* 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 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
2
[ 56908-88-4 ]
[ 56990-02-4 ]
Yield
Reaction Conditions
Operation in experiment
92%
With 4-methylmorpholine N-oxide In tetrahydrofuran for 12 h; Reflux
A solution of compound C (3.29 g, 10 mmol) and 4-methyl-n-oxo morpholine (3.51 g, 30 mmol) were dissolved in 60 mL of tetrahydrofuran and the reaction mixture was heated under reflux for 12 hours. The organic compound was dried over magnesium sulfate and dried over silica gel column chromatography using dichloromethane / petroleum ether (v / v = 2: 3) as eluent. After drying and steaming, the mixture was dried to give the intermediate D (2.42 g, yield 92percent) as a white solid.
Reference：
[1] Patent: CN106946777, 2017, A, . Location in patent: Paragraph 0063-0065
3
[ 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,
4
[ 19752-57-9 ]
[ 68-12-2 ]
[ 56990-02-4 ]
Reference：
[1] Journal of Organic Chemistry, 2003, vol. 68, # 23, p. 8750 - 8766
5
[ 68-12-2 ]
[ 56990-02-4 ]
Reference：
[1] Journal of Organometallic Chemistry, 1981, vol. 215, # 3, p. 281 - 291
6
[ 298-12-4 ]
[ 56990-02-4 ]
Reference：
[1] Angewandte Chemie - International Edition, 2017, vol. 56, # 28, p. 8201 - 8205[2] Angew. Chem., 2017, vol. 129, # 28, p. 8313 - 8317,5
7
[ 145691-59-4 ]
[ 56990-02-4 ]
Reference：
[1] Synlett, 2002, # 2, p. 251 - 254
8
[ 6311-60-0 ]
[ 56990-02-4 ]
Reference：
[1] Journal of Organic Chemistry, 2003, vol. 68, # 23, p. 8750 - 8766
9
[ 626-40-4 ]
[ 56990-02-4 ]
Reference：
[1] Journal of Organic Chemistry, 2003, vol. 68, # 23, p. 8750 - 8766
10
[ 827-94-1 ]
[ 56990-02-4 ]
Reference：
[1] Journal of Organic Chemistry, 2003, vol. 68, # 23, p. 8750 - 8766
11
[ 100-01-6 ]
[ 56990-02-4 ]
Reference：
[1] Journal of Organic Chemistry, 2003, vol. 68, # 23, p. 8750 - 8766
12
[ 1611-92-3 ]
[ 56990-02-4 ]
Reference：
[1] Journal fuer Praktische Chemie (Leipzig), 1934, vol. <2> 139, p. 296,305
[2] Patent: CN106946777, 2017, A,
13
[ 618-58-6 ]
[ 56990-02-4 ]
Reference：
[1] Synlett, 2002, # 2, p. 251 - 254
14
[ 42460-62-8 ]
[ 6311-60-0 ]
[ 56990-02-4 ]
Reference：
[1] Recueil des Travaux Chimiques des Pays-Bas, 1923, vol. 42, p. 151,153,164,168[2] Recueil des Travaux Chimiques des Pays-Bas, 1924, vol. 43, p. 867
15
[ 1611-92-3 ]
[ 108-24-7 ]
[ 56990-02-4 ]
Reference：
[1] Zhurnal Obshchei Khimii, 1954, vol. 24, p. 1043; engl. Ausg. S. 1041
16
[ 56990-02-4 ]
[ 56908-88-4 ]
Reference：
[1] Supramolecular Chemistry, 2011, vol. 23, # 6, p. 480 - 485
[2] Chemistry - A European Journal, 2012, vol. 18, # 24, p. 7473 - 7485
17
[ 56990-02-4 ]
[ 145691-59-4 ]
Yield
Reaction Conditions
Operation in experiment
84%
With sodium tetrahydroborate In methanol at 0 - 20℃; for 1 h;
Example 15 [4-[3,5-Bis-[(4-trifluoromethylphenyl)ethynyl]benzyloxy]-2-methylphenoxy]acetic acid 3,5-Dibromobenzaldehyde (1.7 g, 6.3 mmol) was dissolved in methanol (100 mL) and sodium borohydride (0.250 g, 6.3 mmol) was added at 0° C. The reaction mixture was stirred for 0.5 h at 0° C. and then at 20° C. for another 0.5 h. The reaction mixture was concentrated in vacuo, diluted with brine (250 mL), acidified with hydrochloric acid and extracted with dichloromethane (3*50 mL). Evaporation of the organic solution gave 3,5-dibromo-benzyl alcohol as a white crystalline compound. Yield: 1.4 g (84percent). RF (SiO2, hexanes/ethyl acetate 9:1) 0.25. 1H NMR spectrum (300 MHz, CDCl3, A) 7.59 (d, J=1.5 Hz, 1H); 7.47 (d, J=1.5 Hz, 2H); 4.36 (s, 2H); 1.55 (s, 1H).
84%
With sodium tetrahydroborate In methanol at 0 - 20℃; for 1 h;
Example 15; [4-[3,5-Bis-[(4-trifluoromethylphenyl)ethynyl]benzyloxy]-2-methylphenoxy]acetic acid; 3,5-Dibromobenzaldehyde (1.7 g, 6.3 mmol) was dissolved in methanol (100 mL) and sodium borohydride (0.250 g, 6.3 mmol) was added at 0 °C. The reaction mixture was stirred for 0.5 h at 0 °C and then at 20 °C for another 0.5 h. The reaction mixture was con- centrated in vacuo, diluted with brine (250 mL), acidified with hydrochloric acid and extracted with dichloromethane (3 x 50 mL). Evaporation of the organic solution gave 3,5-dibromo- benzyl alcohol as a white crystalline compound. Yield: 1.4 g (84 percent). RF (Si02, hexanes/ethyl acetate 9:1) 0.25. 1H NMR spectrum (300 MHz, CDCl3, No.H) : 7.59 (d, J=1.5 Hz, 1 H) ; 7.47 (d, J=1.5 Hz, 2 H); 4.36 (s, 2 H); 1.55 (s, 1 H).
Reference：
[1] Chemistry - A European Journal, 2012, vol. 18, # 24, p. 7473 - 7485
[2] Journal of Medicinal Chemistry, 1997, vol. 40, # 21, p. 3442 - 3452
[3] Organic Letters, 2004, vol. 6, # 16, p. 2765 - 2767
[4] Patent: US2009/209588, 2009, A1, . Location in patent: Page/Page column 25
[5] Patent: WO2005/105726, 2005, A1, . Location in patent: Page/Page column 62
[6] Chemical Communications, 2004, # 14, p. 1582 - 1583
[7] Patent: US5457118, 1995, A,
[8] Patent: WO2009/42694, 2009, A1, . Location in patent: Page/Page column 114
[9] Journal of Polymer Science, Part A: Polymer Chemistry, 2014, vol. 52, # 5, p. 707 - 718
18
[ 56990-02-4 ]
[ 145691-59-4 ]
[ 193408-02-5 ]
Reference：
[1] Australian Journal of Chemistry, 1997, vol. 50, # 4, p. 425 - 434
Stage #1: With sodium hydroxide In ethanol at 20℃; for 8 h; Stage #2: With sodium hydroxide In ethanol for 8 h; Reflux
3,5-dibromobenzaldehyde (1 0.56g, 40 mmol) and acetophenone (4.81, 40 mmol) were dissolved in ethanol (80 mL), and sodium hydroxide (0.16g, 4 mmol) was added. The resulting solution was stirred at room temperature for 8 hours. Then, benzamidine hydrochloride (4.70g, 30 mmol), sodium hydroxide (1.60g, 40 mmol) and ethanol (40 mL) were added, and the resulting solution was reacted while heating under reflux for 8 hours. White powder generated was filtered off and washed with ethanol until the liquid became colorless. The powder was further washed with water and ethanol and then dried in vacuum to obtain intermediate N (5.20g, yield: 56percent).
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 sodium tetrahydroborate; In methanol; at 0 - 20℃; for 1h;
Example 15 [4-[3,5-Bis-[(4-trifluoromethylphenyl)ethynyl]benzyloxy]-2-methylphenoxy]acetic acid 3,5-Dibromobenzaldehyde (1.7 g, 6.3 mmol) was dissolved in methanol (100 mL) and sodium borohydride (0.250 g, 6.3 mmol) was added at 0° C. The reaction mixture was stirred for 0.5 h at 0° C. and then at 20° C. for another 0.5 h. The reaction mixture was concentrated in vacuo, diluted with brine (250 mL), acidified with hydrochloric acid and extracted with dichloromethane (3*50 mL). Evaporation of the organic solution gave 3,5-dibromo-benzyl alcohol as a white crystalline compound. Yield: 1.4 g (84percent). RF (SiO2, hexanes/ethyl acetate 9:1) 0.25. 1H NMR spectrum (300 MHz, CDCl3, A) 7.59 (d, J=1.5 Hz, 1H); 7.47 (d, J=1.5 Hz, 2H); 4.36 (s, 2H); 1.55 (s, 1H).
84%
With sodium tetrahydroborate; In methanol; at 0 - 20℃; for 1h;
Example 15; [4-[3,5-Bis-[(4-trifluoromethylphenyl)ethynyl]benzyloxy]-2-methylphenoxy]acetic acid; 3,5-Dibromobenzaldehyde (1.7 g, 6.3 mmol) was dissolved in methanol (100 mL) and sodium borohydride (0.250 g, 6.3 mmol) was added at 0 °C. The reaction mixture was stirred for 0.5 h at 0 °C and then at 20 °C for another 0.5 h. The reaction mixture was con- centrated in vacuo, diluted with brine (250 mL), acidified with hydrochloric acid and extracted with dichloromethane (3 x 50 mL). Evaporation of the organic solution gave 3,5-dibromo- benzyl alcohol as a white crystalline compound. Yield: 1.4 g (84 percent). RF (Si02, hexanes/ethyl acetate 9:1) 0.25. 1H NMR spectrum (300 MHz, CDCl3, No.H) : 7.59 (d, J=1.5 Hz, 1 H) ; 7.47 (d, J=1.5 Hz, 2 H); 4.36 (s, 2 H); 1.55 (s, 1 H).
With sodium borohydrid; In methanol;
PREPARATION 9 3,5-Dibromobenzyl alcohol Sodium borohydride (0.75 g) was added portionwise to a stirred suspension of 3,5-dibromobenzaldehyde (10.46 g) in methanol (50 ml) at 0° C. The mixture was stirred at 0° C. for 30 minutes, allowed to warm to room temperature and then its pH was adjusted to 2 using concentrated hydrochloric acid. Evaporation under vacuum provided a residue which was partitioned between ethyl acetate and water. The organic phase was washed with water, dried (MgSO4), then evaporated under vacuum to furnish the title compound as a solid (10.0 g), m.p. 103°-104° C. Found: C,31.98; H,2.23. C7 H6 Br2 O requires C,31.61; H,2.77percent.
Example 1.1.76: (3-isopropyl-5-(methylsulfonylmethyl)phenyl)methanamine; To stirring solution of 5.0 g (18.9 mmol) of 3,5-dibromobenzaldehyde in 30 mL of MeOH and 25 mL of THF at 0 0C was added 819 mg of NaBH4 in 3 portions. The yellow solution was stirred at 0 0C for 30 min. and then concentrated. Water and EtOAc were added, and 1 N HCl was added to a pH = 7. The organic layer was washed with 25 mL of brine, dried over Na2SO4, filtered, and concentrated. (3,5-dibromophenyl)methanol was used in the next reaction without further purification.
5,10,15,20-tetrakis(3,5-dibromophenyl)porphyrin[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
50.3%
With oxygen; acetic acid; at 130℃; under 11251.1 Torr; for 2h;
Dissolving 160 g of <strong>[56990-02-4]3,5-dibromobenzaldehyde</strong> in a 3 L pressure-resistant reactor equipped with 2.5 L of acetic acid solution.Raise the temperature to 130 C;An oxygen-containing gas (with an oxygen content of 85%) is passed from the bottom of the reactor to the reactor.Control the pressure at 1.5 MPa;42 mL of pyrrole was added dropwise to the reactor in 0.5 h, and after 1.5 h of reaction,Cool down to 30 C to stop the reaction;After cooling, the oxygen-containing gas was released to the gas storage tank, and the reaction product obtained in the reactor was filtered to obtain a filter cake, and the filter cake was washed with 1.0 L of methanol, and then the filter cake was washed with 0.4 L of hot water.After drying, 95 g of product was obtained.The filtrate obtained by filtration can be recovered by atmospheric distillation to be used.The product was characterized according to the detection method of Example 1, and the results showed thatThe resulting product is of the formula (1) wherein R1 and R3 are -Br and R2 is H.The product yield and purity were tested according to the test method of Example 1, and the results showed thatThe product yield was 50.3% and the purity was 99.1%.
45%
With propionic acid; at 140℃; for 12h;Inert atmosphere;
General procedure: A mixture of p-bromobenzaldehyde or <strong>[56990-02-4]3,5-dibromobenzaldehyde</strong>(21.74 mmol), propionic acid 25 mL and (21.74 mmol) ofpyrrole, the mixture was heated at 140 C and stirred vigorouslyunder nitrogen atmosphere for 12 h. after that, water was addedand precipitated was formed, the mixture wasfiltered and the solidwas washed with hot water and methanol obtaining a purple solid.
16.5%
A flask equipped with a reflux condenser and a Dean-Stark trap was charged with a solution of 5.0 g of chloroacetic acid in 150 mL of xylene (isomer mixture). The solution was heated to the boiling point, a solution of 8.7 g (33.0 mmol) of <strong>[56990-02-4]3,5-dibromobenzaldehyde</strong> and 2.3 mL (33.2 mmol) of pyrrole in 50 mL of xylene was gradually added, and the mixture was refluxed for 0.5 h and then for an additional 1 h while bubbling air. The solvent was removed by steam distillation, and the precipitate was filtered off, washed with water, and air-dried at 70C. It was dissolved in chloroform, and the product was filtered off. The product was dissolved in chloroform-trifluoroacetic acid (100 : 1 by volume), the solution was filtered, the filtrate was neutralized with diethylamine until its originally green color changed to red, and the precipitate was filtered off, washed with chloroform, and dried to isolate 1.5 g of 1. The filtrate was combined with the washings and subjected to alumina chromatography. The eluate was concentrated, and the product was precipitated with methanol to isolate an additional 0.2 g of 1. Overall yield 1.7 g (16.5%), Rf 0.87 (benzene-hexane, 2 : 1). Electronic absorption spectrum, lambda, nm (log epsilon): 648 (3.73), 590 (3.91), 550 (3.93), 516 (4.33), 421 (5.64). 1H NMR spectrum (CDCl3-TFA), delta, ppm: -1.14 s (4H, NH), 8.40 t (4H, 4?-H, J = 1.6 Hz), 8.64 d (8H, 2?-H, 6?-H, J = 1.6 Hz), 8.87 s (8H, beta-H). Mass spectrum, m/z (Irel, %): 1167.38 [M - Br + H]+, 1246.64 [M + H]+. C44H22Br8N4. Calculated: M 1246.96.
tris-(dibenzylideneacetone)dipalladium(0); copper(l) iodide; triphenylphosphine; In triethylamine; toluene; at 50℃; for 23h;
A mixture of PMI- 12' (412 mg, [434 MOL),] <strong>[56990-02-4]3,5-dibromobenzaldehyde</strong> (14) (48.0 mg, 181 [MOL),] Pd2 (dba) 3 (17.0 mg, 18.1 [MOL),] PPh3 (29.0 mg, 109 mol), and CuI (8.0 mg, 43 [PMOL)] in toluene/triethylamine [[36] mL (5: 1) ] was stirred at 50 [C] under argon. After 3 h, another identical batch of catalyst was added. After 20 h, the mixture was cooled and passed through a silica column [[CHCL3/HEXANES] (4: 1) ]. Preparative SEC (THF) and a column chromatography [silica, [CHCL3/HEXANES] (9: 1) ] afforded a magenta solid (240 mg, 66%): Analytical data were identical to those as described above
With toluene-4-sulfonic acid; In toluene; for 1h;Heating / reflux;
A suspension of <strong>[56990-02-4]3,5-dibromo-benzaldehyde</strong> (20.0 g, 75.8 mmol, 1.0 equiv; [CAS RN 56990-02-4]), ethane-1,2-diol (12.7 mL, 14.1 g, 227.3 mmol, 3.0 equiv) and p-toluene sulfonic acid monohydrate (0.29 g, 1.52 mmol, 0.02 equiv) in toluene (50 mL) was heated to reflux under Dean-Stark conditions for 1 h. The reaction mixture was extracted with ethyl acetate (3×200 mL), the combined organic phases washed with a sat. solution of sodium carbonate (4×50 mL) and dried over MgSO4. Removal of the solvent by evaporation under reduced pressure yielded 23.3 g (100%) of the title compound. 1H NMR (300 MHz, CDCl3): delta 4.00-4.12 (m, 4H), 5.76 (s, 1H), 7.55-7.56 (m, 2H), 7.65-7.66 (m, 1H). MS (EI): 306.8 [M]+.
83.6%
With toluene-4-sulfonic acid; In toluene; at 110℃; for 4h;Inert atmosphere;
Step 1 (0315) (0316) 1 2 (0317) <strong>[56990-02-4]3,5-dibromo benzaldehyde</strong> 1 (10 g, 37.8 mmol, 1.0 eq), ethane- 1,2-diol (7.0 g,114 mmol, 3.0 eq) and TsOH (0.32g, 1.89 mmol) in toluene (20 mL) was stirred at 110 C for 4 h. The mixture was cooled to 23 C and concentrated, extracted with EtOAc. The organic layer was washed with brine, dried (Na2S04) and concentrated to dryness to give compound 2 (9.2 g, 83.6 %) as an oil.
6.27 g
With toluene-4-sulfonic acid; In toluene; for 5h;Reflux; Dean-Stark;
A mixture of <strong>[56990-02-4]3,5-dibromobenzaldehyde</strong> (5.37 g, 20.37 mmol), ethylene glycol (3.40 mL, 61.10 mmol) and -toluenesulfonic acid monohydrate (78 mg, 0.41 mmol) in anhydrous toluene (30 mL) was heated at reflux under Dean-Stark conditions for 5 h. The reaction mixture was cooled to room temperature and diluted with ethyl acetate (25 mL). The ethyl acetate layer was washed with a saturated aHC03 solution (25 mL). The organic layer was removed and washed with water (1 x 25 mL) and dried with anhydrous MgS04, filtered and evaporated in vacuo to give a colorless viscous liquid (6.27 g). GC-MS (Cl/methane) analysis of the liquid shows the desired 79Br,79Br , 79Br,81Br , product's mass: m/z 306 ( M+> m/z 308 ( M+), and m/z 310 81Br,81Br , , ( M+); Calcd for C9H8Br202: 307.96. XH NMR (400 MHz, CD13): delta 3.97-4.10 (m, 4H, 2x -CH2-0-), 5.74 (s, 1Eta, 0-CH-O), 7.53 (d, J = 1.80 Hz, 2H), 7.63 (appt, J = 1.80 Hz? 1H). XH NMR spectrum of the liquid was consistent with the suggested structure of the product.
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 pyridine; copper(l) cyanide; In DMF (N,N-dimethyl-formamide); at 140℃;
A mixture of 3, [5-DIBROMOBENZALDEHYDE] (1 [G),] copper cyanide (0.331 [G)] and pyridine (0.3 mL) in DMF (30 mL) was heated to [140C] overnight. The solution was allowed to cool to r. t. and dropped into water (30 [ML),] then exctracted with Et20 (15 mL). The organic phase was dried, concentrated in vacuo and the residue was purified by flash chromatography (CH, [CH/ACOET FROM] 95: 5 to 80: 20) to give the title compound (64 mg) as a yellow oil. T. I. c.: CH/AcOEt [8] : 2, Rf=0.52 (detection with 2, [4-DINITROPHENYLHYDRAZINE).] NMR [(CDCI3)] : [6] (ppm) 10.0 (s, [1H)] ; 8.20 (s, [1H)] ; 8.10 (s, [1H)] ; 8.00 (s, [1H).] [IR (NUJOL, CM~1)] : 2235.70 [(C--N)] ; 1700.14 [(C=O).]
With potassium tert-butylate; Methyltriphenylphosphonium bromide; In tetrahydrofuran; at -78 - 20℃; for 1h;
Example 65 3- 4- [3- (4-Chloro-2-phenoxy-phenoxy)-5-ethyl-phenoxy]-2-methyl-phenyl}-propionic acid Step A 1, 3-Dibromo-5-vinyl-benzene A solution of methyltriphenylphosphonium bromide (20.30 g, 56.8 mmol) in dry THF (50 mL) is cooled to 0 C under N2 and then treated with solid potassium te7, t- butoxide (6. 38 g, 56.8 mmol) in portions. The resultant yellow slurry is warmed to rt and stirred for 30 minutes. The mixture is cooled to-78 C, and a solution of 3,5- dibromobenzaldehyde (10.0 g, 37.9 mmol) in THF (50 mL) is added dropwise. The reaction is warmed to rt and stirred for 1 hour. The mixture is poured into ice water containing 1 N HC1 (56 mL) and then extracted with Et20. The organic layer is dried (Na2S04), and the solvent is removed in vacuo to afford crude product that is absorbed on silica gel and purified by flash chromatography using 10/1 hexanes/ethyl acetate to afford 4.56 g (46%) of the title compound. Rf = 0.64 (4/1 hexanes/EtOAc). H NMR (400 MHz, CDC13).
3,5-dibromobenzaldehyde (16.1 g, 61.0 mmol) was added to a cold (ice-water bath) solution of tert-butoxide (13.0 g, 116 mmol), (l,3-dioxolan-2-ylmethyl)tri-n-butylphosphine bromide salt (4.5 M, 32 cm3, 144 mmol) in 400 cm3 of ether under argon. The mixture was stirred at 0-2 C for 2 h. 1.0 M HCl(aq) (300 cm3) was added to the mixture. The reaction was gradually warmed to room temperature and stirred at room temperature for 21 h. The two layers were separated. The aqueous layer was extracted with ether (3 x 200 cm3). The organic layer and the ether extracts were combined, washed with brine (1 x 300 cm3) and dried over anhydrous magnesium sulfate. The solvents were completely removed to leave a yellow solid. The solid was purified by column chromatography of silica gel using ethyl acetate-light petroleum (40-60 C) as eluent to give 3.36 g (19%) of A-1 as a colourless solid; deltaH(200 MHz; CDCl3) 6.68 (1 H, dd, J1A & 16 Hz, vinylH), 7.33 (1 H, d, J16 Hz, vinylH), 7.33 (2 H, m, ArH), 7.63 (1 H, m, ArH), and 9.72 (1 H, d, J7.6 Hz, CHO); m/z [CI(NH3)] 306, 308, 310 (MNH4+), and 288, 290, 292 (M+).
With palladium diacetate; triethylamine; tris-(o-tolyl)phosphine; In N,N-dimethyl-formamide; at 120℃; for 24h;Inert atmosphere;
General procedure: A mixture of 1 or 6 (38 mmol), 2 (18.9 mmol), Pd(OAc)2 (1.3 mmol), and tri-o-tolylphosphine TOP (3.28 mmol) in Et3N/DMF1:5 (120 mL) was stirred under N2 at 120 C for 24 h. After cooling,the resulting mixture was filtered and the solvents evaporated. The crude product was purified by column chromatography (SiO2,hexane). Yield 3.5 g, (60%), white powder, m.p. 125-127 C, UV CH2Cl2(nm): 242, 311. IR (KBr, cm 1): 3443, 3025, 2809, 2738, 1695 (C=O),1590, 1449, 1143, 966, 884, 743, 694, 528. 1H NMR (300 MHz,CDCl3), dH (ppm): 7.13 (d, 2H, CH=, J = 16.5 Hz), 7.23 (d, 2H, CH=,J = 16.5 Hz), 7.27-7.45 (m, 4H, Ar), 7.35 (t, 2H, Ar, J ¼ 1.6 Hz),7.54-7.60 (m, 4H, Ar), 7.87 (t, 2H, Ar, J ¼ 2.0 Hz), 7.92 (s, 1H, Ar),10.09 (s, 1H, HC=O). 13C NMR (75 MHz, CDCl3), dC (ppm): 126.2(CH=), 126.7 (Ar), 127.0 (CH=), 128.2 (Ar), 128.8 (Ar), 130.2 (Ar),130.7 (Ar), 136.6 (Aripso), 137.2 (Aripso), 138.7 (Ar), 192.2 (C=O). MS,EI+ (m/z): 310. Anal. calcd. for C23H18O: C 89.00, H 5.85%. Found:C 89.10, H 5.86%
54.41%
With palladium diacetate; triethylamine; tris-(o-tolyl)phosphine; In N,N-dimethyl-formamide; at 160℃; for 24h;Inert atmosphere;
General procedure: A mixture of styrene 1 (27.02 mmol), p-bromobenzaldehyde or<strong>[56990-02-4]3,5-dibromobenzaldehyde</strong> 6 (27.02 mmol), Pd(OAc)2 (1.3 mmol),and tri-o-tolylphosphine POT (3.9 mmol) in Et3N/DMF 1:4(120 mL) was vigorously stirred under nitrogen atmosphere at160 C for 24 h. After cooling, the resulting mixture wasfiltered andthe solvents evaporated. The crude product was purified by columnchromatography (SiO2, hexane).
General procedure: A stirred mixture of bromo compound (1.0 equiv.), Pd(OAc)2 (0.1/0.2 equiv.) in dry DMF (25mL) under nitrogen was successively treatedwith K2CO3 (3.0/6.0 equiv.) and tetrabutylammoniumbromide (0.1/0.2equiv.)and stirred for 30 min. The vinyl dendron (1.0/2.0 equiv.)wasthen added and the resulting mixture was stirred at 90 C for 12 h,cooled and filtered. The filtrate was evaporated to dryness in vacuo.The residue was extracted with CHCl3 (3 × 100 mL), washed withwater (3 × 100 mL) and dried over anhydrous Na2SO4. Evaporation ofthe organic layer afforded the crude product,whichwas purified by columnchromatography using the eluent as mentioned under each compoundto afford the corresponding conjugated dendrimers.
To a THF solution (0.3 M) of allyl methyl ether (3.1 eq.) at RT was added borane-methyl sulfide complex (1.0 eq.). The solution was stirred at RT for 30 min. To this solution was then added sequentially <strong>[56990-02-4]3,5-dibromobenzaldehyde</strong> (1.0 eq.), Pd(dppf)Cl2 (0.025 eq.) and solid sodium methoxide10 (1.5 eq.). The resulting mixture was heated to reflux for 15 h. The cooled reaction mixture was diluted with water and extracted with ether. The combined organic extracts were dried over MgStheta4, filtered and the filtrate concentrated in vacuo. Purification of the crude product thus obtained by way of flash chromatography (SiO2, 5:95 (v/v) EtOAc : Hex -^ 7:3 (v/v) EtOAc : Hex) afforded the title compound as a colorless oil.
To a THF solution (0.3 M) of allyl methyl ether (3.1 eq.) at RT was added borane- methyl sulfide complex (1.0 eq.). The solution was stirred at RT for 30 min. To this solution was then added sequentially <strong>[56990-02-4]3,5-dibromobenzaldehyde</strong> (1.0 eq.), Pd(dppf)Cl2 (0.025 eq.) and solid sodium methoxide (1.5 eq.). The resulting mixture was heated to reflux for 15 h. The cooled reaction mixture was diluted with water and extracted with ether. The combined organic extracts were dried over MgSO4, filtered and the filtrate concentrated in vacuo. Purification of the crude product thus obtained by way of flash chromatography (SiO2, 5:95 (v/v) EtOAc : Hex -> 7:3 (v/v) EtOAc : Hex) afforded the title compound as a colorless oil.
With trifluoroacetic acid; In tetrahydrofuran; at 95℃; for 0.25h;Microwave irradiation; Sealed tube;
General procedure: To a mixture of oxalacetic acid (2.6 mmol), aldehyde (2.0 mmol) and N-substituted urea/thiourea (2.6 mmol) in THF (3 mL) was added TFA (0.10 mL). The mixture was heated at 95 C for 15 min using microwave irradiation in a sealed tube. Thereafter, the mixture was cooled and the solvent was removed under reduced pressure. 0.5 M NaOH (20 mL) was then added to the residue and the resulting solution was extracted with EtOAc (3×15 mL). Subsequently, the aqueous phase was acidified using concd HCl and extracted with 10% iPrOH in CH2Cl2 (3×15 mL). The combined organic extract was dried over MgSO4 and concentrated under reduced pressure. The residue was washed with Et2O and dried under vacuum to afford the final product.
EXAMPLE 1Synthesis of Compound Represented by Chemical Formula 3The compound represented by Chemical Formula 3 was synthesized according to the following Reaction Scheme 1. First Step: Synthesis of Intermediate Product (A)24.9 g (94.7 mmol) of <strong>[56990-02-4]3,5-dibromobenzaldehyde</strong> and 15.5 g (142.0 mmol) of 2-aminophenol were suspended in 700 ml of an acetic acid (AcOH) solvent. The suspension was reacted at room temperature for 12 hours. Then, the reactant was precipitated in 1,000 ml of water. The solid precipitate was separated through filtration, cleaned with water and methanol, and dried. The obtained solid compound and 23.6 g (104.2 mmol) of 2,3-dichloro-5,6-dicyanobenzenequinone (DDQ) were dissolved in 550 ml of dichloromethane. The solution was reacted at room temperature for one 1 hour. The reaction solvent was distilled and removed under reduced pressure and then, columnized and separated through and dried, obtaining 19.9 g of a white solid intermediate product (A) (yield: 60%).
With lead(IV) tetraacetate; In acetic acid;
Synthesis Example 12 Synthesis of 2-(3,5-dibromophenyl)benzo[d]oxazole 10 g (37.9 mmol) of <strong>[56990-02-4]3,5-dibromobenzaldehyde</strong> and 5 g (45.5 mmol) of 2-aminophenol were dissolved in 200 mL of acetic acid. The solution was agitated at room temperature for 30 minutes. Next, 20.2 g (45.5 mmol) of lead(IV) acetate was added thereto. The resulting product was agitated at 50 C. for 1 hour. Then, water was added to the obtained reactant. The mixture was extracted with ethyl acetate and treated under a reduced pressure to remove the solvent, obtaining 5.7 g (Y=42%) of a white solid.
With tetrakis(triphenylphosphine) palladium(0); sodium carbonate; In ethanol; water; toluene; at 90 - 95℃;Inert atmosphere;
The reactant <strong>[56990-02-4]3,5-dibromobenzaldehyde</strong> (6.44 g, 24.40 mmol, 1 equiv) was added toa mixture of phenylboronic acid (2.41 g, 21.96 mmol, 0.9 equiv), Pd(PPh3)4 (70 mg,1.22 mmol, 0.05 equiv), 2 M aqueous Na2CO3 solution (20 mL), ethanol (40 mL) andtoluene (120 mL). The reaction mixture was stirred at 90-95 C under a nitrogenatmosphere overnight. After cooling to room temperature the organic layer wasseparated and the aqueous layer was extracted with Et2O (3 x 50 mL). The combined organic phases were dried over MgSO4 and evaporated to give a crude solid.Purification by column chromatography afforded 5 as a colorless oil (4.787 g,18.30 mmol, yield 75%). 3,5-Diphenylbenzaldehyde (400 mg) was isolated as themajor side-product.1H NMR (500 MHz, CDCl3): delta = 10.01 (s, CHO), 8.01 (m, 1Haryl), 7.96 (m, 2Haryl),7.59 (m, 2Haryl), 7.49 (m, 2Haryl), 7.43 (m, 1Haryl) ppm 13C NMR (125 MHz, CDCl3): delta =190.6, 144.0, 138.2, 138.2, 135.6, 130.9, 129.1, 128.6, 127.0, 126.8, 123.7ppm. ESI-MS: could not be ionized by the ESI-source.
EXAMPLE 2Synthesis of Compound Represented by Chemical Formula 4The compound represented by Chemical Formula 4 was synthesized according to the following Reaction Scheme 2. First Step; Synthesis of Intermediate Product (D)13.0 g (62.4 mmol) of 9,10-phenanthrenequinone, 24.7 g (93.7 mmol) of <strong>[56990-02-4]3,5-dibromobenzaldehyde</strong>, and 24.7 g (312.2 mmol) of ammonium bicarbonate (NH4HCO3) were dissolved in 700 ml of ethanol. The solution was reacted at 100 C. for 12 hours. The obtained reactant was filtered, separated, cleaned with ethanol, and dried, obtaining 89.4 g of a light yellow intermediate product (D) (yield: 73%).
With tetrakis(triphenylphosphine) palladium(0); sodium carbonate; In 1,2-dimethoxyethane; water; at 95℃; for 24h;Inert atmosphere; Schlenk technique;
A mixture of 3,5-dibromobenzaldehyde (5 mmol), 2,4,6-trimethylphenylboronic acid (12 mmol), Pd(PPh3)4 (0.5 mmol), Na2CO3 (20 mmol) in 50 ml DME and 10 ml H2O was stirred under N2 at 95 for 24 h. After the mixture was washed by water, extracted by ether and evaporated, the residue was purified by flash column chromatography (hexane/ethyl acetate) to afford 3,5-di(2,4,6-trimethylphenyl)benzaldehyde with 85% yield. 1H NMR (250 MHz, CDCl3): delta 10.00 (s, 1H), 7.58 (d, J=1.64 Hz, 2H), 7.16 (t, J=1.65 Hz, 1H), 6.89 (s, 4H), 2.26 (s, 6H), 1.96 (s, 12H). 13C NMR (62.5 MHz, CDCl3): delta 192.543, 142.407, 137.436, 137.201, 137.016, 136.853, 135.660, 129.089, 128.322, 21.110, 20.837.
With tetrakis-(triphenylphosphine)-palladium; anhydrous sodium carbonate In methanol at 80℃; for 18h; Inert atmosphere;
86%
With tetrakis-(triphenylphosphine)-palladium; potassium carbonate In 1,4-dioxane Inert atmosphere; Reflux;
3.5 g
With tetrakis-(triphenylphosphine)-palladium; potassium carbonate In lithium hydroxide monohydrate; toluene for 4h; Inert atmosphere; Reflux;
1 Synthetic Example 1
The method in which Compound G-18 was synthesized in Synthetic Example 1 of the present invention will be described below. In the method for synthesizing Compound G-18, 3,5-dibromobenzaldehyde (3.0 g), 4-methoxycarbonylphenylboronic acid (5.3 g), tetrakis(triphenylphosphine)palladium (0) (0.4 g) and potassium carbonate (2.0 g) were added into a flask, which was then purged with nitrogen. There were added degassed toluene (30 mL) and degassed water (10 mL), and the mixture was refluxed for 4 hours. Thereafter, the reaction solution was cooled to room temperature, and the organic layer was collected by liquid separation and was washed with a saturated saline solution. This organic layer was dried over magnesium sulfate and was filtered, and the solvent was distilled off. The reaction product thus obtained was purified by silica gel chromatography to give 3,5-bis(4-methoxycarbonylphenyl)benzaldehyde (3.5 g) as a white solid.
3.5 g
With tetrakis-(triphenylphosphine)-palladium; potassium carbonate In lithium hydroxide monohydrate; toluene for 4h; Inert atmosphere; Reflux;
1
3.0 g of 3,5-dibromobenzaldehyde, 5.3 g of 4-methoxycarbonylphenylboronic acid, 0.4 g of tetrakis(triphenylphosphine)palladium(0), and 2.0 g of potassium carbonate were added into a flask, and then nitrogen substitution was performed. To this, 30 mL of degassed toluene and 10 mL of degassed water were added, and then the mixture was refluxed for 4 hours. After cooling the reaction solution to room temperature, the organic layer was separated and then washed with saturated brine. The organic layer was dried over magnesium sulfate, filtered, and evaporated off the solvent. The obtained reaction product was purified by chromatography on silica gel to obtain 3.5 g of 3,5-bis(4-methoxycarbonylphenyl)benzaldehyde as a white solid.
General procedure: To a solution of N-(2-oxo-2-substituted)methanesulfonamide (0.676 mmol), selected or appropriate aldehyde (0.879 mmol) and cyanoacetamide (0.072 g, 0.879 mmol) in mixture of 2.5 ml EtOH and 2.5 ml RC(OEt)3 (R?H or CH3) was added anhydrous granulated K2CO3 (0.052 g, 0.372 mmol) in one portion. The mixture was purged with nitrogen for 5 min, and refluxed for 24 hours under the nitrogen atmosphere. The formation of pyrrole was controlled by TLC. After that the reaction temperature was increased to 150 C. and reaction mixture was heated during 10 hours again with simultaneous evaporation of ethanol. Then the mixture was cooled to room temperature, the formed precipitate was collected by filtration and washed on the filter with EtOH (2 mL) and diethyl ether. The mother liquor was evaporated and the residue subjected to column chromatography with MeOH/CH2Cl2=1/40 to 1/20 gradient. 77%; 1H NMR (DMSO-d6) delta: 13.01 (s, 1H), 12.10 (s, 1H), 8.06 (s, 1H), 7.51 (s, 1H), 7.46 (d, J=7.68 Hz, 2H), 7.41 (t, J=7.68 Hz, 1H), 7.36 (s, 2H), 7.23 (t, J=7.24 Hz, 2H); 13C NMR (DMSO-d6) delta 187.9, 159.0, 149.9, 147.6, 138.0, 137.0, 133.3, 132.6, 131.9, 129.3, 128.6, 128.3, 124.0, 121.2, 107.0; HRMS m/z (ESI) calcd for C19H12Br2N3O2 (M+H+) 471.9296. found 471.9301
<strong>[56990-02-4]3,5-dibromobenzaldehyde</strong> (1 0.56g, 40 mmol) and acetophenone (4.81, 40 mmol) were dissolved in ethanol (80 mL), and sodium hydroxide (0.16g, 4 mmol) was added. The resulting solution was stirred at room temperature for 8 hours. Then, benzamidine hydrochloride (4.70g, 30 mmol), sodium hydroxide (1.60g, 40 mmol) and ethanol (40 mL) were added, and the resulting solution was reacted while heating under reflux for 8 hours. White powder generated was filtered off and washed with ethanol until the liquid became colorless. The powder was further washed with water and ethanol and then dried in vacuum to obtain intermediate N (5.20g, yield: 56%).
<strong>[56990-02-4]3,5-dibromobenzaldehyde</strong> (10.56g, 40 mmol) and 4'-bromoacetophenone (7.96, 40 mmol) were dissolved in ethanol (160 mL), and sodium hydroxide (0.16g, 4 mmol) was added. The resulting solution was stirred at room temperature for 8 hours. Then, benzamidine hydrochloride (4.70g, 30 mmol), sodium hydroxide (1.60g, 40 mmol) and ethanol (80 mL) were added, and the resulting solution was reacted while heating under reflux for 8 hours. White powder generated was filtered off and washed with ethanol until the liquid became colorless. The powder was further washed with water and ethanol to obtain an intended intermediate Q (9.38g, yield: 86%).
Stage #1: 3,5-dibromobenzaldehyde; dithiooxamide In nitrobenzene at 150℃; for 0.5h; Inert atmosphere; Microwave irradiation;
Stage #2: With chloranil In tetrahydrofuran; nitrobenzene for 0.166667h; Reflux; Inert atmosphere;
phenanthrene-9,10-dione with 5-bromo-4'-(diphenylamino)-[1,1'-biphenyl]-3-carbaldehyde[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
54.6%
With tetrakis(triphenylphosphine) palladium(0); potassium carbonate; In toluene; at 105℃; for 8h;
(4-(di-phenylamino)phenyl)boronic acid (1.445g, 5.0mmol), <strong>[56990-02-4]3,5-dibromobenzaldehyde</strong> (2.641g, 10mmol) and Pd(PPh3)4 (50mg, 0.10mmol) were suspended in toluene (25mL) and 10mL 2M K2CO3. The reaction was stirred at 105C for 8h and cooled to room temperature. The mixture solution was added 20mL brine and then extracted with CH2Cl2 (40mL), washed with water (2×20mL), dried (MgSO4) and evaporated to dryness. After drying under vacuum, then, it was purified by dichloromethane/petroleum ether (1:3) as an eluent to afford light yellow solid, Yield: 1.168g, 54.6%. FTIR (KBr, cm-1): 3095, 3068, 2942, 2918, 2894, 2866, 1698, 1499, 1506, 1409, 1392, 744; 1H NMR(CDCl3, 400MHz, ppm) delta:10.02 (s, 1H), 7.97 (t, 3H, J=14.8Hz), 7.48 (d, 2H, J=8.66Hz), 7.32 (t, 4H, J=7.42Hz), 7.18 (d, 6H, J=8.67Hz), 7.10 (t, 2H, J=7.42Hz); EI-MS (m/z): 430.3 (M++H), 428.1 (M++H); Anal. Calcd for C25H18BrNO: C, 70.10; H, 4.24; N, 3.27; Found: C, 70.12; H, 4.18; N, 3.32.
General procedure: All chalcones syntheses were carried out using a similar procedure,and the following is representative of the synthesis of3a-f: An ethanolic solution (15 mL) of both acetylpyridine(10 mmol) and benzaldehyde or p-substituted-benzaldehyde(10 mmol) were mixed in a 250-mL Erlenmeyer flask and 2 mLof a 30% aqueous NaOH solution was then added dropwise (usinga Pasteur pipet). In most cases, the reaction mixture turned yellowor orange immediately after NaOH was added. After 12 h, anexcess of cold water was added to the flask while the mixturewas stirred vigorously until a solid precipitate was observed.The solid was collected, washed with cold water, and air-dried.The purity of the crude product was determined at this pointusing 1H NMR spectroscopy. In all cases, the spectroscopic characteristicswere in good agreement with those found in the literaturewith percent yields above 60% for all, which is similar towhat has been reported earlier [16]. All chalcones could be usedimmediately in the next step.
5-tributyl(5-hexylthiophen-2-yl)stannane[ No CAS ]
3,5-bis(5-hexylthiophen-2-yl)benzaldehyde[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
60%
With tetrakis(triphenylphosphine) palladium(0); In N,N-dimethyl-formamide; at 80℃; for 72h;Inert atmosphere; Schlenk technique;
Compound 3 was synthesized according to the literature [22]. A100 mL round-bottomflask was charged with compound 2 (1.81 g,6.85 mmol), Pd(PPh3)4 (800 mg, 0.692 mmol), tributyl(5-hexylth-iophen-2-yl) stannane (9.5 g, 20.6 mmol), and anhydrous DMF(60 mL), and heated to 80 C with stirring for 72 h. The reactionmixture was then cooled down to room temperature, and dilutedwith diethyl ether,filtered through celite. The organic phase waswashed with brine and water and dried over MgSO4. Afterfiltration, solvent was removed to yield the crude product whichwas then chromatographed on silica using a DCM/nhexane= 2:1 solvent mixture as the eluent. The desired productwas a yellow oil (1.80 g, yield 60%).
With tetrakis(triphenylphosphine) palladium(0); potassium carbonate; In ethanol; water; toluene; for 36h;Inert atmosphere; Reflux;
(1) under the protection of N2, 1 mmol of tetrakis(triphenylphosphine)palladium, 10 mmol of <strong>[56990-02-4]3,5-dibromobenzaldehyde</strong>,25 mmol of pyridine-4-boronic acid and 125 mmol of potassium carbonate were dissolved in a mixed solvent of 50 mL of toluene, 50 mL of ethanol and 50 mL of water, and the mixture was heated to reflux for 36 hours, and then allowed to stand for cooling.Extraction with 160 mL of dichloromethane, evaporation of the solvent under reduced pressure, purification by column chromatography (dichloromethane and methanol in volume ratio3:5-bis(4-pyridyl)benzaldehyde is obtained by mixing 80:1.The yield is 90%;
5-(3,5-dibromobenzylidene)-2-thioxoimidazolidin-4-one[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
20%
With piperidine In ethanol at 80 - 90℃;
General synthesis procedure B
General procedure: A mixture of aldehyde (0.5 mmol, 1 equiv 20), compound 21 (1.2 equiv), and few drops of piperidine in EtOH (4 mL) was stirred at 80-90°C (4-12 h) until no starting material remained, assessed by TLC (SiO2, hexane/ethylacetate, 1:1, v/v). The reaction mixture was cooled down to room temperature. The resulting precipitate was filtered and washed successively with water and Et2O (10 mL).
2-(3,5-dibromophenyl)-6-chloro-4-phenylquinazoline[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
47%
With ammonium acetate; iodine; In ethanol; at 70℃; for 24h;Inert atmosphere;
A stream of argon, 2-amino-5-chloro-benzophenone 2.00g (8.63mmol), 3,5- dibromo benzaldehyde 2.28g (8.63mmol), And ammonium acetate 1.66g (21.58mmol) Was dissolved in ethanol 4.3 mL, after addition of iodine 109mg (0.432mmol), The mixture was heated and stirred for 24 hours at 70C . After cooling to room temperature, water 10mL was added, and the precipitated solid was collected by filtration. The resulting solid was washed with water and methanol to yield the desired 2- (3,5-dibromophenyl) -6-chloro-4-phenylquinazoline as a white solid (Yield 1.91 g, 47% yield) .
2-(3,5-dibromophenyl)-4-phenylquinazoline[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
61%
With ammonium acetate; iodine; In ethanol; at 70℃; for 19h;Inert atmosphere;
A stream of argon, 2-aminobenzophenone 500mg (2.54mmol), <strong>[56990-02-4]3,5-dibromo benzaldehyde</strong> 669mg (2.54mmol), And ammonium acetate 448mg (6.34mmol) It was dissolved in ethanol 1.3mL, after the addition of iodine 32mg (0.127mmol), the mixture was heated and stirred for 19 hours at 70C . After cooling to room temperature, 5ml of water was added, and the precipitated solid was collected by filtration. The resulting solid was washed with water and methanol to yield the desired 2- (3,5-dibromophenyl) -4-phenyl-quinazoline as a white solid (yield 686 mg, 61% yield).
With sodium hydroxide; In ethanol; water; at 0 - 5℃; for 1h;
3,5-Dibromobenzaldehyde (20.0 g, 75.8 mmol) were completely dissolved in 400 mL of ethanol and then 1-Tetralone (15.5 g, 106.1 mmol) was added and the temperature was cooled to 0 . Maintaining a 0 to 5 and, dropped 8.5 M NaOH aqueous solution slowly 20 mL. After the addition was completed, the solid compound was filtered and then the resulting mixture was stirred for additional 1 hour. The filtered solid compound was dried and then washed twice with ethanol. Light yellow solid after drying, compound 1-1 Core (22.0 g, 74.0%) was obtained.
1-[1,10-biphenyl]-4-yl-3-(3,5-dibromophenyl)-2-propen-1-one[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
98%
In ethanol; water; at 20℃; for 2h;
1000 ML of ethanol was added 50.8 g of <strong>[56990-02-4]3,5-dibromobenzaldehyde</strong>,37.8 g of acetylbiphenyl, stirred at room temperature,A solution of 14.2 g of 70 ml of water was added dropwise,Stirred at room temperature for 2 hours,TLC detected no starting material and the reaction was stopped. The obtained product was repeatedly washed with water, ethanol,To give 81G as a light yellow solid in 98% yield.
98.49%
With sodium t-butanolate; In ethanol; at 25℃;Inert atmosphere;
(3,5-Dibromobenzaldehyde) (30 g, 113.7 mmol) and 4-acetylbiphenyl (4-Acetylbiphenyl) (23.42 g, 119.4 mmol) and 600 ml of EtOH were added to the reaction flask (16.37 g, 170.5 mmol) was added to the reaction flask and stirred at room temperature overnight at 25 C (passing nitrogen). After filtration, the mixture was rinsed with 100 ml of water and 100 ml of methanol. The solid was washed with 250 ml of pure water and 50 ml of methanol After stirring for 15 minutes, the reaction was repeated 2 to 3 times, and the solid was further stirred with 200 ml of methanol for 15 minutes. The solid was further purified by stirring with 250 ml of ethanol for 15 minutes and dried at 65 C to give 48.5 g of intermediate E as a pale yellow solid. 98.49%.
98%
In ethanol; water; at 20℃; for 2h;
1000 ml of ethanol was added 50.8 g of <strong>[56990-02-4]3,5-dibromobenzaldehyde</strong> in 37.8 gAcetylene biphenyl, stirred at room temperature, dissolved 14.2 g of 70 M aqueous solution,Stirred at room temperature for 2 hours,TLC detects no raw material and stops the reaction.The resulting product was washed repeatedly with water and ethanol to give 81 g of a pale yellow solid in a yield of 98%.
98%
In ethanol; water; at 20℃; for 2h;
In 1000ML ethanol, 50.8 g of <strong>[56990-02-4]3, 5-dibromobenzaldehyde</strong> in 37.8 g of acetylbiphenyl was added, after stirring at room temperature, 14.2 g of a 70 mL aqueous solution was added dropwise, and the mixture was stirred at room temperature for 2 hours, The TLC detected no starting material and stopped the reaction The obtained product was repeatedly washed with water and ethanol to obtain 81 g of pale yellow solid, yield 98%. Nuclear magnetics are shown in CN105384759, CN105085551.
93.5%
With sodium hydroxide; In ethanol; water; at 20℃;
A mixture of 50.0 g (189 mmol) of <strong>[56990-02-4]3,5-dibromobenzaldehyde</strong> and 37.2 g (189 mmol) of the compound 4-acetylbiphenyl was added thereto 1.2 L of ethanol and stirred at room temperature. A 5M aqueous sodium hydroxide solution (70 mL, 350 mmol) is gradually added dropwise to the reaction solution. After stirring overnight at room temperature the precipitate was filtered, washed with water and ethanol, and purified to give a solid78.3 g (yield: 93.5%) of the compound (Intermediate (1)) was obtained.
trans-1-(2-(2,6-dichlorophenyl)vinyl)-3,5-dibromobenzene[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
47%
Triethylphosphite (0.54 mL, 3.10 mmol) and 2,6-dichlorobenzyl bromide (635 mg, 2.65 mmol) were stirred at 150C for 3 hours under an argon atmosphere.Anhydrous DMF (5.0 mL) was added and the reaction was then cooled at 0C for 15 minutes, then NaH (60% in mineral oil, 153 mg, 3.83 mmol) was added and the reaction was stirred for an additional 30 minutes.A solution of 3,5-dibromobenzaldehyde (685 mg, 2.60 mmol) in anhydrous DMF (5.0 mL) was then added and the reaction was stirred at R.T. for 18 h.The organics were extracted into EtOAc (100 mL) and washed with H2O (2x25 mL) and brine (25 mL), dried over Na2SO4, filtered, and concentrated.Flash chromatographic purification over silica (100% hexanes to 95:5 hexanes:EtOAc gradient elution) affordedtrans-1-(2-(2,6-dichlorophenyl)vinyl)-3,5-dibromobenzene (207) as a white solid (496 mg, 47%).1H-NMR (500 MHz, CDCl3)d7.59 (s, 3H), 7.35 (d,J=8.1 Hz, 2H), 7.14 (t,J=8.1 Hz, 1H), 7.10 (d,J=16.6 Hz, 1H), 7.01 (d,J=16.6 Hz, 1H);13C-NMR (125 MHz, CDCl3)d140.37, 134.64, 134.12, 133.67, 133.41, 128.70, 128.68, 128.39, 125.41, 123.30; GC-MS 404m/zM+, C14H8Br2Cl2requires 404; RP-HPLC: >99% pure.
With 4-methylmorpholine N-oxide; In tetrahydrofuran; for 12h;Reflux;
A solution of compound C (3.29 g, 10 mmol) and 4-methyl-n-oxo morpholine (3.51 g, 30 mmol) were dissolved in 60 mL of tetrahydrofuran and the reaction mixture was heated under reflux for 12 hours. The organic compound was dried over magnesium sulfate and dried over silica gel column chromatography using dichloromethane / petroleum ether (v / v = 2: 3) as eluent. After drying and steaming, the mixture was dried to give the intermediate D (2.42 g, yield 92%) as a white solid.
With sodium sulfite In N,N-dimethyl-formamide Heating;
3.3 synthesis of 1-bromophenyl-2-(3,5-dibromophenyl)-1H-benzo[d]imidazole(p-bromine,m-bromine)
General procedure: A solution of 1 mmol of N-bromophenyl-2-amino-aniline,1 to 10 mmol of 3,5-dibromobenzaldehyde and1 ~ 10mmol partial to sodium sulfite dissolved5 ml of DMF,Heating and stirring 24 ~ 48h,DCM extraction,Column chromatography,To give 1-bromophenyl-2- (3,5-dibromophenyl) -1H-benzo [d] imidazole
<strong>[56990-02-4]3,5-dibromobenzaldehyde</strong> (0.2 g, 0.76 mmol) and aniline (0.08 g, 0.86 mmol) were dissolved in ethanol (4 ml) and stirred at room temperature for 3 hours. After completion of the reaction, the reaction mixture was concentrated under reduced pressure and subjected to column chromatography using MC and Hx (= 1: 3) to obtain Compound 2-1 (0.3 g, 88.5%).
With sodium hydroxide; In ethanol; water; at 20℃; for 3h;
<strong>[615-13-4]2-indanone</strong> (50 g, 378 mmol) and 3,5-dibromobenzaldehyde (119.8 g, 454 mmol) were dissolved in ethanol (1500 mL) in a 3000 mL three-0 & gt; C. The aqueous solution of 8.5 M sodium hydroxide (500 mL) was slowly added thereto while maintaining the temperature at 0 C. After stirring at room temperature for 3 hours, the resulting solid was separated by vacuum filtration and washed with methanol. Dried to obtain a yellow solid compound 11-A (134.4 g, yield: 94%).
General procedure: N-nitrobenzenesulfonylhydrazide (NBSH) was prepared by literature procedure.[1]N-nosylhydrazones[2] were prepared by our previous reported procedure: to a stirredsolution of NBSH (2.0 mmol, 1.0 equiv) in methanol (2.0 mL) was added carbonylcompounds (2.2 mmol, 1.1 equiv). Then the resulting mixture was stirred at roomtemperature for 1-2 h. After completion (monitored by TLC), the reaction mixture wasfiltered and the resulting solid was washed with cold diethyl ether and dried underreduced pressure to give pure N-nosylhydrazones. The yields were around 80 % ingeneral.
With copper(l) iodide; 1,10-Phenanthroline; potassium carbonate; In N,N-dimethyl-formamide; at 120℃; for 24h;Inert atmosphere;
To a two-neck flask were added carbazole (1.93 g, 11.5 mmol), <strong>[56990-02-4]3,5-dibromobenzaldehyde</strong> (1.33 g, 5.1 mmol), DMF (20.0 mL), potassium carbonate (2.88 g, 20.9 mmol), 1,10-phenanthroline (0.23 g,1.2 mmol), and copper iodide (2.02 g, 10.6 mmol). The solution was kept stirring under nitrogen atmosphere for 10 min at room temperature and then 120 C for 24 h. Ice water (50.0 mL) was poured to quench the reaction. The gray green crude product was filtrated, washed with water and dried. The resulting solid was obtained by further purification via silica gel column chromatography (PE/DCM = 2/1) to give Cz-27 (1.31 g, 59.0%). 1H NMR (400 MHz, CDCl3) delta 10.22 (s, 1H), 8.23 (s, 2H), 8.17 (d, J = 7.7 Hz, 3H), 8.12 (s, 1H), 7.54 (d, J = 8.0 Hz, 4H), 7.47 (t, J = 7.3 Hz, 4H), 7.35 (t, J = 7.0 Hz, 4H). 13C NMR (100 MHz, CDCl3) delta 191.1, 141.3, 140.9, 140.2, 131.2, 127.1, 126.8, 124.6, 121.6, 121.3, 110.1. MS (MALDI-TOF) m/z: calculated for C31H20N2O: 436.16 [M]; found: 436.3 [M].
(4Z,10R)-12-acetyl-4-[(3,5-dibromophenyl)methylidene]-8,13-dihydroxy-7,10-dimethyl-5,16-dioxatetracyclo[7.7.0.02.6.010.15]hexadeca-1,6,8,12,14-pentaene-3,11-dione[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
62%
With potassium hydroxide; In methanol; water; at 60℃; for 1.5h;
General procedure: Usnic acid 2 (1 mmol, 344 mg) was treated with the bromine--dioxane complex (2 mmol Br2, 0.10 mL, dissolved in dioxane, 14 mL)and several drops of HBr then left for 7 d at room temperature. Thereaction mixture was concentrated in a rotary evaporator and chromatographedover silica gel with elution by CH2Cl2 to yield compound4 (67%). A solution of 4 (1 mmol, 423 mg) in acetone (25 mL) was treatedwith KOAc (150 mg, 1.5 mmol), refluxed for 2 h, diluted with H2O (upto ?50-60 mL), acidified with HCl (1:4) to pH 3-4, and extracted withCH2Cl2 (3-10 mL). The extracts were dried over calcined MgSO4. Thesolvent was removed. The residue was chromatographed over a columnof silica gel with elution by CH2Cl2 to yield compound 5 (90%). A solution of 5 (1 mmol, 342 mg) in MeOH (24 mL) was treated withthe appropriate aldehyde (1.1 mmol) and aqueous KOH (1 mL, 50%),heated at temperature 60 C for 1.5 h, cooled, diluted with H2O (up to?50-60 mL), acidified with HCl (1:4) to pH 3-4, and extracted withCH2Cl2 (3-10 mL). The extracts were dried over calcined MgSO4. Thesolvent was removed. The residue was chromatographed over a columnof silica gel with elution by CH2Cl2.
4-(3,5-dibromophenyl)-3,5-dimethyl-1,7-diphenyl-1,7-dihydropyrazolo[3,4-b:4′,3′-e]pyridine[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
79%
With iron(III) chloride; In dimethyl sulfoxide; at 130℃; for 24h;
General procedure: A mixture of 5-amimoamimo amimo pyrazolepyrazolepyrazole pyrazolepyrazole s (1a-c, 1 , 1.0 mmol), mmol), aromatic aldehydes (2a-t, 0.5 mmol), FeCl3 (12 mg, 0.075 mmol) and DMSO (3 mL) was reacted at 130 C for 24 h. After completion of the reaction, the mixture was cooled to room temperature. In case there are some solids precipitated from the mixture, which were filtered and washed by ethanol/petroleum ether. The remaining solution was poured into the water and extracted with dichloromethane (3×15 mL). The combined organic layers were dried over anhydrous magnesium sulfate and filtered. After removal of the solvent, the residue was purified by flash column chromatography on silica gel using the mixture of petroleum ether/ethyl acetate (v:v, 20:1 to 1:1) as the eluent to afford the target products.
With catena-poly[di-mu-iodido-bis[(1,2-bis(4-chlorophenylthio)propane)copper(I)]]; In neat (no solvent); at 80℃; for 4h;
General procedure: A mixture of aldehyde (1.0mmol), secondary amine (1.0mmol), terminal acetylene(1.1mmol), and the polymer catalyst (~1.0mg) was magnetically stirred at 80 C inan open reaction vessel for hours. The progress of the reaction was monitored byTLC. After completion of the reaction (disappearance of the alkyne spot on TLC),the reaction mixture was cooled to room temperature, dichloromethane (5mL) wasadded, concentrated, and adsorbed on silica gel. The dry silica-adsorbed materialwas passed through a bed of silica gel in a column and elution with a light petroleum:ethyl acetate solvent mixture (in varying proportions) afforded the desiredpropargylamine.
General procedure: 1H-Indole-3-carboxylate methylester 2 (1.0 mmol-equiv.) was refluxed with hydrazine hydrate(12.5 g, 0.25 M) in appropriate ethanol (30 mL) for 2 h. The progressof the reaction was monitored by TLC. After cooling the reactionmixture to room temperature, the mixtures were filtered to givewhite solid crude products without purification. Next, indolehydrazide(3, 1.0 mmol) in ethanol (30 mL) was added dropwiseinto the appropriate aldehyde (1.5 mmol-equiv.) and a few drops ofpropionic acid; the mixture was stirred and refluxed for 2.5 h. Aftercooling, the precipitates were filtered and washed several times bymethanol to yield the crystal substances 4aeu.
Compound A (10 g, 40.737 mmole)And 3,5-dibromobenzaldehyde (11.74g, 44.48mmole) was placed in the reaction tank.After fully removing water, add 230 ml of ethanol.Turn on the agitation,And adding sodium methoxide (0.655g, 12.31mmole),Stir at room temperature for 16 hours.Thereafter,Add 3-pyridine amidoxime salt (3-Amidinopyridinium chloride) (6.7g, 44.34mmole)With sodium hydroxide (3.22g, 80.61mmole),And chasing 30 ml of toluene,Turn on the heating device,Heat to 75 C and react overnight.After the reaction is completed,Filter to take the solid,Heat and stir with 250 ml of toluene and filter the solid.A milky white solid compound D (about 6.3 g) was obtained.
3‐(3,5‐dibromophenyl)‐1‐[4‐(pyridin‐3‐yl)phenyl]prop‐2‐en‐1‐one[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
77.89%
With sodium t-butanolate; In ethanol; at 20℃;
1-(4-pyridin-3-ylphenyl)-ethanone(1-(4-Pyridin-3-yl-phenyl)-ethanone) (33g, 166.8mmole),3,5-dibromobenzaldehyde(3,5-Dibromo-benzaldehyde) (42.06g, 159.34mmole),And 840 ml of ethanol was added to the reaction flask for stirring.Finally, sodium tert-butoxide (22.94 g, 239 mmole) was added and stirred at room temperature.After the reaction has been completed, add 200 ml of deionized water and stir to filter.After filtering the solid with deionized water and methanol,The solid was then filtered with 100 ml of deionized water and 200 ml of methanol for 30 minutes.The solid was dried twice to obtain 55 g of pale yellow solid 3-(3,5-dibromophenyl)-1-(4-pyridin-3-ylphenyl)-acetone(3-(3,5-Dibromo-phenyl)-1-(4-pyridin-3-yl-phenyl)-propanone),The yield was 77.89%.
77.89%
With sodium t-butanolate; In ethanol; at 20℃;
1-(4-Pyridin-3-ylphenyl)-ethanone (33 g, 166.8 mmole),3,5-Dibromo-benzaldehyde (42.06 g, 159.34 mmole), and 840 ml of ethanol were added to the reaction flask for stirring.Finally, sodium tert-butoxide (22.94 g, 239 mmole) was added and stirred at room temperature.After the reaction has been completed, 200 ml of deionized water is added and stirred for filtration. The solid is filtered and washed with deionized water and methanol. The solid is then filtered with 100 ml of deionized water and 200 ml of methanol for 30 minutes, and repeated twice. Dry the solid to give 55 g of pale yellow solid 3-(3,5-dibromophenyl)-1-(4-pyridin-3-ylphenyl)-acetone(3-(3,5-Dibromo-phenyl)-1-(4-pyridin-3-yl-phenyl)-propanone),The yield was 77.89%.
9-(3,5-dibromophenyl)-2-(3,4,5-trimethoxyphenyl)-5,6,7,9-tetrahydro-1H-[1,2,4]triazolo [5,1-b]quinazolin-8-one[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
94%
With toluene-4-sulfonic acid; In N,N-dimethyl-formamide; at 90℃; for 12h;
General procedure: To a mixture of aldehyde (0.3mmol), cyclohexane-1,3-dione or pentane-2,4-dione (0.3mmol), 3-(3,4,5-trimethoxyphenyl)-1H-1,2,4-triazol-5-amine (0.3mmol), p-toluenesulfonic acid (0.015mmol), and DMF (5mL) was added. The resulting solution was stirred at 90C for 12h, and was then treated with saturated sodium bicarbonate solution (15mL) and extracted with EtOAc (3×15mL). The combined organic layers was then dried over anhydrous MgSO4 and evaporated in vacuo. The crude residue was purified by silica gel column chromatography using a mixture of petroleum ether and acetone as an eluent to give the pure solid compounds 7-30 in yields of 53-95%.
1-[7-(3,5-dibromophenyl)-5-methyl-2-(3,4,5-trimethoxyphenyl)-1,7-dihydro-[1,2,4]triazolo [1,5-a]pyrimidin-6-yl]ethanone[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
95%
With toluene-4-sulfonic acid; In N,N-dimethyl-formamide; at 90℃; for 12h;
General procedure: To a mixture of aldehyde (0.3mmol), cyclohexane-1,3-dione or pentane-2,4-dione (0.3mmol), 3-(3,4,5-trimethoxyphenyl)-1H-1,2,4-triazol-5-amine (0.3mmol), p-toluenesulfonic acid (0.015mmol), and DMF (5mL) was added. The resulting solution was stirred at 90C for 12h, and was then treated with saturated sodium bicarbonate solution (15mL) and extracted with EtOAc (3×15mL). The combined organic layers was then dried over anhydrous MgSO4 and evaporated in vacuo. The crude residue was purified by silica gel column chromatography using a mixture of petroleum ether and acetone as an eluent to give the pure solid compounds 7-30 in yields of 53-95%.
Put compound A (10g, 23.03mmole) and 3,5-dibromobenzaldehyde (6.63g, 25.12mmole) in the reaction tank. After fully removing the water, add 150 ml of ethanol and start stirring. Then, sodium methoxide (0.33 g, 6.2 mmole) was added, and the mixture was stirred at room temperature for 16 hours. Thereafter, 3-Amidinopyridinium chloride (3.96 g, 25.13 mmole) and sodium hydroxide (1.6 g, 40.3 mmole) were added, and 30 ml of toluene was added thereto. The heating device was turned on and heated until 75 C and reacted overnight. After the reaction was completed, the solid was collected by filtration, heated and stirred with 250 ml of toluene, and the solid was filtered to obtain a milky white compound G (about 4.7 g).
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