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Halynne R. Lamontagne ; Mélanie Cyr ; Mário C. Vebber ; Sufal Swaraj ; Cory S. Harris ; Jaclyn L. Brusso , et al.
Abstract: Organic thin-film transistors (OTFTs) are an emerging platform for rapid, point-of-source detection and speciation of Δ9 -tetrahydrocannabinol (THC) and cannabidiol (CBD). (F5PhO)2-F16-SiPc semiconductor was implemented into high performance, air-stable n-type bottom gate, bottom contact OTFTs, however, the resulting device performance changes in response to THC and CBD were negligible. We explored the orientation of the corresponding thin films by synchrotron-based grazing incidence wide-angle X-ray scattering (GIWAXS) and angle-dependent near-edge X-ray absorption fine structure (NEXAFS), as well as polarized Raman microscopy. These techniques demonstrate for the first time that (F5PhO)2-F16-SiPc molecules are at a 45–48° orientation to the substrate; comparable to other reported R2-SiPcs. This orientation did not change upon exposure to THC and CBD, which has previously been reported for phthalocyanine-based OTFT cannabinoid sensors. The presence of two bulky axial groups, along with the absence of hydrogens in the molecule and the low reactivity of the silicon atom likely causes the lack of interaction with the cannabinoids. While (F5PhO)2-F16-SiPc may be a successfully air-stable n-type semiconductor for OTFTs, the structural changes performed to make it air stable over traditional nonfluorinated silicon MPcs, are likely responsible for its lack of response to cannabinoid exposure.
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CAS No. : | 771-61-9 |
Formula : | C6HF5O |
M.W : | 184.06 |
SMILES Code : | OC1=C(F)C(F)=C(F)C(F)=C1F |
MDL No. : | MFCD00002156 |
InChI Key : | XBNGYFFABRKICK-UHFFFAOYSA-N |
Pubchem ID : | 13041 |
GHS Pictogram: |
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Signal Word: | Danger |
Hazard Statements: | H314-H302+H312+H332 |
Precautionary Statements: | P280-P301+P330+P331-P280-P305+P351+P338-P310-P302+P352-P301+P312-P304+P340 |
Class: | 8 |
UN#: | 3261 |
Packing Group: | Ⅱ |
* All experimental methods are cited from the reference, please refer to the original source for details. We do not guarantee the accuracy of the content in the reference.
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
90% | With 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; In N,N-dimethyl-formamide; at 0 - 20℃;Inert atmosphere; | Biotin (2.95 g, 12.00 mmol) was dissolved in DMF (10 mL), and Pfp-OH (2.80 g, 15.20 mmol) was added to the biotin solution before EDC.HCl (5.70 g, 29.70 mmol) in DMF (15 mL) were added to the mixture at 0 C over 30 min. The mixture stirred overnight at room temperature under nitrogen atmosphere. The product washed with DCM. White powder was obtained with a yield of 90% (4.50 g). The product was used in the next step without further purification. 1H NMR (D2O): d 1.41-1.69 (m, 6H, CH2), 2.57 (d, 1H,CH2), 2.77-2.85 (m, 3H, CH2), 3.11-3.12 (m, 1H, CH), 4.14 (t, 1H, CH), 4.30 (t, 1H, CH), 6.37 (d, 2H, NH). |
With dicyclohexyl-carbodiimide; In N,N-dimethyl-formamide; at 20℃; | EXAMPLE lO[D-(+)-biotinyl]-L-aspartate alpha-benzyl ester (14)To a suspension of D-Biotin (2.0 g, 8.19 mmol) in DMF (52 mL) was added pentafluorophenol (1.6 g, 15.6 mmol) followed by DCC (2.5 g, 12.3 mmol). The reaction mixture was allowed to stir, under nitrogen atmosphere, overnight at RT. The reaction mixture remained a suspension and was filtered off and concentrated. The residue was taken up into Et2theta and stirred for several minutes after which the suspension was filtered an dried und vacuum to give a white solid (2.58 g) ESI-MS: 411 [M+H]+. The solid was dissolved in DMF (90 mL) and Et3N (1.24 mL, 8.82 mmol, 1.4 equiv.) was added. H-Asp-OBn was added in portions as a solid. After approximately 15 min the reaction mixture became clear and an additional 2h stirring was allowed. The reaction mixture was concentrated under reduced pressure and water was added followed by MeOH (3:1). The solid formed was filtered off, washed with Et2theta and dried under vacuum to give compound 14 as a white solid (2.92 g, 77 %) ESI-MS: 450 [M+H]+. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
70.83% | With potassium fluoride; at 20℃; for 48h;Cooling with ice; | First raw material 4,5-bis (pentafluorophenyl) -3,6-difluoro-phthalonitrile were prepared as follows: A 200ml reaction vessel equipped with a dropping funnel and a thermometer <strong>[1835-65-0]tetrafluorophthalonitrile</strong> 20.1 g ( 100.45mmol), potassium fluoride 13.99g (240.79mmol), was added to the methyl isobutyl ketone 130ml.After cooling with an ice-bath, conducted from the dropping funnel, was added slowly a solution of pentafluorophenol 37.0g (201.02mmol) of methyl isobutyl ketone 70 ml, then the reaction was stirred for 2 days at room temperature It was.Except inorganic salt and the reaction solution was filtered, washed with water using a separatory funnel, was dehydrated with anhydrous sodium sulfate, the reaction solution was concentrated in an evaporator.The concentrate, by re-precipitation purification with toluene / hexane solvent, 4,5-bis (pentafluorophenyl) -3,6-difluoro phthalonitrile, 70.83percent yield (37.4g, 70.81mmol obtained in). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With potassium carbonate; In water; N,N-dimethyl-formamide; at 80℃; for 4.5h;Inert atmosphere; | The intermediate M2,0.42g 0.71g of anhydrous potassium carbonate and 0.58g of pentafluorophenol (M = 184) was added to 14mL of water containing in addition to DMF (M = 73) of the neck round bottom reaction flask.Slowly warmed to 80 under an argon atmosphere.TLC detection reaction process, to walk the plank raw spots disappear stop the reaction.4.5h the reaction ended, 85 deg.] C under reduced pressure (degree of vacuum less than 133Pa) was removed by distillation of DMF, followed by dichloromethane: petroleum ether (v: v) = 3: 1 was dissolved, and its use as eluant, purified by column chromatography to give the pink product M3. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
185.9 mg | With dicyclohexyl-carbodiimide; In ethyl acetate; at 0 - 20℃; for 4.0h; | Compound 8. To a solution of <strong>[66634-97-7]2,4-dimethyl-2-pentenoic acid</strong> (114 mg, 0.889 mmol) in EtOAc(4.0 mL), pentafluorophenol (188.2 mg, 1.02 mmol) and DCC (210.5 mg, 1.02 mmol) were added at 0 C.The reaction mixture was stirred for 1 h at 0 C and 3 h at room temperature and evaporated underreduced pressure to give 16 (185.9 mg, 0.632 mmol) that was used in the next step without furtherpurification. 1H-NMR: (400 MHz, CDCl3): 6.90 (1H, d, J=9.75), 2.8-2.6 (1H, m), 1.95 (3H, s), 1.07 (6H,d, J = 6.6). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
100% | With dicyclohexyl-carbodiimide; In 1,4-dioxane; for 17.0h; | Dicyclohexylcarbodiimide (807 mg, 3.91 mmol) was added to a stirred suspension of4-methyl-3,4-dihydro-2H-1 ,4-benzoxazine-7-carbcxylic acid (CAS 532391-89-2) (685 mg,3.55 mmcl) and pentafluorophenol (653 mg, 3.55 mmcl) in 1,4-dioxane (15 mL). Stirring was continued for 17 h by which time a colorless precipitate had formed. The mixture was filtered and evaporated; the residue was dissolved in CH2CI2 (20 mL) and evaporated to give the crude ester pentafluorophenyl 4-methyl-3,4-dihydro-2H-1 ,4-benzoxazine-7-carboxylate(1.4g, 3.90 mmcl, 100%) as a yellow oily solid which was used in the next step without purification. 1Pr2NEt (523 pL, 388 mg, 3 mmol) was added to a stirred mixture of 1-(3- brcmophenyl)ethanone (199 mg, 1 mmcl) and MgBr2Et2O (646 mg, 2.5 mmcl) in CH2CI2 (10 mL). The resulting suspension was stirred for 15 mm, then pentafluorophenyl 4-methyl-3,4- dihydro-2H-1 ,4-benzcxazine-7-carboxylate (431 mg, 1 .2 mmcl) in CH2CI2 (2 mL) was addeddropwise. After 24 h 1-(3-brcmophenyl)ethanone (199 mg, 1 mmcl), MgBr2Et2O (646 mg,2.5 mmcl), and 1Pr2NEt (523 pL, 388 mg, 3 mmcl) were added and the stirring was continued for further 24 h. 1 N phosphate buffer pH 6 (20 mL) was added, stirred for 10 mm, the organic phase was separated, the aqueous phase was extracted with CHCI3 (10 mL), the combined organic extract was washed with saturated NaHCO3 solution, brine, dried over Na2SO4 andconcentrated in vacuo. The residue was purified by flash chromatography on silica gel (n-hexane/chlcrofcrm =1:1, Rf 0.15) to afford 362 mg of crude product as yellow foam which was used in the next step without further purification. To a solution of crude 1-(3- brcmcphenyl)-3-(4-methyl-3,4-dihydrc-2H- 1 ,4-benzcxazin-7-yl )prcpane-1 ,3-dicne (362 mg) in EtDH (10 mL) hydrazine monohydrate (194 pL, 200 mg, 4 mmcl) was added. The reactionmixture was stirred at 78 00 for 15 h, cooled down to room temperature, the solvent and excess of hydrazine monchydrate were removed on the rotary evaporator. Tcluene (20 mL) was added and the mixture was concentrated to dryness. The crude product (380 mg) waspurified by flash chromatography on silica gel (chloroform/methanol =100:1, Rf 0.26) to afford the product (30 mg, 0.08 mmol, 8% over three steps) as a white solid. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
0.5 g; 3.3 g | Add phenyl dichlorophosphate (6.88 g, 3.04 ml, 32.6 mmol) to the reaction flask, add 200 mL of acetonitrile, cool to -70 C, and slowly add K11 (9.8 g, 32.6 mmol) and triethylamine (3.3 g, 4.53 ml, 32.6 mmol) of acetonitrile (60 mL) was added dropwise, then slowly warmed to room temperature. After reacting overnight, cooled to 0 C, pentafluorophenol (5.4 g, 29.4 mmol) and triethylamine (7.3 g, 10 ml, 72 mmol) of acetonitrile solution 60 mL of liquid was added dropwise to the above solution, stirred at 0 C for 1 hour, raised to room temperature, stirred overnight, then added 100 ml of dichloromethane and 100 ml of water, the organic phase was separated, anhydrous The organic layer was dried (MgSO4) -2 (4.5g), mother liquor separated by silica gel column(50% ethyl acetate / hexane) gave FP14-1 (3.3g) and FP14-2 (0.5g), FP14-2 and FP14-1 were both greater than99%. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
2.5 g; 0.4 g | Phosphorus oxychloride (5 g, 3.04 ml, 32.6 mmol) was added to the reaction flask.Add 200 mL of acetonitrile, cool to -70 C, and slowly add K11 (9.8 g, 32.6 mmol)And a solution of triethylamine (3.3 g, 4.53 ml, 32.6 mmol) in acetonitrile (60 mL)After the addition was completed, the temperature was slowly raised to room temperature, and after cooling overnight, it was cooled to 0 C.Pentafluorophenol (5.4g, 29.4mmol) and triethylamine (7.3g, 10ml,A solution of 72 mmol) of acetonitrile in 60 mL of liquid was added dropwise to the above solution.Stir at 0 C for 1 hour, warm to room temperature and stir overnight.Add 100 ml of dichloromethane and 100 ml of water to separate the organic phase.Dried over anhydrous sodium sulfate and concentrated under reduced pressure.The residue was separated on a silica gel column (0-30%EtOAc /EtOAc)The solid was recrystallized from 10% t-butyl methyl ether / n-hexane.Obtained white solid FP011-2 (3.4g),The mother liquor was separated on a silica gel column (50% ethyl acetate / hexane) to give FP011-1 (2.5 g)And FP011-2 (0.4g), FP011-2 and FP011-1 are both more than 99% pure. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
4.1 g | Phosphorus oxychloride (5 g, 3.04 ml, 32.6 mmol) was added to the reaction flask, 200 mL of acetonitrile was added, and the mixture was cooled to -70 C, and K11 (19.6 g, 65.2 mmol) and triethylamine (6.6 g, 9.06 ml) were slowly added dropwise. , 65.2 mmol) of acetonitrile (60 mL), after completion of dropwise addition, slowly warmed to room temperature, after the reaction overnight, cooled to 0 C, pentafluorophenol (5.4 g, 29.4 mmol) and triethylamine(7.3 g, 10 ml, 72 mmol) of acetonitrile solution 60 mL of liquid was added dropwise to the above solution, stirred at 0 C for 1 hour, raised to room temperature, stirred overnight, then added 100 ml of dichloromethane and 100 ml of water to separate the organic phase Drying over anhydrous sodium sulfate, EtOAc (EtOAc)EtOAc.The methyl ether/hexane was recrystallized to give a white solid FP11 (5.2 g). The crude liquid was separated by silica gel column (50% ethyl acetate/hexane) and FP11 (4.1 g). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
11.5 g | Phosphorus oxychloride (5 g, 3.04 ml, 32.6 mmol) was added to the reaction flask.Add acetonitrile 200mL,Cool to -70 C,Slowly add K11 (9.8g, 32.6mmol)And a solution of triethylamine (3.3 g, 4.53 ml, 32.6 mmol) in acetonitrile (60 mL).After the dropwise addition was completed, the temperature was slowly raised to room temperature, and the reaction was continued overnight.Cool the above mixture to 0 C,Add HA30 (4.93g, 29.4mmol),Cool to -70 C,60 mL of a solution of triethylamine (7.3 g, 10 ml, 72 mmol) in acetonitrile was added dropwise.After the addition, warm up to 0 C,Pentafluorophenol (5.4 g, 29.4 mmol) was reacted for 3 hours.And 60 mL of a solution of triethylamine (7.3 g, 10 ml, 72 mmol) in acetonitrile was added dropwise to the above solution.Stir at 0 C for 1 hour,Raise to room temperature and stir overnight.After adding 100 ml of dichloromethane and 100 ml of water, the organic phase was separated, dried over anhydrous sodiumThe residue was separated on a silica gel column (0-30% ethyl acetate /hexane)11.5g of white solid,The solid was recrystallized from 10% t-butyl methyl ether / hexane.Obtained white solid FP130-2 (4.5g),The mother liquor was separated on a silica gel column (50% ethyl acetate /hexane) to give FP130-1 (3.4 g) and FP130-2 (0.6 g).Both FP130-2 and FP130-1 are more than 99% pure. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With 1,8-diazabicyclo[5.4.0]undec-7-ene; In acetone; at 60℃; for 0.0758333h; | Dissolve 5mmol (0.59g) of 3-methylstyrene in 10mL 1:1 water/acetone solution (5mL water plus 5mL acetone mixedIn homogeneous), a homogeneous solution A was obtained, which was added to the syringe pump a; 8 mmol (2.29 g) of DBH was dissolved in 10 mL of 1:1 water/acetone solution.In a solution (5 ml of water plus 5 ml of acetone mixed uniformly), a homogeneous solution B was obtained, which was added to a syringe pump b; 6 mmol (0.91 g) of DBU was added.And 6mmol (1.10g) of pentafluorophenol dissolved in 10mL of acetone (acetone) to obtain a homogeneous solution C, added to the syringe pump c; injectionThe injection flow rates of pumps a and b were both 0.3 ml/min, and the injection flow rate of syringe pump c was 0.5 ml/min; the first microchannel reactor was reversed.The volume V=5ml, the reaction time 8.33min, the second microchannel reactor reaction volume V=5ml, the reaction time is 4.55min;First and second microchannel reactor inner diameter = 0.5 mm; first microchannel reactor temperature is 70 C, second microchannel reactorThe temperature is 60 C; after two cycles of the second microchannel reactor reaction, the reaction liquid is collected and calculated by HPLC method.The product yield was 74%.Separation by column chromatography to obtain product 3i |