Intramolecular Cyclization of Azido-Isocyanides Triggered by the Azide Anion: An Experimental and Computational Study

This work describes the unprecedented intramolecularcyclizationoccurring in a set of & alpha;-azido-& omega;-isocyanides in the presenceof catalytic amounts of sodium azide. These species yield the tricycliccyanamides [1,2,3]triazolo[1,5-a]quinoxaline-5(4H)-carbonitriles, whereas in the presence of an excess ofthe same reagent, the azido-isocyanides convert into the respectiveC-substituted tetrazoles through a [3 + 2] cycloaddition between thecyano group of the intermediate cyanamides and the azide anion. Theformation of tricyclic cyanamides has been examined by experimentaland computational means. The computational study discloses the intermediacyof a long-lived N-cyanoamide anion, detected by NMRmonitoring of the experiments, subsequently converting into the finalcyanamide in the rate-determining step. The chemical behavior of theseazido-isocyanides endowed with an aryl-triazolyl linker has been comparedwith that of a structurally identical azido-cyanide isomer, experiencing a conventional intramolecular [3 + 2] cycloadditionbetween its azido and cyanide functionalities. The synthetic proceduresdescribed herein constitute metal-free approaches to novel complexheterocyclic systems, such as [1,2,3]triazolo[1,5-a]quinoxalines and 9H-benzo[f]tetrazolo[1,5-d][1,2,3]triazolo[1,5-a][1,4]diazepines.

Automated summary

This study presents the previously unknown intramolecular cyclization of a group of α-azido-ω-isocyanides in the presence of catalytic amounts of sodium azide. These compounds form tricyclic cyanamides [1,2,3]triazolo[1,5-a]quinoxaline-5(4H)-carbonitriles, while an excess of sodium azide leads to the formation of C-substituted tetrazoles through a [3 + 2] cycloaddition reaction. Experimental and computational methods were used to examine the formation of tricyclic cyanamides, revealing the presence of a long-lived N-cyanoamide anion that converts into the final cyanamide. The chemical behavior of these azido-isocyanides with an aryl-triazolyl linker was compared to that of a structurally identical azido-cyanide isomer. The synthetic procedures described in this work offer metal-free approaches to complex heterocyclic systems.