Merrifield Resin Supported Solid Phase Synthesis of 1-Amino-2,4-imidazolidinedione

The two novel ways of solid phase organic synthesis for preparing 1-amino-2,4-imidazolidinedione (4) were developed: (1) Merrifield resin-supported hydroxy substituted benzaldehydes (1a similar to 1c) were reacted with semicarbazide compound to give resin-supported semicarbazone (2a similar to 2c), followed cyclization with ethyl monochloroacetate in the presence of sodium ethoxide, clove with hydrochloric acid solution to give 1-amino-2,4-imidazolidinedione. (2) Merrifield resin-bound aldehyde prepared from Merrifield resin oxidized with DMSO was reacted with semicarbazide compound to give resin-supported semicarbazone 6, then cyclized and clove to give product 4. The cleavage way has advantage of obtaining single and quantitative product and simplifying purified procedure using I mol/L hydrochloric acid solution instead of trifluoroacetic acid solution.