Thiophenecarboxylic acid, directed

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). 

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. 

---