Through-space electrostatic control in a novel regiospecific ring transformation of 1,3,4-trisubstituted maleimides

Molecular Electrostatics

“…Molecular electrostatics is a useful tool in the interpretation, even design, of regioselectivity. [109][110][111] The MEP yields information on those molecular regions that are preferred or avoided by an electrophile or a nucleophile. In the following we present an example for the computer-aided design of the steric preference in a nucleophilic attack of a hydride anion on the sterically unbiased carbonyl group of substituted 5,6-norbornen-7-ones.…”

Applied quantum chemistry

“…An interesting application of MEPs is the study of through-space electrostatic field effect of distant substituents on certain reactions [977,979,1055,1258]. This is especially important in serine proteases which enzymes hydrolyze peptide or ester bonds by making use of an active serine hydroxyl group, cf.…”

“…These substituents may reverse the reactivity order suggested by the charge distribution since the electrostatic potential around the attacked atom, which is a more refined measure of the reactivity than the net charge, is essentially altered by the direct effect of a distant substituent. An example is the hydrolysis of l-ethoxycarbonyl-3-phenylaminomaleimide [1258] where the net charges at carbonyl reaction centres 2 and 5 are 323 and 364 millielectrons, respectively. In spite of the smaller positive charge, hydroxyl attack takes place exclusively at C2.…”

Convenient synthesis of N1-substituted orotic acid derivatives

“…22 We have thus designed a convenient synthetic method for the substituted maleimide 7 from the commercially available maleimide 8 . Bromination of 8 gave the 2,3-dibromosuccinimide mixed with 2-bromomaleimide.…”

“…Treatment of 9 with ethyl chloroformate gave the desired synthetic intermediate 7 , which did not require further purification and was readily converted to N1-substituted orotic acid 1 via an improved procedure. 22,26 …”