DEVELOPMENT OF ORGANOCATALYSTS FOR RING-OPENING POLYMERIZATION (ROP) OF LACTONES

......................................................................................................... ii ACKNOWLEDGMENT ..................................................................................... iv PREFACE ............................................................................................................. v TABLE OF CONTENTS ..................................................................................... vii LIST OF TABLES ............................................................................................... viii LIST OF SCHEMES ........................................................................................... xi LIST OF FIGURES ............................................................................................. xiii CHAPTER 1 ......................................................................................................... 1 CHAPTER 2 ......................................................................................................... 45 CHAPTER 3 ......................................................................................................... 107 CHAPTER 4 ......................................................................................................... 159 CHAPTER 5 ......................................................................................................... 199


LIST OF TABLES
As the world's interest in the aliphatic polyesters emerges, the ring-opening polymerization (ROP) of cyclic lactones has received tremendous attention over the last two decades [27][28][29][30] . The ring-opening polymerization is a type of chain-growth polymerization technique where the polymer chain propagates through the addition of cyclic monomers to an active chain end. 27,31,32 In this process, the initiator opens a cyclic monomer and forms an active center. Depending on the nature of this propagating active center, ROP mechanisms can be illustrated as; cationic, anionic, radical, and covalent. 33 The ROP stands out for end group fidelity, high stereoselectivity and regioselectivity, precise molecular weights and complex polymer architectures. 33 Besides, the ROP of rac-LA using sterically hindered chiral (CH(Me)Ph)2IMes catalyst also formed a highly isotactic PLA at low temperatures. It was suggested that stereocontrol is originated from the steric congestion of the active site, rather than by the chirality of the catalyst. The mechanism for ROP of rac-LA using either achiral or chiral NHCs catalysts was proposed through the chain-end activation mechanism despite the presence of chiral groups close to the active site. However, the reaction rates are lower and require a higher catalyst loading than TBD.
Yet, no significant differences were observed in the selectivity of stereochemistry for the polymerization of rac-LA between TBD, DBU, and MTBD. 38  (Thio)urea/base Cocatalysts. In the light of above advances of organocatalysts, (thio)urea/ base cocatalyst system was assembled to conduct highly selective ROP of cyclic lactones, which resulted in precisely tailored polymers with high end group fidelity and narrow molecular weight distributions (Mw/Mn <1.1). 38 Despite the high selectivity, this catalyst system suffer from low rates for ROP. 46,94 In general, thiourea featuring aryl rings with strong electron-withdrawing substituent groups give faster rates, though it is dependent on the reaction conditions. 47 It is also proven that the high selectivity and activity of ROP of VL are proportional to the magnitude of binding constants of catalysts and the bases. However, when the binding is too strong between base and catalyst, a reduction of the reaction rates was observed. 94,95 The synthetic addition of one and two thiourea moieties to 1-S could increase the rates of the ROP of LA, VL, and CL in non-polar solvents without compromising the high selectivity. 46,96 Higher activity in 2-S was explained by activated thiourea mechanism supported by computational studies (Figure 1.7). However, the 3-S catalyst activity was rendered by intramolecular H-bonding network among the thiourea moieties. As a

Thermal stability of Organocatalysts
The industrial implementation of organocatalyzed polymerizations is limited due to the requirements of high catalyst loading and poor thermal stability. 66 The standard temperature range for industrial polyester production is 150 °C-300 °C. 101 Hence, organic acid and base mixtures have been advanced to mitigate the above-mentioned limitations due to its unique ability to form thermally stable complexes (Figure 1.8).
One step forward to enhance the green features of organocatalyzed ROP is the use of Similarly, TBD has also been used for the ROP of EB in bulk and in diluted conditions at 80 ˚C, but it took days to reach high conversions. 108 Other bases, 1,2,3tricyclohexylguanidine (TCHG) and 1,2,3-triisopropylguanidine (TIPG) have also been tested on the ROP of EB though higher conversions were limited. 108

INTRODUCTION
For more than a decade, the remarkable selectivity of thiourea plus base cocatalysts for monomer (vs polymer) in the ring-opening polymerization (ROP) of lactones has been applied to the formation of highly-adorned and precisely tailored macromolecules. [1][2][3] In the last several years, this class of catalyst has received new attention from several research groups as efforts have been undertaken to increase the activity of these systems without sacrificing their high level of reaction control.      In the Hammett plot of log kobs vs σ (acetone-d6), both m-X-S and p-X-S exhibit a nonlinear plot with a maximum at σ ~0.2, Figure 2 rates. This explanation is consistent with the initial reports of (thio)imidate mediated ROP. 4,5,17 We infer that the thioimidate mechanism appears to 'turn on' at σ ~ 0. These results also suggest that catalyst/reagent interactions are not very similar to those at the transition state. Hence, the community might not be too concerned with the inaccessibility of urea/reagent binding constants as they may not be as meaningful as                            Remarkably, these 'hyperactive' catalysts for ROP remain controlled.

Thioureas in Non
The synthetic addition of one or more (thio)urea H-bond donating arms to the parent (thio)urea has been shown to substantially increase the activity of (thio)urea H-bond donors. 6,14 Our group first disclosed bis-and tris-(thio)urea H-bond donors for ROP, 6,14 and other intramolecular Lewis acid donors have been used. 15 In general, the bis- which were less active for ROP than the flexible 3-carbon tethered 2-O and 2-S reported by our group. 6,14 In the pantheon of conformationally flexible linkers that can be envisaged, only one has been reported. 6 In light of the recent interest in these catalysts, we disclose here several bisurea and bisthiourea H-bond donors for ROP with flexible linkers, most with higher activity and control than the parent 2-X system. We extend previously proposed mechanisms to the (thio)urea plus alkylamine base mediated ROP of LA to explain why thioureas have been observed to be more effective (versus ureas). Mass spectrometry experiments were performed using a Thermo Electron ( Yield: 97%. Characterization matches literature. 6  found m/z = 571.0998. found m/z =599.1311. found m/z = 613.1467. found m/z = 627.1624. found m/z = 711.2563.   Characterization matches literature. 18  found m/z =631.0825. found m/z = 645.1016. After stirring overnight, the reaction mixture was filtered via suction filtration and rinsed with 3 portions of cold CH2Cl2 to provide a pure white powder that was freed of volatiles under high vacuum. Yield: 76%. NMR spectra given below. HRMS: calc.

ROP of Lactide
The most active bis(thio)urea H-bond donors from the VL studies were applied for the ROP of lactide in CH2Cl2 and solvent-free with Me6TREN cocatalyst. 20 Low solubility of bisureas under reaction conditions limited all direct comparisons, but this and previous studies 12 show that the bisthioureas are more effective than the corresponding bisureas for the ROP of LA (Table 3.4). In the case of lactide, weak alkylamine base cocatalysts are used because stronger imine bases (e.g. MTBD) will polymerize lactide in the absence of H-bond donor in a less-controlled ROP. 5,20,21 We speculated that the increased rate observed for bisthiourea (versus bisurea) plus Me6TREN mediated ROP of lactide was due to a change in mechanism between the two species. Indeed, the 1 H For identically substituted ureas and thioureas in the ROP of LA, the thiourea is the more active catalyst, and this is attributed to the pKa of the H-bond donor. The difference in mechanism for the two H-bond donating catalysts presumably arises because any thiourea will be more acidic than its identically substituted (e.g. 3,5bistrifluoromethyl phenyl) urea. 23,24 When a pair of mono-H-bond donors (urea or thiourea) of the same pKa are used as cocatalysts with Me6TREN for the ROP of lactide, the urea is the more active catalyst, Table 3.5. Having identical pKa, such a pair of urea and thiourea will effect enchainment by the same mechanism, and hence, the more polar urea (or imidate) is the more active H-bond donor. When a highly acidic H-bond donor is employed (Table 3.5, last entry), the incipient (thio)imidate displays reduced activity arising from its low basicity, as previously observed. 10,23 These observations are seemingly contrary to the (thio)urea plus strong base mediated ROP of other lactones (e.g. valerolactone or caprolactone). 7,9,11,23 However, in this latter scenario, the stronger base cocatalyst (versus Me6TREN) can deprotonate either the urea or thiourea. 13 In that event, the urea (or resulting imidate) will always be more active than the thiourea (or thioimidate                          We previously reported that electron-deficient aryl ureas have proved to be particularly efficacious compared to thioureas for ROP of δ-valerolactone (VL) and ε-caprolactone (CL) despite the solvent polarity. 10,13 Additionally, we disclosed that a synthetic addition of one or more (thio)urea H-bond donating moieties to 1-O/S, could give an exquisite combination of higher rates and higher selectivity in ROP of lactones. 13,18,19 The activity of 2-O/S catalyst in (non)polar solvents and the effect of confirmation 162 flexibility in between (thio)urea moieties have been well explained. 13 It is proved that

3-O/MTBD cocatalyzed ROP occurs through an activated-urea mechanism where
single urea moiety activates the lactone and that urea is powered by intramolecular Hbonding network by other two urea moieties in nonpolar solvents. 18  Determination of thermal properties-Melting temperatures (Tm) of PLA synthesized in this study were determined by differential scanning calorimetry (DSC) using a Shimadzu differential scanning calorimeter 60 plus that has been calibrated using high purity indium at a heating rate of 5 °C/min. Polymer sample (5 mg) was first heated to As we believe, this is the first study that shows the living polymerization behavior of ROP with higher-order evolution of monomer.

Chemical kinetics of ROP of VL cocatalyzed by 3-O/MTBD in acetone-d6
A kinetic study was conducted in order to establish the reaction order of the monomer

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Experimental results suggest that three monomers could be activated by 3-O, which facilitated in polar solvents. Higher-order kinetics of lactone monomers have been seen previously with metal catalysts, as mentioned in literature. 29 Kinetic studies were also undertaken to elucidate the role of benzyl alcohol and 3-O/MTBD in the ROP of VL.
We observe first-order kinetics in the initiator and also, first-order kinetics in cocatalyst, which is typical behavior for ROP of lactones. 2) It is also proven that bisimidate is not formed even with an additional equivalent of base treatment which can support our proposed mechanism. 13 It is known that more imidate characteristics can be formed using strong bases or/and in polar solvents also, ROP via imidate mediate mechanism could provide faster rates and highly controlled reactions. In this study, it is also observed that more imidate characteristics in reaction conditions preferred in higher-order kinetics (Table 4.2), which explains faster rates for ROP via imidate mediated mechanism. Less imidate characteristics in reaction conditions prefer the first-order evolution of the monomer. isotacticity decreases with low initial monomer concentrations, which suggests epimerization is high when it has high catalyst loading %. Isotactic PLA is highly crystalline, where it can be measured by melting temperature (Tm). When isotacticity decreases, Tm decreases where it shows the loss of crystallinity due to the epimerization.
We observe, loss of crystallinity with low initial monomer concentration where epimerization takes place.
A study by our group has shown that ROP of LA displays second-order kinetics in ( Table 4.4) However, with low initial monomer concentrations, Mw/Mn was slightly broadened, and epimerization was facilitated, which is indicated by low Tm values.
Hence, these observations reinforce the conclusion that the magnitude and the nature of cocatalyst interactions have a dramatic effect on the kinetics of the ROP reaction.

Copolymerization
The Hence, it can follow higher-order kinetics in monomer resulted in higher initial rates.
Yet, these ROPs exhibit living characteristics and remain highly selective.                            Synthesis of ζ-Heptalactone (HL). The procedure to synthesize ζ-heptalactone (HL) was adopted from previous literatures with some modifications. 27 Initially, appropriate amount of m-CPBA (4.6 g, 18 mmol) was subjected to a round bottom flask, followed by the addition of dichloromethane (50 mL) and cycloheptanone (2.10 mL, 27 mmol).
The reaction mixture was stirred at moderate speed for 5 days after which the reaction was quenched with 10% (w/v) sodium thiosulfate. The mixture was then washed with sodium bicarbonate followed by extraction with dichloromethane thrice. After drying with sodium sulfate, rotary evaporation was performed to yield a colorless oil. This oil was then purified by silica-gel column chromatography with 1:1 mixture of ethyl acetate and hexane. Yield: 2.17 g, 95%. Product matched previous literature characterization. 27 Synthesis of η-Nonalactone (NL). The procedure to synthesize η-Nonalactone (NL) was adopted from previous literatures with some modifications. 11 Initially, cyclooctanone  The polymer was then precipitated out of hexane and high vacuum was applied to  The recovery of extracted Au 3+ as gold metal after the pyrolysis was 99%.

Organocatalytic ROP of (thiono)macrolactones
The efficacy of cocatalyst systems for the ROP of newly synthesized (thiono)macrolactones was evaluated. The TCC/BEMP cocatalyzed ROP of macro(thiono)lactones in non-polar solvents proved to be the optimized conditions (  . In general, the polymerization rates of the (thiono)macrolactones are faster than their corresponding oxygenated lactones, which were also observed in previously published reports. 21 It was proposed that the increase in electrostatic charges and the polarity of the C=X (X=O/S) bond of the monomer in the binding of TCC could affect the reaction rates. However, the ROP of tnHL showed lower reaction rates than expected ( High conversions for the ROP of (tn)EB were restricted even with the optimized conditions where only 64% conversion was obtained ( tnEB showed a 1 st order linear evolution, the linearity of the molecular weight versus conversion curve has deviated as it approaches higher conversions ( Figure 5.11).
With the increment of the ring size, it is more prone to higher transesterification reactions, which can interrupt the controlled and living behavior of polymerization of (thiono)macrolactones. As illustrated in Table 5

Crosslinked polymers (CLPs) from poly(thiono)lactones
The poly(thionolactones) synthesized in this study contain thiocarbonyl groups on their polymer backbone. The ability of sulfur to reach higher oxidation states facilitate the inter/intramolecular crosslinking of these polymers. The homopolymer of tnPDL The basic surface analysis was carried out for the carbon (C) and sulfur (S) elements to discover the functional groups involved in crosslinking. As shown in Figure 5.4 (a). the experiment was carried out for C 1s core and S 2p core. The C 1s region always shows significant, intense, and well-separated peak shifts as C changes its oxidation states. 39 In Figure 5.4 (a), the 286.1 eV represents the ester linkage on the polymer backbone.
The peak at 287.0 eV signifies the polymer's carbon-sulfur functional group, which is involved in the formation of the inter/intramolecular crosslinking. The peak with the highest BE (288.9 eV) illustrates the unoxidized/unreacted thiocarbonyl groups on the polymer backbone. Figure 5.4 (b) shows the BEs of S 2p, and the two peaks represent the different oxidation states of the sulfur atom. 40 The peak at 163.9 eV embodies the disulfide (S-S) groups, whereas the peak at 168.3 eV signifies the sulfone (R`R-SO2) groups in the polymer network. However, the peak intensities of the two peaks illustrate that the polymer contains more sulfone groups over disulfide groups, which is also proven by the area under the curve ratio (sulfone groups: disulfide groups is 8:1). The XPS data of S 2p demonstrate sulfone and disulfide groups as the possible functional groups involved in the inter/intra-polymer chain crosslinking process.
A dynamic rheology study was carried out on an ARES G2 rheometer (TA Instruments, USA) to characterize the viscoelastic properties of the PtnPDL-CLP. The mechanical response of the crosslinked polymer was measured as it is deformed under shear stress (or strain), which illustrates the relationship between mechanical behavior and the molecular motion of the polymer. The rheology study was done by measuring shear storage modulus (or storage modulus) (Gʹ) and shear loss modulus (or loss modulus) (G˝) as a function of angular frequency (ω) using parallel plates at room temperature.
The experimental results showed a decrement of Gʹ and an increment of G˝ with the increasing angular frequency (See Figure 5.16), which demonstrates a reduced elastic behavior and an increased viscous behavior of the material; when applying a workforce.
The crossover point of Gʹ and G˝ suggests the formation of a three-dimensional network of the CLP. 41 With the inspiration of the synthesis of PtnPDL-CLP, the oxidation of the homopolymers of tnCL (PtnCL), tnHL (PtnHL), and the di-block copolymer of P(tnPDL-b-CL) was carried out to synthesize their corresponding CLPs (PtnCL-CLP, PtnHL-CLP, and P(tnPDL-b-CL)-CLP). As shown in Figure 5.3(b), the morphology of all CLPs turned out to be opaque, solid, and flexible. Besides, the cross-sectional images of the CLPs taken by the optical microscope showed that all CLPs have a porous polymer network ( Figure 5.3(c)), which occurred due to the crosslinking. Thus, porosity% of each polymer was obtained via the swelling test.
Each of the CLP disk was pre-weighed (Wd) before the test and was immersed in THF for a total of 20 minutes at room temperature (23 ˚C). At 2 minutes intervals, the polymer disk was removed from the solvent, and the excess surface THF was removed by blotting on a filter paper to get the swollen disk weight (Ws). The swelling ratio was determined using equation (1). 40 = ("#$"%)' The final swollen weights (Ws) of the CLP disks were used to calculate the porosity of the polymer material using equation (2), where V is the volume of the CLP disk, and ρ is the density of THF(0.8892 g cm -3 ). 42 Results were averaged on three independent runs.

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The order of increasing swelling ratios for the polymer disks was P(tnPDL-b-CL) > PtnPDL-CLP > PtnHL-CLP > PtnCL-CLP, indicating that the extent of crosslinking has a profound influence on the solvent absorption capability of the CLPs (See Figure 5.17).
Similarly, the calculated porosity% values are proportional to the swelling ratios (Table   5.2), which illustrates that the polymer chain length may affect the porosity of the CLPs.
This observation led us to investigate the crosslinked densities of the CLPs.
Before the calculation of crosslinked densities, the Flory-Huggins polymer-solvent interaction parameter (χ) was calculated by using equation (3). δ1 and δ2 stand for the solubility parameters of the solvent (THF = 18.30 J 1/2 cm −3/2 ) and the polymer respectively, where Vs is the molar volume of the solvent, R is the universal gas constant, and T is the absolute temperature. 43 Here, we use the Hansen solubility parameters of PPDL (17.5 J 1/2 cm −3/2 ) and PCL (19.5 J 1/2 cm −3/2 ) to estimate the interaction parameter (χ) of the CLPs. 44,45 As the solubility parameter is independent on the molar volume of the solvent (Vs), it is a convenient metric when comparing structurally dissimilar polymer networks. 46 Vp is the volume fraction of polymer in the swollen weight, and n stands for the crosslinked density of the polymer. The results in Table 5 The weight of the insoluble CLP piece was monitored over time ( Figure 5.5). Under basic conditions, the polymer showed a rapid degradation compared to acidic and neutral conditions, as observed in previous studies. 21 The CLP degraded to approximately more than half of its original mass after 10 days.

Gold recovery application of CLP
Besides the currency value, gold is a metal with outstanding properties such as good ductility, high thermal/electrical conductivity, and chemical stability. 47 The annual demand for gold is around 4000 t/year and 1500 t of it produced by recycling industrial products, including electronic wastes (e-waste), which have a much higher gold content (300-350 g/t) compared to an economical grade ore (0.3-17 g/t). 48,20 Alkyl cyanides and other alternative leachants, including thiourea, thiosulfate, bromide, iodide, and sodium hypochlorite, have been used to recover gold. Yet, they have their own drawbacks such as toxicity and low efficiency. 20,47,49 Thus; greener approaches have a high demand for gold recovery. In recent studies, high sulfur content polymers and polythioamides have been used to recover gold because of their strong metal coordination properties. 20,50 As it is shown in the XPS data in Figure 5.4, the PtnPDL-CLP has unoxidized C=S on the polymer backbone in addition to crosslinked S-S. Thus, a hypothesis was built up that the CLP might be able to extract gold ions from an aqueous solution.
The PtnPDL-CLP was used to investigate the ability of its metal complexation. In this study, different amount of PtnPDL-CLP was added into the aqueous solution of Au 3+ .
The polymer was stirred in the Au 3+ solution for three days, and it was observed that the solution was fading with time ( Thus, we believe these newly synthesized crosslinked porous polymers have a high potential of using as a polymeric filter in the application of water purification. The organocatalytic ROP of (thiono)macrolactones exhibit characteristics of "living" polymerization in the presence of an H-bond donor. Fast reaction rates were observed for (thiono)macrolactones with TCC/base cocatalyst system in non-polar solvents at elevated temperatures, and it was proven the polymerizations are entropically driven.
The copolymer synthesized from tnPDL and PDL showed altered material properties.
The S-atom's unique reactivity was taken as an advantage to synthesize novel crosslinked polymer materials from homopoly(thiono)lactones and block copolymers via oxidation reaction under mild conditions. The resultant material turned out to be a porous, solid, and flexible polymer. Polymer characterization and material property analysis revealed that the polymer is degradable and has higher thermal stability.
Further, the extent of the porosity and the degree of crosslinking were studied. It was disclosed these polymers could be utilized in gold recovery due to the binary coordination between S and Au 3+ . Thus, we believe those polymers have a high potential of absorbing other heavy metals and can be used for water purification.