5-Nitrothiophene carboxylic acid

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. 

Another potential avenue for future development is extrapolation of these chemistries from benzofused to heteroanellated heterocycles. We have recently been able to show that thicno[2,3-/ ][ 1,4]thiazepine-5-ones (88)69 can be synthesized on solid support from resin-bound 5-chloro-4-nitrothio-phene-2-carboxylic acid (87) using essentially the same synthetic protocols developed in the carbocyclic series (Scheme 17 and Section 3.2.1).5 The starting material, 5-chloro-4-nitrothiophene-2-carboxylic acid, was synthesized in solution from commercially available 5-chlorothiophene-2-carbox-ylic acid. 

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... 

The bromination of 2-cyanothiophen with one equivalent of bromine in the presence of an excess of AICI3 gives 2-cyano-, 4-bromo-2-cyano-, 5-bromo-2-cyano-, and 4,5-dibromo-2-cyano-thiophen in the proportions 16 70 2 12, from which pure 4-bromo-2-cyanothiophen can easily be obtained. Nitration of 2-cyanothiophen in concentrated sulphuric acid led to mixtures of almost equal amounts of 4- and 5-nitrothiophen-2-carboxylic acid. The chloromethyl-ation of 2-acetylthiophen and 2-formylthiophen with ota -bis(chloromethyl) ether in 60—100% sulphuric acid has been studied. An increase in the acidity of the medium promoted the formation of 4-substituted products. From these products some otherwise difficultly obtainable 2,4-disubstituted thiophens were prepared. ... 

Sodium 3-aminothiophene-2-carboxylates were reacted with EMME in boiling toluene in the presence of acetic acid for 4-6 hr to give 3-thienylaminomethylenemalonates (58) in moderate yields (87T3295 88EUP269295). The 5-bromo derivative of compound 58 (R = Br) was prepared in the reaction of 3-amino-5-bromothiophene and EMME, but 2-amino-5-nitrothiophene failed to react (87T3295). 

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