Borsche-Koelsch cinnoline synthesis

What is Borsche-Koelsch cinnoline synthesis?

The Borsche-Koelsch cinnoline synthesis, which yields 4-hydroxycinnolines or 4-hydroxy-3-alkylcinnolines, was first described by Borsche and Koelsch in 1941 and 1943, respectively. To carry out the reaction, the ortho-aminoarylketone is first diazotized in either aqueous or acetic acid solution.

Borsche-Koelsch cinnoline synthesis
Borsche-Koelsch cinnoline synthesis

The resulting diazonium salt solution is then left in the dark at room temperature until it no longer gives a diazo coupling reaction with p-naphthol. The cyclization step, which is dependent on the basicity of the amine, takes anywhere from a few days to 2-3 months to complete. The yield of cinnoline obtained depends on the characteristics of the o-aminoarylketone used. Generally, less basic aminoarylketones yield greater yields of cinnolines in a shorter cyclization time. The synthesized substituted cinnolines have the potential to be used as antimalarial drugs.

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