Stability study of α‐bromophenylacetic acid: Does it represent an appropriate model analyte for chiral separations?

The stability of α‐bromophenylacetic acid (BPAA) in 50% aqueous methanol solution has been tested. CE in different running buffers was used to separate BPAA from the decomposition reaction products α‐hydroxyphenylacetic (mandelic) acid and α‐methoxyphenylacetic acid. Suitable CE separation of all three compounds and other product, bromide, was achieved in 60 mmol/L formate buffer (pH 3.0) at −30 kV in 50 μm (i.d.) poly(vinyl alcohol)‐coated fused silica capillary (30 cm/24.5 cm) with UV detection at 200 nm. The CE method was applied to determine the reaction order of the decomposition of BPAA (0.47 mmol/L) via nucleophilic substitution in 50% aqueous methanol. The first‐order reaction kinetics was confirmed by linear and non‐linear regression, giving the rate constants 1.52 × 10 −4  ±   2.76 × 10 −5 s −1 and 7.89 × 10 −5  ±   5.02 × 10 −6 s −1 , respectively. Additionally, the degradation products were identified by CE coupled to mass spectrometric (MS) detection. The CE–MS experiments carried out in 60 mmol/L formate buffer (pH 3.0) and in 60 mmol/L acetate buffer (pH 5.0) confirmed the results obtained by CE–UV. Furthermore, the stability of BPAA in polar solvents was tested by 1 H NMR experiments. Our results provide strong evidence of the instability and fast degradation of BPAA in 50% aqueous methanol indicating that BPAA is not suitable as the model analyte for chiral separations.