Improved synthesis of a,a'-dibenzylidenecyclohexanone
Yang
Wenzhi, Li Haiying, Wang Shuxiang, Li Jitai, Duan Chunming
(College of Chemistry and Environmental Science, Hebei University, Baoding 071002, China)
Received Feb.24, 2004; Supported by Natural
Science Foundation of Hebei Province, China (299080).
Abstract The paper reported the Claisen-Schmidt
condensation between cyclohexanone and benzaldehyde catalyzed by potassium fluoride
supported on alumina in refluxed methanol and resulted a,a'-dibenzylidenecyclohexanone in 95% yield. The effects of different
factors on this condensation reaction have been discussed and the experimental conditions
were optimized.
Keywords a,a'-Dibenzylidenecyclohexanone;
Claisen-Schmidt condensation; Potassium fluoride supported on alumina
1. INTRODUCTION
The a,a'-bis(substituted benzylidene)
cyclohexanones are used as precursors to potentially bioactive pyrimidine derivatives,[1]
intermediates of agrochemical, pharmaceuticals and perfumes.[2] Preparation of a,a'-bis(substituted benzylidene) cyclohexanones is usually completed
via Claisen-Schmidt condensation between cyclohexanone and aromatic aldehydes catalyzed by
solid NaOH[3-6] or NaOEt,[7] using conventional heating method. It
also has been reported that some compounds, such as bis(p-ethoxyphenyl)telluroxide
(BMPTO),[8] RuCl3,[9] SmI3,[10] Cp2ZrH2,[11]
TiCl3(SO3CF3),[12] were used as catalysts. But
there were some shortcomings in terms of high cost, difficult preparation and especially
reaction conditions. Over the past few years, a considerable number of reactions have been
developed in which inorganic solid supports such as alumina, silica gel and
montmorillonite appeared to be useful in terms of mildness of conditions, yield and
convenience. Our laboratory has reported the Claisen-Schmidt condensation of acetophenone
with various aromatic aldehydes catalyzed by KF/Al2O3 under
ultrasound irradiation, and the results are better than that under conventional heating
condition.[13] In the present communication, we report our results on the KF/Al2O3-
catalyzed condensation reaction between cyclohexanone and benzaldehyde.
2. EXPERIMENTAL
Benzaldehyde were purified by distillation prior to use. Melting points were
uncorrected. IR spectra were recorded on a Bio-Rad FTS-40 spectrometer (KBr). 1HNMR
spectra were measured on Bruker AM-400S (400 MHz) spectrometer using TMS as internal
standard and CDCl3 as solvent. Mass spectra were determined on a VG-7070E
spectrometer (EI, 70eV).
2.1 Preparation of the catalyst (KF-solid supports)
Anhydrous potassium fluoride (20 g) was dissolved in distilled water (80 ml) and mixed
with solid supports (30g), such as neutral alumina, kieselguhr or Molecular
sieve respectively. The mixture was stirred at 65-75 oC for 1h. The water was
removed under reduced pressure. The resulting free flowing powder was dried at 120 oC
for 4 h. The content of KF is about 30% (150mg mixture/mmol KF).
2.2 General procedure
The cyclohexanone (1, 1 mmol) and benzaldehyde (2, 2 mmol) are mixed with
MeOH (2 mL). KF-Al2O3 (150 mg) is added, and the mixture is refluxed
for 8h. After cooling, the mixture was dissolved in CH2Cl2. The
catalyst was removed by filtration and washed with CH2Cl2. The
solvent was evaporated under reduced pressure and the residue was crystallized with
dichloromethane/ethanol to give a,a'-dibenzylidenecyclohexanone.
The authenticity of the products was established by comparing their melting points with
the literature and data of IR and 1H NMR spectra.
3. RESULTS AND DISCUSSION
We first examined the KF coated with different solid supports effects between
cyclohexanone and benzaldehyde. As shown in Table 1, the best results were obtained with
the mixture of composition cyclohexanone:benzaldehyde=1:2 catalyzed by potassium fluoride
supported on alumina, thus, potassium fluoride supported on alumina was chosen as
catalyst. Reaction temperature also significantly affected the yield and increasing the
reaction temperature whichever solid supports coated with potassium fluoride enhanced the
yield.
Table 1 Claisen-Schmidt condensation
between cyclohexanone and benzaldehyde catalyzed by using KF coated with different solid
supports
Solid
support |
Methods |
Time
(h) |
Temperature
(oC) |
Product
yield (%) |
kieselguhr |
A |
16 |
25 |
0 |
B |
8 |
64.6 |
65 |
Molecular sieve (5Å) |
A |
16 |
25 |
37 |
B |
8 |
64.6 |
90 |
alumina |
A |
16 |
25 |
91 |
B |
8 |
64.6 |
93 |
Method A: The reaction was
carried out using magnetic stirrer catalyzed by KF-solid support in methanol.
Method B: The reaction was carried out using magnetic stirrer catalyzed by KF-solid
support in refluxed methanol
The molar ratio of cyclohexanone to catalyst (150mg mixture/mmol KF) was 1:1.
By using optimized
reaction conditions, the effect of the amount of KF/Al2O3 on the
condensation reaction was investigated. Table 2 shows that the yields were highly
dependent on the amount of KF/Al2O3. The molar ratio of KF/Al2O3
to substrate strongly affected the yield of products. The best molar ratio was 1.0-1.2 to
give a,a'-dibenzylidenecyclohexanone in 93-95%
yields, both the ratio of 0.8 and 1.5 led to the decrease of yields (78% and 77%
respectively). In the absence of KF/Al2O3, the condensation did not
take place. The catalyst can be reused two times without significant decrease in activity
after being washed with dichloromethane and activated at 120oC for 3h.
Table2: Effect of the amount of KF/Al2O3
on the reaction of cyclohexanone and benzaldehyde
Entry |
Ratio* |
Product
yield (%),(Reported) |
m.p.
(oC) (Reported) |
1 |
0.5 |
24 |
115-117
(116-117)[9] |
2 |
0.8 |
78 |
3 |
1.0 |
93 |
4 |
1.2 |
95A,
95B
(50-80)[6], (64.5)[8], (70)[11] |
5 |
1.5 |
77 |
*The molar ratio of
catalyst/cyclohexanone. AThe reaction was carried out using magnetic stirrer
catalyzed by KF/Al2O3 in refluxed methanol and isolated yield based
on cyclohexanone. BThe reaction was carried out using magnetic stirrer
catalyzed by NaOH in refluxed methanol for 8h and the molar ratio of catalyst to
cyclohexanone was 0.2.
The effect of the reaction
time was studied. As shown in Table 3, the best results were obtained when reaction time
was 8h. The reaction solution also plays an important role in this reaction. With the
other reaction conditions fixed, the reaction was carried in refluxed solution for 8h,
such as using ethanol, benzene, toluene, diethyl ether, petroleum ether (b.p.,60-90oC)
and dichloromethane, the yields obtained were lower than that
in refluxed methanol.
Table3 The effect of the reaction time on the reaction
of cyclohexanone and benzaldehyde
Entry |
Time
(h) |
Yield,
%* |
1 |
6 |
75 |
2 |
8 |
93 |
3 |
10 |
60 |
The
reaction was carried out using magnetic stirrer catalyzed by KF/Al2O3
in refluxed methanol and the molar ratio of cyclohexanone to catalyst was 1:1.
Different attempts to do selection
of mono-condensation of benzaldehyde for only one side of cyclohexanone were not
successful. For example, we carried out the reaction in ratio (benzaldehyde
/cyclohexanone) of 3:1 and 1:1 respectively. Both the reaction provided the same product a,a'-dibenzylidenecyclohexanone and the yields were obtained 93% and
94% respectively, no a-benzylidenecyclohexanone
was obtained.
The yield of the product was up to 95%, the melting point agrees with
document value (Found: 115-117oC; Reported [9]: 116-117oC).
1H NMR and IR, data are consistent with the literature reported [11].
From the results (Table2, Entry 4) we can deduce that the yields are, in general, higher
than those described in the literatures [6,8,11]. We also did the experiment
catalyzed by NaOH in refluxed methanol for 8h, the condensation of cyclohexanone with
benzaldehyde was carried out with 95% yield (Table2, Entry 4) using stirring. But compared
with the product separation from the unreacted substrates, crystallized from ethanol and
dichloromethane, when using NaOH the disposing of process was more tedious.
4. CONCLUSIONS
It was concluded that the best synthetic conditions of the a,a'-dibenzylidenecyclohexanone
used the mole ratio of KF/Al2O3 to cyclohexanone (1.2/1), chosen the
refluxed methanol for 8h, and the yield of a,a'-dibenzylidenecyclohexanone
was up to 95%. An efficient method for the preparation of a,a'-dibenzylidenecyclohexanone has been provided and the main
advantages of the present procedure are minimally environmental pollution, cheap and
reusable catalyst, easier work-up and better yields.
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