2,3-Dimethylmaleic anhydride (Lancaster), urea (Aldrich), sodium chloride

A mixture of 2,3-dimethylmaleic anhydride (5 g, 39.65 mmol), urea (2.38 g, 39.65 mmol, 1 equiv.) and sodium chloride (8.11 g, 138.8 mmol, 3.5 equiv.) are ground by pestle and mortar to give a uniform mixture. The mixture is transferred to a flask fitted with an air condenser and is heated with stirring at 150 °C until the organic components are seen to fuse. Heating is continued for 30 m with localised heating of the apparatus by hot-air gun where vapours are seen to condense. Boiling water (20 cm³) is then added. The cooled mixture is diluted with water (30 cm³) and extracted (EtOAc, 4 X 50 cm³). The combined organic layers are washed (NaCl sat. aq., 30 cm³), dried (MgSO₄) and concentrated in vacuo. The residue is redissolved in toluene (20 cm³) and concentrated in vacuo to give an orange solid. Purification by dry column vacuum chromatography² (eluting with 0-100 % EtOAc in 40-60 petroleum ether with increments of 10 %) gives 2,3-dimethylmaleimide as a colourless crystalline solid (3.921 g, 79 %).

This and other 2,3-disubstituted maleimides, which are commonly used starting materials in our group, can be conveniently prepared on a multigram scale from the corresponding anhydrides. This simple procedure represents a practical improvement over literature methods as the use of ammonia gas or reaction solvent is not necessary. Purification by dry column vacuum chromatography allows excellent product recovery on a large scale compared to recrystallisation.

¹H NMR (270 MHz, CDCl₃) 1.97 (6H, s, 2 X CH₃).

¹Y. L. Chow, Y. M. A. Naguib, J. Chem. Soc. Perkin Trans. 1, 1984, 1165. ²D. S. Pedersen, C. Rosenbohm, Synthesis, 2001, 2431.