Funnel, Buchner solid addition

A. Ethyl N-benzylcarbamate. A 12-1. three-necked flask fitted with a sturdy Hershberg-type stirrer and two 1-1. addition funnels is immersed in an ice bath and charged with 1 kg. (9.33 moles) of benzylamine, 500 ml. of ice water, and 1.5 kg. of chopped ice. To the stirred mixture 525 g. (4.83 moles) of ethyl chlorocar-bonate is added dropwise while the temperature is maintained at 10-15° (1.0-1.5 hours) (Note 1). An additional 500 ml. of water and 1 kg. of chopped ice are then added to the flask, and a second 525-g. portion (4.83 moles) of ethyl chlorocarbonate is introduced. Simultaneously with this, an ice-cold solution of 400 g. (10 moles) of sodium hydroxide in 1.3 1. of water is added dropwise at such a rate that equal fractions of the ethyl chlorocarbonate and sodium hydroxide solutions are introduced over equal periods of time, the temperature being maintained throughout at 10-15° (2.5-3.0 hours). The reaction mixture is stirred for an additional 30 minutes and is then filtered through a Buchner funnel. The solid product is washed with copious amounts of cold water and is air-dried to yield 1.6 kg. (96%) of glistening while crystals, m.p. 45-47°. 

For purification, transfer the acid to a 150 ml. flask containing 60 ml. of water, boil the mixture under reflux, and then add acetic acid in 5 ml. portions down the condenser until almost all the solid has dissolved avoid an excess of acetic acid by ensuring that the solvent action of each addition is complete before the next portion is added. A small suspension of insoluble impurity may remain. Add 2 g. of animal charcoal, boil the solution again for 10-15 minutes, and then filter it through a preheated Buchner funnel. Cool and stir the filtrate, which will deposit pale cream-coloured crystals of the acid. Collect as before and if necessary repeat the recrystallisation. Yield of pure acid, 9 g. m.p. 227-229°. 

In a 3-I. round-bottomed flask 250 g. of commercial calcium hypochlorite is dissolved in i 1. of warm water and a warm solution of 175 g. of potassium carbonate and 50 g. of potassium hydroxide in 500 cc. of water is added. The flask is stoppered and shaken vigorously until the semi-solid gel which first forms become quite fluid. The suspended solid is removed by filtration on a large Buchner funnel, washed with 200 cc. of water, and sucked as dry as possible with the aid of a rubber dam and an efficient suction pump. The filtrate of approximately 1500 cc. is placed in a 3-I. round-bottomed flask and is ready for the addition of methyl /3-naphthyl ketone. 

In a 500-ml. round-bottomed flask equipped with a reflux condenser and a magnetic stirrer (Note 6) are placed 150 ml. of methanol, 150 ml. of 6N hydrochloric acid, and the total yield of 4,4 -bis(acetamido)azobenzene. The mixture is heated under reflux for 1.5 hours. The reaction mixture is cooled and the violet solid collected on a Buchner funnel (Note 7). The damp product is suspended in 500 ml. of water in a 1-1. beaker equipped with a stirrer, and the mixture is slowly neutralized by the addition of 2.5N sodium hydroxide. In the course of the neutralization, the salt dissolves and the free base separates. The 4,4 -diaminoazo-benzene is collected on a Buchner funnel, washed with water, and dried under reduced pressure. The yield of yellow product, m.p. 238-241° (dec.),is ll-12g. The over-all yield from/ -amino-acetanilide is 52-56%. 

The crude ester is cooled, an equal volume of benzene is added, then the free acid is neutralized by shaking with about 250 cc. of a 10 per cent solution of sodium carbonate (Note 4). The benzene solution is poured into 1300 cc. of a saturated solution of sodium bisulfite (about 60 g. of technical sodium bisulfite per 100 cc.), contained in a wide-neck bottle equipped with an efficient stirrer, and the mixture stirred for two and a half hours. The mixture soon warms up a little and becomes semi-solid. It is filtered through a 20-cm. Buchner funnel and carefully washed, first with 200 cc. of a saturated solution of sodium bisulfite, finally with two 150-cc. portions of benzene (Notes 5 and 6). The white pearly flakes of the sodium bisulfite addition product are transferred to a 3-I. round-bottom wide-neck flask equipped with a mechanical stirrer and containing 700 cc. of water, 175 cc. of concentrated sulfuric acid, and 500 cc. of benzene. The flask is heated on a steam bath under a hood, the temperature being kept at 55°, and the mixture is stirred for thirty minutes (Note 7). The solution is then poured into a separatory funnel, the benzene separated and the water layer extracted with a 200-cc. portion of benzene. The combined benzene solution is shaken with excess of 10 per cent sodium carbonate solution to remove free acid and sulfur dioxide (Note 8). The benzene is washed with a little water and then dried over anhydrous potassium carbonate (Note 9). The benzene is distilled at ordinary pressure over a free flame from a 500-cc. Claisen flask, the solution being added from a separatory funnel as fast as the benzene distils. It is advisable to distil the ester under reduced pressure although it can be done under ordinary pressure. The fraction distilling around n8°/5mm., 130710 mm., 138715 mm., 148725 mm., 155735 mm., or... 

After all the peracetic acid has been added, the reaction mixture is diluted with 80 ml. of water and heated from 35° to 100° over a 20-minute period (Note 2). It is then kept at 100° for 45 minutes. The flask is cooled to 0-5° in an ice bath, and the solid iodoxybenzene is collected on a Buchner funnel and air-dried with suction for 1 hour. Additional material is obtained by concentrating the filtrate to one-fourth of its volume (Caution Note 3). The two crops of crude iodoxybenzene are combined and dried overnight in a desiccator weight 19.6-20.5 g. m.p. 230° Caution Explodes ). Iodometric titration 3 shows the purity to be about 94% (Note 4). 

TsCl was obtained from Aldrich Chemical Company, Inc. and purified by recrystallization according to the following procedure. p-Toluenesulfonyl chloride (85 g) is dissolved in 150 mL of hot CHC13 and 200 ml. of petroleum ether (room temperature) is added in one portion to the clear, colorless solution. The resulting cloudy solution is clarified by addition of ca. 5 g of charcoal, stirred for 1 min, and filtered on a Buchner funnel. The filtrate is concentrated to ca. l/5th of its original volume by rotary evaporation, and the solid which appears is collected by filtration and dried under reduced pressure (25° C, 0.03 mm) to afford 68 g of TsCl as bright white crystals. 

C. 4-Amino-l-tert-butyloxycarbonylpiperidine-4-carboxylic acid (3). A 2000-mL, round-bottomed flask equipped with a magnetic stirbar is charged with a suspension of the hydantoin 2 (40.0 g, 0.8 mol) in 340 mL of THF (Note 12), and 340 mL of 2.0M potassium hydroxide solution (Note 13) is added in one portion. The flask is stoppered and the reaction mixture is stirred for 4 hr (Note 14) and then poured into a 1000-mL separatory funnel. The layers are allowed to separate over 45 min and the aqueous layer is then drained into a 1000-mL round-bottomed flask. This solution is cooled at 0°C while the pH is adjusted to 8.0 by the slow addition of ca. 100 mL of 6.0N HC1 solution. The resulting solution is further acidified to pH 6.5 by slow addition of 2.0 N HC1 solution (Note 15). The white precipitate which appears is collected by filtration on a Buchner funnel and the filtrate is concentrated to a volume of 60 mL to furnish additional precipitate which is collected by filtration. The combined portions of white solid are dried at room temperature under reduced pressure (65°C 0.5 mm) for 12 hr and then suspended in 100 mL of chloroform (Note 16) and stirred for 45 min. The white solid is filtered and then dried under reduced pressure (85°C 0.5 mm) for 24 hr to yield 13.4-14.1 g (64-68%) (Note 17) of the amino acid 3 as a white solid (Note 18). 

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