The tandem of the azido-Ugi and four- or three-component Ugi reactions (Ugi-4CR, Ugi-3CR) becomes a new and unusual approach for the construction of a morpholine-2,5-dione ring functionalized with a tetrazole moiety. Preisolation of Ugi bisamides is an alternative to the one-pot transformation with intramolecular cyclization. Subsequent conversion of the morpholine-2,5-diones enables the preparation of their NH-unsubstituted tetrazole derivatives.

3,4-Disubstituted morpholine-2,5-diones containing a tetrazole moiety are unexpected products of a tandem combination of azido-Ugi and Ugi reactions. The formation of the classical products – Ugi bisamides – is not observed at all in many cases. When the simplest C1-C3 aliphatic aldehydes are used and the reaction conditions are controlled, their isolation is possible. However, when butanal and pentanal as well as para-substituted benzaldehydes are used, only products of post-Ugi transformations, morpholine-2,5-diones, can be isolated. The latter can be synthesized either sequentially from the corresponding Ugi bisamides by post-Ugi transformation or in a one-pot procedure with prolonged stirring of the reaction mixture of four components–α-aminomethyltetrazole, aldehyde, monochloroacetic acid, and isocyanide. A small targeted library of 15 morpholine-2,5-diones containing a tetrazole moiety is obtained by a novel approach. Furthermore, these compounds are able to eliminate the N-tert-butyl group from the tetrazole nitrogen in the presence of acid to form the corresponding NH-unsubstituted tetrazole derivatives of morpholine-2,5-diones.