Oxygen exchange during the reaction of POCl₃ and water

To investigate O exchange during the reaction of POCl₃ and water, natural abundance POCl₃ was reacted with water highly enriched in ¹⁸O, and the resulting H₃PO₄ was isolated as KH₂PO₄. This reaction was conducted with and without tetrahydrofuran (THF) as a solvent, and was controlled in THF and violent in its absence. Approximately 5 × 10^-4M aqueous solutions of the KH₂PO₄ were analyzed using electrospray ionization mass spectrometry, to estimate the proportions of the mass-clumped ^16,17,18O isotope analogues of [H₂PO₄] ^-. During analysis, ∼29% of [H₂PO₄] ^- dehydrated to [PO₃]^-, for which the proportions of the O isotope analogues were also measured. These proportions were compared with those predicted for O exchange at either four or three positions on the P atom of POCl3. The data strongly support O exchange at all four positions, whether or not THF was used to moderate conditions during the reaction. This result clears the way for safe, predictable synthesis of heavy-O labelled orthophosphate from POCl₃ and ¹⁸O enriched water for evaluation as an environmental and biochemical tracer.