Yang Wenzhi, Li Haiying, Wang Shuxiang, Li Jitai, Duan Chunming
(College of Chemistry and Environmental Science, Hebei University, Baoding 071002, China)
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.
The a,a’-bis(substituted benzylidene) cyclohexanones are used as precursors to potentially bioactive pyrimidine derivatives, intermediates of agrochemical, pharmaceuticals and perfumes. 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, using conventional heating method. It also has been reported that some compounds, such as bis(p-ethoxyphenyl)telluroxide (BMPTO), RuCl3, SmI3, Cp2ZrH2, TiCl3(SO3CF3), 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. In the present communication, we report our results on the KF/Al2O3– catalyzed condensation reaction between cyclohexanone and benzaldehyde.
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.
- 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 (%)|
|Molecular sieve (5Å)||A||16||25||37|
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)|
(50-80), (64.5), (70)
*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, %*|
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 : 116-117oC). 1H NMR and IR, data are consistent with the literature reported . 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.
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.