Phospha-Mannich reactions of PH₃ and its analogs

Abstract

The easiest route to form compounds with P–C_sp3–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.

Graphical abstract

Keywords:

• Hydroxymethyl phosphines
• aminomethyl phosphines
• PN-ligands
• P,N-acetals
• phosphaalkenes
• amines
• imines
• iminium salts
• cross-linking
• hydrogels
• immobilization
• flame-proofing

Acknowledgments

We are indebted to Drs. Yulia B. Malysheva and Elena A. Zaburdaeva from the Nizhniy Novgorod State University, and Dr. Vladmir Malakhov from Ludwig-Maximilians-Universität München, for their help in the literature search. Photoshop brushes, developed by Zaen Bien (http://z-design.deviantart.com), were used for Graphical Abstract.