Creatine-Functionalized Graphene Oxide Membrane Reactor for Efficient Synthesis of 2-Amino-4H-Chromene Derivatives

Derivatives of 2-amino-4H-chromene possess diverse pharmacological activities. However, traditional multicomponent synthesis suffers from toxic solvents, long reaction times, and difficulties in balancing catalytic activity and selectivity, which violates green chemistry requirements. Inspired by the nanoconfinement effect in enzymatic catalysis, this work uses graphene oxide (GO) as a two-dimensional scaffold to graft creatine (CR) and construct bifunctional catalytic sites. Thermal regulation of GO interlayer spacing yields an interlayer-confined flow membrane reactor for the three-component condensation of benzaldehyde, malononitrile and dimedone. A near-quantitative conversion of 99.0 ± 1.7% (mean ± SD, n = 3) was achieved within 18 s at room temperature. This nanoconfined membrane catalyst overcomes the defects of classic catalytic systems and provides a novel, practical route for continuous, green and high-yield synthesis of 2-amino-4H-chromene derivatives.