4-Thiophenecarboxylic acid

Optical activity owing to restricted rotation (atropisomerism) has been demonstrated in two phenylthiophenes 2-(6-methyl-2-nitro-phenyI)-3-thiophenecarboxylic acid (41), which rapidly racemized in solution, and 2,5-dimethyl-4- (6 -methyl-2 -nitrophenyl) 3-thio-phenecarboxylic acid (42), which was optically stable (at room temperature). Recently the first bithienyl, 2,2 -dicarboxy-4,4 -dibromo-5,5 -dimethyl-3,3 -bithienyl (43), has been resolved into optical anti-podes which were optically stable. 

The usefulness of the Grignard reagent of 3-bromothiophene is somewhat limited as it can only be prepared by the entrainment method. The simultaneous formation of Grignard reagents from 3-bromothiophene and a fivefold molar excess of ethyl bromide gave, however, a 55% yield of 3-thiophenecarboxylic acid upon carbona-tion. With acetaldehyde, a 55% yield of methyl 3-thienyl carbinol... 

From resonance structure (12) it is obvious that a —I—M-substit-uent strongly deactivates the 2-position toward electrophilic substitution, and one would thus expect that monosubstitution occurs exclusively in the 5-position. This has also been found to be the case in the chlorination, bromination, and nitration of 3-thiophenecarboxylic acid. Upon chlorination and bromination a second halogen could be introduced in the 2-position, although further nitration of 5-nitro-3-thiopheneearboxylic acid could not be achieved. Similarly, 3-thiophene aldehyde has been nitrated to 5-nitro-3-thiophene aldehyde, and it is further claimed that 5-bromo-3-thiopheneboronic acid is obtained upon bromination of 3-thiopheneboronic acid. ... 

Additional examples of the reactivity of the 4-position in thiophenes with —I-j-M-substituent in the 3-position are provided by the bromination of 3-thiophenecarboxylic acid to 2,4,5-tribromothio-phenecarboxylic acid and the recent diacetylation of 2,5-dimethyl-thiophene by Goldfarb et who used the swamping catalyst... 

It has been shown that 2,3-thiophenedicarboxylic acid is preferentially esterified in the 2-position and the dimethyl ester is preferentially hydrolyzed in this position. The structure proof was difficult to achieve as rearrangements occurred. Thus both isomeric amides (195) and (196) were decarboxylized to the N-methylanilide of 3-thiophenecarboxylic acid (197). The same carbomethoxy benzoyl-thiophene, proved to be 2-carbomethoxy-3-benzoylthiophene (198),... 

Polymers formed from the electropolymerization of 3-thiophenecarboxylic acid, 3-cyanothiophene, and 3-nitrothiophene are soluble in acetonitrile. In addition, substitution of alkyl groups with more than six carbon atoms at the 3-position of the thiophene molecule and subsequent polymerization renders the reduced form of the polymer soluble. Indeed, solubility increases with chain length of the alkyl group and the de-doped or reduced forms are truly soluble in solvents such as toluene, THF, and methylene chloride. ... 

Potin D, Launay M, Monatlik F et al (2006) Discovery and development of 5-[(5S,9R)-9-(4-cyanophenyl)-3-(3,5-dichlorophenyl)-l-methyl-2,4-dioxo-l,3,7-triazaspiro[4.4]non-7-ylmethyl]-3-thiophenecarboxylic acid (BMS-587101) - a small-molecule antagonist of leukocyte function associated antigen-1. J Med Chem 49 6946-6949... 

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