Zr(HSO4)4/SiO2 as an efficient alternative catalyst for the claisen-schmidt condensation

Article abstract of DOI:10.1515/znb-2008-1213

Zr(HSO₄)₄/SiO₂ promotes the regio-, stereo- and chemoselective Claisen-Schmidt condensation of aromatic aldehydes with ketones under solvent-free conditions with improved yields. The work-up of the reaction mixture is simple, and the catalyst is easily removed from the products by simple filtration.

Full text of DOI:10.1515/znb-2008-1213

Zr(HSO4)4/SiO2 as an Efficient Alternative Catalyst
for the Claisen-Schmidt Condensation
Bi Bi Fatemeh Mirjalilia, Abddhamid Bamonirib, Masoumeh Alipoura,
and Mohammad Ali Karimi Zarchia
a Department of Chemistry, College of Science, Yazd University, Yazd, P. O. Box 89195-741, Iran
b Department of Chemistry, College of Science, University of Kashan, Kashan, Iran
Reprint requests to Dr. Bi Bi Fatemeh Mirjalili. Fax: +98 351 8210644.
E-mail: fmirjalili@yazduni.ac.ir
Z. Naturforsch. 2008, 63b, 1421 – 1424; received June 4, 2008
Zr(HSO4)4/SiO2 promotes the regio-, stereo- and chemoselective Claisen-Schmidt condensation
of aromatic aldehydes with ketones under solvent-free conditions with improved yields. The work-up
of the reaction mixture is simple, and the catalyst is easily removed from the products by simple
filtration.
Key words: Zr(HSO4)4/SiO2, Claisen-Schmidt Condensation, Crossed Aldol Condensation,
Zirconium Hydrogensulfate, Aldehydes, Ketones, α,β-Unsaturated Ketones
Introduction
(HSO4)2 [3], Al(HSO4)3 [17] and Zr(HSO4)4 [18]
have been used as bulk materials. The supported form
of these acids is preferable because of the high disper-
sion and specific surface area compared with the the
bulk materials, and better accessibility of reactants to
the active sites. Zr(HSO4)4 has been used in reactions
such as Friedel-Crafts acylation [19], cleavage of C=N
bonds [20], acetylation of alcohols [21], and acylal for-
mation [18].
In the Claisen-Schmidt condensation, as a type
of crossed aldol condensation, an aromatic aldehyde
combines with alkyl ketones or aldehydes to form
β-hydroxy ketones, which are easily dehydrated to
form α,β-unsaturated ketones. It is worth mention-
ing that dehydration is especially favorable because
the resulting enone is also conjugated with the aro-
matic ring. The resulting α,β-unsaturated ketones
are useful intermediates for a large variety of com-
pounds. Mixed or crossed aldol condensation is an
effective pathway for the preparation of α,αꢀ-bis
(substituted benzylidene) cycloalkanones as precur-
sors for the synthesis of bioactive pyrimidine deriva-
tives or nikkomycine [1]. Aldol condensation is car-
ried out in the presence of acids or bases such as
silica sulfuric acid [2], Mg(HSO4)2 [3], TiO2 [4],
RuCl3 [5], TiCl3(SO2CF3) [6], KHSO4 [7], [Cp*Rh-
(η6-C6H6)](BF4)2 [8], NaOAc/HOAc [9], ZrCl4 [10],
FeCl3·6H2O [11], LiOH·H2O [12], I2 [13], acid-base
functionalized catalysts [14], polymer-supported sul-
fonic acid [15], DBU-H2O complex [16], among oth-
ers. The use of toxic and expensive reagents, low
yields, long reaction times and formation of a mix-
ture of products are among the drawbacks of the re-
ported procedures. Recently, more attention has been
Results and Discussion
In continuation of our studies on the application of
solid acids in organic synthesis [18, 22 – 27], we have
decided to investigate the Claisen-Schmidt condensa-
tion in the presence of some available catalysts under
various conditions (Table 1).
The results indicate that the silica-supported
Zr(HSO4)4 is the best catalyst system and the best mo-
lar ratio of aldehyde: ketone : 50 % Zr(HSO4)4/SiO2 is
2 : 1 : 0.12. In the preparation of 50 % Zr(HSO4)4/SiO2,
we have used 0.2 mL of HCl (0.5 M) to prevent the
dissociation of Zr(HSO4)4. Meanwhile, we found that
silica-supported HCl in the absence of Zr(HSO4)4 pro-
moted the crossed aldol condensation but gave very
low yields (10 – 15 %).
It is our perception that Zr(HSO4)4 combines the
paid to catalysts for the Claisen-Schmidt condensa- properties of a Lewis acid (Zr4+) and a Brønsted
tion. Previously, inorganic solid acids such as Mg- acid (HSO4−), which are both useful to catalyze the
c
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1422
B. B. Fatemeh Mirjalili et al. · Zr(HSO4)4/SiO2 as a Catalyst for the Claisen-Schmidt Condensation
Scheme 1.
Table 1. Claisen-Schmidt condensation of 4-isopropyl benz-
aldehyde (2 mmol) and cyclohexanone (1 mmol) under vari-
ous conditions.
Claisen-Schmidt condensation. To support this idea,
the Claisen-Schmidt condensation was carried out
separately in the presence of the same amount of
Zr(HSO4)4, ZrCl4, NaHSO4, and H2SO4 (Table 1).
The results show that Zr(HSO4)4 has the highest ef-
ficiency in this reaction.
Various types of cyclic and acyclic ketones were
subjected to different aromatic aldehydes contain-
ing electron-releasing or electron-withdrawing groups
in the presence of 50 % Zr(HSO4)4/SiO2 under
solvent-free conditions at 50 – 60 ◦C (Scheme 1,
Table 2).
The reactions were completed whitin 45 – 60 min
with improved yields, especially from aromatic alde-
hydes with electron-withdrawing groups, and no self-
condensation products were detected. Attempts at
mono-condensation of acetone or cycloalkanones were
not successful and only di-aldol products were ob-
tained.
En- Catalyst
try
Condition/
Solvent
Time (min)/
Yield (%)a
1
2
3
4
5
6
7
8
9
FeCl3 (20 mol-%)
50 – 60 ◦C/–
50 – 60 ◦C/–
50 – 60 ◦C/–
50 – 60 ◦C/–
50 – 60 ◦C/–
50 – 60 ◦C/–
50 – 60 ◦C/–
45/45
45/40
54/30
55/45
45/60
45/15
45/45
AlCl3 (20 mol-%)
ZnCl2 (20 mol-%)
SnCl4 (20 mol-%)
SbCl5 (20 mol-%)
ZrO2 (20 mol-%)
ZrCl4 (20 mol-%)
ZrCl4 (20 mol-%)
NaHSO4 (20 mol-%)
reflux/CH2Cl2 60/52
50 – 60 ◦C/–
45/35
reflux/CH2Cl2 60/41
50 – 60 ◦C/–
45/15
reflux/CH2Cl2 60/10
50 – 60 ◦C/–
45/75
reflux/toluene 60/63
10 NaHSO4 (20 mol-%)
11 H2SO4 (20 mol-%)
12 H2SO4 (20 mol-%)
13 Zr(HSO4)4 (20 mol-%)
14 Zr(HSO4)4 (20 mol-%)
15 Zr(HSO4)4 (20 mol-%)
The stereoselectivity of this method was confirmed
by the formation of a trans double bond in the Claisen-
Schmidt condensation of methyl ketones (Table 2, en-
tries 14 – 19).
reflux/
60/
67
60/67
60/65
60/68
acetonitrile
reflux/THF
reflux/HOAc
reflux/EtOH
reflux/CH2Cl2 60/70
ultrasound/
CH2Cl2
16 Zr(HSO4)4 (20 mol-%)
17 Zr(HSO4)4 (20 mol-%)
18 Zr(HSO4)4 (20 mol-%)
19 Zr(HSO4)4 (20 mol-%)
20 Zr(HSO4)4 (20 mol-%)
The trans stereochemistry of the double bounds
in the adduct of cyclopentanone with 3-nitrobenz-
aldehyde (Table 2, entry 11) was confirmed by NOE
experiments. Irradiation of the cyclopentanone pro-
tons does not change the intensity of the vinylic
protons. The regioselectivity of this method was
examined by crossed aldol condensation of 2-
butanone and 4-methyl-2-pentanone with 4-chloro-
benzaldehyde. Because of the preference for acid-
catalyzed enolization to give the more substituted
enol, under Zr(HSO4)4/SiO2-catalyzed condensation,
the branched-chain ketol was formed in high yield
(Scheme 2).
100/
10
21 Zr(HSO4)4 (20 mol-%)
MW/HOAc
5/42
45/93
23 50 % Zr(HSO4)4/SiO2 (12 mol-%) reflux/CH2Cl2 60/80
22 50 % Zr(HSO4)4/SiO2 (12 mol-%) 50 – 60 ◦C/–
24 40 % Zr(HSO4)4/SiO2 (12 mol-%) 50 – 60 ◦C/–
25 60 % Zr(HSO4)4/SiO2 (12 mol-%) 50 – 60 ◦C/–
26 40 % Zr(HSO4)4/SiO2 (12 mol-%) 50 – 60 ◦C/–
27 50 % Zr(HSO4)4/TiO2 (12 mol-%) 50 – 60 ◦C/–
28 50 % Zr(HSO4)4/SiO2 (8 mol-%) 50 – 60 ◦C/–
29 50 % Zr(HSO4)4/SiO2 (10 mol-%) 50 – 60 ◦C/–
30 50 % Zr(HSO4)4/SiO2 (14 mol-%) 50 – 60 ◦C/–
45/78
45/94
45/81
45/83
45/80
45/85
45/94
a Isolated yield.
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B. B. Fatemeh Mirjalili et al. · Zr(HSO4)4/SiO2 as a Catalyst for the Claisen-Schmidt Condensation
1423
Table 2. Claisen-Schmidt condensa-
tion promoted by 50 % Zr(HSO4)4/SiO2
under solvent-free conditions at 50 –
60 ◦Ca.
Entry Product
Time (min)/ Ref.c M. p.,
Yield (%)b
◦Cd
1
2
3
III: R1,R2 = (CH2)3, Ar = 4-NO2-C6H4
45/78
60/75
45/93
11
11
11
13
12
6
161 – 163
165 – 166
116 – 117
168 – 170
88 – 89
202 – 204
215 – 216
245 – 246
230 – 231
189 – 190
201 – 203
152 – 153
147 – 148
159 – 160
144 – 145
108 – 109
75 – 76
III: R1,R2 = (CH2)3, Ar = 4-CH3-C6H4
III: R1,R2 = (CH2)3, Ar = C6H5
4
III: R1,R2 = (CH2)3, Ar = 3-OCH3, 4-OH-C6H3 50/76
5
6
7
8
III: R1,R2 = (CH2)3, Ar = 2-Cl-C6H4
III: R1,R2 = (CH2)3, Ar = 4-OCH3-C6H4
III: R1,R2 = (CH2)2, Ar = 4-OCH3-C6H4
III: R1,R2 = (CH2)2, Ar = 4-CH3-C6H4
III: R1,R2 = (CH2)2, Ar = 4-NO2-C6H4
III: R1,R2 = (CH2)2, Ar = C6H4
50/88
45/79
45/74
45/73
45/88
45/85
45/87
45/79
45/76
60/87
60/89
60/85
60/75
60/78
60/78
6
11
6
11
12
11
2
10
10
2
9
10
11
12
13
14
15
16
17
18
19
III: R1,R2 = (CH2)2, Ar = 3-NO2-C6H4
III: R1,R2 = (CH2)2, Ar = 2-Cl-C6H4
III: R1,R2 = (CH2)3, Ar = 4-Cl-C6H4
VI: Arꢀ = Ph, Ar = 4-NO2-C6H4
a
Ratio of aldehyde : ketone : 50 % Zr
b
(HSO4c)4/SiO2 was 2 : 1 : 0.12;
isolated
VI: Arꢀ = Ph, Ar = 3-NO2-C6H4
yield; all products are known and were
VI: Arꢀ = Ph, Ar = 4-Cl-C6H4
identified by their melting points, IR and
VI: Arꢀ = Ph, Ar = 4-OMe-C6H4
2
2
d
1H NMR spectra;
determined with
melting points were
Bu¨chi melting point
VI: Arꢀ = Ph, Ar = 4-CH3-C6H4
97 – 98
a
VI: Arꢀ = 4-Cl-C6H4-C=C-, Ar = 4-Cl-C6H4
12
192 – 194
B-540 B.V.CHI apparatus.
Scheme 2.
Additionally, the chemoselectivity of the reaction Experimental Section
was evaluated via a competitive Zr(HSO4)4/SiO2-
catalyzed Claisen-Schmidt reaction of 4-chlorobenz-
aldehyde (2 mmol) with a mixture of cyclohexanone
(1 mmol) and acetone (1 mmol). It was found that cy-
clohexanone reacted with benzaldehyde in high yield.
No chemoselectivity was observed for cyclohexanone
versus acetophenone, or for 4-nitrobenzaldehyde ver-
sus 4-methylbenzaldehyde.
General
Carbonyl compounds were purchased from Fluka, Merck
and Aldrich companies. Zirconium hydrogensulfate was syn-
thesized according to the reported protocol [13]. We have
modified the reported protocol by washing the Zr(HSO4)4
with dry acetone and drying at r. t. Products were charac-
terized by comparison of their spectroscopic data (FT-IR,
1H NMR) and physical properties. IR spectra were run
on a Bruker, Eqinox 55 spectrometer. 1H NMR spectra
were obtained using a Bruker Avance 400 MHz spec-
trometer and a Bruker Avance 500 MHz spectrometer
(DRX). Melting points were determined with a Bu¨chi
melting point B-540 B. V. CHI apparatus. A Kenwood do-
mestic microwave oven, 800 Watt and 1300 MHz, was
used.
Conclusion
Zr(HSO4)4/SiO2 as a solid acid has a high effi-
ciency as catalyst of the Claisen-Schmidt condensa-
tion reaction under solvent-free conditions. This sim-
ple methodology offers several advantages including a
simple work-up, opportunities for scale-up, improved
yields, regio-, and stereo- and chemoselectivity.
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1424
B. B. Fatemeh Mirjalili et al. · Zr(HSO4)4/SiO2 as a Catalyst for the Claisen-Schmidt Condensation
Preparation of silica-supported Zr(HSO )
tom flask. The materials were mixed and heated at 50 – 60 ◦C
for 45 – 60 min. The progress of the reaction was followed
by TLC. After completion of the reaction, the mixture was
cooled to r. t. Dichloromethane was added to the mixture, and
the catalyst was removed by filtration. After evaporation of
the solvent, an oily residue or an impure solid was obtained.
By washing the residue with ethanol and water, usually a yel-
low to orange solid were obtained. The solid was recrystal-
lized from ethanol. All products are known and were iden-
tified by comparison of their physical or spectral data with
those of authentic samples.
4 4
A mixture of 0.3 g of Zr(HSO4)4 and 0.3 g of silica gel
was ground into fine particles. A suspension of this mixture
in 0.5 mL of 0.5 M HCl was stirred for 20 min at r. t. The
solvent of the suspension was evaporated at about 80 – 90 ◦C
until dryness. The obtained solid was dried in a domestic mi-
crowave oven for 20 min at a power of 800 W.
General procedure for crossed aldol condensation of ke-
tones with aldehydes using SiO -Zr(HSO ) under solvent-
2
4 4
free conditions
Acknowledegment
Ketone (1 or 2 mmol), aldehyde (2 mmol) and 50 % SiO2-
Zr(HSO4)4 (0.12 mmol, 0.1 g) were placed in a round bot-
Financial support for this work by the Research Council
of Yazd University is gratefully acknowledged.
[16] I. Cota, R. Chimentao, J. Sueiras, F. Medina, Catal.
Commun. 2008, in press.
[17] B. F. Mirjalili, M. A. Zolfigol, A. Bamoniri, A. Hazar,
J. Braz. Chem. Soc. 2005, 16, 877.
[1] J. Barluenga, A. L. Viado, E. Aguilar, S. Fustero,
B. Olano, J. Org. Chem. 1993, 58, 5972.
[2] P. Salehi, M. Dabiri, M. A. Zolfigol, M. A. Bodaghifard,
J. Braz. Chem. Soc. 2004, 15, 1.
[18] B. F. Mirjalili, M. A. Zolfigol, A. Bamoniri,
N. Sheikhan, J. Chin. Chem. Soc. 2006, 53, 955.
[19] P. Salehi, M. M. Khodei, M. A. Zolfigol, S. Zeinoldini,
Synth. Commun. 2003, 33, 1367.
[3] P. Salehi, M. M. Khodaei, M. A. Zolfigol, A. Keyvan,
Monatsh. Chem. 2002, 133, 1291.
[4] S. Luo, J. L. Falconer, Catal. Lett. 1999, 57, 89.
[5] N. Iranpoor, F. Kazemi, Tetrahedron 1998, 54, 9475
[6] N. Iranpoor, B. Zeynizadeh, A. Aghapour, J. Chem. Res.
(S) 1999, 554.
[7] X. H. Cai, B. Xie, H. Guo, Chem. Pap. – Chem. Zvesti
2006, 60, 318.
[8] H. Terai, H. Takaya, T. Naota, Tetrahedron Lett. 2006,
47, 1705.
[20] F.
Shirini,
M. A.
Zolfigol,
A.
Safari,
I. Mohammadpoor-Baltork, B. F. Mirjalili, Tetra-
hedron Lett. 2003, 44, 7463.
[21] F. Shirini, M. A. Zolfigol, A. Safari, Indian J. Chem.
Sect. B 2005, 201.
[22] A. R. Hajipour, A. Zarei,. L. Khazdooz, B. F. Mirjalili,
N. Sheikhan, A. Zahmatkesh, A. E. Ruoho, Synthesis
2005, 3644.
[23] A. R. Hajipour, B. F. Mirjalili, A. Zarei, L. Khazdooz,
A. E. Ruoho, Tetrahedron Lett. 2004, 45, 6607.
[24] M. A. Zolfigol, I. Mohammadpoor-Baltork, D. Habibi,
B. F. Mirjalili, A. Bamoniri, Tetrahedron Lett. 2003,
44, 8165.
[25] M. A. Zolfigol, I. Mohammadpoor-Baltork, B. F. Mir-
jalili, A. Bamoniri, Synlett 2003, 12, 1877.
[26] F. Shirini, M. A. Zolfigol, A. Safari, I. Mohammad-
poor-Baltork, B. F. Mirjalili, Tetrahedron Lett. 2003,
44, 7463.
[9] A. F. M. M. Rahman, B. S. Jeong, D. H. Kim, J. K. Park,
E. S. Lee, Y. Jahng, Tetrahedron 2007, 63, 2426.
[10] A. Kumar, Akanksha, J. Mol. Catal. A: Chem. 2007,
247, 212.
[11] X. Zhang, X. Fan, H. Niu, J. Wang, Green Chem. 2003,
5, 267.
[12] S. Bhagat, R. Sharma, A. K. Chakraborti, J. Mol. Catal.
A: Chem. 2006, 260, 235
[13] B. Das, P. Thirupathi, I. Mahender, K. R. Reddy, J. Mol.
Catal. A: Chem. 2006, 247, 182.
[14] R. K. Zeidan, M. E. Davis, J. Catal. 2007, 247, 379.
[15] L.-T. An, J.-P. Zou, L.-L. Zhang, Catal. Commun. 2008,
9, 349.
[27] B. F. Mirjalili, M. A. Zolfigol, A. Bamoniri, A. Hazar,
J. Braz. Chem. Soc. 2005, 16, 877.
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