Scalable Photocatalytic Oxidation of Methionine under Continuous-Flow Conditions

Transcription

1 Supporting Information for: Scalable Photocatalytic Oxidation of Methionine under Continuous-Flow Conditions Noémie Emmanuel, Carlos Mendoza, Marc Winter, Clemens R. Horn, Alessandra Vizza, Laurent Dreesen, ǁ,* Benoît Heinrichs,,* Jean-Christophe M. Monbaliu,* Center for Integrated Technology and Organic Synthesis, Department of Chemistry, University of Liège, B-4000 Liège (Sart Tilman), Belgium Nanomaterials, Catalysis & Electrochemistry - NCE, Department of Chemical Engineering, University of Liège, B-4000 Liège (Sart Tilman), Belgium Corning Reactor Technologies, Corning SAS, 7 bis, Avenue de Valvins CS Samois sur Seine, Avon Cedex - France ǁ Biophotonics, Department of Physics, University of Liège, B-4000 Liège (Sart Tilman), Belgium jc.monbaliu@ulg.ac.be Table of contents 1 CONTINUOUS-FLOW SETUP Generalities Pictures of the continuous-flow setup Residence time calculation SUPPLEMENTAL EXPERIMENTAL DATA Chemicals S1-

2 2.2 Nuclear magnetic resonance (NMR) Generalities NMR data and characterization for compounds 2a-c Determination of the conversion of 1a to 2a Typical runs Continuous-flow preparation of ascaridole 2b Continuous-flow preparation of citronellol peroxides 2c,c Off-line purification of methionine sulfoxide 2a Overlap between RB absorption and LED emission Representative 1 H NMR spectra REFERENCES S2-

3 1 Continuous-flow setup 1.1 Generalities A HPLC pump from FLOM Corporation was used ( ml min -1 ; wetted-parts: PTFE, PCTFE, FFKM and ruby). The feed solution was conveyed to the HPLC pump through a section of 1/8 PFA tubing (Swagelok ) equipped with a filter frit and with 1/8 PFA connectors (Swagelok ). The gas flow rate was controlled with a Bronkhorst F210C TM mass flow controller (MFC). A Zaiput Flow Technologies dome-type back-pressure regulator (BPR) was inserted downstream and connected to a cylinder of compressed Argon (set point: 8 barg). LAUDA Proline RP 845 TM thermostats were used for the thermoregulation of the mesofluidic reaction glass modules and the LED illumination setup (Corning Advanced-Flow TM Lab Photo Reactor). In-line NMR analysis was carried out with a 43 MHz Spinsolve TM Carbon NMR spectrometer from Magritek equipped with the flow-through module. 1.2 Pictures of the continuous-flow setup Figure S1. Detailed setup for the continuous-flow preparation of methionine sulfoxide 1a. Corning proprietary. 1.3 Residence time calculation The residence time is calculated according to Equation S1: Residence time min (Equation S1) The total flow rate combines the individual flow rates of all fluids fed into the reactor. The actual gas flow rate is calculated from the flow rate measured by the MFC according to Equations S2-3: -S3-

4 n... (Equation S2) V (Equation S3) For example, the actual volume of O 2 delivered under 8 barg and 30 C when the MFC is set at 15 ml min -1 is 1.9 ml min -1 (see Equations S4-5): n... V mmol (Equation S4) ml (Equation S5) -S4-

5 2 Supplemental experimental data 2.1 Chemicals - (L)-Methionine (CAS , >99.0%, TCI, MSDS) - α-terpinene (CAS , >90%, TCI, MSDS) - Citronellol (CAS , 95%, Sigma-Aldrich, MSDS) - Methanol (CAS , 99.9%, Sigma-Aldrich, MSDS) - Rose Bengal (CAS , TCI, MSDS) - TCPP (CAS , 97%, TCI, MSDS) - Methylene Blue (CAS , 82%, Sigma-Aldrich, MSDS) 2.2 Nuclear magnetic resonance (NMR) Generalities Qualitative in-line reaction monitoring was carried out by 1 H NMR with a 43 MHz Spinsolve TM Carbon NMR spectrometer from Magritek equipped with the flow-through module. Analytical samples were collected and analyzed by 1 H NMR at 400 MHz on a Bruker Avance III HD spectrometer (9.4 Tesla). The chemical shifts are reported in ppm relative to TMS as internal standard or to solvent residual peak NMR data and characterization for compounds 2a-c Methionine sulfoxide (2a). 1 H NMR (D 2 O, 400 MHz): δ = 3.79 (m, 1H), (m, 2H), 2.66 (s, 3H), 2.23 (m, 2H) ppm. The NMR data matched the data obtained for commercial methionine sulfoxide. ESI HRMS m/z C 5 H 12 O 3 NS [M+H] + : calcd Found: Ascaridole (2b). 1 H NMR (CD 3 OD, 400 MHz): δ = 6.5 (dd, 2H), 1.97 (d, 1H), 1.88 (m, 1H), 1.56 (d, 1H), 1.34 (s, 3H), 1.00 (m, 6H). NMR data matched those reported in the literature. 1,2 ESI HRMS m/z C 10 H 16 O 2 Na [M+Na] + : calcd Found: S5-

6 Peroxides of citronellol (2c,c ). 1:1 mixture of two isomers. 1 H NMR (CD 3 OD, 400 MHz): δ = 7.59 (s, 2H), 5.61 (m, 2H), 4.62 (brs, 4H), 4.21 (t, 1H), 3.61 (m, 4H), 2.09 (m, 1H), 1.93 (m, 1H), 1.72 (s, 3H), (m, 8H), 1.30 (s, 6H), 1.13 (m, 2H), 0.92 (m, 6H) ppm. NMR data matched those reported in the literature. 2 ESI HRMS m/z C 10 H 20 O 3 Na [M+Na] + : calcd Found: Determination of the conversion of 1a to 2a The oxidation of 1a was easily monitored by 1 H NMR. Conversion of 1a into 2a was monitored by following the disappearance of signal at 2.55 ppm (triplet, 2H, 1a) and the appearance of the signal 2.65 ppm (singlet, 3H, 2a) as illustrated in Figure S2. The conversion was calculated by using Equation S6 (I is the normalized integration of the corresponding signals): Conversion = 100 I 2.65 ppm 3 I 2.65 ppm I 2.55 ppm 3 2 (Equation S6) Figure S2. 1 H NMR reaction monitoring for the preparation of 2a. -S6-

7 2.3 Typical runs Continuous-flow preparation of ascaridole 2b The HPLC pump used to deliver a solution of 1b (1 M in methanol) and RB (1 mol%) was set to 0.25 ml min -1 and the oxygen flow was set to 7.5 ml min -1 with the MFC, and both fluids were conveyed to the continuous-flow photoreactor through perfluoroalkoxyalkane (PFA) tubing (1/8 O.D.). Mixing and irradiation (white LED, 100% intensity) occurred along the entire reaction channel (2.6 ml internal volume, 2.2 min residence time) under 8 barg of pressure. Process and reaction parameters such as concentration, temperature and residence time were optimized (Table S1). Table S1. Process optimization for the preparation of ascaridole 2b using white light (100% intensity) Continuous-flow preparation of citronellol peroxides 2c,c The HPLC pump used to deliver a solution of 1c (0.1 M in methanol) and RB (5 mol%) was set to 1.5 ml min -1 and the oxygen flow was set to 10 ml min -1 with the MFC, and both fluids were conveyed to the continuous-flow photoreactor through perfluoroalkoxyalkane (PFA) tubing (1/8 O.D.). Mixing and irradiation (white LED, 100% intensity) occurred along the entire reaction channel (2.6 ml internal volume, 1 min residence time) under 8 barg of pressure. Process and reaction parameters such as concentration, temperature and residence time were optimized (Table S2). Entry 1b (M) Flow rate (ml min -1 ) Feed 1 Feed 2 (ml min -1 ) (ml N min -1 ) T ( C) Res. time (min) Conversion (%) RT 1.3 quant RT 1 quant RT 0.9 quant RT RT 2.2 quant RT 1.8 quant RT quant quant. -S7-

8 Table S2. Process optimization for the preparation of citronellol peroxides 2c,c using white light (100% intensity) at 20 C Entry 1c (M) Flow rate (ml min -1 ) Conversion (%) Feed 1 (ml min -1 ) Feed 2 (ml N min -1 ) Res. time (min) 2c 2c' Remaining reactant (%) Off-line purification of methionine sulfoxide 2a The effluent of the reactor was collected and treated with activated charcoal. The resulting mixture was stirred for 2 min at reflux, filtered and then concentrated under reduced pressure or recrystallized with i-proh as an antisolvent. Methionine sulfoxide (2a) was obtained as a white solid (79%). -S8-

9 2.4 Overlap between RB absorption and LED emission Figure S3. A: Overlap between RB absorption and white light emission spectra, B: Overlap between RB absorption and LED 485 emission spectra, C: Overlap between RB absorption and LED 405 emission spectra, D: Overlap between RB absorption and LED 622 emission spectra. -S9-

10 2.5 Representative 1 H NMR spectra Figure S4. Typical in-line 1 H NMR (45 MHz) spectra for 2a. Figure S5. 1 H NMR spectrum (400 MHz) of (L)-methionine 1a in D 2 O. -S10-

11 Figure S6. 1 H NMR spectrum (400 MHz) of methionine sulfoxide 2a in D 2 O. Figure S7. 1 H NMR spectrum (400 MHz) of methionine sulfone in D 2 O. -S11-

12 Figure S8. 1 H NMR spectrum (400 MHz) of α-terpinene 1b in CD 3 OD. Figure S9. 1 H NMR spectrum (400 MHz) of ascaridole 2b in CD 3 OD. -S12-

13 Figure S10. 1 H NMR spectrum (400 MHz) of citronellol 1c in CD 3 OD Figure S11. 1 H NMR spectrum (400 MHz) of peroxides 2c,c in CD 3 OD -S13-

14 3 References (1) Wootton, R. C. R.; Fortt, R.; De Mello, A. J. Org. Process Res. Dev. 2002, 6 (2), (2) Levesque, F.; Seeberger, P. H. Org. Lett. 2011, 13 (19), S14-