Hydrophobic eutectic and hydrophilic melts of gabapentin-lactam & citric acid mixtures; green promoters for selective synthesis of xanthenes/ benzo[b]pyrans and dihydropyrroles

Abstract

Gabapentin-lactam and citric acid form a glassy hydrophobic deep eutectic mixture. Certain non-eutectic molar ratios of the two components are also low-melting mixtures and slight differences can be discerned in their differential calorimetric curves. Yet, they impose different selective promotions on the reaction of malononitrile, arylaldehyde, and dimedone. Interestingly, the reaction mixture selectively gives tetrahydrobenzo[b]pyran-2H-ones or 1,8-dioxo-octahydroxanthenes depending on being carried out in the melted 2/1 or 1/2 molar mixtures of gabapentin-lactam/citric acid. An excellent promoting activity was also observed for the melt of gabapentin-lactam and citric acid mixture in 1/1 molar ratio. This melt proved to be an efficient promoter for synthesis of 4‑hydroxy-2,5-dihydropyrrol-5-ones from the domino reaction of an arylaldehyde, an aniline derivative, water, and an acetylenic ester. No additional organic solvents are required to perform the reactions and the bio-compatible melts can be reused several times after easy separation from the products. The eutectic and the non-eutectic melts preserve their viscous liquid state even upon a long-term storage at ambient temperature.