TITLE:
Conversion of 3,4-Dihydroxypyrrolidine-2,5-Dione to Maleimide through Tosylation and Mechanism Study by DFT
AUTHORS:
Maocai Yan, Zhen Zhang, Jinhui Zhou, Wei Li, Shuai Fan, Zhaoyong Yang
KEYWORDS:
Pyrrolidine-2, 5-Dione, Maleimide, Elimination, Reaction Mechanism, Density Functional Theory
JOURNAL NAME:
Computational Chemistry,
Vol.6 No.3,
July
23,
2018
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.