Synergistic catalytic activity of RuCl3 and OsO4 on the selective oxidation of pregabalin drug molecule: Exploration of scope, reaction mechanism and kinetic modeling

• The kinetic and mechanistic picture of oxidation of pregabalin with alkaline chloramine-T have been clarified.
• The catalytic efficiency of the catalysts used follows the order: (RuCl3 + OsO4) > OsO4 > RuCl3.
• The most noteworthy is the significant synergistic effect of 71-fold in case of (RuCl3 + OsO4) catalyst.

The kinetics and mechanism of (RuCl3 + OsO4) in combination and, RuCl3 and OsO4 alone catalyzed oxidation of pregabalin (PGB) drug with chloramine-T have been investigated at 313 K in aqueous alkaline medium. The kinetic characteristics were found to be varied for each catalyzed reactions. In all the three catalyzed reactions, the reaction rate shows a first-order dependence of rate on [CAT]0 and a negative-fractional-order on [NaOH]. The order of [PGB]0 is found to be unity incase of [OsO4], but it is fractional in both RuCl3 and [RuCl3 + OsO4] catalyzed reactions. The orders with respect to [RuCl3] and [OsO4] are less than one whereas it is unity in case of [RuCl3 + OsO4]. Activation parameters have been evaluated. 2-isobutylsuccinic acid was identified as the oxidation product of PGB. Under identical set of experimental conditions, the reaction rates revealed that all the three catalyzed reactions are about 25 to 71-fold faster than the uncatalyzed reactions. The catalytic efficiency of these catalysts follows the order (RuCl3 + OsO4) > OsO4 > RuCl3. The observed reactivity sequence may be attributed to the different d-electronic configuration of the catalysts. Most noteworthy is the significant catalytic activity of 71-fold in case of (RuCl3 + OsO4) catalyst. It justifies the synergistic effect of (RuCl3 + OsO4) catalyst on the oxidation of PGB drug. An isokinetic relationship is observed with β = 366 K, indicating that enthalpy factors are controlling the rate. The reaction mechanisms put forward and rigorous kinetic models deduced, give the best fit to the experimental results for each catalyzed reactions.

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