2-Thiopheneacetic acid

Side-Chain Derivatization. Reaction of thiophene with aqueous formaldehyde solution in concentrated hydrochloric acid gives 2-chloromethylthiophene [765-50-4]. This relatively unstable, lachrymatory material has been used as a commercial source of further derivatives such as 2-thiopheneacetonitrile [20893-30-5] and 2-thiopheneacetic acid [1918-77-0] (24). Similar derivatives can be obtained by peroxide, or light-catalyzed (25) halogenation of methylthiophenes, eg, Ai-bromosuccinimide/benzoylperoxide on 2-, and 3-methylthiophenes gives the corresponding bromomethylthiophenes. 

The long-standing manufacturing route to 2-thiopheneacetic acid [1918-77-0] has also involved 2-acetylthiophene. Oxidation with potassium permanganate under controlled conditions leads to 2-thiopheneglyoxyhc acid [4075-59-6], which maybe isolated as ammonium salt. The salt is then carried... 

The principal source of 2-thiophenecarboxaldehyde is Great Lakes Fine Chemicals Ltd. in the United Kingdom, whereas 2-acetylthiophene is produced by a number of manufacturers. Some of the 2-acetylthiophene producers continue derivatization to 2-thiophenecarboxyhc acid and 2-thiopheneacetic acid. 

Chemical Name 5-Benzoyl-0i-methyl-2-thiopheneacetic acid... 

CN ejco-a-hydroxy-a-2-thienyl-2-thiopheneacetic acid 6,9,9-trimethyl-9-azabicyclo[3.3.l]non-3-yl ester hydrochloride... 

CyHyNO 21850-61-3) see Benoxaprofen Flunoxaprofen 2 -hydroxy-3-phenylpropiophenone (C15H14O2 3516-95-8) see Etafenone Propafenone (2S-cw)-4-hydroxy-4-phenyI-l,2-pyrroIidinedicarboxyIic acid l-(phenylmethyl) ester (CiyHiyN05 78464-03-6) see Fosinopril a hydroxy-a-phenyl-2-thiopheneacetic acid 2-diethylami-noethyl ester... 

An approach to the synthesis of angularly substituted polycyclics through the Diels-Alder cycloaddition of dihydrothiophenes has been devised (69JA7780). The easily prepared 2,5-dihydro-4-methoxycarbonyl-2-thiopheneacetic acid methyl ester (316) was heated at 180 °C with excess butadiene to yield (317). Desulfurization and double bond reduction of the cycloadduct with W-5 Raney nickel gave (318) which was characterized by conversion to the corresponding diacid and comparison with an authentic sample. Dieckmann cyclization of (318) is known to lead to the 5-methyl-1-hydrindanone (319 Scheme 68). The use of other dienes in the [4 + 2] cycloaddition process will, of course, produce more highly functionalized hydrindanones. 

Therapeutic Function Antiinflammatory Chemical Name 5-Benzoyl-a-methyl-2-thiopheneacetic acid Common Name -Structural Formula ... 

As exemplified by equation (2), the Perkin condensation of o-hydroxybenzaldehydes is an important method for the synthesis of substituted coumarins. An interesting variation on this procedure has been reported recently. Heating a mixture of o-fluorobenzaldehyde, 2-thiopheneacetic acid, acetic anhydride and triethylamine affords directly the coumarin (20 equation 13) instead of the expected cinnamic acid (21). The reaction proceeds similarly with several arylacetic acids. The reaction presumably proceeds through the cinnamic acids (21). The observed product can conceivably arise by direct nucleophilic displacement involving the carboxylate or by an elimination/addition (benzyne) mechanism. The authors note that when 2-fluorobenzaldehyde is replaced by its 2-bromo analog in this reaction, the substituted cinnamic acid (22) is the major product and the corresponding coumarin (20) is obtained only in low yield. It is suggested that since it is known that fluoride is displaced more rapidly in nucleophilic aromatic substitution reactions, while bromo aromatic compounds form benzynes more rapidly, this result is consistent with a nucleophilic displacement mechanism. 

The preparation of 2-thiopheneacetic acid appeared in a Chinese patent (14PAT-1) in the year 2014 in which thiophene was treated with formaldehyde in the presence of FICl affording 2-chloromethylthio-phene.This intermediate was then treated with sodium cyanide and the resulting 2-methylcyano derivatives were hydrolyzed to 2-thio-phe-neacetic acid. 

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