4-Nitro-2-thiophenecarboxylic acids

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. ... 

Optical activity owing to restricted rotation (atropisomerism) has been demonstrated in two phenylthiophenes 2-(6-methyl-2-nitro-phenyI)-3-thiophenecarboxylic acid (41), which rapidly racemized in solution, and 2,5-dimethyl-4- (6 -methyl-2 -nitrophenyl) 3-thio-phenecarboxylic acid (42), which was optically stable (at room temperature). Recently the first bithienyl, 2,2 -dicarboxy-4,4 -dibromo-5,5 -dimethyl-3,3 -bithienyl (43), has been resolved into optical anti-podes which were optically stable. 

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. 

From resonance structure (12) it is obvious that a —I—M-substit-uent strongly deactivates the 2-position toward electrophilic substitution, and one would thus expect that monosubstitution occurs exclusively in the 5-position. This has also been found to be the case in the chlorination, bromination, and nitration of 3-thiophenecarboxylic acid. Upon chlorination and bromination a second halogen could be introduced in the 2-position, although further nitration of 5-nitro-3-thiopheneearboxylic acid could not be achieved. Similarly, 3-thiophene aldehyde has been nitrated to 5-nitro-3-thiophene aldehyde, and it is further claimed that 5-bromo-3-thiopheneboronic acid is obtained upon bromination of 3-thiopheneboronic acid. ... 

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

A range of simple analogs of benzoic acid and phenylalanine, easily obtainable from standard chemical suppliers, were chosen as substrates. These included a large number of hydroxy- and dihydroxybenzoic acids, aminoben-zoic acids, nitrobenzoic acids, fluoro-, difluoro-, trifluoro-, tetrafluoro- and pentafluorobenzoic acids, chlorobenzoic acids, iodobenzoic acids, and methoxybenzoic acids. A number of structures other than those with a six-mem-bered aromatic ring were also tried, including pyridinecarboxaldehydes, alicy-clic carboxylic acids, naphthalenecarboxylic acids, furancarboxylic acids, thiophenecarboxylic acids, nitro-, bromo-, and chlorothiophenecarboxyhc acids. 

In thiophene the -directing power of the sulfur atom still dominates in many cases. Halogenation of 2-thiophenecarboxaldehyde, 2-thiophenecarboxylic acid, and 2-methoxycarbonylthiophene gives mainly or exclusively the 5-substituted isomer. Chloromethyla-tion gives similar results. However, nitration of electronegatively 2-substituted thiophenes gives a mixture of 4- and 5-nitro 2-substituted isomers, in different ratios (Table XXII). 

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. 

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. 

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