Homogeneous polymerization of hydrophobic monomers in a bio-based DL-menthol/1-tetradecanol eutectic mixture by ATRP and RAFT polymerization

Vanessa A. Pereira , Talita C. Rezende , Patrícia V. Mendonça *, Jorge F. J. Coelho and Arménio C. Serra *
University of Coimbra, Centre for Mechanical Engineering, Materials and Processes, Department of Chemical Engineering, Rua Sílvio Lima-Polo II, 3030-790 Coimbra, Portugal. E-mail: patmend@eq.uc.pt; aserra@eq.uc.pt

Received 30th March 2020 , Accepted 17th July 2020

First published on 17th July 2020


A bio-based eutectic mixture (EM), composed of DL-menthol and 1-tetradecanol was investigated for the first time as the solvent for the homogeneous polymerization of different hydrophobic monomers, namely methyl acrylate (MA), methyl methacrylate (MMA), styrene (Sty), butyl acrylate (n-BA), vinyl chloride (VC) and vinyl acetate (VAc), by atom transfer radical polymerization (ATRP) and/or reversible addition–fragmentation chain transfer (RAFT) polymerization. Homopolymers with low dispersity (Đ = [1.05–1.4]) were obtained by both polymerization techniques. The high chain-end functionality of the polymers was confirmed by the synthesis of well-defined block copolymers: PMA-b-PBA by ATRP and PMMA-b-PMA by RAFT. ATRP could be conducted with a catalyst concentration as low as 60 ppm near room temperature, making this an attractive eco-friendly process for the synthesis of tailor-made hydrophobic polymers. In addition, due to phase separation at the end of reaction, both the EM and the catalytic system could be easily recovered and successfully reused in a new ATRP reaction. The system reported could be very attractive from both economic and environmental standpoints.


1 Introduction

The discovery of reversible deactivation radical polymerization (RDRP) techniques represents a major contribution in the field of polymer science, as they allow the design of well-defined polymers with very narrow molecular weight distribution (Đ = Mw/Mn < 1.5) and targeted molecular weight, architecture, topology, composition and functionality.1 Reversible addition–fragmentation chain transfer (RAFT) polymerization and atom transfer radical polymerization (ATRP) are the two most explored RDRP techniques, allowing the polymerization of a wide range of vinyl monomers in different reaction media (bulk, homogeneous and heterogeneous) under mild reaction conditions.2,3 While ATRP is based on the reversible halogen transfer mediated by a metal/ligand catalytic complex (usually copper coordinated with N-containing ligands),4 RAFT polymerization relies on a reversible chain transfer process using a chain transfer agent (CTA or RAFT agent), which is typically a thiocarbonylthio compound.5 After years of research dedicated to the mechanistic aspects of these robust and versatile techniques,6 investigation is now focused on the preparation of advanced materials for different high-value applications (e.g., biomedical field).5,7 Moreover, the development of polymerization conditions aiming at the industrial implementation of these techniques is highly desirable. With respect to this, particularly in ATRP, the metal catalyst concentration required to achieve control has been reduced or even eliminated through the development of several modified ATRP techniques, such as supplemental activator and reducing agent (SARA) ATRP,8,9 activators regenerated by electron transfer (ARGET) ATRP,10 initiators for continuous activator regeneration (ICAR) ATRP,11 electrochemically mediated ATRP (eATRP),12 photo-ATRP13 and metal-free ATRP.14 In the same vein, the replacement of harmful organic solvents, which constitute a significant part of the reaction system, by eco-friendly ones represents a notable improvement in both homogeneous ATRP and RAFT. The majority of the research efforts have been focused on the polymerization of hydrophilic monomers, which can now be conducted in water (even untreated water from natural sources),15,16 which is particularly challenging for ATRP, or in eutectic mixtures (EMs).17,18 This is particularly important not only for large scale production, but also for the preparation of polymers for biomedical applications, facilitating the purification procedures and decreasing costs. However, the polymerization of hydrophobic monomers in homogeneous medium by either ATRP or RAFT has been limited to the use of solvents such as ethanol/water mixtures,19 cyclopentyl methyl ether,20 ionic liquids,21 or others which are petroleum-based in majority of the cases. From an environmental standpoint, preference should be given to solvents derived from natural sources. Therefore, the use of bio-based eco-friendly solvents for the homogeneous synthesis of well-defined hydrophobic polymers, which represent the largest class of polymers, is urgently needed. EMs have recently attracted attention of the scientific community as they are inexpensive, non-toxic and easy to prepare from natural resources.22 In fact, EMs can be obtained by simply mixing two components with high melting points, a hydrogen bond accepter (HBA) and a hydrogen bond donor (HBD), at a specific temperature, to form a mixture that is liquid at room temperature.23 Despite these very attractive features, EMs have been effectively employed only as co-solvents24 or additives25 in homogeneous polymerization of hydrophobic monomers in ATRP techniques. A very recent work reported the synthesis of well-defined poly(methyl methacrylate) (PMMA) in a choline chloride/glycerol = 1/2 (molar) EM by ARGET ATRP in the presence of air.26 However, the polymerization mixture was not homogeneous, as both the monomer and EM are not miscible, and the system failed on the controlled synthesis of other hydrophobic polymers investigated, namely polystyrene (PS), poly(4-vinylpiridine) (P4VP) or poly(2-vinylpiridine) (P2VP). To the best of our knowledge, there are no reports on the RAFT polymerization of hydrophobic monomers in EMs.

In this work, a bio-based hydrophobic EM composed of DL-menthol and 1-tetradecanol, obtained from corn mint oil and nutmeg plant oil respectively, was successfully used as a solvent for the polymerization of different hydrophobic monomers (MA: methyl acrylate, MMA: methyl methacrylate, Sty: styrene, n-BA: n-butyl acrylate, VC: vinyl chloride and VAc: vinyl acetate) by ATRP and/or RAFT under homogeneous conditions. Polymerizations exhibited controlled features, affording polymers with low Đ and chain-end functionality suitable for the preparation of block copolymers. Interestingly, phase separation at high monomer conversion (using the model monomer MA) in ATRP reactions allowed solvent and catalyst recovery and recycling, as well as easy purification of the polymer by simple vacuum drying, increasing the eco-friendly character of the method.

2 Experimental

Materials

MA (99%, Aldrich), n-BA (99% stabilized, Aldrich), MMA (99%, Aldrich), Sty (100%, Aldrich) and VAc (99%, Aldrich) were passed over a sand/alumina column before use to remove the radical inhibitor.

Dimethylsulfoxide (DMSO, analytical grade, Fisher Scientific) was dried with calcium hydride and distilled under reduced pressure before use.

Ethanol (EtOH, Panreac, 99.5%) was distilled under reduced pressure before use.

Deionized purified water (Milli-Q®, Millipore, resistivity >18 MΩ cm) was obtained by reverse osmosis.

DL-Menthol (98%, TCI), 1-tetradecanol (98%, Merck), thiourea dioxide (TDO, 98%, Aldrich), ascorbic acid (AsAc, 99% Fluka), ethyl α-bromoisobutyrate (EBiB, 98%, Aldrich), pentaerythritol tetrakis(2-bromoisobutyrate) (4-EBiB, 97%, Aldrich), ethyl α-bromophenylacetate (EBPA, 97% Sigma-Aldrich), bromoform (CHBr3, 99% Acros) copper(II) bromide (CuBr2, +99% extra pure, anhydrous, Acros), N,N,N′,N′′,N′′-pentamethyldiethylenetriamine (PMDETA, 99% Aldrich), tris[2-(dimethylamino)ethyl]amine (Me6TREN, 99%, Alfa Aesar), tris(2-aminoethyl)amine (TREN 96%, Acros), 4-cyano-4-(phenylcarbonothioylthio)pentanoic acid (CTP, 99% Sigma-Aldrich), 2-(dodecylthiocarbonothioylthio)-2-methylpropionic acid (DDMAT, 98%, Sigma-Aldrich), methyl(phenyl)carbamodithioate (CMPCD, 98%, Sigma-Aldrich), BMIM-PF6 (>98%; TCI (Tokyo Chemical Industry Co. Ltd)) and deuterated chloroform (CDCl3) were used as received.

Metallic copper (Cu(0) wire, d = 1 mm, Sigma Aldrich) was washed with HCl/methanol = 30/70 (v/v) and subsequently rinsed with methanol and dried under a stream of nitrogen following the literature procedures.27

VC (99%) was kindly supplied by CIRES Lda, Portugal and used as received.

The bio-based EM composed of DL-menthol[thin space (1/6-em)]:[thin space (1/6-em)]1-tetradecanol = 2[thin space (1/6-em)]:[thin space (1/6-em)]1 (molar) was prepared by mixing the two compounds under stirring at 60 °C, until a homogeneous liquid was formed, as described in the literature.28

Techniques

The molecular weight parameters of the polymers were determined using a size exclusion chromatography (SEC) setup from Viscotek (Viscotek TDAmax), equipped with a differential viscometer (DV), and right-angle laser light scattering (RALLS, Viscotek), low-angle laser light scattering (LALLS, Viscotek) and refractive index (RI) detectors. The column set consisted of a Viscotek Tguard column, followed by one Viscotek T2000 column (6 μm), one Viscotek T3000 column (6 μm) and one Viscotek LT4000L column (7 μm). The dual piston pump was set with a flow rate of 1 mL min−1. The eluent (THF) was previously filtered through a 0.2 μm filter. The system was also equipped with an on-line degasser. The tests were carried out at 30 °C using an Elder CH-150 heater. Before injection (100 μL), the samples were filtered through a polytetrafluoroethylene (PTFE) membrane with 0.2 μm pores. The system was calibrated with narrow PS standards. The molecular weight (MSECn) and dispersity (Đ) of the synthesized polymers were determined by multidetector calibration (dn/dc PMA = 0.063 mL g−1, dn/dc PMMA = 0.085 mL g−1, dn/dc PS = 0.185 mL g−1, dn/dc PVC = 0.105 mL g−1, dn/dc PVAc = 0.05 mL g−1, and dn/dc PBA = 0.064 mL g−1) using OmniSEC software version 4.6.1.354.

400 MHz 1H nuclear magnetic resonance (NMR) spectra of reaction mixture samples were recorded on a Bruker Avance III 400 MHz spectrometer with a 5 mm TIX triple resonance detection probe, in CDCl3. Monomer conversions (except for VC polymerization) were determined following the decrease of the integral of initial monomer in comparison with the integral of the EM as an internal standard, using MestRenova software version 12.0.0-20080.

The UV/Vis studies were performed with a JASCO V-530 spectrophotometer. The analyses were carried out in the 400–1100 nm range at room temperature. A calibration curve was built using solutions of CuBr2 with a known concentration (from 1.5 to 7.5 mM) in an EM/MA mixture to determine the concentration of recovered copper from ATRP reactions.

Atomic absorption spectroscopy (AAS) was performed on a PerkinElmer (Model 3300, USA) to evaluate the concentration of copper in recovered PMA-Br.

Procedures

Synthesis of hydrophobic polymers by Cu(0)-catalyzed SARA ATRP. For the polymerization of MA, the following procedure was employed. MA (3.0 mL, 32.8 mmol) and EBiB (65.2 mg, 0.3 mmol) were placed in a Schlenk reactor, containing a magnetic stir bar, followed by addition of a solution of CuBr2 (1.6 mg, 7.3 μmol) and Me6TREN (8.5 mg, 40.0 μmol) in the EM (4.0 mL). Cu(0) wire (l = 5 cm) was added to the reactor, which was subsequently sealed with a glass stopper and frozen in liquid nitrogen. The Schlenk reactor containing the reaction mixture was deoxygenated with five freeze–vacuum–thaw cycles and purged with nitrogen. The reactor was placed in a water bath at 30 °C and the reaction was allowed to proceed with stirring. During the polymerization, different reaction mixture samples were collected under a nitrogen flow. The samples were analyzed by 1H NMR spectroscopy to determine the monomer conversion and by SEC to determine the MSECn and Đ of the polymer. The purification step was performed by simply decanting the solvent, as there was phase separation at the end of the reaction. The solid phase containing the polymer, residual monomer and solvent was placed in a fume hood for 24 h, and then dried in a vacuum oven until a constant weight was achieved. The concentration of copper in the final polymer was determined by AAS. The PMA-Br macroinitiator used for chain extension was purified by dissolving the polymer in THF and passing the solution through an alumina column to remove residual copper. The pure polymer was obtained after precipitation in methanol, followed by drying in a vacuum oven.

The polymerizations using other reducing agents or monomers were conducted using the same procedure, but adjusting the polymerization components (e.g., ligand) as needed.

Typical chain extension of the PMA-Br macroinitiator with n-BA by SARA ATRP. A mixture of n-BA (2.0 mL, 13.81 mmol) and pure PMA-Br (404.5 mg, 55.0 μmol, MSECn = 7.3 × 103, Đ = 1.12) obtained at 83.7% monomer conversion by SARA ATRP in EM, was placed in a Schlenk reactor, containing a magnetic stir bar, followed by a solution of CuBr2 (1.2 mg, 6.00 μmol) and Me6TREN (6.4 mg, 28 μmol) in DMSO (2.0 mL). Cu(0) wire (l = 5 cm) was added to the reactor, which was subsequently sealed with a glass stopper and frozen in liquid nitrogen. The Schlenk reactor containing the reaction mixture was deoxygenated with five freeze–vacuum–thaw cycles and purged with nitrogen. The reactor was placed in a water bath at 30 °C and the reaction was allowed to proceed for 2.3 h (convn-BA = 76.2%) with stirring. The monomer conversion was determined by 1H NMR spectroscopy and the MSECn and Đ of the PMA-b-PBA block copolymer were determined by SEC. The final reaction mixture was diluted in THF and passed through an alumina column to remove residual copper. The pure copolymer was obtained after precipitation in methanol, followed by drying in a vacuum oven.
Catalyst and solvent recovery and reuse in SARA ATRP of MA. MA (17.0 mL, 185.7 mmol) and EBiB (369.8 mg, 1.9 mmol) were placed in a Schlenk reactor, containing a magnetic stir bar, followed by addition of a solution of CuBr2 (9.3 mg, 42.0 μmol) and Me6TREN (48.1 mg, 0.2 mmol) in EM (22.7 mL). Cu(0) wire (l = 10 cm) was added to the reactor, which was subsequently sealed with a glass stopper and frozen in liquid nitrogen. The Schlenk reactor containing the reaction mixture was deoxygenated by five freeze–vacuum–thaw cycles and purged with nitrogen. The reactor was placed in a water bath at 30 °C and the reaction was allowed to proceed with stirring until full monomer conversion was achieved.

The final reaction mixture was analyzed by 1H NMR spectroscopy to determine the monomer conversion and by SEC to determine the MSECn and Đ of PMA-Br. The liquid phase (upper phase) was decanted and the concentration of the copper complex in the recovery liquid was estimated by UV/Vis spectroscopy. The Cu(0) wire was weighted before and after polymerization to determine the amount consumed during the reaction. The percentage of catalyst recovery was estimated taking into account the initial amount of CuBr2 used, the amount of Cu(0) consumed and the concentration of CuBr2 in the recovery reaction mixture. Then, both the catalytic complex and the EM recovered were used in another polymerization following our procedure described in the literature.24 The solid phase (lower phase) of the reaction mixture containing the polymer, residual monomer and solvent was placed in a fume hood for 24 h and then dried in a vacuum oven until a constant weight was achieved and analyzed by AAS to determine the concentration of copper in the final polymer.

Synthesis of hydrophobic polymers by RAFT polymerization. For the polymerization of MA, the following procedure was followed. A mixture of MA (3.0 mL, 33.3 mmol), DDMAT (48.6 mg, 0.1 mmol), AIBN (5.5 mg, 33.0 μmol), and EM (6.0 mL) were added to a Schlenk reactor, containing a magnetic stir bar, and frozen in liquid nitrogen. The reactor was deoxygenated by five freeze–vacuum–thaw cycles, purged with nitrogen and placed in an oil bath at 60 °C with stirring. During the polymerization, different reaction mixture samples were collected under a nitrogen flow. The samples were analyzed by 1H NMR spectroscopy to determine the monomer conversion and by SEC to determine the MSECn and Đ of the polymer. The pure polymer was obtained after precipitation in methanol, followed by drying in a vacuum oven.

The polymerizations using other monomers were conducted using the described procedure, but adjusting the polymerization components (e.g., RAFT agent) as needed.

Synthesis of PVC by RAFT polymerization. A 50 mL Ace glass 8645#15 pressure tube, equipped with a bushing and plunger valve, was charged with a mixture of CMPCD (64.7 mg, 0.3 mmol), AIBN (23.3 mg, 0.5 mmol), and EM (5.0 mL) (previously bubbled with nitrogen for about 5 min). Condensed VC (5 mL, 72.8 mmol) was added into the tube, which was subsequently closed. The exact amount of VC was determined gravimetrically. The tube was placed in liquid nitrogen and degassed through the plunger valve by applying reduced pressure and filling the tube with nitrogen for about 20 minutes. The valve was closed and the tube reactor was placed in a water bath at 42 °C with stirring. The reaction was stopped by plunging the tube into ice water. The tube was slowly opened, excess VC was evaporated inside a fume hood and the mixture was precipitated in methanol. The polymer was recovered by filtration and dried in a vacuum oven until a constant weight was achieved. The monomer conversion was determined gravimetrically. SEC was used for the determination of PVC's MSECn and Đ.
Typical chain extension of PMMA-macroCTA with MA by RAFT polymerization. A mixture of PMMA-CTA (666.3 mg, 133.0 μmol, MSECn = 3500, Đ = 1.08), obtained at 51% monomer conversion by RAFT in the EM, MA (3.0 mL, 28.3 mmol), AIBN (5.5 mg, 33.0 μmol) and DMSO (6.0 mL) were added to a Schlenk reactor, containing a magnetic stir bar, and frozen in liquid nitrogen. The reactor was deoxygenated with five freeze–vacuum–thaw cycles, purged with nitrogen and placed in an oil bath at 60 °C with stirring. The reaction was allowed to proceed for 3 h (convMA = 35.3%). The monomer conversion was determined by 1H NMR spectroscopy and the MSECn and Đ of the PMMA-b-PMA block copolymer were determined by SEC. The pure copolymer was obtained after precipitation in methanol, followed by drying in a vacuum oven.

3 Results and discussion

ATRP using reline, which is a choline chloride/urea-based EM, has been successfully employed by our research group for the polymerization of several hydrophilic monomers.17 Very recently, the first RAFT polymerization in a 100% EM has also been reported for the preparation of poly(2-hydroxyethyl methacrylate) (PHEMA).18 However, EMs have only been used as a co-solvent for the controlled polymerization of hydrophobic monomers, due to the lack of solubility of hydrophobic polymers in most EMs.17,18,24 Recently, hydrophobic EMs based on DL-menthol have been reported as cheap, biodegradable and natural-compound based solvents.29,30 In this work, different hydrophobic EMs composed of DL-menthol as the HBA and different HBD compounds, namely acetic acid, lactic acid, lauric acid or 1-tetradecanol, have been investigated for the dissolution of several hydrophobic monomers, such as MA, MMA, Sty, VAc, VC or n-BA. The results showed that all EMs are miscible with the monomers studied (Table S1), which could make them promising polymerization solvents. The mixture composed of menthol and 1-tetradecanol was selected as the solvent for further conducting the polymerization investigation, as the EMs based on acids such as HBDs exhibited very low pH (pH ≈ 6 vs. pH ≈ 2.5, using 1-tetradecanol and acids, respectively), which could lead to catalyst poisoning and loss of control during ATRP.31 Moreover, 1-tetradecanol is a natural-compound based substance obtained from the hydrogenation of its esters, which is found primarily in nutmeg, and also in palm kernel oil and coconut oil.32 Therefore, the final mixture DL-menthol/1-tetradecanol (2/1) is 100% bio-based and thus very promising to be used as a polymerization solvent.

SARA and ARGET ATRP of MA, MMA and Sty

For this study, MA was firstly used as a model monomer in order to compare the results obtained here with those reported in the literature including the ones using reline as a co-solvent in Cu(0)-catalyzed SARA ATRP.24 Polymerization kinetics were followed for different targeted DP values (222, 100 and 50), using 225 ppm of CuBr2 as the deactivator (in comparison with the amount of monomer) at 30 °C in the DL-menthol/1-tetradecanol EM. The results (Table S2) showed first-order kinetics with respect to monomer conversion, an excellent agreement between theoretical and experimental molecular weights with low dispersity (Đ < 1.2), similar to what was reported using ethanol (EtOH)/EM (reline) = 90/10 (v/v) as the solvent.24 As expected, the rate of polymerization decreased with the increase of the targeted DP value due to the decrease in the concentration of the propagating radicals. In addition to linear PMA-Br, a well-defined 4-arm star-shaped polymer (Mthn = 7.2 × 103; MSECn = 7.3 × 103; Đ = 1.06) was also synthesized to confirm the ability of the system to yield different polymer architectures (Table S2, entry 6). In order to evaluate the potential of the developed system, the polymerization features were compared with the ones obtained for the SARA ATRP of MA, under similar conditions, but using different reference solvents: (i) DMSO, which is one of the most commonly used organic solvents in ATRP;33 (ii) EtOH/H2O = 90/10 (v/v), which represents an eco-friendly solvent for the polymerization of hydrophobic monomers34 and (iii) BMIM-PF6/DMSO = 50/50 (v/v), as the EM, which is considered as a “greener” alternative to ionic liquids.35 The results (Table 1) showed that the control over the molecular weight was very good and similar, regardless of the solvent used. The reaction performed in the EM was slower than that using either DMSO or BMIM-PF6/DMSO = 50/50 (v/v) as the solvent (Table 1). However, the reaction rate was similar to that obtained using EtOH/H2O = 90/10 (v/v) as the solvent (kappp = 0.45 h−1vs. 0.42 h−1), which is also a very well-known solvent mixture used in ATRP,19,36,37 showing the relevance of the developed system. To evaluate the limits of the system, the CuBr2 concentration was decreased from 225 ppm to 60 ppm. Kinetics results presented in Fig. 1 show that the rate of reaction was in the same order for the range of CuBr2 concentrations investigated and reasonable control over the PMA-Br molecular weight, yet close to the acceptable upper limit value (Đ < 1.5), could be obtained using a copper concentration as low as 60 ppm.
image file: d0gc01136c-f1.tif
Fig. 1 Kinetic plots of (a) ln[M0]/[M] vs. time and (b) MSECn and Mw/Mnvs. monomer conversion for the SARA ATRP of MA in DL-menthol/1-tetradecanol EM using different concentrations of copper. Conditions: [MA]0/[EBiB]0/[Cu(0)]0/[CuBr2]0/[Me6TREN]0 = 100/1/Cu(0) wire/0.02/0.11 (250 ppm) or 0.015/0.08 (150 ppm) or 0.006/0.03 (60 ppm); Cu(0) wire: l = 5 cm.
Table 1 Reaction rate, monomer conversion and molecular weight parameters of PMA-Br prepared in different solvents at 30 °C by SARA ATRP. Conditions: [MA]0/[EBiB]0/[Cu(0)]0/[CuBr2]0/[Me6TREN]0 = 100/1/Cu(0) wire/0.02/0.11, [MA]0/[solvent]0 = 0.75 (v/v)
Entry Solvent k appp (h−1) t (h) Conv. (%) M thn × 10−3 M SECn × 10−3 Đ
1 BMIM-PF6/DMSO = 50/50 (v/v) 5.78 1.0 96 8.6 6.7 1.08
2 DMSO 4.56 1.0 97 8.2 8.0 1.13
3 EtOH/H2O = 90/10 (v/v) 0.45 5.5 93 8.3 8.5 1.04
4 DL-Menthol/1-tetradecanol 0.42 6.1 80 7.2 7.4 1.16


The very low concentration of the catalyst associated with the use of a bio-based EM makes this system very promising for industrial application as well as for the preparation of polymers that will require minimal or no purification.

The presence of active chain-ends in the polymers prepared in the EM was evaluated by carrying out a chain extension experiment with an isolated PMA-Br macroinitiator (Mthn = 7.2 × 103; MSECn = 7.4 × 103, Đ = 1.12, obtained at 83.7% monomer conversion), with n-BA by SARA ATRP in DMSO. The ensuing PMA-b-PBA block copolymer presented low dispersity (Đ = 1.24) and a complete shift of the SEC trace from the macroinitiator to the extended polymer was observed (Fig. 2), which confirms the high retention of high chain-end functionality of the PMA-Br obtained in the EM solvent. Only a small peak corresponding to the PMA-Br macroinitiator is visible in the SEC trace of the PMA-b-PBA copolymer, corresponding to 9% of unreacted chains.


image file: d0gc01136c-f2.tif
Fig. 2 Normalized SEC traces of the PMA-Br macroinitiator and PMA-b-PBA-Br block copolymer obtained after chain extension by SARA ATRP in DMSO.

The use of DL-menthol/1-tetradecanol as the solvent for ATRP was also investigated for the ATRP systems operating with different non-metallic reducing agents (RAs), namely AsAc,38 Na2S2O4[thin space (1/6-em)]39 and TDO,36 for the polymerization of MA. The results presented in Table 2 show that the polymerizations mediated by either Na2S2O4 or TDO resulted in very low monomer conversion, most probably due to the lack of solubility of these RA in the reaction mixture. AsAc was found to be a promising alternative to Cu(0) as a RA, giving controlled polymers, yet with slightly higher dispersity under the same polymerization conditions (Đ = 1.39, Table 2).

Table 2 Monomer conversion and molecular weight parameters of PMA-Br prepared by SARA or ARGET ATRP, using different reducing agents, in DL-menthol/1-tetradecanol at 30 °C. Conditions: [MA]0/[EBiB]0/[RA]0/[CuBr2]0/[Me6TREN]0 = 222/1/1/0.05/0.25, [MA]0/[solvent]0 = 0.75 (v/v)
Entry RA Technique t (h) Conv. (%) M thn × 10−3 M SECn × 10−3 Đ
a [CuBr2]0/[Me6TREN]0 = 0.02/0.11 (molar). b Not detected by SEC.
1 Na2S2O4 SARA ATRP 22.2 8 1.7
2 TDO ARGET ATRP 21.2 26 5.3 3.8 1.11
3a AsAc ARGET ATRP 3.7 69 6.2 6.6 1.39


The versatility of the new solvent for ATRP was further evaluated through the polymerization of other hydrophobic monomers, namely MMA and Sty. Very good control was obtained for both PMMA-Br and PS-Br (Đ ≈ 1.09, Fig. 3). However, maximum monomer conversion of around 50% was achieved for MMA and 40% for Sty (lower than the one obtained for PMA for the same DP value), most probably due to the lower solubility of these polymers in the EM compared to PMA.


image file: d0gc01136c-f3.tif
Fig. 3 SEC traces of PMMA-Br (red) and PS-Br (blue) prepared by SARA ATRP in DL-menthol/1-tetradecanol at 30 °C and 50 °C, respectively. Conditions: [MMA]0/[EBPA]0/[CuBr2]0/[PMDETA]0/[Cu(0)] = 100/1/0.02/0.11/Cu(0) wire; [Sty]0/[EBiB]0/[CuBr2]0/[Me6TREN]0/[Cu(0)] = 100/1/0.04/0.18/Cu(0); Cu(0) wire: l = 5 cm, [MA]0/[solvent]0 = 0.75 (v/v). The SEC traces of a well-defined PS standard is presented (black) for comparison purposes.

Solvent and catalyst reuse ATRP

In all experiments performed in this work, at the end of the polymerization a complete phase separation between the polymer and EM solvent was observed, (Fig. 4), most probably due to the increase in the molecular weight of the polymer, as it was reported in the system using EtOH/EM = 90/10 (v/v).24 Under the conditions used here, the separation of PMA started to occur (visual observation) at around 35% of conversion (for DP = 100), corresponding to a molecular weight of around 3000. Remarkably, the results showed that even with the precipitation of the polymer, both dispersity (Đ ≈ 1.25) (see Table 3) and chain-end functionality were not affected. It was hypothesized that this phase separation could limit the molecular weight of the obtained polymers. To verify the upper limit of molecular weight of PMA achievable by SARA ATRP in the EM, a polymerization targeting a DP value of 500 (Mthn target = 43[thin space (1/6-em)]240) was performed (Table S2, entry 5). The resulting PMA showed Mthn = 22.1 × 103, MSECn = 19.7 × 103 and Đ = 1.12, which are higher than those of previously synthesized polymers. However, the monomer conversion achieved was 52%, suggesting that in fact the reaction could be limited by the solubility of the polymer in the EM. An additional experiment by increasing the amount of the EM employed was performed to investigate if a higher molecular weight could be achieved (Table S2, entry 6). However, no improvement was observed. Nevertheless, it is worth mentioning that many applications explored for polymers prepared by ATRP, including the ones related with the biomedical field or dispersant, employ polymers with molecular weights below <20k.40–42 The two phases formed at the end of the polymerization were analyzed by 1H NMR in order to confirm their composition. The results showed that the liquid phase (upper phase) was composed of the EM solvent and traces of monomer (Fig. S1), while the solid phase (lower phase) corresponded to the polymer, and traces of monomer and solvent (Fig. S2). Moreover, the liquid phase showed a green colour, which is indicative of the presence of the catalytic complex. The concentration of copper was determined by UV/Vis spectrophotometry and the percentage of catalytic recovery was calculated (Table 3) taking into account the initial concentration of copper and the amount of Cu(0) wire consumed. In the search for environmentally friendly ATRP conditions, this DL-menthol-based EM allows not only the preparation of hydrophobic polymers, with “living” and controlled features, but, it can also potentially provide a straightforward route for inexpensive separation of polymers, by simple decantation of the liquid part of the reaction mixture.
image file: d0gc01136c-f4.tif
Fig. 4 Photograph at the end of a typical SARA ATRP of MA in DL-menthol/1-tetradecanol at 30 °C. Conditions: [MA]0/[EBiB]0/[Cu(0)]0/[CuBr2]0/[Me6TREN]0 = 100/1/Cu(0) wire/0.02/0.11, [MA]0/[solvent]0 = 0.75 (v/v).
Table 3 Molecular weight of PMA-Br, solvent and catalyst recovery parameters after the SARA ATRP of MA in DL-menthol/1-tetradecanol at 30 °C. Conditions: [MA]0/[EBiB]0/[Cu(0)]0/[CuBr2]0/[Me6TREN]0 = 100/1/Cu(0) wire/0.02/0.11, [MA]0/[solvent]0 = 0.75 (v/v)
Polymerization V T (mL) t (h) Conv. (%) M thn × 10−3 M SECn × 10−3 Đ % catalyst recovery (molar) % EM recovery (volume)
a EM containing CuBr2/Me6TREN was recovered from polymerization 1. b Both EM containing CuBr2/Me6TREN and Cu(0) were recovered from polymerization 1. c V T = VMA + VEM.
1 40 5.1 73 6.4 6.1 1.12
21.5 83 7.2 6.9 1.25 55 86
2a 12 5.8 83 7.4 6.0 1.19
21.5 92 8.1 6.9 1.22 54 76
3b 12 22.0 85 7.5 7.5 1.29 58 69


However, for some applications, more standard purification procedures could be required. At the same time, the ability to reuse both the catalytic system and solvent is extremely advantageous from the economic standpoint. In this sense, the recovery and reuse of both the solvent and catalytic system was tested using MA as the monomer. First, a larger scale (40 mL) SARA ATRP reaction was carried out (Table 3, polymerization 1) to allow the recovery of enough solvent for consecutive polymerizations. The results showed that performing a larger scale reaction did not affect the polymerization control, which is a worthy indication considering the future implementation of the method on a larger scale (Table 3, polymerization 1). After ensuring that the monomer conversion reached its maximum value (83%), the reaction was stopped and the liquid phase was analyzed to determine the concentration of copper present. The results showed that it was possible to recover 55% of the catalytic complex (molar) and 86% of the solvent volume, after decantation (Table 3, polymerization 1). For the second polymerization (Table 3, polymerization 2), a precise amount of the EM recovered from the first polymerization, containing the required amount of catalytic system, was used. The EM was also added to the system to correct the volume of the solvent to ensure an appropriate monomer/solvent ratio. Finally, fresh monomer, initiator and a new Cu(0) wire were added to the mixture.

The results showed that the recovery experiment (Table 3, polymerizations 2 and 3) exhibited similar features to the original reaction (Table 3, polymerization 1), with high monomer conversion, good agreement between theoretical and experimental molecular weight, low dispersity and high percentage of solvent recovery. These are very exciting results which suggest that the reported method could be employed for the synthesis of hydrophobic polymers in a more sustainable manner. Encouraged by these data, we decided to also test the reusability of the Cu(0) wire, by adding it to the reactor (after washing and activation) along with the EM containing the catalytic system, for further polymerization (Table 3, polymerization 3). In fact, this experiment demonstrated that the CuBr2/Me6TREN/Cu(0) wire catalytic system can be completely reused with great success, allowing the synthesis of well-defined PMA-Br with similar features to those obtained in the original polymerization (Table 3, polymerization 1 vs. polymerization 3). In addition, the final lower phase containing the polymer was vented in a fume hood for 24 h and then dried under reduced pressure to remove traces of solvent and the unreacted monomer. No additional purification procedures (e.g., washing with solvent) were carried out in order to confirm the concentration of copper present in the polymer at the end of the reaction. Atomic absorption results showed that the copper residue on the recovered polymer was 100 ppm, which could be acceptable for several applications. These are very encouraging results, which suggest that well-defined PMA could be obtained in a straightforward and affordable manner. In depth investigation of the protocol optimization of the recycling process as well as its application to other monomer families is out of the scope of this article and will be reported elsewhere.

RAFT of MA, MMA, Sty, VAc and VC in DL-menthol/1-tetradecanol

For the controlled polymerization of certain vinyl monomers, namely less-activated monomers such as VAc, RAFT polymerization is preferable over ATRP.43 Taking this into account, the bio-based EM was also investigated as a solvent for the RAFT polymerization of VAc and VC (also less-activated monomer), as well as for the previously studied hydrophobic monomers. To the best of our knowledge, there is just one report on RAFT polymerization using a choline chloride-based EM as the solvent for the synthesis of hydrophilic PHEMA.18 The results presented in Table 4 confirmed the possibility to prepare well-defined hydrophobic polymers by RAFT in DL-menthol/1-tetradecanol, with similar results to those reported in the literature using other solvents,44–47 except for Sty and VC, for which the maximum monomer conversion achieved was lower than that reported in the literature (conversion = 80% for Sty and 38% for VC).48,49 However, using the bio-based EM as the solvent, it is possible to achieve better control over molecular weight of PVC (Đ = 1.33, instead of Đ = 1.70).49 It is interesting to note that it was possible to attain higher molecular weight in the RAFT polymerization of MA, MMA and Sty in comparison with the that obtained through ATRP (Table 2, Table S2 and Fig. 3vs.Table 4). We have hypothesized that the higher temperature employed for RAFT polymerization could provide improved solubility of the polymers in the EM. However, a controlled SARA ATRP of MMA was performed in the EM at 60 °C and the results obtained were similar to those observed for the reaction at 30 °C. The fact that a higher percentage of solvent in comparison to the monomer was employed for RAFT polymerizations could also allow better dissolution of the polymers. Nevertheless, similar to what was observed for ATRP, there was phase separation between the polymer and solvent at the end of polymerization, suggesting that the solvent could also be recovered for further use. The high chain-end functionality of the PMMA-macroCTA obtained at very high monomer conversions (98%) by RAFT in DL-menthol/1-tetradecanol was confirmed by the preparation of a well-defined PMMA-b-PMA block copolymer (MSECn = 8.0 × 103; Đ = 1.07), with no sign of dead chains (Fig. S3).
Table 4 Monomer conversion and molecular weight parameters of hydrophobic polymers prepared by RAFT polymerization in DL-menthol/1-tetradecanol. Conditions: [monomer]0/[RAFT agent]0/[AIBN]0 = 250/1/0.25; [monomer]0/[solvent] = 1/2 (v/v)
Entry Monomer RAFT agent T (°C) t (h) Conv. (%) M thn × 10−3 M SECn × 10−3 Đ
1 MA DDMAT 60 3 87 19.1 18.9 1.10
2 MMA CTP 60 16 99 24.7 21.4 1.11
3 Sty DDMAT 60 48 46 12.5 9.9 1.06
4 VAc CMPCD 60 72 81 17.6 13.0 1.13
5 VC CMPCD 42 72 22 3.6 6.4 1.33


The results reported here are extremely encouraging, suggesting that a natural-compound based EM could be used as a solvent for the preparation of complex hydrophobic polymeric structures under homogeneous conditions. The fact that this solvent can be employed in both RAFT polymerization and ATRP expands the range of composition of the targeted copolymers, through the combination of different monomers, and eventually the use of concurrent or sequential ATRP and RAFT to yield complex structures.

4. Conclusions

A hydrophobic EM entirely based on natural compounds (DL-menthol and 1-tetradecanol) is reported for the first time as the only solvent for well-controlled ATRP and RAFT polymerization of several hydrophobic monomers (MA, MMA, Sty, n-BA, VC, and VAc) under homogeneous conditions. The system reported, allowed the recovery of both catalytic system and EM, which could be reused in a subsequent SARA ATRP with no deleterious effect on the polymerization features. The preparation of well-defined PMA-b-PBA (by ATRP) and PMMA-b-PMA (by RAFT) block copolymers proved the “living” character of the polymers synthesized in the EM. The system reported here opens a new route for the preparation of well-defined hydrophobic polymers in a more sustainable manner.

Conflicts of interest

There are no conflicts to declare.

Acknowledgements

Vanessa Pereira acknowledges the FCT (Fundação para a Ciência e Tecnologia) for her doctoral grant (SFRH/BD/138793/2018).

Funding also came from the MATIS (CENTRO-01-0145-FEDER-000014), co-financed by the European Regional Development Fund (FEDER) through the “Programa Operacional Regional do Centro” (CENTRO2020).

This research is sponsored by the FEDER funds through the program COMPETE – Programa Operacional Factores de Competitividade – and by national funds through the FCT – Fundação para a Ciência e a Tecnologia, under the project UID/EMS/00285/2020.

The 1H NMR data was collected at the UC-NMR facility which is supported in part by the FEDER – European Regional Development Fund through the COMPETE Programme (Operational Programme for Competitiveness) and by National Funds through FCT (Portuguese Foundation for Science and Technology) through grants REEQ/481/QUI/2006, RECI/QEQ-QFI/0168/2012, CENTRO-07-CT92-FEDER-002012, and Rede Nacional de Ressonância Magnética Nuclear (RNRMN).

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Footnote

Electronic supplementary information (ESI) available. See DOI: 10.1039/d0gc01136c

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