UNUSUAL STABILITY OF N-METHYLMALEIMIDE CYCLOADDUCTS - CHARACTERIZATION OF ISOBENZOFURAN RETRO-DIELS-ALDER REACTIONS

Many years ago Diels and Thiele noted the unusual stability of maleic anhydride cycloadducts and employed this feature in scavenging anthracene generated in a retro-[4 + 2] reaction. N-methylmaleimide, although nearly identical to maleic anhydride in rates of Diels-Alder reactions, forms even more stable cycloadducts. The rate constants for the four reactions that characterize the furan/N-methylmaleimide system were measured under the conditions used by Lee and Herndon to study the furan/maleic anhydride system. Comparison of the two dienophiles indicates that N-methylmaleimide adducts are ca. 3 kcal.mol-1 more stable than the corresponding exo- and endo-maleic anhydride adducts. Somewhat larger (ca. 4 +/- 0.5 kcal.mol-1) differences in stability were found for the cycloadducts of the much more reactive diene isobenzofuran. N-Methylmaleimide is used as a diene scavenger to obtain rate constants for retro-Diels-Alder reactions of isobenzofuran adducts with maleic anhydride and some substituted analogs. The rates of retro-Diels-Alder reactions of substituted N-methylmaleimide adducts were also determined by an alternative method. The substituents examined enhance the rates of exo retro-Diels-Alder reactions by factors of 15-40, while endo adduct retro-Diels-Alder rates are only slightly affected. Calculations were done at the MP2/6-31G*//HF/6-31G* level to compare the heats of hydrogenation of maleic anhydride and maleimide. The reduction of maleimide is calculated to be 2.5 kcal.mol-1 more exergonic, supporting the experimental observations.