Efficient Synthesis of Quinoxaline Derivatives Catalyzed by p-Toluenesulfonic Acid Under Solvent-Free Conditions

Abstract

A series of quinoxaline derivatives were efficiently synthesized in excellent yields by the reaction of 1,2-diamines and 1,2-diketones with grinding catalyzed by p-toluenesulfonic acid under solvent-free conditions at room temperature. Compared with the classical synthetic method, this new method has the advantages of convenient manipulation and environmental friendliness.

Keywords:

• p-Toluenesulfonic acid
• quinoxaline
• room temperature
• solvent-free conditions

ACKNOWLEDGMENTS

We are grateful to the Open-End Foundation of the Key Laboratory of Organic Synthesis for financial support.

Notes

^a All reactions were performed at 1-mmol scale using 10 mol% of catalyst with grinding under solvent-free conditions.

^b Isolated yields.

^a All reactions were performed at 1-mmol scale using 10 mol% of p-TsOH with grinding at room temperature.

^b Isolated yields.

^a Method A: 1,2-diamine (1 mmol), 1,2-diketone (1 mmol), p-TsOH (0.1 mmol), grinding, solvent free, rt, purified by recrystallization from ethanol.

^b Method B: 1,2-diamine (1 mmol), 1,2-diketone (1 mmol), 10 mol% of iodine in 0.5 mL of CH₃CN, rt, purified by flash column chromatography.

^c Method C: 1,2-diamine (10 mmol), 1,2-diketone (10 mmol), 10 mol% of iodine in 10 mL of DMSO, rt, purified by recrystallization from ethanol.

^d Method D: 1,2-diamine (0.2 mmol), 1,2-diketone (0.2 mmol), 3 mL of 9:1 MeOH-HOAc, at 160 °C, purified by preparative LCMS.