Thiocarbamates, oxidation

The toxic nature of mercury and its compounds has caused concern over environmental pollution, and governmental agencies have imposed severe restrictions on release of mercury compounds to waterways and the air (see Mercury). Methods of precipitation and agglomeration of mercurial wastes from process water have been developed. These methods generally depend on the formation of relatively insoluble compounds such as mercury sulfides, oxides, and thiocarbamates. MetaUic mercury is invariably formed as a by-product. The use of coprecipitants, which adsorb mercury on their surfaces facihtating removal, is frequent. 

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]. 

Ruzo, L.O. and Casida, J.E. Photochemistry of thiocarbamate herbicides oxidative and free radical processes of thiobencarb and diallate, J. Agric. Food Chem., 33(2) 272-276, 1985. 

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. 

Many organosulfur compounds undergo biological oxidation at the sulfur atom to yield products which have pronounced physiological activity or serve as intermediates in generating bioactive compounds. Three examples are the lachrymating agent in onions ( ) (1), the oxo intermediate ( ) in metabolic desulfuration of phosphorothionate insecticides to form potent cholinesterase inhibitors (2), and the sulfoxides QJ produced on metabolism of thiocarbamate herbicides (3). 

Synthesis. Oxidation of -alkyl or -benzyl IJ,IJ-dialkylthio-carbamates with one equivalent of m-chloroperoxybenzoic acid (MCPBA) in chloroform or methylene chloride at -25° to 25°C yields the corresponding carbamoyl sulfoxide (3) in essentially quantitative yield (3-5). The -chloroallyl thiocarbamate sulfoxides (e.g., 4-7) are obtained in the same manner except that the temperature is maintained between -20°C and 0°C for the oxidation and extraction of the reaction mixture with 5% sodium carbonate aqueous solution (7, 8). 

The NMR chemical shifts for the carbamoyl sulfoxides (Table I) support their proposed structures. In examining the oxidation reactions, it is convenient to add MCPBA to a solution of the thiocarbamate in CDCI3 at -20°C and take frequent spectra during oxidation as the reaction mixture warms up to 40°C. Comparison of these spectra with that of the parent compound at -20 to 40°C allows recognition of short-lived intermediates and terminal products. With the parent thlocarbamates for compounds 5-2, the methyl group signals appear as one doublet at 40°C but two... 

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. 

Oxidative desulfurization of the thiourea moiety is known to occur by an in vivo metabolism which forms the corresponding carbonyl compound, although there is no direct evidence for involvement of any activated oxygen species like superoxide, which is distributed widely in living cells. It was found that various thiocarbonyl derivatives such as thioureas, thioamides and thiocarbamates were readily desulfurized with 51 to the corresponding carbonyl compounds in almost quantitative yields at —35°C in CH3CN (equation 82). Desulfurization of thiourea with 02 was previously reported but the yields were comparatively low. ... 

Food Wet oxidation with sulfuric acid, complexation with ammonium tetramethylenedi-thiocarbamate followed by extraction with methyl butyl ketone AAS 20 pg/kg No data lARC 1986 (Method 17)... 

The oxidation of the thiocarbamates to form sulfoxides is another activating process as it has been shown that the sulfoxides are more... 

The reaction of sucrose 2,3-manno-epoxide with potassium thioacetate and ammonium chloride in aqueous ethanol gave the expected 3-5>-acetyl-3-thio-altropyranoside (101). Treatment of 6,6,-dibromo-6,6,-dideoxysucrose hexaacetate with potassium thioacetate and A/, Ak dimethyl thiocarbamate gave the corresponding derivatives of 6,6,-dithiosucrose. The air oxidation of 6,6,-dithiolsucrose gave the bridged 6,6,-episulfide. A detailed conformational study of sucrose 6,6,-dithiol and sucrose 6,6 -episulfide revealed that they are similar but distinguishable (102). 

Freund,168-160 formulating the oxides as substituted 1,2,4-thia-diazolidines (152) and the sulphides as 1,2,4-dithiazolidines (155), justified the assignment of unlike hetero-nuclei on the grounds that sulfides were also obtainable by the action of bromine on alkyl dithiocarbamates (see below), while oxides were unobtainable by the corresponding reaction of alkyl thiocarbamates. Hantzsch and... 

---