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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 lineshape method ANATOLIA
Author(s) -
Edgar Mark,
Hayward Dee,
Zeinali Fatemeh,
Riaz Shahzad,
Weaver George W.
Publication year - 2020
Publication title -
magnetic resonance in chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.483
H-Index - 72
eISSN - 1097-458X
pISSN - 0749-1581
DOI - 10.1002/mrc.4947
Subject(s) - chemistry , isotopomers , coupling constant , analytical chemistry (journal) , nmr spectra database , fluorine , nuclear magnetic resonance spectroscopy , molecule , spectral line , spin (aerodynamics) , coupling (piping) , stereochemistry , nuclear magnetic resonance , crystallography , physics , mechanical engineering , organic chemistry , particle physics , chromatography , astronomy , engineering , thermodynamics
Abstract A simple to use nuclear magnetic resonance analysis method has been tested on complex 1 H, 19 F, and 13 C 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 1 H Δδ = 3.68 and 4.67 Hz for the aromatic hydrogen “triplets”, with 19 F 4 J AA' , 4 J BB' , 4 J XX' , and 4 J YY' coupling constants range from +4.8 to −14.0 Hz and for 13 C‐isotopomers 19 F Δδ of up to 111.56 Hz. A spin‐system of six coupling nuclei (H a H b H c H d F Y F Y' ) 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'‐H d ) 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 (F BB' and F YY' ) 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 19 F nuclear magnetic resonance spectrum of perfluorotoluene (octafluorotoluene) and analysis from 1975 was used as a test data set to assess ANATOLIA.