Synthesis Mechanism of Cyclic Diesters of Lactic and Glycolic Acids as Monomers for Biodegradable Polyesters Generation

Consumption of biodegradable polymers and copolymers based on lactic and gly-colic acids has increased annually throughout the world, and the manufacturing enterprises for their production are continually expanding. This is because materials based on such polymers and copolymers are widely used in medicine as suture material and to fix screws, pins, and bone implants in orthopedics and traumatology, as well as polymeric shells of drug delivery systems in pharmacology. In publications devoted to lactide and glycolide synthesis, most researchers consider the process of cyclization to be intramolecular transesterification proceeding through the nucleophilic attack of a carbonyl group having a partial positive charge of carbon by the terminal hydroxyl group of the oligomer. We have suggested that the cyclization of oligomers of the carboxylic acids can occur by an intermolecular mechanism as well. To prove it, we used the mechanical mixtures of lactic (LAO) and glycolic acids oligomers (GAO) in the ratio of LAO:GAO = 75:25; 50:50 and 25:75%, respectively. Moreover, in the case of the intermolecular mechanism, we should observe formation of 3-methylglycolide (3-MG) in the reaction products. The presence of 3-MG as the product of intermolecular interaction of LAO and GAO in the resulting mixtures was determined by infrared spectroscopy (IR), nuclear magnetic resonance 1Н and 13С spectroscopy (NMR) and by high-performance liquid chromatography (HPLC). IR spectra of cyclization products of all three systems contain characteristic absorption bands related to the cyclic diesters. The results of NMR 13C and HPLC, unlike the results of NMR 1H, unambiguously confirm the presence of 3-MG, as well as glycolide and lactide, in the mixture of the products of cyclization. Thus, the reaction mixture contains 3-MG that is only the intermolecular cycliza-tion product. The mixture contains glycolide and lactide as well. They can be formed both in the process of intermolecular cyclization of lactic and glycolic acids homo-oligomers and during intramolecular cyclization of each of them.

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