Organic Syntheses, CV 3, 167
Submitted by H. E. Carter, R. L. Frank, and H. W. Johnston.
Checked by Nathan L. Drake and Charles M. Eaker.
1. Procedure
Caution! This procedure should be carried out in a hood.
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).
2. Notes
1. The
toluene may be dried by distillation.
2.
Commercial phosgene was used; it was obtained in a tank from the Ohio Chemical Company.
3. The
phosgene is absorbed rapidly for some time, then more slowly as the concentration increases. About 1 hour is required for this step. The amount of
phosgene absorbed is checked by weighing the flask and
delivery tubes occasionally.
4. In order to prevent the escape of
phosgene, a
toluene trap is inserted between the apparatus and the
water pump. For this purpose it is convenient to use a
2-l. flask immersed in an ice bath and containing about
1 l. of toluene. The flask is fitted with an
inlet tube reaching almost to the bottom.
5. It is not practical to remove the
toluene completely; moreover,
toluene does not interfere in the preparation of the derivatives.
6. The derivative may precipitate as an oil. However, crystallization is readily induced by cooling and scratching.
3. Discussion
This preparation is referenced from:
Copyright © 1921-2002, Organic Syntheses, Inc. All Rights Reserved