C–F⋯HO hydrogen bond in 8-fluoro-4-methyl-1-naphthol

Takemura, Hiroyuki; Ueda, Risako; Iwanaga, Takeshi

doi:10.1016/j.jfluchem.2009.05.004

Cited by 30 publications

(24 citation statements)

References 32 publications

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“…Alkorta et al have reported that calculated F,H(N) spin–spin couplings across the hydrogen bond in 2‐fluorobenzamide and related compounds vary from ca 11 to 15 Hz, which are also significantly high, even considering that primary amides are much less acidic (pKa ≈ 17) than 2‐hydroxy‐2‐cyclohexenona (pKa = 10.3). The calculated 1h J F,H(O) for 3 of ca –30 Hz does not appear to be overestimated when considering a F···HO hydrogen bonded system; for instance, in 8‐fluoro‐4‐methyl‐1‐naphthol, the experimental 1h J F,H(O) coupling constant is (−)28.4 Hz . Thus, the 1h J F,H(O) coupling constant can yield information that is fundamental to understanding the role of hydrogen bond in biological systems.…”

Section: Resultsmentioning

confidence: 99%

F···HO intramolecular hydrogen bond as the main transmission mechanism for ^1hJ_F,H(O) coupling constant in 2′‐fluoroflavonol

Fonseca

Ramalho

Freitas

2012

Magnetic Reson in Chemistry

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Flavonoids are useful compounds in medicinal chemistry and exhibit conformational isomerism, which is ruled by intramolecular interactions. One of the main intramolecular forces governing the stability of conformations is the hydrogen bond. Hydrogen bond involving fluorine covalently bonded to carbon has been found to be rare, but it appears in 2′‐fluoroflavonol, although the F···HO hydrogen bond cannot be considered the main effect governing the conformational stability of this compound. Because 19F is magnetically active and suitable for NMR studies, the 1hJF,H(O) coupling constant can be used as a probe for such an interaction in 2′‐fluoroflavonol. In fact, the 1hJF,H(O) coupling was computationally analyzed in this work, and the F···HO hydrogen bond was found to be its main transmission mechanism, which modulates this coupling in 2′‐fluoroflavonol, rather than overlap of proximate electronic clouds, such as in 2‐fluorophenol. Copyright © 2012 John Wiley & Sons, Ltd.

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Section: Resultsmentioning

confidence: 99%

F···HO intramolecular hydrogen bond as the main transmission mechanism for ^1hJ_F,H(O) coupling constant in 2′‐fluoroflavonol

Fonseca

Ramalho

Freitas

2012

Magnetic Reson in Chemistry

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“…NMR analysisf ocusedo nt he multiplicity, h1 J OH···F value,a nd chemicals hift of the alcohol protonsa t2 5 8Ca nd À50 8C, taking into account that the observed values are averaged over the conformer populations.T he results are given in Ta 12 ]cyclohexane. [17,18] With an exceptionally resolved NMR spectrum (Figure 3), we have succeeded to detect an OH signal clearly appearing as at riplet of doublets in CDCl 3 ,a nd the 1 H{ 19 F} analysis proved that there is a1 .4 Hz coupling to fluorine.…”

Section: Nmr Experiments Revealo H···f Coupling Constants For All Invmentioning

confidence: 99%

Intramolecular OH⋅⋅⋅Fluorine Hydrogen Bonding in Saturated, Acyclic Fluorohydrins: The γ‐Fluoropropanol Motif

Linclau

Péron

Bogdan

et al. 2015

Chemistry A European J

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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 h1JOH⋅⋅⋅F values, as illustrated by syn- and anti-4-fluoropentan-2-ol (6.6 and 1.9Hz). 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.

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“…After the debate about the effective ability of fluorine to act as a hydrogen-bond (H-bond, HB) acceptor, [11][12][13][14][15] the occurrence of intermolecular OHF H-bonding is now clearly established through experimental and theoretical evidences. [16][17][18][19][20] The existence of intramolecular hydrogen bonds (IMHBs) involving fluorine has also been scrutinised and highlighted experimentally through NMR techniques for conformationally constrained, [21][22][23] partially flexible, 24 and even fully flexible fluorohydrins. 25 We have recently reported that the intermolecular hydroxyl H-bond donating capacity (or HB acidity) in conformationally fixed fluorohydrins (eg 1, Figure 1) 21 and partially flexible benzyl alcohols (eg 2) 26 is deeply influenced by the conformational preferences dictated by the presence of such IMHBs.…”

Section: Introductionmentioning

confidence: 99%

α‐Fluoro‐o‐cresols: The Key Role of Intramolecular Hydrogen Bonding in Conformational Preference and Hydrogen‐Bond Acidity

et al. 2016

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The conformational preferences of o-cresols driven by fluorination have been thoroughly investigated from a theoretical point of view with quantum chemical methods and compared to those recently reported for benzyl alcohols. Key conformers of both families exhibit a 6-membered intramolecular hydrogen-bond (IMHB) interaction. A significant enhancement of IMHB strength is observed in -fluoro-o-cresols, owing to the simultaneous increase of the aliphatic fluorine hydrogen-bond (HB) basicity and of the aromatic hydroxyl HB acidity, compared to o-fluorobenzyl alcohols, which are characterized by aromatic fluorine atoms and aliphatic hydroxyl groups. In the case of di-and trifluorinated derivatives, the occurrence of a three-centre hydrogen-bond is emphasised and its features discussed. The impact of these structural predilections on ocresol HB properties has been characterised from the estimation of the HB acidity parameter, pKAHY, weighted according to their conformational populations. We find that -fluorination leads to an HB acidity decrease of the hydroxyl group (in contrast with o-fluorination of benzyl alcohols), whereas ,-difluorination results in no significant variation of pKAHY. Finally, an increase of HB acidity is predicted upon methyl perfluorination, which has been confirmed experimentally. Theoretical descriptors based on AIM, NCI and NBO analyses allows rationalizing the predicted trends, and reveal a relationship with the strength of the established OHF IMHB.

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C–F⋯HO hydrogen bond in 8-fluoro-4-methyl-1-naphthol

Cited by 30 publications

References 32 publications

F···HO intramolecular hydrogen bond as the main transmission mechanism for ^1hJ_F,H(O) coupling constant in 2′‐fluoroflavonol

F···HO intramolecular hydrogen bond as the main transmission mechanism for ^1hJ_F,H(O) coupling constant in 2′‐fluoroflavonol

Intramolecular OH⋅⋅⋅Fluorine Hydrogen Bonding in Saturated, Acyclic Fluorohydrins: The γ‐Fluoropropanol Motif

α‐Fluoro‐o‐cresols: The Key Role of Intramolecular Hydrogen Bonding in Conformational Preference and Hydrogen‐Bond Acidity

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C–F⋯HO hydrogen bond in 8-fluoro-4-methyl-1-naphthol

Cited by 30 publications

References 32 publications

F···HO intramolecular hydrogen bond as the main transmission mechanism for 1hJF,H(O) coupling constant in 2′‐fluoroflavonol

F···HO intramolecular hydrogen bond as the main transmission mechanism for 1hJF,H(O) coupling constant in 2′‐fluoroflavonol

Intramolecular OH⋅⋅⋅Fluorine Hydrogen Bonding in Saturated, Acyclic Fluorohydrins: The γ‐Fluoropropanol Motif

α‐Fluoro‐o‐cresols: The Key Role of Intramolecular Hydrogen Bonding in Conformational Preference and Hydrogen‐Bond Acidity

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F···HO intramolecular hydrogen bond as the main transmission mechanism for ^1hJ_F,H(O) coupling constant in 2′‐fluoroflavonol

F···HO intramolecular hydrogen bond as the main transmission mechanism for ^1hJ_F,H(O) coupling constant in 2′‐fluoroflavonol