Simplified Version of the Eschweiler–Clarke Reaction
Klim O. Biriukov, Evgeniya Podyacheva, Ignatii Tarabrin, Oleg I. Afanasyev, Denis Chusov
Abstract
The traditional Eschweiler-Clarke reaction is a three-component process involving formaldehyde, amine, and formic acid. In this work, we showed that the reductive potential of formaldehyde was sufficient to provide methylation of secondary amines in the absence of acidic additives. Various acid-sensitive moieties remain intact under developed conditions. The scalability of the elaborated approach was shown for several products. Synthesis of the antifungal agent butenafine demonstrated the preparative utility of the developed approach.
Topics & Concepts
ChemistryFormic acidFormaldehydeAmine gas treatingCombinatorial chemistryOrganic chemistryComponent (thermodynamics)AntifungalMedicinePhysicsThermodynamicsDermatologyChemical Synthesis and AnalysisAsymmetric Hydrogenation and CatalysisChemical Synthesis and Reactions