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Regioselective Radical Arene Amination for the Concise Synthesis of ortho-Phenylenediamines

James E. Gillespie, Charlotte Morrill and Robert J. Phipps*

*Yusuf Hamied Department of Chemistry, University of Cambridge, Lensfield Road, Cambridge CB2 1EW, U.K., Email:

J. E. Gillespie, C. Morrill, R. J. Phipps, J. Am. Chem. Soc., 2021, 143, 9355-9360.

DOI: 10.1021/jacs.1c05531

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Attractive noncovalent interactions between a sulfamate-protected aniline as anionic substrate and an incoming radical cation is able to guide the latter to the arene ortho position. Subsequent cleavage of the sulfamate group leads directly to ortho-phenylenediamines, key building blocks for a range of medicinally relevant diazoles. This method can deliver both free amines and monoalkyl amines.

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background and hypothesis

General Procedure: Amination of tetrabutylammonium sulfamate salts with NH2 or NHMe transfer reagent

A suspension of tetrabutylammonium sulfamate salt (1 equiv), NH2 or NHMe transfer reagent (1 or 1.5 equiv) and FeBr2 (0.015 equiv) in HFIP (0.5 M) was stirred at 30C for 4 h. The solvent was then removed under a stream of air and HCl in MeOH (1.25 M, 5 equiv) was added. The resulting solution was then stirred at room temperature for 1 h. The solvent was removed under a stream of air and aqueous NaOH was added. The aqueous layer was then extracted with CHCl3 three times. The combined organics were then dried (MgSO4) and concentrated. The crude residue was then purified by silica gel chromatography to give the final product.

Key Words


ID: J48-Y2021