Thiophene-2-carboxamides

Thiophene-2-carbonitrile, 3-azido-synthesis, 4, 807 Thiophene-2-carboxamide 3,5-disubstituted synthesis, 4, 9l9 5-substituted protonation, 4, 755... 

Thiophene-2-carboxamide, 3-amino-diazotization, 4, 810 Thiophene-2-carboxamide, 5-cyano-synthesis, 4, 898, 920... 

In addition to thiodiglycolic acid esters, the use of bis(cyanomethyl)sulfide in the Hinsberg reaction has facilitated the preparation of 5-cyano-thiophene-2-carboxamides. Thus, the condensation of biacetyl with bis(cyanomethyl)sulfide resulted in the efficient preparation of 10 (94% yield). 

Cyclohexyl carbamic acid 3 -carbamoyl-biphenil-3-y 1-ester (l-Methyl-4-(2-chloro-4-hydroxyphenylthio)-piperidine (R)-N-(l-azabicyclo[2.2.2]oct-3-yl)(5-(2-pyridyl)thiophene-2-carboxamide)... 

From a study of the protonation of various 5-X-substituted thiophene-2-carboxamides in aqueous H2SO4, it has been concluded that the thiophene nucleus is more efficient than the benzene ring in relaying the electronic effects of substituents to the reaction centre (80JCS(P2)172l). This follows from the fact that the p-value for the thiophene series (-1.16) is larger than that for benzamides (-0.956). 

Benzo[6]thiophene-2-carboxamides have been prepared by treatment of 2-benzo[6]thienyllithium with isocyanates,564 but are more conveniently obtained from the appropriate acid chloride by the conventional procedure.334,481,548,556,564,686-688 The acid chlorides react with diazomethane to give the diazoketone,218,689 and with dimethylcadmium 76,90 or diethyl ethoxymagnesium malonate218,336... 

Doadt, E. G. Snieckus, V. 3,5-Dilithiated tertiary thiophene 2-carboxamide. Regioselective... 

Irradiation of 3-chloro-A-phenylbenzo[Z ]thiophene-2-carboxamide and triethylamine in benzene/methanol (4/1) yielded [l]benzothieno[2,3-c]quinolin-6(5//)-one (92%)597. 

Earlier, a one-pot procedure based on consecutive Pd-catalyzed aryl-aryl coupling followed by N-C bond formation had been described for the synthesis of phenanthridones and their thiophene analogs <2004OL4759>. The starting materials were 2-iodotoluene and 3-bromothiophene-2-carboxamides or 3-bromobenzo[3]thiophene-2-carboxamides (Equations 40 and 41). The conditions were rather critical in order to prevent the nucleophilic amide group from coordinating with the palladium, tri-2-furylphosphine had to be added to the reaction mixture. Norbornene serves to form a palladacycle which then reacts with the bromoamide. 

Other examples are symmetrical bradykinin antagonists and symmetrical lexitropsins (netropsine, distamycine), active against HTV-I viruses. Non-symmetrical polymethylenic thromboxane synthetase inhibitors are described by Press et al The compounds contain a thiophene-2-carboxamide moiety, separated from an imidazole ring by 3-8 methylene units. Surprisingly, whereas most of the compounds show... 

Scarpelli R et al (2008) Studies of the metabolic stability in cells of 5-(trifluoroacetyl) thiophene-2-carboxamides and identification of more stable class II histone deacetylase (HDAC) inhibitors. Bioorg Med Chem Lett 18(23) 6078-6082... 

Reactivities of Side-chains of Monocyclic Thiophens.—The protonation of various furan- and thiophen-carboxamides in aqueous sulphur acid solution has been investigated by u.v. spectroscopy. The values of pKbh that were calculated using the acidity function and the Bunnett-Olsen linear free-energy relationship indicate the lower basicity of furan- and thiophen-2-carboxamides with respect to that of benzamides and of the 3-derivatives. The kinetics of isomerization of cw-l-(2-thienyl)-2-phenylacrylonitrile, as well as of its 2-furyl and 2-selenienyl analogues, have been studied in a solution of decahydronaph-thalene, with methanesulphonic acid and potassium t-butoxide as catalysts, and the mechanism has been discussed. ... 

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