Computational Study of Ignored Pericyclic Reactions: Rearrangements of 1,2‐Bis(Diazo)Alkanes to 1,2,3,4‐Tetrazines and Subsequent Fragmentations

TL;DR

This paper uses computer simulations to explore a new chemical reaction pathway that can form complex nitrogen-rich rings and predict how to isolate them.

Contribution

The study reveals a previously overlooked electrocyclic reaction pathway for forming 1,2,3,4-tetrazines and identifies conditions for their isolation.

Findings

DFT calculations show that 1,2-bis(diazo)alkanes can form 1,2,3,4-tetrazines via an 8π-electrocyclization.

Substitution patterns strongly influence the feasibility and stability of the reaction products.

Carbene or nitrene intermediates may lead to fragmentation into alkynes or nitriles.

Abstract

An electrocyclic ring closure of bis‐1,3‐dipoles can afford six‐membered heterocycles. This 8π‐electron process was systematically analyzed by DFT calculations with 1,2‐bis(diazo)alkane derivatives as possible precursor compounds and 1,2,3,4‐tetrazines as products. The C2‐symmetry of the transition state of the parent system points to a conrotatory ring closing event. The subsequent (6–2–2) cycloreversions of these elusive nitrogen‐rich heterocycles to alkynes or nitriles and dinitrogen were also computationally investigated. The results show that the reactions are strongly dependent on the substitution pattern, but all are kinetically easily feasible delivering products of differing stability. The calculations can therefore provide important information for experimental endeavors to generate or even isolate so far unknown 1,2,3,4‐tetrazines. The feasibility of carbene or 1,2,3‐triazolyl‐substituted nitrene intermediates for the formation of alkynes is also discussed. The experimental evidence for the proposed processes is enclosed presenting literature known examples of the fragmentation reactions which can most convincingly be explained by the intermediacy of 1,2,3,4‐tetrazine derivatives. Furthermore, the electrocyclic ring closure reactions of five other types of bis‐1,3‐dipoles are calculated, demonstrating that this so far ignored 8π‐electrocyclization process can establish a new route to interestingly composed heterocyclic compounds.

DFT calculations of the 8π‐electrocyclization of 1,2‐bis(diazo)alkanes and of other bis‐1,3‐dipoles reveal that this process can establish a so far ignored route to heterocycles such as 1,2,3,4‐tetrazines. Alternative reaction channels via carbenes or nitrenes leading to fragmentation products are discussed. The computations identified substitution patterns that could allow the characterization or isolation of the elusive 1,2,3,4‐tetrazines. The C2‐symmetric geometries of the transition states point to a conrotatory electrocyclic process.

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