¹H-detected, gradient-enhanced ¹⁵N and ¹³C NMR experiments for the measurement of small heteronuclear coupling constants and isotopic shifts

A suite of ¹H-detected, gradient-enhanced experiments is presented for the measurement of small ¹H-¹⁵N and ¹³C-¹⁵N coupling constants in small organic compounds, where no protons are directly bound to the nitrogens. The experiments are based on modified HMQC pulse sequences and a novel gradient supported half-filter element. The experiments were applied to obtain a complete set of coupling constants in tris(1-pyrazolyl)methane (1), where 6% of the aromatic ring systems were doubly enriched with ¹⁵N. The absolute sign of the ¹H-¹H, ¹H-¹⁵N, ¹³C-¹⁵N, and ¹⁵N-¹⁵N coupling constants was determined by relating them to the sign of a one-bond ¹H-¹³C coupling constant. The experiments also yield multiple bond ¹³C/¹²C isotope effects on the ¹⁵N chemical shifts. The ¹H-¹⁵N and ¹³C-¹⁵N coupling constants in 1 are non-uniform, with some of the short-range coupling constants smaller than the longer range coupling constants. In contrast, all one-bond ¹³C/¹²C isotope effects on the ¹⁵N chemical shifts were observed to be significantly larger than the isotope effects mediated via two or more bonds. The one-bond isotope effect thus provides a valuable tool for assigning ¹⁵N resonances in cases where coupling constant data yield ambiguous results.