4-Chlorobenzhydrylchloride

119-56-2

134-83-8

GENERAL METHODS: NaBH4 (0.6 mol) was added batchwise to a stirred solution of benzophenone (1.0 mol) in methanol (2 vol) at room temperature for 45 min. The reaction mixture was stirred at ambient temperature for 2-3 h (progress of the reaction was monitored by TLC) and subsequently diluted with water (750 mL) and pH adjusted with acetic acid to 4. The reaction mixture was extracted with dichloromethane (2 x 400 mL). The organic layer was washed with water (200 mL), dried over anhydrous sodium sulfate, and the solvent was evaporated under reduced pressure to give the pure diphenylmethanol derivative as a white to off-white solid in 93-97% yield. To a stirred solution of diphenylmethanol derivative (1.0 mol) in toluene (370 mL) at room temperature was sequentially added concentrated HCl (35% aqueous solution, 370 mL) and tetrabutylammonium bromide (0.01 mol). The reaction mixture was stirred at 40-45 °C for 6-7 hours. After confirming the completion of the reaction by TLC, the mixture was cooled to room temperature. The organic layer was separated and concentrated under vacuum to afford the crude diphenylmethyl chloride derivative as a light brown liquid in 95-97% yield. Anhydrous piperazine (5.0 mol) was slowly added to a solution of diphenylmethyl chloride derivative (0.96 mol) in toluene (380 mL) at 60-70 °C for 45-60 minutes. The resulting mixture was heated with stirring at 90-100°C for 8-10 hours. After completion of the reaction, the mixture was cooled and water (380 mL) was added to separate the organic layer. The organic layer was washed with a mixture of concentrated HCl and water (1:1, 2 x 350 mL) and neutralized with 20% NaOH solution (750 mL). The aqueous layer was again extracted with toluene (2 × 300 mL), and the combined organic layers were dried with anhydrous sodium sulfate and concentrated in vacuum to afford the pure diphenylmethylpiperazine compounds (2a-c) as white to off-white solids in 88% yield.