Furan-2-carbaldehyde bromination

Thieno[3,2- ][l]benzofuran 61 was synthesized on a preparative scale starting with benzo[/ ]furan-2-carbaldehyde 344. Condensation of aldehyde 344 with 2-thioxothiazolidin-4-one in the presence of sodium acetate in acetic acid afforded 345, which by base-catalyzed hydrolysis gave 346 in good yield. Upon treatment with bromine, acid 346 was cyclized to give acid 347, which on standard decarboxylation by treatment with copper in quinoline afforded 61 in high yield (Scheme 35) <1997CCC1468>. 

Knoevenagel condensation of the corresponding 3-methylfuran-2-carbaldehyde 379 and 3-methybenzo[4]furan-2-carbaldehyde 382 with diethyl malonate followed by bromination with iV-bromosuccinimide (NBS) in the presence of dibenzoyl peroxide afforded bromides 380 and 383, respectively. Treatment of 380 and 383 with benzylamine, isopropylamine, /-butylamine 3-hydroxypropylamine, aniline and -toluidine in ethanol yielded furo[2,3-c]pyrroles 381 and benzo[4,5]furo[2,3-c]pyrroles 384, respectively (Scheme 41). The yields of furopyrroles 381 are only moderate (16-46%), because these compounds are highly sensitive to acid, and partially polymerized upon silica... 

Thiophene is chlorinated by CI2 or SO2CI2. Bromination occurs by Br2 in acetic acid or with N-bromosuccinimide. Nitration is effected by concentrated nitric acid in acetic acid at 10°C. Further substitution predominantly yields 2,4-dinitrothiophene. Sulfonation with 96% H2SO4 occurs at 30°C within minutes. Benzene reacts extremely slowly under these conditions. This provides the basis for a method to remove thiophene from coal tar benzene (see p 77). Alkylation of thiophenes often gives only poor yields. However, more efficient procedures are the Vilsmeier-Haack formylation, which yields thiophene-2-carbaldehyde, and acylation with acyl chlorides in the presence of tin tetrachloride, to give 2-acylthiophenes. Like furan, thiophene is mercurated with mercury(II) chloride. 

---