Extension of the Self-Consistent Spectrophotometric Acidity Scale In

$ Lev Moissejevitch * Professor Vlasov # Agnes % Ivo, Ivari ^ Ilmar

#eq numbritel punktid ära. Näitan.

Extension of the Self-Consistent

Spectrophotometric Acidity Scale in Acetonitrile,

Unification of Different Acidity Scales

Agnes Kütt †, Ivo Leito *,†, Ivari Kaljurand †, Lilli Sooväli †, Vladislav M. Vlasov ‡, Lev M. Yagupolskii § and Ilmar A. Koppel †

† Institute of Chemical Physics, Department of Chemistry, University of Tartu, Jakobi 2 Str., 51014 Tartu, Estonia. E-mail: [email protected]; Phone: +372 7 375 259; Fax: +372 7 375 264. ‡ Institute of Organic Chemistry, Siberian Branch of the Russian Academy of Science, Novosibirsk 630090, Russia § Institute of Organic Chemistry, Ukrainian National Academy of Science, Murmanskaya Str. 5, Kiev 02094, Ukraine.

Abstract

F F F F F F F F F O CN CN F F F O F CN F F O O O O

∆pK (MeCN) a 4.74 5.10 pK (MeCN) a 13.01 17.75 22.85

The previously composed self#Agnes, siin sõnastasin veidi umber, et jääks rohkem uue asja mulje, mitte vana edasiarendamise mulje. JACS-I jaoks oluline. Self-consistent spectrophotometric acidity scales in acetonitrile (AN) was expanded to rangeranging from 3.7 – to 28.1 pKa units, which is over 24 orders of magnitude. 112

newreported. Altogether 203 acidity measurements werehave been carried out and 49 new compounds were93 acids are included to in the scale. With previous scales altogether 95 compounds are included to the present scale. The relative acidity (∆pKa value) of any two acids on the scale can be obtained by combainingcombining at least two independent sets of measurements. This multiple overlapping measurements makes results more reliableof measurements is essential to achieve high reliability of the pKa values. The overall consistency of the measurements is s = 0.04 pKa units. (#tekstis 0.03).

#Selle lause siiapanemises ma natuke kahtlen#In the area of weaker acids, the scale ishas been built up with well-behaved compounds in AN, which have important matter about correctness of the scale and are excellent basis for further studies.

#Siia mõtleme veel, milliseid olulisemaid tulemusi panna…

#%^Me peame mõtlema, mis on meie cutting edge selles artiklis. Minu meelesst see võiks olla eeskätt see, et on skaala, mis on väga kvaliteetne, igapidi kontrollitud ja seeläbi hea tööriist teistele. Me ei saa eriti rõhutada superhappeid, sest selels vallas pole siin kuigi palju uut võrreldes 1998 aastaga. Peaksime proovida kuidagi sisse panna, et kogu "normaalse" happelisuse ala atsetonitriilis on nüüd kaetud. Mõtted?

Introduction

In previous publications 1, 2 have been established self-consistent spectrophotometric acidiy scales acidity scale in acetonitrile (AN). These scales ) has been established. That scale spans over 12 pKa units and covers significant part of strong acids. The primary goal of the present work is to significantly extend the self-consistent that acidity scale toward weaker acidic direction for several pKa unitsacidities in order to embrace the range of "conventional" acidities (#%^Kahtlane termin, aga asja mote on näidata, et see siin on mingil määral lõplik asi – jällegi vajalik JACSile). The extension of the scale adds many new interesting compounds (eg perfluorophenol, fluorenes etc), ) for which pKa data in acetonitrile have not been available to date. Included are also useful indicator compounds for further studies (eg the families of disulfonimides, phenylmalononitriles and diarylacetonitriles) and also some commoncommonly encountered acids (4- toluenesulfonic acid, picric acid, acetic acid, benzoic acid). Considerable amountnumber of compounds in the scale are different groupsfamilies of stable CH-acids, which prove are excellent reference compounds in building blocks for the scale in very wide area of pKa values. and useful reference compounds for future investigators. #Sellest jutust osa on justkui resultide jutt, aga las olla praegu siin.

Considerable amount of acidity data for various compounds acids in AN has been accumulated. Lately no, however during the recent years little experimental (#tähtis sõna! Massiliselt on arvutuslikke artikleid, mida tuleks siin ka veidi mainida) data of pKa values of acids have has been published. Analysis of the literature 3 , 4 , 5 , 6 , 7 shows that an acidity

scale in the pKa range of 14-27 exists in AN, whereat majority of pKa values still holds over 19 units. Great bulk of measurements are carried out using potentiometry and conductometry as the methods. In present work the spectrophotometric acidity scale of pKa range of 4-28 are reported. We will also compare our data with the data reported in the literature to make conclusions about the contractoin/expansion or deviation of the acidity scales.

AN have many properties that make it a suitable medium for acid-base studies. It has low basicity and very low ability to solvate anions 4 .The low basicity give AN an advantage over the other very popular solvent for acid-base studies – DMSO, which is considerably more basic (stronger acceptor of hydrogen bonds). As AN has high dielectric constant (D = 36.0 4 ) it favours the dissociation of ion pairs into free ions. The autoprotolysis 8 constant of AN is very low – pKauto ≥ 33 , which makes it a good differeating solvent. Additionally, the advantages of AN are its transparency down to 190 nm and relative ease of purification.

Acidity of an acid HA in solvent S refers to the equilibrium

HA + S →← A- + SH+ (1.) and is expressed as dissociation constant Ka or more commonly its negative logarithm pKa.

a(SH + ) ⋅ a(A- ) K = (2.) a a(HA) Because of the complications of measuring the acidity of the medium, a(SH+ ), in nonaqueous solvents, we used a method that eliminates the need for its determination. Our method of acidity measurements is based on measuring relative acidities of the acids HA1 and HA2 according to the following equilibrium:

- → A- + HA (3.) HA 2 + A1 ← 2 1 The relative acidity of the two acids HA1 and HA2 (∆pKa) is defined:

- a(A1 ) ⋅ a(HA2 ) ∆pKa = pKa (HA2 ) − pKa (HA1 ) = − log K = log - (4.) a(HA1 ) ⋅ a(A2 ) The method consist of UV-Vis spectrophotometric titration of a solution, where both of the acids are present, with a transparent acid or base. There is no need for the determination of a(SH+ ) any more.

#Arvutused, mis on avaldatud. Vähemasti natuke peab neist juttu olema. Suurem osa neist on DMSO kohta. Tuleb püüda jõuda tõdemuseni, et arvutused arenevad hoolega, aga vähemasti praegu eksperimendi vastu veel ei saa.

3 , 4 , 5 , 6 , 7 Analysis of the literature shows that an acidity scale in the pKa range of 14-27 exists in AN, whereas the majority of pKa values still holds over 19 units#tagumisest osast ma ei saa hästi aru #meie oma varasem skaala tuleb siia ka sisse tuua, aga on oluline rõhutada, et praegusel on eeliseid: 1. rohkem aineid; 2. kuivades tingimustes tehtud. Mingil määral tuleks ilmselt diskuteerida (tagapool muidugi) ka kokkulangevust, niipalju, kui seda on.

The majority of measurements have been carried out using potentiometric and conductometric methods. In the present work the spectrophotometric acidity scale of pKa range of 4-28 is reported. We will also compare our data with the data reported in the literature to make conclusions about the contraction/expansion or deviation of the acidity scales. #%^seda eespool olevat osa tuleb meil kõigil veel täiendada-kohendada.

AN has many properties that make it a suitable medium for acid-base studies. It has low basicity and very low ability to solvate anions 4 . The low basicity gives AN an advantage in studies of strong acids over the other very popular solvent for acid-base studies – DMSO, which is considerably more basic (stronger acceptor of hydrogen bonds). As AN has high dielectric constant (D = 36.0 4 ) it favors the dissociation of ion pairs into free 8 ions. The autoprotolysis constant of AN is very low, pKauto ≥ 33 , which makes it a good differentiating solvent. Additionally, the advantages of AN are its transparency for Uv radiation down to 190 nm and relative ease of purification.

Acidity of an acid HA in a solvent S refers to the equilibrium

+ HA + S →← A- + SH (5.) and is expressed as dissociation constant Ka or more commonly its negative logarithm pKa.

a(SH + ) ⋅ a(A- ) K = (6.) a a(HA) Because of the complications of measuring the acidity of the medium, a(SH+ ), in nonaqueous solvents, we use (#see annab lausele selle sisu, et me üleüldiselt kogu aeg kasutame sellist meetodit, mitte ainult seekord) a method that eliminates the need for its determination. Our method of acidity measurements is based on measuring relative acidities of the acids HA1 and HA2 according to the following equilibrium:

- → A- + HA (7.) HA 2 + A1 ← 2 1

The relative acidity of the two acids HA1 and HA2 (∆pKa) is defined:

- a(A1 ) ⋅ a(HA2 ) ∆pKa = pKa (HA2 ) − pKa (HA1 ) = − log K = log - (8.) a(HA1 ) ⋅ a(A2 )

The method consist of UV-Vis spectrophotometric titration of a solution, where both of the acids are present, with a transparent acid or base. As can be seen from eq (8.) There is no need for the determination of a(SH+ ) any more.

The acid-base equilibria (5.) in weakly solvating solvents such as AN are more complex than those in water. In addition to the eqilibrium 5., there are other equilibria present in the system 4 . In AN, the poorly solvated anions vigorously form hydrogen-bonded complexes with hydrogen-bond donors present in the solution. When the donor is the conjugate acid of the anion, then the homoassociation process takes plase.place:

K − AHA

A- + AH →← A- ⋅⋅⋅ HA (9.)

K − is the homoassociation constant. AHA

a(A − ⋅⋅⋅ HA) K − = (10.) AHA a(A − ) ⋅ a(HA) If the donor is some other acid, then the heteroassociation process is present. ThisThese side of -reactions have to be supressedsuppressed or taken into account if the accurate acidity data are to be obtained.

#Kas ma saan õigesti aru, et räägime homoaasotsiatioonist ja mitte homokonjugatsioonist? (mu meelest on homoassotsiatsioon sellise asja moodustumine: AH···AH)

Experimental Section

Chemicals. Solution of trifluoromethanesufonic acid (TfOH) (99+ %) or perchloric acid (HClO4) were used as acidic titrant and solutions of triethylamine (99 %), phosphazene bases 9 t-BuP1(pyrr) (≥98 %) or EtP2(dma) (>98 %) were used as basic titrant . Commercial AN with water concentration stated by producer below 0.005 % (determined in our lab by coulometric Karl Fischer titration below 0.004%) was used. Following compounds were the same used earlier: 40, 43, 48 – 50, 52 – 56, 59, 60, 62, 65 – 68, 70 – 77, 80, 82, 86, 87, 89 – 93 1 ; 57, 58, 61, 63, 64, 69, 78, 79, 81, 83, 84, 88 2 . Preparation of following compounds have been previously described: 1 10 ; 2, 13, 14 11; 3 12 ; 4, 17, 18, 20, 31 13 ; 5, 6 14 ; 11, 33, 36, 39, 42, 44, 47, 51 15 ; 22 16 ; 25, 28, 38, 45 17 ; 29 18 ; 46, 26 (additionally was sublimed), 30 (additionally was sublimed twice) 5 ; 24 19 and Aldrich 99+ %; 27 20 ; 32 21 . Samples 7 – 9, 16 were donated by the late Prof. R. W. Taft. Sample 37 was provided by E. M. Arnett 22 . The following chemicals were commercial origin. Some of these were purified prior to use: 12 (Fluka, > 99 % ) was sublimed once; 21 (REAKHIM, “pure”) was sublimed twice; 35 (Aldrich, 95 %) was recrystallized from ethanol and water mixture; 23 (Aldrich, 97 %) and 41 (Aldrich, 95 %) were distilled under reduced pressure. Compounds 10

(REAKHIM, “pure for analysis”), 15 (Carlo Erba, Elemental Analysis Standard), 19 (Aldrich 99 %) and 34 (Aldrich, 99+ %) were used without additional purification.

$ Lev Moissejevitch! To my knowledge, the synthesis of the following compound 2,4,6- (SO2F)3-Phenol (85) is not previously described. Please provide synthesis description and as much characterisation data as possible (1H, 13C, 19F NMR resonances, elemental analysis, purity etc.)!

Experimental Setup. The spectrophotometric titration method used in this work is mostly the same as described earlier 1, 2, 9, 23, 24, 25, 26, 27, 28 #püüame siit mingi valiku teha. Omaenda grupi tööde massilist viitamist ei peeta heaks tooniks. The method is based on UV-Vis spectrophotometric titration of a mixture of two acids with a non-absorbing base to obtain neutral and anionic forms of the solution of mixture. Both acids were also titrated separately to obtain spectra of neutral and ionized forms. From the titration data the relative acidity of the two compounds – the difference of their pKa values (∆pKa) – is obtained. Also tested reversibilty of protonation-deprotonation process. Acids which had no reversibility of the process, did not included to the scale. The protonation-deprotonation process was reversible with all acids in the scale. Equilibria were reached a little longer time in case of weak CH-acids (fluorenes and diarylacetonitriles). Usually sharp isosbestic points of spectra indicates the purity of measured compounds. Fluoro-substituted phenols (23, 24, 32, 41) and compound 46 had not sharp isosbestic point at shorter wavelenght range due to homoassociation processes. Longer wavelenght range that used for calculations UV-Vis spectra were not out of the common.

Calculation Methods. Different kind of calculation methods for ∆pKa were used:

1) General method described previously 1 , 2 , 9 , 2 3 , 2 4 , 2 5 , 2 6 , 2 7 . All data for calculations of ∆pKa were obtained from the UV-Vis spectra of measured acids.

2) In case of some acids (15, 23, 24, 26, 30, 32, 41, 46), it was necessary to take homoassociation into account. It is possible if only one of the acids in equilibrium forms homoassociation complex. The method is described earlier 1 .

3) Both of the acids form homoassociation complexes. In this case, we assume that they also form heteroassociation complexes. We assume that for all the sulfonic acids (71, 73, 75, 76, 77) that the homoassociation constants are very close and also all the heteroassociation constants are very close to the homoassociation constants. In this case, - - it can be shown that the four species, HA1, HA2, A1 , and A2 , are consumed proportionally to their concentrations for the formation of the homo- and heteroassociation complexes, and the relative decrease of their concentrations will cancel out so that the formation of the complexes can be ignored when calculating ∆pKa.

4) If one of the acids (10 and 19) has no suitable spectra (small difference in the spectra of neutral and deprotonated form or no spectra at longer wavelenght area or no specra at all) for calculations described in paragraph 1 and 2, then it is possible to use the calculation method where exact amount of moles of the compounds and added titrant in 9 , 2 5 , 2 6 , 2 7 titration vessel were used for calculations of ∆pKa . It was also necessary to take homoassociation into account. Due to great homoassociation complex forming ability, the measurements and thus calculations of one acid (19) were carried out othervise, two visible compounds and one invisible compound were altogether in titration vessel. This way neutral and fully ionized forms of invisible acids can be easily determined.

Results

The results of measurments are presented in Table 1. All compounds in the scale have at least two independent measurement and the relative acidity of two acids can be obtained by combining at least two independent sets of measurements. This multiple overlapping makes results more reliable.

Altogether 108 new relative acidity measurements were carried out and 47 new compounds were included to the scale. With previous scales 1, 2 the self-consistent acidity scale in AN has been created. Scale extends over 3.7 to 28.1 pKa units, which is over 24 ordres of magnitute. The pKa values of individual acids were found as in previous works 1 , 2 , 9 , 2 3 , 2 4 , 2 5 , 2 6 , 2 7 , 2 8 by minimizing the sum of squares of differences between directly measured ∆pKa values and the assigned pKa values.

nm i 2 u = ∑{∆pKa − [pKa (HA 2 ) − pKa (HA1 )]} (11.) i=1

i The sum is taken over all measurements. ∆pKa is the result of the relative acidity measurements of acids HA1 and HA2. pKa(HA1) and pKa (HA2) are the absolute pKa values for the two acids found by the least squares procedure.

The precision and the consistency of the results can be assessed by using a standard deviation:

u s = (12.) nm − nc

The whole acidity scale in AN has total number of measurements nm = 203, number of pKa values determined nc = 93 – 1 = 92 and the consistency of measurements s = 0.03. This estimate of precision must be interpreted as the precision of single measurements (%# kas on ikka nii?) and not the precision of absolute pKa value. These compounds that are far from reference compound have smaller precision than those nearer.

1 The anchoring point of the scale is as in previous work picric acid with pKa value of 11.00.

The calculation of some acids 10 and 19 was not quite precise because of great homoassociation constant and no appropriate spectra. Therefore, first calculated absolute pKa values of all other acids and then pKa values of these three acids to make pKa values of other acids more reliable. Othervise ∆pKa values of the tree acids may affect consistency of the scale, although difference in absolute pKa values are very small and keeps heavily into measure of consistency of measurements. 2 Same method was used earlier to calculate pKa values of N-aryltrifluromethanesulfon- amides and N,N’-bis(trifluoromethylsulfonyl)benzamidines. In this work is made otherwise and this is the reason why some absolute pKa values are differerent from pKa values of previous works 1, 2.

Two cationic acids of previous scale 1 are removed. The acids of different charge type must be treated separately because of complications of calculation method. The activity coefficients must be used because the ratios of activity coefficients are not equal anymore as in the case of acids with same charge type.

TABLE 1. Continuous Self-Consistent Acidity Scale of Neutral Acids in Acetonitrile.

a b Acid pK a (AN) Directly measured ∆pK a

1 9-C6F5-Fluorene 28.11 1.15 2 (4-Me-C6F4)(C6H5)CHCN 26.96 1.78 0.63 1.96 3 (4-NC5F4)(C6H5)NH 26.34 0.82 0.20 4 (C6H5)(C6F5)CHCN 26.14 1.03 5 (4-Me2N-C6F4)(C6F5)NH 25.12 1.20 0.17 6 (4-Me-C6F4)(C6F5)NH 24.94 0.64 0.45 7 Octafluorofluorene 24.49 0.58 8 Fluoradene 23.90 0.96 9 9-COOMe-Fluorene 23.53 1.05 0.01 10 Acetic acid 23.51 0.68 0.67 11 (C6F5)CH(COOEt)2 22.85 0.73 0.71 12 2-NO2-Phenol 22.85 0.92 0.04 13 (4-Me-C6F4)2CHCN 22.80 0.90

14 (4-Me-C6F4)(C6F5)CHCN 21.94 1.49 0.42 15 Benzoic acid 21.51 0.60 16 9-CN-Fluorene 21.36 0.39 0.25 17 (4-H-C6F4)(C6F5)CHCN 21.11 0.26

18 (C6F5)2CHCN 21.10 1.01 0.53 19 (CF3)3COH 20.55 0.76 0.75 20 (4-Cl-C6F4)(C6F5)CHCN 20.36 -0.01 21 2,4,6-Br3-Phenol 20.35 1.02 0.26 1.03 0.21 1.02 22 (2,4,6-Cl3-C6F2)(C6F5)CHCN 20.13 0.03 0.29 23 2,3,5,6-F4-Phenol 20.12 1.75 0.25 0.00 1.21 0.06 24 2,3,4,5,6-F5-Phenol 20.11 0.42 0.03 0.01 0.48 1.02 0.82 25 (2-C10F7)(C6F5)CHCN 20.08 0.81 26 1-C10F7OH 19.72 0.43 0.80

27 2,4,6-(SO2F)3-Aniline 19.66 0.40 0.34 0.85 28 (2-C10F7)2CHCN 19.32 0.44 29 9-C6F5-Octafluorofluorene 18.88 0.79 0.38 1.19 30 2-C10F7OH 18.50 0.73 0.36 31 (4-CF3-C6F4)(C6F5)CHCN 18.14 0.04 32 4-C6F5-2,3,5,6-F4-Phenol 18.11 0.06 0.46 1.58

33 (4-H-C6F4)CH(CN)COOEt 18.08

34 2,3,4,5,6-Cl5-Phenol 18.02 0.19 35 2,3,4,5,6-Br5-Phenol 17.83 0.75 0.63 0.28 0.59 0.08 0.41 36 (C6F5)CH(CN)COOEt 17.75 0.26

37 4-Me-C6H4CH(CN)2 17.59 1.70 1.46 1.15 38 (2-C10F7)CH(CN)COOEt 17.50 1.10 0.92 0.10 39 (4-Cl-C6F4)CH(CN)COOEt 17.39 0.88 40 2,4-(NO2)2-Phenol 16.66 0.77

41 4-CF3-2,3,5,6-F4-Phenol 16.62 0.27 1.49 0.22 0.54 42 (4-NC5F4)(C6F5)CHCN 16.40 0.60 0.27 43 (4-CF3-C6F4)2CHCN 16.13 0.32 0.05 0.37 44 (4-CF3-C6F4)CH(CN)COOEt 16.08 1.92 0.06 1.51 0.72 45 (4-NC5F4)(2-C10F7)CHCN 16.02 0.70 1.43 46 4-NC5F4-OH 15.40 1.12 1.35 1.32 47 (4-NC5F4)CH(CN)COOEt 14.90 0.69 0.19 48 3-CF3-C6H4CH(CN)2 14.72 0.15 49 Saccharin 14.57 0.84 071 189

0.15 49 Saccharin 14.57 0.84 0.71 1.89 50 4-Me-C6F4CH(CN)2 13.87 0.40 51 (4-NC5F4)2CHCN 13.46 0.87 0.45 0.89 52 C6F5CH(CN)2 13.01 0.48 0.03 0.04 53 4-H-C6F4CH(CN)2 12.98 0.79 0.74 54 2-C10F7CH(CN)2 12.23 1.38 0.26 c 0.62 55 Tos2NH 11.97

56 4-NO2-C6H4CH(CN)2 11.61 0.03 57 4-MeO-C H C(=O)NHTf d 11.60 0.14 6 4 0.28 0.19 58 4-Me-C6H4C(=O)NHTf 11.46 1.21 0.98 59 (C6H5SO2)2NH 11.34 0.60 0.60 0.57 60 4-Cl-C6H4SO2NHTos 11.10 0.49 0.36 61 C6H5C(=O)NHTf 11.06 1.43 0.10 0.07 62 Picric acid 11.00

63 4-F-C6H4C(=O)NHTf 10.65 0.91 0.79 0.87 64 4-Cl-C6H4C(=O)NHTf 10.36 0.82 0.54 65 (4-Cl-C6H4SO2)2NH 10.20 0.15 0.56 -0.01 66 4-CF3-C6F4CH(CN)2 10.19 0.13 1.15 0.14 0.52 1.20 67 4-NO2-C6H4SO2NHTos 10.04 1.06 0.73 1.05 0.46 68 4-Cl-3-NO2-C6H3SO2NHTos 9.71 69 4-NO -C H C(=O)NHTf 9.49 0.53 2 6 4 0.23 70 4-NO -C H SO NHSO C H -4-Cl 9.17 2.3 2 6 4 2 2 6 4 0.56 1.73 71 TosOH 8.6 1.21 0.23 72 (4-NO -C H SO ) NH 8.32 1.3 2 6 4 2 2 0.25 73 1-C H SO H 8.02 0.50 10 7 3 0.19 1.04 74 C H CHTf 7.85 6 5 2 0.54 1.25 75 4-Cl-C H SO H 7.3 6 4 3 0.53 0.51 76 3-NO2-C6H4SO3H 6.78

77 4-NO2-C6H4SO3H 6.73 78 4-MeO-C H C(=NTf)NHTf 6.54 6 4 0.44 1.28 0.23 79 4-Me-C H C(=NTf)NHTf 6.32 0.51 0.75 0.23 6 4 0.05 0.62 80 TosNHTf 6.30 0.5 0.16 0.35 81 C H C(=NTf)NHTf 6.17 6 5 0.36 0.47 1.11 82 C H SO NHTf 6.02 0.59 6 5 2 0.26 83 4-F-C H C(=NTf)NHTf 5.79 0.83 6 4 1.64 84 4-Cl-C H C(=NTf)NHTf 5.69 6 4 0.77 1.37 85 2,4,6-(SO F) -Phenol 5.66 1.25 2 3 0.64 86 4-Cl-C H SO NHTf 5.47 0.42 6 4 2 0.71 87 4-Cl-C H SO(=NTf)NHTos 5.27 6 4 0.53 0.38 1.20 88 4-NO2-C6H4C(=NTf)NHTf 5.13 89 2,4,6-Tf -Phenol 4.93 3 0.41 1.1 90 4-NO -C H SO NHTf 4.52 2 6 4 2 0.05 0.87 91 4-Cl-C H SO(=NTf)NHSO C H -4-Cl 4.47 1.10 1.15 6 4 2 6 4 0.31 92 2,3,5-tricyanocyclopentadiene 4.16 0.74 0.50 93 4-Cl-C6H4SO(=NTf)NHSO2C6H4-4-NO2 3.75 a Absolute pK a values (see the Results) b 1, 2 The numbers on the arrows are the experimental ∆pK a values from this work and previous works c Tos denotes 4-Me-C6H4SO2- d Tf denotes CF3SO2-

TABLE 2. Acidity Data of the Studied Acids Reported in the Literature

pK pK pK pK a a ip a GA No Acid values in values in values values in o k l m (kcal/ mol) DMSO H2O in C7 DME a d 1 9-C6F5-Fluorene 14.7 15.2 b b 2 (4-Me-C6F4)(C6H5)CHCN 13.2 328.2 c c 3 (4-NC5F4)(C6H5)NH 14.5 323.5 b b 4 (C6F5)(C6H5)CHCN 12.8 11.8 325.6 d 5 (4-Me2N-C6F4)(C6F5)NH 13.6 d c 6 (4-Me-C6F4)(C6F5)NH 13.3 7.04 320.0 7 Octafluorofluorene 10.8 e 317.3 8 Fluoradene 10.5 f 6.40 324.9 b 9 9-COOMe-Fluorene 10.35 e 9.2 n 10 Acetic acid 12.3 e 4.75 341.1 p 12.6 g 11 (C6F5)CH(COOEt)2 3.2 g q 12 2-NO2-Phenol 11.0 7.21 329.5 7.23 h 13 (4-Me-C6F4)2CHCN 4.61 b 14 (4-Me-C6F4)(C6F5)CHCN 3.29 7.1 316.1 15 Benzoic acid 11.0 e 4.25 330.0 p 11.1 g 16 9-CN-Fluorene 8.3 e 7.9 n 321.4 b 17 (4-H-C6F4)(C6F5)CHCN 6.7 e 18 (C6F5)2CHCN 7.95 1.85 6.4 312.4 e r 19 (CF3)3COH 10.7 324.0 b b 20 (4-Cl-C6F4)(C6F5)CHCN 7.5 1.09 5.4 311.8 22 (2,4,6-Cl3-C6F2)(C6F5)CHCN 1.10 h h 24 2,3,4,5,6-F5-Phenol 8.9 5.53 320.8 25 (2-C10F7)(C6F5)CHCN 5.5 h 26 1-C10F7OH 8.9 314.0 c b 27 2,4,6-(SO2F)3-Aniline 7.8 ca 7 307.5 28 (2-C10F7)2CHCN -0.68 d 29 9-C6F5-Octafluorofluorene 0.00 5.3 301.8 h 30 2-C10F7OH 7.9 312.4 b 31 (4-CF3-C6F4)(C6F5)CHCN 4.9 -1.39 3.9 307.5 b b 33 (4-H-C6F4)CH(CN)COOEt 4.9 315.6 h h 34 2,3,4,5,6-Cl5-Phenol 7.2 5.26 b 36 (C6F5)CH(CN)COOEt 4.7 3.5 313.5 5.1 e b 37 4-Me-C6H4CH(CN)2 4.85 315.7 38 (2-C10F7)CH(CN)COOEt 3.3 b b 39 (4-Cl-C6F4)CH(CN)COOEt 4.5 3.1 312.5 e, i 40 2,4-(NO2)2-Phenol 5.4 4.10 308.6 b 42 (4-NC5F4)(C6F4)CHCN 3.3 2.2 305.7

b 43 (4-CF3-C6F4)2CHCN 3.3 302.1 b b 44 (4-CF3-C6F4)CH(CN)COOEt 3.0 307.8 45 (4-NC5F4)(2-C10F7)CHCN 1.9 h 46 4-NC5F4-OH 5.4 311.3 b 47 (4-NC5F4)CH(CN)COOEt 3.2 303.5 48 3-CF3-C6H4CH(CN)2 307.0 49 Saccharin 4.0 e 50 4-Me-C6F4CH(CN)2 308.0 b 51 (4-NC5F4)2CHCN 2.4 302.2 b 52 C6F5CH(CN)2 0.3 303.6 53 4-H-C6F4CH(CN)2 305.5 54 2-C10F7CH(CN)2 301.8 b 56 4-NO2-C6H4CH(CN)2 -1.8 299.5 62 Picric acid -1.0 g 0.3 h, k 302.8 66 4-CF3-C6F4CH(CN)2 301.5 71 TosOH 0.90 j b 74 C6H5CHTf2 2.0 301.3 89 2,4,6-(Tf)3-Phenol 291.8 a Reference 29. b Reference 30. c Reference 31. d Reference 10. e Reference 32. f Reference 33. g Reference 34. h Reference 5. i Reference 6. j Reference 35. k Reference 36. l Reference 23, in reference to acid 29. m Reference 37. n Reference 38. o Reference 39. p Reference 40. q Reference 41. r Reference 42.

TABLE 3. Comparison of the pKa Values Determined in The Work with Those Reported in The Literature.

pK values in AN No Acid a Difference This work Literature 10 Acetic acid 23.51 22.3 a +1.2 22.31 b +1.20 c 12 2-NO2-Phenol 22.85 22.0 +0.9 22.1 d +0.8 15 Benzoic acid 21.51 20.7 a +0.8 16 9-CN-Fluorene 21.36 20.8 e +0.6 f 24 2,3,4,5,6-F5-Phenol 20.11 19.5 +0.6 f 26 1-C10F7OH 19.72 19.4 +0.3 f 30 2-C10F7OH 18.50 17.8 +0.7 f 34 2,3,4,5,6-Cl5-Phenol 18.02 17.2 +0.8 g 40 2,4-(NO2)2-Phenol 16.66 15.34 +1.32 16.0 c +0.7 18.40 b –1.74 f 46 4-NC5F4-OH 15.40 15.2 +0.2 62 Picric acid k 11.0 h

71 TosOH 8.6 8.01 i +0.6 8.73 b –0.1 92 2,3,5- tricyanocyclopentadiene 4.16 3.00 j +1.16 a Reference 34. b Reference 43. c Reference 4. d Reference 44. e Reference 45. f Reference 5. g Reference 46. h Reference 47. i Reference 35. j Reference 48. k Anchor compound of present scale.

25 12 10 16 24 15 12 40 26 17 30 46 4034 40 (Literature)

a 62

K 71

p 9 71

92 1 1 9 17 25

pK a(This work)

FIGURE 1. Correlation of acidities of the studied acids and acidities reported in the literature. Narrow line corresponds to ideal situation with unity slope, thick line on the other hand to actual situation. The correlation is pKa(Literature) = 0.72 + 2 0.930pKa(This work); s(intercept)=0.34, s(slope)=0.017, n=12, r =0.997, S=0.209.

For several acids belonging to the scale, the pKa values in AN has been reported to the literature. From the Table 3 and Figure 1 it is clearly seen, on the scale above picric acid, the weaker the acid the greater the difference of pKa values of literature and this work. Usually all of the error sources, most importantly moisture and impurities lead to a contraction (not expansion) of the scale. Unfortunately, great bulk of literature data are for compounds that do not behave very well in AN solution. In our case, the scale is built up with well-behaved compounds (CH- acids with extensive delocalized negative charge) which form no homoassociation and heteroassociation complexes and have intensive spectra. More problematic compounds (eg acetic acid, benzoic acid) are measured in reference to these well-behaved compounds. The relative acidities of the compounds included in the scale can be determined at very high accuracy and many of the error sources influence both

compounds in a similar way and at least partially cancel out. These are the reasons to become sure of validity of pKa data of present work (#%^ võibolla ilusam lause). On the scale below picric acid there are too little data to make conclusions. Acetonitrile solvates anions more weakly than cations what is the main reason why homoassociation is more extensive for some of the anions. In the Table 4 are homoassociation constants used in this work in calculations and constants reported in the literature. In the case of weak acids, homoassociation constans are greater in this work. As thougt different pKa values, the homoassociation constants may be smaller due to different experimental conditions, mainly impurities and larger water content in AN. The homoassotiation constants in Table 4 are not measured directly and therefore must look on these with caution.

TABLE 4. Homoassociation Constants Used in the Calculations of ∆pKa and Homoaccociation Constants of Acids Reported in the Literature.

log K − No Compound AHA This work Literature 10 Acetic acid 4.5 3.67 a, b 3.70 c d, e 12 2-NO2-phenol - 2.0 2.20 f 2.36 g 15 Benzoic acid 3.9 3.60 a, c, h 19 (CF3)3COH 4.8 - 23 2,3,5,6-F4-Phenol 4.2 - 24 2,3,4,5,6-F5-Phenol 4.2 - 26 1-C10F7OH 3.3 - 30 2-C10F7OH 3.8 - 32 4-C6F5-2,3,5,6-F4-Phenol 4.0 - d, e 40 2,4-(NO2)2-Phenol - 2.0 2.08 f 2.14 g 41 4-CF3-2,3,5,6-F4-Phenol 3.6 - 46 4-NC5F4-OH 3.6 - 62 Picric acid - 0 d 0.30 f 71 TosOH 3.0 2.9 i 2.95 j 73 1-C10H7SO3H 2.9 - 75 4-Cl-C6H4-SO3H 3.0 - 76 3-NO2-C6H4-SO3H 2.9 - 77 4-NO2-C6H4-SO3H 2.9 - a Reference 34. b Reference 49. c Reference 50. d Reference 51. e Reference 4. f Reference 47. g Reference 44. h Reference 52. i Reference 35. j Reference 43.

In Table 4, the homoassociation constants of sulfonic acids (71, 73, 75, 76, 77) are not measured in this work but are estimate values by TosOH (71). In the case of sulfonic acids 73, 76 and 77, the implementation of the homoassociation constant makes mostly no difference in the ∆pKa value due to the small concentrations.

Concentrations of substances were too small to associate nitro substituted phenols during the measurements. There are still published some values of homoassociation constants of these compounds (Table 4).

The stability of homoassociation complex of phenols increase as the strength of acids decrease. Certainly there are some exceptions. 2-nitrophenol (12) has no remarkable ability to form homoassociation complex. Substitution of phenol with a nitro group in the ortho position to the hydroxy group reduces homoassociation mainly due to inramolecular hydrogen bond of neural molecul.

The reason why 1-and 2-perfluoronaphtols (26 and 30) have smaller homoassociacion constant is that these substances have stronger ability to delocalize negative charge than perfluorophenol. 1-perfluoronaphthol may have smaller homoassociation constant than 2- perfluoro-naphthol because of sterical hindrance, possibly, but not peri-interaction of OH group and fluorine 5 .

Discussion

Many compounds investigated in this work have also been studied in DMSO, 1,2- dimethoxyethane (DME), heptane (C7) solutions and in the gas phase (see Table 5). To evaluate the effect of structure and solvent on the acidity of studied acids upon changing from AN solution to other media (DMSO, DME, C7, gas phase), the statistical analysis of the data from Table 2 was perfomed. Equation 13. describes the correlation between pKa values in AN and in other media, where a and b are constants.

pKa(AN) = b + a pKa (other media) (13.)

The results of this analysis are given in Table 5.

Also analyzed the relative contributions of resonance and field-inductive effects to the 0 acidities in AN solution, what characterizes the equation 14., where pKa , ρF, ρR are the constants and σF, σR are respectively the substituents field-induction (electronegativity) and resonance effect constants 53 .

0 pKa(AN) = pKa + ρFσF + ρRσR (14.)

The results of this analysis are given in Table 6. It is seen that the sensitivity of the acidity of ethyl aryl cyanoacetates to electronegativity (σF) and resonance effect (σR) of the substituents are significant lowest (of first four series in the Table 6) which indicates weaker delocalization of the negative charge of carbanionic forms of these compounds. In

case of phenols opposite pattern appears – delocalization of the negative charge into ring is considerable. As can be seen from slopes for series 1, 1.3, 2, 3 in Table 5, the solvation effects onto acidity of compounds studied in DMSO, DMF and AN are very close relative to the ones’s in C7 (%# vlasov kirjutas, peab lähemalt uurima).

Acetonitrile versus dimethyl sulfoxide. In Figure 2 the pKa values in of the studied acids are plotted against the corresponding acidities in DMSO. Narrow line corresponds to the overall correlation (see also Table 5 series 1) except where the compounds 71 and 74 have bene eliminated due to (#haruldane sõna: garish deviation) the very large deviations, -4.6 and -6.4 pKa units, in AN respectively. The acidities of these very strong acids such as these two are leveled in DMSO to protonated DMSO solution. Dashed and cannot be reliably determined. The dashed line corresponds to the correlation of all CH- acids (Table 5 series 1.2) except where the compounds 47 and , 51 and yet 74. Thick have been eliminated. The thick (#oleks kena, kui alamperekondade jooned oleksid sama jämedad ja võibolla siis üldkorrelatsiooni oma jämedam) solid line corresponds to the OH-acids (series 1.1) and dotted line to the NH-acids (series 1.3). Compounds 47 (1.3 units stronger in AN) and 51 (1.9 units stronger in AN) in the case of CH-acids and compound 46 (1.3 units stronger in AN) in the case of OH-acids deviates from regression line. Compounds 47, 51 and 46 strongly deviate from the regression line (by 1.3, 1.9 and 1.3 pKa units in AN, respectively). All these are perfluoro-4-pyridinyl group containing compounds and they are stronger in AN solution if anticipatethat it could be expected from the correlation. In the perfluoro-4-pyridinylpyridyl group containing compounds the negative charge is strongly localized on a large scale intothe nitrogen. of the 4-pyridyl fragment.

In DMSO solution anions are even more slightly solvated as in AN and thus these type of dissociated compounds are not in DMSO solution so favored and are therefore weaker in DMSO. #tead, nii vist pole. DMSO on tegelikult märksa kõvem anioonide solvateerimises, kui on MeCN. See ka seletab, miks on enam vähem 10 pKa ühikuline vahe nende kahe keskkonna vahel ja ka seda, miks on happeid, mis on DMSO-s isegi kõvemad, kui vees (vt näiteks seda hiljutist Terrier et al artiklit, kus on just selliseid sees). According to the correlation of pKa values in AN and DMSO, #Huvitav, ega siin ei saa olla mingi taotomeerne vigur? Et tegelikult on see näiteks DMSO-s hoopis NH hape? Kas meil mõnda neist on ka suuremas koguses? Saaks äkki NMR-ga vaadata…

2-nitrophenol (12) also deviates (significantly from the correlation: it is 1.3 units weaker in AN) and it is weaker acid in AN, than could be expected from the correlation. This is probably due to the intramolecular hydrogen bond that take effectis more efficient in AN intensively than in DMSO because DMSO is a much stronger hydrogen bond acceptor than AN [kolthoffi viide!!#]. #kas HPi-ga sellist asja pole? 2,4-dinitrofenooliga?

FIGURE 2. Correlation of the acidities of the studied acids in AN and DMSO. Narrow line corresponds to the overall correlation except compounds 71 and 74, other to the correlation of CH-acids, NH-acids and OH-acids.

Acetonitrile versus gas phase. In Figure 3 are plotted pKa values in AN and gas phase acidities. Narrow in the gas phase have been plotted. The narrow line corresponds to the overall correlation (see also Table 5 series 4), dashed line to NH-acids (series 4.6), dotted line to OH-acids (series 4.1 and 4.2) and thick solid lines to the correlations of different group of CH-acids – diarylacetonitriles (series 4.3), ethyl aryl cyanoacetates (series 4.5) and arylmalononitriles (series 4.4).

#selle lause võiks vist siit tahapoole viia From the Figure 3 and Table 5 it is seen the sequent evidence to the scarce evident that the sensitivity of towards the substituents in ring in the case of ethyl aryl cyanoacetates in AN solution is very low – the slope of the correlation line is the lowest of all. .

The value of the slope of the regression line indicates that in the gas phase there are the acidities are substantially most senstitiv to more sensitive to the structure changes of the compounds than in any otherof the condensed phasephases (see Table 5). Unlike in DMSO solution allindividual correlation lines are found for all the different classes of compounds must correlate individually. In heptan also. Also in heptane the sensitivity to structure of the acidities of the studied compounds towards the structure is considerable compared to AN, DMSO and DME but not as extensive as in the gas phase. In the gas phase 2,4-dinitrophenol (40) deviates from the by a wide margin, in AN according to correlation pKa value ougt to be be from the correlation line being around 3.1 pKa units lowerweaker in acetonitrile than it is.predicted from the correlation. Probably the nitro group in para position is responsible tofor this effect because 2-nitrophenol (12) does not deviate from the regression line. Unfortunately measuring (#ACS ei luba eriti sellseid sõnu nagu unfortunately, pidades neid emotsioonide väljenduseks, mis pole teaduses kohane…) Measuring the pKa value 4-nitrophenol in AN was complicated due to greatthe 54 high homoassociation complex formation capability (log K − = 3.67, 3.52 and 3.15 AHA 51 ) #kas seda saab siin sedasi välja tuua – retsensent küsib – kuidas te siis AcOH mõõdetud saite? and consequently from that due to this the spectra of the compound in solution of different acidity showed irregular behavior at longer wavelenghtwavelength 44 area. Anyway, pKa value of 4-nirophenol is known from the literature – 20.9 (also reported 20.7 51 ). In Figure 3 is we have used the revised value 21.7 with(found from the correlation equation at given in Figure 1. #Siin ma pole kindle, kas ma õigesti aru sain). Using these data we observe that 4-nitrophenol deviates from the correlation of OH-acids by 2.3 pKa units being weaker in AN. than expected and thus supporting the above- mentioned hypothesis.

Recently have been our group has described substituent solvation assisted resonance (SSAR) effects 30 but mostly in DMSO solution. SSAR effects in case of this type of compounds means higher solution acidity. The SSAR effects led to higher solution acidity in the case of #millised ained? See ref 30 on CH hapete kohta. However, in this circumstancesour case it seems to be vice versa – compounds containing strong para- resonance acceptor substituent containing compounds have lower solution acidity in AN. It seems the reason is due to strongerOne of the reasons can be a strong intermolecular H- bond 5 . But , but a detailed mechanism of this effect affordsneeds an additiveadditional study

FIGURE 3. Correlation between pKa values in AN and pKa(GA) values. Narrow line corresponds to the overall correlation, other to the correlation of CH-acids (diarylacetonitriles, ethyl aryl cyanoacetates and arylmalononitriles), NH-acids and phenols with some exceptions. (pKa (GA) = GA·2.30/R·T = GA/1.364).

Table 5 series 2 describes correlation between pKa values of all compounds (except 11) in AN and 1,2-dimethoxyethane (DME). Compound 11 deviates from the correlation having 5.3 units lower acidity in AN if calculate from correlation. The reason is connected with – 37 the strong influence of contact ion pairs for Li salt of C6F5C (COOEt)2 carbanion (% selgitada). However, all the correlations (series 2, 2.1, 2.2, 2.3) show similar sensitivity of acidities of compounds in AN.

Para fluoro substituent. It is interesting to compare different classes of compounds in terms of para fluoro and para hydrogen substituents. For phenylmalononitriles pKa value of compound 52 is slightly lower than pKa value of compound 53. For diphenylacetonitriles (17 and 18) and phenols (23 and 24) the pKa values of two compounds are practically equal. However, for ethyl phenyl cyanoacetates (33 and 36) the difference is 0.3 units. It seems that the more extensive is the delocalisation of negative charge into ring (eg phenols, diarylacetonitriles) the smaller is the difference between these different para-substituted compounds. Differences between compounds 61 and 63 (0.6 units) and 81 and 83 (0.4 units) also proves this. From Table 6 series 5 and series 6 it is seen that the sensitivity of the acidity of these classes of compounds to electronegativity (σF) and resonance effect (σR) of the substituents are rather low. This effect does not appear only in AN but also in DME 37 (see Table 2) and in water 36, 55 but not in the gas phase 39 . The reason for this might be that althought fluorine is an electronegative substituent, it is also a weak resonance donor 53 . The fluorine is in the para position to the acidity centre, which means that the inductive/fiel effect is weakened by the distance but not the resonance effect. Explanation based on MO theory is that due to short bond of fluorine appears overlaping to p-orbitals of fluorine and π-orbitals of ring and this gives more electron density to the ring and lowers the acidity of para-fluoro substituted compounds.

Yagupolskii’s substituents. A principle of building strong electron-acceptor substituents with extensive conjugated chains was introduced by L. M. Yagupolskii and co-workers

56 . N-phenyltrifluoromethanesulfonamides 57, 58, 61, 63, 64, 69 and N,N’- bis(trifluoromethylsulfonyl)benzamidines 78, 79, 81, 83, 84, 88 may be considered as derivates of benzoic acids. It is seen (Table 1) that replacement of one oxygen atom by –N–Tf group in benzoic acid the acidity increases 10.4 pKa units whereas the second replacement of oxygen atom leads to a further increase 4.9 pKa units. The total acidifying effect is 15.3 units. More about these compounds in reference 2. Compounds 87, 91 and 93 can also consider as derivates of sulfonimides 60, 65 and 70 respectively, where an oxygen atom of a sulfonyl group adjacent to the NH acidity center is replaced by =N–Tf fragment. The acidifying effects of the substitution are 5.8, 5.7 and 5.4 units respectively. The sulfonic acids 71, 75 and 77 can be considered as derivates of sulfonic asids 80, 86 and 90 where fragment =O is replaced with =N–Tf and differences between these compounds are 2.3, 1.8 and 2.2 units, respectively. The reason why these differences are not similar to those for benzene sulfonimides (previous section) is that the replacement of oxygen atom with =N–Tf sets to dominate one of the tautomeric forms as NH-acid not OH-acid 1, 57 .

Comparison of CH-acids and phenols. Arylmalononitriles, ethy laryl cyanoacetates and diarylacetonitriles are the CH-acids with the similar substituents studied in this work. Some of the studied phenols have the same substituents that above-mentioned CH-acids. From the correlations between aryl(perfluorophenyl)acetonitriles, arylmalononitriles, ehyl aryl cyanoacetates and substituted phenols accures again the sensitivity of the substituents to the acidity in AN. Increase of the sensitivity is as follows: ehyl aryl cyanoacetates < arylmalononitriles < aryl(perfluorophenyl)acetonitriles < phenols. The coefficient of determination of these correlations – r2 – are usually between 0.97 to 1.00. Correlation between phenols and ethy laryl cyanoacetates is not so good – r2 is equal to 0.95 whereat the most deviating compounds are with the groups of 2-perfluoronaphthyl and perfluorophenyl. This indicates the relevant difference between these two types of compounds – in the case of phenolates the delocalization of negative charge is considerable.

#%kaitsmise hapete joonis (ühest struktuurist teise pKa muutus) (miinused – v6tab palju ruumi, juurde pikk jutt, TMG refereele seda tyypi joonis ei istunud; plussid – hea ylevaatlik, v6ibolla just meeldiks). #%THF

The Scale as a Tool for further Acid-Base Studies. %#Siin rõhutada, et selle skaala suur mote on selles, et teha tulevastele uurijatele elu lihtsamaks. Tuua näiteid (Heemstra Tetrahedron 2004, …) Peab proovima välja tuua omadused, mis meie skaalal on ja mõtted kasutamiseks: The scale has been compiled using primarily compounds with favorable spectral properties and low tendency to homoconjugation, such as phenylmalononitriles, diphenylacetonitriles. #%^võibolla siia päris mingi gradueering, millised on head ained ja millised mitte. The users are advised to use first of all the compounds in group # and only in the case no suitable compound is found turn to group #.

#%Siia võiks veel juhiseid panna tulevastele mõõtjatele.

Small samples of the compounds are available from the authors on request. (#%^Minu lemmiklause siia artiklisse! Kommenteerige!)

$*^% Comments and additional discussion are very welcome!

Conclusions

#kokkuvõte

Acknowledgements

This work was supported by Grants Nos. 0000%^ and 0000%^ from the Estonian Science Foundation.

Supporting Information Available: Synthesis and compound characterization data of compouds, joonised ja k6ik muu, mis läheb sinna###. This Information is available free of charge via the Internet at http://pubs.acs.org.

TABLE 5. Statistical analysis of data from Table 2 in terms of equation 13..

No Series a b s(a) s(b) S r2 n Compounds 1 DMSO All acids, except 71 and 74 0.980 12.31 0.044 0.38 1.167 0.933 36 1 – 10, 12, 15, 16, 18 – 20, 24, 26, 27, 30, 31, 33, 34, 36, 37, 39, 40, 42 – 44, 46, 47, 49, 51, 52, 56, 62 1.1 OH-acids, except 12 and 46 0.884 11.80 0.036 0.32 0.406 0.989 9 10, 15, 19, 24, 26, 30, 34, 40, 62 1.2 CH-acids, except 47 and 51 1.038 12.91 0.013 0.10 0.247 0.997 19 1, 2, 4, 7 – 9, 16, 18, 20, 31, 33, 36, 37, 39, 42 – 44, 52, 56 1.3 NH-acids 1.083 10.60 0.047 0.54 0.428 0.994 5 3, 5, 6, 27, 49 2 DME All acids, except 11 0.941 14.58 0.036 0.25 0.494 0.980 16 1, 4, 9, 14, 16 – 18, 20, 25, 29, 31, 36, 38, 39, 42, 45 2.1 Diarylacetonitriles and ethyl aryl cyanoacetates 1.044 14.21 0.029 0.16 0.262 0.993 12 4, 14, 17, 18, 20, 25, 31, 36, 38, 39, 42, 45 2.2 Diarylacetonitriles 1.034 14.30 0.036 0.22 0.300 0.992 9 4, 14, 17, 18, 20, 25, 31, 42, 45 2.3 Fluorenes 0.927 14.25 0.084 0.84 0.609 0.984 4 1, 9, 16, 29 3 C7 All acids 0.756 19.39 0.036 0.13 0.315 0.982 10 6, 8, 13, 14, 18, 20, 22, 28, 29, 31 4 GA All acids 0.559 -110.27 0.058 13.37 2.834 0.702 41 2 – 4, 6 – 8, 10, 12, 14 – 16, 18 – 20, 24, 26, 27, 29, 30, 31, 33, 36, 37, 39, 40, 42, 43, 44, 46 – 48, 50 – 54, 56, 62, 66, 74, 89 4.1 OH-acids, except 10, 15, 26, 30 0.635 -129.53 0.060 13.87 1.422 0.957 7 12, 19, 24, 40, 46, 62, 89 4.2 OH-acids, except also 40 0.651 -133.87 0.029 6.70 0.679 0.992 6 12, 19, 24, 46, 62, 89 4.3 Diarylacetonitriles 0.643 -127.15 0.048 11.00 0.943 0.962 9 2, 4, 14, 18, 20, 31, 42, 43, 51 4.4 Arylmalononitriles 0.559 -111.78 0.084 18.82 0.830 0.880 8 37, 48, 50, 52 – 54, 56, 66 4.5 Ethyl aryl cyanoacetates 0.369 -67.29 0.014 3.12 0.098 0.996 5 33, 36, 39, 44, 47 4.6 NH-acids 0.571 -109.17 0.006 1.38 0.052 1.000 3 3, 6, 27

TABLE 6. Statistical analysis of data from Table 1 in terms of equation 14..

0 0 2 No Series pKa ρF ρR s(pKa ) s(ρF) s(ρR) S r n Compounds 1 Ethyl aryl cyanoacetates 4-X-C6F4CH(CN)COOEt 18.08 -3.41 -4.86 0.00 0.01 0.01 0.00 1.000 4 33, 36, 39, 44 2 Aryl malononitriles 4-X-C6F4CH(CN)2 12.90 -4.31 -7.73 0.08 0.23 0.39 0.12 0.998 4 50, 52, 53, 56 3 Diarylacetonitriles (4-X-C6F4)(C6F5)CHCN 20.98 -4.47 -8.03 0.10 0.27 0.45 0.14 0.996 5 14, 17, 18, 20, 31 4 Phenols a 4-X-C6F4OH 19.96 -5.19 -9.28 0.13 0.38 0.60 0.20 0.994 5 23, 24, 32, 41 and 5 N-aryltrifluoromethane- sulfonamides 4-X-C6H4C(=O)NHTf 11.09 -2.09 -2.34 0.12 0.25 0.33 0.16 0.976 5 57, 58, 61, 63, 64, 69 6 N,N’-bis(trifluoromethylsulfonyl)benzamidines 4-X-C6H4(=NTf)NHTf 6.15 -1.35 -1.50 0.10 0.21 0.28 0.13 0.960 5 78, 79, 81, 83, 84, 88 a 5 4-Me-C6F4OH pKa value in AN 20.3 units, in correlation used revised value 21.0, that led to significantly improvement correlation. Revised value calculated with correlation at Figure 1.

References

1. Leito, I.; Kaljurand, I.; Koppel, I. A.; Yagupolskii, L. M.; Vlasov, V. M. J. Org. Chem. 1998, 63, 7868-7874.

2. Yagupolskii, L. M.; Petrik, V. N.; Kondratenko, N. V.; Sooväli, L.; Kaljurand, I.; Leito, I.; Koppel I. A. J. Chem. Soc., Perkin Trans., 2. 2002, 11, 1950-1955.

3. Izutsu, K. Acid-Base Dissociation Constants in Dipolar Aprotic Solvents. IUPAC Chemical Data Series No. 35, Blackwell Scientific, Oxford, 1990.

4. Coetzee, J. F. Prog. Phys. Org. Chem. 1967, 4, 45-92.

5. Vlasov, V. M.; Sheremet, O. P. Izv. Sib. Otd. Akad. Nauk SSSR, Ser. Khim. 1982, 114-120.

6. Chantooni, M. K.; Kolthoff, I. M. J. Phys. Chem. 1976, 80, 1306-1310.

7. (a) Bykova, L. N.; Petrov, S. I. Usp. Khim. 1970, 39, 1631-1660. (b) Dyumaev, K. M.; Korolev, B. A. Usp. Khim. 1980, 49, 2065-2085.

8. Kolthoff, I. M.; Chantooni, M. K. Jr. J. Phys. Chem. 1968, 72, 2270-2272.

9. Kaljurand, I; Kütt, A.; Sooväli, L.; Rodima, T.; Mäemets, V.; Leito, I.; Koppel, I. A. J. Org. Chem. 2005, 70, 1019-1028.

10. Vlasov, V. M.; Yakobson, G. G. Zh. Org. Khim. 1981, 17, 242-250.

11. Vlasov, V. M.; Zakharova, O. V.; Yakobson, G. G. Izv. Sib. Otd. Akad. Nauk SSSR, Ser. Khim. 1975, 80-94.

12. Vlasov, V. M.; Os'kina, I. A.; Starichenko, V. F. Zh. Org. Khim. 1997, 33(5), 660- 664

13. Vlasov, V. M.; Yakobson, G. G. Zh. Org. Khim. 1973, 9, 1024-1031.

14. (a) Vlasov, V. M.; Terekhova, M. I.; Petrov, E. S.; Shatenshtein, A. I. Zh. Org. Khim. 1981, 17(10), 2025-2031. (b) Vlasov, V. M.; Yakobson, G. G. Zh. Org. Khim. 1981, 17(10), 2192-2201.

15. Vlasov, V.M.; Zakharova, O. V.; Yakobson, G. G. Izv. Sib. Otd. Akad. Nauk SSSR, Ser. Khim. 1977, 127-136.

16. Oskina, I. A.; Vlasov, V. M. Izv. Sib. Otd. Akad. Nauk SSSr, Ser. Khim. 1984, 4, 102- 113.

17. Vlasov, V. M.; Yakobson, G. G. Zh. Org. Khim. 1976, 11, 2418-2426.

18. Vlasov, V. M.; Yakobson, G. G.; Petrov, E. S.; Shatenshtein, A. I. J. Fluorine Chem. 1977, 9(4), 321-325.

19. Vlasov, V. M.; Yakobson, G. G. Usp. Khim. 1974, 43, 1642-1668.

20. Gandelsman, L. Z.; Trushanina, L. I. Ukr. Khim. Zh. 1990, 56, 1118.

21. McLoughlin, V. C. R. ; Thrower, J. Chem. Ind. 1964, 36, 1557.

22. Troughton, E. B.; Molter, K. E.; Arnett, E. M. J. Am. Chem. Soc. 1984, 106, 6726- 6735.

23. Rõõm, E.-I.; Kaljurand, I.; Leito, I.; Rodima, T.; Koppel, I. A.; Vlasov, V. M. J. Org. Chem. 2003, 68, 7795-7799.

24. Leito, I.; Rodima, T.; Koppel, I. A.; Schwesinger, R.; Vlasov, V. M. J. Org. Chem. 1997, 62, 8479-8483.

25. Kaljurand, I.; Rodima, T.; Leito, I.; Koppel, I. A.; Schwesinger, R. J. Org. Chem. 2000, 65, 6202-6208.

26. Rodima, T.; Kaljurand, I.; Pihl, A.; Mäemets, V.; Leito, I.; Koppel, I. A. J. Org. Chem. 2002, 67, 1873-1881.

27. Kaljurand, I. ; Rodima, T; Pihl, A.; Mäemets, V.; Leito, I.; Koppel, I. A.; Mishima, M. J. Org. Chem. 2003, 68, 9988-9993.

28. Inamo, M.; Kohagura, T.; Kaljurand, I.; Leito, I. Inorg. Chim. Acta. 2002, 340, 87-96.

29. Bordwell, F. G.; Branca, J. C.; Bares, J. E.; Filler, R. J. Am. Chem. Soc. 1988, 53, 4, 780-782.

30. Koppel, I. A.; Koppel, J.; Pihl, V.; Leito, I.; Mishima, M.; Vlasov, V. M.; Yagupolskii, L. M.; Taft, R. W. J. Chem. Soc. Perkin Trans. II 2000, 1125-1133.

31. Koppel, I. A.; Koppel, J.; Maria, P.-C.; Gal, J.-F.; Notario, R.;Vlasov, V. M.; Taft, R. W. Int. J. Mass Spectrom. Ion Processes. 1998, 175, 61-69.

32. Bordwell, F.G. Acc. Chem. Res. 1988, 21, 456-463.

33. Ritchie, C. D.; Uschold, R. E. J. Am. Chem. Soc. 1968, 90, 2821-2824.

34. Kolthoff, I. M.; Chantooni Jr, M. K.; Bhowmik, S. J. Am. Chem. Soc. 1968, 90, 23- 28.

35. Fujinaga, T; Sakamoto, I. J. Electroanal. Chem. 1977, 85, 185-201.

36. Kortüm, G.; Vogel, W.; Andrussov, K. Dissotziationskonstanten Organischen Säuren in wasseriger Lösung. London, Butterworths, 1961.

37. Vlasov, V. M.; Petrov, E. S.; Zakharova, O.V.; Shatenshtein, A. I.; Yakobson, G. G. Zh. Org. Khim. 1979, 15, 138-146.

38. Lebedeva, T. I., Petrov, E. S., Shatenshtsein, A. I. Zh. Org. Khim. 1977, 8, 905-909.

39. Koppel, I. A.; Taft, R. W.; Anvia, F.; Zhu, S.-Z.; Hu, L.-Q.; Sung, K.-S.; DesMarteau, D. D.; Yagupolskii, L. M.; Yagupolskii, Y. L.; Ignat’ev, N. V.; Kondratenko, N. V.; Volkonskii, A. Y.; Vlasov, V. M.; Notario, R.; Maria, P.-C. J. Am. Chem. Soc. 1994, 116, 3047-3057.

40. Bartmess, J. E. Negative Ion Energetics Data; Mallard, W. G.; Linstrom, P. J., Eds.; NIST Standard reference Database Number 69, August 1997, National Institute of Standards and Technology, Gaithersburg MD, 20899 (http://webbook.nist.gov).

41. Kebarle, P.; McMahon, T.B. J. Am. Chem. Soc. 1977, 99, 2222-2230.

42. Taft, R.W.; Koppel, I. A.; Topsom, R.D.; Anvia, F. J. Am. Chem. Soc. 1990, 112, 2047-2052.

43. Jasinski, T.; El-Harakany. A. A.; Halaka, F. G.; Sadek, H. Croat. Chem. Acta 1987, 51, 1-10.

44. Kolthoff, I. M.; Chantooni, M. K., Jr. J. Am. Chem. Soc. 1969, 91, 4621-4625.

45. Galezowski, W.; Stanczyk, M.; Jarczewski, A. Can. J. Chem. 1997, 75, 285-288.

46. Juillard, J.; Loubinoux, B. C. R. Acad. Sci., Ser. C. 1967, 264, 1680-.

47. Kolthoff, I. M.; Chantooni, M. K. Jr. J. Am. Chem. Soc. 1965, 87, 4428-4436.

48. Webster, O. W. J. Am. Chem. Soc. 1966, 88, 3046-3050.

49. Kolthoff, I. M.; Chantooni, M. K., Jr. J. Am. Chem. Soc. 1975, 97, 1376-1381.

50. Kolthoff, I. M. Anal. Chem. 1974, 46, 13, 1992-2003.

51. Coetzee, J. F.; Padmanabhan, G. R. J. Phys. Chem. 1965, 69, 9, 3193-3196.

52. Kolthoff, I. M.; Chantooni, M. K., Jr. J. Phys. Chem. 1966, 70, 856-866.

53. Hansch, C.; Leo, A.; Taft, R. W. Chem. Rev. 1991, 91, 165-195.

54. Kolthoff, I. M.; Chantooni, M. K. Jr.; Bhowmik, S. J. Am. Chem. Soc. 1966, 88, 5430-5439.

55. Tables of Rate and Equilibrium Constants of Heterolytic Organic Reactions; Palm, V. Ed.; VINITI: Moscow-Tartu, 1975-1985.

56. (a) Kondratenko, N. V.; Popov, V. I.; Radchenko, O. A; Ignat’ev, N. V.; Yagupolskii, L. M. Zh. Org. Khim. 1986, 22, 1716-1721. (b) Yagupolskii, L. M. Aromatic and Heterocyclic Compounds with Fluorine-Containing Substituents; Nauokova Dumka: Kiev, 1988; p 319.

57. Yagupolskii L. M.; Kondratenko, N. V.; Iksanova, S. V. Zh. Org. Khim. 1995, 31, 747-752.