Preparation of d,l-Phenylalanine by Amidocarbonylation of Benzyl Chloride

The preparation of d,l-phenylalanine via amidocarbonylation of benzyl chloride with acetamide and CO/H(2) is described. The rate of the reaction is dependent upon the CO pressure below 250 bar, but independent of the hydrogen pressure. A reaction temperature of 100 degrees C gives optimum yields. A relatively large amount of the catalyst, Co(2)(CO)(8), is needed for complete conversion because of inhibition caused by hydrogen chloride which is formed during the reaction. Addition of NaHCO(3) removes HCl as insoluble NaCl, resulting in improved conversion and selectivity of the reaction. It also allows the use of a stoichiometric amount of acetamide, whereas a 2- to 3-fold excess of acetamide is needed for complete conversion of benzyl chloride without NaHCO(3). Amidocarbonylation of benzyl alcohol gave d,l-phenylalanine in only 8% yield.