Determination of the substitution pattern of di- and trisubstituted pyrazines by 15N, 13C and 1H NMR spectroscopy

The substitution pattern of di- and trisubstituted pyrazines can be elucidated by a combination of NMR methods, especially in mixtures by gradient selected H-1,N-15 HMBC experiments at the natural abundance level. In the case of disubstituted pyrazines, it allows one to distinguish between 2,3-/2,5- and 2,6-disubstituted isomers. Another advantage is the determination of N-15 NMR chemical shifts including the assignments even at relatively low concentrations. The reliability of this method was verified by experimental data resulting from H-1 NMR and long-range heteronuclear correlation experiments such as FLOCK and H-1,C-13 HMBC experiments. Carbon-carbon coupling constants derived from INADEQUATE experiments were taken into account as additional tests. Thirty-one commercially available di- and trisubstituted pyrazines were measured in order to identify their substitution patterns and to obtain chemical shift information. As a result, fully assigned H-1, C-13 and N-15 NMR data of these pyrazines are reported. Copyright (C) 2000 John Wiley & Sons, Ltd.