2-Thienylacetic acid

Through careful studies of the experimental conditions, it has become possible to apply the Willgerodt reaction to the synthesis of thienylacetic acids from acetylthiophenes. " ... 

Earlier investigations have shown that powerful antispasmodic activity occurs in various basic esters of a-substituted thienylglycolic acids, thienylacetic acids, and thienylpropionic acids of the general type (256), (cf. reference 5 for details). One such compound, the... 

Cefalotin Cefalotin, (6/ -frfl )-3-[(acetyloxy)methyl]-8-oxo-7-[(2-thienylacetyl) amino]-5-thia-l-azabicyclo[4.2.0]oct-2-en-2-carboxylic acid (32.1.2.1), is synthesized by direct interaction of 2-thienylacetic acid chloride with 7-aminocephalosporanic acid in the presence of sodium bicarbonate [70-74]. 

Recently, a new method was developed for the synthesis of both symmetrical and unsymmetrical derivatives of dithienylmaleic anhydride 165 and 173-176 based on the condensation of thienylacetic acid with halo ketones 168 and 171 at 70-90°C. The key feature occurs in the presence of atmospheric oxygen acting as an oxidant for the intermediate lactones (10RUP2378273) (Scheme 53). 

The following data are closely related to the results of a Russian team, who synthesized lactone- and lactam-bridged photochromes and studied their transformations. 2,5-Dimethyl-3-thienylacetic acid with a-chloro ketone in base gives ester 206, which undergoes cyclization when heated with K2CO3 in DMF under an inert atmosphere to give lactone 207 in 70-75% yields (Scheme 61). The reaction can be performed in situ without isolation of the ester (06ZOR1827)... 

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. 

The preparation of cyanomethylbenzo[6]thiophenes by reaction of halomethylbenzo[6]thiophenes with alkali metal cyanides is discussed in Section VI,D, 4. Reduction of cyanomethylbenzo[6]thiophenes affords (2-aminoethyl)benzo[6]thiophenes (Section VI, H, 2), and they give the corresponding benzo[6]thienylacetic acid on alkaline hydrolysis (Section VI,M, 3). 

Thioindoxyl and its 6-ethoxy derivative undergo the Reformatsky reaction with ethyl bromoacetate to give the corresponding 3-benzo-[6]thienylacetic acid, on alkaline hydrolysis of the reaction mixture.569... 

Benzo[6]thienylacetic acid and its 6-ethoxy derivative are obtained in low yield from the corresponding thioindoxyl by the Reformatsky reaction with ethyl bromoacetate.509 4-Benzo[6]thienylacetic acid is obtained by successive dehydrogenation and hydrolysis of the ester mixture shown in Eq. (10).355,448 7-Benzo[6]thienylacetic acid may be prepared similarly.303... 

Amides143,311,508,509 and esters 143,692 of benzo[6]thienylacetic acids are prepared by the usual methods. 

Thienylacetamido)cephalosporanic acid sodium salt may be produced from 2-thienylacetyl chloride, obtainable by treatment of 2-thienylacetic acid [Ernst, Berichte, 19 (1886) 3281] with thionyl chloride in a conventional manner. The 2-thienylacetyl chloride is then reacted with 7-aminocephalosporanic acid and then converted to the sodium salt using sodium hydroxide. 

The reaction was of general applicability not only internal but also terminal alkynes reacted in the same way, e.g. 1-hexyne was converted into hexanoic acid (58%) and 2-ethynylthiophene to 2-thienylacetic acid (54%). By contrast, heating terminal alkynes in chloroform with HTI afforded alkynyl or alkenyl phenyliodonium salts the former in refluxing methanol rearranged to methyl carboxylates [11],... 

Various Reactions in the Side-Chains of Thiophens. - The preparation of various iV-substituted thieno[3,2-/]morphans from 2,5-dimethylthieno[3,2-/Jmorphan has been described. Several thiophen isosteres of proto-berberine alkaloids have been prepared, starting from amides between 3-thienylacetic acid and substituted )3-phenylethylamine or 3-(3-thienyl)ethyl-amine, followed by classical cyclization to dihydroisoquinolines, reduction to the tetrahydro system, and Mannich-type reaction with formaldehyde. 

Benzo[ ]-3-thienylacetic acid 3 promotes plant growth, as does the corresponding indole compound. 

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