Conventional and microwave-assisted reaction of N-hydroxymethylphthalimide with arylamines: synthesis of N-(arylaminomethyl)-phthalimides

An efficient and easy synthesis of compounds: 2-Phenylaminomethyl-isoindole-1,3-dione (5a), 2-[(2-Clorophenylamino)methyl]-isoindole-1,3-dione (5b), 2-[(3-Clorophenylamino)methyl]-isoindole-1,3-dione (5c), 2-[(4-Clorophenylamino)methyl)-isoindole-1,3-dione (5d), 2-[(2-Fluorophenylamino)methyl]-isoindole-1,3-dione (5e), 2-[(3-fluorophenylamino)methyl]-isoindole-1,3-dione (5f), 2-[(4-Fluorophenylamino)methyl]-isoindole-1,3-dione (5g), 2-[(2-Nitrophenylamino)methyl]-isoindole-1,3-dione (5h), 2-[(3-Nitrophenylamino)methyl]-isoindole-1,3-dione (5i), 2-[(4-Nitrophenylamino)methyl]-isoindole-1,3-dione (5j), 2-[1H-(1,2,4)Triazol-3-yl-aminomethyl)-isoindole-1,3-dione (5k) and 2-([1,2,4]-Triazole-4-yl-aminomethyl)-isoindole-1,3-dione (5l), is described. The general synthesis procedure starts from N-hydroxymethylphthalimide 3 and aryl- and [1,2,4-triazol-3- and 4-yl]-amines 4a-l by conventional and solvent-free microwave-mediated. The reaction of 3 with 4l turned out to be a very rapid and high-yielding one. A comparison of these two methods has been made. Three probable mechanisms of formation of N-(arylaminomethyl)-phthalimides (one in the solution phase and two in the microwave-accelerated conditions are proposed. Crystallographic analyses of 5d furnished the correct conformation of this molecule. Ab initio molecular orbital calculations of 5d using 6-31G* basis set were performed and the results were comparable to the X-ray data.

phthalimide; N-hydroxymethylphthalimide; spectroscopy; X-ray crystallography; M.O. calculations