NMR spectral analysis of strongly second-order 6-, 8-, 9- and 10- spin-systems (1 H-19 F, 19 F-19 F and 13 C-19 F) in perfluorotoluyl- and tetrafluoro-pyridyl- aromatics using the line-shape method ANATOLIA
2019-11-25T12:27:23Z (GMT) by
A simple to use nuclear magnetic resonance analysis method has been tested on complex 1H, 19F, and 13C multiplets. This open‐source line‐shape analysis method analysis of total lineshape (ANATOLIA)1 provides some significant advantages over traditional assign‐iterate methods of NMR spectral analysis by avoiding false minima and progressing optimisation to the global minimum. The target molecules are 1‐perfluorotol‐4‐yl‐2‐perfluorotol‐4‐yl‐oxymethyl‐1H‐benzimidazole (molecule‐I) and 1‐tetrafluoropyrid‐4‐yl‐2‐tetrafluoropyrid‐4‐yl‐thio‐1H‐benzimidazole (molecule‐II) which were produced as part of a family of fluorinated drug scaffolds prepared for anticancer and antiparasitic screening. Spectra display significant second‐order effects with 1H Δδ = 3.68 and 4.67 Hz for the aromatic hydrogen “triplets”, with 19F 4JAA’, 4JBB’, 4JXX’, and 4JYY’ coupling constants range from +4.8 to −14.0 Hz and for 13C‐isotopomers 19F Δδ of up to 111.56 Hz. A spin‐system of six coupling nuclei (HaHbHcHd FYFY’) was analysed in 12 s, a spin‐system of nine coupling fluorine nuclei (AA’BB’CCC‐YY’) was analysed within 2 min, and 10 coupling nuclei (XX’YY’ZZZ‐BB’‐Hd) was optimised in 6 min using a laptop computer. ANATOLIA was also robust enough to be able to yield accurate spectral values from inaccurate input values. In both compounds, a fluorine–fluorine coupling constant was identified between the two fluoro‐aromatic rings (FBB’ and FYY’) of +4.05 and +4.67 Hz and attributed to a through‐space interaction. Ab initio structure optimisations and coupling constant calculations provided useful input data for spectral analysis. A modern 19F nuclear magnetic resonance spectrum of perfluorotoluene (octafluorotoluene) and analysis from 1975 was used as a test data set to assess ANATOLIA.