To overcome this slow reaction rate, we turned to microwave reaction conditions. Gratifyingly, reacting 2-Cl and (S)-1-phenylethan-1-amine at 200 °C for 24 hours led to 58% isolated yield for 3-H-1PhEt. Under these forcing conditions, an important consideration is whether nucleophilic aromatic substitution (SNAr) reactions at the aryl halides start to take place when X = halogen. In our trials, we did not observe significant levels of SNAr reactivity when 2.1 equiv of amine was reacted with tetraacid 2-Cl. However, when 12 equivalents of (S)-1-phenylethan-1-amine were reacted with 2-Cl, we did observe core-diaminosubstituted derivatives in the resulting product mixture. Mechanistic Insights. Our first attempted synthesis of 3-H-1PhEt under microwave conditions was performed at 200 °C for 2 hr of reaction time and resulted in 11% isolated yield. Both running the reactions for longer (200 °C for 24 hours) or with more equivalents of nucleophile (12 equiv. amine, 200 °C for 2 or 24 hours) improved the isolated yield, to 58% and 46%, respectively. It is worth noting that the excess amine approach is not feasible under microwave conditions when X = halogen because of the competitive SNAr reactions. From a mechanistic perspective, these observations suggest that in AcOH solvent, the reaction is likely taking place under overall equilibrating conditions. To gain more insight into the reaction process, we performed a 1 H NMR time-course study of the reaction between 2-H and (S)-1-phenylethan-1-amine in d4-acetic acid at 110 °C. Upon dissolving only 2-H, the 1 H NMR spectrum reflects the presence of a complex mixture of anhydrides corresponding to intermediates with or without symmetry around the central benzene ring. Although we cannot rule out cyclic anhydride formation, we believe that mixed acetic anhydride formation is more likely based on the solubility of the reaction intermediates. Upon addition of the amine and heating for 5 minutes, a number of different intermediates are detected by 1 H NMR spectroscopy and formation of the desired MDI product is first observable after 20 minutes of reaction time. After 19 hours, the mixture resolves itself into being primarily four species, three with symmetry around the benzene core and one without. After 11 days of reaction time, the desired product constitutes only 18% of the product mixture, which highlights the value of microwave reaction conditions for achieving higher yields on a reasonable time scale. The NMR spectrum of the reaction after a total of 31.5 days at 110 °C shows that the product distribution reaches a roughly 1:1:1 ratio of 3-H-1PhEt, 4-H-1PhEt, and 5-H-1PhEt (Figure ).