AMINO ACIDS; 13. INVESTIGATIONS ON THE SYNTHESIS OF DL-SERINE FROM α-HALOACRYLIC ACID DERIVATIVES

Article abstract of DOI:10.1016/S0040-4020(01)86062-2

The alkoxide-catalyzed addition of alcohols 2 to α-chloroacrylonitrile (1) at -35 degC gives rise to 3-alkoxy-2-chloropropanenitriles 3; at 0-5 degC with excess 2 alkyl 3-alkoxy-2-chloropropanimidates 4 are obtained.The yields of 3 or 4 decrease with increasing pK_a values of the alcohols 2.In the basecatalyzed 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 6 with increasing pK_a values of 5.The 3-alkoxy-2-chloropropanoates 8, 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 10.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), O-benzyl-DL-serine (12b), and O-benzyl-DL-serine benzyl ester hydrochloride (11b*HCl) are possible by variation of the hydrogenation conditions.