Thermodynamic Deprotonation of N , N '-Disubstituted Thiobarbituric Acids in Water-Dioxane Mixtures MANOJ

Thermodynamic deprotonation constants [pKa] of dimethyl thiobarbituric acid [DMTBA], diphenyl thiobarbituric acid [DPTBA], di-o-tolyl thiobarbituric acid[DOTTBA], di-m-tolyl thiobarbituric acid [DMTTBA], di-p-tolyl, thiobarbituric acid [DPTTBA], di-o-xylyl thiobarbituric acid [DOXTBA], di-p-xylyl thiobarbituric acid [ DPXTBA], di- naphthyl thiobarbituric acid [DANTBA] and di-naphthyl thiobarbituric acid [DBNTBA] have been determined in different mole fraction of dioxane [ 0.175 – 0.350 ] at 20, 30, and 40 ± 0.100C. The plot of the thermodynamic deprotonation constant [ ] versus the mole fraction of dioxane is linear at all the given temperatures. The mean ionic radii for thiobarbiturate ions, being in the region of 2.10 – 2.70 A0, slightly increases with dioxane percentages. The values of G0, H0 and S0 have been evaluated. The effect of temperature as well as medium effect are briefly discussed.


INTRODUCTION
The studies on the behaviour of the heterocyclic imines and enols are of current interest in biopolymers and in the physical chemistry of drug action.It is desirable that more information is gathered about similar model systems.Thiobarbituric acids containing enolic and emine groups in a benzenoid heterocyclic ring system has been selected as one such model compounds Analytical applications of this family of compounds have been extensively examined in recant years.A

EXPERIMENTAL
The N, N' diaryl substituted thiobarbituric acids were synthesised by the method described elsewhere 7 , recrystallized before use and purity was checked by elemental analysis UV and IR spectra.The other chemicals used were of Anala R and G.R grades of B.D.H or E. Merck unless otherwise stated.Dioxane was purified as recommended. 7An aqueous solution (10%) of tetra methyl ammonium hydroxide (TMAH) titrant was standardized against potassium hydroxide and diluted to 0.1 M, the proportions of dioxane and water being the same as used in preparing the titre solutions.
The titration procedure for determining the deprotonation constants was same as outlined by Albert and Sergeant 8 .Generally 0.01 M substituted thiobarbituric acids were titrated without the addition of inert salt.The measurements of pH were made on an expanded scale pH -meter [ELICO, Model No. pH 821 Hyderabad].The instrument was standardized against Phthalate and borax buffers before and after each titration.
In a thermo stated (20, 30 and 40 ± 0.01 0 C) titration vessel, accomodating a glass electrode, a limb of saturated KCl bridge and a micro burette of 5.0 ml capacity, 0.5 M of thiobarbituric acids in the appropriate dioxane water composition was taken and contents stirred magnetically.The initial volume of titre solution was 48 ml in all the cases to allow for the change in the total volume of solution on the addition of titrant.For practical purposes, the error caused by volume correction is almost negligible [Less than 0.01 pH unit for the inner five readings of a set of pH titrations] with a maximum error of 0.018 pH unit 9 .About 10 min.after the settings, the titration was started by adding 0.5 ml aliquots of 0.1 M TMAH at a time and noting the highest stable pH.The titrations, carried out in duplicate, were reproducible within 0.01 pH unit.

Calculation
The thermodynamic deprotonation constant pK T a values have been determined by the pH -titration method employing a glass and saturated calomel electrode in cells with a liquid junctions potential.The relationship of Van Vitert and The values of the correction factor log U 0 H , were obtained experimetally 11 and those of the mean coefficient were (r ± ) computed by interpolation of the data given by Harned and Owen 12 .Here the assumption has been made that the mean activity coefficients are same on both the molal and molar scales.The deprotonation of thiobarbituric acids [HA] in an aqueous medium gives [H + ] and thiobarbiturate anion (A -).In such a medium, the equilibrium constant is given as follows ... (2)   ... (3)   Assuming  HA , the mean activity coefficients of unionized acid, is unity, the final form of equations for computing pK T a in the dioxane -water mixture is obtained by equations 1 and 3. .

..(4)
A correction for hydrolysis of the salt, which may be significant at the end of the titration (ie at pH > 10) was applied by substituting for in equations 3 and 4. The hydroxyl ion activity was computed from the relationship 13 .
The ionic product of water, pK w , has been obtained from the data of Agarwal 14 in different dioxane -water mixtures.

RESULT AND DISSCUSSION
The pk T a values of N,N' disubstituted thiobarbituric acids in different dioxane -water mixtures at 20, 30 and 40 0 C are given in table -1.The pk T a values of these acids in all media invariably decrease with increasing temperature.The average pk T a usually falls within a spread of ±0.02 but not beyond ±0.03 in any instance.The empirical data for the mole fraction of dioxane (n 2 ) and G°, H°a nd S° values are given in tables 2 and 3 respectively.

Effect of medium
The pk T a values of the acids are influenced by the intrinsic basicity of the solvent.The deprotonation equilibrium for substituted thiobarbituric acids is an inorganic reaction and therefore the changes in pk T a values with dioxane should be accounted for by the electrostatic and specific solvation effects, considering its acid dissociation involving a net increase of ions.
The decrease in the dielectric constant of the reaction medium enhances the electrostatic forces between the oppositely charged ions and thus facilitates the formation of molecular species which should increase the pk T a [table -1].This prediction has been simply confirmed for other reagents on the basis of previous studies. 15 -16 has been proposed 17 -18 that the free energy of deprotonation of acids in solutions at its infinite dilution might be expressed as the sum of an electrostatic term [el] sensitize to the environment and a non-electrostatic term (nonel) insensitive to the environment and independent of temperature. .

..(8)
If the electrostatic part is expressed by Born's formula 19 , the equation ( 8) takes the following form.
Where r+ and r-denote the radii of the solvated ions and D is the dielectric constants of medium.Hence

Further, as
The equation simplifies as conventionally, pk T a is plotted against 1/D assuming G°n onel to be in dependent of solvent when values of substituted thiobarbituric acids are

Mole Fraction of dioxane
For substituted thiobarbituric acids, the change in pk T a with mole fraction of dioxane (n 2 ) is of considerable magnitude.Generally, the difference in pk T a in aqueous medium (n 2 = 0) and aqueous dioxane medium (n 2 = 0.350) is of the order of 1.8 -2.50 pk T a units.When pk T a values of these thiobarbituric acids are plotted against n 2 , straight line relationship are encountered (Fig. 1).The experimental values of pk T a indicate a maximum deviation form linearity of the order of 0.05 or about 0.5% in pk T a .
The goodness of fit in these instance was judged by calculating the correlation coefficient (m) defined by Where x and y are mean values of x(pk T a )   and y(n 2 ), respectively.The summations are extended to all pairs (x,y) available.Linear proportionality is readily indicated between two variables 19 when the values of m is +1.0.
Since the values of m is nearly +1.0 at 20, 30 and 40 0 C for all the substituted thiobarbituric acids [table -2], it implies that there is quite a high probability of a linear relationship between pk T a and (n 2 ).A similar behaviour is found for several other acids 20 in aqueous-dioxane medium likewise linear proportionality is also obtained for some other mixed water solvents e.g.acetic acid, propionic acid, butyric acid and benzoic acid in methanol-water mixture. 21

Mean ionic radii (r ± )
To provide an electrostatic interpretation of the medium effect on deprotonation process, Born's solvation energy equation -9 has been simplified by king 22 as where r ± , mean ionic radii, equal to The values of r ± have been computed via equation -10 at different percentage and are in the range 2.15 -2.75A 0 .It is evident from this computation process the value of r ± increase slightly with aqueous dioxane concentrations.It is difficult to explain this variation with change in solvent composition.Similar increase in r ± values has been encountered while studying the acids dissociation of other acids. 23,24 rmodynamic functions for ionic equilibria The pK T a values have been determined with a precision of ±0.02 to ±0.03 and hence the error in G° is believed to be close to ±0.03 and ±0.04 Kcal.Mole -1 .The values of S° given in Table -3 are accurate to ± 0.20 cal.mole -1 K -1 .
The positive values of H° found in aqueous as well as aqueous-dioxane mixture for all substituted thiobarbituric acids proves that acid dissociation at temperatures up to 40 0 C is endothermic.The positive value of H° encountered here may be ascribed to the breaking of the covalent bond between hydrogen and oxygen atoms of -OH group of thiobarbituric acids.Further it is evident that the magnitude of change in H° with solvent composition is relatively small and falls within the range of experimental error.It is because of this that slopes of straight lines in the plots of pK T a against n 2 ( fig. 1) do not differ markedly and are nearly the same and parallel at these temperatures for all the thiobarbituric acids.
The of S° are found to decrease with increase in dioxane content of the solvent medium for all thiobarbituric acids, thereby proving that is dependent of solvent composition.The negative value of entropy has been explained as arsing due to deprotonation of the legand since the sum of the total of the number of water molecules bound is more than water molecules originally accompanying the un dissociate thiobarbituric acids.
When acid dissociates in two media, the free energy change for transfer reaction from one medium to the other is given by 2.303 RT pK T a .For instance with DPTBA, G°( aq) and G°( Hass10 was used to determine the H + concentration from the values read on pH -meter [B]....(1) n2=0.175) are 3.31 and 4.30 K cal.mol -1 respectively at 30 0 C and G° changes by 0.99 Kcal mol -1 in the transfer reaction.and this results in a change of 3.25 cal mol -1 in entropy.
pK T a (S-W) values i.e., pK T a (S)-pK T a (W) [Where S and W refer to mixed solvents and water respectively] of thiobarbeturic acids at 30 0 C are given inTable -4.The change in pK T a (S-W) which is found to be different for the different acids for the same percentage of dioxane is probably due to the presence of different substituents which cause a great change in the distribution of electron density in the ring and hence the electron density at any particular point is also affected.AKNOWLEDGMENTSThe authors thank to Department of chemistry, Sahu Jain (P.G.) College, Nazibabad and R. S. M. (PG) College, Dhampur for providing the necessary facilities.