Ambient Temperature Synthesis of a Versatile Macromolecular Building Block: CyclopentadienylCapped Polymers Andrew J. Inglis, Thomas Paulöhrl and Christopher BarnerKowollik Preparative Macromolecular Chemistry, Karlsruhe Institute of Technology (KIT), Engesserstr. 18, 76128 Karlsruhe, Germany Experimental Section 1. Materials Methyl acrylate (Acros), methyl methacrylate (Acros) and styrene (Merck) were passed through a column of basic alumina prior to use and stored at 19 C. Isobornyl acrylate (Aldrich, technical grade) was purified by vacuum distillation (121 C, 24 mbar). Copper (I) bromide (Fluka) was purified by sequential washing with sulphurous acid, acetic acid and ethanol, followed by drying under reduced pressure. THF was distilled over sodium and benzophenone prior to use. Anisole ( 99 %, Fluka), 2,2 bipyridyl (bpy, 99%, SigmaAldrich), copper (II) bromide ( 99%, Fluka), methyl 2 bromopropanoate (98 %, Aldrich), methyl 2bromo 2methylpropanoate ( 99 %, Aldrich), nickelocene (NiCp 2, 99 %, Strem Chemicals), N N N N N pentamethylethylenetriamine (Merck), sodium cyclopentadienide (NaCp, 2.0 M in THF, Aldrich), sodium iodide ( 99 %, Fluka) and tributylphosphine (95 %, Acros) were used as received. 2. Measurements The structures of the synthesized compounds were confirmed by 1 HNMR spectroscopy using a Bruker AM 400 spectrometer at 400 MHz for hydrogen nuclei. All samples were dissolved in CDCl 3. The δ scale is referenced to the internal standard trimethylsilane (δ = 0). GPC measurements were performed on a Polymer Laboratories PLGPC 50 Plus Integrated System, comprising an autosampler, a PLgel 5µm beadsize guard column (50 x 7.5 mm) followed by one PLgel 5μm Mixed E column (300 x 7.5 mm), three PLgel 5µm Mixed C columns (300 x 7.5 mm) and a differential refractive index detector using THF as the eluent at 35 C with a flow rate of 1 ml min 1. The GPC system was calibrated using linear poly(styrene) standards ranging from 160 to 6 10 6 g mol 1 and linear poly(methyl methacrylate) standards ranging from 700 to 2 10 6 g mol 1. Mass spectra were recorded on a LXQ mass spectrometer (ThermoFisher Scientific) equipped with an atmospheric pressure ionization source operating in the nebulizerassisted electrospray mode. The instrument was calibrated in the m/z range 195 1822 using a standard comprising caffeine, MetArg PheAla acetate (MRFA), and a mixture of fluorinated phosphazenes (Ultramark 1621) (all from Aldrich). A constant spray voltage of 4.5 kv and a dimensionless sweep gas flow rate of 2 and a dimensionless sheath gas flow rate of 12 were applied. The capillary voltage, the tube lens offset voltage and the capillary temperature were set to 60 V, 110 V and 275 C respectively. The LXQ was coupled to a Series 1200 HPLC system (Agilent) that consisted of a solvent degasser (G1322A), a binary pump (G1312A) and a highperformance autosampler (G1367B), followed by a thermostatted column compartment (G1316A). Separation was performed on two mixed bed GPC columns (Polymer Laboratories, Mesopore 250 x 4.6 mm, particle dia. 3µm) with precolumn (Mesopore 50 x 4.6 mm) operating at 30 C. THF at a flow rate of 0.3 ml min 1 was used as the eluent. The mass spectrometer was 1
coupled to the column in parallel to an RI detector (G1362A with SS420x A/D) in a setup described previously. [2] A 0.27 ml min 1 aliquot of the eluent was directed through the RI detector and 30 µl min 1 infused into the electrospray source after postcolumn addition of a 0.1mM solution of sodium iodide in methanol at 20 µl min 1 by a micro flow HPLC syringe pump (Teledyne ISCO, Model 100DM). The polymer solutions (20 µl) with a concentration of ~ 3 mg ml 1 were injected into the HPLC system. 3. Synthesis 3.1 ATRP of styrene bromide, which was then sealed with a rubber septum, evacuated and backfilled with nitrogen. To another Schlenk tube was added styrene and PMDETA and equipped with a rubber septum. The monomer/ligand mixture was then deoxygenated by three consecutive freezepumpthaw cycles and subsequently transferred to the copper (I) bromide via cannula. The tube was sealed under a nitrogen atmosphere and placed in a thermostatic oil bath held at 90 C. After the polymerization mixture reached the desired temperature, methyl 2bromopropanoate (MBP) was added. The initial ratio of [styrene]:[mbp]:[cu I Br]:[PMDETA] was 100:1:1:1. The polymerization was stopped by cooling the mixture in an icebath and exposure to oxygen. After dilution with THF, the mixture was passed through a short column of neutral alumina to remove the copper catalyst. Poly(styrene) was isolated by twofold precipitation in cold methanol. GPC (THF): M n = 1600 g mol 1, PDI = 1.06. 3.2 ATRP of methyl methacrylate bromide, copper (II) bromide and bpy which was then sealed with a rubber septum, evacuated and backfilled with nitrogen. To another Schlenk tube was added methyl methacrylate (MMA) and acetone (50:50) and equipped with a rubber septum. The monomer solution was then deoxygenated by three consecutive freezepumpthaw cycles and subsequently transferred to the first Schlenk tube via cannula. The tube was sealed under a nitrogen atmosphere and placed in a thermostatic oil bath held at 50 C. After the polymerization mixture reached the desired temperature, methyl 2bromo2 methylpropanoate (MBMP) was added. The initial ratio of [MMA]:[MBMP]:[Cu I Br]:[Cu II Br]:[bpy] was 50:2:0.105:125:0.25. The polymerization was stopped by cooling the mixture in an icebath and exposure to oxygen. The mixture was passed through a short column of neutral alumina to remove the copper catalyst. Poly(methyl methacrylate) was isolated by twofold precipitation in cold hexane. GPC (THF): M n = 2700 g mol 1, PDI = 1.09. 3.3 ATRP of isobornyl acrylate bromide which was then sealed with a rubber septum, evacuated and backfilled with nitrogen. To another Schlenk tube was added isobornyl acrylate (iboa) and ethyl acetate (4:1) along with PMDETA and equipped with a rubber septum. The monomer solution was then deoxygenated by three consecutive freezepumpthaw cycles and subsequently transferred to the first Schlenk tube via cannula. The tube was sealed under a nitrogen atmosphere and placed in a thermostatic oil bath held at 77 C. After the polymerization mixture reached the desired temperature, methyl 2bromopropanoate (MBP) was added. The initial ratio of [iboa]:[mbp]:[cu I Br]:[PMDETA] was 100:1:0.5:0.75. The polymerization was stopped by cooling the mixture in an icebath and exposure to oxygen. The mixture was passed through a short column of neutral alumina to remove the copper catalyst. Poly(isobornyl acrylate) was isolated by twofold precipitation in cold methanol. GPC (THF): M n = 4200 g mol 1, PDI = 1.22. 3.4 ATRP of methyl acrylate bromide and bpy, which was then sealed with a rubber septum, evacuated and backfilled with nitrogen. To another Schlenk tube was added methyl acrylate (MA) and anisole (67:33) and equipped with a rubber septum. The monomer solution was then deoxygenated by three consecutive freezepumpthaw cycles and subsequently transferred to the copper (I) bromide via cannula. The tube was sealed under a nitrogen atmosphere and placed in a 2
thermostatic oil bath held at 90 C. After the polymerization mixture reached the desired temperature, methyl 2bromopropanoate (MBP) was added. The initial ratio of [MA]:[MBP]:[Cu I Br]:[bpy] was 200:1:1:2. The polymerization was stopped by cooling the mixture in an icebath and exposure to oxygen. After dilution with THF, the mixture was passed through a short column of neutral alumina to remove the copper catalyst. Poly(methyl acrylate) was isolated by twofold precipitation in cold methanol. GPC (THF): M n = 2800 g mol 1, PDI = 1.29. 4. Results and Discussion 4.1 Reactions with NaCp Extrapolating from our previous efforts, [1] the use of NaCp to achieve the desired substitution reaction was trialed on PSBr 1, PMMABr 2, PiBoABr 3 and PMABr 4. Figure S1 shows the 1 HNMR spectra of the reaction products from the treatment of PSBr 1 with a 2fold excess and a 10fold excess of NaCp. 3.5 Reaction of bromide terminated polymers with NaCp Typical Procedure A solution of bromide terminated polymer (0.18 mmol) in anhydrous THF (2.0 ml) was prepared under a nitrogen atmosphere. To this solution was added a 2fold excess, and in a second experiment a 10fold excess of NaCp. The reaction mixture was stirred overnight at ambient temperature. The polymeric material was then isolated by precipitation in an appropriate solvent. 3.6 Reaction of bromide terminated polymers with NiCp 2 Typical Procedure A solution of bromide terminated polymer (0.18 mmol), tributylphosphine (0.36 mmol, 2 eq.) and sodium iodide (1.08 mmol, 6 eq) in anhydrous THF (2.0 ml) was prepared under a nitrogen atmosphere. Separately, a stock solution of NiCp 2 in anhydrous THF (0.18 mol L 1 ) was prepared under a nitrogen atmosphere. The NiCp 2 solution (2.0 ml, 4 eq.) was then added to the polymer solution and allowed to stir overnight at ambient temperature. At the end of the reaction, the mixture was passed through a short column of basic alumina to remove the precipitated nickel (II) bromide and the polymer recovered by precipitation. The resulting polymer was then dissolved in chloroform and washed three times with distilled water. The Cpcapped polymers were then isolated by precipitation from the chloroform solution into an appropriate solvent. Figure S1. 1 HNMR spectra of the reaction products of PS Br 1 with a 2fold excess (A) and a 10fold excess (B) of NaCp. It may be observed that using a 2fold excess does produce the desired Cpcapped polymer, however a small amount of starting material remains, as indicated by the presence of a signal (labeled e*) at around 4.5 ppm. Using a 10fold excess produces quantitative conversion into the desired Cpcapped polymer, a result which is consistent with our earlier findings. [1] Despite this favourable result, the use of NaCp with the poly(acrylates) and poly(methacylate) proved to be problematic. Figure S2 shows the ESIMS spectra of PMMABr 2 and those of the respective reaction products after treatment with a 2fold excess and a 10fold excess of NaCp. As can clearly be observed, a number of different products are formed, none of which are the desired Cpcapped polymer (marked by the dotted lines). It is interesting to note that higher excesses of the NaCp leads to the formation of different products. As of yet, the products cannot be conclusively identified and, not being the principal 3
treatment proved to be problematic and the recorded spectra was of the solid residue remaining after the reaction mixture solvent was removed under reduced pressure. Figure S4 shows the ESIMS spectra of the PMABr 4 and those of the reaction products after treatment with a 2fold excess and a 10fold excess of NaCp. Figure S2. ESIMS spectra of PMMABr 2 (A) and the reaction products after treatment with 2fold excess of NaCp (B) and after treatment with 10fold excess NaCp (C). The dotted lines represent the m/z value at which the desired Cpcapped polymer is expected. focus of the current investigation, we have left these products as unidentified. However, the analysis still clearly shows that NaCp cannot be used to achieve the desired outcome. Figure S3. ESIMS spectra of PiBoABr 3 (A) and the reaction products after treatment with 10fold excess of NaCp (B). The dotted lines represent the m/z value at which the desired Cpcapped polymer is expected. Figure S3 compares the ESIMS spectra of PiBoABr 3 and the reaction product after treatment with a 10 fold excess of NaCp. Similarly, a number of unidentified products are observed. It should also be noted that precipitation of the polymer after the Figure S4. ESIMS spectra of PMABr 4 (A) and the reaction products after treatment with 2fold excess of NaCp (B) and after treatment with 10fold excess NaCp (C). The dotted lines represent the m/z value at which the desired Cpcapped polymer is expected. Interestingly, using a 2fold excess of NaCp, the dominant series have m/z values that are in excellent agreement with the theoretical values of the required Cpcapped polymer, however none of the characteristic signals arising from a Cpmoiety were detected in the 1 HNMR spectrum (data not shown). Increasing to a 10fold excess, however, results in the formation of many more (unidentified) and different sideproducts. It should be noted here that 1 HNMR spectra were recorded for all NaCp experiments, however none revealed any signals characteristic of a Cpmoiety (excluding the PS example). 4.2 Reactions with NiCp 2 The reaction of PSBr 1 with the NiCp 2 /PBu 3 /NaI reagent also cleanly led to the required PSCp 5, as clearly shown by the 1 HNMR spectroscopic analysis (Figure S5). 4
Table S1. Experimental and Theoretical m/z values for first peak in the isotopic distributions of the zoom spectrum in Figure S6 and their assignment. m/z expt ion assignment formula m/z theor Δ m/z 1503.5 2 (n = 13) + Na + [C 70H 113BrO 28Na] + 1503.7 0.2 1489.8 1525.8 1523.8 1509.6 1553.0 6 (n = 13) + Na + II + Na + III + Na + IV + Na + V* + Na + [C 75H 118O 28Na] + [C 75H 122O 30Na] + [C 75H 120O 30Na] + [C 74H 118O 30Na] + 1489.8 1525.8 1523.8 1509.8 0.2 Figure S5. 1 HNMR spectra of PSBr 1 and PSCp 5. The ESIMS and 1 HNMR spectra of PMMABr 2 and PMMACp 6 are presented within the main manuscript. Here, Figure S6 shows a zoom region (m/z = 1480 1576) of the above mentioned mass spectra. A comparison of the experimental m/z values with those of the theoretical structures are presented in Table S1. It is highlighted here that the sideproducts of the ATRP are carried through the functionalization procedure, thus the presented ESI MS data confirms the quantitative transformation. Similarly, the ESIMS and 1 HNMR spectra of PiBoABr 3 and PiBoACp 7 are presented in the main manuscript. Here, however, is presented a zoom region (m/z = 1590 1820) of the above mentioned mass spectra (Figure S7). The signal labeled a is assigned to an unidentified (yet bromide containing) species. The experimental m/z values are compared to those of the theoretical structures in Table S2. It is observed that the signal labeled a shifts to lower m/z values in agreement with a transformation from bromide to Cp functionality (signal labeled as a* ). Upon close inspection of the data presented in Table S2, the m/z value of a* is close to that of 3. However, the change in the isotopic pattern that occurs from a to a* leads to the conclusion that 3 and a* are different species. Therefore, it is concluded that the transformation is quantitative. Figure S6. ESIMS spectra (1480 1576 m/z zoom region) of PMMABr 2 (A) and PMMACp 6 (B). The romannumeric labeling is carried over from the main manuscript. Figure S7. ESIMS spectra (1590 1820 m/z zoom region) of PiBoABr 3 (A) and PiBoACp 7 (B). 5
Table S2. Experimental and Theoretical m/z values for first peak in the isotopic distributions of the zoom spectrum in Figure S7 and their assignment. Table S3. Experimental and Theoretical m/z values for first peak in the isotopic distributions of the zoom spectrum in Figure S9 and their assignment. m/z expt ion assignment formula m/z theor Δ m/z 1645.9 3 (n = 7) + Na + [C 95H 147BrO 16Na] + 165 0.1 1659.8 1632.1 1646.1 a 7 (n = 7) + Na + a* [C 100H 152O 16Na] + 1632.1 Figure S8 shows the ESIMS spectra of PMABr 4 and PMACp 8. The dominant species in the spectrum of the starting material (bromide functional polymer) is observed to completely shift to lower m/z values in accordance with the formation of the required Cpcapped polymer. A zoom of the 844 946 m/z region is presented in Figure S9, the experimental m/z values of which are compared to those of the theoretical structures in Table S3. m/z expt ion assignment formula m/z theor Δ m/z 877.3 4 (n = 8) + Na + [C 36H 55BrO 18Na] + 877.2 0.1 863.5 8 (n = 8) + Na + [C 41H 60O 18Na] + 863.4 0.1 Figure S10 shows the 1 HNMR spectra of PMABr 4 alongside that of PMACp 8. The transformation is characterized by the disappearance of the signal of the proton in the alpha position to the terminal bromide (labelled e) and the appearance of peaks at 6.45.8 ppm and 2.9 ppm, assignable to the Cp functionality. Figure S8. ESIMS spectra of PMABr 4 and PMACp 8. Figure S10. 1 HNMR spectra of PMABr 4 and PMACp 8. [1] A. J. Inglis, S. Sinnwell, M. H. Stenzel, C. BarnerKowollik, Angew. Chem. 2009, 121, 2447, Angew. Chem. Int. Ed. 2009, 48, 2411. [2] T. Gruendling, M. Guilhaus, C. BarnerKowollik Anal. Chem. 2008, 80, 9615. Figure S9. ESIMS spectra (844 946 m/z zoom region) of PMABr 4 (A) and PMACp 8 (B). 6