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

摘要

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