Syntheses of Bromo-N-heterocycles through Dibromohydantoin-Promoted Tandem C–H Amination/Bromination

Abstract

Herein, we report a metal-free radical tandem C–H amination and bromination reaction with dibromohydantoin (DBH) as both the amination and bromination reagents and water as the main solvent. The reaction involves in intramolecular C–H amination and electrophilic bromination using cheap commercially available DBH. The products represent heterocyclic building blocks, readily modifiable by classical cross-coupling reactions.

Recent Update on Transition Metal‐Free C(sp2)−H Bond Halogenation in (Hetero) Arenes

“…Ma et al . also developed an alternative methodology [39] for bromination using DBH as the bromine source instead of NaBr/PhI(OAc) 2 or K 2 S 2 O 8 [38] in a transition metal‐free step‐economic methodology for amination/bromination process.…”

Synthesis of Six‐Membered N‐Heterocycle Frameworks Based on Intramolecular Metal‐Free N‐Centered Radical Chemistry

“…[16] In light of the above results, we next tended our attention to the tandem intramolecular CÀ H amination and bromination of 2-biaryl phosphamides to synthesize 5'-bromodibenzophosphamides. [17] After a series screening of hypervalent bromine reagents (including N-bromosuccinimide (NBS), dibromohydantoin (DBH) and tribromoisocyanuric acid (TBCA), we found that DBH was the most efficient reagent and the 5'-bromo-dibenzophosphamide was obtained Scheme 1. Methods for the synthesis of N-heterocycle compounds.…”

“…It is interesting that the dibromo-dibenzophosphamides were also obtained when 3.0 equivalent DBH was used in CH 3 CN (Scheme 5). [17] If the substituent was electrondonating methoxyl, we obtained the tribromo-phosphamide. While when the 4'-CF 3 -substituted substrate was used, the corresponding monobromo-phosphamide was isolated in good yield.…”

“…Later, we found that using DBH as the only reagent and water as solvent could also achieve this transformation (Scheme 14). [17] It is noted that the only waste of this reaction is hydantoin, which can be recycled to produce DBH.…”

“…of DBH in water could also give the corresponding dibromodibenzosulfoximines products in moderate to good yields with excellent diastereoselectivity (Scheme 20). [17] The plausible mechanism was shown in scheme 21. Firstly, sulfide 8 is oxidized to sulfoximine 11 through fulfilimine 10 or sulfoxide 9.…”