Synthesis of Novel bis-1,5-Disubstituted-1H-Tetrazoles by an Efficient Catalyst-Free Ugi-Azide Repetitive Process

Abstract

A series of five novel bis-1,5-disubstituted-1H-tetrazoles (bis-1,5-DS-1H-T) were quickly prepared by a catalyst-free Ugi-azide repetitive process from easily accessible starting materials in excellent yields, either at room temperature (88%-95%) or using mild MW-heating conditions (80%-91%). These molecules may have a wide range of applications, such as chelating agents, organocatalysts and luminescent materials, and mainly as bioactive compounds.

One‐Pot Construction of Bis‐Heterocycles through Isocyanide Based Multicomponent Reactions

“…The easily accessible amines, aldehydes, isocyanides, and TMSN 3 were added sequentially in methanol solvent to get the spacer linked BHCs (Scheme 52). [86] The desired products were obtained in excellent yields either on room temperature stirring (88-95 %) or using mild MW heating conditions (80-91 %).…”

<strong>Synthesis of <em>bis</em>-heterocycles type spacer containing 1,5-disubstituted-1<em>H</em>-tetrazoles</strong>

“…As a part of our research, we recently reported the synthesis of bis-heterocycles via the two efficient I-MCR strategies: the Ugi-Azide (UA) [18][19][20][21][22][23][24] and the Groebke-Blackburn-Bienaymé (GBB) reactions [25][26][27]. The combination of I-MCRs with efficient post-transformation processes like annulation [21,22] or cascade process [23,24] improve their synthetic potency.…”

“…It is to be mentioned that, there are only three previous reports on the synthesis of bisheterocycles type spacer via UA methodology [20,[28][29]. Scheme 1.…”

Expedient Access to Novel Bis‐tetrazolopiperazines via Ugi‐azide Reactions

“…For example, Wanner and co‐workers obtained about 9% of a bis‐tetrazole derivative as a by‐product of an Ugi‐azide reaction designed to obtain a 1,5‐DS‐1 H ‐T from 3,3‐diphenylpropylamine, paraformaldehyde, tert ‐butylisocyanide, and TMSN 3 . In addition, Gámez‐Montaño and co‐workers very recently reported the successful synthesis of five novel bis‐tetrazole derivatives using primary amines .…”

“…Because of their similarities in their physicochemical properties, 1,5‐DS‐1 H ‐T are bioisosteres of the cis ‐amide bonds of peptides . Moreover, 1,5‐DS‐1 H ‐T is the core of the in clinical phase drug BMS‐317180 (Fig.…”