Ring–chain tautomerism and protolytic equilibria of 3-hydroxy-3-phosphonoisobenzofuranone studied by 1H, 13C and 31P NMR-controlled titrations

Abstract

Treatment of 3-chloro-3-(dimethylphosphono)isobenzofuranone (3) with NaI in acetonitrile caused its monodemethylation to sodium 3-chloro-3-(methylphosphonato)isobenzofuranone (4). Compound 4 hydrolyzed in aqueous solution slowly to 3-hydroxy-3-(methylphosphono)isobenzofuranone (5). Upon refluxing in water, 4 demethylated simultaneously with the hydrolysis of the chloride, to afford 3-hydroxy-3-phosphonoisobenzofuranone (6). NMR spectra of the 3-hydroxyphosphonoisobenzofuranone derivatives 5 and 6 were found to be pH dependent. Raising the pH of the aqueous solutions to 10 by adding Na₂CO₃ caused changes in their ¹³C and ³¹P spectra, indicating opening of the isobenzofuranone ring and the formation of ortho-phosphonatoformylbenzoate anions (7) and (8). Acidification of solutions of 7 and 8 yielded 5 and 6, via ortho-phosphonoformylbenzoic acids (9) and (10), respectively, as putative intermediates. The facile formation of the cyclic tautomers 3, 4, 5 and 6, is interpreted in terms of the strong electron withdrawing effect of the phosphonyl group. High-resolution 1D and 2D NMR spectra observing nuclei ¹H, ¹³C and ³¹P established the molecular structures. Macroscopic dissociation constants were determined for a triprotic acid of type H₃L. Using sensor nuclei ¹H, ¹³C and ³¹P in advanced techniques of NMR controlled titrations confirmed concerted protolytic and ring–chain tautomeric equilibria. Probabilities of different sequences of protonation are discussed.