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Conversion of 3,4-Dihydroxypyrrolidine-2,5-Dione to Maleimide through Tosylation and Mechanism Study by DFT

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  1. 1 School of Pharmacy, Jining Medical University, Rizhao, China
  2. 2 Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
Computational Chemistry·Volume 06, Issue 3·Pages 47–56·Published 20 July 2018·DOI10.4236/cc.2018.63004
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Abstract

Pyrrolidine-2,5-dione and maleimide are important scaffolds of many organic substances, and their derivatives are now attracting more and more interests from researchers in organic synthesis, medicinal chemistry, and drug development. Tosyloxy (-OTs) group is an important functional group widely used in organic synthesis, because it can be readily prepared from alcohols and is an excellent leaving group. However, surprisingly, substances bearing tosyloxy groups on pyrrolidine-2,5-dione or maleimide scaffolds are very rare. In this study, we discovered that, when treated with TsCl/Et3N, trans-3,4-dihydroxypyrrolidine-2,5- dione will eliminate a TsOH molecule to form monotosyloxymaleimide. Thermodynamic and kinetic factors affecting this reaction were investigated by theoretical computation using density functional theory (DFT), and the possible reaction mechanism was proposed based on the computation results. Our results showed that tosylates of trans -3,4-dihydroxypyrrolidine- 2,5-dione, either monotosylate or ditosylate, are thermodynamically instable and may spontaneously convert to maleimides. This knowledge could be useful in understanding the properties of pyrrolidine-2,5-diones and maleimides, as well as the related organic synthesis.

KeywordsPyrrolidine-25-DioneMaleimideEliminationReaction MechanismDensity Functional Theory
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