Supporting Information

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1 Supporting Information Urea Anions: Simple, Fast, and Selective Catalysts for Ring-Opening Polymerizations Binhong Lin and Robert M. Waymouth* Department of Chemistry, Stanford University, Stanford, California, 9435, United States * TABLE OF COTETS Materials... S2 General Considerations... S2 Preparation of Ureas... S2 Polymerizations... S2 Transesterifications... S3 Figure S. omonuclear Decoupled MR Spectrum of poly(l-la)... S4 Figure S2. Differential Scanning Calorimetry of poly(l-la)... S4 Figure S3. MR Spectra of 5 and KOMe / 5... S5 Table S. k obs of Polymerization of VL Using DBU with Ureas or TU as Cocatalysts... S6 Figure S4. Comparison of KOMe and K/PyO in CL ROP... S6 Figure S5. ROP of CL with Different Ureas... S7 Figure S6. vs Conversion for LA, VL, TMC-Bn and ipp... S8 Table S2. M n, theo and M n, MR... S8 Figure S7. M n, MR vs Conversion and M n, GPC vs M n, MR... S9 Figure S8. MR Spectra of poly(vl 43 )-b-poly(la 2 )... S9 Table S3. k obs of ROP for All Monomers and Ureas... S Figure S9. Methylated Urea (Single -Bond Donor)... S Figure S. Counter-ion Effect (Ureas)... S Figure S. Counter-ion Effect (TU)... S Figure S2. MALDI-TOF Spectrum poly(tmc-bn)... S2 Figure S3. MALDI-TOF Spectrum of poly(cl)... S2 Figure S4. Urea... S3 Figure S5. Urea 2... S3 Figure S6. Urea 3... S4 Figure S7. Urea 4... S4 Figure S8. Urea 5... S5 Figure S9. Urea 6... S5 Figure S2. Urea 7... S6 Figure S2. Urea 7b... S6 References... S7 S

2 Materials All materials were purchased from Sigma-Aldrich unless otherwise specified. Sodium methoxide (aome, 95%), potassium methoxide (KOMe, 95%), sodium hydride (a, 95%), - pyrenebutanol (PyO, 99%),,8-diazabicyclo[5.4.]undec-7-ene (DBU, 98%), and L-lactide (LA or L-LA, Purac, 99%) were used as received. δ-valerolactone (VL, technical grade) was dried over calcium hydride (Ca 2, Strem Chemicals Inc., 95%) and distilled. ε-caprolactone (CL, technical grade) was dried by sequentially storing the monomer with 3 separate portions of activated molecular sieves for at least two days each. Potassium hydride (K, in paraffin) was washed 5 times with pentane in an 2 -filled glovebox. -[3,5-bis(trifluoromethyl)phenyl]-3- cyclohexylthiourea (TU), benzyl 5-methyl-2-oxo-,3-dioxane-5-carboxylate (TMC-Bn) 2,3 and 2- isopropoxy-2-oxo-,3,2-dioxaphospholane (ipp) 4 were prepared by literature methods. Benzoic acid (99.5%) was recrystallized from toluene twice and dried under high vacuum. Dichloromethane (DCM, Fisher Scientific, 99.9%) and tetrahydrofuran (TF, Fisher Scientific, 99.9%) were dried over alumina in a solvent tower system. Tetrahydrofuran-d 8 (Cambridge Isotope Laboratory, 99.5%) was dried by storing with molecular sieves. General Considerations MR spectra were collected on 3 Mz, 4 Mz, 5 Mz and 6 Mz Varian Instruments at 2 C, with shifts referenced to residual solvent peaks and reported in ppm relative to tetramethylsilane. omonuclear-decoupled MR spectroscopy was performed on a 4 Mz MR, with the decoupler set.6 ppm. Polystyrene calibrated (calibrated from M p = 5 to 275,) molecular weights were determined using a Viscotek GPCMax with two Waters columns (3 mm by 7.7 mm) in TF at 35 C at a flow rate of ml/min and Viscotek S358 refractive index detector. Differential scanning calorimetry (DSC) was performed on an aluminum sealed sample (~3mg) using a TA Instrument Q2 under nitrogen. A rate of C for heating and cooling between 4 C and 2 C was used and the melting point data was determined during the second cycle. MALDI-TOF spectra were obtained on a Bruker Microflex (nitrogen laser of 337 nm) operating in linear mode. The polymer sample solutions ( mg/ml TF) and a dithranol solution (matrix, mg/ml TF) were mixed in a : volume ratio, μl of which was then spotted onto the MALDI-TOF sample plate before being air-dried. Preparation of Ureas The appropriate isocyanate was dissolved in TF and the corresponding amine was added gravimetrically. After a few minutes, TF was removed under vacuum. The crude was purified by washing with DCM using vacuum filtration (washed instead with toluene for the -methyl substituted urea). The final product was kept under vacuum overnight. The products were stored in an 2 -filled glovebox. General Polymerizations All polymerizations were carried out in an 2 -filled glovebox. Stock solutions of initiators and urea anion were prepared by dissolving either methoxide/urea, or alcohol/urea/metal hydride in TF. The appropriate amount of stock solution was then added to a 4 ml vial containing a stir bar and a TF solution of the monomer. Aliquots of the reactions were quenched by excess benzoic acid and were then removed from the glovebox for analysis. Polymerization of VL Using DBU with Urea, Urea 4 or TU In an 2 -filled glovebox, a stock solution containing 6.9 mg of PyO (.25 mmol), 9.5 mg of DBU (.625 mmol) and.625 mmol of, 4, or TU in ml of TF was prepared in a 4 ml vial. Then.2ml of the stock solution was added to 5 mg of VL in a separate vial containing a stir bar. Aliquots of the S2

3 reaction were removed and each added to mg of benzoic acid to be quenched. The aliquots were taken out of the glovebox, and the solvent was removed. Polymerization of LA (Low Catalyst Loading at.%, DP, Table, Entry 4) In an 2 - filled glovebox,.4 mg of PyO (.5 mmol) and 72 of mg L-LA (.5 mmol) were dissolved in.4 ml of TF in a 4 ml vial containing a micro stir bar. A stock solution containing.6 mg of K (.5 mmol) and 8.7 mg of 2 (.45 mmol) in.5 ml of TF was prepared in a separate vial. Then.5 ml of the stock solution containing the catalyst was added to the LA solution. At 5 s, the reaction was quenched by the addition of.3 ml of TF containing about mg benzoic acid. The reaction mixture was taken out of the glovebox and the solvent was removed. Analysis: 89% conversion by MR, M n, (vs. PS) = 9.8 kda, =.. Polymerization of LA (Low Catalyst Loading at.%, DP) In an 2 -filled glovebox, 44 mg of L-LA ( mmol) were dissolved in.8 ml of TF in a 4 ml vial containing a micro stir bar. A stock solution containing 2.8 mg of KOMe (.4 mmol) and 83.3 mg of 2 (.2 mmol) in 4 ml of TF was prepared in a separate vial. Then. ml of the stock solution containing the initiator and the catalyst was added to the L-LA solution. Aliquots of the reaction were removed and each added to about mg of benzoic acid to be quenched. The aliquots were taken out of the glovebox and the solvent was removed. Analysis (s): 87% conversion by MR, M n, (vs. PS) = 94.7 kda, =.4. Transesterification of VL with -Pyrenebutanol In an 2 -filled glovebox, a stock solution containing.6 mg of K (.4 mmol) and 58 mg of (.2 mmol) in.75 ml of TF was prepared in a 4 ml vial. A second stock solution of 25mg of VL (.25 mmol) in.38ml of TF was prepared in a separate vial,. ml of which was then added to 69. mg of PyO (.25 mmol) in a third vial containing a stir bar. Then. ml of the first stock solution was added to the third vial to initiate the reaction. Aliquots of the reaction were removed and each added to about mg of benzoic acid to be quenched. The aliquots were removed from the glovebox and analyzed by MR. The conversions were determined by integrating the peaks at 4.26 ppm (starting material: VL) and the peaks at ppm (products: PyO-poly(VL) and PyO-VL). k obs, initial = 9.8 ± 2. min -. Transesterification of Ethyl Acetate with -Pyrenebutanol In an 2 -filled glovebox, a stock solution containing.6 mg of K (.4 mmol) and 58 mg of (.2 mmol) in.75 ml of TF was prepared in a 4 ml vial. A second stock solution of mg of ethyl acetate (.25 mmol) in.39 ml of TF was prepared in a separate vial,. ml of which was then added to 69. mg of PyO (.25 mmol) in a third vial containing a stir bar. Then. ml of the first stock solution was added to the third vial to initiate the reaction. Aliquots of the reaction were removed and each added to about mg of benzoic acid to be quenched. The aliquots were removed from the glovebox and analyzed by MR. Conversion was calculated by determining the areas of the peaks at.25 ppm (ethyl acetate C 3 in -OC 2 C 3 ) and at.23 ppm (ethanol C 3 ). The peaks were slightly overlapping, so the area under the ethanol C 3 peak was determined by integrating the right half of the signal, which is then multiplied by 2. The integration of the ethyl acetate peak was determined by integrating both C 3 peaks, from which the area of the ethanol C 3 peak was then subtracted. k obs, initial =.5 ±. min -. S3

4 Figure S. omonuclear Decoupled MR Spectrum of poly(l-la). The polymer was prepared with KOMe / (:5) and L-lactide (target DP = 2, 96% conversion). The clean single peak at 5.6 suggests minimal epimerization of the stereocenter in the polymer sample Power Output (mw) Temperature ( C) Figure S2. Differential Scanning Calorimetry of poly(l-la). The sample is identical to the one in Figure S above (T m = 7 C). S4

5 Figure S3. MR Spectra of 5 and KOMe / 5. This is a comparison of the MR spectra (in TF-d 8 ) of 5 only (top) and KOMe + 5 (:, bottom). Upon reaction with KOMe, one of the - peaks of 5 (8.3 ppm in the top spectrum) is lost, while the other (7.92 ppm in the top spectrum, overlapping with one of the aryl C- signal) coalesce with the O- peak from the MeO generated, and shift to 6.98 ppm in the bottom spectrum, indicating the formation of a 5 - / MeO adduct. S5

6 Table S. k obs of Polymerization of VL Using DBU with Ureas or TU as Cocatalysts a pk a k obs (min - ) relative k obs TU urea 4 (similar structure) urea (similar pk a ) a See the experimental section above for reaction conditions and procedure. ln([m ]/[M]) R² = ln([m] /[M]) R² = Time (minutes) Time (minutes) 2 5 R² = R² = M n 5 M n Figure S4. Comparison of KOMe and K/PyO in CL ROP. Left: [K] % =. M, [PyO] % =. M, [5 234 ] % =.3 M, CL % = M in TF. Right: [KOMe] % =. M, [4 234 ] % =.3 M, CL % = M in TF. If KOMe is replaced by K/PyO, reaction kinetics behave similarly (linear st order monomer plot, molecular weight grows linearly with conversion and molecular weight distribution remains low until high conversion). S6

7 ln([m] /[M]) Example st Order Monomer Plot (CL) R² = R² =.9997 R² = R² =.9998 R² = R² = R² = Time (Minutes) U-7 U-6 U-5 U-4 U-3 U-2 U- Example M n Growth (CL) M n, GPC U-7 U-6 U-4 U Molecular Weight Distribution (CL).2 U-7 U-6. U-4 U Figure S5. ROP of CL with Different Ureas. Representative st order plots, traces of M n vs conversion and evolution of molecular weight distribution for the ring-opening polymerization of CL for different ureas. Reaction conditions: [KOMe] % =. M, [urea 234 ] % =.3 M, CL % = M in TF. st order plots are linear, molecular weight grows linearly with conversion and molecular weight distribution remains low up to high conversion (see Table, entries,, 2 and 4). S7

8 LA VL.2.2 U-6. U-. U-4 U TMC-Bn ipp.2. U-4 U-2 U-3.2. U-4 U Figure S6. vs Conversion for LA, VL, TMC-Bn and ipp. Molecular weight distribution remains low up to high conversion (~9%) for all the monomers using different ureas (see Table, entries 7 - VL, 5 - TMC). For LA, each data point is from each individual polymerization quenched at the corresponding time points. Table S2. M n, theo and M n, MR Conversion M n, theo. (kda) M n, MR (kda) LA a VL b CL c Comparison of number average molecular weight (M n ) calculated from [M] /[I] and conversion (M n, theo ) and experimental number average molecular weight (M n, MR ), determined by MR end-group analysis. [Monomer] =. M in TF, 25 C. a [Urea ] =.3 M, [KOMe] =. M. b [Urea 6] =.3 M, [KOMe] =. M. c [Urea 5] =.3 M, [K] =. M, [PyO] =.2 M. S8

9 5 5 M n, MR 5 LA VL M n, GPC 5 y =.644x R² = CL M n, MR Figure S7. M n, MR vs Conversion and M n, GPC vs M n, MR. Left: M n, MR and conversion (see data in Table S2). The experimental molecular weights determined by MR end-group analysis grow linearly with conversion. Right: M n, GPC and M n, MR (also see Figure 3). K % =. M, RO % =.2 M, 5 % =.3 M and [CL] % = M. M n, GPC scales linearly with M n, MR. (a) (b) (c) (d) Figure S8. MR Spectra of poly(vl 43 )-b-poly(la 2 ). (a) Lactide alpha-proton peaks (monomer: 5.4 ppm, polymer: 5.5 ppm). (b) δ-valerolactone delta-proton peaks (monomer: 4.33 ppm, polymer: 4.6 ppm). Transesterification peaks (neighboring LA / VL) are minimal, but would otherwise be between the monomer and polymer peaks (c and d), observed in the final block copolymer if the more reactive poly(la) block is synthesized before the poly(vl) block. S9

10 Table S3. k obs of ROP for All Monomers and Ureas k obs (min - ) Urea CL VL ipp TMC b LA 7.8 ±. 7.2 ±. a 6.8 ± ± ± ± ± ± ± ±. 3.3 ± ±.5.75 ±..822 ± ± ±..37 ± ± ±. 66. ±. c.39 ±..825 ±..7 ±..8 ± ±.5 See Equation and Figure 4. Unless otherwise specified, reaction conditions were: KOMe % =. M, urea 234 =.3 M, [Monomer] % = M. a KOMe % =.5 M, urea 234 =.45 M, [Monomer] % = M. b KOMe % =.5 M, urea 234 =.5 M, [Monomer] % =.5 M. c KOMe % =. M, urea 234 =.5 M, [Monomer] % = M. O Me (a) (b) (c) Figure S9. Methylated Urea (Single -Bond Donor). Characterization of the polymerization of CL with KOMe and -methyl substituted urea 7b in TF ([CL] = M). k obs =.42 min -, whereas its nonsubstituted counterpart 7 s k obs is.8 min -. (a) -methyl substituted urea 7b, a single -bond donor. (b) is much higher than its non-substituted counterpart. (c) GPC trace of a crude sample (7 s, 35% conv., =.3) at low conversion shows bimodal distribution whereas its non-substituted counterpart produces a single narrow monomodal peak. S

11 Urea + MOMe + CL Urea + M + PyO+ CL aome.4 a.2 KOMe.2 K 5 5 Figure S. Counter-ion Effect (Ureas) Left: KOMe vs aome reaction conditions: [MOMe] % =. M, [7 234 ] % =.5 M in TF. Right: K vs a reaction conditions: [PyO] % =. M, [M] % =. M, [5 234 ] % =.3 M in TF. Though no differences in k obs were observed for KOMe (4.6 min - ) and aome (4.7 min - ) or K and a, the polydispersity of polymer prepared with aome is much higher. On the other hand, there are no counter-ion differences that are observed between K and a in terms of k obs (K:.5 min -, a:.5 min - ) and molecular weight distributions. This suggests the presence of impurities in the commercial aome (Aldrich) that causes transesterification, broadening the molecular weight distribution of the polymer. Therefore, in the next figure, the comparison of counter-ions of TU anions were studied using a and K..8.6 TU + M + PyO + LA.4.2 a K 5 Figure S. Counter-ion Effect (TU). Reaction conditions [PyO] % =. M, [M] % =. M, [TU 234 ] % =.3 M in TF. k obs, K+ =.3 ±.8 min - and k obs, a+ =.67 ±.5 min -. The reaction with sodium ion appears to yield slightly broader molecular weight distributions than the reaction with potassium ion, especially at high conversions. Also there is a rate difference between the two reactions. S

12 n=3 n=3 n=32 n= m/z Figure S2. MALDI-TOF Spectrum poly(tmc-bn). The poly(tmc-bn) sample (9% conversion, DP = 33) was prepared with []:[KOMe] = :3 in TF. The main peaks correspond to the potassium adducts of linear poly(tmc-bn) with a MeO end group. Minimal secondary peaks reveal minimal transesterification of the OBn group and thus good selectivity of the urea anion catalyst. n=59 n=6 n=6 n= m Figure S3. MALDI-TOF Spectrum of poly(cl). The poly(cl) sample (8% conversion) was prepared with [KOMe] =. M, [7] =.3 M and [CL] = M. The peaks correspond to the potassium adducts of linear poly(cl) with a MeO end group. S2

13 CF 3 CF 3 O F 3 C CF 3 Figure S4. Urea. 7% yield. MR (CD 3 OD): δ 8. (4, s), 7.58 (2, s). 5 CF 3 O F 3 C CF 3 Figure S5. Urea 2. 87% yield. MR (DMSO-d 6 ): δ 9.52 (, s), 9.38 (, s) 8.5 (2, s), 8. (, s), 7.66 (2, m), 7.54 (, t), 7.37 (, d). 6 S3

14 CF 3 O F 3 C Figure S6. Urea 3. 79% yield. MR (DMSO-d 6 ): δ 9.39 (, s), 8.98 (, s), 8.3 (2, s), 7.63 (, s), 7.49 (2, d), 7.3 (2, t), 7. (, t). 7 CF 3 O F 3 C Figure S7. Urea 4. 84% yield. MR (CD 3 OD): δ 7.99 (2, s), 7.47 (, s), 3.58 (, m),.5-2. (, m). 8 S4

15 O F 3 C Figure S8. Urea 5. MR (DMSO-d 6 ): δ 9.4 (, s), 8.79 (, s), 8.2 (, s), 7.57 (, d), (3, m), 7.29 (3, m), 6.99 (, t). 9 O Figure S9. Urea 6. 94% yield. MR (DMSO-d 6 ): δ 8.66 (2, s), 7.46 (4, d), 7.28 (4, t), 6.96 (2, t). 9 S5

16 O Figure S2. Urea 7. 9% yield. MR (DMSO-d 6 ): δ 8.27 (, s), 7.36 (2, d), 7.2 (2, t), 6.86 (, t), 6.6 (, d), 3.45 (, m),.-.9 (, m). O Me Figure S2. Urea 7b. % yield. MR (CDCl 3 ): δ 7.38 (2, d), 7.27 (2, t), 7. (, t), 6.3 (, br), 4. (, m), 2.87 (3, s),.-.9 (). S6

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