Thiocarbamic acids formation

It has been reported <1998CC2315> that a similar [2+2] intramolecular cyclization of (2-cyclohex-l-enyl-2-methyl-propionyl)phenyl-thiocarbamic acid O-methyl ester leads to the formation of tricyclic thietane in 85% yield (Table 2). 

The reactivity of a,/9-unsaturated ketones and carboxylic acids shows much similarity to that of a-halo ketones and acids. The reactive position here though is displaced to the j3-carbon atom so that reaction with thiocarbamic acids gives rise to the formation of six-membered rings ... 

A major route to 2-amino-6/f-l,3,4-thiadiazines is by the condensation of a-haloketones with thiosemicarbazides (Section 6.17.7.2.2(ii)). Replacement of the thiosemicarbazide by a thiocarbamic acid or by a thiocarbazide results in formation of 3,6-dihydro-2//-l,3,4-thiadiazin-2-ones. Likewise, replacement with an A -arylthiohydrazide yields a 4//-l,3,4-thiadiazin-5(6/f)-one (Section 6.17.7.2.2(ii)). 3,6-Dihydro-27/-thiadiazin-2-ones are also available by the condensation of alkyl-hydrazines with a-(methoxycarbonylsulfenyl)alkylaryl ketones (Section 6.17.7.2.2(vi)), while the ring closure of (arylhydrazonoalkylthio)acetic acids with dicyclohexylcarbodiimide provides an alternative route to 4 -l,3,4-thiadiazin-5(677)-ones (Section 6.17.7.1.2). 2-Phenylimino-3-aryl-2,3-dihydro-l,3,5-thiadiazin-6-ones result from treatment of a-hydrazono-j8-ketoesters with aryl-isothiocyanates (Section 6.17.7.2.2(iv)). 

Fig. 8.22. (a) Formation of thiocarbamic acids from dithiocarbamates. (b) Their decomposition produces light sulfur compounds (CS2 and H2S)... 

The analogous N-thiocarboxyanhydrides have now been investigated. It was hoped that these thiocarbamates would be more stable to side reactions below pH 11 (decarboxylation) and those above pH 11 (NCA hydrolysis and hydantoic acid formation). While the His-NTA and those of Gly and Ala did prove more useful than the corresponding NCA in each case, the usefulness of the NTA derivatives was found limited by epimer formation of up to 20%. "... 

Salt formation with Brmnsted and Lewis acids and exhaustive alkylation to form quaternary ammonium cations are part of the rich derivati2ation chemistry of these amines. Carbamates and thiocarbamates are formed with CO2 and CS2, respectively the former precipitate from neat amine as carbamate salts but are highly water soluble. 

Replacement of halogen leads to formation of a C-S bond in many cases when alkyl or aryl halides are allowed to react with thiocarbonic acid derivatives such-as thiocarbamates, thiourea, dithiocarbamates, or xanthates. The importance of this method is due to the fact that the intermediates are readily converted into thiols by hydrolysis ... 

Problems associated with the formation of by-products in this procedure can be alleviated by tbe use of (9-dimethylaminoethyl-Atalkyl (or aryl) thiocarbamates (10) in place of tbe O-ethyl derivatives (9). In this modification, most of the by-products can be removed using an aqueous acid extraction. 

Previous work in our laboratory showed that thiocarbamates altered surface lipid synthesis by inhibiting formation of the precursor very long chain fatty acids [1,3]. Recent work has provided more evidence (P.B. Barrett and J.L. Harwood, this volume) that the thiocarbamates are oxidised to their sulphoxides and it is the latter which are responsible for the specific inhibition of fatty acid elongases. In germinating peas, as in leek, we have found separate chain-length specific elongases. The stearate and arachidate elongases are located in the endoplasmic reticulum and are much more sensitive to sulphoxides than to the parent thiocarbamate. 

In summary, thiocarbamates have been shown to specifically affect very long chain fatty acid (and wax/cutin/suberin) synthesis in a variety of plant tissues in vivo. This effect is most likely due to the formation of a more active metabolite (possibly a sulfoxide) and can be reversed by safening agents. It seems probable that effects on fatty acid elongation are important in the mechanism of action of thiocarbamates. 

In summary, ethofumesate appears to inhibit wax synthesis through preventing the formation of the precursor very long chain fatty acids. While the compound has parallels with thiocarbamates, its selective... 

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