Thiophene 2- carboxylic acid, conformation

The benzene ring has been proposed as an isosteric replacement in a dipeptide to enforce either the tram l1 1 or the cis conformation 312>31 (Scheme 1). Similarly, 2-(amino-methyl)pyrrole-l-acetic acid (8, R = H) has been proposed as a cis peptide bond mimic,141 having the same number of atoms between the amino and carboxylic acid functions as in a dipeptide. Several other amino- and carboxy-substituted aromatic structures have been used as spacers in peptides 2-, 3-, and 4-aminobenzoic acids (Abz, e.g., 7), 2-, 3-, and 4-(amino-methyl)benzoic acids (Amb, e.g., 2), 2-, 3-, and 4-(aminophenyl)acetic acids (APha, e.g., 5), 2- (4), 3-, and 4-(aminomethylphenyl)acetic acid (Ampa), (aminomethyl)pyrrole-, -thiophene-, and -furancarboxylic acids 6, (aminomethyl)pyrrole- 8 and -thienylacetic acids, and aminobiphenylcarboxylic acids. 

In the crystalline state the 2-thiophene, 2-selenophene, and 2-tellurophene carboxylic acids adopt a (X.O)-trans conformation (see Section II.D) whereas the 2-furoic acid is in the reversed (X,0)-cis conformation. 

When five equivalents of lithium metal were employed in the Birch reduction of thiophene-2-carboxylic acid, ring-opened 5-mercapto product and p,Y-unsaturated carboxylic acid were obtained. Upon heating at 150-160°C, dehydration to the corresponding p,Y-unsaturated 5-thiolactone occurred. It is noteworthy that the double bond was in a cis conformation. Substituted thiophene-2-carboxylic acids exhibited similar behavior (Scheme 117). 

The chiral polythiophene, poly(3- (.S )-5-amino-5-carboxyl-3-oxapcntyl -2,5-thiophenylene) hydrochloride, l-POWT, ring-functionalized with the amino acid L-serine, has been synthesized by Inganas and coworkers,69,168 and was found to exhibit pH-dependent UV-visible, fluorescence emission, and CD spectra. At a pH equal to the isoelectric point of the amino acid, the poly thiophene chains separate and adopt a nonplanar right-handed helical conformation. Increasing the pH leads to a more planar conformation of the backbone and aggregation of the polymer chains. 

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