Thiourea condensation with ethyl acetoacetate

Although the antithyroid activity of compounds incorporating an enolizable thioamide function was discussed earlier, this activity was in fact first found in the pyrimidine series. The simplest compound to show this activity, methylthiouracil (80) (shown in both enol and keto forms), is prepared quite simply by condensation of ethyl acetoacetate with thiourea.Further work in this series shows that better activity was obtained by incorporation of a lipophilic side chain. Preparation of the required dicarbonyl compound starts with acylation of the magnesium enolate of the unsyrametrically esterified malonate, 81, with butyryl chlo-... 

Methylthiouracil Methylthiouracil, 6-methyl-2-thio-2,4-(lH,3H)-pyrimidindione (25.2.3), is synthesized in a completely analogous manner by condensing ethyl acetoacetate with thiourea in the presence of sodium ethoxide [14]. 

Hinkel, L. E., Hey, D. H. The condensation of benzaldeyde and ethyl acetoacetate with urea and thiourea. Reel. Trav. Chim. Pays-Bas 1929,48, 1280-1286. 

Saxena et al. (2005) have reported a quick method for the condensation reaction of an aldehyde, ethyl acetoacetate, and urea or thiourea to synthesize substituted 3,4-dihydropyrimidin-2(lH)-ones using iodine-alumina as the catalyst under microwave irradiation and solvent-free conditions. This method required 1 min with a variety of aromatic, substituted aromatic, and heterocyclic aldehydes however, no aliphatic aldehyde has been nsed. 

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