Synthesis Of Polyesters Via Acid-Eliminating Melt Polycondensation

Modern society relies on polyesters with applications ranging from fabrics,catering containers,agricultural films to medical devices.As a representative of polyesters,polyethylene terephthalate（PET）has reached an annual production of over 70 million metric tons worldwide.With the development of polyester products to the field of functional materials,new polymerization strategies are required for the synthesis of these polyesters.Currently,the large-scale synthesis of polyester depends on a transesterification method based on the melt polycondensation process.According to Flory’s polycondensation theory,obtaining high molecular weight（HMW）polyester requires a strict stoichiometry of dicarboxylic acid/diol（1:1）.Accordingly,dicarboxylic acid and excess diol are used as the monomers for esterification to give hydroxyl-terminated prepolymers;and then the excess amount of diols are removed through the transesterification between the prepolymers.A stoichiometry of dicarboxylic acid/diol is achieved by this transesterification process,thereby realizing the synthesis of HMW polyesters.However,low-boiling-point diols are needed in the transesterification,so that the regenerated diols can be discharged from the reaction system by distillation.Therefore,for macrodiol monomers with high boiling point and low vapor pressure,e.g.,poly（ethylene glycol）（PEG）,they cannot be separated by distillation and only produce low molecular weight oligomers.Moreover,these diols are the starting materials of many high-value polyesters,which can be applied in the fields of in vivo drug delivery,tissue engineering scaffolds,medical adhesives,and so forth.Other synthetic methods of polyesters,including ring-opening polymerization,acid chloride acylation,etc.,are inappropriate for the low-cost large-scale synthesis due to the need for specific monomers and cumbersome post-treatment.In conclusion,the existing synthetic strategies are uable to take into account the two aspects of effectiveness and low cost,making it an urgent need to develop a new strategy for the polymerization involving macrodiols.Recently,with the extension of polyesters to the fields that are in close contact with the human body,e.g.,biomedical materials,catering utensils,and disposable appliances,the residue of metal catalyst in polyester is strictly restricted.To date,the synthetic methods of polyester including transesterification require the use of biologically toxic metal catalysts,which limits their applications in the abovementioned fields.Although the direct esterification strategy based on the autocatalysis of dicarboxyl acids was proposed by Carothers as early as 1929,only low molecular weight oligomers can be obtained by this strategy.Based on a new understanding of the reason why HMW polyester cannot be achieved under the autocatalysis of dicarboxyl acids,that is,it is not due to the thermodynamic factors（the low equilibrium constant of esterification and the difficulty of removing water from the high-viscosity melt）that was traditionally believed,but is caused by the kinetic deviation of the stoichiometry of dicarboxylic acid/diol from 1:1.In Chapter 2,to overcome the difficulty of obtaining HMW products using macrodiols,a novel carboxyl-ester transesterification（CET）was developed,where an excess amount of the sublimable dicarboxyl acid is first esterified with a macrodiol to obtain carboxyl-terminated prepolymers.Then,the exchange reaction between the terminal carboxyl groups and terminal ester bonds of the prepolymers is constantly conducted to remove the excess dicarboxyl acid,thus achieving the strict stoichiometry of dicarboxylic acid/diol.Herein,this CET strategy was first reported on the polycondensation to polyester,and it has been successfully empolyed to the polymerization of PEG diols,soybean oil-based diols,and other macrodiol monomers.Thus,a series of HMW polyesters were synthesized via CET.In the obtained HMW biodegradable PEG,since the dicarboxyl acid component is acted as the linking segment and is as low as less than 5%by mass fraction,it can still be called PEG in the broad sense.The experimental results demonstrate that the biodegradable PEG,like the normal PEG with the same molecular weight,exhibits excellent protein resistance performance,cytocompatibility and“stealth”effect in vivo.At the same time,the biodegradable PEG can be used to modify small therapeutic molecules and increase their circulation time in blood.Furthermore,the biodegradable PEG can be degraded into small molecules under enzymatic catalysis in vivo and excreted through the kidneys,while normal HMW PEG can easily be accumulated in the kidneys,rasing the theat to cause toxic effects.Therefore,this HMW biodegradable PEG is expected to be served as a safe chemical modifier of drug molecules to improve their delivery efficiency and therapeutic effects.In Chapter 3,according to the CET mechanism,two PEG diols were reacted with mercaptosuccinic acid（MSA）to afford a series of amphiphilic PEG derivatives,in which the PEG₂₀₀-and PEG_10k-containing segments exhibit hydrophobic and hydrophilic properties,respectively.The derivative can self-assemble into micelles and thereafter cross-linked by oxidizing the mercapto groups of the MSA unit into disulfide bonds,thus affording a core-cross-linked full PEG nanodrug carrier with good biocompatibility.This carrier endows the as-prepared paclitaxel（PTX,an anticancer drug）-loaded nanodrug with reduction responsiveness to selectively break disulfide bonds in a high-concentration glutathione microenvironment inside cancer cells,thereby releasing PTX and killing cancer cells.Compared with free PTX,the nanodrug not only significantly prolongs the circulation time of the loaded PTX in blood,but also spares the side effects,for example,liver damage caused by free PTX,while maintaining excellent antitumor activities.Therefore,this full PEG carrier is promising for delivering hydrophobic anticancer drugs to treat a series of malignant tumors including breast cancer.In Chapter 4,the CET has also been applied to a soybean oil-based diol（SOD）monomer prepared from soybean oil.The SOD was successfully polymerized with dicarboxylic acids to obtain HMW soybean oil-based polyesters.As a comparison with the traditional direct esterification and transesterification,the molecular weights of soybean oil-based polyesters synthesized by CET are increased by 1 to 2 orders of magnitude.These soybean oil-based polyesters not only show good thermal properties and high transmittance,but also exhibit adhesive properties comparable to commercial pressure-sensitive adhesives.In addition,the introduction of quaternary ammonium salt groups into the unsaturated fatty chains of soybean oil-based polyesters via thiol-ene“click”reaction endows these polyesters with bacteriostatic rate over 99%,which is very promising for empolying in the field of biomaterials,e.g.,antibacterial adhesives.In Chapter 5,in order to solve the problem of catalyst residues,a catalyst-free polycondensation（CFP）was proposed to synthesize a series of HMW aliphatic polyesters.In this CFP strategy,a primary diol and an excess of dicarboxyl acid that can form cyclic anhydride are used as monomers.Under the conventional two-step melt polycondensation process,carboxyl-terminated prepolymers are first obtained,and then the strict stoichiometry of dicarboxylic acid/diol is achieved through a tandem reaction mechanism involving proton transfer,anhydride formation,and re-esterification.Within reasonable polymerization time（<8h）,the molecular weight of the polyester can reach up to 88 k Da.The mechanism had also been fully confirmed by the experimental data and computational calculation.In Chapter 6,based on the understanding that the dicarboxyl acid unit which can form cyclic anhydride needs to be located in the chain ends of the polyester in CFP,a slight excess（1-2%）of ethylene glycol is first esterified with terephthalic acid and then reacted with these anhydride-formable dicarboxyl acids,thus forming the carboxyl-terminated prepolymers.After CFP,the mass fraction of the anhydride-formable diacid component is reduced to a negligible level below 1%,thereby realizing the catalyst-free synthesis of HMW aromatic polyesters including PET.The experimental results confirmed that that the CFP strategy can not only produce catalyst-free polyesters with comparable performance to existing commercial products,but also avoid the negative effects of catalyst residues.Therefore,this CFP technology is expected to be applied in fields with high safety requirements,such as medical devices and catering containers,and to advance the current polyester process with existing equipment without increasing costs.