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.