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.

Tetrazoles via Multicomponent Reactions.

The readily accessible α-diazo carbonyl compounds are distinguished by their high reactivity, which opens up a variety of preparative applications under modified conditions. Wolff rearrangements of these compounds, induced thermally, photochemically, or catalytically, afford ketenes. Free and complexed carbenes, 1,3-dipoles, 1,3-diradicals, and the antiaromatic oxirenes have been considered as intermediates or transition states. The present progress report attempts to integrate preparative and theoretical aspects.

The Wolff Rearrangement of α-Diazo Carbonyl Compounds

Studies of the 1,2 hydrogen shift in carbenes, nitrenes, and vinylidenes are reviewed. The key role of this isomerization in these unstable intermediates in organic reactions is elucidated. Isomerization possibilities of the as yet unidentified H/sub 2/CN/sup +/ in the formation of HCN and HNC in interstellar space is discussed. The photodissociation of formaldehyde is explained on the basis of an unstable intermediate, hydroxycarbene. 94 references are cited. (BLM)

The 1,2 hydrogen shift: a common vehicle for the disappearance of evanescent molecular species

A water-soluble lignin-carbohydrate complex (LCC) isolated from beech (Fagus crenata) MWL was investigated. Results from gelfiltration chromatography and the infrared spectrum of the LCC treated with alkali under mild conditions indicated that the LCC contained alkali-labile bonds. Decrease of uronic acid content and the detection of 4-O-methylglucose in the sodium borohydride-reduced LCC suggested the presence of an ester linkage between lignin and glucuronic acid in the glucuronoxylan. Conductometric titration also indicated the existence of glucuronic acid ester linked to lignin. From these results, it is concluded that the LCC contained an ester linkage between lignin and glucuronoxylan and that about one-third of the glucuronic acid present in the LCC was involved in this ester linkage.

Ester linkages between lignin and glucuronoxylan in a lignin-carbohydrate complex from beech (Fagus crenata) wood

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

A Convenient Synthesis of Phenyldiazomethane

The Thermal and the Photolytic Decomposition of 1-Phenyldiazoethane

5-halo-1-phenyltetrazoles

Preparation and decomposition of azo compounds. XLVI. Stereochemistry of eight-membered cyclic azo compounds

The benzylation of 1-benzylidene-5-phenyl-3-pyrazolidinium oxide (2a) gives five products including the “head to head” dimer of 2 (7) and the ring-opened 1-benzyl-1-cinnamoylbenzalhydrazone (4a). Similar behavior was also observed with ylides bearing various substituents at the 4 and 5 positions.

J.‐P. Anselme

Papers

A Convenient Synthesis of Phenyldiazomethane

The Thermal and the Photolytic Decomposition of 1-Phenyldiazoethane

5-halo-1-phenyltetrazoles

Preparation and decomposition of azo compounds. XLVI. Stereochemistry of eight-membered cyclic azo compounds

Benzylation of 1‐Benzylidene‐3‐Pyrazolidinium Oxides