Received: December 10, 2020 Electrochemistry Accepted: January 4, 2021 Published online: January 13, 2021 The Electrochemical Society of Japan https://doi.org/10.5796/electrochemistry.20-65154 Note Electrochemistry, 89(2), 121–124 (2021) The 65th special feature "Fluorine Chemistry and Materials for Electrochemistry" pKa Determination of Strongly Acidic C-H Acids Bearing a (Perfluoroalkyl)sulfonyl Group in Acetonitrile by Means of Voltammetric Reduction of Quinone Akira KOTANI ,a,*,§ Hikaru YANAI ,b Takashi MATSUMOTO ,b and Hideki HAKAMATA a a Department of Analytical Chemistry, School of Pharmacy, Tokyo University of Pharmacy and Life Sciences, 1432-1 Horinouchi, Hachioji, Tokyo 192-0392, Japan b Department of Synthetic Organic Chemistry, School of Pharmacy, Tokyo University of Pharmacy and Life Sciences, 1432-1 Horinouchi, Hachioji, Tokyo 192-0392, Japan * Corresponding author: [email protected] ABSTRACT A voltammetric method has been developed for the determination of the acid dissociation constant (pKa) of (RfSO2)2CHR (Rf = perfluoroalkyl), which is a strongly acidic molecule that serves as an acid catalyst. In acetonitrile solution containing small quantity of the acid, the reduction peak potential of quinone caused by the acid shifted to a more positive side accompanied by an increase in the acidity of the acid. This relationship was in good agreement with an equation derived from the Nernst equation. The present finding has been successfully applied to the determination of the pKa of the acids in acetonitrile with values ranging from 7 to 17. © The Author(s) 2020. Published by ECSJ. This is an open access article distributed under the terms of the Creative Commons Attribution 4.0 License (CC BY, http://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse of the work in any medium provided the original work is properly cited. [DOI: 10.5796/electrochemistry.20-65154]. Keywords : pKa, (perfluoroalkyl)sulfonyl Group, C-H Acid, Voltammetry 1. Introduction ICR) mass spectrometer is less accessible for common usage. As a scale of the solution acidity, the acid dissociation constant (pKa) 12 The (trifluoromethyl)sulfonyl group (Tf = CF3SO2) is one of the has been well-established. The experimental values are usually strongest electron-withdrawing groups. Recently, several Tf-derived determined by means of potentiometry, UV spectrometry, and 13–15 strong acids, exemplified by TfOH and Tf2NH, have been used in capillary electrophoresis. High-performance liquid chromatog- various fields of chemistry.1 Although gem-bis[(trifluoromethyl)- raphy (HPLC), isothermal titration calorimetry, and voltammetry 12,16–19 sulfonyl]alkanes, depicted as Tf2CHR, also serve as superacidic have been also utilized. These methods are performed mainly molecules2 in a gas phase,3 until recently the application of such in aqueous media, thus their application is limited to weak acids. molecules and the corresponding conjugate bases (stable carban- Although potentiometric and UV spectrometric titrations can be ions) have been significantly limited due to the lack of reliable performed in non-aqueous media as well, the pKa determination synthetic methods.4 Against such a background, Yanai and of strongly acidic compounds, including superacidic C-H acids, coworkers successfully developed an effective method for the requires complicated experimental procedures and measurements 12,20 incorporation of the (RfSO2)2CH group (Rf = perfluoroalkyl) into of multiple samples. several nucleophilic compounds.5 The C-H (carbon) acids thus In our voltammetric study of quinones in an unbuffered aqueous obtained have found applications as Brønsted acid catalysts for media, a small amount of acid was found to cause a new peak, called organic reactions.6 Lithium salts derived from the acids have also a prepeak, at a more positive potential than that of the original been utilized as electrolytes or additives to lithium-ion secondary reduction peak of quinone.21 The potential of the prepeak was 7,8 batteries. As such, the acidity of (RfSO2)2CHR and related C-H shifted to a more positive side accompanied by an increase in the acids in organic solvents would be fundamental and essential acidity of the compounds, i.e. the appearance of a prepeak potential information in such applications. However, their acidities have not is dependent on the acidity of compounds. Based on this finding, been fully investigated and the relationship between acidity and herein we report that the measurement of the quinone prepeak chemical structure has yet to be elucidated.9–11 potential in acetonitrile has a practical utility for determining the For strongly acidic compounds, the gas-phase acidity (GA), pKa values of C-H acids with a wide range of acidity. The pKa which is defined as a Gibbs energy change associated with the measurement in acetonitrile has already been conducted for a wide dissociation of the acid molecule, is used as an experimental range of common acids,20 therefore the current work allows for the parameter.3 However, the GA does not include any effects by comparing of the acidity of C-H acids with those of other acids on a solvation to the acid dissociation equilibrium. In addition, its single solution acidity scale. measurement with a Fourier transform ion cyclotron resonance (FT- 2. Experimental §ECSJ Active Member A. Kotani orcid.org/0000-0002-0113-3353 All chemicals and solvents were of reagent grade. Vitamin K3 > % H. Yanai orcid.org/0000-0003-4638-5113 (VK3, 99 ) and LiClO4 were purchased from FUJIFILM Wako T. Matsumoto orcid.org/0000-0003-0639-9262 Pure Chemical (Osaka, Japan). As reference acids, to prepare a H. Hakamata orcid.org/0000-0002-2964-9685 calibration curve, 4-chlorobenzenesulfonic acid (CBSA), p-toluene- 121 Electrochemistry, 89(2), 121–124 (2021) sulfonic acid (TSA), methanesulfonic acid (MSA), trifluoroacetic acid (TFA), saccharin (SAC), and 2,4-dinitrophenol (DNP) were purchased from Tokyo Chemical Industry (TCI, Tokyo, Japan) and purified by recrystallization or distillation. Sulfuric acid (SA) was used and also purchased from TCI without further purification. (RfSO2)2CHR and the related C-H acids were prepared according to a previous report.5 Voltammetry was conducted with an electrochemical analyzer (HZ-7000, Hokuto Denko, Tokyo, Japan). A plastic formed carbon (PFC) working electrode (3 mm diameter disk, Tsukuba Materials Information Laboratory, Ltd., Ibaraki, Japan), an Ag/AgCl reference electrode (Supporting Information), and a Pt counter electrode were inserted through the lid in the beaker-type electrochemical cell. ¹1 ¹1 Acetonitrile containing 3 mmol L VK3 and 0.1 mol L LiClO4 Figure 2. Relationship between the Ep/2 of the prepeak and the was used as an electrolyte cocktail. To prepare a test solution for pKa,AN of the reference acids. voltammetry, 4.0 mL of the electrolyte cocktail was mixed with 0.1 mL of acetonitrile containing 20 mmol L¹1 of each acid. Before measurements of voltammogram, argon gas (Ar > 99.99%) was slightly shifted to the negative side, appearing at ¹0.522 V vs. Ag/ thoroughly purged to remove dissolved oxygen in the test solution. AgCl. Although the exact mechanism for the peak potential shift is During the measurement of the voltammogram, Ar gas was passed complicated, in which the peak potential is probably affected by ¹1 above the test solution. The scan rate was set at 20 mV s . VK3 diffusion and its reaction rate, our results have proposed an analytical method for the determination of pKa by measurements of 3. Results and Discussion the prepeak of VK3. In a similar way, measurements of linear sweep voltammetry of Linear sweep voltammetry of VK3 was carried out in an VK3 were performed in the presence of CBSA, SA, MSA, TFA, ¹1 ¹1 acetonitrile solution containing 3 mmol L VK3 and 0.1 mol L SAC, or DNP. The Ep/2 of prepeaks caused by these reference acids LiClO4 using a PFC electrode. As shown in Fig. 1A, a reduction were +0.408, +0.363, +0.345, +0.084, ¹0.012, and ¹0.105 V vs. peak of VK3 was observed at a potential of ¹0.498 V vs. Ag/AgCl Ag/AgCl, respectively. The pKa values in acetonitrile (pKa,AN)of on a voltammogram scanned from +0.6 V to ¹0.6 V vs. Ag/AgCl. the reference acids obtained from literature are as follows: CBSA, As an example, in the presence of TSA, a prepeak was observed at a 7.16; TSA, 8.01; SA, 8.70; MSA, 9.97; TFA, 12.65; SAC, 14.57; 22 potential of +0.307 V vs. Ag/AgCl (Fig. 1B). From the prepeak DNP, 16.66. In Fig. 2, the Ep/2 of prepeak was plotted against the caused by the TSA on the voltammogram, the half-peak potential reported pKa,AN values of the references. A correlative relationship (Ep/2) of a prepeak of VK3 was found to be +0.391 V vs. Ag/AgCl. between Ep/2 of the prepeak and pKa,AN was found and expressed by In this measurement, the reduction peak potential of VK3 was a regression equation as follows: Ep=2 ¼0:05907 pKa;AN þ 0:86646 ðr ¼ 0:986Þð1Þ The appearance of the prepeak can be ascribed to the increased availability of protons from the acid to quinone. And the appearance of the prepeak can be affected by an electrochemical reaction rate such as a kinetic current, which has been proposed by Koutecký and 23 Brdička. Here, we describe the validity regarding a pKa value obtained by the potential measurements of the prepeak caused by an acid. In a polar aprotic solvent containing the acid, the voltammetric reduction of quinone (Q) is known to involve a one-electron transfer with a one-proton transfer to produce the protonated monoanion radical (QH•).18,24,25 Q þ eÀ þ Hþ QH• ð2Þ Based on the explanation for the diffusion current in the unbuffered medium,26 the reduction potential for Eq.