Alessandro
Pellis
*,
Fergal P.
Byrne
*,
James
Sherwood
,
Marco
Vastano
,
James W.
Comerford
and
Thomas J.
Farmer
University of York, Department of Chemistry, Green Chemistry Centre of Excellence, Heslington, York, YO10 5DD, UK. E-mail: ale.pellis@york.ac.uk; alessandro.pellis@gmail.com; fergal.byrne@york.ac.uk
First published on 7th March 2019
With increased awareness of environmental issues caused by traditional petrochemical processes, both academia and industry are making enormous efforts towards the development of sustainable practices using renewable biomass as a feedstock. In this work, the biocatalyzed synthesis of polyesters derived from renewable monomers was performed in safer, bio-derivable organic solvents. Candida antarctica lipase B (CaLB), an enzyme belonging to the Ser-hydrolase family (adsorbed on methacrylic resin, also known as Novozym 435) was tested for its performance in the synthesis of adipate- and furandicarboxylate-based polyesters. In addition, the traditional solvents toluene and tetrahydrofuran were compared with a series of green solvents, 2,2,5,5-tetramethyloxolane, 2-methyltetrahydrofuran, 2,5-dimethyltetrahydrofuran and pinacolone for the enzymatic polymerizations. We can conclude that the monomer conversions and molecular masses of the obtained polyesters in all the tested alternative solvents were suitable, and in some cases superior, with CaLB immobilized via physisorption on acrylic resin being the optimal biocatalyst for all reactions. Strikingly, it was found that for the majority of the new solvents, lower reaction temperatures gave comparable monomer conversions and polymers with similar molecular weights whilst pinacolone yielded better polymers with Mn > 2000 Da and conversions of over 80%.
Examples of green alternatives to traditional low polarity solvents, such as toluene and hexane, have been presented in recent years. Terpenes and their derivatives have been demonstrated as valuable bio-based hydrocarbon solvents (e.g. limonene and para-cymene) but despite having similar solubility properties, they possess higher boiling points (>170 °C) rendering their removal difficult and energy intensive, and furthermore exhibit aquatic toxicity. 2-Methyltetrahydrofuran (2-MeTHF) is a volatile ether which can be produced by the chemocatalytic treatment of biomass, and its use has been demonstrated in several applications.5–7 Now regularly used in chemical process development, 2-MeTHF is arguably the most successful neoteric bio-based solvent. More recently, a bio-derivable alternative to toluene has been described. 2,2,5,5-Tetramethyloxolane (TMO) possesses a comparable boiling point (112 °C) to toluene (111 °C) and although it is an ether, it does not form hazardous peroxides.8 Several esters and ketones have also recently been suggested as alternatives to toluene, displaying a similar solubility profile and performance in chemical reactions.9
Along with the need for safer organic media, there has been great interest in the development of sustainable, non-toxic catalysts, particularly in the form of low cost biocatalysts, that can be used as catalysts in non-aqueous environments.10 Lipases, in their immobilized form, have emerged as key biocatalysts for the synthesis of short chain esters, chiral pharmaceutical compounds and polymers such as polyesters and polyamides.11–13 In particular, Candida antarctica lipase B (CaLB) physically adsorbed on polymethylacrylate beads (also known as Novozym 435) resulted in a highly active and stable biocatalyst in organic media.14,15 Further to this, Novozym 435 has been shown to be active when used in conjunction with various green solvents such as the synthesis of fatty esters,16 and the esterification of 2-phenylpropionic acid in a flow system.17
In the present work, a series of enzymatically-synthesized furan-functionalized bio-based polyesters were prepared via polycondensation in a selection of neoteric solvents; 2-methyltetrahydrofuran (2-MeTHF), 2,5-dimethyltetrahydrofuran (DMeTHF), TMO and pinacolone. Traditional solvents toluene and tetrahydrofuran (THF) were used as a comparison.14 In addition, several immobilized formulations of Candida antarctica lipase B (covalently immobilized or adsorbed) and a cutinase from Aspergillus (Novozym® 51032) immobilized via adsorption were tested as biocatalysts. The collected data allowed the interactions between solvent, monomer and enzyme to be examined, and it was found that the new generation of solvents produced superior polymers (higher monomers conversion and molecular masses) at a lower reaction temperature than the traditional solvents or with no solvent.
The solvents were chosen so that they would dissolve the monomers and the resulting polymer (except for toluene at 50 °C where BDO is initially only partially soluble) while allowing the enzyme to remain active. Biocatalysts lose most of their activity in extremely polar solvents (due to water stripping) and in solvents containing halogen atoms such as chloroform.16,17 In addition, it was required that the solvent could be easily removed after the reaction, so they needed to be volatile, preferentially in the ideal 70–139 °C range, as set by the CHEM21 solvent selection guide.19 Boiling points higher than this makes recovery by distillation increasingly energy intensive; any lower and fugitive emissions can cause air pollution. All the solvents (except THF) used in this study were within this range. Esters and protic solvents were not used due to the likelihood of side-reactions. These requirements considered, four green solvents were suitable for investigation; pinacolone, TMO, DMeTHF and 2-MeTHF. Toluene has similar dipolarity to the green solvents, but lacks the coordinating oxygen of the oxolane family of solvents. As shown in Fig. 1, all the tested solvents were found to be suitable media for the reaction since poly(1,4-butylene adipate) was obtained in all cases but with different monomer conversion rates.
The reaction was initially conducted at 85 °C, which was reported as the optimal temperature for the polymerization of the same monomers in solventless bulk reaction systems (Fig. 1A and B).20 1,8-Octanediol (ODO) was also investigated as an alternative to BDO for comparison. Toluene, TMO and pinacolone were used as the initial reaction media. No significant differences in terms of monomer conversions were observed at 85 °C in either the BDO or ODO systems. Molecular masses were also similar, although pinacolone produced a polymer with a particularly high molecular mass in the BDO system.
The temperature of both reactions was reduced to 30 and 50 °C to accommodate the lower boiling solvents (2-MeTHF, DMeTHF and THF). In the case of the ODO reaction, there was very little difference in performance between solvents in terms of monomer conversion and polymer molecular mass except in the case of pinacolone, which at 30 °C achieved excellent conversions (80%) and a Mn > 2000 Da, showing a significant advantage in terms of productivity and lower energy consumption. The indifference to the choice of solvent permits the selection of an environmentally friendly option instead of the petrol-based toluene or THF.
Conversely, the reaction of BDO at 50 °C illustrated clear differences between each solvent. It can be seen that both conversions and molecular masses increased using pinacolone despite the lower temperature, whereas the reaction in toluene was suppressed (monomers conversions of 45% vs. >83% and Mn of 744 Da vs. >2000 Da). The monomer conversion also appeared to increase across the series of ethers DMeTHF and 2-MeTHF vs. THF, with the obtained Mn following a similar trend.
It is impressive that the reaction performed in pinacolone at 30 and 50 °C was superior to the previously reported solventless process; the polycondensation in pinacolone gave monomer conversions of 90% and Mn of 2500 Da in comparison to a similar conversion of 89% but a slightly lower Mn (2200 Da) obtained in the solventless bulk reaction system at higher operational temperature (85 °C).20 Moreover, the Đ of the polymers synthesized in pinacolone (Đ = 1.20) is also slightly lower than those produced in the melt (Đ = 1.31) therefore constituting another advantage of using pinacolone as a component of the reaction mixture (for the complete set of data please see ESI, Tables S1 and S2†).
The reaction was also carried out at 30 °C to reduce the energy demand of the process further. A similar trend was observed at this temperature as at 50 °C, but it was found that toluene was unable to dissolve either diol at this temperature, leading to rather low Mn (<1000 Da).
Overall, the green aspects of the new process described in this work are excellent. While an organic solvent has been utilized, a green solvent has been demonstrated to be better than two traditional solvents, toluene and THF. In addition, the monomer conversions and molecular mass of the polymers have been improved, resulting in a superior quality polymer, with the reaction temperature being significantly reduced.
Enzyme | Immobilization method | Catalog code | Activity [PLU g−1] | Vendor |
---|---|---|---|---|
Candida antarctica lipase B | Covalently immobilized | IMMCALB-T2-150 | 5000 | Chiralvision |
Cutinase from Aspergillus (NZ 51032, cutinase1) | Adsorbed on acrylic resin | IMML51-T1-350 | 3000 | |
Recombinant Candida antarctica lipase B | Adsorbed on Purolite's highly hydrophobic carrier ECR1030M | — | 14300 | c-Lecta |
The best results in terms of conversions and molecular masses were obtained with Novozym 435, the CaLB formulation used throughout this work. The 2nd best performing preparation was the adsorbed CaLB from c-Lecta which was also the enzyme found to be the most stable at the operational conditions (magnetic stirring at 400 rpm). While all the other preparations were quickly ground into powders within 15 min of reaction, the c-Lecta preparation was relatively stable (minor visible sediment) for up to 2 h, at which point it started to be destroyed by the vigorous agitation used.
The CaLB from Chiralvision ranked 3rd while the cutinase from Aspergillus purchased from the same company was the least active enzyme for the above-mentioned reaction (see ESI, Fig. S1–S12† for the complete set of data).
The recycling of the biocatalyst was not in the scope of the present manuscript since alternative reaction systems that allow the preservation of the biocatalyst's integrity and its reuse for over 8 cycles have already been reported.21,22
Monomer conversions were lower in the polymerization of both BDO and ODO with diethyl-2,5-furandicarboxylate compared to with dimethyl adipate. The BDO system at 50 °C showed toluene and THF to be the worst performing solvents (Fig. 2A). Interestingly, no improvement in conversion was obtained using toluene when the reaction temperature was increased to 85 °C, unlike in the adipate system. When ODO was used in 50 °C reactions, toluene, DMeTHF and 2-MeTHF were all found to obtain the best monomer conversion (39–41%), followed by pinacolone and TMO, with THF being the worst solvent (29, 24 and 20% respectively). Swelling of the resin support was suspected of being the cause of the differences in conversion, but an investigation into this did not produce a valid relationship between solvent polarity and swelling.
From Fig. 3 it is possible to observe the thermal degradation profiles of poly(1,4-butylene adipate) (PBA) synthesized in different solvents and at different temperatures. The onset temperature of degradation (Td) is related to the molecular weight of the obtained oligomers. The PBA synthesized in toluene at 50 °C has a degradation temperature significantly lower than the samples synthesized in TMO and pinacolone (T10% = 193 °C for toluene vs. 346 °C and 357 °C for TMO and pinacolone respectively, Fig. 3A). For the reactions conducted in the three above mentioned solvents at 85 °C, with the molecular weights rather similar, no major differences in the degradation temperatures were observed, with the synthesized PBA having a T10% of 342–353 °C (Fig. 3B). In Fig. 3C, the decomposition temperature of PBA synthesized in THF, MeTHF and DMeTHF at 30 °C is shown. As expected, the thermal degradation profiles represent the polymer's molecular mass as shown in Fig. 1A. The complete set of TGA data reporting the temperature at which degradation reaches 5%, 10% and 50% for the samples plotted in Fig. 3 is presented in Table 2.
Fig. 3 TGA of PBA synthesized in (A) TOL, TMO and PIN at 50 °C; (B) TOL, TMO and PIN at 85 °C and (C) THF, MeTHF and DMeTHF at 30 °C. |
Solvent | Reaction T [°C] | T 5 [°C] | T 10 [°C] | T 50 [°C] |
---|---|---|---|---|
TOL | 50 | 159 | 193 | 367 |
TMO | 335 | 346 | 388 | |
PIN | 347 | 357 | 389 | |
TOL | 85 | 317 | 343 | 389 |
TMO | 301 | 342 | 387 | |
PIN | 336 | 353 | 389 | |
THF | 30 | 329 | 347 | 390 |
MeTHF | 342 | 359 | 393 | |
DMeTHF | 237 | 292 | 395 |
The DSC analysis of selected samples was also performed and clearly shows that all synthesized polymers: poly(1,4-butylene adipate), poly(1,8-octylene adipate), poly(1,4-butylene 2,5-furandicarboxylate) and poly(1,8-octylene 2,5-furandicarboxylate), have crystalline characteristics. The DSC data also show a clear difference in the melting (Tm) and crystallization (Tc) temperatures of the polymers, again related to their molecular weight. Oligomers having higher molecular masses melt and crystallize at higher temperatures compared to the oligomers synthesized at the same operational temperature (Table 3).
Solvent | Reaction T [°C] | T c [°C] | First Tm [°C] | Second Tm [°C] |
---|---|---|---|---|
TOL | 50 | −7 | 12 | 19 |
TMO | 24 | 40 | — | |
PIN | 25 | 41 | 47 | |
TOL | 85 | 25 | 41 | 47 |
TMO | 21 | 35 | 38 | |
PIN | 28 | 42 | 47 | |
THF | 30 | 24 | 40 | 43 |
MeTHF | 28 | 42 | 47 | |
DMeTHF | 12 | 29 | 33 |
In this work, all the solvents are aprotic and therefore do not form specific interactions to stabilize negative charges. It can be observed that increasing the number of methyl substitutions on the THF motif reduces the relative proportion of electron donating surface area (Fig. 5). DMeTHF is less basic than the other ethers examined. Ketones have a more prominent oxygen atom compared to ethers in terms of the electronegative surface area of the molecule but are less basic; pinacolone follows this trend. Without heteroatoms, toluene has a hydrophobic profile. Aromatic solvents are polarizable whereas ethers and ketones have a permanent dipole.
By modelling the diol reactants, 1,4-butanediol (Fig. 4, top) and 1,8-octanediol (Fig. 4, bottom), we observed that their lowest energy (and therefore most relevant) conformation are markedly different. 1,4-Butanediol preferentially forms an intramolecular hydrogen bond, while 1,8-octanediol does not. This suggests that in solution 1,8-octanediol is capable of two hydrogen bonds with either the solvent or potentially the ester reactant or another molecule of 1,8-octanediol. The intramolecular hydrogen bond of 1,4-butanediol reduces the dipole moment of the molecule, yet the reduction of electron density from the unbonded alcohol functionality increases its hydrogen bond donating ability towards a second, intermolecular hydrogen bond.
Hydrogen bonding and van der Waals force contributions to the chemical potential of species in solution can be separated to evaluate the specific interactions between solvent and diol and how this might influence the polymerization. COSMOtherm calculations at 30, 50, and 85 °C indicate 1,8-octanediol is more stable than 1,4-butanediol in all solvents, which may account for its reduced reactivity. At 50 °C, 25% of the energy of total solvent interaction between 1,4-butanediol (lowest energy conformation) and pinacolone is due to hydrogen bonding. This increases up to 35% with ether solvents. van der Waals forces are approximately equivalent for all solvents. Toluene is unable to engage in hydrogen bonding with 1,4-butanediol and so we would expect the intramolecular hydrogen bond of 1,4-butanediol to be preserved. In the oxygen-containing solvents it is possible to replace this interaction with an intermolecular hydrogen bond with the solvent. If this occurs prior to reaction, it may explain the difference in monomer conversion between toluene and the other solvents for the polymerization of dimethyl adipate at 50 °C (Fig. 1). At 85 °C, the entropic penalty of an intramolecular hydrogen bond creating a seven-membered ring structure may well negate the enthalpic benefit, restoring reactivity to that observed for TMO and pinacolone.
Pinacolone was demonstrated to be the best solvent for this process, producing superior polymers with higher molecular masses (Mn >2000 Da and conversions of over 80%) at significantly lower temperatures than the traditional solventless process (30 or 50 °C compared to 85 °C).
Footnote |
† Electronic supplementary information (ESI) available: 1H-NMR spectra and conversions, GPC-calculated number average molecular weights, weight average molecular weights, dispersity data, products photographs and molecular modelling data. See DOI: 10.1039/c8gc03567a |
This journal is © The Royal Society of Chemistry 2019 |