Disulfides dithiocarbamic acid ester

Dithiocarbamic acid esters from bisthiuram disulfides... 

In a weakly alkaline solution, isothiocyanate reacts with the a-amino group of cysteine (Figure 2.64). The reaction of isothiocyanates with cystine leads to the cleavage of disulfide bond (-S-S-) with the formation of cysteine sulfenic acid and a dithiocarbamic acid ester. Dehydration of this ester yields 5-amino-l,3-thiazine-4-one-3-thione derivative and elimination of hydrogen sulfide produces a cyclic 2-thiazoline-4-carboxylic acid derivative (Figure 2.65). Reaction of cystine with thiocyanates (R-S-C=N), formed by spontaneous isomerisation of isothiocyanates, produces disulfide Cys-S-S-R and -thiocyanoalanine, which cyclises to 2-thiazoline derivative (Figure 2.66). 

These are easily prepared by the reaction of amines with carbon disulfide (1) in the presence of alkali (Scheme 17).2 The synthesis of dithiocarba mates (4) was first reported by Debus in 1850. Dithiocarba mates (4) form metal chelates, and sodium dimethyl dithiocarbamate is used in quantitative inorganic analysis for the estimation of metals, e.g. copper and zinc. Dithiocarba mates are also employed as vulcanisation accelerators and antioxidants in the rubber industry, and as agricultural fungicides.3 The parent dithiocarbamic acids are unstable, decomposing to thiocyanic acid and hydrogen sulfide however, the salts and esters are stable compounds. Dithiocarba mates (4) are oxidised by mild oxidants to the thiuram disulfides (38) (Scheme 17). 

In order to obtain cyclization of an N-a-carboxy dithiocarbamic acid (CLXXXI) to the thiazolidin-5-one-2-thione (CLXIII), dehydrating agents are necessary. These same products may, however, be obtained by simply warming the a-amino carboxylic acid esters with carbon disulfide, especially when there is an aromatic ring attached to the -carbon atom (method D). In this way a-(methylamino) phenylacetic acid and carbon disulfide yield 3-methyl-4-phenylthiazolidin-5-one-2-thione [121) (Table 24). 

Aromatic amines are too weak to undergo the above reactions they do add to carbon disulfide but the resulting dithiocarbamic acids cannot form salts the resulting unstable free acids decompose at once with evolution of hydrogen sulfide and formation of isothiocyanates which add the excess of amine and thus give thioureas as final products 93,94 a small amount of sulfur catalyses the formation of the thioureas.95 Treatment of salts of the dithiocarbamic acids obtained in this way with chloroformic esters in chloroform at 0° leads to loss of COS and alcohol and formation of isothiocyanates in high yield.96... 

Thus, 1-aminothiohydantoins (223) can be made in good yields by reaction of ethyl 2-hydra-zinoacetate with a suitable alkyl thiocyanate <92MI 302-02). Similarly, an a-amino acid, heated with a dithiocarbamic ester, gives a thiohydantoin. An adaptation of this is a one-pot procedure from amino acid, amine, carbon disulfide and base without isolating the dithiocarbamic ester (Scheme 156) <835391 >. 

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