Synthesis And Characterization Of Novel Biodegradable Polymers From 5-Hydroxylevulinic Acid

Synthesizing biodegradable polymers such as polylactic acid from renewable biomass resource is one feasible way to solve the problems of environment pollution and resource shortage in current polymer industries. In this work, novel biodegradable polymers have been synthesized from biomass via a new synthetic route. In brief, 5-hydroxylavulinic acid (5-HLA), an apparent hydroxyl acid monomer, was first synthesized from levulinic acid (LA), a platform chemical derived from biomass resources; then, novel aliphatic polyesters including poly(5-hydroxylevulinic acid) (PHLA), poly(5- hydroxylevulinic acid -co- diol)s (PHLA-DO), poly(5-hydroxylevulinic acid -co- lactic acid)s (PHLA-LA) were synthezied via melt polycondensation of 5-HLA or co-polycondensation of 5-HLA with diols or lactic acids. The monomer synthesis, the polycondensation and copolycondensation reactions, the polymerization mechanism, the structures and properties and in vitro degradation behaviors of the resulting polymers and copolymers were studied systemically.In the synthesis of 5-HLA, LA was first brominated using liquid bromine (Br₂) to give an intermediate product methyl 5-bromolevulinate (5-MBL), which was then hydrolyzed in one step to produce 5-HLA. After extraction of the hydrolysis product with diethyl ether and then recrystallization of the extract in chloroform, pure 5-HLA crystal was obtained with a yield of 28% (based on LA). In the bromization reaction of LA, the reaction conditions such as reaction temperature, drop rate of Br₂ and reaction medium were optimized. Methyl 3-bromolevulinate (3-MBL) in the side product was partially converted to methyl 5-bromolevulinate (5-MBL) through a rearrangement reaction, thus the side product was partially reused and the yield of 5-MBL was enhanced from an ever reported value of 30% to 45%. The one-step hydrolysis of 5-MBL resulted in shorter reaction time and higher yield and is thus better than the two-step hydrolysis reported in literature.In an attempt to synthesize a lactone monomer form 5-HLA using BF₃·OEt₂ as catalyst, 1,6,9,13-tetraoxadispiro [4.2.4.2] tetradecane-2,10-dione (or altaicadispirolactone, ADPL), a dimer of the 5-HLA, rather than the expected γ-keto-δ-valerolactone (KVL) was synthesized. ADPL is one of the chemical components of Anemone altaica C.A.May, a traditional Chinese medicinal herb. Structure of the dimer was characterized by GC-MS, ¹H-NMR, ¹³C-NMR, FT-IR, element analysis and polycrystal/single crystal XRD, respectively. Two plausible mechanisms for the cyclolactonization reaction were presented. However, this compound is too steady to be polymerized in ring-opening manner.Then, the melt polycondensation of 5-HLA was studied and low molecular weight poly(5-hydroxylevulinic acid (PHLA) was synthesized for the first time. The effects of reaction conditions such as catalyst type and amount, reaction time and reaction temperature on the polycondensation were examined. It was found that catalysts including Sn, SnO, SnCl₂·2H₂O and Sn(Oct)₂ exhibited catalytic activity for the polycondensation reaction, among which SnCl₂·2H₂O was the most effective one when it was used together with p-toluenesulfonic acid (TSA). PHLA with M_W of about 2550 was synthesized in the presence of SnCl₂·2H₂O/TSA at 170℃ and under reduced pressure for 18 hours. The microstructure and thermal properties of PHLA were characterized with FTIR, ¹H-NMR, ¹³C-NMR, DSC and TGA. It was found that PHLA possesses unexpected high glass transition temperature (M_n = 1600, T_g, 128 ℃). This is very different from ordinary aliphatic polyesters which usually have T_gs lower than 60℃. The high T_g is attributed to the formation of intra- and intermolecular hydrogen bonds because of existence of a characteristic keto-enol tautomerizm equilibrium in the polymer structure.Because of the existence the enol structure of 5-HLA, it is no longer merely a bifunctional hydroxyl acid monomer, but a trifunctional monomer. To utilize the enol hydroxyl of 5-HLA or PHLA, 5-HLA or oligomer of 5-HLA was copolycondensed with diol monomers such as butanediol (BDO), 1,3-propanediol (PDO) and ethylene glycol (EG). Crosslinked polymers were synthesized for the first time from these apparent 2-2 functional monomer systems via the esterification of the hydroxyl withthe carboxyl and the etherification of enol hydroxyl with the alcohol hydroxyl. Briefly, in a preferable synthesis route, 5-HLA was first dehydrated together with BDO under vacuum, and then a catalyst was added into the resulting prepolymer and the reaction was continued at atmospheric pressure, as a result, an crosslinked polymer was produced in short time. It is no longer soluble but swellable in tetrahydrofuran (THF, a good solvent for PHLA). The change of gel content was tracked with time under various reaction conditions: diols, monomer ratios, reaction temperature and catalyst amount. The crosslinking reaction was accelerated with increasing temperature or catalyst concentration or using longer diol. The gel content and T_g of the copolymer could be manipulated by changing the monomer feed ratio. The length of the diol also affects the T_g. For the 5-HLA/BDO system, crosslinked polymers PHLA-BDO were produced within a 5-HLA/BDO molar ratio range from 95/5 to 20/80, and gel contents higher than 90% were reached in a 5-HLA/BDO molar ratio range from 40/60 to 80/20. The T_gs range from -35.6℃ to 65.1℃. Therefore, both soft crosslinked elastomers and rigid semi-crosslinked polymers could be obtained. But the rigid semi-crosslinked polymers changed to soft elastomers with decreased T_gs after extraction with THF. The decrease of T_g of the crosslinked polymer (compared with PHLA) may be attributed to the destroy of the hydrogen bonds because of the formation of the crosslinking point. The FT-IR spectrum of crosslinked PHLA-BDO validates the existence of ester bond, vinyl ether and double bond in the chain structure. This demonstrates the crosslinking mechanism suggested.As an attempt to increase the molecular weight of PHLA and T_g of poly(L-lactic acid) (PLLA) and poly(D,L-lactic acid) (PDLLA), the copolycondensation of 5-HLA with L-lactic acid (LLA) and D,L-lactic acid (DLLA) was carried out respectively. The effects of the reaction conditions including monomer feed ratios, reaction temperature, catalyst amount and reaction time were investigated, and the structure and thermal properties of the resulting copolymer were studied. But in the copolycondensation with high 5-HLA/LLA or 5-HLA/DLLA ratio, the molecular weight of PHLA-LLA and PHLA-DLLA were not increased as compared with PHLA homopolymer. Obvious increase in molecular weight was only observed when thecontent of L-lactic acid or DL-lactic acid was higher than 90%. In copolycondensation with low 5-HLA/LLA ratio, addition of small amount of 5-HLA resulted in an obvious increase of T_g of the PHLA-LLA copolymer as compared with the PLLA homopolymer with same molecular weight. But it was not the case for PHLA-DLLA. Only when the content of 5-HLA is high enough, the T_g of PHLA-DLLA could be raised.The in vitro degradation behaviors of PHLA, PHLA-BDO, PHLA-LLA and PHLA-DLLA were examined at 37℃. It was found that PHLA degraded more rapidly in phosphate buffer saline (PBS) than in deionized water, but the sample degraded in PBS was no longer soluble in THF. Therefore, most of the degradation was performed in deionized water. Because of the hydrolytically sensitive aliphatic ester bonds in the structures of these polymers, they degraded readily in water. Weight loss appeared from the beginning of the degradation process possibly because of the lower molecular weight or existence of sol in the crosslinked samples. The weight loss of PHLA reached 40% after 4 weeks. But PHLA-BDO degraded more slowly because of crosslink. Its weight loss only reached 30% after 6 weeks. The degradation rate of PHLA-LLA and PHLA-DLLA was different according to the type of lactic acid and monomer ratios. Crystalline PHLA-LLA degraded more slowly than amphorous PHLA-DLLA.