KF-melamine formaldehyde resin (KF-MFR) as a versatile and efficient heterogeneous reagent for aldol condensation of aldehydes and ketones under microwave irradiation

Article abstract of DOI:10.1002/cjoc.201190227

KF-Melamine formaldehyde resin (KF-MFR) was demonstrated to be a highly efficient heterogenious catalyst for cross-aldol condensation under microwave irradiation. In this synthesis, various aldehydes and ketones were condensed together in the presence of supported KF on melamine-formaldehyde resin to afford different chalcone derivatives in good to excellent yields. KF-MFR proved to have unique termal and chemical resistance and can be reused for many consecutive runs without remarkable loss in catalytic activity. Copyright

Full text of DOI:10.1002/cjoc.201190227

FULL PAPER
KF-Melamine Formaldehyde Resin (KF-MFR) as a Versatile and
Efficient Heterogeneous Reagent for Aldol Condensation of
Aldehydes and Ketones under Microwave Irradiation
Rezaie, Ramin*,a
Heidary, Mohammada
Soltani Rad, Mohammad Navidb
Behrouz, Somayehb
a Department of Chemistry, Islamic Azad University, Firouzabad Branch, Iran
b Department of Chemistry, Faculty of Basic Sciences, Shiraz University of Technology, Shiraz 71555-313, Iran
KF-Melamine formaldehyde resin (KF-MFR) was demonstrated to be a highly efficient heterogenious catalyst
for cross-aldol condensation under microwave irradiation. In this synthesis, various aldehydes and ketones were
condensed together in the presence of supported KF on melamine-formaldehyde resin to afford different chalcone
derivatives in good to excellent yields. KF-MFR proved to have unique termal and chemical resistance and can be
reused for many consecutive runs without remarkable loss in catalytic activity.
Keywords KF-MFR, ketones, aromatic aldehydes, aldol reaction, microwave chemistry
Introduction
there is still a need for establishing straightforward and
easy strategies for accessing α,β-unsaturated carbonyl
compounds. Melamine-formaldehyde resin (MFR) is the
most useful thermosetting materials,13 extensively used
for manufacturing the composite and panels in indus-
try.14 The melamine-formaldehyde resins are used in
textile coatings treatment. On the other hand, micro-
wave irradiation is a well known technique to promote
the synthesis of a variety of compounds, where chemi-
cal reactions are remarkably accelerated due to molecu-
lar polarity of reactants.5 As a part of our program to-
wards the non-traditional approaches to the experimen-
tal set up of organic reactions, the concept of "Micro-
wave Induced Organic Reaction Enhancement" (MORE)
chemistry has been utilized for the rapid and efficient
synthesis of chalcones using KF-MFR under solvent
free microwave irradiation condition. The reaction is
shown in Eq. 1.
Since 1990, chemists have payed much more interest
in the application of solvent free synthetic methods in
organic reactions.1 Claisen-Schmidt,2 knoevenagel,2
aldol and crossed-aldol condensation2 are well known
and fully established reactions, which are widely em-
ployed for the synthesis of carbonyl compounds due to
the operational simplicity, easier work-up, good yield
and eco-friendly nature. Among these reactions, aldol
condensation is the most employed name reaction for
carbon-carbon bond formation in various carbonyl
compounds.3 Chalcones are known scaffolds to have
multi-pharmaceutical and industrial applications. Chal-
cones can be traditionally prepared by classical Claisen-
Schmidt condensation in the presence of many organic
and inorganic bases,4 using conventional heating, mi-
crowave and/or ultrasonic irradiation techniques.5 Aldol
condensation can be catalyzed by various heterogeneous
Lewis acids as supports including Mg(HSO4)2,6 silica
sulfuric acid,7 CsOH-SiO2,8 Mg/Al mixed oxides,9
Results and discussion
FeCl3•6H2O,10 KF-Al2O3 and polymer supported sul-
11
The first step of this synthetic approach began with
optimization of the reaction conditions. Initially, the
effect of various organic and inorganic bases supported
on MFR was studied by achieving the microwave as-
sisted reaction of 4-chlorobenzaldehyde and acetophe-
none as a model reaction. The results are depicted in
Table 1.
As the data in Table 1 indicate, the presence of the
base is critically essential for reaction process and thus,
as it was expected, in the absence of base (using MFR
support alone) the reaction did not proceed even after
phonic acid.12 Although many of these reagents and
supports are seems to be useful for aldol condensations,
however, many of these entries are suffered from many
disadvantageous such as non-reusability, low thermal
and chemical resistance, toxicity, harsh reaction condi-
tion, tedious work-up procedure, prolonged reaction
times, poor yields and low selectivity. Furthermore,
among many of these methods the strong acidic or basic
conditions are usually employed, which can be hazard-
ous to sensitive functional group in a molecule. Thus,
* E-mail: soltani@sutech.ac.ir; nsoltanirad@gmail.com; rezaieramin@yahoo.com; Tel.: 0098-711-7261392; Fax: 0098-711-7354523
Received October 8, 2010; revised January 7, 2011; accepted February 26, 2011.
Chin. J. Chem. 2011, 29, 1221— 1226
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Rezaie et al.
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Table 2 Effect of various support-KF on reaction of 4-chloro
benzaldehyde with acetophenone under microwave irradiation
Entry
Support
Time/min
Yielda/%
45
1
2
3
4
5
6
7
8
none
MFR
30
8
92
Table 1 Effect of various supported MFR-bases on reaction of
4-chloro benzaldehyde with acetophenone under microwave irra-
diation
Silica gel
Alumina
15
15
16
18
16
12
72
78
Montmorillonte K-10
Clay
63
82
Kaolin
54
Zeolite
75
a Isolated yield.
In another study, we investigated the effect of irra-
diation power on model reaction; hence, we exposed the
reaction into various microwave powers in the presence
of KF-MFR. The results are shown in Table 3. As can
be seen in Table 3, the best irradiation power was as-
signed to be 50 W and thus it was employed to all reac-
tions that have been carried out in this paper.
Entry
MFR-basea
MFR
Time/min
Yieldb/%
trace
92
1
2
3
4
5
6
7
8
60
8
MFR-KF
MFR-DABCO
MFR-DMAP
MFR-MgO
MFR-Cs2CO3
MFR-K2CO3
MFR-DBU
14
18
15
10
12
15
65
56
The best ratio for KF and MFR was found 20 mmol
of KF per 3.3 g of MFR. Thus, in this case, we exam-
ined the reusability of KF-MFR reagent for successive
five runs on model reaction. Through each runs, no
fresh KF-MFR was added and the reaction media was
suspended in anhydrous chloroform, filtered and
KF-MFR cake was washed twice with dichloromethane.
The recycled KF-MFR was then dried in vacuum oven
(50 ℃, 10 min) and reused consecutively for the next
run. The results are depicted in Table 4.
61
86
78
71
a 10 mmol base was supported on 1.65 g of MFR. b Isolated yield.
prolongating the reaction time to 1 h or increasing mi-
crowave irradiation power. KF supported on MFR (Ta-
ble 1, Entry 2) was the most efficient base and hence it
was the base of choice. Using other supported organic
bases on MFR, including DABCO, DMAP and DBU
(Table 1, Entries 3, 4 and 8) as well as inorganic bases
supported on MFR (Table 1, Entries 5—7) also afforded
the good yields of the corresponding chalcone; however,
in longer times for completion.
As data in Table 4 imply, the slight decrease in iso-
lated yields was observed for five consecutive conden-
sations of 4-chloro benzaldehyde with acetophenone in
the presence of recycled KF-MFR under microwave
irradiation (50 W) for 8 min. Thus, the MFR-KF can be
reused without any environmental discharge.
The choice of the solid support for absorption of mi-
crowave irradiation is of a great significance. In this
case, we evaluated the potency of several KF-supported
solid supports on the model reaction (Table 2). In the
absence of support, the reaction was achieved; however,
moderate yield of chalcone after longer reaction time
was attained (Table 2, Entry 1). MFR (Table 2, Entry 2)
proved to be the most efficient support for conversion of
4-chlorobenzaldehyde and acetophenone into corre-
sponding chalcone. Other supports such as silica gel,
alumina, montmorillonte K-10, clay and Zeolite (Table
2, Entries 3—8) also afforded good yields of chalcone
in longer reaction times.
To realize the superiority of the microwave assisted
method in comparison with conventional heating
method, we compared the aldol condensation under mi-
crowave irradiation with that of solvent assisted method
using KF-MFR. In that context, we carried out the
model reaction under both microwave and solvent as-
sisted methods and the results are summarized in Table
5.
As it can be seen in Table 5, using microwave irra-
diation under solvent free condition can dramatically
enhance the reaction yields and considerably shorten the
reaction times, while using conventional heating method
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Chin. J. Chem. 2011, 29, 1221— 1226

Aldol Condensation of Aldehydes and Ketones under Microwave Irradiation
Table 3 Effect of various microwave power (Watt) on reaction
diation to afford the corresponding chalcone in excellent
of 4-chloro benzaldehyde with acetophenone
yields. All attempts for attaining 2-benzylidene-cyclo-
alkanone adduct from one side of cyclopentanone or
cyclohexanone were not successful and mixtures of
2-benzylidene-cycloalkanone and 2,6-dibenzylidene-
cycloalkanone products were obtained even if the equal
ratios of aldehyde and cycloalkanone were employed
(Table 6, Entries 1—7). It was observed that there is a
remarkable tendency for formation of 2,6-dibenzyli-
dene-cycloalkanone rather than 2-benzylidene-cyclo-
alkanone and it is rationalized that the formation of ex-
tra double bond provides the longer chain conjugate
bonds in 2,6-dibenzylidene-cycloalkanone which results
in lower energy and more stability. Other aldehydes and
ketones were efficiently condensed to afford the corre-
sponding chalcones. Additionally, it was observed that
the presence of electro-withdrawing as well as electro-
releasing group on both aldehyde and/or ketones has
marginal effect on reaction efficiency (Table 6, Entries
8—14).
Entry
x
10
20
30
40
50
60
70
80
90
100
Time/min
Yielda/%
52
1
2
8
8
8
8
8
8
8
8
8
8
56
3
60
4
79
5
92
6
85
7
85
8
9b
10b
80
We were questioned about the special characteristic
of MFR that causes it to become the suitable solid sup-
port for hosting KF. In literature the abilities of MFR
for hosting several cations were proved.23 Since the
presence of cavities between triazine cores, presence of
multi-coordinating nitrogen atoms as well as the possi-
bility of hydrogen bonds, we suggest the following Fig-
ure 1 which can demonstrate the plausible interaction of
MFR with K＋ and F－. As it is shown in Figure 1, MFR
is capable to host both cation and anion by chelation and
also hydrogen bonds formation respectively. To prove
the possibility of KF-hosting by melamine formalde-
hyde resin, an analytical technique such as inductively
coupled plasma (ICP) was used for determination of the
amount of hosted K＋ and F－ in MFR. To ensure no
surface absorption of KF by MFR, the KF-MFR was
stirred and sonicated for 1 h and washed with deionized
water and this work was repeated consecutively for ten
times. At this stage the filtrate water showed no pre-
cipitation with silver nitrat－e solution which is indication
of no further leakage of F . The residual KF-MFR was
dried in vacuum oven at 100 ℃ and analyzed by in-
ductively coupled－plasma (ICP). The ICP test indicated
the presence of F and K＋ in 12.43% and 13.21% re-
spectively. Thus, the MFR can be used as a suitable
solid support for both cations and anions. We also
witnessed that molecules having electron-rich aromatic
residues can better interact on the surface of MFR in
comparison with other solid supports, this fact
78
60
a Isolated yield. b Slight burning was occurred at this power.
Table 4 Reusability studying of MFR-KF on consecutive reac-
tion of 4-chloro benzaldehyde with acetophenone after five runs
Run
P/W
50
Time/min
Yielda/%
1
8
8
8
8
8
92
90
87
85
80
2
50
3
50
4
50
5
50
a Isolated yield.
in various aprotic solvents such as DMF, THF, MeCN,
DMSO and HMPA the reactions proceed in lower yields
and much longer reaction times. Furthermore, using
solvents having acidic hydrogen for example MeCN,
Me2CO and/or DMSO can complicate the reaction by
condensing with active carbonyls and provide the side
products.
Having obtained the optimized reaction condition;
therefore, we extended it to other aldehyde-ketone aldol
condensation reactions. The results are summarized in
Table 6. As shown in Table 6, various structurally di-
verse ketones and aldehydes were successfully con-
densed together using KF-MFR under microwave irra-
Table 5 Comparison between microwave and solvent assisted aldol condensation on model reaction using KF-MFR
Microwave assisted method at
50 W using KF-MFR
Solvent assisted method at reflux condition using KF-MFR
THF MeCN DMSO
Yielda/% Time/h Yielda/% Time/h Yielda/% Time/h Yielda/% Time/h Yielda/% Time/h
61 12 73 20 68 24 53 18 49 36
DMF
HMPA
Yielda/%
Time/min
8
92
a Isolated yield.
Chin. J. Chem. 2011, 29, 1221— 1226
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Rezaie et al.
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Table 6 Cross-Aldol condensation of ketones with aromatic aldehydes in the presence of MFR under solvent-free microwave irradiation
conditions
m.p./℃
Entry
1
Ketone
Aldehyde
Product
Time/min Yielda/%
Found
Reported
11711
6
7
7
8
7
5
87
89
91
89
93
93
115—117
2
3
4
5
6
146—148 147—14815
201—203 203—20411
158—159
168—170
15911
17015
189—191 188—19111
7
6
93
224—226
56—58
2256
8
8
8
6
6
2
8
92
92
89
90
89
95
55—5816
9
106—108 107—10917
10
11
12
13
96—98
90—92
97—9818
19
—
20
124—126
111—113
—
21
—
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Chin. J. Chem. 2011, 29, 1221— 1226

Aldol Condensation of Aldehydes and Ketones under Microwave Irradiation
Contiuned
m.p./℃
Entry
Ketone
Aldehyde
Product
Time/min Yielda/%
Found
Reported
14
5
97
128—129 124—12622
aIsolated yield.
Experimental
General
All products were characterized by comparison of
1
their physical and spectral data (m.p., H NMR and IR)
with those of authentic samples. All chemicals used in
this research was purchased from Merck or Fluka
chemical companies. Melamine formaldehyde resin
(MFR) was purchased in its pulverized shape from Fars
Chemical Industries Co. Supports used in Table 2 in-
cluding silica gel (Grade 633, pore size 60 Å, 200—425
mesh, CAS No. 112926-00-8), alumina (neutral, Type
WN-3, CAS No. 1344-28-1), montmorillonite K-10
(CAS No. 1318-93-0), zeolite (CAS No. 1318-02-1) and
Kaolin [Al2Si2O5(OH)4, CAS. No. 1332-58-7] were
prepared from Merck, Fluka, Sigma-Aldrich and Acros
chemical companies. Clay (mineral) was attained from
the potsherd. Melting points of all products were deter-
mined in open glass capillaries on Mettler FP51 melting
1
point apparatus, and all are uncorrected. H NMR spec-
tra were recorded on a Brüker AC 500 MHz spectrome-
ter. IR spectra were recorded on a Brüker Penssor-27
infrared spectrometer. A laboratory microwave oven
BP-210 manufactured by Microwave Research and Ap-
plications, Inc was used at different power levels for all
the experiments. The progress of the reaction was fol-
lowed with TLC using silica-gel SILG/UV 254 plate.
Silica gel 60, 0.063—0.200 mm (70—230 mesh ASTM)
was used for column chromatography.
Figure 1 Schematic view for potential hosting of K＋ and F－
by MFR.
can be rationalized by the potential interaction (π-π*)
between electrondeficient triazine core and electron-rich
residues.
Because KF-MFR has interesting properties as well
as thermal and chemical stabilities, ease of handling,
cheapness and wide availability, it can be considered as
a useful alternative support for various organic trans-
formations.
Preparation of KF-melamine formaldehyde resin
(KF-MFR)
To well-crashed powder of pure melamine-formal-
dehyde resin (MFR)24 (3.3 g, 0.02 mol), was added a
solution of KF (1.16 g, 0.02 mol) in 50 mL distillated
water. Then, the suspension was stirred for 24 h at room
temperature and the mixture was evaporated in vacuum.
the KF-MFR was washed with absolute EtOH (50 mL)
and dried in vacuum oven at 50 ℃ overnight and
stored in desiccator.
Conclusions
In summary, we have introduced KF-MFR as a ver-
satile and highly efficient and reusable heterogeneous
reagent for synthesis of chalcones via aldol condensa-
tion under solvent free microwave irradiation condition.
The full optimization condition was explained for above
reaction and various chalcone derivatives were synthe-
sized in good to excellent yields using KF-MFR.
Typical experimental procedure
To a test tube equipped with a stopper, containing
KF-MFR (1.0 g) was added acetophenone (1.2 g, 0.01
mol) and benzaldehyde (1.5 g, 0.014 mol). The mixture
was then heated under microwave irradiation at 50 W
Chin. J. Chem. 2011, 29, 1221— 1226
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Rezaie et al.
FULL PAPER
for 8 min (1 min×8). The progress of the reaction was
followed by TLC. When TLC monitoring indicates no
further progress in reaction, the irradiation was stopped
and the reaction mixture was cooled. Then reaction
mixture was suspended in dichloromethane 50 mL and
filtered. The solid residue was washed with anhydrous
CHCl3, dried (in a vacuum oven at 50 ˚C for 30 min)
and stored in desiccator for subsequent use. The filtrate
was evaporated resulting in an oily crude product. The
crude product was recrystallized from hot petroleum
ether to afford the pure product as a pale yellow crys-
tals.
6
7
8
9
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The authors are thankful to Islamic Azad University,
Firouzabad Branch Research Council and Center of
Excellence in Development of Chemical Methods for
partial support of this work.
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Chin. J. Chem. 2011, 29, 1221— 1226