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. 2024 Nov 18;19(22):e202400688.
doi: 10.1002/asia.202400688. Epub 2024 Oct 18.

Ammonium Zincates as Catalysts for the Microwave-Enhanced Synthesis of Symmetric Piperazines by Regioselective Opening of Aziridines

Matteo Alberti  1 , Andrea Dariol  1 , Nicola Panza  1 , Giorgio Abbiati  2 , Alessandro Caselli  1
Affiliations

Ammonium Zincates as Catalysts for the Microwave-Enhanced Synthesis of Symmetric Piperazines by Regioselective Opening of Aziridines

Matteo Alberti et al. Chem Asian J. .

Abstract

2,5-disubstituted N,N'-alkylpiperazines represent an interesting target in organic synthesis both for pharmaceutical or agrochemical applications and as a promising class of ligands in coordination chemistry. We report here a microwave-enhanced synthesis of these compounds starting from non-activated N-alkyl aziridines in the presence of catalytic amounts of simple ammonium metallates. A remarkable TOF of 2787.9 h-1 has been observed in the case of [TBA]2[ZnI4] as the catalyst (catalyst loading 0.1 mol %) and with an almost complete selectivity (up to 97 %) in favor of both diastereoisomers (meso and chiral form) of the target 2,5-disubstituted piperazines, obtained in 1 : 1 ratio. The two isomers are easily separated, because the meso form precipitates in pure from the reaction crude. A stereochemical investigation and the unprecedented isolation of 2,6-disubstituted N,N'-alkylpiperazines allowed us to shed light on the reaction mechanism.

Keywords: Homogeneous catalysis; Metallates; Microwave chemistry; Piperazine; Zinc.

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Conflict of interest statement

There are no conflicts to declare.

Figures

Scheme 1
Scheme 1
[TBA][FeX4] catalyzed synthesis of 5‐substituted 1,3‐oxazolidin‐2‐ones by reaction of aziridines with CO2 under mild reaction conditions (RT, 0.1 MPa of CO2) and formation of symmetric pyperazines 2 and 2’ as by‐products.
Scheme 2
Scheme 2
[TBA]2[ZnI4] catalyzed synthesis of 1,4‐bis(tosyl)piperazine 2 r.
Scheme 3
Scheme 3
Proposed mechanism for the aziridine dimerization to piperazines catalyzed by [TBA][ZnI4]2−.
See this image and copyright information in PMC

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