Novel Synthetic Routes to Quaternary Pyridinium Salts and their Antifungal Activity

• Published in: Croatica Chemica Acta Vol. 95; no. 1; pp. 1 - 8
• Main Authors: Busic, Valentina, Vrandecic, Karolina, Siber, Tamara, Roca, Suncica, Tomicic, Vice, Gaso-Sokac, Dajana
• Format: Journal Article Paper
• Language: English
• Published: Zagreb Croatica Chemica Acta 01-01-2022; Croatica Chemica Acta, Croatian Chemical Society; Hrvatsko kemijsko društvo
• Subjects: Acetone; antifungal activity; Antifungal agents; Chloride; Choline; Chromatography; deep eutectic solvents; dihaloalkanes; Ethanol; Eutectic reactions; Fungicides; Malaria; Mass spectrometry; microwave synthesis; Niacinamide; Nicotinamide; NMR spectroscopy; Nuclear magnetic resonance spectroscopy; Nucleophiles; Organic solvents; Pyridine; pyridine derivatives; Pyridines; quaternization; Solvents; Ultrasonic imaging; ultrasound synthesis; Urea; Croatia; United States > US; Germany
• ISSN: 0011-1643; 1334-417X
• DOI: 10.5562/cca3903

Eleven pyridine derivatives were prepared by quaternization reactions by different synthetic routes: conventional, microwave, and ultrasound. Since acetone and other solvents used in conventional quaternization reactions are harmful, attempts were made to replace the organic solvents with more environmentally friendly alternative - deep eutectic solvents. The reactions were carried out using pyridine-3-aldoxime, pyridine-4-aldoxime, isonicotinamide and nicotinamide as nucleophiles and three different dihaloalkanes as electrophiles: diiodopropane, dibromopropane and diiodohexane. The results showed that the microwave method using acetone as solvent was significantly faster and gave higher yields than the conventional method. In contrast, synthesis in the eutectic solvents choline chloride: urea gave significantly lower yields. The structures of the synthesized compounds were confirmed by [.sup.1]H and [.sup.13]C NMR spectroscopy, mass spectrometry and elemental analysis. The antifungal activity of all compounds was tested at two different concentrations (10 and 100 [micro]g [mL.sup.-1]) against Botrytis cinerea, Fusarium culmorum, Macrophomina phaseolina and Sclerotinia sclerotiorum in vitro. All tested compounds showed excellent inhibitory activity against the studied phytopathogenic fungal species at a concentration of 100 [micro]g [mL.sup.-1]. Keywords: antifungal activity, dihaloalkanes, deep eutectic solvents, microwave synthesis, quaternization, pyridine derivatives, ultrasound synthesis.