Quantum‐Chemical Modeling of One‐Pot Assembly of 1‐Formyl‐2‐Pyrazolines from Alkylaryl Ketones, Arylacetylenes, Hydrazine, and Formic Acid

Abstract The assembly mechanism of 1‐formyl‐2‐pyrazoline from alkylaryl ketones, arylacetylenes, hydrazine and formic acid has been investigated in some detail using the B2PLYP‐D2/6‐311+G**//B3LYP/6‐31+G* quantum‐chemical approach. We ascertained that the first stage of the assembly involves the C ‐vinylation reaction of acetophenone with phenylacetylene catalyzed by the KOBu t /DMSO superbase, followed by the Z ‐ E isomerization of the dienolate ion. Neutralization of the latter leads to a mixture of α , β ‐ and β , γ ‐unsaturated ketones. The kinetically most favorable route for the subsequent assembly of 1‐formyl‐2‐pyrazoline is found to involve (i) addition of hydrazine to the C═C bond of the α , β ‐unsaturated ketone, (ii) cyclization of the β ‐hydrazinyl ketone, and (iii) formylation of 2‐pyrazoline. The β , γ ‐unsaturated ketone is found to convert into the β , γ ‐unsaturated formylhydrazone, which is consistent with experiment. The transformation of β , γ ‐unsaturated formylhydrazone to 1‐formyl‐2‐pyrazoline proceeds through the hydration of formylhydrazone, resulting in the formation of β , γ ‐unsaturated ketone, which subsequently isomerizes into the α , β ‐unsaturated ketone. The high barrier of the isomerization accounts for the long duration of the corresponding stage of the synthesis (1 h, 100 °C).