Nucleophilic Aromatic Substitution Reactions in 3,6-Bis(3,5-dimethyl-1H-pyrazol-1-yl)-1,2,4,5-tetrazine

Abstract

1,2,4,5-Tetrazines, also known as s-tetrazines or sym-tetrazines (symmetric tetrazines), are the most studied isomers in this family of molecules. These compounds exhibit a panel of rare and useful characteristics that make them attractive for several applications in different domains, ranging from materials science, functional molecular systems for the development of sensors and optical switches, electroactive polymers or as building blocks in solar cells, to coordination chemistry and biochemical sciences. Thus, the demand for various tetrazine derivatives that can be used as precursor compounds for the synthesis of novel compounds is high. These derivatives can be prepared by aromatic nucleophilic substitution (SNAr) at the 3- and 6-positions of an adequate tetrazine precursor, particularly if the initial 3 and 6 substituents are good leaving groups such as halogens, thiolates, sulfonates or azolyl groups. 3,6-Bis(3,5-dimethyl-1H-pyrazol-1-yl)-1,2,4,5-tetrazine is a very versatile reagent for which the replacement of the 3,5-dimethylpyrazolyl groups by N-, O- and C-based nucleophiles via SNAr reaction is very well documented. The goal of this work is the synthesis of a series of different asymmetric and symmetric tetrazines. These compounds are synthesized from the same precursor – 3,6-bis(3,5-dimethyl-1H-pyrazol-1-yl)-1,2,4,5-tetrazine under different experimental conditions that illustrate the marked difference in the reactivity of s-tetrazine rings towards different types of nucleophiles.