The mechanistic duality of (thio)urea organocatalysts for ring-opening polymerization

Among the various catalysts for ROP, H-bonding organocatalysts stand out in the precise level of reaction control they are able to render during ROP. The H-bonding class of organocatalysts are thought to effect ROP via dual activation of both monomer and chain end. (Thio)urea mediated ROP has experienced a renaissance as a new polymerization mechanism-mediated by imidate or thioimidate species-facilitates new modes of reactivity and new synthetic abilities. Indeed, the urea class of H-bond donors has been shown to be more active than their corresponding thioureas. The imidate mechanism remains highly active in polar solvents and exhibits remarkable control-and \u27living\u27 behavior-under solvent-free conditions, and a broad range of temperatures is accessible. The advancements in synthetic abilities have all evolved through a greater understanding of reaction mechanism. Through the continued synergistic advances of catalysis and material, the (thio)urea class of catalyst can find use in a host of potential applications, research and industrial environments

Urea and Thiourea H‑Bond Donating Catalysts for Ring-Opening Polymerization: Mechanistic Insights via (Non)linear Free Energy Relationships

Hammett-style free energy studies of (thio)­urea/MTBD mediated ring-opening polymerization (ROP) of δ-valerolactone reveal the complicated interplay of reagents that give rise to catalysis through one of two mechanisms. The operative mechanism depends most greatly on the solvent, where polar solvents favor a (thio)­imidate mechanism and nonpolar solvents favor a classic H-bond mediated ROP. Data suggest that the transition state is only adequately modeled with ground state thiourea–monomer interactions in the H-bonding pathway, and elusive urea/reagent ground state binding interactions may be irrelevant and, hence, not worth pursuing. However, neither relationship is robust enough to be predictive in the absence of other data. Isotope effects suggest that the base/alcohol binding event is directly observable in the ROP kinetics. New opportunities for catalysis emerge, and a reason for the observed mechanism change is proposed

Coupled equilibria in H-bond donating ring-opening polymerization: The effective catalyst-determined shift of a polymerization equilibrium

In the classic view of catalysis, a catalyst cannot alter the thermodynamically-determined endpoint of a reversible reaction. This conclusion is predicated on the assumption that the catalyst does not perturb the energy of product or reactant or does so to an equal extent. In the H-bond mediated ring-opening polymerization (ROP) of lactone monomers, the strength of the interactions of thiourea with product and reactant are not equal, and the magnitudes of these interactions are of similar energy to the free energy of reaction. The total monomer concentration at equilibrium in the thiourea/base cocatalyzed ROP of lactones is shown to be a function of the initial concentration of thiourea. Because the binding of thiourea to monomer and the polymerization reaction itself are both reversible, the application of varying amounts of thiourea catalyst directly alters the total amount of monomer in the reaction solution at equilibrium, which can be recovered at the end of the reaction

Triclocarban: Commercial Antibacterial and Highly Effective H-Bond Donating Catalyst for Ring-Opening Polymerization

The antibacterial compound, triclocarban (TCC), is shown to be a highly effective H-bond donating catalyst for ring-opening polymerization (ROP) when applied with an H-bond accepting base cocatalyst. These ROPs exhibit the characteristics of “living” polymerizations. TCC is shown to possess the high activity characteristic of urea (vs thiourea) H-bond donors. The urea class of H-bond donors is shown to remain highly active in H-bonding solvents, a trait that is not displayed by the corresponding thiourea H-bond donors. Two H-bond donating ureas that are electronically similar to TCC are evaluated for their efficacy in ROP, and a mechanism of action is proposed. This “off-the-shelf” H-bond donor is among the most active and most controlled organocatalysts for the ROP of lactones

Triclocarban: Commercial Antibacterial and Highly Effective H‑Bond Donating Catalyst for Ring-Opening Polymerization

The antibacterial compound, triclocarban (TCC), is shown to be a highly effective H-bond donating catalyst for ring-opening polymerization (ROP) when applied with an H-bond accepting base cocatalyst. These ROPs exhibit the characteristics of “living” polymerizations. TCC is shown to possess the high activity characteristic of urea (vs thiourea) H-bond donors. The urea class of H-bond donors is shown to remain highly active in H-bonding solvents, a trait that is not displayed by the corresponding thiourea H-bond donors. Two H-bond donating ureas that are electronically similar to TCC are evaluated for their efficacy in ROP, and a mechanism of action is proposed. This “off-the-shelf” H-bond donor is among the most active and most controlled organocatalysts for the ROP of lactones

H‑Bonding Organocatalysts for the Living, Solvent-Free Ring-Opening Polymerization of Lactones: Toward an All-Lactones, All-Conditions Approach

The developing urea class of H-bond donors facilitates the solvent-free ROP of lactones at ambient and elevated temperatures, displaying enhanced rates and control versus other known organocatalysts for ROP under solvent-free conditions. The ROPs retain the characteristics of living polymerizations despite solidifying prior to full conversion, and copolymers can be accessed in a variety of architectures. One-pot block copolymerizations of lactide and valerolactone, which had previously been inaccessible in solution phase organocatalytic ROP, can be achieved under these reaction conditions, and one-pot triblock copolymers are also synthesized. For the ROP of lactide, however, thioureas remain the more effective H-bond donating class. For all (thio)­urea catalysts under solvent-free conditions and in solution, the more active catalysts are generally more controlled. A rationale for these observations is proposed. The triclocarban (TCC) plus base systems are particularly attractive in the context of solvent-free ROP due to their commercial availability which could facilitate the adoption of these catalysts

Bis- and Tris-Urea H‑Bond Donors for Ring-Opening Polymerization: Unprecedented Activity and Control from an Organocatalyst

A new class of H-bond donating ureas was developed for the ring-opening polymerization (ROP) of lactone monomers, and they exhibit dramatic rate acceleration versus previous H-bond mediated polymerization catalysts. The most active of these new catalysts, a tris-urea H-bond donor, is among the most active organocatalysts known for ROP, yet it retains the high selectivity of H-bond mediated organocatalysts. The urea cocatalyst, along with an H-bond accepting base, exhibits the characteristics of a “living” ROP, is highly active, in one case, accelerating a reaction from days to minutes, and remains active at low catalyst loadings. The rate acceleration exhibited by this H-bond donor occurs for all base cocatalysts examined. A mechanism of action is proposed, and the new catalysts are shown to accelerate small molecule transesterifications versus currently known monothiourea catalysts. It is no longer necessary to choose between a highly active or highly selective organocatalyst for ROP

Coupled equilibria in H-bond donating ring-opening polymerization: The effective catalyst-determined shift of a polymerization equilibrium

In the classic view of catalysis, a catalyst cannot alter the thermodynamically-determined endpoint of a reversible reaction. This conclusion is predicated on the assumption that the catalyst does not perturb the energy of product or reactant or does so to an equal extent. In the H-bond mediated ring-opening polymerization (ROP) of lactone monomers, the strength of the interactions of thiourea with product and reactant are not equal, and the magnitudes of these interactions are of similar energy to the free energy of reaction. The total monomer concentration at equilibrium in the thiourea/base cocatalyzed ROP of lactones is shown to be a function of the initial concentration of thiourea. Because the binding of thiourea to monomer and the polymerization reaction itself are both reversible, the application of varying amounts of thiourea catalyst directly alters the total amount of monomer in the reaction solution at equilibrium, which can be recovered at the end of the reaction