Eschweiler-Clarke Reaction

This reaction allows the preparation of tertiary methylamines from secondary amines via treatment with formaldehyde in the presence of formic acid. The formate anion acts as hydride donor to reduce the imine or iminium salt, so that the overall process is a reductive amination. The formation of quaternary amines is not possible.

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Mechanism of the Eschweiler-Clarke Reaction

Recent Literature

(Z)-Selective Enol Triflation of α-Alkoxyacetoaldehydes: Application to Synthesis of (Z)-Allylic Alcohols via Cross-Coupling Reaction and [1,2]-Wittig Rearrangement
K. O. Biriukov, E. Podyacheva, I. Tarabrin, O. I. Afanasyev, D. Chusov, J. Org. Chem., 2024, 89, 3580-3584.