The hydrogenation of histidine methyl ester

Abstract

This investigation undertakes the synthesis of an N-acetylated imidazoline derivative of histidine methyl ester. The synthetic method involved hydrogenating a sample of histidine methyl ester using an acetic anhydride solvent and a platinum oxide catalyst. The reaction was carried out at room temperature and at a pressure of 60 psi. Four reaction products were found using this layer chromatography developed with five per cent methanol in chloroform.

From previous work with the hydrogenation products of imidazole, three products were expected for the reduction of histidine methyl ester, namely, the unreduced N-acetylhistidine methyl ester, the partially reduced imidazoline derivative and the completely reduced imidazolidine derivative. The fourth product was suspectded of being an alcohol or acid (COOH) imidazoline derivative.

A number of chromatographic methods were investigated for purifying the imidazoline derivative, the desired product. Silica gel G proved suitable for the separation of N-acetylhistidine methyl ester, a major contaminant. Under the conditions used, two successive column runs were necessary to remove N-acetylhistidine methyl ester.

Hydrazinolysis of the residue obtained after removal of the substituted histidine ester resulted in a white solid having a melting point of 92-94°C. The hydrazide, while impure, appeared to contain as a major component the hydrazide derived from an N-acetylated imidazoline derivative of histidine methyl ester. This was supported by the fact that the hydrazide showed a strong UV absorbance at approximately 280nm corresponding to the N, N-diacetylimidazoline ring.