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 permanganate (stopped-flow technique) RAHAMATALLA M MULLA, GURUBASAVARAJ C HIREMATH and SHARANAPPA T NANDIBEWOOR* PG Department of Studies in Chemistry, 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- Permanganates ions 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 Mn(VII) + S ¾¾® Mn(VI) + products, During oxidation by permanganate, it is evident 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 manganate ion, 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 oxygen 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.