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Synlett 2004(15): 2836-2837  
DOI: 10.1055/s-2004-835662
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© Georg Thieme Verlag Stuttgart · New York

Dimethyl 1,2,4,5-Tetrazine-3,6-dicarboxylate

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;
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Publication Date:
25 November 2004 (online)

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Introduction

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.

Scheme 1

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