Organic Syntheses, Coll. Vol. 1, p.21 (1941); Vol. 9, p.4 (1929).
One hundred and thirty-one grams (3 moles) of freshly distilled acetaldehyde (Note 1)
is added to 100 cc. of ether
in a 2-l. bottle
and cooled to 5° in an ice bath (Note 2)
. One hundred and eighty grams (3.4 moles) of ammonium chloride
dissolved in 550 cc. of water is then added, followed by an ice-cold solution of 150 g. (3.1 moles) of sodium cyanide
in 400 cc. of water. The sodium cyanide
must be added slowly and with frequent cooling to prevent loss of acetaldehyde
After the sodium cyanide
solution is added, the bottle is stoppered securely, placed in a mechanical shaker
, and shaken for four hours at room temperature. At the end of this time the solution is transferred to a 3-l. distilling flask
and 600 cc. of concentrated hydrochloric acid
(sp. gr. 1.19) is added (Hood
) (Note 3)
The solution in the flask is distilled over a free flame until separation of salt prevents further heating. It is then transferred to a large evaporating dish
, placed on a steam bath
and evaporated to dryness (Note 4)
The residue remaining in the dish after evaporation is stirred thoroughly with 800 cc. of 95 per cent alcohol
. After filtration the alcohol is distilled on a steam bath and the last traces are removed under vacuum. While still warm the residue is dissolved in 500 cc. of 95 per cent alcohol
containing 2 per cent of hydrochloric acid
, and cooled. Two hundred cubic centimeters of ether
is added, and the solution is filtered. This treatment should remove all but the last traces of sodium chloride
and ammonium chloride
. The alcohol and ether
are removed by distillation and the last of the free hydrochloric acid
is removed by distillation under diminished pressure.
The alanine hydrochloride
remaining in the flask is dissolved in 1500 cc. of water, and transferred to a metal pail of about 2-l. capacity
. Two hundred and twenty grams of yellow lead oxide
is added and the mixture is boiled gently for one hour. During the boiling small amounts of water are added at intervals in order to maintain the original volume (Note 5)
. Upon cooling, the lead chloride
crystallizes; it is filtered off and the solution is again boiled one hour with 100 g. of lead oxide
. Twenty grams of freshly precipitated lead hydroxide
is added slowly and the boiling is continued for ten minutes. Following this the solution is again cooled and filtered (Note 6)
. The chloride content should now be equivalent to not more than 50–75 cc. of a normal solution (Note 7)
The solution is evaporated by boiling to a volume of about 400 cc., and 600 cc. of 95 per cent alcohol
is added. When thoroughly cooled, 100–120 g.
is filtered off. This is washed with 200 cc. of alcohol
and a pure white product is obtained.
A further crop of 40–50 g.
may be obtained by removing the alcohol and water until a volume of about 100 cc. remains, and then adding 250 cc. of alcohol
and cooling to 0°. The total yield is 140–160 g.
per cent of the theoretical amount) (Note 8)
so prepared is sufficiently pure for most purposes. It may be recrystallized by dissolving in the least amount of hot water (about 450 cc.) and adding two volumes of alcohol
A one-half gallon (2-l.) ginger-ale bottle
is convenient for this purpose. The necks of these bottles are small and will hold a wire securely.
Caution must be observed during the addition of the hydrochloric acid
as much hydrogen cyanide
is evolved. During the first part of the subsequent distillation it is necessary to prevent fumes from escaping from the receiver
into the room.
During the evaporation a layer of crystals forms on the surface and must be continually broken. A blast of air blowing over the surface agitates the liquid sufficiently and allows free evaporation.
The volume of the solution must be kept large during the treatment with lead oxide
as lead chloride
will not crystallize from concentrated alanine
If the solution at this point still contains ammonium salts another treatment with 100 g. of lead oxide
An aliquot portion of the solution is titrated with silver nitrate
by the Volhard method. The result of this titration is used in calculating the amount of silver oxide
which must be added.
A slightly lower yield of alanine
may be obtained conveniently from the evaporated
by treatment with aniline
and G. J. Cox and Harriette King, private communications).
Slowly and with stirring, 100 g. (0.65 mole, 59 cc.) of cold (1–4°) α-bromopropionic acid (Note 1)
is added to 3 l. (44.5 moles, 2700 g.) of cold (1–4°) concentrated aqueous ammonia
(sp. gr. 0.9) (Note 2)
in a 1-gal. glass-stoppered bottle
, and the mixture is allowed to stand at room temperature for at least four days (Note 3)
. The solution is concentrated to a volume of 300 cc. (Note 4)
, filtered, and concentrated further to 200 cc. The solution is cooled to room temperature and 1 l. of methyl alcohol (Note 5)
added. After chilling overnight in a refrigerator (0–4°) the crystals are filtered with suction and washed with 250 cc. each of methyl alcohol
and ether (Note 6)
. The yield is 42–48 g.
of crude alanine
For purification the crude product is dissolved in 200 cc. of water (warming if necessary), 1 l. of methyl alcohol
is added, and the mixture chilled overnight. After washing as before, the yield is about 38–42 g.
per cent of the theoretical amount) of purified dl-alanine
, m. p. 295°
(dec.) on the Maquenne block (Note 7)
. This product is free of bromide
and contains only traces of ammonia
. If an especially pure product is desired the material may be reprecipitated from methyl alcohol
once more in the same manner (Note 8)
Temperatures above 40° reduce the yield, and chilling after mixing does not increase it. Less than four days' standing gives a reduced yield, but longer standing does not increase the yield.
Evaporation may be done in an evaporating dish under a hood, or better by distillation at reduced pressure, using a water pump
with a trap
. Heating should be gentle at first to avoid violent ebullition. The ammonia
may be recovered if desired by absorption in ice water.
Filtration is best done with suction on a Büchner funnel
. Washing with ether
can be omitted without reducing the yield.
In a capillary tube
the product melts with decomposition at 275–280°
, and the melting point varies somewhat with the rate of heating.
The last traces of ammonia
may be removed by adding 10 g. of permutit when dissolving for the second time, then shaking the mixture thoroughly for three minutes and filtering before the methyl alcohol
This preparation is referenced from:
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