Sébastien Naud* Laboratoire de Synthèse Organique (UMR-CNRS 6513; FR-CNRS 2465), Université de Nantes, UFR des Sciences et des Techniques , 2 rue de la Houssinière, B.P. 92208, 44322 Nantes cedex 3, France e-Mail: sebastien.naud@chimie.univ-nantes.fr;
Aza heterocyclic compounds, due to their presence in a number of biologically active compounds such as alkaloids, are very important in the field of medicinal and therapeutic chemistry. They can be synthesized through various ways, the hetero Diels-Alder reaction being one of them.
[1]
[2]
For example, dimethyl 1,2,4,5-tetrazine-3,6-dicarboxylate (1) has been extensively used for the synthesis of nitrogen-containing heterocyclic compounds through inverse electron demand hetero Diels-Alder reactions.
[3]
Herein, I would like to discuss this reagent.
Dimethyl 1,2,4,5-tetrazine-3,6-dicarboxylate (1) is a bright-red crystalline solid and can be synthesized on large scale through four steps from ethyl diazoacetate (2) (Scheme 1).
[4]
[5]
Its synthesis starts with a base-promoted dimerization of ethyl diazoacetate (2) followed by acidification of the sodium salt (3) with concentrated hydrochloric acid and esterification to afford the diester (5). Finally, oxidation with nitrous gas affords 1 in 34% overall yield.
