Patent GB-734928-A (GB)
Title: Process for the production of glutamine, its salts and glutamic acid
Filed: 1952-02-27
Abstract: A process for the production of glutamine or glutamic acid or their salts comprises heating together a -halogen-g -butyrolactone and ammonia to yield g -hydroxy-a -aminobutyramide, reacting said g -hydroxy-a -aminobutyramide with an alkaline earth hydroxide and an acid followed by an ammoniacal organic solvent to yield a -amino-g -butyrolactone, reacting said a -amino-g -butyrolactone at an elevated temperature with hydrogen cyanide or an alkali metal cyanide and hydrolysing the g -cyan-a -aminobutyric acid or salt thus obtained.  A modified process comprises reacting a -halogen-g -butyrolactone with hydrogen cyanide at an elevated temperature to yield g -cyan-a -halogenbutyric acid, heating said g -cyan-a -halogenbutyric acid with ammonia to yield g -cyan-a -aminobutyric acid hydrohalide, reacting said g -cyano-a -aminobutyric acid hydrohalide with an ammoniacal organic solvent to yield g -cyan-a -amino-butyric acid and heating said g -cyan-a -amino-butyric acid or salt thereof with a hydrolysing agent at an elevated temperature.  A further modified process comprises reacting the said g -cyan-a -halogenbutyric acid with a hydrolysing agent at an elevated temperature and heating the product with ammonia to form glutamine or glutamic acid or salts thereof.  The product of hydrolysis depends on the reagent employed, glutamine or its salts being obtained when hydrogen peroxide or concentrated sulphuric acid is used and glutamic acid or its salts when such hydrolysing agents as dilute sulphuric acid, concentrated or dilute hydrochloric acid or an alkali are used. Alkaline earth hydroxides mentioned for the conversion of the g -hydroxy-a -aminobutyramide are barium and calcium hydroxides and ammoniacal organic solvents with which the salt of a -aminobutyrolactone may be reacted are ammoniacal solutions of trichlorethylene or of methylene chloride.  In examples the potassium salt of glutamine is obtained by heating a -bromobutyrolactone with ammonia water to form g -hydroxy-a -aminobutyramide, converting the latter to a -amino-butyrolactone hydrobromide by treatment with barium hydroxide and sulphuric acid, treating the hydrobromide with ammoniacal methylene chloride or trichlorethane to obtain the free a -amino-butyrolactone, converting the latter into g -cyan-a -aminobutyric acid potassium salt by heating with potassium cyanide and warming the product with hydrogen peroxide (1); glutamine is obtained by passing dry hydrogen cyanide gas into a solution of a -aminobutyrolactone, prepared as in (1), in hot alcohol to obtain g -cyan-a -aminobutyric acid and dissolving the latter in hydrogen peroxide (2); glutamine is obtained by heating a -bromobutyrolactone with hydrogen cyanide to obtain a -amino-g -cyanbutyric acid hydrobromide and treating the product successively with ammoniacal trichloroethylene and hydrogen peroxide (3); and a -chloro-g -butyrolactone is heated with hydrogen cyanide to obtain g -cyan-a -chlorobutyric acid which is treated with ammonia water to obtain g -cyan-a -aminobutyric acid hydrochloride which is then treated with ammoniacal trichloroethylene and hydrolysed with dilute sulphuric acid to obtain glutamine.