Kinetics and Mechanism of Oxidation of Methimazole by Chlorite in Slightly Acidic Media

Abstract

The kinetics and mechanism of the oxidation of methimazole (1-methyl-3H-imidazole), MMI, by chlorite in mildly acidic environments were studied. It is a complex reaction that gives oligo-oscillations in chlorine dioxide concentrations in excess chlorite conditions. The stoichiometry is strictly 2:1, with the sulfur center being oxidized to sulfate and the organic moiety being hydrolyzed to several indeterminate species. In excess MMI conditions over chlorite, the sulfinic acid and sulfonic acid were observed as major intermediates. The sulfenic acid, which was observed in the electrochemical oxidation of MMI, was not observed with chlorite oxidations. Initial reduction of chlorite produced HOCl, an autocatalytic species in chlorite oxidations. HOCl rapidly reacts with chlorite to produce chlorine dioxide, which, in turn, reacts rapidly with MMI to produce more chlorite. The reaction of chlorine dioxide with MMI is competitive, in rate, with the chlorite-MMI and HOCl-ClO2(-) reactions. This explains the oligo-oscillations in ClO2 concentrations.

Novel Selective Spectrophotometric Methods for the Determination of Methimazole in Pure Form and in Pharmaceutical Formulation

“…system, therefore the absence of this group will retard the reaction pathway. So, it can be concluded that this method can be considered as a stability-indicating method for methimazole determination (7).…”

“…It was found that the ratio was 1.439:1.13 pointing out to a ratio of 1:1 (KMnO4 to Methimazole). Accordingly, the reaction pathway is suggested to proceed as [7]: According to the suggested mechanism of oxidation, the method is based on the presence of the thiol group which is oxidized by the MnO4 -/OH -…”

“…In the USP, methimazole has been assayed by silver nitrate precipitation method [1]. Various methods based on different analytical procedures have been described in literature for the determination of methimazole including Ultraviolet-Visible (UV-Vis) spectrophotometry [2][3][4][5][6][7], derivative spectrophotometry [8], Raman spectroscopy [9,10], resonance light scattering spectroscopy [11], chemiluminescence [12][13][14], fluorescence [15,16], capillary electrophoresis [17], immunoassay [18], molecularly imprinted biomimetic sensing [19], Thin Layer Chromatography (TLC) [20] and High Performance Liquid Chromatography (HPLC) [21][22][23][24][25]. Methimazole has been also determined using electrochemical methods by using different chemically modified electrodes through introducing various electron mediators on its surface [26][27][28][29][30][31][32][33].…”

Trapping Reactions of the Sulfenyl and Sulfinyl Tautomers of Sulfenic Acids

“…We tested the silyl enol ether trap’s ability to distinguish between tautomers generated in the aqueous peroxidation of methimazole, 9 , Scheme . A recent report suggested sulfenyl 10 and S-oxide 11 tautomers, but not the sulfinyl 12 . In the absence of a trap, the nominal sulfenic acid mass is seen, attributable to any tautomer.…”

“…A recent report suggested sulfenyl 10 and S-oxide 11 tautomers, but not the sulfinyl 12. 26 In the absence of a trap, the nominal sulfenic acid mass is seen, attributable to any tautomer. However, in the presence of the 1- trimethylsiloxycyclohexene, adducts attributable to all three tautomers are observed as shown in Figure 3; quantification of the SIC areas assigned to tautomers 10, 11, and 12 gives a relative abundance as 100:54:1, respectively.…”