Methyl thiophene-2-carboxylate

Dihydrothieno[3,4-Z ]thiophene (131) was prepared by two methods. In the first (Scheme 8), chloromethylation of methyl thiophene-2-carboxylate (132) forms methyl 2,3-bischloromethyl-thiophene-5-carboxylate (133) (85%) cyclization of 133 with sodium sulfide in methanol yields (66%) methyl 4,6-dihydrothieno[3,4-i]-thiophene-2-carboxylate (134). Peroxide oxidation of 134 gives 2-methoxycarbonyl-4,6-dihydrothieno[3,4-h]thiophene 5,5-dioxide (135) and hydrolysis of 134 followed by metaperiodate oxidation furnishes the sulfoxide (91). Thienothiophene (131) was produced by hydrolysis and decarboxylation of 134. As indicated above, the sulfoxide (91) was used for the synthesis of thieno[3,4-6]thiophene (3). 

Treatment of the sulfone 35 with three equivalents of butyllithium gave an intermediate selectively dimetalated at C-2 and the adjacent methyl group. Subsequent reactions of this species with aromatic or heteroaromatic esters, such as methyl thiophene-2-carboxylate, and final acid induced elimination of water, gave a series of thieno[ 3,2 -6] thiophene 1,1-dioxide systems, for example 36 <07S1827>. On the other hand, 3-methylthiophene undergoes selective deprotonation at C-5 upon treatment with lithium 2,2,6,6-tetramethylpiperidide (LiTMP), giving access to a 2,4-disubstituted thiophene derivatives <07JOC 1031>. 

Scheme 89 Use of Mc4NN03 in Tf20 for nitration of methyl thiophene-2-carboxylate [137]...

Nitronium triflate (Tf0N02) which is readily generated in dichloromethane from tetramethylammonium nitrate (McqN NOa") and triflic anhydride, can be used as a nitrating agent. Its application for the nitration of methyl thiophene-2-carboxylate afforded 5-nitro- and 4-nitro-substituted isomeric products in 91% combined yield (Scheme 89) [137]. 

However, the 60 % conversion was achieved using Selectfluor for the overnight performed fluorination reaction of methyl thiophene-2-carboxylate derivative 13 [14],... 

Electrochemical Reactions.— The electrochemical oxidation of 2- and 3-methylthiophens with methanolic ammonium bromide as electrolyte on a carbon or platinum anode gives 5-bromo-2-methylthiophen and 2-bromo-3-methylthiophen as main products. Electrochemical oxidation of methyl thiophen-2-carboxylate on a graphite anode in methanolic sulphuric acid gives the cis and trans forms of (133). Methyl thiophen-3-carboxylate yields (134). On the other hand, electrolysis of thiophen-2-carboxylic acid in DMF on platinum electrodes gives (135). ... 

Pharmaceuticals and Agrochemicals. Thioglycohc acid and its esters are useful as a raw material to obtain biologically active molecules. In cephalosporine syntheses, (4-pyridyl)thioacetic acid [10351 -19-8] (65) and trifluoromethane (ethyl) thioglycolate [75-92-9] (66) are used as intermediates. Methyl-3-ainino-2-thiophene carboxylate can be used as intermediate for herbicidal sulfonylureas (67) and various thiophenic stmctures (68). 

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. 

Using these assumptions and conventions, Imoto and co-workers have correlated a number of series of reactions of thiophenes and furans. The reactions studied are the acid-base equilibria pK values) and the acid catalyzed methylations (thiophenes only) of thiophene-and furan-carboxylic acids and the alkaline hydrolyses of their ethyl esters the side-chain bromination of the a-acetylthiophenes, and the a-mercuration of thiophenes and the polarographic half-wave potentials of the methyl esters of thiophene- and furan-carboxylic acids and of nitrothiophenes. The pK values were determined and the ester hydrolyses studied for all three substitution orientations in the thiophene series. For the 4-R-2-Y and 5-R-2-Y series, the p-values do not appear significantly different and the data could probably be combined into a single series unfortunately, however, no limits of accuracy are reported for the p-values, and some of the raw data are not readily available so recalculation is not easily possible. For the 5-R-3-Y series the p-values deviate considerably from the other values however, whereas they are higher for the pK values, they are lower for the ester hydrolyses, and it is possible that the differences are neither systematic nor significant. 

Chamical Nama 4-Methyl-3-[ [ 1 -oxo-2-(propylamino) propyl] amino]-2-thiophene carboxylic acid methyl ester... 

A thermophilic strain M. goodii X7B was reported to carry out desulfurization of BT and DBT [38], The growth of the strain on various sulfur substrates including DBT, BT, 4,6-dimethyl DBT, 5-methyl BT, 2-thiophene carboxylic acid and propylmercaptan was studied at 45°C and varying degree of growth was observed. A mechanism of sulfur removal was proposed for BT based on metabolites identified by GC-MS (Fig. 7 [125]). 

Tetramethylhydrazine, see Dimethylamine Tetramethylsuccinonitrile, see Aldicarb Tetrazene, see Naphthalene 2-Thiazolidinethione-4-carboxylic acid, see Captan 1.1 -Thiobis-ethane, see Phorate 3.3 -Thiobis(methylene)-1.2.3-benzotriazin-4(3Afl-one, see Azinnhos-methyl Thiomalic acid, see Malathion Thiomethylbenzazimide, see Azinphos-methyl Thiophene, see Benzene Thiophenol, see Fonofos Thiophosphoric acid, see Phorate Thiram monosulfide, see Thiram o-Tolualdehyde, see oXylene m-Tolualdehyde, see m-Xylene p-Tolualdehyde, see p-Xylene Toluene, see Benzene. 2-ChlorobiDhenyl. 4 Chlorobinhenyl. Isobutylbenzene, Methylcyclohexane, Styrene, p-Xylene... 

Thiophene- and benzo[6]thiophene-carboxylic acids undergo all the normal reactions of an aromatic carboxylic acid (63AHC(1)1, 70AHC(11)177). They can be converted to acid chlorides, amides and esters the esters can be used to make hydrazides. Benzo[6]thiophene-2-carboxylic acid chloride has been converted to the methyl ketone with dimethylcadmium and to the diazoketone with diazomethane. Bromodecarboxylation of the silver salts (Hunsdiecker reaction) has been used to prepare the dibromo compounds (340) and (341). 

Esters, amides, and primary alcohols are obtained from benzo[6]-thiophene carboxylic acids by standard procedures.337 481,585 692 093,695 Acid chlorides undergo the Arndt-Eistert reaction,337,568,689 react with diethyl ethoxymagnesium malonate to give the corresponding methyl ketone,144 557 and are reduced to the aldehyde with 1 ithium tri-ferf-butoxy aluminohydride.33 7... 

Homologues of thiophene occur in coal-tar they may be prepared by Fittig s synthesis and in other ways. Their properties are similar to those of the analogous benzene derivatives for example, thiotolene, methyl thiophene, is converted into thiophene carboxylic acid by oxidizing agents —... 

Thienopyrimidinones of formula 3a were made by the method shown in Figure 6. Methyl aminothiophene carboxylate 12 was condensed with thiophosgene followed by treatment with an alkylamine to provide thiophene... 

Raney-Ni added at 45 to a stirred soln. of 4-nitro-5-isobutyl-2-thiophene-carboxylic acid in aq. NHg whereupon the temp, rises to 60 , then the temp, allowed to fall to 45 , finally stirred 4 hrs. at 60-65 4-amino-7-methyl-caprylic acid. Y 84%.—In acetic anhydride, no desulfuration occurs and moderate yields of 4-acetylamino-2-thiophenecarboxylic acids are obtained. F. e. s. Y. L. Gol dfarb, B. P. Fabrichnyi, and I. F. Shalavina, 29, 3636 (1959) C. A. 54, 19638h. 

Using these assumptions and conventions, Imoto and co-workers have correlated a number of series of reactions of thiophenes and furans. The reactions studied are the acid-base equilibria values) and the acid catalyzed methylations (thiophenes only) of thiophene-and furan-carboxylic acids and the alkaline hydrolyses of their ethyl esters the side-chain bromination of the a-acetylthiophenes, and the a-mercuration of thiophenes and the polarographic half-wave potentials of the methyl esters of thiophene- and furan-carboxylic acids and of nitrothiophenes. The values were determined and the... 

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