Improving the reactivity of phenylacetylene macrocycles toward topochemical polymerization by side chains modification

Summary The synthesis and self-assembly of two new phenylacetylene macrocycle (PAM) organogelators were performed. Polar 2-hydroxyethoxy side chains were incorporated in the inner part of the macrocycles to modify the assembly mode in the gel state. With this modification, it was possible to increase the reactivity of the macrocycles in the xerogel state to form polydiacetylenes (PDAs), leading to a significant enhancement of the polymerization yields. The organogels and the PDAs were characterized using Raman spectroscopy, X-ray diffraction (XRD) and scanning electron microscopy (SEM).


1-General remarks
Chemical reagents were purchased from Sigma-Aldrich Co. Canada, Alfa Aesar Co., TCI America Co. or Oakwood Products Inc. and were used as received. Solvents used for organic synthesis were obtained from Fisher Scientific (except THF from Sigma-Aldrich Co. Canada) and purified with a Solvent Purifier System (SPS) (Vacuum Atmosphere Co., Hawthorne, USA). Other solvents were obtained from Fisher Scientific and were used as received. Tetrahydrofuran (THF) and triethylamine (Et 3 N) used for Castro- Stephens-Sonogashira reactions were degassed 30 minutes prior to use. All anhydrous and air sensitive reactions were performed in oven-dried glassware under positive argon pressure. Analytical thin-layer chromatographies were performed with silica gel 60 F254, 0.25 mm pre-coated TLC plates (Silicycle, Québec, Canada). Compounds were visualized using 254 nm and/or 365 nm UV wavelength and/or aqueous sulfuric acid solution of ammonium heptamolybdate tetrahydrate (10 g/100 mL H 2 SO 4 + 900 mL H 2 O). Flash column chromatographies were performed on 230-400 mesh silica gel R10030B (Silicycle, Québec, Canada). Nuclear magnetic resonance (NMR) spectra were recorded on a Varian Inova AS400 spectrometer (Varian, Palo Alto, USA) at 400 MHz ( 1 H) and 100 MHz ( 13 C). High-resolution mass spectra (HRMS) were recorded with an Agilent 6210 Time-of-Flight (TOF) LC-MS apparatus equipped with an ESI or APPI ion source (Agilent Technologies, Toronto, Canada). UV-visible absorption spectra were recorded on a Varian diode-array spectrophotometer (model Cary 500) using 3-mm path length quartz cells. Scanning electron microscopy (SEM) images were taken using a S3 JEOL JSM-6360 LV. X-ray diffraction was recorded on Siemens X-rays Diffractometer (Model S3 D5000). DSC measurements were done on a Mettler Toledo (DSC 823e).

Gelation test
To test the gelation properties of PAMs in a given solvent, we proceeded as follow: in a vial, a PAMs was dissolved in a solvent. After dissolution by sonication, the vial was sealed and heated until a clear solution was obtained. The clear solution was allowed to slowly cool down at room temperature. The stability of the gel was confirmed by tube inversion.

SEM imaging
Organogel obtained in cyclohexane was deposited on a stainless steel substrate and allowed to dry for 3-4 days. Then, gold particles were sputtered on dried gel prior to imaging. Compound 2. A round bottom flask equipped with a magnetic stir bar is charged with compound 1 (14.0 g, 35.9 mmol), water (72 mL), NaOH (5.02 g, 125 mmol) and 2chloroethanol (8.67 g, 108 mmol). The reaction mixture is heated to 82°C and KI ( 596 mg, 3.59 mmol) is added. The reaction is then stirred overnight and allowed to cool to rt.

2-Experimental procedures and datas
The mixture is acidified with HCl to pH=5 and the solid is filtered under vacuo. The filtrate is washed with MeOH, EtOAc and with an hexanes in EtOAc 1:1 mixture to afford compound 2 (9.54 g, 61% yield) as a white amorphous powder. 1  Compound 3. A round bottom flask equipped with a magnetic stir bar is charged with compound 2 (4.50 g, 11.6 mmol), 6-ClHOBt (1.78 g, 10.5 mmol), DIC (1.47 g, 11.6 mmol), dodecylamine (2.24 g, 12.8 mmol) and THF (58 mL). The reaction mixture is stirred overnight and allowed to cool down. The mixture is then diluted with EtOAc and the organic layer is wash with water (3x), brine and dried with Na 2 SO 4. The solvents are removed under reduced pressure and the crude product is directly charged without further purification in a round bottom flask equipped with a magnetic stir. Imidazole (1.84 g, 27.2 mmol), TBSCl (1.96 g, 12.9 mmol) and DMF (10 mL) are then added and the mixture is stirred for 1h in an ultrasonic bath. The mixture is then diluted with EtOAc and the organic layer is washed with water (3x), brine and dried with Na 2 SO 4 . The crude product is then purified by flash chromatography on silica gel using 10% hexanes in acetone as eluant to afford compound 3 (3.41 g, 57% yield, 2 steps) as a white amorphous Hz, 2H), 3.39 (q, J = 6.5 Hz, 2H), Compound 5. A round bottom flask equipped with a magnetic stir bar is charged with compound 4 (3.00 g, 2.78 mmol), K 2 CO 3 (767 mg, 5.55 mmol), THF (14 mL) and MeOH (14 mL). The reaction is stirred until complete disappearance of the starting product by TLC. The mixture is then diluted with CH 2 Cl 2 and washed with water. The organic layer is then dried with Na 2 SO 4 and the solvent are removed under reduced pressure. The crude product is used directly with further purification and is charged in a round bottom flask equipped with a magnetic stir bar under nitrogen with 3,5-diiodooctylbenzene (3.33 g, 7.53 mmol) and Et 3 N (25 mL). PdCl 2 (PPh 3 ) 2 (71 mg, 0.10 mmol) and CuI (19 mg, 0.10 mmol) are then added and the mixture is stirred overnight. The mixture is diluted with CH 2 Cl 2 and the organic layer is washed with NH 4 Cl, water, brine and dried with Na 2 SO 4 .
The solvent is removed under reduced pressure and the crude product is purified by flash chromatography on silica gel using hexanes to 6% hexanes in acetone as eluents to afford
Propargylic alcohol (507 mg, 9.05 mmol) is then added and the mixture is stirred overnight. The reaction is then diluted with CH 2 Cl 2 and the organic layer is washed with NH 4 Cl, water and brine. The organic layer is then dried with Na 2 SO 4 and the solvent are removed under reduced pressure. The crude product is purified by flash chromatography on silica gel using 5% CH 2 Cl 2 in acetone as eluant to afford compound 7 (598 mg, 89% and CH 2 Cl 2 (10 mL). The reaction is stirred until complete disappearance of the starting product by TLC. The mixture is then diluted with CH 2 Cl 2 and washed with water. The S12 organic layer is then filtered on celite, dried with Na 2 SO 4 and the solvent are removed under reduced pressure. The crude product was directly used with further purification.   5; 143.6; 132.5; 132.3; 131.8; 129.8; 123.1; 117.4; 117.3; 100.4; 100.0; 93.9; 93.8;84.9; 74.8; 62.7; 62.6; 47.9; 40.2

PAM3.
A round bottom flask equipped with a magnetic stir bar was charged with compound 10 (380 mg, 0.28 mmol), THF (1.4 mL), MeOH (1.4 mL) and K 2 CO 3 (9 mg, 0.07 mmol). The reaction mixture was stirred until complete disappearance of the starting product by TLC, diluted with CH 2 Cl 2 , washed with water (3x), dried with sodium sulfate and the solvent was removed under reduced pressure. The resulting product was charged without further purification in a round bottom flask equipped with a magnetic stir bar with TBAF 1.0 M solution in THF (1.12 mL, 1.12 mmol) and THF (4.2 mL). The reaction mixture was stirred until complete disappearance of the starting product by TLC, diluted with CH 2 Cl 2 , washed with water (3x), dried with sodium sulfate and the solvent was removed under reduced pressure. The resulting product was charged without further purification in a round bottom flask equipped with a magnetic stir bar with degassed S15 pyridine (5 mL). Another round bottom flask equipped with a magnetic stir bar was charged with CuCl (1.14 g, 11.6 mmol), CuCl 2 (241 mg, 1.79 mmol) and degassed pyridine (23 mL) under N 2 atmosphere. The first solution was added dropwise to the catalyst solution over 4 days using a syringe pump and the reaction mixture was stirred for an additional 7 days. The reaction mixture was diluted with CHCl 3 and poured in water. The organic layer was extracted successively with water, 25% aqueous NH 4 OH, water, 10% aqueous acetic acid, water, 10% aqueous NaOH and brine. The organic layer was dried with sodium sulfate and the solvent was removed under reduced pressure. The crude product was purified by flash chromatography on silica gel using CHCl 3 to 5% acetone in CHCl 3 as eluents to afford PAM3 (45 mg, 16 % yield over 3 steps) as a white amorphous powder. 1 H NMR and 13 C NMR: Due to the poor solubility of PAM3 in common organic solvent, acquisition of clean spectrum was not afforded. The