Determination of pKa values for new Schiff bases derived from benzaldehyde and salicylaldehyde with glycine and ß-alanine

T wo new Schiff base acids, namely benzylidene glycine(I) and salicylidene ß-alanine(II) were prepared by new procedure using sodium hydroxide as catalyst. The main aim of the project was the determination of pKa values for these acidic imines using conductivity method, the method as found simple, precise and accurate for determination of pKa of compounds, All conductivities parameters of benzylidene glycine and salicylidene ß-alanine and their sodium salts in deionized water were mentioned . The variation of acidities of acids(I) and(II) were also included. The thermodynamic reactions parameters namely ∆G°, ∆H and ∆S° for these ionization reactions of acids were discussed and interpreted .


Introduction
The acid dissociation constant was among the most frequently used physio chemical parameters and its determination was of interst to a wide range of research fields.The conductivity method was applied originally and previously for the determination of ionization constants for numerous mono basic carboxylic acid [1].Also conductivities were applied for the determination of thermodynamic dissociation constants for salicylic [ 2 ] acid in binary mixed solvent systems at 298K.Electric conductivity was used in the determination of acidity constants of perfluoroalkanoic [3] acids, The previous method was used in the determination of acid dissociation constants of some mono basic organic acids [4] in acetonitril and dissociation constants of cysteine [5] in aqueous solutions .Conductance measurements were applied in studying dissociation and association constants with thermodynamic functions of alanine [6] in DMF mixtures.In 2013 a group of workers [ 7 ] were developed and compared fourteen methods of pKa values Azzouz and Maree had determined pKa values for anumber of acid imines derived from benzoyl acetonedimedone [8] and benzoyl acetonitrile [9].This manuscript was a continuation of previous study [10].It deals with synthesis of Schiff bases derived from benzaldehyde and salicylaldehyde with some amino acids by a new developed method.The main purpose of this investigation was to determine the influence of temperature in the range (293-333) K° on pKa values for ionization reactions of imines with particular attention to the thermodynamic parameters namely ∆G° , ∆H and ∆S° which were included and discussed.

Experimental
All chemicals used throughout this work were supplied from Fluka, Aldrich and Molecule companies.They were benzaldehyde, salicylaldehyde, glycine and ß-alanine while ethanol was bought (pure) from local market.Schiff bases (I) and (II) under study were prepared by using standard method [11], or by mixing equimolar (10 -2 mole) amounts of benzaldehyde, salicylaldehyde with appropriate amount of glycine and ß-alanine respectively.About 15 ml of absolute ethanol with 0.01 mole of sodium hydroxide were added.The final mixture was refluxed, cooled, followed by filtration and recrystallization from ethanol.Pure Schiff bases [8] (I) and (II) had a melting points of 195C° (decomp.) and 120C° respectively.Deionized water was prepared after multiple redistillation of water.It has a conductivity range value of (0.2-1.0) *10 -6 ohm -1 .cm - .A stock solutions of Schiff bases (I)-(II) of concentration (10 -3 ) mol.dm -3 were prepared, followed by dilution to the required concentration as in Tables 3-4.Similary the sodium salt of Schiff bases (I)-(II) were prepared using a similar procedure adopted elsewhere [9].A stock solution of each salt was prepared of concentration (10 -3 ) mol.dm -3 and diluted to the required concentration range as in Table (1)(2).All solutions of Schiff bases and their sodium salts were maintained at fixed temperature range (293-333)K° by using a thermostat.

Results and discussion
At the beginning of this investigation , it was thought of great importance to confirm the chemical structures of Schiff bases (I)-(II).These were accomplished by physical method using melting points beside UV-IR spectra mentioned in a previous manuscript [10].This encourage the workers in this investigation to determine the acidities of Schiff bases (I)-(II) as measured by pKa at temperature range (293-333)K° in deionized water, using a conductivity measurements.The equivalent conductance versus the square root of concentration solutions of sodium salts of Schiff bases (I)-(II) at temperatures stated were shown in Tables (1-2).Now when such data were plotted versus each other, these showed an inverse straight lines as in fig. 1 of correlation coefficient range value 0.9759-0.9958.
These confirm the idea of strong electrolyte [12] for these sodium salts.

fig (2): The relationship between equivalent conductances and square root of c o n c e n t r a t i o n for benzylidene glycine at different temperatures.
The intercepts of these lines as fixed on eachplot represent the equivalent conductances of the salt at infinite dilution (Ʌ °) at any temperature under study.
Similarly various concentrations of Schiff bases (I)-(II) as in tables (3-4) were prepared, followed by measurements of their specific and equivalent conductances at temperature range (293-333)K° .Now the equivalent conductances at infinite dilution (Ʌ °) of Schiff bases (I)-(II) were calculated [12,13] on the basis of independent ion migration of ions.The last was applied in the determination of Ʌ ° for some imines derived benzoyl acetone and dimedon , as explained in our previous communication [14].Now it become possible to evaluate the degree of dissociation (α) and the ionization constant of acids (I)-(II) using equations (1-2) at temperature range (293-333)K° , as in tables (3)(4) .
These tables (3)(4) showed that Ʌ ° value for any acid (I) or (II) was increased by increasing temperature, These results confirm [15] the previous study on Ʌ ° of phenolic imines derived from benzoyl acetonitrile upon elevation of temperatures.
It was cleared from table (3) that ionization constants values of benzylidene glycine were depressed by an elevation of temperatures in the range (293-333)K°.These means that ionization reactions of such acidic compound were directed toward reactant product.On the contrary to that ionization constants values of salicylidene ß-alanine were increased by elevation of temperature.The reason for such variation in results were due to the difference in structures of acids (I) and (II), as agreed with theortical expectation.Table (5) showed a comparison between pKa values for acids (I) and (II) at temperature range (293-333)K°.At any constant temperature, the acidity of salicylidene ß-alanine was greater than benzylidene glycine .In order to interprett the values collected in table (5), this need to consider the pKa values of glycine and ß-alanine from literature as in table ( 6)

Table(6) : pKa values of some amino acids
Proton lost (pKp) ton gained(pKa) Amino acids 937796 233513 glycine 9387 2334 ß-alanine The isolectric point (pI) for glycine and ß-alanine was determined [13] from an equation (3).The a verage enthalpy or heat for ionization ∆H + was +8.0272 KJ.mole .This means ionization reaction was occurred after absorption of heat .On the contrary to that ,the average enthalpy for ionization of benzylidene glycine has a negative sign of average value-26.667,or the ionization in benzylidene glycine was occurred after liberation of heat energy .These positive or negative values of enthalpies of ionization in salicylidene ß-alanine and benzylidene glycine could be interpreted due to the presence of intramolecular and intermolecular hydrogen bonding in these systemes respectively.This last observation was confirmed in literature [17] by the fact the salicylaldehyde nucleus which has the same intramolecular hydrogen bond.Hence its derivative was expected to contain the intramolecular hydrogen bonding.The change in entropy ΔS° for this ionization reaction was calculated from Gibbs energy of from as in equation ( 6) ΔG° = ΔH -T ΔS°….. (6).For mono protoic acid HA, the ionization reaction was directed towared an increase in random of the system.Hence ΔS° as expected theortically has appositive sign.These negative signs of ΔS° values for salicylidene ß-alanine and benzylidene glycine as in tables (7)(8) were contrary to our expectation.This only happened by strong interaction between polar solvent deionized water molecule with negative anion (A -) for mono protoic acid HA.While other systems, such as association [18] reaction between phenols with benzyl mono benzylidene aniline and ionization [19] reactions of some acids and basic imines derived from 3 and 4 acetyl pyridines .This investigation was in agreement with other pKa studies on imines derived from benzoyl acetone with dimedone [9] and benzoyl acetonitrile using conductivity measurements.

Conclusion
1-Two acid Schiff bases benzylidene glycine and salicylidene ß-alanine were prepared [8] by developed method using sodium hydroxide as a new catalyst.

2-
The conductance measurements were applied to the determination of pKa values for these acid Schiff bases.This method was found simple, precised and accurate.3-The determination of pKa by conductance method, led to the believe of existence of acid Schiff bases in isoelectric point.

4-
The thermodynamic parameters of ionization of acid Schiff bases confirmed that ionization reactions occurred in non-spontaneous process, in endothermic or exothermic reaction depending on structure of acid and accompanied by a decrease of random of systems.
Whene applying last equation to glycine and ßalanine, resulted to pI values of 6.0650 and 6.105 respectively.These values were closed to pKa values of benzylidene glycine and salicylidene ß-alanine, bearing in mind the difference in structures between Schiff bases under investigation and amino acids mentioned.Hence the near pKa values of benzylidene glycine and salicylidene ß-alanine with pI values of glycine and ß-alanine, led the workers in this investigation to confirm the existence of acids (I)-(II) as in isoelectric points.At such point the carboxyl proton was lost and combined with nitrogen Schiff base 1 resulted to the formation of nitrilium ion as conjugated acid of amine in Schiff base HN = C.The change of free energy ΔG° ionization reactions of acid Schiff base (I) and (II) were calculated from equation (4).ΔG° = -RTlnKa…….(4).All ΔG° values tabulated in tables (7-8) had apositive signs.This means, that ionization reactions occurred in non spontaneous process.Since Schiff bases (I)-(II) have a convalent bonding, therefore, they were difficult to be ionized as compared with ionic bonds.The heats of ionizations reactions of acids under investigation were also calculated from intergrated Vant Hoff equation number(5) .The plot of lnKa versus T -1 for salicylidene ß-alanine and benzylidene glycine at different temperatures showed a straight lines of correlation coefficient range value of 0.9668-0.9108.