Eschweiler‐Clarke Methylation

Abstract

The preparation of tertiary methylamines from primary or secondary amines by means of the treatment of those amines with an excess amount of aqueous formaldehyde and formic acid is generally known as the Eschweiler–Clarke methylation. The study finds that in this reaction, the formate anion donates its proton to reduce the imine or iminium salt, so that carbon dioxide is evolved. Thus this process is known as reductive amination of formaldehyde. The reductive amination that occurs on phenylethylamine and results in the formation of tetrahydroisoquinolines is also referred to as the Clarke–Eschweiler cyclization. The reaction has application in the methylation of primary and secondary amines.

Put a Ring on It: Improving the Thermal Stability of Molybdenum Imides through Ligand Rigidification

“…We then synthesized a new ligand, N,N -dimethyl-5,6,7,8-tetrahydoquinolin-8-amine (dmthqa), by the Eschweiler-Clarke methylation of 5,6,7,8-tetrahdroquinolin-8-amine using formic acid and paraformaldehyde; dmthqa is a rigid analogue of 2-( N,N- dimethylamino)methylpyridine (dmampy) (Figure ). The structure of the new ligand was supported by 1 H NMR spectroscopy and direct treatment of dmthqa with an ethereal solution of ( t BuN) 2 MoCl 2 ·dme led to the isolation of ( t BuN) 2 MoCl 2 ·dmthqa ( 3b , Figure ).…”