* 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.
Stage #1: With n-butyllithium In diethyl ether; benzene at 0℃; for 1 h; Inert atmosphere Stage #2: at 20℃;
The compounded 4' (10 mmol, 2.21 g) was added to a mixture of 30 ml of ether and 30 ml of benzene, and n-butyllithium (10 mmol, 1.6 M, 6.25 ml) was slowly added dropwise at 0°C under nitrogen atmosphere. After stirring at 0° C. for 1 hour, methyl iodide (15 mmol, 2.13 g) was slowly added dropwise to the reaction system. After completion of the dropwise addition, the reaction was warmed up to room temperature. The reaction was completed by TLC and the reaction was completed. 60 ml of a saturated aqueous solution of ammonium chloride was added to the reaction system, the aqueous layer was extracted with toluene, the organic layers were combined, washed with saturated brine (100ml*3), dried over anhydrous sodium sulfate, and the organic phase was concentrated and purified by column chromatography. Compound 4''' (7.3 mmol, 1.61 g, 73percent).
Reference：
[1] Patent: CN107814795, 2018, A, . Location in patent: Paragraph 0028; 0029
3
[ 83-53-4 ]
[ 13720-06-4 ]
Reference：
[1] Chemische Berichte, 1931, vol. 64, p. 953
4
[ 7647-01-0 ]
[ 75-15-0 ]
[ 7446-70-0 ]
[ 83-53-4 ]
[ 13720-06-4 ]
Reference：
[1] Chemische Berichte, 1931, vol. 64, p. 953
5
[ 83-53-4 ]
[ 124-38-9 ]
[ 16650-55-8 ]
Reference：
[1] Organic Process Research and Development, 2011, vol. 15, # 1, p. 112 - 122
[2] Bioorganic and Medicinal Chemistry Letters, 2001, vol. 11, # 20, p. 2769 - 2773
[3] Journal of the Chemical Society, 1958, p. 1426
Stage #1: With n-butyllithium In diethyl ether; hexane at 0℃; for 0.333333 h; Stage #2: at 0 - 20℃; for 1 h;
To a 150 ml flask was added 1,4-dibromonaphthalene (2.0 g, 7.0 mmol) and anhydrous ether (50 ml). After cooling to 0 °C n-BuLi (3.1 ml of 2.5 M in hexanes, 7.7 mmol) was added dropwise and stirred for 20 minutes after which anhydrous DMF (1.62 ml, 21 mmol) was added. The reaction was then warmed to ambient temperature and after 1 h the reaction was quenched with water (10 ml), stirred for 10 minutes, and extracted with ether (3x). The ether layer was dried over anhydrous NA2S04, passed through a silica plug, and concentrated to afford 1.02 g (62percent) of product as a pure off- white solid : LH NMR (300 MHz, DMSO-D6) : 8 7.80-7. 85 (2H, m), 8.10 (1H, d, J = 7.7 Hz), 8.20 (1H, d, J = 7.7 Hz), 8. 32 (1H, m). 9.24 (1H, m), 10.42 (1H, s). Anal. for CIIH7BRO : Calc'd: C: 56.20 H: 3.00 Found: C: 56.13 H: 2.98
62%
Stage #1: With n-butyllithium In diethyl ether; hexane at 0℃; for 0.333333 h; Stage #2: at 20℃; for 1 h;
Step 1: 4-Bromo-1 -naphthaldehyde (P20a)To a solution of 1,4-dibromonaphthalene (2.0 g, 7.0 mmol) in dry Et20 (50 mL) was added n5 BuLi (2.5M in hexanes, 3.1 mL, 7.7 mmol) at 0°C and the solution was stirred for 20 mm. ThenDMF (1.62 mL, 21 mmol) was added and the solution was warmed to rt and stirred at this temperature for 1 h, quenched with water and extracted with Et20 (3x). The combined organic layers were washed with brine, dried over Na2504, filtered, concentrated and purified by CC (PE/EA = 50/1) to give compound P20a (1.02 g, 62percent) as an off- white solid.
Reference：
[1] RSC Advances, 2014, vol. 4, # 63, p. 33474 - 33477
[2] Patent: WO2004/103941, 2004, A2, . Location in patent: Page 16
[3] Patent: WO2013/178362, 2013, A1, . Location in patent: Page/Page column 107
[4] Angewandte Chemie - International Edition, 2017, vol. 56, # 42, p. 13094 - 13098[5] Angew. Chem., 2017, vol. 56, p. 13274 - 13278,5
[6] Bioorganic and Medicinal Chemistry Letters, 2007, vol. 17, # 4, p. 902 - 906
[7] Patent: EP2159217, 2010, A1, . Location in patent: Page/Page column 58
11
[ 83-53-4 ]
[ 50672-84-9 ]
Yield
Reaction Conditions
Operation in experiment
56%
With n-butyllithium In tetrahydrofuran; <i>N</i>-methyl-acetamide; water
Example 39 Preparation of 5,6-dichloro-2-[4-[(2,4-dioxothiazolidin-5-ylidene)methyl]naphth-1-yl]benzimidazole To a solution of 1,4-dibromonaphthalene (1.00 g, 3.50 mmol) in tetrahydrofuran (15 mL) were added n-butyllithium (1.6 mol/L; 3.1 mL) and dimethylformamide (0.54 mL, 7.0 mmol) sequentially at =78° C. under nitrogen atmosphere, and the mixture was stirred for 15 min. Water was added, and the mixture was extracted with ethyl acetate. The organic layer was combined, washed with brine and dried on anhydrous sodium sulfate. The solvent was removed under reduced pressure, and the residue was purified by column chromatography (8:1 hexane/ethyl acetate) to afford 4-bromo-1-naphthalenecarboxaldehyde (458 mg, 56percent). 1H NMR (400 MHz, CDCl3) δ (ppm) 7.6-7.8 (m, 2H), 7.78 (d, J=7.8 Hz, 1H), 7.94 (d, J=7.8 Hz, 1H), 8.34 (dd, J=8.2, 1.6 Hz, 1H), 9.25 (dd, J=8.2,1.6 Hz, 1H), 10.3 (s, 1H)
Reference：
[1] Patent: US2002/120144, 2002, A1,
12
[ 83-53-4 ]
[ 92616-49-4 ]
Yield
Reaction Conditions
Operation in experiment
31%
at 125℃; for 16 h;
CuCN (5.0g, 56.3mmol) was added to a solution of 1,4-dibromonaphthalene (20g, 70.4mmol) in DMF (250mL),the mixture was reacted for 16hrs at 125°C, evaporated under reduced pressure. Aqueous ammonia (200mL) and EA(200mL) were added to the residue, the mixture was stirred for 1h and organic phase was seperated. The organic phasewas in turn washed with water (100mL33) and saturated brine (100mL), dried over anhydrous magnesium sulfate,filtered, evaporated under reduced pressure. The residue was purified with silica chromatography (PE:EA = 10:1) togive compound 3-d (5.1g, yield 31percent). LC-MS (ESI): m/z = 232 [M+H]+.
26%
at 125℃;
[00285] Step A: 4-Bromo- 1 -naphthonitrileA mixture of 1 ,4-dibromonaphthalene (24.06g, 84mmol) and copper cyanide (6.02g, 67mmol) in DMF (85mL) was heated to 125°C overnight. The mixture was partially concentrated to remove DMF and the resulting residue washed with aqueous ammonium hydroxide and extracted with ethyl acetate. The organic layer was concentrated and purified by chromatography to yield 4-bromo-l -naphthonitrile (5.13g, 26percent).
26%
at 130℃; for 12 h; Inert atmosphere
General procedure: A mixture of 3a-3g (0.1 mol for 3a-3e and 3g; 0.4 molfor 3f) and CuCN (26.87 g, 0.3 mol for 3a-3e and 3g; 21.49g, 0.24 mol for 3f) in DMF (300 mL) were stirred at 130°C in N2 atmosphere for 12 h, when TLC analysis indicated completion of reaction. On cooling to room temperature, the reaction mixture was diluted with CH2Cl2 (900 mL) and the resulting mixture was further stirred for 1 h and filtered off. The filtrate was washed with 5percent brine (500 mL 5), dried (Na2SO4) and evaporated on a rotary evaporator to afford a black oil, which was purified by column chromatography to afford the pureproduct 4a-4g.
With bromine; In dichloromethane; at -30 - 20℃; for 72.25h;Inert atmosphere;
In a 100 ml flask 5,00g (0,039 mol, 1 equiv.) naphtalene is dissolved in 75 ml dichloromethane. The flask is placed under inert atmosphere and cooled to -30C, after which 25,00 g (0,156 mol, 4 equiv.) Br2 is added dropwise. Fifteen minutes after the complete addition of bromine, the reaction is continued for 72h at room temperature. The reaction is quenched using 1M NaHSO3. The organic phase is driedby means of Mg504 and the volatiles are evaporated. The compound is crystallised using cold dichloromethane (-18C), by slow addition of hexanes, resulting in a yield of 70%. From the mother liquor, an additional 17% could be recuperated by column chromatography using hexanes.
80%
With bromine; In dichloromethane; at -30 - -25℃;Irradiation;
In a 100 ml three-necked bottle, naphthalene (10 mmol, 1.28 g) and dichloromethane (50 ml) were added, cooled to -30C, and bromine (30 mmol, 4.79 g) was slowly added dropwise, and reacted at -30C to -25C under light, TLC. Detection to the point of raw material disappears. The reaction was completed, quenched with saturated aqueous NaHSO3, and the organic layer was washed with saturated aqueous NaHSO3 solution (40 ml*3), washed with 2M aqueous sodium hydroxide solution (40 ml*3), and dried over anhydrous sodium sulfate. The organic solvent was concentrated and subjected to column chromatography. Purification gave white powder Compound 4' (8 mmol, 2.29 g, 80%).
With bromine; In chloroform; N,N-dimethyl-formamide; at 0 - 30℃; for 24h;
A solution of bromine (120.9 ml, 3 eqv) in chloroform (400 ml) is added over 6 h to a solution of naphthalene (100 g) in chloroform (200 ml) and DMF (19 ml) at 0-10 0C. The reaction is stirred at 0-30 0C (for example 20-30 0C) for up to about 24 h and then chloroform (100 ml) is added. The reaction mixture is washed with aqueous sodium bisulphite (1 x 600 ml), then washed with 5% aqueous sodium bicarbonate (1 x 300 ml), then water (300 ml), then evaporated. The residue is crystallised from methanol (2600 ml), by heating to 65-70 0C, and cooling to 20-30 0C for 3-4 h. The product is filtered, and dried under vacuum at 50-55 C (dry weight 117 g).
With bromine; iron; In tetrachloromethane; at 20℃; for 5h;
To a mixture of naphthalene (25.635 g, 200 mmol), Fe powder(113 mg, 2 mmol) and CCl4 (190 mL) was slowly added Br2 (20 mL,400 mmol). The mixture was then stirred for 5 h at roomtemperature. NaOH aq was added to neutralize the solution.Et2O (250 mL) and brine (100 mL) were added and the organic layerwas separated, dried over Na2SO4,filtered, and concentrated invacuo to give a crystalline solid. Recrystallization from EtOH(twice) gave 1,4-dibromonaphthalene (4.226 g, 44% yield) [31].Pale yellow solid; 1H NMR (300 MHz, CDCl3) delta 7.63 (s, 2H), 7.65 (dd,J = 6.7, 3.4 Hz, 2H), 8.25 (dd, J = 6.1, 3.2 Hz, 2H) ppm; MS (EI) m/z(relative intensity) 126 (100, M+-Br2), 205 (18, M+-Br), 285 (79, M+).
Bromine (Bromine, 3.71 mL, 72.44 mmol) in a 120 C 1bromonaphthalene(10 g, 48.29 mmol) was slowly added dropwiseto the solution. After stirring the mixture for 3 hours, it dropped to room temperature. With NaOH aqueous solution to removethe unreacted bromine, and the mixture was extracted with dichloromethane. By using a sublimation apparatus separatingthe 1,4bromonaphthaleneand 1,5bromonaphthaleneto give a white solid (yield: 67%).
To a <strong>[2298-07-9]4-bromo-1-naphthylamine</strong> obtained in the second step, a mass fraction of 40% hydrobromic acid solution was added in a molar ratio of <strong>[2298-07-9]4-bromo-1-naphthylamine</strong> to hydrobromic acid of 1.0:2.5, and heated at 50 C for 1 h. Cooling, adding 0.5 times volume of acetonitrile; according to the molar ratio of <strong>[2298-07-9]4-bromo-1-naphthylamine</strong> to sodium nitrite 1.0:1.05, adding 30% sodium nitrite solution to the reaction system, and then 4-bromo The molar ratio of 1-naphthylamine to sodium fluoroborate is 1.0:1.2. The mass fraction of sodium fluoroborate solution is added dropwise to the reaction system, and the mixture is stirred at -5 C for 0.5 h, then 4-bromo- The molar ratio of 1-naphthylamine to cuprous bromide is 1.0:1.2. The obtained reaction system is slowly added to a solution of cuprous bromide in dilute hydrobromic acid. The quality of cuprous bromide in a cuprous bromide solution in dilute hydrobromic acid The number of parts is 30%, and after stirring at -5 C for 0.5 h, an equal volume of toluene is added to the reaction system, washed twice with an aqueous solution of sodium sulfite, washed with water until neutral, separated, and dried over magnesium sulfate. , the solvent is removed by rotary evaporation to obtain crude 1,4-dibromonaphthalene;Step 4: Refinement and purification process:The crude 1,4-dibromonaphthalene obtained in the third step is purified by recrystallization, and the crude 1,4-dibromonaphthalene obtained in the third step is completely dissolved in 95% ethanol, followed by cooling, crystallization, filtration and drying. High purity 1,4-dibromonaphthalene is obtained.The 1,4-dibromonaphthalene product prepared in this example had a purity of 99.0% and a total yield of 71.7%.
With bromine; In 1,2-dimethoxyethane; at 25℃; under 750.075 Torr; for 6h;
50 g of L-type zeolite HSZ-500 KODIC (hereinafter referred to as "zeolite A") manufactured by Tosoh Corporation was placed in a 100 g glass flask made of glass and zeolite A was heated to 250 C. while reducing the pressure inside the flask with a diaphragm pump For 3 hours.Thereafter, the zeolite A was pretreated by allowing the diaphragm pump to cool while decompressing it, flowing nitrogen gas into the flask and replacing it with a nitrogen atmosphere.The average pore diameter of the pores of zeolite A is 0.8 nm.This average pore size was obtained by calculation.Also, the Si / Al ratio of zeolite A is 6.1.Next, 2.2 g of 1-bromonaphthalene, 4.4 g of pretreated zeolite A (200 parts by mass based on 100 parts by mass of 1-bromonaphthalene), 5.3 mL of dimethoxyethane (the concentration of 1-bromonaphthalene is 2. 0 mol / L), and a magnetic stir bar were charged in a glass reaction vessel having a volume of 50 mL.While stirring the reaction solution using a magnetic stirrer bar,1.2 mL (3.7 g, 2.2 equivalents to 1-bromonaphthalene)of bromine (Br2) was reactedunder ice cooling by a cold bathThe reaction was carried out by slowly dropping it into the solution.After the dropwise addition of bromine was completed, the cooling bath was removed and the mixture was stirred for 6 hours under a pressure of 0.1 MPa (gauge pressure) and a temperature of 25 C.Thereafter, the reaction was stopped by dropping a sodium hydrogen sulfite aqueous solution having a concentration of 10 mol / L into the reaction solution under ice cooling by a cold bath.Deposits were generated from the reaction solution by dropwise addition of an aqueous solution of sodium hydrogensulfite, so that the precipitate was filtered and dried to obtain white crystals.Analysis of the obtained white crystals by gas chromatography revealed that two kinds of compounds, 1,4-dibromonaphthalene and 1,5-dibromonaphthalene, were obtained, and no other by-products were detected.The conversion of 1-bromonaphthalene was 98%, the yield of 1,4-dibromonaphthalene was 68%, and the yield of 1,5-dibromonaphthalene was 12%.Therefore, the ratio of the yield of 1,5-dibromonaphthalene to the total of the yield of 1,4-dibromonaphthalene and the yield of 1,5-dibromonaphthalene (hereinafter referred to as "1,5-dibromonaphthalene yield ratio" It is 15%).
To a 150 ml flask was added <strong>[83-53-4]1,4-dibromonaphthalene</strong> (2.0 g, 7.0 mmol) and anhydrous ether (50 ml). After cooling to 0 C n-BuLi (3.1 ml of 2.5 M in hexanes, 7.7 mmol) was added dropwise and stirred for 20 minutes after which anhydrous DMF (1.62 ml, 21 mmol) was added. The reaction was then warmed to ambient temperature and after 1 h the reaction was quenched with water (10 ml), stirred for 10 minutes, and extracted with ether (3x). The ether layer was dried over anhydrous NA2S04, passed through a silica plug, and concentrated to afford 1.02 g (62%) of product as a pure off- white solid : LH NMR (300 MHz, DMSO-D6) : 8 7.80-7. 85 (2H, m), 8.10 (1H, d, J = 7.7 Hz), 8.20 (1H, d, J = 7.7 Hz), 8. 32 (1H, m). 9.24 (1H, m), 10.42 (1H, s). Anal. for CIIH7BRO : Calc'd: C: 56.20 H: 3.00 Found: C: 56.13 H: 2.98
62%
Step 1: 4-Bromo-1 -naphthaldehyde (P20a)To a solution of <strong>[83-53-4]1,4-dibromonaphthalene</strong> (2.0 g, 7.0 mmol) in dry Et20 (50 mL) was added n5 BuLi (2.5M in hexanes, 3.1 mL, 7.7 mmol) at 0C and the solution was stirred for 20 mm. ThenDMF (1.62 mL, 21 mmol) was added and the solution was warmed to rt and stirred at this temperature for 1 h, quenched with water and extracted with Et20 (3x). The combined organic layers were washed with brine, dried over Na2504, filtered, concentrated and purified by CC (PE/EA = 50/1) to give compound P20a (1.02 g, 62%) as an off- white solid.
In a stream of argon, 30.0 g of <strong>[83-53-4]1,4-dibromonaphthalene</strong> and 300 mL of dehydrated THF were loaded into a 1,000-mL eggplant flask, and the mixture was cooled to -65C. After that, 72 mL of a solution (1.6 M) of n-butyllithium in hexane were charged into the flask, and the resultant mixture was subj ected to a reaction for 30 minutes. After that, 25 mL of dehydrated N,N-dimethylformamide were dropped into the flask, and the temperature of the resultant mixture was gradually increased. Then, the mixture was subjected to a reaction at room temperature for 4 hours. Then, 4N hydrochloric acid and toluene were added to the resultant for separation and extraction. After that, an organic layer was washed with clean water and a saturated salt solution, and was dried with sodium sulfate. A coarse product obtained by concentrating the dried product was purified by silica gel chromatography (toluene), and the resultant solid was dried under reduced pressure. As a result, 20. 8 g of a white solid were obtained. The solid was identified as Intermediate 10 by FD-MS.
With (R)-(+)-2,2'-bis(diphenylphosphino)-1,1'-binaphthalene; sodium t-butanolate;tris-(dibenzylideneacetone)dipalladium(0); In toluene; at 70℃;
To a solution of <strong>[83-53-4]1,4-dibromonaphthalene</strong> (500 mg, 0.002 mol), Pyrrolidine (0.18 mL, 0.0021 mol), (R)-(+)-2,2'-Bis(diphenylphosphino)-1,1'-binaphthyl (0.022 g, 0.000035 mol), Sodium tert-butoxide (0.24 g, 0.0024 mol) in Toluene (5.00 mL, 0.0469 mol) was added Tris(dibenzylideneacetone)dipalladium(0) (0.008 g, 0.000009 mol), and the mixture was heated at 70 C. overnight. The reaction was cooled, quenched by addition of water and the mixture was extracted with DCM (3×), washed with water, brine, dried (Na2SO4), filtered and concentrated. The residue was purified by flash chromatography (0 to 25% hexanes/DCM) to obtain 400 mg (80%). Reference: Jean, L.; Rouden, J.; Maddaluno, J.; Lasne, M-C. J. Org. Chem. 2004, 69, 8893-8902.
With tetrakis(triphenylphosphine) palladium(0); potassium carbonate; In ethanol; water; toluene; at 110℃;
28.6 g 1,4-dibromonaphalene and 17.2 g 2-naphthyl boric acid product were placed into a three-neck flask (2 L), to which 600 mL toluene and 150 mL ethanol were added to dissolve the solid. The resulting mixture was aerated with nitrogen gas for 15 minutes and then, 150 mL aqueous K2CO3 solution (3.0 eq., 2M) and 2.3 g Pd(PPh3)4(2 mol %) were sequentially added. The reaction was heated up to 110 C. performed overnight at the temperature, and after the reaction finished, the resulting mixture was absorbed with activated carbon and filtered by suction filtration. The solvent was removed by rotary evaporation and the residual was dried and recrystallized with toluene and ethanol to produce 31.0 g Intermediate n in 93% yield
93%
With tetrakis(triphenylphosphine) palladium(0); potassium carbonate; In ethanol; water; toluene; at 110℃;Inert atmosphere;
28.6 g of <strong>[83-53-4]1,4-dibromonaphthalene</strong> and 17.2 g of 2-naphthaleneboronic acid were added to a 2L three-neck flask and 600 mL of toluene was added.Dissolve it with 150 mL of ethanol, purge with nitrogen for 15 minutes, and add 150 mL of an aqueous solution of K2CO3 (3.0 eq., 2 M).Finally 2.3 g of Pd(PPh3)4 (2 mol %) was added. The temperature was raised to 110C and the reaction was completed overnight. Add activated carbon adsorption, suction filtration, remove solvent, dryDrying, recrystallization from toluene and ethanol gave 31.0 g of intermediate n in a yield of 93%.
58%
With tetrakis(triphenylphosphine) palladium(0); potassium carbonate; In toluene; for 24h;Inert atmosphere; Reflux;
2.86 g (10 mmol) of <strong>[83-53-4]1,4-dibromonaphthalene</strong> and 1.72 g (10 mmol) of Intermediate-2 were introduced under nitrogen and dissolved in 40 ml of toluene0.58 g (0.5 mmol) of Pd (PPh3) 4 and 15 ml (30 mmol) of 2M K2CO3 were added, respectively, and refluxed for 24 hours.After the completion of the reaction, the temperature of the reaction mixture was cooled to room temperature, 150 ml of MC and 150 ml of H2O were added to extract the MC layer,Dried over MgSO4, concentrated and then columned with Hex: EA = 4: 1 to yield Intermediate-15, 1.93 (58%).
58%
With tetrakis(triphenylphosphine) palladium(0); potassium carbonate; In toluene; for 24h;Inert atmosphere; Reflux;
2.86 g (10 mmol) of <strong>[83-53-4]1,4-dibromonaphthalene</strong> and 1.72 g (10 mmol) of naphthalene-1-ylboronic acid were introduced under nitrogen, After 0.58 g (0.5 mmol) of Pd(PPh3)4 and 15 ml (30 mmol) of 2M K2CO3 were added, the mixture was refluxed for 24 hours, After the reaction was completed, the reaction mixture was cooled to room temperature, 150 ml of MC and 150 ml of H2O were added to extract the MC layer. The product was dried over anhydrous MgSO4 and concentrated. The product was
1,4-bis(4-methyldiphenylamino)naphthalene[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
62%
With tris-(o-tolyl)phosphine; sodium t-butanolate;palladium diacetate; In toluene; at 20℃;Heating / reflux;
Pd (II) acetate (78 mg, 0.35 mmol) and tri-o-tolylphosphine (0.21 g, 0.7 mmol) were stirred at room temperature in anhydrous toluene (50 mL) for 15 minutes, whereupon 1, 4-dibromonaphthalene (5.00 g, 17.48 mmol), 4-methyldiphenylamine (6.44 g, 35.13 mmol), and sodium-t-butoxide (4.20 g, 43.7) were added. The mixture was heated to reflux under nitrogen overnight, then cooled to room temperature, whereupon HCl (-20 mL) was added slowly. The mixture was filtered and the filtrate was passed through a basic alumina column. The toluene was removed to yield an orange solid. The solid was recrystallized from hexanes to yield a tan solid 5.3 g (62 percent).
With n-butyllithium; In tetrahydrofuran; N-methyl-acetamide; water;
Example 39 Preparation of 5,6-dichloro-2-[4-[(2,4-dioxothiazolidin-5-ylidene)methyl]naphth-1-yl]benzimidazole To a solution of 1,4-dibromonaphthalene (1.00 g, 3.50 mmol) in tetrahydrofuran (15 mL) were added n-butyllithium (1.6 mol/L; 3.1 mL) and dimethylformamide (0.54 mL, 7.0 mmol) sequentially at =78 C. under nitrogen atmosphere, and the mixture was stirred for 15 min. Water was added, and the mixture was extracted with ethyl acetate. The organic layer was combined, washed with brine and dried on anhydrous sodium sulfate. The solvent was removed under reduced pressure, and the residue was purified by column chromatography (8:1 hexane/ethyl acetate) to afford 4-bromo-1-naphthalenecarboxaldehyde (458 mg, 56%). 1H NMR (400 MHz, CDCl3) delta (ppm) 7.6-7.8 (m, 2H), 7.78 (d, J=7.8 Hz, 1H), 7.94 (d, J=7.8 Hz, 1H), 8.34 (dd, J=8.2, 1.6 Hz, 1H), 9.25 (dd, J=8.2,1.6 Hz, 1H), 10.3 (s, 1H)
With tetraethyl ammonium aqueous solution;tetrakis(triphenylphosphine) palladium(0); In tetrahydrofuran; water; toluene; at 100℃; for 24h;
Synthesis of Compound 19; 100 mg (0.215 mmol) of intermediate C was dissolved in 1 ml of THF and then, a mixture of 24.6 mg (0.086 mmol) of 1,4-dibromobenzene and 10 mg (0.009 mmol) of tetrakis(triphenylphosphine)palladium(0) (Pd(PPh3)4) dissolved in 2 ml of toluene was added thereto. 2 ml of 20% tetraethyl ammonium aqueous solution was added to the mixed solution and the mixed solution was stirred for 24 hours at 100 C. After cooling down the resultant to room temperature, the resultant product was separated and purified using a absorption silica gel column chromatography to obtain 69.0 mg of compound 19 (Yield: 95%). The structure of Compound 19 was identified through 1H NMR spectroscopy.1H-NMR (300 MHz, CDCl3): delta7.67(d, 2H), delta7.60(dd, 2H), delta7.44(d, 2H), delta7.37(s, 2H), delta7.32(s, 2H), delta6.95(m, 4H), delta6.89(m, 2H), delta6.85(m, 2H), delta6.76(m, 4H), delta6.73(m, 2H), delta6.67(m, 2H), delta6.58(m, 2H), delta6.48(m, 2H), delta6.42(m, 2H), delta3.73(m, 6H)
With potassium carbonate;tetrakis(triphenylphosphine) palladium(0); In tetrahydrofuran; water; for 24h;Heating / reflux;
Example 26 : Preparation of compound 85; [273][274] 26-A. Preparation of compound 26a[275] Under N atmosphere, <strong>[83-53-4]1,4-dibromonaphthalene</strong> (5 g, 17.5 mmol),4-bromophenylboronic acid (3.5 g, 17.5 mmol), and Pd(PPh ) (1.0 g, 0.88 mmol) were3 4 <n="83"/>added to a 2 M aqueous solution of potassium carbonate (10 rnL) and THF (200 rnL). The mixture was refluxed under stirring for about 24 hours. After completing the reaction, the mixture was cooled to normal temperature. The organic layer was separated from the reaction mixture, dried over magnesium sulfate, and distilled under reduced pressure. The residue was purified by column chromatography to prepare compound 26a (4.8 g, 75%). MS [M] = 362
1,4-bis[N-(4-diphenylaminophenyl)-N-phenylamino] naphthalene[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
16%
In o-xylene; water; toluene;
(Synthesis of 1,4-bis[N-(4-diphenylaminophenyl)- N-phenylamino]-naphthalene (8)) 26.5 g of N,N,N'-triphenyl-1,4-phenylenediamine, 9.0 g of 1,4-dibromonaphthalene, 6.0g of sodium t-butoxide and 0.008 g of palladium t-butylphosphinebromide dimmer were dissolved in 200 mL of o-xylene. The reaction was carried out at a temperature of 70C for 5 hours under a nitrogen atmosphere. After the reaction, the resulting reaction mixture was extracted with a mixture of water/toluene and the organic layer was dehydrated over anhydrous magnesium sulfide, followed by concentration. The resulting concentrate was fractionated by chromatography on a column of silica gel and the desired fractions were concentrated under reduced pressure to provide solid. The solid was recrystallized from toluene and was then subjected to sublimation purification, thereby providing 3.9 g of 1,4-bis[N-(4-diphenylamino-phenyl)-N-phenylamino]naphthalene (1) as yellow solid. The yield was 16%.
1,4-bis[9-(2-naphthyl)-10-anthryl]naphthalene[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
66%
With potassium carbonate;tetrakis(triphenylphosphine) palladium(0); In water; methoxybenzene; for 24h;Heating / reflux;
Example 15 : Preparation of compound 34; [215][216] Under N atmosphere, 1,4-dibromonaphthalene (1.5 g, 5.2 mmol),<strong>[597554-03-5]10-(2-naphthyl)anthracene-9-boronic acid</strong> (4.0 g, 11.4 mmol), Pd(PPh ) (0.3 g, 0.263 4 mmol) were added to a 2 M aqueous solution of potassium carbonate (80 mL) and anisole (100 mL). The mixture was refluxed under stirring for about 24 hours. After completing the reaction, the mixture was cooled to normal temperature. The organic layer was separated from the reaction mixture, filtered to obtain a solid. The solid was recrystallized from THF and EtOH to prepare a compound 34 (2.5 g, 66%). MS [M+H] = 733 [217]
1,4-bis(10-phenylanthracene-9-yl)naphthalene[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
77%
With potassium carbonate;tetrakis(triphenylphosphine) palladium(0); In tetrahydrofuran; water; for 24h;Heating / reflux;
Example 14 : Preparation of compound 33; [211]- P[212] Under N atmosphere, <strong>[83-53-4]1,4-dibromonaphthalene</strong> (1 g, 3.5 mmol), lO-phenylanthracene-9-boronic acid (2.62 g, 8.75 mmol), Pd(PPh ) (0.3 g, 0.3 mmol) were added to a 2 M aqueous solution of potassium carbonate (70 mL) and THF (150 mL). The mixture was refluxed under stirring for about 24 hours. After completing the reaction, the mixture was cooled to normal temperature. The organic layer was separated from the reaction mixture, filtered to obtain a solid. The solid was re- crystallized from THF and EtOH to prepare a compound 33 (1.7 g, 77%). MS [M] = 632
With potassium carbonate;tetrakis(triphenylphosphine) palladium(0); In water; methoxybenzene; for 24h;Heating / reflux;
Example 18 : Preparation of compound 41; [227] <n="78"/>[228] Under N atmosphere, <strong>[83-53-4]1,4-dibromonaphthalene</strong> (1 g, 3.5 mmol), the compound 6e(3.27 g, 7.69 mmol) prepared in 6-E of Example 6, and Pd(PPh ) (0.2 g, 0.18 mmol) were added to a 2 M aqueous solution of potassium carbonate (100 mL) and anisole (100 mL). The mixture was refluxed under stirring for about 24 hours. After completing the reaction, the mixture was cooled to normal temperature. The organic layer was separated from the reaction mixture, filtered to obtain a solid. The solid was recrystallized from THF and EtOH to prepare a compound 41 (2.45 g, 83%). MS [M] = 884
With potassium carbonate;tetrakis(triphenylphosphine) palladium(0); In water; methoxybenzene; for 24h;Heating / reflux;
Example 17 : Preparation of compound 38; [223][224] Under N atmosphere, <strong>[83-53-4]1,4-dibromonaphthalene</strong> (1 g, 3.5 mmol), the compound 5e(3.27 g, 7.69 mmol) prepared in 5-E of Example 5, and Pd(PPh ) (0.2 g, 0.18 mmol)3 4 were added to a 2 M aqueous solution of potassium carbonate (100 mL) and anisole (100 mL). The mixture was refluxed under stirring for about 24 hours. After completing the reaction, the mixture was cooled to normal temperature. The organic layer was separated from the reaction mixture, filtered to obtain a solid. The solid was recrystallized from THF and EtOH to prepare a compound 38(2.3 g, 75%). MS [M] = 884
With potassium phosphate; copper(l) iodide; In 1,4-dioxane; for 15h;Heating / reflux;
Preparation of 4'-naphthyl-<strong>[56525-79-2]3,6-diphenylcarbazole</strong> Reaction 6As depicted in Reaction 6, a solution of 1Og (31.3 mmol) of carbazole, 13.5g (31.3 mmol) of 1,4-dibromonaphthalene, CuI, diaminohexane and K3PO4 in dioxane was refluxed for 15 hours. After completion of the reaction, the reaction mixture was <n="32"/>extracted with ethyl acetate. After the solvent was removed under reduced pressure, the residue was purified by column chromatography to give the title compound. The product was collected by filtration under reduced pressure and dried. Yield: 6percent. MS (El) (Calcd. for C34H22BrN: 523.09, Found: 523).
With 18-crown-6 ether; copper; potassium carbonate; In nitrobenzene;Reflux;
239 g of 9H-carbazole (233.24 mmol, 1 eq) and 100 g of <strong>[83-53-4]1,4-dibromonaphthalene</strong> (349.85 mmol, 1.5 eq) and 3 g of copper (Cu) of (46.65mmol, 0.2eq), were added in an 2L round flask (46.65 mmol, 0.2eq), 31 g of 18-crown-6 (116.62 mmol, 0.5eq) and 64.5 g (446.48 mmol, 2eq) of potassium carbonate (K2CO3) were added to nitrobenzene. 1,000 ml of the mixture was stirred under reflux. After the completion of the reaction, nitrobenzene was distilled off under reduced pressure, extracted with dichloromethane (CH2Cl2)/water (H2O), and the CH2Cl2 layer was dried over magnesium sulfate (MgSO4). Silica-gel column purification gave 71.2 g of compound 1-1 in 82% yield.
62%
With potassium phosphate; copper(l) iodide; (S,S)-1,2-diaminocyclohexane; In 1,4-dioxane; for 24h;Heating;
Bromo-1,4-naphthalene 14.6g (51mmol) and 9H-carbazole 1.45g (8.7mmol) was dissolved in 1,4-dioxane copper iodide 0.31g (1.6mmol), trans-1,2-diaminocyclohexane 1.9g (16.9mmol), the third one was added potassium phosphate 22.8g (107mmol) then 1,4 and stir for 24 hours at the boiling point of dioxane. After cooling to room temperature, the reaction was extracted using ethyl acetate After removing the solvent under reduced pressure and then, 15 of ethyl acetate and hexane: using a silica gel with a solution of a volume ratio of 1 as a developing solvent It was the purified by a chromatography. After separation of the desired target compound, the target compound was dried under reduced pressure through the 9-(4-bromo-1-yl)-9H-carbazole (compound 10, 2.00g) was obtained in 62% yield.
35%
With potassium phosphate; copper(l) iodide; In 1,4-dioxane; for 15h;Heating / reflux;
Preparation of 9-(4'-bromonaphthyl)-carbazole Reaction 1As depicted in Reaction 1 , 3.3g (20 mmol) of carbazole, 8.6g (40 mmol) of 1 ,4-dibromonaphthalene, CuI, diaminohexane and K3PO4 were dissolved in dioxane and refluxed for 15 hours. After completion of the reaction, the reaction mixture was extracted with ethyl acetate. After the solvent was removed under reduced pressure, the residue was purified by column chromatography to give the title compound. The product was collected by filtration under reduced pressure and dried. Yield: 35%. MS (El) (Calcd. for C22Hi4BrN: 371.03, Found: 371).
With copper(l) iodide; trans-1,2-Diaminocyclohexane; In 1,4-dioxane; for 24h;Reflux;
9H-Carbazole (9H-carbazole) 1g (6.3mmol), 1,4-dibromo-naphthalene (<strong>[83-53-4]1,4-dibromonaphthalene</strong>) 3.6g (12.6mmol), CuI1.2g (6.3mmol), trans-1,2-diaminocyclohexane (trans-1,2-diaminocyclohexane) 0.7g (6.3mmol), placed in the K3PO42.6g (12.6mmol) 1,4- dioxane (1.4-dioxane) was refluxed for one day. After cooling to room temperature after completion of the reaction it was isolated by extraction with EA / H2O (Sat'd NaHCO3). The organic layer was dried over MgSO4 and evaporated under reduced pressure to remove the solvent. Separation using a short filter (Short filter) to obtain the desired product compound 175-3.
With tetrakis(triphenylphosphine) palladium(0); potassium carbonate; In ethanol; water; toluene;Reflux; Inert atmosphere;
The 2.86g (0.01mole) 1,4-bromonaphthyl, phenylboronic acid 1.21g (0.01mole), potassium carbonate 4.15g (0.03mole), toluene 50 ml, ethanol 30 ml and water 30 ml mixed, under the nitrogen atmosphere, by adding four (triphenylphosphine) palladium 0.23g (0.0002mole), heating to reflux for reaction, monitoring board to the reaction is complete, the end of the reaction, the reaction liquid turns on lathe does, by adding 100 ml of methylene chloride, the silica gel and completely dissolved, filtrate plus 100 water, washing with water, the organic phase is separated, fasten it dry and heat two times with ethanol, filtered, get 2.3g solid intermediate G1-2, the yield is 80%.
With sodium carbonate;tetrakis(triphenylphosphine) palladium(0); In 1,2-dimethoxyethane; water; toluene; for 8h;Heating / reflux;
Under an argon current, to a three-necked flask, 81.9 g of phenylboronic acid, 200 g of dibromonaphthalene, 16.2 g of tetrakis (triphenylphosphine) palladium (Pd(PPh3)4), 1,050 ml of 2M Na2CO3 solution, 3.4 L of dimethoxyethane, and 3L of toluene were charged, and the mixture was refluxed for 8 hours. The reactant was extracted with toluene and water, followed by drying with anhydrous sodium sulfate. The resultant was concentrated under reduced pressure, and the obtained crude product was subjected to column purification, whereby the following Intermediate 1 was obtained as 70 g of white powder. By an FD-MS (field desorption mass spectrometry) analysis, main peaks of m/z = 282 and m/z = 284 with respect to C16H11Br = 283 were obtained, so the white powder was identified as the following Intermediate 1.
With sodium carbonate;tetrakis(triphenylphosphine) palladium(0); In ethanol; toluene; at 120℃; for 12h;
5.4 g (44 mmol) of phenylboronic acid, 18.9 g (66 mmol) of <strong>[83-53-4]1,4-dibromonaphthalene</strong>, 2.0 g (1.76 mmol) of Pd(PPh3)4, 14.0 g (132 mmol) of Na2CO3, 200 mL of toluene, and 100 mL of ethanol were stirred under reflux at 120C for 12 hours. After the reaction completed, the reaction product was washed with distilled water, and extracted with ethylacetate, after which the resultant organic layer was dried with MgSO4, evaporated using a rotary evaporator to remove the solvent, and then purified using column chromatography, thus obtaining 9.1 g (32.14 mmol) of Compound 3-1.
With sodium carbonate;tetrakis(triphenylphosphine) palladium(0); In Dimethyl ether; water; for 8h;Reflux; Inert atmosphere;
Under an argon atmosphere, 230g of <strong>[83-53-4]1,4-dibromonaphthalene</strong>, 121g of 2-formylphenylboronic acid and 18.5g of tetraxis(triphenylphosphine)palladium(0) were placed in a flask. 2.4L of dimethyl ether (DME) and 1.2L of a 2M aqueous sodium carbonate solution were added to this flask, and the resultant was refluxed with stirring while heating for 8 hours. After cooling to room temperature, an aqueous phase was removed. An organic phase which had been separated was washed with water and saturated brine, and then dried with magnesium sulfate. After the magnesium sulfate was filtered out, the organic phase was concentrated. The resulting residue was purified by means of silica gel column chromatography, whereby 170g (yield: 67%) of 1-bromo-4-(2-formylphenyl) naphthalene was obtained.
67%
With sodium carbonate;tetrakis(triphenylphosphine) palladium(0); In 1,2-dimethoxyethane; water; for 8h;Inert atmosphere; Reflux;
(A-1) Synthesis of 1-bromo-4-(2-formylphenyl)naphthalene Under the atmosphere of argon, 230g of <strong>[83-53-4]1,4-dibromonaphthalene</strong>, 121g of 2-formylphenylboronic acid and 18.5g of tetrakis(triphenylphosphine)palladium(O)were placed in a flask. To the resulting mixture, 2.4 L of dimethoxyethane (DME) and 1.2 L of an aqueous 2M sodium carbonate solution were added, followed by stirring under reflux for 8 hours. After cooling to the room temperature, an aqueous phase was removed, and an organic phase was washed with water and saturated saline, and dried with magnesium sulfate. After filtering off magnesium sulfate, the organic phase was concentrated. The residues were purified by silica gel coiumn chromatography, whereby 170g (yield 67%) of 1-bromo-4-(2-formylphenyl)naphthalene as an intended product was obtained.
67%
With tetrakis(triphenylphosphine) palladium(0); sodium carbonate; In 1,2-dimethoxyethane; water; for 8h;Inert atmosphere; Reflux;
Argon atmosphere, 1,4-dibromo-naphthalene 230g, 121g 2- formyl phenylboronic acid, tetrakis (triphenylphosphine) In a flask with palladium (0), and 18.5g, dimethoxy THF (DME) 2.4L , aqueous 2M sodium carbonate solution was added to 1.2L, and the mixture was stirred under reflux heating for 8 hours. After cooling to room temperature (25 ), to remove the water layer. The organic layer was washed with water and brine, dried over magnesium sulfate. After magnesium sulfate was separated by filtration, and the organic layer was concentrated. The residue was purified by silica gel column chromatography to give the 1-bromo-4- (2-formyl-phenyl) naphthalen-170g (67% yield) desired.
(E)-N-[(4-bromonaphthalen-1-yl)methylidene]hydroxylamine[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
With hydroxylamine; In ethanol; water;
Step A: Preparation of 4-bromo-1-naphthalenecarboxaldehyde oxime An aqueous solution of hydroxylamine (1.25 mL, 50% in water) was added to a stirred solution of 4-bromo-1-naphthalenecarboxaldehyde (3.7 g, 15.7 mmol, prepared from commercially available 1,4-dibromonaphthalene by the method described in European Journal of Organic Chemistry 2006, 10, 2329-2335) in ethanol (30 mL). After stirring at room temperature for 3 h, the reaction mixture was concentrated under reduced pressure to provide the title compound as a pale yellow solid (3.8 g). 1H NMR (Me2S(O)-d6): delta 11.60 (s, 1H), 8.81 (s, 1H), 8.71 (d, 1H), 8.24 (d, 1H), 7.95 (d, 1H), 7.74 (m, 3H).
With sodium carbonate;trans-bis(triphenylphosphine)palladium dichloride; In toluene; at 100℃; for 3h;
Preparation of Compound (119)Compound (118) (9.2 g, 33.9 mmol), 1,4-dibromonaphthalene (8.8 g 30.8 mmol) and trans-dichlorobistriphenylphosphine palladium (II) (Pd(PPh3)2Cl2 (2.1 g, 3.1 mmol) were dissolved in toluene (300 mL). After adding 2 M sodium carbonate solution (150 mL), the mixture was heated to 100 C., and reacted at the same temperature for 3 hours. The reaction mixture was extracted with dichloromethane (300 mL), and the extract was washed with aqueous sodium chloride solution (300 mL), dried over anhydrous magnesium sulfate, and filtered. After evaporating the organic layer under reduced pressure, the solid obtained was recrystallized from tetrahydrofuran (100 mL) to obtain the desired compound (119) (7.7 g, 17.7 mmol).
With tetrakis(triphenylphosphine) palladium(0); potassium carbonate; In tetrahydrofuran; water; toluene; at 80℃;
The [Reaction Scheme 12] [Formula 2-a] (5g, 0.012mol), [formula b-2] (6.64g, 0.014mol) obtained from,Tetrakis (triphenylphosphine) palladium (0.28g, 0.001mol), potassium carbonate (3.34 g, 0.024mol) and the mixture toluene 25 mL, tetrahydrofuran, 25mL, 10 mL of water were placed. The temperature of the reactor temperature was raised to 80 degrees and stirred overnight.When the reaction is complete cool down the temperature of the reactor to room temperature and concentrated under reduced pressure and extracted with ethyl acetate. Separated by column chromatography and recrystallized with toluene and acetone to give the [formula 22] (3g). (37.3%). The [Reaction Scheme 14] In the Formula 2-b] Instead of using a 1,4-dibromo-naphthalene, and [Formula 2-a] except that instead of the phenyl boronic acid and anthracene is, using the same method [Chemical Formula 6 got the -h] (28.5 g). (Yield: 84.3%)
84.3%
With tetrakis(triphenylphosphine) palladium(0); potassium carbonate; In water; toluene; for 24h;Reflux;
The procedure of Synthesis Example 1-4 was repeated except that <strong>[83-53-4]1,4-dibromonaphthalene</strong> was used instead of 1-bromo-4-iodobenzene to obtain 28.5 g of . (Yield: 84.3%)
With sodium carbonate;tetrakis(triphenylphosphine) palladium(0); In ethanol; water; toluene; at 120℃; for 2h;
Preparation of Compound (262); In toluene (200 mL) and ethanol (100 mL), dissolved were Compound (261) (7.1 g, 23.8 mmol), <strong>[83-53-4]1,4-dibromonaphthalene</strong> (7.5 g, 26.2 mmol) and tetrakispalladium (O) triphenylphosphine (Pd(PPh3)4) (2.8 g, 2.4 mmol). To the solution, aqueous 2M sodium carbonate solution (120 mL) was added, and the mixture was stirred at 120 C. under reflux for 2 hours. Then, the mixture was cooled to 25 C., and the reaction was quenched by adding distilled water (200 mL). The reaction mixture was extracted with ethyl acetate (100 mL), and the extract was dried under reduced pressure. Recrystallization from tetrahydrofuran (10 mL) and methanol (200 mL) gave the objective compound (262) (6.6 g, 14.4 mmol).
CuCN (5.0g, 56.3mmol) was added to a solution of 1,4-dibromonaphthalene (20g, 70.4mmol) in DMF (250mL),the mixture was reacted for 16hrs at 125C, evaporated under reduced pressure. Aqueous ammonia (200mL) and EA(200mL) were added to the residue, the mixture was stirred for 1h and organic phase was seperated. The organic phasewas in turn washed with water (100mL33) and saturated brine (100mL), dried over anhydrous magnesium sulfate,filtered, evaporated under reduced pressure. The residue was purified with silica chromatography (PE:EA = 10:1) togive compound 3-d (5.1g, yield 31%). LC-MS (ESI): m/z = 232 [M+H]+.
27%
In N,N-dimethyl-formamide; at 130℃; for 12h;Inert atmosphere;
To a dry 1 L round bottom flask were added compound A (1,4-dibromonaphthalene, 57.19 g, 200 mmol), CuCN (10.75 g, 120 mmol) and DMF (600 mL), and the resulting mixture was stirred at 130C. under nitrogen atmosphere for 12 hours. The reaction mixture was cooled to room temperature and transferred to a 5 L flask. Ethyl acetate (1.8 L) was added, and the resulting mixture was stirred at room temperature for 2-3 hours to give a grayish brown slurry. The slurry was filtered by suction, and the filtrate was collected. The filter cake was washed with a small amount of ethyl acetate, and the washing liquid was combined into the filtrate. The filtrate was washed with water (1 L5), dried over anhydrous sodium sulfate, and evaporated on a rotary evaporator to remove the solvent. To the resulting yellow solid was added ethyl acetate-petroleum ether (400 mL, a volume ratio of 1:3), and the resulting mixture was warmed to 70C. and stirred to give a clear solution. After the solution was cooled slowly with stirring to room temperature, a yellow slurry was obtained. The slurry was filtered by suction, the filtrate was collected which was evaporated to dryness on a rotary evaporator, and the resulting residue was purified by silica gel column chromatography, and eluted with ethyl acetate-petroleum ether (1:50?1:30) to obtain a pure product of B as a white solid, 12.53 g; yield: 27%; m.p. : 103-104C.; 1H NMR (DMSO-d6, 400 MHz), delta 8.26-8.31 (m, 1H, Ar-H), 8.13-8.18 (m, 1H, Ar-H), 8.07 (s, 2H, Ar-H), 7.85-7.92 (m, 3H, Ar-H).
26%
In N,N-dimethyl-formamide; at 125℃;
[00285] Step A: 4-Bromo- 1 -naphthonitrileA mixture of 1 ,4-dibromonaphthalene (24.06g, 84mmol) and copper cyanide (6.02g, 67mmol) in DMF (85mL) was heated to 125C overnight. The mixture was partially concentrated to remove DMF and the resulting residue washed with aqueous ammonium hydroxide and extracted with ethyl acetate. The organic layer was concentrated and purified by chromatography to yield 4-bromo-l -naphthonitrile (5.13g, 26%).
26%
In N,N-dimethyl-formamide; at 130℃; for 12h;Inert atmosphere;
General procedure: A mixture of 3a-3g (0.1 mol for 3a-3e and 3g; 0.4 molfor 3f) and CuCN (26.87 g, 0.3 mol for 3a-3e and 3g; 21.49g, 0.24 mol for 3f) in DMF (300 mL) were stirred at 130C in N2 atmosphere for 12 h, when TLC analysis indicated completion of reaction. On cooling to room temperature, the reaction mixture was diluted with CH2Cl2 (900 mL) and the resulting mixture was further stirred for 1 h and filtered off. The filtrate was washed with 5% brine (500 mL 5), dried (Na2SO4) and evaporated on a rotary evaporator to afford a black oil, which was purified by column chromatography to afford the pureproduct 4a-4g.
With tetrakis(triphenylphosphine) palladium(0); potassium carbonate; In water; toluene; at 100℃; for 48h;Schlenk technique; Inert atmosphere;
This compound is synthesized by the Suzuki coupling reaction (Suzuki coupling reaction) methods. 100 mL 2 gu shrink (Schlenk) flask, 1,4-dibromo-naphthalene of the condenser is installed (4g, 14.0mmol), 4- methoxyphenyl boronic acid (2.34g, 15.4mmol) and a catalytic tetrakis(triphenylphosphine)palladium(0) (0.485 g, 3 mol%, 0.42 mmol) and 20 mL of toluene to dissolve 10 bungan stirring, 2M K2CO3 aqueous solution 14 mL was added, and then nitrogen stream under 100 It was stirred at reflux for 48 hours. When the reaction was completed, extraction with ether, the organic layer was washed brine and water.MgSO4, dried over, filtered and the solvent of the resulting solution under reduced pressure, and then separated by column chromatography (Silica, Hexane), and dried under vacuum (yield 75%).
Example 1, Step aA solution of 1,4-dibromonaphthalene (1.0 g, 3.49 mmol) in toluene (10 niL) was purged with 2 for 10 minutes. Then tributyl(l-ethoxyvinyl)tin (1.38 g, 3.84 mmol) was added followed by Pd(Ph3P)2Cl2 (251 mg, 0.349 mmol). The reaction mixture was purged with 2 for 10 minutes and allowed to reflux at 100 C overnight. The reaction mixture was quenched with saturated KF solution (10 mL) and stirred at room temperature for 2 hrs. The reaction mixture was filtered through a diatomaceous earth (Celite) plug, and the organic layer was separated and concentrated in vacuo. To the resulting residue, 3 N HC1 (20 mL) was added at RT and stirred for 2 hrs. Then the reaction mixture was extracted with EtOAc, washed with brine, dried over Na2S04 and concentrated in vacuo. The crude was purified by flash chromatography (ISCO, EtOAc: petroleum ether, 20:80) to obtain bromide la (600 mg). LC/MS (Condition 8): Rt = 1.99 min. XH NMR (CDCI3, delta = 7.26 ppm, 400 MHz): delta 8.75-8.73 (m, 1H), 8.36-8.34 (m , 1H), 7.85 (d, J = 7.8, 1H), 7.76 (d, J = 7.8, 1H), 7.69-7.65 (m , 2H ), 2.76 (s, 3H ). LC/MS: Anal. Calcd. for [M+H]+ Ci2H10BrO: 248.98; found 249.0.
With dichloro bis(acetonitrile) palladium(II); 1,8-bis[3'-(N-ethyl-imidazolium-1-yl)propoxy]anthraquinone hexafluorophosphate; tetrabutylammomium bromide; potassium carbonate; silver(l) oxide; In ethanol; water; at 60℃; for 14h;
General procedure: Application example 1General procedure for the coupling reaction of Suzuki-Miyaura.In a typical reaction,Will be a halogenated aromatic hydrocarbon (0.5 mmol),Phenylboronic acid (0.6 mmol), base (1.2 mmol),Cyclic nitrogen heterocyclic carbene palladium complex (0.2 mol %)Add to the mixed solvent (3mL, methanol / water = 3 / 1, V / V),This reaction system was stirred in air at a temperature of 60 Torr C. After the end of the expected reaction time, the reaction is stopped,Water (20 mL) was then added to the mixed system of the reaction.Dichloromethane (10 mL) was added and the mixture began to separate.The organic layer was then washed three times with water (10 mL each time).Drying with anhydrous magnesium sulfate, the solution was filtered,The solvent was concentrated to 5 mL.The product is obtained by GC analysis or column separation.
84%
With tetrakis(triphenylphosphine) palladium(0); sodium carbonate; In water; toluene; at 80℃; for 24h;Inert atmosphere;
A general Pd-catalyzed coupling reaction procedure is explained with the case of 1,4-diphenylnaphthalene 14DPN: A mixture of <strong>[83-53-4]1,4-dibromonaphthalene</strong> (0.57 g, 2.0 mmol), phenylboronic acid (0.55 g, 4.5 mmol), sodium carbonate (0.54 g, 5.0 mmol), water (5 mL) and toluene (32 mL) in a 100 mL two-necked round bottom flask was sealed with septa and deoxygen by bubbling with nitrogen gas for 40 minitues. Afterwards tetrakis(triphenylphosphine)palladium (47 mg, 0.045 mmol) was quickly added into the mixture by opening the septum, and the mixture was deoxygen for additional 10 minitues. The reaction was kept at 80 C uner a nitrogen atmosphere for 24 hours. After cooled down to room temperature, the reaction was extracted with ethylacetate and water for three times. The oragnic layer was collected, and the solvent was removed by a rotary evaporator. The residue was purified by silica gel chromatagraphy with hexane and dichloromethane (15:1) as the elute to afford a white solid, 1,4-diphenylnaphthalene 14DPN (0.47 g, 1.68 mmol), in a 84 % yield.
With potassium carbonate;tetrakis(triphenylphosphine) palladium(0); In ethanol; water; toluene; at 20 - 40℃; for 2h;
Example 1.32.15 g (7.5 mmol) of 1 ,4-dibromonaphthalene and 0.95 g (1.8 mmol) of the boron compound from example I.2 were dissolved in 40 ml of toluene at 40C. Thereafter, a solution of 3.0 g of potassium carbonate, 20 ml of water and 8 ml of ethanol, and 0.5 g (0.43 mmol) of tetrakistriphenylphosphinepalladium(O) were added. The mixture was stirred at room temperature for 2 h. It was extracted with dichloromethane and purified by chromatography on silica gel with 10: 1 petroleum ethertoluene. This gave 0.61 g (56%) of the title compound as a red compound. Rf (1 :9 toluene:petroleumether) = 0.56.
With I2; n-butyllithium; In tetrahydrofuran; hexane;
Synthesis Example 11-Iodo-4-bromonaphthalene100 g (350 mmol) of 1,4-dibromonaphthalene are initially introduced in 1 l of THF, cooled to -70° C., and 235 ml of n-BuLi (1.6 M in hexane, 370 mmol) are added dropwise.After 1 h, 103 g of I2 (406 mmol) in 250 ml of THF are added dropwise, the mixture is stirred at -70° C. for a further 2 h, warmed to 0° C. and quenched by the addition of 50 ml (644 mmol) of aqueous NaHSO3 solution (w=39percent).The phases are separated, and the aqueous phase is extracted once with MTB.The combined organic phases are washed with saturated sodium chloride solution, dried over sodium sulfate, filtered and evaporated in a rotary evaporator.The residue is purified by column chromatography (SiO2, heptane), and the further purification is carried out by recrystallisation from isopropanol, giving 1-iodo-4-bromonaphthalene as a yellow solid.
100 g (350 mmol) of 1,4-dibromonaphthalene are initially introduced in 1 l of THF, cooled to -70° C., and 235 ml of n-BuLi (1.6 M in hexane, 370 mmol) are added dropwise. After 1 h, 103 g of I2 (406 mmol) in 250 ml of THF are added dropwise, the mixture is stirred at -70° C. for a further 2 h, warmed to 0° C. and quenched by the addition of 50 ml (644 mmol) of aqueous NaHSO3 solution (w=39percent). The phases are separated, and the aqueous phase is extracted once with MTB. The combined organic phases are washed with saturated sodium chloride solution, dried over sodium sulfate, filtered and evaporated in a rotary evaporator. The residue is purified by column chromatography (SiO2, heptane), and the further purification is carried out by recrystallisation from isopropanol, giving 1-iodo-4-bromonaphthalene as a yellow solid.
With potassium carbonate; In N,N-dimethyl-formamide; at 110℃; for 6h;Green chemistry;
General procedure: To a suspension of halobenzenes (1.0 mmol), styrene (1.2 mmol), K2CO3 (2.0 mmol) and Pd/NH2-SiO2 (0.05 mol%) are added to a 25 mL round-bottom flask equipped with a magnetic stirrer. 5.0 mL of distilled dry DMF is added and the reaction mixture is stirred at 110 ?C with heating on an oil bath for 4-6 h. The reaction is monitored by TLC (or GC if necessary). On completion of the reaction, the mixture is filtered and the filtrate poured into water (50 mL) and extracted with CH2Cl2 (3×15 mL).The combined organic phases are dried over Na2SO4 or MgSO4, filtered and evaporated in vacuum. The mixture is then purified by column chromatography over silica gel or recrystallization to afford a product with high purity.
With magnesium; ethylene dibromide; In tetrahydrofuran; at 35℃; for 1h;Sonication; Inert atmosphere;
General procedure: A mixture of magnesium turnings (0.027g, 1.1mmol), bromobenzene (0.15g, 1mmol), bis(tri-n-butyltin) oxide (0.60g, 1mmol) and 1,2-dibromoethane (0.094g, 0.5mmol) as initiator in dry THF (5mL) was sonicated for 1h in an ultrasonic cleaning bath at around 35C, with monitoring of the reaction by TLC. Once the reaction finished, aqueous saturated NH4Cl solution (40mL) was added and extracted with ethyl acetate (3×20mL). The combined extracts were washed with brine (60mL) and dried over anhydrous magnesium sulfate. The solvent was removed under reduced pressure and the crude product was purified by column chromatography with silica gel doped with 10% of KF to retain the tri-n-butyltin bromide formed during the reaction.
With magnesium; ethylene dibromide; In tetrahydrofuran; at 35℃; for 1h;Sonication; Inert atmosphere;
General procedure: A mixture of magnesium turnings (0.036g, 1.5mmol), bromobenzene (0.15g, 1mmol), tri-n-butyltin chloride (0.49g, 1.5mmol) and 1,2-dibromoethane (0.094g, 0.5mmol) as initiator in dry THF (5mL) was sonicated for 1h in an ultrasonic cleaning bath at around 35C, with monitoring of the reaction by TLC. Once the reaction finished, aqueous saturated NH4Cl solution (40mL) was added and extracted with ethyl acetate (3×20mL). The combined extracts were washed with brine (60mL) and dried over anhydrous magnesium sulfate. The solvent was removed under reduced pressure and the product was isolated by column chromatography with silica gel doped with 10% of KF to retain tri-n-butyltin halides formed during the reaction. 4 (0.286, 0.78mmol, 78%) eluted with 98:2 (hexane/diethyl ether).
4,4'-(naphthalene-1,4-diyl)dibenzaldehyde[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
83.3%
With tetrakis(triphenylphosphine) palladium(0); sodium carbonate; In ethanol; water; toluene; at 90℃; for 24h;Inert atmosphere;
Synthesis of 4,4'-(naphthalene-1,4-diyl)dibenzaldehyde:30 mL toluene, 10 mL ethanol and 15 mL 2 MNa2CO3aq. were added to a mixture of 1 g <strong>[83-53-4]1,4-dibromonaphthalene</strong>(3.5 mmol), 0.8 g (4-formylphenyl)boronic acid(5.33 mmol) and 0.32 g Pd(PPh3)4 (0.28 mmol). Then thesuspension was heated at 90 C with stirring under an argon atmosphere. After 24 h, the mixture was cooled toroom temperature and extracted with CH2Cl2 and driedover MgSO4 before removing the solvent. Finally, the residuewas purified by column chromatography on silica gelusing CH2Cl2 and petroleum ether (2:1) as eluent to givea white solid, with a yield of 83.3% (0.98 g).
73.1%
With bis-triphenylphosphine-palladium(II) chloride; In tetrahydrofuran; toluene; at 90℃;Inert atmosphere;
A.Compound 1,4-dibromo-naphthalene (500 mg, 1.75 mmol)4-formylphenylboronic acid (576.77 mg, 3.85 mmol),Bis (triphenylphosphine) palladium dichloride Pd (PPh3) 2Cl2 (122.8 mg, 0.18 mmol)Was dissolved in 40 mL of a mixed solvent of toluene and tetrahydrofuran(Vtoluene: VTHF = 1: 1)The reaction was refluxed at 90 C under nitrogen,Thin layer chromatography to the reaction is complete.After the resulting solution was spin off the organic solvent,Extracted with ethyl acetate,Organic layer washed three times,Saturated NaCl solution once,Dried over anhydrous sodium sulfate,The solvent was evaporated under reduced pressure.The crude product was passed through a pure dichloromethane column,4,4 '- (naphthalene-1,4-diyl) benzaldehyde (pale yellow powder, 429.7 mg, yield 73.1%).
In a dry 250 ml flask 3,00g (10 mmol, 1 equiv.) <strong>[83-53-4]1,4-dibromonaphtalene</strong> is dissolved in 150 ml dry diethyl ether. The mixture is placed under inert atmosphere and cooled to -78C. Subsequently, 5,5 ml (0,011 mol, 1,1 equiv.) of a 2M solution of BuLl is slowlydripped in. After continuing the reaction for 30 mm at -30C, 3,44 g (0,020 mol, 1,5equiv.), the mixture is cooled to -78C and added by means of a cannula to a 250m1flask containing 17,26g (0,lmol, 10 equiv.) diethylchlorophosphate in diethylether at -78C. The mixture is allowed to warm to room temperature and after lh it is quenchedusing 200 ml water. The compound is extracted three times by means of dichloromethane, the combined organic fractions are washed three times with 1M NaOH, dried using Mg504 and the volatiles are evaporated. Purification was performed using column chromatography and the compound was isolated in 74% yield as a whitesolid.?H-NMR (300MHz, CDCI3): 5 1.31 (6H, t, J=7.2Hz, 2x CH3); 4.01-4.28 (4H, m, 2x CH2); 7.66 (2H, m, 2x CH arom); 7.87 (1H, dxd,J=7.7Hz, 2.8Hz, C3H arom); 8.08 (1H, dxd, J=16.OHz, 7.7Hz, C2H arom);8.32-8.37 (1H, m, CHarom); 8.53-8.57 (1H, m, CH arom). ?3C-NMR.(75MHz, CDCI3): 5 16.4 (2x CH3, d, J=6.9Hz); 62.5 (2x CH2, d, J=4.9Hz); 124.9 (CqP, d,J=184.6Hz); 127.2 (CHarom, d, J=3.5Hz); 127.9 (CHarom); 128.0 (CHarom); 128.3 (CHarom);129.0 (C3Harom, d, J=17.3Hz); 129.6 (CqBr, d, J=4.6Hz); 132.2 (Cq CqP, d, J=13.9Hz); 133.8(Cq CqBr, d, J=11.5Hz); 134.6 (C2Harom, d, J=9.2Hz). 31P-NMR (121MHz, CDCI3): 5 18.96.MS (ESI): m/z (%): 685/687/689 (2M-i-H, 15/30/15), 343/345 (M-i-H, 100/100). IR (cm1) vmax: 1165 (P-OEt); 1248 (P=O); 1617; 1560; 1503; 1477. MP: 56.4-56.9 C (EtOAc). Chromatography: hexanes/EtOAc 60/40 Rf= 0.23. Yield: 74%
4-(4-(4-(diphenylamine)phenyl)naphthalen-1-yl)-N,N-diphenylaniline[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
85%
With tris-(dibenzylideneacetone)dipalladium(0); sodium carbonate; In tetrahydrofuran; water; at 75℃; for 24h;Inert atmosphere;
3 mmol of <strong>[83-53-4]1,4-dibromonaphthalene</strong>, 6.0 mmol of 4- (diphenylamine) phenylboronic acid, 0.3 mmol of tris (dibenzylideneacetone) dipalladium was added to the reactor,After evacuation and nitrogen circulation for 3 times, the reaction system was incubated under nitrogen and 50 mL of anhydrous tetrahydrofuran solution was added,30ml concentration of 2mol / L Na2CO3 aqueous solution, the reaction system temperature adjustment to 75 , reflux reaction 24hAfter completion of the reaction, the reaction solution was poured into an aqueous solution of saturated ammonium chloride, extracted twice with methylene chloride,The organic phase was washed with an aqueous solution of sodium chloride, dried and evaporated to remove the solvent. The crude product was purified by silica gel column chromatography to obtain a solid product. Yield: 85%.
10195] 48.0 ml (120 mmol) of n-butyllithium (2.5M in hexane) are added at -78 C. with vigorous stirring to a solution of 31.9 g (120 mmol) of 1 ,4-dibromonaphthalene in 1000 ml of THF. The mixture is stirred at -78 C. for 1 h, then allowed to warm to 0 C., 10.4 g (50 mmol) of anthraquinone are added, and the mixture is stirred at 0C. for a further 3 h. After 15 ml of acetic acid have been added, the mixture is evaporated to dryness, the residue is taken up in 500 ml of DMF, 28.4 g (150 mmol) of tin(II) chloride are added, and the mixture is refluxed for 5 h. After cooling, 200 ml of 2N hydrochloric acid are added, the mixture is stirred for a further 1 h, the solid is filtered off with suction, washed three times with 200 ml of 2N hydrochloric acid each time, three times with 300 ml ofwater each time and three times with 200 ml of ethanol each time, dried under reduced pressure and recrystallised from NMP. Yield: 25.9 g (44 mmol), 88.0% of theory; purity: 98% according to ?H-NMR.
With tetrakis(triphenylphosphine) palladium(0); potassium carbonate; In water; toluene; at 100℃; for 8h;Inert atmosphere;
7 g (19.43 mmol) Intermediate M-24, 1,4 dibromonaphthalene 8.3g (29.15mmol)and tetrakis triphenylphosphinepalladium 0.23g (0.194mmol) were placed in a flask, and under a nitrogen atmosphere, it was dissolved in toluene 190 ml, and then an aqueous solution 60ml of dissolved potassium carbonate 4.3g(29.14 mmol) was added, and stirred at reflux at 100 C for 8 h. After completion of the reaction, it was extracted with ethyl acetate, the extract was dried over magnesium sulfate, filtered and the filtrate was concentrated under reduced pressure. The product was purified by silica gel column chromatography using n-hexane / dichloromethane (9: 1 volume ratio) to obtain intermediate M-25 of the desired compound 7.9 g (78% yield).
With tetrakis(triphenylphosphine) palladium(0); potassium carbonate; In tetrahydrofuran; water; at 70℃; for 5h;
7.25 g (27.0 mmol) of Intermediate A-1, 11.6 g (40.5 mmol) of <strong>[83-53-4]1,4-dibromonaphthalene</strong>, 1.27 g (1.1 mmol) of Pd(PPh3)4, and 6.82 g (50 mmol) of K2CO3were dissolved in 200 ml of a mixed solution of THF/H2O (at a volume ratio of 2/1), and then, the resultant solution was stirred at a temperature of 70 C. for 5 hours. After the reaction solution was cooled to room temperature, 60 ml of water was added thereto, and an extraction process was performed thereon three times by using 60 ml of ethylether. An organic layer collected therefrom was dried by using magnesium sulfate, and then, the residual obtained by evaporating a solvent therefrom was separation-purified by silica gel chromatography to obtain 7.65 g (yield: 81.5%) of Intermediate A-2.
76%
With tetrakis(triphenylphosphine) palladium(0); potassium carbonate; In tetrahydrofuran; water; at 70℃; for 5h;
After the intermediate 2-1 5.90g (22.0 mmol), 1,4- dibromo naphthalene 12.4g (44.0mmol), and the Pd (PPh(sub)3(/sub)) 4 (tetrakis (triphenylphosphine)palladium) 1.27g (1.1 mmol) and K 2 CO 3 4.50g (33 mmol)were melted in the THF / H 2 O (2/1 volume ratio) mixture 200ml itwas stirred in 70 for 5 hours. After thereacting solution was cooled with the room temperature the water 60ml was added andit extracted in the ethyl ether 60ml with 3 time. The residue drying to themagnesium sulfate and disappeared the solvent and was the obtained organiclayer obtained was refined to the silica gel pipe chromatography after dividingand the intermediate 2-2 5.81g (yield 76%) was obtained.
With tris-(dibenzylideneacetone)dipalladium(0); 2,2'-bis-(diphenylphosphino)-1,1'-binaphthyl; sodium t-butanolate; In toluene; for 4h;Reflux;
14.0 g (0.083 mol) of diphenylamine in a 250 mL reactor,<strong>[83-53-4]1,4-dibromonaphthalene</strong> 26.2 g (0.092 mol), Pd (dba) 3 1.5 g (0.001 mo2), BINAP 1.0 g (0.002 mol),16.0 g (0.166 mol) of sodium t-2butoxide was dissolved in 140 mL of toluene and refluxed for 4 hours.TLC was confirmed whether the reaction was completed, and the filter was hot filtered when the reaction was completed. The organic layer was dried and separated by column chromatography,The separated solution was recrystallized from dichloromethane and hexane to give 15.6 g (50.1%).
49%
With tris-(dibenzylideneacetone)dipalladium(0); tri-tert-butyl phosphine; sodium t-butanolate; In o-xylene; at 160℃; for 48h;
Pd2 (dba) 3 160.1 mg (0.17 mmol) and t-Bu3P 70.7 mg (0.35 mmol) of o-xylene dissolved in 50 ml after 10 bungan room temperature in agitation. Compound I-6 5 g (17.48 mmol), diphenylamine, 3.25 g (19.23 mmol), and t-BuONa 1 g (10.49mmol) was added and 160 48 hours under reflux sikimyeo stirring. After the reaction was added to cold 20 ml of distilled water and extracted with ethyl acetate. The solvent was evaporated and then the filter was dried with magnesium sulfate. After column chromatography Intermediate I-7 (4- bromo -N, N- diphenyl-1-naphthalene-amine) was obtained through the 3.21 g (yield: 49%).
29%
With tris(dibenzylideneacetone)dipalladium(0) chloroform complex; 2,2'-bis-(diphenylphosphino)-1,1'-binaphthyl; sodium t-butanolate; In toluene; for 12h;Inert atmosphere; Reflux;
<strong>[83-53-4]1,4-dibromonaphthalene</strong> (1.0 g, 3.50 mmol) And diphenylamine (0.54 g, 3.18 mmol) and sodium tert-butoxide (0.61 g, 6.36 mmol) Placed in a three-neck round bottom flask and under nitrogen Pd2 (dba) 3 (0.030 g, 0.032 mmol) and BINAP (2,2'-bis (diphenylphosphino) -1,1'-binaphthyl) (0.040 g, 0.064 mmol) Dissolved in 80 mL of anhydrous toluene, and stirred for 12 hours while refluxing. TLC was performed under chloroform: hexane = 1: 3 and the progress of the reaction was confirmed. After the reaction was completed, the reaction mixture was extracted with chloroform and H2O. Chloroform layer A small amount of H2O was removed with MgSO4. MgSO4 was filtered off, evaporated and subjected to silica gel column chromatography under chloroform: hexane = 1: 3. The obtained product was dissolved in a small amount of chloroform, reprecipitated with methanol, and filtered to obtain 0.38 g (yield: 29%) of a white solid compound (4).
With tetrakis(triphenylphosphine) palladium(0); potassium carbonate; In tetrahydrofuran; water; at 70℃; for 5h;
6.59g intermediate 2-1 (22.0 mmol),1,4-bromonaphthalene 12.4g (44.0 mmol)Pd (PPh3) 4 (tetrakis (triphenylphosphine) palladium), 1.27g (1.1mmol) and K2CO3 4.5g (33mmol) of THF/H2O (2/1 by volume) mixed solution and then dissolved in 200ml, After stirring for 5 hours and then at 70 ,After cooling to room temperature was added to 60ml of water and extracted three times with 60ml ethyl ether.Drying the obtained organic layer with magnesium sulfate and separating therefrom obtained by evaporation of the solvent the residue was purified by silica gel column chromatography to afford 5.98g of intermediate 2-2 (75% yield).
With tetrakis(triphenylphosphine) palladium(0); potassium carbonate; In tetrahydrofuran; water;Reflux;
In a 5L round flask, 80 g (479.24 mmol, 1 eq) of compound 1-a and 205 g (718.86 mmol, 1.5 eq) of compound 1-b, Pd (PPh3)4 27.7 g (24.04 mmol, 0.05 eq), 200 g (1442.77 K2CO3) mmol, 3eq), and THF (tetrahydrofurane) 3.2 L, H2O 700 mL was added and stirred under reflux. After the reaction was completed, the mixture was extracted with MC(CH2Cl2)/ H2O, and the MC layer was dried with MgSO4. Silica-gel column purification gave 125 g of Compound 1-1 in 80% yield.
73%
With tetrakis(triphenylphosphine) palladium(0); potassium carbonate; In tetrahydrofuran; water; at 80℃;
After the starting material <strong>[83-53-4]1,4-dibromonaphthalene</strong> (223.81 g, 782.7 mmol) was dissolved in THF in a round bottom flask, (2-nitrophenyl)boronic acid (87.1 g, 521.8 mmol), Pd(PPh3)4 (26.1 g, 30.15 mmol), K2CO3 (216.34 g, 1565.3 mmol), water was added and stirred at 80 C. After the reaction was completed, the organic layer was extracted with CH2Cl2 and water, dried over MgSO4, concentrated, and the resulting compound was silicagel column and recrystallized to obtain the product 124.99 g (73% yield).
In a 100 ml three-necked flask, compound 4' (10 mmol, 2.86 g), THF (50 ml), and n-butyllithium (11 mmol, 1.6 M, 6.88 ml) were gradually added dropwise under nitrogen atmosphere at -78C. After reacting at -78 C. for 2 hours, 5 ml of a THF solution of triisopropyl borate (15 mmol, 3.03 g) was slowly added dropwise to the reaction system. After completion of the dropwise addition, the reaction mixture was slowly warmed to room temperature and stirred overnight. After the disappearance of the starting material by TLC, the reaction was completed. The mixture was quenched with dilute hydrochloric acid (20%, 20 ml), stirred at room temperature for 3 hours, then extracted with ethyl acetate (50 ml*3), and the combined organic phases were washed with saturated brine (100 ml*3) and dried over anhydrous sodium sulfate. The organic phase was concentrated and purified by column chromatography to give compound 3' (7.6 mmol, 1.91 g, 76%).
To a magnetically stirred solution of <strong>[83-53-4]1,4-dibromonaphthalene</strong> 14 (57.19 g, 200 mmol) in dried THF (600 mL) cooled at 78 C under N2 was added dropwise 1.6Mn-BuLi in n-hexane (125 mL, 200 mmol) via syringe. After addition, the resulting mixture was stirred at this temperature for another 0.5 h, followed by addition of B(i-PrO)3 (75.23 g, 400 mmol) in a dropwise manner via syringe. The reaction mixture was slowly warmed to room temperature and stirred at room temperature for another 1 h. The reaction mixture was slowly poured into ice-water (600 mL) with concentrated hydrochloric acid (10 mL) while stirring. The precipitates formed were collected via vacuum filtration, washed with cooled water, and triturated with EtOAc/n-hexane to yield 4-bromonaphthalene-1-boronic acid 15. White solid; 46.16 g (92%). A varying amount of boronic anhydride was found to exist in the sample of 15 and therefore 15 was directly used in the next step without further structural characterization.
1.5 g
Add <strong>[83-53-4]1,4-dibromonaphthalene</strong> (2.86g, 10.0mmol) and THF (50ml) to the reactor, protect with nitrogen, cool down to -78 C, slowly add n-butyl lithium (6.88ml, 11.0mmol), drop After the addition was completed, the reaction was kept for 2 hours, and then triisopropyl borate (3.03 g, 15.0 mmol) was added dropwise. After the completion of the dropwise addition, the mixture was slowly stirred to room temperature and stirred until the reaction was completed. It was quenched by the addition of 6M diluted hydrochloric acid (20 ml) and stirred at room temperature for 3 hours.Then extracted with ethyl acetate (50 ml).Dry over anhydrous sodium sulfate and concentrate the organic phase.Column chromatography (ethyl acetate / n-hexane system) was purified to afford compound 2b: (4-bromonaphthalene-1-yl)boronic acid 1.5 g.
With tetrakis(triphenylphosphine) palladium(0); potassium carbonate; In tetrahydrofuran; water; at 70℃; for 5h;
10273] 5.90 g (22.0 mmol) oflntermediate 1-1, 16.9 g (44.0 mmol) of 1,4-dibromonaphthalene, 1.27 g (1.1 mmol) of tetrakis(triphenylphosphine)palladium (Pd(PPh3)4), and 4.50 g (33 mmol) of K2C03 were dissolved in 200 mE of a mixture solution of THF/H20 (at a volume ratio of 2:1), and stirred at 70 C. for 5 hours. The resulting solution was allowed to cool to room temperature. Then, an organic layer was extracted three times therefrom by using each of 60 mE of water and 60 mE of ethylether. The obtained organic layer was dried by using Mg504. Then, a solvent was removed therefrom by evaporation. The obtained residue was separated and purified through a silica gel chromatography to thereby obtain 6.30 g of Intermediate 1-2 (yield: 64%).
With tetrakis(triphenylphosphine) palladium(0); potassium carbonate; In ethanol; water; toluene; at 80℃; for 16h;
1,4-Dibromonaphthalene (10 g, 34.69 mmol),4- (1-Phenyl-1H-benzimidazol-2-yl) phenylboronic acid (23.17 g, 76.91 mmol)Potassium carbonate (24.16 g, 157.96 mmol) andPd (PPh3) 4 (4.04 g) was placed in a reaction flask,Then add 150 ml of toluene,Ethanol 30 ml and deionized water 60 ml,Stir and reflux at 80 C for 16 hours.After the reaction was added 100 ml of deionized water and stirred to room temperature, the solid was filtered off, and then added to 250 ml of tetrahydrofuran was heated with stirringTo the solid solution, through a silica gel column, concentrated by distillation, ethyl acetate was added and the solid was filtered off,Drying of compound A1 (11 g, 47.33% yield) as a white solid.
With tri-tert-butyl phosphine; palladium diacetate; sodium t-butanolate; In toluene; at 50 - 60℃;
1,4-dibromonaphthalene (2 g, 6.99 mmol) and di-m-tolylamine (2.89 g, 14.687 mmol) were added in a reaction flask. After the toluene was sufficiently dry, dry toluene (30 mL) was added thereto, and then the mixture was heated and stirred. Sodium t-butoxide (1.74 g, 18.18 mmol) was added when the mixture was heated to 50 C., and the mixture was heated and stirred again. Pd(OAc)2 (0.047 g, 0.21 mmol) and tri-tert-butylphosphine (0.12 g, 0.56 mmol) were added when the temperature reached 60 C., and the reaction underwent overnight. After the reaction completed, deionized water (50 mL) was added, and the mixture was stirred for 30 minutes. Solid was filtered, and the organic layer was collected after removing the aqueous layer from the filtrate. The organic layer was purified through silicon chromatography, and the purified organic layer and the solid filtered were combined and concentrated via distillation. Methanol (100 mL) was added for precipitation, and the precipitate was filtered to obtain Compound A3 (3 g) as a pale-yellow solid. 1H NMR (400 MHz, CDCl3, delta):delta 8.03-7.965 (dd, 3H); 7.345-7.24 (m, 7H); 7.12-7.06 (t, 6H); 6.91-6.86 (s, 6H); 6.85-6.8 (d, 6H); 6.85-6.74 (d, 6H).
With tri-tert-butyl phosphine; palladium diacetate; sodium t-butanolate; In toluene;
1,4-dibromonaphthalene (5 g, 17.48 mmol) and bis(4-(2-phenylpropan-2-yl)phenyl)amine (14.9 g, 36.71 mmol) were added in a reaction flask. After the toluene was sufficiently dry, dry toluene (50 mL) was added thereto, and then the mixture was heated and stirred. Sodium t-butoxide (4.36 g, 45.4 mmol) was added when the mixture was heated to 50 C., and the mixture was heated and stirred again. Pd(OAc)2 (0.117 g, 0.525 mmol) and tri-tert-butylphosphine (0.302 g, 1.399 mmol) were added when the temperature reached 60 C., and the reaction underwent overnight. After the reaction completed, deionized water (300 mL) was added, and the mixture was stirred for 30 minutes. Solid was filtered, and the organic layer was collected after removing the aqueous layer from the filtrate. The organic layer was purified through silicon chromatography, and the purified organic layer and the solid filtered were combined and concentrated via distillation Methanol (350 mL) was added for precipitation, and the precipitate was filtered to obtain Compound A10 (8.5 g) as a pale-green solid. 1H NMR (400 MHz, CDCl3, delta): delta 8.0-7.92 (m, 3H); 7.33-7.23 (m, 32H); 7.2-7.12 (m, 6H); 7.07-7.00 (d, 13H);
The compounded 4' (10 mmol, 2.21 g) was added to a mixture of 30 ml of ether and 30 ml of benzene, and n-butyllithium (10 mmol, 1.6 M, 6.25 ml) was slowly added dropwise at 0C under nitrogen atmosphere. After stirring at 0 C. for 1 hour, methyl iodide (15 mmol, 2.13 g) was slowly added dropwise to the reaction system. After completion of the dropwise addition, the reaction was warmed up to room temperature. The reaction was completed by TLC and the reaction was completed. 60 ml of a saturated aqueous solution of ammonium chloride was added to the reaction system, the aqueous layer was extracted with toluene, the organic layers were combined, washed with saturated brine (100ml*3), dried over anhydrous sodium sulfate, and the organic phase was concentrated and purified by column chromatography. Compound 4''' (7.3 mmol, 1.61 g, 73%).
With tetrakis(triphenylphosphine) palladium(0); potassium carbonate; In 1,4-dioxane; at 100℃; for 4h;Inert atmosphere;
572 mg of 1,4-dibromo-naphthalene was placed in a 100 mL flask.Add 20mL dioxane and 20mL 2mol/LPotassium carbonate solution, stir well,Continue to add 176mg of cyclopropylboronic acid and 100mg of tetrakis(triphenylphosphine)palladium.Then, nitrogen gas was exchanged for 10 minutes, heated under a nitrogen atmosphere and heated to reflux at 100C for 4 hours, and the reaction was monitored by HPLC. After the reaction was completed,The reaction solution was added with 20 mL of ethyl acetate for extraction, and the solution was extracted twice in succession.Then add saturated brine was washed twice, each time 20mL, the organic phase was combined and concentrated under reduced pressure, and filtered to give 1-bromo-4-cyclopropyl-naphthalene 430mg, the yield was 87%;The purity is 96.5%.
With tetrakis(triphenylphosphine) palladium(0); sodium carbonate; In ethanol; water; toluene; for 5h;Reflux; Inert atmosphere;
Stepl. Add 20-1 lOOmmol to a mixed solvent of toluene, ethanol and water, add 1 equivalent of 20-2, 3 equivalents of sodium carbonate, 0.01 equivalent of tetrakistriphenylphosphine palladium under nitrogen protection, and react at reflux temperature. 5h, after completion of the reaction, the silica gel column was passed to obtain 85 mmol of product 20-3.
With tetrakis(triphenylphosphine) palladium(0); potassium carbonate; In ethanol; water; toluene; at 120℃; for 3h;Inert atmosphere;
Step5:Under nitrogen protection,Intermediate 202-2 (4.09 g, 8.4 mmol), <strong>[83-53-4]1,4-dibromonaphthalene</strong> (2.63 g, 9.2 mmol), tetrakistriphenylphosphine palladium (0.09 g, 0.08 mmol), potassium carbonate ( 3.48 g, 25.2 mmol), 60 mL of toluene, 20 mL of ethanol and 20 mL of distilled water were stirred at 120 C for 3 h.After the end of reaction is stopped with distilled water, extracted with ethyl acetate, the organic layer was dried over MgSO4, the solvent was removed by distillation under reduced pressure,After purification by silica gel column chromatography, intermediate 202-3 was obtained.(3.52 g, 74%).
73%
With tetrakis(triphenylphosphine) palladium(0); potassium carbonate; In ethanol; water; toluene; at 120℃; for 3h;Inert atmosphere;
Step1: Under the protection of nitrogen, intermediate 1-4 (4.09 g, 8.4 mmol) was added to the reaction vessel. 1,4-dibromochloride (2.63g, 9.2mmol), Tetrakistriphenylphosphine palladium (0.09g, 0.08mmol), Potassium carbonate (3.48 g, 25.2 mmol), toluene 60 mL, 20mL of ethanol and 20mL of distilled water, Stir at 120 C for 3 h. After the reaction is over, the distilled water stops the reaction. The organic layer was dried over MgSO 4 and evaporated and evaporated. After that, it was purified by silica gel column chromatography toield Intermediate 231-1 (3.47 g, 73%).
With palladium diacetate; potassium carbonate; In tetrahydrofuran; water; at 80 - 90℃;Inert atmosphere; Sealed tube;
11 mmol of 2-phenylbenzeneboronic acid,Ment <strong>[83-53-4]1,4-dibromonaphthalene</strong>, mmol potassium carbonate,20 mL of organic solvent (a mixed solvent of tetrahydrofuran and water in a volume ratio of 4:1),20 mL of deionized water was added to the sealed tube in turn.After adding inert gas (argon) for 10 min, add 0.3 gPalladium catalyst (palladium acetate, 10%),After 5 minutes of inert gas,After sealing the sealed tube, it is placed in an oil bath environment of 80~90 C for 45~50 h.The reaction product was extracted with ethyl acetate as an extractant.Dry the organic layer,With petroleum ether (60 ~ 90 C)For the eluent,Intermediate 3 was isolated as a white solid by silica gel column chromatography.The yield was 92%;
<strong>[83-53-4]1,4-dibromonaphthalene</strong> (2.86 g) was diluted with tetrahydrofuran (THF) (50 mL) and cooled to a temperature of -78 C. n-BuLi (2.5M in hexane, 4.3 mL) was slowly added dropwise thereto. After the reaction mixture was stirred for 1 hour while maintaining the temperature thereof, trimethyl borate (1.1 g) was added thereto and heated to room temperature. When the reaction was completed after stirring at room temperature for 15 hours, 12N HCl (1 mL) was added dropwise thereto and stirred again for 1 hour. An organic layer extracted therefrom there times by using diethyl ether was dried by using MgSO4, filtered under reduced pressure, and distilled under reduced pressure. The residue obtained therefrom was washed by using hexane to obtain Intermediate 3-1 (2.1 g, 82%). (0467) C10H8BBrO2 [M]+ Calcd. 249.98 Found 249.98.
82%
Dilute <strong>[83-53-4]1,4-dibromonaphthalene</strong> (2.86 g) with tetrahydrofuran (THF) (50 mL),And cooled to a temperature of -78 C. Slowly add n-BuLi (2.5M,In hexane, 4.3 mL).After the reaction mixture was stirred for 1 hour while maintaining its temperature,To this was added trimethyl borate (1.1 g) and it was warmed to room temperature.When the reaction was complete after stirring at room temperature for 15 hours,12N HCl (1 mL) was added dropwise thereto and stirred again for 1 hour.The organic layer was extracted three times with diethyl ether by using MgSO4,Filter under reduced pressure and distill under reduced pressure. The residue obtained therefrom was washed with hexane to obtain Intermediate 3-1 (2.1 g, 82%).
With potassium phosphate; copper(l) iodide; In toluene; at 110℃; for 12h;Inert atmosphere;
General procedure: Under a nitrogen atmosphere, (33.2 g, 100 mmol) of compound M2-1,(28.2g, 100mmo1) Compound M2-2,(9.55g, 50mmol) cuprous iodide,(5.7g, 50mmol) trans-cyclohexanediamine,(31.8g, 100mmol) potassium phosphate and 250mL toluene were added to a 500mL three-necked flask, heated and stirred to 110 C for 12 hours,Finish the reaction, cool to room temperature, filter the filtrate with suction, remove most of the solvent by rotary evaporation, and wash with dichloromethane for 3 times.The organic liquid was collected and purified by column chromatography on silica gel with a yield of 75%.
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