4 thiophene 3-carboxamide

Reactivities of Side-Chains of Monocyclic Thiophens. - The protonation behaviour of some 3-, 4-, and 5-substituted thiophene-carboxamides in aqueous sulphuric acid solution has been studied by the u.v. technique. + values were determined by and Bunnett-Olsen methods using multivariate analysis, mission of electronic effects was obtained... 

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. ... 

P. L. Podolin, J. F. Callahan, B. J. Bolognese, Y. H. Li, K. Carlson, T. G. Davis, G. W. Mellor, C. Evans, A. K. Roshak, J. Pharmacol. Exp. Then 2005, 312, 373-381. Attenuation of murine collagen-induced arthritis by a novel, potent, selective small molecule inhibitor of 1 kappa B kinase 2, TPCA-1 (2-[(aminocarbonyl)amino]-5-(4-fluorophenyl)-3-thiophene-carboxamide), occurs via reduction of proinflammatory cytokines and antigen-induced T cell proliferation. 

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). 

HPA = (4-pyridylthio)aceticacid 2-fur = 2-furoate a-fur = a-furoate = ([Pg.116]

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)... 

Regioselactive g-metallation of ir-excessive five ring heterocycles is not a novel reaction. Oxazoline and pyridine as well as carboxylate- and carboxamide -substituted heterocycles have been lithiated. From the point of synthetic utility thiophenes have been shown to be useful substrates after careful optimization of reaction conditions furans have been of less utility. 

Thiophenes can function either as a diene or as a dienophile in an intramolecular Diels-Alder reaction (90CC405). The 7V-(2-thienyl)allene carboxamide (182) on heating at 130°C leads to (183) by a [4 + 2] cycloaddition in which the thiophene functions as a 4ir component, followed by the usual extrusion of sulfur. 

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). 

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. 

Benzo[6]thiophene-2,3-quinones are reported to undergo several interesting transformations. Oxidation of 5-chIorobenzo[6]thiophene-2,3-quinone with H202 in the presence of ammonia gives 5-chloro-l,2-benzisothiazole-3-carboxamide (Scheme 157) (70AHC(11)177). 

Acetaminothiophene has been prepared by a Hofmann rearrangement of thiophene-3-carboxamide (equation 49), or by a Beckmann rearrangement of the 3-acetylthiophene oxime (Section 3.14.3.4). Dimethyl 4-amino-2,3-thiophenedicarboxylate was formed in excellent yield from the oxime of the 4-ketotetrahydrothiophene diester, which is readily available by addition of thioglycolate to dimethyl fumarate, followed by a Dieckmann cyclization (equation 50 Section 3.15.2.2.2). 

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. 

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... 

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