Process for preparing cyclic esters comprising unsaturated functional groups and polyesters prepared from same

Inventors

Markland, Peter • Zhang, Xi

Assignees

Evonik Operations GmbH • Evonik Corp

Abstract

Disclosed herein are process for preparing cyclic esters comprising unsaturated functional groups. Also disclosed are copolymers prepared from the cyclic esters. The copolymers can be used to form microparticles, polymer micelles, etc., which are useful in drug delivery applications.

Core Innovation

The invention relates to a process for preparing a cyclic ester of a specified general formula in which each x is the same integer from 0 to 12, and where substituents R1a, R1b (when present), and R2 have definitions restricted to hydrogen or functional groups including hydroxy, amino, thio, halogen, or substituted or unsubstituted C1-C6 alkyl, C1-C6 alkoxy, C1-C6 alkylthio, C1-C6 alkylamino, and substituted or unsubstituted C1-C6 hydroxyalkyl. The process also permits an optional bond in the cyclic ester structure and requires that each R1a is the same and each R1b is the same.

The process comprises heating a liquid reaction medium that contains an oligomeric alpha-hydroxyacid having an n value that is an integer from 2 to 30, or a salt thereof, under conditions of about 150°C to about 300°C to form the cyclic ester. During this heating, a composition comprising the cyclic ester is removed from the liquid reaction medium, and the liquid reaction medium can be limited so that it does not include a solvent for dissolving the oligomeric alpha-hydroxyacid.

In embodiments described in the provided material, the cyclic esters include 3,6-di(prop-2-yn-1-yl)-1,4-dioxane-2,5-dione and 3,6-diallyl-1,4-dioxane-2,5-dione, and the oligomeric alpha-hydroxyacids can include 2-hydroxy-4-pentynoic acid and 2-hydroxy-4-pentenoic acid. The disclosure further describes copolymers formed from these cyclic esters with lactide, glycolide, and caprolactone, including an oxidation of the unsaturation to a carboxylic acid, and states usefulness in biomedical/drug delivery contexts such as microparticles and polymeric micelles.

Claims Coverage

The provided claim set contains one independent claim centered on heating an oligomeric alpha-hydroxyacid (or salt) in a liquid reaction medium at about 150°C to about 300°C while removing a cyclic-ester-containing composition. Dependent claims further define the cyclic ester structure, the solvent-free reaction medium, distillation pressure, transesterification catalyst, polymerization pressure, and specific alpha-hydroxyacid and cyclic ester examples.

Across the provided claims, the claim coverage centers on forming a cyclic ester defined by x and constrained substituent groups by heating an oligomeric alpha-hydroxyacid (or salt) in a liquid reaction medium at about 150°C to about 300°C while removing a cyclic-ester-containing composition, with dependent claims further narrowing solvent presence, specifying distillation pressure, optionally adding a transesterification catalyst, constraining polymerization pressure ranges, and specifying particular alpha-hydroxyacid and cyclic ester examples.

Stated Advantages

Documented Applications