On the Practical Limits of Determining Isolated Product Yields and Ratios of Stereoisomers: Reflections, Analysis, and Redemption

Abstract

This paper examines the limits of accuracy in reporting isolated product yields (i.e., recovery of total mass from chromatography or extractions) as well as ratios of isomers determined by HPLC, GC, or NMR methods. Attention is directed to the magnitude of errors encountered in the HPLC or GC measurements of such ratios when these measurements are conducted without accurate calibrations or determinations of response factors for the particular isomers. Accurately defined mixtures of compounds (prepared by volumetric means) were examined by the above methods and the obtained measurements compared with the actual composition. The relative errors between actual content and the measured values are listed for all comparisons. In addition, accuracy in the determination of weight of a sample as a function of scale was also examined. The results are tabulated for comparison and suggestions are made to the reader as to how to avoid inaccurate reporting of experimental parameters. The authors hope that disclosure of these facts will result in new editorial policies requiring that a phrase ‘dr or er ratios reported in this paper have not been validated by calibration’ be inserted into general experimental descriptions. In addition, such editorial policy should also discourage the use of terms ‘de’ and ‘ee’, as these descriptors do not provide accurate and meaningful information about stereoisomer composition. This latter issue has already been suggested in the literature on several occasions.