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

Abstract

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 60mmol/L formate buffer (pH 3.0) at -30kV in 50μm (i.d.) poly(vinyl alcohol)-coated fused silica capillary (30cm/24.5cm) with UV detection at 200nm. The CE method was applied to determine the reaction order of the decomposition of BPAA (0.47mmol/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 60mmol/L formate buffer (pH 3.0) and in 60mmol/L acetate buffer (pH 5.0) confirmed the results obtained by CE-UV. Furthermore, the stability of BPAA in polar solvents was tested by 1H 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.