4<i>H</i>-Benzo[<i>d</i>][1,3]oxazin-4-ones and Dihydro Analogs from Substituted Anthranilic Acids and Orthoesters

• Main Authors: Joel K. Annor-Gyamfi, Richard A. Bunce
• Format: Article
• Language: English
• Published: MDPI AG 2019-10-01
• Series: Molecules
• Subjects: 4<i>h</i>-benzo<i>[d]</i>[1,3]oxazin-4-ones; 1,2-dihydro-4<i>h</i>-benzo<i>[d]</i>[1,3]oxazin-4-ones; heterocyclization; anthranilic acid; orthoesters
• Online Access: https://www.mdpi.com/1420-3049/24/19/3555

A one-pot route to 2-alkyl and 2-aryl-4<i>H</i>-benzo[<i>d</i>][1,3]oxazin-4-ones (also known as 4<i>H</i>-3,1-benzoxazin-4-ones) has been developed and studied. The method involves the reaction of aryl-substituted anthranilic acids with orthoesters in ethanol catalyzed by acetic acid. Additionally, we have also investigated the reaction under microwave conditions. Not all of the substrates were successful in yielding the target heterocycles as some of the reactions failed to undergo the final elimination. This process led to the isolation of (&#177;)-2-alkyl/aryl-2-ethoxy-1,2-dihydro-4<i>H</i>-benzo<i>[d]</i>[1,3]oxazin-4-ones. The formation of the dihydro analogs correlated with the electron density on the aromatic ring: Electron-donating groups favored the 4<i>H</i>- benzo<i>[d]</i>[1,3]oxazin-4-ones, while electron-withdrawing groups tended to favor the dihydro product. Substituting a pyridine ring for the benzene ring in the substrate acid suppressed the reaction.