Efficient Transformation of Azides to Primary Amines Using the Mild and Easily Accessible CeCl₃·7H₂O/NaI System

Abstract

Because of the nitrogen functionality, the azido group plays an important role in the synthesis of amines, and numerous reduction methods of azides to primary amines are reported. Recent reports have highlighted the capability of NaI as a useful reagent for this transformation when it is used in combination with a Lewis acid promoter. However, these methods often suffer from harsh reaction conditions; for this reason, the development of a simple and efficient protocol using NaI in presence of inexpensive and readily available cerium salts Lewis acids would extend the scope of this organic transformation. In continuation of our interest on the use of the CeCl3.7H2O/NaI system, in this paper we report how azides undergo reduction by NaI in the presence of CeCl3.7H2O in refluxing acetonitrile under neutral conditions to produce the corresponding primary amines. The rate and yield of the reaction are considerably improved by employing this microwave-assisted procedure, and this may be of value for the preparation of densely functionalized molecules having biological and pharmaceutical activities.

Chemoselective Aromatic Azido Reduction with Concomitant Aliphatic Azide Employing Al/Gd Triflates/NaI and ESI‐MS Mechanistic Studies

“…Most recently, Marcantoni and co‐workers17 reported a versatile method for aliphatic azido reductions using CeCl 3 ⋅ 7H 2 O (1.5 equiv)/NaI (9 equiv) at reflux for 24 h and also studied the effect of microwave irradiation. However, it is well known that a number of amines or imines decompose at higher temperatures and in prolonged reactions.…”

“…Various mechanisms have been proposed for such metal‐assisted reduction of azides 16. 17 Comprehensive mechanistic investigations usually require kinetic data gained by monitoring over long timescales, usually by UV, IR, or NMR spectroscopy. However, these techniques are often not suitable for the short timescales required for investigating transient species as unequivocal assignments of UV and IR bands or NMR peaks and couplings, particularly for more complex or transient structures, may be challenging and sometimes unfeasible.…”

Microwave‐Assisted Cerium(III)‐Promoted Cyclization of Propargyl Amides to Polysubstituted Oxazole Derivatives

“…Given that the use of microwave irradiation often decreases reaction times and reduces the required temperature compared to reactions performed under thermal conditions, [25] the effect of using microwave control of temperature/time (the microwave controls the irradiation power to maintain the fixed temperature) with a single-mode microwave reactor equipped with a cooling system for automatic microwave regulation was examined. [26] Gratifyingly, CeCl 3 · 7H 2 O/NaI promoted cyclization under these conditions lead to the formation of the trisubstituted oxazole 5a in 50 % yield in only 60 min (Table 1, entry 3). Acetonitrile remained the solvent of choice; other solvents, such as ethanol and water, led to low yields of oxazole and decomposition of the propargyl amide substrate (Table 1, entries 1 and 2).…”

Aluminium chloride hexahydrate: an efficient and versatile reagent in organic synthesis

“…15 Li et al 16 found that Zn/AlCl 3 .6H 2 O could be used as an effective reagent for the reduction of azides to the corresponding primary amines in water or aq. ethanol at ambient condition.…”