Single cobalt atom catalysis for the construction of quinazolines and quinazolinones via the aerobic dehydrocyclization of ethanol†

Abstract

The synthesis of N-heterocycles through the aerobic dehydrocyclization of ethanol is still significant and challenging since ethanol is the largest renewable small molecule feedstock but with high dehydrogenation activation energy. Herein, a single Co catalyst (Co₁@NC-50) with oxidase-like active sites (CoN₄) has been fabricated for the construction of quinazolines and quinazolinones using ethanol as the C₂-synthon. The merits of this approach include the use of air as the oxidant and abundant metal recyclable catalyst, free of additives, high step and atom economy, and broad substrate scope, showing great potential for application in drug synthesis. The mechanistic insights are also gained: (1) ethanol dehydrogenation is the rate-determining step of this reaction, which is mainly implemented by ˙O₂⁻; (2) the CoN₄ site exhibits a strong ability for adsorption of O₂ and ethanol, and it has the lowest ethanol dehydrogenation energy barrier than CuN₄ and FeN₄. To the best of our knowledge, this is the first example of single atom catalysis for the synthesis of N-heterocycles using ethanol as the C₂-synthon.