Kinetic Study of Solvent Effect on the Hydrolysis of

Mono-3, 5-Dimethylaniline Phosphate

Shashibala Kindo¹, Manish K. Rai¹, Ramsingh Kurrey¹,Joyce Rai²

¹School of Studies in Chemistry, Pt. Ravishankar Shukla University, Raipur -492010, Chhattisgarh, India.

²Chhattisgarh Concil of Science and Technology, Raipur,492014, Chhattisgarh, India.

Abstract:

The hydrolysis of phosphate esters is one of the most fundamental chemical and biochemical reaction. The kinetic solvent effect on the hydrolysis of mono-3, 5-dimethylaniline phosphate has been studied in aqueous mixtures of varying compositions (0-40% v/v) of some protic and aprotic solvents at four different temperatures. The rate of reactions increases with increasing proportion of solvents. Activation parameters (E_a, ΔH^≠, ΔG^≠, -ΔS^≠) have been evaluated. The significance of these parameters have been explained on the basis of solvent-solute interaction, solvent of the transition state of the medium.

Keywords: Hydrolysis, mono-3, 5-dimethylaniline phosphate, Solvent effect, Activation parameters.

Introduction

Phosphorus is an essential element for all life as the building block of many structural and functional components of living organisms^1,2. Phosphorus has a significant role in living systems, and so the reactions of phosphate esters in solution and in enzyme are of the great importance³. Most of the phosphorus in living system exists in the form of phosphate. Phosphate based compounds are key ingredients in biological system⁴. They play a key role in life processes⁵, in living organism for growth, development and maintenance of all plants and animals. Phosphate esters are the building blocks of life, and are involved in facilitating all cellular processes, from cellular signaling to protein synthesis⁶. Phosphate esters are widely used in variety of industries, including plastics, foams, paints, furniture building materials⁷ and electronics⁸. They are used as plasticizers, as flame retardants, as stabilizer for antifoaming and additives to floor polishes, lubricants, lacquers and hydraulic fluids⁹. Most chemical reactions are carried out in solution. Solvent play an important role in determining chemical reactivity¹⁰. Chemical reactions can be affected by the solvent through several kinds of interactions. Studies on solvent effects are generally carried out by means of relationships between reactivity properties that is reaction rate or several types of selectivity and empirical parameters representing different kinds of solute- solvent interactions¹¹.The rate of an elementary chemical reaction may change by order of magnitude when the solvent is changed^. The role of the solvent in governing a chemical reaction is far from passive¹².Therefore a proper understanding of solvent effects is essential to any model of chemical reactivity. Solvent influence both chemical reactivity and reaction rates. The importance of solvent effects has long stimulated attempts to define solvent polarity in terms of empirical parameters, based on diverse solvent sensitive reference processes. The aims of such attempts have been to obtain better parameters of solvent polarity by choosing solvent dependent standard systems and examining the change in parameters of that system when the solvent is changed¹³.Kinetic solvent effects on chemical reaction in different media are usually correlated in terms of “solvent polarity”, which sums up all the specific and non specific interaction of the media with initial and transition state¹⁴. This will also provide knowledge about dissociation and association of the molecules that gives probable mechanism of the reaction which is useful in various branches of chemistry. 

Materials and methods

Materials-

Ammonium molybdate (98%, Aldrich): 8.30 g of ammonium molybdate was dissolved in 100 ml of distilled water.

 2, 4-diaminophenoldihydrochloride (amidol solution, 98%, Aldrich): 1.40 g of amidol (impure, brownish black in colour) was taken in a conical flask covered with a carbon paper,    2.0 g of activated charcoal and 10.0 ml of distilled water were added into the flask and were shaken for 20 min. The colourless amidol solution was filtered into the flask containing 100 ml of 20 % sodium metabisulphite. The reagent was kept in a dark and cool place.

 Hydrochloric acid of A. R. quality was used. It was standardized by 0.1 N sodium tetraborate (Borax) solution. Triple distilled water was used in preparation of all the solutions.

Synthesis of momo-3,5dimethylaniline phosphate

Mono-3,5-dimethylaniline phosphate was synthesized by literature method¹⁵ in our laboratory, which involves the reaction on 3,5-dimethylaniline and phosphorus pentaoxide in 1:1 mole ratio. Parent compound are dissolved in benzene and stirred well for half an hour. Then P₂O₅ was added in small installment during stirring. The whole reaction mixture was stirred for twelve hours kept at room temperature over night. Then 100 ml of distilled water was introduced into the flask and shaken well. Two layer were separated. Aqueous layer contained mono-3,5-dimethylanilinenphosphate. The benzene layer was rejected. In the aqueous layer, few drops of phenolphthalein were added. Saturated solution of barium hydroxide was added drop by drop till pink colour appeared. Thus the Barium salt of mono ester obtained as white solid was washed several times with distilled water with few drops of acetic acid to remove inorganic phosphate. The confirmation of compound as done by elemental and IR spectral analysis.

(a)      Elemental analysis (%); calculated (observed):C, 28.5 (26.3); H, 3.0 (2.6); N,4.2 (3.5)

(b)     IR spectrum analysis: The IR spectrum of mono-3,5-dimethylaniline phosphate was recorded by FTIR Model 136 Shimadzu. ʋ (KBr) (cm^-1) : 3150.10 (N-H); 3265.20  (O-H); 1606.65 (C=C); 1290.70 (P=O); 760.12 (P-N); 1108.20 (C-H).

Kinetic measurements

Progress of kinetic study of hydrolysis of monoester was followed spectrophotometrically using Allen’s modified method¹⁶. The method involves quantitative estimation of inorganic phosphate formed from the ester during hydrolysis. The inorganic phosphate forms a phosphomolybdate complex [(NH₄)₃PO₄.12MoO₃] with ammonium molybdate. A mixture of sodium- meta- bisulphate and 2, 4-diaminophenol dihydrochloride (amidol) reduces this complex to molybdenum blue. The blue colour is fully developed in about 10 minutes and remains stable for 30 minutes. The intensity of the blue colour is directly proportional to the amount of free phosphoric acid. The optical density of this blue colour was measured by Systronic Spectrophotometer at 735 nm.

Result and discussion-

The kinetics of hydrolysis of mono-3,5-dimethyl aniline phosphate has been studied in 2 mol dm^-3 HCl at 40, 50, 60 and 70^oC. The rate of reaction increase with increase in percentage of methanol, ethanol, 1,4-dioxane and DMSO from 0 to 40% (v/v) in binary aqueous mixture at different temperature (40, 50, 60 and 70^oC). Pseudo first order rate constant obtained which are summarized in Table (1).

Table 1: Kinetic rate data for the hydrolysis of mono-3,5-dimethyl aniline phosphate at   

               Different temperature and various solvent of different compositions.

The result shows that in Table (1) the rate constant values are gradually increasing with the addition of methanol, ethanol, 1,4-dioxane and dimethylsulfoxide. Methanol and ethanol are regarded as protic solvents, dioxane is regarded as polar aprotic solvent while dimethylsulfoxide (DMSO) is regarded as dipolar aprotic solvent. Protic solvents are strong hydrogen –bond donors whereas diprotic solvent are not. Protic solvents will interact strongly with solutes which are strong hydrogen-bond acceptors. Many dipolar aprotic solvents e.g. DMF & DMSO are powerful bases and hydrogen-bond acceptors, so that they have strong interactions with solutes which are strong hydrogen- bond donors. The increasing trend in the values of rate constants need to be discussed in the light of Hughes and Ingold^{17, 18} predictions according to which an increase in the dielectric constant values of the reaction media causes an increase in the rate when there is concentration or construction of charges on the transition state and causes a decrease in the rate when there is diffusion or destruction of charges on the transition state. The values of dielectric constants of the reaction media go on increasing with gradual addition of solvent. Here our findings are fully in accordance with the qualitative prediction of Hughes and Ingold.

The solvents of methanol, ethanol, 1,4-dioxane and dimethylsulfoxide exerted greater accelerating effect on rate. Intermolecular association of this solvent occurs in such type of binary mixtures .The possible factors influencing the rate are solute- solvent interaction, the dielectric constant and the salvation changes of reactant and transition state¹⁹ .Highest rates are obtained in dimethylsulfoxide and the lowest rates are found  in ethanol. The observed solvent composition effect can also be explained on the basis of an increase in the acidity of the medium with decrease in the water concentrations. The dipolar aprotic solvent DMSO exerted greater acceleration effect on the rate than those on the other solvents. According to the Hughes and Ingold theory, the rate of reaction between an ion and a dipolar molecule, must increase as the polarity of the solvent decreases due to the dispersal of the charge on the activated complex.

Activation parameters

Stability and reactivity of a compound are expressed in terms of energy. A study of effect induced by changes in temperature is expected to furnish information on the energy requirements of the hydrolytic reaction. A small increase in temperature or small decrease in activation energy will greatly increase the fraction of collisions occurring with sufficient energy to convert reactants into products via transition state. The rate of hydrolysis is found to be highly elevated by increasing the temperature by 10^oC.The activation parameters ∆H^≠, ∆G^≠, -∆S^≠ exhibit non linear variation with solvent composition for mixed solvent systems. These parameters are shown in Table (2) .The values of the entropy of activation ∆S^≠ are negative in all solvent mixtures investigated. This indicates that in all of these solvent mixtures the transition state is preferentially solvated by water molecules.

Table 2: Activation parameter for the hydrolysis of mono3,5-dimethyl aniline phosphate

E_a, ΔH ^≠, ΔG ^≠, in kJ mol^-1 and ΔS ^≠, in JK^-1 mol^-1.

Conclusion

The rate of reaction increases with increases in % of ethanol, methanol, 1, 4-dioxane and DMSO from 0 to 40 % ( v/v) in binary aqueous mixtures at various temperatures (40, 50, 60 &70^oC) at 2.0 mol dm^-3 HCl. Highest rates are obtained in DMSO and lowest rates in ethanol. The main factors involved in the kinetic solvent study are solute-solvent interaction and salvation changes of reactant and transition state. The activation parameters ∆H^≠, ∆G^≠,-∆S^≠, exhibit simple variation with solvent compositions for mixed solvent system. The values of the entropy of activation -∆S^≠ are negative in all solvent mixtures investigated. This shows that in all of these solvent mixtures the polar transition state is preferentially solvated by water molecules .The ∆H^≠ and ∆G^≠ values decreases with increase of ethanol, methanol , 1,4-dioxane  and DMSO-water mixtures.

Acknowledgement

The authors are thankful to the Pt. Ravishankar Shukla University, Raipur for providing University Fellowship to one of the authors ( Shashibal Kindo)  and also grateful to Head of School of Studies in Chemistry, Pt. Ravishankar Shukla University, Raipur (India) for providing laboratory facilities.

References

1.     Karl, D. M. (2014). Microbially Transformation of Phosphorus in the Sea: New Views of an Old Cycle. Annu. Rev. Marrine Sci. 6, 279-337.

2.     Kolodiazhnyi,O.I. (2021). Phosphorus Compounds of Natural Origin: Prebiotic, Stereochemistry, Stereochemistry, Application, Symmetry,13, 889.

3.     Deaegere, A. and Karplus, M. (1992). Hydrolysis Rate Difference between Cyclic and Acyclic phosphate ester: Solvation versus Strain. J. Am. Chem. Soc. 115, 5316-5317.

4.     Katz, M. J., Moon, S.Y., Mondlock, J. E., Beyzavi, M. H., Stephenson, C. J., Hupp, J. T and Farha, O. K. (2015). Exploiting parameter space in MOFs: a 20 –fold enhancement of phosphate –ester hydrolysis with UiO-66-NH₂.Chem. Sci. 6, 2286-2291.

5.     Cao, X., Mabrouki, M., Mello, S.V., Leblance, R. M.; Rastogi, V. K.,Cheng, T.C., Defrank, J.J.(2005). The interaction between OPH and paraoxon at the air –water interface studied by AFM and epifluorescence microscopies. J. Colloids & Surfaces. B: Biointerfaces, 40, 75.

6.     Barrozo, A., Nelson, D. B., William, N. H. and Kamerlin, S. C. L. (2017). The effect of magnesium  ions on triphosphate hydrolysis. Pure Apple. Chem. 89(6): 715- 727.

7.     Saquib, Q., Al-Salem, A. M.,Siddiqui, M. A., Ansari, S. M.,Zhang,,X. and Al-Khedhairy, A. A. (2022). Oranophosphorus Flame Retardant TDCPP Displays Genotoxic and Carcinogenic Risks in Human Liver Cells. Cells, 11,195.

8.     Chen, M., Koekkoek, J. and Lamoree , M. (2022). Organophosphate ester metabolites in human breast milk determined by online solid phase extraction coupled to high pressure liquid chromatography tandem mass spectrometry. Environment International,159, 107049.

9.     Olivero-Verbel, R., Moreno,T., Fernández-Arribas, J., Reche.C., Minguillon, M. C., Martins, V., Querol, Q., Johnson-Restrepo, B., and Eljarrat, E.(2021). Organophosphate esters in airborne particles from subway stations. Science of the Total Environment. 769, 145105.

10.  Ghosh, K. K. and Patle, S. K. (2002). Kinetic solvent effects on reaction rates for the acidic hydrolysis of dihydoxamic acid. 41A, 758-762.

11.  Harifi-Mooda, A. R., Habibi-Yangjehb, A. and  Gholamia, M. R.(2008).Kinetics study of a Diels-Alder reaction in mixtures of an ionic liquid with molecular solvents. J. Phys. Org. Chem.  21, 783–788.

12.  Pross, A.(1995).Theoratical and Physical Principles of Organic Reactivity. J Wiley & Sons. New York, Part B.

13.  Riechardt, C.(1998). Solvents and Solvent Effects in organic Chemistry, 2nd ed.; VCH; Winsheim Germany.

14.  Yadav, H. and Bhoite, S. A. (2015), Stydy of Solvent Effects on the Acidic hydrolysis of    Mono –n-ethyl-o-touidine Phosphate.Acta Ciencia Indica, XL,(2) 67.

15.  Chhetri, N. and Bhoite, S. A. (2018). Micellar catalyzed hydrolysis of mono-2,3-dichloroaniline phosphate. Journal of Dispersion Science and Technology. 39 (5),         644-654.

16.  Allen, R.J.L. (1940),The Estimation of Phosphorus.Biochem.J.34,858-865.

17.  Ingold, C. K. and Hughes, E. D. (1953). Stucture and Mechanism in Organic Chemistry, Bell and sons, London, 310, (3),45.

18.   Hughes, E.D.and Ingold, C.K. (1935). Mechanism of substitution at a saturated carbon atom. PartIV. A discussion of constitutional and solvent effect on the mechanism, kinetics, velocity and orientation of substitution. J.Chem.Soc. 255.

19.  Choure, N. and Bhoite, S.(2009).Kinetic study of solvent effects on the hydrolysis of di-2-chloroaniline phosphate in dioxane and dimethylnsulfoxide-water medium, J.Ind.Chem.Soc. 86,1335-1337.