Substituent effects on the regioselectivity of maleamic acid formation and hydrogen chloride addition to N-aryl maleimides

Itaconic anhydride reacts with aryl amines to give a substituent controlled equilibrium mixture of regioisomeric (Z)-2-methyl-and (Z)-3-methyl-4-oxo-4-(arylamino) but-2-enoic acids. Electron-donating groups favor nucleophilic attack on C-5 carbonyl, while the presence of electron-withdrawing groups enhances the bias for attack on C-2 carbonyl. The treatment of (Z)-2-methyl-and (Z)-3-methyl-4-oxo-4-(arylamino) but-2enoic acids with SOCl2-Et3N in THF provided the corresponding maleimides in high yields while under the same conditions the maleic anhydride aryl amine addition products gave predominately the corresponding 3-chloro-1-arylpyrrolidine-2,5-diones and maleimides in substituent dependent ratio