Homogenization offers access to quinoxalines in minutes: a solvent-free, catalyst-free protocol with a near-zero E-factor†

A reagent-free, catalyst-free, sustainable methodology was developed for fast and effortless synthesis of quinoxalines by mixing and homogenizing the substrates in a mini cell homogenizer. The mechanochemical agitation between several aromatic (and heteromatic) 1,2-diamines and various 1,2-dicarbonyl compounds with stainless steel balls in simple polypropylene vials at 4000 rpm afforded the corresponding quinoxalines and pyrido[2,3-b]pyrazines via cyclocondensation within a few minutes mostly in quantitative yields. The use of an equimolar ratio of substrates and complete conversion ensured quick access to quinoxalines in a sufficiently pure form offering the additional advantages of a work-up free and purification-free approach. As eliminated water molecules in the process do not contribute to waste, the E-factor of the method is practically zero.