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12.3.1.2.1.1.1 Variation 1: Use of Formamide

DOI: 10.1055/sos-SD-012-00398

Grimmett, M. R.Science of Synthesis, (200212340.

Introduced in 1953 by Bredereck and Theilig, the method reacts α-diketones, α-hydroxy ketones, α-halo ketones, α-amino ketones, α-acyloxy esters, and (under reducing conditions) α-hydroxyimino ketones with formamide. Yields of imidazoles 31 are reported to be as high as 90 and seldom below 40% (Scheme 18),[‌66‌‌72‌,‌76‌] but in the author's laboratory it is difficult to achieve yields of this level with 2030% being more characteristic. Nevertheless, the process is simple and convenient enough to make it an appealing route to a range of 4-substituted and 4,5-disubstituted imidazoles. The replacement of ammonia by formamide reduces any decomposition of α-hydroxy ketones or α-diketones. With added aldehyde, the method can be adapted to make 2,4,5-trisubstituted imidazoles.[‌66‌,‌70‌]

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References