Glycol-functionalized ionic liquids for high-temperature enzymatic ring-opening polymerization

Article abstract of DOI:10.1039/c8ra07733a

Enzymatic ring-opening polymerization (ROP) is a benign method for preparing polyesters, such as polylactides and other polylactones. These reactions are typically carried out at relatively high temperatures (60-130 °C), however, there is a deficiency of enzyme-compatible solvents for such thermally-demanding biocatalytic processes. In this study, we have prepared a series of short-chained glycol-grafted ionic liquids (ILs) based on a phosphonium, imidazolium, pyridinium, ammonium, or piperidinium cationic headgroup. Most of these glycol-grafted ILs exhibit relatively low dynamic viscosities (33-123 mPa s at 30 °C), coupled with excellent short-term thermal stabilities with decomposition temperatures (T_dcp) in the 318-403 °C range. Significantly, the long-term thermal stability under conditions matching those for enzymatic ROP synthesis (130 °C for 7 days) is excellent for several of these task-specific ILs. Using Novozym 435-catalyzed ROP, these ILs are demonstrated to be viable solvents for the enzymatic production of reasonable yields (30-48%) of high molecular mass (M_w ～20 kDa) poly(l-lactide) and poly(?-caprolactone) compared to solventless conditions (12-14 kDa).

Full text of DOI:10.1039/c8ra07733a

RSC Advances
View Article Online
View Journal | View Issue
PAPER
Glycol-functionalized ionic liquids for high-
temperature enzymatic ring-opening
Cite this: RSC Adv., 2018, 8, 36025
polymerization†
a
b
Lennox O. Afriyie,a Nathaniel E. Larmb and Gary A. Baker
*
Hua Zhao,
Enzymatic ring-opening polymerization (ROP) is a benign method for preparing polyesters, such as
polylactides and other polylactones. These reactions are typically carried out at relatively high
temperatures (60–130 ꢀC), however, there is a deficiency of enzyme-compatible solvents for such
thermally-demanding biocatalytic processes. In this study, we have prepared a series of short-chained
glycol-grafted ionic liquids (ILs) based on a phosphonium, imidazolium, pyridinium, ammonium, or
piperidinium cationic headgroup. Most of these glycol-grafted ILs exhibit relatively low dynamic
viscosities (33–123 mPa
s
at 30 ꢀC), coupled with excellent short-term thermal stabilities with
decomposition temperatures (Tdcp) in the 318–403 ꢀC range. Significantly, the long-term thermal
stability under conditions matching those for enzymatic ROP synthesis (130 ꢀC for 7 days) is excellent for
several of these task-specific ILs. Using Novozym 435-catalyzed ROP, these ILs are demonstrated to be
viable solvents for the enzymatic production of reasonable yields (30–48%) of high molecular mass (Mw
ꢁ20 kDa) poly(L-lactide) and poly(3-caprolactone) compared to solventless conditions (12–14 kDa).
Received 17th September 2018
Accepted 17th October 2018
DOI: 10.1039/c8ra07733a
rsc.li/rsc-advances
conventional ILs are typically reported to be thermally stable at
these temperatures, they can slowly decompose when sub-
Introduction
jected to long-term thermal stresses. Thermal decomposition
of alkylammonium salts follows a Hoffmann-type b-elimina-
tion in the presence of base to yield an amine and alkene while
imidazolium ionic liquids degrade to alkylimidazole and
imidazole, or even smaller fragments.5 The degraded ions can
negatively impact the enzymatic polymerization reaction.
Therefore, it is crucial to design thermally-stable ILs compat-
ible with such prolonged, high-temperature enzymatic
applications.
Enzymatic ring-opening polymerization (ROP) is a benign
approach compared with metal-catalyzed methods for
synthesizing biodegradable polyesters such as polylactides
(PLAs) and polylactones. Among various reaction systems,
ionic liquids (ILs) have been identied as novel reaction media
alternatives to conventional organic solvents (e.g., toluene,
heptane) in enzymatic ROP reactions. Common ILs being
evaluated for enzymatic ROP include those based on imida-
zolium and pyridinium cations (such as 1-butyl-3-
methylimidazolium, BMIM+) paired to anions such as tetra-
uoroborate (BF4ꢂ), hexauorophosphate (PF6ꢂ), or bis(tri-
uoromethylsulfonyl)imide (Tf2Nꢂ).1–4 However, inconsistent
results have been reported in terms of molecular mass and
yields for polylactides and polylactones produced by enzy-
matic ROP in these ILs.1 As indicated by our group previously,
one important reason is the lack of ne control over reaction
conditions such as the water content in ILs and enzymes.2
Another reason is tied to the requirement for long-term
thermal stability of ILs due to the fact that the reaction is
conducted at fairly high reaction temperatures (up to 130–150
ꢀC) over a period of as long as 7–10 days. Although
Ionic liquids are frequently stated to possess high thermal
stabilities; the onset decomposition temperatures (Tonset)‡ for
many ILs reportedly range from 200–400 ꢀC.6,7 In general,
imidazolium salts are more thermally stable than alky-
lammonium, piperidinium, or pyridinium-based ILs. Mean-
ꢂ
while, ILs containing anions like Tf2Nꢂ, PF6ꢂ, and BF4 are
generally more stable than those comprising dicyanamide,
nitrate, halide, amino acid, or carboxylate anions.7
Phosphonium-based ILs typically have very high thermal
stability (300–400 ꢀC), however, alkyl-substituted phospho-
nium salts typically exhibit high melting points (i.e., solid or
viscous/waxy liquid at room temperature).8,9 Ether-
functionalized phosphoniums can, however, be prepared as
room-temperature liquids possessing low viscosity (35–85
mPa s) coupled with high decomposition temperatures of
aDepartment of Chemistry and Biochemistry, University of Northern Colorado, Greeley,
CO 80639, USA. E-mail: hua.zhao@unco.edu; huazhao98@gmail.com
bDepartment of Chemistry, University of Missouri, Columbia, MO 65211, USA
† Electronic supplementary information (ESI) available. See DOI:
10.1039/c8ra07733a
‡ Tonset is the intersection of the baseline mass and the tangent of the mass
dependence on the temperature curve as decomposition occurs.
This journal is © The Royal Society of Chemistry 2018
RSC Adv., 2018, 8, 36025–36033 | 36025

View Article Online
RSC Advances
Paper
ꢁ400 C for a 10% mass loss.10 Toward further improving the
ꢀ
Experimental
Materials
thermostability of phosphonium solvents, the Wasserscheid
group11 established that tetraphenylphosphonium bis(tri-
uoromethylsulfonyl)imide ([PPh4][Tf2N]) has a Tonset value of
420 ꢀC and a long-term thermal stability (1% mass loss due to
thermal decomposition per year at 301 ꢀC). However, this salt
displays a high melting point of 134 ꢀC, although a eutectic
composition of [PPh4][Tf2N] : Cs[Tf2N] ¼ 1 : 2.13 (i.e., 32 mol%
The following enzymes and chemicals were purchased from
Sigma-Aldrich (St. Louis, MO): L-(ꢂ)-lactide (Catalog
#367044), Candida antarctica lipase B (CALB) immobilized on
acrylic resin (Novozym 435; Catalog #L4777, Batch
#SLBP0766V, purchased in March 2016), and polymer-bound
triphenylphosphine (100–200 mesh, extent of labeling:
ꢁ3.0 mmol gꢂ1 loading, polystyrene with 2% cross-linked
with divinylbenzene) (Catalog #366455). Both 2-bromoethyl
methyl ether produced by BeanTown Chemical (Hudson,
NH), and lithium bis(triuoromethylsulfonyl)imide (Li
[Tf2N]) produced by Matrix Scientic (Columbia, SC) were
supplied by VWR (Radnor, PA). Diethylene glycol mono-
methyl ether, triethylene glycol monomethyl ether, lithium
bis(pentauoroethanesulfonyl)imide (Li[beti]), and 3-capro-
lactone were purchased from TCI America (Portland, OR). 1-
Butyl-3-methylimidazolium hexauorophosphate ([BMIM]
[PF6], high purity) and 1-butyl-3-methylimidazolium bis(tri-
uoromethylsulfonyl)imide ([BMIM][Tf2N], synthesis grade)
were obtained through VWR and were products of Merck
KGaA (EMD Millipore Corporation, Billerica, MA).
ꢀ
[PPh4][Tf2N]) yields a slightly lower melting point of 98.6 C.
The Davis group12 evaluated the long-term thermal stability of
triphenyl(P,P,P-triphenylphosphine imidato-kN)-phosphorus
paired with various anions (mp > 120 C) at 200 ꢀC, 250 ꢀC,
ꢀ
and 300 ꢀC for 96 h in air, and identied the most stable
anions as C6H5SO3ꢂ, (C6H5SO2)2Nꢂ, benzene(disulfonyl)ami-
date (BDSAꢂ), bis(peruoroethanesulfonyl)imide (betiꢂ),
Tf2Nꢂ, and TfOꢂ. Therefore, although alkyl-substituted phos-
phonium ILs are promising in terms of thermal stability, they
can be associated with relatively high melting points or
viscosities and may not otherwise represent ideal solvents for
enzymatic ROP reactions.
To overcome these obstacles, we aimed to formulate so-
called “task-specic ionic liquids” designed to be thermally
stable, highly uid, and biocompatible. Task-specic ionic
liquids are a subset of ILs functionalized to display properties
or reactivities suitably targeted for particular applications.13,14
It is known that symmetrical alkyl chains or a long-chain alkyl
Preparation of glycol-functionalized ILs
group on the cation can dramatically increase the melting We modied literature methods36,37 to synthesize our glycol-
point and viscosity of the resulting IL. On the other hand, functionalized ILs. Our preparation of phosphonium-type ILs
appending glycols or their derivatives are known to be bene- is described next as a general procedure. The rst step was the
cial for achieving low melting point salts with reduced bromination of glycol, which followed the Appel reaction (see
viscosities. Therefore, polyglycols have been incorporated into ESI of ref. 38) except for 2-bromoethyl methyl ether which was
cationic or anionic units to produce the liquid state of ion- acquired from a commercial source. Glycol monomethyl ether
conductive polymers.15,16 In particular, various ILs have been (ꢁ20 g, 1.0 molar equiv.) was dissolved in 100 mL of acetonitrile,
synthesized by graing alkyloxy substituents (ether or alcohol followed by the addition of tetrabromomethane (1.2 molar
groups) onto an imidazolium17–28 or pyridinium ring.29,30 The equiv.). The mixture was stirred at room temperature until
inclusion of alkyloxy or alkyloxyalkyl groups can adequately complete dissolution of CBr4. Polystyrene supported-
lower the melting points of the resulting organic salts, yielding triphenylphosphine (PS-Ph3P, 1.2 molar equiv.) was added in
room-temperature ILs in many cases. The low viscosity arising portions and the mixture was stirred at room temperature for
from the incorporation of alkoxy chains has been justied by 24 h. The solid was removed by ltration. Activated carbon was
molecular dynamics (MD) simulations as resulting from the added into the light-brownish solution and stirred for 1 h to
less effective assembly between exible alkoxy chains as remove color. Aer ltering off the solid carbon, the solvent was
compared to their more rigid alkyl chain counterparts.31 In evaporated under vacuum, producing bromoglycol mono-
addition, MD simulations also suggest a reduction of inter- methyl ether.
molecular correlation (particularly tail–tail segregation) and
Bromoglycol monomethyl ether (ꢁ20 g) was mixed with 1.1
cation–anion specic interactions due to the incorporation of molar equiv. of tributylphosphine in anhydrous acetonitrile and
the ether chain, which is responsible for the faster dynamics in reuxed for 24 h to produce the bromide salt. The silver nitrate
ether-functionalized imidazolium ILs compared to alkyl- test conrmed the presence of bromide anion. Following the
substituted ones.32 Following this rationale, our strategy reaction, solvent was evaporated under vacuum. The crude
toward enzymatic ROP compatible ILs involved the synthesis product was extracted three times by n-hexane (or n-heptane) to
of a series of ILs carrying polyether-substituted cations paired remove excess reactant (tributylphosphine) and any byproduct
with anions such as Tf2Nꢂ, as ILs containing this anion are (such as tributylphosphine oxide).
frequently enzyme-compatible.33–35 With the targeted glycol-
An aqueous solution of lithium bis(triuoromethylsulfonyl)
functionalized IL series in hand, we further evaluated how imide (Li[Tf2N], 1.05 molar equiv.) was added dropwise to an
the thermal stability of the resulting IL contributed to the equivalent of bromide salt predissolved in water. A turbid
performance of high-temperature enzymatic ring-opening mixture formed immediately. The reaction mixture was stirred
polymerization.
at room temperature for 20 min, and then allowed to sit for at
least 2 h to allow the formation of two discrete layers. Aer
36026 | RSC Adv., 2018, 8, 36025–36033
This journal is © The Royal Society of Chemistry 2018

View Article Online
Paper
RSC Advances
adequate phase separation, the bottom IL layer was separated, PCH2CH2OCH2CH2OCH2CH2OCH3). 31P-NMR (162 MHz,
taken up in CH2Cl2, and thoroughly washed with distilled water CDCl3, [ppm]) d ¼ 33.7. 13C-NMR (101 MHz, CDCl3, [ppm]) d ¼
three times. Following this treatment, a silver nitrate test of the 13.24, 13.60, 19.06, 19.54, 19.85, 20.35, 23.43, 23.48, 23.68,
aqueous layer previously contacting the IL was negative for the 23.74, 23.90, 24.17, 58.89, 63.75, 63.83, 69.98, 70.35, 70.45,
presence of halides. Aer drying the organic solvent with 71.85, 76.74, 77.06, 77.37, 118.29, 121.49.
Na2SO4 followed by ltration, the IL was obtained aer removal
(2-(2-(2-Methoxyethoxy)ethoxy)ethoxy)ethyl-tributylphosphonium
of CH2Cl2 under vacuum. The resulting IL was collected, rinsed bis(triuoromethylsulfonyl)imide (6, [Me(OCH2CH2)4-PBu3][Tf2N]).
by n-hexane twice (for non-phosphonium salts, diethyl ether 1H-NMR (400 MHz, CDCl3, [ppm]) d ¼ 0.97 (9H, t, 3CH3CH2CH2-
was used), and dried in a vacuum oven (25 mmHg) at 80 ꢀC for CH2), 1.51 (12H, m, 3CH3CH2CH2CH2), 2.16 (6H, t, 3CH3CH2CH2-
1
three days. H, 13C, and 31P NMR data conrmed the structure CH2), 2.51 (2H, t, PCH2CH2OCH2CH2OCH2CH2OCH2CH2OCH3),
and purity of the ILs.
3.37 (3H, s, PCH2CH2OCH2CH2OCH2CH2OCH2CH2OCH3), 3.53–
2-Methoxyethyl-triethylphosphonium bis(triuoromethylsulfonyl) 3.62 (12H, m, PCH2CH2OCH2CH2OCH2CH2OCH2CH2OCH3), 3.66–
imide (1, [MeOCH2CH2-PEt3][Tf2N]). 1H-NMR (400 MHz, CDCl3, 3.67 (2H, m, PCH2CH2OCH2CH2OCH2CH2OCH3). 13C-NMR (101
[ppm]) d ¼ 1.22–1.31 (9H, m, 3CH3CH2), 2.17–2.26 (6H, m, MHz, CDCl3, [ppm]) d ¼ 13.23, 19.02, 19.49, 19.77, 20.28, 23.40,
3CH3CH2), 2.43–2.49 (2H, m, PCH2CH2OCH3), 3.56 (3H, s, 23.44, 23.74, 23.90, 58.92, 63.78, 63.85, 70.00, 70.42, 70.45, 70.50,
PCH2CH2OCH3), 3.69–3.75 (2H, m, PCH2CH2OCH3). 31P-NMR 70.57, 71.94, 118.29, 121.48.
(162 MHz, CDCl3, [ppm]) d ¼ 39.1. 13C-NMR (101 MHz, CDCl3,
1-Ethyl-3-(2-methoxyethyl)imidazolium
bis(tri-
[ppm]) d ¼ 5.39, 5.45, 12.22, 12.71, 18.87, 19.37, 58.99, 64.97, uoromethylsulfonyl)imide (7, [MeOCH2CH2-Et-Im]
65.04, 118.26, 121.45.
[Tf2N]). 1H-NMR (400 MHz, CDCl3, [ppm]) d ¼ 1.55 (3H, t,
2-Methoxyethyl-tributylphosphonium bis(triuoromethylsulfonyl) CH3CH2–), 3.36 (3H, s, CH3OCH2CH2–), 3.70 (2H, t, CH3OCH2-
imide (2, [MeOCH2CH2-PBu3][Tf2N]). 1H-NMR (400 MHz, CDCl3, CH2–), 4.25 (2H, q, CH3CH2ꢂ), 4.35 (2H, t, CH3OCH2CH2ꢂ), 7.34
[ppm]) d ¼ 0.97 (9H, t, 3CH3CH2CH2CH2, J ¼ 7.2), 1.51 (12H, m, (1H, m, CH3CH2NCHCHN), 7.42 (1H, m, CH3CH2NCHCHN),
3CH3CH2CH2CH2), 2.09–2.17 (6H, m, 3CH3CH2CH2CH2), 2.48 8.70 (1H, s, NCHN). 13C-NMR (101 MHz, CDCl3, [ppm]) d ¼
(2H, m, PCH2CH2OCH3), 3.35 (3H, s, PCH2CH2OCH3), 3.68–3.76 15.04, 45.28, 49.90, 58.87, 69.83, 118.18, 121.37, 121.58, 123.43.
(2H, m, PCH2CH2OCH3). 31P-NMR (162 MHz, CDCl3, [ppm]) d ¼
N-(2-Methoxyethyl)pyridinium bis(triuoromethylsulfonyl)
33.7. 13C-NMR (101 MHz, CDCl3, [ppm]) d ¼ 13.18, 19.04, 19.51, imide (8, [MeOCH2CH2–Py][Tf2N]). H-NMR (400 MHz, CDCl3,
1
19.85, 20.35, 23.36, 23.41, 23.68, 23.83, 58.99, 65.17, 65.24, [ppm]) d ¼ 3.33 (3H, s, CH3OCH2CH2–), 3.83 (2H, t, CH3OCH2-
118.27, 121.47.
CH2–), 4.77 (2H, t, CH3OCH2CH2–), 8.03 (2H, m), 8.51 (1H, m),
2-Methoxyethyl-tributylphosphonium
bis(penta- 8.81 (2H, m). 13C-NMR (101 MHz, CDCl3, [ppm]) d ¼ 59.03,
uoroethanesulfonyl)imide
(3,
[MeOCH2CH2-PBu3] 62.01, 69.93, 118.17, 121.36, 128.17, 145.07, 145.72.
[beti]). 1H-NMR (400 MHz, CDCl3, [ppm]) d ¼ 0.966 (9H, m,
(2-Methoxyethyl)triethylammonium bis(triuoromethylsulfonyl)
1
3CH3CH2CH2CH2), 1.49–1.51 (12H, m, 3CH3CH2CH2CH2), 2.12– imide (9, [MeOCH2CH2-Et3N][Tf2N]). H-NMR (400 MHz, CDCl3,
2.16 (6H, m, 3CH3CH2CH2CH2), 2.47–2.51 (2H, m, PCH2CH2- [ppm]) d ¼ 1.31 (9H, t, –N(CH2CH3)3), 3.32–3.42 (11H, m,
OCH3), 3.34 (3H, s, PCH2CH2OCH3), 3.59–3.84 (2H, m, PCH2- –N(CH2CH3)3 and CH3OCH2CH2–), 3.72 (2H, m, CH3OCH2CH2–
CH2OCH3). 31P-NMR (162 MHz, CDCl3, [ppm]) d ¼ 33.7. 13C- ). 13C-NMR (101 MHz, CDCl3, [ppm]) d ¼ 7.39, 53.91, 56.66,
NMR (101 MHz, CDCl3, [ppm]) d ¼ 13.16, 19.00, 19.48, 19.82, 59.13, 65.53, 118.26, 121.45.
20.32, 23.37, 23.40, 23.66, 23.82, 58.70, 70.37, 71.32, 111.50,
111.88, 116.63, 119.50.
N-(2-Methoxyethyl)-N-methylpiperidinium bis(triuoromethylsulfonyl)
imide (10, [MeOCH2CH2-Me-Pip][Tf2N]). 1H-NMR (400 MHz, CDCl3,
(2-Methoxyethoxy)ethyl-tributylphosphonium
uoromethylsulfonyl)imide (4, [Me(OCH2CH2)2-PBu3] –NCH2CH2CH2CH2–), 3.12 (3H, s, –NCH3), 3.33–3.40 (5H, m,
bis(tri- [ppm]) d ¼ 1.72 (2H, m, –NCH2CH2CH2–), 1.90 (4H, m,
[Tf2N]). 1H-NMR (400 MHz, CDCl3, [ppm]) d ¼ 0.97 (9H, t, CH3OCH2CH2–), 3.45 (2H, m, –NCH2CH2CH2CH2–), 3.55 (2H,
3CH3CH2CH2CH2), 1.51 (12H, m, 3CH3CH2CH2CH2), 2.16 (6H, t, m, –NCH2CH2CH2CH2–), 3.78 (2H, m, CH3OCH2CH2–). 13C-
3CH3CH2CH2CH2), 2.51 (2H, m, PCH2CH2OCH2CH2OCH3), 3.34 NMR (101 MHz, CDCl3, [ppm]) d ¼ 19.96, 20.54, 49.15, 59.01,
(3H, s, PCH2CH2OCH2CH2OCH3), 3.49 (2H, m, PCH2CH2- 62.53, 65.58, 118.22, 121.41.
OCH2CH2OCH3), 3.61 (2H, m, PCH2CH2OCH2CH2OCH3), 3.83
(2H, m, PCH2CH2OCH2CH2OCH3). 31P-NMR (162 MHz, CDCl3,
Enzymatic ROP of lactide
[ppm]) d ¼ 33.7. 13C-NMR (101 MHz, CDCl3, [ppm]) d ¼ 13.20,
13.54, 19.00, 19.48, 19.84, 20.33, 23.39, 23.44, 23.50, 23.72, The water contents of all solvents, monomers, and enzymes
23.88, 24.05, 24.19, 58.72, 63.70, 63.77, 70.39, 71.34, 118.26, were assayed by Karl Fischer (KF) titration (Mettler Toledo C20X
121.45.
compact coulometric titrator; detection limit ꢁ1 ppm water) at
(2-(2-Methoxyethoxy)ethoxy)ethyl-tributylphosphonium bis(- 20 ꢀC. Hydranal® Coulomat AG was used as the analyte for the
triuoromethylsulfonyl)imide (5, [Me(OCH2CH2)3-PBu3][Tf2N]). titration. A typical enzymatic ROP reaction was conducted as
1H-NMR (400 MHz, CDCl3, [ppm]) d ¼ 0.97 (9H, t, 3CH3CH2- follows: the substrate (0.5 g L-lactide) was mixed with 0.25 mL of
CH2CH2), 1.51 (12H, m, 3CH3CH2CH2CH2), 2.16 (6H, t, 3CH3- solvent (or noted otherwise), followed by the addition of 100 mg
CH2CH2CH2), 2.51 (2H, t, PCH2CH2OCH2CH2OCH2CH2OCH3), of Novozym 435. The reaction vial was tightly sealed and then
ꢀ
3.35 (3H, s, PCH2CH2OCH2CH2OCH2CH2OCH3), 3.50–3.62 (8H, immersed in an oil bath (130 C) aer initiating stirring (210
m, PCH2CH2OCH2CH2OCH2CH2OCH3), 3.78–3.87 (2H, m, rpm). At the completion of reaction, the reaction mixture was
This journal is © The Royal Society of Chemistry 2018
RSC Adv., 2018, 8, 36025–36033 | 36027

View Article Online
RSC Advances
Paper
cooled to room temperature and then 2.0 mL of deutero- were determined by GPC equipped with a LC-20AD Shimadzu
chloroform (CDCl3) was added to dissolve the polyester under HPLC, SPD-20A UV-visible dual-wavelength detector at 210 nm,
vigorous agitation. For 1H NMR analysis, a 50 mL reaction and two PLgel MIXED-B 10 mm, 300 ꢃ 7.5 mm columns (Agilent)
aliquot was withdrawn and diluted with an additional 1.0 mL of eluted with 1.0 mL minꢂ1 THF at 30 C.40 Calibration was ach-
ꢀ
CDCl3, followed by centrifugation (2000ꢃg, 2 min). For gel ieved by using polystyrene standards from 570 to 62 500 (Mw).41
permeation chromatography (GPC) analysis—a type of size
exclusion chromatography, SEC—a 50 mL reaction aliquot was
withdrawn and diluted into 1.0 mL of THF. This mixture was
Results and discussion
Synthesis of glycol-functionalized ILs
centrifuged before GPC injection (the GPC experimental
conditions are described in the Polymer characterization
section below). To obtain the nal solid product, aer evapo-
rating chloroform, the polymer was precipitated by adding ice-
cold methanol and was then separated by centrifugation or
vacuum ltration. The polyester was air-dried for 24 h.
As illustrated in Scheme 1, the preparation of glycol-graed ILs
comprises three primary steps: bromination of the glycol, qua-
ternization of a phosphine (or imidazole, pyridine, alkylamine,
or alkylpiperidine), and ion metathesis. The rst reaction (i.e.,
bromination) is the most challenging step. Dibromination of
glycol (HO–PEGn–OH) with PBr3 has been shown to be effec-
tive.36,37 The direct monobromination of glycol monomethyl
ether (MeO–PEGn–OH) using PBr3 has been reported to prepare
MeO–PEGn–Br,42–45 however, this reaction can also generate di-
brominated by-product (Br–PEGn–Br) which can prove difficult
to separate from the main product. To improve this reaction,
Et3N was added as a base during bromination to neutralize
hydrobromic acid produced in the presence of trace water (i.e.,
hydrobromic acid is known to induce the dibromination reac-
tion46). However, this process typically involves highly
exothermic neutralization between Et3N and HBr/H3PO3,
resulting in a large quantity of ammonium salts, making the
reaction difficult to control. On the other hand, the Appel
reaction38 can be conducted under mild conditions using tri-
phenylphosphine and tetrabromomethane. However, removal
of triphenylphosphine (Ph3P) and triphenylphosphine oxide
(Ph3PO) at the completion of reaction still poses a separations
challenge. Traditionally, the removal is accomplished by
tedious column chromatography using large volumes of
solvents. The Lipshutz group47 reported that mixing the product
Enzymatic ROP of 3-caprolactone
The substrate (0.5 g of 3-caprolactone; density: 1.03 g mLꢂ1) was
dissolved in 0.25 mL of solvent, followed by the addition of
100 mg of Novozym 435. The reaction mixture was sealed tightly
and stirred (210 rpm) at 70 ꢀC in an oil bath. At the completion
of reaction, the reaction mixture was cooled to room tempera-
ture and 2.0 mL of CDCl3 was added to dissolve the polyester
under vigorous agitation. For 1H NMR analysis, a 50 mL aliquot
was withdrawn and diluted with 1.0 mL of CDCl3, followed by
centrifugation. For GPC analysis, 50 mL aliquot was withdrawn
and diluted with 1.0 mL THF, and the mixture was centrifuged
prior to GPC injection. To obtain the nal solid product, aer
evaporating chloroform, the polymer was precipitated by add-
ing ice-cold methanol and was then separated by centrifugation
or vacuum ltration. The recovered polyester was air-dried for
24 h.
Polymer characterization
The L-lactide conversion was monitored via 1H NMR analysis with Merrield resin and NaI in acetone led to an effective
(Bruker Avance II 400 MHz NMR) by comparing the peak area of removal of trace Ph3P/Ph3PO. However, this process is highly
the methine group (CH) adjacent to the carbonyl in the mono- sensitive to moisture and oxygen because iodide can be easily
mer (5.04 ppm) and in the polymer (5.16 ppm).3 Similarly, oxidized to I2, contaminating the product and coloring it brown.
1
monomer 3-caprolactone conversion was determined from H A recent study suggested that Ph3PO could be complexed by
NMR experiments by comparing the integrated signal areas for ZnCl2 in ethanol to form a precipitate whereas Ph3P can be
the methylene groups next to the carbonyl group within the oxidized to its oxide form by 10% H2O2 solution before per-
monomer 3-caprolactone (CL, 4.23 ppm) and the poly(3-capro- forming the complexing step.48 However, this method report-
lactone) (PCL, 4.07 ppm).39 The mass-average molecular mass edly fails to precipitate trace amounts of Ph3PO, with <1% still
(Mw) and polydispersity index (PDI ¼ Mw/Mn) of the polyester remaining in solution.48 On the other hand, polymer-bound
Scheme 1 Synthesis of glycol-functionalized phosphonium ionic liquids.
36028 | RSC Adv., 2018, 8, 36025–36033
This journal is © The Royal Society of Chemistry 2018

View Article Online
Paper
RSC Advances
triphenylphosphine (particularly, polystyrene-bound Ph3P with to a nal water content below 200 ppm. The studied ILs have
2% cross-linking with divinylbenzene, designated PS-Ph3P) has densities within the range of 1.2–1.5 g cmꢂ3 at 30 ꢀC. In general,
shown the advantage of convenient workup via simple ltra- glycol-functionalized ILs carrying the Tf2Nꢂ anion show rela-
tion.49–51 Therefore, aer examining all of the above options, we tively low viscosities (h ¼ 33–123 mPa s at 30 ꢀC). As bench-
adopted the PS-Ph3P method to carry out the bromination of marks, comparison is made with the prototypical, well-studied
glycol monomethyl ether, as detailed in the Experimental.
ILs [BMIM][Tf2N] (11) (h ¼ 41.4 mPa s at 30 ꢀC) and [BMIM][PF6]
A common side reaction occurring during alkylation of (12) (h ¼ 205.8 mPa s). Different cation cores have a major
electron-rich phosphines (such as tributylphosphine, Bu3P) is inuence on the dynamic viscosities, as illustrated by the
oxidation to yield the corresponding phosphine oxide.52 observed general trend of decreasing viscosity in the order
Therefore, aer completion of the second step in glycol- piperidinium (10) > ammonium (9) > pyridinium (8) > phos-
functionalized IL synthesis (i.e., the phosphine alkylation phonium (1) > imidazolium (7). Glycol-functionalization also
step), the byproduct oxide (e.g., Bu3PO) and excess starting leads to a reduced viscosity, as shown by the lower viscosity of
phosphine are removed by n-hexane extraction. This extraction 33.1 mPa s for [MeOCH2CH2-Et-Im][Tf2N] (7) versus 41.4 mPa s
step was repeated again on the nal Tf2Nꢂ IL obtained by anion for [BMIM][Tf2N] (11). Likewise, a longer glycol chain generally
metathesis, before subjecting the uid to prolonged drying in reduces the viscosity, as exemplied by the [RPBu3][Tf2N] type
a vacuum oven. It should be noted that common Tf2Nꢂ ILs are ILs, where R is the glycol group Me(OCH2CH2)n (the number of
frequently rinsed with diethyl ether or ethyl acetate, however, ethylene oxide (EO) units, n ¼ 1, 2, 3 and 4; see entries 2 and 4–6
both of these solvents are miscible with the glycol-appended in Table 1). A less symmetrical cation tends to have a lower
phosphonium ILs prepared in this study.
viscosity as evidenced by a viscosity of 36.0 mPa s for
[MeOCH2CH2-PEt3][Tf2N] (1) compared with 122.5 mPa s for
[MeOCH2CH2-PBu3][Tf2N] (2). It is important to note that our
physical characterization data are consistent with known liter-
ature values. For example, our measured dynamic viscosity for
[MeOCH2CH2-PEt3][Tf2N] (1) of 36.0 mPa s at 30 ꢀC accords with
the literature value of 44 mPa s at 25 ꢀC.10 Similarly, a dynamic
Physical properties of glycol-functionalized ILs
Initially, we determined the dynamic (absolute) and kinematic
viscosities, as well as the densities of the synthesized ILs at
30 ꢀC (Table 1). All ILs were intensively dried in a vacuum oven
Table 1 Viscosities and densities (measured at 30 ꢀC) and scanning thermogravimetry-determined short-term thermal stabilities of ILsa
Dynamic viscositya
(mPa s)
Kinematic viscositya
Densitya
Tder
Tdcp
Transition
shape d
Residual
char e
b
c
IL
(mm2 sꢂ1
)
(g cmꢂ3
1.368
1.237
1.286
1.215
1.195
1.203
1.458
)
(ꢀC)
468
449
425
445
448
450
468
(ꢀC)
1
2
3
4
5
6
7
[MeOCH2CH2-PEt3]
[Tf2N]
[MeOCH2CH2-PBu3]
[Tf2N]
[MeOCH2CH2-PBu3]
[beti]
[Me(OCH2CH2)2-PBu3]
[Tf2N]
[Me(OCH2CH2)3-PBu3]
[Tf2N]
[Me(OCH2CH2)4-PBu3]
[Tf2N]
[MeOCH2CH2-Et-Im]
[Tf2N]
36.0
122.5
163.4
95.5
26.3
362
354
318
319
318
335
401
M
M
M
M
M
M
S
2.6%
1.0%
0.9%
1.4%
1.7%
2.2%
3.4%
99.0
127.1
78.6
79.8
66.8
90.2
75.0
33.1
22.7
8
9
[MeOCH2CH2-Py][Tf2N]
[MeOCH2CH2-Et3N]
[Tf2N]
44.5
61.4
29.5
44.4
1.508
1.383
456
427
403
380
M
S
2.8%
0.0%
10
[MeOCH2CH2-Me-Pip]
[Tf2N]
84.2
59.0
1.426
453
399
S
0.3%
11
12
[BMIM][Tf2N]
[BMIM][PF6]
41.4
205.8
28.9
151.1
1.430
1.362
464
472
406
424
S
S
1.5%
0.5%
a
The viscosity and density data were acquired using an Anton Paar SVM 3000 viscometer; measurements were made at 30 ꢀC. Thermogravimetric
analysis (TGA) scans were measured on a TA Instruments TGA Q50 under a nitrogen atmosphere (60 mL minꢂ1) using Pt pans with a heating rate of
10 ꢀC minꢂ1
.
Tder is determined from the maximum in the rst-derivative prole of the TGA scan. Tdcp is the decomposition temperature
b
c
measured as the onset of decomposition, using the common criterion of 10% total mass loss. Uncertainties in the temperatures are estimated
d
to be on the order of ꢄ2–3 ꢀC. The TGA mass loss behavior is qualitatively characterized on the basis of whether it occurs essentially in
a single, discrete step (S) or exhibits multiple step (M) thermal decomposition. The latter is generally associated with an early mass loss step
which occurs at a temperature 50–100 ꢀC below the primary event within the vicinity of Tder. It should be noted that, for this reason, proles
e
that display some multi-step thermal decomposition character generally have lower effective Tdcp values. The amount of carbon char residue is
determined from the relative mass remaining at 600 ꢀC; a residue amount on the order of ꢄ1–2% should be considered within the error of the
measurement baseline.
This journal is © The Royal Society of Chemistry 2018
RSC Adv., 2018, 8, 36025–36033 | 36029

View Article Online
RSC Advances
Paper
viscosity of 61.4 mPa s at 30 ꢀC for [MeOCH2CH2-Et3N][Tf2N] (9) those for PLA synthesis) or at 200 ꢀC for 24 h. As summarized in
falls in line with the reported value of 85 mPa s at 25 ꢀC.10 The Table 2, many ILs investigated exhibit excellent long-term
anions have some impact on the viscosity as well: the Tfꢂ2Nꢂ stability at 130 ꢀC, with the notable exceptions of ILs 3, 4, 5,
anion tends to lead to a lower viscosity than betiꢂ and PF6 (2 6, and 12. It also appears that longer glycol-chains lead to lower
vs. 3, 11 vs. 12 in Table 1).
long-term thermal stability. This can be seen by comparison of
The short-term thermal stabilities of the prepared ILs were ILs 2, 4, 5, and 6 (one, two, three, and four EO units, respec-
evaluated on the basis of two parameters obtained from scan- tively) which display mass losses of 0.0%,ꢀ 2.5%, 4.3%, and
ning thermogravimetric analysis (TGA): the derivative temper- 14.6%, respectively, aer being held at 130 C for 7 days. The
ature Tder, determined from the maximum of the rst-derivative reduced long-term stability (i.e., 14.9% mass loss aer 7 days at
prole of the TGA thermogram, and the decomposition 130 ꢀC) of [BMIM][PF6] (12) suggests the inherent instability of
temperature Tdcp, dened as the decomposition temperature the PF6ꢂ anion since [BMIM][Tf2N] (11) is comparably far more
measured using the prevalent criterion of a 10% total mass loss stable under these conditions. In the course of a 24 h exposure
ꢀ
(Fig. S1–S12 in ESI† and Table 1). In terms of Tder values, glycol- to 200 C, many ILs show relatively minor mass losses <1.0%
functionalized ILs generally have stabilities (Tder z 420–470 ꢀC) (Table 2), although visual changes are universally apparent (i.e.,
similar to conventional saturated hydrocarbon side chain ILs development of light to deep brown coloration). It is already
such as 11 and 12, with a thermal stability that decreases to well-established that trivial levels of IL decomposition unde-
some extent in the order phosphonium (1) z imidazolium (7) > tectable by standard TGA or NMR analysis can be observed by
pyridinium (8) > piperidinium (10) > ammonium (9). Short- changes in spectroscopic features (i.e., colored and/or uores-
chain glycol functionalization has no outward effect on cent impurities).54 Notably, the ILs 3, 4, 5, 6, and 12 showed
thermal stability (7 vs. 11). Similarly, for a given cationic moiety, signicant mass losses aer 24 h at 200 ꢀC (5.0%, 7.5%, 10.4%,
the glycol chain length has minimal impact on Tder (compare 4– 13.0%, and 8.5% mass loss, respectively). Based on these
6 with 2). In terms of Tdcp values, again short-chain glycol outcomes for long-term thermal exposure relevant to ROP
functionalization reveals no signicant effect on apparent conditions, we conclude that, with the exception of ILs 3, 4, 5, 6,
thermal stability (7 vs. 11), however, this parameter reveals that and 12, the remaining ILs appear promising as thermally-
ꢀ
lengthening of the glycol chain (compare 2, 4, 5, and 6) lowers suitable media for enzymatic ROP at 130 C.
ꢀ
the thermal stability by some 19–36 C. Based on Tdcp values,
the cation core exerts a greater inuence over the thermal
stability, according to the trend of decreasing thermostability:
pyridinium (8) z imidazolium (7) z piperidinium (10) >
ammonium (9) > phosphonium (1). A comparison between 2
and 3 reveals that the Tf2Nꢂ anion is marginally more thermally
stable than the betiꢂ anion, in terms of Tder. Similarly, the
difference in the long-term thermal stability observed for the
Tf2Nꢂ and betiꢂ salts of [MeOCH2CH2–PBu3]+ (2 and 3 in Table
2) is consistent with the observation that DHvap values for betiꢂ-
containing 1-alkyl-3-methylimidazolium ILs are ꢁ5% lower
than their Tf2Nꢂ counterparts of the same alkyl chain length.53
Longer-term thermal stability was examined by incubating
Enzymatic ROP of L-lactide and 3-caprolactone
Firstly, we examined the enzymatic ROP of L-lactide catalyzed by
Novozym 435 at 130 ꢀC under various solvent conditions (Table
3). As pointed out in our earlier study, the enzymatic polymer-
ization can be greatly affected by the batch conditions and water
content of the enzyme.2 When no solvent was employed, poly(L-
lactide) (PLLA) was produced with a molecular mass (Mw) of
12 400 Da in 36% yield and with a PDI of 1.14 (trial 1 in Table 3).
This solventless result serves as a reference point for compar-
ison. When an organic solvent (i.e. dimethylacetamide, DMA),
or a conventional IL (i.e., [BMIM][PF6] or [BMIM][Tf2N]) was
employed as solvent (trials 2–4), similar molecular masses in
the range of 11 500–13 000 Da were obtained, although there
ꢀ
the ILs at 130 C for 7 days (reaction conditions which match
Table 2 Summary of long-term thermal stability of ILsa
% Mass loss and color
change for 130 ꢀC
treatment for 7 days
% Mass loss and color
IL
change for 200 ꢀC treatment for 24 h
1
2
3
4
5
6
7
8
[MeOCH2CH2-PEt3][Tf2N]
[MeOCH2CH2-PBu3][Tf2N]
[MeOCH2CH2-PBu3][beti]
[Me(OCH2CH2)2-PBu3][Tf2N]
[Me(OCH2CH2)3-PBu3][Tf2N]
[Me(OCH2CH2)4-PBu3][Tf2N]
[MeOCH2CH2-Et-Im][Tf2N]
[MeOCH2CH2-Py][Tf2N]
[MeOCH2CH2-Et3N][Tf2N]
[MeOCH2CH2-Me-Pip][Tf2N]
[BMIM][Tf2N]
No change
No change
0.60% (light brown)
1.5% (dark brown)
5.0% (light brown)
7.5% (v. dark)
10.4% (v. dark)
13.0% (v. dark)
0.27% (light brown)
0.27% (dark brown)
0.58% (light brown)
0.30% (dark brown)
0.28% (v. light brown)
8.5% (dark brown)
3.3% (no color change)
2.5% (no color change)
4.3% (no color change)
14.6% (no color change)
No change
No change
No change
No change
No change
9
10
11
12
[BMIM][PF6]
14.9% (white precipitate)
a
The mass loss was determined aer open air heating in an oven at a xed temperature.
36030 | RSC Adv., 2018, 8, 36025–36033
This journal is © The Royal Society of Chemistry 2018

View Article Online
Paper
RSC Advances
Table 3 Enzymatic ROP of L-lactide and 3-caprolactone under different reaction conditionsa
Trial Substrate
Solvent (water content)
T (ꢀC) Reaction time (days) Conversion (%) Yield (%) Mwb (Da) PDI
1
2
3
4
5
6
7
8
L-Lactide
L-Lactide
L-Lactide
L-Lactide
L-Lactide
L-Lactide
L-Lactide
L-Lactide
No solvent
Dimethylacetamide (0.01 wt%)
[BMIM][PF6] (0.01 wt%)
130
130
130
130
130
130
130
130
7
7
7
7
7
7
7
7
85.3
95.2
92.4
94.5
84.9
86.3
96.5
75.5
36
46
24
6
12
34
28
10
12 400
11 500
11 900
13 000
21 100
17 600
12 600
12 200
1.14
1.54
2.15
1.48
1.89
2.13
2.38
1.84
[BMIM][Tf2N] (0.01 wt%)
[CH3OCH2CH2-PEt3][Tf2N] (0.01 wt%)
[CH3OCH2CH2-PBu3][Tf2N] (0.01 wt%)
[CH3OCH2CH2-PBu3][Tf2N] (1.7 wt%)
[CH3OCH2CH2-PBu3][Tf2N] (0.01 wt%,
0.5 mL)
9
L-Lactide
[CH3OCH2CH2-PBu3][Tf2N] (0.01 wt%,
1.0 mL)
[CH3OCH2CH2-PBu3][beti] (0.02 wt%)
130
130
7
79.2
6
6800
1.84
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
L-Lactide
L-Lactide
L-Lactide
L-Lactide
L-Lactide
L-Lactide
L-Lactide
L-Lactide
L-Lactide
7
7
7
7
7
7
7
7
7
2
2
2
2
2
2
2
2
2
69.2
74.5
87.2
87.5
80.0
90.0
78.6
92.5
88.0
96.8
87.8
96.9
52.1
70.1
95.7
94.3
96.4
96.1
32
12
14
4
14 500
15 400
13 400
14 000
13 200
23 000
17 300
19 000
11 300
13 800
18 500
18 900
9100
2.19
1.38
1.38
1.71
1.97
1.55
1.29
1.58
1.76
1.71
1.94
1.59
1.19
1.35
1.60
1.34
1.39
1.69
[CH3(OCH2CH2)2-PBu3][Tf2N] (0.02 wt%) 130
[CH3(OCH2CH2)3-PBu3][Tf2N] (0.02 wt%) 130
[CH3(OCH2CH2)4-PBu3][Tf2N] (0.01 wt%) 130
[CH3(OCH2CH2)4-PBu3][Tf2N] (0.04 wt%) 130
[MeOCH2CH2-Et-Im][Tf2N] (0.03 wt%)
[MeOCH2CH2-Py][Tf2N] (0.03 wt%)
[MeOCH2CH2-Et3N][Tf2N] (0.03 wt%)
[MeOCH2CH2-Me-Pip][Tf2N] (0.03 wt%)
20
10
14
20
16
37
55
48
15
30
42
32
11
11
130
130
130
130
70
70
70
70
70
70
70
70
70
3-Caprolactone No solvent
3-Caprolactone [BMIM][PF6] (0.01 wt%)
3-Caprolactone [CH3OCH2CH2-PBu3][Tf2N] (0.02 wt%)
3-Caprolactone [CH3OCH2CH2-PBu3][beti] (0.02 wt%)
3-Caprolactone [CH3(OCH2CH2)2-PBu3][Tf2N] (0.02 wt%)
3-Caprolactone [MeOCH2CH2-Et-Im][Tf2N] (0.03 wt%)
3-Caprolactone [MeOCH2CH2-Py][Tf2N] (0.03 wt%)
3-Caprolactone [MeOCH2CH2-Et3N][Tf2N] (0.03 wt%)
3-Caprolactone [MeOCH2CH2-Me-Pip][Tf2N] (0.03 wt%)
14 300
12 300
16 200
17 300
18 100
a
General reaction conditions (unless otherwise noted): 0.5 g of L-lactide or 3-caprolactone, 0.25 mL of solvent, 100 mg of Novozym 435, gentle
b
stirring (210 rpm) at 130 or 70 ꢀC for 7 or 2 days. GPC-derived Mw values were based on results calibrated using polystyrene standards. Based
on GPC analysis.
appears to be wide variation in the observed yield (6–46%) and 14 000 Da for trials 11, 12 and 13, respectively) in comparison to
PDI (1.48–2.15). Using the same batch of lipase (Batch trial 6 involving a phosphonium IL bearing a single EO unit
#SLBP0766V, purchased in March 2016) in [BMIM][PF6], this glycol pendant chain. In addition, we observed that the choice
study synthesized PLLA with Mw ¼ 11 900 Da, PDI 2.15 and yield of cationic core had a heavy inuence over the ROP reaction
24% (trial 3 in Table 3) while our earlier study (see trial 6 in (trials 15–18). Using the imidazolium-based IL [MeOCH2CH2-Et-
Table 1 of ref. 2) obtained PLLA with a Mw of 11 500 Da, PDI 1.41 Im][Tf2N] (trial 15) gave the highest molecular mass (23 000 Da),
and yield 12%; the molecular masses are comparable, however, despite a relatively low yield of 10%. The rank of IL cations in
the higher yield reported in this study is likely due to the lower terms of the resulting PLLA Mw was observed to be: imidazolium
water content (0.01 wt%) in [BMIM][PF6] (vs. 0.02 wt% in the (23 000 Da) > ammonium (19 000 Da) > phosphonium (17 600
earlier study2).
Da) z pyridinium (17 300 Da) > piperidinium (11 300 Da). The
On the other hand, the glycol-functionalized phosphonium ranking based on PLLA yield differs as the following: phos-
ILs [CH3OCH2CH2-PEt3][Tf2N] (1) and [CH3OCH2CH2-PBu3] phonium (34%) > ammonium (20%) > piperidinium (16%) z
[Tf2N] (2) afforded signicantly improved Mw (21 100 and pyridinium (14%) > imidazolium (10%). Through comparing
17 600 Da, respectively) whilst the latter IL gave a higher yield trials 10 and 6 in Table 3, it appears the betiꢂ-based IL produces
(34%) (see trials 5 and 6 in Table 3). The water content within a slightly lower Mw than the Tf2Nꢂ analogue. The observed PLLA
the studied ILs was generally controlled within the 0.01– Mw, yield, and PDI results are illustrated by Fig. S13 in the ESI.†
0.03 wt% range (100–300 ppm). We observed lower molecular
We further examined the enzymatic ROP of 3-caprolactone at
masses at higher water contents, illustrated by the ROP of L- 70 ꢀC in various glycol-functionalized ILs (Table 3, trials 20–27).
lactide in [CH3OCH2CH2-PBu3][Tf2N] containing 0.01% (trial 6) When no solvent was used, poly(3-caprolactone) (PCL) was
versus 1.70% water (trial 7), leading to Mw values of 17 600 and produced with a Mw of 13 800 Da in 37% yield with a 1.71 PDI
12 600 Da, respectively; a similar trend was observed for trials (trial 19). In [BMIM][PF6] (trial 20 in Table 3), PCL was obtained
13 and 14. Employing ILs with longer glycol chains (i.e., two to with a Mw of 18 500 Da, 55% yield and 1.94 PDI, which is
four EO units) attached to the phosphonium cation as ROP comparable with our earlier results (a Mw 20 700 Da, 46% yield
media led to lower molecular masses (15 400, 13 400 and and 1.86 PDI)2 although different batches of Novozym 435 were
This journal is © The Royal Society of Chemistry 2018
RSC Adv., 2018, 8, 36025–36033 | 36031

View Article Online
RSC Advances
Paper
Fig. 1 Correlation between the mass-average molecular mass (Mw) for Novozym 435-catalyzed ROP-produced polyester and the dynamic
viscosity (30 ꢀC) of the IL medium (the number next to each symbol indicates the IL shown in Table 1) for (a) poly(L-lactide) and (b) poly(3-
caprolactone) synthesis.
used. The PCL Mw is again inuenced by the identity of the catalyzed ring-opening polymerization for illustration.
cationic headgroup of the IL: phosphonium (18 900 Da) > Comparing with a solventless condition, these task-specic ILs
piperidinium (18 100 Da) z ammonium (17 300 Da) > pyr- led to higher molecular masses (Mw z 20 000 Da) of poly(L-
idinium (16 200 Da) > imidazolium (12 300 Da). The PCL yield lactide) and poly(3-caprolactone) in reasonable yields. In addi-
decreases in the order phosphonium (48%) > imidazolium tion to the importance of the long-term thermal stability of the
(42%) > pyridinium (32%) > ammonium (11%), piperidinium ionic liquid, there appear to be other confounding factors
(11%). A corresponding summary of Mw, yield, and PDI for ROP- responsible for achieving high yields and molecular masses,
produced PCL is provided in Fig. S14 in the ESI.† Overall, the with the viscosity of the solvent also playing a non-trivial role.
phosphonium-based IL [CH3OCH2CH2-PBu3][Tf2N] (2) enabled
the synthesis of a relatively high molecular mass PCL in high
yield.
Conflicts of interest
Based on the data compiled within Tables 1 and 3, it appears
that neither Mw nor yields of ROP-derived polyesters exhibit any
straightforward correlation with the short-term thermal
stability of the studied ILs. Although ILs with poor long-term
stability (ILs 3, 4, 5, 6, and 12 in Table 2) all led to relatively
low Mw (trials 10, 11, 12, 13, and 3, respectively, in Table 3),
some thermally-stable ILs also gave low Mw polymers (e.g., trials
4 and 18, Table 3). Therefore, there are clearly other important
and confounding factors operative beyond the long-term
thermal stability of ILs. The viscosity shows a more puzzling
effect on Mw, as demonstrated in Fig. 1. For PLLA synthesis at
130 ꢀC, a loose correlation suggests a higher viscosity leading to
a lower Mw (Fig. 1a), however, for PCL synthesis at 70 ꢀC
(Fig. 1b), there is a slow increase in Mw with an increase in
viscosity. These trends possibly arise due to mass transfer being
the limiting factor for PLLA synthesis, making a reduced
viscosity benecial, whereas the rapid dissolution of 3-capro-
lactone (a liquid) into low-viscosity ILs becomes disadvanta-
geous for PCL synthesis, resulting in more substrate
stabilization.
There are no conicts to declare.
Acknowledgements
H. Z. acknowledges support from a Henry Dreyfus Teacher-
Scholar Award (2012–2018) and startup funds from the
University of Northern Colorado. G. A. B. acknowledges support
for this research from the Research Corporation for Science
Advancement.
References
1 H. Zhao, J. Chem. Technol. Biotechnol., 2018, 93, 9–19.
2 H. Zhao, G. A. Nathaniel and P. C. Merenini, RSC Adv., 2017,
7, 48639–48648.
3 M. Yoshizawa-Fujita, C. Saito, Y. Takeoka and M. Rikukawa,
Polym. Adv. Technol., 2008, 19, 1396–1400.
´
´
4 K. A. Barrera-Rivera, A. Marcos-Fernandez, R. Vera-Graziano
´
and A. Martınez-Richa, J. Polym. Sci., Part A-1: Polym. Chem.,
2009, 47, 5792–5805.
¨
5 A. Emova, L. Pfutzner and P. Schmidt, Thermochim. Acta,
2015, 604, 129–136.
6 E. M. Siedlecka, M. Czerwicka, S. Stolte and P. Stepnowski,
Curr. Org. Chem., 2011, 15, 1974–1991.
7 Y. Cao and T. Mu, Ind. Eng. Chem. Res., 2014, 53, 8651–8664.
8 K. J. Fraser and D. R. MacFarlane, Aust. J. Chem., 2009, 62,
309–321.
Conclusions
We have synthesized a series of thermally-stable glycol-
functionalized ILs possessing fairly low viscosities based on
various cationic moieties, including phosphonium, imidazo-
lium, pyridinium, ammonium, and piperidinium salts. We
demonstrate that these new ionic solvents are suitable media
for high-temperature enzymatic reactions, using Novozym 435-
˜
9 A. F. Ferreira, P. N. Simoes and A. G. M. Ferreira, J. Chem.
Thermodyn., 2012, 45, 16–27.
36032 | RSC Adv., 2018, 8, 36025–36033
This journal is © The Royal Society of Chemistry 2018

View Article Online
Paper
RSC Advances
10 K. Tsunashima and M. Sugiya, Electrochem. Commun., 2007, 33 F. van Rantwijk and R. A. Sheldon, Chem. Rev., 2007, 107,
9, 2353–2358. 2757–2785.
11 M. Scheuermeyer, M. Kusche, F. Agel, P. Schreiber, F. Maier, 34 H. Zhao, J. Chem. Technol. Biotechnol., 2016, 91, 25–50.
¨
H.-P. Steinruck, J. H. J. Davis, F. Heym, A. Jess and 35 M. Moniruzzaman, K. Nakashima, N. Kamiya and M. Goto,
P. Wasserscheid, New J. Chem., 2016, 40, 7157–7161. Biochem. Eng. J., 2010, 48, 295–314.
12 A. Benchea, B. Siu, M. Soltani, J. H. McCants, E. A. Salter, 36 Z. S. Breitbach and D. W. Armstrong, Anal. Bioanal. Chem.,
A. Wierzbicki, K. N. West and J. H. J. Davis, New J. Chem.,
2017, 41, 7844–7848.
2008, 390, 1605–1617.
37 C.-M. Jin, C. Ye, B. S. Phillips, J. S. Zabinski, X. Liu, W. Liu
and J. M. Shreeve, J. Mater. Chem., 2006, 16, 1529–1535.
38 R. F. Landis, A. Gupta, Y.-W. Lee, L.-S. Wang, B. Golba,
B. Couillaud, R. Ridolfo, R. Das and V. M. Rotello, ACS
Nano, 2017, 11, 946–952.
13 J. H. J. Davis, Chem. Lett., 2004, 33, 1072–1077.
14 R. Giernoth, Angew. Chem., Int. Ed., 2010, 49, 2834–2839.
15 H. Ohno, Bull. Chem. Soc. Jpn., 2006, 79, 1665–1680.
16 H. Ohno, Electrochemical Aspects of Ionic Liquids, John Wiley
& Sons, Hoboken, NJ, 2005.
39 U. Piotrowska, M. Sobczak, E. Oledzka and C. Combes, J.
Appl. Polym. Sci., 2016, 133, 43728.
17 H. Ohno, Y. Nakai and K. Ito, Chem. Lett., 1998, 27, 15–16.
´
18 M. Yoshizawa and H. Ohno, Chem. Lett., 1999, 28, 889–890. 40 M. Mena, A. Lopez-Luna, K. Shirai, A. Tecante, M. Gimeno
´
19 M. Yoshizawa and H. Ohno, Electrochim. Acta, 2001, 46,
1723–1728.
20 J. Pernak, A. Czepukowicz and R. Pozniak, Ind. Eng. Chem.
Res., 2001, 40, 2379–2383.
21 L. C. Branco, J. N. Rosa, J. J. Moura Ramos and
C. A. M. Afonso, Chem.–Eur. J., 2002, 8, 3671–3677.
22 J. Fraga-Dubreuil, M.-H. Famelart and J. P. Bazureau, Org.
Process Res. Dev., 2002, 6, 374–378.
and E. Barzana, Bioprocess Biosyst. Eng., 2013, 36, 383–387.
41 D. Omay and Y. Guvenilir, Biocatal. Biotransform., 2013, 31,
132–140.
42 J. Olejniczak, J. Sankaranarayanan, M. L. Viger and
A. Almutairi, ACS Macro Lett., 2013, 2, 683–687.
43 M. B. Harney, R. R. Pant, P. A. Fulmer and J. H. Wynne, ACS
Appl. Mater. Interfaces, 2009, 1, 39–41.
44 M. Chen, H. Zhu, S. Zhou, W. Xu, S. Dong, H. Li and J. Hao,
Langmuir, 2016, 32, 2338–2347.
´
23 J. Pernak, A. Olszowka and R. Olszewski, Pol. J. Chem., 2003,
77, 179–187.
45 A. K. Mandal, S. Sreejith, T. He, S. K. Maji, X.-J. Wang,
S. L. Ong, J. Joseph, H. Sun and Y. Zhao, ACS Nano, 2015,
9, 4796–4805.
24 U. Domanska and A. Marciniak, J. Chem. Thermodyn., 2005,
37, 577–585.
25 Q. Liu, M. H. A. Janssen, F. van Rantwijk and R. A. Sheldon, 46 M. M. Cecchini, A. Bendjeriou, N. Mnasri, C. Charnay, F. De
Green Chem., 2005, 7, 39–42.
Angelis, F. Lamaty, J. Martinez and E. Colacino, New J.
Chem., 2014, 38, 6133–6138.
47 B. H. Lipshutz and P. A. Blomgren, Org. Lett., 2001, 3, 1869–
1871.
48 D. C. Batesky, M. J. Goldfogel and D. J. Weix, J. Org. Chem.,
2017, 82, 9931–9936.
26 E. Kuhlmann, S. Himmler, H. Giebelhaus and
P. Wasserscheid, Green Chem., 2007, 9, 233–242.
27 M. Wang, X. Xiao, X. Zhou, X. Li and Y. Lin, Sol. Energy Mater.
Sol. Cells, 2007, 91, 785–790.
28 G. Laus, G. Bentivoglio, H. Schottenberger, V. Kahlenberg,
¨
H. Kopacka, T. Roder and H. Sixta, Lenzinger Ber., 2005, 84, 49 P. Hodge and E. Khoshdel, J. Chem. Soc., Perkin Trans. 1,
71–85. 1984, 195–198.
29 A. M. Leone, S. C. Weatherly, M. E. Williams, H. H. Thorp 50 H. M. Relles and R. W. Schluenz, J. Am. Chem. Soc., 1974, 96,
and R. W. Murray, J. Am. Chem. Soc., 2001, 123, 218–222. 6469–6475.
30 J. Pernak and M. Branicka, J. Surfactants Deterg., 2003, 6, 51 G. Anilkumar, H. Nambu and Y. Kita, Org. Process Res. Dev.,
119–123. 2002, 6, 190–191.
31 L. J. A. Siqueira and M. C. C. Ribeiro, J. Phys. Chem. B, 2009, 52 P. A. Sibbald, J. Chem. Educ., 2015, 92, 567–570.
113, 1074–1079.
32 G. D. Smith, O. Borodin, L. Li, H. Kim, Q. Liu, J. E. Bara,
53 H. Luo, G. A. Baker and S. Dai, J. Phys. Chem. B, 2008, 112,
10077–10081.
D. L. Gin and R. Nobel, Phys. Chem. Chem. Phys., 2008, 10, 54 R. E. Del Sesto, T. M. McCleskey, C. Macomber, K. C. Ott,
6301–6312.
A. T. Koppisch, G. A. Baker and A. K. Burrell, Thermochim.
Acta, 2009, 491, 118–120.
This journal is © The Royal Society of Chemistry 2018
RSC Adv., 2018, 8, 36025–36033 | 36033