Second-Generation Synthesis and Analytical Application of TBBA for Chiral Analysis of Amino Acids and Oligopeptides by 1 H and 19 F NMR Spectroscopy

High Resolution Image Download MS PowerPoint Slide A concise and efficient second-generation synthesis of 2-(2-(trifluoromethyl)-1 H -benzo[ d ]imidazol-1-yl)benzoic acid (TBBA) has been developed. The synthesis affording enantiomerically pure TBBA atropisomers was significantly streamlined through optical resolution by diastereomeric salt formation, enabling preparation on a 32 mmol scale. The applicability of TBBA as a chiral derivatizing agent in the solid-phase synthesis of amino acid derivatives was demonstrated, allowing determination of the absolute configuration and optical purity by 1 H and 19 F NMR spectroscopy. Furthermore, 19 F NMR analyses were successfully carried out on a low-field benchtop NMR spectrometer, including samples dissolved in nondeuterated solvents.