Synthesis of tetrahydroimidazo [1,5-b] i̇soxazole 2,3-diethyl dicarboxylate derivatives

The cycloaddition reactions of 1,3-dipoles developed by Huisgen in the 1960s have been systematically applied in organic chemistry (Huisgen, 1961). The reactions of nitrones, first synthesized by Beckmann (Beckmann, 1890) in 1890, with dipolarophiles having double or triple bonds can yield 5-membered heterocyclic compounds (Hamer and Macaluso, 1964). Heterocyclic systems formed as a result of 1,3-dipolar cycloaddition reactions of nitrones have made nitrones important for many alkaloids and natural compounds because they carry nitrogen atoms in their structures (Padwa, 1987). The synthesis of compounds containing the tetrahydroimidazole ring is of great importance due to their potential antibacterial and anticarcinogenic activity (Coskun et al., 1997). The tetrahydroimidazo[1,5-b]isoxazoline double ring system has been synthesized by reacting 3-Imidazolin-3-oxides with polarophiles such as DMAD and -pinene (Coskun et al., 2001), methyl thio isocyanate (Coskun and Tat, 2003), phenyl propanoic acid alkyl esters (Coskun and Yılmaz, 2006). In our study, a series of 3-imidazolin-3-oxides were reacted with DEAD (Diethylacetylene di carboxylate) at 65oC in DMSO to give diethyl 5,6-substitutedphenyl-3a-phenyl-3a,4,5,6-Tetrahydroimidazo[1,5-b] isoxazole 2,3-dicarboxylates in moderate yields. Keywords: Cycloaddition, 1,3-Dipolar Cycloaddition, Diethylacetylene Dicarboxylate, Nitrone