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

## TL;DR

Researchers improved the synthesis of TBBA and showed it can be used to analyze the chirality of amino acids and peptides using NMR spectroscopy.

## Contribution

A streamlined synthesis of enantiomerically pure TBBA and its application for chiral analysis using low-field NMR.

## Key findings

- TBBA synthesis was optimized for large-scale production of enantiomerically pure atropisomers.
- TBBA was successfully used for chiral analysis of amino acids and oligopeptides via 1H and 19F NMR.
- 19F NMR analysis was feasible on low-field benchtop instruments with non-deuterated solvents.

## Abstract

A concise and efficient second-generation synthesis of
2-(2-(trifluoromethyl)-1H-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 1H and 19F NMR spectroscopy. Furthermore, 19F NMR analyses were successfully carried out on a low-field
benchtop NMR spectrometer, including samples dissolved in nondeuterated
solvents.