetonitrile at r.t.
a
Isolated yields
Table 2 Synthesis of b-acetamido-b-phenylpropiophenone (3a) in
the presence of 65 mol% [HO3S(CH2)4MIM][HSO4] in different
solvents at r.t.
References
1. Chen L, Huang XJ, Li YQ, Zhou MY, Zheng WJ (2009) Monatsh
Chem 140:45
Entry
Solvent
Time (min)
Yield (%)a
2. Zhang P, Zhang ZH (2009) Monatsh Chem 140:199
3. Weber L (2002) Drug Discov Today 7:143
4. Strubing D, Neumann H, Klaus S, Hubner S, Beller M (2005)
Tetrahedron 61:11333
5. Yu L, Chen B, Huang X (2007) Tetrahedron Lett 48:925
6. Thompson LA, Ellman JA (1996) Chem Rev 96:555
7. Dolle RE, Nelson KH (1996) J Comb Chem 1:235
8. Casimir JR, Turetta C, Ettouati L, Paris J (1995) Tetrahedron Lett
36:4797
1
2
3
4
a
EtOH
90
30
30
25
Trace
35
CH2Cl2
CHCl3
47
Solvent-free
76
Isolated yields
Table 3 Synthesis of b-acetamido ketones 3a–3l using [HO3S
(CH2)4MIM][HSO4] (65 mol%) as catalyst at room temperature
under solvent-free conditions
9. Godfrey AG, Brooks DA, Hay LA, Peters M, McCarthy JR,
Mitchell D (2003) J Org Chem 68:2623
10. Dallemagne P, Rault S, Severicourt M, Hassan KM, Robba M
(1986) Tetrahedron Lett 27:2607
11. Jeffs PW, Redfearn R, Wolfram J (1983) J Org Chem 48:3861
12. Paleo MR, Dominguez D, Castedo L (1993) Tetrahedron Lett
34:2369
13. Dakin HD, West R (1928) J Biol Chem 78:745
14. Buchanan GL (1988) Chem Soc Rev 17:91
15. Bhatia B, Reddy MM, Iqbal J (1994) J Chem Res (S) 713
16. Bahulayan D, Das SK, Iqbal J (2003) J Org Chem 68:5735
17. Pandey G, Singh RP, Garg A, Singh VK (2005) Tetrahedron Lett
46:2137
18. Khodaei MM, Khosropour AR, Fattahpour P (2005) Tetrahedron
Lett 46:2105
19. Ghosh R, Maiti S, Chakraborty A (2005) Synlett 115
20. Ghosh R, Maiti S, Chakraborty A, Chakraborty S, Mukherjee AK
(2006) Tetrahedron 62:4059
21. Heravi MM, Ranjbar L, Derikvand F, Bamoharram FF (2007)
J Mol Catal A Chem 276:226
22. Rafiee E, Shahbazi F, Joshaghani M, Tork F (2005) J Mol Catal A
Chem 242:129
Entry Productsa
R
Time (min) Yield (%)b Mp (°C)
1
3a
3b
3c
3d
3e
3f
H
25
25
20
45
30
30
30
20
20
30
25
76
86
94
68
78
74
90
76
91
72
69
80
103–105
105–108
145–147
100–103
181–183
138–140
147–149
80–82
2
3-Cl
3
4-Cl
4
3-Br
5
2-NO2
3-NO2
4-NO2
3-Me
4-Me
3-OH
4-OH
6
7
3g
3h
3i
8
9
108–110
135–137
182–184
105–107
10
11
12
a
3j
3k
3l
4-OMe 25
1
All products were characterized by H NMR and IR spectroscopy
and comparison with authentic samples [17–24]
23. Khan AT, Parvin T, Choudhury LH (2007) Tetrahedron 63:5593
24. Nagarapu L, Bantu R, Puttireddy R (2007) Appl Catal A 332:304
25. Verma AK, Attri P, Chopra V, Tiwari RK, Chandra R (2008)
Monatsh Chem 139:1041
b
Isolated yields
26. Dabiri M, Salehi P, Baghbanzadeh M (2007) Monatsh Chem
138:1191
27. Cole AC, Jensen JL, Ntai I, Tran KLT, Weaver KJ, Forbes DC,
James J, Davis H (2002) J Am Chem Soc 124:5962
28. Arfan A, Bazureau JP (2005) Org Process Res Dev 9:743
29. Qiao K, Yokoyama C (2006) Catal Commun 7:450
the reaction, the mixture was poured into ice-cold water
and stirred thoroughly, which resulted in precipitation of
the desired b-acetamido ketones. The precipitated solid
was isolated by filtration and washed with diethyl ether.
The pure product was obtained by recrystallization from
123

1502
A. Davoodnia et al.
30. Wasserscheid P, Sesing M, Korth W (2002) Green Chem 4:134
31. Davoodnia A, Bakavoli M, Barakouhi Gh, Tavakoli-Hoseini N
(2007) Chin Chem Lett 18:1483
32. Davoodnia A, Roshani M, Malaeke SH, Bakavoli M (2008) Chin
Chem Lett 19:525
33. Seifi N, Zahedi-Niaki MH, Barzegari MR, Davoodnia A, Zhiani
R, Aghaei Kaju A (2006) J Mol Catal A Chem 260:77
34. Wang W, Shao L, Cheng W, Yang J, He M (2008) Catal Com-
mun 9:337
123