Organic Syntheses, Coll. Vol. 4, p.55 (1963); Vol. 30, p.7 (1950).
A. Triethyl α-phthalimidoethane-α,α,β-tricarboxylate. Three hundred and twenty-seven grams (1.0 mole) of diethyl sodium phthalimidomalonate2
and 735 g. (6.0 moles) of ethyl chloroacetate
) are placed in a 2-l. Claisen flask
fitted with a reflux condenser
and rubber stoppers
. The mixture is heated under reflux in an oil bath
at 150–160° for 2.25 hours. The excess ethyl chloroacetate
is removed by distillation at 30 mm. until the heating bath temperature reaches 150° and no more distillate is obtained (Note 1)
. The brown residual mass is cooled and then extracted with 1250 ml. of ether
. The oil dissolves, leaving a solid residue which is separated by filtration and washed with 750 ml. of ether
. The combined ether
extracts are distilled to remove ether
, and the residual oil is heated on a steam bath
under reduced pressure (35 mm.) to remove traces of ethyl chloroacetate
. The yield of triethyl α-phthalimidoethane-α,α,β-tricarboxylate
, dried at 45° for 48 hours, is 373–389 g.
) (Note 2)
B. DL-Aspartic acid.
A mixture of 383 g. of the above crude product
, 1 l. of concentrated hydrochloric acid
, 1 l. of glacial acetic acid
, and 1 l. of water is boiled under reflux in a 5-l. round-bottomed flask
for 2–3 hours. The reflux condenser is then replaced by a fractionating column
, and the mixture is slowly distilled until the temperature at the head of the column has risen to 108°. This requires about 13 hours. The distillate amounts to 1.5 l. (Note 3)
The residual mixture is allowed to cool, and the phthalic acid
which crystallizes is removed by filtration and washed with 350 ml. of 1% hydrochloric acid (Note 4)
. The combined filtrate and washings are distilled nearly to dryness on a steam bath under reduced pressure; the bulk of the hydrochloric and acetic acids remaining is removed by slowly adding 300 ml. of water through a dropping funnel
while the distillation under reduced pressure is continued. The dark brown residue is warmed on a steam bath with 700 ml. of water, is allowed to cool, and is filtered to remove a small amount of black insoluble matter. The filtrate is decolorized with 2 g. of Norit
, 200 ml. of hot water being used to wash the Norit
. The volume of the combined filtrate and washings, amounting to about 1.2 l., is measured accurately, and a small portion is analyzed for chloride (Note 5)
. An amount of pyridine
corresponding exactly to the chloride content is added, diluted with 500 ml. of 95% ethanol
. The DL-aspartic acid
, which crystallizes at once, is separated by filtration after the mixture has stood for 24 hours at room temperature and is washed with 50–100 ml. of cold water (Note 6)
Although this product cannot be purified by distillation, it contains almost the theoretical amount of nitrogen
as shown by Kjeldahl analysis.
During the first few hours the distillate contains ethyl acetate
; the distillate obtained during the first hour, amounting to 137 ml., distils below 99° and on saturation with sodium chloride
yields 115 ml. of crude ethyl acetate
The total amount of chloride found should be less than 1 mole.
The mother liquor contains too little DL-aspartic acid
to justify its recovery. When the filtrate and washings are evaporated to a syrup and treated with 500 ml. of 95% ethanol
, the pyridine hydrochloride
dissolves completely, leaving 8–9 g.
of crude glycine
which yields little or no sparingly soluble DL-aspartic acid
on treatment with a minimum quantity of cold water.
The final mother liquor from the recrystallization of DL-aspartic acid
yields a small quantity (about 0.5 g.
) of glycine
The purity of the recrystallized DL-aspartic acid
was established by nitrogen analysis by the Kjeldahl and Van Slyke methods. The decomposition point of this product is 325–348°.
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