3-Aminothiophene-4-carboxamides

There is considerable interest in the chemistry of triazines as some of these compounds show pronounced antimalarial, antimicrobial and antiviral activity (76JCS(Pl)252l). Therefore two types of thiophenes annelated with a triazine ring will be mentioned. Thieno[2,3-d]-1,2,3-triazines were synthesized by cyclization of diazotized 2-aminothiophene-3-carboxamides (equation 55) (73M1586). Treatment of 3-alkylthio-6-styryl-5-oxo-2,5-dihydro-l,2,4-triazines with phosphorus pentasulfide in pyridine yields thieno[2,3-e]-l,2,4-triazines (equation 56) (78CI(L)585). Probably a thiation with subsequent cycloaddition and elimination of a hydride ion is involved. 

Treating 2-aminothiophene-3-carboxamides 31 with trichloroacetonitrile in basic media gave the corresponding 28 [89ZN(B)488],... 

Sodium cyanate, a reagent with a short shelf life, requiring frequent titration, has been used in cold, dilute acetic acid to convert o-aminoamides to 2-ureidobenzamides (155), which can be cyclized to quinazoline-2,4-diones (see 1) by heating at 100°C with 7 N hydrochloric acid, 8 N sodium hydroxide,257 or simply in water.258 No yields were published. Ammonium thiocyanate, similarly acidified, was used to convert 2-aminothiophene-3-carboxamide to 2-thioxothieno[2,3-d]pyrimidin-4-ones (see 12).255... 

Diazotization followed by cyclization has been used to prepare fused thiophene derivatives. Thus diazotization of 3-aminothiophene-2-carboxamides in cone. HC1 leads to thieno-1,2,3-triazines (Scheme 122) (75CRV241). A similar reaction was also observed with the 4-carboxamide derivatives. With 2,4-dicarboxamides as substrates the 3-diazo group preferred to cyclize with the 2-carboxamide group. 

The single crystal X-ray diffraction of carboxamide 267 indicates that this type of thiophene exists only in the ketone form, 5-aminothiophen-3(2//)-one, which is consistent with the results of the H and C NMR spectra <2006JOC8006>. 

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