Synthesis of 15N-labelled urea and methylenediurea

A new technique was developed for the large-scale synthesis of 15N-labelled urea at low enrichment levels. The synthesis is based on nucleophilic displacement of the phenoxide ion from phenyl carbonate and uses anhydrous ammonia as the nucleophile. In previous reports a copper catalyst was used; however, in this study it was found that the copper resulted in product decomposition and tar formation, which makes product purification difficult. A novel set of reaction conditions was developed: no catalyst was used, and no product decomposition or tar formation occurred. The reaction product was easily purified, and consistently high yields of 15N-labelled urea were obtained. 15N-labelled methylenediurea was prepared by the dilute solution reaction of formalin with 15N-labelled urea. The methodology developed for the reclamation of unreacted urea resulted in minimum loss of labelled urea. High performance liquid chromatography has been used to determine the chemical purity of both urea and methylenediurea. (author)