Solid-state ¹⁷O NMR study of 2-acylbenzoic acids and warfarin

We report synthesis and solid-state ¹⁷O NMR characterization of four site-specifically ¹⁷O-labeled 2-acylbenzoic acids (2-RC(O)C₆H₄COOH) where R=H and CH₃): 2-[3-¹⁷O]formylbenzoic acid, 2-[1,2-¹⁷O₂]formylbenzoic acid, 2-[3-¹⁷O]acetylbenzoic acid, and 2-[1,2,3-¹⁷O₃]acetylbenzoic acid. In the solid state, both 2-formyl- and 2-acetyl-benzoic acids exist as the cyclic phthalide form each containing a five-membered lactone ring and a cyclic hemiacetal/hemiketal group. Static and magic-angle-spinning ¹⁷O NMR spectra were recorded at 14.1 and 21.1T for these compounds, from which the ¹⁷O chemical shift and nuclear quadrupolar coupling tensors were determined for each oxygen site. These results represent the first time that ¹⁷O NMR tensors are fully characterized for lactone, cyclic hemiacetal, and cyclic hemiketal functional groups. We also report solid-state ¹⁷O NMR data for the cyclic hemiketal group an anticoagulant drug, warfarin. Experimental ¹⁷O NMR tensors in these compounds were compared with computational results obtained with a periodic DFT code BAND.