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alpha-Fluoro-o-cresols: the key role of intramolecular hydrogen bonding in conformational preference and hydrogen-bond acidity

alpha-Fluoro-o-cresols: the key role of intramolecular hydrogen bonding in conformational preference and hydrogen-bond acidity
alpha-Fluoro-o-cresols: the key role of intramolecular hydrogen bonding in conformational preference and hydrogen-bond acidity
The conformational preferences of o-cresols driven by fluorination were thoroughly investigated from a theoretical point of view with quantum-chemical methods, and the results were compared to those recently reported for benzyl alcohols. The key conformers of both families exhibit a six-membered intramolecular hydrogen-bond (IMHB) interaction. A significant enhancement in the strength of the IMHB is observed in ?-fluoro-o-cresols, owing to a simultaneous increase in the hydrogen bond (HB) basicity of the aliphatic fluorine and the HB acidity of the aromatic hydroxyl relative to that observed for o-fluorobenzyl alcohols, which are characterized by aromatic fluorine atoms and aliphatic hydroxyl groups. In the cases of the di- and trifluorinated derivatives, the occurrence of a three-centered HB is emphasized, and its features are discussed. The impact of these structural predilections on the HB properties of o-cresol was characterized from the estimation of the HB acidity parameter, pKAHY, weighted according to their conformational populations. We found that ?-fluorination led to a decrease in the HB acidity of the hydroxyl group (in contrast with the o-fluorination of benzyl alcohols), whereas ?,?-difluorination resulted in no significant variation in pKAHY. Finally, an increase in the HB acidity was predicted upon methyl perfluorination, which was confirmed experimentally. Theoretical descriptors based on atoms in molecules, noncovalent interactions, and natural bond orbital analyses allowed rationalization of the predicted trends and revealed a relationship with the strength of the established OH???F IMHB
1439-4235
2702-2709
Bogdan, Elena
bd2b4c26-9ae0-42eb-8397-3c8d95f48060
Quarré de Verneuil, Alexis
3f1a4f4b-7abc-4d01-94aa-83e38aea69dd
Besseau, François
436e47fa-e4a7-4a44-b5e4-476eb04184d9
Compain, Guillaume
f88510bf-ad1a-4a67-8855-43303979f2d0
Linclau, Bruno
19b9cacd-b8e8-4c65-af36-6352cade84ba
Le Questel, Jean-Yves
38aea4ae-64a3-43b7-8049-ea2f351459f2
Graton, Jérôme
12432694-552e-4a40-9935-9ff7c77fbf07
Bogdan, Elena
bd2b4c26-9ae0-42eb-8397-3c8d95f48060
Quarré de Verneuil, Alexis
3f1a4f4b-7abc-4d01-94aa-83e38aea69dd
Besseau, François
436e47fa-e4a7-4a44-b5e4-476eb04184d9
Compain, Guillaume
f88510bf-ad1a-4a67-8855-43303979f2d0
Linclau, Bruno
19b9cacd-b8e8-4c65-af36-6352cade84ba
Le Questel, Jean-Yves
38aea4ae-64a3-43b7-8049-ea2f351459f2
Graton, Jérôme
12432694-552e-4a40-9935-9ff7c77fbf07

Bogdan, Elena, Quarré de Verneuil, Alexis, Besseau, François, Compain, Guillaume, Linclau, Bruno, Le Questel, Jean-Yves and Graton, Jérôme (2016) alpha-Fluoro-o-cresols: the key role of intramolecular hydrogen bonding in conformational preference and hydrogen-bond acidity. ChemPhysChem, 17 (17), 2702-2709. (doi:10.1002/cphc.201600453).

Record type: Article

Abstract

The conformational preferences of o-cresols driven by fluorination were thoroughly investigated from a theoretical point of view with quantum-chemical methods, and the results were compared to those recently reported for benzyl alcohols. The key conformers of both families exhibit a six-membered intramolecular hydrogen-bond (IMHB) interaction. A significant enhancement in the strength of the IMHB is observed in ?-fluoro-o-cresols, owing to a simultaneous increase in the hydrogen bond (HB) basicity of the aliphatic fluorine and the HB acidity of the aromatic hydroxyl relative to that observed for o-fluorobenzyl alcohols, which are characterized by aromatic fluorine atoms and aliphatic hydroxyl groups. In the cases of the di- and trifluorinated derivatives, the occurrence of a three-centered HB is emphasized, and its features are discussed. The impact of these structural predilections on the HB properties of o-cresol was characterized from the estimation of the HB acidity parameter, pKAHY, weighted according to their conformational populations. We found that ?-fluorination led to a decrease in the HB acidity of the hydroxyl group (in contrast with the o-fluorination of benzyl alcohols), whereas ?,?-difluorination resulted in no significant variation in pKAHY. Finally, an increase in the HB acidity was predicted upon methyl perfluorination, which was confirmed experimentally. Theoretical descriptors based on atoms in molecules, noncovalent interactions, and natural bond orbital analyses allowed rationalization of the predicted trends and revealed a relationship with the strength of the established OH???F IMHB

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Fluorocresols_Bogdan_PCCP-resubmitted.pdf - Accepted Manuscript
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Accepted/In Press date: 30 May 2016
e-pub ahead of print date: 27 June 2016
Published date: 5 September 2016
Organisations: Organic Chemistry: Synthesis, Catalysis and Flow

Identifiers

Local EPrints ID: 400849
URI: https://eprints.soton.ac.uk/id/eprint/400849
ISSN: 1439-4235
PURE UUID: 48c04e28-047e-49f5-ab8b-dac95b04d44f
ORCID for Bruno Linclau: ORCID iD orcid.org/0000-0001-8762-0170

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Date deposited: 28 Sep 2016 14:40
Last modified: 15 Aug 2019 05:18

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