¹H NMR Spectral Simplification with Achiral and Chiral Lanthanide Shift Reagents. Clenbuterol. Method for Direct Optical Purity Determination

Abstract

The 60 MHz IH NMR spectra of clenbuterol, 1, have been studied in CDC13 solution with the achiral shift reagent, tris(6,6,7,7,8,8,8-hepta-fluoro-2,2-dimethyl-3,6-octanedionato)europiur(IIII), 2, and the 511 Copyright 0 I V X Y by Marcel I k k k e r . IIIL Downloaded by [The University of Manchester Library] at 09:15 20 November 2014 5 12 MARTIN AND ROTHCHILD chiral reagent tris[3-(heptafluoropropylhydroxyn1ethyl-ene)-(+)-canphorato]europiunr(III), 3 . Use of 3 resulted in observable enantiomeric shift differences, AAd, for the %-butyl, NHzf benzylic CH and the aryl proton signals. Values of A A d as high as 135.1 Hz (2.25 ppm) and 86.5 Hz (1.44 ppn) were seen for the methine and aryl protons, respectively, with a solution 0.1035 molal in 1 and a a:& molar ratio of 0.551. The aryl resonance is especially well suited for direct optical purity determinations of 1.

Quantitative NMR spectroscopy of biologically active substances and excipients

“…Using qNMR spectroscopy it is sufficient to find, out of the multitude of NMR signals, a single baseline separated resonance for each component of interest. Besides the application of elaborative pulse sequences and line shape fitting techniques [7] an optimal separation of overlapping resonances can be achieved by changing the kind of solvent [8][9][10][11][12][13][14] or the pH value of the test solution [15][16][17][18][19], by applying different sample concentrations [20][21][22], or by adding auxiliary reagents such as cyclodextrins [23][24][25] or lanthanide shift reagents [23,26]. In some cases, the temperature also affects the signal separation [27,28].…”