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SN2 versus E2 reactions in a complex microsolvated environment: theoretical analysis of the equilibrium and activation steps of a nucleophilic fluorination

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Abstract

The reactivity of the fluoride ion towards alkyl halides is highly dependent on the solvating environment. In polar aprotic solvents with large counter-ions is highly reactive and produces substantial E2 product, whereas in polar protic solvents leads to slow kinetics and high selectivity for SN2 reactions. The use of a more complex environment with stoichiometric addition of tert-butanol to acetonitrile solvent is able to module the reactivity and selectivity of tetrabutylammonium fluoride (TBAF). In the present work, we have performed a detailed theoretical analysis of this complex reaction system by density functional theory, continuum solvation model, and including explicit tert-butanol molecules. A kinetic model based on the free energy profile was also used to predict the reactivity and selectivity. The results indicated that the TBAF(tert-butanol) complex plays the key role to increase the SN2 selectivity, whereas higher aggregates are not relevant. The E2 product is formed exclusively via free TBAF, because the solvating tert-butanol in the TBAF(tert-butanol) complex inhibits the E2 pathway. Our analysis suggests that diols or tetraols could produce an improved selectivity.

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The datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request.

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Funding

The authors thank the agencies CNPq, FAPEMIG, and CAPES for support.

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Authors and Affiliations

  1. Departamento de Ciências Naturais, Universidade Federal de São João del-Rei, São João del-Rei, MG, 36301-160, Brazil

    Fernando M. Lisboa & Josefredo R. Pliego Jr.

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  1. Fernando M. Lisboa
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  2. Josefredo R. Pliego Jr.
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Contributions

Josefredo R. Pliego Jr. contributed to the study conception and design. Material preparation and data collection were performed by Fernando M. Lisboa. Analysis was performed by Fernando M. Lisboa and Josefredo R. Pliego Jr. The first draft of the manuscript was written by Josefredo R. Pliego Jr. and all authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.

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Correspondence to Josefredo R. Pliego Jr..

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This paper belongs to Topical Collection: XXI-Brazilian Symposium of Theoretical Chemistry (SBQT2021).

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The coordinates of the optimized structures are available.

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Lisboa, F.M., Pliego, J.R. SN2 versus E2 reactions in a complex microsolvated environment: theoretical analysis of the equilibrium and activation steps of a nucleophilic fluorination. J Mol Model 28, 159 (2022). https://doi.org/10.1007/s00894-022-05160-5

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