Synthesis of 1,5-Disubstituted-1H-Tetrazole-Bis-1,2,3-Triazole Hybrids via a One-Pot Five-Component/Pseudo-Three-Component Reaction Sequence

Abstract

A new strategy is described for the first time to synthesize a heterocyclic hybrid system of 1,5-disubstituted-1H-tetrazole-bis-1,2,3-triazoles through a double one-pot sequence. The approach involves (i) a one-pot five-component process to obtain the key 1,5-DS-T-bis-propargyl compounds 11a–n, using propargylamine as an orthogonal reagent, followed by (ii) a pseudo-three-component reaction consisting of a double CuAAC process with aromatic azides to afford the target hybrids 6a–n in moderate yields. The protocol is operationally simple, proceeds under mild reaction conditions, and some products were purified by recrystallization from methanol. Notably, this is the first example of a higher-order multicomponent sequence combined with a classical pseudo-multicomponent reaction, underscoring the synthetic utility of this approach for the rapid assembly of structurally complex hybrid scaffolds relevant to medicinal chemistry. Finally, the feasibility of accessing the target hybrids in a truly one-pot manner was demonstrated starting from propargylamine, with the overall process forming six C–N bonds, one C–C bond, and one N–N bond within a single operation.