Lanthanide nitrates as Lewis acids in the one-pot synthesis of 1,2,4-oxadiazole derivatives

Abstract

Neste trabalho relatamos o uso de nitratos de lantanídeos [Ln(NO 3 ) 3 ] atuando como catalisador na síntese de uma única etapa de derivados de 3-benzoíla-e 3-acetila-1,2,4-oxadiazóis a partir de cetonas, nitrilas e ácido nítrico. Este é o primeiro exemplo da síntese em única etapa de preparação de derivados benzoíla e acetila-1,2,4-oxadiazóis, usando acetofenonas com grupos doadores de elétrons.In this work we report the use of lanthanide nitrates [Ln(NO 3 ) 3 ] acting as catalyst in direct onepot synthesis of 3-benzoyl-and 3-acetyl-1,2,4-oxadiazoles derivatives from ketones, nitriles and nitric acid. This is the first example of one-pot synthesis of benzoyl-and acetyl 1,2,4-oxadiazoles derivatives preparation using acetophenones derivates with electron-donator groups.Keywords: lanthanide nitrates, Lewis acids, 1,2,4-oxadiazole derivates IntroductionLanthanide compounds have been extensively used as Lewis acids in the different reactions including asymmetric catalysis. The most important compounds include the use of chlorides, 1 triflates, 2 p-toluenesulphonates, 3 dithiocarbamates complexes, 4 alkoxides 5 and others. 6 On the other hand, the oxadiazole group is a key element of a number of biological activity such as ligands of benzodiazepine receptor, 7 inhibidor of protein tyrosine phosphatase, 8 agonists of muscarinic receptors, 9 antiinflammatory agents, 10 antiviral agents, 11 cardiovascular 12 and other medicinal activity. 13 Also, 1,2,4-oxadiazole compounds have been applied as ligands of metal complexes 14 and liquid crystalline materials. 15,16 Synthesis of 1,2,4-oxadiazole derivatives by using ketones, nitriles and nitric acid as starting materials and Fe(NO 3 ) 3 as catalyst has been reported by Itoh et al. 17 However, this method has the disadvantage of low reaction rates and drastic conditions, resulting in low reaction yields. Recently, yttrium triflate [Y(OTf) 3 ] 18 was applied instead of Fe(NO 3 ) 3 by using the same reaction condition in the synthesis of various 1,2,4-oxadiazole with low reaction times and good yields. Nonetheless, neither of these methodologies could be successfully applied in the synthesis of 1,2,4-oxadiazole contained electron-donating.In the present work, we have proposed a simple methodology for the one-pot synthesis of 1,2,4-oxadiazole derivates, by using lanthanide nitrates prepared in situ as Lewis acids. We have investigated the rule of different ions on the reaction. Experimental GeneralAll reagents were commercially available and used without any purification. 1 H and 13 C NMR spectra were recorded on a Varian 300-MHz spectrometer. Mass spectrometer spectra were recorded on a Shimadzu GC-MS-QP 5000 gas chromatograph-mass spectrometer equipped with a 30 m × 0.25 mm × 0.25 mm capillary Lanthanide Nitrates as Lewis Acids in the One-Pot Synthesis of 1,2,4-Oxadiazole Derivatives J. Braz. Chem. Soc. 1438 column of fused silica, Supelco Simplicity 1 TM . All reactions were monitored by TLC. Flash column chromatography was carried out using 200-300 mesh silica gel ...