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Intramolecular OH⋅⋅⋅Fluorine Hydrogen Bonding in Saturated, Acyclic Fluorohydrins: The γ-Fluoropropanol Motif
- Source :
- Chemistry (Weinheim an Der Bergstrasse, Germany)
- Publication Year :
- 2015
- Publisher :
- Wiley, 2015.
-
Abstract
- Fluorination is commonly exercised in compound property optimization. However, the influence of fluorination on hydrogen-bond (HB) properties of adjacent functional groups, as well as the HB-accepting capacity of fluorine itself, is still not completely understood. Although the formation of OH⋅⋅⋅F intramolecular HBs (IMHBs) has been established for conformationally restricted fluorohydrins, such interaction in flexible compounds remained questionable. Herein is demonstrated for the first time-and in contrast to earlier reports-the occurrence of OH⋅⋅⋅F IMHBs in acyclic saturated γ-fluorohydrins, even for the parent 3-fluoropropan-1-ol. The relative stereochemistry is shown to have a crucial influence on the corresponding (h1) JOH⋅⋅⋅F values, as illustrated by syn- and anti-4-fluoropentan-2-ol (6.6 and 1.9 Hz). The magnitude of OH⋅⋅⋅F IMHBs and their strong dependence on the overall molecular conformational profile, fluorination motif, and alkyl substitution level, is rationalized by quantum chemical calculations. For a given alkyl chain, the "rule of shielding" applies to OH⋅⋅⋅F IMHB energies. Surprisingly, the predicted OH⋅⋅⋅F IMHB energies are only moderately weaker than these of the corresponding OH⋅⋅⋅OMe. These results provide new insights of the impact of fluorination of aliphatic alcohols, with attractive perspectives for rational drug design.
- Subjects :
- Quantum chemical
chemistry.chemical_classification
Hydrogen bond
Chemistry
Stereochemistry
Organic Chemistry
quantum calculations
Drug design
chemistry.chemical_element
General Chemistry
Nuclear magnetic resonance spectroscopy
Full Papers
fluorination
Catalysis
NMR spectroscopy
Computational chemistry
Intramolecular force
intramolecular interactions
hydrogen bonds
Alkyl substitution
Fluorine
Alkyl
Subjects
Details
- ISSN :
- 09476539
- Volume :
- 21
- Database :
- OpenAIRE
- Journal :
- Chemistry - A European Journal
- Accession number :
- edsair.doi.dedup.....a4f5482749f89c61209e30feec9134e1