Base-to-Base Organocatalytic Approach for One-Pot Construction of

Sep 7, 2016 - Viko LadeltaJoey D. KimPanayiotis BilalisYves GnanouNikos Hadjichristidis. Macromolecules 2018 51 (7), 2428-2436. Abstract | Full Text ...
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Base-to-Base Organocatalytic Approach for One-Pot Construction of Poly(ethylene oxide)-Based Macromolecular Structures Yening Xia, Ye Chen, Qilei Song, Shuangyan Hu, Junpeng Zhao,* and Guangzhao Zhang Faculty of Materials Science and Engineering, South China University of Technology, Guangzhou 510640, People’s Republic of China S Supporting Information *

ABSTRACT: A base-to-base organocatalytic approach has been developed for one-pot synthesis of poly(ethylene oxide)block-polyesters and poly(ethylene oxide)-based polyurethanes. Ethylene oxide is first polymerized from a diol in the presence of a phosphazene superbase; then a thiourea is added to be deprotonated by the strongly basic alkoxide, which attenuates the basicity of the catalytic system and thus allows for controlled polymerization of the subsequently added cyclic ester from the polyether chain end or for step-growth polymerization of an added diisocyanate with the macrodiol which is free from anionic homopolymerization of the diisocyanate. The approach shows several advantages in addition to the one-pot facile character, e.g., a wide applicability toward different “second monmers” including (but not limited to) ε-caprolactone, L-lactide, and diisocyanate, and a low amount of “second catalyst” required as the deprotonated thiourea itself serves as the mildly or weakly basic organocatalyst. Impact of the Nsubstituent, i.e., pKa of the thiourea, on the catalytic efficacy of the deprotonated thiourea has also been preliminarily revealed.

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istry.14−22 A majority of preliminary studies exploring for new organocatalysts and catalytic mechanisms are accompanied or closely followed by attempts to use the organocatalytic systems for rational design and precise synthesis of various macromolecular structures,23,24 and some of them have already revealed new opportunities to develop efficient and more expedient approaches. For example, one-pot sequential ROP of EO (or monosubstituted epoxides) and cyclic esters/carbonate, e.g., ε-caprolactone (CL), trimethylene carbonate (TMC), δvalerolactone, and its derivatives, has been realized recently by a few organocatalytic approaches, including the use of a single organocatalyst25,26 or a “catalyst switch” strategy.27−29 Comparatively, the “catalyst switch” strategy has shown good versatility in terms of monomer varieties, better convenience as easily handled nonpolar solvent or bulk conditions are applicable, higher efficiency in terms of catalyst amount and reaction time needed, and better control over structure and molar mass of the copolymers at high conversions. In the previously developed base-to-acid process, the ROP of an epoxide, catalyzed by a phosphazene superbase (t-BuP4), is conducted first; then an acidic organocatalyst (diphenyl phosphate, DPP) is added in excess to neutralize the alkoxide and switch to an acidic catalytic condition, which allows for controlled ROP of the second monomer and thus the achievement of well-defined polyether−polyesters block copolymers (Scheme 1a).27,28 Such endeavor has opened up a new avenue to facile synthesis of block copolymers from monomers suited to

INTRODUCTION Block copolymers constituted by poly(ethylene oxide) (PEO) and aliphatic polyesters, termed herein as PEO−polyesters, represent an important class of polymeric materials that have received extensive attention for their attractive physicochemical properties, such as biodegradability, biocompatibility, amphiphilicity, and double or multiple crystallinity, derived from the two types of blocky components, as well as for the promising prospects they have shown for biomedical applications including drug delivery, controlled release, gene therapy, tissue engineering, etc.1−6 For the synthesis of polymers based on PEO and polyesters, ring-opening polymerization (ROP) of ethylene oxide (EO) 7,8 and cyclic esters (also cyclic carbonates),9−13 respectively, has been the most widely employed approach to achieve controlled molar masses, narrow molar mass distributions (ĐM), and tailored macromolecular structures. Therefore, one-pot sequential ROP of EO and a cyclic ester is apparently the most convenient route to the corresponding block copolymer, which is seemingly facile as PEO and polyester both start and grow with hydroxyl/alkoxide species. However, it has remained a major challenge as the initiating/catalytic systems that suits EO (or cyclic ester) can be inactive or lead to uncontrolled ROP for the other. Hence, the synthesis of PEO−polyesters generally requires multiple steps of polymerization, isolation, and purification. In fact, most of the synthetic processes reported in the literature have appealed to commercially available PEOs to be used as macroinitiators for the ROP of cyclic esters.4−6 Because of the rising demand for “greener” and metal-free polymeric materials, organocatalytic polymerization has blossomed unprecedentedly in the past 15 years into an appealing research area and a powerful toolbox in polymer chem© XXXX American Chemical Society

Received: July 17, 2016 Revised: August 27, 2016

A

DOI: 10.1021/acs.macromol.6b01542 Macromolecules XXXX, XXX, XXX−XXX

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Scheme 1. (a) Previously Developed Base-to-Acid “Catalyst Switch” Strategy for Sequential ROP of EO and Cyclic Ester/ Carbonate, Which Has Been Shown, in the Present Study, To Be Incompetent When the Second Monomer Is L-Lactide; (b) Sequential ROP of EO and Cyclic Ester/Carbonate; (c) One-Pot Synthesis of PEO-Based Polyurethane via the Novel Base-toBase Organocatalytic Approach

Figure 1. Formulas of the thioureas used in this study.

of cyclic esters (or carbonates), including LAs, have been achieved by using organocatalysts with relatively mild basicity compared to t-BuP4,14,19 a (stong) base-to-(mild) base “catalyst switch” strategy has appeared to be a rational choice, which is referred to herein as the base-to-base (organocatalytic) approach. We have envisaged that addition of a protic compound at the end of the t-BuP4-catalyzed ROP of EO would trigger a proton exchange reaction, neutralize the strongly basic alkoxide, and meanwhile generate a new anionic species with the basicity better suited to the subsequent ROP of the cyclic ester. For this purpose, the protic compound needs to be appropriately chosen in terms of acidity (pKa). Namely, it should be acidic enough to readily transfer proton to the alkoxide (PEO chain end); nevertheless, its deprotonated form should maintain adequate basicity to promote efficient ROP of the second monomer. On the basis of such a consideration, we have chosen, in this work, thioureas (TUs) to be the precursors of

different catalysts, but some shortcomings have also been manifested. The organic salt (phosphazenium diphenyl phosphate) generated by the neutralization reaction has no catalytic activity and even shows a retardation effect, which makes it necessary to apply a large excess of DPP with regard to the alkoxide species in the switching step, to ensure a reasonable polymerization rate of the second monomer.27 Because of the acidic nature of the second catalyst, common organic solvents which are weakly basic, e.g. tetrahydrofuran (THF) and dimethyl sulfoxide, are not applicable, and complete conversion of the first monomer (epoxide) needs to be strictly ensured. More importantly, another type of valuable cyclic ester, the lactides (LAs), cannot be involved in this procedure as they are far less sensitive to Brønsted acid catalysts compared to cyclic monoesters and carbonates.30−32 Therefore, it is of great interest for us to modify the strategy accordingly and/or seek for alternative means to compensate for such shortcomings. In view of the fact that controlled ROP B

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Table 1. Conditions and Results of Sequential ROP of EO and Cyclic Esters Performed via the Base-to-Base Organoctalytic Approacha entry

TU

[M]0/[OH]0/[t-BuP4]0/ [TU]0b

temp (°C)

timec (h)

conv (%)

Mn,theord (kg mol−1)

Mn,NMRe (kg mol−1)

Mn,SECf (kg mol−1)

ĐM f

EO1 EO1CL1 EO1CL2 EO1CL3 EO2 EO2LLA1 EO2LLA2 EO2LLA3 EO3 EO3TMC1 EO3TMC2 EO3TMC3

− TU1 TU2 TU3 − TU1 TU2 TU3 − TU1 TU1 TU2

58/1/0.1/0 51/1/0.1/0.12 51/1/0.1/0.12 51/1/0.1/0.12 59/1/0.1/0 16/1/0.1/0.12 16/1/0.1/0.12 16/1/0.1/0.12 109/1/0.08/0 75/1/0.08/0.1 75/1/0.08/0.1 75/1/0.08/0.1

40 RT 40 40 40 RT RT RT 40 RT 40 RT

48 24 20 20 48 6 6 6 48 24 18 24

−g >99 6 0 −g >99 >99 0 −g 24 71 38

5.1 16.7 5.8 − 5.2 9.8 9.8 − 9.6 13.3 20.5 15.4

5.5 16.6 6.5 − 5.3 9.3 9.0 − 9.6 13.5 19.6 15.1

5.6 21.1 6.9 − 5.3 9.9 9.3 − 10.3 15.8 20.7 17.5

1.04 1.11 1.04 − 1.05 1.09 1.14 − 1.07 1.04 1.17 1.05

a

Data given for each entry are related to the synthesis of PEO precursors (in the case of homopolymers) or the second block (in the case of triblock copolymers). bFeed ratio of monomer, hydroxyl groups, t-BuP4, and thiourea. cReaction time for the ROP of EO (for entries of PEO precursors) or the second monomer (for entries of block copolymers). dTheoretical number-average molar mass calculated from feed and monomer conversion. e Number-average molar mass calculated from 1H NMR spectra of the isolated product using integrals of the characteristic signals. fNumber-average molar mass and molar mass distribution obtained from SEC analysis (THF, 35 °C, PEO standards). gThe conversion of EO is not determined in this work, which should be complete according to refs 15 and 24 and references cited therein. distribution (Mw/Mn or ĐM) of the (co)polymers. Nuclear magnetic resonance (NMR) spectra were recorded at room temperature (RT) on a Bruker AV400 NMR spectrometer operating at 400 MHz using CDCl3 as solvent, and 1H NMR spectra were used to calculate the monomer conversion using integrals of the characteristic signals from the monomer and polymer as well as the number-average molar mass (Mn,NMR) using integrals of the characteristic signals from the end group and/or (co)polymer main body. Differential scanning calorimetry (DSC) measurements were performed on a NETZSCH DSC204F1 system in a nitrogen flow. The sample was quickly heated to 150 °C, kept at this temperature for 3 min to remove thermal history, cooled to −150 °C, and heated again to 150 °C at the same heating and cooling rates (5, 10, or 20 K min−1). Polymer Synthesis. Poly(ε-caprolactone)-b-Poly(ethylene oxide)-b-Poly(ε-caprolactone) Triblock Copolymers. Typical procedure of EO1CL1 (Table 1): ca. 40 mL of clean THF, 0.14 mL of BD (1.6 mmol), and 0.40 mL of t-BuP4 solution (0.32 mmol of t-BuP4) were charged into a reaction flask. 9.2 mL of EO (184 mmol) was slowly condensed into the flask at −20 °C ([EO]0 = 3.7 M). The flask was then sealed by a stopcock, and the temperature was slowly elevated to 40 °C. After heating and stirring for 48 h, the flask was cooled down to RT. Then 0.1 mL of the reaction mixture was withdrawn in an argon flow and injected into a mixture of 5 mL of THF and a few drops of AcOH. The solution was then used for SEC measurement (THF). Theoretical number-average molecular weight (Mn,theor, assuming complete EO conversion) = 5.1 kg mol−1. Mn,SEC = 5.6 kg mol−1 and ĐM = 1.04. About 7.0 mL of living PEO solution containing ca. 0.53 mmol of (PEO−OH + PEO−O−) and 0.053 mmol of PEO−O− was withdrawn with a syringe in an argon flow and injected into another reaction flask prechanged with a 5.0 mL of THF solution containing 16.1 mg of TU1 (0.067 mmol), upon which the brownish-yellow color of PEO solution became slightly darker, indicating the occurrence of proton transfer reaction and the generation of a new anionic species. After 1 h of stirring, 3.0 mL of CL (27 mmol) was added, and the reaction mixture was stirred at RT ([CL]0 = 1.8 M). A 0.1 mL aliquot was withdrawn in 1 h and injected in a mixture of 0.6 mL of CDCl3 and 1 drop of acetic acid for 1H NMR measurement to determine the conversion of CL. After the withdrawal of another aliquot at 24 h, the reaction was finally quenched by addition of 0.5 mL of acetic acid. Then the solution was poured into diethyl ether to precipitate PCL-b-PEO-b-PCL triblock copolymer. The white powder was then collected, dried in a vacuum, and used for SEC (THF) and 1H NMR analysis. Conv(CL) > 99%; Mn,theor(PCL) = 11.6 kg mol−1 ÷ 2, Mn,theor(PCL-b-PEO-b-PCL) =

the second catalysts (Figure 1 and Scheme 1b), as their acidities lie between those of aliphatic alcohols and the commonly used acidic organocatalysts.33 Moreover, as inspired by previous studies on step-growth polymerization (SGP) of macrodiols with diisocyanates catalyzed by mildly basic organocatalysts,34−37 we have also been interested to investigate into the applicability of such a base-to-base approach on the one-pot cascade synthesis of PEO-based polyurethanes (PU), namely, sequentially performed organocatalytic ROP and SGP (Scheme 1c).

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EXPERIMENTAL SECTION

Chemicals. ε-Caprolactone (CL; 99%), 1,4-butanediol (BD; 99%), tetrahydrofuran (THF; AR), benzenedimethanol (BDM; 99%), and isophorone diisocyanate (IPDI; 99%) were purchased from Aladdin. CL and BD were dried over calcium hydride and distilled under vacuum; THF was dried successively by molecular sieve (4 Å), calcium hydride, and n-butyllithium; BDM was dried by azeotropic distillation of THF prior to use; IPDI was stored in an inert atmosphere and used without further purification. Trimethylene carbonate (TMC; 98%), 1,3-dicyclohexylthiourea (TU1; 98%), 1,3-diphenylthiourea (TU2; 98%), and 1,3-bis[3,5-bis(trifluoromethyl)phenyl]thiourea (TU3; 98%) were purchased from TCI. TMC was recrystallized from distilled toluene, dried by azeotropic distillation of THF, and dissolved in purified THF into a 0.3 g mL−1 solution; each of the TUs was dried by azeotropic distillation of THF and dissolved in a desired amount of purified THF prior to use. Ethylene oxide (EO; 99.5%), t-BuP4 (0.8 M in n-hexane), and L-lactide (LLA; 98%) were purchased from Aldrich. EO was first condensed in a Schlenk flask and dried by stirring with calcium hydride in an ice−water bath for 4 h, then cryo-condensed into a graduated flask precharged with n-butyllithium, and stirred there in an ice−water bath for 1 h (EO is toxic by inhalation, and we recommend great caution in the process of drying and transferring); t-BuP4 was used as received; LLA was recrystallized from distilled ethyl acetate, dried by azeotropic distillation of THF, and dissolved in purified THF into a 0.2 g mL−1 solution. Instrumentation. Size exclusion chromatography (SEC) coupled with RI and UV detectors was conducted in THF at 35 °C using two identical PLgel columns (5 μm, MIXED-C) at a flow rate of 1.0 mL min−1, or in N,N-dimethylformamide (DMF) with LiBr (0.05 M) at 50 °C using the same columns and flow rate. Calibration was done with a series of poly(ethylene oxide) (PEO) standards (Fluka) to obtain number-average molar mass (Mn,SEC) and molar mass C

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Table 2. Conditions and Results of One-Pot Synthesis of PEO-Based Polyurethanes via the Base-to-Base Organocatalytic Approacha entry

TU

Mn.SEC(PEO)b (kg mol−1)

ĐM(PEO)b

temp (°C)

time (h)

Mn,SEC(PU)c (kg mol−1)

ĐM(PU)c

EOPU1

TU1

1.5

1.10

30

EOPU2

TU2

2.1

1.17

30

EOPU3

TU3

2.2

1.17

30

24 72 24 72 24 72 120 48d

31.5 40.5 52.6 67.8 7.1 11.6 14.4 21.7

1.69 1.50 1.51 1.59 1.88 1.79 1.79 1.52

50 a

[OH]0/[t-BuP4]0/[TU]0/[IPDI]0 = 1/0.05/0.06/0.5; [OH]0 = 0.24 M. bNumber-average molar mass and molar mass distribution of the PEO-diol (precursor of PU) obtained from SEC analysis (DMF, 50 °C, PEO standards). cNumber-average molar mass and molar mass distribution of the PEO-based PU obtained from SEC analysis (DMF, 50 °C, PEO standards). dHeating at 50 °C for 48 h after reaction at 30 °C for 120 h. 16.7 kg mol−1. Mn,SEC = 21.1 kg mol−1, ĐM = 1.11. 1H NMR (400 MHz, CDCl3): δ/ppm = 4.24−4.21 (−PEO−CH2CH2OCO−PCL), 4.19−3.92 (−CH2CH2CH2CH2CH2OCO−), 3.77−3.52 (−CH 2 CH 2 O−), 3.48−3.44 (−PEO−OCH 2 CH 2 CH 2 CH 2 O− PEO−), 2.43−2.19 (−OCOCH2CH2CH2CH2CH2−), 1.77−1.56 (−OCOCH 2 CH 2 CH 2 CH 2 CH 2 −), 1.43−1.33 (−OCOCH 2 CH 2 CH 2 CH 2 CH 2 −); M n,NMR (PCL) = 11.2 kg mol −1 ÷ 2, Mn,NMR(PCL-b-PEO-b-PCL) = 16.6 kg mol−1. Poly(L-lactide)-b-Poly(ethylene oxide)-b-Poly(L-lactide) Triblock Copolymers. Typical procedure of EO2LLA2 (Table 1): The synthesis of PEO followed the same procedure as described above, using ca. 30 mL of THF, 0.15 mL of BD (1.7 mmol), 0.42 mL of tBuP4 solution (0.34 mmol of t-BuP4), and 10.0 mL of EO (200 mmol) ([EO]0 = 5.0 M). Mn,theor = 5.2 kg mol−1, Mn,SEC = 5.3 kg mol−1, and ĐM = 1.05. About 7.5 mL of living PEO solution containing ca. 0.85 mmol of (PEO−OH + PEO−O−) and 0.085 mmol of PEO−O− was withdrawn and injected into another reaction flask prechanged with 5.0 mL of THF solution containing 22.9 mg of TU2 (0.10 mmol), upon which the brownish-yellow PEO solution became bright green. After 1 h of stirring, 10.0 mL of THF solution containing 2.0 g of LLA (13.9 mmol) was added, and the reaction mixture was stirred at RT ([LLA]0 = 0.62 M). A 0.1 mL aliquot was withdrawn in 2 h and injected in a mixture of 0.6 mL of CDCl3 and 1 drop of acetic acid for 1H NMR measurement to determine the conversion of LLA. After the withdrawal of another aliquot at 6 h, the reaction was finally quenched by addition of 0.5 mL of acetic acid. Then the solution was poured into diethyl ether to precipitate PLLA-b-PEO-b-PLLA triblock copolymer. The white powder was then collected, dried in a vacuum, and used for SEC (THF) and 1H NMR analysis. Conv(LLA) > 99%; Mn,theor(PLLA) = 4.6 kg mol−1 ÷ 2, Mn,theor(PLLA-b-PEO-b-PLLA) = 9.8 kg mol−1, Mn,SEC = 9.3 kg mol−1, and ĐM = 1.14. 1H NMR (400 MHz, CDCl3): δ/ppm = 5.30−5.10 (−CH(CH3)OCO−), 4.41−4.23 (−OCOCH(CH3)OH) and (−PEO−CH2CH2OCO−PLLA), 3.77− 3.51 (−CH2CH2O−), 3.48−3.45 (−PEO−OCH2CH2CH2CH2O− PEO−), 1.61−1.44 (−OCOCH(CH3)−); Mn,NMR(PLLA) = 3.7 kg mol−1 ÷ 2 and Mn,NMR(PLLA-b-PEO-b-PLLA) = 9.0 kg mol−1. Poly(trimethylene carbonate)-b-Poly(ethylene oxide)-b-Poly(trimethylene carbonate) Triblock Copolymers. Typical procedure of EO3TMC1 (Table 1): The synthesis of PEO used ca. 40 mL of THF, 0.1 mL of BD (1.1 mmol), 0.23 mL of t-BuP4 solution (0.18 mmol of t-BuP4), and 12.0 mL of EO (240 mmol) ([EO]0 = 4.6 M). Mn,theor = 9.6 kg mol−1, Mn,SEC = 10.3 kg mol−1, and ĐM = 1.07. About 7.0 mL of living PEO solution containing ca. 0.39 mmol of (PEO−OH + PEO−O−) and 0.032 mmol of PEO−O− was withdrawn and injected into another reaction flask prechanged with 5.0 mL of THF solution containing 9.2 mg of TU1 (0.038 mmol). After 1 h of stirring, 10.0 mL of THF solution containing 3.0 g of TMC (29.4 mmol) was added, and the reaction mixture was stirred at RT ([TMC]0 = 1.3 M). A 0.1 mL aliquot was withdrawn in 24 h and injected in a mixture of 0.6 mL of CDCl3 and 1 drop of acetic acid for 1 H NMR measurement to determine the conversion of TMC; then the

reaction was quenched by addition of 0.5 mL of acetic acid. The solution was poured into diethyl ether to precipitate PTMC-b-PEO-bPTMC triblock copolymer. The white powder was then collected, dried in vacuum, and used for SEC (THF) and 1H NMR analysis. Conv(TMC) = 24%; Mn,theor(PTMC) = 3.7 kg mol−1 ÷ 2, Mn,theor(PTMC-b-PEO-b-PTMC) = 13.3 kg mol−1, Mn,SEC = 15.8 kg mol−1, and ĐM = 1.04. 1H NMR (400 MHz, CDCl3): δ/ppm = 4.32− 4.27 (−PEO−CH2CH2OCOOCH2−PTMC), 4.27−4.20 (−OCOOCH2CH2CH2−), 3.77−3.49 (−PEO−CH2CH2OCOO−PTMC) and (−CH2CH2O−), 3.48−3.44 (−PEO−OCH2CH2CH2CH2O− PEO−), 2.10−2.00 (−OCOOCH 2 CH 2 CH 2 −), 1.95−1.89 (−PTMC−OCOCH2CH2CH2OH); Mn,NMR(PTMC) = 3.8 kg mol−1 ÷ 2 and Mn,NMR (PTMC-b-PEO-b-PTMC) = 13.5 kg mol−1. Poly(ethylene oxide)-Based Polyurethane. Typical procedure of EOPU2 (Table 2): 391.4 mg (2.8 mmol) of BDM was charged in a reaction flask and dissolved in 5 mL of THF, followed by cryoevaporation of THF and drying of BDM under vacuum for 1 h. 18 mL of clean THF was condensed into the flask. After complete dissolution of BDM, 0.35 mL of t-BuP4 solution (0.28 mmol of t-BuP4) was added, and the flask was cooled at −20 °C. Then 5 mL of EO (100 mmol) was slowly condensed into the flask ([EO]0 = 4.3 M, [OH]0 = 0.24 M). The flask was then sealed by a stopcock, and temperature was slowly elevated to 50 °C. After heating and stirring for 48 h, the flask was cooled down to RT. Then a few drops of the reaction mixture was withdrawn in an argon flow and diluted with 1 mL of DMF with 1 drop of AcOH. The solution was then used for SEC measurement (DMF and THF). Mn,theor = 1.6 kg mol−1, Mn,SEC(DMF) = 2.1 kg mol−1, ĐM(DMF) = 1.17, Mn,SEC(THF) = 1.7 kg mol−1, and ĐM(THF) = 1.04. To the living PEO solution was added 1.5 mL of THF solution containing 75.3 mg of TU2 (0.33 mmol), upon which the brownishyellow PEO solution turned bright green. After 1 h of stir, the reaction flask was warmed up to 30 °C and 0.60 mL of IPDI (2.8 mmol) was added. The reaction mixture became more and more viscous apparently while maintaining the bright green color. Aliquots were withdrawn in 24 and 72 h, a few drops each, for SEC analysis (DMF) to monitor the increase of molar mass. The reaction was finally quenched by addition of 0.5 mL of acetic acid, and 5 mL of THF was also added for dilution. Then the solution was poured into a cold (−20 °C) mixture of diethyl ether and methanol (9/1, v/v) to precipitate the product, which was then collected, dried under vacuum, and used 1 H NMR analysis. Mn,SEC = 67.8 kg mol−1 and ĐM = 1.59. 1H NMR (400 MHz, CDCl3): δ/ppm = 7.31−7.29 (aromatic protons), 4.58− 4.53 (−OCH2C6H4CH2O−), 4.28−4.14 (−OCH2CH2OCONH−), 3.85−3.50 (−CH2CH2O−), 2.95−2.85 (−OCONHCH2−), and 1.75−0.80 (aliphatic protons in IPDI moiety).

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RESULTS AND DISCUSSION Sequential ROP of EO and CL with t-BuP4 as a single catalyst failed in the achievement of well-defined block copolymer, confirming the necessity of “catalyst switch” even with the ratio D

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Figure 2. SEC trace (left, RI signal in THF at 35 °C) and 1H NMR spectra (right) of a representative triblock copolymer synthesized by sequential ROP of EO and CL via the base-to-base organocatalytic approach (EO1CL1 in Table 1).

Scheme 2. Illustration of Plausible “Chain-End Activation” by Proton Exchange or Hydrogen Bonding between Alkoxide and Thiourea Species during the ROP of the Second Monomer in the Process Depicted in Scheme 1b

isolated by precipitation. The 1H NMR spectrum presents all the characteristic signals with fitting integrals from the end group, from the main bodies of the two blocky components, and from the monomeric units linking different blocks (Figure 2). Size exclusion chromatography (SEC) analysis shows a unimodal distribution with low ĐM (Figure 2 and Table 1).46 This is quite different from the “classic” anionic ROP of lactones initiated by alkali metal alkoxide, which usually suffers from significant inter- and intramolecular transesterification, the consequent high ĐM, and formation of cyclic oligomers (especially at high conversion).42−45 Therefore, it can be inferred that the introduction of TU/DTU brings about equilibrium between dormant and active chain ends, so that a low concentration of the alkoxide species is maintained due to the large pKa difference between TU and aliphatic alcohol which helps suppress the transesterification scrambling reaction. It is not yet to conclude whether the active species is a “free” oxyanion (with phosphazenium cation being the counterion) or an associate with TU via hydrogen bonding (Scheme 2).47 Except from chain-end activation, monomer activation through hydrogen bonding with DTUs may not be ruled out, as proposed by a recent publication on the ROP of cyclic esters catalyzed by combined alkali metal alkoxide and TUs.48 However, the present results seem to imply that in our system hydrogen donor may not be the key role that DTU plays for the catalysis because the catalytic efficiency of DTU drops as the acidity (capability for hydrogen bond formation) of TU increases (see below). Moreover, THF (a hydrogen acceptor) is used as the polymerization solvent in this study which is very likely to lower the possibility of hydrogen bond formation between DTU and the monomer and thus weaken the strength of DTU for activating the monomer.

of [t-BuP4]0/[OH]0 being 0.1 (Figure S1). An attempt was made via the base-to-acid approach to sequentially polymerize EO and LLA (Scheme 1a). However, no sign of LLA polymerization was shown even upon prolonged time (up to 1 week) and elevated temperature (40−110 °C). Acids that are stronger than DPP, such as trifluoromethanesulfonic acid,32 are not used in case of side reactions occurring on the polyether chains and/or THF (similar to the situation of cationic polymerization of cyclic ethers).38 Then we turned to thioureas which have much greater pKa values than DPP,39 indicating that the deprotonated thioureas (DTUs) are highly likely to be basic enough to activate terminal hydroxyls and polymerize cyclic esters therefrom. Differing from the base-to-acid approach where the deprotonated acid has no catalytic activity and it is the excess acid that catalyzes the ROP of the second monomer, in the present approach the DTU itself serves as the second catalyst, and therefore large excess of TU is in principle unnecessary. To compensate for the possible errors in the calculated amount of alkoxide, 1.2 equiv of TU (0.1−0.8 mol % of the second monomer, Table 1) was added after the ROP of EO to switch the catalytic condition (Scheme 1b), upon which the color of the reaction mixture changed and varied with different TUs (see Experimental Section), indicating the generation of a new anionic species other than the polyether alkoxide. With DTU1 as the catalyst, conversion of CL reached 92% in 1 h, indicating a higher polymerization rate than DPP-catalyzed ROP reported previously.27,30,40 This is probably due to the anionic character of the active species (alkoxide with bulky organic counterion).41−45 After 24 h, long before which a complete conversion of CL should have been reached, the reaction was quenched by addition of acetic acid and the PCLb-PEO-b-PCL triblock copolymer (EO1CL1 in Table 1) was E

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Figure 3. SEC trace (left, RI signal in THF at 35 °C) and 1H NMR spectrum (right) of a representative PLLA-b-PEO-b-PLLA triblock copolymer synthesized by sequential ROP of EO and LLA via the base-to-base organocatalytic approach (EO2LLA1 in Table 1).

not give rise to ROP of TMC at RT or 40 °C in 24 h. Heating at 60 °C for 48 h resulted in a nearly complete conversion whereas a substantially high ĐM (>1.3) indicating extensive occurrence of transfer reactions. Further optimization of the base-to-base organocatalytic approach for sequential ROP of EO and cyclic carbonates is necessary and in process. Recently, synthesis of polyurethanes via organocatalytic SGP of diol and diisocyanate has been achieved using basic organocatalysts that are less basic than t-BuP4 such as Nheterocyclic carbene and cyclic guanidine.34−37 However, to our knowledge, one-pot cascade organocatalytic synthesis of polyether-based PUs by sequential anionic ROP and SGP has not been investigated yet. In the present study, to reveal the applicability of the base-to-base approach for one-pot organocatalytic construction of PEO-based macromolecular structures other than block copolymers, attempts have been made to sequentially perform anionic ROP of EO and base-catalyzed SGP of the generated macrodiol with diisocyanate in such a manner. BDM was used as a representative starting diol to indicate the possibility and convenience of incorporating functional groups in the PU product by using functional initiators. To demonstrate the necessity of attenuating the basicity between the two polymerization steps, a control experiment without “catalyst switch” was first performed. Namely, IPDI was added to the PEO solution ([t-BuP4]0/ [OH]0 = 0.05) directly after t-BuP4-catalyzed anionic ROP of EO, upon which an insoluble gel-like product was generated almost instantly (Scheme 1c and Figure S6). Homopolymerization of isocyanate under such a strongly basic (anionic) condition yielding polyamide (polyisocyanate) type segments is the most probable cause,51 and cross-linking (gelation) occurs due to the difunctional nature of IPDI as a monomer for chaingrowth polymerization.52 Detailed analysis of this product and its formation is out of the scope of the present study, as it is obviously not the PEO-based PU originally targeted at. In other attempts, TUs were added after the ROP of EO as the attenuator of the basicity as well as the precursor of the second catalyst for the SGP step, and the results are listed in Table 2. In the experiment with TU1, a small amount of insoluble product appeared upon addition of IPDI. Interestingly, the swollen-gel-like substance suspended in the solution and dissolved gradually until complete disappearance was observed in ca. 12 h. It thus seems that homopolymerization of isocyanate also occurred, though to a much lower extent as

The base-to-base organocatalytic approach has also shown good applicability for sequential ROP of EO and LLA. TU1 was first used as the catalyst precursor for LLA (EO2LLA1 in Table 1) leading to complete conversion of LLA in 2 h. After quenching the reaction at 6 h and isolation of the product by precipitation, NMR and SEC analysis reveals a well-defined PLLA-b-PEO-b-PLLA triblock copolymer (Figure 3 and Figure S2). Crystallizability of both blocks is revealed by DSC measurement (Figure S3). DTUs with lower basicity derived from TU2 and TU3 (Figure 1) showed nearly complete loss of capability for the ROP of CL (EO1CL2 and EO1CL3 in Table 1). Even at 40 °C, the conversion of CL reached only 6% in the presence of DTU2. On the other hand, DTU2 showed good catalytic activity toward the more base-sensitive LLA, as full conversion of LLA was reached in 2 h and ĐM remained low upon prolonged reaction time (EO2LLA2 in Table 1), similar to the results obtained with DTU1. However, the least basic DTU3 was unable to polymerize LLA (EO2LLA3 in Table 1). The different polymerizability of CL and LLA further confirms base type catalysis in the hydroxyl-DTU system and the expected base-to-base feature of the entire sequential ROP process. Increasing the ratio of [t-BuP4]0/[OH]0 to 0.2 leads to a higher ĐM for PCL-b-PEO-b-PCL (Figure S4), indicating a higher overall basicity after the switching step, which does not seem to have a profound influence on PLLA-b-PEO-b-PLLA probably because PLLA chains are relatively more tolerant toward transesterification reaction. It was reported that TMC derivative polymerized faster than CL under a basic condition.49 Indeed, TMC was able to polymerize in the cases of both DTU1 and DTU2 at room temperature (RT). However, conversions achieved were much lower after the same reaction time (EO3TMC1 and EO3TMC3 in Table 1). More interestingly, less basic DTU2 led to a higher conversion than DTU1. Although a sound conclusion is not yet to be drawn, the polymerization− depolymerization equilibrium of six-membered cyclic carbonate under anionic conditions is considered a possible explanation,50 which leads to different kinetic features of the ROP and thus monomer converion varies at the same reaction time with different catalysts used. A higher conversion has been reached at 40 °C with DTU1 (EO3TMC2 in Table 1); however, the SEC trace shows a typical sign of inter- and intramolecular transesterification type side reaction (Figure S5).27 DTU3 does F

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Figure 4. SEC traces (left, RI signal in DMF at 50 °C) of EOPU2 (precipitated) and its PEO precursor, and 1H NMR spectrum (right) of EOPU2, obtained from sequentially performed ROP and SGP via the base-to-base organocatalytic approach using TU2 as the precursor of the second catalyst.

three for one-pot cascade synthesis of PEO−PU via the baseto-base organocatalytic approach.

compared with the previous case due to the attenuated basicity. Because of the low ceiling temperature, especially under basic conditions,51 the N-substituted polyisocyanate segments depolymerized as the free isocyanate groups were consumed in the reaction with hydroxyls. The depolymerization of polyisocyanate is known to have a high probability of generating cyclic trimers (1,3,5-tri-N-substituted isocyanurates) which is too stable to further degrade into free isocyanates and thus would break the stoichiometric equality between isocyanate and hydroxyl groups needed to achieve high molar mass of PU. However, this does not seems to be the case herein since the increase of Mn,SEC is not noticeably affected (EOPU1 in Table 2, Figure S7), and no signal of isocyanurate moieties has been found in the 1H NMR spectra of the isolated PU product. Such a result seems to imply that the terminals of the initially generated polyisocyanate segments were amide groups hydrogen-bonded with DTU1 (similarly as depicted in Scheme 2), instead of free amidate anions, so that backbiting reaction was inhibited and depolymerization led only to the regeneration of isocyanate groups.53 Nevertheless, it is still considered that TU1 is not fully competent for the task as isocyanate polymerization-depolymerization process would have a retarding effect on the SGP. Experiments with TU2 and TU3 were conducted in the same manner. Differently, no insoluble product was generated and the reaction solutions remained homogeneous throughout the entire processes, indicating the nonoccurrence of isocyanate homopolymerization which is consistent with their lower pKa values compared to that of TU1 (lower basicity of the corresponding DTUs). In the presence of DTU2, high viscosity was observed in only 1 h, and relatively high molar mass was obtained according to the SEC analysis (EOPU2 in Table 2 and Figure 4, left). The 1H NMR spectrum of the isolated product further evidences the achievement of the expected PU structure derived from BDM-initiated PEO and IPDI (Figure 4, right). On the other hand, the SGP with DTU3 proceeded much slower as indicated by lower Mn,SEC achieved after the same or even longer reaction time at 30 °C (even after prolonged reaction time at elevated temperature, EOPU3 in Table 2) and the evident presence of PEO precursor in the SEC trace of the SGP product before precipitation (Figure S7). Obviously, the lower pKa of TU3 leads to an insufficient basicity (poor catalytic efficacy) of DTU3 for the SGP of PEO-macrodiol with IPDI as compared with DTU2. Therefore, the results obtained so far have clearly suggested that TU2 be best candidate of the

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CONCLUSIONS In conclusion, deprotonated thioureas have shown the prospect of being effective basic organocatalysts for the ROP of CL/ LLA/TMC and SGP of PEO macrodiol with a diisocyanate, provided the N-substituents and polymerization conditions are appropriately chosen. On this basis, sequential ROP of EO and such monomers can be performed in a facile and, in most cases, controlled manner via switching the catalyst from a strong base (for EO) to a mild base (for cyclic ester/carbonate/SGP) by introduction of a thiourea between the two polymerization steps. Such a base-to-base approach benefits from a good applicability with regard to monomer/polymerization types and low catalyst loading and is therefore considered a promising strategy to establish a versatile platform for one-pot organocatalytic construction of a broad range of PEO- or polyetherbased macromolecular structures. The catalytic mechanism, kinetic details, and the usability of other types of catalyst precursors (ureas, amides, imides, guanidines, imidazolium salts, etc.) and monomers (e.g., lactones with different ring sizes, substituted epoxides, lactones, and cyclic carbonates) are of great interest to us and are under further investigation.

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ASSOCIATED CONTENT

S Supporting Information *

The Supporting Information is available free of charge on the ACS Publications website at DOI: 10.1021/acs.macromol.6b01542. Additional 1H NMR spectra, SEC and DSC traces (PDF)

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AUTHOR INFORMATION

Corresponding Author

*E-mail: [email protected] (J.Z.). Notes

The authors declare no competing financial interest.

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ACKNOWLEDGMENTS The financial support of National Natural Science Foundation of China (21504024), Ministry of Science and Technology of China (2012CB933802) and Fundamental Research Funds for Central Universities is acknowledged. G

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