Org. Synth. 1934, 14, 46
GLYCINE ETHYL ESTER HYDROCHLORIDE
Submitted by C. S. Marvel
Checked by Louis F. Fieser and S. L. Judkins.
In a 3-l. round-bottomed flask are placed 500 cc. (400 g., 8.7 moles) of absolute alcohol which has been saturated in the cold with hydrochloric acid gas (Note 1), 870 cc. (680 g., 14.8 moles) of 96 per cent alcohol (Note 2), and 70 g. (1.03 moles) of methyleneaminoacetonitrile (Note 3). This mixture is refluxed on a steam bath for three hours (Note 4). During the refluxing, ammonium chloride separates. After the reaction is complete, the hot alcohol solution is filtered with suction and the filtrate cooled, thus allowing the glycine ester hydrochloride to separate in fine white needles. The product is filtered with suction, sucked as dry as possible on the filter, and then allowed to dry in the air. The yield is about 110 g. The alcohol from the filtrate is distilled (Note 5) until about one-third of its volume is left; it is cooled again, when a second crop of crystals is obtained. The total yield of product, m.p. 142–143°, varies from 125 to 129 g. (87–90 per cent of the theoretical amount). If a very pure product is desired, the material may be re-crystallized from absolute alcohol.
The 500 cc. of absolute alcohol
is cooled in an ice bath
and treated with dry hydrogen chloride until 163 g.
has been added, an amount sufficient for saturation. The solution should be protected from the moisture of the air with a calcium chloride tube
It is important to use the strengths of alcohol specified in the directions if the best yields are to be obtained, and it is advisable to test the alcohol with a hydrometer
just before using. The 870 cc. of 96 per cent alcohol
contains just enough water for the hydrolysis. If, therefore, a less concentrated alcohol is used, the glycine ester hydrochloride
does not form so readily and does not separate so easily from solution. Experiments using 96 per cent alcohol
saturated with hydrochloric acid
and 870 cc. of 96 per cent alcohol
gave about 8 to 10 g.
less product. A more dilute alcohol than 96 per cent
gives a much poorer grade and yield of the glycine ester hydrochloride
and not a rubber stopper
should be used during the refluxing, as rubber stoppers will cause the product to be colored.
It is important that no water get into the alcohol, as glycine ester hydrochloride
is quite soluble in water. Concentration of the filtrate on the steam bath should not be done in an open vessel
because the solution will take up moisture and the product will not crystallize.
Glycine ethyl ester hydrochloride
has been prepared by the action of absolute alcohol
and hydrogen chloride
from glycyl chloride
by the action of ammonia3
on chloroacetic acid
, and subsequent hydrolysis with alcoholic hydrochloric acid
; by the action of hydrogen chloride
and alcohol on methyleneaminoacetonitrile
and by the reduction of ethyl cyanoformate6
or the corresponding imido ester hydrochloride.7
This preparation is referenced from:
Chemical Abstracts Nomenclature (Collective Index Number);
glycine ester hydrochloride
hydrochloric acid (7647-01-0)
ammonium chloride (12125-02-9)
chloroacetic acid (79-11-8)
Glycine ethyl ester hydrochloride (623-33-6)
ethyl cyanoformate (623-49-4)
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