Nucleophilic Attack at Heterocyclic Nitrogen: Unusual Reactivity of the Benzotriazole Heterocyclic Ring

Abstract

Grignard reagents attack 1‐imidoylbenzotriazoles at the imidoyl carbon atom and also at the benzotriazolyl N‐2 and N‐3 atoms leading to complex reaction mixtures, the composition of which allowed identification of the main reaction paths. Mechanisms are discussed. Previous examples of nucleophilic attack on pyridine‐like nitrogen atoms are reviewed. The 1‐imidoylbenzotriazoles were prepared from amides with benzotriazole and phosphoryl chloride. Amides derived from secondary amines give α‐(benzotriazol‐1‐yl) enamines.

Nucleophilic Attack on Nitrogen in Tetrazines by Silyl-Enol Ethers

“…[13] In contrast to cycloaddition reactions, direct addition reactions of nucleophiles to N-containing aromatics have rarely been described in the literature, and are generally limited to 1,2,3-benzotriazoles, 1,2,3triazines, and 1,2,4,5-tetrazines. [14,15] To the best of our knowledge, there are only three reports in the literature on the addition of hard organometallic reagents, such as RLi or RMgX, to the tetrazine core. [14,16,17] Neugebauer and Siegel were first to react unsubstituted s-tetrazine with methyl magnesium iodide to give 1,4-dihydro-1-methyl-s-tetrazine, [17] which was corroborated independently at the same time by…”

“…In contrast to cycloaddition reactions, direct addition reactions of nucleophiles to N -containing aromatics have rarely been described in the literature and are generally limited to 1,2,3-benzotriazoles, 1,2,3-triazines, and 1,2,4,5-tetrazines. , To date, there is only a limited number of reports on the addition of hard organometallic reagents, such as RLi or RMgX, to the tetrazine core. ,, After this work was published on ChemRXiv, Boger and co-workers reported the selective N1/N4-cycloaddition of s -tetrazine, which is likely to occur via an initial azaphilic attack of an enamine . In the context of our research on the chemistry of 3-monosubstituted s -tetrazines and specifically 3-bromotetrazine (3-Br-Tet) ( 1 ), a small s -tetrazine building block for the labeling of macromolecules previously reported by our group and others, , we investigated their reactivity with silyl-enol ethers.…”

A Versatile Direct Approach to ortho‐Substituted Azobenzenes from Benzotriazoles

“…The benzotriazole ring is extremely stable and only rarely was ring cleavage encountered to give mostly products of nitrogen extrusion. For example, Grignard reagents open and modify the triazole ring and afford a variety of products 2. Other methods for opening the benzotriazole ring are by photolysis and pyrolysis,3 however, no actual ring opening of benzotriazole that has led to isolable azobenzenes has been reported 1d…”

Reaction of N-Nonaflylbenzotriazole with Silyl Enol Ethers

“…9,10 Other ring-cleavage reactions of benzotriazoles are known to occur upon treatment of benzotriazoles with Grignard reagents affording phenylenediamines in low to medium yield. [11][12][13] Katritzky also described domino reactions of some benzotriazole derivatives that proceeded via a ring-opening-ring-closure sequence to afford 1,2,4-triazolo[1,5-a]quinoxaline 14 and benzo[c]tetrazolo [1,5e]triazepine. 15…”