Solvent‐free synthesis and 1,3‐dipolar cycloaddition reactions of N‐methyl‐C‐(2‐furyl) nitrone in a ball mill and anticancer activities of the new cycloadducts

Abstract

An efficient method of mechanochemistry for the synthesis of N-methyl-C-(2-furyl) nitrone and intermolecular 1,3-dipolar cycloaddition reactions with activated alkenes and electron deficient alkynes has been studied by employing ball milling technique. This method is found to accelerate significantly the reaction rate and improved yields of isoxazolidine and isoxazoline derivatives.A comparative study with the corresponding solvent-free microwave-induced reaction showed the superiority of the ball milling method. Significant anticancer activity of the new molecules have made this protocol more attractive. All the new isoxazolidine and isoxazoline derivatives have been screened for anticancer activities and were found to be active.

Catalyst-free mechanochemistry as a versatile tool in synthetic chemistry: a review

“…A catalyst, solvent-free mechanochemical (ball milling) route for the synthesis of isoxazolidines ( 170 ) and isoxazolines ( 171 ) from N -methyl- C -(2-furyl)nitrone ( 167 ) via intermolecular 1,3-dipolar cycloaddition reactions with functionalized alkenes ( 168 ) or alkynes ( 169 ) at rt was demonstrated by Chakraborty (Scheme 54). 124 Initially, the N -methyl- C -(2-furyl)nitrone ( 167 ) was synthesized from furfural ( 165 ) by reacting with N -methylhydroxylamine hydrochloride ( 166 ) using NaHCO 3 under mechanochemical (ball milling) conditions. The synthesized nitrone was then ball milled with maleimide ( 168 ) or symmetrically disubstituted acetylenes ( 169 ) to form 170 and 171 via an intermolecular 1,3-dipolar cycloaddition reaction.…”