1,3-Dipolar cycloaddition reaction of 4,5-dihydro-1H-imidazole 3-oxides with alkynes

Abstract

4,5-Dihydro-1H-imidazole 3-oxides bearing different substituents at positions 1 and 2 of the heterocycle were shown to react with a wide range of acceptor-substituted alkynes forming corrsponding cycloadductsderivatives of 1,2,3,7a-tetrahydroimidazo[1,2-b]isoxazole. High regioselectivity of this process stipulated by conjugation of the nitrogen atom with the nitrone group was revealed.

Transformation of 1,2,3,7a-tetrahydroimidazo[1,2-b]isoxazole derivatives into isoxazoles

“…99-100 °C (hexane). 1 Reaction of compound 1h with bromine. A solution of bro mine (0.31 mL) in CHCl 3 (0.064 mL of Br 2 in 3 mL of CHCl 3 ) was added dropwise with stirring to a solution of compound 1h (50 mg, 0.12 mmol) cooled to 0 °C.…”

“…1 Dimethyl 7a (4 dimethylaminophenyl) 2,2,3,3 tetramethyl 1,2,3,7a tetrahydroimidazo[1,2 b]isoxazole 6,7 dicarboxylate (1e). 1) 2,3 Bis(hydroxyamino) 2,3 dimethylbutane sulfate (3.6 g, 13.6 mmol) and 4 (dimethylamino)benzaldehyde (2.0 g, 13.6 mmol) were dissolved in MeOH and refluxed under argon until the starting aldehyde was completely consumed (TLC monitoring).…”

“…157.5-159 °C (hexane-AcOEt). 1 4 A solu tion of compound 1a (0.015 g, 0.04 mmol) and TsOH (0.008 g, 0.05 mmol) in MeOH (1.5 mL) was kept at ~20 °C for 2 days. The solution was concentrated, the residue was made alkaline to pH 9 with an aqueous Na 2 CO 3 solution, the product was ex tracted with CHCl 3 (3×10 mL), and the extract was dried with MgSO 4 and concentrated.…”

“…62-63 °C (hexane). 1 B. Catalysis by PhCOCl or BF 3 . A 1.5 fold molar excess of boron trifluoride etherate or benzoyl chloride was added to a solution of compound 1c in anhydrous DMSO d 6 (0.5 mL), and the reaction mixture was kept for 1 day.…”

“…The yield was 0.010 g (47%). 1 Dimethyl 3 (4 dimethylaminophenyl)isoxazole 4,5 dicarb oxylate (2d). A solution of dimethyl acetylenedicarboxylate (0.01 mL, 0.07 mmol) in CHCl 3 (1 mL) was added to a solution of 2 (4 dimethylaminophenyl) 4,4,5,5 tetramethyl 2 imid azoline 1 oxide (16 mg, 0.06 mmol) in CHCl 3 (2 mL).…”