Unusual Expansion of the 1,2,4,5‐Tetrazine Ring in [1,2,4]Triazolo[4,3‐b][1,2,4,5]tetrazines Leading to [1,2,4,6]Tetrazepine Systems

Abstract

Expansion of the tetrazine ring has first been found to occur when [1,2,4]triazolo[4,3‐b][1,2,4,5]tetrazines were allowed to react with CH‐active compounds in acetonitrile in the presence of triethylamine to give the unexpected series of 8,9‐dihydro‐7H‐[1,2,4]‐triazolo[4,3‐b][1,2,4,6]tetrazepine derivatives.

Synthesis of novel [1,2,4]triazolo[1,5-b][1,2,4,5]tetrazines and investigation of their fungistatic activity

“…The reactions of 2 with (diacetoxyiodo)benzene in acetonitrile gave the target products 3a,b,g, however, both yields and purities of these compounds proved to be higher when trifluoroethanol was used as a solvent. larly to isomeric triazolo[4,3-b][1,2,4,5]tetrazines [36], these derivatives do not form ipso-substitution products with the displacement of a leaving group in the tetrazine ring by the action of CH-acids. Instead, a nucleophile attack on the nitrogen atom of the tetrazine ring does occur followed by ring-opening and ring closure (Scheme 4).…”

“…The reactions of new triazolo[1,5- b ][1,2,4,5]tetrazines with some CH-active compounds, such as malononitrile, ethyl cyanoacetate and diethyl malonate, have been studied. Similarly to isomeric triazolo[4,3- b ][1,2,4,5]tetrazines [ 36 ], these derivatives do not form ipso -substitution products with the displacement of a leaving group in the tetrazine ring by the action of CH-acids. Instead, a nucleophile attack on the nitrogen atom of the tetrazine ring does occur followed by ring-opening and ring closure ( Scheme 4 ).…”

“…It has been found that triazolo[1,5- b ][1,2,4,5]tetrazines 3 do not enter the characteristic for isomeric [4,3- b ]-annulated derivative reactions with malonic ester, leading to expansion of the tetrazine ring and the formation of triazolotetrazepines [ 36 ]. At the same time, a more active malononitrile reacts easily with compounds 3a , j to afford triazolopyrimidines 6a , b ( Scheme 4 ).…”

Reactions of 3,6-Bis(3,5-dimethyl-4-R-pyrazol-1-yl)-1,2,4,5-tetrazines with Indole and 1,3,3-Trimethyl-2-methyleneindoline

“…It has been found that indole doesn't react with (8) Expansion of the tetrazine ring has first been found to occur when [1,2,4] were allowed to react with CH-active compounds in the presence of triethylamine. 13 The structure of 9 was strictly proved by 1 H NMR spectroscopy and X-ray analysis ( Figure 4). Figure 3.…”

Three-Component Reaction of 3,3-Difluorocyclopropenes, s-Tetrazines, and (benzo) Pyridines

“…Simple s -tetrazines are deeply colored, weakly basic compounds that can behave as reversible oxidizers and readily accept electrons, forming stable anion radicals. Being highly electron-deficient, s -tetrazines are prone to nucleophilic attack at the carbon atom (with S, N, O nucleophiles) and more rarely at nitrogen (with active C-nucleophiles). Besides normal aromatic nucleophilic substitution at carbons, the S N (ANRORC) mechanism becomes operative, for example, in the Chichibabin hydrazination of monosubstituted s -tetrazines .…”