We carried out the mechanochemical solid-state polymerization of acrylamide and several kinds of vinyl monomer of bioactive compounds and reached several important conclusions from a series of such studies. The monomers prepared on the basis of the structural criteria derived from quantum chemical considerations underwent facile mechanochemical solidstate polymerizations to give corresponding polymeric prodrugs essentially quantitatively. Thus this method eliminates the need for any work-up of the reaction mixture. One of the most striking properties observed in such polymers is that the resulting polymeric prodrugs are of very low heterogeneity (narrow molecular weight distribution), which is of great value in pharmaceuticals for highly functionalized polymeric prodrugs. Therefore, the present reactions seem to be applicable to a wide variety of vinyl monomers of an important bioactive compound with different physicochemical properties and thus provide a novel and simple methodology for syntheses of polymeric prodrugs through a totally dry process. We have synthesized a novel polymeric prodrug possessing the derivative of 4-methylcatechol (4MC) as a side chain by mechanochemical solid-state polymerization. 1-Benzoyl-4-methylcatechol (Bz4MC) was selected as a hydrophobic compound of 4MC. It was suggested that Bz4MC was a potent stimulator on neurotrophic factor. The mechanochemical copolymerization of the methacryloyl derivative of Bz4MC and the water-soluble monomer proceeded to completion, and the polymeric prodrug produced possessed a narrow molecular weight distribution. These polymeric prodrugs were hydrolyzed to completion. The rate of hydrolysis can be controlled by the composition.