Abstract
Most organic solvents used in quaternization reactions are volatile, hazardous, toxic and form by-products, thus inducing health issues and pollution. Deep eutectic solvents are greener alternatives, but they have not been tested yet in the quaternization reaction. Here we propose eutectic solvents in the quaternization reaction of nicotinamide with substituted 2-bromoacetophenones. The reaction was performed at 80 °C by three synthetic approaches: conventional during 2–6 h, microwave during 20 min and ultrasonic during 3 h. The highest yields of about 98% were obtained by microwave. The most suitable eutectic solvents were choline chloride with either urea, oxalic or levulinic acid. The use of deep eutectic solvents has several advantages: environmental benignity, biodegradability, easy purification and simple preparation. All tested compounds showed antifungal activities against Botrytis cinerea, Colletotrichum acutatum, Alternaria radicina and Fusarium graminearum at 10 and 100 µg/mL.
Similar content being viewed by others
References
Bušić V, Pavlović H, Roca S, Vikić-Topić D, Gašo-Sokač D (2017) Microwave-assisted quaternization of various pyridine derivatives and their antibacterial activity. Croat Chem Acta 90:425–433. https://doi.org/10.5562/cca2937
Bušić V, Vrandečić K, Siber T, Roca S, Vikić-Topić D, Gašo-Sokač D (2019) A rapid microwave induced synthesis of isonicotinamide derivatives and their antifungal activity. Croat Chem Acta 92:125–135. https://doi.org/10.5562/cca3527
Cella R, Stefani HA (2009) Ultrasound in heterocyclic chemistry. Tetrahedron 65:2619–2641. https://doi.org/10.1016/j.tet.2008.12.0272620
Choi HE, Yoo MS, Choi JH, Lee JY, Kim JH, Lee JK, Kim GI, Park Y, Chi YH (2011) BRN-103, a novel nicotinamide derivative, inhibits VEGF-induced angiogenesis and proliferation in human umbilical vein endothelial cells. Bioorg Med Chem Lett 1:6236–6241. https://doi.org/10.1016/j.bmcl.2011.09.022
Hayyan A, Mjalli FS, Al-Nashef IM, Al-Wahaibi T, Al-Wahaibi YM, Ali Hashim M (2012) Fruit sugar-based deep eutectic solvents and their physical properties. Thermochim Acta 541:70–75. https://doi.org/10.1016/j.tca.2012.04.030
Marek J, Malinak D, Dolezal R, Soukup O, Pasdiorova M, Dolezal M, Kuca K (2015) Synthesis and disinfection effect of the pyridine-4-aldoxime based salts. Molecules 20:3681–3696. https://doi.org/10.3390/molecules20033681
Peng M, Shi L, Ke S (2017) Nicotinamide-based diamides derivatives as potential cytotoxic agents: synthesis and biological evaluation. Chem Cent J 11:109. https://doi.org/10.1186/s13065-017-0338-5
Pernak J, Rogoża J (2000) Synthesis of 3-substituted pyridinium salts. ARKIVOC 2000(vi):889–904. https://doi.org/10.3998/ark.5550190.0001.606
Pidlypnyi N, Kaul S, Wolf S, Martin Drafz MHH, Schmidt A (2014) Syntheses and characterization of N-(indolyl)pyridinium salts and of their ylides. Z Naturforsch 69b:605–614. https://doi.org/10.5560/ZNB.2014-3324
SAS/STAT (2008) User’s guide, version 9.2. SAS Institute Inc., Cary
Siber T, Bušić V, Zobundžija D, Roca S, Vikić-Topić D, Vrandečić K, Gašo-Sokač D (2019) An improved method for the quaternization of nicotinamide and antifungal activities of its derivatives. Molecules 24:1001. https://doi.org/10.3390/molecules24061001
Wu Z, Hu D, Kuang J, Cai H, Wu S, Xue W (2012) Synthesis and antifungal activity of N-(substituted pyridinyl)-1-methyl(phenyl)-3-(trifluoromethyl)-1H-pyrazole-4-carboxamide derivatives. Molecules 17:14205–14218. https://doi.org/10.3390/molecules171214205
Wu Q, Liu C, Yang J, Guan A, Ma H (2017) Design, synthesis, and herbicidal activity of novel quaternary ammonium salt derivatives. Pestic Biochem Physiol 143:246–251. https://doi.org/10.1016/j.pestbp.2017.05.006
Author information
Authors and Affiliations
Corresponding author
Additional information
Publisher's Note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Rights and permissions
About this article
Cite this article
Bušić, V., Roca, S., Vikić-Topić, D. et al. Eco-friendly quaternization of nicotinamide and 2-bromoacetophenones in deep eutectic solvents. Antifungal activity of the products. Environ Chem Lett 18, 889–894 (2020). https://doi.org/10.1007/s10311-020-00973-3
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s10311-020-00973-3