Effect of the structure of phosphylating agents on their reaction with ethanolamine, an ambident nucleophile

The reactions of a series of phosphylating agents (RR′P(O)X) with ethanolamine have been examined, and relative yields of the products from the nucleophilic amino and hydroxyl moieties determined. In general the amount of O-phosphylation increased as R and R′ were changed from dimethylamino through alkoxy to methyl and as the leaving group (X) was changed from OP(O)RR′ to CN. The only exceptions occurred when R was dimethylamino and X was Cl. When X was F, only O-phosphylation was observed. Thus, a wide range of essentially continuously varying selectivities was found.The results are discussed in terms of the amount of charge transfer involved in the formation of the transition state which is assumed to be determined by the electrophile. When the charge transfer is small, the contributions to the activation energy of such factors as solvation and ionization potential of the nucleophile are most important, resulting in N-phosphylation. As the amount of charge transfer increases, the energy of bond formation becomes the dominant factor and O-phosphylation is preferred.