Investigations on the synthesis of DL-serine from α-haloacrylic acid derivatives (Aminoacids ; 13)

Abstract

The alkoxide-catalyzed addition of alcohols to α-chloroacrylonitrile at -35°C gives rise to 3-alkoxy-2-chloropropanenitriles; at 0–5°C with excess alkyl 3-alkoxy-2-chloropropanimidates are obtained. The yields of 3 or 4 decrease with increasing pKa values of the alcohols. In the base-catalyzed addition of phenols 5 to 1, a temperature-dependent addition equilibrium is set up in which the position of equilibrium is shifted in favour of the addition products with increasing pKa values of 5. The 3-alkoxy-2-chloropropanoates, which are readily accessible by hydrolysis of 4, react smoothly with sodium azide in the presence of a phase transfer catalyst to furnish the 3-alkoxy-2-azidopropanoates. Starting from benzyl 2-azido-3-benzyloxy-propanoate (10b), the specific syntheses of DL-serine (14), DL-serine hydrochloride (14·HCl), DL-serine methyl ester hydrochloride (13a·HCl), 0-benzyl-DL-serine (12b), and 0-benzyl-DL-serine benzyl ester hydrochloride (11b·HCl) are possible by variation of the hydrogenation conditions.