(4-Bromophenyl)methanol(CAS: 873-75-6) is a reactive chemical. It has been demonstrated to inhibit the reaction between ethyl formate and biphenyl by cleaving the molecule and creating a specific new site.
Application In Synthesis of [ 873-75-6 ]
* 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.
Reference：
[1] Angewandte Chemie - International Edition, 2007, vol. 46, # 43, p. 8266 - 8269
4
[ 873-75-6 ]
[ 1670-14-0 ]
[ 23449-08-3 ]
Reference：
[1] Organic and Biomolecular Chemistry, 2015, vol. 13, # 24, p. 6723 - 6727
5
[ 873-75-6 ]
[ 589-17-3 ]
Yield
Reaction Conditions
Operation in experiment
98%
With oxalyl dichloride In dichloromethane at 20℃; Reflux
General procedure: To 16 (0.6 g, 0.6 mmol) was added dichloromethane (5 mL) in a round-bottom flask. After 10 min, oxalyl chlorideor oxalyl bromide was added (0.6 mmol). The reaction mixture was magnetically stirred at room temperature. Uponcessation of gas evolution, 4 was added (0.5 mmol), and the reaction mixture was heated to reflux. After thereaction was complete according to TLC analysis, the mixture was cooled to room temperature and filtered. Thesolid on the funnel was washed with dichloromethane (3 × 10 mL), and the filtrate was concentrated under reducedpressure to afford the desired product 5 in an essentially pure state based on 1H and 13C NMR spectroscopicanalyses.
81.6%
With dmap; thionyl chloride In dichloromethane at 20℃; for 0.166667 h; Cooling with ice
[0193] To a solution of (4-bromo-phenyl)-methanol (19.0 g, 0.1015 mol) in dichloromethane (190 mL) was added thionyl chloride (18.89 mL 0.2539 mol) slowly at ice temperature and catalytic DMAP. Resulting reaction mass was stirred at room temperature for 10 minutes. Reaction mass was concentrated, diluted with ethyl acetate (500 mL) and washed with sodium bicarbonate solution (200 mL) , Organic layer was washed with water (2 x 200 mL) , dried over anhydrous sodium sulphate and filtered . Volatiles were concentrated under reduced pressure to obtain the product as pale yellow liquid (17.0 g, 81.6 percent).
80%
With 1,2,3-Benzotriazole; thionyl chloride In dichloromethane for 1.08333 h;
Thionyl chloride (121 J..LL, 1.67 mmol) was added to benzotriazole (239 mg, 2.0 mmol).The resulting solution was dissolved in CHzClz (5 mL). After 5 min, this solution wasadded slowly to the solution of the alcohol 9a in CHzClz (10 mL). The benzotriazole saltstarted to precipitate. After 1h of reaction, the salt was filtered. The organic phase waswashed by water and NaOH solution (0.5 M). The organic phase was dried over MgS04and the solvent was removed under reduced pressure to give the desired chlorinatedcompound as a yellow oil (m = 220 mg, 80 percent). 1H NMR (300 MHz, CDCh): 8 (ppm) 4.91(dd, J = 12.0, 30.8 Hz, 2H), 7.18 (d, J = 8.0 Hz, 2H), 7.49 (d, J = 7.9 Hz, 2H).
Reference：
[1] Beilstein Journal of Organic Chemistry, 2014, vol. 10, p. 1397 - 1405
[2] Organic Letters, 2013, vol. 15, # 1, p. 108 - 111
[3] Organic and Biomolecular Chemistry, 2013, vol. 11, # 24, p. 4016 - 4024
[4] Bulletin of the Korean Chemical Society, 2010, vol. 31, # 11, p. 3434 - 3436
[5] Organic Letters, 2018, vol. 20, # 10, p. 3061 - 3064
[6] Patent: WO2015/95821, 2015, A1, . Location in patent: Paragraph 0193
[7] Patent: WO2017/134188, 2017, A1, . Location in patent: Page/Page column 61
[8] Molecules, 2011, vol. 16, # 7, p. 5665 - 5673
[9] Journal of the Chemical Society, 1935, p. 1815,1818
[10] Journal of the American Chemical Society, 1951, vol. 73, p. 2813,2818
[11] Gazzetta Chimica Italiana, 1888, vol. 18, p. 239
[12] Canadian Journal of Chemistry, 1983, vol. 61, p. 1472 - 1480
[13] Tetrahedron Letters, 2014, vol. 55, # 19, p. 3045 - 3048
[14] Chemical Communications, 2017, vol. 53, # 54, p. 7545 - 7548
With 1H-imidazole; tert.-butylhydroperoxide; tetra-(n-butyl)ammonium iodide In water at 80℃; for 7 h; Green chemistry
General procedure: To a mixture of benzyl alcohol (108 mg, 1.0 mmol) and TBHP(180 mg, 2.0 mmol) in water (3 ml), the catalyst TBAI (73.8 mg,0.2 mmol), imidazole (136 mg, 2.0 mmol), and MeOH (2 ml)were added, and the mixture was stirred at 80 °C for 8 h. Theprogress of the reaction was monitored by TLC. After completionof reaction, the reaction mixture was cooled to room temperature.Then MeOH was distilled out, and the organic productwas extracted with ethyl acetate (3 × 10 ml), repeatedly washedwith distilled water (4 × 5 ml) to remove the unreacted TBHP,dried with anhydrous sodium sulfate, and the solvent was evaporatedunder reduced pressure to afford methyl benzoate (112mg, yield 82percent).
Stage #1: With copper(l) iodide; bis(benzonitrile)palladium(II) dichloride; tri-tert-butyl phosphine; triethylamine In tetrahydrofuran at 70℃; Stage #2: With tetrabutyl ammonium fluoride In tetrahydrofuran at 20℃; for 3 h;
General procedure: 4.1.4.1. General procedure for the coupling of a terminal alkynewith an aryl halide using a palladium-catalyzed cross-coupling (Sonogashira)protocol. To an oven-dried round-bottom flask or screwcap tube equipped with a magnetic stir bar were added the arylhalide, the terminal alkyne, PdCl2(PPh3)2 or PdCl2(PhCN)2 (w2 molpercent per aryl halide), CuI (w4 mol percent per aryl halide), and in the case ofusing PdCl2(PhCN)2, alsow4 mol percent per aryl halide of HP(tert-Bu)3. Asolvent system of TEA and/or THF was added depending on thesubstrates. Upon completion, the reaction was quenched witha saturated solution of NH4Cl. The organic layer was then dilutedwith diethyl ether or CH2Cl2, and washed with water or saturatedNH4Cl (1). The combined aqueous layers were extracted withhexanes, diethyl ether, or CH2Cl2 (2). The combined organic layerswere dried over MgSO4 and filtered, and the solvent was removedfrom the filtrate in vacuo to afford the crude product, which waspurified by column chromatography (silica gel). Eluents and otherslight modifications are described below for each compound.4.1.4.2. General procedure for deprotection of TIPS-protected alkynesusing TBAF. In a round-bottomed flask equipped witha magnetic stir bar, the protected alkyne was dissolved in THF([protected alkyne]0.05e0.1 M). TBAF in THF (1.0 M, 1.1 equiv peralkyne) was added. The mixture was stirred at rt for 0.5 h or untilthe reaction was complete (monitored by TLC). The reaction wasquenched with a saturated solution of NH4Cl. The organic layer wasthen diluted with ethyl acetate. The organic layer was dried overMgSO4 and filtered, and the solvent was removed from the filtratein vacuo to afford the crude product, which was purified by columnchromatography (silica gel).
Reference：
[1] Angewandte Chemie - International Edition, 2004, vol. 43, # 29, p. 3814 - 3818
[2] Chemistry - A European Journal, 2013, vol. 19, # 29, p. 9452 - 9456
[3] Patent: US2013/266644, 2013, A1,
[4] Synthesis (Germany), 2014, vol. 46, # 3, p. 348 - 356
[5] Patent: CN105622638, 2016, A,
[6] Patent: US9758545, 2017, B2,
[7] Patent: WO2018/14802, 2018, A1,
15
[ 79-24-3 ]
[ 873-75-6 ]
[ 131981-75-4 ]
Reference：
[1] Advanced Synthesis and Catalysis, 2008, vol. 350, # 13, p. 1975 - 1978
16
[ 873-75-6 ]
[ 122-52-1 ]
[ 38186-51-5 ]
Yield
Reaction Conditions
Operation in experiment
90%
at 120℃; for 24 h; Inert atmosphere
To a 20 mL tubular reactor was added 4-bromobenzyl alcohol (93.0 mg, 0.50 mmol)(3.8 mg, 0.01 mmol, 2 molpercent), protected by vacuum nitrogen and then heated to 120 ° C under solvent-free conditions 24h After the TLC monitoring reaction was complete, the product was purified by column chromatography and the yield was 90percent.
Reference：
[1] Patent: CN106543221, 2017, A, . Location in patent: Paragraph 0030; 0031; 0032; 0033
[2] Green Chemistry, 2018, vol. 20, # 15, p. 3408 - 3413
Reference：
[1] Tetrahedron Asymmetry, 2003, vol. 14, # 22, p. 3435 - 3446
[2] European Journal of Organic Chemistry, 2000, # 23, p. 3825 - 3834
20
[ 873-75-6 ]
[ 108-98-5 ]
[ 6317-56-2 ]
Reference：
[1] Journal of Organic Chemistry, 2009, vol. 74, # 4, p. 1664 - 1672
21
[ 873-75-6 ]
[ 107834-03-7 ]
Reference：
[1] Journal of Medicinal Chemistry, 1998, vol. 41, # 13, p. 2390 - 2410
22
[ 873-75-6 ]
[ 63697-96-1 ]
Reference：
[1] Chemistry - A European Journal, 2013, vol. 19, # 29, p. 9452 - 9456
23
[ 288-32-4 ]
[ 873-75-6 ]
[ 86718-08-3 ]
Reference：
[1] Advanced Synthesis and Catalysis, 2017, vol. 359, # 10, p. 1631 - 1636
[2] Synthesis, 2010, # 9, p. 1505 - 1511
[3] Green Chemistry, 2012, vol. 14, # 5, p. 1268 - 1271
24
[ 873-75-6 ]
[ 1066-54-2 ]
[ 275386-60-2 ]
Yield
Reaction Conditions
Operation in experiment
66%
With bis-triphenylphosphine-palladium(II) chloride; copper(l) iodide; tri-tert-butyl phosphine In triethylamine at 130℃; for 4 h; Inert atmosphere; Microwave irradiation
To a solution of (4-bromophenyl) methanol (935mg, 5mmol) in dry TEA was added Pd (PPh3) 2Cl2 (175mg, 0.25mmol) , CuI (48mg, 0.25mmol) and P (t-Bu) 3 (51mg, 0.25mmol) under N2 atmosphere. The reaction mixture was stirred for 5mins, followed by addition of ethynyltrimethylsilane (980mg, 10mmol) dropwise. The reaction mixture was then microwaved at 130 for 4hrs. The reaction mixture was cooled to room temperature, filtered over celite. Solvents were removed from the filtrate in vacuo, then the residue was extracted by EtOAc/H2O 3 times. The organic layer was combined, washed with brine, dried over Na2SO4 and further pufrified by silica gel column chromatography (PE/EA4/1) to give 670mg of (4- ( (trimethylsilyl) ethynyl) phenyl) methanol as a brown oil (66) .[0633]To a solution of (4- ( (trimethylsilyl) ethynyl) phenyl) methanol (250mg, 1.23mmol) in THF was added TBAF (500mg, 2.45mmol) in portions at 0. The reaction mixture was stirred at 0 to room temperature for 3hrs. Solvents were removed from the mixture in vacuo, and the residue was extracted by EtOAc/H2O 3 times. The organic layer was combined, washed with brine, dried over Na2SO4 and further pufrified by silica gel column chromatography (PE/EA4/1) to give 170mg of (4-ethynylphenyl) methanol as a brown oil (100) . 1H NMR (400Hz, CDCl3) δ7.45-7.49 (m, 2H) , 7.21-7.26 (m, 2H) , 4.69 (s, 1H) , 4.65 (s, 2H) .
1.274 g
With bis-triphenylphosphine-palladium(II) chloride; copper(l) iodide; diethylamine; triphenylphosphine In N,N-dimethyl-formamideMicrowave irradiation; Heating; Inert atmosphere
A solution of 4-Bromobenzyl alcohol (1.276 g, 6.82 mmol), Ethynyltrimethylsilane (1.061 ml, 7.51 mmol), PdCl2(PPh3)2 (24 mg, 0.034 mmol), Copper iodide (52 mg, 0.273 mmol), Triphenylphosphine (358 mg, 1.365 mmol), Diethylamine (10.70 ml, 102 mmol) in 2 ml of dry DMF (dimethylformamide) was heated under argon in a microwave oven at 150° C. for 30 min. The mixture was filtered. The filtrate was acidified with 1 M HCl and extracted 3 times with ether. The combined organic layers were washed with bicarbonate and water, dried over MgSO4 and concentrated to afford 3 (1.274 g, 6.23 mmol, 91percent yield) as a brown solid.
Reference：
[1] Chemistry - A European Journal, 2017, vol. 23, # 50, p. 12190 - 12197
[2] Synthesis (Germany), 2014, vol. 46, # 3, p. 348 - 356
[3] Angewandte Chemie - International Edition, 2004, vol. 43, # 29, p. 3814 - 3818
[4] Patent: WO2018/14802, 2018, A1, . Location in patent: Paragraph 0364
[5] Chemistry - A European Journal, 2013, vol. 19, # 29, p. 9452 - 9456
[6] Chemistry - An Asian Journal, 2011, vol. 6, # 10, p. 2816 - 2824
[7] Patent: CN105622638, 2016, A, . Location in patent: Paragraph 0328
[8] Patent: US9758545, 2017, B2, . Location in patent: Page/Page column 19; 20; 26
With palladium diacetate; sodium carbonate In water; N,N-dimethyl-formamide at 70℃;
To a solution of (4-bromophenyl)methanol (500 mg, 2.94 mmol) and [4-(methoxycarbonyl) phenyl]boronic acid (550 mg, 3.53 mmol) in DMF (20 mL) was added Pd(OAc)2 (200 mg, 735 μmol) and Na2CO3 (3 g in 20 mL H2O). The reaction mixture was allowed to stir at 70 °C. After 48 h, an extraction with EtOAc was performed; the organic layers were combined and washed with brine, dried over MgSO4, filtrated and concentrated in vacuo. Column chromatography (EtOAc/Hept 1:4) yielded the product (170 mg, 24percent) as white crystals. RF = 0.3 (EtOAc/Hept 1:1). 1H NMR (400 MHz, CDCl3) δ 8.15-8.06 (m, 2H), 7.70-7.58 (m, 4H), 7.52-7.43 (m, 2H), 4.77 (d, J = 3.1 Hz, 2H), 4.07-3.67 (m, 3H), 1.75 (br s, 1H, OH) ppm. FTIR = 3305, 3032, 1718, 1604, 1432, 1399, 1286, 1271, 1220, 1111, 765 cm-1. HRMS (EI) calcd for C15H14O3 (M)+ 242.0942, found 242.0919.
Reference：
[1] Bioorganic and Medicinal Chemistry, 2014, vol. 22, # 20, p. 5593 - 5603
27
[ 873-75-6 ]
[ 73183-34-3 ]
[ 302348-51-2 ]
Yield
Reaction Conditions
Operation in experiment
90%
With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; potassium acetate In 1,4-dioxane at 85℃; Inert atmosphere
p-Bromobenzyl alcohol (Compound 1, 1.0 g, 5.35 mmol) was dissolved in 10 mL of dry 1,4-dioxane solution, and boranoic acid pinacol ester (247 mg, 5.88 mmol), potassium acetate and pdCl 2 ( Dppf), under N2 protection, heat to 85 ° C to stir the reaction. After the reaction was completed by thin layer chromatography, the solvent was evaporated under reduced pressure, and ethyl acetate (200 ml) was added and thenThe organic phase was dried over anhydrous sodium sulfate and concentrated under reduced vacuo.The crude product was purified by column chromatography (mobile phase ethyl acetate: petroleum ether = 1:8-1:4)Obtained 181 mg of a pale yellow oily liquid with a yield of 90percent.
1500 mg
With dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2; potassium acetate In 1,4-dioxane at 90℃; for 16 h;
A mixture of (4-bromophenyl)methanol (1 g, 5.35 mmol), 4,4,5,5-tetramethyl-2-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1,3,2-dioxaborolane (4.07 g, 16.04 mmol), KOAc (1.05 g, 10.69 mmol) and Pd(dppf)Cl2.CH2Cl2 (873.27 mg, 1.07 mmol) in 1,4-Dioxane (20 mL) was stirred at 90 C for 16 hours. After cooling to r.t., the mixture was concentrated to give the crude product. The crude product was purified by flash chromatography on silica gel (EtOAc in PE = 0 to 50percent) to give the product (1500 mg) as oil. H NMR (400MHz DMSO-d6) __ = 7.63 (d, 2H), 7.32 (d, 2H), 5.23 (t, 1H), 4.51 (d, 2H), 1.29 (s, 12H).
Reference：
[1] Patent: CN108148098, 2018, A, . Location in patent: Paragraph 0058; 0059; 0060
[2] Journal of the American Chemical Society, 2018, vol. 140, # 19, p. 6109 - 6121
[3] Patent: US2012/184520, 2012, A1, . Location in patent: Page/Page column 17
[4] Patent: CN107445885, 2017, A, . Location in patent: Paragraph 0177; 0180
[5] Patent: WO2018/98499, 2018, A1, . Location in patent: Page/Page column 215
28
[ 873-75-6 ]
[ 481054-89-1 ]
Reference：
[1] Organic and Biomolecular Chemistry, 2013, vol. 11, # 9, p. 1463 - 1467
[2] Organic and Biomolecular Chemistry, 2013, vol. 11, # 9, p. 1463 - 1467
In the inert gas N2 atmosphere, after dehydration and deoxidation treatment to the reaction bottle after adding 4 - bromobenzoic acid (100 mg, 0.5 mmol), for adding liquid-[...] borane (289 mul, 2 mmol), reacting at room temperature 12 hours, the reaction out of the glove box, in order to have three methoxybenzene (83.67 mg, 0.5 mmol) as the internal standard, CDCl3 for dissolving, stirring 10 minutes, sampling, with nuclear magnetic resonance. Calculated 1 H and the yield is 95%. The product of nuclear magnetic data: The residue is added to the sample in 1 g silica gel, in order to 3 ml methanol as a solvent, 50 C lower reaction 3 h, the borate further hydrolysis alcohol, after the reaction, extracted with ethyl acetate three times, the combined organic layer, dried with anhydrous sodium sulfate, the solvent is removed under reduced pressure, through the silica gel (100 - 200 mesh) column chromatography purification, ethyl acetate/hexane (1:5) mixture as the eluent, to obtain the pure primary alcohol, separation and the yield is 93%.
4-(hydroxymethyl)phenyl-terminated poly(9,9-di-n-hexylfluorene-2,7-diyl), Mn 2900 Da, Mw/Mn 1.6; monomer(s): 2,7-dibromo-9,9-di-n-hexylfluorene; 4-bromobenzyl alcohol[ No CAS ]
With bis-triphenylphosphine-palladium(II) chloride; copper(l) iodide; tri-tert-butyl phosphine; In triethylamine; at 130℃; for 4h;Inert atmosphere; Microwave irradiation;
To a solution of (4-bromophenyl) methanol (935mg, 5mmol) in dry TEA was added Pd (PPh3) 2Cl2 (175mg, 0.25mmol) , CuI (48mg, 0.25mmol) and P (t-Bu) 3 (51mg, 0.25mmol) under N2 atmosphere. The reaction mixture was stirred for 5mins, followed by addition of ethynyltrimethylsilane (980mg, 10mmol) dropwise. The reaction mixture was then microwaved at 130 for 4hrs. The reaction mixture was cooled to room temperature, filtered over celite. Solvents were removed from the filtrate in vacuo, then the residue was extracted by EtOAc/H2O 3 times. The organic layer was combined, washed with brine, dried over Na2SO4 and further pufrified by silica gel column chromatography (PE/EA4/1) to give 670mg of (4- ( (trimethylsilyl) ethynyl) phenyl) methanol as a brown oil (66) .[0633]To a solution of (4- ( (trimethylsilyl) ethynyl) phenyl) methanol (250mg, 1.23mmol) in THF was added TBAF (500mg, 2.45mmol) in portions at 0. The reaction mixture was stirred at 0 to room temperature for 3hrs. Solvents were removed from the mixture in vacuo, and the residue was extracted by EtOAc/H2O 3 times. The organic layer was combined, washed with brine, dried over Na2SO4 and further pufrified by silica gel column chromatography (PE/EA4/1) to give 170mg of (4-ethynylphenyl) methanol as a brown oil (100) . 1H NMR (400Hz, CDCl3) delta7.45-7.49 (m, 2H) , 7.21-7.26 (m, 2H) , 4.69 (s, 1H) , 4.65 (s, 2H) .
With bis-triphenylphosphine-palladium(II) chloride; copper(l) iodide; In tetrahydrofuran; at 50℃; for 16h;Inert atmosphere;
4-bromobenzyl alcohol (3 g, 16 mmol, 1 eq.), cuprous iodide (0.3 g, 1.6 mmol, 0.1 eq) and bis(triphenylphosphine) palladium dichloride (0.57 g, 0.8 mmol, 0.05 eq.) was dissolved in tetrahydrofuran (50 ml) solution under nitrogen atmosphere. Added trimethylsilylacetylene (7.8 g, 80 mmol, 5 eq). Mixed system after the reaction at 50 C for 16 hours, and spin dry solvent under reduced pressure, the residue was purified by chromatography on silica gel column to give brown solid 4-trimethylsilylethynylbenzyl alcohol (1.5 g, crude).
1.274 g
With bis-triphenylphosphine-palladium(II) chloride; copper(l) iodide; diethylamine; triphenylphosphine; In N,N-dimethyl-formamide;Microwave irradiation; Heating; Inert atmosphere;
A solution of 4-Bromobenzyl alcohol (1.276 g, 6.82 mmol), Ethynyltrimethylsilane (1.061 ml, 7.51 mmol), PdCl2(PPh3)2 (24 mg, 0.034 mmol), Copper iodide (52 mg, 0.273 mmol), Triphenylphosphine (358 mg, 1.365 mmol), Diethylamine (10.70 ml, 102 mmol) in 2 ml of dry DMF (dimethylformamide) was heated under argon in a microwave oven at 150 C. for 30 min. The mixture was filtered. The filtrate was acidified with 1 M HCl and extracted 3 times with ether. The combined organic layers were washed with bicarbonate and water, dried over MgSO4 and concentrated to afford 3 (1.274 g, 6.23 mmol, 91% yield) as a brown solid.
With trifluorormethanesulfonic acid; trifluoroacetic acid; for 4h;
A solution of 4-bromobenzyl alcohol (1.87 g, 10 mmol) in CF3CO2 H (19 mL) and CF3S03 H (1 ML) was treated with PENCILAMINE (1.49 g, 10 mmol). The reaction mixture was stirred for another 4 h then concentrated. The resulting residue was dissolved in 2 M NAOH (20 mL), cooled to 0 C and treated with a second solution of di-tert-butyl dicarbonate in 1,4-dioxane (10 mL) in a dropwise manner. After stirring for 16 h 3 N HC1 was added until the solution became pH 2 and the resulting solution was extracted with ethyl acetate (3 x 50 mL). The combined organic layers were washed with sat. aq NaCl, dried over MGSO4 and concentrated. The remaining residue was dissolved in DMF (15 mL) and treated with K2CO3 (2 g, 14. 4 mmol) and MeI (1 mL, 16 mmol). After the addition was complete, the reaction mixture was stirred for 16 h and filtered to remove solid, which was washed by ethyl acetate (200 mL). The filtrate was washed with sat. aq NaCl, dried over MGSO4 and concentrated. Purification by flash column chromatography (10% ethyl acetate in heptane) provided the desired product (2.5 g, 58%, 3 steps) as an OIL. 1H NMR (CDC13), 8 7.43 (d, J = 8 Hz, 2 H), 7.18 (d, J = 8 Hz, 2 H), 5.36 (D, J = 7 Hz, 1 H), 4.35 (DD, J = 9,30 Hz, 1 H), 3.75 (m, 5 H), 1.36 (s, 9 H).
EXAMPLE 43 Synthesis of 4-(2-methyloctanoyl)benzoic acid Into a flask were charged 6.15 g (32.9 mmol) of 4-bromobenzyl alcohol, 50 ml of dried dichloromethane, 4 ml (41.8 mmol) of ethyl vinyl ether and 0.20 g (0.8 mmol) of pyridinium-p-toluene sulfonate, which was reacted at room temperature for 20 hours with stirring. This reaction product was washed with water, dried on anhydrous magnesium sulfate, and the solvent was distilled off to obtain 8.51 g of an oily 4-bromobenzyl-(1-ethoxy) ethyl ether.
Manufacturing Example 44-1-1 2-(4-Bromo-benzyloxy)-5-methyl-pyridine; To an N,N-dimethylformamide (50.0 mL) solution of 4-bromobenzyl alcohol (4.54 g, 24.3 mmol) was added sodium hydride (1.00 g, 25.0 mmol, 60% in oil) under nitrogen atmosphere at 0 C., which was stirred for 30 minutes at room temperature. <strong>[2369-19-9]<strong>[2369-19-9]2-Fluoro-5-methylpyridin</strong>e</strong> (1.80 g, 16.2 mmol) was then added at 0 C., and stirred for 5 hours at room temperature. Water was added to the reaction solution at room temperature, which was then extracted with ethyl acetate. The organic layer was separated and washed with saturated aqueous sodium chloride, and the solvent was evaporated under a reduced pressure. The residue was purified by silica gel column chromatography (ethyl acetate:heptane=1:15) to obtain the title compound (2.67 g, 59.3%).1H-NMR Spectrum (CDCl3) delta (ppm): 2.24 (3H, s), 5.30 (2H, s), 6.70-6.72 (1H, m), 7.31-7.33(2H, m), 7.38-7.41 (1H, m), 7.46-7.49 (2H, m), 7.95-7.96 (1H, m).
59.3%
To an N,N-dimethylformamide (50.0 mL) solution of 4-bromobenzyl alcohol (4.54 g, 24.3 mmol) was added sodium hydride (1.00 g, 25.0 mmol, 60% in oil) under nitrogen atmosphere at 0 C., which was stirred for 30 minutes at room temperature. <strong>[2369-19-9]<strong>[2369-19-9]2-Fluoro-5-methylpyridin</strong>e</strong> (1.80 g, 16.2 mmol) was then added at 0 C., and stirred for 5 hours at room temperature. Water was added to the reaction solution at room temperature, which was then extracted with ethyl acetate. The organic layer was separated and washed with saturated aqueous sodium chloride, and the solvent was evaporated under a reduced pressure. The residue was purified by silica gel column chromatography (ethyl acetate:heptane=1:15) to obtain the title compound (2.67 g, 59.3%). 1H-NMR Spectrum (CDCl3) delta (ppm): 2.24 (3H, s), 5.30 (2H, s), 6.70-6.72 (1H, m), 7.31-7.33 (2H, m), 7.38-7.41 (1H, m), 7.46-7.49 (2H, m), 7.95-7.96 (1H, m).
Stage #1: 4-bromobenzenemethanol With sodium hydride In N,N-dimethyl-formamide at 0 - 20℃; for 0.833333h;
Stage #2: 2-fluoro-4-methylpyridine In N,N-dimethyl-formamide at 0 - 20℃; for 2.5h;
43.1.1
Manufacturing Example 43-1-1 2-(4-Bromo-benzyloxy)-4-methyl-pyridine; To a mixture of 4-bromobenzyl alcohol (4.54 g, 24.3 mmol) and N,N-dimethylformamide (50.0 mL) were added sodium hydride (1.00 g, 25.0 mmol, 60% in oil) was added at 0° C. under nitrogen atmosphere, which was stirred for 50 minutes at room temperature. 2-Fluoro-4-methylpyridine (1.80 g, 16.2 mmol) was then added thereto at 0° C., and stirred for 2 hours and 30 minutes at room temperature. Water was added to the reaction solution at room temperature, which was then extracted with ethyl acetate. The organic layer was separated, washed with saturated aqueous sodium chloride, and filtered. The filtrate was evaporated under a reduced pressure, and the residue was purified by silica gel column chromatography (ethyl acetate:heptane=1:15) to obtain the title compound (2.65 g, 58.8%).1H-NMR Spectrum (CDCl3) δ (ppm): 2.28 (3H, s), 5.31 (2H, s), 6.60-6.61 (1H, m), 6.69 -6.71(1H, m), 7.29-7.32 (2H, m), 7.46-7.48 (2H, m), 8.00-8.01 (1H, m).
58.8%
Stage #1: 4-bromobenzenemethanol With sodium hydride In N,N-dimethyl-formamide at 0 - 20℃; for 0.833333h;
Stage #2: 2-fluoro-4-methylpyridine In N,N-dimethyl-formamide at 0 - 20℃; for 2.5h;
43.1.1
To a mixture of 4-bromobenzyl alcohol (4.54 g, 24.3 mmol) and N,N-dimethylformamide (50.0 mL) were added sodium hydride (1.00 g, 25.0 mmol, 60% in oil) was added at 0° C. under nitrogen atmosphere, which was stirred for 50 minutes at room temperature. 2-Fluoro-4-methylpyridine (1.80 g, 16.2 mmol) was then added thereto at 0° C., and stirred for 2 hours and 30 minutes at room temperature. Water was added to the reaction solution at room temperature, which was then extracted with ethyl acetate. The organic layer was separated, washed with saturated aqueous sodium chloride, and filtered. The filtrate was evaporated under a reduced pressure, and the residue was purified by silica gel column chromatography (ethyl acetate:heptane=1:15) to obtain the title compound (2.65 g, 58.8%). 1H-NMR Spectrum (CDCl3) δ (ppm): 2.28 (3H, s), 5.31 (2H, s), 6.60-6.61 (1H, m), 6.69-6.71 (1H, m), 7.29-7.32 (2H, m), 7.46-7.48 (2H, m), 8.00-8.01 (1H, m).
Reference Example 6: 1-bromo-4-[(difluoromethoxy)methyl]benzene; To a solution of 4-bromobenzyl alcohol (5.6 g) in acetonitrile (15 ml), sodium sulfate (0.28 g) was added. While warmed to 45C, <strong>[1717-59-5]2,2-difluoro-2-(fluorosulfonyl)acetic acid</strong> (1.78 g) was slowly dropwise added, and the mixture was heated and refluxed at 45C for 4 hours. The reaction solution was poured into water, the mixture was extracted with diethyl ether and the organic layer was washed with water and dried over anhydrous sodium sulfate. The solvent was distilled off in vacuo and the residue obtained was purified with silica gel column chromatography (hexane:ethyl acetate=19:1 to 17:3) to afford the above-identified compound (0.88 g).
With sodium sulfate; In acetonitrile; at 10 - 45℃;
(A) 1-Bromo-4-((difluoromethoxy)methyl)benzene 2,2-Difluoro-2-(fluorosulfonyl)acetic acid (476 mg) was added to a mixture of (4-bromophenyl)methanol (1.00 g), sodium sulfate (76 mg) and acetonitrile (20 mL) at 45 C., and the resulting mixture was stirred at the same temperature for 3 hours and subsequently stirred at room temperature for 2 days. Water was added to the reaction mixture, followed by extraction with ethyl acetate. The organic layer was washed with brine and then dried over anhydrous magnesium sulfate, and the solvent was distilled off under reduced pressure. The residue was purified by silica gel column chromatography (ethyl acetate/hexane) to obtain the title compound as a crude product (195 mg). 1H NMR (300 MHz, CDCl3) delta 4.85 (2H, s), 6.01-6.57 (1H, m), 7.22-7.25 (2H, m), 7.50-7.53 (2H, m).
With sodium sulfate; In acetonitrile; at 20 - 45℃; for 3h;
At 45 C,2,2-difluoro-2- (fluorosulfonyl)Acetic acid(476 mg)Was added to a solution of (4-bromophenyl) methanol (1.00 g)Sodium sulfate (76 mg)And acetonitrile (20 mL)Of the mixture,The resulting mixture was stirred at room temperature for 3 hours and then at room temperature for 2 days.Water was added to the reaction mixture, followed by extraction with ethyl acetate.The organic layer was washed with brine, dried over anhydrous magnesium sulfate and the solvent was removed by distillation under reduced pressure.The residue was purified by silica gel column chromatography (ethyl acetate / hexane) to give the title compound as a crude product (195 mg).
With potassium carbonate; In N,N-dimethyl-formamide; at 80℃; for 2h;
A typical synthetic procedure is as follows. 1,7-dibromo perylene diimide (1, 77 mg, 0.1 mmol) was dissolved into 5 mL of dimethylformamide (DMF). To which alkyl alcohol (R-OH, 0.5 mmol) and potassium carbonate (K2CO3, 70 mg, 0.5 mmol) were added. The resulted mixture was then allowed reacted under 80C for 1-4 hours. The reaction mixture was then powered into 15 mL water and the red solid was then re-dissolved in 20 mL dichloromethane (DCM) and washed with 1N hydrochloric acid and then water each for 3 times. Then, DCM layer was dried over Na2SO4. After removal of DCM, the residue was applied to chromatography with CH2Cl2/ethyl acetate (100:0-100:2) as eluents to afford the desired products 4.
With tert.-butylhydroperoxide; tetra-(n-butyl)ammonium iodide; In 1,1,2-trichloroethane; water; at 90℃; for 12h;
General procedure: To a solution of alcohols 1 (0.1 mmol) in TCE (1.0 mL) was added n-Bu4NI (20 mol%) and N, N-disubstituted formamides 2 (0.5 mmol), followed by adding a solution of TBHP (6.0 equiv., 70% aqueous solution). The resulting mixture was stirred at 90 oC until it completed. When the reaction was finished, the reaction mixture was cooled to room temperature and poured into saturated Na2S2O3 solution (3.0 mL), extracted with EtOAc (3×8.0 mL), then washed with saturated brine. The combined organic layers were dried over anhydrous Na2SO4. After removing the solvents in vacuo, the residue was purified by flash column chromatography on silica gel or preparative TLC on GF 254 to afford the desired products 3.
70%Chromat.
General procedure: Various N,N-dimethyl benzamides were obtained followinga simple procedure which involves charging the reactionmixture containing benzyl alcohols (1mmol), catalyst(20wt%) and DMF (5mL) into a two necked 50mL roundbottom flask (RBF) and stirred for 10min at RT and then70% aqueous TBHP (5mmol) was introduced dropwiseto the mixture under continuous stirring at RT. The RBFwas fitted with a water condenser and heated for 24h at100C. After 24h, the reaction mixture was cooled to RTand catalyst was then separated by filtration. The reactionmixture was diluted with 100mL of DW and extractedusing ethyl acetate (2 × 60mL). The combined organiclayer was dried using Na2SO4and concentrated underrotatory evaporator. The crude products were purified bychromatography using silica gel, hexane and ethyl acetate.Similarly a range of N,N-substituted benzamides werealso obtained by taking the stoichiometric amount of variousN-substituted formamides in 5mL of toluene keepingother parameters constant.
With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; potassium acetate; In water; dimethyl sulfoxide; at 85℃; for 18h;Inert atmosphere;
The compound 1(1 eq, 0.53 mmol) was dissolved in DMSO (2 mL) followed by the addition of potassium acetate (3 eq, 1.59 mmol), bis(pinacolato)diboron (1.1 eq, 0.59 mmol) and Pd(dppf)Cl2 (0.2 eq, 0.11 mmol). The mixture was deoxygenated by three successive argon bubbling/vaccum cycles. The reaction was then heated at 85C under argon for 18h. Water (5 mL) was added and the resulting black solution was extracted 3 times with EtOAc (3 x 10 mL). The combined organic extracts were washed with brine, dried, filtered and evaporated under vaccum. The resulting paste was purified using column chromatography (silica gel, 70/30 Hex/EtOAc) to afford the desired compound (Rf = 0.3) as a colourless oil (113 mg, 91%). 1H-NMR (CDCI3, 600 MHz) delta 7.79 (d, J = 7.7 Hz, 2H), 7.36 (d, J = 7.7 Hz, 2H), 4.71 (s, 2H), 1.35 (s, 12H); 13C-NMR (CDC13, 150 MHz) delta 144.1, 135.2, 126.2, 83.9, 65.4, 25.0.
90%
With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; potassium acetate; In 1,4-dioxane; at 85℃;Inert atmosphere;
p-Bromobenzyl alcohol (Compound 1, 1.0 g, 5.35 mmol) was dissolved in 10 mL of dry 1,4-dioxane solution, and boranoic acid pinacol ester (247 mg, 5.88 mmol), potassium acetate and pdCl 2 ( Dppf), under N2 protection, heat to 85 C to stir the reaction. After the reaction was completed by thin layer chromatography, the solvent was evaporated under reduced pressure, and ethyl acetate (200 ml) was added and thenThe organic phase was dried over anhydrous sodium sulfate and concentrated under reduced vacuo.The crude product was purified by column chromatography (mobile phase ethyl acetate: petroleum ether = 1:8-1:4)Obtained 181 mg of a pale yellow oily liquid with a yield of 90%.
With potassium acetate;bis-triphenylphosphine-palladium(II) chloride; In 1,4-dioxane; at 80℃; for 24h;Inert atmosphere;
Under an argon atmosphere, (4-bromophenyl)methanol (3.0 g) and bis(pinacolato)diboron (4.5 g) was dissolved in dioxane (35 ml), and dichlorobis(triphenylphosphine)palladium(II) (567 mg) and potassium acetate (4.7 g) were added thereto, followed by stirring at 80 C. for 1 day. The reaction mixture was concentrated under reduced pressure, and then a saturated aqueous sodium hydrogen carbonate solution was added thereto, followed by extraction with CHCl3. The organic layer was dried over Na2SO4 and concentrated under reduced pressure. The obtained residue was dissolved in DME (35 ml) and water (18 ml), and tert-butyl {2-[(3-bromobenzyl)(methyl)amino]-2-oxoethyl}carbamate (3.5 g) was added thereto under an argon atmosphere. In addition, sodium carbonate (3.1 g) and tetrakis(triphenylphosphine)palladium (339 mg) were added thereto, followed by stirring at 70 C. for 1 day. The reaction mixture was concentrated under reduced pressure, and then a saturated aqueous sodium hydrogen carbonate solution was added thereto, followed by extraction with CHCl3. The organic layer was dried over Na2SO4 and concentrated under reduced pressure. The obtained residue was purified by silica gel column chromatography (hexane/EtOAc) to obtain tert-butyl {2-[[4'-(hydroxymethyl)biphenyl-3-yl]methyl}(methyl)amino]-2-oxoethyl}carbamate (2.8 g).
With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; potassium acetate; In 1,4-dioxane; at 80℃; for 6h;Inert atmosphere;
(3) 1 g of 1- (4-bromobenzene) ethanol was dissolved30 ml 1,4-dioxane solution,Two equivalents of bis (pinacolato) diboron,3 equivalents of potassium acetate,5% equivalent of [1,1'-bis (diphenylphosphino) ferrocene] palladium dichloride Under argon atmosphere at 80 C,After 6 hours of reaction, the product was obtained by column chromatography.
1500 mg
With dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2; potassium acetate; In 1,4-dioxane; at 90℃; for 16h;
A mixture of (4-bromophenyl)methanol (1 g, 5.35 mmol), 4,4,5,5-tetramethyl-2-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1,3,2-dioxaborolane (4.07 g, 16.04 mmol), KOAc (1.05 g, 10.69 mmol) and Pd(dppf)Cl2.CH2Cl2 (873.27 mg, 1.07 mmol) in 1,4-Dioxane (20 mL) was stirred at 90 C for 16 hours. After cooling to r.t., the mixture was concentrated to give the crude product. The crude product was purified by flash chromatography on silica gel (EtOAc in PE = 0 to 50%) to give the product (1500 mg) as oil. H NMR (400MHz DMSO-d6) _ = 7.63 (d, 2H), 7.32 (d, 2H), 5.23 (t, 1H), 4.51 (d, 2H), 1.29 (s, 12H).
16 g
With bis-triphenylphosphine-palladium(II) chloride; potassium acetate; In 1,4-dioxane; at 85℃; for 3h;Inert atmosphere;
4-Bromobenzyl alcohol (15 g, 80.2 mmol), bis(pinacolato)diboron (30.6 g, 120.3 mmol), potassium acetate (23.6 g, 240 mmol) and Pd (PPh3)2Cl2 (5.6 g, 8 mmol) were added to 150 mL of dioxane, and the mixture was stirred at 85 C. for 3 hours under a nitrogen atmosphere. The reaction solution was filtered and concentrated under reduced pressure, and then extracted with water and ethyl acetate. The organic layer was dried over anhydrous sodium sulfate and filtered. The filtrate was concentrated under reduced pressure. The residues were purified by column chromatography (eluent: petroleum ether:ethyl acetate 60:1-10:1) to give 16 g of title product.
General procedure: In a typical experiment, to a solution of HReO4 (5.0 mol %) in toluene (3 mL) was added the 4-methylphenyl sulfoxide (1.0 mmol) and the alcohol (1.0 mmol). The reaction mixture was heated at reflux temperature under air atmosphere (the reaction times are indicated in the Tables 1-3) and the progress of the reactions was monitored by TLC or 1H NMR. Upon completion, the reaction mixture was evaporated and purified by silica gel column chromatography with n-hexane to afford the carbonyl compounds and 4-methylphenyl sulfide, which are all known compounds.
With tert.-butylhydroperoxide; tetra-(n-butyl)ammonium iodide; In 1,1,2-trichloroethane; water; at 90℃; for 12h;
General procedure: To a solution of alcohols 1 (0.1 mmol) in TCE (1.0 mL) was added n-Bu4NI (20 mol%) and N, N-disubstituted formamides 2 (0.5 mmol), followed by adding a solution of TBHP (6.0 equiv., 70% aqueous solution). The resulting mixture was stirred at 90 oC until it completed. When the reaction was finished, the reaction mixture was cooled to room temperature and poured into saturated Na2S2O3 solution (3.0 mL), extracted with EtOAc (3×8.0 mL), then washed with saturated brine. The combined organic layers were dried over anhydrous Na2SO4. After removing the solvents in vacuo, the residue was purified by flash column chromatography on silica gel or preparative TLC on GF 254 to afford the desired products 3.
65%Chromat.
General procedure: Various N,N-dimethyl benzamides were obtained followinga simple procedure which involves charging the reactionmixture containing benzyl alcohols (1mmol), catalyst(20wt%) and DMF (5mL) into a two necked 50mL roundbottom flask (RBF) and stirred for 10min at RT and then70% aqueous TBHP (5mmol) was introduced dropwiseto the mixture under continuous stirring at RT. The RBFwas fitted with a water condenser and heated for 24h at100C. After 24h, the reaction mixture was cooled to RTand catalyst was then separated by filtration. The reactionmixture was diluted with 100mL of DW and extractedusing ethyl acetate (2 × 60mL). The combined organiclayer was dried using Na2SO4and concentrated underrotatory evaporator. The crude products were purified bychromatography using silica gel, hexane and ethyl acetate.Similarly a range of N,N-substituted benzamides werealso obtained by taking the stoichiometric amount of variousN-substituted formamides in 5mL of toluene keepingother parameters constant.
With tert.-butylhydroperoxide; tetra-(n-butyl)ammonium iodide; In 1,1,2-trichloroethane; water; at 90℃; for 12h;
General procedure: To a solution of alcohols 1 (0.1 mmol) in TCE (1.0 mL) was added n-Bu4NI (20 mol%) and N, N-disubstituted formamides 2 (0.5 mmol), followed by adding a solution of TBHP (6.0 equiv., 70% aqueous solution). The resulting mixture was stirred at 90 oC until it completed. When the reaction was finished, the reaction mixture was cooled to room temperature and poured into saturated Na2S2O3 solution (3.0 mL), extracted with EtOAc (3×8.0 mL), then washed with saturated brine. The combined organic layers were dried over anhydrous Na2SO4. After removing the solvents in vacuo, the residue was purified by flash column chromatography on silica gel or preparative TLC on GF 254 to afford the desired products 3.
Example 3 Synthesis of (4-((Trimethylsilyl)ethynyl)phenyl)methanol (3) A solution of 4-Bromobenzyl alcohol (1.276 g, 6.82 mmol), Ethynyltrimethylsilane (1.061 ml, 7.51 mmol), PdCl2(PPh3)2 (24 mg, 0.034 mmol), Copper iodide (52 mg, 0.273 mmol), Triphenylphosphine (358 mg, 1.365 mmol), Diethylamine (10.70 ml, 102 mmol) in 2 ml of dry DMF (dimethylformamide) was heated under argon in a microwave oven at 150 C. for 30 min. The mixture was filtered. The filtrate was acidified with 1M HCl and extracted 3 times with ether. The combined organic layers were washed with bicarbonate and water, dried over MgSO4 and concentrated to afford 3 (1.274 g, 6.23 mmol, 91% yield) as a brown solid.
With potassium-t-butoxide In toluene at 110℃; for 48h;
97%
With potassium-t-butoxide In toluene at 20 - 110℃; for 48h;
8 A method for preparing 2-(4-bromophenyl)benzo[d]thiazole includes the following experimental steps:
At room temperature, add o-aminothiophenol 1a (0.6 mmol), toluene solvent and 4-bromobenzyl alcohol 2b (0.2 mmol) to the reactor in sequence, stir at room temperature to fully dissolve them, and add to the preparation of Example 1 in sequence The obtained HKUST-1-400 catalyst (20mg), potassium tert-butoxide (0.2mmol), after dissolving, continue the reaction and place it at 110°C for 2 days. After the completion of the reaction is detected by TLC, the Cu-MOF derivative HKUST is filtered out first -1-400 catalyst and then column chromatography to obtain the target compound 3b with a yield of 97%.
96%
With (phthalocyaninato)iron(II); sodium tertiary butoxide In toluene at 120℃; for 36h; Inert atmosphere;
90%
With tetrabutylammonium bromide In N,N-dimethyl-formamide at 80℃; for 1.66667h;
2.6. General procedure for the synthesis of benzimidazoles or benzothiazoles in the presence of Pd(II)Cl2-BTP(at)MNPs catalyst
General procedure: A mixture of alcohol (1 mmol), 1,2-phenylenediamine or 2-aminothiophenol(1 mmol), Pd(II)Cl2-BTPMNPs (0.019 g, containing 0.09mol% Pd) and (1 mmol) tetrabutylammonium bromide (TBAB, 0.01 g)in DMF (5 mL) in a round-bottomed flask equipped with a condenser wasstirred at 80 °C. The progress of the reaction was monitored by TLC(eluent: n-Hexane/EtOAc, 4: 1 for benzimidazoles and n-Hexane/EtOAc, 6: 1 for benzothiazoles). The catalyst was separated by permanentmagnet and washed with EtOAc (10 mL). The crude product waspurified by recrystallization from EtOAc or EtOH to afford the purebenzimidazole. The benzothiazoles was obtained by recrystallizationfrom n-hexane/EtOAc (10: 1).
80%
With cobalt sulphate heptahydrate; lithium perchlorate; trifluoroacetic acid In water monomer; acetonitrile at 20℃; for 2.5h; Electrochemical reaction;
79%
With C15H20MnN2O3S(1+)*Br(1-); potassium hydroxide In neat (no solvent) at 140℃; Inert atmosphere; Green chemistry;
75%
With sodium tertiary butoxide In toluene at 100℃; for 24h; Schlenk technique; Sealed tube; Green chemistry;
73%
With bis(3,5-di-(tert-butyl)-2-hydroxyazobenzolato)nickel(II); potassium-t-butoxide; oxygen In toluene at 80℃; for 10h;
69%
With di-tert-butyl peroxide In diphenylether at 120℃; for 6h;
2.2 Catalytic Reactions
General procedure: In a representative catalytic experiment, benzyl alcohol(0.135g, 1mmol), 2-aminophenol (0.204mL, 2mmol),and diphenyl ether (0.1mL) as an internal standard weredissolved in xylene (4mL). The solution was added intoa round bottom flask. The Fe-MOF catalyst with pre-calculatedquantity was then introduced to the reactor. Thecatalyst amount was worked out regarding the iron/ benzylalcohol molar ratio. The reaction mixture was stirred undermagnetic stirring for 5min to dispense the catalyst in the liquidphase. Subsequently, di-tert-butyl peroxide (tBuOOtBu,0.63mL, 3mmol) was added dropwise to the reactor. Themixture was magnetically stirred at 120°C for 360min.Samples were taken at different time periods, quenched withNaCl solution (5% w/w, 1mL). The organic ingredients wereafterwards extracted into ethyl acetate phase (3mL), driedwith Na2SO4,and analyzed by GC concerning the internalstandard. The desired product, 2-phenylbenzo[d]oxazole,was isolated by silica gel column chromatography. 1HNMR, 13C NMR, and GC-MS experiments were performedto verify the product structure. To explore the recyclability,the iron-based framework was collected by centrifugation,washed thoroughly with methanol to remove product andexcess reagents, heated under vacuum on a Shlenkline at120°C for 3h, and reutilized for new catalytic experiment.
With porous borocarbonitride In N,N-dimethyl-formamide for 48h; Inert atmosphere; Irradiation; Green chemistry; chemoselective reaction;
With sodium iodide; In water; acetonitrile; at 20℃; for 3h;Electrochemical reaction;
General procedure: A solution in undivided cell of benzyl alcohols (1.0 eq, 0.30 mmol), morpholine (5.0 eq, 1.50 mmol) and sodium iodide (5.0 eq, 1.50 mmol) in co-solvent between acetonitrile and water with ratio 3:1 (4 mL). The reaction was applied constant current at 100 mA via graphite rod as anode and platinum plate as cathode from power supply. The reaction was stirred at room temperature for 3 hours. The reaction mixture was washed with Na2S2O8 (1x10 mL) following water (2x10 mL) and the organic portion was extracted with EtOAc (3x10 mL). The organic layer was eliminated water by Na2SO4. After filtration and removal of the solvent under reduced pressure, the crude product was purified by silica gel column chromatography to afford amide products 3aa, 3ca, 3fa, 3ga, 3ia, 3ja and 3la-3na.
With oxygen; sodium hydroxide; In water; at 25℃; for 24h;
General procedure: Unless otherwise noted, reactions were carried out as following: a mixture of alcohol 1 (1.00mmol, 2.0 equiv), amine 2 (0.50 mmol), sodium hydroxide (0.50 mmol) and Au/HAP (45 mg, 1.69wt%) were vigorously stirred in 0.5 mL H2O at 40 C for 24 h under oxygen balloon. After completion of the reaction, the mixture is cooled to room temperature, diluted with ethyl acetate. The catalyst was separated by centrifugation and washed with ethyl acetate (3 x 15.0 mL). The combined organic layer was washed by saturated NaCl solution and dried over anhydrous magnesium sulfate and the solvent was removed under vacuum. The residue was purified by flash chromatography on a short silica gel (eluent: petroleum ether/ethyl acetate = 10:1, 2:1, or 1:1) toafford the corresponding amide 3.
With dipotassium peroxodisulfate; iron(III) chloride hexahydrate In water; dimethyl sulfoxide at 100℃; for 12h;
3
General procedure: A dried reflux tube equipped witha magnetic stir bar charged with benzothiazole derivative (0.5 mmol 1.0equiv), benzylalcohol derivative (1.5mmol 3.0equiv), FeCl3·6H2O (0.1equiv), K2S2O8 (2.0 equiv), DMSO/H2O (2:1 mL) and the reaction vessel was placedin a 100°C oil bath for 12 h under air. After cooling to room temperature,the mixture was diluted with ethyl acetate and directly filtered through a padof celite and washed with water. The organic phase was dried over NaSO4and removed under reduced vacuum. The residue was purified by columnchromatography eluting with ethyl acetate and hexane to afford thedesired product.
With potassium carbonate; In acetone; for 6h;Reflux;
General procedure: <strong>[3470-50-6]6-Hydroxy-1-tetralone</strong> (0.3 g, 1.85 mmol) was suspended in acetone (15 mL) containing K2CO3 (3.70 mmol). The reaction was treated with an appropriately substituted arylalkyl bromide (2.035 mmol) and heated under reflux for 6 h. The reaction progress was monitored using silica gel TLC with ethyl acetate:petroleum ether (1:2) as mobile phase. Upon completion, the reaction was filtered through a pad of celite and concentrated in vacuo. The crude thus obtained was purified by recrystallization from cyclohexane.
With di-tert-butyl peroxide; In diphenylether; at 120℃; for 6h;
General procedure: In a representative catalytic experiment, benzyl alcohol(0.135g, 1mmol), 2-aminophenol (0.204mL, 2mmol),and diphenyl ether (0.1mL) as an internal standard weredissolved in xylene (4mL). The solution was added intoa round bottom flask. The Fe-MOF catalyst with pre-calculatedquantity was then introduced to the reactor. Thecatalyst amount was worked out regarding the iron/ benzylalcohol molar ratio. The reaction mixture was stirred undermagnetic stirring for 5min to dispense the catalyst in the liquidphase. Subsequently, di-tert-butyl peroxide (tBuOOtBu,0.63mL, 3mmol) was added dropwise to the reactor. Themixture was magnetically stirred at 120C for 360min.Samples were taken at different time periods, quenched withNaCl solution (5% w/w, 1mL). The organic ingredients wereafterwards extracted into ethyl acetate phase (3mL), driedwith Na2SO4,and analyzed by GC concerning the internalstandard. The desired product, 2-phenylbenzo[d]oxazole,was isolated by silica gel column chromatography. 1HNMR, 13C NMR, and GC-MS experiments were performedto verify the product structure. To explore the recyclability,the iron-based framework was collected by centrifugation,washed thoroughly with methanol to remove product andexcess reagents, heated under vacuum on a Shlenkline at120C for 3h, and reutilized for new catalytic experiment.
at 23℃; for 1.5h;Inert atmosphere; Cooling with ice;
A 5-mL reactionvial was equipped with a stir bar, a rubber septum, and an argon inlet needle.The vial was charged with t-butoxypyridine(3) (1.2 mmol) and dry PhCH3(1 mL), and was allowed to stir at 0 C. MeOTf (1.2 mmol) was added dropwise tothe reaction mixture over 5 min. Upon complete addition, the reaction wasallowed to stir for 1h. The alcohol (1 mmol) dissolved in dry PhCH3or dry DCM (1 mL) depending upon the solubility of the alcohol, was added over30 seconds to the reaction mixture. The ice bath was removed and the reactionmixture was allowed to stir at room temperature (~ 23 C) for 1.5h. When thereaction was complete by TLC, the mixture was diluted in Et2O or DCMdepending upon the solubility of the product. Et2O was preferredbecause the hydroxypyridine/pyridone byproduct (5) was less soluble in this solvent than DCM. The diluted reactionmixture was washed with water (10 mL), then brine (10 mL). The organic fractionwas dried over anhydrous sodium sulfate, filtered, and concentrated in vacuo to isolate the crude productmixture. The crude mixture was purified by flash chromatography to yield thepure t-butyl ether.
With palladium diacetate; sodium carbonate; In water; N,N-dimethyl-formamide; at 70℃;
To a solution of (4-bromophenyl)methanol (500 mg, 2.94 mmol) and [4-(methoxycarbonyl) phenyl]boronic acid (550 mg, 3.53 mmol) in DMF (20 mL) was added Pd(OAc)2 (200 mg, 735 mumol) and Na2CO3 (3 g in 20 mL H2O). The reaction mixture was allowed to stir at 70 C. After 48 h, an extraction with EtOAc was performed; the organic layers were combined and washed with brine, dried over MgSO4, filtrated and concentrated in vacuo. Column chromatography (EtOAc/Hept 1:4) yielded the product (170 mg, 24%) as white crystals. RF = 0.3 (EtOAc/Hept 1:1). 1H NMR (400 MHz, CDCl3) delta 8.15-8.06 (m, 2H), 7.70-7.58 (m, 4H), 7.52-7.43 (m, 2H), 4.77 (d, J = 3.1 Hz, 2H), 4.07-3.67 (m, 3H), 1.75 (br s, 1H, OH) ppm. FTIR = 3305, 3032, 1718, 1604, 1432, 1399, 1286, 1271, 1220, 1111, 765 cm-1. HRMS (EI) calcd for C15H14O3 (M)+ 242.0942, found 242.0919.
With [Ru(eta6-p-cymene)Cl2]2; caesium carbonate; 2-((diphenylphosphino)amido)pyridine; In toluene; at 120℃; for 18h;Schlenk technique; Inert atmosphere;
General procedure: Cs2CO3 (0.6 mmol,195.6 mg) and toluene (1 mL) were added to a Schlenk tube under a N2 atmosphere. [RuCl2(eta6-p-cymene)]2 (0.005 mmol, 3.1 mg), L1 (0.01 mmol, 2.8 mg), alcohols (1.1 mmol) and ketones (1.0 mmol) were added in that order and the Schlenk tube was closed and stirred at 120C for 18 h. The reaction mixture was cooled to room temperature, quenched with water and extracted with ethyl acetate (20 mL x 3). The combined extracts were dried over anhydrous sodium sulfate and concentrated in vacuo. The product was purified by column chromatography using petroleum ether/ethyl acetate as eluent to give the corresponding product (Figs. S22-S47 in Supporting Information).
86%
With C16H14IrN2O3; caesium carbonate; In tert-Amyl alcohol; for 6h;Reflux;
Acetophenone (120mg, 1mmol), cat.1 (5.4mg, 0.01mmol, 1.0mol%), cesium carbonate (33mg, 0.1mmol,0.1equiv.), 4- bromobenzyl alcohol (206mg, 1.1mmol) and tert-amyl alcohol (ImL) were sequentially added to a 5mL round bottomed flask. Anti-After the reaction mixture was refluxed for 6 hours in air, cooled to room temperature. The solvent is removed by rotary evaporation, then purified by column chromatography (developingSolvent: petroleum ether / ethyl acetate) to give the pure title compound Yield: 86%
83%
With C38H36Cl4Ir2N4; caesium carbonate; In tert-Amyl alcohol; for 12h;Reflux;
Acetophenone (60 mg, 0.5 mmol),Cat. [Ir] (5.4 mg, 0.005 mmol, 1.0 mol%),Cesium carbonate (33 mg, 0.2 mmol, 0.2 equiv.),4-bromobenzyl alcohol (103 mg, 0.6 mmol)And tert-amyl alcohol (1 mL) were successively added to a 5 mL round bottom flask.The reaction mixture was refluxed in air for 12 hours,Cool to room temperature.Rotate the solvent to remove the solvent,And then passed through a column chromatography (developing solvent:Petroleum ether / ethyl acetate) to give the pure title compound,Yield: 83%
With di-isopropyl azodicarboxylate; triphenylphosphine; In tetrahydrofuran; toluene; at 0 - 20℃; for 16h;Inert atmosphere;
General procedure: To a stirred and ice-bath cooled mixture of the phenol (1 equiv) in anhydrous THF (9 ml), was added the alcohol (1 equiv). Triphenylphosphine (PPh3) (1.1 equiv) was added portionwise to this mixture and the system was kept under nitrogen by evacuation and filling with nitrogen three times. Subsequently, diisopropyl azodicarboxylate (DIAD) (94 wt % solution in toluene, 1.1 equiv) was added in a strictly dropwise fashion. The reaction mixture was first stirred for 1h at 0C and then overnight at room temperature. After completion of the reaction as indicated by TLC, the reaction mixture was concentrated under reduced pressure. The residue was extracted with EtOAc (2x) and the combined extract was washed successively with saturated aqueous NaHCO3 and sodium chloride (NaCl) solutions, dried over anhydrous MgSO4 and concentrated in-vacuo affording an oily residue. The crude oil was chromatographed on flash column to yield the desired ether derivative.
General procedure: Under a nitrogen atmosphere 0.075 g (0.2 mmol) of2,5-dibromo-3,4-dinitrothiophene were dissolved in 8 mLof anhydrous toluene and treated with 10 molpercent of the catalyst(catalysts I?IV). The mixture was then subjected toultrasound irradiation for 5 min and then stirred at roomtemperature for additional 25 min. Then, 0.5 mmol of theboronic acid, 1.6 mmol of potassium phosphate, and 2 mLof water were added, and the mixture was heated underreflux at 100°C for 48 h. After cooling to room temperature,the mixture was dried over magnesium sulfate andchromatographed (petroleum ether/dichloromethane 1:3).
The [(IPr) AuCl] (6mg, 0.01mmol, 1mol%), AgOTf (2.6mg, 0.01mmol, 1mol%), phenylacetylene (102mg, 1mmol), 1,4- dioxane (1ml) and water (36ul, 2equiv.) were successively added to 5ml microwave tube.After the reaction mixture was microwaved at 120 reactor for one hour, cooled to room temperature.Thereto was added [Cp * IrCl2]2(8mg, 0.01mmol, 1mol%), potassium tert-butoxide (34mg, 0.3mmol, 0.3equiv.), 4- bromobenzyl alcohol (224mg, 1.2mmol).After the reaction mixture was microwaved at 130 reactor and then reacted for 2 hours, cooled to room temperature.Filtered, and solvent was removed by rotary evaporation, then purified by column chromatography (developing solvent: petroleum ether / ethyl acetate) to give the pure title compound Yield: 80%
DL-1-phenylethanol (122 mg, 1.0 mmol), cat. [Ir] (5.3 mg, 0.01 mmol, 1 mol%) and tert-amyl alcohol (1 mL) were successively added to a 5 mL round bottom flask. The reaction mixture was refluxed in air for 6 hours and then cooled to room temperature. Then, cesium carbonate (33 mg, 0.1 mmol, 0.1 equiv.) And 4-bromobenzyl alcohol (206 mg, 1.1 mmol) were added, refluxed in air for 6 hours and then cooled to room temperature. The solvent was removed by rotary evaporation, and then the title compound was purified by column chromatography (developing solvent: petroleum ether / ethyl acetate), yield: 89%
81%
With [Co(N,N'-bis(alpha-pyridyl)-2,6-diaminopyridine)Cl2]; sodium hydroxide; In toluene; at 120℃; for 24h;Inert atmosphere; Molecular sieve; Schlenk technique;
General procedure: Under an N2 atmosphere, a mixture of secondary alcohol (0.5 mmol), primary alcohol (0.6 mmol), 1a (5 mol %), NaOH (0.1 mmol), 4 A molecular sieve (0.6 g), and toluene (1.5 mL) was added into a 25 mL Schlenk tube equipped with a stirring bar. The mixture was heated to 120 C under a slow and steady N2 flow for 24 h. After cooling to ambient temperature, 6 mL water was added and the aqueous solution extracted with ethyl acetate (3 x 5 mL). The combined extracts were dried over anhydrous Na2SO4, and concentrated under reduced pressure. The crude product purified on a short flash chromatography column.
With tetra-(n-butyl)ammonium iodide; at 120℃; for 24h;Inert atmosphere;
To a 20 mL tubular reactor was added 4-bromobenzyl alcohol (93.0 mg, 0.50 mmol)(3.8 mg, 0.01 mmol, 2 mol%), protected by vacuum nitrogen and then heated to 120 C under solvent-free conditions 24h After the TLC monitoring reaction was complete, the product was purified by column chromatography and the yield was 90%.
With potassium hydroxide; In 1,4-dioxane; at 110℃; for 20h;Inert atmosphere;
A 50 ml three-necked flask equipped with a stirring reflux device was charged with 1 mmol of 2-diphenylphosphineaniline, 1.5 mmol of p-bromobenzyl alcohol, 1 mmol of bis Dicyclohexylphosphine propane,mmol RuCl2 (PPh3) 3,1 mmol potassium hydroxide, 20 ml dioxane, the temperature was 110 C, heated for 20h under a nitrogen atmosphere, cooledHowever, filtration and recrystallization of the resulting solid from a mixed solvent of CH 2 Cl 2 and petroleum ether gave product 6 in a yield of 87%.
With 1H-imidazole; tert.-butylhydroperoxide; tetra-(n-butyl)ammonium iodide; In water; at 80℃; for 7h;Green chemistry;
General procedure: To a mixture of benzyl alcohol (108 mg, 1.0 mmol) and TBHP(180 mg, 2.0 mmol) in water (3 ml), the catalyst TBAI (73.8 mg,0.2 mmol), imidazole (136 mg, 2.0 mmol), and MeOH (2 ml)were added, and the mixture was stirred at 80 °C for 8 h. Theprogress of the reaction was monitored by TLC. After completionof reaction, the reaction mixture was cooled to room temperature.Then MeOH was distilled out, and the organic productwas extracted with ethyl acetate (3 × 10 ml), repeatedly washedwith distilled water (4 × 5 ml) to remove the unreacted TBHP,dried with anhydrous sodium sulfate, and the solvent was evaporatedunder reduced pressure to afford methyl benzoate (112mg, yield 82percent).
5-(4-bromophenyl)-3-(4-methylphenyl)-1,2,4-oxadiazole[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
40%
With sodium ethanolate; copper diacetate In toluene at 110℃; for 24h;
9 Example 9
0.5 mmol of 4-methylbenzamide oxime, 1.0 mmol of 4-bromobenzyl alcohol was placed in the reaction tube, and then 0.05 mmol of Cu(OAc) 2, 0.5 mmol of C2H5ONa, 2.5 mL of toluene were added in sequence, and stirred at 110 ° C. After reacting for 24 h, the product was extracted with ethyl acetate, dried over anhydrous sodium sulfate.Ethyl acetate = 20:1) purified to a white solid.That is, 5-(4-bromophenyl)-3-(4-methylphenyl)-1,2,4-oxadiazole. Yield 40%,
With tetrakis(triphenylphosphine) palladium(0); potassium carbonate; In ethanol; water; N,N-dimethyl-formamide; at 90℃;
General procedure: 4-Hexylbromobenzene (510 mg, 2.25 mmol) and (4-(hydroxymethyl)phenyl)boronic acid (341 mg, 2.25 mmol) were dissolved in a mixture of 40 mL DMF/EtOH/H2O in a ratio of 2:1:1. Anhydrous potassium carbonate (1.24g, 8.98 mmol) and tetratriphenylphosphine palladium (194 mg, 0.17 mmol) were added and stirred at 90 overnight . The reaction mixture was cooled to room temperature and ethanol was removed by rotary evaporation. The residue was poured into water and extracted with ethyl acetate three times. The combined organic phase was dried over Na2SO4, filtered and the solvent was removed by rotary evaporation. The crude product was purified by flash chromatography to afford the intermediate (11a) as white solid (492 mg ,86%). 1H NMR (400 MHz, DMSO-d6): delta 9.55 (s, 1H), 7.50-7.42 (m, 4H), 7.20 (d, J = 8.0 Hz, 2H), 6.82 (d, J = 8.0 Hz, 2H), 2.56 (t, J = 7.5 Hz, 2H), 1.62-1.50 (m, 2H), 1.33-1.19 (m, 6H), 0.85 (t, J = 6.8 Hz, 3H).
With tetrabutylammomium bromide; palladium diacetate; sodium carbonate; In water; at 150℃; for 0.333333h;Sealed tube;
Compound 1 (1 eq, 5.35 mmol), 4-(Trifluoromethyl)phenylboronic acid (1 eq, 5.35 mmol), TBAB (1 eq, 5.35 mmol), Na2C03 (3 eq, 16.05 mmol) were dissolved in 11 mL of water. Palladium acetate (0.4 % eq, 0.021 mmol) was then added and the reaction was stirred in a scelled tube and heated at 150C. After 20 min, the tube is slowly cooled down to rt and opened with caution. The biphase mixture is poured onto 10 mL of EtOAc and extracted (3 x 10 mL). The combined organic phases were dried and filtered. After removal of the solvent under reduced pressure, the remaining black oil was purified using column chromatography (silica gel, 80/20 Hex/EtOAc) to afford the desired compound (Rf = 0.2) as a colourless solid (1.29 g, 96%). 1H-NMR (CDC13, 600 MHz) delta 7.69 (s, 4H), 7.60 (d, J = 8.1Hz, 2H), 7.47 (d, J = 8.1Hz, 2H), 4.77 (s, 2H); 13C-NMR (CDCI3, 150 MHz) delta: 144.5, 141.1, 139.3, 129.1, 127.7, 127.6, 127.5, 125.9, 124.4, 65.1;ESI-MS m/z for C14HnF30 [MH]+, [MNa]+;
With N-ethyl-N,N-diisopropylamine In water at 20℃; for 1h; Green chemistry;
2.6. General procedure of acylation of alcohols catalyzed by DMAP-functionalized polymeric nanoreactors in aqueous systems
General procedure: To a DMAP nanoreactor solution (32 mg of P(MAPMA4-co-MMA30)-b-P(OEGMA70) in 1 mL deionized water obtained by the solvent exchange method, 5 mol%), alcohol (0.1 mmol), 3 equiv. of anhydride, 1.5 equiv. of auxiliary base (DIPEA) were added. The reaction solution was vigorously stirred at room temperature. After completion of the reaction, cold ether was added to extract product and residual starting materials. The product and conversion were analyzed by GC-MS. The temperature of the aqueous solution was raised above its LCST. The nanoreactors were separated from the water layer after the aqueous phase was centrifuged at 10,000 g for 30 min. At last, the recovered catalyst was used for the next run after washing with cold ether carefully.
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