Synergistic catalysis on Fe-N x sites and Fe nanoparticles for efficient synthesis of quinolines and quinazolinones via oxidative coupling of amines and aldehydes.

Zhiming Ma,Yong Yang,Tao Song,Youzhu Yuan

doi:10.1039/c9sc04060a

Abstract

In this paper, we developed a reusable heterogeneous non-precious iron nanocomposite comprising metallic Fe-Fe3C nanoparticles and Fe-N x sites on N-doped porous carbon, which allows for highly efficient synthesis of quinolines and quinazolinones via oxidative coupling of amines and aldehydes using H2O2 as the oxidant in aqueous solution under mild conditions. A set of quinazolines and quinazolinones were synthesized in high yields with a broad substrate scope and good tolerance of functional groups. Characterization and control experiments disclose that a synergistic effect between the metallic Fe nanoparticles and built-in Fe-N x sites is primarily responsible for the outstanding catalytic performance. Furthermore, the iron nanocomposite could be readily recovered for successive use without appreciable loss in catalytic activity and selectivity. This work provides an expedient and sustainable method to access pharmaceutically relevant N-heterocycles.

Highlights

The development of reusable earth-abundant and inexpensive non-precious metal catalysts for innovative organic synthesis is a key technology for a more sustainable production of ne chemicals, pharmaceuticals and agrochemicals
A er identifying the optimal reaction conditions and the catalytically active sites, we subsequently explored the generality of this protocol for the synthesis of 2-substituted quinazolines
We developed a reusable heterogeneous earthabundant iron nanostructured catalyst comprising metallic Fe and Fe3C nanoparticles as the core covered by a few layers of Ndoped graphitic carbon and coordinated Fe–Nx sites as well in a facile and cost-effective manner

Summary

Introduction

The development of reusable earth-abundant and inexpensive non-precious metal catalysts for innovative organic synthesis is a key technology for a more sustainable production of ne chemicals, pharmaceuticals and agrochemicals. Given the importance of N-heterocycles, a number of synthetic methods have been developed over the past few decades.[8] Despite these signi cant advances, the most classical and general approaches for the synthesis of quinazolines and quinazolinones still strongly rely on the condensation between o-aminobenzylamines and aldehydes followed by the oxidation of the resulting aminal intermediates in the laboratory and industry This protocol generally requires the use of a large excess of toxic oxidants, such as DDQ,[9] MnO2,10 PhI(OAc)[2,11] and NaClO,[12] or homogeneous transition metal complexes ligated with well-de ned ligands,8d,13 which signi cantly limit its practical application, especially for pharmaceutical synthesis. The catalyst could be recycled several times without signi cant loss in catalytic activity

Results and discussion

Conclusion

Conflicts of interest