3-Substituted Thiophenes. VII. Derivatives of 3-Aminothiophene

Synthesis and Antitumour Activity of New Derivatives of Flavone-8-acetic Acid (FAA). Part 31): 2-Heteroaryl Derivatives

“…Flavone-8-acetic Acid Derivatives phene-3-carboxylic acid readily gave the precursors to 5m and 5n, treatment of thiophene-2-carboxylic acid with sodium hypochlorite which is reported [9] to give 5-chlorothiophene-2-carboxylic acid, the precursor to 5s, was found to be unsatisfactory and this was better prepared from 2-chlorothiophene by bromination, lithium-halogen exchange and carboxylation. Similarly direct chlorination of thiophene-3carboxylic acid which is reported [10] to give either the 5chloro-or 2,5-dichloro-product was found to be difficult to control and, in our hands, gave only the trichloroacid corresponding to 5o. Lithium-halogen exchange of a suitable precursor followed by carboxylation proved to be a good general method and was used to obtain the precursor acids to 5p,q,r and s starting from 3,4-dibromothiophene [11] , 3bromo-2-chlorothiophene, 2,3-dibromothiophene, and 2bromo-5-chlorothiophene respectively.…”

Mechanism of Inactivation of γ-Aminobutyric Acid Aminotransferase by (S)-4-Amino-4,5-dihydro-2-thiophenecarboxylic Acid

“…Incubation of 22 with PLP followed by treatment with sodium borohydride (Scheme ) gave a product that was characterized by electrospray ionization mass spectrometry (Figure ), although some decomposition (about 35%) occurred during handling. Most aminothiophenes are unstable, and decomposition occurs via polymerization of the thiophene ring, possibly because of the ease of tautomerization of aminothiophenes (Scheme ). In fact, the C-5 proton of 22 readily exchanges in D 2 O, as observed in the NMR spectrum (data not shown), consistent with a rapid tautomerization.…”

Straightforward Synthesis of 3‐Aminothiophenes Using Activated Amides

“…The synthesis of 3-aminothiophenes was for the first time reported by Steinkopf in 1926 by reduction of 3-nitrothiophenes. [13] Few decades later, this motif was accessed through either a Hoffmann [14] or a Curtius rearrangement [15,16] of the corresponding 3-thiophenecarboxamide or -carbonyl chloride, and more recently, palladium-catalyzed amination of 3-halothiophenes was reported by Watanabe. [17] However, the number of direct methods for the synthesis of the 3-aminothiophene nucleus, as an alternative of thiophene functionalization, is very limited.…”