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Open AccessArticle

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

1
Department of Mechanochemistry, Institute of Geotechnics, Slovak Academy of Sciences, Watsonova 45, 04001 Košice, Slovakia
2
Department of Chemistry, Biochemistry and Biophysics, University of Veterinary Medicine and Pharmacy, Komenského 73, 04181 Košice, Slovakia
3
NMR Laboratory, Faculty of Science, P. J. Šafárik University, Moyzesova 11, 04001 Košice, Slovakia
4
Department of Pharmacognosy and Botany, University of Veterinary Medicine and Pharmacy, Komenského 73, 04181 Košice, Slovakia
5
Advanced Materials Department, Jožef Stefan Institute, Jamova cesta 39, 1000 Ljubljana, Slovenia
*
Author to whom correspondence should be addressed.
Dedicated to the memory of Assoc. prof. Dr. Peter Kutschy from Faculty of Science, P. J. Šafárik University in Košice.
Academic Editors: Vjekoslav Štrukil and Alejandro Baeza Carratalá
Molecules 2019, 24(18), 3347; https://doi.org/10.3390/molecules24183347
Received: 2 July 2019 / Revised: 29 July 2019 / Accepted: 11 September 2019 / Published: 14 September 2019
(This article belongs to the Special Issue Recent Development of Mechanochemical Synthesis)
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. View Full-Text
Keywords: mechanochemistry; isomerization; oximation mechanochemistry; isomerization; oximation
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MDPI and ACS Style

Baláž, M.; Kudličková, Z.; Vilková, M.; Imrich, J.; Balážová, Ľ.; Daneu, N. Mechanochemical Synthesis and Isomerization of N-Substituted Indole-3-carboxaldehyde Oximes . Molecules 2019, 24, 3347.

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