N-乙酰苯丙胺

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: In a one l., three necked, creased flask provided with a stirrer, thermometer, condenser topped with a drying tube and a short length of Gooch tubing connected to a small Erlenmeyer flask was placed 18.7 g (0.106 moles) of N-(alpha-methylphenethyl) acetamide, 15.9 g (0.159 moles) of succinic anhydride and 500 ml of dry methylene chloride. The flask and contents were cooled to 0°-5°, and from the Erlenmeyer flask through the Gooch tubing, 55.5 g (0.424 moles) of anhydrous aluminum chloride was added in small portions over a period of approximately 0.5 hour. A sharp exotherm occurred after each of the first additions, but the temperature was not allowed to exceed 8°. During the addition, the succinic anhydride slowly dissolved and gradually a grayish green gum was deposited. After five hours at 0°-5°, the cooling bath was removed, and the stirred mixture allowed to warm to room temperature (19°-22°), then stirred for another twenty-four hours. At the end of this time, the reaction mixture consisted of a reddish orange gum and a pale-colored solvent. The mixture was cooled in an ice bath, and with vigorous stirring 200 ml of 3 N hydrochloric acid added at 20°. The mixture was stirred until the color of the viscous red gum became grayish white. The stirrer was then stopped, the layers allowed to separate, and the lower methylene chloride layer removed by suction from the reaction vessel. Another 300 ml of methylene chloride was added to the flask, the contents stirred for five minutes, then allowed to settle and the lower layer drawn off as before. provided with a stirrer thermometer, condenser topped with a drying tube The flask and contents were cooled to 0°-5° to exceed 8° During the addition the cooling bath was removed The mixture was cooled in an ice bath with vigorous stirring 200 ml of 3 N hydrochloric acid added at 20° The mixture was stirred until the color of the viscous red gum to separate the lower methylene chloride layer removed by suction from the reaction vessel Another 300 ml of methylene chloride was added to the flask the contents stirred for five minutes

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: Seventy three and six tenths g (0.2 moles) of rac. amphetamine sulfate was suspended in 150 ml of water and to the stirred suspension, a solution of twenty g (0.5 moles) of sodium hydroxide in 200 ml of water was added. The liberated oil was collected by three extractions with 200-ml portions of toluene. The combined extracts were dried over anhydrous K2CO3, then the drying agent removed by filtration. To the filtrate, 100 ml of acetic anhydride (1.0 mole) was added in portions and the resulting solution refluxed for two hours. The toluene, excess anhydride and acetic acid were distilled in the rotary evaporator and the residual oil distilled in a simple Claisen still collecting the fractions that boiled at 120°-126°/7 mm, yield 63.3 g (89%) of a colorless oil that spontaneously set to a mass of crystals, mp 91°-93°. The liberated oil was collected by three extractions with 200-ml portions of toluene The combined extracts were dried over anhydrous K2CO3 the drying agent removed by filtration the resulting solution refluxed for two hours The toluene, excess anhydride and acetic acid were distilled in the rotary evaporator the residual oil distilled in a simple Claisen still collecting the fractions that boiled at 120°-126°/7 mm, yield 63.3 g (89%) of a colorless oil

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: Seventy three and six tenths g (0.2 moles) of rac. amphetamine sulfate was suspended in 150 ml of water and to the stirred suspension, a solution of twenty g (0.5 moles) of sodium hydroxide in 200 ml of water was added. The liberated oil was collected by three extractions with 200-ml portions of toluene. The combined extracts were dried over anhydrous K2CO3, then the drying agent removed by filtration. To the filtrate, 100 ml of acetic anhydride (1.0 mole) was added in portions and the resulting solution refluxed for two hours. The toluene, excess anhydride and acetic acid were distilled in the rotary evaporator and the residual oil distilled in a simple Claisen still collecting the fractions that boiled at 120°-126°/7 mm, yield 63.3 g (89%) of a colorless oil that spontaneously set to a mass of crystals, mp 91°-93°. The liberated oil was collected by three extractions with 200-ml portions of toluene The combined extracts were dried over anhydrous K2CO3 the drying agent removed by filtration the resulting solution refluxed for two hours The toluene, excess anhydride and acetic acid were distilled in the rotary evaporator the residual oil distilled in a simple Claisen still collecting the fractions that boiled at 120°-126°/7 mm, yield 63.3 g (89%) of a colorless oil

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: The commercially available precursor to dextroamphetamine is 1R,2S-(−)-norephedrine. Attempts were made to O-acetylate the norephedrine free base, but produced mostly N-acetylamphetamine according to an analysis of the carbonyl region of the infrared spectra. In one experiment, norephedrine free base in acetic acid was treated with 0.5 equivalents of sulfuric acid and then treated with 1.1 equivalents of acetic anhydride with heating to 63° C. to obtain a clear solution. Catalytic reduction followed by basification gave an oil that was composed of 13.96% amphetamine and 68% norephedrine, an indication that the acetylation procedure on a sulfate salt was only partially successful. In another experiment, a 10 mol portion of norephedrine hydrochloride was acetylated with a 20% excess of acetic anhydride in 2 mL acetic acid/g of salt and progress of the reaction followed fours (Table 2). The reaction mixture was diluted with 130 mL water and subjected to catalytic hydrogenation for 22 hours to obtain 10.4 g of oil. The long reaction time is attributed to the presence of acetic acid in the reduction mixture. Yield of amphetamine from norephedrine hydrochloride based on the weight of product and HPLC analysis is 66% (Experiments A and B). For these experiments, it can be seen that the best results were obtained with the salts of phenylpropylamine or norephedrine, particularly the hydrochloride salt.

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: In a one l., three necked, creased flask provided with a stirrer, thermometer, condenser topped with a drying tube and a short length of Gooch tubing connected to a small Erlenmeyer flask was placed 18.7 g (0.106 moles) of N-(alpha-methylphenethyl) acetamide, 15.9 g (0.159 moles) of succinic anhydride and 500 ml of dry methylene chloride. The flask and contents were cooled to 0°-5°, and from the Erlenmeyer flask through the Gooch tubing, 55.5 g (0.424 moles) of anhydrous aluminum chloride was added in small portions over a period of approximately 0.5 hour. A sharp exotherm occurred after each of the first additions, but the temperature was not allowed to exceed 8°. During the addition, the succinic anhydride slowly dissolved and gradually a grayish green gum was deposited. After five hours at 0°-5°, the cooling bath was removed, and the stirred mixture allowed to warm to room temperature (19°-22°), then stirred for another twenty-four hours. At the end of this time, the reaction mixture consisted of a reddish orange gum and a pale-colored solvent. The mixture was cooled in an ice bath, and with vigorous stirring 200 ml of 3 N hydrochloric acid added at 20°. The mixture was stirred until the color of the viscous red gum became grayish white. The stirrer was then stopped, the layers allowed to separate, and the lower methylene chloride layer removed by suction from the reaction vessel. Another 300 ml of methylene chloride was added to the flask, the contents stirred for five minutes, then allowed to settle and the lower layer drawn off as before. provided with a stirrer thermometer, condenser topped with a drying tube The flask and contents were cooled to 0°-5° to exceed 8° During the addition the cooling bath was removed The mixture was cooled in an ice bath with vigorous stirring 200 ml of 3 N hydrochloric acid added at 20° The mixture was stirred until the color of the viscous red gum to separate the lower methylene chloride layer removed by suction from the reaction vessel Another 300 ml of methylene chloride was added to the flask the contents stirred for five minutes

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: Seventy three and six tenths g (0.2 moles) of rac. amphetamine sulfate was suspended in 150 ml of water and to the stirred suspension, a solution of twenty g (0.5 moles) of sodium hydroxide in 200 ml of water was added. The liberated oil was collected by three extractions with 200-ml portions of toluene. The combined extracts were dried over anhydrous K2CO3, then the drying agent removed by filtration. To the filtrate, 100 ml of acetic anhydride (1.0 mole) was added in portions and the resulting solution refluxed for two hours. The toluene, excess anhydride and acetic acid were distilled in the rotary evaporator and the residual oil distilled in a simple Claisen still collecting the fractions that boiled at 120°-126°/7 mm, yield 63.3 g (89%) of a colorless oil that spontaneously set to a mass of crystals, mp 91°-93°. The liberated oil was collected by three extractions with 200-ml portions of toluene The combined extracts were dried over anhydrous K2CO3 the drying agent removed by filtration the resulting solution refluxed for two hours The toluene, excess anhydride and acetic acid were distilled in the rotary evaporator the residual oil distilled in a simple Claisen still collecting the fractions that boiled at 120°-126°/7 mm, yield 63.3 g (89%) of a colorless oil