A Unified View to Brшnsted Acidity Scales: Do We Need Solvated Protons?

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A uniﬁed view to Brønsted acidity scales: do we need solvated protons?† Cite this: Chem. Sci.,2017,8, 6964 a a b a a Eno Paenurk, Karl Kaupmees, Daniel Himmel, Agnes Kutt,¨ Ivari Kaljurand, Ilmar A. Koppel,a Ingo Krossing*b and Ivo Leito *a

The most comprehensive solvent acidity scale spanning 28 orders of magnitude of acidity was measured in the low-polarity solvent 1,2-dichloroethane (DCE). Its experimental core is linked to the uniﬁed acidity scale

(pHabs) in an unprecedented and generalized approach only based on experimental values. This enables future measurements of acid strengths and acidity adjustments in low polarity solvents. The scale was cross-validated computationally. The purely experimental and computational data agree very well. The ﬀ H2O i.e. DCE scale includes 87 bu er systems with pHabs values between 13.0 and +15.4, similar to water at Received 30th March 2017 hypothetical and extreme pH values of 13.0 to +15.4. Unusually, such high acidities in DCE are not Accepted 3rd August 2017 realized via solvated protons, but rather through strongly acidic molecules able to directly donate their DOI: 10.1039/c7sc01424d proton, even to weak bases dissolved in the solution. Thus, in all examined cases, not a single solvated Creative Commons Attribution 3.0 Unported Licence. rsc.li/chemical-science proton is present in one liter of DCE.

lab as well as on an industrial scale in non- to weakly polar aprotic Introduction 3 solvents with relative dielectric constants r roughly between 2 and 6 The proton is undoubtedly one of the most important particles in 14 (such as alkanes, substituted arenes, ethers or haloalkanes). the universe. The most prominent phenomenon associated with it Azeotropic dehydrations in non-polar toluene with toluene- – acidity‡1–3 – is so important to nature that living organisms even sulfonic acid present a popular example. Thus, acid chemistry in have a sense for it. Acid–base reactions are ubiquitous, but are non-polar and non-basic solvents has been used in practice for This article is licensed under a mainly investigated in polar and/or “protic” solvents containing decades. However, wouldn’t it be fundamentally interesting to ionizable protons at concentrations that allow for a direct learn about the medium acidity of this and other popular mixtures measurement, e.g. by conductivity. Similarly, superacid chemistry in quantitative terms, in order to rigorously compare reaction Open Access Article. Published on 07 August 2017. Downloaded 10/3/2021 2:12:20 AM. is mainly done in highly polar, protic media like HF/SbF5 mixtures conditions in one solvent to another? 4 or the legendary “magic acid” HSO3F/SbF5. This overall polarity of Towards this general goal of the thermodynamically sound a solvent medium physically arises from the hydrogen bond donor evaluation of acidity, we have now derived a general approach to 5 and acceptor capacity, polarizability and dipole moment of its establish unied acidities in solvent media only on the basis of molecules and the dipole density that allow for stabilizing inter- experimental values. This fundamental development is applied actions with the dissolved ions, thus lowering their chemical here to the exemplarily selected low-polarity solvent 1,2- 3 ¼ potential (partial molar free energy, i.e. rate of change of the free dichloroethane (DCE, r 10.36 (ref. 7)). Due to its low basicity, energy of the system with respect to the change in the number of but sufficient polarity to dissolve polar and ionic compounds at molecules of the respective species that are added to the system). measurable concentrations/activities, DCE is a suitable solvent If the medium is non-polar, the solvation of ions, including H+,is for studying acids and also superacids. The scale covers 28 weak and their chemical potential is high.5 Thus, paradoxically, orders of magnitude of acidity and is linked to the unied 5 8 the highest acidities should be achievable in an environment that acidity scale (pHabs scale). It is based on our earlier work on is as non-polar as possible. In agreement with this, numerous – the high acidities in DCE (stronger acids than picric acid, e.g. acid-catalyzed – chemical reactions are carried out both in the spanning about 15 orders of magnitude). Finally, we support the experimental results by a cross-validation based on quantum-chemical calculations with consideration of solvation a Institute of Chemistry, University of Tartu, Ravila 14a Str, 50411 Tartu, Estonia. effects by the SMD,9 rCCC,10 and COSMO-RS11,12 models. E-mail: [email protected] bInstitut fur¨ Anorganische und Analytische Chemie and Freiburger Materialforschungs- zentrum (FMF), Albert-Ludwigs-Universitat¨ Freiburg, Albertstr. 21, 79104 Freiburg, Germany. E-mail: [email protected] Definitions and concepts † Electronic supplementary information (ESI) available: Detailed description of the equilibria, activities, anchoring approach and experiments. See DOI: Acidity in non-aqueous media, and especially the comparison of 10.1039/c7sc01424d acidity across media or even phase boundaries, is not common

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knowledge and quantitative views remain sparse. Therefore, we a given solvent of less than 12 to obtain micro-molar ion start with essential denitions and concepts. concentrations that can be easily measured. In low polarity media, the choice of such acids is very limited. Only extreme acids are able pH and the chemical potential of the proton to generate ions in low polarity media to a measurable/isolable extent. A drastic example is H[HCB F ] that even protonates pH is the most popular measure for medium acidity. In its 11 11 + the very non-polar medium liquid carbon dioxide giving the salt standard denition, pH ¼log(a(H , S)), it is a measure for the S H(CO ) +[HCB F ] .19 Since low polarity solvents weakly solvate solvated proton’s chemical potential m (H+, S) in the solvent/ 2 2 11 11 abs ions, the extent of ion–ion interactions and aggregation increases medium S. The molecular acidity of an acid HA in a solvent S drastically in such media. Therefore, eﬀects like ion-pairing and is described by the equilibrium (1), others have to be evaluated and correction schemes have to be + applied to obtain the “real acidity” data (cf. ESI Sections 2 and 3†). HA(solv.) % A(solv.) +H(solv.) (1) In addition, traces of basic impurities like water compete with the + + ﬀ and the available activity a(H , S) of solvated protons H(solv.) solventbasefortheprotonandthereforehaveadramatice ect on

formally determines the equilibrium pHS value in S, i.e. its acidity the acid dissociation, e.g. by formation of (also further solvated) + ff in medium S (and limited to medium S). Decreasing the pH of H3O .Thise ect is evaluated in a later section. a solution by one unit increases the proton’schemicalpotential and thus the solution’saciditybyRT ln 10 ¼ 5.71 kJ mol 1 at Superacidity standard conditions (25 C, 1 bar). The intrinsic molecular acidity Superacidity refers to the highest acidity and can be used in of HA in S is quantitatively given by its acidity constant Ka,S (eqn relation to media or molecules. Thus, we differentiate between (1)), used as the negative decadic logarithm pKa,S. two principal types of superacidity: þ aðH ; SÞ$aðA ; SÞ Medium superacidity. Medium superacidity was initially Ka;S ¼ (2) aðHA; SÞ dened by Gillespie as the acidity of a medium that is “stronger Creative Commons Attribution 3.0 Unported Licence. than sulfuric acid”.20 In the context of the unied acidity scale, a superacidic medium is one where the chemical potential of the Importantly, the pHS values as dened above – using refer- – proton lies higher than that in 100% sulfuric acid. Although the ence states in medium S are bound to the medium S and 21 cannot be used to compare acidities in different solvents/media. Hammett function H0 is most frequently used to assess superacidity,22 it does not directly express the proton’s chemical Unied acidity scale potential and thus should not be considered a thermodynamic acidity scale (see ref. 5 and 10).§ In the unied acidity scale, the 13 Following the seminal work of Bartmess, we introduced the absolute chemical potential of the proton in neutral{ liquid  – This article is licensed under a ideal proton gas at one bar as a uni ed and medium- H2SO4 was assessed as the threshold for superacidity: if – m + m + 1 independent reference state for acidity and as a thermody- a medium S has abs(H ,S)< abs(H ,H2SO4 (l)) or 975 kJ mol , 5 namic zero point. The chemical potential of this reference state 5,10 H2O k it is superacidic. This corresponds to a pHabs below 22.4. “ ” m ð þ; Þ¼ 1 ¼ proton gas is set to abs H g 0 kJ mol and pHabs 0. Molecular superacidity. Molecular superacidity refers to an Open Access Article. Published on 07 August 2017. Downloaded 10/3/2021 2:12:20 AM. The independence of this reference state from any medium acidic molecule/molecular ion, which, in a given solvent/ allows for a unied comparison of acidities in terms of chemical medium S, is a stronger acid than sulfuric acid, i.e. it has ff potentials or the corresponding pHabs values in di erent media a lower pKa,S value in this solvent/medium than sulfuric acid. In 23 on an absolute basis. For example, water with a pHwater of 0 has the gas phase, a superacidic molecule or molecular ion has

apHabs of 193.5 (with the published Gibbs hydration energy of a lower gas phase acidity (GA) value than the gaseous H2SO4 D + ¼ 1 14–16 the gaseous proton ( solv.G (H ,H2O) 1105 kJ mol ). In molecule.  order to express pHabs in a more familiar way, it is useful to shi H2O it by 193.5 units, to obtain so-called pHabs values ð H2O ¼ : Þ 17 The equilibrium acidity scale in DCE pHabs pHabs 193 5 , which are a direct continuation of aqueous pH values and identical to them in water. This means Buffer solutions are a superior means to measure the self- that the chemical potential of the proton in any solvent/ consistent equilibrium acidity scale in DCE, both for reasons medium with pHH2O 5 is the same as pH 5. abs water of the measurable concentrations of ions as well as the stability of the protochemical potential. The buffers used herein, i.e. Acidity measurements in low polarity media mixtures of acids and bases, keep the acidity at an approxi- Acidity measurements in low polarity media become increasingly mately constant value and allow for the reliable and reproduc- difficult and only limited examples are known.8 An acidity scale ible measurement of the chemical potential. In the simplest was even measured in the very non-polar n-heptane,18 butitis case, a 1 : 1 mixture of an acid with a salt of its conjugate base

obvious that protons solvated by heptane itself are not present in buﬀers at the buﬀer point pHS ¼ pKa,S. To construct a self- solution, as protonated n-heptane would decompose with the loss consistent ladder of relative acidities, protonation equilibria

of H2 or an alkane and rearrange instantly to a more stable between a large number of acid pairs (involving all acids on the branched tertiary carbenium ion. With the commonly used notion scale) have to be evaluated24 in the solvent S according to

that acidity relies on dissolved ions, it needs acids with a pKa,S in equilibrium (3),

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HA1 (solv.) +A2 (solv.) % A1 (solv.) +HA2 (solv.) (3) salt tetraphenylarsonium-tetraphenylborate (TATB) from one medium to the other, the chemical potential difference of both where HA1 and HA2 are the two acids. Their relative acidity ions is about the same between the solvents and the Gibbs ff D di erence pKa,S in solvent S can therefore be calculated as transfer energy of each ion just amounts to half of the follows (4): measurable sum.27 Although this assumption is disputed,28 any error or difference between these reference ions will systemat- log K ¼ DpKa;S ¼ pKa;SðHA2ÞpKa;SðHA1Þ À Á ically add to the single ion quantities, so that the overall a A ; S $aðHA ; SÞ 1 À 2 Á H2O ¼ log (4) structure of the pHabs scale will remain intact. aðHA1; SÞ$a A2 ; S General approach

However, the direct measurement in DCE gives values slightly Neither the medium pK of acids nor pH values are ff D ff a,DCE DCE di ering from pKa,S (eqn (4)) due to ion-pairing e ects. Those experimentally accessible (see below). Despite this, we can D are denoted as pKip (ip stands for ion-pairing). In this work, the construct a thermodynamically consistent pHH2O scale using 8 abs acidity scale in DCE is presented, composed of a total of 226 single ion Gibbs transfer energies from water to DCE via suitable D pKip measurements between 87 acids. For the construction of Born–Fajans–Haber cycles (BFHCs, see ESI Section 6 for details†). ff the scale, the sum of the squares of the di erences between the TheonlyacidinTable2forwhichsufficient experimental data for D ff experimental pKip values and the di erences between the such a connection to aqueous pH exists is HCl. Fortunately, the assigned pKip,rel values was minimized. Taking picric acid as Gibbs solvation energies of single ions cancel out in this calcu- a reference acid by arbitrarily assigning a value of 0.0 to its pKip,rel lation or can be replaced by one single ion Gibbs transfer energy, 8 value gave a self-consistent pKip,rel ladder (Table 2). It should be namely that of the chloride ion. According to these calculations, noted that in principle every acid could be taken as the reference detailed in the ESI in Section 5,† a1:1HCl/Cl buffer mixture in ff acid without a ecting the accuracy of the procedure. Using picric DCE has an acidity that corresponds to pH 2.5 in water. With the

Creative Commons Attribution 3.0 Unported Licence. acid is rather traditional (it is also used as the reference acid in knowledge that HCl has a pKa,rel of 0.2 vs. picric acid (Table 2), we 24 D acetonitrile ). To obtain the pKa,DCE values, all pKip,rel values obtain the simply applicable universal formula (5) that is valid for were corrected (by up to 0.51 units, see ESI, Section 3†) for the all our measured acids: logarithmic diﬀerence of the ion-pair dissociation constants að ; Þ D H2O A DCE pKd of the acids under study using the Fuoss model as pH ¼ 2:3 þ pK ; þ log abs a rel að ; Þ (5) described in the methods section and the ESI (Section 2†).25 Thus, HA DCE

one obtains the corrected thermodynamic pKa,rel values with respect to picric acid (Table 2). The compiled self-consistent H2O Using formula (5), we obtain a measured pHabs range in DCE acidity scale in Table 2 spans 28.4 orders of magnitude. The between +15.4 for the weakest acid 9-COOMe-uorene and 13.0 This article is licensed under a overall reliability of the logarithmic acidity constant values was for the strongest acid CN-TCNP in 1 : 1 (neutral acid : acid anion) 8 checked using the consistency standard deviation. For both buffer solutions. Such 1 : 1 buffer solutions correspond to the so- 1 H O pKip,rel and pKa,rel values, it is 0.04 log units or 0.23 kJ mol , ff 2 called bu er point (BP) and the corresponding pHabs can be

Open Access Article. Published on 07 August 2017. Downloaded 10/3/2021 2:12:20 AM. which can be considered very good for a low polarity solvent. H2Oð Þ termed as pHabs BP and calculated via eqn (6).

H2Oð Þ¼ : þ K pHabs BP 2 3 p a;rel (6) H2O Anchoring the DCE scale to pHabs values H2Oð Þ The pHabs BP values for all of the acids are presented in Table 2. Using the acids from Table 2, DCE solutions of well- The construction of a pH scale hitherto required in all cases abs   H2Oð Þ de ned uni ed acidity, i.e. pHabs BP values, can be prepared the Gibbs solvation energy for at least one ion, for example the  + on the basis of our data together with eqn (5) and (6) by any rst- hydration energetics of the gaseous proton (Dsolv.G (H ,H2O) ¼ year chemist. For higher ion concentrations, a correction scheme 1105 kJ mol 1).14–16 This value is not directly accessible by for non-ideality (Debye–Huckel¨ eﬀects) is deposited in the ESI, experimental methods, and was obtained by the extrapolation Section 7.† of the hydration thermodynamics of gaseous ion–water clusters to the bulk solvent. According to the authors, it is tainted with an error bar of at least 8 kJ mol 1 or 1.4 pH units! Advan- Cross validation: quantum-chemical tageously, in the pHH2O scale proposed herein, large single ion abs solvation models vs. experimental data Gibbs solvation energies can be removed or replaced by single ion Gibbs transfer energies, which are typically lower by 1–2 Several terms sum up to the overall Gibbs solvation energy as orders of magnitude. This reduces the overall uncertainty in the calculated by quantum chemistry. For small ions and mole- chemical potential assessment. Still, for partitioning the cules, the electrostatic part is very sensitive to the chosen calotte chemical potential of dissolved ionic compounds into single ion radii or isodensity surface and dominates the overall solvation values, so-called extrathermodynamic assumptions have to be thermodynamics. For large ions and molecules, the van-der- introduced. The most used assumption by far is the so-called Waals interaction as well as the cavity energy becomes “TATB assumption”.26 It assumes that when transferring the increasingly important. Thus, here we decided to use the

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medium sized HNTf2/NTf2 system for model building. An chemical potentials of the neutral acid and of the dissociated evaluation of the favorable performance of this system by proton as well as the acid anion according to the relation (8)

comparing calculated (rCCC model) and experimental pKasof 29 HNTf (DCE) % H+(DCE) + [NTf ] (DCE) HNTf2 in MeCN or DMSO was published. For validation, the 2 2 (8) pKa,rel (HNTf2, DCE) of 12.0 from Table 2 was set into eqn (6). H2Oð Þ¼ : þð : Þ¼: are equal. Therefore, although the actual concentration of the We obtain pHabs BP 2 3 12 0 9 7 for HNTf2 in DCE solvated protons H+(DCE) is vanishingly small in DCE, the at the buﬀer point BP (i.e. pHS ¼ pKa,S). As described above, the solution contains a manifold of bound protons at the same main error source in this value is the uncertainty of DtrG (Cl , chemical potential in the neutral acid moelcules! This means DCE / H2O), obtained with the TATB assumption. Eqn (7) that, if a basic molecule is immersed into the solution, it will be

À Á þ DsolvG ðHNTf 2; DCEÞþDsolvG NTF2 ; DCE þ GAðHNTf 2ÞþDsolvG ðH ; H2OÞ pHH2OðBPÞ¼ (7) abs RT ln 10

can be used for a cross validation with the solvation models. For protonated by the neutral, non-dissociated acid present – here 10 30 this, we augmented our published calculated rCCC and SMD HNTf2(DCE) – and not by the hardly existing solvated protons! data set with COSMO-RS11,12 solvation calculations (see ESI D Section 14 for details†). By combining the experimental solv.- Is it possible to obtain true medium pKa values in DCE? + 1 G (H ,H2O) ( 1105 kJ mol ) and the experimental gas phase 1 31 In order to transfer the obtained relative pKa,rel values, with acidity (1199 kJ mol ) of HNTf2 with the quantum-chemically respect to picric acid, to medium pKa,DCE values, we need the

Creative Commons Attribution 3.0 Unported Licence. calculated Gibbs solvation energies of HNTf and NTf ,we 2 2 reliable medium pK of at least one of the acids we measured, obtained the validation data in Table 1. a,DCE as an anchor point. Our calculation of the pK value of HNTf Pleasingly and supporting our experimental ndings, the a,DCE 2 in DCE gave rather robust values all rounding to 33, irrespective of calculated pHH2OðBPÞ values between 6.7 and 10.7 collected abs the solvation model used (range: 32.6–33.1, Table 1).30 Even taking in Table 1, and obtained with the diﬀerent quantum-chemical the lowest pKa,DCE of 32.6, this would imply that in a 0.01 M solvation models, agree within 1.0/+3.0 pH units to the solution of HNTf in pure DCE only 5 10 18 mol acid per liter is experimental one at 9.7. This corresponds to 5.7/+17.1 kJ 2 dissociated. This is unmeasurable! An additional problem arises mol 1 at standard conditions. It should be noted that, in from the low basicity of DCE: tiny traces of more basic impurities, addition to the error in the calculated Gibbs solvation energies,  This article is licensed under a + 14–16 especially water, have an enormous in uence on acid dissociation the Dsolv.G (H ,H2O) value has an estimated error bar of 8 and make medium pK determinations (nearly) impossible. kJ mol 1 or 1.4 pH units. In the end, it cannot be decided a,DCE Even well dried DCE (around 0.15 ppm) still contains around whether the experimental or one of the quantum chemically 10 5 mol L 1 of water. A rough SMD calculation gave a pK H2Oð Þ a,DCE Open Access Article. Published on 07 August 2017. Downloaded 10/3/2021 2:12:20 AM. calculated pHabs BP values is more accurate. + valueof13.6fortheH3O cation in DCE (see ESI Sections 7 and 13 for details†). According to the law of mass action this means that Does one need solvated protons for protonation of bases? even at a 2.5 10 14 mol L 1 (!) concentration of water, 50% of all

H2O solvated protons would be attached to water molecules and not to One may be surprised that neither our experimental pHabs H2O DCE. Even in buﬀered solutions, we see no chance for directly values (Tables 1 and 2) nor our pHabs calculations based on quantum-chemical solvation models (Table 1) require knowledge measuring pKa,DCE or pHDCE values in this case. Therefore, and in order to obtain estimates of true medium pK values (eqn (2)), of the medium pHDCE or any information about the solution a,DCE thermodynamics of the solvated proton in DCE. The reason is the scale was reconstructed with the corrected pKa,rel values and the computationally assessed medium pKa,DCE value of HNTf2. that the proton bound in neutral HNTf2 is in equilibrium with the solvated proton in DCE. Thus, in chemical equilibrium, the Since all values in Table 1 round to 33, we used this value as an anchor point (entry 72 in Table 2).

Table 1 Cross-validation data of the experimentally assessed relation versus D G 5 rCCC, SMD and COSMO-RS derived values (eqn (7)). solv. The DCE acidity scale: explanation and 1 values are in kJ mol discussion of the entries in Table 2 D G D G pK , solv. solv. a H2O The columns pKip,rel,pKa,DCE and pH ðBPÞ of Table 2 illus- (HNTf2, (NTf2 , DCE abs H2Oð Þ trate the diﬀerent levels of complexity in data treatment and the Model DCE) DCE) (HNTf2)pHabs BP corresponding depth of information that can be obtained. In rCCC 26 177 32.9 9.9 short: SMD 15 148 32.6 6.7 pK – accurately measured experimental and strictly ion- COSMO-RS 20 176 33.1 10.7 ip,rel Exp. ———9.7 pair (molecular) acidities of compounds relative to picric acid in DCE. The relative values are reliable, but their absolute

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Table 2 Acidity scale in 1,2-dichloroethane; see the text for in-depth explanations of the data Creative Commons Attribution 3.0 Unported Licence. This article is licensed under a Open Access Article. Published on 07 August 2017. Downloaded 10/3/2021 2:12:20 AM.

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Table 2 (Contd.) Creative Commons Attribution 3.0 Unported Licence. This article is licensed under a Open Access Article. Published on 07 August 2017. Downloaded 10/3/2021 2:12:20 AM.

a b Estimates of absolute acidities in terms of aqueous pH of 1 : 1 HA/A buﬀer solution in DCE of the respective acid. pKip,rel value of picric acid is c d e arbitrarily set to 0. Tos represents the 4-Me-C6H4SO2-group. Tf represents the CF3SO2-group. X-TCNP represents 2-X-1,1,3,3-tetracyanopropene. f Reference acid for the pKa,DCE values with a computational pKa,DCE value of 33.

magnitudes are arbitrary. The relative values are robust within the pKa,rel – estimate of the relative (to picric acid) pKa value

medium, as are approximations used in other nonpolar media, obtained from pKip,rel via correction for ion-pairing (using the and depend less on impurities than the absolute values and are Fuoss equation25). – thus useful for comparing acids, e.g. to rationalize synthesis pKa,DCE the common measure of (molecular) acidity of conditions or design electrochemical cells within DCE. compounds, i.e. ionic acidity values as dened by the negative

decadic logarithm of eqn (1). In non-polar media pKa,S values are very diﬃcult or impossible to measure directly, but can be

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derived from pKa,rel by anchoring to a robust computational Solvent effects on acidity: ¼ value (here: pKa,DCE(HNTf2) 33). The values are dependent on the medium and thus are strictly non-comparable between a comparison to the gas phase and different media. MeCN H2Oð Þ – pHabs BP medium acidity (as opposed to molecular acidity) of a 1 : 1 buffer solution expressed in relation to the Many acids studied in this work were investigated in acetonitrile (MeCN) and in the gas phase (Table S1 in the ESI†). pKa,DCE aqueous pH scale. It is derived experimentally from the pKip,rel values in Table 2 at the buffer point (BP), corrected to relative and pKa,MeCN are very well correlated (Fig. S3, ESI†), as described H2O by (9): pKa,rel and anchored to the pHabs scale via the experimental procedure delineated above. The values correspond to the pK ¼ 1.08 pK + 33.0, s(slope) ¼ 0.02; s(intercept) ¼ thermodynamic proton activity in water at the same pH values, a,DCE a,MeCN 0.2; n ¼ 44; R2 ¼ 0.992; S ¼ 0.6 (9) and are comparable between different media. This indirectly supports the quality of the results and provides a convenient tool to predict the acidities of strong acids in MeCN, which cannot be directly measured in that Do acids exist that allow for direct pK determination in DCE? a solvent. As expected, DCE is about 8% more differentiating than ff InthecourseofdirectpKa measurements, when increasing MeCN. The intercept at 33 is just the di erence between the the acidity of the solution, traces of H2O, rather than DCE standard Gibbs solvation energies of the proton in the two 1 1 molecules, will be protonated. With the SMD-calculated media, i.e. in MeCN (1058 kJ mol ) and DCE (869 kJ mol ). + ff 1 medium pKa,DCE(H3O ) of 13.6, 0.01 M of an acid HA (as This di erence of 189 kJ mol converted into the log-scale by 5 1 afunctionofpKa,DCE(HA)) and in DCE with 10 Mwater division through 5.71 kJ mol gives 33.

contamination (0.14 ppm), only acids with pKa,DCE values Creative Commons Attribution 3.0 Unported Licence. below 6.7 are suitable for direct medium pKa,DCE measure- Why are the DCE and GA values poorly correlated? ments. This is 23 orders of magnitude more acidic than the Given the inertness of DCE as a solvent, one could expect a good strongest acid CN-TCNP included within Table 2 (entry 87; correlation between the acidities in DCE and the gas phase. The pK 29.7). However, do acids with such pK values exist in a,DCE a reality is very diﬀerent. The correlation across all acid families is DCE? Halogenated derivatives of closo-dodecaborane or next to non-existent. It thus turns out that even such a low- 1-carba-undecaborane acids may have such acidities.30 polarity and inert solvent as DCE is by its inuence on acid Our computational estimates of their medium pK values a,DCE ionization much more similar to polar aprotic solvents (MeCN) in DCE are 0.1 for H [B F ]and1.6 for H[CB F ], 2 12 12 11 12 than to the gas phase. Better correlations are obtained when which means that they should be fully dissociated in DCE This article is licensed under a acidities within families are compared (see ESI, Fig. S4†). The solutions! The strongest acid prepared to date is poor correlation can be rationalized from a thermodynamic H[HCB F ],32 which is only weaker by 21 kJ mol 1 33 than 11 11 cycle (S-BFHC 3 in ESI†) for the protonation equilibrium H[CB11F12],andthusitisalsoexpectedtobesuﬃciently between two acids. Thus, the relation between medium pKa,S Open Access Article. Published on 07 August 2017. Downloaded 10/3/2021 2:12:20 AM. dissociated in DCE.** values and GA values can be derived as:

DpKa ¼ pKaðHA2ÞpKaðHA1Þ DGA þ DD GðanionsÞDD GðacidsÞ ¼ solv solv (10) Can we reach superacidity in DCE? RT ln 10

Medium superacidity. From the pKa,rel of sulfuric acid H2Oð Þ A linear correlation would require that the Gibbs solvation ( 2.2), we can calculate a pHabs BP of 0.1 for a sulfuric acid buffer in DCE, which is very far off the 22.4 we suggest for energy difference between a certain acid and its anion is iden- neutral sulfuric acid as a medium. The main reason is that tical for all acids. Obviously, this is not at all the case. a conjugate acid anion (here: [HSO4] )ismuchlesssolvated andthusmuchmorebasicinDCEthaninproticsolvents. Conclusions ff ð H2Oð Þ¼ : Þ Even our strongest acid bu er pHabs BP 13 0 , including the molecular superacid CN-TCNP, is more than 9 orders of Using acids from Table 2, buffer solutions of a well-dened magnitude away from showing medium superacidity as composition can be prepared spanning an acidity range of over dened above. But, with the above delineated calculated 28 pH units (or 160 kJ mol 1), which is double the pH window of

pKa,DCE values of the carborane acids, it is clear that medium water. Considering an acid/base catalyzed reaction, this means an superacidity may be reached in DCE, yet only with special and acceleration or slow-down factor of 1028. This corresponds to the diﬃcult to prepare acids, and is awaiting experimental diﬀerence between one millisecond and the age of the universe! It

realization. is as yet unclear if medium pKa,DCE and pHDCE values can ever be Molecular superacidity. H2O By contrast, 55 entries in Table 2 are directly measured in DCE. Despite this, experimental pHabs molecular superacids in DCE holding a lower medium pKa,DCE values were established in this work that describe the solvated value than sulfuric acid. proton’sthermodynamicswithoutanyknowledgeoftheproton’s

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H2O Fig. 1 Relation between the medium acidities in water and DCE and the pHabs scale and the limiting activities of the solvated proton in these media.

specic solvation and its activity in DCE. The quality of the COSMOTherm36 program was used to calculate COSMO-RS H2O derived pHabs values mainly depends on the quality of the Gibbs solvation energies. extrathermodynamic assumption (in our case the TATB assumption) and the accuracy of the so obtained single ion transfer thermodynamics. This approach is general and can be transferred Creative Commons Attribution 3.0 Unported Licence. Conflicts of interest to any solvent S, given that at least one acid is known for which the transfer energies from water to S exist for all particles. The general There are no conicts to declare. relation between aqueous acidities and the range of our buffer acidities measured is shown in Fig. 1. One can easily see that with our used buffer systems, the protolytic window of water is by far List of abbreviations/compendium exceeded, if compared on the unied acidity scale. However,

according to our assessed medium pKa,DCE values, even in our most acidic buffer system CN-TCNP, the proton concentration of Unied It allows a unied view to acidity over phase and This article is licensed under a its buffer in DCE of 10 29.7 mol L 1 is much less than one proton acidity medium boundaries. It is set absolute with the 24 1 per liter. The latter would correspond to 1.6 10 mol L .This pHabs value with respect to the reference state clearly shows that for measurable acid thermodynamics, solvated proton gas protons do not need to exist in the medium. Rather, the bound pKa,S Negative decadic logarithm of the medium acidity Open Access Article. Published on 07 August 2017. Downloaded 10/3/2021 2:12:20 AM. proton in the solvated neutral acid, being in equilibrium with the constant in the solvent S ionic solvated proton, has the same chemical potential and pKa,DCE Negative decadic logarithm of the medium acidity accounts for the protonation event. However, especially for non- constant in the solvent DCE pK Negative decadic logarithm of the medium acidity polar media and in unbuffered solutions, impurities may deter- a,H2O constant in the solvent H O mine the pH . Thus, chemical reactions inuenced by acidity may 2 S pK Negative decadic logarithm of the relative (to proceed in an unpredictable way, ifnotruninacarefullyselected ip,rel picric acid) acidity constant of the acid–titrant buffer, for example selected from the 87 systems collected in Table base ion pair (here the solvent is DCE, unless 2. The good correlations between the pK values and the cor- a,DCE stated otherwise) responding pKa values in MeCN, as well as in heptane and DMSO pKa,rel Directly measured pKip,rel corrected for ion-pairing (Fig. S7 and S8 in the ESI, respectively†), suggest that the values in effects according to the Fuoss-model to a true Table 2 can, in principle, be reliably transferred to other organic relative (to picric acid) acidity constant (here the solvents. solvent is DCE, unless stated otherwise) a(H+, S) Activity of the solvated proton in solvent/medium S a(H+, DCE) Activity of the solvated proton in solvent DCE Quantum chemical methods + a(H ,H2O) Activity of the solvated proton in solvent H2O Quantum chemical calculations on the SMD model were done pHS Negative decadic logarithm of the activity of the with the same procedure as in ref. 30. rCCC calculations were solvated proton a(H+, S) in solvent/medium S 11,12 done with the same procedure as in ref. 10. COSMO-RS input pHDCE Negative decadic logarithm of the activity of the + les (.cosmo and .energy) were created with the COSMO34 solvated proton a(H , DCE) in solvent DCE 35 pH Negative decadic logarithm of the activity of the module of the Turbomole program system according to the H2O + “BP_TZVPD_FINE_C30_1501.ctd” formalism. The solvated proton a(H ,H2O) in solvent H2O

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S The liquid medium the acidity is investigated in. It 12 A. Klamt, V. Jonas, T. Burger¨ and J. C. W. Lohrenz, J. Phys. 102 may be a molecular solvent like DCE or a strong Chem. A, 1998, , 5074. acid itself 13 J. E. Bartmess, J. Phys. Chem., 1994, 98, 6420. 14 M. D. Tissandier, K. A. Cowen, W. Y. Feng, E. Gundlach, M. H. Cohen, A. D. Earhart, J. V. Coe and T. R. Tuttle, J. Phys. Chem. A, 1998, 102, 7787. 15 M. D. Tissandier, K. A. Cowen, W. Y. Feng, E. Gundlach, Acknowledgements M. H. Cohen, A. D. Earhart, T. R. Tuttle and J. V. Coe, J. Phys. Chem. A, 1998, 102, 9308. This work was supported by the Albert-Ludwigs-Universit¨at Frei- 16 C. P. Kelly, C. J. Cramer and D. G. Truhlar, J. Phys. Chem. B, burg and the Freiburger Materialforschungszentrum (FMF). It was 2006, 110, 16066. funded through the DFG and the ERC project UniChem, number 17 A. Suu, L. Jalukse, J. Liigand, A. Kruve, D. Himmel, 291383. The work at Tartu was supported by the EU through the I. Krossing, M. Roses and I. Leito, Anal. Chem., 2015, 87, European Regional Development Fund (TK141 “Advanced mate- 2623. rials and high-technology devices for energy recuperation 18 E.-I. Ro˜om,˜ I. Kaljurand, I. Leito, T. Rodima, I. A. Koppel and systems”) and by the institutional research grant IUT20-14 from V. M. Vlasov, J. Org. Chem., 2003, 68, 7795. the Ministry of Education and Science of Estonia. 19 S. Cummings, H. P. Hratchian and C. A. Reed, Angew. Chem., Int. Ed., 2016, 55, 1382. Notes and references 20 R. J. Gillespie and T. E. Peel, in Advances in physical organic chemistry, ed. V. Gold and D. Bethell, Elsevier Academic ‡ We exclusively use the term “acidity” for proton acidity according to Arrhenius, – Brønsted and Lowry.1–3 Press, London, 2003, vol. 9, pp. 1 24. 54 § From principal thermodynamic considerations, the H0 curve follows dH0 ¼ 21 L. P. Hammett and A. J. Deyrup, J. Am. Chem. Soc., 1932, , RT ln 10 (dm(H+) dm(BH+)+dm(B)) and is “contaminated” by the indicator

Creative Commons Attribution 3.0 Unported Licence. 2721. base system’s chemical potential change. 22 (a) M. J. Jorgenson and D. R. Hartter, J. Am. Chem. Soc., 1963, { “Neutral” means that the pH is half of the pK of autoprotolysis. It is H2SO4 85, 878; (b) R. J. Gillespie and T. E. Peel, J. Am. Chem. Soc., “ ” commonly addressed as 100% H2SO4 . 95 k 1973, , 5173; (c) R. J. Gillespie and J. Liang, J. Am. Chem. This indicates that the acidity level rise from water to pure sulfuric acid is about 110 Soc., 1988, , 6053. ten orders of magnitude higher (!) than the H0 value of pure sulfuric acid of 11.9 would suggest. As the main reason for this, we assume that the desolvation of the 23 (a) I. A. Koppel, R. W. Ta, F. Anvia, S.-Z. Zhu, L.-Q. Hu, proton is accompanied by a desolvation of the protonated indicator base, which K.-S. Sung, D. D. DesMarteau, L. M. Yagupolskii and dampens the H0 curve. Y. L. Yagupolskii, J. Am. Chem. Soc., 1994, 116, 3047; (b) ** However, a further problem arises from the fact that even the slightly weaker E. Raamat, K. Kaupmees, G. Ovsjannikov, A. Trummal, carborane acids like H[HCB Cl ] and H[HCB Br H ]37,38 as well as the H [B X ] This article is licensed under a 11 11 11 6 5 2 12 12 39 A. Kutt,¨ J. Saame, I. Koppel, I. Kaljurand, L. Lipping, (X ¼ Cl, Br) acids are known to decompose many solvents including dichloro- methane37 and thus most probably also DCE by elimination of HCl and formation T. Rodima, V. Pihl, I. A. Koppel and I. Leito, J. Phys. Org. of carbocations. Chem., 2013, 26, 162. ¨ Open Access Article. Published on 07 August 2017. Downloaded 10/3/2021 2:12:20 AM. 24 A. Kutt, I. Leito, I. Kaljurand, L. Soovali, V. M. Vlasov, 1 S. A. Arrhenius, Z. Phys. Chem., 1887, 1, 631. L. M. Yagupolskii and I. A. Koppel, J. Org. Chem., 2006, 71, 2 J. N. Brønsted, Recl. Trav. Chim. Pays-Bas, 1923, 42, 718. 2829. 3 T. M. Lowry, J. Chem. Technol. Biotechnol., 1923, 42, 43. 25 K. Abdur-Rashid, T. P. Fong, B. Greaves, D. G. Gusev, 4 G. A. Olah, Superacid chemistry, Wiley, Hoboken, N.J., 2nd J. G. Hinman, S. E. Landau, A. J. Lough and R. H. Morris, edn, 2009. J. Am. Chem. Soc., 2000, 122, 9155. 5 D. Himmel, S. K. Goll, I. Leito and I. Krossing, Angew. Chem., 26 R. Alexander and A. J. Parker, J. Am. Chem. Soc., 1967, 89, Int. Ed., 2010, 49, 6885. 5549. 6(a) G. Wypych, Handbook of solvents, ChemTec Publ, Toronto, 27 Y. Marcus, M. J. Kamlet and R. W. Ta, J. Phys. Chem., 1988, 2001; (b) H. Clavier and H. Pellissier, Adv. Synth. Catal., 2012, 92, 3613. 354, 3347. 28 R. Schurhammer and G. Wipﬀ, J. Mol. Struct.: THEOCHEM, 7 C. Reichardt and T. Welton, Solvents and solvent eﬀects in 2000, 500, 139. organic chemistry, Wiley-VCH, Weinheim, Germany, 4th 29 J. F. Kogel,¨ T. Linder, F. G. Schroder, J. Sundermeyer, edn, 2011. S. K. Goll, D. Himmel, I. Krossing, K. Kutt, J. Saame and 8A.Kutt,¨ T. Rodima, J. Saame, E. Raamat, V. Maemets, I. Leito, Chem.–Eur. J., 2015, 21, 5769. I. Kaljurand, I. A. Koppel, R. Y. Garlyauskayte, 30 L. Lipping, I. Leito, I. Koppel, I. Krossing, D. Himmel and Y. L. Yagupolskii, L. M. Yagupolskii, E. Bernhardt, I. A. Koppel, J. Phys. Chem. A, 2015, 119, 735. H. Willner and I. Leito, J. Org. Chem., 2011, 76, 391. 31 I. Leito, E. Raamat, A. Kutt, J. Saame, K. Kipper, I. A. Koppel, 9 A. V. Marenich, C. J. Cramer and D. G. Truhlar, J. Phys. Chem. I. Koppel, M. Zhang, M. Mishima, L. M. Yagupolskii, B, 2009, 113, 6378. R. Y. Garlyauskayte and A. A. Filatov, J. Phys. Chem. A, 10 D. Himmel, S. K. Goll, I. Leito and I. Krossing, Chem.–Eur. J., 2009, 113, 8421. 2011, 17, 5808. 32 T. Kuppers,¨ E. Bernhardt, R. Eujen, H. Willner and 11 A. Klamt, J. Phys. Chem., 1995, 99, 2224. C. W. Lehmann, Angew. Chem., Int. Ed., 2007, 46, 6346.

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