Safe and Efficient Reductive Methylation of Primary and Secondary Amines Using N-Methylpyrrolidine Zinc Borohydride

Abstract

An efficient, general procedure for reductive methylation of primary and secondary amines with 37% formaldehyde using N-methylpyrrolidine zinc borohydride (ZBHNMP) as a reducing agent gave the corresponding tertiary amines in excellent yields. The reaction was carried out in tetrahydrofuran under neutral conditions at 0–10 °C.

Keywords:

• Amine
• formaldehyde
• reductive methylation
• ZBHNMP

ACKNOWLEDGMENT

Financial support of this work from the Research Council of Mazandaran University is gratefully acknowledged.

Notes

^a All reactions were carried out in THF at 0–10 °C, and the molar ratio of amine/formaldehyde/reductant was 2:1:4.

^b All products were characterized spectroscopically (¹H NMR, IR) and showed physical and spectral data in accordance with their expected structure by comparison with authentic samples.

^c Yields refer to pure isolated products.