Pyrazolidin-3,5-diones are an important motif in heterocyclic chemistry, which is highly interesting for pharmaceutical applications. One example is Phenylbutazone, an anti-rheumatic drug in human and veterinary medicine. Additionally, many pyrazolidin-3,5-dione derivatives are regularly tested on their pharmaceutical activity.^[1]

In classic heterocycle chemistry, the hydrazinic bond is established by ring closure using the corresponding hydrazine derivatives.^[2] Most of them are toxic and require an upstream preparation due to low availability. Therefore, we now present a novel and sustainable synthetic approach to pyrazolidin-3,5-diones using electric current as oxidizing reagent.

This electroorganic approach has some major advantages. Firstly, less or no reagent waste is produced.^[3] Secondly, this transformation is an easy and elegant way to build the hydrazine moiety in pyrazolidin-3,5-diones. Thirdly, the required malonic acid diamides can be prepared in high yields from easy available starting materials.^[4]

References:

[1] G. Deng, W. Li, J. Shen, H. Jiang, K. Chen, H. Liu, Bioorg. Med. Chem. Lett. 2008, 18, 5497–5502.

[2] U. Funke, H.-F. Grützmacher, Chem. Ber. 1989, 122, 1503–1508.   

[3] H. J. Schäfer, A. J. Bard, M. Stratmann, Organic Electrochemistry, Encyclopedia of Electrochemistry, Wiley-VCH, Weinheim, 2004.

[4] C.-T. Chen, Y.-S. Chan, Y.-R. Tzeng, M.-T. Chen, Dalton Trans. 2004, 17, 2691–2696.