Ruthenium catalyzed oxidative conversion of isatins to anthranilic acids: Mechanistic study

Oxidation of isatins (isatin, 5-methylisatin, 5-bromoisatin, and 5-nitroisatin) to their corresponding anthranilic acids was performed with sodium N-bromo-p-toluenesulfonamide or bromamine-T (BAT) as an oxidant and ruthenium trichloride (Ru(III)) as a catalyst in HCl medium at 30 +/- 0.1 degrees C. The four reactions follow identical kinetics with a first-order dependence each on [BAT](o) and [Ru(III)], zero-order on [Isatin], and inverse fractional-order on [H(+)]. Activation parameters have been deduced for the composite reaction. The rates satisfactorily correlate with the Hammett U relationship and the reaction constant p is -0.36 signifies that the electron donating groups accelerate the reaction while the electron withdrawing groups retard the rate. An isokinetic relationship is observed with beta = 360 K, indicating that enthalpy factors control the reaction rate. Oxidation products of isatins were identified as their corresponding anthranilic acids by GC-MS analysis and the yields were found to be > 90%. Under similar experimental conditions, the kinetics of Ru(III)-catalyzed oxidation of isatins with BAT has been compared with that of uncatalyzed reactions, revealing that the catalyzed reactions are three to fourfold faster. The observed results have been explained by a plausible mechanism and the related rate law has been deduced. The method adopted for the oxidation of isatins to anthranilic acids in the present work offers several advantages and can be scaled up to industrial operation. (c) 2008 American Institute of Chemical Engineers.