Tetrazole derivatives are a prime class of heterocycles, very important to medicinal chemistry and drug design due to not only their bioisosterism to carboxylic acid and amide moieties but also to their metabolic stability and other beneficial physicochemical properties. Although more than 20 FDA-approved drugs contain 1 H- or 2 H-tetrazole substituents, their exact binding mode, structural biology, 3D conformations, and in general their chemical behavior is not fully understood. Importantly, multicomponent reaction (MCR) chemistry offers convergent access to multiple tetrazole scaffolds providing the three important elements of novelty, diversity, and complexity, yet MCR pathways to tetrazoles are far from completely explored. Here, we review the use of multicomponent reactions for the preparation of substituted tetrazole derivatives. We highlight specific applications and general trends holding therein and discuss synthetic approaches and their value by analyzing scope and limitations, and also enlighten their receptor binding mode. Finally, we estimated the prospects of further research in this field.

5-halo-1-phenyltetrazoles

Tetrazoles via Multicomponent Reactions.

The aim of this review is providing an overview of the various representative literature procedures for the preparation of tetrazoles via isocyanide-based reactions. These reactions have been divided into four classes including two-component reactions (2CRs), Passerini-azide three-component reactions (PA-3CRs), Ugi-azide four-component reactions (UA-4CRs) and Ugi-azide three-component reactions (UA-3CRs).

Synthesis of tetrazoles via isocyanide-based reactions

http://www.chtf.stuba.sk/~szolcsanyi/education/files/Chemia%20heterocyklickych%20zlucenin/Prednaska%203/Doplnkove%20studijne%20materialy/Tetra-%20and%20Pentazoles/Three-Component%20Strategy%20toward%20Tetrazoles.pdf

Three-component strategy toward 5-membered heterocycles from isocyanide dibromides.

Recent progress in the application of N-halo reagents in the synthesis of heterocyclic compounds

1,4-Bis[1-(2-hydroxyethyl)-1H-tetrazol-5-yl]-1,4-dimethyl-2-tetrazene (12a), 1,4-bis[1-isopropoxycarbonylmethyl-1H-tetrazol-5-yl]-1,4-dimethyl-2-tetrazene (12b), and 1,4-bis[1-carboxymethyl-1H-tetrazol-5-yl]-1,4-dimethyl-2-tetrazene (13) have been synthesized as new nitrogen-rich compounds. The tetrazenes were obtained by oxidation of the corresponding tetrazolylhydrazines using bromine. Moreover, a new method to prepare tetrazolylhydrazines in high yield using 5-bromotetrazoles has been developed. 12a, 12b, and 13 were characterized using vibrational spectroscopy (IR, Raman), mass spectrometry, and multinuclear NMR spectroscopy. The crystal structures of 12a, 12b, and 13 were determined using single crystal X-ray diffraction. Furthermore, the energetic properties of 12a, 12b, and 13 have been investigated using DSC and bomb calorimetric measurements. The sensitivity data toward impact and friction has been determined using BAM methods.

5-halo-1-phenyltetrazoles

Citations

Tetrazoles via Multicomponent Reactions.

Synthesis of tetrazoles via isocyanide-based reactions

Three-component strategy toward 5-membered heterocycles from isocyanide dibromides.

Recent progress in the application of N-halo reagents in the synthesis of heterocyclic compounds

Synthesis of functionalized tetrazenes as energetic compounds.

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