Hydrolysis Pathways for Aminophosphazenes

The hydrolysis behavior of the aminocyclotriphosphazenes (NPR₂)₃, where R = NH₂, NHCH₃, NHCH₂COOC₂H₅, NHCH₂CONHCH₃, N₂C₃H₃ (imidazolyl), NHCH₂CF₃, NHCH₂C₆H₅, NHC₆H₅, NC₄H₄ (pyrrolyl), NC₄H₈ (pyrrolidino), NC₅H₁₀ (piperidino), and NC₄H₈O (morpholino), has been examined in water or aqueous dioxane, acid, and base. The ease of hydrolysis in aqueous dioxane declined with changes in R in the order N₂C₃H₃ > NHCH₂COOC₂H₅ > NHC-H₂CONHCH₃ > NH₂ > NHCH₃ > NHC₆H₅ > NHCH₂C₆H₅ > NHCH₂CF₃ > NC₄H₄, NC₄H₈, NC₅H₁₀, and NC₄H₈O. Two different but interconnected mechanistic pathways appear to be followed. In the first, hydrolytic removal of one amino residue from phosphorus occurs to yield species of type N₃P₃R₅OH before cleavage of the phosphazene ring takes place. In the second, cleavage of the phosphazene ring is a fast reaction following protonation of the ring nitrogen atoms. Those compounds which contained amino acid ester or amide side groups hydrolyzed only after prior initial conversion of the ester or amide units to free carboxylic acid groups. Comparisons are made with the behavior of the open-chain high polymers of formula (NPR₂)_n, where R = NHCH₃, NHCH₃ and N₂C₃H₃, NHCH₂COOC₂H₅, and NHCH₂CONHCH₃, and the overall trends are considered in terms of the potential biomedical behavior of these compounds.