The replacement of mineral acids by sulfonic resins in the synthesis of rac-5-(4-hydroxyphenyl)hydantoin from p-hydroxymandelic acid and urea: Comparison of alternative methods Original Research Article

The sulfonic acid resin Dowex® 50W × 8 can be used to replace mineral acids in the reaction between p-hydroxymandelic acid and urea in water or NaCl solutions. The synthesis of p-hydroxymandelic acid is efficiently carried out using NaOH to promote the reaction between phenol and glyoxylic acid. Alternatively, KF/alumina can be used to obtain methyl p-hydroxymandelate by reaction of phenol with methyl 2-hydroxy-2-methoxyacetate, although, this process is carried out in an organic solvent and gives a lower yield. A comparison between the three alternative methods for the synthesis of 5-(4-hydroxyphenyl)hydantoin shows that the direct route from glyoxylic acid, urea and phenol is the most efficient method, although the p-hydroxymandelic acid route would be an interesting alternative if its heterogeneous synthesis were optimized.