The Bucherer-bergs reaction in deep eutectic solvents: Accessing spiro-oxindole-hydantoins

Hydantoins and their derivatives represent an important group of heterocycles due to their diverse biological and pharmacological activities. The Bucherer-Bergs reaction is a useful multicomponent reaction for the synthesis of hydantoins. In this paper we report our results on a particular Bucherer-Bergs reaction on N -benzylisatins in three types of Deep Eutectic Solvents (DESs): betaine/sorbitol/water (DES A), ammonium carbonate/sorbitol/water (DES B) and Betaine/Sorbitol/D 2 O (DES C). DES A presented the best performance and DES B is an example of a reactive DES (RDES). DES B which incorporates both the NH 3 and CO 2 reactants (ammonium carbonate) – although affording lower yields - reinforces an emerging concept in sustainable synthesis. The DES reactions could be carried out at lower temperatures than in the conventional solvent system of MeOH/water. It was also possible to perform up to 5 reaction cycles in the case of one particular Bucherer-Bergs reaction in DES A. Extensive physicochemical properties of these novel DESs were determined, that included, surface tension, viscosity, refractive index and Kamlet-Taft Parameters. The Bucherer-Bergs reaction was carried out using organocatalysts in MeOH/water, DES A and DES B but only racemic products were obtained. Additionally, to gain insights on possible catalytic intervention of the DES, the kinetics of the DES reaction was compared with that of the conventional solvent (MeOH/H 2 O) and the DES A system gave comparative results, despite a temperature off-set of 35 °C. • The first reported Bucherer-Bergs, Multicomponent reaction (MCR) in a Deep Eutectic Solvent (DES). • Preparation of a novel Reactive Deep Eutectic Solvent (RDES) and proof of concept demonstration. • Ability to conduct up to 5-reaction cycles with one DES. • Extensive physico-chemical characterization of the DESs.