Silica gel-Supported Palladium Catalyst for the Acyl Sonogashira Reaction

EXPERIMENTAL SECTION

Preparation of Pd-SH-SILICA

A solution of 1 g silica in toluene (10 mL) was stirred with excess (3-mercaptopropyl)-trimethoxysilane (500 mg) at 100 ℃ for 10 h. The solution was filtered, and the residue was quickly washed with toluene and dichloromethane and air-dried (theoretical SH loading 0.99 mmol gm−1). Then the dried solid material SH-SILICA (200 mg) was dispersed in a THF (2 mL) solution containing palladium acetate (20 mg) and stirred at room temperature until disappearance of yellow color.20 The deep orange solid silica was filtered and the residue was washed with dichloromethane. The resulting solid material was dried in air (Pd loading 0.4 mmol gm−1). It was denoted as Pd-SH-SILICA.

Catalytic Acyl Sonogashira Reaction

In a typical acyl Sonogashira reaction, the catalyst, Pd- SH-SILICA (45 mg) was added in dry toluene (5 mL), followed by alkynes (1 mmol), acyl chloride (1.2 mmol) and triethylamine (1.2 mmol) in a small glass vial. The resulting solution was stirred at room temperature for 15 h and monitored by thin-layer chromatography (TLC). After completion of the reaction, the product was monitored by GC analysis. All of the products were known. As an example, 1H and 13C NMR of the compound (Table 1, entry 1) were observed and compared with literature. So, the reaction mixture was filtered and the solvent was completely evaporated under reduced pressure. The residue was extracted with ethyl acetate and washed twice with water, and concentrated under reduced pressure. The residue was then purified through column chromatography using the solvent ratio of hexane and ethyl acetate (10 : 1). 1, 3-diphenylprop- 2-yn-1-one (table 1, entry 1)12: 1H NMR (CDCl3400 MHz): δ 8.23 (dd, J = 7.7 Hz, 2H), 7.69 (dd, J = 7 Hz, 2H), 7.64 (m, 1H), 7.42−7.55 (m, 5H) ppm; 13C NMR (CDCl3,100 MHz): δ 178.0, 137.0, 134.1, 133.0, 130.8, 129.6, 128.7, 120.1, 93.1, 86.8 ppm. Anal. Calcd for C15H10O: C,87.38; H, 4.85; Found: C, 87.27; H, 4.92.

Synthesis of Pyrazoles

After 15 h, explanation as above, without filtration the mother solution was kept at 80 oC and added hydrazine hydrate (2 mmol in 1 mL methanol) solution. The reaction mixture was stirred for additional 2 h. After cooling to room temperature, the solvent was removed under reduced pressure and then the reaction mixture was diluted with water (5 mL) and extracted with dichloromethane (2×5 mL). The organic layer was dried over anhydrous sodium sulfate and concentrated under reduced pressure. The crude products were purified by silica gel column chromatography (hexane/ethyl acetate, 4:1) to afford the pure pyrazoles. Both compound were characterized by spectral data and compared with literature. 3, 5-Diphenyl-1H-pyrazole (Scheme 1, R = H, 56% yield):2829 1H NMR (CDCl3, 400 MHz) δ 7.74 (d, J= 7.6 Hz, 4H) 7.34–7.45 (m, 6H), 6.85 (s, 1H) ppm; 13C NMR (CDCl3, 100 MHz): δ 148.8, 132.3, 128.8, 128.2, 125.7, 100.1 ppm. Anal. Calcd for C15H12N2: C, 81.82; N, 12.73; H, 5.45; Found: C, 81.61; N, 12.82; H, 5.50. 3-Phenyl-5-(4-methoxyphenyl)-1H-pyrazole (Scheme 1, R=OMe, 62% yield):28 1H NMR (CDCl3, 400 MHz) δ 7.80 (d, 2H), 7.73 (d, J= 8.8 Hz, 2H), 7.40 (m, 3 H), 7.00 (d, J= 8.8 Hz, 2H), 6.90 (s, 1 H), 3.84 (s, 3 H) ppm; 13CNMR (CDCl3): δ 148.9, 148.1, 159.8, 131.5, 128.7, 127.9, 126.9, 125.6, 123.6, 114.1, 99.5, 55.5 ppm. Anal. Calcd for C16H14N2O: C, 76.80; N, 11.20; H, 5.60; Found: C, 76.75; N, 10.87; H, 5.82.

Catalyst Recycling

After the completion of a reaction, the mixture was centrifuged and toluene solution was decanted. The solids were washed with acetone, water and again acetone, isolated by centrifugation between washes, then dried at 50 oC and used for next run.