Synthesis of bis(1,5‐disubstituted tetrazoles) via double four component Azido‐Ugi reaction

Abstract

A double four component Azido‐Ugi reaction of isocyanide, TMSN3, aldehyde, and 4,4′‐sulfonyldianiline with two amine functional groups in MeOH at 65°C has been described. The synthesis of pharmacologically and structurally interesting compounds with two 1,5‐disubstituted tetrazole rings via a reaction from available and inexpensive reagents under a convenient process and mild reaction conditions has been reported. Modifications in the structure of the reaction product could be followed by varying the aldehyde or isocyanide component. The products are new and were well described by Mass, 1H NMR, and 13C NMR spectral studies.

Metal-free oxoammonium salt-mediated C(sp3)–H oxidative Ugi-azide multicomponent reaction

“…2 c ,5 Those include the four-MCR Ugi-type 5,6 or three-MCR Passerini-type 7 reactions, in which the carboxylic acid component is replaced with a nucleophilic azide reagent XN 3 (generally TMSN 3 ) (Scheme 1a). 8 In particular, the Ugi-azide MCRs provide access to the privileged α-amino tetrazole motifs widely present in bioactive compounds. 1–3 However, there are still structural substrate limitations since the formation of the reactive imine or iminium ion key intermediate relies on the effective condensation of an amine with a carbonyl compound.…”