4liphatic and aromatic amino-acids can be converted into their NN-dimethyl derivatives by reductive condensation with formaldehyde and hydrogen in the presence of palladised charcoal. Aromatic nitro-acids can be reduced and N-methylated in one operation.IN connection with investigations on the relative configurations of the naturally occumng amino-acids, carried out several years ago in this laboratory under the direction of Dr. F. Barrow, it became necessary to prepare the NN-dimethyl derivatives of some of them in an optically active form. The methods hitherto employed for the resolution of the simple amino-acids are not directly applicable to their dimethyl derivatives, but in preliminary experiments NNdimethylalanine was resolved by means of its (-)-menthy1 ester (Halliday, Thesis, Univ. of London, 1938), and optically pure (+)-dimethyl-L-aZanine was isolated. This method was, however, not so successful when extended to other dimethylamino-acids, and attention was therefore directed to their preparation by the direct methylation of the unsubstituted aminoacids.* A review of the literature revealed that, although the behaviour of a large number of aminoacids towards all the usual methylating agents had been examined, there is a t present no satisfactory method available for the conversion of amino-acids into their dimethyl derivatives : methyl iodide in the presence of alkali leads to betaines, occasionally accompanied by mono-or di-alkylamino-acids ; diazomethane leads to the methyl esters or mixtures thereof with the corresponding betaines; formaldehyde in the presence of formic acid has little value except for glycine and a-aminoisobutyric acid, whose NN-dimethyl derivatives were obtained in satisf actory yield (Clarke, Gillespie, and Weisshauss, J . Aruter. Chew. Soc., 1933, 55, 4571.Reductive condensation of amines with aldehydes or ketones in the presence of hydrogen and a catalyst (Skita and his co-workers, Ber., 1928, 61, 1151 et seq.) has been frequently employed in recent years for the alkylation of amines. It has now been applied to amino-acids and peptides, furnishing a simple and convenient method for the preparation of both their mono-and their di-alkyl derivatives.The reaction was first applied to the methylation of DL-alanine, a mixture of the amino-acid and formaldehyde being submitted to catalytic reduction in aqueous solution in the presence of palladised charcoal. Reduction proceeded readily a t ordinary temperature and pressure, and NN-dimethyl-DL-alanine was isolated in almost quantitative yield. This method was then subsequently extended, with complete success, to glycine and the inactive forms of valine, leucine, phenylglycine, and phenylalanine.Aromatic amino-carboxylic and amino-sulphonic acids may also be thus methylated, anthranilic and sulphanilic acids being readily converted into their dimethyl derivatives. It is of interest that the aromatic amino-acids may be replaced by the corresponding nitro-acids which are reduced and then methylated in one operation ; the three isomeric di...