Influence of fluorine substituents on the NMR properties of phenylboronic acids Błażej Gierczyk, a * Marcin Kaźmierczak, a Łukasz Popenda, c Andrzej Sporzyński, b Grzegorz Schroeder a and Stefan Jurga c,d The paper presents results of a systematic NMR studies on fluorinated phenylboronic acids. All possible derivatives were studied. The experimental 1 H, 13 C, 19 F, 11 B, and 17 O spectral data were compared with the results of theoretical calculations. The relation between the calculated natural bond orbital parameters and spectral data (chemical shifts and coupling constants) is discussed. The first examples of 10 B/ 11 B isotopic effect on the 19 F spectra and 4 J FO scalar coupling in organic compounds are reported. Copyright © 2014 John Wiley & Sons, Ltd. Keywords: arylboronic acid; NMR; spectroscopy; DFT calculation Introduction Arylboronic acids have attracted increasing interest because of their new applications in organic synthesis, catalysis, supramolec- ular chemistry, and material engineering. [1–3] Moreover, their biomedical applications are intensively studied. Boronic acids make a most promising group of chemoreceptors for sensing of glucose and other biologically important dioles [1,4–6] as well as bacterial or animal cells. [7] They are also important drugs, [8–11] showing various biological activities (antibacterial, [12–14] antiviral, [13,15–17] antifungal, [12] and anticancer [13,18] ). Boronyl group-containing molecules are studied as a drug delivery systems of a low cytotoxicity and immu- nogenicity. [15,19,20] The compounds containing 10 B isotope are used in the so-called boron neutron-capture therapy of cancer. Various boronic acids are used as boron-carrying molecules for this pur- pose. [21–24] Boronic acids can be regarded as Lewis acids. Their acidity depends on the substituents in phenyl ring. Introduction of elec- tron-withdrawing substituents increases the acidity of boronic acids and has been observed for fluorine substituents. Thus, fluorinated boranes were investigated as additives to polymer electrolytes as the anion binding species enhancing the mobility of lithium cations and increasing the cation transference number. [25–27] Cyclic esters of fluoro-substituted phenylboronic acids have been recently investigated. It has been established that introduc- tion of a fluorine substituent into the phenyl ring resulted in increased Lewis acidity of the catechol esters, with the highest effect for 2-fluoro derivative. However, no correlation between the Gutmann acceptor number and the number of fluorine atoms in the molecule has been observed. The pentafluoro-substituted derivative was the strongest Lewis acid among the ones studied, with acidity comparable to that of tris(pentafluorophenyl)borane, considered as one of the strongest organoboron acids. [28] Other cyclic esters of this acid were also investigated. The differences in Lewis acidity have been discussed on the basis of electronic and geometric parameters. [29] Fluoride sensing by boronic acids can also be enhanced by the introduction of fluorine substituent into phenyl ring. [30,31] Molecular and crystal structures of fluoro-substituted phenylboronic catechol esters have been recently investi- gated. [32] It was found that the substitution does not influence the molecular geometry very much, and that this geometry is alike in the isolated species and crystals. In all species investigated, weak interactions play the key role in determining their geometry. There has been no systematic investigation of spectral properties of these compounds. One fluoroarylboronic acid (4) has been studied by solid-state NMR, [33] while for 2,3-difluorophenylboronic acid, the experimental and calculated NMR spectra have been reported. [34] The paper presents a comprehensive NMR spectro- scopic characterization ( 1 H, 11 B, 13 C, 19 F, and 17 O) of all fluoro- substituted phenylboronic acids (Fig. 1) and is a continuation of our previous NMR studies on boronic acids and its derivatives. [35–38] Experimental Materials All studied boronic acids were commercial products of Sigma- Aldrich and CombiBlocks companies. Deuterated solvents (Sigma-Aldrich) used for measurements were dehydrated, deoxygenated, and distilled before use. Labeling of boronic acids was made by dissolving of 50 mg of a given acid in * Correspondence to: Błażej Gierczyk, Faculty of Chemistry, Adam Mickiewicz University in Poznań, Umultowska 89b, 61–614 Poznań, Poland. E-mail: hanuman@amu.edu.pl a Faculty of Chemistry, Adam Mickiewicz University in Poznań, Umultowska 89b, 61-614 Poznań, Poland b Faculty of Chemistry, Warsaw University of Technology, Noakowskiego 3, 00- 664 Warsaw, Poland c NanoBioMedical Centre, Adam Mickiewicz University in Poznań, Umultowska 85, 61-614 Poznań, Poland d Faculty of Physics, Adam Mickiewicz University in Poznań, Umultowska 85, 61-614 Poznań, Poland Magn. Reson. Chem. 2014, 52, 202–213 Copyright © 2014 John Wiley & Sons, Ltd. Research article Received: 20 November 2013 Revised: 28 December 2013 Accepted: 16 January 2014 Published online in Wiley Online Library: 11 February 2014 (wileyonlinelibrary.com) DOI 10.1002/mrc.4051 202