A. Benzyl chloroformate. A 3-l. round-bottomed flask is fitted with a rubber stopper carrying an exit tube and a delivery tube extending to the bottom of the flask. The tubes are equipped with stopcocks so that the reaction flask may be disconnected. In the flask is placed 500 g. of dry toluene (Note 1), and the apparatus is weighed. The flask is then cooled in an ice bath, and phosgene (Note 2) is bubbled into the toluene until 109 g. (1.1 moles) has been absorbed (Note 3). The exit gases are passed through a flask containing toluene to remove any phosgene and then through a calcium chloride tube to a gas trap.

After the absorption of phosgene is completed the connection to the phosgene tank is replaced by a separatory funnel. The reaction flask is gently shaken while 108 g. (104 ml., 1 mole) of redistilled benzyl alcohol is added rapidly through the separatory funnel. The flask is allowed to stand in the ice bath for 30 minutes and at room temperature for 2 hours. The solution is then concentrated under reduced pressure, at a temperature not exceeding 60°, in order to remove hydrogen chloride, excess phosgene (Note 4), and the major portion of the toluene. The residue weighs 200–220 g. and contains 155–160 g. of benzyl chloroformate (91–94% based on the benzyl alcohol) (Note 5). The amount of benzyl chloroformate present in this solution may be estimated by preparing the amide from a small aliquot portion, or it may be safely calculated by assuming a minimum yield of 90% based on the benzyl alcohol used.

B. Benzyl carbamate. A measured aliquot (suitably 10 ml.) of the solution of benzyl chloroformate, prepared as described above, is added slowly and with vigorous stirring to 5 volumes of cold concentrated ammonium hydroxide (sp. gr. 0.90), and the reaction mixture is allowed to stand at room temperature for 30 minutes. The precipitate is filtered with suction, washed with cold water, and dried in a vacuum desiccator. The yield of practically pure benzyl carbamate, melting at 85–86°, is 7.0–7.2 g. (91–94% based on the benzyl alcohol used in A). Pure benzyl carbamate melting at 87° is obtained by recrystallizing the slightly impure material from 2 volumes of toluene.

C. Carbobenzoxyglycine. A solution of 7.5 g. (0.1 mole) of glycine in 50 ml. of 2 N sodium hydroxide is placed in a 200-ml. three-necked flask fitted with a mechanical stirrer and two dropping funnels. The flask is cooled in an, ice bath, and 17 g. (0.1 mole) of benzyl chloroformate (21–24 g. of the solution obtained in A) and 25 ml. of 4 N sodium hydroxide are added simultaneously to the vigorously stirred solution over a period of 20–25 minutes. The mixture is stirred for an additional 10 minutes. The toluene layer is separated, and the aqueous layer is extracted once with ether. The aqueous solution is cooled in an ice bath and acidified to Congo red with concentrated hydrochloric acid (Note 6). The precipitate is filtered, washed with small portions of cold water, and dried in the air. It is practically pure carbobenzoxyglycine; it weighs 18–19 g. (86–91%) and melts at 119–120°. The material may be recrystallized from chloroform; it then melts at 120° (Note 7).