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Environ Chem Lett (2015) 13:125129 DOI 10.1007/s10311-015-0494-6
ORIGINAL PAPER
Rapid synthesis of 1,6-naphthyridines by grindstone chemistry
Afaf M. Abdel Hameed
Received: 14 October 2014 / Accepted: 12 January 2015 / Published online: 24 January 2015 Springer International Publishing Switzerland 2015
Abstract Many methods to prepare heterocyclic compounds involve toxic solvents and reagents. There is therefore a need to design cleaner synthetic procedures. 1,6-Naphthyridine derivatives are used in many applications such as cancer chemotherapy, antibacterials, antivirals and antiproliferatives. Here, we report the solvent-free and catalyst-free synthesis of 1,6-naphthyridine derivatives. Synthesis is done by grinding of 2 mmol of ketones, 2 mmol of malononitrile and 1 mmol of amines in a mortar at room temperature for 57 min. 1,2-Dihydro[1,6]-naphthyridine derivatives were obtained in 9097 % yields.
Keywords 1,2-Dihydro[1,6]-naphthyridines
Eco-friendly Grindstone chemistry Environmentally
friendly techniques Multicomponent
AbbreviationsDMSO Dimethyl sulfoxide
1H-NMR Proton nuclear magnetic resonance spectroscopy
13C-NMR Carbon nuclear magnetic resonance spectroscopy
TLC Thin layer chromatography IR Infrared spectroscopy
Introduction
Different families of nitrogen-containing heterocycles are currently used in medicinal chemistry for their pronounced
biological activities. For instance, 1,6-naphthyridines are being explored for cancer chemotherapy as an antitumor agent (Li et al. 2003). In addition, 1,6-naphthyridines possess a well-documented biological activity, including antibacterial agent (Suresh et al. 2003), antiviral agent (Bedard et al. 2000) and antiproliferative activity (Rudys et al. 2010), and act as an inhibitor of human immunodeciency virus infection integrase for the treatment of acquired immune deciency syndrome (Zhuang et al. 2003). A series of novel 1,6-naphthyridine derivatives were prepared as potential inhibitors of human topoisomerase (Singh et al. 2003), anticonvulsive agents (Austin et al. 2003), potential antimalarials, p38 mitogen-activated protein kinase inhibitors (Hunt et al. 2003) and spleen tyrosine kinase inhibitors (Cywin et al. 2003). The biological activities of these compounds prompted us to synthesize them via a new, green eco-friendly method.
Most of the methodologies reported for the synthesis of 1,6-naphthyridines involve multi-step sequences (Colandrea and Naylor 2000; Suzuki et al. 2007; Zhou et al. 2007), expensive catalyst (Chandra et al. 2008; Colandrea and Naylor 2000; Zhang et al. 2000), an inert atmosphere (Turner. 1990; Zhang et al. 2000) and length reaction time (Colandrea and Naylor 2000). Recently, a convenient synthesis of 2-(phosphoryl) alkyl-substituted 1,6-naphthyridines has been reported by (Lemport et al. 2009). Specically, they...