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

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 120^oC for 3h.

Table2: Effect of the amount of KF/Al₂O₃ on the reaction of cyclohexanone and benzaldehyde