Immobilization of Phosphamide on the TiO₂ Surface for Heterogeneous Phase Catalytic Appel Reaction

Global consumption of triphenylphosphine (Ph₃P) for phosphorus-mediated organic synthesis and production of the dead-end triphenylphosphine oxide (Ph₃PO) waste is exceptionally high. Recycling Ph₃PO and/or use of it as a reaction mediator gained significant attention. On the other end, phosphamides, traditionally used as a flame redundant, are stable analogues to Ph₃PO. Herein, via a low temperature condensation reaction of methyl 4-(aminomethyl)benzoate (AMB) and diphenyl phosphinic chloride (DPPC), methyl 4-((N,N-diphenylphosphinamido)methyl)benzoate (1) has been synthesized and hydrolysis of the ester functional group of 1 leads to a phosphamide with a carboxylate terminal, 4-((N,N-diphenylphosphinamido)methyl)benzoic acid (2). The presence of phosphamide functionality (NH─P═O) in 2 can be confirmed by its characteristic Raman vibration at 999 cm^-1 with expected P-N and P═O bonds distances from the single-crystal X-ray structure. In-situ hydrolysis of [Ti(OiPr)₄] in the presence of 2 followed by hydrothermal heating results in immobilization of 2 on a ca. 5 nm TiO₂ surface (2@TiO₂). The covalent attachment of 2 via coordination through the carboxylate terminal to the TiO₂ nanocrystal's surface has been established via multiple spectroscopic and microscopic studies. 2@TiO₂ is further used as the heterogeneous mediator for the catalytic Appel reaction, halogenation of alcohol (typically mediated by phosphine), with a fair catalytic conversion and a recorded TON up to 31. The major advantage of the heterogeneous approach studied herein is the recovery of used 2@TiO₂ from the reaction mixture via centrifugation only leaving the organic product in the supernatant, which is limiting in Ph₃P-mediated homogeneous catalysis. Time-resolved Raman spectroscopy confirms amino phosphine as the active species formed in-situ during the catalytic Appel reaction. Post-catalytic characterization of the material recovered after catalysis from the reaction mixture confirms the chemical integrity and that can further be utilized for another two catalytic runs. The developed reaction scheme showcases the use of a phosphamide as a reactive analogue to Ph₃PO for an organic reaction in a heterogeneous approach, and the same strategy can be explored further as a general scheme for other phosphorus-mediated reactions.