Ionization constants of some hydroxypyrones in water and in 80(w/w) dimethyl sulphoxidendash;water at 25 deg;C

摘要

J. CHEM. SOC. PERKIN TRANS. 11 1983 Ionization Constants of Some Hydroxypyrones in Water and in 80 (w/w)Dimethyl Sulphoxide-Water at 25 "C Sau-Fun Tan, Kok-Peng Ang," and Harilakshmi Jayachandran Department of Chemistry, National University of Singapore, Kent Ridge, Singapore 051 1 The ionization constants of some hydroxypyrones have been measured spectrophotometrically at 25 "Cin water and in 80 (w/w) dimethyl sulphoxide-water. A few of them are exceptionally strongly acidic. The pKavalues of these compounds are discussed in relation to their molecular structures. A plot of the pK, in water against the corresponding PKa in 80 (w/w) dimethyl sulphoxide-water is linear, although ApK, varies from negative values for the weaker acids to positive values for the stronger acids.Possible solvent effects have been suggested. Hydroxypyrones in aqueous solutions have significantly Table 1.pKa of hydroxypyrones at 25 "C higher acidities than those of phenols owing to the positively charged character of the pyrone rings.' The formation of PKSHin 80 resonance-stabilised anions, and an interplay of electron- (w/w) APK withdrawing effect of acetyl substituents and intramolecular Compound pKH20(in water) DMSO-water pKHz0-pKsH hydrogen-bonding effect have been invoked to explain the (1) 8.21 a 10.94 -2.73 observed pKa values. To study further the structural effects on (2) 8.68 It 11.56 -2.88 -1.89acidity, several related hydroxypyrones have been prepared (3) 4.94 a 6.83 (4) 5.26 6.19 -0.93and their ionization constants measured both in water and in (5) 3.9380 (w/w) DMSO-water. The latter solvent system has been (6) 3.83 5.30 -1.37 5.68 -1.85chosen as it possesses many desirable proper tie^.^*^ The (7) 4.06 5.1 1 -1.05 ionization constants of those hydroxypyrones previously (9) 1.25 0.13 1.12 measured in water have now been determined in 8O'x, (w/w) 9.21 11.72 -2.51 DMSO-water for inclusion in the discussion.(10) 4.07 (1 1) 1.59 1.43 0.16 (12) 1.61 1.19 0.42 Results and Discussion (13) 0.15 -0.5 * 0.7 * The pK, values of the compounds studied are summarised in K. P. Ang and S. F. Tan, J. Chem. SOC.,Perkin Trans. 2, 1979, Table 1 ; detailed results are given in Supplementary Public- 1525. ation No. 23510 (19 pp.).? The acidities of these compounds * Approximate value.may be discussed conveniently in three groups. Compounds (1) and (2), which are 3-hydroxy-4-pyrones, are the least acidic. Table 2. U.V.absorption maxima and chemical shifts of hydroxy Compounds (3)-(8) are 4-hydroxy-2-pyrones. Although they protons of hydroxyprones may also exist, at least theoretically, in the tautomeric 2- hydroxy-4-pyrone forms, i.r. and U.V. spectra (Table 2) show absorptions in regions characteristic of a-pyrones. They are In 80(w/w) 60"much more acidic than compounds (1) and (2) mainly because Compd. DMSO-water In water In CHCIJ In CDC13 of resonance stabilisation of their anions and the absence of this mode of stabilisation for the anions of (1) and (2). (1) 268 265 270 * 8.9br 273 276 * 8.3brCompounds (4)-(8) are acyl derivatives of compound (3).(2) 275 (3) 285 282 284 * 11.2brThe electron-withdrawing effect of the acyl group at C-5 (4) 310 305 310 16.68 causes higher acidities of compounds (5)-(7) than com-(5) 260 223 268 12.31pound (3). That compound (4), which is isomeric with com- 290 (sh) 257 (sh) 295 (sh)pound (3,with the acyl group at C-3, is less acidic than com- 285 (sh) 'pound (3), has been explained by the acid-weakening effect (6) 258 257 260 10.35 of the very strong intramolecular hydrogen-bonding which 275 (sh) 280 (sh) 275 (sh) more than counterbalances the acid-strengthening electron- (7) 256 232 266 1 1.65 withdrawing effect of the carbonyl group, Hydrogen-bonding 310 254 (sh) 315 effects in compounds (5)-(7) are comparatively weaker, as (8) 268 305 (sh) 230 17.9conjugate chelate rings similar to that in compound (4) are 305 (sh) 270 (sh) 31 1 not probable owing to the lower double-bond character of the (9) 270 27 1 268 16.4brC(4)-C(5) than the C(3)-C(4) bond in an cx-pyrone ring.This 320 314 310 19.1 difference in hydrogen-bond strength is clearly reflected in (10) 345 340 245 the chemical shifts of the OH protons in the respective n.m.r. 228 spectra (Table 2). The replacement of a methyl group by a (11) 278 275 312 -16v br phenyl group either at C-6 or in the acyl side chain apparently 347 342 makes relatively small differences in the acidities of com- (12) 275 275 312 -14v br 350 342pounds (5)-(7). Compound (8), with acetyl groups at both (13) 281 282 322 16.3 361 355 (at 0 "C) t For details of Supplementary Publications see Notice to Authors * In 'H,DMSO.No. 7 in J. Chem. SOC.,Perkin Trans. 2, Index Issue. 472 J. CHEM. SOC. PERKIN TRANS. I1 1983 CH3amp;OH oOH 0 CH3i0 C6H5 (7) 0A0 (10) C-3 and -5, shows a very low field OH in its n.m.r. spectrum. PKa measurement of this compound by a spectrophotometric method is however complicated by changes which take place in its electronic spectra in solution. Its Xmx. in non-polar solventsoccursaround 31 1 nm but shifts in more polar solvents to shorter wavelengths and in 80 (w/w) DMSO-water it occurs at 268 nm. Moreover, in the last mentioned solvent, the absorption intensity decreases slowly with time, reaching a steady value after a few hours.Such changes suggest a possible tautomeric change from the predominance of the a-pyrone form in the solid state and in non-polar solvents to the y-pyrone form in the more polar solvents, although the anion derived from either form should be the same. All the other compounds currently studied do not show changes in their electronic spectra within the time taken for pKa measurements. Compounds (9)--(13) are exceptionally strong acids. They differ from the other compounds in being theenolized forms of cyclic anhydrides, that is, 6-hydroxy-2-pyrones. Whereas compounds (9) and (1 1)--(13) are completely enolised in the solid state as well as in solutions as shown by i.r., u.v., and n.m.r.spectra, compound (10) appears to enolise only in polar solvents. Compound (9) has previously been studied.' The high acidities of compounds (10)-(13), which are substituted glutaconic anhydrides, reinforce the previous assignment of the first pK, of compound (9) to 6-OH rather than to the 4-OH. Consistent with this, compound (10) is isomeric with but more acidic than compound (3), while compound (11) is isomeric with but more acidic than compounds (4) and (5). OH cCH H 56 CH3 ORH 0 okoH (12) The anions formed from 6-hydroxy-2-pyrones have greater symmetry and have more extensively delocalised negative charges than the anions from 4-hydroxy-2-pyrones. The pK, values of compounds (11) and (12) are comparable showing that the methyl substituent at C-4 has little effect on acidity.Compound (13) is the strongest acid among the ones currently studied. U.V. spectra indicate that it is fully ionized in solu- ~.tion; Lux. and E~ of compound (13) in DMSO-water remaining unchanged upon the addition of alkali. Conduct- ance measurements in 80 (w/w) DMSO-water further support this view. Molar conductance of solutions of com-pound (13), hydrochloric acid, and picric acid of similar concentration are found to be comparable. At a concentration of 10-4~,A, of compound (13) (33.41 SZ-' cm2 mol-') is slightly lower than that of hydrochloric acid (38.75 R-' cm2 mol-') probably owing to the larger size of its anion, but slightly higher than that of picric acid (26.12 R-l cm2 mol-I).That its pKa is even lower than pK, of compound (9) could possibly be interpreted as due to contribution from two highly sym- metrical and equivalent structures to its resonance-stabilised anion. The anion of compound (9) is slightly less symmetrical due to the presence of a strong intramolecularly hydrogen- bonded ring between 4-OH and 3-acetyl group, as confirmed by the n.m.r. spectrum of its mono-sodium salt in 2H6DMS0 (amp;H 17.32). ApKa is ca. 0.6 between compounds (3) and (4), and 1.5 between (3) and (5) in 80 (w/w) DMSO-water solvent; the difference being due to the introduction of the electron- withdrawing acetyl group. ApK, between compounds (10) J. CHEM. SOC. PERKIN TRANS. 11 1983 and (1 l), is, however, much larger, ca.2.6 units. Allowing for the absence of an acetyl group, compound (10) still seems to be less acidic than expected probably owing to incomplete enolization of the 6-carbonyl group, whereas the 5-acetyl group in compound (11) promotes complete enolization. A comparison of U.V. spectra of (10) in CHCI3, ethanol, water, and 80 (w/w) DMSO-water shows that enolization, while absent in chloroform, is not complete in the latter three more polar sohents. The pKa values of compounds (1)-(8) measured in 80 (w/w) DMSO-water are higher than those measured in water, the ApKa being larger for the less acidic compounds. Although the effects of solvent changes on acidities especially in mixed solvents could be complex, the above observed trend may be qualitatively expected from the lower dielectric constant and poorer solvating power of DMSO for anions compared to water. However, it is interesting to note that for the strongly acidic compounds (9)-(13), the PKa values in 80 (w/w) DMSO-water are slightly lower than those obtained in aqueous solution.It is possible that for these compounds differences in solvation effect on the very extensively delocal- ised anions are less important while the greater basicity of DMSO than water could contribute towards the observed decrease in PKa in the DMSO-water mixture. A plot of the pKa values in 80 (w/w) DMSO-water against the corre- sponding values in water is linear with a slope of 1.4.A similar linear relationship with a slope of 1.48 has been observed for phenol^.^ Experimental Materials.-Compound (4) was commercially available.Compounds (12) and (13) were prepared as described below. The rest were synthesized according to literature proce- dures 5-7 and characterized by i.r. and 'H n.m.r. spectra. All compounds were purified by repeated crystallization. Triply distil led water and spect ropho t ometric grade dimethyl sulphoxide were used for preparing the solvent mixture. Buffer solutions were prepared from carbonate-free sodium hydroxide solution. Indicators were purified according to the method of Baughman and Kreevoy.2 3-Acetylglutaconic Anhydride (12).-Glutaconic anhydride (320 mg), fused sodium acetate (350 mg), and freshly distilled acetic anhydride (1 ml) were mixed and left to stand for 10-1 5 min.The dark red precipitate obtained was filtered and dis- solved in the minimum amount of water. The solution was neutralised with concentrated HCl and extracted several times with CHCI,. The CHCI, layer was dried over anhydrous Na2S04 and evaporated to yield a sticky solid which was recrystallized repeatedly from CHCl,-n-hexane to give pale beige needles of 3-acetylglutaconic anhydridk, m.p. 105 "C (Found: C,54.35; H, 4.15. Gamp;04requires C, 54.55; H, 3.9). 3,5-Diacetyl-4-me thy tglutaconic Anhydride (13).-p-Met h yl-glutaconic anhydride (3.2 g) was refluxed with acetic anhy- dride (8 ml) and fused sodium acetate (3.7 g) for ca. 1 h on the water bath. The red solid that formed on cooling was filtered, and dissolved in the minimum amount of water and neutralised with concentrated HCl.The cream solid that separated was filtered and washed with a little water. Re-crystallization from CHC13-n-hexane yielded pale beige needles of 3,5-diacetyl-4-methylglutaconic anhydride, m.p. 120 "C(Found: C, 57.0; H, 4.75. CloHloOs requires C, 57.15; H, 4.75). Spectrophotometric Measurements.-Measurements were made with a Perkin-Elmer spectrophotometer 551 on trip- licate solutions at 25 "C using matched 1 cm silica cells. The experimenta1 details and methods of calculation of the pKa values are described in refs. 1 and 8. The stability of all the compounds was checked by recording the U.V. spectra at regular intervals.The pKa value for compound (13) in 80 (w/w) DMSO-water is approximate since very strong acid solutions were used to determine pK,. The approximate pK, value, marked with an asterisk, is included in Table 1 for the purposes of discussion. For compounds (1)-(3), (3, (6), (9) (second PKa), and (lo), the PKa values in 80 (w/w) DMSO-water were measured using suitable indicators. In other cases, appropriate buffers or HCl solutions were used. Activity coefficients were calculated using the Davies equ- ati~n.~Each pKa value was corrected for the influence of the ionization of the pyrone or the indicator on the pH of the solution. Compounds (11) and (13) were unstable in very strong acids. Hence D1for these compounds was determined by plotting (D -D2)/H+as a function of D according to equation (1) where D, D1, and D2 have the usual meaning.' Conductance Measurements in 80 (w/w) DMSO-Water.-Conductances of a number of solutions of hydrochloric acid, compound (13), and picric acid of similar concentrations (in the range 10-3-10-4~) were measured at 25 "C using a Wayne Kerr autobalance universal bridge B642.The solutions were thermostatted at 25 "C for a minimum of 30 min before taking readings. References 1 K. P. Ang and S. F. Tan, J. Chem. SOC.,Perkin Trans. 2, 1979, 1525. 2 E. H. Baughman and M. M. Kreevoy, J. Phys. Chem., 1974, 78,421. 3 M. Georgieva, G. VeIinov, and 0. Budevsky, Anal. Chim. Acta, 1977, 90, 83. 4 J. C. Halle, R. Graboriand, and R. Schaal, Bull. SOC.Chim. Fr., 1970, 2047. 5 M. A. Butt and J. A. Elvidge, J. Chem. SOC.,1963,4483. 6 N. Bland and J. F. Thorp, J. Chem. SOC.,1912, 101, 856. 7A. K. Kiang, S. F. Tan, and W. S. Wong, J. Chem. SOC.C, 1971, 2721. 8 K. P. Ang and T. W. S. Lee, Aust. J. Chem., 1977,30, 521. 9 C. W.Davies, 'Ion Association,' Butterworths, London, 1962. Received 7th July 1982; Paper 2/1150