Synthesis and ring‐opening polymerization of new monoalkyl‐substituted lactides

Abstract

New monoalkyl‐substituted lactides were synthesized by reaction of α‐hydroxy acids with 2‐bromopropionyl bromide, and polymerized with various catalysts in the presence of benzyl alcohol by ring‐opening polymerization (ROP). The classic tin(II) 2‐ethylhexanoate (Sn(Oct)2) catalyst was leading to polymers with narrow distribution and predictable molecular weights, in polymerizations in bulk or toluene at 100 °C. The polymerization rate was corresponding to the steric hindrance of the alkyl substituents, such as butyl, hexyl, benzyl, isopropyl, and dimethyl groups. A yield of 83% was obtained with the hexyl‐substituted lactide after 1 h of polymerization. Excellent conversions (97%) could be achieved by using the alternative catalyst 4‐(dimethylamino)pyridine (DMAP). This latter organic catalyst was most efficient in polymerizing the more steric‐hindered lactides with good molecular weight and polydispersity control, in comparison to the tin(II) 2‐ethylhexanoate and tin(II) trifluoromethane sulfonate [Sn(OTf)2] catalysts. The efficiency of the DMAP catalyst and the variability of the monomer synthesis route for new alkyl‐substituted lactides allow to prepare and to envision a wide range of new functionalized polylactides for the elaboration of tailored materials. © 2004 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 42: 4379–4391, 2004

Poly(hexyl‐substituted lactides): Novel injectable hydrophobic drug delivery systems

“…Next to other alkyl-substituted lactides, we described the synthesis and characterization of new polylactides obtained from monohexyl-substituted lactide and dihexyl-substituted lactide [poly(monohexylsubstituted lactide) and poly(dihexyl-substituted lactide)], which were shown to have low glass transition temperatures (T g < À158C) compared to a standard PLA with the analogue molecular weight. 18 On the basis of these initial results, the new hydrophobic substituted polylactides could be favorable and interesting for applications as injectable semisolid materials for drug delivery comparable to the reported hydrophobic poly (ortho esters). 21,22 Moreover, the increased hydrophobicity of these PLA-polymers could lead to further interesting properties in colloidal systems, for example, in terms of encapsulation efficiency and release of hydrophobic drugs.…”

“…18 The synthesis steps of the here investigated poly(monohexyl-(PmHLA 6) and dihexyl-(PdiHLA 7) substituted lactides) are presented in Scheme 1. The synthesis of the new monohexyl-substituted lactide (mHLA) 4 is based on a ''two step one pot'' reaction of 2-hydroxyoctanoic acid 2 with 2-bromopropionyl bromide leading to an intermediate ester 3, which undergoes ringclosing after changing to basic reaction conditions with triethylamine.…”

“…18 The strategy of substitution of the methyl ligand of the lactide monomer by an other substituent and thereof the synthesis of new functionalized polylactide-based materials by ROP can be achieved by using new reac-tive catalysts, for example, tin(II) trifluoromethane sulfonate and 4-dimethylaminopyridine. [18][19][20] These catalysts facilitate the ROP of very steric hindered monomers with a good control of molecular weight and molecular weight distribution.…”

“…18 The strategy of substitution of the methyl ligand of the lactide monomer by an other substituent and thereof the synthesis of new functionalized polylactide-based materials by ROP can be achieved by using new reac-tive catalysts, for example, tin(II) trifluoromethane sulfonate and 4-dimethylaminopyridine. [18][19][20] These catalysts facilitate the ROP of very steric hindered monomers with a good control of molecular weight and molecular weight distribution. Next to other alkyl-substituted lactides, we described the synthesis and characterization of new polylactides obtained from monohexyl-substituted lactide and dihexyl-substituted lactide [poly(monohexylsubstituted lactide) and poly(dihexyl-substituted lactide)], which were shown to have low glass transition temperatures (T g < À158C) compared to a standard PLA with the analogue molecular weight.…”

New Poly(Hydroxylauric-co-Lactic Acid) Liquid Polymer for Dissolving Lipophilic Drugs

“…Copolymerization can actually be done by ring-opening polymerization (ROP). This method is actually used to produce biomedical grade PLA with controlled molecular weight and narrow polydispersities (Trimaille et al, 2004). However, ROP needs dilactides to be synthesized first before the final PLA polymerization.…”