Ethyl dithioacetate

Methyl-5-oxo-l,5-dihydro-8-carbamoyl-l,2,4-triazolo[4,3-c]pyrimidines 577 and 578 were prepared by the cyclization of 576 with acetic anhydride and ethyl oxalate, respectively (89PHA604).The 4-methyl-l,2-dihydropyra-zolo[3,4-d]pyrimidine-3,6-dione 579 also was obtained in the latter case, as a consequence of breaking the amide bond and releasing the amine moiety. Coupling ethyl dithioacetate and 5-chloro-4-hydrazinopyrimidine (580) afforded the triazolo[4,3-c]pyrimidine 581 (89H239) (Scheme 114). 

Ethyl dithioacetate is commercially available from Aldrich and Fluka. 

Formaldehyde benzyl ethyl dithioacetal Chloromethyl ethyl sulfide (11 g) and a-toluene-thiol (12.4 g) react very vigorously, with evolution of hydrogen chloride, and control by cooling is necessary. After being kept overnight, the mixture is fractionated in a vacuum, affording the dithioacetal, b.p. 165°/19 mm, in 60% yield. 

An ene-type reaction of ethyl dithioacetate and dithiopropionate with amino-borane 99 has been reported [60]. While the reaction of dithiopropionate 98 (R=Me) halted at the stage of the S-boryl intermediate 100 (80%), the corresponding intermediate formed from dithioacetate 98 (R=H) rearranged to C-bo-ryl dithioester 101 (96%). When 2 equiv of 99 was used for 98 (R=H), 101 further reacted with 99 to give 1 2 adduct 102 (Scheme 22). 

The reaction has not been extensively applied although a few examples in the literature exist. For example, Scott et al. have used this reaction in the synthesis of thiazolyl bisamide CSF-IR kinase inhibitors for the treatment of cancer. The 2-methyl-5-aminothiazoles with different substituents were prepared via condensation of aminoacetonitrile and ethyl dithioacetate followed by cyclization and then coupled with carboxylic acid to yield bis-amides that were tested for in vivo activity. 

Synthesis from Acylhydrazines. The condensation of acyl hydrazines and ethyl dithioacetate in boiling ethanol furnishes 5-aryl-2-methyl-l,3,4-thiadiazoles, but 1,3,4-oxadiazoles are formed as main products in some cases. Under suitable conditions, the intermediate thioacetylacylhydrazines may be isolated. ... 

The lithiated enol ether (33) is a masked equivalent of the enolate of acetaldehyde,while ethyl dithioacetate has been used as an equivalent to the dianion... 

Ethyl dithioacetate is the starting material for a general synthesis of y-hydroxy-a-keto-acids outlined in Scheme 6 The dithioacetate thus acts as a synthon of the dianion (17). 

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