Patent GB-687485-A (GB)
Title: Improved method for the production of amino acids
Filed: 1949-07-04
Abstract: A method of making a -amino monocarboxylic acids and salts thereof comprises hydrolysing a hydantoin having the general formula <FORM:0687485/IV (b)/1> wherein R and R1 each represents hydrogen or a monovalent organic radicle having a carbon atom thereof attached to the hydantoin nucleus, by heating said hydantoin together with aqueous barium hydroxide to a temperature above 115 DEG  C., at a superatmospheric pressure, thereafter precipitating the barium as a water-insoluble barium salt to leave the resultant a -amino monocarboxylic acid compound dissolved in the liquor, removing the precipitate and crystallizing the a -amino monocarboxylic acid compound from the liquor.  The hydrolysis products comprise barium carbonate, ammonia and a water-soluble barium salt of the a -amino monocarboxylic acid.  The a -amino monocarboxylic acid may be recovered in free form or as an alkali metal salt by precipitating the barium as an insoluble salt, removing the precipitate and concentrating the liquor to crystallize the amino acid compound. Precipitating agents mentioned are the sulphates, acid sulphates, carbonates and bicarbonates of ammonium, potassium and sodium, carbon dioxide and sulphuric acid.  Alkali metal sulphates or carbonates yield alkali metal salts of the amino acid product and after removal of the precipitated barium salt these may be crystallized or converted to the free acid by acidification. Sulphuric acid or carbon dioxide yields the amino acid in free form when employed to precipitate the barium and when ammonium salts are used the ammonium salt of the amino acid obtained dissociates on evaporation and free amino acid is obtained.  An alkali metal sulphate or carbonate is preferably used in separating barium from hydrolysates containing tryptophane since alkali metal salts of the latter are more soluble than the free acid, which may be subsequently precipitated by adjusting the pH of the solution to a value of 5 to 8, preferably 7 to 8, with hydrochloric, hydrobromic, sulphuric or acetic acids. Impure or discoloured products may be purified by washing with a liquid aliphatic monohydric alcohol such as methyl, ethyl, propyl, isopropyl or butyl alcohol, ethyl alcohol being preferred, and any dissolved amino acid may be recovered by crystallization after evaporation.  The hydantoin is hydrolysed with an aqueous slurry of barium hydroxide in an autoclave, preferably from which air has been swept by steam, nitrogen or other inert gas and the reaction mixture is preferably cooled as quickly as possible when the reaction is complete, as indicated by the ammonia content of the solution.  The barium is then precipitated and the amino acid or salt recovered. When obtaining free amino acids the evaporation of the filtrate is carried out under vacuum.  In examples: (1) and (2) methionine is prepared from 5-(b -methylmercaptoethyl) hydantoin, comparison between barium hydroxide, lime and ammonia as hydrolysing agents being made in (1) and comparison between boiling under atmospheric pressure and using higher temperatures and pressures being made in (2), (3) a -aminobutyric acid, dl-valine, dl-leucine, dl-isoleucine, dl-phenylalanine, dl-tryptophane and b -(4-hydroxy-3-methoxy-phenyl) alanine are obtained by hydrolysis of hydantoins having in the 5-position as a substituent: an ethyl, isopropyl, isobutyl, sec.-butyl, benzyl, (3-indolyl methyl) or (4-hydroxy-3-methoxy benzyl) group with barium hydroxide under pressure, the barium being removed by filtration after the addition of ammonium carbonate and the desired products are obtained by evaporation of the filtrate under vacuum.  Other hydantoin starting materials mentioned are 5,5-dimethyl- and 5-ethyl-5-methyl hydantoins.