Microwave-Assisted Stereoselective Heterocyclization to Novel Ring <span style="font-variant: small-caps">d</span>-fused Arylpyrazolines in the Estrone Series

• Main Authors: Gergő Mótyán, Barnabás Molnár, János Wölfling, Éva Frank
• Format: Article
• Language: English
• Published: MDPI AG 2019-02-01
• Series: Molecules
• Subjects: arylpyrazolines; heterocyclization; microwave; stereoselectivity; steroids
• Online Access: https://www.mdpi.com/1420-3049/24/3/569

Microwave-assisted syntheses of novel ring <span style="font-variant: small-caps;">d</span>-condensed 2-pyrazolines in the estrone series were efficiently carried out from steroidal &#945;,&#946;-enones and hydrazine derivatives. The ring-closure reaction of 16-benzylidene estrone 3-methyl ether with hydrazine in acetic acid resulted in a 2:1 diastereomeric mixture of two 16,17-<i>cis</i> fused pyrazolines, which is contrary to the former literature data for both stereoselectivity and product structure. However, the cyclization reactions of a mestranol-derived unsaturated ketone with different arylhydrazines in acidic ethanol furnished the heterocyclic products in good to excellent yields independently of the substituents present on the aromatic ring of the reagents applied. The MW conditions also permitted the ring-closure reaction with <i>p</i>-nitrophenylhydrazine which is unfavorable under conventional heating. Moreover, the transformations led to the heterocyclic compounds stereoselectively with a 16&#945;,17&#945;-<i>cis</i> ring junction without being susceptible to spontaneous and promoted oxidation to pyrazoles.