Mechanochemical Synthesis and Isomerization of N-Substituted Indole-3-carboxaldehyde Oximes †

Abstract

Performing solution-phase oximation reactions with hydroxylamine hydrochloride (NH2OH·HCl) carries significant risk, especially in aqueous solutions. In the present study, four N-substituted indole-3-carboxaldehyde oximes were prepared from the corresponding aldehydes by solvent-free reaction with NH2OH·HCl and a base (NaOH or Na2CO3) using a mechanochemical approach, thus minimizing the possible risk. In all cases, the conversion to oximes was almost complete. The focus of this work is on 1-methoxyindole-3-carboxaldehyde oxime, a key intermediate in the production of indole phytoalexins with useful antimicrobial properties. Under optimized conditions, it was possible to reach almost 95% yield after 20 min of milling. Moreover, for the products containing electron-donating substituents (-CH3, -OCH3), the isomerization from the oxime anti to syn isomer under acidic conditions was discovered. For the 1-methoxy analog, the acidic isomerization of pure isomers in solution resulted in the formation of anti isomer, whereas the prevalence of syn isomer was observed in solid state. From NMR data the syn and anti structures of produced oximes were elucidated. This work shows an interesting and possibly scalable alternative to classical synthesis and underlines environmentally friendly and sustainable character of mechanochemistry.

Phosphonic Acid Analogs of Fluorophenylalanines as Inhibitors of Human and Porcine Aminopeptidases N: Validation of the Importance of the Substitution of the Aromatic Ring

“…Basing on the possible stabilization of Z-isomer by intramolecular hydrogen bonding (Scheme 2) we speculate that it is the final product. A similar effect was recently described for 1-methoxyindole-3-carboxaldehyde oxime [49]. We were also going to obtain compounds 1 substituted additionally with chlorine, bromine and iodine.…”

Mechanochemical method: a powerful tool to obtain ω-poly(ethylene glycol)-functionalized structures and curcumin analogues

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Secondary Metabolites of Purpureocillium lilacinum

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