Oxidation of Some Biologically Important Organic Substrates by Lipopathic Cr(VI) and Mn(VII): Kinetics and Mechanistic Study

Abstract

The search for novel oxidants has been ongoing due to the advancements in the synthesis of complex organic molecules under different reaction conditions. Most oxidation reactions employ inorganic oxidants with metal ions of Cr(VI), Mn(VII), Ce(IV), Fe(III), Ru(IV), V(V) etc. However, the poor solubility of these inorganic oxidants in nonaqueous media restricts their use for the oxidation of water insoluble organic substrates. To undertake reactions of organic substrates in organic homogeneous media, tailor made lipopathic oxidants are of much interest. Onium ions (generally refer to hypervalent ammonium, phosphonium, arsonium, tellurium ions etc,) having alkyl groups are attached as counterions to carry the oxidant from aqueous medium into organic medium. Due to amphipathic characteristics of these onium ions and resultant ion pair characteristics with the anionic counterpart the solubility, reactivity, and redox potentials of the oxidants vary significantly. These reagents are found to be mild, chemoselective and regioselective.With an objective to develop new efficient, selective and mild oxidation protocols, the oxidizing ability of some lipopathic oxidants namely cetyltrimethylammonium dichromate (CTADC), cetyltrimethylammonium permanganate (CTAP) and cetyltrimethylammonium cericnitrate (CTACN) has been explored by our research group using cetyltrimethylammonium (CTA) ion as the onium counterion for anionic dichromate, permanganate and cericnitrate. The CTA ion is well known for its amphipathicity, which is having the characteristics of being solubilized in both aqueous and non-aqueous media. Unlike other quaternary ammonium ions (tetrabutyl or tetraoctyl ammonium ions), the CTA ion has a relatively small head group with more exposed charge and a well-balanced hydrophobic group to carry the ions to both water and organic media and thus is a magic amphiphile. Its balanced amphiphilic system makes it capable to form various artificial organized assemblies such as micelles, reverse micelles, microemulsions, vesicles etc. The preliminary reports on oxidation of various mono- and bi-functional organic substrates by CTADC and CTAP show their mildness and chemoselectivity. The present research work aims at employing CTADC and CTAP to study the oxidative metabolism of some established drugs such as acetaminophen, epinephrine, isoniazid, carbamazepine and norfloxacin having multiple functional groups in nonaqueous medium.To achieve the objectives, the oxidation product(s) were isolated and characterized. The reaction kinetics was studied using UV-vis spectrophotometric method in different media with varied polarities and also in micro-heterogeneous systems generated due to the presence of surfactants. Suitable mechanisms have been proposed and supplemented by proper evidences such as deuterium kinetic isotope effect, solvent kinetic isotope effect, effect of medium, effect of temperature, effect of surfactants etc. The selectivity, mildness and biomimetic characteristics of the oxidative cleavage have been discussed and compared with that of the existing literature reports. Possibilities to utilize these oxidants as biomimetic chemical oxidation model have been explored primarily to synthesize the selective metabolites of drug candidates and to study the mechanism of oxidation at lipid-solution interfaces.The present thesis entitled, “Oxidation of some biologically important organic substrates by lipopathic Cr(VI) and Mn(VII) : Kinetics and mechanistic study” comprises of seven chapters...