Unlocking Amides through Selective C–N Bond Cleavage: Allyl Bromide-Mediated Divergent Synthesis of Nitrogen-Containing Functional Groups

Abstract

We report a new set of reactions based on the unlocking of amides through simple treatment with allyl bromide, creating a common platform for accessing a diverse range of nitrogen-containing functional groups such as primary amides, sulfonamides, primary amines, N-acyl compounds (esters, thioesters, amides), and Nsulfonyl esters. The method has potential industrial applicability, as demonstrated through gram-scale syntheses in batch and in a continuous flow system.

Metal‐ and Catalyst‐Free Synthesis of 2‐Substituted‐Phthalimides Using 2‐(Arenesulfonyl)Phthalimide as Key Reagents

“…Melting points are General procedure for the preparation of N-substituted arenesulonyl phthalimides (3) and arenesulfonyl succinimide (5): Prepared by modification of reported methodology. [18,21,24,25,29] In a dry flask, a mixture of arenensulfonyl chloride (1 equiv., 30.98 mmol,)…”

“…General procedure for the preparation of N ‐substituted arenesulonyl phthalimides (3) and arenesulfonyl succinimide (5) : Prepared by modification of reported methodology [18,21,24,25,29] . In a dry flask, a mixture of arenensulfonyl chloride (1 equiv., 30.98 mmol,) and imide (1.1 Equiv., 33.98 mmol,) in acetonitrile (150 mL) was cooled to 0 °C in an ice bath for 30 min under nitrogen.…”

Ammonia surrogates in the synthesis of primary amines

“…27 Glutarimide and succinimide have been subjected to similar conditions to those for phthalimide; 23 b ,28 nevertheless, their cleavage poses more significant challenges. Recently, Lin and co-workers 29 developed a straightforward method for cleaving N -aryl substituted glutarimides using allyl bromide as the promoter. The exact mechanism remains uncertain, but this method offers a convenient approach to obtain primary aromatic amines by employing glutarimide as a surrogate for ammonia (refer to Fig.…”

Classes of Amides that Undergo Selective N–C Amide Bond Activation: The Emergence of Ground-State Destabilization

“…Recently, methods on transition-metal-free N–C bond cleavage of activated amides have been reported. − …”