Synthesis of functionalized isoxazole–oxindole hybrids via on water, catalyst free vinylogous Henry and 1,6-Michael addition reactions

Abstract

Various 3-substituted-3-hydroxy isoxazole–oxindole hybrids were synthesized via the vinylogous Henry reaction of 3,5-dimethyl-4-nitroisoxazole and isatin using water as a reaction medium under catalyst free conditions at 50 C. Systematic studies were carried out to understand the role of the water on the reaction by using D2O, brine, ethylene glycol and PEG-400 as a reaction medium along with organic solvents. Among all of these, water (0.170 mol concentration) was found be more efficient giving desired products in 82–99% yields in 45–120 min. Further the quaternary centre (3 alcohol) generated was used for the creation of a double bond which was again used for a 1,6-Michael reaction to produce highly functionalized isoxazole–oxindole derivatives.