Bio-based N-alkyl-2-pyrrolidones by Pd-catalyzed reductive N-alkylation and decarboxylation of glutamic acid

Abstract

Environmental regulations boost the search for new safer and less toxic bio-based solvents to replace controversial high-boiling solvents such as N-methyl-2-pyrrolidone and N,N-dimethylformamide in the chemical industry. Recently, N-alkyl-2-pyrrolidones and 5-methyl-N-alkyl-2-pyrrolidones were proposed as attractive alternative solvents for many applications. Here, we report a bio-based two-step chemocatalytic system for the synthesis of a broad range of N-alkyl-2-pyrrolidones starting from glutamic acid and C₃–C₅ carbonyl compounds. In the first step N-mono-alkylated derivatives of glutamic acid were synthesized in high yields (>85%) by a mild and efficient Pd-catalyzed reductive N-alkylation. Subsequently, thermally induced lactamization to the corresponding N-alkylpyroglutamic acid followed by Pd-catalyzed decarboxylation at 250 °C under inert atmosphere resulted in N-alkyl-2-pyrrolidones. Hydrolytic degradation was partially counteracted by the neutralization of the N-alkylpyroglutamic acid substrate with a base, resulting in yields up to 82%. Finally, both reaction steps were successfully combined in a one-pot process using the same Pd/Al₂O₃ catalyst in different conditions of gas atmosphere and temperature.