Ethyl 2,4-difluoroimidazole 5-carboxylate

Interest has been restricted this year to studies of photoelimination of nitrogen from arenediazonium salts and attempts to characterize the resulting aryl cations. Nanosecond laser photolysis techniques have been used to examine the photodecomposition of diazonium tetrafluoroborates. Aryl cations could not directly be detected, but evidence from bleaching experiments indicates that, in water, the phenyl cation has a lifetime of about 500 ps. The isolation of the ether (131) as the sole product of photodecomposition of the diazonium salt (132) in methanol demonstrates that rearrangement of the intermediate aryl cation does not occur. Both heterolytic and homolytic pathways have been described for photodecompositions of arenediazonium salts complexed with crown ethers. A useful synthetic application of this conversion is the formation in 53% yield of ethyl 2,4-difluoroimidazole-5-carboxylate (133) on irradiation of the diazonium fluoroborate (134). ... 

Takahashi, K. Kirk, K.L. Cohen, L.A. Photochemistry of diazonium salts. 5. Syntheses of ethyl 2,4-difluoroimidazole-5-carboxylate and related compounds. J. Org. Chem. 1984, 49, 1951-1954. 

Difluoroimidazole 1571 has been prepared from 5-fluoroimidazole-4-carboxylic acid ethyl ester 1568. The ester 1586 is converted into the carbonyl azide 1569, which undergoes Curtius rearrangement in tert-huVf alcohol to produce 4-/-butyloxycarbonylamino-5-fluoroimidazole 1570. In situ diazotization of the resulting amine and irradiation produces 4,5-difluoroimidazole 1571 (Scheme 405) <2001JFC(107)147>. 

Both 4,5-difluoro- and 2,4-difluoroimidazoles have been prepared. The former was synthesized from ethyl 4-fluoroimidazole-5-carboxylate through a Curtius rearrangement that provided the Boc-protected 4-fluoro-5-aminoimidazole. In situ depro-... 

The synthesis of 4,5-difluoroimidazole has also been described by Kirk using a photochemical Schiemann reaction (Scheme 59) [74]. Curtius rearrangement of the acyl azide, prepared in two steps from ethyl 4-fluoroimidazole-5-carboxylate via hydrazide, afforded the key intermediate Boc-protected 5-fluoroimidazol-4-carboxylate. In situ Boc deprotection followed by diazotization of the amine and photolysis of the diazonium tetrafluoroborate afforded 4,5-difluoroimidazole. 

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