Patent GB-812541-A (GB)
Title: Process for the production of n,n-dibenzylamino acids
Filed: 1955-07-08
Abstract: The invention comprises nitriles of the formula: <FORM:0812541/IV (b)/1> (wherein R is hydrogen or an alkyl radical and n is zero or 1 to 8, except that when R is hydrogen n is not zero) and their preparation by condensing at an elevated temperature dibenzylamine with the appropriate a -hydroxynitrile.  This process may be combined with subsequent hydrolysis of the nitrile with a strong acid to give first the corresponding amide and then the corresponding N:N-dibenzylamino acid.  The condensation is preferably effected in ethanol, and the hydrolysis of the nitrile is preferably effected with concentrated sulphuric acid and that of the amide with aqueous hydrochloric acid, advantageously containing acetic acid.  The above processes may also be combined with resolution of the N:N-dibenzylamino acids by reacting L-(+)- or D-(-)-threo-1-p-nitrophenyl-2-aminopropane-1:3-diol with a mixture in any proportions of the enantiomorphs of the acid in an aqueous aliphatic alcohol containing at most 6 carbon atoms, separating the resulting sparingly soluble salt of one of the said enantiomorphs with the optically active diol and liberating the enantiomorph therefrom.  In examples: (1) lactonitrile and dibenzylamine give N:N - dibenzyl - a  - aminopropionitrile, this is hydrolysed with sulphuric acid to N:N-dibenzyl - a  - aminopropionamide and this is hydrolysed with hydrochloric acid to N:N-dibenzyl - DL - a  - alanine hydrochloride, from which the free base is liberated; (2) N:N - dibenzyl - a  - aminobutyronitrile, the corresponding amide and N:N-dibenzyl-DL-a -aminobutyric acid are similarly prepared; (3) N:N - dibenzyl - a  - aminovaleronitrile and the corresponding amide are prepared as in (1) and the latter is hydrolysed with a hydrochloric/acetic acid mixture to N:N-dibenzyl-DL - norvaline; (4) N:N - dibenzyl - a  - aminoisovaleronitrile, the corresponding amide and N:N - dibenzyl - DL - valine are similarly prepared; (5) N:N-dibenzyl-a -aminoisocapronitrile, the corresponding amide and N:N-dibenzyl - DL - leucine are similarly prepared; (6) DL-N:N-dibenzylalanine and L - (+) - threo - 1 - p - nitrophenyl - 2 - aminopropane - 1:3 - diol (hereinafter called the L-diol) are refluxed in aqueous alcohol to give, on crystallization, the salt of the L-diol with the L - (-) - N:N - dibenzylalanine; the L-diol is recovered from the mother liquors by addition of sodium hydroxide and after removal of this the filtrate is worked up to give D - (+) - N:N - dibenzylalanine which is immediately converted to a salt with D-(-)-threo - 1 - p - nitrophenyl - 2 - aminopropane-1:3-diol; from the salt of the L-diol with L - (-) - N:N - dibenzylalanine the free amino acid is liberated and this is then hydrogenolysed in presence of a carbon palladium catalyst to give L-(+)-alanine hydrochloride; (7) DL - N:N - dibenzylvaline is similarly resolved and the L-(-)-isomer similarly hydrogenolized to L-(+)-valine; (8) DL-N:N-dibenzylnorvaline is similarly resolved and the L - (-) - isomer hydrogenolysed to L - (+)-norvaline; (9) DL-N:N-a -dibenzyl-aminobutyric acid is resolved similarly and the L - (-) - siomer hydrogenolysed to L - (+) - a  - aminobutyric acid; (10) DL-N:N-dibenzylleucine is resolved similarly and the L-(-)-isomer hydrogenolysed to L-(-)-leucine.  Specifications 423,735, 512,691, [both in Group IV], 770,575 and 812,543 are referred to.