Rate Accelerated Organocatalytic Ring-Opening Polymerization of L-Lactide via the Application of a Bis(thiourea) H-bond Donating Cocatalyst.
ABSTRACT: A cocatalyst system consisting of an alkylamine base and a bis(thiourea) featuring a linear alkane tether is shown to dramatically increase the rate of ring-opening polymerization (ROP) of L-lactide versus previously disclosed monothiourea H-bond donors. Rate acceleration occurs regardless of the identity of the alkylamine cocatalyst, and the ROP remains controlled yielding poly(lactide) with narrow molecular weight distributions, predictable molecular weights and high selectivity for monomer. This H-bond mediated ROP of L-lactide constitutes a rare, clear example of rate acceleration with bis(thiourea) H-bond donors versus monothioureas, and the bis(thiourea) is shown to remain highly active for ROP at fractional percent catalyst loadings. Activation at a single monomer ester by both thiourea moieties is implicated as the source of rate acceleration.
Project description:Organocatalysts typically used for the ring-opening polymerization (ROP) of cyclic ester monomers are applied to a thiolactone, ?-thiocaprolactone (tCL). In the absence of an H-bond donor, a nucleophilic polymerization mechanism is proposed. Despite the decreased ability of thioesters and thiols (versus esters and alcohols) to H-bond, H-bonding organocatalysts-a thiourea in combination with an H-bond accepting base-are also effective for the ROP of tCL. The increased nucleophilicity of thiols (versus alcohols) is implicated in the increased Mw/Mn of the poly(thiocaprolactone) versus poly(caprolactone), but deleterious transesterification is suppressed in the presence of a thiourea. The thioester monomer, tCL, is shown to be thermodynamically similar to ?-caprolactam but kinetically similar to ?-caprolactone.
Project description:Thiourea (TU)/amine base cocatalysts are commonly employed for well-controlled, highly active "living" organocatalytic ring-opening polymerizations (ROPs) of cyclic esters and carbonates. In this work, several of the most active cocatalyst pairs are shown by (1)H NMR binding studies to be highly associated in solution, dominating all other known noncovalent catalyst/reagent interactions during ROP. One strongly binding catalyst pair behaves kinetically as a unimolecular catalyst species. The high selectivity and activity exhibited by these ROP organocatalysts are attributed to the strong binding between the two cocatalysts, and the predictive utility of these binding parameters is applied for the discovery of a new, highly active cocatalyst pair.
Project description:For the first time, the controlled ring-opening polymerization (ROP) of ?-thionocaprolactone (tnCL) is conducted. The organocatalytic ROP of tnCL occurs without carbonyl scrambling, leading to homopoly(?-thionocaprolactone) (PtnCL). The ROP by base catalysts alone is proposed to proceed via a nucleophilic mechanism, while the addition of an H-bond donating thiourea (TU) is shown to provide excellent reaction control. The increased reaction control provided by the TU occurs in the virtual absence of binding between tnCL and TU, and a mechanistic account for this observation is discussed. The monomer ring strain is measured and found to be similar to ?-valerolactone (VL). Copolymers with VL are synthesized, and the resulting analysis of the copolymer materials properties provides the only known physical characterizations of poly(thio(no)ester-co-ester)s.
Project description:Poly(ethylene phosphates) are promising polymers for use in biomedical applications. Catalytic ring-opening polymerization (ROP) of cyclic ethylene phosphate monomers (CEPMs) is the most effective approach for obtaining these polymers. The mechanism of coordination ROP of CEPMs remains unclear. We report, for the first time, the results of DFT modeling of CEPM ROP. In these calculations by Gaussian-09 program package with the B3PW91/DGTZVP basis set, we explored methyl ethylene phosphate (MeOEP) ROP catalyzed by dimeric and monomeric catalytic species derived from heteroleptic complex [(BHT)Mg(μ-OBn)(THF)]₂ (Mg1, BHT = 2,6-di-tert-butyl-4-methylphenolate). Analysis of the reaction profiles for the binuclear and mononuclear reaction mechanisms allowed us to conclude that the ROP of MeOEP is preferentially catalyzed by mononuclear Mg complexes. This estimation was confirmed by comparative polymerization experiments using MeOEP and traditional monomers ε-caprolactone (εCL), racemic lactide (rac-LA), and l-lactide (l-LA) initiated by Mg1. ROP of MeOEP proceeds at an extremely high rate due to the substantially lower activation barrier calculated for mononuclear mechanism in comparison with that of cyclic esters that polymerize without the dissociation of BHT-Mg binuclear species. We also demonstrated the use of MeOEP as a "monomerization" agent in the synthesis of MeOEP-lactide block copolymers. Comparison of the multiple acceleration of l-LA ROP after MeOEP prepolymerization and formation of atactic PLA blocks in rac-LA polymerization with the heterotactic PLA formation during Mg1-catalyzed homopolymerization also confirmed the mononuclear nature of the polyphosphate-containing catalytic particles.
Project description:Organocatalysis is an important branch of catalysis for various organic transformations and materials preparation. Polymerizations promoted by organic catalysts can produce polymeric materials without any metallic residues, providing charming materials for high-value and sensitive domains such as biomedical applications, microelectronic devices and food packaging. Herein, we describe a fluorinated alcohol based catalytic system for polypeptide synthesis via catalytic ring-opening polymerization (ROP) of ?-amino acid N-carboxyanhydride (NCA), fulfilling cocatalyst free, metal free, high rate and high selectivity. During polymerization, the fluorinated alcohol catalyst forms multiple dynamic hydrogen bonds with the initiator, monomer and propagating polymer chain. These cooperative hydrogen bonding interactions activate the NCA monomers and simultaneously protect the overactive initiator/propagating polymer chain-ends, which offers the whole polymerization with high activity and selectivity. Mechanistic studies indicate a monocomponent-multifunctional catalytic mode of fluorinated alcohol. This finding provides a metal free and fast approach to access well-defined polypeptides.
Project description:Poly(lactic acid) has been extensively investigated in the biomedical field because of its good biocompatibility and biodegradability. As an important method of poly(lactic acid) synthesis, metal complex-catalyzed ring-opening polymerization (ROP) of lactide can achieve a controllable lactide polymerization through the selection of appropriate ligands and metals. In this study, a novel metal (LTi-O)2 complex was synthesized and structurally characterized. (LTi-O)2 showed a relatively high catalytic activity and controllability of Poly(D, L-lactide) (PDLLA) molecular weights (polydispersity index of 1.02-1.22) in the ROP of D,L-lactide. The kinetic equation of D,L-LA ROP catalyzed by (LTi-O)2 could be expressed as-d[M]/dt = k[M]2[(LTi-O)2]1, and the reaction activation energy was 95.67 kJ·mol-1. Physical/chemical properties and biocompatibility evaluation results showed that PDLLA obtained through the (LTi-O)2-catalyzed ROP of D,L- lactide exhibited a good degradation performance and excellent biocompatibility.
Project description:Cyclic polylactide (<i>c</i>PLA) is a structural isomer of linear polylactide (PLA) although it possesses unique functionalities in comparison to its linear counterpart. Hitherto, the control of stereochemical purity in conventional <i>c</i>PLA synthesis has not been achieved. In this study, highly stereochemically pure <i>c</i>PLA was synthesized in the absence of a metal catalyst and organic solvent, which required high consumption of the residual monomer. The synthesis was conducted in supercritical carbon dioxide under CO? plasticizing polymerization conditions in the presence of an organocatalyst and thiourea additives. In comparison with the stereocomplexes synthesized through conventional methods, <i>c</i>PLA from l-lactide (<i>c</i>PLLA) and <i>c</i>PLA from d-lactide (<i>c</i>PDLA) were synthesized with higher stereochemical purity and improved thermal stability. Moreover, the method presented herein is environmentally friendly and thus, applicable on an industrial level.
Project description:A family of chiral zinc amido-oxazolinate complexes are shown to be highly active and isoselective initiators for the ring-opening polymerization (ROP) of rac-lactide, yielding isotactic stereoblock polylactides (PLA) with P m up to 0.91. This represents the highest isoselectivity observed with zinc-based catalysts for ROP of rac-lactide.
Project description:In the presence of a small molecular protic initiator, immortal ring-opening polymerization (ROP) of lactide (LA) is a highly efficient strategy to synthesize polylactide in a controllable manner, while using polymeric alcohol as an initiator has been less investigated. A series of polymeric alcohols (PS⁻OH) composed of styrene and 4.3%⁻18% hydroxyl functional styrene (diethyl(hydroxy(4-vinylphenyl)methyl)phosphonate, St⁻OH) were synthesized through reversible addition-fragmentation transfer (RAFT) polymerization. Using PS⁻OH as an initiator, the immortal ROP of rac-LA was catalyzed by dibutylmagnesium (MgnBu₂) under various ratios of monomer to hydroxyl group within PS⁻OH to generate polystyrene-g-polylactide (PS⁻g⁻PLA) copolymers with different graft lengths. After thermal annealing at 115 °C, the PLA domain aggregated to nanospheres among the PS continuum. The size of the nanospheres, varying from 130.1 to 224.2 nm, was related to the graft density and length of PS⁻g⁻PLA. Nanoporous films were afforded through chemical etching of the PLA component.
Project description:We describe the rational design of a linked, bis-thiourea catalyst with enhanced activity relative to monomeric analogues in a representative enantioselective anion-abstraction reaction. Mechanistic insights guide development of this linking strategy to favor substrate activation though the intramolecular cooperation of two thiourea subunits while avoiding nonproductive aggregation. The resulting catalyst platform overcomes many of the practical limitations that have plagued hydrogen-bond-donor catalysis and enables use of catalyst loadings as low as 0.05 mol %. Computational analyses of possible anion-binding modes provide detailed insight into the precise mechanism of anion-abstraction catalysis with this pseudo-dimeric thiourea.