Aust. J. Chem.

, 1993, 46, 185-194

Acid-Base Equilibria of Substituted Pyridine N-Oxides i N , -Dimethylformamide n N and Dimethyl Sulfoxide

Lech ChmurzyriskiA>B and Zygmunt WarnkeA
A

Department of Chemistry, University of G d d s k , 80-952 Gdahk, Poland. Author to whom correspondence should be addressed.

Abstract Acidity constants have been determined potentiometrically for a variety of conjugate acids of substituted pyridine N-oxides in N,N-dimethylformamide (dmf) and dimethyi sulfoxide (dmso). The pKa values in these solvents varied in the same direction and correlated with the pKa values of these species in water and in the protophobic aprotic solvent acetonitrile. Further, a linear relationship has been established between the pK, values in the two protophilic aprotic solvents under study. The most basic substituted pyridine N-oxides exhibited a weak tendency towards cationic homoconjugation in dmf, whereas in the more basic dmso the homoconjugation equilibrium was not established for any of the heterocyclic N-oxides. The phenomenon of cationic homoconjugation was also not observed with pyridine as a representative of heterocyclic amines, both in dmf and dmso. This finding complies with the results obtained in other polar aprotic solvents.

Introduction
N,N-Dimethylformamide (dmf) is an aprotic protophilic solvent of very weak acidity and relatively strong basicity. It exhibits differentiating properties with regard to acids.' It has also been found that uncharged acids with 'hard' anions are weaker in this solvent than in water. For instance, hydrochloric acid, substituted benzoic acids and phenols are weak acids in dmf, while perchloric, picric and hydrobromic acids are completely dissociated in this ~ o l v e n t On the other hand, .~ cationic acids, BH+, are 2-10 times as strong as in water. The group of aprotic protophilic solvents also includes dimethyl sulfoxide (dmso). Its basicity is comparable with that of water and slightly higher than that of dmf.3-5 dmso, like drnf, exhibits differentiating properties with regard to some acid^.^,^ The tendency towards homoconjugation in dmso has been found to be weaker than in dmf.8$9
Thomas, A. B., and Rochow, E. G., J. Am. Chem. Soc., 1957, 79, 1843. Sears, P. G., Wolford, R. K., and Dawson, L. R., J. Electrochem. Soc., 1957, 103, 633. Kolthoff, I. M., and Reddy, T. B., Inorg. Chem., 1962, 1, 189. Ritchie, C., and Uschold, R., J. Am. Chem. Soc., 1967, 89, 1721. Amett, E. M., Prog. Phys. Org. Chem., 1963, 1, 363. Kolthoff, I. M., Chantooni, M. K., Jr, and Bhowmik, S., J. Am. Chem. Soc., 1968, 90, 23. Kolthoff, I. M., and Chantooni, M. K., Jr, J. Am. Chem. Soc., 1968, 90, 5961. Kolthoff, I. M., Chantooni, M. K., Jr, and Smagowski, H., Anal. Chem., 1970, 42, 1622. Chantooni, M. K., Jr, and Kolthoff, I. M., J. Phys. Chem., 1973, 77, 527.
00049425/93/020185$05.00

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Manuscript received 19 May 1992

L. Chmurzyhki and Z. Warnke

The primary objective of this study was to determine the equilibrium constants for acid dissociation of a variety of conjugate acids of substituted pyridine N-oxides in dmso and dmf. Further, it was aimed at checking if the pKa values of the cationic conjugate acids of substituted pyridine N-oxides in the protophilic aprotic solvents correlate linearly with the pK, values in the protophobic aprotic solvent acetonitrile, and the amphiprotic solvent water. One of the purposes was also to check whether there exists a linear correlation between the pKa values of the cationic acids in both drnf and dmso. It is known that the problem of correlation of the acidity constants, in various solvent^,^^^^-^^ is especially complex with cationic BH+ acids.6 For instance, no constant differences have been found in Finally, the pK, values in aprotic solvents such as dmso, dmf and a~etonitrile.~ it was of interest to prove whether, and to what extent, the enhanced (relative to acetonitrile) basicities of drnf and dmso suppress cationic homoconjugation, as was the case with anionic homoconjugation.6~9~14 Experimental
Purification of the substituted pyridine N-oxides as well as the preparation and purification of the perchlorates of these N-oxides have been described elsewhere.15-l7 The quinoline N-oxide and pyridine perchlorates were obtained in a similar way. Tetrabutylammonium picrate and perchlorate were prepared and purified, whereas picric acid and tetrabutylammonium chloride (both from Fluka AG) were purified as described previously.18 Tetrabutylammonium 2,6-dinitrophenolate was prepared by mixing together equimolar quantities of purified 2,6dinitrophenol and a 40% aqueous tetrabutylammonium hydroxide solution. The salt was crystallized twice from ethyl acetate. drnf was preliminarily purified by azeotropic distillation with benzene. To 1dm3 of drnf were added 100 cm3 of benzene an 50 cm3 of water, and the mixture was distilled under atmospheric pressure, the water-benzene azeotrope boiling at 343-348 K being collected. The drnf remaining was shaken with BaO and left for several days. Then the solvent was filtered and distilled in a nitrogen atmosphere under reduced pressure. The purified drnf had a specific S conductivity of the order of 8 x l 0 - ~ cm-' and less. The distillate was kept over previously sintered and dried 4A molecular sieves. dmso was kept over dried 4A molecular sieves for 24 h. It was then dried for several days over CaHz (5 g dm-3). After decantation, dmso was distilled in a nitrogen atmosphere under reduced pressure. The specific conductivity of the purified solvent was of the order of 6x10-' S cm-l. Both the equipment and procedure applied for the potentiometric and conductometric measurements have been described e l ~ e w h e r e . l ~ The glass indicator electrode was -~~ calibrated in both solvents against buffer solutions containing tetrabutylammonium picrate mol dm-3) and picric acid (c. lo-' rnol dm-3) at a fixed ionic (c.

I. M., Anal. Chem., 1974, 46, 1992. Clare, B. W., Cook, D., KO, E. F. G., Mac, Y. C., and Parker, A. J., J. Am. Chem. Soc., 1966, 88, 1911. l2 Chantooni, M. K., Jr, and Kolthoff, I. M., J. Phys. Chem., 1974, 78, 839. l3 Pawlak, Z., and Magohki, J., J. Chem. Soc., Faraday Trans. 1, 1982, 78, 2807. l4 Kolthoff, I. M., and Chantooni, M. K., Jr, J. Phys. Chem., 1966, 70, 856. l5 Chmurzyliski, L., Pawlak, Z., and Myszka, H., J. Mol. Struct., 1982, 80, 235. l6 Chmurzyliski, L., Pawlak, Z., and Myszka, H., Pol. J. Chem., 1985, 59, 639. l7 Wawrzydw, A., Sokolowski, K., Chmurzyhki, L., and Liwo, A., J. Mol. Struct., 1988, 174, 235. l8 Chmurzyliski, L., Wawrzyn6w, A., and Pawlak, Z., Electrochim. Acta, 1990, 35, 665. l9 Chmurzyliski, L., Wawrzyn6w, A., and Pawlak, Z., J. Chem. Soc., Faraday Trans. 1, 1989, 85, 4269. 20 Chmurzyliski, L., Pol. J. Chem., 1991, 65, 1387.
lo Kolthoff,
l1

Acid-Base Equilibria of Pyridine N-Oxides

The reference calomel electrode was modified by replacing the aqueous KC1 solution with a 0.1 mol dm-3 tetrabutylammonium chloride solution in the appropriate solvent (dmf or dmso). All measurements were carried out at 298 l f0.1 K.

Results and Discussion

Conductometric Measurements

According to literature data,2t21 the extent of dissociation of perchlorates of substituted pyridine N-oxides should be large in dmf and dmso. To verify this, electrical conductivity measurements of dmf and dmso solutions of pyridine N-oxide perchlorate (as a representative of this class of compounds) were performed over a range of low concentrations. Some of the results in dmf are shown in Fig. 1 where molar conductivity is related to the square root of molar concentration. The quantitative interpretation of the results of the conductivity measurements was made by using methods and procedures described previously.1s-20

93

Fig. 1 Molar conductivity of pyridine . N-oxide perchlorate against square root of concentration in N, N-dimethylformamide at 298.1 K.

The association constants determined for pyOH+ with perchlorate anion in dmf and dmso were 1.58 and 6.51 mol dm-3 with standard deviations of 0.10 and 0 06, respectively. Values of the parameter of closest approach, d, equal to 3 5 and 6 . 3 A were employed in the case of dmf and dmso, respectively. Parameter d was calculated as the sum of solvodynamic radii of the cation and anion as determined from the Stokes equation.22 These association constants correspond to degrees of dissociation higher than 90% of the pyridine N-oxide perchlorate

'' Robinson, R. A., and Stokes, R. H., 'Electrolyte Solutions' (Butterworths: London 1959).

Sears, P. G., Lester, G. R., and Dawson, L. R., J. Phys. Chem., 1956, 60, 1433.

L. Chmurzyriski and Z. Warnke

in dilute (c. mol dm-3) dmf and dmso solutions. This means that the salt is virtually completely dissociated in both solvents. By employing the literature data for the limiting conductivities of the perchlorate ion in dmso21 and dmf23 and the experimentally found limiting conductance values of pyridine N-oxide perchlorate in both solvents, the limiting conductivities for the protonated cation of pyridine N-oxide in dmf and dmso were calculated. They are respectively 47.7 and 24-3 S cm2 mol-l. Potentiometric Measurements The utility of the glass electrode for pH measurements in dmf8 and dmso3@ has been verified previously. The picric buffer used in this study is characterized by a linear response over a wide cHA/cA- range (cHA and CA- are analytical concentrations of picric acid and tetrabutylammonium picrate, respectively) and by a slope matching the theoretical Nernst value (61.23 in dmf and 61.70 in dmso). The results of potentiometric measurements, carried out in the standardizing system, are shown in Fig. 2 for both solvents. For each series of e.m.f. measurements in the standardizing system, the values of the standard and slope, s, were calculated from the relationship of e.m.f. against e.m.f., E O , I o ~ ( c ~ ~ / c The )calculations were based on the dissociation reaction of picric ~- . acid under the assumption of complete dissociation of tetrabutylammonium picrate in both solvents. The pK, values taken for picric acid in dmf and dmso were ~ 1.4 and -1 . o , respectively. However, the pK, values reported for picric acid in either solvent differ markedly from each other. For instance, in dmso they range from -1.9 through -1.0 to -0 .5,6 while in dmf the variability of these values

Fig. 2. Calibration graphs for the glass electrode in the standardizing system tetrabutylammonium picratepicric acid in N,N-dimethylformarnide and dimethyl sulfoxide, at 298.1 K.

23

Prue, J. E., and Sherington, P. J., Trans. Faraday Soc., 1961, 57, 1795.

Acid-Base Equilibria of Pyridine N-Oxides

Fig. 3. E.m.f. against 10g(cB/cBH+)for relatively basic pyridine N-oxides: 2-methylpyridine N-oxide, 3-methylpyridine N-oxide, 4-methylpyridine N-oxide, and Cmethoxypyridine N-oxide in N,N-dimethylformamide, at 298.1 K. The curve for the pyridine system is included for comparison.

Fig. 4. Plots of e.m.f. against I o ~ ( c B / c ~ ~ + )weakly basic heterocyclic N-oxides: for Cnitropyridine N-oxide, Cchloropyridine N-oxide, and quinoline N-oxide in N,Ndimethylformamide, at 298 - 1 K.

L. Chmurzyhki and Z. Warnke

extends from 1 . 4 2 through 1.6,8 2-9,24 3-6525 up to 3.8.26 This dispersion of the results is indicative of serious problems encountered in their determination in both solvents; these problems are due to enhanced dissociation of picric acid in dmf and dmso on one hand, and to appreciable influence of trace amounts of acid-base impurities on the pKa values on the other hand. It thus becomes obvious that the pKa value of the standard, determined with significant error, reflects on the pK, values of the cationic acids under study. It should be kept in mind, however, that pKa orders rather than absolute values are of interest. Nevertheless, the pKa values put up for use should be regarded as estimates and, for this reason, their optimization during calculations of the equilibrium constants was performed.

pyridine N-oxide

pyridine

Fig. 5. Plots of e.m.f. against Iog(cB/cBH+)for pyridine N-oxides: Cnitropyridine N-oxide, pyridine N-oxide, Cphenylpyridine N-oxide, and 4methoxypyridine N-oxide in dimethyl sulfoxide, at 298-1 K. The curve for the pyridine system is included for comparison.
24 25

26

Simon, W., and Heilbronner, E., Helv. Chim. Acta, 1955, 38, 508. Petrov, S. M., and Umanskij, J. I., Zh. Fiz. Khim., 1967, 41, 1374. Demange-Guerin, G., and Badoz-Lambiling, J., Bull. Soc. Chim. I+.,

1964, 3277.

Acid-Base Equilibria of Pyridine N-Oxides

On the basis of the E0 and s values determined from measurements in the standardizing system as well as of the e.m.f. variations in the systems considered, the concentration acid dissociation constants, K,, were calculated. Moreover, in systems where equilibria of cationic homoconjugation are established, respective equilibrium constants, KBHB+, were also determined. Computation of the equilibrium constants was accomplished by Kostrowicki and Liwo's general method,27 whose utility for the determination of equilibrium constants for protolytic reactions was checked in acetonitrile solutions of substituted pyridine N-oxide~.l~-~O investigation^^^-^^^ revealed its superiority over Kolthoff's The classical method.29 For the sake of brevity, the results of the potentiometric measurements are presented graphically for selected N-oxide systems only (Figs 3-5). For comparison, plots of e.m.f. against 10g(cB/cBH+)for the pyridine systems are included in Figs 3 and 5. The pK, values determined for the protonated substituted pyridine N-oxides in dmf and dmso are summarized in Table 1. Inspection of their magnitudes and standard deviations leads to the conclusion that in most systems the acid dissociation constants are well determinable in both solvents. Only with 4nitropyridine N-oxide are the pK, values indeterminable in both solvents (the numerical values of the logarithms of the standard deviations are several fold higher than the logarithms of the constants). All the remaining pK, values in dmso can be regarded as quite easily determinable, whereas in dmf the least basic (with the exception of knitropyridine N-oxide) systems of 4-chloropyridine and pyridine N-oxides have such large standard deviations that the acid dissociation constants must be regarded as tentative.
Table 1. pK, values of pyridine N-oxides in dmf and dmso at 298.1 K (values in parentheses are standard deviations) For comparison, the pK, values for pyridine are included together with those for the species in aqueous solutions, pKaW System CMethoxypyridine N-oxide 4-Methylpyridine N-oxide CPhenylpyridine N-oxide 3-Methylpyridine N-oxide 2-Methylpyridine N-oxide CChloropyridine N-oxide Pyridine N-oxide CNitropyridine N-oxide Pyridine Klotufar, C., Krasovec:, F., and Kusar, M., Croat. Chem. Acta, 1968, 40, 23. Perrin, D. D., 'Dissociation Constants of Organic Bases in Aqueous Solutions' (Butterworths: London 1965). Christensen, J. J., Hansen, L. H., and Izatt, R. M., 'Handbook of Proton Ionization Heats and Related Thermodynamic Quantities' (Brigham Young University Press: Provo, Utah, 1976). ~ i f f eH. H., and Doak, G., J. Am. Chem. Soc., 1955, 77, 4441. , pKa values were indeterminable from potentiometric measurements.
A

~ p~~~~~~ ~ ~

pKaW

'

Kostrowicki, J., and Liwo, A., Talanta, 1990, 37, 645. Chmurzydski, L., Pol. J. Chem., 1992, 66, 1165. 29 Kolthoff, I. M., and Chantooni, M. K., Jr, J. Am. Chem. Soc., 1965, 87, 4428.
27
28

L. Chmurzyliski and Z. Warnke

The pKa values reveal that the substituted pyridine N-oxides are stronger bases in both solvents than in water, although the difference in the basicities is not as large as in the case of protophobic aprotic solvents. For instance, the difference between the pKa values in acetonitrile and water is equal to or greater than 10 units.28 As shown in Table 1, the differences between the pKa values in dmf and water attain approximately 2 units, and those between dmso and water are of the order of 1 . 5 pKa units. The variations of the pKa values of the protonated N-oxides comply (if the standard deviations are taken into account) with the calculated variations in the protonation energy owing to ~ u b s t i t u t i o n , ~ ~ with the rank order of the pKa values of these species in polar protophobic aprotic solvent^,^^^^^ as well as with the sequence determined in amphiprotic solvents of the methanol32 type and water (cf. Table 1). Owing to the agreement in the sequence of the pKa values in the solvents studied and water, the p ~ a d m f and pKadmsO values could be correlated with those in aqueous solutions, pKaW,to give the following linear relationships:

with correlation coefficients of 0.9472 and 0.9847, respectively. According to the considerations of our previous paper,30 the values of the slope (a) and intercept (b) in the correlation line between pKa values of various solvents reflect the difference between the solvation of the conjugate acids and bases. Roughly, the slope a is proportional to the difference of specific contributions to solvation energies, whereas the intercept b reflects mainly non-specific solvation of charged species. For polar aprotic solvents the order of a and b reflects their polarity. Values of a greater than 1 indicate that in amphiprotic solvents such as water the solvation energy difference is shifted in favour of the base, and therefore water has a levelling effect on acidity. Almost identical slopes and similar intercepts in equations (1) and (2) reveal a very close capacity for dmf and dmso to differentiate the strength of cationic acids. A similar conclusion was drawn by Kolthoff and coworkers8 regarding uncharged acids. In view of the fact that a correlation was e ~ t a b l i s h e d ~ ~ between the pKa values in acetonitrile and water (a = 1.8, b = 8-56), an attempt has now been made to correlate the pKa values of the protonated pyridine N-oxides in acetonitrile (MeCN) and the two solvents studied. The following relationships were obtained:

with correlation coefficients of 0.9453 and 0.9958, respectively. The slopes, a, close to each other, and very similar intercepts, b , can serve as further confirmation Chmurzyliski, L., Liwo, A., and Tempczyk, A., Z. Naturforsch., Teil B, 1989, 44, 1263. Chmurzydski, L., J. Chem. Soc., Faraday Dam. 1 , 1991, 87, 1729. 32 Chmurzyliski, L., J. Solution Chem., 1992, 21, 171. 33 Chmurzyliski, L., and Liwo, A., J. Solution Chem., 1991, 20, 731.
30
31

Acid-Base Equilibria of Pyridine N-Oxides

of a similar differentiating capacity of these solvents with regard to cationic acids. However, a comparison of the a values in equations (3) and (4) leads to the conclusion that drnf has a stronger differentiating capacity than dmso. Moreover, the higher than unity a values and the respectively high values of intercepts b indicate enhanced differentiating properties of acetonitrile as compared with the two remaining solvents. In summary, account being taken of the differentiating capacity of the solvents with regard to cationic acids, the solvents considered can be arranged as follows: MeCN > dmf > dmso. A similax ranking was reported by Kolthoff for substituted benzoic acids.Q The correlation established between the pKa values of the protonated pyridine N-oxides in dmf and dmso and the pKa values in water suggested the existence of a linear correlation also between the pKa values in dmf and dmso. Consequently, the following relationship was found:

where the correlation coefficient is 0-9776. The a value higher than unity confirms somewhat enhanced differentiating properties of dmf with respect to dmso. Equation (5) is inconsistent with equations (3) and (4) due to fact that different experimental points (see Table 1) have been applied to the three considered linear correlations. With the introduction of self-consistency between the three above equations, equation (5) can be presented in the following form:

Parker and coworkersl1 found that uncharged acids do not obey such a correlation well enough. Kolthoff and Chantooni6 saw the reason for the weak correlation in the poor precision of the determination of pKa in these solvents, particularly in dmf. Most probably, however, the main reason for the large dispersion of the experimental points was that these workers attempted to correlate the pKa values of various types of acids including phenols, benzoic acids, acetic acids, etc. A good correlation can be expected within a particular class of compounds only. This suggestion has been supported by acquisition of such a correlation for a variety of substituted pyridine N-oxides under study. Existence of the aforementioned correlations leads to the conclusion that in isoelectric aprotic solvents the differences in pKa values of cationic acids can also provide a measure of the differences in the basicity of the solvents. In order to compare the basicities of the pyridine N-oxide and the parent amine in both solvents, measurements of the acidity constants of the pyridinium cation were made. A comparison of the pKa values between pyridine and pyridine N-oxide shows that the parent amine is a stronger base, by c. 1.5-2 pKa units, than its N-oxide in these solvents. The difference is smaller than in protophobic aprotic solvents (2.5-3- 5 The pKa value determined in dmf for quinoline N-oxide, 2.25 (standard deviation 0.54), suggests comparable basicities of mono- and bi-cyclic N-oxides in aprotic protophilic solvents. , Attempts made to calculate cationic homoconjugation constants, KBHB+showed the complete absence of homoconjugation in dmso both with the heterocyclic
34

Chmurzyliski, L., Pol. J. Chem., 1992, 66, 333.

L. Chmurzyliski and Z. Warnke

N-oxides and the parent amines. In dmf a residual cationic homoconjugation was detected. The equilibrium constant for this reaction could be determined for one of the most basic N-oxides, 4methylpyridine N-oxide; this amounted to 1.45 (with standard deviation 0.01). It is lower by more than two orders of magnitude than that determined in acetonitrile.lg Detection of the residual cationic homoconjugation in dmf, together with complete suppression of this equilibrium in dmso solutions, provides further qualitative support in favour of the stronger basicity of dmso relative to dmf.

Acknowledgment
Financial support of this work through the Polish Scientific Research Council,

KBN, under grant DS/5300-40026-2 is gratefully acknowledged.