The Antagonist Effect of Nitrogen Lone Pair: 3JHF versus 5JHF

The long‐range scalar coupling constant between proton and fluorine nuclei, 5JHF, is observed to be larger than 3JHF in the pyrimidinyl moiety of voriconazole. A set of smaller molecules is chosen (fluorobenzene, N‐methyl‐2‐fluoropyridine, N‐methyl‐3‐fluoropyridine, 3‐fluoropyridine, 5‐pyrimidine, a...

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Published inChemphyschem Vol. 19; no. 11; pp. 1358 - 1362
Main Authors Barbosa, Thaís M., Viesser, Renan V., Martins, Lucas G., Rittner, Roberto, Tormena, Cláudio F.
Format Journal Article
LanguageEnglish
Published Germany Wiley Subscription Services, Inc 05.06.2018
Subjects
Coherence
Coupling (molecular)
coupling constants
Couplings
fluorinated compounds
Fluorine
Molecular chains
Molecular orbitals
Nitrogen
NMR
Nuclei (nuclear physics)
orbital decomposition analysis
pyrimidinyl moiety
Quantum phenomena
coupling constants
NMR
pyrimidinyl moiety
orbital decomposition analysis
fluorinated compounds
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Summary:The long‐range scalar coupling constant between proton and fluorine nuclei, 5JHF, is observed to be larger than 3JHF in the pyrimidinyl moiety of voriconazole. A set of smaller molecules is chosen (fluorobenzene, N‐methyl‐2‐fluoropyridine, N‐methyl‐3‐fluoropyridine, 3‐fluoropyridine, 5‐pyrimidine, and 2‐fluoropyridine) to evaluate the influence of the nitrogen atom in the experimental JHF values. Spectral aliased pure shift heteronuclear single quantum coherence spectroscopy (SAPS‐HSQC) is applied to determine the relative sign between the JCF and JHF scalar couplings. Theoretical calculations show that the 3JHF and 5JHF coupling constants can be described mainly by a Fermi contact (FC) transmission mechanism. A decomposition analysis of JHF in terms of localized molecular orbital (LMO) contributions allows us to determine that the interaction involving the nitrogen lone pair (LPN) is the main reason for the larger 5JHF compared to 3JHF. Our analysis indicates that delocalization of LPN has a positive contribution to the long‐range coupling, while a negative one is observed for 3JHF. Counterintuitive experimental values for vicinal and long‐range JHF coupling constants are related to the different values and signs of the contribution of nitrogen lone pair (see picture) to the 3JHF and 5JHF coupling‐constant pathway.
Bibliography:These authors contributed equally to this study.
ISSN:1439-4235
1439-7641
DOI:10.1002/cphc.201800073