Cu(I) Mediated Azidation of Halobenzenes, and Cu Catalysed Selective Azide Reduction to Corresponding Amines

Abstract

Aryl amines are synthesized from halobenzenes via copper mediated reactions employing sodium azide under mild conditions in ethanol/water. The reaction proceeds stepwise via the aryl azide, which is reduced to the corresponding amine in‐situ. The methodology allows syntheses of amines from corresponding para‐, meta‐ and ortho‐bromobenzenes bearing electron withdrawing groups. Bifunctional halobenzenes bearing alkanoyl chains with terminal bromides are selectively transformed, generating an aniline and an aliphatic azide, as this azide position is stable to reduction. A one‐pot multistep sequence for preparation of the target amines was designed. The azide formation is mediated by CuI while elemental Cu is generated simultaneously, which is deposited onto the employed PTFE stirring bar used in the reaction. The Cu films were quantified and analysed by SEM/EDS. The Cu, either deposited or in solution, is responsible for the azide reduction, possibly involving nitrene intermediates. An application of the modified stirring bars as a heterogeneous catalyst for a click reaction is demonstrated.

Copper(I) Chloride Mediated Amination of Halobenzenes via Azides: Scope, Mechanistic Aspects, and C–C Cleavage Reactions

“…The last solvent volume was carefully blown away under a stream of Ar, and the mixture was analyzed as described above. The NMR data for 4f (orange crystalline solid, 83% from 1f ; 76% from 1fb ), 4g (55%), 4h (48%), and 3l (67%), NMR yields in brackets, is in agreement with our previous report …”

“…It has been previously suggested that similar copper-mediated in situ amination reactions proceed via highly reactive nitrene intermediates, ,, which may be copper-stabilized . We have proposed a similar pathway for the amination in EtOH/water . The presence of the TEMPO conjugates suggests that nitrenes are involved in the amine formation.…”

“…Triazenes are known to transform into amines and may form aryl azides . We have recently reported an alternative protocol for the synthesis of 4e …”

“…The latter allows the isolation of amine−azide 4a in a yield of >60%. Although reaction times are longer and yields are slightly lower compared to our previous protocol, 31 it does not require the additive sodium ascorbate and a base but produces the amine−azides in higher purity, unlike those reactions in EtOH/water. This latter solvent mixture gave trace amounts of aliphatic impurities presumably formed through side reactions that were not observed in DMF/water.…”

“…Furthermore, it gives straightforward access to versatile amine–azides as the reaction produces selectively aryl amines and alkyl azides from bifunctional precursors. This can be used to construct complex nitrogen-rich compounds via multi-step procedures …”