J. Chem. Sci., Vol. 117, No. 1, January 2005, pp. 33–42. © Indian Academy of Sciences.

Kinetic, mechanistic and spectral investigation of ruthenium (III)- catalysed oxidation of atenolol by alkaline (stopped-flow technique)

RAHAMATALLA M MULLA, GURUBASAVARAJ C HIREMATH and SHARANAPPA T NANDIBEWOOR* PG Department of Studies in , Karnatak University, Dharwad 580 003, India e-mail: [email protected]

MS received 10 October 2003; revised 26 December 2003

Abstract. Kinetics of ruthenium (III) catalyzed oxidation of atenolol by permanganate in alkaline medium at constant ionic strength of 0×30 mol dm3 has been studied spectrophotometrically using a rapid kinetic accessory. Reaction between permanganate and atenolol in alkaline medium exhibits 1 : 8 stoichiometry

(atenolol : KMnO4). The reaction shows first-order dependence on [permanganate] and [ruthenium (III)] and apparently less than unit order on both atenolol and alkali concentrations. Reaction rate decreases with increase in ionic strength and increases with decreasing dielectric constant of the medium. Initial addition of reaction products does not affect the rate significantly. A mechanism involving the formation of a complex between catalyst and substrate has been proposed. The active species of ruthenium (III) is 2+ understood as [Ru(H2O)5OH] . The reaction constants involved in the different steps of mechanism are calculated. Activation parameters with respect to the slow step of the mechanism are computed and dis- cussed and thermodynamic quantities are also calculated.

Keywords. Kinetics; permanganate; stopped-flow technique; oxidation of atenolol; ruthenium(III) catalysis.

1. Introduction (scheme 1) and one in which a hypomanganate is formed in a two-electron step followed by rapid re- oxidize a greater variety of sub- action12 (scheme 2). strates and find extensive applications in organic 4-(2-Hydroxy-3-isopropylaminopropoxy)phenyl- syntheses,1–7 especially after the advent of phase- acetamide commercially known as atenolol (ATN), transfer catalysis,3,4,6 which permits the use of sol- a b-adrenoreceptor blocking agent, is commonly used vents such as methylene chloride and benzene. Kinetic studies constitute an important source of mechanistic information on the reaction, as demonstrated by results k1 · Mn(VII) + S ¾¾1® Mn(VI) + S , referring to unsaturated acids in both aqueous1,3,7 8 and non-aqueous media. 1 · k2 During oxidation by permanganate, it is evident Mn(VII) + S ¾¾® Mn(VI) + products, that the Mn(VII) in permanganate is reduced to vari- 1 1 where S = substrate, k2 ä k1. ous oxidation states in acidic, alkaline and neutral media. Furthermore, the mechanism by which this Scheme 1. multivalent oxidant oxidizes a substrate depends not only on the substrate but also on the medium9 used k1 for the study. In strongly alkaline media, the stable Mn(VII) + S ¾¾3® Mn(V) + products, 10,11 2– reduction product is the , MnO . k1 4 Mn(VII) + Mn(V) ¾¾4® 2 Mn(VI), No mechanistic information is available to distin- guish between direct one-electron reduction to Mn(VI) 1 1 where S = substrate, k4 ä k3.

Scheme 2. *For correspondence 33 34 Rahamatalla M Mulla et al as antihypertensive drug.13 It is also used for anti- solid formed on cooling was recrystallised from the angina treatment to relieve symptoms, improve toler- same solvent. Using the required amount of recrys- ance and as an anti-arrhythmic to regulate heartbeat tallised sample, a stock solution of K2MnO4 was and present infections. It is also used in management prepared in aqueous KOH. The solution was stan- of alcohol withdrawal, in anxiety states, migraine dardized by measuring the absorbance on a Peltier prophylaxis, hyperthyroidism and tremors. accessory (temperature control) attached Varian Ruthenium (III) acts as an efficient catalyst in many Cary 50 Bio UV–Vis spectrophotometer with a 1 cm redox reactions, particularly in an alkaline medium.14 quartz cell at 608 nm (e = 1530 ± 20 dm3 mol–1 cm–1). The catalysis mechanism can be quite complicated The Ru(III) solution was prepared by dissolving a due to the formation of different intermediate com- known weight of RuCl3 (sd Fine-Chem) in HCl plexes, free radicals and different oxidation states of (0×20 mol dm–3). Hg was added to the Ru(III) solution, ruthenium. The kinetics of fast reaction between to reduce any Ru(IV) formed during the preparation – ruthenate (VII), RuO4, and manganate (VI), i.e. of the Ru(III) stock solution, which was set aside for 2– 15 MnO 4 , have been studied, where the reaction is 24 h. The Ru(III) concentration was then assayed by presumed to proceed via an outer-sphere mechanism. EDTA titration.19 The uncatalysed reaction between atenolol and per- All other reagents were of analytical grade and manganate in an alkaline medium has been studied their solutions were prepared by dissolving the req- previously.16 A microscopic amount of ruthenium uisite amounts of the samples in doubly distilled (III) is sufficient to catalyze the reaction and a variety water. NaOH and NaClO4 were used to provide the of mechanisms are possible. Herein, we describe the required alkalinity and to maintain the ionic strength results of the title reaction in order to understand the respectively. active species of oxidant, reductant and catalyst in such media and to arrive at a plausible mechanism. 2.3 Kinetic measurements

2. Experimental All kinetic measurements were performed under pseudo-first order conditions with excess of [at- 2.1 Devices – enolol] over [MnO4] at a constant ionic strength of 0×30 mol dm–3. The reaction was initiated by mixing Since the initial reaction was too fast to be monitored – previously thermostatted solutions of MnO4 and at- by the usual methods, kinetic measurements were enolol, which also contained the necessary quantities performed on a Peltier accessory (temperature con- of Ru(III), NaOH and NaClO4, to maintain the requi- trol) attached Varian Cary 50 Bio UV–Vis spectro- red alkalinity and ionic strength respectively. The photometer connected to a rapid kinetic accessory temperature was uniformly maintained at 25 ± 0.1°C. (HI-Tech SFA-12). IR, NMR, fluorimetry and mass The course of reaction was followed by monitoring spectral studies were performed by Nicolet Impact- – the decrease in the absorbance of MnO4 in a 1 cm 410 FT IR, Brucker 300 MHz, and Pesciex Qstar quartz cell of Peltier accessory (temperature control) Polsar LC-MS/MS-TOF. attached Varian Cary 50 Bio UV–Vis spectrophoto- meter connected to a rapid kinetic accessory (Hi- 2.2 Materials: Chemicals and catalyst Tech SFA-12), at its absorption maximum of 526 nm as a function of time. The application of Beer’s law All chemicals used were of reagent grade. Solution to permanganate at 526 nm is verified, giving e = of atenolol (M/s SS Antibiotics Pvt Ltd, Aurangabad, 2083 ± 50 dm3 mol–1 cm–1 (literature e = 2200 dm3 –1 –1 India) was prepared by dissolving the appropriate mol cm ). The first-order rate constants, (kc) were amount of recrystalised sample in double distilled evaluated by the plots of log (At–A¥) versus time by water. The solution of KMnO4 (BDH) was prepared fitting the data to the expression At = A¥ + (A0 – –kc.t by dissolving the appropriate amounts of sample in A¥)e , where At, A0 and A¥ are absorbances of doubly distilled water and standardized17 against permanganate at time t, 0 and ¥ respectively. The (CO2H)2. K2MnO4 solution was prepared as descri- first-order plots in almost all cases are linear to 80% 18 bed by Carrington and Symons as follows: A solu- completion of the reaction and kc is reproducible –3 tion of KMnO4 was heated to boiling in 8×0 mol dm within ±5%. During the course of measurements, the KOH solution until a green colour appeared. The solution changes from violet to blue and then to

Ruthenium (III)-catalysed oxidation of atenolol by alkaline permanganate 35 green. The spectrum of the green solution is identi- indicating that the surface does not have any signifi- 2– cal to that of MnO 4 . It is probable that the blue cant effect on the rate. color originates from the violet of permanganate and Regression analysis of experimental data to obtain the green from the manganate, excluding the accu- the regression coefficient r and standard deviation S mulation of hypomanganate. It is also evident from of points from the regression line was done using a figure 1 that the absorbance of permanganate de- Pentium-IV personal computer. creases at 526 nm whereas the absorbance of man- ganate increases at 608 nm. 3. Results The effect of dissolved on the rate of reaction was studied by preparing the reaction 3.1 Stoichiometry and product analysis mixture and following the reaction in an atmosphere of N2. No significant difference is observed, bet- Reaction mixtures containing an excess permanga- ween the results. In view of the ubiquitous contami- nate concentration over atenolol and constant [ruthe- nation of basic solutions by carbonate, the effect of nium (III)], 0×05 mol dm–3 NaOH, and adjusted to carbonate on the reaction was also studied. Added ionic strength of 0×30 mol dm–3 was allowed to react carbonate has no effect on reaction rate. However, for 6 h. at 25 ± 0.1°C. The remaining permanganate fresh solutions were used during the experiments. was then analysed spectrophotometrically. The results – In view of the modest concentration of alkali used indicated that eight moles of MnO4 are consumed by in the reaction medium, attention was also given to one mole of atenolol as given by the reaction: the effect of the surface of the reaction vessel on the kinetics. The use of polythene or acrylic ware and OH quartz or polyacrylate cells gave the same results, CH3 NH CH O CH2 CH CH2 CH 0.5 3

- – Ru(III) + 8 MnO4 + 9 OH 1 O

CH2 C NH2

2 O CH COOH 2 4 CH3 3 5 + HOOC NH CH 3 2 6 CH 4 O 3

1 CH C + 8 MnO2– 4 2 - 4 + NH3 + 5 H2O. 3 O

(1) 2 Absorbance For identification of the products, the reaction mix- ture containing excess of atenolol was kept to allow 1 completion of reaction. The reaction product, 4-car-

boxy methoxy phenyl acetic acid, was extracted with ether and recrystallised from aqueous alcohol, 0.0 and its purity checked by HPLC. 4-Carboxy methoxy 450 500 550 600 650 700 phenyl acetic acid was also characterised by its IR

spectrum, which showed a band at (u) 1690 cm–1 l (nm) due to acid >C=O stretch and a broad band at Figure 1. Spectroscopic changes occurring in the Ru(III) 2845 cm–1 due to O–H stretch. It was further charac- catalysed oxidation of atenolol by permanganate with 1 –3 –4 terised by H NMR spectrum (DMSO), where it [ATN] = 1×5 ´ 10 , [MnO4] = 1×5 ´ 10 [Ru(III)] = 1×0 ´ 10–6, [OH–] = 0×05, and I = 0×30 mol dm–3 at 25°C, scanning showed a singlet at 9×6 d due to two carboxylic time interval = 120 s. OH’s, a doublet (J = 9 Hz) at 6×94 d due to C3- and

36 Rahamatalla M Mulla et al

C5-protons, another doublet (J = 9 Hz) at 7×20 d due (r ³ 0×9998, S £ 0×0131) up to 85% completion of the to C2- and C6-protons, a singlet at 3×53 d due to me- reaction (figure 2) indicate a reaction order of unity – thylene protons of -CH2- and another singlet at in [MnO4]. This is also confirmed by variation of – 4×58 d due to methylene protons of ph-O-CH2- res- [MnO4], which did not result in any change in the pectively. Mass spectra ESI technique (solvents: pseudo first-order rate constants, kC (table 1). The acetonitrile + water + ammonium acetate) gave substrate concentration was varied in the range (M+ + 17) (ammoniated) 228 and (M+) m/z 211. 1×0 ´ 10–3 to 1×0 ´ 10–2 mol dm–3 at 25°C, while Ammonia was identified by use of Nessler’s re- keeping all other reactant concentrations and condi- agent.20 The product, Ni(II), remained in the aqueous tions constant, including ruthenium (III) catalyst. The layer and it was identified by its dimethyl glyoxime kc values increased with increase in concentration of complex.21 atenolol indicating an apparently less than unit order N-(isopropyl) amino carboxylic acid, which is dependence on [atenolol] (table 1). soluble in water, was identified by the spot test.22 It Ruthenium (III) concentration was varied in the was observed that the 4-carboxy methoxy phenyl 8×0 ´ 10–7 to 8×0 ´ 10–6 mol dm–3 range, at constant acetic acid and N-(isopropyl) amino carboxylic acid concentration of permanganate, atenolol, alkali and do not undergo further oxidation under the present ionic strength. The order in [Ru(III)] is found to be kinetic conditions. unity (table 1) from the linearity of the plots of log kc vs log [Ru(III)] (r ³ 0×9995, S £ 0×0122). The effect 3.2 Spectrofluorimetric studies of alkali on the reaction has been studied at constant concentrations of atenolol, potassium permanganate, ruthenium (III) and a constant ionic strength of The fluorescence study was carried out in methanol –3 as solvent for good dissolution of the pure and pro- 0×30 mol dm . The rate constants increased with duct compound. No interference of the solvent increasing [alkali] and the order less than unity (ta- methanol was seen in the fluorescent study. Fluores- ble 1). cence studies of pure compound atenolol and the product of the reaction of atenolol with permanga- 3.4 Effect of relative permittivity and ionic strength nate in presence of ruthenium (III) catalyst in aque- ous alkaline medium were carried out. Excitation for The effect of relative permittivity (eT) on the rate the atenolol was observed at 370 nm and emission constant has been studied by varying the t-butanol– now at 411 nm with intensity 106. Excitation of the product was observed at 370 nm and emission was Time (s) at 416 nm with considerable decrease in fluorescent 0 15 30 45 60 75 90 intensity to 36×62, due to quenching. 0

3.3 Reaction orders -0.4 -0.8 As permanganate oxidation of atenolol in alkaline medium proceeds with measurable rate in the absence -1.2 of ruthenium (III), the catalysed reaction is under- 5 stood to occur in parallel paths with contributions -1.6 4 from both the catalysed and uncatalysed paths. log Abs 3 -2 2 Thus, the total rate constant (kT) is equal to the sum of the rate constants of the catalysed (kC) and un- -2.4 1 catalysed (kU) reactions, so kC = kT–kU. Hence, the reaction orders have been determined from the -2.8 slopes of log kC vs log concentration plots by vary- -3.2 ing the concentrations of reductant, Ru(III), and al- kali in turn, while keeping the others constant. Figure 2. First-order plots of Ru(III)-catalysed oxida- Potassium permanganate concentration was varied tion of permanganate by atenolol in aqueous alkaline me- –5 –4 –3 – 4 –3 in the range of 2×0 ´ 10 to 2×0 ´ 10 mol dm , dium at 25°C. [MnO4] ´ 10 (mol dm ); (1) 0×2, (2) 0×4, and the linearity of plots of log absorbance vs time (3) 1×0, (4) 1×5, (5) 2×0.

Ruthenium (III)-catalysed oxidation of atenolol by alkaline permanganate 37

Table 1. Effect of variation of [KMnO4], [ATN], [Ru(III)] and [OH] on Ru(III)-catalysed –3 oxidation of atenolol by KMnO4 in aqueous alkaline media at 25°C and I = 0×30 mol dm . 102 (s–1) 4 3 6 – 10 [MnO4] 10 [ATN] 10 [Ru(III)] [OH ] –3 –3 –3 –3 (mol dm ) (mol dm ) (mol dm ) (mol dm ) kT ku kc expt. kc cal.

0×2 1×5 1×0 0×05 4×64 1×12 3×52 3×48 0×4 1×5 1×0 0×05 4×66 1×14 3×52 3×48 1×0 1×5 1×0 0×05 4×67 1×13 3×54 3×48 1×5 1×5 1×0 0×05 4×65 1×16 3×49 3×48 2×0 1×5 1×0 0×05 4×62 1×09 3×53 3×48

1×5 1×0 1×0 0×05 3×63 0×86 2×77 2×70 1×5 1×5 1×0 0×05 4×65 1×16 3×49 3×48 1×5 3×0 1×0 0×05 6×99 2×04 4×95 5×02 1×5 6×0 1×0 0×05 10×0 3×54 6×46 6×47 1×5 1×0 1×0 0×05 13×5 5×54 7×93 7×41

1×5 1×5 0×8 0×05 3×97 1×16 2×81 2×78 1×5 1×5 1×0 0×05 4×65 1×16 3×49 3×48 1×5 1×5 2×0 0×05 8×21 1×16 7×05 6×95 1×5 1×5 4×0 0×05 15×3 1×16 14×2 13×9 1×5 1×5 8×0 0×05 29×4 1×16 28×3 28×0

1×5 1×5 1×0 0×02 2×50 0×58 1×92 1×87 1×5 1×5 1×0 0×05 4×65 1×16 3×49 3×48 1×5 1×5 1×0 0×08 6×07 1×50 4×57 4×43 1×5 1×5 1×0 0×10 6×50 1×60 4×90 4×86 1×5 1×5 1×0 0×20 8×00 2×01 5×99 6×08

I1/2 Ru(III) catalyst. Attempts to measure the relative 0.8 0.6 0.4 0.2 0 permittivities were not successful. However, they 23 1.44 were computed from the values of pure liquids. No reaction of the solvent with the oxidant occurs under 1.76 the experimental conditions employed. The rate 1.51.50 1.701.7 constant, kC, increases with decreasing relative per-

mittivity of the medium. The plot of log kC vs 1/eT is

kc kc 1.64 1.56 linear with a positive slope (figure 3) (r ³ 0×9989, S £ 0×0141).

1.58 3 + log 1.62 The effect of ionic strength was studied by varia- tion of the NaClO concentration in the reaction 1.52 4 medium. The ionic strength was varied from 0×05 to 1.68 –3 1.46 0×5 mol dm at constant concentrations of perman- ganate, atenolol, ruthenium (III) and alkali. It is 1.4 1.74 found that the rate constant decreases with increas- 1.26 1.32 1.38 1.44 1.501.5 1.56 ing concentration of NaClO4. The plot of log kC vs 2 1/2 1/åT ´ 10 I is linear with a negative slope (figure 3)

1/2 (r ³ 0×9997, S £ 0×0112). Figure 3. Plots of log kc vs I and log kc vs 1/eT. –3 – –4 [ATN] = 1×5 ´ 10 , [MnO4] = 1×5 ´ 10 , [Ru(III)] = 1×0 ´ –6 – –3 10 , [OH ] = 0×05, and I = 0×30 mol dm at 25°C. 3.5 Effect of initially added products

The initially added products, such as manganate, and water content in the reaction mixture with all other 4-carboxy methoxy phenyl acetic acid, do not have conditions kept constant, including concentration of any significant effect on the rate of the reaction.

38 Rahamatalla M Mulla et al

Table 2. Thermodynamic activation parameters for Ru(III)-catalysed oxidation of alkaline permanga- nate by atenolol in alkaline media with respect to the slow step of scheme 3. (a) Effect of temperature

Temp. (K) 298 303 308 313 318 k ´ 10–5 (dm3 mol–1 s–1) 2.10 2.31 2.51 2.75 2.99

(b) Effect of temperature on K1 in Ru(III)-catalysed oxidation of alkaline permanganate by atenolol in alkaline medium

Temp. (K) 298 303 308 313 318 3 –1 K1(dm mol ) 15.0 18.3 21.6 25.1 29.4

(c) Activation parameters

–1 # –1 # –1 –1 # –1 Parameters Ea (kJ mol ) log A DH (kJ mol ) DS (JK mol ) DG (kJ mol ) Catalysed reaction 13×7 ± 0×7 7×74 ± 0×4 11×2 ± 0×6 –25×1 ± 1×3 18×8 ± 1×0 Uncatalysed reaction16 24 ± 3 – 21 ± 3 –200 ± 10 82 ± 4

(d) Thermodynamic quantities for the first equilibrium of scheme 3

Thermodynamic quantities DH (kJ mol–1) DS (JK–1 mol–1) DG (kJ mol–1) Values 25×9 ± 1×4 110 ± 6 –7×8 ± 0×4

3.6 Test for free radicals 4. Discussion

– To test for the intervention of free radicals, the reac- Permanganate ion, MnO4, is a powerful oxidant in tion mixture was mixed with acrylonitrile monomer aqueous alkaline media. As it exhibits many oxida- and kept for 24 h under nitrogen atmosphere. On di- tion states, the stoichiometric results and pH of the lution with methanol, white precipitate of polymer reaction media play important roles. Under the pre- was formed, indicating that intervention of free radi- vailing experimental conditions at pH > 12, the re- cals in the reaction does occur. The blank experi- duction product of Mn(VII), i.e. Mn(VI), is stable ment of reacting either permanganate and ruthenium and further reduction of Mn(VI) might be stopped.10,11 (III) or atenolol and ruthenium (III) alone with acry- Diode array rapid scan spectrophotometric (DARSS) lonitrile did not induce polymerization under the studies have shown that at pH > 12, the product of same conditions. Initially added acrylonitrile de- Mn(VII) is Mn(VI) and no further reduction is ob- creases the rate indicating free radical intervention, served as reported by Simandi et al.10 However, on as in the earlier work.24 prolonged standing, the green Mn(VI) is reduced to Mn(IV) under our experimental conditions. 3.7 Effect of temperature Permanganate in alkaline media exhibits various oxidation states, such as Mn(VII), Mn(V) and Mn(VI). Rates of reaction were measured at different tem- The colour of the solution changes from violet to peratures under varying atenolol concentrations. blue and further to green excluding the accumulation Rate of reaction increases with increase of tempera- of hypomanganate. The violet colour originates ture. The rate constants, k, of the slow step of from the pink of the permanganate and the blue from scheme 3 are obtained from the slope of the plot of the hypomanganate during the course of the reaction. [Ru(III)]/kc vs 1/[atenolol] (r ³ 0.9996, S £ 0.0121) Colour change in the KMnO4 solution from the vio- and used to calculate the activation parameters. The let Mn(VII) ion to the dark green Mn(VI) ion through values of k (dm3 mol–1 s–1) are given in table 2. The the blue Mn(IV) ion has been observed. activation parameters corresponding to these con- It is interesting to identify the probable species of stants were evaluated from the plot of log k vs 1/T ruthenium(III) chloride in alkaline media. Electronic 25 (r ³ 0.9989, S £ 0.0135) and are tabulated in table 2. spectral studies have confirmed that ruthenium

Ruthenium (III)-catalysed oxidation of atenolol by alkaline permanganate 39

3+ (III) chloride exists in hydrated form as [Ru(H2O)6] . ATN to give a complex (C), which reacts with one In the present study in alkaline media it is quite mole of the alkali permanganate species in a slow 2+ probable that the species [Ru(H2O)5OH] might as- step to form a free radical derived from atenolol and III 3–x 2– sume the general form [Ru (OH)x] . The value of the product MnO 4 with regeneration of catalyst, ruthe- x would always be less than six because there are no nium (III). Such complex formation between sub- definite reports of any hexahydroxy species of ru- strate and catalyst has also been observed in earlier thenium. The remainder of the coordination sphere work,29,30 which is also supported by the observed is filled by water molecules. Hence under the ex- fractional order in [OH–] and [atenolol]. The free perimental conditions [OH–] ä [RuIII], ruthenium radical derived from atenolol combines with per- (III) is mostly present26 as the hydroxylated species, manganate species in a fast step to form a diol. This 2+ [Ru(H2O)5OH] . diol reacts with six more moles of permanganate The reaction between permanganate and atenolol species in further fast steps to yield the products in alkaline media in presence of ruthenium (III) has shown in scheme 3. the stoichiometry of 1 : 8 with first-order dependence The probable structure of the complex (C) is given – on [MnO4] and [ruthenium (III)] and less than unit- in chart 1. order dependence on both [alkali] and [atenolol]. No Spectral evidence for such a catalyst-substrate effect of added products is observed. The apparent complex was obtained from the UV-Vis spectra of order of less than unity in [OH–] may be an indication atenolol and a mixture of ruthenium (III) and ateno- of the formation of permanganate species as alkali lol. A hypsochromic shift, lmax, of »5 nm from 343 2– permanganate, MnO4.OH , from permanganate ion to 338 nm is observed together with hyperchromicity in a prior-equilibrium step.27,28 Formation of the at 338 nm. 2– MnO4.OH species in alkaline media was further The thermodynamic quantities for the first equili- supported by the Michaelis–Menten plot (figure 4) brium step in scheme 3 can be evaluated as follows. which is linear with a positive intercept. Based on The hydroxyl ion concentration (as in table 1) is varied the experimental results, a mechanism can be pro- at different temperatures. The plots of [Ru(III)]/kc vs posed in which all the observed orders with respect 1/[OH–] (r ³ 0×9999, S £ 0×0113) should be linear as to each constituent such as oxidant, catalyst, reductant shown in figure 4. From the slopes and intercepts, – and OH may be well accommodated. Here the hy- the values of K1 are calculated at different tempera- droxylated species of ruthenium (III) reacts with tures and are given in table 2. A vant Hoff plot was made for the variation of K1 with temperature [i.e., log K1 versus 1/T (r ³ 0×9998, S £ 0×0128)] and the 1/[OH–] ´ 10–1 (dm3 mol–1) values of the enthalpy of reaction DH, entropy of re- 6 4 2 0 action DS and free energy of reaction DG, were cal- 0 culated. These values are also given in table 2. A comparison of the latter values with those obtained 4

1 for the slow step of the reaction shows that these s)

3 –

s) values mainly refer to the rate-limiting step, suppor- 3 – dm ting the fact that the reaction before the rate-deter- 3 dm 2 (mol

5 mining step is fairly slow and involves high activation (mol 31 10 5

´ energy.

3 10

´ kc 2 In the presence of catalyst, the reaction is under- kc 4 stood to occur in parallel paths with contributions

[Ru(III)]/ from the uncatalysed and catalysed paths. Thus the 1 5

2+ 0 6 OH H C OH O 2 0 0.3 0.6 0.9 1.2 3 OH2 -3 3 -1 HC HN H C HC H C O CH C Ru 1/[ATN] x10 (dm mol ) 2 2 2 H C NH OH 3 2 OH 2 Figure 4. Verification of rate law (2) in the form of (3) (conditions as in table 1). Chart 1.

40 Rahamatalla M Mulla et al

2– O OH K – 1 O Mn Mno4 + OH O O

OH CH3 CH O CH2 CH CH2 NH CH3 K 2+ 2 + [Ru(H2O)5OH] Complex(C) + H2O O

CH2 C NH2 OH CH . 3 2– O CH CH CH NH CH O 2 CH OH 3 k 2+ Complex(C) + O Mn + MnO2– + [Ru(H O) OH] + H O slow 4 2 4 2 O O O CH2 C NH2 OH CH . 3 O CH CH CH NH CH OH OH 2 CH CH3 3 O CH CH CH NH CH 2– 2 O CH3 OH O fast + MnO2– + O Mn 4 CH C 2 O NH O 2 O CH2 C NH2

OH OH CH OH OH 3 CH CH 3 O CH2 CH CH NH CH O CH2 CH CH NH CH3 CH3 fast + OH + NH3 O O CH C 2 CH C NH 2 - 2 O OH OH CH3 CH O CH2 CH CH NH CH3 2– O CH COOH O 2 CH OH fast 3 O + 6 O Mn + HOOC NH CH CH C CH3 2 _ O O O O CH2 C _ O 2– + 6 MnO + 4 H2O 4 Scheme 3.

Ruthenium (III)-catalysed oxidation of atenolol by alkaline permanganate 41

# total rate constant (kT) is equal to the sum of the rate value of DS indicates that the complex (C) is more 33 constants of the catalysed (kc) and uncatalysed (ku) ordered than the reactants. The observed modest reactions: enthalpy of activation and the higher rate constant of the slow step (compared to k ) indicate that the rate = rate –rate . c cat total uncat oxidation presumably occurs by inner-sphere Scheme 3 leads to the rate law (3) below. mechanism. This conclusion is supported by earlier work.34,35 d[MnO-] Rate=- 4 = The effect of ionic strength on the rate can be un- dt derstood essentially on the basis of ionic species as kKK[ATN][MnO]-[Ru(III)][OH-] 12TT4 TT .in scheme 3. The effect of solvent on the reaction -- (1+K2[ATN])(1+K2[Ru(III)])(1+K1[MnO4])(1+K1[OH]) rate has been described in detail in the literature.36 (2) Increasing the content of t-butanol in the reaction – The terms (1 + K1[MnO4]) and (1 + K2[Ru(III)]) in medium leads to an increase in the rate of reaction, the denominator of (2) approximate to unity in view which seems to be contrary to the expected interac- – of the low concentrations of MnO4 and ruthenium tion between neutral and anionic species in media of (III) used (omitting the subscripts T and f ). In terms lower relative permittivity. However, an increase in of rate constants, the rate of reaction with decreasing dielectric con- stant may be due to stabilization of the complex (C) rate ==-kCTkkU at low relative permittivity, which is less solvated [MnO-] – 4 than MnO4 at higher dielectric constant because of its larger size. Spectrofluorimetric studies reveal KKK[ATN][Ru(III)][OH-] 12 . (3) -- that the fluorescence intensity is quenched, which 1+K[OH]+K[ATN]+KK[OH][ATN] 37 1212 may be due to the electron transfer reaction. Equation (3) can be rearranged to the following form, which is used for the verification of the rate law. 5. Conclusion

[Ru(III)] 1 – = It is interesting that the oxidant species [MnO4] re- - kC kK1K2[ATN][OH] quires a pH > 12 for reaction, below which the system becomes disturbed and the reaction proceeds further +1+1+1. (4) to give the reduced product of the oxidant, Mn(IV), kK[ATN] - k 2 kK1[OH] which slowly develops yellow turbidity. Hence, it becomes apparent that in carrying out this reaction According to (4), the plots of [Ru(III)]/kc versus – the role of pH in a reaction medium is crucial. It is 1/[ATN] and [Ru(III)]/kc versus 1/[OH ] (r ³ 0×9996, S £ 0×0121) and (r ³ 0×9999, S £ 0×0113) are also noteworthy that under the conditions studied, linear with an intercept supporting the Ru(III)- the reaction occurs as two successive one-electron atenolol complex, and which is verified in figure 4. reductions (scheme 3) rather than as a two-electron From the slope and intercept of such plots, the values reduction in a single step (scheme 2). Ruthenium 3 (III) is known to be an efficient catalyst especially of K1, K2 and k are calculated to be 15×0 ± 0×75 dm mol–1, 4×20 ± 0×21 ´ 102 dm3 mol–1 and 2×10 ± 0×1 ´ in alkaline media, a micro amount of ruthenium (III) 5 3 –1 –1 is sufficient to catalyse the title reaction with meas- 10 dm mol s . The value of K1 is in agreement 32 urable rate. The overall mechanistic sequence de- with the earlier value. Using these K1, K2 and k values, the rate constants under different experimen- scribed here is consistent with products, mechanistic tal conditions were calculated by (3) and compared and kinetic studies. with experimental data, with which there is good agreement (table 1). Appendix A The difference in the activation parameters for the catalysed (kc) and uncatalysed (ku) reactions (table According to scheme 3 2) explains the catalytic effect on the reaction. The catalyst, Ru(III), forms a complex with atenolol that ratecat = ratetotal–rateuncat is more reducible than atenolol itself. Hence, the – – catalyst lowers the energy of activation. The negative = kK1K2[ATN]f [MnO4]f [OH ]f [Ru(III)]f. (A1)

42 Rahamatalla M Mulla et al

The total concentration of atenolol [ATN]T, is given 12. Panari R G, Chougale R B and Nandibewoor S T by (subscripts T and f stand for total and free), 1998 Pol. J. Chem. 72 99 13. White M, Fourney A, Mikes E and Leenen F H H [ATN]T = [ATN] f + [C] 1999 Am. J. Hypertension 12 151 14. Swarnalaxmi N, Uma V, Sethuram B and Navaneeth = [ATN] f + K2[ATN]f [Ru(III)] = [ATN] (1 + K [Ru(III)]). Rao T 1987 Indian J. Chem. A26 592 f 2 15. Bailar J C, Emeleus H J, Nyholm R S and Dickenson Therefore, A F 1975 Comprehensive inorganic chemistry (Oxford: Pergamon) vol. 3, p. 810 [ATN] f = [ATN]T/(1 + K2[Ru(III)]). (A2) 16. Gurubasavaraj H M, Kulkarni R M and Nandibewoor S T 2003 J. Chem. Soc., Perkin Trans. II (communi- Similarly, cated) – – – 17. Jeffery G H, Bassett J, Mendham J and Denney R C [OH ] f = [OH ]T/(1 + K1[MnO4]), (A3) 1996 Vogel’s text book of quantitative chemical – – [Ru(III)] f = [Ru(III) ]T/(1 + K2[ATN ]), (A4) analysis 5th edn (Essex, UK: ELBS, Longman) p. 371 – – – 18. Carrington A and Symons M C R 1956 J. Chem. Soc. [MnO4] f = [MnO4]T/(1 + K1[OH ]). (A5) 3373 19. Reddy C S and Vijayakumar T 1995 Indian J. Chem. Substituting (A2)–(A5) in (A1) we get A34 615; 1970 Chem. Abstr. 72 50624 d[MnO-] 20. Ref. 17, p. 679 rate=- 4 = 21. Ref. 17, p. 462 dt 22. Feigl F 1975 Spot tests in organic analysis (Amster- kKK[ATN][MnO]-[Ru(III)][OH-] dam: Elsevier) p. 250 12TT4 TT . -- 23. Lide D R (ed.) 1992 CRC hand book of chemistry (1+K2[ATN])(1+K2[Ru(III)])(1+K1[MnO4])(1+K1[OH]) and physics 73rd edn (London: CRC Press) pp. 8–51 (A6) 24. Bhattacharya S and Benerjee P 1996 Bull. Chem. Soc. Jpn. 69 3475 25. Cotton F A and Wilkinson G 1996 Advanced inorga- References nic chemistry (New York: Wiley Eastern) p. 153 26. Kamble D L and Nandibewoor S T 1998 J. Phys. 1. Stewart R 1965 In Oxidation in organic chemistry – Org. Chem. 11 171 Part A (eds) K B Wiberg (New York: Academic Press) 27. Panari R G, Chougale R B and Nandibewoor S T 2. Freeman F 1976 Rev. React. Species Chem. React. 1 1998 J. Phys. Org. Chem. 11 448 179 28. Vivekanandan S, Venkatarao K, Sanatappa M and 3. Lee D G 1980 Oxidations of organic compounds by Shanmuganathan S P 1983 Indian J. Chem. A22 permanganate ion and hexavalent chromium (La 244 Salle, IL: Open Court) 29. Rao S V and Jagannadham V 1985 React. Kinet. 4. Lee D G 1982 In Oxidation in organic chemistry – Catal. Lett. 27 239 Part D (ed.) W S Trahanovsky (New York: Aca- 30. Upadyaya S K and Agarwal M C 1980 Indian J. demic Press) p. 147 Chem. A19 478 5. Simandi L I 1983 In The chemistry of functional 31. Rangappa K S, Raghavendra M P, Mahadevappa D S groups (eds) S Patti and Z Rappoport (Chichester: and Channagouda D 1998 J. Org. Chem. 63 531 Wiley), suppl. ch. 13 32. Chimatadar S A, Kini A K and Nandibewoor S T 6. Lee D G, Lee E J and Brown K C 1987 Phase trans- 2003 Indian J. Chem. A42 1850 fer catalysis, new chemistry, catalysts and applications 33. Weissberger A 1974 Investigation of rates and ACS symposium series No. 326 (Washington DC: mechanism of reactions in techniques of chemistry Am. Chem. Soc.) p. 82 (ed.) E S Lewis (New York: Wiley Interscience) vol. 7. Fatiadi A J 1987 Synthesis 106 85 4, p. 421 8. Perez-Benito J F and Lee D G 1987 J. Org. Chem. 52 34. Martinez M, Pitarque M A and Eldik R V 1996 J. 3239 Chem. Soc., Dalton Trans. 2665 9. Gardner K A, Kuehnert L L and Mayer J M 1997 35. Farokhi S A and Nandibewoor S T 2003 Tetrahedron Inorg. Chem. 36 2069 56 7595 10. Simandi L I, Jaky M, Savage C R and Schelly Z A 36. Amis E S 1966 Solvent effects on reaction rates and 1985 J. Am. Chem. Soc. 107 4220 mechanisms (New York: Academic Press) 11. Nadimpalli S, Rallabandi R and Dikshitulu L S A 37. Lakowicz J R 1986 Principles of fluorescence spec- 1993 Transition Met. Chem. 18 510 troscopy (New York: Plenum) p. 257