The First Inexpensive, Simplified and Large Scale Synthesis of p-tertbutylcalix[7]

Transcription

1 Supporting Information for The First Inexpensive, Simplified and Large Scale Synthesis of p-tertbutylcalix[7] and [9]arenes Mouna Ferchichi 1,3, Erwann Jeanneau 1, Jean-Claude Sollier 2, Faouzi Meganem 3, Ulrich Darbost 1,* and Isabelle Bonnamour 1,* Table of contents S1 1. Crystallographic data S3 Table S1. Selected Crystal data for p-tert-butylcalix[7]arene S4 Figure S1: Crystal structure of p-tert-butylcalix[7]arene S4 Table S2. Selected Crystal data for p-tert-butylcalix[9]arene S4 Figure S2: Crystal structure of p-tert-butylcalix[9]arene S H NMR, 13 C NMR, 13 C-DEPT NMR, IR, Mass spectra and HPLC Chromatograms of p-tert-butylcalix[7 and 9]arenes S5 Figure S3: 1 H NMR Spectrum of p-tert-butylcalix[7]arene S5 Figure S4: 13 C NMR Spectrum of p-tert-butylcalix[7]arene S6 Figure S5: 13 C-DEPT NMR Spectrum of p-tert-butylcalix[7]arene S7 Figure S6: Mass Spectrum of p-tert-butylcalix[7]arene S8 Figure S7: IR Spectrum of p-tert-butylcalix[7]arene S9 Figure S8: HPLC Chromatogram of p-tert-butylcalix[7]arene S10 Figure S9: 1 H NMR Spectrum of p-tert-butylcalix[9]arene S11 Figure S10: 13 C NMR Spectrum of p-tert-butylcalix[9]arene S12 Figure S11: 13 C-DEPT NMR Spectrum of p-tert-butylcalix[9]arene S13 Figure S12: Mass Spectrum of p-tert-butylcalix[9]arene S14 Figure S13: IR Spectrum of p-tert-butylcalix[9]arene S15 Figure S14: Chromatogram HPLC of p-tert-butylcalix[9]arene S16 3. HPLC Chromatograms of figure 3 S17 Figure S15: Chromatogram HPLC of Etalon S17 Figure S16: Chromatogram HPLC of Mixture A S18 Figure S17: Chromatogram HPLC of Mixture B S19 Figure S18: Chromatogram HPLC of Mixture C S20 Figure S19: Chromatogram HPLC of Mixture D S21 Figure S20: Chromatogram HPLC of Mixture E S22 Figure S21: Chromatogram HPLC of Mixture F S23 4. HPLC Chromatograms of table 1 S24 - S1

2 Figure S22: Chromatogram HPLC of Entry 1 S24 Figure S23: Chromatogram HPLC of Entry 2 S25 Figure S24: Chromatogram HPLC of Entry 3 S26 Figure S25: Chromatogram HPLC of Entry 4 S27 Figure S26: Chromatogram HPLC of Entry 5 S28 Figure S27: Chromatogram HPLC of Entry 6 S29 Figure S28: Chromatogram HPLC of Entry 7 S30 Figure S29: Chromatogram HPLC of Entry 8 S31 Figure S30: Chromatogram HPLC of Entry 9 S32 Figure S31: Chromatogram HPLC of Entry 10 S33 5. General protocols S General procedure for p-tert-butylcalix[7] and [9]arenes synthesis S Procedure for the purification and isolation of p-tert-butylcalix[7] and [9]arenes S Technical Scheme of the semi-industrial unit S36 - S2

3 1. Crystallographic data A suitable crystal was mounted on a Nonius Kappa CCD diffractometer using Mo K radiation ( = Å). Intensities were collected at 150 K by means of the COLLECT software. Reflection indexing, Lorentz-polarization correction, peak integration, and background determination were carried out with DENZO. Frame scaling and unitcell parameters refinement were made with SCALEPACK. An analytical absorption correction was applied using the modeled faces of the crystal. The structures were solved by direct methods with SIR97. The remaining non-hydrogen atoms were located by successive difference Fourier map analyses. H-atoms were placed geometrically and included in the refinement using soft restraints on the bond lengths and angles to regularize their geometry (C-H in the range Å and O-H = 0.82 Å) and isotropic atomic displacement parameters (U(H) in the range times U eq. of the adjacent atom). In the last cycles of the refinement, the hydrogen atoms were refined using a riding mode. The structure refinement was carried out with CRYSTALS. Table S1. Selected Crystal data for p-tert-butylcalix[7]arene Empirical formula C 81 H 104 N 2 O 7 Formula weight g/mol Temperature 150 K Wavelength Å Crystal system Triclinic Space group P 1 Unit cell dimensions a = (2) Å α = (1). b = (2) Å β = (1). c = (3) Å γ = (9). Volume (10) Å 3 Z 2 Density (calculated) Mg/m 3 Absorption coefficient 0.07 mm -1 F(000) 1320 Crystal size 0.38 x 0.37 x 0.30 mm 3 Theta range for data collection 1.4 to Index ranges -18 h 18, -19 k 19, -24 l 24 reflections 8678 with I > 2.0σ(I), wr(f 2 ) Figure S1: Projection of the p-tert-butylcalix[7]arene molecules showing the trimeric substructure (rings 1,2,7) and tetrameric substructure (rings 3-6), with disorder and H-atoms omitted for clarity. Cyclic intramolecular H-bonding depicted by dashed blue lines. - S3

4 Table S2. Selected Crystal data for p-tert-butylcalix[9]arene Empirical formula C 99 H 126 O 9.6(C 3 H 6 O) Formula weight g/mol Temperature 150 K Wavelength Å Crystal system Triclinic Space group P 1 Unit cell dimensions a = (3) Å α = (1). b = (3) Å β = (2). c = (5) Å γ = (2). Volume 5487(2) Å 3 Z 2 Density (calculated) Mg/m 3 Absorption coefficient 0.07 mm -1 F(000) 1968 Crystal size 0.42 x 0.37 x 0.36 mm 3 Theta range for data collection 0.7 to Index ranges -21 h 21, -23 k 24, -27 l 27 reflections with I > 2.0σ(I), wr(f 2 ) Figure S2: General view of the p-tert-butylcalix[9]arene molecule, down the (1 0 0) projection, with disorder for some tert-butylphenol groups, and H-atoms omitted for clarity. Cyclic intramolecular H-bonding depicted by dashed blue lines. - S4

5 2. 1 H NMR, 13 C NMR, 13 C-DEPT NMR, IR, Mass spectra and HPLC Chromatograms of p-tert-butylcalix[7 and 9]arenes Figure S3: 1 H NMR Spectrum of p-tert-butylcalix[7]arene tbu OH CH S5

6 Figure S4: 13 C NMR Spectrum of p-tert-butylcalix[7]arene tbu OH CH S6

7 Figure S5: 13 C-DEPT NMR Spectrum of p-tert-butylcalix[7]arene tbu OH CH S7

8 Figure S6: Mass Spectrum of p-tert-butylcalix[7]arene tbu CH 2 7 OH Intens. x MS, min #(8-9) m/z Intens. x MS, min #(8-9) m/z - S8

9 Figure S7: IR Spectrum of p-tert-butylcalix[7]arene tbu CH 2 7 OH 101, , ,50 989,81 939,93 912,94 736,42 793,93 699, , , , , ,10 816,62 782,95 %T , , ,15 872, , , ,79 71,5 4000, ,0 cm-1 - S9

10 Figure S8: Chromatogramm HPLC of p-tert-butylcalix[7]arene tbu CH 2 7 OH - S10

11 Figure S9: 1 H NMR Spectrum of p-tert-butylcalix[9]arene tbu OH CH S11

12 Figure S10: 13 C NMR Spectrum of p-tert-butylcalix[9]arene tbu OH CH S12

13 Figure S11: 13 C-DEPT NMR Spectrum of p-tert-butylcalix[9]arene tbu OH CH S13

14 Figure S12: Mass Spectrum of p-tert-butylcalix[9]arene LCQ #46-55 RT: AV: 10 SB: NL: 1.59E7 T: + c ESI Full ms [ ] tbu OH CH m/z LCQ #47-53 RT: AV: 7 SB: NL: 3.83E6 T: - c ESI Full ms [ ] tbu CH OH m/z - S14

15 Figure S13: IR Spectrum of p-tert-butylcalix[9]arene 99, ,48 945,72 913,92 666,81 726,33 92 %T , ,70 tbu 1392, , , , ,69 875,79 815,77 785, , ,91 82 CH OH , ,20 74,3 4000, ,0 cm-1 - S15

16 Figure S14: Chromatogramm HPLC of p-tert-butylcalix[9]arene tbu CH 2 9 OH - S16

17 3. HPLC Chromatograms of figure 3 * Figure S15: Chromatogramm HPLC of Etalon - S17

18 Figure S16: Chromatogramm HPLC of Mixture A - S18

19 Figure S17: Chromatogramm HPLC of Mixture B - S19

20 Figure S18: Chromatogramm HPLC of Mixture C - S20

21 Figure S19: Chromatogramm HPLC of Mixture D - S21

22 Figure S20: Chromatogramm HPLC of Mixture E - S22

23 Figure S21: Chromatogramm HPLC of Mixture F - S23

24 4. HPLC Chromatograms of table 1 Figure S22: Chromatogramm HPLC of Entry 1 - S24

25 Figure S23: Chromatogramm HPLC of Entry 2 - S25

26 Figure S24: Chromatogramm HPLC of Entry 3 - S26

27 Figure S25: Chromatogramm HPLC of Entry 4 - S27

28 Figure S26: Chromatogramm HPLC of Entry 5 - S28

29 Figure S27: Chromatogramm HPLC of Entry 6 - S29

30 Figure S28: Chromatogramm HPLC of Entry 7 - S30

31 Figure S29: Chromatogramm HPLC of Entry 8 - S31

32 Figure S30: Chromatogramm HPLC of Entry 9 - S32

33 Figure S31: Chromatogramm HPLC of Entry 10 - S33

34 5. General protocols Solvents were purified and dried by standard methods prior to use. Flash column chromatography was performed using silica gel (Kieselgel-60, nm, Merck). Reactions were monitored by TLC on POLYGAM SIL G/UV 254 (Macherey-Nagel) silica gel plate and visualized by UV light. 1 H NMR and 13 C NMR spectra were recorded at 300 and 400 MHz on a Bruker Avance DRX/ALS 300 or DRX 400 spectrometer and unless otherwise stated deuterated chloroform was used as solvent. The 1 H-spectra were recorded in ppm and referenced to the residual CHCl 3 signal located at C-NMR spectra were recorded in ppm and referenced to the residual CHCl 3 signal found at Multiplicities in the NMR spectra are described as: s = singlet, d = doublet, t = triplet, q = quartet, m = multiplet, br = broad; coupling constants are reported in Hz. Mass spectra were acquired on a ThermoFinnigan LCQ Advantage ion trap instrument, detecting positive ions (+) or negative ions (-) in the ESI mode. Samples (in chloroform) were infused directly into the source (5 L/min) using a syringe pump. The following source parameters were applied: spray voltage kv, nitrogen sheath gas flow 5 20 arbitrary units. The heated capillary was held at 200 C. High resolution mass spectra were acquired on a ThermoFinnigan MAT 95 XL and Brucker Micro TOF Q. Low resolution mass spectra were run on a ThermoFinnigan LCQ Advantage spectrometer. Ion masse/charge (m/z) ratios are reported as values in atomic mass units. Infrared spectra were recorded on a Perkin-Elmer Instruments FT- IR spectrometer as a neat sample. The composition of the crude mixture was systematically determined by using an inverse phase HPLC. HPLC analyses were performed using a KONTRON instrument consisting of a series 2 pumps, an HPLC DETECTOR 430 UV/VIS detector set at 281 nm, and a 4.6 mm id (Internal Diameter), 25 cm, EC 250/4.6 NUCLEOSIL C18 HPLC column packed with 5 µm, non-end-crapped, silica-based particles. The separation of p-tert-butylcalix[n]arenes was accomplished with a mixture of two eluants A and B. Eluant A consisted of 99 % CH 3 CN with 1 % AcOH (acetic acid). Eluant B consisted of 57 % CH 2 Cl 2 and 43 % MTBE (methyltert-butylether) in a 12:9 ratio and 1 % AcOH. A and B set at a flow route of 0.8 ml/min and a pressure of 45 Bars. An isocratic run using a 80/20 mixture of A and B for 25 min was found suitable for separation of p-tert-butylcalix[4-12]arenes. (Note: a significant shift in retention times was observed as a function of temperature (T = 30 C)). 5.1 General procedure for p-tert-butylcalix[7] and [9]arenes synthesis Twenty-five liters of 1,2-dichloroethane were first introduced into the reactor. Then p-tert-butylphenol (1000 g, 6.65 mol, 1 eq), PTSA (1300 g, 6.83 mol, 1.03 eq.) and finally s-trioxane (660 g, 7.32 mol, 1.1 eq) were introduced through the top of the reactor. The system was closed and after 10 min of vigorous stirring, heating was started. After 2h the reaction mixture changed from a colourless clear solution to a colourless cloudy mixture. Every hour, an aliquot of reaction mixture was collected through the bottom of reactor and analyzed by HPLC. After 4 hours the reaction mixture became dark green and the HPLC analysis has shown that the reaction was complete (20 % in p-tertbutylcalix[7]arene and 10 % in p-tert-butylcalix[9]arene). After allowing the mixture going back to room temperature, the bottom valve was opened and all the mixture was collected in a 50 litres can. The crude was then transferred in a mixing decanter. Then, in order to quench the reaction, 5 litres of HCl (1M) were added. The two liquid layers were mixed together during 1 hour and were then separated. The organic layer was reloaded, and then washed again with 5 litres of HCl (1M). The two layers were separated and the aqueous layers were recombined and reloaded, then were washed with 5 litres of 1,2-dichloroethane in order to recover a maximum of organic layer. After separation, the organic layers were recombined, and finally washed twice with 5 litres of distilled water until ph = 7. Organic layer was separated, collected, and introduced into a vacuum evaporator. Heating was set up at 45 C, under a 20 mm Hg vacuum, allowing the 1, 2-dichloroethane to be evaporated. After removal of all the solvent, the resulting dark solid was dried under vacuum in order to remove the traces of solvents. 900 g of crude dark solid were obtained. - S34

35 5.2 Procedure for the purification and isolation of p-tert-butylcalix[7] and [9]arenes The resulting crude compound was purified by portions of 50 g. First, the crude was refluxed during four hours in hexane (60 g/l). Once the solution cold, a precipitate (P1) was separate by filtration from the mother liquors which were concentrated (Mixture B, 729 g). Starting from the evaporated mother liquors mixture B, a sequence of treatment/filtration in hot acetone (68 g/l), drive to 5 precipitates (P2a to P2e) and a final mother liquor mixture C (600 g). This mixture C was filtrated through silica gel (eluant 5/5 CH 2 Cl 2 /heptane) leading to a white solid. A final recrystallization of this solid acetone/ethanol drove to 96 g of the pure p-tert-butylcalix[7]arene E (purity > 98 %). Once they have been mixed together, the collected precipitates P2b-2c became the mixture D (37.6 g). A recrystallization of mixture D in chloroform/acetonitrile led to 25 g of the pure p-tert-butylcalix[9]arene F as a white crystalline solid (purity > 98 %). Scheme 1 Procedure s Synoptic of purification for the obtention of pure p-tert-butylcalix[7] and [9]arenes. - S35

36 5.3 Technical Scheme of the semi-industrial unit - S36