Thiocarbamate-S-oxide

As the thiocarbamate S-oxides behave similarly to those of the alkylmercapto-s -triazines in other respects, it would be of interest to investigate their reactivity to haemoglobin. 

Metathesis products (XCN+RSH) tend to be favored in anhydrous organic solvents, whereas addition products tend to be favored in aqueous medium. Examples of such reactions include the hydrolysis of HOSCN to give thiocarbamate-S-oxide (84) ... 

The experimentally determined and the deduced limiting rate laws agree at both pH 4 and 7. However, the proposed mechanism does not account for all the observed kinetic phenomena, which clearly indicate the presence of an alternative mechanism at pH>7 and [SCN ]o<[HOSCN]t ,o- The disproportionation of HOSCN/OSCN in a bimolecular reaction can be a feasible explanation 81,86). However, at pH>ll, OSCN is known to hydrolyze to thiocarbamate-S-oxide 84). 

The reaction of OSCN with OH at neutral pH is too slow to account for the observation of thiocarbamate-S-oxide at neutral pH (unpublished results). However, we have observed thiocarbamate-S-oxide during the decomposition of (SCN)2 under certain conditions neutral pH (impublished results), which suggests that unexplored alternative mechanisms may exist for the production of SCN -derived species. 

The l3C chemical shifts of methyl derivatives with sulfur substituents [e.g., SH, -S, -SCH3, -SSCH3, -SSSCHj, -S(0)CH3, -S02CH3, -S(CH3)2+, -SC(0)CH3, -SC(S)CH3, and -SC(S)SCH3] (130,131) and of vicinal and gem-inal bis-sulfides (290) have been reported. Freeman and co-workers have published similar studies on thiols, sulfides, disulfides, and sulfinic and sulfonic acid derivatives (131,132,433) and Tseng and Bowler (434), on thiocarbamates, their S-oxides and S,5-dioxides [R-X-C(0)-NR 2 with X = S, SO, S02]. 

The present review concentrates on the developments reported in the last few years (1992 to May 1997) and mostly on carbon-carbon bond forming reactions. Other classes of compounds are generally not discussed, including thiocarbo-nates, dithiocarbonates and thiocarbamates. The chemistry of thiocarbonyl S-oxides is presented and compared. 

S-oxidation occurs almost exclusively by FMO (Fig. 10.17). Sulfides are oxidized to sulfoxides and sulfones, thiols to disulfides, ahd thiocarbamates, mercaptopyrimidines, and mercaptoimidazoles (i.e., the antithyroid drug methimazole) via sultenates (RSOFI) to sultihates (RSO2H), all of which are eliminated in the urine. 

Figure 1. Oxidation and other reactions of dialiate and triallate indicating mutagenic activities of the products in the S. typhimurium TA 100 assay (revertants/ nanomole without activation/with activation / designates no data available). 2-Chloroacrolein is a dialiate metabolite in the mouse liver microsome-NADPH system. Dichloroallylsulfonic acid is a urinary metabolite of dialiate. The other compounds are potential metabolites of the respective thiocarbamates. The thio-carbamate sulfoxides are unstable at 25°C.

As in the case of propachlor mercapturic acid sulfoxide, the biological significance of xenobiotic mercapturic acids that contain oxidized sulfur is not known. Casida et al. (39) have reported that sulfoxidation of some thiocarbamate herbicides is a beneficial step in the detoxication process. However, cysteine conjugates can exhibit adverse biological activities. Smith (40) has reviewed work on the metabolism of the toxic principle in kale and has shown that C-S lyase action on S-methylcysteine sulfoxide produces the toxic principle. Virtanen ( ) has reviewed the processes in other plants that lead to the production of compounds with biological activity from -substituted cysteine sulfoxides. 

Numerous organic and inorganic sulfur compounds are adsorbed at the oxide-free surfaces of Au and Pt electrodes and can be detected by Mode II [62]. These compounds include thioalcohols, thioethers, thiophenes, thiocarbamates, organic thiophosphates, and numerous inorganic compounds. Adsorption is a prerequisite to detection and therefore at least one nonbonded electron pair must reside on the S-atom. The kinetics for detection of adsorbed S-compounds are quite favorable at pHs from 0 to 14. Since alcohol and amine groups are detected only under highly acidic and/or alkaline conditions, the detection of sulfur compounds under mildly acidic conditions is highly selective. 

---