http://pubs.acs.org/doi/abs/1.121/op536 Supporting Information for Acrylates via Metathesis of Crotonates http://dx.doi.org/1.121/op536 Dirk Schweitzer* and Kristi D. Snell Metabolix 21 Erie Street Cambridge, MA 2139, U.S.A. Email: dirkschweitzer@gmail.com Table of Contents 1.) Chemicals Used S2 2.) HPLC Analysis of the Carboxylic Acids S3 3.) HPLC Analysis of the Ethyl Esters S4 4.) HPLC Analysis of the n-butyl Esters & Ethyl Cinnamate Reaction S5 5.) Self-Metathesis Screening Experiments S6 6.) General Procedure for Reactions using a Gas as a Reagent S7 7.) Ethylene-free Reaction S8 8.) Solvent Screen of the Cross-Metathesis S9 9.) Temperature and Pressure Screen of the Ethylene Cross-Metathesis S1 1.) Cross-Metathesis Equilibrium Determination S12 11.) Time-Course of the Cross-Metathesis with Ethylene S16 12.) Reaction Pathway Control Experiments S18 13.) Optimal Reaction Temperature of Metathesis Catalysts S19 Page S1 of S19
http://pubs.acs.org/doi/abs/1.121/op536 1.) Chemicals Used All utilized chemicals were purchased from commercial suppliers and used as received. Specifically, the metathesis catalysts were purchased from Aldrich (Grubbs I, CAS number: 172222-3-9; Grubbs II, 24647-72-3; Hoveyda-Blechert, 1 31224-4-8; 2-Pr-Py, 82912-44-3) and Strem Chemicals (Re 2 O 7, 1314-68-7; di-ruod, 3481-97-3; catmetium RF3, 119427-5-9; Zhan 1B, 91887-76-5; immobilized Zhan 1B; ibu-c8, 894423-99-5; SB-H, 934538-12-2; SB-NO 2, 934538-4-2). Figure S-1. Catalysts evaluated in this study. The reagents were purchased from Aldrich (crotonic acid), Alfa-Aesar (acrylic acid, ethyl crotonate), and TCI America (maleic acid, fumaric acid, ethyl crotonate, ethyl acrylate, diethyl maleate, diethyl fumarate, n-butyl crotonate, n-butyl acrylate, ethyl cinnamate). All reaction solvents were anhydrous Sure-Seal grade from Aldrich, while HPLC-grade solvents were used for analytical work. Ethylene (Chemical Pure grade, p max ~ 255 psi) and propylene (polymer-grade, p max ~ 115 psi) were purchased from Airgas. 1 It is also known as the 2 nd generation Hoveyda-Grubbs catalyst. Page S2 of S19
Acrylic Acid Maleic Acid Fumaric Acid Crotonic Acid http://pubs.acs.org/doi/abs/1.121/op536 2.) HPLC Analysis of the Carboxylic Acids Phenomenex Reverse Phase HPLC Column (Luna 5 µm C18(2) 1 Å, 15 x 2 mm, Stationary Phase: C18 with TMS end capping, Cat. No. F-4252-B), C18 SecurityGuard cartridge (2 x 4 mm, Phenomenex Cat. No. AJ-4286, KJ-4282 holder), 4 C column and detector temperature, samples diluted so that they are in 1 % MeCN in H 2 O, 5 μl injection volume, mobile phases.1 % TFA in H 2 O and.1 % TFA in MeCN,.5 ml/min flow rate, 21 nm detection,. to 4. min: 1 % H 2 O isocratic; 4. to 4.5 min: to 1 % MeCN/H 2 O gradient; 4.5 to 1. min: 1 % MeCN/H 2 O isocratic; 1. to 12.5 min: 1 % MeCN/H 2 O to 1 % H 2 O gradient; 12.5 to 16. min: 1 % H 2 O isocratic. Datafile Name:212621-C18-2.lcd Sample Name:.8% acids standard 9 Detector A Ch1 21nm 8 9 7 8 6 7 5 6 4 3 2 1 5 4 3 2 1-1. 1. 2. 3. 4. 5. 6. 7. 8. 9. 1. 11. 12. 13. 14. 15. min Substance t R (min) Maleic Acid 1.9 Fumaric Acid 2.6 Acrylic Acid 3.4 impurity within TFA 6.4 Crotonic Acid 7.1 p-meophoh (acrylic acid stabilizer) 8.4 Figure S-2. HPLC chromatogram of the carboxylic acids used in this study. Page S3 of S19
Ethyl Acrylate Diethyl Maleate Diethyl Fumarate http://pubs.acs.org/doi/abs/1.121/op536 3.) HPLC Analysis of the Ethyl Esters Phenomenex Reverse Phase HPLC Column (Luna 5 µm C18(2) 1 Å, 15 x 2 mm, Stationary Phase: C18 with TMS end capping, Cat. No. F-4252-B), 4 C column and detector temperature, samples diluted so that they are in 1/1 MeCN/H 2 O, 5 μl injection volume, mobile phases H 2 O and MeCN,.5 ml/min flow rate, 21 nm detection,. to 6. min: 3 % MeCN/H 2 O isocratic; 6. to 8. min: 3 to 6 % MeCN/H 2 O gradient; 8. to 1. min: 6 % MeCN/H 2 O isocratic; 1. to 11. min: 6 % to 3 % MeCN/H 2 O gradient; 11. to 16. min: 3 % MeCN/H 2 O isocratic. Calibration curves were used to determine the absolute amount of each ester present. Datafile Name:212521-C18-16.lcd Sample Name:.16 % standards Detector A Ch1 21nm 1 9 9 8 7 8 7 6 6 5 5 4 4 3 3 2 2 1 1. 1. 2. 3. 4. 5. 6. 7. 8. 9. 1. 11. 12. 13. 14. 15. min Substance t R (min) dead volume.9 Ethyl Acrylate 3.5 Diethyl Maleate 4.7 5.5 Diethyl Fumarate 8.7 Figure S-3. HPLC chromatogram of the ethyl esters used in this study. Page S4 of S19
Ethyl Acrylate Diethyl Fumarate Ethyl Cinnamate http://pubs.acs.org/doi/abs/1.121/op536 4.) HPLC Analysis of the n-butyl Esters and Ethyl Cinnamate Reaction Phenomenex Reverse Phase HPLC Column (Luna 5 µm C18(2) 1 Å, 15 x 2 mm, Stationary Phase: C18 with TMS end capping, Cat. No. F-4252-B), 4 C column and detector temperature, samples diluted so that they are in 1/1 MeCN/H 2 O, 5 μl injection volume, mobile phases H 2 O and MeCN,.5 ml/min flow rate, 21 nm detection,. to 16. min: 35 to 8 % MeCN/H 2 O gradient; 16. to 17. min: 8 % to 35 % MeCN/H 2 O gradient; 17. to 2. min: 35 % MeCN/H 2 O isocratic. Calibration curves were used to determine the absolute amount of each ester present. Detector A Ch1 21nm Datafile Name:213716-C18-14.lcd Sample Name:DS5-95-2 yl each 4 35 3 25 2 9 8 7 6 5 15 1 2 5 1. 1. 2. 3. 4. 5. 6. 7. 8. 9. 1. 11. 12. 13. 14. 15. 16. 17. 18. 19. min Substance t R (min) dead volume.9 6.5 7.9 Detector A Ch1 21nm 8 Datafile Name:21386-EtCinC18-3.lcd Sample Name:DS6-32-Bu-method 4 3 9 7 6 5 4 3 8 7 6 5 4 2 1 1. 1. 2. 3. 4. 5. 6. 7. 8. 9. 1. 11. 12. 13. 14. 15. 16. 17. 18. 19. min Substance t R (min) dead volume.9 Ethyl Acrylate 2.9 Diethyl Fumarate 5.1 Ethyl Cinnamate 8. Figures S-4. HPLC chromatograms of the n-butyl esters and some components of the ethyl cinnamate reaction. 3 2 Page S5 of S19
http://pubs.acs.org/doi/abs/1.121/op536 5.) Self-Metathesis Screening Experiments Scheme S-5. Self-metathesis catalyst and substrate screening experiments. In a sealed tube, the neat substrate (2 g, ethyl crotonate (EtCr) or ethyl acrylate (EtAc)) or a solution of the substrate in dioxane (2 g in 6 g dioxane, crotonic acid (CA) or acrylic acid (AA)) and the catalyst (~ 2 mg: EtCr ~.13 mol %, EtAc ~.12 mol %, CA ~.1 mol %, AA ~.8 mol %) were held under stirring at RT overnight. The reaction mixtures were analyzed using HPLC. Table S-5. Results of the self-metathesis screening experiments. Page S6 of S19
http://pubs.acs.org/doi/abs/1.121/op536 6.) General Procedure for Reactions using a Gas as a Reagent All metathesis reactions using a gas as one of the reactants were conducted in a 5522-series Parr reactor (45 ml internal volume, 35 C maximum temperature, 3 psi maximum pressure, mechanical stirring at 18 rpm, attached H 2 O cooling). Figure S-6. Parr reactor experimental set-up for reactions using a gas. To the Parr reactor internal glass vessel were added the substrate (.35 mol, 4. g of ethyl crotonate, 49.8 g of n-butyl crotonate, or 61.7 g of ethyl cinnamate) followed by a weighted amount of catalyst. After assembly of the Parr reactor, under stirring, its contents were degassed 3 times with N 2 (8 to 1 psi). The internal pressure was now allowed to lower to psi, at which point the metathesis partner gas (ethylene or propylene) was introduced up to the desired pressure. Following the disconnection of the gas cylinder, the contents of the Parr reactor were heated to the desired temperature for the desired amount of time. After cooling to room temperature, the Parr reactor was opened, and a sample of the reaction solution was analyzed by HPLC. At the end of the most successful reactions, such as experiments 13, 155, and 158, the pressure at room temperature had dropped by about 15 psi from the initial 255 psi. Page S7 of S19
Ethyl Acrylate http://pubs.acs.org/doi/abs/1.121/op536 7.) Ethylene-free Reaction Scheme S-7. Ethylene-free experiments. Datafile Name:213125-C18-9.lcd Sample Name:DS6-27 Datafile Name:213125-C18-3.lcd Sample Name:DS6-31 Detector A Ch1 21nm 4 9 Detector A Ch1 21nm 4 9 35 8 35 8 3 7 3 7 25 6 25 6 2 5 2 5 15 4 15 4 1 3 1 3 2 5 1. 1. 2. 3. 4. 5. 6. 7. 8. 9. 1. 11. 12. 13. 14. 15. min 2 5 1. 2.5 5. 7.5 1. 12.5 15. 17.5 min Figures and Table S-7. Results of the ethylene-free experiments. Page S8 of S19
http://pubs.acs.org/doi/abs/1.121/op536 8.) Solvent Screen of the Cross-Metathesis Scheme S-8. Experiments to screen the solvent, metathesis partner, catalyst, and temperature-dependence of the cross-metathesis of ethyl crotonate. Figure and Tables S-8. Results of the solvent, metathesis partner, catalyst, and temperature-dependence screens of the cross-metathesis of ethyl crotonate. Page S9 of S19
http://pubs.acs.org/doi/abs/1.121/op536 9.) Temperature and Pressure Screen of the Ethylene Cross-Metathesis Scheme S-9. Experiments to screen the temperature- and pressure-dependence of the cross-metathesis of ethyl crotonate with ethylene. Table and Figure S-9.1. Results of the T and p screen of the cross-metathesis of ethyl crotonate with ethylene. Page S1 of S19
http://pubs.acs.org/doi/abs/1.121/op536 Table and Figure S-9.2. Experiments numbers of the T and p screen of the crossmetathesis of ethyl crotonate with ethylene and pressure-dependence of the achieved turn-over number. Page S11 of S19
Ethyl Acrylate Ethyl Acrylate Ethyl Acrylate Ethyl Acrylate Ethyl Acrylate Ethyl Acrylate http://pubs.acs.org/doi/abs/1.121/op536 1.) Cross-Metathesis Equilibrium Determination Scheme S-1. Equilibrium determination experiments. Product Compositions R = Ethyl forward Reaction + Ethylene backward Reaction Ethyl Acrylate + Propylene Datafile Name:2131128-C18-59.lcd Sample Name:DS5-19 Detector A Ch1 21nm 45 9 4 8 35 7 3 6 25 5 2 4 15 3 1 2 5 1. 1. 2. 3. 4. 5. 6. 7. 8. 9. 1. 11. 12. 13. 14. 15. min.5 mol % HB catalyst Datafile Name:2131213-C18-26.lcd Sample Name:DS5-76 15 Detector A Ch1 21nm 9 125 8 7 1 6 75 5 4 5 3 25 2 1. 1. 2. 3. 4. 5. 6. 7. 8. 9. 1. 11. 12. 13. 14. 15. min Datafile Name:2131213-C18-2.lcd Sample Name:DS5-79.1 mol % HB catalyst Datafile Name:2131213-C18-29.lcd Sample Name:DS5-9 Detector A Ch1 21nm 4 Detector A Ch1 21nm 15 9 9 35 8 125 8 3 25 7 6 1 7 6 2 5 75 5 15 4 5 4 1 3 3 2 5 1. 1. 2. 3. 4. 5. 6. 7. 8. 9. 1. 11. 12. 13. 14. 15. min 25 2 1. 1. 2. 3. 4. 5. 6. 7. 8. 9. 1. 11. 12. 13. 14. 15. min Datafile Name:2131213-C18-23.lcd Sample Name:DS5-91.2 mol % HB catalyst Datafile Name:2131213-C18-32.lcd Sample Name:DS5-92 Detector A Ch1 21nm 4 9 Detector A Ch1 21nm 2 9 35 8 175 8 3 7 15 7 25 6 125 6 2 5 1 5 15 4 75 4 1 3 5 3 2 5 1. 1. 2. 3. 4. 5. 6. 7. 8. 9. 1. 11. 12. 13. 14. 15. min 2 25 1. 1. 2. 3. 4. 5. 6. 7. 8. 9. 1. 11. 12. 13. 14. 15. min Page S12 of S19
http://pubs.acs.org/doi/abs/1.121/op536 Figures and Tables S-1-Et. Results of the equilibrium determination experiments for R = Ethyl. The equilibrium composition can easily be calculated from this data. ethyl crotonate -22.714 x + 93.75 = 51.286 x + 54.35 74. x = 39.4 x(catalyst loading) =.5324 Thus, area %, y, of ethyl crotonate at equilibrium = 81.656 %. ethyl acrylate -51.286 x + 45.65 = 22.714 x + 6.25 74. x = 39.4 x(catalyst loading) =.5324 Thus, area %, y, of ethyl acrylate at equilibrium = 18.344 %. If the total absorbance area were 1,,,, ethyl crotonate would be represented by 816,56, and ethyl acrylate would be represented by 183,44,. Page S13 of S19
http://pubs.acs.org/doi/abs/1.121/op536 Using our ethyl ester calibration curves, these values would correspond to.7814 mmol/ml of ethyl crotonate and.43571 mmol/ml of ethyl acrylate, for a total number of 1.21675 mmol within 1 ml of solution. Thus, the equilibrium state of the R = ethyl metathesis reaction contains 64.19 mol % of ethyl crotonate and 35.81 mol % of ethyl acrylate. Product Compositions R = n-butyl forward Reaction + Ethylene backward Reaction + Propylene 35 Detector A Ch1 21nm Datafile Name:2131128-C18-3.lcd Sample Name:DS6-24.5 mol % HB catalyst Detector A Ch1 21nm 2 Datafile Name:2131213-C18-1.lcd Sample Name:DS6-28 3 9 8 175 9 8 25 7 15 7 2 6 125 6 5 1 5 15 4 75 4 1 3 5 3 2 5 1. 2.5 5. 7.5 1. 12.5 15. 17.5 min 2 25 1. 2.5 5. 7.5 1. 12.5 15. 17.5 min Datafile Name:2131213-C18-4.lcd Sample Name:DS6-25.1 mol % HB catalyst Datafile Name:2131213-C18-13.lcd Sample Name:DS6-29 45 Detector A Ch1 21nm Detector A Ch1 21nm 4 9 225 9 35 8 2 8 7 3 6 25 5 2 4 15 3 1 2 5 1. 2.5 5. 7.5 1. 12.5 15. 17.5 min 175 7 15 6 125 5 1 4 75 3 5 2 25 1. 2.5 5. 7.5 1. 12.5 15. 17.5 min Datafile Name:2131213-C18-6.lcd Sample Name:DS6-26.2 mol % HB catalyst Datafile Name:2131213-C18-16.lcd Sample Name:DS6-3 Detector A Ch1 21nm 3 Detector A Ch1 21nm 4 9 275 9 35 8 25 8 3 7 225 2 7 25 6 175 6 2 5 15 5 15 4 125 1 4 1 3 75 3 2 5 1. 2.5 5. 7.5 1. 12.5 15. 17.5 min 5 2 25 1. 2.5 5. 7.5 1. 12.5 15. 17.5 min Page S14 of S19
http://pubs.acs.org/doi/abs/1.121/op536 Figures and Tables S-1-n-Bu. Results of the equilibrium determination experiments for R = n-butyl. The equilibrium composition can easily be calculated from this data. n-butyl crotonate -27.571 x + 9.35 = 9.286 x + 5.1 x(catalyst loading) =.3415 Thus, area %, y, of n-butyl crotonate at equilibrium = 8.934 %. n-butyl acrylate -9.286 x + 49.9 = 27.571 x + 9.65 x(catalyst loading) =.3415 Thus, area %, y, of n-butyl acrylate at equilibrium = 19.66 %. If the total absorbance area were 1,,,, n-butyl crotonate would be represented by 89,34, and n-butyl acrylate would be represented by 19,66,. Using our n-butyl ester calibration curves, these values would correspond to.592 mmol/ml of n-butyl crotonate and.33421 mmol/ml of n-butyl acrylate, for a total number of.84341 mmol within 1 ml of solution. Thus, the equilibrium state of the R = n-butyl metathesis reaction contains 6.37 mol % of n-butyl crotonate and 39.63 mol % of n-butyl acrylate. Page S15 of S19
Ethyl Acrylate Ethyl Acrylate Ethyl Acrylate http://pubs.acs.org/doi/abs/1.121/op536 11.) Time-Course of the Cross-Metathesis with Ethylene Scheme S-11. Time-course experiments. Product Compositions + Ethylene + Ethylene Datafile Name:2131216-C18-29.lcd Sample Name:DS6-19 2.5 min [.4 h] mixing time Datafile Name:2131216-C18-3.lcd Sample Name:DS6-23 4 Detector A Ch1 21nm Detector A Ch1 21nm 5 35 9 45 9 3 8 7 4 35 8 7 25 6 3 6 2 5 25 5 15 4 2 4 3 1 2 5 1. 1. 2. 3. 4. 5. 6. 7. 8. 9. 1. 11. 12. 13. 14. 15. min 15 3 1 2 5 1. 2.5 5. 7.5 1. 12.5 15. 17.5 min Datafile Name:2131216-C18-38.lcd Sample Name:DS6-1 2 min [.33 h] mixing time Datafile Name:2131216-C18-13.lcd Sample Name:DS6-17 4 Detector A Ch1 21nm 5 Detector A Ch1 21nm 35 9 45 9 3 8 4 8 7 35 7 25 6 3 6 2 5 25 5 15 4 2 4 1 5. 1. 2. 3. 4. 5. 6. 7. 8. 9. 1. 11. 12. 13. 14. 15. min 3 2 1 15 3 1 2 5 1. 2.5 5. 7.5 1. 12.5 15. 17.5 min Datafile Name:2131216-C18-44.lcd Sample Name:DS6-12 1 h, 2 min [1.33 h] mixing time Datafile Name:2131216-C18-18.lcd Sample Name:DS6-21 Detector A Ch1 21nm 4 9 Detector A Ch1 21nm 45 9 35 8 4 8 3 7 35 7 25 6 3 6 2 5 25 5 15 4 3 1 2 5 1. 1. 2. 3. 4. 5. 6. 7. 8. 9. 1. 11. 12. 13. 14. 15. min 2 4 15 3 1 2 5 1. 2.5 5. 7.5 1. 12.5 15. 17.5 min Page S16 of S19
Ethyl Acrylate http://pubs.acs.org/doi/abs/1.121/op536 Datafile Name:2131216-C18-47.lcd Sample Name:DS6-13 2 h, 4 min [2.67 h] mixing time Datafile Name:2131216-C18-21.lcd Sample Name:DS6-2 Detector A Ch1 21nm Detector A Ch1 21nm 4 9 45 9 35 8 4 8 3 7 35 7 25 6 3 6 2 5 4 15 3 1 2 5 1. 1. 2. 3. 4. 5. 6. 7. 8. 9. 1. 11. 12. 13. 14. 15. min 25 5 2 4 15 3 1 2 5 1. 2.5 5. 7.5 1. 12.5 15. 17.5 min Figures and Tables S-11. Results of the time-course experiments. Page S17 of S19
Ethyl Acrylate Diethyl Fumarate Ethyl Acrylate Diethyl Maleate Diethyl Fumarate http://pubs.acs.org/doi/abs/1.121/op536 12.) Reaction Pathway Control Experiments Scheme S-12. Reaction pathway control experiments. Datafile Name:21361-C18-7.lcd Sample Name:DS5-77 Datafile Name:21361-C18-11.lcd Sample Name:DS5-78 Detector A Ch1 21nm 3 9 Detector A Ch1 21nm 5 45 9 25 8 7 4 35 8 7 2 6 3 6 15 5 25 5 4 2 4 1 3 15 3 5 2 1. 1. 2. 3. 4. 5. 6. 7. 8. 9. 1. 11. 12. 13. 14. 15. min 1 2 5 1. 1. 2. 3. 4. 5. 6. 7. 8. 9. 1. 11. 12. 13. 14. 15. min Figures and Table S-12. Results of the reaction pathway control experiments. Page S18 of S19
Ethyl Acrylate Ethyl Cinnamate Ethyl Acrylate http://pubs.acs.org/doi/abs/1.121/op536 13.) Optimal Reaction Temperature of Metathesis Catalysts Datafile Name:2131128-C18-9.lcd Sample Name:DS6-37 Datafile Name:2131128-C18-83.lcd Sample Name:DS6-98 4 Detector A Ch1 21nm Detector A Ch1 21nm 4 35 9 8 35 9 8 3 7 3 7 25 6 25 6 2 5 2 5 15 4 15 4 1 3 1 3 2 5 1. 2.5 5. 7.5 1. 12.5 15. 17.5 min 2 5 1. 1. 2. 3. 4. 5. 6. 7. 8. 9. 1. 11. 12. 13. 14. 15. min Detector A Ch1 21nm Datafile Name:2131128-C18-36.lcd Sample Name:DS6-68 6 9 5 4 8 7 6 3 5 4 2 3 1 2 Table and Figures S-13.. 2.5 5. 7.5 1. 12.5 15. 17.5 min Results of the experiments to determine the optimal reaction temperature of various metathesis catalysts. Page S19 of S19 1