H3PW12O40/SiO2: An eco-friendly alternative for the stereo-, regio- and chemoselective Claisen-Schmidt condensation

Article abstract of DOI:10.1002/jccs.200800104

H₃PW₁₂O₄₀/SiO₂ or (PW/SiO ₂) promotes the regio-, stereo- and chemoselective Claisen-Schmidt condensation with improved yields.

Full text of DOI:10.1002/jccs.200800104

694
Journal of the Chinese Chemical Society, 2008, 55, 694-697
Note
H3PW12O40/SiO2: An Eco-friendly Alternative for the Stereo-, Regio- and
Chemoselective Claisen-Schmidt Condensation
BiBi Fatemeh Mirjalili* and Zahra Zaghaghi
Department of Chemistry, College of Science, Yazd University, P.O. Box 89195-741, Yazd, Iran
H3PW12O40/SiO2 or (PW/SiO2) promotes the regio-, stereo- and chemoselective Claisen-Schmidt
condensation with improved yields.
Keywords: Dodecatungstophosphoric acid; H3PW12O40/SiO2; Aldol condensation;
Claisen-Schmidt condensation; a,b-Unsaturated ketones; Heteropoly acids.
INTRODUCTION
Claisen-Schmidt condensation as a type of crossed
Table 1. Claisen-Schmidt condensation of 2 mmol of 3-nitro-
benzaldehyde and 1 mmol of cyclohexanone in various
conditionsa
aldol condensation is an effective pathway for the prepara-
tion of a,b-bis(substituted benzylidene)cycloalkanones as
precursors for the synthesis of bioactive pyrimidine deriva-
ties or nikkomycine.1 Crossed aldol condensation is always
carried 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(h6-C6H6)](BF4)2,8 NaOAc/HOAc,9
ZrCl4,10 FeCl3.6H2O,11 LiOH.H2O,12 I2,13 Al2O3-MgO14
acid-base functionalized catalyst15 and polymer supported
sulphonic acid,16 among others. The use of toxic and ex-
pensive reagents, low yields, long reaction times and for-
mation of a mixture of products are among the drawbacks
of the reported procedures. Recently, more attention has
been paid to Claisen-Schmidt condensation.
Entry
Catalyst
Condition/solvent Yielda (%)
1
PW(0.06 g)
PW(0.06 g)
Reflux/toluene
Reflux/acetonitrile
Reflux/THF
Reflux/HOAc
Reflux/EtOH
Reflux/CH2Cl2
50-60 °C/-
65
52
50
70
75
80
75
35
-
2
3
PW(0.06 g)
4
PW(0.06 g)
5
PW(0.06 g)
6
PW(0.06 g)
7
PW(0.06 g)
8
PW(0.06 g)
Ultrasound/CH2Cl2
50-60 °C/-
9
SiO2
10
11
12
13
14
15
16
17
18
19
20
60% PW/SiO2(0.06 g)
60% PW/TiO2(0.06 g)
60% PW/ZrO2(0.06 g)
40% PW/SiO2(0.06 g)
50% PW/SiO2(0.06 g)
70% PW/SiO2(0.06 g)
60% PW/SiO2(0.04 g)
60% PW/SiO2(0.05 g)
60% PW/SiO2(0.08 g)
60% PW/SiO2(0.06 g)b
60% PW/SiO2(0.06 g)b
50-60 °C/-
90
62
85
80
85
90
82
85
90
88
82
RESULTS AND DISCUSSION
50-60 °C/-
In continuation of our studies on the application of
solid acids in organic synthesis17-22 we report a simple, effi-
cient and selective protocol for the Claisen-Schmidt con-
densation in the presence of (H3PW12O40) or (PW). It is ob-
vious that bulk PW has a low surface area. The high surface
area can be achieved by dispersing the PW on some solid
supports with high surface areas. Thus, we have used silica,
titania or zirconia supported H3PW12O40 for Claisen-Schmidt
condensation (Table 1).
50-60 °C/-
50-60 °C/-
50-60 °C/-
50-60 °C/-
50-60 °C/-
50-60 °C/-
50-60 °C/-
50-60 °C/-
50-60 °C/-
a Isolated yield.
b Catalyst reused in three successive runs; the catalyst was
filtered, washed with dry acetone and dried in a domestic
microwave oven for 20 min at a power of 100.
The results have indicated that the PW/SiO2 was the
best one among others. In the preparation of PW/SiO2, we
have used 0.2 mL of HCl (0.5 M) to prevent the PW disso-
* Corresponding author. Fax: +98 351 821 0644; E-mail: fmirjalili@yazduni.ac.ir

H3PW12O40/SiO2: An Alternative for Claisen-Schmidt Condensation
ciation. Meanwhile, we found that solid matrices which
J. Chin. Chem. Soc., Vol. 55, No. 3, 2008 695
The stereoselectivity of this method was confirmed
were prepared from similar HCl solutions succeeded in
Claisen-Schmidt condensation in a very low yield (10-
15%) in the absence of PW. Various types of ketones were
subjected to aromatic aldehydes in the presence of 60%
PW/SiO2 under solvent-free conditions at 50-60 °C with
improved yields of only di-aldol products (Scheme I, Table
2).
by the formation of a trans double bond in the Claisen-
Schmidt condensation of methyl ketones (Table 2, entries
13-18). Regioselectivity of this method was examined by
crossed aldol condensation of 2-butanone and 4-methyl-2-
pentanone with 4-chlorobenzaldehyde (Scheme II). Be-
cause of the preference for acid catalyzed enolization to
give more substituted enol, under PW/SiO2-catalyzed con-
densation, the branched-chain ketol was formed with high
yield (Scheme II).
Scheme I
Additionally, the chemoselectivity of the reaction
was evaluated via a competitive PW/SiO2 catalyzed reac-
tion of 4-chlorobenzaldehyde (2 mmol) with a mixture of
cyclohexanone (1 mmol) and acetone (1 mmol). It was
found that cyclohexanone reacted with benzaldehyde in a
high yield. No chemoselectivity was observed for cyclo-
hexanone versus acetophenone or 4-nitrobenzaldehyde
versus 4-methyl benzaldehyde. Due to confirmation of the
reusability of catalyst, after reaction, PW/SiO2 was recov-
ered by filtration and washed with acetone several times.
The catalyst activity gradually declined in successive runs
(Table 1, entries 19-20), which indicated that loss of cata-
Table 2. Claisen-Schmidt condensation of ketones with aldehydes promoted 60% PW-SiO2
under solvent-free conditions at 50-60 °Ca
Entry
Product
Yield (%)b
Ref.c
M.P. °C
1
III: R1,R2 = (CH2)3, Ar = 3-NO2-C6H4
III: R1,R2 = (CH2)3, Ar = 4-CH3-C6H4
III: R1,R2 = (CH2)3, Ar = -C6H5
92
84
80
45
87
85
75
75
73
87
71
75
74
82
81
76
75
11
11
11
13
12
13
13
13
11
11
02
10
10
02
02
02
11
89-90
165-166
116-117
168-170
88-89
2
3
4
III: R1,R2 = (CH2)3, Ar = 3-OCH3, 4-OH-C6H3
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 = 2,4-Di-Cl, -C6H3
III: R1,R2 = (CH2)2, Ar = 4-CH3-C6H4
III: R1,R2 = (CH2)2, Ar = 2-Cl-C6H4
III: R1,R2 = (CH2)2, Ar = 4-NO2-C6H4
VI: Ar¢ = Ph, Ar = 4-NO2-C6H4
5
6
202-204
215-216
217-219
245-246
152-153
230-231
159-160
144-145
108-109
75-76
7
8
9
10
11
12
13
14
15
16
17
VI: Ar¢ = Ph, Ar = 3-NO2-C6H4
VI: Ar¢ = Ph, Ar = 4-Cl-C6H4
VI: Ar¢ = Ph, Ar = 4-OMe-C6H4
VI: Ar¢ = Ph, Ar = 4-CH3-C6H4
97-98
VI: Ar¢ = 4-Cl-C6H4-C = C-, Ar = 4-Cl-C6H4
192-194
a The molar ratio of aldehyde(mmol): ketone(mmol): catalyst(g) is 2: 2(1): 0.06 and the time
of reaction is 60 minutes.
b Isolated yield.
c All products are known and were identified by their melting points, TR and 1H NMR
spectra.

696 J. Chin. Chem. Soc., Vol. 55, No. 3, 2008
Mirjalili and Zaghaghi
Scheme II
lyst activity was very low.
vent of the filtrate was then evaporated and the crude prod-
uct was crystallized from ethanol and consequently the
pure product was obtained in a 82% yield; m.p.: 108-109
°C, (Lit: 107-109 °C).2
In sum, PW/SiO2 as a solid acid has a high efficiency
and has catalyzed the Claisen-Schmidt condensation reac-
tion in solvent-free conditions. This plain methodology of-
fers several advantages including a simple work up, scale
up, improved yields, regio-, stereo- and chemoselectivity,
and a recyclable catalyst with a very clean reaction.
ACKNOWLEDGMENT
The financial support of this work by the Research
Affairs Department of Yazd University is gratefully ac-
knowledged.
EXPERIMENTAL
General
Chemicals were purchased from Fluka, Merck and
Aldrich chemical companies. Yields refer to isolated prod-
ucts. The products were characterized by comparison of
Received October 18, 2007.
REFERENCES
1
their spectral (IR and H-NMR) and physical data with
1. Barluenga, J.; Viado, A. L.; Aguilar, E.; Fustero, S.; Olano,
B. J. Org. Chem. 1993, 58, 5972.
authentic data.
2. Salehi, P.; Dabiri, M.; Zolfigol, M. A.; Bodaghifard, M. A. J.
Braz. Chem. Soc. 2004, 15, 1.
Preparation of various supported 12-tungstophos-
phoric acids (60%w/w)
3. Salehi, P.; Khodaei, M. M.; Zolfigol, M. A.; Keyvan, A.
Monatsh. Chem. 2002, 133, 1291.
The mixtures of 0.6 g of 12-tungstophosphoric acid
and 0.4 g of silicagel, TiO2 or ZrO2 were separately ground
into fine particles. A suspension of each mixture and 0.2
mL of HCl 0.5 M and 1 mL of methanol were stirred for 20
min at room temperature. The solvent of each suspension
was evaporated at about 80-90 °C until dryness. The ob-
tained solids were dried in a domestic microwave oven for
20 min at a power of 100.
4. Luo, S.; Falconer, J. L. Catal. Lett. 1999, 57, 89.
5. Iranpoor, N.; Kazemi, F. Tetrahedron 1998, 54, 9475.
6. Iranpoor, N.; Zejnizadeh, B.; Aghapour, A. J. Chem. Res.
(S), 1999, 554.
7. Cai, X. H.; Xie, B.; Guo, H. Chem. Pap. - Chem. Zvesti
2006, 60, 318.
8. Terai, H.; Takaya, H.; Naota, T. Tetrahedron Lett. 2006, 47,
1705.
Synthesis of 4-chlorobenzylidene acetophenone, a typ-
ical procedure
9. Rahman, A. F. M. M.; Jeong, B. S.; Kim, D. H.; Park, J. K.;
Lee, E. S.; Jahng, Y. Tetrahedron 2007, 63, 2426.
10. Khodaei, M. M.; Bahrami, K.; Khedri, M. J. Chin. Chem.
Soc. 2007, 54, 807.
A mixture of 0.28 g (2 mmol) of 4-chlorobenzalde-
hyde, 0.24 g (2 mmol) of acetophenone and 0.06 g of 60%
PW/SiO2 was stirred at 50-60 °C for 60 min. The progress
of the reaction was monitored by TLC (eluent, dichloro-
methane : ether, 80:20). After the completion of the reac-
tion, CH2Cl2 was added to the mixture and filtered. The sol-
11. Zhang, X.; Fan, X.; Niu, H.; Wang, J. Green Chem. 2003, 5,
267.
12. Bhagat, S.; Sharma, R.; Chakraborti, A. K. J. Mol. Catal. A:
Chem. 2006, 260, 235.
13. Das, B.; Thirupathi, P.; Mahender, I.; Reddy, K. R. J. Mol.

H3PW12O40/SiO2: An Alternative for Claisen-Schmidt Condensation
J. Chin. Chem. Soc., Vol. 55, No. 3, 2008 697
Catal. A: Chem. 2006, 247, 182.
19. Zolfigol, M. A.; Mohammadpoor-Baltork, I.; Habibi, D.;
Mirjalili, B. F.; Bamoniri, A. Tetrahedron Lett. 2003, 44,
8165.
14. Shiau, S. Y.; Ko, A-N. J. Chin. Chem. Soc. 2006, 53, 1539.
15. Zeidan, R. K.; Davis, M. E. J. Catal. 2007, 247, 379.
16. An, L-T.; Zou, J-P.; Zhang, L-L. Catal. Commun. 2008, 9,
349.
20. Zolfigol, M. A.; Mohammadpoor-Baltork, I.; Mirjalili, B. F.;
Bamoniri, A. Synlett 2003, 12, 1877.
17. Hajipour, A. R.; Zarei, A.; Khazdooz, L.; Mirjalili, B. F.;
Sheikhan, N.; Zahmatkesh, A.; Ruoho, A. E. Synthesis 2005,
3644.
21. Shirini, F.; Zolfigol, M. A.; Safari, A.; Mohammadpoor-
Baltork, I.; Mirjalili. B. F. Tetrahedron Lett. 2003, 44, 7463.
22. Mirjalili, B. F.; Zolfigol, M. A.; Bamoniri, A.; Hazar, A. J.
Braz. Chem. Soc. 2005, 16, 877.
18. Hajipour, A. R.; Mirjalili, B. F.; Zarei, A.; Khazdooz, L.;
Ruoho, A. E. Tetrahedron Lett. 2004, 45, 6607.