* 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 hexanes; diethyl ether at -78℃; for 0.333333 h; Cooling with acetone-dry ice Stage #2: With hexachloroethane In hexanes; diethyl ether at -78 - 20℃; for 3.5 h;
A solution of 1,3,5-tribromobenzene (9.44 g, 30 mmol) in 120 mL of ether was cooled to -78 °C in a dry ice/acetone bath. n-Butyllithium (13.2 mL of 2.5 M solution in hexanes, 33 mmol) was added dropwise over 10 min. The resulting mixture was stirred at -78 °C for an additional 10 min, then hexachloroethane (7.15 g, 30.2 mmol) was added in small portions over 3 min. The reaction mixture was then stirred for 15 min at -78 °C, followed by 3.2 h at rt. The mixture was partitioned between 100 mL of water and 100 mL of EtOAc. The aqueous layer was separated and extracted with an additional 100 mL of EtOAc. The combined organic layers were then dried over MgSO4 filtered, and concentrated in vacuo to give 472 as a pale brown solid (7.72 g, 95percent): 1H NMR (CDCl3, 300 MHz) δ 7.57 (t, 1 H), 7.47 (d, 2 H).
Reference：
[1] Patent: EP1208091, 2006, B1, . Location in patent: Page/Page column 23
[2] Journal of Medicinal Chemistry, 2006, vol. 49, # 2, p. 727 - 739
[3] Tetrahedron Letters, 1997, vol. 38, # 9, p. 1559 - 1562
14
[ 626-39-1 ]
[ 19752-57-9 ]
Reference：
[1] Chemistry - A European Journal, 2008, vol. 14, # 16, p. 4948 - 4960
[2] Synthesis, 2003, # 1, p. 79 - 90
[3] Chemistry - A European Journal, 2003, vol. 9, # 20, p. 5011 - 5022
[4] Helvetica Chimica Acta, 2017, vol. 100, # 4,
[5] Helvetica Chimica Acta, 2000, vol. 83, # 11, p. 2865 - 2883
[6] Journal of Organic Chemistry, 2004, vol. 69, # 10, p. 3336 - 3339
[7] Journal of Organic Chemistry, 2002, vol. 67, # 15, p. 5327 - 5332
[8] Angewandte Chemie - International Edition, 2014, vol. 53, # 13, p. 3436 - 3441[9] Angew. Chem., 2014, vol. 126, # 13, p. 3504 - 3509,6
15
[ 626-39-1 ]
[ 98-80-6 ]
[ 16372-96-6 ]
Yield
Reaction Conditions
Operation in experiment
96%
With potassium carbonate In ethanol; water at 50℃; for 5 h; Inert atmosphere; Schlenk technique
General procedure: A Schlenk tube was charged with a suspension of aryl halide (1.0mmol), arylboronic acid (1.2 mmol), potassium carbonate (276 mg,2.0 mmol) and Pd/HCCP-DABP (20 mg, 0.3 molpercent) in EtOH-H2O (3 mL,v:v=1:1), evacuated, and backfilled with nitrogen. The resulting reaction mixture was stirred at 50 °C for 2.5 h. After completion of the reaction,the mixture was cooled and extracted with CH2Cl2. The combined organic phase was dried, evaporated and purified by column chromatographyon silica gel to give the coupling product. The aqueous phasewas filtered and the solid was washed with CH2Cl2 and reused in further reactions as the recovered catalyst.
69%
With tetrakis(triphenylphosphine) palladium(0); potassium carbonate In tetrahydrofuran; water at 90℃; for 6 h;
1,3,5-tribromobenzene (14.6 g, 46 mmol), phenylboronicacid (5.6 g, 46mmol), Pd (PPh3) 4 (1.6 g, 1.4mmol), K2CO3 (19.2 g, 14mmol), THF (100 ml), put H2O (50 ml) and the mixture was stirred under reflux for 6 hours in 90 . When the reaction is complete cool the temperature of the reaction to room temperature, and was extracted with CH2Cl2 and water wipe. The organic layer was dried over MgSO4, isolated by using silicagel column The concentrated and the organic product generated by Core 1-1-8-C1 9.8 g (69percent) is obtained.
65%
With tetrakis(triphenylphosphine) palladium(0); sodium carbonate In 1,2-dimethoxyethane; water for 8 h; Reflux; Inert atmosphere
In an argon atmosphere, a mixture of 1,3,5-tribromobenzene (9.44 g, 30 mmol), phenylboronic acid (1.22 g, 10 mmol), tetrakis(triphenylphosphine) palladium (231 mg, 0.2 mmol), DME (50 mL), and a 2 M aqueous solution of sodium carbonate (10 mL, 20 mmol) was allowed to react for 8 h while refluxing under heating. After cooling the reaction solution to room temperature, the water layer was separated and removed, and the organic layer was dried over magnesium sulfate. Then, the insolubles were removed by filtration, and the organic solvent was evaporated off under reduced pressure. The obtained residue was purified by silica gel column chromatography to obtain the intermediate B-9 (2.03 g, yield: 65percent).
63%
With tetrakis(triphenylphosphine) palladium(0); potassium carbonate In tetrahydrofuran; water at 80℃; for 16 h;
Intermediate I-5 4.31 g (10 mmol), 2-Chloro-4,6-diphenyl-1,3,5-triazine 2.68 g (10 mmol), Pd (PPh3) 4 ( tetra-kis(triphenylphosphine) palladium ) 0.58 g ( 0.5 mmol ) and 4.14 g K2CO3 ( 30 mmol ) and THF / H2O ( 2/1 volume ratio) mixed solution Was dissolved in 60 mL , it was stirred at 80°C for 16 hours. After cooling to room temperature the reaction solution was added to 40 mL water in aButyl ether and extracted three times with 50 mL. The combined organic layers were dried over magnesium sulfate, and the resulting glass by evaporation of the solventSeparating residues jelgwan by silica chromatography to give the compound 2A 3.38 g ( yield 63percent) . The resulting compound isAnd MS / FAB One It was confirmed.Instead of Intermediate I-5 using a phenylboronic acid and 2-Chloro-4,6-diphenyl-1,3,5-triazine in place of 1,3,5- tribromobenzene It was used except that by using the same method as that of Compound 2A of the above Synthesis Example 1 , Intermediate A-20To give the 1.97 g ( 63percent yield). The resulting compound was confirmed by LC-MS
63%
With tetrakis(triphenylphosphine) palladium(0); potassium carbonate In tetrahydrofuran; water at 80℃; for 12 h;
12.6 g (40 mmol) of 1,3,5-tribromobenzene, 3.66 g (30 mmol) of phenylboronic acid,3.4 g (1.5 mmol) of Pd (PPh3) 4 and 12.6 g (90 mmol) of K2CO3 were dissolved in 350 mL of a THF / H2O mixed solvent (in a volume ratio of 2/1)The reaction solution was stirred at a temperature of 80 ° C for 12 hours.The resulting reaction solution was cooled to room temperature,The organic layer was extracted three times by using 60 mL of water and 60 mL of ethyl acetate.The organic layer thus collected was dried with magnesium sulfate,The residue obtained after the solvent was evaporated from the silica gel column chromatography was used to separate and purify the residue,To obtain 5.9 g of intermediate I-8 (yield: 63percent).The compounds thus produced were determined by using LC-MS.
60.56%
With bis-triphenylphosphine-palladium(II) chloride; sodium carbonate In toluene for 3 h; Reflux
[173] After mixing 1,3,5-tribromobenzen (40 g, 127.06 mmol), phenyl boronic acid (17.04 g, 139.7 mmol), PdCl(PPh3)2 (1.78 g, 2.54 mmol), toluene 500 mL, and Na2CO3 (2 M, 130 mL), the mixture was stirred under reflux. After 3 hours, the mixture was cooled to room temperature, and distilled water was added. The mixture was extracted with ethyl acetate (EA) and dried with magnesium sulfate. After drying under reduced pressure, the resulting product was separated through a column to obtain compound 1-8 (24 g, 76.9 mmol, 60.56 percent).
55%
With tetrakis(triphenylphosphine) palladium(0); sodium carbonate In ethanol; water; toluene at 90℃; for 8 h; Inert atmosphere
Next, under an Ar atmosphere,In a 1 L three-necked flask,10.0 g of 1,3,5-tribromobenzene,7.20 g of phenyl boronic acid, 9.54 g of Pd (PPh 3) 4,And 20.4 g of sodium carbonate were added,In a mixed solvent of 430 mL of toluene and 210 mL of water at 90 ° C.,And the mixture was heated and stirred for 8 hours.After air cooling,Water was added to separate the organic layer and the solvent was distilled off.The obtained crude product was purified by silica gel column chromatography (using a mixed solvent of dichloromethane and hexane)Recrystallization was performed with a toluene / hexane mixed solvent,5.45 g (55percent yield) of compound F as a white solid was obtained.
Reference：
[1] Reactive and Functional Polymers, 2017, vol. 110, p. 38 - 46
[2] Patent: KR2016/69021, 2016, A, . Location in patent: Paragraph 0155-0157
[3] Journal of the American Chemical Society, 1990, vol. 112, # 22, p. 8024 - 8034
[4] Patent: KR2015/53913, 2015, A, . Location in patent: Paragraph 0533-0535
[5] Patent: KR2015/127023, 2015, A, . Location in patent: Paragraph 0409; 0560; 0561; 0562; 0563; 0564
[6] Patent: CN106565689, 2017, A, . Location in patent: Paragraph 0342; 0343; 0344; 0345; 0346
[7] Patent: WO2013/162284, 2013, A1, . Location in patent: Paragraph 172; 173
[8] Patent: JP2016/124792, 2016, A, . Location in patent: Paragraph 0092; 0094
[9] Journal of Medicinal Chemistry, 2008, vol. 51, # 20, p. 6348 - 6358
[10] Inorganic Chemistry, 2018, vol. 57, # 9, p. 5692 - 5700
Reference：
[1] Journal of Organic Chemistry, 2004, vol. 69, # 25, p. 8982 - 8983
[2] European Journal of Organic Chemistry, 2009, # 15, p. 2562 - 2575
[3] Chemical Communications, 2014, vol. 50, # 57, p. 7586 - 7589
[4] Journal of Organic Chemistry USSR (English Translation), 1988, vol. 24, # 3, p. 516 - 522[5] Zhurnal Organicheskoi Khimii, 1988, vol. 24, # 3, p. 577 - 583
[6] Patent: US2010/261701, 2010, A1, . Location in patent: Page/Page column 240
27
[ 626-39-1 ]
[ 124-41-4 ]
[ 621-23-8 ]
[ 20469-65-2 ]
[ 74137-36-3 ]
Reference：
[1] Organic Preparations and Procedures International, 2003, vol. 35, # 2, p. 225 - 227
28
[ 626-39-1 ]
[ 626-41-5 ]
[ 74137-36-3 ]
Reference：
[1] Monatshefte fuer Chemie, 1886, vol. 7, p. 630
29
[ 626-39-1 ]
[ 124-41-4 ]
[ 626-41-5 ]
[ 74137-36-3 ]
Reference：
[1] Monatshefte fuer Chemie, 1886, vol. 7, p. 630
[2] Monatshefte fuer Chemie, 1886, vol. 7, p. 630
30
[ 626-39-1 ]
[ 68-12-2 ]
[ 56990-02-4 ]
Yield
Reaction Conditions
Operation in experiment
95%
Stage #1: With magnesium In tetrahydrofuran at 20℃; for 0.0833333 h; Inert atmosphere; Large scale Stage #2: With methylmagnesium chloride In tetrahydrofuran for 3.5 h; Reflux; Inert atmosphere; Large scale Stage #3: at 0 - 10℃; for 2 h; Inert atmosphere; Large scale
under the protection of nitrogen gas the 25kg of tetrahydrofuran, 400g of tribromobenzene and Fresh magnesium tablets 500g were added to reaction kettle and stirred for 5min at room temperature. cooled down the reaction to 0°C then catalytic amount 120g of Methylmagnesium chloride was added and raised the temperature to reflux. After the initiation , control temperature to 55-60 ° C for adding tribromobenzene 4kg in batches , after about 3 hours of addition the temperature was raised to reflux insulation for 30 minutes; cooled down the reaction to 0°C, then 1.5kf of DMF was added drop wise and addition was completed within 1hour. And then slowly raising temperature to 5-10 ° C and incubated for 1 hour. After the reaction, add 15percent hydrochloric acid for acidification , temperature controlled at 10 ° C for 1 hour. The solution is then allowed to stand for separation. Water phase was extracted with ethyl acetate , The organic phase was combined, concentrated, the17.5kg of petroleum ether was added, the temperature was raised to reflux and then cooled to 0 ° C, and the temperature was maintained for 1 hour. The product subjected to centrifugation and drying to give 3,5-dibromobenzaldehyde. Content of 99.5percent (GC), the yield of 95percent.
70%
Stage #1: With n-butyllithium In diethyl ether at -78℃; for 0.75 h; Inert atmosphere; Schlenk technique Stage #2: for 1 h; Inert atmosphere; Schlenk technique
Compound 2 was synthesized according to the literature [22].Briefly, a suspension of 1,3,5-tribromobenzene (4.0 g,12.7 mmol) inanhydrous diethyl ether (100 mL) at -78 C was treated dropwisewith butyllithium (2.5 M, 5.3 mL, 13.5 mmol). After 45 min, DMF(2.8 g, 38.3 mmol) was droped into the mixture, which was thenstirred for another 1 h. Diluted HCl (40 mL, 2 mol/L) was added,then organic phase was removed, and a brown solid was obtained.The crude product was purified by column chromatography (silicagel) using DCM/n-hexane = 1/10 as eluent and recrystallized fromdiethyl ether/n-hexane to give needle compound 2 (2.34 g, 70percent).
Reference：
[1] Patent: CN106083546, 2016, A, . Location in patent: Paragraph 0023
[2] Chemistry - A European Journal, 2003, vol. 9, # 1, p. 130 - 139
[3] Macromolecules, 2010, vol. 43, # 7, p. 3325 - 3330
[4] Electrochimica Acta, 2015, vol. 179, p. 187 - 196
[5] Journal of Materials Chemistry A, 2017, vol. 5, # 26, p. 13757 - 13762
[6] Macromolecules, 2005, vol. 38, # 22, p. 9389 - 9392
[7] Dalton Transactions, 2013, vol. 42, # 35, p. 12688 - 12698
[8] Journal of Medicinal Chemistry, 1993, vol. 36, # 21, p. 3197 - 3201
[9] Australian Journal of Chemistry, 1997, vol. 50, # 4, p. 425 - 434
[10] Journal of Organic Chemistry, 1999, vol. 64, # 25, p. 9286 - 9288
[11] Inorganica Chimica Acta, 2010, vol. 363, # 12, p. 2857 - 2864
[12] Journal of Polymer Science, Part A: Polymer Chemistry, 2014, vol. 52, # 5, p. 707 - 718
31
[ 626-39-1 ]
[ 56990-02-4 ]
Yield
Reaction Conditions
Operation in experiment
45%
With magnesium In hexane; dichloromethane; ethyl acetate; N,N-dimethyl-formamide
STR12 Preparation of 3,5-dibromobenzaldehyde 1.344G (56 mM) of magnesium was added to a solution of 15-7G(50 mM) of 1,3,5-tribromobenzene and the mixture was stirred at room temperature after 5 hours, most of the metal was digested. To the resulting brown Grignard solution was added 7.5 mL (0.1M) of N,N-dimethylformamide at 0° under nitrogen. The resulting mixture was stirred overnight at room temperature. Solvent was removed in vacuo at room temperature. The residue was taken up in 200 mL of ethyl acetate and washed with 6*50 mL of saturated sodium chloride solution, dried over anhydrous MgSO4. Solvent was removed to give a crude solid, which was dissolved in minimum amount of CH2 Cl2 and applied on silica gel. Elution with 1:9 mixture of ether:hexane containing methylene chloride gave 45percent yield of the desired aldehyde as white solid.
Reference：
[1] Patent: US5256777, 1993, A,
[2] Patent: US5294610, 1994, A,
32
[ 626-39-1 ]
[ 97165-77-0 ]
Yield
Reaction Conditions
Operation in experiment
75%
Stage #1: With isopropylmagnesium chloride; lithium chloride In tetrahydrofuran at -15℃; for 0.25 h; Stage #2: With N,N-dimethyl-formamide In tetrahydrofuran at 0℃; for 2 h; Stage #3: With ammonia; iodine In tetrahydrofuran; water at 20℃; for 2 h;
General procedure: To a flask containing dried LiCl (0.35 g, 8.24 mmol) was added iPrMgCl (2 M in THF, 4.1 mL) and THF (5 mL) at 15° C. After beingstirred for 15 min, 3-bromo-1-benzonitrile (1.46 g, 8.03 mmol) inTHF (1 mL) was added to the reaction mixture and the obtainedmixture was stirred for 15 min. Then, DMF (1.3 mL, 12 mmol) wasadded at 0° C and the mixture was stirred for 2 h. Then, aq NH3 (7 mL, 28-30percent) and I2 (4.06 g, 16 mmol) were added to the reaction mixture. After being stirred for 2 h at room temperature, the reactionmixture was poured into satd aq Na2SO3 solution and was extracted with CHCl3 (3∗30 mL). The organic layer was dried over Na2SO4 and filtered. After removal of the solvent, the residue waspurified by short column chromatography on silica gel (eluent:hexane/ethyl acetate=9:1, v/v) to provide pure 1,3-dicyanobenzene (0.73 g) in 71percent yield. Most nitriles mentioned in this work are commercially availableand were identified by comparison with the authentic samples.
Reference：
[1] Australian Journal of Chemistry, 1997, vol. 50, # 4, p. 425 - 434
[2] Journal of Polymer Science, Part A: Polymer Chemistry, 2014, vol. 52, # 5, p. 707 - 718
36
[ 626-39-1 ]
[ 62-53-3 ]
[ 102664-66-4 ]
Yield
Reaction Conditions
Operation in experiment
75%
With tris-(dibenzylideneacetone)dipalladium(0); 2,2'-bis-(diphenylphosphino)-1,1'-binaphthyl; sodium t-butanolate In toluene for 72 h; Inert atmosphere; Reflux
A mixture of aniline (7.4 g, 79.4 mmol), 1,3,5-tribromobenzene 3 (5.0 g, 15.88 mmol), tris(dibenzylideneacetone) dipalladium(0) [Pd2(dba)3(0), 0.11 g, 0.25 mol percent], rac-2,2'-bis(diphenylphosphino)-1,1'-binapthyl (BINAP, 0.22 g, 0.75 mol percent), and sodium t-butoxide (7.63 g, 79.4 mmol) in anhydrous toluene (250 mL) was heated to refluxing temperature under nitrogen for a period of 72 h. The reaction mixture was cooled to room temperature and washed with water (100 mL). The organic layer was dried over anhydrous sodium sulfate (Na2SO4). After evaporation of the solvent, a crude brown color solid was obtained. Excess aniline was then removed by distillation at 130 °C under reduced pressure of 101 mmHg. It was further purified by chromatography (SiO2). The resulting light brown product 1,3,5-tris(phenylamino)benzene 4, TPAB, was obtained in 75percent yield (4.18 g). FT-IR (KBr) υmax 3403 (m), 3375 (m), 3078 (w), 3019 (w), 2945 (s), 1612 (m), 1591 (vs), 1518 (m), 1496 (s), 1469 (m), 1431(w), 1456 (m), 1409 (m), 1365 (w), 1295 (m), 1269 (w), 1246 (m), 1,171 (m), 1073 (w), 1030 (w), 897 (w), 834 (w), 820 (w), 802 (w), 756 (m), 721 (w), 700 (m), 688 (m), 613 (w), and 558 (w) cm−1; UV-vis (CHCl3, 1.0 × 10−5 M) λmax (ε) 289 nm (4.80 × 104 L mol−1 cm−1); 1H-NMR (500 MHz, CDCl3) δ 7.25 (t, J = 7.8 Hz, 6H), 7.08 (d, J = 7.7 Hz, 6H), 6.92 (t, J = 7.3 Hz, 3H), 6.32 (s, 3H), and 5.60 (s, 3H, N–H); 13C-NMR (125 MHz, CDCl3) δ 145.4, 142.7, 129.3, 121.3, 118.7, and 99.0.
With tetrakis(triphenylphosphine) palladium(0); potassium carbonate In 1,4-dioxane; water; toluene for 24 h; Reflux
500 mL reactor to tribromobenzene 25 g (79 mmol), phenyl boronic acid 23.3 g (191 mmol), potassium carbonate 32.9 g (238 mmol), tetrakistriphenylphosphinepalladium, 6.12 g (3 mmol), distilled water 50 In the mL, 125 mL toluene and 125 mL 1,4dioxaneis stirred and refluxed for 24 hours. After completion of the reaction by separating the reaction layer and the organic layer was concentrated under reduced pressure. Recrystallized with toluene and methanol to give the 8-a 21 g. (85percent yield)
63%
With tetrakis(triphenylphosphine) palladium(0); potassium carbonate In tetrahydrofuran; water at 65℃; for 12 h; Inert atmosphere
1,3,5-Tribromobenzene (20.0 g, 63.5 mmol), phenylboronic acid (18.8 g, 154 mmol), and Pd(PPh3)4 (3.75 g, 3.25 mmol)were added to 300 mL of anhydrous THF. Then, 2M K2CO3 solution(100 mL), which was dissolved in H2O, was added to the reactionmixture. The mixture was heated to 65 °C for 12 h under nitrogen. Aftercompletion of the reaction, the reaction mixture was extracted withCHCl3 and water. The organic layer was dried with anhydrous MgSO4and filtered. The solvent was evaporated. The product was isolated viasilica gel column chromatography by using CHCl3: n-hexane (1: 20) asthe eluent to afford a white solid (12.4 g, 63percent). 1H NMR (300 MHz,CDCl3): δ = 7.70 (s, 3H), 7.60 (d, 4H), 7.44(t, 4H), 7.36 (t, 2H); EI + -Mass: 310.
62%
With potassium carbonate In tetrahydrofuran; water at 70℃; for 5 h;
6.3g (20.0 mmol) of 1,3,5-tribromobenzene, 4.88g (40.0 mmol) of 1-phenylboronic acid, 2.31 g (2.0 mmol) of Pd(PPh3)1, and 16.6 g (120.0 mmol) of K2CO3 were dissolved in 120 mL of a mixed solution THF/H2O (2:1) to obtain a solution, which was then stirred at about 70°C for about 5 hours. The reaction solution was cooled to room temperature, followed by three times of extraction with 120 mL of water and 100 mL of diethylether. The organic phase was collected, and was dried using magnesium sulfate to evaporate the solvent. The residue was separated and purified using silica gel column chromatography to obtain 3.83 g of Intermediate I-11 (Yield: 62 percent). This compound was identified using LC-MS and NMR. C18H13Br : M+ 308.2 1H NMR (CDCl3, 400MHz) δ (ppm) 7.70 (s, 3H), 7.62-7.58 (m, 4H), 7.48-7.47 (t, 1H), 7.46-7.42 (m, 3H), 7.41-7.35 (m, 2H)
61%
With tetrakis(triphenylphosphine) palladium(0); potassium carbonate In tetrahydrofuran; water at 65℃; for 5 h; Inert atmosphere
1,3,5-Tribromobenzene (20 g, 62 mmol), Pd(PPh3)4 (3.57 g, 3.1mmol) were added to 300 mL of dry THF solution, thenphenylbronic acid (32 g, 155 mmol) and 2 M K2CO3 solution (50 mL), which was dissolved in H2O, was added to the reaction mixture. The reaction mixture was heated to 65°C for 5 h under nitrogen. After the reaction was finished,extracted with diethyl ether and water. The organic layer was dried with anhydrous MgSO4 and filterd. The solvent was evaporated. The product was isolated by silica gel column chromatography using CHCl3:hexane (1:15) eluent to afforda white solid (Yield 61percent). 1H NMR (300 MHz, CDCl3) δ 7.7(s, 3H), 7.6 (d, 4H), 7.45 (t, 4H), 7.4 (t, 2H).
60%
With tetrakis(triphenylphosphine) palladium(0); potassium carbonate In toluene for 5 h; Inert atmosphere; Reflux
1,3,5-tribromobenzene (20 g, 63 mmol) and Pd(PPh3)4 (4.36 g, 3.7 mmol) were dissolved in 500 mE of an anhydrous toluene solvent under a nitrogen atmosphere to prepare a mixture. Phenylboronic acid (17 g, 140 mmol) and 50 mE of a 2M K2C03 solution were added thereto. The obtained mixture was heated for 5 hours while being refluxed under the nitrogen atmosphere. When a reaction was complete, the resultant was extracted with chloroform and distilled water and treated with anhydrous magnesium sulfate. The obtained resulting material was purified by using chloroform:hexane (a volume ratio of 1:10) as an eluting solvent through a silica gel column to obtain 11.8 g of a white solid (a yield of 60.0percent).
55.3%
With tetrakis(triphenylphosphine) palladium(0); potassium carbonate In toluene at 80℃; Inert atmosphere
4.85 g (19.88 mmol) of Intermediate (1), 5.0 g (1.90 mmol) of 1,3,5-tribromobenzene,0.92 g of Pd (pph3) 4 was placed in a flask, and 100 ml of anhydrous toluene was added under nitrogen atmosphere and stirred.To this was added 10.0 ml of 2M K2CO3.At this time, the mixture was stirred while maintaining the temperature at about 80 .After the reaction, the reaction mixture was extracted with chloroform and water.The product in the chloroform layer was separated and purified by column chromatography using a 1: 10 mixture ratio (volume ratio) of chloroform: hexane after removal of the solvent using an evaporator,To obtain 2.702 g (yield: 55.3percent) of a white solid compound (Intermediate (2)).
51%
With sodium carbonate In ethanol; water; toluene for 24 h; Heating / reflux
To a solution of 1,3,5-tribromobenzene (10.0 g, 31.8 mmol), phenylboronic acid (9.68 g, 79.4 mmol), and sodium carbonate (25.3 g, 0.24 mol) in a mixture of toluene (150 ml), ethanol (30 ml), and water (75 ml), tetrakis(triphenylphosphine)palladium (1.84 g, 5 mol percent) was added. The reaction mixture was stirred while refluxing for 24 hours and quenched with conc. HCl (20 ml). Then it was cooled to room temperature and extracted with ethyl ether (3*50 ml). The combined organic extracts were dried over MgSO4 and concentrated under vacuum. Purification by column chromatography (n-hexane) afforded 3,5-(diphenyl)bromobenzene (9.82 g, 51percent)
35%
With tetrakis(triphenylphosphine) palladium(0); sodium carbonate In 1,2-dimethoxyethane; water at 77℃; for 16 h; Inert atmosphere
Under argon atmosphere, a mixture of 1, 3, 5-tribromobenzene (1000 g, 3.18 mol), phenylboronic acid (775 g, 6.35 mol), tetrakis(triphenylphosphine)palladium(0) (147 g, 128 mmol), sodium carbonate (2021 g, 19.1 mol), water (17 L), and DME (17 L) was stirred at 77° C. for 16 h. After cooling to room temperature and adding water, the reaction liquid was extracted with toluene. The toluene layer was concentrated under reduced pressure. The obtained residue was purified by silica gel column chromatography to obtain the compound B2-1 (342 g, 35percent yield).
Reference：
[1] Patent: KR2015/130797, 2015, A, . Location in patent: Paragraph 0467-0472
[2] Synthesis, 2004, # 13, p. 2181 - 2185
[3] Dyes and Pigments, 2018, vol. 158, p. 42 - 49
[4] Patent: EP2447250, 2012, A1, . Location in patent: Page/Page column 37
[5] Bulletin of the Korean Chemical Society, 2014, vol. 35, # 10, p. 3041 - 3046
[6] Journal of Materials Chemistry C, 2016, vol. 4, # 17, p. 3833 - 3842
[7] Crystal Growth and Design, 2011, vol. 11, # 6, p. 2654 - 2659
[8] Patent: US2018/19403, 2018, A1, . Location in patent: Paragraph 0071
[9] Patent: KR2016/31310, 2016, A, . Location in patent: Paragraph 0425; 0428; 0429
[10] Patent: US6998487, 2006, B2, . Location in patent: Page/Page column 52
[11] Journal of Materials Chemistry, 2010, vol. 20, # 29, p. 6131 - 6137
[12] Patent: US2018/222844, 2018, A1, . Location in patent: Paragraph 0187; 0193; 0194
[13] Patent: WO2009/21107, 2009, A1, . Location in patent: Page/Page column 32
[14] Patent: US2010/190994, 2010, A1, . Location in patent: Page/Page column 24
[15] Patent: EP2502908, 2012, A1, . Location in patent: Page/Page column 40
[16] Journal of Nanoscience and Nanotechnology, 2016, vol. 16, # 8, p. 8796 - 8799
[17] Journal of Nanoscience and Nanotechnology, 2018, vol. 18, # 3, p. 2166 - 2170
[18] Journal of Organic Chemistry, 2018, vol. 83, # 5, p. 2640 - 2646
38
[ 626-39-1 ]
[ 24388-23-6 ]
[ 103068-20-8 ]
Yield
Reaction Conditions
Operation in experiment
57%
With tetrakis(triphenylphosphine) palladium(0); potassium carbonate In tetrahydrofuran; water at 80℃;
After the starting material 1,3,5-tribromobenzene (38.59g, 122.6mmol) was dissolved in THF in a round bottom flask, 4,4,5,5-tetramethyl-2-phenyl-1,3,2-dioxaborolane (50.03 g, 245.2mmol), Pd (PPh3) 4 (4.25g, 3.7mmol), K2CO3 (101.66g, 735.5mmol), water was added and the resulting mixture was stirred at 80 C. After the reaction was completed, the organic layer was dried and extracted with water and CH2Cl2 over MgSO4, and concentrated to a silicagel column, and the resulting compound was recrystallized product 21.61g (yield: 57percent) was obtained.
Reference：
[1] Journal of Materials Chemistry, 2008, vol. 18, # 28, p. 3376 - 3384
[2] Patent: KR2015/122343, 2015, A, . Location in patent: Paragraph 0162; 0173; 0175; 0176; 0177
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With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; potassium acetate In N,N-dimethyl-formamide at 90℃; for 24 h; Inert atmosphere
Synthesis of Compound 1: Anhydrous DMF (10 mL) was purged with N2 and then transferred via a cannula into a three-neck round bottomed flask charged with 1, 3, 5-tribromobenzene (1.00 g, 3.17 mmol) and bis (pinacolato) diboron (2.54 g, 9.53 mmol) . Potassium acetate (1.87 g, 19.0 mmol) and Pd(dppf)Cl2 (0.087 g, 0.12 mmol) were then quickly added into the flask. The resulting mixture was stirred vigorously and heated at 90 °C for 24 hours. After cooling down to room temperature, deionized water (120 mL) was added. Black precipitate was collected by filtration, and washed with deionized water three times, which was dried under vacuum (98percent yield) .
88%
With potassium acetate In 1,4-dioxane at 80℃; Inert atmosphere
A mixture of 1,3,5-tribromobenzene (7.96 g, 25.3 mmol), bis(pinacolato)diboron (21.2 g, 83.5 mmol), [1,1'-Bis(diphenylphosphino)ferrocene]dichloropalladium (2.78 g, 3.79 mmol), potassium acetate (22.3 g, 228 mmol) in anhydrous 1,4-dioxane (400 mL) was degassed for 80 minutes. Mixture was then heated to 80° C. overnight under argon. After cooling to room temperature, the remaining solids were filtered off. The filtrate was dried under vacuum, redissolved in methylene chloride (400 mL) then washed with water (2.x.300 mL) and brine (300 mL). Organic layer was dried over sodium sulfate and loaded onto silica gel. A silica plug (11percent ethyl acetate in hexanes) and precipitation from methylene chloride/methanol gave 4 (9.76 g, 88percent yield).
71.3%
With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; potassium acetate In N,N-dimethyl-formamide at 85℃; for 24 h; Inert atmosphere
Under a nitrogen atmosphere, 250ml three-necked flask 1,3,5-bromobenzene (15.74g, 50mmol), United pinacolato ester (41.9g, 0.165mol, TCI), potassium acetate (48.58g, 0.495mol), 1,1'- bis (diphenylphosphino) ferrocene palladium dichloride (4.08g, 5mmol) and dimethylformamide (300ml), 85 The reaction mixture was stirred under heating 24h.After completion of the reaction naturally cooled, the reaction solution was extracted with ethyl acetate, washed with saturated brine three times, the resulting organic layer was dried over anhydrous magnesium sulfate.Filtration, the resulting filtrate was removed under reduced pressure to remove the solvent.Separated by column chromatography, the mobile phase was chloroform.After the spin-dry vacuum dried to give a white powder 16.25g, yield 71.3percent.
69%
With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; potassium acetate In 1,4-dioxane at 90℃; Schlenk technique; Inert atmosphere
10108] In a flame-dried Schlenk tube under argon atmosphere, 1,3,5-tribromobenzene (200 mg, 0.64 mmol) and S2Pin2 (731.3 mg, 2.88 mmol) were dissolved in 20 ml 1,4-dioxane. Flame dried KOAc (471.1 mg, 4.8 mmol) was added quickly to the mixture followed by PdC12 (dppf) (15.5 mg, 0.029 mmol). The mixture was heated at 90° C. overnight. The progress of reaction was tracked by TLC (9 hexanes: 1 ethyl acetate) and visualization was achieved in an iodine chambet Two spots (Rf 0.20 and RI 0.25) were observed and heating was stopped and allowed to cool down to room temperature. 20-30 ml ethyl acetate was added to quench the reaction. 30 ml DI water was added to extract the aqueous phase and 30 ml brine (2x) was used to wash the organic phase, dried over anhydrous MgSO4 and filtered. After concentrating down the filtrate, hexanes: ethyl acetate (9:1) mixture was used to elute Rf 0.25 in silica column chromatography to yield white powder [6 9percent, 200 mgI. 1R NMR (300.0 MHz, CDC13): ö 8.36 (s, 3R; CR), ö 1.32 (s, 36R; CR3). 13C {1R} NMR (75.5 MRz, CDC13): ö144.14 (CR), ö 83.79 (CCR3), ö 24.96 (CR3), n.o. (CS).
57%
With potassium acetate In dimethyl sulfoxide at 80℃; for 20 h; Inert atmosphere
EXAMPLE 1 <Synthesis of 1,3,5-tris(2,2'-bipyridin-6-yl)benzene (compound 6)> 8.6 g of 1,3,5-tribromobenzene, 25.0 g of bis(pinacolato)diboron, 24.1 g of potassium acetate, 250 ml of dimethyl sulfoxide previously dewatered with Molecular Sieves 4A, and 1.4 g of PdCl2(dppf)-CH2Cl2 were put into a nitrogen-purged reactor, then heated, and stirred at 80°C for 20 hours. After cooled to room temperature, the reaction liquid was put into 1000 ml of water, and stirred for 30 minutes. The precipitate was collected through filtration, and the precipitate was washed with methanol to obtain a crude product. The crude product was dissolved in 200 ml of ethyl acetate, the insoluble matter was removed through filtration, and the filtrated was concentrated to dryness to obtain 7.1 g (yield 57percent) of a white powder, 1,3,5-tris(4,4,5,5-tetramethyl-[1,3,2]dioxabororan-2-yl)benzene. 2.5 g of the obtained 1,3,5-tris(4,4,5,5-tetramethyl-[1,3,2]dioxabororan-2-yl)benzene, 3.8 g of 6-bromo-[2,2']-bipyridine, 32.3 ml of aqueous 1 M potassium carbonate solution, 0.3 g of tetrakis(triphenylphosphine)palladium(0), 108 ml of toluene and 27 ml of ethanol were put into a nitrogen-purged reactor, and heated under reflux with stirring for 18 hours. After cooled to room temperature, this was processed for liquid-liquid separation with 100 ml of water and 100 ml of toluene added thereto, and the organic layer was further washed with 100 ml of water. The organic layer was dewatered with anhydrous magnesium sulfate and then concentrated to obtain a crude product. The crude product was purified through column chromatography (carrier: NH silica gel, eluent: chloroform/n-hexane) to obtain 1.1 g (yield 38percent) of a white powder, 1,3,5-tris(2,2'-bipyridin-6-yl)benzene (compound 6).
Reference：
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[2] Patent: WO2015/157239, 2015, A1, . Location in patent: Paragraph 00121; 00122
[3] Patent: US2011/196158, 2011, A1, . Location in patent: Page/Page column 7; 8
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[5] Patent: CN103396355, 2016, B, . Location in patent: Paragraph 0062-0064
[6] Patent: US2016/178766, 2016, A1, . Location in patent: Paragraph 0106; 0107; 0108
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1,3,5-tribromobenzene (20 g, 64 mmol) was dissolved in 500 mL of ether and cooled to -78 C.Of 2.5M n-Butyllithim 39.6mL was added slowly. After stirring at -78 C for 2 hours, 6.5 mL of N,N-dimethylacetamide dissolved in 50 mL of ether was slowly added. And the mixture was stirred at room temperature for 17 hours. 350 mL of HCl (10%) was added to the reaction solution to terminate the reaction. Dichloromethane and gave after using water by neutralizing the organic layer was removed and the water layer, the remaining water layer was removed using a Magnesium sulfate.The organic layer was filtered through silica gel and celite under reduced pressure, and the resulting filtrate was concentrated and then recrystallized from ethanol to obtain 7.5 g (yield: 43%) of intermediate (2)
Sodium methoxide (25 g; WAKO) was added to a DMF (250 mL) solution of 1,3,5-tribromobenzene (75 g; TCI) and the resulting mixture was stirred at 90° C. for 15 minutes. The reaction mixture was concentrated, aqueous ammonium chloride (400 mL) and ethyl acetate (400 mL) were added to extract the reaction mixture, the organic layer was washed with saturated brine (200 mL.x.2), and the organic layer was dried. The solvent was evaporated under reduced pressure and the residue was purified by column chromatography (n-hexane) to give the title compound (39.2 g).1H-NMR (CDCl3); 8 (ppm) 3.97 (3H, s), 6.98 (2H, m), 7.25 (1H, m)
under the protection of nitrogen gas the 25kg of tetrahydrofuran, 400g of tribromobenzene and Fresh magnesium tablets 500g were added to reaction kettle and stirred for 5min at room temperature. cooled down the reaction to 0C then catalytic amount 120g of Methylmagnesium chloride was added and raised the temperature to reflux. After the initiation , control temperature to 55-60 C for adding tribromobenzene 4kg in batches , after about 3 hours of addition the temperature was raised to reflux insulation for 30 minutes; cooled down the reaction to 0C, then 1.5kf of DMF was added drop wise and addition was completed within 1hour. And then slowly raising temperature to 5-10 C and incubated for 1 hour. After the reaction, add 15% hydrochloric acid for acidification , temperature controlled at 10 C for 1 hour. The solution is then allowed to stand for separation. Water phase was extracted with ethyl acetate , The organic phase was combined, concentrated, the17.5kg of petroleum ether was added, the temperature was raised to reflux and then cooled to 0 C, and the temperature was maintained for 1 hour. The product subjected to centrifugation and drying to give 3,5-dibromobenzaldehyde. Content of 99.5% (GC), the yield of 95%.
70%
Compound 2 was synthesized according to the literature [22].Briefly, a suspension of 1,3,5-tribromobenzene (4.0 g,12.7 mmol) inanhydrous diethyl ether (100 mL) at -78 C was treated dropwisewith butyllithium (2.5 M, 5.3 mL, 13.5 mmol). After 45 min, DMF(2.8 g, 38.3 mmol) was droped into the mixture, which was thenstirred for another 1 h. Diluted HCl (40 mL, 2 mol/L) was added,then organic phase was removed, and a brown solid was obtained.The crude product was purified by column chromatography (silicagel) using DCM/n-hexane = 1/10 as eluent and recrystallized fromdiethyl ether/n-hexane to give needle compound 2 (2.34 g, 70%).
With potassium carbonate; In ethanol; water; at 50℃; for 5h;Inert atmosphere; Schlenk technique;
General procedure: A Schlenk tube was charged with a suspension of aryl halide (1.0mmol), arylboronic acid (1.2 mmol), potassium carbonate (276 mg,2.0 mmol) and Pd/HCCP-DABP (20 mg, 0.3 mol%) in EtOH-H2O (3 mL,v:v=1:1), evacuated, and backfilled with nitrogen. The resulting reaction mixture was stirred at 50 C for 2.5 h. After completion of the reaction,the mixture was cooled and extracted with CH2Cl2. The combined organic phase was dried, evaporated and purified by column chromatographyon silica gel to give the coupling product. The aqueous phasewas filtered and the solid was washed with CH2Cl2 and reused in further reactions as the recovered catalyst.
69%
With tetrakis(triphenylphosphine) palladium(0); potassium carbonate; In tetrahydrofuran; water; at 90℃; for 6h;
1,3,5-tribromobenzene (14.6 g, 46 mmol), phenylboronicacid (5.6 g, 46mmol), Pd (PPh3) 4 (1.6 g, 1.4mmol), K2CO3 (19.2 g, 14mmol), THF (100 ml), put H2O (50 ml) and the mixture was stirred under reflux for 6 hours in 90 . When the reaction is complete cool the temperature of the reaction to room temperature, and was extracted with CH2Cl2 and water wipe. The organic layer was dried over MgSO4, isolated by using silicagel column The concentrated and the organic product generated by Core 1-1-8-C1 9.8 g (69%) is obtained.
67%
With tetrakis(triphenylphosphine) palladium(0); potassium carbonate; In tetrahydrofuran; water; at 60℃; for 15h;
1,3,5-tribromobenzene (9.3 g) and phenylboronic acid (3.6 g), Pd(PPh3)4(1 g), and K2CO3 (12 g) were diluted with THF (120 ml) and water (40 ml), and the mixed solution was stirred under reflux at a temperature of 60 C. for 15 hours. When the reaction was completed, the temperature was lowered to room temperature, and an extraction process was performed thereon three times by using ethyl acetate. The extract obtained therefrom was dried by using magnesium sulfate anhydrous, and then, was subjected to filtration under reduced pressure and distillation under reduced pressure. The filtrate obtained therefrom was separated and purified by column chromatography, thereby obtaining Intermediate 2-1 (6.2 g, 67%). [M+] C12H8Br2 calc'd: 309.90; found: 309.93 .
65%
With tetrakis(triphenylphosphine) palladium(0); sodium carbonate; In 1,2-dimethoxyethane; water; for 8h;Reflux; Inert atmosphere;
In an argon atmosphere, a mixture of 1,3,5-tribromobenzene (9.44 g, 30 mmol), phenylboronic acid (1.22 g, 10 mmol), tetrakis(triphenylphosphine) palladium (231 mg, 0.2 mmol), DME (50 mL), and a 2 M aqueous solution of sodium carbonate (10 mL, 20 mmol) was allowed to react for 8 h while refluxing under heating. After cooling the reaction solution to room temperature, the water layer was separated and removed, and the organic layer was dried over magnesium sulfate. Then, the insolubles were removed by filtration, and the organic solvent was evaporated off under reduced pressure. The obtained residue was purified by silica gel column chromatography to obtain the intermediate B-9 (2.03 g, yield: 65%).
63%
With tetrakis(triphenylphosphine) palladium(0); potassium carbonate; In tetrahydrofuran; water; at 80℃; for 16h;
Intermediate I-5 4.31 g (10 mmol), 2-Chloro-4,6-diphenyl-1,3,5-triazine 2.68 g (10 mmol), Pd (PPh3) 4 ( tetra-kis(triphenylphosphine) palladium ) 0.58 g ( 0.5 mmol ) and 4.14 g K2CO3 ( 30 mmol ) and THF / H2O ( 2/1 volume ratio) mixed solution Was dissolved in 60 mL , it was stirred at 80C for 16 hours. After cooling to room temperature the reaction solution was added to 40 mL water in aButyl ether and extracted three times with 50 mL. The combined organic layers were dried over magnesium sulfate, and the resulting glass by evaporation of the solventSeparating residues jelgwan by silica chromatography to give the compound 2A 3.38 g ( yield 63%) . The resulting compound isAnd MS / FAB One It was confirmed.Instead of Intermediate I-5 using a phenylboronic acid and 2-Chloro-4,6-diphenyl-1,3,5-triazine in place of 1,3,5- tribromobenzene It was used except that by using the same method as that of Compound 2A of the above Synthesis Example 1 , Intermediate A-20To give the 1.97 g ( 63% yield). The resulting compound was confirmed by LC-MS
63%
With tetrakis(triphenylphosphine) palladium(0); potassium carbonate; In tetrahydrofuran; water; at 80℃; for 12h;
12.6 g (40 mmol) of 1,3,5-tribromobenzene, 3.66 g (30 mmol) of phenylboronic acid,3.4 g (1.5 mmol) of Pd (PPh3) 4 and 12.6 g (90 mmol) of K2CO3 were dissolved in 350 mL of a THF / H2O mixed solvent (in a volume ratio of 2/1)The reaction solution was stirred at a temperature of 80 C for 12 hours.The resulting reaction solution was cooled to room temperature,The organic layer was extracted three times by using 60 mL of water and 60 mL of ethyl acetate.The organic layer thus collected was dried with magnesium sulfate,The residue obtained after the solvent was evaporated from the silica gel column chromatography was used to separate and purify the residue,To obtain 5.9 g of intermediate I-8 (yield: 63%).The compounds thus produced were determined by using LC-MS.
60.56%
With bis-triphenylphosphine-palladium(II) chloride; sodium carbonate; In toluene; for 3h;Reflux;
[173] After mixing 1,3,5-tribromobenzen (40 g, 127.06 mmol), phenyl boronic acid (17.04 g, 139.7 mmol), PdCl(PPh3)2 (1.78 g, 2.54 mmol), toluene 500 mL, and Na2CO3 (2 M, 130 mL), the mixture was stirred under reflux. After 3 hours, the mixture was cooled to room temperature, and distilled water was added. The mixture was extracted with ethyl acetate (EA) and dried with magnesium sulfate. After drying under reduced pressure, the resulting product was separated through a column to obtain compound 1-8 (24 g, 76.9 mmol, 60.56 %).
55%
With tetrakis(triphenylphosphine) palladium(0); sodium carbonate; In ethanol; water; toluene; at 90℃; for 8h;Inert atmosphere;
Next, under an Ar atmosphere,In a 1 L three-necked flask,10.0 g of 1,3,5-tribromobenzene,7.20 g of phenyl boronic acid, 9.54 g of Pd (PPh 3) 4,And 20.4 g of sodium carbonate were added,In a mixed solvent of 430 mL of toluene and 210 mL of water at 90 C.,And the mixture was heated and stirred for 8 hours.After air cooling,Water was added to separate the organic layer and the solvent was distilled off.The obtained crude product was purified by silica gel column chromatography (using a mixed solvent of dichloromethane and hexane)Recrystallization was performed with a toluene / hexane mixed solvent,5.45 g (55% yield) of compound F as a white solid was obtained.
To a 2200 mL three-necked flask were added 2.60 g (8.26 mmol) of the compound a and 150 ml of dehydrated diethyl ether, and the mixture was stirred under -70 C. in a nitrogen atmosphere. 5.0 ml (1.65 mol / l n-hexane solution, 8.25 mmol) of n-butyl lithium was added dropwise at -70 C.Within 60 minutes and stirred for 2 hours.A solution of 2.40 g (9.09 mmol) of compound b in 30 ml of dehydrated diethyl ether was added all at once and the mixture was further stirred for 2 hours. After returning the reaction mixture to room temperature, 100 ml of methanol was added to terminate the reaction.After distilling off the solvent, the obtained viscous substance was purified by silica gel column chromatography (hexane: ethyl acetate = 19: 1 ? 4: 1) to obtain 2.59 g (5.18 mmol) of the objective compound c, , Yield 63%.
With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; potassium carbonate; In 1,4-dioxane; water; at 100℃; for 48h;Inert atmosphere;
4-[N-(tert-Butoxycarbonyl)amino]phenylboronic acid (1.00 g, 4.22 mmol) was dissolved in 5:1 dioxane/H2O mixture (60 mL), and 1,3,5-tribromobenzene (0.31 g, 1.00 mmol), Pd(dppf)Cl2 (0.20 g, 0.27 mmol), and K2CO3(0.80 g, 5.80 mmol) were added sequentially. The resulting mixture was stirred in a preheated (100 C) oil bath for 48 h under argon atmosphere. After the mixture had cooled to room temperature, it was poured into brine and extracted twice with dichloromethane. The combined organic extracts were washed three times with water, dried over anhydrous Na2SO4, filtered, and evaporated. The residue was purified using column chromatography (silica gel, petroleum ether-ethyl acetate 30:1 as eluent) to yield 0.40 g (61 %) white solid. NMR (400 MHz, CDCl3) delta 7.69 (s, 3H), 7.64 (d, J = 8.6 Hz, 6H), 7.49 (d, J = 8.4 Hz, 6H), 1.56 (s, 27H).
(Example 2); (Method of producing Exemplified Compounds Nos. 35 and 60); Pd (PPh3) a Br ; BtOH2 Na2C03 aq. i i i Br Br toluene/ETOH-CHC13 Me Me Me Mu i... Br HN : i i i l r i I 4 ff il¢tr3 Pd (dba) 2/P (tBu) 3 BrrS) rirBr TITY tBuONa xylene (1w (Synthesis of Intermediate (IV)) In a stream of nitrogen, 25.8 g (82 mmol) of tribromobenzene and 109.5 g (0.491 mol) of <strong>[100622-34-2]anthracene-9-boronic acid</strong> were dissolved in a deaerated mixture solvent of 1 1 of toluene and 500 ML of ethanol and then the whole was stirred. A sodium carbonate aqueous solution prepared by dissolving 86. 8 g of anhydrous sodium carbonate in 800 ml of water was added dropwise into the solution. In a stream of nitrogen, the resulting mixture was stirred for 1 hour in an oil bath heated to 80C, followed by the addition of 14.2 g (12.3 mmol) of tetrakis (triphenylphosphine) palladium. Then, the mixture was heated and stirred for about 4 hours in an oil bath heated to 80C. The temperature of the reaction solution was returned to room temperature and further cooled to 5C, followed by filtering the precipitated crystal out. The crystal was dissolved in a mixture solvent of chlorobenzene and heptane under heating and then purified by silica gel column chromatography (CHLOROBENZENE : heptane = 1 : 3), resulting in 25 g of Intermediate (III).
PREPARATION 6 3-(3,5-Dibromophenoxy)pyridine Sodium hydride (3.24 g of a 60% dispersion in mineral oil) was added portionwise to a stirred mixture of 3-hydroxypyridine (15.4 g), 1,3,5-tribromobenzene (76.4 g), cuprous oxide (11.6 g) and collidine (400 ml). When evolution of hydrogen had ceased, the mixture was heated at 200 for 8 hours and then cooled. The cool mixture was diluted with ethyl acetate and water, basified with aqueous ammonia (SG 0.880) and then filtered. The filtered residue was washed with ethyl acetate, then the washings and organic phase of the filtrate combined, washed with saturated brine and dried (MgSO4). The ethyl acetate was evaporated under vacuum, the collidine removed by distillation under vacuum and the residue chromatographed on silica gel using ether:hexane (1:4) as eluent. The earlier fractions gave, after evaporation under vacuum, recovered tribromobenzene (42.5 g). The later fractions were evaporated under vacuum to afford the title compound as an oil (18.55 g); delta (CDCl3): 7.07(2H,s), 7.22-7.26(2H,m), 7.42 (1H,s), 8.42(1H,s), 8.47(1H,d). Found: C,40.49; H,2.17; N,4.19. C11 H7 Br2 NO requires C,40.16; H,2.14; N,4.26%.
With ammonia; In 2,3,5-trimethyl-pyridine; hexane; ethyl acetate; mineral oil;
PREPARATION 3 1,3-Dibromo-5-(4-fluorophenoxy)benzene Sodium hydride (3.24 g of 60% suspension in mineral oil was added portionwise to a stirred mixture of 1,3,5-tribromobenzene (76.4 g), 4-fluorophenol (18.16 g), and cuprous oxide (11.6 g) in collidine (400 ml) at room temperature. When evolution of hydrogen had ceased the mixture was heated under reflux with stirring for 8 hours. It was then cooled and filtered. The residue was washed with ethyl acetate followed by concentrated aqueous ammonia, and the combined filtrate and washings were partitioned between ethyl acetate and water. The organic layer was washed twice with brine and evaporated. The residue was dissolved in ethyl acetate, and the solution was filtered, washed several times with citric acid solution and dried (MgSO4). The solvent was evaporated, and the residue was dissolved in hot hexane. The solution was filtered and the filtrate was evaporated. The residue was chromatographed on silica using hexane as eluent to give the title compound as an oil (18.21 g), Rf 0.31(SS 2). Found: C,41.71; H,1.97. C12 H7 Br2 FO requires C,41.66; H,2.04%.
With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; potassium acetate; In N,N-dimethyl-formamide; at 90℃; for 24h;Inert atmosphere;
Synthesis of Compound 1: Anhydrous DMF (10 mL) was purged with N2 and then transferred via a cannula into a three-neck round bottomed flask charged with 1, 3, 5-tribromobenzene (1.00 g, 3.17 mmol) and bis (pinacolato) diboron (2.54 g, 9.53 mmol) . Potassium acetate (1.87 g, 19.0 mmol) and Pd(dppf)Cl2 (0.087 g, 0.12 mmol) were then quickly added into the flask. The resulting mixture was stirred vigorously and heated at 90 C for 24 hours. After cooling down to room temperature, deionized water (120 mL) was added. Black precipitate was collected by filtration, and washed with deionized water three times, which was dried under vacuum (98% yield) .
88%
With potassium acetate;(1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; In 1,4-dioxane; at 80℃;Inert atmosphere;
A mixture of 1,3,5-tribromobenzene (7.96 g, 25.3 mmol), bis(pinacolato)diboron (21.2 g, 83.5 mmol), [1,1'-Bis(diphenylphosphino)ferrocene]dichloropalladium (2.78 g, 3.79 mmol), potassium acetate (22.3 g, 228 mmol) in anhydrous 1,4-dioxane (400 mL) was degassed for 80 minutes. Mixture was then heated to 80 C. overnight under argon. After cooling to room temperature, the remaining solids were filtered off. The filtrate was dried under vacuum, redissolved in methylene chloride (400 mL) then washed with water (2×300 mL) and brine (300 mL). Organic layer was dried over sodium sulfate and loaded onto silica gel. A silica plug (11% ethyl acetate in hexanes) and precipitation from methylene chloride/methanol gave 4 (9.76 g, 88% yield).
71.3%
With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; potassium acetate; In N,N-dimethyl-formamide; at 85℃; for 24h;Inert atmosphere;
Under a nitrogen atmosphere, 250ml three-necked flask 1,3,5-bromobenzene (15.74g, 50mmol), United pinacolato ester (41.9g, 0.165mol, TCI), potassium acetate (48.58g, 0.495mol), 1,1'- bis (diphenylphosphino) ferrocene palladium dichloride (4.08g, 5mmol) and dimethylformamide (300ml), 85 The reaction mixture was stirred under heating 24h.After completion of the reaction naturally cooled, the reaction solution was extracted with ethyl acetate, washed with saturated brine three times, the resulting organic layer was dried over anhydrous magnesium sulfate.Filtration, the resulting filtrate was removed under reduced pressure to remove the solvent.Separated by column chromatography, the mobile phase was chloroform.After the spin-dry vacuum dried to give a white powder 16.25g, yield 71.3%.
69%
With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; potassium acetate; In 1,4-dioxane; at 90℃;Schlenk technique; Inert atmosphere;
10108] In a flame-dried Schlenk tube under argon atmosphere, 1,3,5-tribromobenzene (200 mg, 0.64 mmol) and S2Pin2 (731.3 mg, 2.88 mmol) were dissolved in 20 ml 1,4-dioxane. Flame dried KOAc (471.1 mg, 4.8 mmol) was added quickly to the mixture followed by PdC12 (dppf) (15.5 mg, 0.029 mmol). The mixture was heated at 90 C. overnight. The progress of reaction was tracked by TLC (9 hexanes: 1 ethyl acetate) and visualization was achieved in an iodine chambet Two spots (Rf 0.20 and RI 0.25) were observed and heating was stopped and allowed to cool down to room temperature. 20-30 ml ethyl acetate was added to quench the reaction. 30 ml DI water was added to extract the aqueous phase and 30 ml brine (2x) was used to wash the organic phase, dried over anhydrous MgSO4 and filtered. After concentrating down the filtrate, hexanes: ethyl acetate (9:1) mixture was used to elute Rf 0.25 in silica column chromatography to yield white powder [6 9%, 200 mgI. 1R NMR (300.0 MHz, CDC13): oe 8.36 (s, 3R; CR), oe 1.32 (s, 36R; CR3). 13C {1R} NMR (75.5 MRz, CDC13): oe144.14 (CR), oe 83.79 (CCR3), oe 24.96 (CR3), n.o. (CS).
57%
With potassium acetate;dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2; In dimethyl sulfoxide; at 80℃; for 20h;Inert atmosphere;
EXAMPLE 1 <Synthesis of 1,3,5-tris(2,2'-bipyridin-6-yl)benzene (compound 6)> 8.6 g of 1,3,5-tribromobenzene, 25.0 g of bis(pinacolato)diboron, 24.1 g of potassium acetate, 250 ml of dimethyl sulfoxide previously dewatered with Molecular Sieves 4A, and 1.4 g of PdCl2(dppf)-CH2Cl2 were put into a nitrogen-purged reactor, then heated, and stirred at 80C for 20 hours. After cooled to room temperature, the reaction liquid was put into 1000 ml of water, and stirred for 30 minutes. The precipitate was collected through filtration, and the precipitate was washed with methanol to obtain a crude product. The crude product was dissolved in 200 ml of ethyl acetate, the insoluble matter was removed through filtration, and the filtrated was concentrated to dryness to obtain 7.1 g (yield 57%) of a white powder, 1,3,5-tris(4,4,5,5-tetramethyl-[1,3,2]dioxabororan-2-yl)benzene. 2.5 g of the obtained 1,3,5-tris(4,4,5,5-tetramethyl-[1,3,2]dioxabororan-2-yl)benzene, 3.8 g of 6-bromo-[2,2']-bipyridine, 32.3 ml of aqueous 1 M potassium carbonate solution, 0.3 g of tetrakis(triphenylphosphine)palladium(0), 108 ml of toluene and 27 ml of ethanol were put into a nitrogen-purged reactor, and heated under reflux with stirring for 18 hours. After cooled to room temperature, this was processed for liquid-liquid separation with 100 ml of water and 100 ml of toluene added thereto, and the organic layer was further washed with 100 ml of water. The organic layer was dewatered with anhydrous magnesium sulfate and then concentrated to obtain a crude product. The crude product was purified through column chromatography (carrier: NH silica gel, eluent: chloroform/n-hexane) to obtain 1.1 g (yield 38%) of a white powder, 1,3,5-tris(2,2'-bipyridin-6-yl)benzene (compound 6).
General procedure: To a flask containing dried LiCl (0.35 g, 8.24 mmol) was added iPrMgCl (2 M in THF, 4.1 mL) and THF (5 mL) at 15 C. After beingstirred for 15 min, 3-bromo-1-benzonitrile (1.46 g, 8.03 mmol) inTHF (1 mL) was added to the reaction mixture and the obtainedmixture was stirred for 15 min. Then, DMF (1.3 mL, 12 mmol) wasadded at 0 C and the mixture was stirred for 2 h. Then, aq NH3 (7 mL, 28-30%) and I2 (4.06 g, 16 mmol) were added to the reaction mixture. After being stirred for 2 h at room temperature, the reactionmixture was poured into satd aq Na2SO3 solution and was extracted with CHCl3 (3?30 mL). The organic layer was dried over Na2SO4 and filtered. After removal of the solvent, the residue waspurified by short column chromatography on silica gel (eluent:hexane/ethyl acetate=9:1, v/v) to provide pure 1,3-dicyanobenzene (0.73 g) in 71% yield. Most nitriles mentioned in this work are commercially availableand were identified by comparison with the authentic samples.
Tert-butyllithium in pentane (1.6M, 7.72 mL) was added dropwise to a solution of 1 ,3,5 tribromobenzene (0.972 g, 3.09 mmol) in anhydrous ether (30 mL) at -78 C under a flow of nitrogen gas. After 2 h, 2-Fluoro-/V-methoxy-/V- methyl-benzamide (1.132 g, 6.18 mmol) dissolved in anhydrous ether (5 mL) was added dropwise and the reaction mixture was allowed to slowly come to room temperature and stirred for 24 h. After 24 h, the reaction mixture was quenched with water (30 ml_) and the products were extracted with ether (2 x 50 ml_). The combined organic phases were washed with brine, dried over anhydrous sodium sulfate, and the solvent was removed under reduced pressure. Purification using flash chromatography (silica gel, hexanes:ethyl acetate, gradient 95:5 to 60:40) afforded 2-1 ,3-bis(2-fluoro-benzoyl)-5-bromobenzene 10 (0.617 g, 6.18 mmol) in a 50% yield.
With tris-(dibenzylideneacetone)dipalladium(0); 2,2'-bis-(diphenylphosphino)-1,1'-binaphthyl; sodium t-butanolate; In toluene; for 72h;Inert atmosphere; Reflux;
A mixture of aniline (7.4 g, 79.4 mmol), 1,3,5-tribromobenzene 3 (5.0 g, 15.88 mmol), tris(dibenzylideneacetone) dipalladium(0) [Pd2(dba)3(0), 0.11 g, 0.25 mol %], rac-2,2'-bis(diphenylphosphino)-1,1'-binapthyl (BINAP, 0.22 g, 0.75 mol %), and sodium t-butoxide (7.63 g, 79.4 mmol) in anhydrous toluene (250 mL) was heated to refluxing temperature under nitrogen for a period of 72 h. The reaction mixture was cooled to room temperature and washed with water (100 mL). The organic layer was dried over anhydrous sodium sulfate (Na2SO4). After evaporation of the solvent, a crude brown color solid was obtained. Excess aniline was then removed by distillation at 130 C under reduced pressure of 101 mmHg. It was further purified by chromatography (SiO2). The resulting light brown product 1,3,5-tris(phenylamino)benzene 4, TPAB, was obtained in 75% yield (4.18 g). FT-IR (KBr) upsilonmax 3403 (m), 3375 (m), 3078 (w), 3019 (w), 2945 (s), 1612 (m), 1591 (vs), 1518 (m), 1496 (s), 1469 (m), 1431(w), 1456 (m), 1409 (m), 1365 (w), 1295 (m), 1269 (w), 1246 (m), 1,171 (m), 1073 (w), 1030 (w), 897 (w), 834 (w), 820 (w), 802 (w), 756 (m), 721 (w), 700 (m), 688 (m), 613 (w), and 558 (w) cm-1; UV-vis (CHCl3, 1.0 × 10-5 M) lambdamax (epsilon) 289 nm (4.80 × 104 L mol-1 cm-1); 1H-NMR (500 MHz, CDCl3) delta 7.25 (t, J = 7.8 Hz, 6H), 7.08 (d, J = 7.7 Hz, 6H), 6.92 (t, J = 7.3 Hz, 3H), 6.32 (s, 3H), and 5.60 (s, 3H, N-H); 13C-NMR (125 MHz, CDCl3) delta 145.4, 142.7, 129.3, 121.3, 118.7, and 99.0.
tert-Butyllithium in pentane (1.6 M, 7.72 mL) was added dropwise to a solution of 1,3,5-tribromobenzene (0.972 g, 3.09 mmol) in anhydrous ether (30 mL) at -78 C under a flow of nitrogen gas. After 2 h, <strong>[198967-24-7]2-fluoro-N-methoxy-N-methyl-benzamide</strong> (1.132 g, 6.18 mmol) dissolved in anhydrous ether (5 mL) was added dropwise and the reaction mixture was allowed to slowly come to room temperature and stirred for 24 h. After 24 h, the reaction mixture was quenched with water (30 mL) and the products were extracted with ether (2 * 50 mL). The combined organic phases were washed with brine, dried over anhydrous sodium sulfate, and the solvent was removed under reduced pressure. Purification using flash chromatography (silica gel, hexanes/ethyl acetate, gradient 95:5 to 60:40) afforded 1,3-bis(3-fluorobenzoyl)-5-bromobenzene (0.617 g, 6.18 mmol, 50% yield). 1H NMR (500 MHz, CDCl3): delta 8.16 (2H, m), 8.12 (1H, pentet, J = 1.4 Hz), 7.61-7.56 (4H, m), 7.30 (2H, td, J = 7.5 Hz, 1.0 Hz), 7.20-7.16 (2H, m). 13C NMR (125 MHz, CDCl3): delta 191.23, 160.40 (d, J = 254 Hz), 139.67, 133.61, 134.29 (d, J = 8.6 Hz), 131.12 (d, J = 1.9 Hz), 129.31, 125.79 (d, J = 13.8 Hz), 124.79 (d, J = 3.8 Hz), 123.18, 116.70 (d, J = 21 Hz). 19F NMR (470 MHz, CDCl3): delta -109.73 to -109.78 (1F, m). HRMS (ESI) calculated for C20H11BrF2O2H+ (M+H)+ 400.99833, found 400.99857.
1,3,5-tris(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzene (IC-2) A mixture of 1,3,5-tribromobenzene (7.00 g, 22.24 mmol), bis(pinacolato)diboron (18.82 g, 74.11 mmol), [1,1'-bis(diphenyl-phosphino)ferrocene]-dichloropalladium(II) (1.79 g, 2.45 mmol), potassium acetate (14.84 g, 151.20 mmol), and anhydrous 1,4-dioxane (70 mL) (Aldrich) was degassed with bubbling argon for 30 minutes at room temperature. The reaction was then heated to 100 C. on a hot plate with a silicone oil bath and was stirred overnight for 16 hours while maintaining an argon atmosphere. Consumption of the starting material was confirmed by thin-layer chromatography and the reaction was cooled to room temperature. The mixture was filtered and washed with dichloromethane, and the filtrate was dried. The product was then recrystallized from hexanes (Aldrich). The recrystallized product was collected to yield compound IC-2 (7.66 g, 76%). Confirmed by LCMS (APCI): calculated for C24H39B3O6 (M+H): 457. Found: 457.
With potassium acetate;
1,3,5-tris(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzene (Intermediated Compound 2 [IC-2]) A mixture of 1,3,5-tribromobenzene (7.00 g, 22.24 mmol), bis(pinacolato)diboron (18.82 g, 74.11 mmol), [1,1'-bis(diphenyl-phosphino)ferrocene]-dichloropalladium(II) (1.79 g, 2.45 mmol), potassium acetate (14.84 g, 151.20 mmol), and anhydrous 1,4-dioxane (70 mL) was degassed with bubbling argon for 30 minutes at room temperature. The reaction was then heated to 100 C. on a hot plate with a silicone oil bath and was stirred overnight for 16 hours while maintaining an argon atmosphere. Consumption of the starting material was confirmed by thin-layer chromatography and the reaction was cooled to room temperature. The mixture was filtered and washed with dichloromethane, and the filtrate was dried. The product was then recrystallized from hexanes. The recrystallized product was collected to yield compound IC-2 (7.66 g, 76%). Confirmed by LCMS (APCI): calculated for C24H39B3O6 (M+H): 457. Found: 457.
With tetrakis(triphenylphosphine) palladium(0); sodium hydroxide; In tetrahydrofuran; water; at 80 - 90℃;
Sub 1-4-1 (5.7g, 20mmol) placed in a round bottom flask, Sub 1-5-1 (6.3g, 20mmol), Pd(PPh3)4 (0.7g, 0.6mmol), NaOH (2.4g, 60mmol), THF (60mL), water (30mL) are added. Then heated to reflux while 80 C~90 C. After completion of reaction, diluted with distilled water at room temperature and extracted with methylene chloride and water. To the compound produced was concentrated by drying the organic layer with MgSO4 silicagel column and recrystallized Sub 1-6-1, 6.8g (yield: 71%) was obtained.
71%
With tetrakis(triphenylphosphine) palladium(0); caesium carbonate; In ethanol; water; toluene; for 20h;Reflux;
In a 250ml reaction flask, 5.0g (17.4mmol) of the compound [119-4], 7.1g (22.6mmol) of the compound [119-5], 0.6g (0.5mmol) of tetrakis triphenylphosphine palladium (0) 8.5 g (26.1 mmol) of cesium carbonate was dissolved in 120 ml of toluene, 10 ml of ethanol and 20 ml of distilled water were added, and the mixture was refluxed with stirring for 20 hours. After completion of the reaction, the reaction mixture was slowly cooled to room temperature and extracted with distilled water and ethyl acetate. The organic layer was separated, dried over anhydrous magnesium sulfate, and filtered. The filtrate was concentrated under reduced pressure and purified by column chromatography to give 8.3 g (71%) of intermediate compound [119-6].
H3BTMB was synthesized by the method described in Tetrahedron 66 (2010) 3553-3563. Specifically, a mixture containing 1,3,5-tribromobenzene (0.500 g), m-methoxycarbonyl phenylboronic acid (1.0560 g), K3PO4 (2.3586 g), and Pd(PPh3)4 (0.0550 g) was stirred in 1,4-dioxane (50 mL) in a nitrogen atmosphere at 90 C. for 3 days. The reaction mixture was cooled to room temperature, and the solvent was evaporated. The residue was dissolved in CH2Cl2, washed with water, and dried over MgSO4. The product was purified by silica gel column chromatography, which used CH2Cl2/n-hexane=(2:1Delta1:0) for elution, and the third main product was obtained. The obtained product was recrystallized with CH2Cl2/n-hexane. The recrystallized product was dissolved in 45 mL of MeOH, 25 mL of 6-N NaOH aqueous solution was added to the reaction mixture, and the mixture was refluxed at 95 C. overnight. The reaction mixture was cooled to room temperature, 20 mL of concentrated HCl was added thereto, and the mixture was stirred for 1 hour. The white precipitate was filtered and vacuum-dried, thereby obtaining H3BTMB with a yield of 88%. FIG. 1a) shows the single crystal X-ray structure of the resulting H3BTMB. In the following Examples, anions derived from H3BTMB are noted as BTMB or BTMB3-.
With tetrakis(triphenylphosphine) palladium(0); sodium carbonate; In ethanol; water; toluene; at 100℃; for 22h;Inert atmosphere;
1-bromo-3,5-di-tert-butylbenzene (20.1 g, 77.4 mmol) was dissolved in THF (400 mL) underAr at ?78 °C. 1.64 M solution of n?BuLi in n-Hexane (100 mL, 164 mmol) was slowly added.After the solution was stirred at ?78 °C for 1.5 h, triisopropyl borate (44.0 mL, 189 mmol)dissolved in THF (60.0 mL) was immediately added. The solution was stirred overnight atroom temperature. Et2O and 10percent HCl aq. were added to the solution, the organic layer wasseparated and dried over MgSO4, then filtered. The solvent was removed by evaporation toyield 2 as a white solid (21.2 g, crude). And 2, 1,3,5-tribromobenzene (48.7 g, 155 mmol),Pd(PPh3)4 (1.79 g, 1.55 mmol), Na2CO3 (16.4 g, 155 mmol) were dissolved in toluene (678 mL),EtOH (255 mL) and H2O (110 mL) under Ar. The solution was stirred 22 h at 100 °C. Et2O andCH2Cl2 was added to the solution and the organic layer was separated and dried over MgSO4,and then filtered. The solvent was removed by evaporation, and the residue was purified by column chromatography on silica gel (eluent : n-Hexane) to yield 3 as a white solid (16.8 g,39.6 mmol, 2 steps 63 percent).
With aluminum tri-bromide; potassium nitrate; In neat (no solvent); for 0.25h;Catalytic behavior;
General procedure: Liquid substrate (benzene or bromobenzene) was added to a 50-mL round bottom flask. In different experiments, the volume of substrate was 5 mL, 2.5 mL or 1 mL. Then, different amounts of oxidising agent KNO3 (1.5 mmol, 2.5 mmol or5 mmol) and anhydrous AlBr3 as catalyst and bromine source (3.75 mmol, 7.5 mmol or 15 mmol) were added to the flask.The reaction mixture was stirred briefly. Then, the timing was started. Two minutes before stopping the reaction, the reaction mixture was stirred again. There was no constant stirring, because, as discussed in our previous work (Rahu et al. 2018), it has a perturbing effect to the bromine formation. Reactions were stopped at different timepoints (15, 30, 60, 120 or 240 min) by adding 25 mL of saturated NaHCO3 solution to remove unreacted AlBr3 and neutralise the solution and 10 mL of Na2S2O3 solution to be sure there is no excessive bromine in the reaction mixture. Then, 10 mL of diethyl ether was added, and the reaction mixture was stirred properly. Afterwards the organic layer was analysed by GC-MS. In preliminary experiments, where benzene was used as a substrate, an extra purification step was performed to separate mainproducts (bromobenzene and nitrobenzene) to analyse them with NMR (see Supplementary data for spectrums).
5,5′,5’’-(benzene-1,3,5-triyl)tris(thiophene-2-carbonitrile)[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
93%
With tetrakis(triphenylphosphine) palladium(0); potassium carbonate; Trimethylacetic acid; In N,N-dimethyl acetamide; toluene; at 110℃; for 48h;Inert atmosphere;
General procedure: A mixture of aryl bromide (1 eq.), 2-thiophenecarbonitrile (3 eq.per site), K2CO3 (1.5 eq. per site), pivalic acid (0.15 eq. per site) andPd(PPh3)4 (4 mol % per site) in a solvent mixture of dry N,Ndimethylacetamide/toluene 50:50 (v/v %), C:0.23 M, was stirredunder argon atmosphere at 110 C during 48h. The reaction mixturewas then diluted with water, filtered on Celite and washed withdiethyl ether. The solidwas resolubilized in THF/diethyl ether 50:50(v/v %) and centrifuged (15 min, 4000 rpm, rt). The white solid waseliminated and the solution evaporated to give a product whichwas purified by successive recrystallizations in appropriate solvents:3, 4 and 6 in 1-butanol and 5 in toluene at room temperature.Yields: (3) 35%, yellow solid; (4) 45%, orange solid; (5) 72%, redsolid; (6) 93%, green solid. All amounts were calculated based oneach reactive site (-Br) of the starting precursor.
In N,N-dimethyl-formamide; at 180℃; for 48h;Inert atmosphere;
S41: Add 1,3,5-tribromobenzene (1.56g, 5.0mmol), copper cyanide (6.75g, 75.0mmol) and 50mL to a 250mL round bottom flask equipped with a stir barDry N, N-dimethylformamide.S42: The mixture under the protection of argon was reacted at 180 C for 48 hours.After cooling to room temperature, the solvent of N, N-dimethylformamide was removed by vacuum distillation. The obtained solid was dissolved in DCM and washed with brine, and then the mixture was extracted with DCM three times. The organic phase was collected and dried with MgSO4. After removing the solvent, the crude product was purified by column chromatography and recrystallized several times with DCM / hexane to obtain the product.
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