Preparation of secondary amines through efficient alkylation of n-substituted trifluoroacetamides

✍ Scribed by J.Eric Nordlander; David B. Catalane; Thomas H. Eberlein; Lee V. Farkas; Robert S. Howe; Randall M. Stevens; Nicholas A. Tripoulas; Roger E. Stansfield; Jana L. Cox; Mark J. Payne; Alfred Viehbeck

• Book ID: 104237411
• Publisher: Elsevier Science
• Year: 1978
• Tongue: French
• Weight: 223 KB
• Volume: 19
• Category: Article
• ISSN: 0040-4039
• DOI: 10.1016/s0040-4039(01)85789-0

✦ Synopsis

Trifluoroacetamides are attractive intermediates for the Gabriel-like1 transformation of primary to secondary amines through a sequence of acylation, ionization, alkylation, and hydrolysis. Overalkylation is precluded, and the trifluoroacetyl group is readily introduced' to furnish a carboxamide of exceptional acidity 2a and, later, ease of saponification. 2a,3 51 _a RNH2+RNHCCF3+ RNCCF3, "'1 RINH Such reactions have in fact been carried out by several workers, 4,s but no convenient and efficient general procedure can yet be said to have been developed.

We wish to report that characteristically high yields of secondary amines are produced following saponification when N-alkyl or -aryl trifluoroacetamides are primary-alkylated in tetrahydrofuran using potassium hydride as base and 18-crown-6 as alkylation catalyst. We believe the method should find wide applicability.