Theoretical Design and Calculation of a Crown Ether Phase-Transfer-Catalyst Scaffold for Nucleophilic Fluorination Merging Two Catalytic Concepts

Abstract

Fluorinated organic molecules are playing an increased role in the area of pharmaceuticals and agrochemicals. This fact demands the development of efficient catalytic fluorination processes. In this paper, we have designed a new crown ether with four hydroxyl groups strategically positioned. The catalytic activity of this basic scaffold was investigated with high levels of electronic structure theory, such as the ONIOM approach combining MP4 and MP2 methods. On the basis of the calculations, this new structure is able to solubilize potassium fluoride in toluene solution much more efficiently than 18-crown-6 (18C6). In addition, the strong interaction of the new catalyst with the SN2 transition state leads to a very important catalytic effect, with a predicted free energy barrier of 23.3 kcal mol(-1) for potassium fluoride plus ethyl bromide reaction model. Compared with experimental data and previous theoretical studies, this new catalyst is 10(4) times more efficient than 18C6 for nucleophilic fluorination of alkyl halides. The catalysis is predicted to be selective, leading to 97% of fluorination and only 3% of elimination. Catalytic fluorination of the aromatic ring has also been investigated, and although the catalyst is less efficient in this case, our analysis has indicated further development of this strategy can lead to more efficient catalysis.

Counter‐ion and solvent effects in the C‐ and O‐alkylation of the phenoxide ion with allyl chloride

“…Thus, considering the important role of counter‐ion for C‐alkylation, it seems possible to design a phase‐transfer catalyst that leads to C‐alkylation as the main product. An example is the new hydro‐crown phase‐transfer catalyst, where both the counter‐ion and hydrogen bonds could bind the oxygen of the phenoxide ion and to induce C‐alkylation.…”

Thermodynamic Calculations to Determine the Optimal Composition of Oxide Catalysts

“…This process occurs under control of kinetics. With the goal of creating a thermodynamic method of calculating the optimal composition of the bismuth-molybdenum catalyst, the following notation to analyse the process of redistribution of electrons between the tetrahedra can be applied: (9) In the ensemble of tetrahedrons of the oxide catalyst lattice, the redistribution of the electrons occurs according to the scheme (10) where K C is the equilibrium constant of the redistribution of electrons or charges between tetrahedron cations.…”

“…Currently, to study the structure of catalysts, catalytic systems, and mechanisms of catalytic reactions, quantum‐chemical and thermodynamic methods are widely used. In one such work, high catalytic activity of the complex of the new dibenzo‐18‐crown‐6 ether with KF in the reaction of fluorination of organic compounds was discovered using combined semiempirical and ab initio quantum chemical calculation methods.…”

Preparation and characterization of a novel silica–KF composite and facile fluorination of aromatic substrates

“…Crown ethers act as catalysts for fluorination reaction via trapping of potassium ions by oxygen atoms, leaving the fluoride anion free. 10,11 Tetrabutyl ammonium fluoride (TBAF) on the other hand, is an excellent source of reactive fluoride anion, because of steric hindrance by four butyl groups. However, it is hygroscopic, thermally labile and also very expensive.…”