Abstract: NIR dyes have become popular for many applications, including biosensing and imaging. For this reason, the mol. switch mechanism of the xanthene dyes makes them useful for in vivo detection and imaging of bioanalytes. Our group has been designing NIR xanthene-based dyes by the donor-acceptor-donor approach; however, the equilibrium between their opened and closed forms varies depending on the donors and spacer. We synthesized donor-acceptor-donor NIR xanthene-based dyes with an alkyne spacer via the Sonogashira coupling reaction to investigate the effects of the alkyne spacer and the donors on the maximum absorption wavelength and the mol. switching (ring opening) process of the dyes. We evaluated the strength and nature of the donors and the presence and absence of the alkyne spacer on the properties of the dyes. It was shown that the alkyne spacer extended the conjugation of the dyes, leading to absorption wavelengths of longer values compared with the dyes without the alkyne group. In addition, strong charge transfer donors shifted the absorption wavelength towards the NIR region, while donors with strong π-donation resulted in xanthene dyes with a smaller equilibrium constant DFT/TDDFT calculations corroborated the exptl. data in most of the cases. Dye 2 containing the N,N-dimethylaniline group gave contrary results and is being further investigated.
Abstract: Commercially available and inexpensive potassium bis(trimethylsilyl)amide (KHMDS) serves as an efficient transition metal-free catalyst for the catalytic sp C−H silylation of several terminal alkynes including two pharmaceuticals. Overall, the presented system allows the synthesis of various attractive silylacetylenes under mild conditions, making this approach an environmentally benign and sustainable alternative to existing synthetic solutions.
* 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.
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5
[ 79-22-1 ]
[ 768-60-5 ]
[ 7515-17-5 ]
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[ 7515-17-5 ]
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7
[ 768-60-5 ]
[ 7515-17-5 ]
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8
[ 500-05-0 ]
[ 768-60-5 ]
[ 725-14-4 ]
Yield
Reaction Conditions
Operation in experiment
44%
for 36 h; Reflux
(a) 4'-Methoxybiphenyl-4-carboxylic acid (7b).; Method A.Coumalic acid (1.06 g, 7.56 mmol) and 4-ethylnyl anisole were dissolved in diglyme and brought to reflux for 36h. The reaction was then allowed to cool and the solvent was removed under reduced pressure. The resultant slurry was then recrystallized from ethanol to yield 754 mg (44percent) of a light tan solid.
Stage #1: With bis-triphenylphosphine-palladium(II) chloride; copper(l) iodide; triethylamine In acetonitrile at 20℃; for 0.5 h; Inert atmosphere Stage #2: at 20℃; Inert atmosphere
General procedure: 2-iodoaniline (500.2 mg, 2.28 mmol, 1.0 equiv) was dissolved in Et3N (4.5 mL). The resulting solution was added with PdCl2(PPh3)2 (32.1 mg, 0.046 mol, 0.02 equiv) and CuI (17.4 mg, 0.091mmol, 0.04 equiv). The orange-yellow solution was degassed by bubbling with a stream of argon into the solution at room temperature for 30 min. After degassing, phenylacetylene (0.30 mL,279.0 mg, 2.73 mmol, 1.2 equiv) was added as a neat liquid into the solution via syringe. The resulting dark brown solution was allowed to stir at room temperature under argon atmosphere overnight. The reaction was quenched by addition of sat. aq. NH4Cl. The separated aqueousphase was extracted with EtOAc (3x times). The combined organic phases were washed with sat. aq. NaCl, dried over anh. Na2SO4, filtered and concentrated to a crude product. The crudeproduct was purified by SiO2 column chromatography eluting with 0-10percent EtOAc-hexane to give 398.2 mg (90percent) of 2-(phenylethynyl)aniline as an orange solid.
75%
With sodium hydroxide In toluene at 130℃; for 72 h;
General procedure: To a stirred solution of the corresponding 2-iodoaniline (6, 1 mmol) in toluene (3 mL) under argon atmosphere were added Pd/CuO-Fe3O4 (50 mg), NaOH (400 mg, 10 mmol), and the corresponding alkyne (2, 1.5 mmol). The resulting mixture was stirred at 130 °C until the end of reaction (see Table 6). The catalyst was removed by a magnet and the resulting mixture was quenched with water and extracted with EtOAc. The organic phases were dried over MgSO4, followed by evaporation under reduced pressure to remove the solvent. The product was purified by chromatography on silica gel (hexane/ethyl acetate) to give the corresponding compounds 7. Yields are included in Table 6. Then, to a stirred solution of 7 (1 mmol) in toluene (4 mL) was added ZnBr2 (225 mg, 1 mmol). The resulting mixture was stirred at 130 °C during 24 h. The mixture was quenched with water and extracted with EtOAc. The organic phases were dried over MgSO4, followed by evaporation under reduced pressure to give the pure products 8 in quantitative yields. Physical and spectroscopic data for compounds 7 and 8, as well as literature for known compounds, follow.
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To a solution of 2-bromobenzaldehyde (1.85 g, 10 mmol) and 4- methoxyphenyl acetylene (1.58 g, 12 mmol) in 40 mL of triethylamine were added dichlorobis(triphenylphosphine) palladium(ll) (140 mg, 2 molpercent) and copper(l) iodide (20 mg, 1 molpercent). The reaction mixture was heated at 5O0C under nitrogen for 3 hours. The reaction mixture was cooled to room temperature and the ammonium salt was removed by filtration. The filtrate was concentrated under reduced pressure. Purification of the crude compound by column chromatography (SilicaGel 230-400 mesh; 10percent ethyl acetate in hexanes as eluent) afforded of 2- (4-methoxy phenylethynyl) benzaldehyde (2.1 g, 89percent).
89%
at 50℃; for 3 h;
To a solution of 2-bromobenzaldehyde (1.85 g, 10 mmol) and 4-methoxyphenyl acetylene (1.58 g, 12 mmol) in 40 mL of triethylamine were added dichlorobis(triphenylphosphine)palladium(II) (140 mg, 2 mol percent) and copper (I) iodide (20 mg, 1 mol percent). The reaction mixture was heated at 50° C. under nitrogen for 3 h. The reaction mixture was cooled to room temperature and the ammonium salt was removed by filtration. The filtrate was concentrated under reduced pressure. Purification of the crude compound by column chromatography (silica gel 230-400 mesh; 10percent ethyl acetate in hexanes as eluent) afforded 2-(4-methoxyphenylethynyl)benzaldehyde (2.1 g, 89percent). The above compound (2.06 g, 8.73 mmol) and t-butylamine (3.83 g, 52.4 mmol) were stirred under nitrogen for 24 h at room temperature. The resulting mixture was extracted with ether and the organic layer was dried over anhydrous Na2SO4, and concentrated to give the imine (2.4 g, 94percent), which was used in the next step without further purification. To a solution of the above imine (2.39 g, 8.2 mmol) in 100 mL anhydrous DMF was added (0.156 g, 0.82 mmol) copper (I) iodide, and the solution was flushed with nitrogen. The reaction mixture was heated at 100° C. for 4 h. The mixture was cooled to room temperature, and diluted with ether (200 mL). The organic layer was washed with saturated aqueous ammonium chloride (3.x.100 mL). The organic layer was dried over anhydrous Na2SO4 and concentrated to give the crude compound as a dark colored solid. Purification by column chromatography (silica gel 230-400 mesh; 10percent ethylacetate in hexanes as eluent) afforded 3-(4-methoxyphenyl)isoquinoline (1.064 g, 55percent), as a white solid. The 3-(4-methoxyphenyl)isoquinoline (1.05 g, 4.47 mmol) was suspended in 30 mL hydroiodic acid and 12 mL of acetic acid was added. The reaction mixture was stirred at 110° C. for 2 h, then cooled to room temperature. The precipitate formed was filtered off, washed with acetic acid (2.x.5 mL) and dried under vacuum, to give a yellow solid. The crude compound was purified by triturating with 5percent methanol in ether to give 4-isoquinolin-3-yl-phenol (0.83 g, 84percent) as a white powder. Selected data: MS (ES) m/z: 222.89, 221.86; MP 218-219° C.
84%
With potassium carbonate In N,N-dimethyl-formamide at 100℃; for 13 h; Green chemistry
General procedure: A mixture of aryl halide (1mmol), terminal alkyne (1mmol), K2CO3 (2mmol) and MNPFemTriazNHCAg complex (6) (100mg) in DMF (5mL) was stirred at 100°C. The progress of reaction was monitored by TLC. After completion, the reaction mixture was quenched in ice cold water and 6 was separated by external magnet. The reaction mixture was extracted with ethyl acetate (3×25mL). Evaporation of solvent in vaccuo followed by column chromatography over silica gel using petroleum ether/ethyl acetate afforded desired Sonogashira coupling products.
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With diisopropylamine;copper(l) iodide; bis(benzonitrile)palladium(II) dichloride; tri-tert-butyl phosphine; In 1,4-dioxane; toluene; at 20℃;
In a glove box, a schlenk tube was charged with Pd(PhCN)2Cl2 mg, 0.16 mmol) and CuI (21 mg, 0.11 mmol). Under argon counterflow, anhydrous dioxane (50 mL), P(t-Bu)3 (2.7 mL of 0.123 M solution in toluene, 0.33 mmol), HN(i-Pr)2 (1.8 mL, 13 mmol), <strong>[35578-47-3]4,4'-dibromobenzil</strong> (2.0 g, 5.4 mmol), and 4-ethynylanisole (1.80 g, 13.6 mmol) were added to the schlenk tube sequentially. After stirring at room temperature overnight, the reaction mixture was diluted with ethyl acetate and filtered through a pad of celite with EtOAc rinsing. The solvent was removed under reduced pressure and the product was purified by column chromatography (silica gel, hexanes: dichloromethane = 2:3 (v/v)) to give bright yellow solid (2.45 g, 96%). ¹H NMR (300 MHz, CDCl3, delta) : 7.93 (d, J= 8.8 Hz, 4H), 7.60 (d, J= 8.3 Hz, 4H), 7.48 (d, J= 9.3 Hz, 4H), 6.88 (d, J= 8.8 Hz, 4H), 3.82 (s, 6H). ¹3CeH} NMR (75 MHz, CDCl3, delta): 193.31, 160.25, 133.41, 131.79, 131.59, 130.64, 129.84, 114.42, 114.14, 94.56,87.49, 55.33. HRMS-FAB (m/z): [M + H]+ calcd for C32H2304,471.1596; found, 471.1595. Anal. Calcd for C32H2204: C, 81.69; H, 4.71. Found: C, 81.37; H, 4.58.
L: Nitrogen was bubbled through a mixture of <strong>[14482-51-0]2-bromo-3,5-dichloropyridine</strong> K (6.2 g, 27.2 mmol), l-ethynyl-4-methoxybenzene (3.58 g, 27.2 mmol) and Pd(PPh3)2Cl2 (0.96 g, 1.36 mmol) in piperidine (100 mL) for 15 minutes. CuI (0.26 g, 1.36 mmol) was added and the nitrogen gas flow maintained for 1.5 hours as the reaction was stirred. The mixture was diluted with Et2O (250 mL) and washed with H2O (200 mL). The aqueous extract was then washed with Et2O (2 x 200 mL) and all the organic extracts combined. These were then washed with H2O (3 x 200 mL) and brine, dried (MgSO4), filtered and concentrated. The residue was purified by chromatography (1:6 EtOAc, hexane) providing the coupled product L as an orange solid (5.3 g, 66percent). 1H NMR (300 MHz, CDCl3): delta 8.43 (d, J = 2.2 Hz, IH), 7.75 (d, J= 2.2 Hz, IH), 7.55 (d, J= 8.7 Hz, 2H), 6.87 (d, J= 8.7 Hz, 2H), 3.83 (s, 3H).
With triethylamine;bis-triphenylphosphine-palladium(II) chloride; copper(l) iodide; In tetrahydrofuran; at 0 - 20℃;
Bis(triphenylphosphine)palladium(II) chloride (6.3 mg, 0.009 mmol) was added to a solution of <strong>[233770-01-9]3-bromo-5-iodopyridine</strong> (0.5 g, 1.76 mmol), 4-ethyne-anisole (0.26 g, 1.93 mmol), copper(I) iodide (2 mg, 0.009 mmol) in triethylamine (2.5 mL) and anhydrous tetrahydrofuran (10 mL) at 0 C. The mixture was stirred over night at room temperature and the solvent was evaporated. Ethyl acetate and water was added and the organic phase was collected, washed with brine, dried over sodium sulfate and concentrated. Purification by column chromatography, using 0 - 10 % ethyl acetate in n-heptane as eluent, gave 0.49 g (96% yield) of the title compound: 1H NMR (DMSO-J6) delta 8.70 (m, 2 H), 8.25 - 8.27 (m, 1 H), 7.52 - 7.56 (m, 2 H), 7.00 - 7.04 (m, 2 H), 3.81 (s, 3 H).
In diethylene glycol dimethyl ether; for 36h;Reflux;
(a) 4'-Methoxybiphenyl-4-carboxylic acid (7b).; Method A.Coumalic acid (1.06 g, 7.56 mmol) and 4-ethylnyl anisole were dissolved in diglyme and brought to reflux for 36h. The reaction was then allowed to cool and the solvent was removed under reduced pressure. The resultant slurry was then recrystallized from ethanol to yield 754 mg (44%) of a light tan solid.
With copper(l) iodide; In water; dimethyl sulfoxide; at 20℃;
General procedure: N-(2,4-dimethoxybenzyl)-N-methyl-3-phenylprop-2-yn-1-amine (5a). CuI (20 mg, 0.10 mmol) was added to a solution of phenylacetylene(510.6 mg, 5.0 mmol), HCHO (36% aq., 2 mL),<strong>[102503-23-1]N-methyl(2,4-dimethoxybenzyl)amine</strong> (1.09 g, 6.0 mmol) in DMSO (10.0mL). The resulting yellow green solution was stirred at room temperatureovernight and then diluted with H2O (10 mL), extracted with Et2O (15 mL x 3). The combined extractswas washed with H2O (2 x), brine (2 x) respectively, dried over Na2SO4, filtered, concentrated. Theresultant yellow oil was purified through flash column chromatography (silica gel, EtOAc/Hex = 1:6 to1:3) to give the product (5a, 1.14 g, 96%).
With bis-triphenylphosphine-palladium(II) chloride; copper(l) iodide; triethylamine; In acetonitrile; at 120℃; for 0.5h;Microwave irradiation; Inert atmosphere;
Example 4 [00613] Preparation of Cpd 31 [00614] Step A: A mixture of <strong>[6942-39-8]methyl 2-bromo-5-fluorobenzoate</strong> (699 mg, 3.0 mmol), 1- ethynyl-4-methoxybenzene (475 mg, 3.6 mmol), Cul (28.5 mg, 0.15 mmol), PdCl2(Ph3P)2 (105 mg, 0.15 mmol), Et3N (0.83 mL, 606 mg, 6.0 mmol) and acetonitrile (3.0 mL) was irradiated in a microwave reactor, under argon at 120 C for 0.5 hours. The mixture was then cooled and chromatographed (silica gel, ethyl acetate in hexanes, 0-10%) to give the alkyne intermediate as a brown oil, used directly in the next step. MS m/z 285.1 [M+H]+.
With palladium diacetate; triethylamine; triphenylphosphine; In acetonitrile; at 80℃; for 4h;Inert atmosphere;
General procedure: A mixture of substituted <strong>[95104-21-5]2-chloroquinoline-3-carbonitrile</strong>s 1(a-h) (0.25mmol), phenylacetylene (0.26mmol), Pd(OAc)2 (5mol%)and PPh3 (10mol%) in CH3CN (2mL) and TEA (2equiv) were stirred under N2 at 80C, after completion of reaction (as monitored by TLC), solvent was evaporated and further Pd(OAc)2 (5mol%), PPh3 (10mol%), K2CO3 (1.5equiv) and 4mL of methanol were added under aerobic condition at 80C upto completion. The mixture was concentrated in vacuo and residue was purified by column chromatography on silica gel using EtOAc/hexane as eluent.
3- Cyano-2-(4-methoxyphenylethynyl)pyridine (28b). N,N-Diisopropylamine (10 mL) and tetrahydrofuran (10 mL) were added to <strong>[20577-26-8]2-bromo-3-cyanopyridine</strong> 2790 (400 mg, 2.2 mmol), bis(triphenylphosphine)palladium(ll) dichloride (76 mg, 0.1 1 mmol), copper(l) iodide (40 mg, 0.22 mmol) and sodium ascorbate (25 mg, 0.12 mmol) under argon. The mixture was stirred at 40C for 30 min. 4-Methoxyphenylethyne (290 mg, 2.2 mmol) was added and the mixture was stirred at 40C for 12 h. Evaporation and chromatography (petroleum ether / ethyl acetate 5:1? 1 :3) gave 3-cyano-2-(4- methoxyphenylethynyl)pyridine 28b (400 mg, 81%) as a pale buff powder: mp 1 18- 120C; 1H NMR (CDCI3) delta 3.83 (3 H, s, Me), 6.90 (2 H, d, J = 9.5 Hz, Ph 3,5-H2), 7.30 (1 H, dd, J = 8.0, 4.9 Hz, 5-H), 7.62 (2 H, d, J = 9.5 Hz, Ph 2,6-H2), 7.93 (1 H, dd, J = 6.2, 3.1 Hz, 4-H), 8.75 (1 H, dd, J = 4.9, 1.7 Hz, 6-H); 13C NMR (CDCI3) (HMBC) delta 55.32 (OMe), 85.01 (ethyne 2-C), 96.94 (ethyne 1-C), 1 12.94 (5-C), 1 14.22 (Ph 3,5- C2), 1 16.09 (C?N), 121.45 (3-C), 134.23 (Ph 2,6-C2), 139.74 (4-C), 146.36 (6-C), 152.74 (2-C), 161.05 (Ph 4-C); MS m/z 257.0670 (M + Naf (C15H10N2NaO requires 257.0691 ).
81%
General procedure: Compound 24 (150 mg, 0.80 mmol) in THF (5 mL) was stirredwith CuI (15.2 mg, 80 lmol) and (Ph3P)2PdCl2 (28 mg, 40 lmol)in Pri2NH (5 mL) under Ar at 45 C for 30 min. Phenylethyne 21a(163 mg, 1.6 mmol) was added. The mixture was stirred at 40 Cfor 5 d. Evaporation and chromatography (petroleum ether/EtOAc3:1) gave 25a (80 mg, 50%) as a pale buff powder.
With triethylamine; for 0.5h;Sonication; Green chemistry;
General procedure: A mixture of (4a-c) (1mmol), arylacetylene (1mmol), Pd(PPh3)2Cl2 (2.5mol%), CuI nanoparticles (2.5mol%) in Et3N (5mL) was sonicated at 20KHz frequency and 50W power, for desired times (checked by TLC). After completed the reaction the mixture was filtered and the solvent was evaporated in vacuo. The products were purified by silica gel column chromatography using n-hexane as an eluent in 65-88% yield.
General procedure: 2-Iodophenol (1.14mmol, 250mg) and Pd(Ph3P)2Cl (5mol%, 40mg) were placed in a 20mL microwave vial, and purged with N2. Dry THF (0.8mL) was added and the mixture was stirred until the iodophenol was completely dissolved. Then dry triethylamine (2mL) and a solution of CuI (3mol%, 5.4mg) in triethylamine (1mL) were added and the mixture was stirred for 10min. 4-Ethynylanisole (1.2 equiv., 180.3mg) in THF (0.5mL) was then added under N2, and the mixture was stirred in the microwave reactor for 30minat 40C. The corresponding 3-iodopyridine (1.2 equiv., 279.6mg) in dry CH3CN (3.7mL) was added under N2, and the reaction mixture was heated in the microwave reactor at 100C for 30min. The reaction was monitored with TLC and LC-MS. After cooling, the solvents were evaporated and the product was purified on silica followed by preparative HPLC (25?100% B over 25min).
With bis-triphenylphosphine-palladium(II) chloride; 1,8-diazabicyclo[5.4.0]undec-7-ene; di(1-adamantyl)benzylphosphonium hydrobromide; In dimethyl sulfoxide; at 100℃; for 1h;Schlenk technique; Inert atmosphere;
General procedure: In a flame-dried Schlenk tube under nitrogen atmosphere, 3-bromopyridine-2-amine (1a; 173 mg,1.00 mmol), Pd(PPh3)2Cl2 (17.5 mg, 0.025 mmol), and (1-Ad)2PBn*HBr (22.6 mg, 0.050 mmol) were dissolved in anhyd DMSO (1.50 mL). Phenylacetylene (2a; 122 mg, 1.20 mmol) and DBU (457 mg, 3.00 mmol) were added via syringe and the reaction mixture was stirred in a preheated oil bath at 100 °C until complete conversion of compound 1a (monitored by TLC). Then, KOt-Bu (281 mg, 2.5 mmol) and anhyd DMSO (1.00 mL) were added and the mixture was stirred at 100 °C until completion of the reaction (monitored by TLC). After cooling to r.t., de-ionized H2O (2.00 mL) was added and the aqueous layer was extracted three times with EtOAc. The combined organic phases were first washed twice with de-ionized H2O and then dried with anhyd Na2SO4. The solvents were removed under reduced pressure.The residue was adsorbed onto Celite® and purified by column chromatography on a SNAP 100 g cartridge (EtOAc?n-hexane33percent) using a Biotage SP-1 flash chromatography purification system to give pure compound 4a as a colorless solid.
4-cyano-3-(4-methoxyphenylethynyl)pyridine[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
72%
General procedure: Compound 34 (91.5 mg, 0.5 mmol) was stirred with (PPh3)4Pd(30 mg, 25 lmol), CuI (9.6 mg, 50 lmol) and Na ascorbate (9.9 mg,50 lmol) in THF (5 mL) and Pri2NH (5 mL) at 40 C under Ar for30 min. PhC?CH 21a (102 mg, 1.0 mmol) was added and the mixturewas stirred at 40 C under Ar for 16 h. Cooling, evaporationand chromatography (petroleum ether/EtOAc 4:1?1:3) gave 35a(55 mg, 50%) as a pale buff powder.
With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; copper(l) iodide; triethylamine; In toluene; for 24h;Reflux;
General procedure: 2-(Methylthio)benzoxazoles or 2-(methylthio)benzothiazoles 1 (0.5 mmoles) were dissolved in 3 mL toluene. To the resulted solution were added the corresponding alkyne 2 (3 eq.), triethylamine (3 eq.), CuI (20 mol%) and Pd(dppf)Cl2 (10 mol%) and the mixture was stirred to reflux in air for 24 hours.The solvent was removed in vacuo and the residue was column cromatographed using various solvent mixtures to yield pure products 3.
General procedure: A one dram vial equipped with a stir bar was charged with <strong>[54198-88-8]2-(chloromethyl)pyrimidine</strong> (12.mg,0.070 mmol), 4-bromothiophenol (13.06 mg, 0.070 mmol), and cesium carbonate (95.37 mg, 0.290 mmol). The solids were then dissolved in MeCN (0.145 mL) and stirred at 90 C for 20 min before the vial was removed from the heat. At this time 2-ethynylpyridine (9.55 lL, 0.095 mmol) and [1,1?-bis(diphenylphosphino)ferrocene]dichloropalladium (II) (5.34 mg, 0.010 mmol) were added to the reaction mixture followed by a thirty second purge with argon. The reaction vessel was allowed to stir at 90° C for an additional fourhours. After being allowed to cool to room temperature the crude reaction mixture was filtered over a thin celite plug in a phase separator with EtOAc (10 mL) and the resulting organics concentrated before crude product was purified using Gilson reverse phase automated system (30x50 mm column, 15-65percent MeCN in 0.1percent Aq. TFA, 5 min gradient). Fractions containing product by LC/MS were pooled and quenched with sat. sodium bicarbonate before being extracted with DCM (5 mL) and dried to afford 2-[[4-[2-(2-pyridyl)ethynyl]phenyl]sulfanylmethyl]pyrimidine (14c, 12.2 mg, 0.04 mmol, 55percent) as a brown oil.
2,6-bis(4-methoxyphenylethynyl)dithieno[3,2-b:2',3'-d]thiophene[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
18%
With copper(l) iodide; tetrakis(triphenylphosphine) palladium(0); triethylamine; triphenylphosphine; In N,N-dimethyl-formamide; at 100℃; for 48h;Inert atmosphere;
General procedure: 2,6-Dibromodithieno[3,2-b:2',3'-d]thiophene (1)33 (150 mg, 0.424 mmol), phenylacetylene (0.15 mL, 1.37 mmol), Pd(PPh3)4 (30 mg, 0.043 mmol), PPh3 (22.3 mg, 0.086 mmol), Et3N (7.5 mL), CuI (20 mg, 0.106 mmol) and DMF (7.5 mL) were mixed together and heated at 100 C for 78 h in a Schlenk tube equipped with a magnetic stirring bar and a reflux condenser under N2 atmosphere. The reaction was quenched with a saturated solution of ammonium chloride (30 mL) and extracted with CHCl3 (100 mL) three times. Then, the combined organic phase was washed with brine, anddried over MgSO4. Evaporation of the solvent under vacuum resulted in a solid residue. The residue was adsorbed in silica gel (Wako gel, C-300) and purified by column chromatography using hexane as eluent and recrystallization from hexane afforded the desired compound 2a as yellow prisms (40 mg, 24%)
3-(2,4-bis(trifluoromethyl)phenyl)-1-(4-methoxyphenyl)benzo[f][1,7]naphthyridine[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
26%
General procedure: In an ace pressure tube equipped with a magnetic stirring bar, 1.0 equiv of 3-aminoquinoline, 0.4 equiv. of substituted aromatic or heteroaromatic aldehydes, 20 mol percent of Yb(OTf)3, 20 mol percent of CuI, 0.5 equiv. of 4A° molecular sieves and 5-10 mL of acetonitrile was added. Reaction mixture was stirred at reflux temperature. After completion of the imine formation as indicated by the TLC, to the above reaction mixture 0.8 equiv. of 1-ethynyl-4-methoxybenzene (5) added and stirred at reflux temperature. After completion of the reaction as indicated by SiO2 TLC, dichloromethane (DCM, 10 mL) was added to the crude reaction mass and then filtered through Celite® pad and the combined organic layer was washed with brine (10 mL) and extracted with DCM (2x10 mL) dried over MgSO4. After removing of solvent under vacuum, the crude product was purified by column chromatography eluting with ethyl acetate/hexane afforded the corresponding products (6a-n).
2-fluoro-4-(6-methoxy-2-(4-methoxyphenyl)benzofuran-3-yl)pyridine[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
General procedure: To a solution of the 2-Iodo-5-methoxyphenol (1mmol, 252mg) and the 4-Ethynylanisole (1.2 equiv., 166mg) in dry THF (1.6mL, 0.6M of the Iodophenol), at 0C under N2, was added CH3MgBr (THF solution, 2.3M, 2 equiv., 0.792mL) dropwise. The mixture was allowed to warm to room temperature, and Pd(Ph3P)2Cl (3mol%, 21.3mg) was added before the mixture was heated to 65C for 2h under N2. The reaction mixture was then cooled to room temperature and the THF was removed under reduced pressure. DMSO (2mL) was added to the residue followed by addition of 2-Fluoro-4-iodopyridine (1.2 equiv., 269.7mg) and the mixture was heated to 80C for 4h under N2. The mixture was cooled to room temperature and diluted with EtOAc, washed with H2O and brine. The organic phase was dried over Na2SO4, concentrated and purified on silica followed by preparative HPLC (25?100% B over 25min).
2-fluoro-4-(5-fluoro-2-(4-methoxyphenyl)benzofuran-3-yl)pyridine[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
58%
General procedure: To a solution of the 2-Iodo-5-methoxyphenol (1mmol, 252mg) and the 4-Ethynylanisole (1.2 equiv., 166mg) in dry THF (1.6mL, 0.6M of the Iodophenol), at 0C under N2, was added CH3MgBr (THF solution, 2.3M, 2 equiv., 0.792mL) dropwise. The mixture was allowed to warm to room temperature, and Pd(Ph3P)2Cl (3mol%, 21.3mg) was added before the mixture was heated to 65C for 2h under N2. The reaction mixture was then cooled to room temperature and the THF was removed under reduced pressure. DMSO (2mL) was added to the residue followed by addition of 2-Fluoro-4-iodopyridine (1.2 equiv., 269.7mg) and the mixture was heated to 80C for 4h under N2. The mixture was cooled to room temperature and diluted with EtOAc, washed with H2O and brine. The organic phase was dried over Na2SO4, concentrated and purified on silica followed by preparative HPLC (25?100% B over 25min).
General procedure: To a solution of the 2-Iodo-5-methoxyphenol (1mmol, 252mg) and the 4-Ethynylanisole (1.2 equiv., 166mg) in dry THF (1.6mL, 0.6M of the Iodophenol), at 0C under N2, was added CH3MgBr (THF solution, 2.3M, 2 equiv., 0.792mL) dropwise. The mixture was allowed to warm to room temperature, and Pd(Ph3P)2Cl (3mol%, 21.3mg) was added before the mixture was heated to 65C for 2h under N2. The reaction mixture was then cooled to room temperature and the THF was removed under reduced pressure. DMSO (2mL) was added to the residue followed by addition of 2-Fluoro-4-iodopyridine (1.2 equiv., 269.7mg) and the mixture was heated to 80C for 4h under N2. The mixture was cooled to room temperature and diluted with EtOAc, washed with H2O and brine. The organic phase was dried over Na2SO4, concentrated and purified on silica followed by preparative HPLC (25?100% B over 25min).
General procedure: To a solution of the 2-Iodo-5-methoxyphenol (1mmol, 252mg) and the 4-Ethynylanisole (1.2 equiv., 166mg) in dry THF (1.6mL, 0.6M of the Iodophenol), at 0C under N2, was added CH3MgBr (THF solution, 2.3M, 2 equiv., 0.792mL) dropwise. The mixture was allowed to warm to room temperature, and Pd(Ph3P)2Cl (3mol%, 21.3mg) was added before the mixture was heated to 65C for 2h under N2. The reaction mixture was then cooled to room temperature and the THF was removed under reduced pressure. DMSO (2mL) was added to the residue followed by addition of 2-Fluoro-4-iodopyridine (1.2 equiv., 269.7mg) and the mixture was heated to 80C for 4h under N2. The mixture was cooled to room temperature and diluted with EtOAc, washed with H2O and brine. The organic phase was dried over Na2SO4, concentrated and purified on silica followed by preparative HPLC (25?100% B over 25min).
3-(4-fluorophenyl)-6-methoxy-2-(4-methoxyphenyl)benzofuran[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
67%
General procedure: To a solution of the 2-Iodo-5-methoxyphenol (1mmol, 252mg) and the 4-Ethynylanisole (1.2 equiv., 166mg) in dry THF (1.6mL, 0.6M of the Iodophenol), at 0C under N2, was added CH3MgBr (THF solution, 2.3M, 2 equiv., 0.792mL) dropwise. The mixture was allowed to warm to room temperature, and Pd(Ph3P)2Cl (3mol%, 21.3mg) was added before the mixture was heated to 65C for 2h under N2. The reaction mixture was then cooled to room temperature and the THF was removed under reduced pressure. DMSO (2mL) was added to the residue followed by addition of 2-Fluoro-4-iodopyridine (1.2 equiv., 269.7mg) and the mixture was heated to 80C for 4h under N2. The mixture was cooled to room temperature and diluted with EtOAc, washed with H2O and brine. The organic phase was dried over Na2SO4, concentrated and purified on silica followed by preparative HPLC (25?100% B over 25min).
3-(3,4-difluorophenyl)-2-(4-methoxyphenyl)benzofuran[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
60%
General procedure: 2-Iodophenol (1.14mmol, 250mg) and Pd(Ph3P)2Cl (5mol%, 40mg) were placed in a 20mL microwave vial, and purged with N2. Dry THF (0.8mL) was added and the mixture was stirred until the iodophenol was completely dissolved. Then dry triethylamine (2mL) and a solution of CuI (3mol%, 5.4mg) in triethylamine (1mL) were added and the mixture was stirred for 10min. 4-Ethynylanisole (1.2 equiv., 180.3mg) in THF (0.5mL) was then added under N2, and the mixture was stirred in the microwave reactor for 30minat 40C. The corresponding 3-iodopyridine (1.2 equiv., 279.6mg) in dry CH3CN (3.7mL) was added under N2, and the reaction mixture was heated in the microwave reactor at 100C for 30min. The reaction was monitored with TLC and LC-MS. After cooling, the solvents were evaporated and the product was purified on silica followed by preparative HPLC (25?100% B over 25min).
6-methoxy-2-(4-methoxyphenyl)-3-(4-(trifluoromethyl)phenyl)benzofuran[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
73%
General procedure: To a solution of the 2-Iodo-5-methoxyphenol (1mmol, 252mg) and the 4-Ethynylanisole (1.2 equiv., 166mg) in dry THF (1.6mL, 0.6M of the Iodophenol), at 0C under N2, was added CH3MgBr (THF solution, 2.3M, 2 equiv., 0.792mL) dropwise. The mixture was allowed to warm to room temperature, and Pd(Ph3P)2Cl (3mol%, 21.3mg) was added before the mixture was heated to 65C for 2h under N2. The reaction mixture was then cooled to room temperature and the THF was removed under reduced pressure. DMSO (2mL) was added to the residue followed by addition of 2-Fluoro-4-iodopyridine (1.2 equiv., 269.7mg) and the mixture was heated to 80C for 4h under N2. The mixture was cooled to room temperature and diluted with EtOAc, washed with H2O and brine. The organic phase was dried over Na2SO4, concentrated and purified on silica followed by preparative HPLC (25?100% B over 25min).
3-(3,4-difluorophenyl)-6-methoxy-2-(4-methoxyphenyl)benzofuran[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
45%
General procedure: To a solution of the 2-Iodo-5-methoxyphenol (1mmol, 252mg) and the 4-Ethynylanisole (1.2 equiv., 166mg) in dry THF (1.6mL, 0.6M of the Iodophenol), at 0C under N2, was added CH3MgBr (THF solution, 2.3M, 2 equiv., 0.792mL) dropwise. The mixture was allowed to warm to room temperature, and Pd(Ph3P)2Cl (3mol%, 21.3mg) was added before the mixture was heated to 65C for 2h under N2. The reaction mixture was then cooled to room temperature and the THF was removed under reduced pressure. DMSO (2mL) was added to the residue followed by addition of 2-Fluoro-4-iodopyridine (1.2 equiv., 269.7mg) and the mixture was heated to 80C for 4h under N2. The mixture was cooled to room temperature and diluted with EtOAc, washed with H2O and brine. The organic phase was dried over Na2SO4, concentrated and purified on silica followed by preparative HPLC (25?100% B over 25min).
With piperazine; 1,1'-bis-(diphenylphosphino)ferrocene; palladium diacetate; In tetrahydrofuran; at 50℃; under 2585.81 Torr; for 24h;
General procedure: 1a-1e (0.5mmol) and alkynyl reagent 2a-2o (0.60mmol), Pd(OAc)2 (0.025mmol, 0.0056g) and dppf (0.025mmol, 0.0138g), piperazine (1mmol, 0.0861g) in THF (2mL) was added to a 20mL silica tubes. The autoclave was closed, flushed three times with CO, pressurized with 50psi of CO, and heated at 50C for 24h. After the completion of the reaction, the reactor was cooled down to room temperature, the crude products were extracted with ethyl acetate and water, and the organic layer were purified by column chromatography on silica gel using dichloromethane or ethyl acetate/petroleum ether as eluent. All products 3aa-3ea were identified by comparing their spectral data with those of authentic samples.
With bis-triphenylphosphine-palladium(II) chloride; copper(l) iodide; ethylenediamine; at 180℃; for 1.5h;Microwave irradiation; Inert atmosphere;
General procedure: Microwave Heating:To a flame dried 35 mL microwave vial with a teflon coated cap, 25 mL of ethylene diaminewas added via syringe and degassed with nitrogen for 20 minutes. To this vessel was added504 mg (1.5 mmol) of bis(2-bromophenyl)amine (3), 66 mg (0.30 mmol) of copper iodide,and 219 mg (0.30 mmol) of bis(triphenylphosphine)palladium dichloride sequentially whilestirring under nitrogen. Next 3.0 mmol of aryl acetylene was added dropwise via syringe.The reaction flask was heated for 1.5 hours at 180 C in a microwave reactor. Uponcompletion, the reaction was then poured over ice, extracted into dichloromethane (3 x 35mL) and the combined organic layers were washed with water three times before purifyingon an amine treated KP-NH silica flash column using hexanes and ethyl acetate as eluent.Fractions include primarily bis(tolan)amines (4a-f), 9-substituted acridines (5a-f), andcarbazole (6) depending on conditions.
2-(4-methoxyphenyl)benzo[b]furan-6-carboxylic acid[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
75%
With copper(l) iodide; L-proline; sodium hydroxide; In dimethyl sulfoxide; at 80℃; for 12h;Inert atmosphere; Sealed tube;
General procedure: A sealable reaction tube equipped with a magnetic stirrer bar was charged with 2-iodophenols 1 (1 mmol), alkynes 2 (1 mmol), NaOH (2 mmol), CuI (0.1 mmol), proline (0.3 mmol) and DMSO (5 mL), and the reaction vessel placed in an oil bath at 80 C under N2 . After stirring the mixture at this temperature for 12 h, it was cooled to room temperature and diluted with ethyl acetate, washed with water and brine, dried over by MgSO4. After the solvent was removed under reduced pressure, the residue was purified by column chromatography on silica gel to afford the corresponding product.
5-chloro-1-[1-(4-methoxyphenyl)vinyl]-2-phenyl-1H-indole[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
71%
With silver trifluoromethanesulfonate; In neat (no solvent); at 20℃; for 4h;Inert atmosphere; Green chemistry;
General procedure: Fe3O4SiO2-bipy-AuCl3 (16 mg, 0.01 mmol) and AgOTf (8 mg,0.03 mmol) were added to a mixture of 2-(phenylethynyl)aniline(0.2 mmol) and phenylacetylene (0.4 mmol) under Ar at roomtemperature. The reaction mixture was stirred at room temperature.During this procedure the reaction mixture became a deep blackliquid very quickly. After 4 h the resulting mixture was diluted withethyl acetate and the supported catalyst was magnetically separated.The reaction solution was evaporated and the residue was purifiedby column chromatography on silica gel (eluting with hexane/ethylacetate = 25:1) to give the desired product 3a. The recovered catalystwas washed with MeOH (2 × 2 mL) and air-dried. When appropriate itcould be used directly for the next run.
With copper(l) iodide; 3-(diphenylphosphino)benzoic acid; palladium diacetate; potassium carbonate; In tetrahydrofuran; water; at 50℃;Green chemistry;
General procedure: In a 10 mL round bottom flask containing 2 mL of (1 : 4) THF-H2O, Pd(OAc)2 (0.02 mmol), 3-(diphenylphosphino)benzoic acid (L 4 ), (0.04 mmol), CuI (0.05 mmol), 2-bromo benzaldehyde (1 mmol), phenylacetylene (1.2 mmol). K2CO3 (2 mmol), were added and the reaction mixture was stirred at 50 °C for 2 h until the completion of the starting materials as monitored by TLC. Then NH4OAc (1.5 mmol) was added and again the whole reaction mixture was stirred at same temperature for additional 2 hours. After the formation of desired product 4a as confirmed by TLC, the reaction mixture was extracted with ethyl acetate (10 mL) and water (10 mL) and the organic layer was washed with aqueous saturated brine solution and dried over Na2SO4. The solvent was removed under vacuum, and the residue was purified by flash column chromatography on silica gel using ethyl acetate/ hexanes as the eluent to afford the desired product 4a.
With sodium azide; sodium L-ascorbate; In ethanol; at 80℃; for 0.25h;Green chemistry;
General procedure: In a 50 mL round bottom flask alkyl/ aryl halide (1.0 mmol), sodium azide (1.2 mmol), alkyne (1.0 mmol), Cu-AcP-Am-Fe3O4(at)SiO2 (40 mg) and sodium ascorbate (29 mg, 0.15 mmol) were mixed and stirred in 5 mL ethanol. The reaction was allowed to proceed for 20 min at 80 C. Reactions were monitored by Thin Layer Chromatography (TLC) using aluminium backed silica gel 60 (F254) plates eluting with 20% ethyl acetate-petroleum ether (Rf = 0.46). After completion of the reaction, the catalyst was separated magnetically using bar magnet. Finally, the resulting solution was extracted with ethyl acetate and dried over anhydrous Na2SO4 the solvent was removed under reduced pressure then the product was purified by column chromatography over silica gel using EtOAc /Petroleum ether as eluent.
With potassium fluoride; sodium azide; silver carbonate; In N,N-dimethyl-formamide; at 50℃; for 6.0h;
General procedure: to a solution of phenylacetylene (1a)(0.055 mL, 0.5 mmol), 2,6-di-tert-butyl-4-methylphenol(BHT) (2a) (133 mg, 0.6 mmol), NaN3 (39 mg, 0.6 mmol)and KF (58 mg, 1.0 mmol) in DMF (1 mL) at 50 C, Ag2CO3(41 mg, 0.15 mmol) was added. The reaction mixture wasthen stirred for 6 h when TLC conformed that substrate 1a was consumed. The resulting reaction mixture was cooled toroom temperature and extracted by dichloromethane(3×15 mL). The organic layer was washed with brine(3×40 mL), dried over MgSO4 and concentrated. Purificationof the crude product via flash column chromatography (silicagel; petroleum ether) and concentratinon in vacuo affordedthe desired product of 3a-N2/3a-N1 in 91% yield.
With copper(l) iodide; tetrakis(triphenylphosphine) palladium(0); triethylamine; In tetrahydrofuran; at 70℃; under 7.50075e-05 Torr; for 10h;Inert atmosphere;
In this embodiment, a white light emitting material is synthesized, and the chemical structure formula of the white light emitting material is as follows:The preparation method includes the following steps:(1) 5.0 mmol of tris (4-iodophenyl) amine, 21.0 mmol of 4-methoxyphenylacetylene, 30.0 mL of tetrahydrofuran,7.0mL of triethylamine was placed in a 100mL double-necked flask equipped with a stir bar and connected to a reflux tube;(2) The above reaction mixture is evacuated with a vacuum pump so that the pressure reaches 1x10-2Pa, and then nitrogen is passed in,Repeat the evacuation and nitrogen flow three times to maintain the nitrogen atmosphere of the reaction system;(3) adding 0.125 mmol of tetra (triphenylphosphine) palladium and 0.8 mmol of cuprous iodide to the above reaction solution under a nitrogen environment;(4) The above reaction mixture was heated to 70 C. under the protection of nitrogen and kept at reflux for 10 hours.The solvent was then evaporated to dryness on a rotary evaporator and washed with a small amount of ethyl acetate to give a yellow powder.Purified by column chromatography (silica gel column model: Yantai Jiangyou F-254 200-300 mesh,The mobile phase is a mixed solvent of methylene chloride and n-hexane, and the volume ratio of methylene chloride to n-hexane is 1:30).A white solid powder was obtained, that is, the white light-emitting material.The obtained white solid powder was characterized by carbon spectrum and proton spectrum.
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