Experimental and Theoretical Investigation of the Reaction of Secondary Amines with Maleic Anhydride

The reaction of secondary amines, namely 1-methylpiperazine, pyrrolidine, morpholine, 2-methylpiperidine, and diethylamine, with maleic anhydride has been investigated experimentally and theoretically at the DFT level. Under kinetic control, i.e. at −78°C or −15°C, amines add across the C=O functionality exclusively and the initially formed addition products isomerize to the corresponding N-substituted maleimic acid derivatives. In contrast to the acyclic α,β-unsaturated carbonyl compounds, amine does not add across the C=C functionality in maleic anhydride even under thermodynamic control. This behaviour of maleic anhydride can be rationalized on the basis of the local condensed Fukui functions, which reveal that the carbonyl carbon atoms in maleic anhydride are much harder than in an acyclic α,β-unsaturated carbonyl compound, such as acrolein. This prompts the amines to attack the carbonyl group in maleic anhydride exclusively.