The First Century of Isocyanide Chemistry

Until the late 1950s, the chemistry of the isocyanides had remained a rather empty area of organic chemistry, despite several important reactions of the isocyanides having 

For many years, the availability of the isocyanides was very poor, as only these two classical methods of preparing them were known, and each had moderate yields. The smell of the then-available isocyanides was described as horrifying and having continuing complaints in the neighborhood about the vile odor [8]. It was also assumed that the isocyanides were generally toxic. 

It is no wonder therefore that very few investigations were made on the reactivity of isocyanides. However, in 1910 Oliveri-Mandala and Alagna [40] discovered the formation of the N-substituted tetrazoles by the a-additions of hydrazoic acid onto the isocyanides and the subsequent rearrangements into their final products. 

Between 1921 and 1931,Passerini introduced and investigated the reaction which bears his name [8-10], forming the products 16 from carbonyl compounds 1, carboxylic acids 3A and isocyanides 13. The discovery of the P-3CR was a milestone in the development of isocyanide-based MCRs, as it was the introduction of the first practicably irreversible MCR of these compounds. 

The greatest variety of the MCRs of type II are those of the isocyanides 13. They are the only compounds in organic chemistry, that contain a divalent carbon atom C . All of its chemical reactions correspond to strongly exothermic transitions of C into CIV [8]. Usually, an a-adduct of the isocyanide is formed, such as 15. This can be an isolatable compound, or it may undergo rearrangement into its final product 18. 

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