Thiophenes diazo coupling

Furan undergoes phenylation rather than diazo coupling on reaction with ben-zenediazonium salts, and thiophene similarly yields 2- or 2,5-diaryl derivatives rather than coupled products. However, 2,5-dimethylfuran and 2-/-butylfuran give coupled products with 2,4-dinitrobenzenediazonium ion (Scheme 26). 

Intramolecular diazo coupling can be also achieved <85JCS(Pl)l3l). Starting from suitable (o-aminophenyl)thiophenes various isomeric thieno[c]cinnolines have been obtained (Scheme 24). The reaction can proceed either at an a- or at (3-position of the thiophene ring. 

As mentioned in Section 3.14.2.4, one of the consequences of ipso attack could be side-chain functionalization. Examples of nitration and diazo coupling of a methyl group attached to thiophene are known. 

The reaction of an azepinium ion (3), generated in situ, with a number of aromatic substrates (benzene, anisole, phenol, furan and thiophene) usually gave aryl-2//-azepines [e.g. (4) from benzene] as the major products.7 In the case of reaction with pyrrole, however, a ring-opened compound (5) was the major product. Some condensed thiophenes have been shown8 to give products of substitution at C(l). For example, (6a) gave (6b) on diazo coupling. 

Acylamido-4,5,6,7-tetrahydrobenzo[b]thiophenes undergo the Mannich reaction,375 Vilsmeier-Haack formylation,376 diazo coupling,377 and thiocyanation378 to give the 3-CH2NHR, 3-CHO, 3-N=NAr, and 3-SCN derivatives, respectively the last can be cyclized to 95 (X = S, Y = NHAc).378... 

Acylation and metallation studies on monomers, dimers, trimers, and tetramers containing linked thiophen, pyridine, pyrimidine, furan, benzofuran, benzothiophen, and indole moieties have been published/ Deuteriation, halogenation, and diazo-coupling reactions of 2-oxo- and 2-thioxo-l,2-dihy-dropyrimidinium salts have been studied and compared with results for 2,2-dialkyl-1,2-dihydropyrimidinium and 2,3-dihydro-1,4-diazepinium salts in order to demonstrate the effect of an adjacent 0x0- or thioxo-group on the properties of a 1,5-diazopentadienium system/ Vilsmeier formylation of, and tautomerism in, 2-hydroxypyrazolo[5,l-h]quinazolone and l-phenylpyrazolo[5,l-A]-quinazoline-2,9-dione have been studied/ The pyrazolo[3,4-c]pyrazole (71) has been methylated and acetylated, the major products being (72)/ ... 

This is the first example of a direct coupling of a diazo compound in a / position of the thiophene nucleus. The Beckmann rearrangement with the ketoxime of 2-thienylketone was found to give poor yields of the aceto-2-thiopheneamide. Furthermore, the Schmidt reaction using hydrazoic and sulphuric acids was investigated and did give rise to aceto-2-thiopheneamide but probably as an eutectic with the isomeric 2-thenoylmethylamide. 

Aminothiophene-2-carboxylic acid has been diazotized with isoamyl nitrite to form the diazo-nium salt which, on thermolysis, loses CO2. The resultant diazonium salt has been coupled with 2-naphthol. Similarly, 3-aminobenzo[i)]thiophene-2-carboxylic acid has been converted to the corresponding diazonium salt. This preferential loss of CO2 from or/Ao-diazonium carboxylates is unprecedented <89TL2345>. 

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