Organic Syntheses, CV 1, 21
Submitted by E. C. Kendall and B. F. McKenzie.
Checked by C. S. Marvel and W. W. Moyer.
1. Procedure
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 by volatilization.
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 again brought to a boil and the calculated amount of
silver oxide (Note
7) is added to remove the last of the chlorides. The
silver chloride is filtered off and the
lead is precipitated with
hydrogen sulfide. After filtering off the
lead sulfide, a light strawcolored solution remains.
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. of
alanine 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. (
52–60 per cent of the theoretical amount) (Note
8).
Alanine 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.
2. Notes
2. 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.
3. 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.
4. 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.
5. The volume of the solution must be kept large during the treatment with
lead oxide as
lead chloride will not crystallize from concentrated
alanine solutions.
6. If the solution at this point still contains ammonium salts another treatment with
100 g. of lead oxide is necessary.
7. 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.
8. A slightly lower yield of
alanine may be obtained conveniently from the evaporated
alanine hydrochloride by treatment with
aniline (Benedict,
1 and G. J. Cox and Harriette King, private communications).
Submitted by Walter C. Tobie and Gilbert B. Ayres.
Checked by John R. Johnson and R. B. Hasbrouck.
1. Procedure
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. (
65–70 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).
2. Notes
3. 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.
4. 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.
6. Filtration is best done with suction on a
Büchner funnel. Washing with
ether can be omitted without reducing the yield.
7. In a
capillary tube the product melts with decomposition at
275–280°, and the melting point varies somewhat with the rate of heating.
8. 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 is added.
3. Discussion
This preparation is referenced from:
Copyright © 1921-2002, Organic Syntheses, Inc. All Rights Reserved