General method for nucleophilic aromatic substitution of aryl fluorides and chlorides with dimethylamine using hydroxide-assisted decomposition of N,N-dimethylforamide

ABSTRACT

A practical and convenient procedure for the nucleophilic aromatic substitution of aryl fluorides and chlorides with dimethylamine was developed using a hydroxide-assisted thermal decomposition of N,N-dimethylforamide. These conditions are tolerant of nitro, nitrile, aldehyde, ketone, and amide groups but will undergo acyl substitution to form amides for methyl esters and acyl chlorides. Isolated yields of the products range from 44% to 98%, with the majority being greater than 70% for 17 examples.

GRAPHICAL ABSTRACT

KEYWORDS:

• Aniline derivatives
• aryl halides
• dimethylamine
• DMF decomposition
• nucleophilic aromatic substitution

Acknowledgments

We thank the National Center for Research Resources (5P20RR016464-11) and the National Institute of General Medical Sciences (8 P20 GM103440-11) from the National Institutes of Health and the National Science Foundation (IIA-1301726) for their generous funding, as well as Jungjae Koh for his help in acquiring 400-MHz ¹H NMR spectra and John Greaves for aquiring ESI HRMS.