2-thiophenecarboxylate

The mercaptals obtained by the acid catalyzed reaction of J3-ketoesters, e.g., ethyl acetoacetate, with methyl thioglycolate (73) undergo the Dieckmann cyclization with alcoholic potassium hydroxide at lower temperatures to give ethyl 3-hydroxy-5-methyl-2-thiophenecarboxylate (74) in 75% yield. ° Besides ethyl acetoacetate, ethyl a-ethylacetoacetate, ethyl benzoyl acetate, and ethyl cyclopentanonecarboxylate were also used in this reaction/ It is claimed that /8-diketones, hydroxy- or alkoxy-methyleneketones, or /8-ketoaldehyde acetals also can be used in this reaction. From acetylacetone and thioglycolic acid, 3,5-dimethyl-2-thiophenecarboxyl-ic acid is obtained. ... 

Halogenated- ,/S-unsaturated ketones or aldehydes are reacted with methyl thioglycolate and cyclized with alkali alcoholate/ Thus jS-bromobenzalacetone (75) gives methyl 3-methyl-5-phenyl-2-thio-phenecarboxylate (76) and from a-methyl-j5-chlorocrotonaldehyde (77), 4,5-dimethyl-2-thiophenecarboxylate (78) is obtained. 

Using a,jS-dihalogenonitriles instead of carbonyl derivatives in the reaction with methyl thioglycolate leads to methyl 3-amino-2-thio-phenecarboxylates. Thus, a, -dichlorobutyronitrile (79) gave methyl 3-amino-5-methyl-2-thiophenecarboxylate (80)... 

It now seems definitely proved that the thiothiophthene (86) rearranged reversibly to a thiophene (87) under the influence of alkali and not to a thiepin derivative, The dimethyl ether of (87) has been oxidized to 4-methylsulfonyl-2-thiophenecarboxylic acid (88)... 

Finally, certain 3-substituted compounds can be prepared by utilizing the - meta) directing powet (cf. Section IV,B) of some groups in the 2-position which afterward can be removed. 3-Nitrothiophene is prepared by nitration of 2-thiophenesulfonyl chloride and by removal of the sulfonic acid group of the 4-nitro-2-sulfonyl chloride formed with superheated steam. Another approach to 3-nitrothio-phene is to nitrate 2-cyanothiophene, separate the 4-nitro-2-cyano-thiophene from the 5-isomer, hydrolyze, and decarboxylate. A final method of preparation of 3-nitrothiophene is by simultaneous de-bromination and decarboxylation of 5-bromo-4-nitro-2-thiophene-carboxylic acid obtained through the nitration of methyl 5-bromo-2-thiophenecarboxylate. 

Archer, owing to very unfortunate coincidences, had mistaken acid potassium tartrate for the acetylamino acid. Goldfarb et al. prepared authentic 5-acetylamino-2-thiophenecarboxylic acid, mp 230 232°C (methyl ester, mp 171-171.5°C ethyl ester, mp 161°C), through reduction of 5-nitro-2-thiophenecarboxylic acid with Raney nickel in acetic anhydride and proved the structure by Raney nickel desulfurization to 8-aminovaleric acid. They also confirmed that the acid mp 272-273°C (methyl ester, mp 135-136°C ethyl ester, mp 116-117°C) is 4-acetylamino-2-thiophenecar boxy lie acid as originally stated by Steinkopf and Miiller. The statement of Tirouflet and Chane that the acid obtained upon reduction and acetylation of 5-nitro-2-thiophenecarboxylic acid melts at 272°C must result from some mistake as they give the correct melting point for the methyl ester. 

The amount of 4-substitution is in certain cases even more strongly dependent upon the type of reaction. Thus the bromination of 2-thiophenealdehyde gives only 5-bromo-2-thiophenealdehyde. > The reason for this has been discussed. Also 2-thiophenecarboxylic acid gives the 5-isomer upon bromination and chlorination. Whereas a -j-M-substituent, as mentioned before, strongly activates... 

Carboxyl groups are easily removed during nitration especially at higher temperatures. A detailed study on the nitration of 5-bromo-2-thiophenecarboxylic acid showed that the proportion of 2,4-dinitro-5-bromothiophene increased with the concentration of sulfuric and nitric acid. The mechanism of this decarboxylative nitration... 

In the absence of oxygen, these thiolene-2-ones are rather stable and have been kept at 0°C for several months. 3-Hydroxythiophene, on the other hand, which has been prepared in low yield from 3-thio-phenemagnesium bromide in the same way as the 2-isomer, or through decarboxylation of 3-hydroxy-2-thiophenecarboxylic acid, "" is very unstable. Its IR spectrum indicates that it also exists as a tautomeric mixture largely in its enolic form. ... 

Sodium thenoate is bromodecarboxylated in low yield, slower than sodium anisate, but more rapidly than sodium benzoate. However, the Hunsdiecker reaction with silver salts has been used preparatively for the synthesis of 2,3-dibromo-4-nitrothiophene from 3-bromo-4-nitro-2-thiophenecarboxylic acid. ... 

Fatty acids are prepared by acylating thiophene with acid chlorides and reducing the ketones (218) to alkylthiophenes according to Wolff-Kishner or Clemmensen. The latter are then acetylated and oxidized by hypochlorite to 5-alkyl-2-thiophenecarboxylic acids, > ... 

CN 4-methyl-3-[[l-oxo-2-(propylamino)propyl]amino]-2-thiophenecarboxylic acid methyl ester monohydrochloride... 

CN 5-nitro-2-thiophenecarboxylic acid [3-(5-nitro-2-furanyl)-2-propylidenfc]hydrazide... 

C7H,j05S 97-05-2) see Domiodol 3-sulfo-2-thiophenecarboxylic acid (C5H4O5S2 59337-95-0) see Tenoxicam sulfuric acid zinc salt (1 1) heptahydrate (H 405SZn 7446-20-0) see Pyrithione zinc... 

C4H4S 110-02-1). see Clopidogrel hydrogensulfate Oxitefonium bromide Penthienate methobromide Suprofen 2-Thiophenecarboxylic acid Tiaprofenic acid Ticlopidine Tiemonium iodide Tienilic acid... 

The beneficial effect of added phosphine on the chemo- and stereoselectivity of the Sn2 substitution of propargyl oxiranes is demonstrated in the reaction of substrate 27 with lithium dimethylcyanocuprate in diethyl ether (Scheme 2.9). In the absence of the phosphine ligand, reduction of the substrate prevailed and attempts to shift the product ratio in favor of 29 by addition of methyl iodide (which should alkylate the presumable intermediate 24 [8k]) had almost no effect. In contrast, the desired substitution product 29 was formed with good chemo- and anti-stereoselectivity when tri-n-butylphosphine was present in the reaction mixture [25, 31]. Interestingly, this effect is strongly solvent dependent, since a complex product mixture was formed when THF was used instead of diethyl ether. With sulfur-containing copper sources such as copper bromide-dimethyl sulfide complex or copper 2-thiophenecarboxylate, however, addition of the phosphine caused the opposite effect, i.e. exclusive formation of the reduced allene 28. Hence the course and outcome of the SN2 substitution show a rather complex dependence on the reaction partners and conditions, which needs to be further elucidated. 

Reduction of 1-adamantanecarbonyl chloride at carbon or mercury leads to the quantitative formation of 1-adamantanecarboxaldehyde [80]. Mubarak [81] investigated the reduction of 2-thiophenecarbonyl chloride at both carbon and mercury the starting material appears to undergo a two-electron reduction to form an acyl anion, which leads to l,2-di(2-thienyl)ethene-l,2-diol di(2-thiophenecarboxylate) as the major product and to 2-thiophenecarboxaldehyde as the minor product. 

Condensation reaction of thioglycolic acid derivatives with a,P-acetylenic esters, which upon treatment with base result in the formation of 3-hydroxy-2-thiophenecarboxylic acid derivatives. 

Certain 3-halothiophenes were successfully coupled with a series of amines in the presence of a palladium-BINAP catalyst system. The proper choice of the substituents on the thiophene ring as well as the choice of the halide were crucial for the success of the process (6.76.), 3-Bromo-2-thiophenecarboxylic acid derivatives, for example, coupled readily, while the conversion of 4-bromo-2-cyanothiophene failed completely.107... 

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