Pyridazines by Acetylenic 1,2,4-Triazole Cyclization/Fragmentation

Significance

While developing synthetic routes towards agricultural fungicides, Syngenta chemists found that bromination of 1,2,4-triazolyl alkynols 1 led to the formation of a precipitate that was identified as the fused trizolium salts 2 in excellent yields. Treatment of these salts with aqueous alkali rapidly formed 3-alkyl-5-arylpyridazines 3 in poor to excellent yields. The reaction undoubtedly proceeds via an intermediate bromonium ion (R. C. Larock, Q. Huang, J. A. Hunter J. Org. Chem. 2002, 67, 3437-3444). Although the scope was limited to focused fungicidal precursors and terminal acetylenes were shown to fail, the current methodology represents the first case of the formation of substituted pyridazines from 1,2,4-tri­azoles.