Castor Oil as a Renewable Reaction Medium for Sustainable Domino Synthesis of Functionalized Epoxyisoindolyl Ureas

Abstract

Abstract The development of renewable reaction media that can replace conventional organic solvents without affecting reaction performance is highly desirable for the advancement of sustainable chemical processes. In this study, the properties of Castor oil as a bio-based solvent were investigated in the context of a domino multicomponent synthesis of functionalized epoxyisoindolyl ureas. This synthesis involved a tandem condensation/Diels–Alder sequence, with the use of furfurylamine, phenyl isocyanate, and various N-substituted maleimides. In the absence of a catalyst and under mild reaction conditions, the desired products were obtained in satisfactory yields and with generally high diastereoselectivity without the need for chromatographic purification. In the course of the investigation, it was established that among the vegetable oils under consideration, Castor oil demonstrated the highest reaction efficiency. Furthermore, it was ascertained that this oil could be easily recovered and reused. Its superior performance is attributed to its high hydrogen-bonding capability and favorable Hansen solubility parameter profile, which enhance substrate solubilization and facilitate hydrogen bond-assisted organization of the reacting species. The use of Fourier-transform infrared (FTIR) monitoring and DFT calculations has provided support for a proposed mechanism in which the rapid formation of a urea intermediate occurs prior to the intermolecular cycloaddition reaction. In comparison with conventional stepwise protocols, the present methodology integrates multiple bond-forming events into a single operation, thereby reducing purification requirements while employing a renewable and recyclable reaction medium. The findings of this study demonstrate that Castor oil provides an effective platform for sustainable domino synthesis and highlight the potential of vegetable-oil-based solvents for greener multicomponent transformations.