Phospha-Mannich reactions of PH3 and its analogs

The easiest route to form compounds with P–Csp3–N linkage(s) is phosphorus-based Mannich-type reactions (phospha-Mannich reactions) between phosphines (R3P, R2PH, RPH2, PH3), carbonyl compounds (mainly CH2O) and amines (R2NH, RNH2, NH3). Because of toxicity and inflammability, applications of PH3 and its liquid analog (Me3Si)3P in such reactions are rare. Stable, less toxic, and non-pyrophoric adducts of PH3 with CH2O, i.e., tris(hydroxymethyl)phosphine (HOCH2)3P and tetrakis(hydroxymethyl)phosphonium (HOCH2)4P+ salts, are often used as both P- and C-sources in phospha-Mannich reactions, providing many acyclic and cyclic P,N-ligands, among which 1,3,5-triaza-7-phosphaadamantane (PTA) is most known. Phospha-Mannich reactions of (HOCH2)4P+ salts with urea form condensation products that are used to impart fire retardance to cotton materials, the most important and oldest area of application of the salts. The use of (HOCH2)3P and (HOCH2)4P+ salts as cross-linking agents in protein-based hydrogel manufacturing, enzyme immobilization on NH2-containing supports, and leather tanning, is also based on phospha-Mannich reactions and ability to form P–CH2–N linkages with amino acids residues. Mechanistic aspects of phospha-Mannich reactions are discussed.