SYNTHESIS OF DL-ALANINE (2-Aminopropanoic acid)

• Place 2 litres (1760g, 36 mol) of concentrated ammonia solution (d 0.88, 35% w/w) (1) in a large (e.g. Winchester) bottle, cool thoroughly in an ice bath and pour in slowly 77g (0.5 mol) of 2-bromopropanoic acid. 

• Close the bottle with a rubber bung held in place with wire, and leave at room temperature for 4 days. 

• Concentrate the solution to about 250 ml by distillation under reduced pressure using a rotary evaporator; apply the vacuum with caution in the initial stages when most of the excess of ammonia is being removed. 

• Filter, concentrate further to 150 ml, cool in ice and add 750 ml of methanol with swirling. 

• Leave the resulting suspension overnight in a refrigerator, and then filter off the crude alanine with suction and wash it with 200 ml of methanol. 

• Dissolve the product in 150 ml of water, reprecipitate the alanine by adding 750 ml of methanol and filter and wash as before. The yield of almost pure DL-alanine, m.p. 295-296 °C (decomp.), is 30g (67%).

Notes to keep in mind:

1. Alternatively use 225g of 'ammonium carbonate', 175 ml of water and 250 ml (4.5 mol) of concentrated ammonia solution. 'Ammonium carbonate' is a mixture of roughly equimolar amounts of ammonium hydrogen carbonate and ammonium carbamate (NH₄HCO₃⋅NH₂CO₂NH₄).

Cognate preparations:Glycine (aminoacetic acid)

• Use 47g (0.5 mol) of chloroacetic acid (CAUTION: the compound causes blistering if it is allowed to come into contact with the skin) and 2 litres of concentrated ammonia solution. 

• Allow the reaction to proceed for 2 days, concentrate to 60 ml and precipitate the crude glycine by adding 360 ml of methanol. 

• This material contains ammonium chloride as the chief impurity; remove most of this by stirring the crystals with 150 ml of methanol and refiltering. 

• Finally purify the glycine by dissolving it in 50 ml of hot water and adding 250 ml of methanol; the yield is 25g (67%), m.p. c. 252-254 °C (decomp.).

DL-Valine (2-amino-3-methylbutanoic acid):

• Use 60g (0.33 mol) of 2-bromo- 3-methylbutanoic and 400 ml (7.25 mol) of concentrated ammonia solution. 

• Allow reaction to proceed at room temperature for 7 days. 

• Concentrate the solution to 50 ml and filter the resulting thin paste. 

• Dissolve the solid in 1 50 ml of hot water, decolourise with 1g of charcoal, filter hot and dilute the filtrate with 150 ml of ethanol. 

• Cool at 0°C overnight, filter off the purified DL-valine and wash with 10 ml of cold ethanol. 

• The yield is 12.5g (32%); m.p. 280-282 °C (decomp.). A further 2g may be isolated by concentrating the mother-liquor to about 25 ml and adding an equal volume of ethanol.

DL-Norvaline (2-aminopentanoic acid):

• Prepare as for valine, using 2-bromo-pentanoic acid; m.p. c. 300 °C (decomp.).

DL-Norleucine (2-aminohexanoic acid):

• Use 65g (0.33 mol) of 2-bromo-hexanoic acid and 400 ml of concentrated ammonia. 

• Ensure that the bung is securely wired to the reaction bottle and allow the latter to stand in a warm place (50-55 °C) for 30 hours. 

• Filter the amino acid at the pump and keep the filtrate (A) separately. 

• Wash the amino acid well with methanol to remove the ammonium bromide present. Concentrate the filtrate (A) almost to dryness and add 150 ml of methanol. 

• A second crop of amino acid contaminated with ammonium bromide is thus obtained; wash it with methanol and recrystallise from hot water, thus affording a further 6g of pure dl- norleucine. The total yield is 28g -(65%); the decomposition point is about 325 °C.

DL-holeucine (2-amino-3-methylpentanoic acid):

• Allow 65g (0.33 mol) of 2-bromo-3-methylpentanoic acid to react with 400 ml of concentrated ammonia solution as for valine. 

• Concentrate the resulting solution to about 130 ml, filter off a first crop of crude product and wash with 20 ml of ethanol. 

• Further concentrate the aqueous filtrate to about 60 ml to obtain a second crop of crude product, and wash it with 10 ml of water followed by 10 ml of ethanol. 

• Dissolve the combined product (28g) in 400 ml of hot water, decolourise with charcoal and add 200 ml of rectified spirit. 

• Cool well in ice, and filter off the pure DL-isoleucine; yield 16.5g (38%), m.p. 278-280 °C (decomp.). 

• A further 5g may be recovered by concentrating the recrystallisation mother-liquor to 40 ml and diluting with an equal volume of ethanol.