* All experimental methods are cited from the reference, please refer to the original source for details. We do not guarantee the accuracy of the content in the reference.
Reference：
[1] Journal of Organic Chemistry, 2012, vol. 77, # 7, p. 3127 - 3133
5
[ 2142-63-4 ]
[ 41877-24-1 ]
Yield
Reaction Conditions
Operation in experiment
87%
at -20℃;
100 g of bromoacetophenone was slowly added dropwise to 500 ml of sulfuric acid nitric acid mixture (volume ratio 1: 7, minus 20 degrees), and the temperature was stirred overnight. The reaction mixture was filtered through ice water to give 107 g of 2-nitro-5-bromoacetophenone as a yellow solid in 87percent yield.
33%
at 0℃; for 1 h;
To nitric acid (fuming, 2 mL, 25.1 mmol) was slowly added sulfuricacid (2.5 mL, 25.1 mmol) at 0 C and the mixture was stirredat same temperature for 15 min. To the solution was slowly added27 (3.34 mL, 25.1 mmol) at 0 C with vigorous stirring and the mixturewas stirred at same temperature for 1 h. The mixture waspoured into ice-water and extracted with EtOAc. The organic layerwas washed with satd NaHCO3 solution and brine, dried overMgSO4, concentrated, and purified by column chromatography (silicagel, hexane/EtOAc = 100/0 to 90/10) to give the title compound(2.04 g, 33percent) as pale yellow crystals. 1H NMR (400 MHz, DMSO-d6)d 2.58 (3H, s), 7.92–8.00 (H, m), 8.02–8.08 (2H, m).
Reference：
[1] Patent: CN102898374, 2016, B, . Location in patent: Paragraph 0027-0029
[2] Chemical Communications, 2015, vol. 52, # 2, p. 331 - 334
[3] Bioorganic and Medicinal Chemistry, 2016, vol. 24, # 11, p. 2504 - 2518
[4] Journal of the American Chemical Society, 1996, vol. 118, # 34, p. 8127 - 8135
Reference：
[1] Journal of the American Chemical Society, 2016, vol. 138, # 41, p. 13493 - 13496
[2] Journal of the American Chemical Society, 2006, vol. 128, # 33, p. 10694 - 10695
[3] Angewandte Chemie - International Edition, 2018, vol. 57, # 7, p. 1968 - 1972[4] Angew. Chem., 2018, vol. 130, p. 1986 - 1990,5
9
[ 2142-63-4 ]
[ 1836-06-2 ]
[ 1450-75-5 ]
Yield
Reaction Conditions
Operation in experiment
15%
With (difluoroboryl)dimethylglyoximatocobalt(II) bis(acetonitrile); water; 3-cyano-1-methylquinolinium cation In acetonitrile at 20℃; for 5 h; Inert atmosphere; Irradiation; Green chemistry
1-methyl-3-cyanoquinoline salt as a photosensitizer, Cobalt oxime complex 2 as a cobalt catalyst, 5mL acetonitrile was added2.69 mg (1 × 10 -2 mmol) photosensitizer and 2.80 mg (6 × 10 -3 mmol) cobalt catalyst, Replacing the atmosphere with Ar atmosphereAnd then0.2 mmol of 3'-bromoacetophenone (R1 is COCH3, R3 is Br, R2, R4 are independently H) and 2 mmol of H2O. Room temperature, high pressureMercury lamp irradiation 5h. After the reaction was completed, the H2 production was detected by GC (TCD) and the conversion of benzene by GC (FID), And then separated by column. 1H NMR and MS identified products were 3'-bromo-2-hydroxyacetophenone, 3'-bromo-4-hydroxyacetophenone and 3'-bromo-6-hydroxyacetophenone. The conversion of 3'-bromoacetophenone was 32percent, the yield of coupling products was 2percent, 15percent and 15percent, respectively, and the yield of H2 was 8percent.
Reference：
[1] Patent: CN107324975, 2017, A, . Location in patent: Paragraph 0130-0131
10
[ 2142-63-4 ]
[ 1878-67-7 ]
Yield
Reaction Conditions
Operation in experiment
92.3%
Stage #1: for 14 h; Reflux Stage #2: With sulfuric acid; acetic acid In water at 20 - 30℃; for 6 h; Reflux
In 1000ml three-necked flask of sublimed sulfur were added 24g (0.75mol), 100g3- bromoacetophenone (0.5mol) and 65.4g (0.75mol) morpholine was stirred at reflux for 14 hours. Cooling to 20 ~ 30 , stirring joined by glacial acetic acid 260ml, 75ml and 52ml distilled water mixed with concentrated sulfuric acid solution dubbed refluxing was continued for 6 hours. The reaction mixture was poured into ice water, stirring to brown solid precipitated was filtered. The solid was dissolved 300ml20percent aqueous sodium hydroxide solution and filtered. The filtrate was placed in an ice bath, 2mol / L of hydrochloric acid to adjust pH = 1 ~ 2, crystallization, filtration, 60 dried to give 99.2g of yellow solid 2, a yield of 92.3percent.
Reference：
[1] Patent: CN105348195, 2016, A, . Location in patent: Paragraph 0005; 0015
11
[ 2142-63-4 ]
[ 2725-82-8 ]
Yield
Reaction Conditions
Operation in experiment
65%
With titanium tetrachloride In 1,2-dichloro-ethane for 3 h; Reflux
General procedure: A solution of 2-chloro-1-[4-(propan-2-yl)phenyl]ethanone (1 g, 5.1 mmol) in dichloroethane (DCE) (10 mL) was placed in a 50 mLthree-mouth round-bottomed flask equipped with a reflux condenser, a calcium chloride drying tube, a thermometer and a magnetic stirring bar. To the stirred reaction solution at room temperature, tickle (0.115 mL, 25percent) followed by PMHS (0.7 g, 12.2 mmol) were added from a syringe. The reaction mixture was heated to reflux and progress of the reaction monitored by thin layer chromatography (tlc) and stopped after three hours. The gelatinous reaction mixture was taken up in hexane (15 mL) and filtered under a plug of celite. The filter cake was washed with hexane (50 mL) and the filtrate concentrated in vacuo.
Reference：
[1] Bulletin of the Chemical Society of Ethiopia, 2018, vol. 32, # 1, p. 179 - 184
[2] Journal of Organic Chemistry, 1937, vol. 2, p. 276,283
[3] Chemical and Pharmaceutical Bulletin, 1968, vol. 16, # 12, p. 2456 - 2462
[4] Journal of Physical Chemistry, 1983, vol. 87, # 23, p. 4622 - 4627
12
[ 2142-63-4 ]
[ 1798-85-2 ]
Reference：
[1] Bulletin of the Academy of Sciences of the USSR, Division of Chemical Science (English Translation), 1966, p. 218 - 222[2] Izvestiya Akademii Nauk SSSR, Seriya Khimicheskaya, 1966, # 2, p. 240 - 245
[3] Patent: EP1382603, 2004, A1, . Location in patent: Page 206
13
[ 2142-63-4 ]
[ 96761-85-2 ]
Yield
Reaction Conditions
Operation in experiment
93%
With ethylenediamine; trifluoroacetic acid In nitromethane for 36 h; Reflux
General procedure: To a solution of aryl methyl ketone (1, 1.5mmol) in dry nitromethane (1.5mL) was added trifluoroacetic acid (0.045 mL, 0.6mmol) and ethylenediamine (0.020 mL, 0.3mmol). The mixture was stirred at reflux and detected by TLC. After completion of the reaction, the reaction mixture was cooled to room temperature, quenched with saturated NH4Cl, extracted with Ethyl acetate. Combined organic layers were washed with brine, dried over Na2SO4, and concentrated. The residue was purified by silica gel column chromatography to give product 2.
79%
With para-dodecylbenzenesulfonic acid In neat (no solvent) at 130℃; for 4 h; Green chemistry
General procedure: A mixture of acetophenone (3 mmol) and DBSA (0.6 mmol) was heated at 130 °C in a preheated oil bath for 3–8 hours. After completion of the reaction as indicated by thin layer chromatography (TLC), the reaction mixture was cooled to room temperature and diluted with equal volumes of saturated solution of NaHCO3 and brine (5 mL + 5 mL). The resulting solution was extracted with ethyl acetate (10 mL × 3) and the organic layers were combined, dried over anhydrous Na2SO4 and evaporated under reduced pressure to dryness. The crude product obtained was purified by silica gel (60–120 mesh size) column chromatography using 1–2percent ethyl acetate in heptane as the eluent to afford the desired products in pure form.
Reference：
[1] Tetrahedron Letters, 2012, vol. 53, # 19, p. 2436 - 2439
[2] Comptes Rendus Chimie, 2013, vol. 16, # 3, p. 252 - 256
[3] Journal of Chemical Research, 2007, # 12, p. 720 - 721
[4] Synthetic Communications, 2012, vol. 42, # 24, p. 3579 - 3588
[5] Journal of the Chemical Society, Perkin Transactions 2: Physical Organic Chemistry (1972-1999), 1988, p. 1251 - 1258
[6] Chemische Berichte, 1990, vol. 123, # 4, p. 859 - 867
[7] Angewandte Chemie (International Edition in English), 1997, vol. 36, # 15, p. 1604 - 1607
[8] Journal of Materials Chemistry, 2011, vol. 21, # 34, p. 12958 - 12963
[9] Journal of Materials Chemistry, 2012, vol. 22, # 8, p. 3447 - 3456
[10] Journal of Materials Chemistry, 2012, vol. 22, # 10, p. 4502 - 4510
14
[ 75-16-1 ]
[ 2142-63-4 ]
[ 30951-66-7 ]
Yield
Reaction Conditions
Operation in experiment
90%
at 0 - 20℃; for 4 h;
A solution of 3N METHYLMAGNESIUM bromide (6.53 mL, 19.59 mmol, 3 eq) in diethyl ether was cooled to 0 °C and treated with 3-bromoacetophenone (1.3 g, 6.53 MMOL). The reaction was stirred at room temperature for 4 h. The reaction was diluted with ethyl acetate and water. The layers were separated and the organic was washed with saturated sodium bicarbonate, 2N HCI, brine and dried over magnesium sulfate. The solvent was removed at reduced pressure and purified on the MPLC (Biotage) eluted with 5-10percent ethyl acetate-hexane to afford 1.2 g (90 percent) of the product. Rf = 0.22 (silica, ethyl acetate: hexanes, 1: 9) ; H-NMR (DMSO-D6) 8 7.63 (t, J = 1.8 Hz, 1H), 7.45 to 7.35 (m, 2H), 7.25 (t, J = 7.7, 1H), 5.15 (s, 1H), 1.39 (s, 6H).
90%
Stage #1: at 0 - 20℃; for 4 h; Stage #2: With water In diethyl ether; ethyl acetate
Example 22; Method H-15; Preparation of 2-(3-Bromo-phenyl)-propan-2-ol; A solution of 3N methylmagnesium bromide (6.53 mL, 19.59 mmol, 3 eq) in diethyl ether was cooled to 0 °C and treated with3-bromoacetophenone (1.3 g, 6.53 mmol). The reaction was stirred at room temperature for 4 h. The reaction was diluted with ethyl acetate and water. The layers were separated and the organic was washed with saturated sodium bicarbonate, 2N HCI, brine and dried over magnesium sulfate. The solvent was removed at reduced pressure and purified on the MPLC (Biotage) eluted with 5-10percent ethyl acetate-hexane to afford 1.2 g (90 percent) of the product. Rf = 0.22 (silica, ethyl acetate: hexanes, 1: 9) ; 1H-NMR (DMSO-d6) 6 7.63 (t, J = 1.8 Hz, 1H), 7.45 to 7.35 (m, 2H), 7.25 (t, J = 7. 7, 1H), 5.15 (s, 1H), 1.39 (s, 6H).
90%
Stage #1: at 0℃; for 4 h; Stage #2: With water In diethyl ether; ethyl acetate
Preparation of 2-(3-Bromo-phenvl)-propan-2-ol. A solution of 3N methylmagnesium bromide (6.53 mL, 19.59 mmol, 3 eq) in diethyl ether was cooled to 0 0C and treated with3-bromoacetophenone (1.3 g, 6.53 mmol). The reaction was stirred at room temperature for 4 h. The reaction was diluted with ethyl acetate and water. The layers were separated and the organic was washed with saturated sodium bicarbonate, 2N HCl, brine and dried over magnesium sulfate. The solvent was removed at reduced pressure and purified on theMPLC (Biotage) eluted with 5-10percent ethyl acetate - hexane to afford 1.2 g (90 percent) of the product. Rf = 0.22 (silica, ethyl acetate:hexanes, 1:9); 1H-NMR (DMSO-d6) 7.63 (t, J = 1.8 Hz, IH), 7.45 to 7.35 (m, 2H), 7.25 (t, J = 7.7, IH), 5.15 (s, IH), 1.39 (s, 6H).
Reference：
[1] Journal of the American Chemical Society, 2017, vol. 139, # 28, p. 9467 - 9470
[2] Journal of the American Chemical Society, 2017, vol. 139, # 28, p. 9467 - 9470
22
[ 2142-63-4 ]
[ 7194-78-7 ]
Reference：
[1] Patent: WO2005/97136, 2005, A1, . Location in patent: Page/Page column 28-29
[2] Chemical Communications, 2013, vol. 49, # 35, p. 3640 - 3642
[3] Advanced Synthesis and Catalysis, 2013, vol. 355, # 8, p. 1517 - 1522
[4] Advanced Synthesis and Catalysis, 2018, vol. 360, # 17, p. 3345 - 3355
[5] Chemistry - A European Journal, 2014, vol. 20, # 24, p. 7241 - 7244
[6] Patent: WO2015/42397, 2015, A1, . Location in patent: Paragraph 000969
[7] Chemical Communications, 2015, vol. 51, # 52, p. 10524 - 10527
[8] Organic and Biomolecular Chemistry, 2017, vol. 15, # 20, p. 4320 - 4327
[9] Advanced Synthesis and Catalysis, 2017, vol. 359, # 14, p. 2390 - 2395
[10] Organic Letters, 2017, vol. 19, # 17, p. 4556 - 4559
23
[ 2142-63-4 ]
[ 62-53-3 ]
[ 23699-65-2 ]
Reference：
[1] Chemistry - A European Journal, 2007, vol. 13, # 9, p. 2701 - 2716
24
[ 2142-63-4 ]
[ 23699-65-2 ]
Reference：
[1] Bulletin de la Societe Chimique de France, 1969, p. 2342 - 2355
25
[ 2142-63-4 ]
[ 106134-16-1 ]
Reference：
[1] Journal of the American Chemical Society, 2013, vol. 135, # 45, p. 16849 - 16852
[2] Turkish Journal of Chemistry, 2015, vol. 39, # 2, p. 244 - 254
[3] Australian Journal of Chemistry, 2015, vol. 68, # 10, p. 1529 - 1534
[4] Bioorganic and Medicinal Chemistry Letters, 2017, vol. 27, # 8, p. 1660 - 1664
[5] Australian Journal of Chemistry, 2017, vol. 70, # 6, p. 660 - 668
26
[ 2142-63-4 ]
[ 52780-14-0 ]
[ 134615-22-8 ]
Yield
Reaction Conditions
Operation in experiment
97%
With trans-[OsCl2(py){2,6-bis[4’-(S)-isopropyloxazolin-2-yl]pyridine}]; caesium carbonate In isopropyl alcohol at 82℃; for 4 h; Inert atmosphere; Schlenk technique
General procedure: The catalyst [0.4 mol percent (complexes 12-22) or 0.2 mol percent (dinuclearcomplex 24)] and the ketone (2.5 mmol) were placed in a three-bottomSchlenk flask under dry argon atmosphere and 2-propanol (45 mL) wasadded. After stirring the mixture for 15 min at 82 °C, 5 ml of a 0.06Msolution of base (Cs2CO3) in 2-propanol (0.3 mmol) were added. Thereaction was monitored by gas chromatography using an HP-6890equipment. The corresponding alcohol and ketone were the only productsdetected in all cases. The conversion and e.e.values were determinedby GC with a Supelco β-DEX 120 chiral capillary column.
95%
With bis(1,5-cyclooctadiene)diiridium(I) dichloride; C37H35FeN2P; hydrogen; potassium carbonate In methanol at 20℃; for 12 h; Glovebox; Autoclave
General procedure: In a nitrogen-filled glovebox, a stainless steel autoclave was charged with [Ir(COD)Cl]2(3.4 mg, 0.005 mmol) andL2(6.6 mg, 0.11 mmol) in 1.0 mL of dry MeOH. After stirring for 1h at room temperature, a solution of the substrates1(1.0 mmol) andK2CO3(6.9 mg, 0.05 mmol) in 2.0 mL of MeOH was added to the reaction mixture, and then the hydrogenation was performed at room temperature under an H2pressure of 20 bar for 12 h. The solvent was then evaporated and the residue was purified by flash column chromatography to give the corresponding hydrogenation product which was analyzed by chiral HPLC to determine the enantiomeric excesses.
4% ee
With formic acid; C23H32ClN2O2RuS; triethylamine In acetonitrile at 20℃; for 480 h;
General procedure: To a ketone (2.4 mmol) placed in a vial 1 mL of CH3CN solution of the preformed ruthenium catalyst (24 μmol) and formic acid/triethylamine azeotropic mixture (1 mL) were added. The mixture was then stirred at room temperature and the progress of the reaction was monitored by TLC until the specified conversion was achieved. After evaporation of the solvents, 4 mL of CH2Cl2 and 1.5 mL of 10percent aqueous HCl solution were added to the residue. The layers were separated and the water layer was extracted twice with 2 mL of CH2Cl2. The combined organic layers were dried over Na2SO4 and the solvent was evaporated in vacuo. The residual oil was purified by column chromatography on silica gel using chloroform (dried over CaCl2) as eluent to afford the appropriate alcohol. The enantiomeric excess was determined by GC analysis using a Supelco cyclodextrin β-DEX 120 capillary column (20 m × 0.25 mm ID and 0.25 μm film thickness). The results of the reduction are summarized in Table 1.
80% ee
With formic acid; C23H32ClN2O2RuS; triethylamine In acetonitrile at 20℃; for 24 h;
General procedure: To a ketone (2.4 mmol) placed in a vial 1 mL of CH3CN solution of the preformed ruthenium catalyst (24 μmol) and formic acid/triethylamine azeotropic mixture (1 mL) were added. The mixture was then stirred at room temperature and the progress of the reaction was monitored by TLC until the specified conversion was achieved. After evaporation of the solvents, 4 mL of CH2Cl2 and 1.5 mL of 10percent aqueous HCl solution were added to the residue. The layers were separated and the water layer was extracted twice with 2 mL of CH2Cl2. The combined organic layers were dried over Na2SO4 and the solvent was evaporated in vacuo. The residual oil was purified by column chromatography on silica gel using chloroform (dried over CaCl2) as eluent to afford the appropriate alcohol. The enantiomeric excess was determined by GC analysis using a Supelco cyclodextrin β-DEX 120 capillary column (20 m × 0.25 mm ID and 0.25 μm film thickness). The results of the reduction are summarized in Table 1.
82 % ee
With formic acid; C23H30ClN2O2RuS; triethylamine In acetonitrile at 20℃; for 18 h;
General procedure: To a ketone (2.4 mmol) placed in a vial, 1 mL of CH3CN solution of preformed ruthenium catalyst (24 lmol) and formic acid/triethylamine azeotropic mixture (1 mL) were added. The mixture was then stirred at room temperature and the progress of the reaction was monitored by TLC until the specified conversion was achieved. After evaporation of the solvents, 4 mL of CH2Cl2 and 1.5 mL of 10percent aqueous HCl solution were added to the residue. The layers were separated and the water layer was extracted twice with 2 mL of CH2Cl2. The combined organic layers were dried over Na2SO4 and the solvent was evaporated in vacuo. The oily residue was purified by column chromatography on silica gel using chloroform (dried over CaCl2) as eluent to afford the appropriate ketone. The enantiomeric excess was determined by GC analysis using a Supelco cyclodextrinb-DEX 120 capillary column (20 m 0.25 mm I.D. and 0.25 lm film thickness).
56 % ee
With formic acid; C23H32ClN2O2RuS; triethylamine In acetonitrile at 20℃; for 96 h;
General procedure: To a ketone (2.4 mmol) placed in a vial, 1 mL of CH3CN solution of preformed ruthenium catalyst (24 lmol) and formic acid/triethylamine azeotropic mixture (1 mL) were added. The mixture was then stirred at room temperature and the progress of the reaction was monitored by TLC until the specified conversion was achieved. After evaporation of the solvents, 4 mL of CH2Cl2 and 1.5 mL of 10percent aqueous HCl solution were added to the residue. The layers were separated and the water layer was extracted twice with 2 mL of CH2Cl2. The combined organic layers were dried over Na2SO4 and the solvent was evaporated in vacuo. The oily residue was purified by column chromatography on silica gel using chloroform (dried over CaCl2) as eluent to afford the appropriate ketone. The enantiomeric excess was determined by GC analysis using a Supelco cyclodextrinb-DEX 120 capillary column (20 m 0.25 mm I.D. and 0.25 lm film thickness).
86.6 % ee
With bis(1,5-cyclooctadiene)diiridium(I) dichloride; (RC,SFc)-1-[bis(3,5-di-tert-butylphenyl)phosphino]-2-[1-N-(6-methylpyridin-2-ylmethyl)aminoethyl] ferrocene; potassium <i>tert</i>-butylate; hydrogen In ethanol at 25 - 30℃; for 18 h; Autoclave
General procedure: To a 20 mL hydrogenation vessel were added the catalyst precursor [{Ir(cod)Cl}2] (1.7 mg, 2.53 μmol), ligand 2f (4.5 mg, 6.06 μmol), and anhydrous EtOH (3 mL) under a nitrogen atmosphere. The mixture was stirred for 1.0 h at 25–30 °C to give a clear yellow solution. After placing the vessel in an autoclave, the ketone (10 mmol) and t-BuOK (28 mg, 0.253 mmol) were added. The autoclave was replaced with H2 three times, and the reaction mixture was stirred at room temperature until no obvious hydrogen pressure drop was observed. After releasing the hydrogen pressure, the reaction mixture was filtered through a short silica gel column. The solvent in the filtrate was removed to determine the yield and the product obtained was analyzed by HPLC to determine the enantiomeric excess.
85 % ee
With dichloro(mesitylene)ruthenium(II) dimer; (1S,2R)-1-((E)-(3-(dimethyl(phenyl)silyl)-2-hydroxy-5-methoxybenzylidene)amino)-2,3-dihydro-1H-inden-2-ol; sodium formate In water at 30℃; for 48 h; Schlenk technique
General procedure: In a Schlenk tube, the chiral ligand (0.05mmol) and the metallic precursor (0.025mmol) were dissolved in water (4mL). After one hour of stirring at 30°C, sodium formate (10mmol) and the ketone (1mmol) were added to the aqueous solution. The solution was maintained at 30°C until total reduction of the ketone. The formed alcohol was separated from the catalyst by simple extraction with pentane (2×8mL), and the organic layer was dried over MgSO4, and concentrated in vacuo. The crude residue was distilled in order to purify the alcohol.
84 % ee
Stage #1: With dimethylsulfide borane complex; 3-(5-((3R,5S)-5-(hydroxydiphenylmethyl)pyrrolidin-3-yloxy)-5-oxopentyl)-1-methyl-1H-imidazol-3-ium hexafluorophosphate In tetrahydrofuran at 70℃; for 0.5 h; Inert atmosphere; Schlenk technique Stage #2: With hydrogenchloride In waterInert atmosphere; Schlenk technique
General procedure: In a schlenk tube, BH3·SMe2(0.55 mmol, 275 L) was added inthe solution of IL 5 (28 mg, 10 molpercent) dissolved in THF (1 mL), undernitrogen atmosphere. The homogenous mixture was stirred andheated at 70C for 30 min. Later, a solution of ketone (0.5 mmolin THF (0.5 mL)) was added within 30 min. After the addition wascompleted, the solvent was evaporated under vacuum. An aqueoussolution of 1M HCl (5 mL) was added and the product was extractedwith DCM. The solvent was dried on anhydrous sodium sulfateand evaporated under reduced pressure. Crude residue was furtherpurified by column chromatography on silica gel using hexane-ethyl acetate as eluent. Enantiomeric excesses of all alcohols weredetermined by HPLC analysis using Chiralcel OD–H/AD–H chiralcolumn, isopropanol-n-hexane as mobile phase and HPLC condi-tions are given in SI.
46.8 % ee
With seeds of Linum usitatissimum In aq. phosphate buffer at 25℃; for 72 h; Microbiological reaction
General procedure: Studies were previously performed to determine the optimal reaction conditions among the parameters: amount ofbiocatalyst (2 g, 5 g, 10 g, and 20 g), time of reaction (24 h, 48, 72, and 96 h), use of co-solvent isopropyl alcohol in theproportions (v/v) 2, 5, and 10percent in distilled water and a buffer solution previously prepared from Na2HPO4–KH2PO4, withpH 6.0, 7.0, and 8.0, using 50 mg of acetophenone as pattern substrate. Therefore, the reactions were carried out in the bestreaction conditions among the parameters tested, using 50 mg of substrate and 20 g of biocatalyst in a buffer solution (Na2HPO4–KH2PO4), pH 6.0, over a period of 72 h at 25C without a co-solvent. In these reaction conditions, 70.4percent ofbioconversion and an ee of 93.7percent were obtained for pattern acetophenone. All biotransformation reactions were performedusing a modified methodology proposed by Machado et al. [11]. Whole seeds of Linum usitatissimum L. were washed with 5percentsodium hypochlorite and rinsed with sterile distilled water. Each individual carbonyl substrate, 1–14 (50 mg), was added to asuspension of 20 g of L. usitatissimum seeds in 40 mL of a buffered solution (Na2HPO4–KH2PO4), pH 6.0, and incubated at25C in an orbital shaker (175 rpm) for 72 h. Controls were similarly processed, except that no substrates were added. Allreactions were performed in triplicate. The course of all reactions was monitored by TLC (Merck, silica gel 60 F254) and thesubstances revealed by spraying with vanillin solution. After completion of the reaction, each suspension was filtered andwashed with water, and the aqueous solutions were extracted with CH2Cl2 (3 50 mL). The organic phases were dried withNa2SO4 and removed in a rotator evaporator. The reaction products were purified by column chromatography on silica gel60 VETEC with a binary mixture of hexane–ethyl acetate (8:2, v/v) as eluent to afford the (S)-alcohols (Scheme 1). The opticalrotations were measured on a PerkinElmer 241 digital polarimeter.
84 % ee
With bis(1,5-cyclooctadiene)iridium(I) tetrafluoroborate; formic acid; sodium formate; (1R,2R)-N1,N-di(naphthalen-1-yl)cyclohexane-1,2-diamine In methanol; water at 70℃; for 22 h; Inert atmosphere
General procedure: In a pressure tube, 0.5 molpercent of metal precursor [C16H24BF4Ir](2.48 mg, 0.005 mol) and 1 molpercent of chiral amine ligand (3.66 mg,0.01 mmol) were dissolved in 2 mL of water and methanol (ratio1:1) and stirred at room temperature for 1 h under argon atmo-sphere. Then formic acid (2.5eq, 0.1 mL), sodium formate (2.5eq,170 mg) and 1eq of ketone substrate (1 mmol) were introduced.The reaction mixture was stirred at 500 rpm and heated at 70C for22 h. After that, the tube was cooled to room temperature; and theorganic compound was extracted with either with ethyl acetate orCH2Cl2, then the solution was dried over Na2SO4, filtrated and con-centrated under reduced pressure. The crude material was purifiedby flash column chromatography on silica gel using cyclohex-ane/ethyl acetate as gradient eluent (90:10–7:3). After evaporation,alcohols were obtained as oil or solid. The products were identifiedby NMR. The conversion and the enantioselectivity were deter-mined by chiral GC or chiral HPLC analysis (Scheme 1).
85 % ee
at 20℃; for 1 h; Inert atmosphere
General procedure: Ruthenium complex (3.7 mg, 0.004 mmol), ketone (2 mmol) andNaOiPr (0.4 mL, 0.1 M) were dissolved in degassed iPrOH (10 mL) and the mixture was stirred under nitrogen atmosphere at appropriate temperature. A small volume of sample was taken from reaction mixture and diluted with diethyl ether (1:1), and rapidly filtered using a short silica pad. The conversion and enantiomeric excess were determined by GC using Agilent HP-Chiral 20B column(30 m, 0.25 mm, 0.25 mm) and by HPLC using Supelco AD-H, OD-Hchiral columns.
87 % ee
With C43H47ClFeIrN2P; potassium <i>tert</i>-butylate; hydrogen In ethanol at 20℃; for 16 h; Autoclave
General procedure: (RC, SFe)-1-[2-(bis(3,5-dimethylphenyl)phosphino)ferrocenyl]N-(6-pyridyl-2-methyl)ethylamine (12.6 mg, 0.022 mmol), [Ir(COD)Cl2 (7.32 mg, 1 mmol)Was added to a 25 mL Schlenk reaction tube,Vacuum / nitrogen three times, 2 mL of anhydrous ethanol was purged with nitrogen, and the mixture was stirred at room temperature for 1 hour. Acetophenone (4.8 g, 40 mmol) was added to a 100 mL autoclave, Add 30 mLThe nitrogen-substituted absolute ethanol, Then, the reaction liquid is added into the reaction kettle,After replacing the hydrogen three times, the pressure was increased to 20 atm,The mixture was stirred at room temperature for 24 hours, TLC showed that the reaction was complete and the product was obtained as a pale yellow liquid (R)-1-phenylethanol 2.2 g in 90.9percent yield and 78percent ee.
56 % ee
With C23H33ClN2O2RuS; potassium hydroxide In isopropyl alcohol at 40℃; for 48 h;
General procedure: To a solution of ketone (0.55 mmol) in 2-propaol (0.5 mL) placed in a vial a 1 mL of 2-propanol solution of preformed ruthenium catalyst (11 μmol) and 0.1M KOH in 2-propanol solution (0.5 mL) were added. The mixture was stirred at 40 oC for 48 h. To reaction mixture 1 mL of water was added, neutralized with 10percent hydrochloric acid and extracted 3x4 mL of CH2Cl2. The organic layer was dried over MgSO4 and concentrated under reduced pressure. The residue oil was purified with a column chromatography on silica gel using dichloromethane as eluent to afford appropriate ketone. The enantiomeric excess of alcohols was determined by HPLC analysis using a Chiracel OD-H column, hexane:i-PrOH (95:5 or 98:2), 1 mL/min. The enantiomeric excess of 1-(2-methylphenyl)ethanol and 1-(4-methylphenyl)ethanol were determined by comparison of the value and sign of specific rotation.
67 % ee
With C23H33ClN2O2RuS; potassium hydroxide In isopropyl alcohol at 40℃; for 48 h;
General procedure: To a solution of ketone (0.55 mmol) in 2-propaol (0.5 mL) placed in a vial a 1 mL of 2-propanol solution of preformed ruthenium catalyst (11 μmol) and 0.1M KOH in 2-propanol solution (0.5 mL) were added. The mixture was stirred at 40 oC for 48 h. To reaction mixture 1 mL of water was added, neutralized with 10percent hydrochloric acid and extracted 3x4 mL of CH2Cl2. The organic layer was dried over MgSO4 and concentrated under reduced pressure. The residue oil was purified with a column chromatography on silica gel using dichloromethane as eluent to afford appropriate ketone. The enantiomeric excess of alcohols was determined by HPLC analysis using a Chiracel OD-H column, hexane:i-PrOH (95:5 or 98:2), 1 mL/min. The enantiomeric excess of 1-(2-methylphenyl)ethanol and 1-(4-methylphenyl)ethanol were determined by comparison of the value and sign of specific rotation.
Reference：
[1] Molecular Catalysis, 2018, vol. 456, p. 75 - 86
[2] Tetrahedron Letters, 2018, vol. 59, # 8, p. 719 - 722
[3] Angewandte Chemie, 1995, vol. 107, # 18, p. 2165 - 2166
[4] Angewandte Chemie, 1995, vol. 107, # 18, p. 2165 - 2166
[5] Journal of Organometallic Chemistry, 1997, vol. 547, # 1, p. 97 - 101
[6] Journal of the American Chemical Society, 2001, vol. 123, # 51, p. 12917 - 12918
[7] Tetrahedron Asymmetry, 2004, vol. 15, # 13, p. 1965 - 1967
[8] Chemistry - A European Journal, 2004, vol. 10, # 2, p. 425 - 432
[9] Advanced Synthesis and Catalysis, 2005, vol. 347, # 9, p. 1193 - 1197
[10] Tetrahedron, 2005, vol. 61, # 47, p. 11244 - 11252
[11] Tetrahedron Asymmetry, 2006, vol. 17, # 8, p. 1179 - 1185
[12] Chemical Communications, 2005, # 24, p. 3050 - 3052
[13] Chemical Communications, 2005, # 35, p. 4447 - 4449
[14] Chemical Communications, 2004, # 18, p. 2070 - 2071
[15] Synlett, 2006, # 8, p. 1155 - 1160
[16] Journal of Organic Chemistry, 2000, vol. 65, # 10, p. 3116 - 3122
[17] Tetrahedron Letters, 2004, vol. 45, # 5, p. 951 - 953
[18] Tetrahedron Asymmetry, 2007, vol. 18, # 10, p. 1159 - 1162
[19] Chemical Communications, 2007, # 28, p. 2977 - 2979
[20] Tetrahedron Asymmetry, 2008, vol. 19, # 7, p. 816 - 821
[21] Tetrahedron Asymmetry, 2008, vol. 19, # 8, p. 912 - 920
[22] Patent: WO2008/77610, 2008, A1, . Location in patent: Page/Page column 18-19
[23] Tetrahedron Asymmetry, 2008, vol. 19, # 16, p. 1992 - 1997
[24] Organic Letters, 2008, vol. 10, # 14, p. 2979 - 2982
[25] Organic Letters, 2008, vol. 10, # 19, p. 4391 - 4391
[26] Monatshefte fur Chemie, 2008, vol. 139, # 7, p. 793 - 798
[27] Journal of Organic Chemistry, 2009, vol. 74, # 12, p. 4608 - 4611
[28] Tetrahedron Asymmetry, 2009, vol. 20, # 13, p. 1521 - 1525
[29] Dalton Transactions, 2009, # 15, p. 2764 - 2776
[30] Organic Letters, 2010, vol. 12, # 14, p. 3238 - 3241
[31] Tetrahedron Asymmetry, 2010, vol. 21, # 18, p. 2258 - 2264
[32] Catalysis Communications, 2010, vol. 11, # 7, p. 584 - 587
[33] Catalysis Communications, 2010, vol. 11, # 5, p. 373 - 377
[34] Organic and Biomolecular Chemistry, 2010, vol. 8, # 20, p. 4536 - 4539
[35] Advanced Synthesis and Catalysis, 2010, vol. 352, # 14-15, p. 2621 - 2628
[36] Chinese Chemical Letters, 2010, vol. 21, # 12, p. 1403 - 1406
[37] Catalysis Communications, 2011, vol. 12, # 12, p. 1118 - 1121
[38] Tetrahedron Asymmetry, 2012, vol. 23, # 11-12, p. 834 - 837
[39] Tetrahedron Asymmetry, 2012, vol. 23, # 14, p. 1106 - 1110
[40] Tetrahedron Asymmetry, 2012, vol. 23, # 14, p. 1106 - 1110
[41] Advanced Synthesis and Catalysis, 2012, vol. 354, # 17, p. 3250 - 3258
[42] Biocatalysis and Biotransformation, 2012, vol. 30, # 5-6, p. 469 - 475
[43] Inorganic Chemistry, 2013, vol. 52, # 10, p. 6193 - 6198
[44] Tetrahedron Asymmetry, 2013, vol. 24, # 11, p. 643 - 650
[45] Tetrahedron Asymmetry, 2013, vol. 24, # 11, p. 643 - 650
[46] Organic Letters, 2013, vol. 15, # 17, p. 4560 - 4563
[47] Chemistry - An Asian Journal, 2013, vol. 8, # 12, p. 3108 - 3115
[48] Tetrahedron Asymmetry, 2013, vol. 24, # 24, p. 1567 - 1571
[49] Comptes Rendus Chimie, 2014, vol. 17, # 5, p. 403 - 412
[50] Applied Organometallic Chemistry, 2014, vol. 28, # 7, p. 517 - 522
[51] European Journal of Organic Chemistry, 2006, # 16, p. 3606 - 3616
[52] Journal of Molecular Catalysis A: Chemical, 2015, vol. 398, p. 184 - 189
[53] Journal of Organic Chemistry, 2015, vol. 80, # 7, p. 3538 - 3546
[54] Chemistry of Natural Compounds, 2015, vol. 51, # 4, p. 752 - 755[55] Khim. Prir. Soedin., 2015, # 4, p. 645 - 647,3
[56] Journal of Molecular Catalysis A: Chemical, 2016, vol. 411, p. 196 - 202
[57] Catalysis Communications, 2016, vol. 74, p. 122 - 125
[58] Journal of Organometallic Chemistry, 2016, vol. 819, p. 189 - 193
[59] Patent: CN103012498, 2016, B, . Location in patent: Paragraph 0049; 0050; 0051; 0052; 0053
[60] European Journal of Inorganic Chemistry, 2018, vol. 2018, # 12, p. 1383 - 1393
[61] Tetrahedron Letters, 2018, vol. 59, # 22, p. 2184 - 2188
[62] Tetrahedron Letters, 2018, vol. 59, # 22, p. 2184 - 2188
[63] Chemistry and Biodiversity, 2018, vol. 15, # 6,
[64] Organometallics, 2018, vol. 37, # 24, p. 4608 - 4618
27
[ 52780-14-0 ]
[ 52780-14-0 ]
[ 2142-63-4 ]
[ 134615-22-8 ]
Reference：
[1] Journal of Molecular Catalysis B: Enzymatic, 2012, vol. 83, p. 23 - 28
[2] Angewandte Chemie - International Edition, 2018, vol. 57, # 8, p. 2085 - 2090[3] Angew. Chem., 2018, vol. 130, # 8, p. 2107 - 2112,6
28
[ 2142-63-4 ]
[ 67-63-0 ]
[ 52780-14-0 ]
[ 67-64-1 ]
[ 134615-22-8 ]
Reference：
[1] Chemistry - A European Journal, 2012, vol. 18, # 35, p. 10843 - 10846
Reference：
[1] Advanced Synthesis and Catalysis, 2016, vol. 358, # 10, p. 1618 - 1624
34
[ 2142-63-4 ]
[ 110-60-1 ]
[ 5724-81-2 ]
[ 74877-08-0 ]
[ 176707-77-0 ]
Reference：
[1] Green Chemistry, 2017, vol. 19, # 2, p. 361 - 366
35
[ 1885-46-7 ]
[ 2142-63-4 ]
[ 101975-23-9 ]
Yield
Reaction Conditions
Operation in experiment
71%
Stage #1: With tris-(dibenzylideneacetone)dipalladium(0); potassium hydroxide; tert-butyl XPhos In 1,4-dioxane; water at 100℃; Inert atmosphere Stage #2: With potassium hydroxide In 1,4-dioxane; water; acetonitrile at 20℃; for 0.0333333 h;
General procedure: [a] Reactions were performed on a 0.5 mmol scale to determine yields by 19F NMR spectroscopy with PI1CF3 as an internal standard added after the reaction.; Note: The hydroxylation reaction was set-up under an inert atmosphere according to the literature procedure. [Anderson, K. W.; Ikawa, T.; Tundel, R. E.; Buchwald, S. L. J. Am. Chem. Soc. 2006, 128, 10694.] To an oven-dried 4 mL vial was added Pd2(dba)3 (9.2 mg, .010 mmol, 4.0 mol percent Pd), 2-Di-tert-butylphosphino-2',4',6'-triisopropylbiphenyl (lBu- XPhos, 17.0 mg, .040 mmol, 8.0 mol percent), KOH (1.0-3.0 equiv), degassed H20 (150-300 μ) and dioxane (250-500 μΚ). The aryl halide (0.5 mmol, 1.0 equiv) was added (solid aryl halides were weighed into the vial prior to adding solvent, and liquid aryl bromides were added neat by syringe after the addition of solvent). The vial was sealed with a Teflon-lined cap and heated at 100 °C for 1-18 h. The solution was allowed to cool, and the reaction was diluted with acetonitrile (500-750 μ, such that the total volume of dioxane and acetonitrile is 1.0 mL) and 6M KOH (700-850 μ, such that the final aqueous solvent volume is 1.0 mL). The resulting mixture was stirred rapidly at room temperature, and HCF20Tf (210 μ, 1.5 mmol, 3.0 equiv) was added at once. Note: the reactions are exothermic. The mixture was stirred vigorously for 2 minutes. The reaction was diluted with ]0 (8 mL) and extracted with ether (2 x 8 mL). The combined organic layers were dried over MgS04, concentrated, and purified by silica gel chromatography.
With potassium phosphate tribasic heptahydrate; C45H53ClFeNO2PPd In water; toluene at 100℃; for 3 h; Inert atmosphere
General procedure: Potassium phosphate (0.75 mmol) and IIe (1 mol percent) was added to the solution of aryl halides (0.25 mmol) and cyclopropylboronic acid (0.5 mmol) in toluene (2.0 mL) and water (100 μL). The mixture was heated to 100 °C for a proper time under nitrogen atmosphere and cooled to room temperature. Water (10 mL) was added and the mixture was extracted with EtOAc (3.x.15 mL), evaporated and purified by chromatography on silica gel.
With titanium tetrachloride; In 1,2-dichloro-ethane; for 3h;Reflux;
General procedure: A solution of 2-chloro-1-[4-(propan-2-yl)phenyl]ethanone (1 g, 5.1 mmol) in dichloroethane (DCE) (10 mL) was placed in a 50 mLthree-mouth round-bottomed flask equipped with a reflux condenser, a calcium chloride drying tube, a thermometer and a magnetic stirring bar. To the stirred reaction solution at room temperature, tickle (0.115 mL, 25%) followed by PMHS (0.7 g, 12.2 mmol) were added from a syringe. The reaction mixture was heated to reflux and progress of the reaction monitored by thin layer chromatography (tlc) and stopped after three hours. The gelatinous reaction mixture was taken up in hexane (15 mL) and filtered under a plug of celite. The filter cake was washed with hexane (50 mL) and the filtrate concentrated in vacuo.
1) Production of 3-(1-hydroxy-1-methylethyl)phenylboronic acid In a nitrogen atmosphere with cooling with ice, 5.29 mL of 3'-bromoacetophenone was added to 25 mL of 2 M methylmagnesium iodide/diethyl ether solution and 100 mL of diethyl ether, and stirred for 20 minutes. Water and 2 N hydrochloric acid were added to the reaction liquid, extracted with ethyl acetate, washed with aqueous saturated sodium hydrogencarbonate solution and saturated saline water, and dried with anhydrous magnesium sulfate. The solvent was evaporated away under reduced pressure to obtain crude 2-(3-bromophenyl)propan-2-ol.
With Lactobacillus kefiri P2; at 25℃; for 64h;pH 4.5;Green chemistry; Enzymatic reaction;
General procedure: Lactobacillus kefiri P2 was added from its glycerol stock by inoculation to 10mL MRS mixture (MgSO4.7H2O 11.5% (w/v), K2HPO4 2 g/L, pepton [Oxoid] 10 g/L, yeast extract 2% glucose, [Difco] 5 g/L, C2H3NaO2.3H2O 5 g/L, salt solution [MgSO4.7H2O 11.5% (w/v), triamonium citrate 2 g/L], Tween 80 1 mL/L) followed by 48 h growth at 37 C. From this mixture, overnight grown bacterial cells were inoculated to 100m LMRS mixture at 10% concentration. Then, pH of medium was adjusted to 4.5 with 1M HCI. This mixture was shaken for 2 hours, and then 1 mmol of substrate (1-16) was directly added to this mixture and incubated on an orbital shaker at 150 rpm with an incubation temperature of 25 C for 64 h incubation period. After the catalytic reaction was complete, the supernatant was separated. The aqueous phase was saturated with NaCI and extracted with dichloromethane. After the organic phases were combined, they were dried over anhydrous Na2SO4 and filtered to remove the salt. The liquid was removed in a vacuum to remove dichloromethane and the crude product was characterizedby NMR analysis. After the crude product was purified using column chromatography, ee was determined using chiral HPLC. The absolute configurations of the alcohols were determined by comparing the literature values of the specific rotation.
With potassium tert-butylate; isopropyl alcohol;[ruthenium(II)(eta6-1-methyl-4-isopropyl-benzene)(chloride)(mu-chloride)]2; (11bR,11'bR)-4,4'-(9,9-dimethyl-9H-xanthane-4,5-diyl)bis[dinaphtho[2,1-d:1',2'-f][1,3,2]dioxaphosphepin]; at 40 - 80℃; for 29h;Product distribution / selectivity;
[RuCl2(p-cymene]2 (N) (1.22 mg, 2 mumol) and a chiral diphosphonite ligand such as XI (0.010 mmol) were heated in dry isopropanol (2.5 ml) at 80 C. under argon for 1 h. Once the mixture had been cooled to room temperature, a base NaOH (0.04 mmol; 0.5 ml of a 0.08 M solution in isopropanol) or KOC(CH3)3 (0.04 mmol; 0.5 ml of a 0.08 M solution in isopropanol) were added, then a ketone such as acetophenone (0.4 mmol) was added. The reaction mixture was stirred at 40 C. under argon over a defined period (typically 16-96 h). Samples were taken from the reaction solution and put through a small amount of silica gel before the GC analysis to determine the conversions and the ee values by gas chromatography.
With sodium hydroxide; isopropyl alcohol;[ruthenium(II)(eta6-1-methyl-4-isopropyl-benzene)(chloride)(mu-chloride)]2; (11bR,11'bR)-4,4'-(9,9-dimethyl-9H-xanthane-4,5-diyl)bis[dinaphtho[2,1-d:1',2'-f][1,3,2]dioxaphosphepin]; at 40 - 80℃; for 17h;Product distribution / selectivity;
[RuCl2(p-cymene]2 (N) (1.22 mg, 2 mumol) and a chiral diphosphonite ligand such as XI (0.010 mmol) were heated in dry isopropanol (2.5 ml) at 80 C. under argon for 1 h. Once the mixture had been cooled to room temperature, a base NaOH (0.04 mmol; 0.5 ml of a 0.08 M solution in isopropanol) or KOC(CH3)3 (0.04 mmol; 0.5 ml of a 0.08 M solution in isopropanol) were added, then a ketone such as acetophenone (0.4 mmol) was added. The reaction mixture was stirred at 40 C. under argon over a defined period (typically 16-96 h). Samples were taken from the reaction solution and put through a small amount of silica gel before the GC analysis to determine the conversions and the ee values by gas chromatography.
With sodium formate; In water; at 40℃; for 4h;
General procedure: A typical procedure was as follows [32]: GH-catalyst, HCOONa (20 mg, 0.3 mmol), ketones (2.0 mmol), and 2.0 mL water were added in a 10 mL round bottom flask. The mixture was allowed to react at 40 8C for 4 h. During the reaction, it was monitored constantly by TLC. The conversion and ee value could be determined by chiral GC using a Supelco b-Dex 120 chiral column (30 m 0.25 mm (i.d.), 0.25 mm film) or HPLC analysis with UV-vis detector using Daicel OJ-H chiral column (10.46 cm*25 cm).
With trans-[OsCl2(py){2,6-bis[4?-(S)-isopropyloxazolin-2-yl]pyridine}]; caesium carbonate; In isopropyl alcohol; at 82℃; for 4h;Inert atmosphere; Schlenk technique;
General procedure: The catalyst [0.4 mol % (complexes 12-22) or 0.2 mol % (dinuclearcomplex 24)] and the ketone (2.5 mmol) were placed in a three-bottomSchlenk flask under dry argon atmosphere and 2-propanol (45 mL) wasadded. After stirring the mixture for 15 min at 82 C, 5 ml of a 0.06Msolution of base (Cs2CO3) in 2-propanol (0.3 mmol) were added. Thereaction was monitored by gas chromatography using an HP-6890equipment. The corresponding alcohol and ketone were the only productsdetected in all cases. The conversion and e.e.values were determinedby GC with a Supelco beta-DEX 120 chiral capillary column.
95%
With bis(1,5-cyclooctadiene)diiridium(I) dichloride; C37H35FeN2P; hydrogen; potassium carbonate; In methanol; at 20℃; under 15001.5 Torr; for 12h;Glovebox; Autoclave;
General procedure: In a nitrogen-filled glovebox, a stainless steel autoclave was charged with [Ir(COD)Cl]2(3.4 mg, 0.005 mmol) andL2(6.6 mg, 0.11 mmol) in 1.0 mL of dry MeOH. After stirring for 1h at room temperature, a solution of the substrates1(1.0 mmol) andK2CO3(6.9 mg, 0.05 mmol) in 2.0 mL of MeOH was added to the reaction mixture, and then the hydrogenation was performed at room temperature under an H2pressure of 20 bar for 12 h. The solvent was then evaporated and the residue was purified by flash column chromatography to give the corresponding hydrogenation product which was analyzed by chiral HPLC to determine the enantiomeric excesses.
With potassium tert-butylate; hydrogen; isopropyl alcohol;C6H14N2*2C27H26NO2P*2Cl(1-)*Ru(2+); at 20℃; under 18751.9 Torr; for 24h;Product distribution / selectivity;
Examples 5-15 Procedure for the hydroqenation of aromatic ketonesThese experiments were performed in small autoclaves that can be pressurized to 25 bar. To a glass liner for an autoclave 2 mmol of substrate is added. To the substrate is added 0.1 mol% of preformed catalyst of example 3 and 10 mul of a 1 M solution of KOtBu in iPrOH. To this 3.7 ml iPrOH is added. The liner is put into one of the parallel autoclaves and, while stirring, 25 bars of hydrogen pressure is applied. After 24 hours the autoclave is carefully vented and the glass liner is taken out. From the reaction mixture a sample is taken and filtered over a silica plug to prepare a GC sample. The sample containing the product alcohol is analyzed by chiral GC.According to this procedure the following substrates were reacted:
With (S,S)-DPENDS; C36H24Cl2O18P2RuS6(6-)*6Na(1+); hydrogen; potassium hydroxide; In water; at 30℃; under 37503.8 Torr; for 3h;Autoclave;
General procedure: To a 60 mL stainless autoclave with a glass liner and magnetic stirrer were added PEG-400, H2O, RuCl2(TPPTS)2, (S,S)-DPENDS, KOH, and reactant. Hydrogen was introduced to the desired pressure after the reaction mixture had been purged with H2 five times. The products were extracted by n-hexane and analyzed by GC-960 with a FID detector and beta-DEX120 capillary column (30 m × 0.25 mm, 0.25 mum film) at 115 C. The enantiomeric excess (ee value) was calculated from the equation: ee (%) = 100 × (R - S)/(R + S).
With formic acid; C23H32ClN2O2RuS; triethylamine; In acetonitrile; at 20℃; for 480h;
General procedure: To a ketone (2.4 mmol) placed in a vial 1 mL of CH3CN solution of the preformed ruthenium catalyst (24 mumol) and formic acid/triethylamine azeotropic mixture (1 mL) were added. The mixture was then stirred at room temperature and the progress of the reaction was monitored by TLC until the specified conversion was achieved. After evaporation of the solvents, 4 mL of CH2Cl2 and 1.5 mL of 10% aqueous HCl solution were added to the residue. The layers were separated and the water layer was extracted twice with 2 mL of CH2Cl2. The combined organic layers were dried over Na2SO4 and the solvent was evaporated in vacuo. The residual oil was purified by column chromatography on silica gel using chloroform (dried over CaCl2) as eluent to afford the appropriate alcohol. The enantiomeric excess was determined by GC analysis using a Supelco cyclodextrin beta-DEX 120 capillary column (20 m × 0.25 mm ID and 0.25 mum film thickness). The results of the reduction are summarized in Table 1.
With formic acid; C23H32ClN2O2RuS; triethylamine; In acetonitrile; at 20℃; for 24h;
General procedure: To a ketone (2.4 mmol) placed in a vial 1 mL of CH3CN solution of the preformed ruthenium catalyst (24 mumol) and formic acid/triethylamine azeotropic mixture (1 mL) were added. The mixture was then stirred at room temperature and the progress of the reaction was monitored by TLC until the specified conversion was achieved. After evaporation of the solvents, 4 mL of CH2Cl2 and 1.5 mL of 10% aqueous HCl solution were added to the residue. The layers were separated and the water layer was extracted twice with 2 mL of CH2Cl2. The combined organic layers were dried over Na2SO4 and the solvent was evaporated in vacuo. The residual oil was purified by column chromatography on silica gel using chloroform (dried over CaCl2) as eluent to afford the appropriate alcohol. The enantiomeric excess was determined by GC analysis using a Supelco cyclodextrin beta-DEX 120 capillary column (20 m × 0.25 mm ID and 0.25 mum film thickness). The results of the reduction are summarized in Table 1.
With formic acid; C23H30ClN2O2RuS; triethylamine; In acetonitrile; at 20℃; for 18h;
General procedure: To a ketone (2.4 mmol) placed in a vial, 1 mL of CH3CN solution of preformed ruthenium catalyst (24 lmol) and formic acid/triethylamine azeotropic mixture (1 mL) were added. The mixture was then stirred at room temperature and the progress of the reaction was monitored by TLC until the specified conversion was achieved. After evaporation of the solvents, 4 mL of CH2Cl2 and 1.5 mL of 10% aqueous HCl solution were added to the residue. The layers were separated and the water layer was extracted twice with 2 mL of CH2Cl2. The combined organic layers were dried over Na2SO4 and the solvent was evaporated in vacuo. The oily residue was purified by column chromatography on silica gel using chloroform (dried over CaCl2) as eluent to afford the appropriate ketone. The enantiomeric excess was determined by GC analysis using a Supelco cyclodextrinb-DEX 120 capillary column (20 m 0.25 mm I.D. and 0.25 lm film thickness).
With formic acid; C23H32ClN2O2RuS; triethylamine; In acetonitrile; at 20℃; for 96h;
General procedure: To a ketone (2.4 mmol) placed in a vial, 1 mL of CH3CN solution of preformed ruthenium catalyst (24 lmol) and formic acid/triethylamine azeotropic mixture (1 mL) were added. The mixture was then stirred at room temperature and the progress of the reaction was monitored by TLC until the specified conversion was achieved. After evaporation of the solvents, 4 mL of CH2Cl2 and 1.5 mL of 10% aqueous HCl solution were added to the residue. The layers were separated and the water layer was extracted twice with 2 mL of CH2Cl2. The combined organic layers were dried over Na2SO4 and the solvent was evaporated in vacuo. The oily residue was purified by column chromatography on silica gel using chloroform (dried over CaCl2) as eluent to afford the appropriate ketone. The enantiomeric excess was determined by GC analysis using a Supelco cyclodextrinb-DEX 120 capillary column (20 m 0.25 mm I.D. and 0.25 lm film thickness).
With bis(1,5-cyclooctadiene)diiridium(I) dichloride; (RC,SFc)-1-[bis(3,5-di-tert-butylphenyl)phosphino]-2-[1-N-(6-methylpyridin-2-ylmethyl)aminoethyl] ferrocene; potassium tert-butylate; hydrogen; In ethanol; at 25 - 30℃; under 15201 Torr; for 18h;Autoclave;
General procedure: To a 20 mL hydrogenation vessel were added the catalyst precursor [{Ir(cod)Cl}2] (1.7 mg, 2.53 mumol), ligand 2f (4.5 mg, 6.06 mumol), and anhydrous EtOH (3 mL) under a nitrogen atmosphere. The mixture was stirred for 1.0 h at 25-30 C to give a clear yellow solution. After placing the vessel in an autoclave, the ketone (10 mmol) and t-BuOK (28 mg, 0.253 mmol) were added. The autoclave was replaced with H2 three times, and the reaction mixture was stirred at room temperature until no obvious hydrogen pressure drop was observed. After releasing the hydrogen pressure, the reaction mixture was filtered through a short silica gel column. The solvent in the filtrate was removed to determine the yield and the product obtained was analyzed by HPLC to determine the enantiomeric excess.
With dichloro(mesitylene)ruthenium(II) dimer; (1S,2R)-1-((E)-(3-(dimethyl(phenyl)silyl)-2-hydroxy-5-methoxybenzylidene)amino)-2,3-dihydro-1H-inden-2-ol; sodium formate; In water; at 30℃; for 48h;Schlenk technique;
General procedure: In a Schlenk tube, the chiral ligand (0.05mmol) and the metallic precursor (0.025mmol) were dissolved in water (4mL). After one hour of stirring at 30C, sodium formate (10mmol) and the ketone (1mmol) were added to the aqueous solution. The solution was maintained at 30C until total reduction of the ketone. The formed alcohol was separated from the catalyst by simple extraction with pentane (2×8mL), and the organic layer was dried over MgSO4, and concentrated in vacuo. The crude residue was distilled in order to purify the alcohol.
General procedure: In a schlenk tube, BH3·SMe2(0.55 mmol, 275 L) was added inthe solution of IL 5 (28 mg, 10 mol%) dissolved in THF (1 mL), undernitrogen atmosphere. The homogenous mixture was stirred andheated at 70C for 30 min. Later, a solution of ketone (0.5 mmolin THF (0.5 mL)) was added within 30 min. After the addition wascompleted, the solvent was evaporated under vacuum. An aqueoussolution of 1M HCl (5 mL) was added and the product was extractedwith DCM. The solvent was dried on anhydrous sodium sulfateand evaporated under reduced pressure. Crude residue was furtherpurified by column chromatography on silica gel using hexane-ethyl acetate as eluent. Enantiomeric excesses of all alcohols weredetermined by HPLC analysis using Chiralcel OD-H/AD-H chiralcolumn, isopropanol-n-hexane as mobile phase and HPLC condi-tions are given in SI.
With seeds of Linum usitatissimum; In aq. phosphate buffer; at 25℃; for 72h;pH 6.0;Microbiological reaction;
General procedure: Studies were previously performed to determine the optimal reaction conditions among the parameters: amount ofbiocatalyst (2 g, 5 g, 10 g, and 20 g), time of reaction (24 h, 48, 72, and 96 h), use of co-solvent isopropyl alcohol in theproportions (v/v) 2, 5, and 10% in distilled water and a buffer solution previously prepared from Na2HPO4-KH2PO4, withpH 6.0, 7.0, and 8.0, using 50 mg of acetophenone as pattern substrate. Therefore, the reactions were carried out in the bestreaction conditions among the parameters tested, using 50 mg of substrate and 20 g of biocatalyst in a buffer solution (Na2HPO4-KH2PO4), pH 6.0, over a period of 72 h at 25C without a co-solvent. In these reaction conditions, 70.4% ofbioconversion and an ee of 93.7% were obtained for pattern acetophenone. All biotransformation reactions were performedusing a modified methodology proposed by Machado et al. [11]. Whole seeds of Linum usitatissimum L. were washed with 5%sodium hypochlorite and rinsed with sterile distilled water. Each individual carbonyl substrate, 1-14 (50 mg), was added to asuspension of 20 g of L. usitatissimum seeds in 40 mL of a buffered solution (Na2HPO4-KH2PO4), pH 6.0, and incubated at25C in an orbital shaker (175 rpm) for 72 h. Controls were similarly processed, except that no substrates were added. Allreactions were performed in triplicate. The course of all reactions was monitored by TLC (Merck, silica gel 60 F254) and thesubstances revealed by spraying with vanillin solution. After completion of the reaction, each suspension was filtered andwashed with water, and the aqueous solutions were extracted with CH2Cl2 (3 50 mL). The organic phases were dried withNa2SO4 and removed in a rotator evaporator. The reaction products were purified by column chromatography on silica gel60 VETEC with a binary mixture of hexane-ethyl acetate (8:2, v/v) as eluent to afford the (S)-alcohols (Scheme 1). The opticalrotations were measured on a PerkinElmer 241 digital polarimeter.
With bis(1,5-cyclooctadiene)iridium(I) tetrafluoroborate; formic acid; sodium formate; (1R,2R)-N1,N-di(naphthalen-1-yl)cyclohexane-1,2-diamine; In methanol; water; at 70℃; for 22h;Inert atmosphere;Catalytic behavior;
General procedure: In a pressure tube, 0.5 mol% of metal precursor [C16H24BF4Ir](2.48 mg, 0.005 mol) and 1 mol% of chiral amine ligand (3.66 mg,0.01 mmol) were dissolved in 2 mL of water and methanol (ratio1:1) and stirred at room temperature for 1 h under argon atmo-sphere. Then formic acid (2.5eq, 0.1 mL), sodium formate (2.5eq,170 mg) and 1eq of ketone substrate (1 mmol) were introduced.The reaction mixture was stirred at 500 rpm and heated at 70C for22 h. After that, the tube was cooled to room temperature; and theorganic compound was extracted with either with ethyl acetate orCH2Cl2, then the solution was dried over Na2SO4, filtrated and con-centrated under reduced pressure. The crude material was purifiedby flash column chromatography on silica gel using cyclohex-ane/ethyl acetate as gradient eluent (90:10-7:3). After evaporation,alcohols were obtained as oil or solid. The products were identifiedby NMR. The conversion and the enantioselectivity were deter-mined by chiral GC or chiral HPLC analysis (Scheme 1).
With C50H47Cl2N3P2Ru; C50H47Cl2N3P2Ru; sodium isopropylate; isopropyl alcohol; at 20℃; for 1h;Inert atmosphere;
General procedure: Ruthenium complex (3.7 mg, 0.004 mmol), ketone (2 mmol) andNaOiPr (0.4 mL, 0.1 M) were dissolved in degassed iPrOH (10 mL) and the mixture was stirred under nitrogen atmosphere at appropriate temperature. A small volume of sample was taken from reaction mixture and diluted with diethyl ether (1:1), and rapidly filtered using a short silica pad. The conversion and enantiomeric excess were determined by GC using Agilent HP-Chiral 20B column(30 m, 0.25 mm, 0.25 mm) and by HPLC using Supelco AD-H, OD-Hchiral columns.
With C43H47ClFeIrN2P; potassium tert-butylate; hydrogen; In ethanol; at 20℃; under 15201 Torr; for 16h;Autoclave;
General procedure: (RC, SFe)-1-[2-(bis(3,5-dimethylphenyl)phosphino)ferrocenyl]N-(6-pyridyl-2-methyl)ethylamine (12.6 mg, 0.022 mmol), [Ir(COD)Cl2 (7.32 mg, 1 mmol)Was added to a 25 mL Schlenk reaction tube,Vacuum / nitrogen three times, 2 mL of anhydrous ethanol was purged with nitrogen, and the mixture was stirred at room temperature for 1 hour. Acetophenone (4.8 g, 40 mmol) was added to a 100 mL autoclave, Add 30 mLThe nitrogen-substituted absolute ethanol, Then, the reaction liquid is added into the reaction kettle,After replacing the hydrogen three times, the pressure was increased to 20 atm,The mixture was stirred at room temperature for 24 hours, TLC showed that the reaction was complete and the product was obtained as a pale yellow liquid (R)-1-phenylethanol 2.2 g in 90.9% yield and 78% ee.
With C23H33ClN2O2RuS; potassium hydroxide; In isopropyl alcohol; at 40℃; for 48h;
General procedure: To a solution of ketone (0.55 mmol) in 2-propaol (0.5 mL) placed in a vial a 1 mL of 2-propanol solution of preformed ruthenium catalyst (11 mumol) and 0.1M KOH in 2-propanol solution (0.5 mL) were added. The mixture was stirred at 40 oC for 48 h. To reaction mixture 1 mL of water was added, neutralized with 10% hydrochloric acid and extracted 3x4 mL of CH2Cl2. The organic layer was dried over MgSO4 and concentrated under reduced pressure. The residue oil was purified with a column chromatography on silica gel using dichloromethane as eluent to afford appropriate ketone. The enantiomeric excess of alcohols was determined by HPLC analysis using a Chiracel OD-H column, hexane:i-PrOH (95:5 or 98:2), 1 mL/min. The enantiomeric excess of 1-(2-methylphenyl)ethanol and 1-(4-methylphenyl)ethanol were determined by comparison of the value and sign of specific rotation.
With C23H33ClN2O2RuS; potassium hydroxide; In isopropyl alcohol; at 40℃; for 48h;
General procedure: To a solution of ketone (0.55 mmol) in 2-propaol (0.5 mL) placed in a vial a 1 mL of 2-propanol solution of preformed ruthenium catalyst (11 mumol) and 0.1M KOH in 2-propanol solution (0.5 mL) were added. The mixture was stirred at 40 oC for 48 h. To reaction mixture 1 mL of water was added, neutralized with 10% hydrochloric acid and extracted 3x4 mL of CH2Cl2. The organic layer was dried over MgSO4 and concentrated under reduced pressure. The residue oil was purified with a column chromatography on silica gel using dichloromethane as eluent to afford appropriate ketone. The enantiomeric excess of alcohols was determined by HPLC analysis using a Chiracel OD-H column, hexane:i-PrOH (95:5 or 98:2), 1 mL/min. The enantiomeric excess of 1-(2-methylphenyl)ethanol and 1-(4-methylphenyl)ethanol were determined by comparison of the value and sign of specific rotation.
With potassium tert-butylate; (Rc,Sp)-N-5,6,7,8-tetrahydroquinolinyl-1-(2-diphenylphosphino)ferrocenylethylamine manganese; isopropyl alcohol; at 20℃; for 2h;Inert atmosphere;
General procedure: a) Add 1-acetylnaphthalene (0.17g, 1mmol), potassium tert-butoxide (22mg, 0.2mmol) and catalyst (7mg, 0.01mmol) to a 50ml round-bottomed flask, and then add them to the round-bottomed flask. 30 ml of isopropanol was replaced with nitrogen for 10 times, and the reaction was stirred. The reaction temperature was 20 C. The reaction was stopped after 2 hours of reaction. The reaction was detected by GC, and the conversion was determined to be 94%. The ee value measured by LC was 93%.
100 g of bromoacetophenone was slowly added dropwise to 500 ml of sulfuric acid nitric acid mixture (volume ratio 1: 7, minus 20 degrees), and the temperature was stirred overnight. The reaction mixture was filtered through ice water to give 107 g of 2-nitro-5-bromoacetophenone as a yellow solid in 87% yield.
33%
With sulfuric acid; nitric acid; at 0℃; for 1h;
To nitric acid (fuming, 2 mL, 25.1 mmol) was slowly added sulfuricacid (2.5 mL, 25.1 mmol) at 0 C and the mixture was stirredat same temperature for 15 min. To the solution was slowly added27 (3.34 mL, 25.1 mmol) at 0 C with vigorous stirring and the mixturewas stirred at same temperature for 1 h. The mixture waspoured into ice-water and extracted with EtOAc. The organic layerwas washed with satd NaHCO3 solution and brine, dried overMgSO4, concentrated, and purified by column chromatography (silicagel, hexane/EtOAc = 100/0 to 90/10) to give the title compound(2.04 g, 33%) as pale yellow crystals. 1H NMR (400 MHz, DMSO-d6)d 2.58 (3H, s), 7.92-8.00 (H, m), 8.02-8.08 (2H, m).
With tert.-butylhydroperoxide; In N,N-dimethyl-formamide; at 80℃; for 50h;Schlenk technique;
General procedure: The oxidation of alkanes (e.g., ethylbenzene) was conducted in a 25-mL Schlenk tube. Typically, ethylbenzene (0.5 mmol), catalyst (10 mol% based on Ni), tert-butyl hydroperoxide (TBHP; 1.5 mmol), and DMF (2 mL) were added to the tube and heated at 80 C. After reaction, the catalyst was isolated from the mixture solution by centrifugation, then washed with DMF and methanol. The liquid mixtures were then analyzed by gas chromatography mass spectrometry (Agilent Technologies 7890B-5977A) on a chromatograph equipped with a 0.25 mm × 30 m HP-5MS capillary column.
With sodium carbonate;(1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; In tetrahydrofuran; for 6h;Heating / reflux;
EXAMPLE 7 Preparation of 1-[3-(2-Chloro-pyridin-4-yl)-phenyl]-ethanone 2-Chloropyridine-4-boronic acid (11.0 g, 69.9 mmol), 3-Bromoacetophenone (11.2 mL, 83.9 mmol, 1.2 eq.), Na2CO3 (35 mL, 244.65 mmol, 3.5 eq.) and dppfPdCl2 (572 mg, 0.07 mmol, 0.01 eq.) were mixed in THF (200 mL). The mixture was heated to reflux and continued at this temperature for 6 hours. It was then cooled and concentrated in vacuo. The residue was partitioned between DCM and water (100 mL/40 mL). The layers were separated and the aqueous layer was washed further with DCM (2×40 mL). The combined organic layer was dried (Na2SO4) and filtered. The filtrate was concentrated, and the residue was chromatographed using 1/1 hexane/EtOAc to give 1-[3-(2-Chloro-pyridin-4-yl)-phenyl]-ethanone as a white solid (9.5 g, 58%). MS: m/z 232.1 [MH+].
A solution of 3N METHYLMAGNESIUM bromide (6.53 mL, 19.59 mmol, 3 eq) in diethyl ether was cooled to 0 C and treated with 3-bromoacetophenone (1.3 g, 6.53 MMOL). The reaction was stirred at room temperature for 4 h. The reaction was diluted with ethyl acetate and water. The layers were separated and the organic was washed with saturated sodium bicarbonate, 2N HCI, brine and dried over magnesium sulfate. The solvent was removed at reduced pressure and purified on the MPLC (Biotage) eluted with 5-10% ethyl acetate-hexane to afford 1.2 g (90 %) of the product. Rf = 0.22 (silica, ethyl acetate: hexanes, 1: 9) ; H-NMR (DMSO-D6) 8 7.63 (t, J = 1.8 Hz, 1H), 7.45 to 7.35 (m, 2H), 7.25 (t, J = 7.7, 1H), 5.15 (s, 1H), 1.39 (s, 6H).
90%
Example 22; Method H-15; Preparation of 2-(3-Bromo-phenyl)-propan-2-ol; A solution of 3N methylmagnesium bromide (6.53 mL, 19.59 mmol, 3 eq) in diethyl ether was cooled to 0 C and treated with3-bromoacetophenone (1.3 g, 6.53 mmol). The reaction was stirred at room temperature for 4 h. The reaction was diluted with ethyl acetate and water. The layers were separated and the organic was washed with saturated sodium bicarbonate, 2N HCI, brine and dried over magnesium sulfate. The solvent was removed at reduced pressure and purified on the MPLC (Biotage) eluted with 5-10% ethyl acetate-hexane to afford 1.2 g (90 %) of the product. Rf = 0.22 (silica, ethyl acetate: hexanes, 1: 9) ; 1H-NMR (DMSO-d6) 6 7.63 (t, J = 1.8 Hz, 1H), 7.45 to 7.35 (m, 2H), 7.25 (t, J = 7. 7, 1H), 5.15 (s, 1H), 1.39 (s, 6H).
90%
Preparation of 2-(3-Bromo-phenvl)-propan-2-ol. A solution of 3N methylmagnesium bromide (6.53 mL, 19.59 mmol, 3 eq) in diethyl ether was cooled to 0 0C and treated with3-bromoacetophenone (1.3 g, 6.53 mmol). The reaction was stirred at room temperature for 4 h. The reaction was diluted with ethyl acetate and water. The layers were separated and the organic was washed with saturated sodium bicarbonate, 2N HCl, brine and dried over magnesium sulfate. The solvent was removed at reduced pressure and purified on theMPLC (Biotage) eluted with 5-10% ethyl acetate - hexane to afford 1.2 g (90 %) of the product. Rf = 0.22 (silica, ethyl acetate:hexanes, 1:9); 1H-NMR (DMSO-d6) 7.63 (t, J = 1.8 Hz, IH), 7.45 to 7.35 (m, 2H), 7.25 (t, J = 7.7, IH), 5.15 (s, IH), 1.39 (s, 6H).
4.1 2-(3-Bromophenyl)propan-2-ol Under a stream of argon, 6.5 g of 3-bromoacetophenone are placed in a round-bottomed flask and dissolved in 544 ml of diethyl ether and 272 ml of tetrahydrofuran. The mixture is cooled at 0 C. using an ice bath, and 100 ml of a 1M solution of methylmagnesium bromide in dibutyl ether are added thereto, dropwise. The mixture is stirred at 0 C. for 1 h and 400 ml of a saturated aqueous solution of ammonium chloride are added. The organic phase is separated, dried over magnesium sulphate and concentrated under reduced pressure. 10.0 g of compound are obtained. 1H NMR (DMSO-d6, delta in ppm): 1.45 (s, 6H); 5.15 (s, 1H); 7.25 (t, 1H); 7.4 (d, 1H); 7.45 (d, 1H); 7.65 (s, 1H).
7.1 2-(3-Bromophenyl)propan-2-ol Under an argon stream, 6.5 g of 3-bromoacetophenone are placed in a round-bottomed flask and dissolved in 544 ml of diethyl ether and 272 ml of tetrahydrofuran. The mixture is cooled to 0 C. using an ice bath, and 100 ml of a 1M solution of methylmagnesium bromide in dibutyl ether are added thereto, dropwise. The mixture is stirred at 0 C. for 1 h and 400 ml of a saturated aqueous solution of ammonium chloride are added. The organic phase is separated, dried over magnesium sulphate and concentrated under reduced pressure. 10.0 g of compound are obtained. 1H NMR (DMSO-d6, delta in ppm): 1.45 (s, 6H); 5.15 (s, 1H); 7.25 (t, 1H); 7.4 (d, 1H); 7.45 (d, 1H); 7.65 (s, 1H).
34 g of 3-cyclopropyl bromobenzene was synthesized from 50 g of 3-bromoacetophenone by a method described in J. Org. Chem., 41, 2263 (1976), and 2 9 of this product was used to prepare 520 mg of the title compound as a white solid by the method described in Production Example 427.1H-NMR (DMSO-d6) delta: 0.63(m, 2H), 0.90(m, 2H), 1.83(m, 1H), 3.20(m, 4H), 3.30(m, 4H), 6.54(d, J=8.0Hz, 1H), 6.68(s, 1H), 6.72(d, J=8.0Hz, 1H), 7.10(t, J=8.0Hz, 1H)
A 100-ml round-bottom flask fitted with a stirbar, condenser, and septum was flushed with N2 and charged with 3-bromoacetophenone (2.50 g) and anhydrous pyridine (20 mL), followed by selenium dioxide (2.8 g). The reaction mixture was heated to 100 C. After one hour, the reaction was cooled to room temperature and pyridine was distilled off under reduced pressure. The resulting thick oil was partitioned between 50 ml 1N HCl and 50 ml EtOAc. The aqueous phase was extracted once more with 50 ml EtOAc, and the combined organic phase was dried over sodium sulfate and concentrated in vacuo. The resulting crude acid was azeotroped with 10 ml of anhydrous toluene. To a 100-ml round-bottom flask containing the crude acid were added anhydrous DMF (20 ml), Cs2C03 (4.11 g), and methyl iodide (3.58 g) sequentially. The mixture was heated at 40 C for 1 hour under N2, cooled to room temperature, diluted with 200 ml saturated NH4Cl solution, and extracted two times with 200 ml EtOAc/hexanes (1/1). The combined organic phase was dried over Na2S04, concentrated in vacuo, and purified by column chromatography on silica gel (25% EtOAc/hexanes) to provide the desired product. ¹H NMR (CDCl3) : 8.22 (s, 1H), 8.01 (d, J=8 Hz, 1H), 7.83 (d, J=8 Hz, 1H), 7.44 (t, J=8 Hz, 1H), 4.0 (s, 3H) MS: m/e 243/245 (M+1)+
With pyridine; selenium(IV) oxide; at 100℃; for 16h;
[000969] A suspension of Compound 261 A (6.00 g, 30.15 mmol) and Se02 (5.02 g, 45.22 mmol) in pyridine (50 mL) was stirred at 100 C for 16 h. It was filtered to remove the resultant solid and the filtrate was evaporated to remove pyridine. The residue was dissolved in aqueous NaOH solution (5% w/w, 200 mL) and extracted with diethyl ether (100 mL x 2). The aqueous was adjusted to pH 1 with con. HCl to form a solid, which was filtered and dried to afford Compound 261B.
In 5,5-dimethyl-1,3-cyclohexadiene; for 21.0h;Reflux;
10.0 g of 3-bromoacetophenone (50.2 mmol, 1.0 equiv.), 18.0 g of N, N-dimethylformamide dimethylacetal (150.7 mmol, 3.0 equiv.), and 50 ml of xylene were refluxed overnight (21 hours), a little raw material was not reacted and the reaction was stopped. The reaction solution was cooled and concentrated to remove xylene. 150 ml of petroleum ether was added to the residue, and a solid precipitated under stirring, followed by filtration to obtain 7.0 g of 1-(3-bromo-phenyl)-3-dimethylamino-prop-2-en-1-one as a yellow solid, 55.1%.
39%
at 95.0℃; for 6.0h;
To a 50 ml three-necked flask was added 1.97 g (0.01 mol) of 3-bromoacetophenone, 6.6 ml (0.05 mol) of N, N-dimethylFormamide dimethyl acetal, stirred until it completely dissolved, heated to 95 C reflux reaction 6h, cooled to room temperature,After dilution with 30 ml of anhydrous acetone, the solvent was removed by distillation under reduced pressure and the title product was obtained by column chromatography (petroleum ether: ethyl acetate = 1: 3)1- (3'-bromophenyl) -3-dimethylamino-2-propen-1-one (9) 0.77 g, yield 39%.
at 150.0℃; for 12.0h;
Combine l-(3~bromo~phenyi)~ethanone (10 g, 50.2 mmol) and dimethylformamide dimethylacetal (60 g, 502 mmol) in a sealed tube, heat to 150 C for 12 hours. Cool the solution and evaporate the excess dimethylformamide dimethylacetal. Purify residue by column chromatography to obtain the title compound (3.05 g, 12.0 mmol) as a white solid. MS (m/z): 254.1 (M).
Reflux;
A mixture of m-bromoacetophenone (10 mmol) and DMF-DMA (20 mmol) was refluxed overnight. The reaction mixture was allowed to cool and poured into water, and extracted with ethyl acetate. After the organic layer of the extract was washed with brine three times, it was collected and dried over magnesium sulfate. After removing the solvent, the crude product was subjected to silica gel column chromatography and purified with ethyl acetate / n-hexane mixture (50%) as an eluent to obtain compound 2a.
With sodium hydroxide; tetrabutylammomium bromide; In dichloromethane; water; at 20℃; for 3h;
To a stirred solution of 3'-bromoacetophenone (20 g, 100 mmol) and 3-fluoro-2- methyl benzadehyde (5.8 g, 42 mmol) in dichloromethane was added 100 mL 50% aq NaOH and tetrabutylammonium bromide (0.2 g, 0.6 mmol). The resulting solution was stirred vigorously at room temperature for 3 hour. LCMS showed the reaction had completed. The reaction mixture was quenched with 1 N HCl cautiously and extracted with dichloromethane. The organic layer was washed with brine, dried and concentrated under reduced pressure. The crude product was recrystallized from ether/hexane to give 14 g of white solid in 65% yield, (characterized by LCMS and 1H NMR). LRMS (M+H+) m/z = 516.9
With ammonium acetate; In acetic acid; at 100℃; for 5h;
9-Phenanthrenecarboxyaldehyde (4.29 g), 3'-bromoacetophenone (8.28 g), ammonium acetate (20.5 g), and acetic acid (52 ml) were stirred in air at 100C for 5 hr, and the supernatant was removed. Methanol was added thereto for washing the remaining viscous liquid. After the removing of the washings, the viscous liquid was purified by silica-gel column chromatography and suspension washing with methanol and then dried by heating under reduced pressure to obtain a target compound 9 (3.00 g).
1-Bromo-3-(1-[4-{ethoxy}phenyl]-vinyl)-benzene To a solution of commercially available 1-bromo-4-ethoxy-benzene [588-96-5] (0.1 g, 25 mmol, 1.0 eq) in tetrahydrofuran (20 mL) was added dropwise a solution of n-butyllithium (1.6 M solution in hexane, 14.0 mL, 0.9 eq) at -78 C. After stirring 30 min at -78 C. 3-bromoacetophenone (3.7 mL, 1.1 eq) in tetrahydrofuran (20 mL) was added dropwise. The mixture was allowed to warm up to room temperature and stirred for 2 h, then treated with 1 N HCl (10 mL), extracted with ethyl acetate, dried (sodium sulfate) and concentrated in vacuo. The crude was dissolved in acetic acid (50 mL) and sulfuric acid (10 mL) and the mixture was warmed to 75 C. for 30 min, cooled to room temperature and 1 N NaOH was added up to pH=7. The aqueous phase was extracted with dichloromethane (3*10 mL), dried (sodium sulfate) the solvent was removed and the residue was purified by column chromatography (cyclohexane) to afford the title compound as a colorless oil (2.3 g, 30%); Mass (calculated) C16H15BrO [303]; MH+ not observed. LC Rt=2.43 min (5 min method)
potassiumhexacyanoferrate(II) trihydrate[ No CAS ]
[ 2142-63-4 ]
[ 6136-68-1 ]
Yield
Reaction Conditions
Operation in experiment
68%
With [Pd{C6H4(CH2N(CH2Ph)2)}(mu-Br)]2; tetrabutylammomium bromide; potassium carbonate; In N,N-dimethyl-formamide; at 130℃; for 0.166667h;Microwave irradiation;
General procedure: A mixture of the aryl halide (1 mmol), K4[Fe(CN)6]·3 H2O (0.22 mmol, 92.9 mg), TBAB (1 mmol, 322.4 mg), palladacycle catalyst (0.5 mmol %, 4.7 mg), and K2CO3 (1 mmol, 138.2 mg) was added to DMF (3 mL) in a round-bottomed flask equipped with a condenser and placed into the Milestone microwave. Initially using a microwave power of 600 W the temperature was ramped from room temperature to 130 C, this taking approximately 1 min, and then held at this temperature until the reaction was completed. During this time, the power was modulated automatically to keep the reaction mixture at 130 C. The mixture was stirred continuously using an appropriate magnet during the reaction. After the reaction was completed, the mixture was cooled to room temperature and diluted with water (30 ml) and ethyl acetate (30 ml). The organic layer was dried over MgSO4, filtered, and the solvent was evaporated using rotary evaporator. The residue was purified by silica gel column chromatography or by recrystallization using ethanol and water. The products were characterized by comparing their mp, IR, 1H, 13C NMR spectra with those found in the literature. [19] and [20]
With potassium fluoride; copper(l) iodide; palladium diacetate; catacxium A; In N,N-dimethyl-formamide; at 90℃; for 12h;Inert atmosphere;
General procedure: 2-Trimethylsilylpyridine (1.2mmol), the aryl halide (1mmol), palladium acetate (0.10mmol), CataXCium A (0.2mmol), CuI (76mg, 0.4mmol) and KF (2.20mmol) were combined in reaction tubes in a Radleys green-house parallel synthesiser under a flow of nitrogen and degassed DMF (1ml) was added. The resulting suspensions were stirred at 90 oC under nitrogen for 12 hours. Reactions were analysed by LC-MS at 1mg/1ml in methanol to determine the yield.
With potassium phosphate tribasic heptahydrate; C45H53ClFeNO2PPd; In water; toluene; at 100℃; for 3h;Inert atmosphere;
General procedure: Potassium phosphate (0.75 mmol) and IIe (1 mol %) was added to the solution of aryl halides (0.25 mmol) and cyclopropylboronic acid (0.5 mmol) in toluene (2.0 mL) and water (100 muL). The mixture was heated to 100 C for a proper time under nitrogen atmosphere and cooled to room temperature. Water (10 mL) was added and the mixture was extracted with EtOAc (3×15 mL), evaporated and purified by chromatography on silica gel.
With potassium phosphate; tetrakis(triphenylphosphine) palladium(0); In ethanol; water; toluene; at 20 - 100℃; for 16h;Inert atmosphere;
To a stirred solution of 1-(3-bromophenyl) ethan-1-one (2 g, 10 mmol) in toluene: EtOH: water (1: 1: 1, 40 mL) at room temperature under an argon atmosphere were added cyclopropylboronic acid (1.2 g, 15 mmol), potassium phosphate (4.2 g, 20 mmol) and purged under argon for 15 mm. Then Pd(PPh3)4 (580 mg, 0.5 mmol) was added to the reaction mixture at room temperature. The reaction mixture was stirred at 100 C for 16 h. After consumption of starting material (monitored by TLC), the reaction mixture was diluted with water (50 mL) and extracted with EtOAc (2 x 50 mL). The combined organic extracts were dried over sodium sulfate, filtered and concentrated in vacuo. The crude material was purified by column chromatography using 5-20% EtOAc: Hexane to afford ]-(3-cyclopropylphenyl) ethan-1-one (1.25 g, crude) as colorless liquid. TLC: 20% EtOAc Hexane (R1 0.4).
With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; potassium phosphate; In water; toluene; at 100℃; for 3h;Inert atmosphere;
To a solution of Compound 60A (7.96 g, 40 mmol) in toluene (100 mL) was added cyclopropylboronic acid (6.88 g, 80 mmol), PdCl2(dppf) (326 mg, 0.4 mmol), K3PO4(25.4 g, 120 mmol), and H2O (5 mL) and heated at 100oC under nitrogen atmosphere for 3 hours. The reaction mixture was concentrated under reduced pressure. The residue was purified by column chromatography on silica gel (100% petroleum ether) to affordCompound 78A: LC-MS (ESI) m/z: non-ionizable compound under routine conditions used;1H-NMR (CDCl3, 400 MHz): delta (ppm) 0.72-0.76 (m, 2H), 0.98-1.03 (m, 2H), 1.92-1.98 (m, 1H), 2.59 (s, 3H), 7.25-7.35 (m, 2H), 7.66-7.73 (m, 2H).
With caesium carbonate; In water; dimethyl sulfoxide; at 110℃;Inert atmosphere;
Step 8; To a solution of 51 (200 mg, 6 mmol) in DMSO and water, 1-(3-bromophenyl)ethanone (200 mg), cesium carbonate (400 mg), and Pd(PPh3)2Cl2 (30 mg) were added. The solution was then stirred under nitrogen atmosphere at 110C overnight. The reaction mixture was cooled, and then partitioned between ethyl acetate and water. The organic layer was washed sequentially with water and brine, and then dried over sodium sulfate. The solvent was evaporated off to yield target compound 52 (170 mg, y. 89%).
With Ru(cod)TFA2; mandyphos M002; ammonium acetate; ammonia; hydrogen; In methanol; water; at 90℃; under 30003.0 Torr; for 48h;Autoclave; Inert atmosphere;
General procedure: General procedure for the asymmetric reductive amination using ammonium chloride as the ammonium salt.All manipulations were done under an atmosphere of nitrogen. The methanol and water were deoxygenated by 5 vacuum/nitrogen cycles prior to use.The reactions were carried out in small autoclaves that can be pressurized to 50 bar. To a 2OmL glass vial is added immol of the oxime, 0,O2Smmol of preformed catalyst, lOmmol NH4CI and 2mL degassed methanol, immol NH3 (added as a 7M solution in methanol) and 20iiL water. The glass vial is put into the parallel autoclave under an atmosphere of nitrogen gas and 40 bar of hydrogen is applied and the autoclave is heated to 90C and agitated. After 48 hours the autoclave is cooled to 20C and then the hydrogen pressure is released. The methanol is evaporated off and NaOH(aq) is added to the residue to pH>11. The mixture is extracted with diethylether. The combined ether fractions are dried over MgSO4, filtered and concentrated under vacuum to afford the amine product. The products were analyzed by chiral HPLC and 1H and 13C NMR spectroscopy and were in accordance with authentic samples.Small scale reactions using a Josiphos and a Mandyphos ligand and ammonium acetate as ammonium source.The reactions were carried out according to the procedure described for examples 1-12 above but with the difference that the catalyst was formed by adding a solution of the desired amount of Ru(cod)TFA2 in methanol to the ligand in 1:1 ratio and heating to 50C until a clear solution was obtained. The solution was then added to a vial containing the ketone, ammonium acetate, water and NH3 in methanol.
General procedure: [a] Reactions were performed on a 0.5 mmol scale to determine yields by 19F NMR spectroscopy with PI1CF3 as an internal standard added after the reaction.; Note: The hydroxylation reaction was set-up under an inert atmosphere according to the literature procedure. [Anderson, K. W.; Ikawa, T.; Tundel, R. E.; Buchwald, S. L. J. Am. Chem. Soc. 2006, 128, 10694.] To an oven-dried 4 mL vial was added Pd2(dba)3 (9.2 mg, .010 mmol, 4.0 mol % Pd), 2-Di-tert-butylphosphino-2',4',6'-triisopropylbiphenyl (lBu- XPhos, 17.0 mg, .040 mmol, 8.0 mol %), KOH (1.0-3.0 equiv), degassed H20 (150-300 mu) and dioxane (250-500 muKappa). The aryl halide (0.5 mmol, 1.0 equiv) was added (solid aryl halides were weighed into the vial prior to adding solvent, and liquid aryl bromides were added neat by syringe after the addition of solvent). The vial was sealed with a Teflon-lined cap and heated at 100 C for 1-18 h. The solution was allowed to cool, and the reaction was diluted with acetonitrile (500-750 mu, such that the total volume of dioxane and acetonitrile is 1.0 mL) and 6M KOH (700-850 mu, such that the final aqueous solvent volume is 1.0 mL). The resulting mixture was stirred rapidly at room temperature, and HCF20Tf (210 mu, 1.5 mmol, 3.0 equiv) was added at once. Note: the reactions are exothermic. The mixture was stirred vigorously for 2 minutes. The reaction was diluted with ]0 (8 mL) and extracted with ether (2 x 8 mL). The combined organic layers were dried over MgS04, concentrated, and purified by silica gel chromatography.
(E)-1-(3-bromophenyl)-3-(2,6-dimethoxyphenyl)prop-2-en-1-one[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
98%
General procedure: A 50 mL flask was charged with substituted acetophenone (5 mmol) and a solution of sodium hydroxide (10 mmol) in a 4:1 (v/v) mixture of ethanol/H2O (25 mL), and the resulting mixture was stirred at room temperature for 5 min. A substituted benzaldehyde (5 mmol) was then added to the reaction, and the resulting mixture was stirred at room temperature. The reaction was then monitored byTLC using ethyl acetate/petroleum ether (1:4 or 1:2 v/v) as the solvent system. Upon completion of the reaction, the crude product was filtered off and recrystallized from a mixture of dichloromethane and ethanol or purified by column chromatography over silica gel eluting with a mixture of petroleum ether and ethyl acetate to give the pure product.
With chloro(1,3-bis(2,6-di-i-propylphenyl)imidazol-2-ylidene)gold(I); water; In methanol; at 110℃; for 6h;
The catalyst [(IPr) AuCl] (3.1mg, 0.5mol%), 3- bromophenyl acetylene (1mmol), in methanol (1ml) and water (0.5ml) was added successively 25ml reactor.After the reaction mixture was reacted for 6 hours at 110 , cooled to room temperature.Rotary evaporation to remove the solvent, then purified by column chromatography (eluent: petroleum ether / ethyl acetate) to give pure title compound, yield: 93%
With chloro(1,3-bis(2,6-di-i-propylphenyl)imidazol-2-ylidene)gold(I); water; silver trifluoromethanesulfonate; In methanol; at 120℃; for 6h;
The 3'-bromophenylacetylene (181 mg, 1.0 mmol), cat. [Au] (6 mg, 1 muM %), AgOTf (2.6 mg, 1 muM %), water (36 mg, 2 mmol) and methanol (1 ml) are added to the 25 mL of Claisen tube or. After closing the reaction at 120 C for 6 hours, cooling to room temperature. Then adding formic acid amine (315 mg, 5 mmol) and cat. [Rh] (6.2 mg, 1 mmol %), the reaction mixture in oil bath heated to 80 C, reaction 12 hours, cooling to room temperature. Rotary evaporation of the solvent and add a certain amount of ethyl acetate and water extraction, the organic phase of the resulting product after concentrated hydrochloric acid the reflux process, rotary evaporation to remove the solvent, the final petroleum ether washing and filtering to obtain the pure target compound, yield: 83%
(2E)-1-(3-bromophenyl)-3-(quinoxalin-2-yl)prop-2-en-1-one[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
95%
This procedure is based on our previous report27 and vogels procedure36. To a conical flask containing NaOH solution (1.5eq, 10 mL H2O) was added substituted acetophenones (1mmole) in ethanol (10 mL), and the reaction mixture was stirred for 10 minutes to allow enolate formation, to this was added quinoxaline-2- carbaldehyde 1 (1mmole) and the reaction mixture was stirred till completion. After completion of the reaction, as monitored by TLC the reaction mixture was poured in an ice bath and was acidified using conc. HCl. The solid obtained was then filtered, dried and recrystallized using Ethanol. The quinoxalinyl chalcone 2a-n were then characterized using IR, NMR (1H, 13C) and HR-MS spectroscopy. The purity was checked by HPLC measurements using mobile phase consisting methanol and water in the ratio 90:10.
With dihydrogen peroxide; In water; acetonitrile; at 55℃; for 12h;
General procedure: With the dissolution of substrate (0.4 mmol) in CH 3 CN (2 mL), Pd0/RGO (0.01 g), H 2 O (0.5 mL), and GO (0.01 g) were orderly added into apressure bottle (35 mL). The mixture was dispersed by ultrasound forabout 30 min at 25 C. Then H 2 O 2 (30 wt%, 4 mmol) was cautiously added dropwise. Immediately, the reaction system was heated to 55 Cwith lid closed until the process was fully completed (detected by TLC).Subsequently, Pd0/RGO and GO were removed by centrifuge. Themixture was extracted by deionized water and ethyl acetate. After thelayers were separated, the organic part was washed with deionizedwater, dried with anhydrous NaSO 4 , ltered and evaporated by reducedpressure distillation. Finally, purication of the crude product wascarried out by column chromatography. For 14, 18, 24, 40 (Table 2),excess hydrogen peroxide was added after half of the total reaction time.
With (difluoroboryl)dimethylglyoximatocobalt(II) bis(acetonitrile); water; 3-cyano-1-methylquinolinium cation; In acetonitrile; at 20℃; for 5h;Inert atmosphere; Irradiation; Green chemistry;
1-methyl-3-cyanoquinoline salt as a photosensitizer, Cobalt oxime complex 2 as a cobalt catalyst, 5mL acetonitrile was added2.69 mg (1 × 10 -2 mmol) photosensitizer and 2.80 mg (6 × 10 -3 mmol) cobalt catalyst, Replacing the atmosphere with Ar atmosphereAnd then0.2 mmol of 3'-bromoacetophenone (R1 is COCH3, R3 is Br, R2, R4 are independently H) and 2 mmol of H2O. Room temperature, high pressureMercury lamp irradiation 5h. After the reaction was completed, the H2 production was detected by GC (TCD) and the conversion of benzene by GC (FID), And then separated by column. 1H NMR and MS identified products were 3'-bromo-2-hydroxyacetophenone, 3'-bromo-4-hydroxyacetophenone and 3'-bromo-6-hydroxyacetophenone. The conversion of 3'-bromoacetophenone was 32%, the yield of coupling products was 2%, 15% and 15%, respectively, and the yield of H2 was 8%.
With pyridoxal 5'-phosphate; beta-nicotinamide adenine dinucleotide hydrate; In dimethyl sulfoxide; at 37℃; for 16h;pH 9.0;Green chemistry; Enzymatic reaction;
General procedure: cascadeThe reductive amination of ketones using the AlRed/PtxD cas-cade system were carried out in 2 mL Eppendorf tubes in a finalvolume of 0.5 mL. To a mixture containing 50 mM HEPES bufferand 1 mM PLP was added 7.5 mM n-butylamine and 5 mM ketonein DMSO, 1 mM NAD(P)+, 100 mM Na2HPO3·5H2O, with Ec-YghD(1 mg/mL), PtxD (1 mg/mL) and 2 mg/mL of purified SpuC enzyme.The reactions were placed in a shaking incubator at 37C and250 rpm for 16 h. The reactions were quenched by addition of 2 MNaOH (50 L), followed by extraction with methyl tert-butyl ether(300 L). The organic phase was dried on MgSO4and analysedon normal phase chiral HPLC, using analytical methods previouslydescribed [5].
With carbon tetrabromide; caesium carbonate; In acetonitrile; at 80℃; for 6h;Inert atmosphere;
In an oven dried 100 mL round bottomed flask 1-nitrosonaphthalene-2-ol 4a or 2-nitrosophenol 4b (1.0 mmol), acetophenones 5a-k (1.0 mmol), CBr4 (0.5 mmol, 165 mg),Cs2CO3 (2.1 mmol, 682 mg) and 10 mL CH3CN were added successively and the reactionmixture was heated for 6h at 80 C under nitrogen atmosphere. After completion of thereaction (progress was monitored by TLC; SiO2, Hexane/EtOAc = 9:1), the reaction mixturewas allowed to cool at room temperature and then solvent was removed under vacuum. Thecrude product was purified by using column chromatography over silica gel using hexane /ethyl acetate = 9:1 as an eluent to obtain the desired products (3a-f, 3h-3i, 3k, 3m, 3w, 3x) inhigh yields..
With tetrakis(triphenylphosphine) palladium(0); potassium carbonate; In ethanol; water; toluene; at 80℃;
3'-Bromoacetophenone (10g, 50.23mmole)Placed in a reaction tank with <strong>[86-58-8]quinolin-8-ylboronic acid</strong> (9.12 g, 52.75 mmole).Add 120 ml of toluene.Potassium carbonate (18.05 g, 130.6 mmole) was dissolved in 70 ml of deionized water and added to the reaction tank.Add tetrakis(triphenylphosphine)palladium (Pd(PPh3)4) (1.74g, 1.507mmole)And 30 ml of ethanol to turn on heating and stirring.Heat up to 80 C reaction and reverseIt should be overnight.After the reaction is completed,Add 300 ml of deionized water,After stirring for 30 minutes, the stirring was stopped and allowed to stand for stratification.After removing the water layer,Purified by silica gel chromatography,Concentrated to thick,A pale yellow liquid compound E (about 5.5 g) was obtained.
1-[3-(6-benzyloxy)pyridazin-3-yl]acetophenone[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
51%
With bis(bipyridine)nickel(II) bromide; tetrabutylammomium bromide; In ethylene dibromide; N,N-dimethyl-formamide; at 20℃;Inert atmosphere; Electrochemical reaction;
General procedure: To an undivided electrochemical cell, fitted with an iron/nickel (64/36) rod as the anode and surroundedby a nickel foam as the cathode, were added DMF (50 mL), tetrabutylammonium bromide (1.2 mmol, 400mg), and 1,2-dibromoethane (2.5 mmol, 215 muL). The mixture was electrolyzed under argon at a constantcurrent intensity of 0.2 A at room temperature for 15 min. The current was then stopped, and the NiBr2bpycomplex (0.4 mmol, 150 mg), 3-amino- or 3-alkoxy/aryloxy-6-chloropyridazine (4 mmol), and aromatic orheteroaromatic halides (8 mmol) were sequentially added. The solution was electrolyzed at 0.2 A at roomtemperature until one of the starting materials was totally consumed. A saturated aqueous solution of EDTAsodium salt (100 mL) was added to the mixture, and the solution was extracted with dichloromethanecontaining 2-5% methanol (3 × 100 mL). The combined organic layers were dried over MgSO4, filtered,and evaporated under vacuum. The crude product was purified by flash chromatography on silica, elutedwith a gradient of solvents (pentane/acetone). For some polar cross-coupling compounds, a mixture ofacetone/methanol (95/5) was necessary.
2-(3-bromophenyl)-7-(trifluoromethyl)quinoline-4-carboxylic acid[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
2.04%
With potassium hydroxide; In ethanol; at 80℃;
To a solution of <strong>[343-69-1]6-(trifluoromethyl)indoline-2,3-dione</strong> (100 mg, 465 m mol) and l-(3- bromophenyl)ethanone (111 mg, 558 m mol) in ethanol (2 mL) was added KOH (78.2 mg, 1.39 mmol) and the mixture was then stirred at 80 C overnight. After the reaction was completed, the mixture was adjusted to pH ~6 by addition of HO Ac. The resulting solution was then concentrated in vacuo and the residue was purified by preparative HPLC to give 2-(3- bromophenyl)-7-(trifluoromethyl)quinoline-4-carboxylic acid (3.8 mg, 9.5 m mol, 2.04 % yield). ppm 8.89-8.96 (m, 1H), 8.60-8.67 (m, 1H), 8.52-8.58 (m, 2H), 8.31-8.38 (m, 1H), 7.94-8.04 (m, 1H), 7.74-7.82 (m, 1H), 7.57 (s, 1H). MS obsd. (ESI+) [(M+H)+]:395.0.
2,6-bis(3-bromophenyl)-1-pentyl-4-(4-(1,2,2-triphenylvinyl)phenyl)pyridin-1-ium tetrafluoroborate[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
31.39%
Will contain 1- (3-bromophenyl) ethan-1-one (2.5eq, 4.69g, 23.56mmol) andA two-necked 250 ml bottom flask of 2 (1.0 eq, 2.00 g, 5.55 mmpl) was evacuated and refilled with argon.20 ml of anhydrous toluene was added to the flask.The reaction mixture was then heated to 80 C and kept at reflux and stirred overnight.After diethyl ether was added to the flask and kept at 0 C, a red solid was filtered.A red solid (1 eq, 250 mg, 346.49 mumol) was charged into a 250 ml two-necked flask, evacuated and refilled three times with argon.15 ml of EtOH was added to the flask.Hexane-1-amine (1.5 eq, 45.3 mg, 519.43 mumol) was then added to the flask, and the reaction mixture was heated to 90 C. and kept at reflux overnight.After adding diethyl ether to the flask and keeping the temperature cold, the yellow solid was filtered(2,6-bis (3-bromophenyl) -1-pentyl-4- (4- (1,2,2-triphenylvinyl) phenyl) pyridin-1-ium tetrafluoroborate ). In this embodiment, the 2,6-bis (3-bromophenyl) -1-pentyl-4- (4- (1,2,2-triphenylvinyl) phenyl) pyridine-1- The yield of onium tetrafluoroborate was 31.39%.
With mesitylenesulfonylhydroxylamine; In acetonitrile; at 20 - 70℃; for 3h;
General procedure: To a round bottom flask, equipped with a magnetic stirring bar, was added ketone 1 (0.5 mmol, 1.0 equiv.) and acetonitrile (2 mL) at room temperature. To this stirred solution, freshly prepared O-(Mesitylsulfonyl)hydroxylamine 2 (2.0 equiv.) was added. The reaction mixture was stirred for the specified duration and temperature. The progress of the reaction was monitored by TLC. After completion, the reaction mixture was diluted with ethyl acetate (10 mL) and washed with a saturated aqueous NaHCO3 solution (3 x 5 mL). The combined organic layer was washed with brine solution and dried over anhydrous Na2SO4. Solvent was removed under reduced pressure to get the crude product. The reaction that required elevated temperature was stirred first at room temperature for 2 hours after addition of MSH and then heated at 70 C for the specified time.
Chemistry
Pharmaceutical Intermediates
Inhibitors/Agonists
Material Science
For Research Only
110K+ Compounds
Competitive Price
1-2 Day Shipping
