A variety of phthalimide derivatives have been synthesised effectively in high-temperature, high-pressure H2O/EtOH mixtures (HTHP-H2O/EtOH) as the solvent. This clean method is based on the condensation of o-phthalic acid and amines and affords phthalimide compounds as pure crystals in most cases, because of the dehydrating effect and change in solvation properties of H2O/EtOH at high pressures and temperatures. After conducting a series of model reactions, it was found that a mixture, 1/1 v/v H2O/EtOH, was appropriate for obtaining good yields combined with high purity of the phthalimides. Moderate to excellent yields were obtained depending on the nature of the amine. Aromatic amines generally afforded higher yields than aliphatic ones except for 3-hydroxypropylamine, where a yield up to 95% was obtained.