Aldol condensation of cycloalkanones with aromatic aldehydes catalysed with TiCi3(SO3CF3)

Article abstract of DOI:10.1039/a809827a

Efficient cross-aldol condensation of cyclopentanone, cyclohexanone and 1-indanone with various aromatic aldehydes is catalysed with TiCl₃(SO₃CF₃) at room temperature in excellent yields.

Full text of DOI:10.1039/a809827a

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554 J. CHEM. RESEARCH (S), 1999
J. Chem. Research (S),
1999, 554^555y
Aldol Condensation of Cycloalkanones with
Aromatic Aldehydes Catalysed with
TiCl3(SO3CF3)y
N. Iranpoor,* B. Zeynizadeh, and A. Aghapour
Chemistry Department, College of Sciences, Shiraz University, Shiraz 71454, Iran
Efficient cross-aldol condensation of cyclopentanone, cyclohexanone and 1-indanone with various aromatic
aldehydes is catalysed with TiCl3ꢀSO3CF3† at room temperature in excellent yields.
Owing to the importance of the methylene structural unit
found in many naturally occurring compounds and anti-
biotics and the use of a,a0-bis(substituted)benzylidene-
cycloalkanones as precursors for synthesis of bioactive
pyrimidine derivatives,1 the condensation of cyclopentanone
and cyclohexanone with aromatic aldehydes is of special
interest. In addition to the use of strong acidic or basic con-
the use of anhydrous RuCl3 as catalyst for cross-aldol con-
densation of aliphatic cycloalkanones and aromatic
aldehydes but the reaction was performed in a sealed tube
at 120 8C.10
In the course of our studies11 on catalytic reactions of
12
TiCl3ꢀSO3CF3†
we observed that this compound can
act as a very e¤cient catalyst for cross-aldol condensation
reaction of cycloalkanones with aromatic aldehydes without
occurrence of any self-condensation of ketones.
Cyclopentanone and cyclohexanone as examples of aliphatic
and 1-indanone as an example of aromatic cycloalkanones
were condensed with di¡erent aromatic aldehydes such as
d
ditions2a for aldol-condensation reactions, the use of some
metal ions or organometallic compounds as catalyst or
9
reagent has been reported.3 Very recently, we reported
Table 1 Cross-condensation of cycloalkanones and aromatic
aldehydes catalysed with TiCl3ꢀSO3CF3† at room temperature
under solvent-free conditions
benzaldehyde,
4-chloro-,
4-nitro,
4-methyl-
and
4-methoxy-benzaldehyde and cinnamaldehyde in the
presence of 0.1^0.2 molar equivalent of TiCl3ꢀSO3CF3† at
room temperature under solvent free conditions or in
dichloromethane. The yields of the aldol products obtained
were found to be excellent. The results obtained for conden-
sation of cyclohexanone and cyclopentanone are shown in
Table 1. The condensation reactions of solid aldehydes such
as 4-chloro- and 4-nitro-benzaldehyde were performed in
CH2Cl2 (Table 1, Entries 4, 5, 11; Table 2, Entries 4, 5).
Di¡erent attempts to do selective monocondensation from
only one side of cyclopentanone or cyclohexanone were
not successful and mixtures of mono- and di-aldol products
were obtained.
Mol% of catalyst/t (h)/
Entry Ketone Aldehyde
O
Product
O
Ref.
yield(%)a
+ PhCHO
1
9
13a
9
10/0.7/99
O
O
O
O
O
+ 4-MeC6H4CHO
10/0.3/98
15/0.8/99
2
3
Me
Me
O
O
O
+ 4-MeOC6H4CHO
MeO
OMe
Cl
+ 4ClC6H4CHOb
Condensation of 1-indanone with aromatic aldehydes was
also performed at room temperature in excellent yields. The
results obtained are shown in Table 2.
10/2/96
14
9
4
5
6
Cl
+ 4-N2OC6H4CHOb
10/1.5/97
In order to compare the reactivity of TiCl3ꢀSO3CF3† with
O2N
NO2
O
O
O
O
O
O
TiCl4,
the
reaction
of
cyclohexanone
with
10/1/98
9
9
+ PhCH=CHCHO
+ PhCHO
4-chlorobenzaldehyde was studied in the presence of 10
15/1.5/96
7
Table
2 Cross-condensation of 1-indanone and aromatic
aldehydes with 20 mol% of TiCl3ꢀSO3CF3† at room temperature
+ 4-MeC6H4CHO
15/1/98
15/2/97
13b
9
8
9
under solvent-free conditions
Me
Me
O
O
O
O
t (h)/yield(%)a
Entry Ketone Aldehyde
O
Product
Ref.
15
+ 4-MeOC6H4CHO
MeO
OMe
O
+ PhCHO
1
3.5/96
15/2.2/99
13c
CH
+ 3-ClC6H4CHO
10
O
O
O
O
Cl
Cl
O
O
O
O
2
3
4
5
6
+ 4-MeC6H4CHO
2.8/97
16
16
17
CH
CH
CH
Me
OMe
Cl
+ 4-O2NC6H4CHOb
+ PhCH=CHCHO
9
9
15/2.5/95
15/3/94
11
12
O
O
O
O
O2N
NO2
+ 4-MeOC6H4CHO
+ 4-ClC6H4CHOb
+ 4-O2NC6H4CHOb
+ PhCH=CHCHO
2.5/96
3/97
aYield refers to isolated product. bThe reaction was performed in
CH2Cl2 (3 ml).
O
O
2.3/97
5/96
18
19
CH
NO2
CHCH CH
* To receive any correspondence (e-mail: iranpoor@chem.susc.ac.ir).
y This is a Short Paper as de¢ned in the Instructions for Authors,
Section 5.0 [see J. Chem. Research (S), 1999, Issue 1]; there is
therefore no corresponding material in J. Chem. Research (M).
aYield refers to isolated product. bThe reaction was performed in
CH2Cl2 (3 ml).

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J. CHEM. RESEARCH (S), 1999 555
Table 3 Comparison of the condensation reaction of p-chlorobenzaldehyde and cyclohexanone in the presence of different catalysts
Entry
Catalyst
Mole% of catalyst
t/h
T 8C
Yield (%)
1
2
3
4
5
6
7
8
9
TiCl3ꢀSO3CF3†
TiCl4
CF3SO3H
aq. 85% H2SO4
HCl
10
10
10
10
30
30/10/10
2
4
2
2
2
2
1
25
25
25
25
25
25
96
20
25
45
25
35
95^98
94
52
HCl CF3SO3H SiO2
Ba(OH)22c
^
2
reflux
120/sealed
80
RuCl130
12
5
Co(II)/bipyridyl/DMF4
10
Concentration of HCl entries 5 and 6 was calculated with the assumption that hydrolysis of TiCl3ꢀSO3CF3† produces three molar
equivalents of HCl, one molar equivalent of CF3SO3H and one molar equivalent of SiO2. Except in entries 1, 7 and 8 the yield is referred to
GC yield. The reaction was performed under the same reaction conditions as with TiCl3ꢀSO3CF3†. The reaction condition was according to
the literature.4
the residue chromatographed on a short column of silica gel using
CCl4 CH2Cl2 (3:2) as eluent. The pure 2,6-dibenzylidene-
cyclohexanone was obtained as yellow crystals in 99% yield (1.35 g),
mp 116^117 8C (lit.9 117 8C).
mole% of TiCl4 under the same reaction conditions as with
TiCl3ꢀSO3CF3) (Table 3, Entry 2). The reaction was not
complete and only 20% of the product was obtained after
4 h. Addition of 10 mole% of triethylamine did not improve
the yield of the reaction. This observation is similar to the
results reported for condensation of aromatic aldehydes
and aromatic ketones in a non-catalytic reaction with
TiCl4.20 In comparison, the same reaction with
TiCl3ꢀSO3CF3† produces the condensation product in
96% yield after 2 h (Table 1, Entry 4). This result ruled
out the possibility that the reaction may be catalysed by
the water which is produced through the condensation
reaction since both TiCl4 and TiCl3ꢀSO3CF3) can hydrolyse
in the presence of water.12 To obtain further evidence,
we studied the e¡ects of di¡erent acidic catalysts on the
condensation reaction of p-chlorobenzaldehyde with
cyclohexanone. The results of this study are in Table 3.
Comparison of the results obtained by our method with
some of those reported show the e¤ciency of this method.
In conclusion, the possibility of performing e¤cient and
catalytic cross-condensations of both aliphatic and aromatic
cycloalkanones with aromatic aldehydes at room tempera-
ture with excellent yields, easy procedure and simple
work-up and ease of handling of TiCl3ꢀSO3CF3† as a solid
titanium(iv) compound make this reagent a very suitable
catalyst for this type of reactions.
We thank Shiraz University Research Council for partial
support of this work. The assistance of Mr. N. Maleki
in running the NMR spectra and Dr. A. A. Jarahpoor
in running mass spectra is also acknowledged.
Received, 17th December 1998; Accepted, 24th May 1999
Paper E/8/09827A
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Experimental
All the products are known compounds and were characterized by
comparison of their physical data with those of known samples.
Infrared spectra were recorded on Perkin-Elmer IR-1I57 G and
781 spectrometers, NMR spectra on a Bruker Avance DPX-250
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General Procedure.öIn a round bottomed £ask was placed a
mixture of ketone (5 mmol) and aldehyde (10 mmol). Then
0.5^0.75 mmol of TiCl3ꢀSO3CF3† was added and stirred at room tem-
perature for 0.3^3 h [in the case of solid aldehydes (Tables 1, 2),
CH2Cl2 (3 ml) was also added]. The completion of the reaction
was monitored with GLC or TLC. The mixture was dissolved in
20 mL of acetone^water (40:1) and ¢ltered. The acetone solution
was dried with anhydrous sodium sulfate. The solvent was evaporated
and the residue chromatographed on a short column of silica gel using
CCl4 CH2Cl2 (3:2) as eluent. The product was obtained as yellow
crystals in 94^99% yield (Tables 1, 2).
Typical Procedure for Cross-aldol Condensation of Cyclohexanone
and Benzaldehyde.öTo a mixture of cyclohexanone (0.49 g, 5 mmol)
and benzaldehyde (1.06 g, 10 mmol), TiCl3ꢀSO3CF3† (0.15 g
0.5 mmol) was added and stirred at room temperature for 42 min until
solidi¢cation. The completion of the reaction was monitored with
GLC or TLC, taking small samples and dissolving in
dichloromethane. The mixture was dissolved in 20 mL of
acetone^water (40:1) and ¢ltered. After drying the organic solution
with anhydrous sodium sulfate, the solvent was evaporated and
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