Development and Demonstration of a Safer Protocol for the Synthesis of 5-Aryltetrazoles from Aryl Nitriles

Abstract

The search for a faster, safer protocol for the direct synthesis of 5-aryltetrazoles from aryl nitriles in the presence of sodium azide and an amine hydrochloride salt led to the discovery of a buffered system comprised of BnNH 2 , BnNH 2 •HCl, and NaN 3 . After optimization of reaction conditions and a thorough investigation of reaction safety, the procedure was demonstrated for the synthesis of several hundred grams of 4-chloro-2-(2Htetrazol-5-yl)phenol. The generality of the developed reaction conditions was established by a small-scale reactivity screen using 16 additional aryl and heteroaryl nitrile substrates.

Impregnated copper ferrite on mesoporous graphitic carbon nitride: An efficient and reusable catalyst for promoting ligand‐free click synthesis of diverse 1,2,3‐triazoles and tetrazoles

“…By contrast, tetrazole scaffolds with impressive functionality have attracted unprecedented interest over the last decade mainly due to their distinct applications in various areas of science . The wide applicability of tetrazoles has prompted extensive attempts toward the development of new and practical strategies for their synthesis, however, the [3 + 2] cycloaddition of organic nitriles with an azide anion remain by far the most efficient and sustainable route for the synthesis of diverse 5‐substituted 1 H ‐tetrazoles . The investigation was initiated using 1 mmol of benzonitrile ( 6a ) and NaN 3 (1.2 mmol) as model substrates in the presence of the catalyst under various conditions (Table ).…”

Allylic azides: synthesis, reactivity, and the Winstein rearrangement

“…These reagents have been used on large scales. [38][39][40][41][42][43][44] However, improper use has resulted in explosions. 45 Reactions involving nucleophilic azides (e.g.…”

Three‐Dimensional Heterocycles by Iron‐Catalyzed Ring‐Closing Sulfoxide Imidation

“…[8] Its use in catalyzed nitrene transfer reactions has led to convenient methods for C À H bond aminations. [10][11][12][13] We [14] and others [12b, 15] used combinations of iron catalysis and organoazides in sulfur imidations. [10][11][12][13] We [14] and others [12b, 15] used combinations of iron catalysis and organoazides in sulfur imidations.…”

“…[9] In many cases,o rganoazides have been applied as nitrene precursors,w hich is attractive because molecular nitrogen is the only byproduct being released during substrate activation. [10][11][12][13] We [14] and others [12b, 15] used combinations of iron catalysis and organoazides in sulfur imidations. [16] As ar esult, sulfilimines and sulfoximines were obtained, which proved interesting for asymmetric synthesis [17] and applications in crop protection and medicinal chemistry.…”