Kinetics and Mechanism of MnII Catalyzed Periodate Oxidation of p-anisidine: Effect of pH

The stoichiometry for the initial part of the reaction, MnII catalysed periodate oxidation of p-anisidine (PMA), has been found to be 1 mol of PMA consuming 2 mol of periodate ion. The kinetic-mechanistic study of reaction in acetone-water medium was made spectrophotometrically by noting the increase in the absorbance of reaction intermediate. Reaction is first order in reactants and catalyst each. A decrease in dielectric constant of the medium results in decrease in the rate of reaction suggesting an iondipole type interaction. Free radical scavengers do not affect the reaction rate. A special type of ratepH profile shows a maximum at pH = 7.0. This pH effect also suggests the involvement of at least three differently reactive reactant species in the reaction and this fact has been considered by us while deriving the rate law. Under pseudo first order conditions [IO4-] >> [PMA] and in agreement with the derived rate law, the 1/kcat versus [H+] plot passes through the minimum and the results can be fitted to the equation: 1/kcat = (K2 / kK3K4 [H+]) + {(Kw+ Kb K2) / kK3K4 Kw} + Kb[H+] / kK3K4 Kw where kK3K4 is the empirical composite rate constant, Kw is ionic product of water, K2 is acid dissociation constant of H4IO6and Kb is base dissociation constant of PMA. The experimental value of [H+]min is in good agreement with the value calculated by using the derived rate law equation and is characteristic of the substrate involved relating to the base dissociation constant of PMA. The value of thermodynamic parameters have been evaluated. © 2014 BCREC UNDIP. All rights reserved


Introduction
p-anisidine has been enlisted [1] as toxic in the toxic release inventory of US EPA, 2001 and placed in group 3 of international agency for research on cancer which includes the chemicals that are not classifiable as to carcinogenicity in humans. Reports are available on the kinetic-mechanistic studies for the uncatalysed non-Malapradian periodate oxidation of aromatic amines [2][3][4][5][6][7][8][9][10]. Some of the recent reports include the Mn II catalyzed periodate oxidation of 2,4-xylidine [11], 2,6-xylidine [12], N-methylaniline [13], p-toluidine [14] and 4chloro, 2-methyl aniline [15]. The kineticmechanistic studies have been made on Mn II catalyzed periodate oxidation of p-anisidine (PMA) in acetone-water medium and the results of these studies are being presented and discussed in this paper. Special effect of pH on the rate of reaction has been observed in terms of rate-pH profile giving a maximum at a pH. We have proved in this communication that this maximum is characteristic of the substrate involved and relates to the base dissociation constant of p-anisidine. This pH effect also suggests the involvement of at least three differently reactive reactant species in the reaction and this fact has been considered by us while deriving the rate law. The studies are important as these may provide conditions required for developing methods for detection and treatment of p-anisidine.

Kinetics Procedure
The reaction was studied in a spectrophotometric cell and initiated by adding temperature equilibrated NaIO4 solution of known concentration to the reaction mixture containing the PMA, Mn II and buffer and maintained at the desired temperature (± 0.1 0 C).
The progress of the reaction was followed by recording the absorbance on Shimadzu double  beam spectrophotometer (UV-1800), at 455 nm, i.e., the λmax of the reaction intermediate absorbs. λmax was not found to change with change in time under experimental conditions. Desired temperature was maintained with the help of a high precision thermostatic control. Guggenheim's method was used for evaluation of pseudo first order rate constants, kobs.

Product Analysis
Reaction mixture containing oxidant in excess was left for fourteen hours to ensure completion of the reaction. Initially, the solution turned yellow, thereafter brown and finally the solid product settled down on standing. The observed changes are given in Figure 1. Reaction mixture was filtered and the filtrate was extracted with petroleum ether (40-60 o C) (CAS No. 8032-32-4, Analytical reagent grade, CDH, India). The extract was evaporated at room temperature (30±2 o C) to get a scarlet colored product which was found to be single when subjected to thin layer chromatography (TLC) using plate thickness of 0.5 mm, silica gel 'G' as adsorbent, chloroform+ acetone+ benzene in the ratio 4:6:4 ml used as eluent and 30 minutes as the time for development. It was recrystallised in ether and characterized as 4methoxy-1,2-benzoquinone on the basis of positive test for quinine [17], M.P. 87 o C (literature value 88 o C [18]), UV spectrum (in CHCl3 giving absorption maxima at 400 nm, which suggested the presence of quinonoid structure in the compound (literature values 406.5 nm, 4methoxy-1, 2-benzoquinone [19]). The IR spectrum of this compound (in KBr) showed the presence of bands at 2976 cm -1 (s) (due to ring C−H stretch), 1674 cm -1 (s) (indicating the presence of C=O on benzoquinone pattern with the possibility that the position of this band got lowered due to +I effect of methoxy group [20][21][22][23]), 3280 cm -1 (s) (may be due to overtones of C=O stretch). Further, the bands at 1520 cm -1 (s) and 1400 cm -1 (s) may be due to C==C ring stretch. The bands at 1238 cm -1 (m) to 1040 cm -1 (m) may be due to the asymmetric and symmetric C−O−C stretch and at 746 cm -1 (s)(m) and 824 cm -1 (m) (due to out of plane C=C and C−H bending mode). The observed values are in good agreement with those reported / expected for 4-methoxy-1,2-benzoquinone.

Stoichiometry
Unreacted periodate was estimated iodimetrically. log(a-x) versus time plot (where a-x is the concentration of unreacted periodate) followed the pseudo first order behavior up to a point after which the inflexion was obtained. It was taken as the point corresponding to the completion of first stage of reaction for which the kinetics was studied. The results indicated the stoichiometry to be 1 mol PMA: 2 moles NaIO4 for the reaction as in Eq. (1). (1)

Preliminary Observations
On mixing the reactants, the solution turned light yellow within 3 seconds of mixing. As already shown in Figure 1, this color changes in to brown and finally the product is obtained on keeping for long time. These observations indicate the formation of more than one intermediate prior to the formation of final reaction product. The rapid scan of the orange solution showed the λmax of the intermediate, C4, to be 455 nm ( Figure 2). The UV-VIS spectra of IO4 -, PMA and Mn II indicated these to show no absorption in visible region. Hence, for following the kinetics the absorbance changes were recorded at 455 nm at which only the intermediate C4 absorbs.

Rate Law
The kinetics was studied under pseudo order conditions by keeping periodate concentration in excess. Guggenheim's method was used for evaluation of pseudo first order rate con-

Effect of pH, Dielectric Constant of the Medium, and Free Radical Scavengers
As the reacting species are differently protonated, it was considered necessary to study the effect of pH on the reaction rate and hence, the reaction was studied in the pH range 5.5-8.0. kcat versus [H + ] plot indicates a maximum at pH = 7.0 (Table 1, Figure 3).
An increase in the acetone (2.5 -10 %) led to a decrease in the rate (42 %). For the reaction between an ion and a dipole, the Laidler as well as Amis equation [27], suggests a linear relationship between log kcat and l/D. Further, according to Amis, the slope is negative if the reacting ion is anion. A plot between log kcat vs l/D was found to be linear (Figure 4), with negative slope indicating that the reaction is an iondipolar type involving a direct bimolecular attack of p-anisidine on H4IO6 -or IO4 -(i.e. periodate monoanion which has been assumed to be the reactive species in the pH range in which the present studies were made, based on the evidences already available in literature [2,26]). Also, the negative slope is in accordance with Amis equation for ion-dipolar type reaction.
Free radical scavengers, like acrylamide, allyl acetate and allyl alcohol had no effect on the reaction rate indicating no involvement of free radicals in the reaction mechanism.

Effect of Temperature and Evaluation of Thermodynamic Parameters
The rate constants were determined at four different temperatures (35-50 o C) Arrhenius plot was a staright line ( Figure 5). The values of different thermodynamic parameters viz. activation energy (∆E), entropy of activation (∆S # ), Arrhenius frequency factor (A), free energy of activation (∆G # ) and enthalpy of activation (∆H # ) were found by using commonly known equations and these are given in Table  2. The value of ∆G # was temperature dependent. A high negative value of ∆S # is suggestive of solvent interactions and the probability that the transition state may be solvated. Small value of activation energy is characteristic of catalyzed reaction.

Special Features of the Reaction
Some important features of this reaction are as follows. Firstly, faster color changes in the reaction mixture relative to the separation of product on standing for long time indicates the formation of the colored intermediate on a time scale of minutes and that of the final product on a time scale of hours. The overall reaction appears to involve several steps and possibly several transient intermediates, in addition to comparatively stable one C4, during the oxidation of PMA into a 4-methoxy-1,2-benzoquinone. Secondly, the kinetic order of one in periodate against the requirement of two periodate molecules for each PMA molecule in the stoichiometry (Equation 1) requires the involvement of only one periodate in the rate determining step and second IO4 -ion to be consumed in a fast step leading to the formation of Since the concentration of C4 increases continuously with time and reaches a limiting value, its concentration can not be in steady state. Thirdly, kcat versus pH plot indicates the presence of at least three differently reactive reactant species (which is periodate in this system) in the pH region chosen for study [25]. Finally, the observation that free radical scavengers have no effect on reaction rate rules out the involvement of free radicals in the oxidation mechanism. The high negative value of entropy of activation supports the involvement of solvation effects in this reaction as given in the proposed molecular mechanism (Scheme I).
While proposing a suitable mechanism for the reaction under study, the speciation of PMA and periodate should be considered. In aqueous solutions, periodate is transformed into the three forms in water including orthoperiodic acid with equilibria and dissociation constants [26] given below: H4IO6 -⇄ H3IO6 2-+ H + , K2 = 4.35 × 10 -9 (4) The value of K1 indicates that in the pH range 4.5-9.5 species H5IO6 shall be practically non-existent and hence only species H4IO6 -and H3IO6 2-need be considered for explaining observed pH -dependence. Based on this premise, the equilibrium or free concentration of H4IO6 -, [H4IO6 -] shall be related to the total periodate concentration [IO4 -]0 by Equation (5): In the reaction mechanism proposed later, species H4IO6 -has been considered reactive. In aqueous solution, PMA, undergoes the following acid-base equilibrium with Kb = 22.9 × 10 -10 [24] in Equation (6).
Since in the studied pH-range, both CH3OC6H4NH2 and CH3OC6H4N + H3 exist, these species have been taken into account. From equilibrium (6), the equilibrium or free concentration of amine, [PMA], is given by Equation (7). where [PMA]0 is the total concentration of CH3OC6H4NH2.
To explain the observed pH-dependence, it is necessary to assume PMA and H4IO6 -to be reactive species. On this basis to explain the observed kinetics, rate law (Equation 2), and pH-dependence, the following mechanism is proposed: [C4] → [C5] (product) (12) The proposed mechanism in Equations (8-11) leads to the rate law (13).
On substituting the values of concentrations of the reactive species [PMA] and [H4IO6 -] from Eq. (5) and (7) in Equation (13) The kcat and pH data were fitted to Equation (17) and the best fit value of composite rate constant kK3K4 was found to 2.94×10 7 dm 6 mol -2 s -1 . The plot comprising of the experimental data and calculated data is shown in Fig. 6 It is noteworthy that the calculated value of [H + ]min is in satisfactory agreement with the experimental value of [H + ]min of 1.0×10 -7 mol dm -3 obtained from kcat versus pH plot (Figure 3). This goes in strong support of the derived rate law and the proposed mechanism.

Molecular Mechanism
The detailed mechanism for the reaction is given in Scheme-I wherein IO4 -has been assumed as the oxidizing species in the light of the fact that the present studies were carried out in the pH range in which periodate monoanion is the reactive species [2,25]. The first step in the proposed mechanism is the bimolecular reaction between p-anisidine and Mn II to form an intermediate C1, which, in turn, is attacked by periodate ion to form an intermediate ternary complex C2. The formation of intermediates C1 and C2 in a rapid step having low values of equilibrium constants, K3 and K4, is assumed in the proposed gross mechanism. The catalytic role of Mn 2+ appears to be due to the f o r m a t io n o f a te rn a ry c o m pl e x , [(PMA)Mn(H4IO6)] + , in which manganese helps in electron transfer. Further the proposed mechanism matches the kinetic and product studies, as given in scheme-I. The formation of a charged intermediate complex C2 by the attack of IO4 -on the nitrogen of anilino group and stabilization of positive charge on nitrogen of this group, has already been established and supported by LFER studies for the uncatalyzed periodate oxidation of aromatic amines [7,8]. In addition, a high negative value of entropy of activation and the effect of dielectric constant on the reaction rate support the involvement of solvation effects in this reaction. The intermediate C2 is unstable and attacked by water molecule to give intermediate C3. C3 is attacked by another periodate molecule in fast step to give quinoneimine C4. The overall reaction appears to involve several steps and possibly several transient intermediates, in addition to comparatively stable one C4.
The kinetic order of one in periodate against the requirement of two periodate molecules for each PMA molecule in the stoichiometry requires the involvement of only one periodate in the rate determining step and second IO4 -ion to be consumed in a fast step leading to the formation of the intermediate, C4. The last step seems to be the hydrolysis of C4 to give the benzoquinone C5, as the final product of oxidation separated and identified as 4-methoxy-1,2benzoquinone. The observation that free radical scavengers have no effect on reaction rate rules out the involvement of free radicals in the oxidation mechanism.

Conclusion
Mn II catalysed periodate oxidation of panisidine (PMA) is first order in reactants and catalyst each. A decrease in dielectric constant of the medium results in decrease in the rate of reaction suggesting thereby, the ion-dipole type of reaction. Free radical scavengers do not affect the reaction rate. One mol of PMA reacts with two moles of periodate during the initial part of reaction. The main reaction product is 4-methoxy-1,2-benzoquinone. Results under pseudo-first order conditions, [IO4 -] >> [PMA], are in agreement with the derived rate law. In agreement with the rate law the 1/kcat versus pH plot passes through a minimum. Rate-pH profile shows a maximum at a pH of 7.0. This value is characteristic of the substrate and relates to its base dissociation constant by [H + ]min = (K2 Kw / Kb) 1/2 . This pH effect also suggests the involvement of at least three differently reactive reactant species in the reaction.