Synthesis of 1-Benzylpiperazine (BzP)from Organic Syntheses Collective Volume V, p 88-91
ProcedureA solution of 24.3 g. (0.125 mole) of piperazine hexahydrate in 50 ml. of absolute ethanol, contained in a 250-ml Erlenmeyer flask, is warmed in a bath at 65°C as there is dissolved in the solution, by swirling, 22.1 g. (0.125 mole) of piperazine dihydrochloride monohydrate (Note 1). As warming in the bath at 65°C is continued, there is added during 5 minutes, with vigorous swirling or stirring, 15.8 g (14.3 ml, 0.125 mole) of recently distilled benzyl chloride. The separation of white needles comes almost immediately. After the solution has been stirred for an additional 25 minutes at 65°C, it is cooled, and the unstirred solution is kept in an ice bath for about 30 minutes. The crystals of piperazine dihydrochloride monohydrate are collected by suction filtration, washed with three 10ml portions of ice-cold absolute ethanol, and then dried. Recovery of the dihydrochloride is 21.5-22.0 g. (97-99%) (Note 2). The combined filtrate and washings from the piperazine dihydrochloride are cooled in an ice bath and treated with 25 ml of absolute ethanol saturated at 0°C with dry hydrogen chloride (Note 3). After the solution has been well mixed, it is cooled for 10-15 minutes in an ice bath. The precipitated white plates of 1-benzylpiperazine dihydrochloride are collected by suction filtration, washed with dry benzene, and dried. The product, which melts at about 280°C with decomposition, after sintering at about 254°C (Note 4), amounts to 29-29.5g. (93-95%). A solution of this salt in 50ml of water is made alkaline (pH > 12) with about 60 ml of 5N sodium hydroxide, then extracted twelve times with 20ml portions (Note 5) of chloroform. The combined extracts are dried over anhydrous sodium sulfate, and the pale brown oil (Note 6) remaining after removal of solvent is distilled at reduced pres in a Claisen flask. The yield of pure 1-benzylpiperazine, bp 122-124°C/2.5 mmHg, is 14.3-16.5 g. (65-75%). Notes
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