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CAS No. : | 709-63-7 | MDL No. : | MFCD00000401 |
Formula : | C9H7F3O | Boiling Point : | - |
Linear Structure Formula : | - | InChI Key : | HHAISVSEJFEWBZ-UHFFFAOYSA-N |
M.W : | 188.15 | Pubchem ID : | 69731 |
Synonyms : |
|
Num. heavy atoms : | 13 |
Num. arom. heavy atoms : | 6 |
Fraction Csp3 : | 0.22 |
Num. rotatable bonds : | 2 |
Num. H-bond acceptors : | 4.0 |
Num. H-bond donors : | 0.0 |
Molar Refractivity : | 41.64 |
TPSA : | 17.07 Ų |
GI absorption : | High |
BBB permeant : | Yes |
P-gp substrate : | No |
CYP1A2 inhibitor : | No |
CYP2C19 inhibitor : | No |
CYP2C9 inhibitor : | No |
CYP2D6 inhibitor : | No |
CYP3A4 inhibitor : | No |
Log Kp (skin permeation) : | -5.59 cm/s |
Log Po/w (iLOGP) : | 1.9 |
Log Po/w (XLOGP3) : | 2.62 |
Log Po/w (WLOGP) : | 4.06 |
Log Po/w (MLOGP) : | 2.82 |
Log Po/w (SILICOS-IT) : | 3.18 |
Consensus Log Po/w : | 2.92 |
Lipinski : | 0.0 |
Ghose : | None |
Veber : | 0.0 |
Egan : | 0.0 |
Muegge : | 2.0 |
Bioavailability Score : | 0.55 |
Log S (ESOL) : | -2.87 |
Solubility : | 0.256 mg/ml ; 0.00136 mol/l |
Class : | Soluble |
Log S (Ali) : | -2.63 |
Solubility : | 0.443 mg/ml ; 0.00235 mol/l |
Class : | Soluble |
Log S (SILICOS-IT) : | -3.62 |
Solubility : | 0.045 mg/ml ; 0.000239 mol/l |
Class : | Soluble |
PAINS : | 0.0 alert |
Brenk : | 0.0 alert |
Leadlikeness : | 1.0 |
Synthetic accessibility : | 1.09 |
Signal Word: | Warning | Class: | N/A |
Precautionary Statements: | P261-P305+P351+P338 | UN#: | N/A |
Hazard Statements: | H315-H319-H335 | Packing Group: | N/A |
GHS Pictogram: |
* 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.
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
63% | With trimethylsilyl bromide; potassium nitrate In dichloromethane at 20℃; for 16 h; | General procedure: In a Nalgene.(R). bottle, to acetophenone (2 mmol) in dichloromethane (10 mL), potassium nitrate (4 mmol) and chloro/bromotrimethylsilane (8 mmol) were added. The heterogeneous mixture was stirred vigorously at 60 °C (for chlorination) or room temperature (for bromination) until the reaction went to completion (monitored by 1H NMR spectroscopy). The reaction mixture was then filtered and solvent removed under reduced pressure. The chlorinated/brominated acetophenone derivatives were obtained upon purification by flash chromatography (silica gel) with hexane as eluent. The products were characterized by comparing their spectroscopic data with those of the authentic samples. |
0.6% | With bromine; sodium hydrogencarbonate; acetic acid; sodium chloride In hexane; water; ethyl acetate | Example 41 2,2-Dibromo-1-(4-trifluoromethyl-phenyl)-ethanone. This compound was synthesised by the general procedure represented in Scheme 2, a stirred solution of 1-(4-trifluoromethyl-phenyl)-ethanone (1 g, 5.3 mmol)) and acetic acid (50 ml) was refluxed 1 h, then bromine (0.35 ml, 6.9 mmol) was added dropwise and the mixture refluxed 3 h. After cooling at room temperature, water (50 ml) was added and the mixture extracted with CH2Cl2 (50 ml), the organic layer was washed with water (50 ml), a solution of NaHCO3 saturated (50 ml) and finally with NaCl solution (50 ml), the organic layer was dried over sodium sulphate and the solvent evaporated under reduced pressure. The resulting residue was purified by column chromatography, using a mixture of ethyl acetate:hexane (1:8) as eluent giving two compounds, the titled compound 41 as a yellow solid (45percent) m.p.: 40-41° C., 1H-NMR (CDCl3): δ8.2 (d, J=8.3 Hz, 2H, Ar), 7.8 (d, J=8.3 Hz, 2H, Ar), 6.6 (s, 1H, CH); 13C-NMR (CDCl3): δ184.1 (CO), 134.7 (q, J=272.9 Hz, C-CF3), 132.7 (C-CO), 129.2 (CH), 124.8 (CH), 119.5 (q, J=33.09, CF3), 38.2 (CH); M/z (EI): 348, 346, 344 (M+, 1, 6, 1percent), 173 (M-CHBr2, 100percent); HPLC: Column μ Bondapack C18, 5 μm, 300 A, (300*3.9 mm), Purity 97percent, r.t.=9.96 min, acetonitrile/H2O (0.05percent H3PO4+0.04percent Et3N) 50/50. The second compound was identified as 2-bromo-1-(4-trifluoromethyl-phenyl)-ethanone (0,6percent), described as the example 40. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
87% | With N-Bromosuccinimide In ethyl acetate at 40℃; | 10 mmol 4-trifluoromethyl acetophenone is added to a 100 mL round bottom flaskAnd 11mmol of N-bromosuccinimide (NBS),35mL of ethyl acetate dissolved,Then add 1g of Amberlyst 15 ion exchange resin as catalyst.The reaction solution was warmed to 40°C to react. After TLC tracks the reaction,The reaction solution was filtered to remove Amberlyst 15 ion exchange resin,The filtrate was evaporated to dryness and column chromatography (eluent: petroleum ether/dichloromethane) gave white crystals.Yield 87percent. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
3.4 - 11.7 %Chromat. | With bromine In chloroform at 25 - 28℃; for 3.5 - 24 h; | 2.82g (14. [99MMOL, LEQ.) OF 4APOS;-TRIFLUOROMETHYLACETOPHENONE] were dissolved in 7. [5ML] (8. 35g, 134. [53MMOL,] 8.97eq.) of ethylene glycol. While the solution was controlled to have an internal temperature [OF 25-28APOS;C,] a chloroform solution obtained by diluting 3.60g (22.53mmol, 1.50eq.) [OF BR2] with 2. [2ML] of chloroform was added to the solution, followed by stirring for 24hr with an internal temperature [OF 25-26C.] 3.5hr and 24hr after the start of the reaction, the progress of the reaction was checked by gas chromatography. The results are shown in Table 3. Table 3 Time Compound A1 C1 D 3. 5h 11. 7percent 54. 2percent 0. 3percent 24h 3. 4percent 88. 6percent 0. 8percent 1 : Compound A Compound C Compound D ouzo Br p Br bu Xf, () I CF) ()' Br L'r'3 |
91.09 %Chromat. | With bromine In chloroform at 28 - 32℃; for 15 h; | [106G (0. 56MOL, LEQ. ) OF 4APOS;-TRIFLUOROMETHYLACETOPHENONE WERE DISSOLVED] in [281ML] (313g, 5. [04MOL,] 9. [00EQ.)] of ethylene glycol. While the solution was controlled to have an internal temperature [OF 28-32C,] a chloroform solution obtained by diluting 108g (0. 68mol, 1.21eq.) of Br2 with [56ML] of chloroform was added to the solution, followed by stirring for [15HR] with an internal temperature of [29-32DUC.] The resulting reaction separated into an upper and lower layer. Then, the lower layer was washed with [2percent BRINE,] followed by drying with anhydrous sodium sulfate, filtration and vacuum drying, thereby obtaining 165g of a crude product of a brominated acetal represented by the following formula. The yield was 94percent. The analytical results of the crude product by gas chromatography are shown in Table 4, and [ITS 1H-NMR] spectrum was as follows. Table 4 Compound A1 C1 D1 Total Others 0. 6percent 96. 9percent 0. 9percent 1. 6percent 1 : Compound A Compound C Compound D o n o Br p Br 'bu ZIG CF3 CF CF3 3 [1H-NMR] (standard substance: TMS, solvent: [CDCL3),] [8PPM] : 3.64 (s, 2H), 3.83-3. 98 (m, 2H), 4.14-4. 30 (m, 2H), 7.64 (Ar-H, 4H). Separately, water was poured into the above-obtained upper layer, followed by extraction with ethyl acetate. The collected organic layer was dried with anhydrous sodium sulfate, followed by filtration, concentration and vacuum drying, thereby obtaining 6g of a brominated acetal of the above formula. The yield was 3percent. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
26.0 - 29.2 %Chromat. | at 26 - 28℃; for 3.5 - 24 h; | [2. 82G (14. 99MMOL, LEQ. ) OF 4APOS;-TRIFLUOROMETHYLACETOPHENONE WERE] dissolved in 5. [6ML] of methanol. While the solution was controlled to have an internal temperature [OF 26-27C,] a methanol solution obtained by diluting 3.60g (22. [53MMOL,] 1.50eq.) of Br2 with [1.] [4ML] of methanol was added to the solution, followed by stirring for 24hr with an internal temperature [OF 26-28C.] 3.5hr and 24hr after the start of the reaction, the progress of the reaction was checked by gas chromatography. The results are shown in Table 2. Table 2 Time Compound A1 B1 D 3. 5h 29. 2percent 53. 8percent 9. 5percent 24h 26. 0percent 45. 3percent 25. 3percent : Compound A Compound B Compound D 0 CH30 OCH3 0 Br I Br Br / CF) () CF3 CF-Br 3 3 |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
1: 17 (unit not given) 2: 6 (unit not given) 3: 45 <unit not given> | With potassium fluoride; copper(l) iodide In N,N-dimethyl-formamide at 80℃; for 24h; | |
1: 45 (unit not given) 2: 17 (unit not given) 3: 6 <unit not given> | With potassium fluoride; copper(l) iodide In N,N-dimethyl-formamide at 80℃; for 24h; | |
1: 45 (unit not given) 2: 6 (unit not given) 3: 17 <unit not given> | With potassium fluoride; copper(l) iodide In N,N-dimethyl-formamide at 80℃; for 24h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
80% | To methyltriphenylphosphonium bromide (i4.2 g,39.9 mmol) was added THF (44 mE). The suspension wascooled to 00 C. and potassium tert-butoxide (4.47 g, 39.9mmol) was added. The resulting yellow suspension wasstirred at 00 C. for 45 minutes. To the suspension was addeda solution of 1 -(4-(trifluoromethyl)phenyl)ethanone (5.0 g,26.6 mmol) in THF (22 mE) dropwise. The resulting mixture was then brought up to room temperature slowly and stirredfor 16 hours. Reaction mixture was diluted with hexanes (150 mE) and stirred for 20 mm. The resulting precipitatewas filtered, rinsed with hexane and the filtrate was concentrate. More hexanes (200 mE) was added to the residue and stirred for 20 mm. The resulting precipitate was filtered through celite and the filtrate was concentrated to provide 1 -(prop-i-en-2-yl)-4-(trifluoromethyl)benzene (3.98 g,80%) ?H NMR (400 MHz, CDC13) oe 7.61-7.53 (m, 4H), 5.44 (s, 1H), 5.22-5.17 (m, 1H), 2.17 (dd, J=i.3, 0.7 Hz, 3H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
80% | With sodium hypophosphite monohydrate; 5%-palladium/activated carbon; hypophosphorous acid; In water; at 100℃; | General procedure: Method B: in a round bottom flask, to a solution of ketone (1mmol) and Pd/C 5wt% (50% in water) (212mg, 0.1mmol, 10mol%) in CPME (1mL) was added a mixture of sodium hypophosphite monohydrate (3mmol), hypophosphorous acid 50% in water (1mmol) in water (2mL). The reaction mixture was heated at 100C between 2 and 16h. Same treatment as Method A was performed. (0038) Method C: the same procedure was followed replacing the thermal activation by a sonochemical activation during 5h. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
96.7% | In isopropyl alcohol; | (b) Hydrogenation [Substrate:Catalyst Ratio 498:1] p-Trifluoromethylacetophenone (0.384 g, 2 mmol) was added to a dry vial. Then a portion (2 ml) of the catalyst solution was added followed by sodium 2-propoxide solution (90 mul of 0.1M solution in 2-propanol). The mixture was stirred at ambient temperature under nitrogen for 2 h. This gave 1-(p-trifluoromethylphenyl)ethanol Yield 96.7%, ee 73.8%. The initial turnover number, integrated over 1 h, was 412 h-1. |
96% | With [RhCl2(p-cymene)]2; dimethylamine borane; In tetrahydrofuran; at 70℃; for 24h;Inert atmosphere; Sealed ampoule; | General procedure: To an oven dried, argon purged, ampoule containing [Ru(p-cymene)Cl2]2 (15.3 mg, 0.05 mmol, 2.5 mol%), substrate (1 mmol) and dry thf (to make a total of 3 mL), a solution of dimethylamine borane in thf was added. The ampoule was sealed and heated at 70 C for 24 hours then cooled to room temperature; Method A - The reaction mixture was diluted with CH2Cl2 (30 mL) and passed through a short pad of silica followed by diethyl ether (100 mL). The solvents were concentrated in vacuo to afford the crude product. |
96% | With Cp*Ir(6,6'-dionato-2,2'-bipyridine)(H2O); hydrogen; In tert-Amyl alcohol; at 30℃; under 760.051 Torr; for 12h;Green chemistry; | General procedure: To an oven-dried 5 mL round-bottom flask were added ketone (1 mmol), cat. 7 (2.7 mg, 0.5 mol %) and tert-amyl alcohol (1 mL). Next, vacuum was applied to the flask followed by filling with H2 gas and keeping the flask attached to a balloon filled with H2 gas. The mixture was heated at 30 C for 12 h. After completion of the reaction, the solvent was removed by evaporation under reduced pressure. The alcohols were isolated and purified by filtering a hexanes/ethyl acetate (5:1) solution of the crude product through a pad of silica gel, and then removing the solvent under reduced pressure. The conversion and purity of the alcohol products was assessed using NMR spectroscopy. |
95% | With [(N,N?-bis(diisopropylphosphino)-2,6-diaminopyridine)Mn(CO)3][Br]; potassium tert-butylate; hydrogen; In toluene; at 130℃; under 37503.8 Torr; for 20h;Glovebox; Autoclave; | General procedure: In a glove box, an autoclave was charged with the desired ketone (0.5 mmol), toluene (2 mL), Mn complex 1 (14 mg, 5 mol%) followed by t-BuOK (5.6 mg, 10 mol%), in this order. The autoclave is then closed and charged with H2 (50 bar). |
94% | With sodium tetrahydroborate; In ethanol; at 0 - 20℃; for 4h; | To a cold solution of 4'-(trifluoromethyl)acetophenone (10 g, 53.15 mmol) in ethanol (55 mL) was added NaBH4in small portions at 0 C and the resulting mixture was stirred at rt for 4 h. The reaction mixture was quenched with 1 N HCI (50 mL) and extracted with CH2CI2(3 chi 100 mL). The combined organic layer was washed with saturated NaHC03, brine, dried over anhydrous Na2S04and concentrated under reduced pressure to afford 9.5 g (94%) of 1-(4- (Trifluoromethyl)phenyl)ethanol as a pale yellow liquid.1H-NMR (400 MHz, CDCI3); 6 7.6 (d, J = 8.0 Hz, 2H), 7.49 (d, J = 8.4 Hz, 2H), 4.94-5.0 (m, 1 H), 1 .86 (s, 1 H), 1 .51 (d, J = 6.8 Hz, 3H). |
94% | With Cp*Ir(6,6'-dionato-2,2'-bipyridine)(H2O); isopropyl alcohol; at 82℃; for 6h;Inert atmosphere; Green chemistry; | The 4 - trifluoromethyl acetophenone (188 mg, 1.0 mmol), cat. [Ir] (1.1 mg, 0 . 002 mmol, 0.2 muM %) and isopropyl alcohol (5 ml) are added to the 25 ml Kjeldahl tube, N2Protection , 82 C reaction 6 h. Cooling to room temperature, rotary evaporation to remove the solvent, then through the column chromatography (developing solvent: petroleum ether/ethyl acetate) to obtain the pure target compound, yield: 94% |
91% | With bis(2-hydroxyethyl)ammonium formate; palladium dichloride; In N,N-dimethyl-formamide; at 20℃; for 2h;Inert atmosphere; | General procedure: (Table 2, entry 4): To a solution of acetophenone (1) (120 mg, 1.00 mmol) in [BHEA][HCO2] (5.00 mL, 39.7 mmol) was added PdCl2 (17,7 mg, 10.0 mol%) at rt and the mixture was stirred at the same temperature for 6 h under argon atmosphere. The mixture was poured into brine (10 mL) and extracted with EtOAc (10 × 10 mL). The organic layer was washed with brine (100 mL) and dried with MgSO4. After removal of the solvent, the residue was subjected to column chromatography (Merck kieselgel 60, phi = 2.0 cm, l = 11.5 cm; EtOAc-hexane, 1:5) to give 1-phenylethanol (2) as colorless oil; yield: 110 mg (90%). |
91% | With bis(2-hydroxyethyl)ammonium formate; palladium dichloride; In N,N-dimethyl-formamide; at 20℃; for 2h;Inert atmosphere; | General procedure: To a solution of 4'-(trifluoromethyl)acetophenone (3e) (188 mg, 1.00 mmol) in DMF (5.00 mL) was added [BHEA][HCO2] (5.00 mL, 39.7 mmol) and PdCl2 (35.5 mg, 20.0 mol %) at rt and the reaction mixture was stirred at the same temperature for 2 h under argon atmosphere. The mixture was poured into brine (10 mL) and extracted with Et2O (10 10 mL). The organic layer was washed with brine (150 mL) and dried with MgSO4. After removal of the solvent, the residue was subjected to column chromatography (Merck Kieselgel 60, Phi=2.0 cm, l=7.5 cm; EtOAc-hexane, 1:5) to give 1-(4-trifluoromethylphenyl)ethanol (4e) as colorless oil; yield: 174 mg (91%). |
89% | With sodium hypophosphite monohydrate; 5%-palladium/activated carbon; tetrabutyl-ammonium chloride; In 2-methyltetrahydrofuran; water; at 60℃; for 4h;Schlenk technique; | General procedure: In a Schlenk tube (10mL), a solution of ketone compound (1mmol), tetrabutylammonium chloride (20mg, 72mumol, 7mol%), and Pd/C 5% wt (50% in water) (55mg, 26mumol, 2.6mol%) in 2-MeTHF (1mL) was stirred at room temperature (20C) for 10-20min. To this mixture was added a solution of sodium hypophosphite monohydrate (424mg, 4mmol, 4equiv) in water (2.5mL). The reaction mixture was heated at 60C. After dilution in CH2Cl2 (10mL), water (10mL) was added. The aqueous phase was extracted with CH2Cl2 (2×20mL). The combined organic layers were dried (Na2SO4), filtered, and concentrated. Purification by flash chromatography on silica gel was performed for products 4a, 5a, 10a, 12a, 15a, and 19c. 4.2.1 4-(1-Hydroxyethyl)benzoic acid methyl ester [84851-56-9]11d (1a) (0021) Procedure A; 2.7h; colorless oil (170mg, 94%). 1H NMR (300MHz, CDCl3) delta (ppm)=1.51 (d, 3H, J=6.5Hz, CH3), 1.84 (brs, 1H, OH), 3.91 (s, 3H, OCH3), 4.97 (q, 1H, J=6.5Hz, CH-OH), 7.45 (d, 2H, J=8.3Hz, Harom), 8.02 (d, 2H, J=8.3Hz, Harom). |
78% | General procedure: To a solution of [CpRu(PPh3)2Cl] (1 mol%) and solid aldehyde (1.0 mmol) in toluene (3 ml) was added PhSiH3 (1.2 mmol). The reaction mixture was stirred at reflux temperature under an air atmosphere (the reaction times are indicated in Table 4). Then, TBAF (1.0 mmol) was added and the reaction mixture was stirred at room temperature during 30 min. After evaporation, the reaction mixture was purified by silica gel column chromatography with ethyl acetate:n-hexane (1:3) to afford the corresponding alcohols. | |
71% | 4'-(Trifluoromethyl)acetophenone (19A) (0.507 g, 2.69 mmol) was dissolved in ethanol (27 mL) and to the resulting solution was added sodium borohydride (0.120 g, 3.17 mmol). The reaction was stirred at room temperature for about 15 hours and was then concentrated in vacuo to provide a residue which was dissolved in dichloromethane. The organic phase was washed with water several times, dried over MgSO4, filtered and concentrated in vacuo to provide compound 19B (0.359 g, 71%), which was used without further purification. | |
99%Spectr. | With hydrogen; In 1-butyl-3-methylimidazolium hexafluorophosphate; at 20℃; under 760.051 Torr; for 24h; | General procedure: The palladium nanoparticles on SWNTs were prepared in [BMIM][PF6]. The SWNTs (5 mg) was grounded in IL (1 ml) for 30 min, and then Pd(II) acetate (0.018 mmol) was dissolved in the solution. The Pd(II) acetate was in situ reduced in IL with 1 atm of hydrogen for 5 min at room temperature. The aryl ketone (0.3 mmol) was added to this solution under 1 atm of hydrogen at room temperature. After the >99% completion of the reaction was checked by TLC, the products were extracted with ethyl ether. The ethereal phase was concentrated and analyzed by 1H NMR. |
With sodium tetrahydroborate; In methanol; at 20℃;Schlenk technique; | General procedure: The ketone (1mmol) was dissolved in MeOH (5cm3) in a schlenk tube, then NaBH4 (3mmol) was added slowly and the mixture was stirred at r.t. for o/n. The solvent was removed and the mixture was dissolved in DCM (10 cm3), washed with water (10cm3), filtered and solvent removed. a small amount of the residue was dilluted inEtOAc and then injected on the GC to determine the conversion. | |
> 99%Chromat. | General procedure: In a glovebox (nitrogen atmosphere)a vial was charged with complex 4b (0.0125mmol, 2.5 mol%), the corresponding ketone (0.5 mmol), diphenylsilane(1.5 equiv., 0,75 mmol) and THF (2.0 mL). The reaction mixture was stirred in apreheated oil bath at 70 C for 24 h. The mixture was cooled on an ice bath andwas treated with n-dodecane (100 mL) as GC standard (for GC-analysis),methanol (1.0 mL), and aqueous sodium hydroxide solution (1.0 mL) with vigorousstirring (Caution: The reaction mixture bubbled enthusiastically upon theaddition of the base). The reaction mixture was stirred for 60 min at 0 C andwas then extracted with diethyl ether (2x 10.0 mL). The combined organic layerswere washed with brine, dried over anhydrous Na2SO4,filtered, and concentrated in vacuum. The yield was monitored by GC (30 mRxi-5ms column). The products were compared with authentic samples. | |
96%Chromat. | With 1-(2-pyrimidyl)-3-(methyl) imidazoline-2-ylidene tetraacetonitrileruthenium(II)hexafluorophosphate; potassium hydroxide; In isopropyl alcohol; at 80℃; for 1h;Schlenk technique; | General procedure: The ketone (1.0 mmol), KOH (0.2 mmol) and 2 mL of iPrOHwere placed in a Schlenk tube. Anisole (0.25 mmol) was addedas an internal GC standard. The mixture was heated at 80 Cand then catalyst solution (0.01 mmol, 0.001 mmol, or0.0001 mol of ruthenium complexes in iPrOH (1 mL) wasinjected. Aliquots (0.2 mL) were taken at fixed time intervals,quenched with 1 mL of H2O and extracted with 3 mL of Et2O.The product yields were determined by GC analysis. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
68% | Ti(OiPr)4 (31.5 mL, 106 mmol) was added to (p-trifluoromethyl)acetophenone 108 (10.0 g, 53.1 mmol) in NH3 (2.0 M in EtOH, 133 mL) and the resultant mixture was stirred at rt for 6 h. NaBH4 (3.01 g, 79.7 mmol) was added at 0 C, and the resultant suspension was stirred at rt for 3 h, then poured into 2.0 M aq NH4OH (200 mL). The resultant suspension was filtered (eluent EtOAc) and the aqueous layer was extracted with EtOAc (2*80 mL). The combined organic extracts were extracted with 1.0 M aq HCl (3*50 mL) and the combined aqueous extracts were washed with EtOAc (3*30 mL), treated with 2.0 M aq NaOH until pH>8 was observed, then extracted with EtOAc (4*50 mL). The combined organic extracts were washed with brine (200 mL), then dried and concentrated in vacuo to give (RS)-117 as a pale yellow oil (6.84 g, 68%);43 δH (400 MHz, CDCl3) 1.40 (3H, d, J 6.6, C(α)Me), 1.59 (2H, br s, NH2), 4.20 (1H, q, J 6.6, C(α)H), 7.48 (2H, d, J 7.8, C(2)H, C(6)H), 7.59 (2H, d, J 7.8, C(3)H, C(5)H). | |
52% | A mixture of 1-(4-(trifluoromethyl)phenyl)ethanone (400 mg, 2.13 mmol), Ti(O-i-Pr)4 (1.25 mL, ∼4.25 mmol) and ammonia in EtOH (2 M, 5.30 mL, ∼10.6 mmol) was stirred under argon at room temperature for 24 h NaBH4 (120 mg, 3.19 mmol) was then added, and the resulting mixture was stirred for another 24 h. The pH of the reaction mixture was adjusted to pH 2 using HCl (6 M), and washed with tert-butyl methyl ether (TBME) (3 × 20 mL). Using NaOH (pellets) the pH was adjusted to ca 10, and the mixture was extracted with TBME (6 × 30 mL). The combined organic phase was dried over MgSO4, and the solvent was removed under reduced pressure to give 210 mg (1.11 mmol, 52%) of a yellow oil. 1H NMR (400 MHz, CDCl3) δ: 7.58 (m, 2H), 7.46 (m, 2H), 4.19 (q, J = 6.7, 1H), 1.38 (d, J = 6.7, 3H), 1.51 (s, 2H, NH2). 13C NMR (100 MHz, CDCl3) δ: 152.1 (q, J = 1.1), 129.4 (q, J = 31.5), 126.5 (2C), 125.8 (q, J = 3.8, 2C), 124.6 (q, J = 270.9), 51.4, 25.1. | |
With dichloro(pentamethylcyclopentadienyl)rhodium (III) dimer; ammonium formate; In methanol; at 70℃; for 7h;Inert atmosphere; | General procedure: The corresponding ketone (20 mmol, 1.0 eq) and CH3OH (20 mL) were added to a 250 mL Schlenk tube containing [RhCp*Cl2]2 (61.8 mg, 100 μmol, 0.005 equiv) and HCOONH4 (6.36 g, 100 mmol, 5.0eq). The brown mixture was frozen, and the whole system was evacuated. The system was closed and then stirred at 70 C for 7 h. After the dark green resulting solution was cooled to room temperature, 1M aqueous HCl solution (38.4 mL) was added, and the mixture was washed twice with CH2Cl2 (5 mL) to remove the neutral compounds. After addition of a cold 12 M aqueous NaOH solution (3.6 mL) to the aqueous layer, the mixture was extracted six times with CH2Cl2 (12 mL). The combined organic layers were dried over anhydrous Na2SO4. Filtration and evaporation under reduced pressure gave crude amine,which was used without purification. All the crude corresponding amine was dissolved in dichloromethane (50 mL), and TCCA (trichloroisocyanuric acid) (3.2 g, 14 mmol) was added in a250 ml round-bottom flask at 0 C. Then, the mixture was stirred at ambient temperature during 1 h. Triethylamine (6.0 g, 6 mol) dissolved in dichloromethane (50 mL) was added, and the resulting mixture was washed with water (200 mL) and hydrochloric acid (1 M, 200 mL)successively. The organic layer was dried over anhydrous sodium sulfate. After concentration under reduced pressure, purification by column chromatography on silica gel (n-hexane/EtOAc:40/1) afforded pure product. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
84% | With dimethylsulfide borane complex In tetrahydrofuran for 0.25h; cooling; Title compound not separated from byproducts; | |
With hydrogenchloride; n-butyllithium; PMHS; chiral titanocene 1,1'-binaphth-2,2'-diolate 1.) benzene, hexane, 6 d, 2.) benzene, hexane, acetone; Yield given. Multistep reaction. Yields of byproduct given. Title compound not separated from byproducts; | ||
With dichloro(benzene)ruthenium(II) dimer; (R,R)-(-)-N,N'-dimethyl-1,2-diphenyl-1,2-ethylenyl-diphenyldithiourea; potassium-t-butoxide In isopropanol at 82℃; for 48h; Yield given. Yields of byproduct given. Title compound not separated from byproducts; |
With (3aS)-1-methyl-3, 3-diphenyl-tetrahydro-pyrrolo[1,2-c][1,3,2]oxazaborole borane complex In dichloromethane at -20℃; Yield given. Yields of byproduct given. Title compound not separated from byproducts; | ||
With potassium isopropoxide; (1S,3R,4R)-2-azabicyclo[2.2.1]heptane-3-(R)-methylmethanol In isopropanol at 20℃; for 1h; Title compound not separated from byproducts; | ||
With Rhizopus arrhizus In ethanol for 168h; Title compound not separated from byproducts; | ||
With (p-cymene)ruthenium(II) chloride; (S,S)-1,2-diphenyl-1,2-diaminoethane; potassium-t-butoxide In water monomer; isopropanol at 22℃; for 4h; Title compound not separated from byproducts; | ||
With (p-cymene)ruthenium(II) chloride; (1R,2R)-N-(p-sulfonylbenzolsulfonyl)-1,2-diaminocyclohexane; potassium-t-butoxide In water monomer; isopropanol at 22℃; for 4h; Title compound not separated from byproducts; | ||
With Merulius tremellosus ono991 In acetone at 28℃; for 72h; Title compound not separated from byproducts; | ||
Stage #1: 1-(4-trifluoromethylphenyl)ethanone With copper difluoride; phenylsilane; (S)-(1,1'-binaphthalene)-2,2'-diylbis(diphenylphosphine) In toluene at 20℃; for 3h; Stage #2: With hydrogenchloride Title compound not separated from byproducts; | ||
With dimethylsulfide borane complex; chiral deriv. of oxazaboralodinone Title compound not separated from byproducts; | ||
With (R)-3,5-xyl-MeO-BIPHEP; copper chloride (I) In toluene at -50℃; for 1h; Title compound not separated from byproducts; | ||
With copper difluoride; phenylsilane; (S)-(1,1'-binaphthalene)-2,2'-diylbis(diphenylphosphine) In toluene at 20℃; for 3h; Title compound not separated from byproducts; | ||
With (-)-C5Me5FeC10H10N; mesitylphenylsilane In tetrahydrofuran at 20℃; Title compound not separated from byproducts; | ||
With PMHS; copper chloride (I); sodium tertiary butoxide In toluene at -78 - 20℃; for 3h; Title compound not separated from byproducts; | ||
With chiral Zn(OTf)2*C5H5FeC5H3(CHNCPh3)(C3H3NO-i-Pr); benzo[1,3,2]dioxaborole In dichloromethane at -15℃; Title compound not separated from byproducts; | ||
With potassium-t-butoxide; hydrogen In isopropanol at 20℃; for 4h; Title compound not separated from byproducts; | ||
With potassium-t-butoxide In isopropanol at 50℃; for 24h; | ||
With (R)-1-[(1R,4R,5R,6S)-5,6-Me2CO2-2-aza-3-norbornyl]ethanol; potassium isopropoxide; isopropanol at 20℃; for 1h; Title compound not separated from byproducts; | ||
With N-(p-toluenesulfonyl)-(1R,2R)-diphenylethylenediamine; anhydrous sodium formate at 40℃; for 2h; Title compound not separated from byproducts; | ||
With anhydrous sodium formate at 40℃; for 2h; Title compound not separated from byproducts; | ||
With [(S)-BrXuPHOS]2RuCl2(S,S-DPEN); potassium-t-butoxide; hydrogen In dichloromethane; isopropanol at 20 - 22℃; for 20h; Title compound not separated from byproducts; | ||
With potassium-t-butoxide; isopropanol; (R)-(3-benzylamino-2-hydroxy)propyl trityl ester In toluene at 20℃; for 1h; Title compound not separated from byproducts; | ||
With (S)-(3-benzylamino-2-mercapto)propyl trityl ester; potassium-t-butoxide; isopropanol In toluene at 20℃; for 1h; Title compound not separated from byproducts; | ||
With di-μ-chlorobis-[(η6-p-cymene)chlororuthenium(II)]; anhydrous sodium formate; (1R, 2S)-2-(methylamino)-1-phenylpropan-1-ol hydrochloride at 20℃; Title compound not separated from byproducts; | ||
With C49H47O2N2(1+)*BF4(1-); diphenylsilane; trifluoromethane sulfonic acid silver salt In tetrahydrofuran at 0℃; for 48h; Title compound not separated from byproducts; | ||
With anhydrous sodium formate In water monomer at 60℃; Title compound not separated from byproducts; | ||
With 1,2-O-isopropylidene-3-O-Ph2P-5-deoxy-5-tBuS-D-xylofuranose; bis[chlorido(η2,η2-cycloocta-1,5-diene)rhodium(I)]; diphenylsilane In toluene at -15℃; Title compound not separated from byproducts; | ||
With di-μ-chlorobis-[(η6-p-cymene)chlororuthenium(II)]; poly(ethylene glycol)-N-pTos-1,2-diphenylethylenediamine; anhydrous sodium formate In water monomer at 40℃; for 2h; Title compound not separated from byproducts; | ||
With [Ru(μ-Cl)(η(5)-pentamethylcyclopentadienyl)]4; potassium-t-butoxide; hydrogen In isopropanol for 0.7h; Title compound not separated from byproducts; | ||
With formic acid; Ru-(R,R)-Ts-dpen; triethylamine In water monomer at 40℃; for 1.3h; Title compound not separated from byproducts; | ||
With formic acid; imidazolium salt unit attached to (1S,2S)-TsDPEN; triethylamine at 20℃; for 24h; Title compound not separated from byproducts; | ||
With potassium-t-butoxide; hydrogen In isopropanol at 25℃; for 18h; Title compound not separated from byproducts; | ||
With potassium hydroxide; 9-amino-9-deoxyepicinchonine In isopropanol at -20℃; for 30h; Title compound not separated from byproducts; | ||
With potassium-t-butoxide; hydrogen In dichloromethane; isopropanol for 8h; cooling; Title compound not separated from byproducts; | ||
With air; anhydrous sodium formate at 40℃; for 0.166667h; Title compound not separated from byproducts; | ||
With Trimethyl borate In (2)H8-toluene at 20℃; for 1h; Title compound not separated from byproducts.; | ||
In formic acid; triethylamine at 50℃; for 10h; | ||
With air; phenylsilane In toluene at -60℃; for 18h; Title compound not separated from byproducts.; | ||
With anhydrous sodium formate In water monomer at 40℃; for 2h; Title compound not separated from byproducts.; | ||
With trichlorosilane In toluene at -20℃; for 16h; Title compound not separated from byproducts.; | ||
With potassium-t-butoxide; hydrogen In isopropanol; <i>tert</i>-butyl alcohol at 20℃; for 6h; | 40 Hydrogenation of 4-Trifluoromethylacetophenone using Complex(R,S)-13d Complex R,S-13d (3.0 mg; 0.0025 mmol; 0.005 equiv) was placed in a reaction vessel, which was pressurized with argon and vented five times. Argon-degassed isopropanol (2 mL) was added and the mixture was stirred for 15 min. 4-Trifluoromethylacetophenone (94 mg; 0.5 mmol) dissolved in 1 mL of argon-degassed isopropanol was added and was washed in with 1.0 mL of argon-degassed isopropanol. Potassium tert-butoxide in tert-butanol (1M; 0.05 mL; 0.05 mmol; 0.1 equiv) in 0.5 mL of argon-degassed isopropanol was added and was washed in with 0.5 mL of argon-degassed isopropanol. The reaction mixture was pressurized with argon and vented five times and then pressurized to 300 psig with hydrogen and stirred at ambient temperature for 6 h. The vessel was vented, then pressurized with argon and vented five times, and the solution was assayed by chiral GC to indicate 99.8% conversion to 1-(4-trifluoromethylphenyl)ethanol with 60.0% ee. Chiral GC [Cyclosil-B (J&W Scientific), 40° C. to 100° C. at 70° C./min, hold at 100° C. for 15 minutes, 100° C. to 170° C. at 15° C./min, hold at 170° C. for 7 min]: tR=16.7 min (4-trifluoromethylacetophenone), tR=20.7 min [1-(4-trifluoromethylphenyl)ethanol, enantiomer 1], tR=20.9 min [1-(4-trifluoromethylphenyl)ethanol, enantiomer 2]. | |
With potassium-t-butoxide; hydrogen In isopropanol at 25℃; for 1h; Title compound not separated from byproducts.; | ||
With sodium isopropanolate; isopropanol at 20℃; for 2h; Title compound not separated from byproducts.; | ||
With potassium hydroxide; hydrogen In isopropanol at 40℃; for 3h; Title compound not separated from byproducts.; | ||
With (S)-2-((1-formylpyrrolidine-2-carbonyl)amino)propane-1,3-diyl diacetate; trichlorosilane In dichloromethane at -20℃; for 16h; Inert atmosphere; enantioselective reaction; | ||
With C58H56Cl2N2P2Ru; potassium-t-butoxide; hydrogen In isopropanol at 25℃; for 3h; Inert atmosphere; optical yield given as %ee; | ||
With RuCl2[(R,S)-Josiphos][(S)-Me-bimaH]; potassium-t-butoxide; hydrogen; triphenylphosphine In toluene; <i>tert</i>-butyl alcohol at 25℃; for 8h; Inert atmosphere; Autoclave; optical yield given as %ee; enantioselective reaction; | ||
82 % ee | With potassium-t-butoxide; hydrogen In toluene; <i>tert</i>-butyl alcohol at 25℃; for 8h; | 22 Several aromatic ketones were reduced using the same process described in Example 19. The hydrogenation conditions and results were shown in Table 3. Table 3. Asymmetric hydrogenation of simple aryl ketones catalyzed by RuCl2[(R,5)-Josiphos)][(5)-Me-bimaH)][(λS',ιS)-8] complex. a ee (%yPI1R2 YieldEntry Substrate S/C ratio Time (h) (config (atm) (%)b1 acetophenone 1,000 8 2 100 96 (5)2 acetophenone 10,000 20 12 100 96 (5)3d acetophenone 50,000 40 10 100 97 (5)4-MeO-acetopheno 4 5,000 20 16 95 97 (S) ne4-CF3-acetophenon5 5,000 20 8 90 82 (5) e2-Me-acetophenon6 5,000 20 8 100 95 (5) e7 3 -Br-acetophenone 5,000 20 6 100 92 (5) ,oCM 1,000 8 12 92 94 (5) a Hydrogenation conditions: [ketone] = 0.3-1.9 M, [(i?5,5)-8] = 0.04-0.3 mM, [KO-^-C4H9] = 15-20 mM, [PPh3] = 1.0-3.4 mM, t = 25 0C, solvent = toluene/t-BuOH (9/1). b Determined by GC. c Absolute configuration (config) determined from [α]D. d Toluene/t-BuOH (7/3). e Yield determined by 1H NMR; ee determined by HPLC. |
With bis[dichlorido(η5-1,2,3,4,5-pentamethyl-cyclopentadienyl)rhodium (III)]; C21H28N2O2S; sodium isopropanolate; lithium chloride In isopropanol at 20℃; for 0.5h; Inert atmosphere; optical yield given as %ee; enantioselective reaction; | ||
Stage #1: 1-(4-trifluoromethylphenyl)ethanone With phenylsilane; copper (II) acetate; (S)-4-phenyl-4,5-dihydro-3H-dinaphtho[2,1-c;1',2'-e]phosphepine In toluene at -20℃; for 5h; Inert atmosphere; Stage #2: With methanol; N,N,N-tributylbutan-1-aminium fluoride In tetrahydrofuran for 2h; optical yield given as %ee; enantioselective reaction; | ||
With trans-[RuH(BH4){(R)-2,2'-bis(diphenylphosphino)-1,1'-binaphthyl}{(R,R)-1,2-diphenylethylenediamine}]; potassium-t-butoxide; hydrogen In isopropanol at 30 - 32℃; optical yield given as %ee; enantioselective reaction; | ||
Stage #1: 1-(4-trifluoromethylphenyl)ethanone With [(4S,5S)-1,3-bis[2,6-diisopropylphenyl]-4,5-di-tert-butylimidazolidine-2-ylidene][1,5-cyclooctadiene]-iodo-rhodium(I); diphenylsilane In tetrahydrofuran at 25℃; for 3h; Stage #2: With sodium hydroxide In tetrahydrofuran; methanol for 0.166667h; enantioselective reaction; | ||
With (2S,1'S,2'R)-1-formyl-piperidine-2-carboxylic acid (2-methoxy-1,2-diphenyl-ethyl)-amide; trichlorosilane In chloroform-d1 at 20℃; for 16h; Inert atmosphere; optical yield given as %ee; enantioselective reaction; | ||
With formic acid; C28H28ClN2O2RuS; triethylamine at 28℃; for 2h; optical yield given as %ee; enantioselective reaction; | ||
With bis[dichlorido(η5-1,2,3,4,5-pentamethyl-cyclopentadienyl)rhodium (III)]; (S)-tert-butyl 1-((1-benzyl-1H-1,2,3-triazol-4-yl)methylamino)-3-methyl-1-thioxobutan-2-ylcarbamate; sodium isopropanolate; isopropanol; lithium chloride at 20℃; for 0.166667h; Inert atmosphere; optical yield given as %ee; enantioselective reaction; | ||
With dichloro(benzene)ruthenium(II) dimer; C16H23NO4; potassium-t-butoxide In isopropanol at 70℃; for 21h; Inert atmosphere; enantioselective reaction; | ||
With C68H78Cl2N2O6P2Ru; hydrogen; potassium hydroxide In isopropanol at 20℃; for 12h; Autoclave; optical yield given as %ee; enantioselective reaction; | ||
With D-glucose; D-glucose dehydrogenase; recombinant Sporobolomyces salmonicolor carbonyl reductase M242D mutant; NADPH In dimethyl sulfoxide at 20℃; aq. phosphate buffer; Enzymatic reaction; optical yield given as %ee; enantioselective reaction; | ||
With potassium-t-butoxide; hydrogen; copper (II) acetate; 4-(4-trifluoromethyl-phenyl)-4,5-dihydro-3<i>H</i>-4-phospha-cyclohepta[2,1-<i>a</i>;3,4-<i>a</i>']dinaphthalene In isopropanol at 10℃; for 16h; Inert atmosphere; Autoclave; optical yield given as %ee; enantioselective reaction; | ||
With di-μ-chlorobis-[(η6-p-cymene)chlororuthenium(II)]; {2-[(S)-1-aminoethyl]phenyl}methanol; isopropanol; potassium hydroxide at -10℃; for 5h; Inert atmosphere; optical yield given as %ee; enantioselective reaction; | 4.3. General procedure for the transfer hydrogenation of aromatic ketones General procedure: A mixture of [RuCl2(p-cymene)]2 (1.5 mg, 0.0025 mmol) and (S)-4a (3.0 mg, 0.02 mmol) in 2 mL of 2-propanol was stirred at 80 °C for 30 min under argon atmosphere. After cooling to room temperature, 2-propanol (15 mL), KOH (0.6 mL, 0.1 M in 2-propanol), acetophenone (0.5 mmol, dissolved in 5 mL of 2-propanol) were added. The resulting solution was stirred at -10 °C, and the reaction was monitored by GC or HPLC. The mixture was neutralized with dilute HCl and 2-propanol was removed under reduced pressure. The residue was diluted with ethyl acetate (25 mL) and the organic solution was washed with brine (3 × 20 mL) and dried over anhydrous MgSO4. After evaporation of the solvent, the residue was subjected to short column chromatography on silica gel (hexane/ethyl acetate as eluent) for ee and conversion determination. | |
With bis[chlorido(η2,η2-cycloocta-1,5-diene)rhodium(I)]; C7H7O3S(1-)*C9H14N3O(1+); potassium-t-butoxide; potassium hydroxide In isopropanol at 80℃; for 20h; Inert atmosphere; | ||
Multi-step reaction with 2 steps 1.1: ferrous acetate; 1,2-bis((2S,5S)-2,5-dimethylphospholano)benzene / tetrahydrofuran / 65 °C / Inert atmosphere 1.2: 45 h / 20 °C / Inert atmosphere 2.1: water monomer; sodium hydroxide / tetrahydrofuran; methanol / 0 - 20 °C / Inert atmosphere | ||
82 % ee | With potassium-t-butoxide; hydrogen In toluene; <i>tert</i>-butyl alcohol at 25℃; for 8h; | 22 Several aromatic ketones were reduced using the same process described in Example 19. The hydrogenation conditions and results were shown in Table 3. TABLE 3 Asymmetric hydrogenation of simple aryl ketones catalyzed byRuCl2[(R,S)-Josiphos)][(S)-Me-bimaH)][(RS,S)-8] complex.a P/H2 Yieldee (%)b Entry Substrate S/C ratio (atm) Time (h)(%)b (config)c 1 acetophenone 1,000 8 2 100 96 (S) 2 acetophenone 10,000 20 12 100 96 (S) 3d acetophenone 50,000 40 10 100 97 (S) 4 4-MeO-acetophenone 5,000 20 16 95 97 (S) 54-CF3-acetophenone 5,000 20 8 90 82 (S) 6 2-Me-acetophenone 5,000 20 8 100 95 (S) 7 3-Br-acetophenone 5,000 20 6 100 92 (S) 8e 5,000 20 24 95 99 (R) 9 1,000 8 12 92 94 (S) 10 1,000 8 12 100 97 (S) aHydrogenation conditions: [ketone] = 0.3-1.9M, [(RS,S)-8] = 0.04-0.3 mM, [KO-t-C4H9] = 15-20 mM, [PPh3] = 1.0-3.4 mM, t = 25° C., solvent = toluene/t-BuOH (9/1).bDetermined by GC.cAbsolute configuration (config) determined from [α]D.dToluene/t-BuOH (7/3).eYield determined by 1H NMR; ee determined by HPLC. |
With formic acid; di-μ-chlorobis-[(η6-p-cymene)chlororuthenium(II)]; triethylamine; N-((1R,2R)-2-aminocyclohexyl)-4-methylbenzenesulfonamide at 40℃; for 24h; optical yield given as %ee; enantioselective reaction; | 4.3. Asymmetric transfer hydrogenation in formic acid/triethylamine (Investigation scale) General procedure: A suspension of the [RuCl2(arene)]2 (0.001 mmol) and ligand (0.0027 mmol) in CH2Cl2 (0.5 mL) was stirred at 20 °C for 30 min. After removal of CH2Cl2 by a stream of N2, the ketone (0.1 mmol) in a physical mixture of HCO2H/Et3N (5/2 mol ratio, 0.25 mL) was added. The reaction mixture was stirred vigorously at 40 °C for the specified number of hours. Samples were withdrawn from the reaction mixture and the solvent was removed under a stream of N2. The samples were then dissolved in the HPLC eluent, filtered through silica and analysed by HPLC for determination of conversion and ee. Note: on scale-up the pressure built-up of CO2 must be taken into account. | |
With (R)-2,2',6,6'-tetramethoxy-4,4'-bis(di-3,5-dimethylphenylphosphine)3,3'-bipyridine; phenylsilane; Co(OAc)2.4H2O In toluene at 40℃; for 60h; Molecular sieve; Under air; optical yield given as %ee; enantioselective reaction; | ||
With bis[dichlorido(η5-1,2,3,4,5-pentamethyl-cyclopentadienyl)rhodium (III)]; lithium formate; L-prolinamide In water monomer at 35℃; for 18h; optical yield given as %ee; enantioselective reaction; | ||
With di-μ-chlorobis-[(η6-p-cymene)chlororuthenium(II)]; (3R,3aR,6R,6aS)-6-(benzyloxy)-hexahydrofuro-N-(2(tosylamino)ethyl)furo[3,2-b]furan-3-amine; potassium-t-butoxide; isopropanol at 25℃; for 24h; Inert atmosphere; optical yield given as %ee; enantioselective reaction; | ||
96 %Chromat. | With stems and germinated seed of Brassica oleracea variety italica In water monomer at 20℃; for 48h; optical yield given as %ee; enantioselective reaction; | |
Stage #1: 1-(4-trifluoromethylphenyl)ethanone With diethylzinc(II); 2,6-bis((R)-4-phenyl-4,5-dihydrooxazol-2-yl)pyridine In tetrahydrofuran; toluene at 20℃; for 20h; Inert atmosphere; Stage #2: With sodium hydroxide In tetrahydrofuran; methanol; diethyl ether; toluene for 0.5h; Inert atmosphere; optical yield given as %ee; enantioselective reaction; | ||
With (S)-(+)-2-(5-phenyl-4,5-dihydro-1,3-oxazol-2-yl)pyridine; trichlorosilane In chloroform at -20℃; for 16h; Inert atmosphere; optical yield given as %ee; enantioselective reaction; | ||
With anhydrous sodium formate In water monomer at 40℃; enantioselective reaction; | ||
With RuCl2P(C6H5)3C5H5FeC5H3CHP(C6H5)2CH3COCH2CHCH(CH3)2N; potassium isopropoxide; isopropanol at 20℃; for 0.333333h; optical yield given as %ee; enantioselective reaction; | ||
With (S,S)-DPENDS; C36H24Cl2O18P2RuS6(6-)*6Na(1+); hydrogen; potassium hydroxide In water monomer at 30℃; for 3h; Autoclave; optical yield given as %ee; enantioselective reaction; | 4.2. Typical procedure for asymmetric hydrogenation of aromatic ketones 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 β-DEX120 capillary column (30 m × 0.25 mm, 0.25 μm film) at 115 °C. The enantiomeric excess (ee value) was calculated from the equation: ee (%) = 100 × (R - S)/(R + S). | |
88.2 % ee | With [(R,R)-Teth-TsDpen RuCl]; hydrogen In methanol at 60℃; for 16h; enantioselective reaction; | |
88 % ee | With anhydrous sodium formate In water monomer at 40℃; for 12h; enantioselective reaction; | |
Multi-step reaction with 2 steps 1: (Cp*RhTsDPEN)+CF3SO3-; tetrabutylammonium bromide; anhydrous sodium formate / water monomer / 20 °C / Inert atmosphere; Schlenk technique; Sonication 2: Supelco Β-Dex 120 chiral column / Resolution of racemate | ||
86 % ee | With triruthenium dodecacarbonyl; (R,R)-4-methyl-N-{2-[(pyridin-2-ylmethyl)-amino]cyclohexyl}benzenesulfonamide In isopropanol at 80℃; for 48h; Inert atmosphere; Schlenk technique; enantioselective reaction; | General procedure for asymmetric transfer hydrogenation of ketones: General procedure: A mixture of catalyst (2 mol%) and Ru3 (CO)12 (0.67 mol%) in IPA (10 cm3) wasstirred at 80 °C under an inert atmosphere in a schlenk tube for 30 min. To this solution, ketone (1 mmol) was added and the resulting mixture was stirred at 80 °Cfor 48 h. The reaction mixture was filtered through a short column of silica using (EtOAc:hexane 1:1), a small amount of the filtrate was dilluted in EtOAc and then injected on the GC to determine the conversion and enantiomeric excess. |
46 % ee | With 1,4-diaza-bicyclo[2.2.2]octane; [Ru(η6-p-cymene)(κ2-o-{(11bS)-3H-dinaphtho(2,1-c:1',2'-e)phosphepin-4(5H)-yl}C6H4SO3)Cl] In methanol at 60℃; for 15h; Autoclave; Overall yield = 99 %Chromat.; enantioselective reaction; | |
20 % ee | With carbonylhydridotris(triphenylphosphine)iridium(I); C32H43N4P; isopropanol; potassium hydroxide at 40℃; for 5h; Schlenk technique; Inert atmosphere; enantioselective reaction; | ATH of aromatic ketones General procedure: To a 50mL Schlenk tube were added Ir complex (0.005mmol) and ligand 5 (0.005mmol). Under nitrogen atmosphere, freshly distilled and degassed iPrOH (10mL) were introduced. After stirring at 40°C for 30min, an appropriate amount of KOH/iPrOH solution was then added. The mixture was continually stirred for another 15min, ketone was then introduced and the mixture was stirred at 40°C for a certain period of time. At the end of experiment, the reaction products were analyzed by GC using a chiral CP-Chiralsil-Dex CB column. |
85.8 % ee | With C40H41FeNP2; tris(3,5-dimethylphenyl)phosphine; potassium-t-butoxide; hydrogen; copper (II) acetate In isopropanol at 15℃; for 12h; Inert atmosphere; Overall yield = 76 %; Overall yield = 626 mg; | |
74 % ee | With N-{(1R,2R)-2-[3-(3,5-dimethoxyphenyl)propylamino]-1,2-diphenylethyl}-4-methylbenzenesulfonamide ruthenium chloride; hydrogen In methanol at 60℃; for 16h; Inert atmosphere; Sealed tube; | |
84 % ee | With water monomer; anhydrous sodium formate at 40℃; enantioselective reaction; | |
84 % ee | With anhydrous sodium formate In water monomer at 40℃; for 4h; | Typical catalytic procedure 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). |
46 % ee | With hydrogen; 1,4-dithiothreitol In aq. phosphate buffer; dimethyl sulfoxide at 40℃; for 96h; Overall yield = 16 %Spectr.; enantioselective reaction; | |
88.2 % ee | With N-{(1R,2R)-2-[3-(3,5-dimethoxyphenyl)propylamino]-1,2-diphenylethyl}-4-methylbenzenesulfonamide ruthenium chloride; hydrogen In methanol at 60℃; for 16h; | |
65 % ee | With formic acid; [Cp*Ir(H2O)((R)-8-amino-5,6,7,8-tetrahydroquinoline)]SO4 In methanol; water monomer at 70℃; for 6h; enantioselective reaction; | Method A The ATH procedure when formic acid or sodium formate was used as the hydrogen donor. To a solution of the substrate (0.5mmol) in a 1:1 mixture methanol and water (2mL), [Cp Ir(H2O)(L)]SO4 (0.0025mmol) and hydrogen donor (2.5mmol, 5equiv) were added. The reaction mixture was stirred at 70°C for a fixed time (3h for 2-cyanoacetophenones, 6h for acetophenones and 24h for β-ketoesters). The reaction mixture was quenched with brine (4mL) and extracted with ethyl acetate (2×5mL). The combined organic layers were dried over Na2SO4 and concentrated in vacuo. |
78 % ee | With Ru/Al2O3/2ttp; hydrogen; potassium hydroxide; (2S)-N-phenylpyrrolidine-2-carboxamide In isopropanol at 30℃; for 10h; Autoclave; Overall yield = 57 %; enantioselective reaction; | Heterogeneous enantioselective hydrogenation reaction; general procedure General procedure: The hydrogenation was performed in a 20 mL stainless autoclave with a magnetic stirrer bar. The desired amounts of 1.0%Ru/γ-Al2O3/2tpp(20 mg), iPrOH (2 mL), KOH (0.18 mol L-1), L-proline derivative 1 and substrate (Substrate/Ru/proline derivative 1 = 300 : 1 : 27.4) were added into the autoclave and this was then sealed and purged with pure hydrogen several times (reaction pressure, PH2: 6.0 MPa). After the reactants were heated to 30 °C, the reaction timing began. After completion of the reaction (10 h), the organic phase was dried over MgSO4 and the conversion and enantiomeric excess were determined by GC analysis according to literature.17 With the exception of aromatic alcohol, no other products were detected (GC-MS and NMR). |
46 % ee | With trimethylamine-N-oxide; C38H38FeO6Si2; hydrogen In water monomer; isopropanol at 70℃; for 18h; Inert atmosphere; Autoclave; Schlenk technique; enantioselective reaction; | |
78 % ee | With fruits of Ligustrum lucidum (glossy privet) In aq. phosphate buffer; dimethyl sulfoxide at 20℃; for 144h; Overall yield = 5 %; enantioselective reaction; | |
With dichloro(benzene)ruthenium(II) dimer; formic acid; 1-[4-[4-[[[(1S,2S)-2-amino-1,2-diphenylethyl]amino]sulfonyl]phenoxy]butyl]-3-methyl-1H-imidazolium mono(trifluoroacetate); triethylamine at 20℃; for 24h; Inert atmosphere; Ionic liquid; Optical yield = 85 %ee; | Typical Procedure of RCATH General procedure: Acetophenone (120 mg, 1.0 mmol) was added to a solution of ionic ligand (0.012 mmol) and [RuCl2(benzene)]2 (2.5 mg, 0.005 mmol) in [bmim][PF6] (1.0 mL) with stirring under N2, followed by additionof a formic acid-triethylamine azeotropic mixture31) (bp 108 °C/29 mmHg, 0.5 mL). The reaction mixture was stirred at rt for 24 h. Next, n-hexane (5 mL×3) was added to the reaction mixture and the products were extracted by decantation of the upper layer, and the residual IL phase was dried in vacuo for 30 min. Acetophenone (120 mg, 1.0 mmol) and formic acid-triethylamine azeotropic mixture (0.5 mL) were added to the remaining IL solution, and the next cycle of the reaction was started. | |
65 % ee | With C28H36ClNOP2Ru; potassium-t-butoxide; hydrogen In ethanol at -40℃; for 16h; Autoclave; Inert atmosphere; enantioselective reaction; | |
40 % ee | With (R)-N-(3-amino-3-phenylpropyl)-4-methylbenzenesulfonamide; C10H14*Ru(1+)*Cl(1-)*C16H20N2O2S; anhydrous sodium formate In water monomer; dimethyl sulfoxide at 40℃; for 48h; Schlenk technique; enantioselective reaction; | |
24 % ee | With (S)-N-(3-amino-1-phenylpropyl)-4-methylbenzenesulfonamide; C10H14*Ru(1+)*Cl(1-)*C16H20N2O2S; anhydrous sodium formate In water monomer; dimethyl sulfoxide at 40℃; for 48h; Schlenk technique; enantioselective reaction; | |
46 % ee | With trimethylamine-N-oxide; C38H38FeO6Si2; hydrogen In water monomer; isopropanol at 70℃; for 18h; Autoclave; enantioselective reaction; | |
89 % ee | With (R)-bis[[N-(2-diphenylphosphinite-2-phenyl)ethyl]-1,1'-ferrocenylmethyldiamine(dichloro η6-p-cymene ruthenium(II))]; sodium hydroxide In isopropanol at 82℃; for 0.5h; Inert atmosphere; Schlenk technique; enantioselective reaction; | |
84 % ee | With (S)-bis[[N-(2-diphenylphosphinitepropyl)]-1,1'-ferrocenylmethyldiamine(dichloro η6-p-cymene ruthenium(II))]; sodium hydroxide In isopropanol at 82℃; for 0.33h; Inert atmosphere; Schlenk technique; enantioselective reaction; | |
86 % ee | With bis(1,5-cyclooctadiene)iridium(I) tetrafluoroborate; formic acid; anhydrous sodium formate; (1R,2R)-N<SUP>1</SUP>,N-di(naphthalen-1-yl)cyclohexane-1,2-diamine In methanol; water monomer at 70℃; for 22h; Inert atmosphere; Overall yield = 86 %; enantioselective reaction; | 2.4. Procedure for the reduction of ketone with [C16H24BF4Ir] andchiral amine ligand 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). |
73 % ee | With dichloro(o-isopropoxyphenylmethylene)(tricyclohexylphosphine)ruthenium(II); potassium-t-butoxide; (1R,2R)-N-(p-toluenesulfonyl)-1,2-diphenylethylenediamine In tetrahydrofuran; isopropanol at 30℃; for 20h; Inert atmosphere; Glovebox; enantioselective reaction; | |
82 % ee | With phenylsilane; C42H30BF5S In neat (no solvent) at 20℃; for 96h; Inert atmosphere; Glovebox; Overall yield = 57 %; Overall yield = 12.8 mg; enantioselective reaction; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With magnesium 1.) diethyl ether; Yield given. Multistep reaction; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
87% | With tris(2,2'-bipyridyl)ruthenium dichloride; dioxane dibromide; sodium L-ascorbate; In acetonitrile; at 20℃; for 8h;Irradiation; Green chemistry; | General procedure: To an oven-dried round bottom flask equipped with a magnetic stir bar was charged with dioxane dibromide (1.1 equiv.), tris(2,2?-bipyridyl)ruthenium(II) chloride (2 mol%), acetoarylone (AA, 1.0 equiv.), sodium ascorbate (3.0 equiv.) and dry CH3CN. The mixture was irradiated under a 5W Blue LED bulb at a distance of 5 cm under open-air atmosphere. After stirring at room temperature for 8-10 h, the solvent was removed under reduced pressure and the residue was purified by either recrystallization or filtration thru short pad silica gel column chromatography using hexane-ethyl acetate mixtures. The purity of the compound was confirmed by IR, 1H and 13CNMR measurements, vide infra. |
59% | With water; hydrogen bromide; dimethyl sulfoxide; at 20 - 70℃; for 9.5h; | <strong>[709-63-7]4-Trifluoromethylacetophenone</strong> (11.14 mmol, 2.096 g) was dissolved in dimethyl sulfoxide (13 mL), and 48% hydrobromic acid (5.4 mL) was gradually added at room temperature. After 9.5 hours of stirring at 70C, the reactor was cooled to room temperature. The reaction solution was poured into water and stirred for about 16 hours. The precipitated solid was recovered by filtration, washed with water and dried by means of a vacuum pump to give the desired product as a yellow solid(1.3116 g, yield 59%). ?"?H-NMR (ppm in DMSO-de)d 8.27 (ABq, J=8.3 Hz, 2H), 7.90 (ABq, J=8.3 Hz, 2H),6.97 (br.s, 2H, H20), 5.68 (br.s, 1H) |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
76% | With tert.-butylhydroperoxide; palladium(II) bis(diketonate) In benzene at 56℃; | |
68% | With manganese(II) bromide; water; lithium perchlorate; copper dichloride In acetonitrile at 60℃; for 8h; Sealed tube; Inert atmosphere; Electrochemical reaction; regioselective reaction; | |
66% | With dihydrogen peroxide In water; acetonitrile at 55℃; for 12h; | 2.4. General procedure for Wacker oxidation of olefins 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. |
43% | With [Fe(meso-tetraphenylporphyrinato)]mesylate; 4,4,5,5-tetramethyl-[1,3,2]-dioxaboralane In toluene at 25℃; for 4h; Glovebox; regioselective reaction; | General procedure for the oxidation of olefins. General procedure: The reaction was performed in a 15 mL tube equipped with a Teflon-coated magnetic stirrerbar. In a glove box, Fe(TPP)OMs (0.01 mmol, 10 mol%) and the olefin (0.1 mmol) werestirred in toluene (1 mL) at 25 °C. After Fe(TPP)OMs was dissolved completely, HBpin (0.12mmol, 1.2 eq) in toluene (1 mL) were added and stirred at 25 °C for the indicated time underair. The reaction mixture was passed through a short silica gel pad and concentrated in vacuo.The crude product was purified by silica gel column chromatography with the given eluent. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
99% | With D-glucose In aq. phosphate buffer at 25℃; for 24h; stereoselective reaction; | Preparative-Scale Synthesis of Enantiomeric β-Phenylalcohols (S)-2a-2i, (S)-2m and (S)-2n by Resting Cells General procedure: For isolation and characterization of the bioreduction product, the reaction was performedon a preparative scale: 300 g resting cells of R. rubra AS 2.2241 were resuspended in 1000 mL of Na2HPO4-KH2PO4 buffer (100 mM, pH 7.0) with 50 g glucose and 10 mM of each substrate (1a-1i,1m and 1n). The reaction mixture was incubated at 25°C and shaken at 220 rpm for 24 h. The cellswere removed by centrifugation and the supernatant was saturated with NaCl. The supernatantwas extracted with EtOAc (1000 mL 3). The organic phases were washed with brine, dried overNa2SO4, filtered and concentrated in vacuo. The residue was purified by flash chromatography onsilica gel (eluent: EtOAc/PE 1:20) to give the enantiomerically pure alcohols 2a-2i, 2m, 2n. The isolatedyield and ee of preparative-scale are comparable to those obtained from screening biotransformations.The spectroscopic data (1H and 13 C NMR, and HPLC retention times) of enantiomerically alcohols 2a-2i, 2m and 2n are in agreement with those obtained for racemic forms, as described in theSupplementary Materials. |
97% | With sodium t-butanolate; <i>tert</i>-butyl alcohol; (S)-2,2',6,6'-tetramethoxy-4,4'-bis(di(3,5-xylyl)phosphino)-3,3'-bipyridine In toluene at 0℃; for 14h; enantioselective reaction; | |
92% | With dichloro(pentamethylcyclopentadienyl)rhodium (III) dimer; C31H40N2O8S; sodium isopropylate; lithium chloride In tetrahydrofuran; isopropyl alcohol at 20℃; for 3h; Inert atmosphere; Schlenk technique; enantioselective reaction; |
92% | With [ruthenium(II)(η6-1-methyl-4-isopropyl-benzene)(chloride)(μ-chloride)]2; N-(tert-butoxycarbonyl)-L-valine-(6-amido-1-O-benzyl-6-deoxy-2,3-O-isopropylidene-α-D-mannofuranose); potassium <i>tert</i>-butylate; lithium chloride In tetrahydrofuran; isopropyl alcohol at 20℃; for 3h; enantioselective reaction; | |
91% | Stage #1: 1-(4-trifluoromethylphenyl)ethanone With copper acetylacetonate; (S)-Xyl-P-Phos In toluene at -20℃; for 12h; Stage #2: With sodium hydroxide In water; toluene for 3h; optical yield given as %ee; stereoselective reaction; | |
89% | Stage #1: 1-(4-trifluoromethylphenyl)ethanone With [RhCl2(p-cymene)]2; isopropyl alcohol; lithium chloride; Boc-L-alanine(2S)-hydroxypropylamide In tetrahydrofuran at 30℃; for 0.25h; Inert atmosphere; Stage #2: With sodium isopropylate In tetrahydrofuran at 30℃; for 0.25h; Inert atmosphere; optical yield given as %ee; enantioselective reaction; | |
85% | With 2-(N-morpholino)ethanesulfonic acidbuffer; NAD; isopropyl alcohol at 30℃; for 20h; acetone powder of Geotrichum candidum; | |
84% | Stage #1: 1-(4-trifluoromethylphenyl)ethanone With (S)-1-methyl-3,3-diphenyl-hexahydropyrrolo[1,2-c][1,3,2]oxazaborole In tetrahydrofuran at 0℃; for 0.166667h; Stage #2: With dimethylsulfide borane complex In tetrahydrofuran for 0.583333h; | 4.1 A solution of 4-trifluoromethyl acetophenone (1.88 g; 10 mmol) in dry THF (10 ml) was cooled in an ice bath and treated with freshly prepared solid (S)-2-methyl oxaborolidine (0.54g; 2 mmol). After 10 min., a solution of 2M borane-methyl sulfide complex (3 ml; 6 mmol) in THF was added dropwise over 5 min. TLC at the end of 30 min. showed that the starting material had been converted to a more polar product. The reaction was quenched with about 5 ml of CH3OH carefully until effervescence stopped; volatiles were removed in vacuo. The residue was dissolved in CH2Cl2 and washed with 1N HCl, water, 10% NaHCO3 solution and brine. Concentration in vacuo gave 2g of a yellow gum. Flash silica gel chromatography (FSGC) using 10-20% EtOAc in hexanes furnished the desired chiral alcohol (1.6 g; 84%) as a colorless oil. TLC Rf = 0.6 in 25% EtOAc:hexanes. |
77% | With Rhodotorula mucilaginosa 4056 In various solvent(s) | |
68% | Stage #1: 1-(4-trifluoromethylphenyl)ethanone With polymethylhydrosiloxane; (S)-(1,1'-binaphthalene)-2,2'-diylbis(diphenylphosphine) In toluene at 20℃; for 9h; Inert atmosphere; Stage #2: With tetrabutyl ammonium fluoride; water In tetrahydrofuran; diethyl ether for 0.5h; optical yield given as %ee; enantioselective reaction; | |
67% | With Synechocystis sp. PCC 6803 for 96h; Irradiation; Microbiological reaction; | |
66% | With triiron dodecarbonyl; C52H58N4P2; hydrogen; potassium hydroxide In methanol at 45℃; for 10h; enantioselective reaction; | |
50% | With seeds of Bauhinia variegata L. (Fabaceae) In water; dimethyl sulfoxide at 40℃; for 48h; Green chemistry; enantioselective reaction; | |
42% | With glucose dehydrogenase; D-glucose; ketoreductase from Pichia glucozyma; nicotinamide adenine dinucleotide phosphate In aq. buffer at 30℃; Enzymatic reaction; enantioselective reaction; | |
With D-glucose; D-glucose dehydrogense; Pyrococcus furiosus alcohol dehydrogenase In dimethyl sulfoxide at 37℃; | ||
With potassium <i>tert</i>-butylate; hydrogen In isopropyl alcohol; <i>tert</i>-butyl alcohol at 18 - 20℃; for 1h; | ||
With chiral dipyridylphosphine Ru; potassium <i>tert</i>-butylate; hydrogen In isopropyl alcohol; <i>tert</i>-butyl alcohol at 20℃; for 24h; | ||
With D-glucose; D-glucose dehydrogenase; NADPH In dimethyl sulfoxide at 20℃; | ||
96 % ee | Stage #1: 1-(4-trifluoromethylphenyl)ethanone With phenylsilane In toluene at -20℃; for 24h; Stage #2: With hydrogenchloride In water; toluene | Reaction conditions: 100 mg-42 g substrate, substrate concentration = 0.6-1 M toluene, >99% conversion is observed in all cases. |
94 % ee | Stage #1: 1-(4-trifluoromethylphenyl)ethanone With phenylsilane In toluene at -20℃; for 6h; Stage #2: With hydrogenchloride In water; toluene | Reaction conditions: 100 mg-42 g substrate, substrate concentration = 0.6-1 M toluene, >99% conversion is observed in all cases. |
Stage #1: 1-(4-trifluoromethylphenyl)ethanone With aluminum(III) nitrate nonahydrate; sodium hydroxide; polymethylhydrosiloxane; copper(II) nitrate trihydrate; sodium carbonate; (S)-(1,1'-binaphthalene)-2,2'-diylbis(diphenylphosphine) In toluene at 20℃; Inert atmosphere; Stage #2: With tetrabutyl ammonium fluoride In tetrahydrofuran; diethyl ether for 0.5h; | ||
87.0 % ee | With potassium <i>tert</i>-butylate; hydrogen In isopropyl alcohol; <i>tert</i>-butyl alcohol at 20℃; for 4.5h; Heating / reflux; | 14 Dichlorotris(triphenylphosphine)ruthenium(II) (14.4 mg; 0.015 mmol) and ligand 1a (7.9 mg; 0.018 mmol; 1.2 equiv based on Ru) were combined in a flask and purged with argon for 15 min. Argon-degassed isopropanol (3 mL) was added and the mixture was heated to reflux for 30 min and then cooled to ambient temperature to afford a rose-red 5.0 mM solution of the ruthenium complex of 1a. 4-Trifluoromethylacetophenone (5f) (188 mg; 1.0 mmol) was added to a pressure vessel, a pressure head was attached, and the vessel was evacuated and filled with argon ten times. Argon-degassed isopropanol (3.0 mL) was added and the vessel was evacuated and filled with argon five times. 1.0 mL of the solution of the ruthenium complex of 1a (0.005 mmol; 0.005 equiv) was added, the vessel was evacuated and filled with argon five times, and the mixture was stirred for 5 min. A 1.0 M solution of potassium tert-butoxide in tert-butanol (50 uL; 0.05 mmol; 0.05 equiv) was added affording an immediate color change from pale red to orange, and the vessel was evacuated and filled with argon ten times, then with hydrogen five times and pressurized to 40 psig (2.72 barg) hydrogen. The vessel was sealed and stirred vigorously for 2 h, during which time slow hydrogen uptake was noted. The vessel was sampled and analyzed by chiral GC to indicate 98.3% conversion and 87.2% ee for (S)-1-(4-trifluoromethylphenyl)ethanol (S-6f). The reaction was stopped after 4 h by evacuating and filling with argon five times and the solution was stripped to afford 0.19 g, which analyzed at 99.0% conversion, 87.0% ee S-6f. 1H NMR (CDCl3) δ 7.604 (d, 2H, J=7.70 Hz); 7.485 (d, 2H, J=7.97 Hz); 4.965 (q, 1H, J=6.05 Hz); 1.505 (d, 3H, J=6.60 Hz). Chiral GC [Cyclosil-B (J&W Scientific), 40° C. to 100° C. at 70° C./min, hold at 100° C. for 15 minutes, 100° C. to 170° C. at 15° C./min, hold at 170° C. for 7 min]: tR=14.7 min (5f), tR=20.0 min (R-6f), tR=20.2 min (S-6f). |
With D-glucose; D-glucose dehydrogenase; recombinant Sporobolomyces salmonicolor carbonyl reductase M242L/Q245P mutant; NADPH In dimethyl sulfoxide at 20℃; aq. phosphate buffer; Enzymatic reaction; optical yield given as %ee; enantiospecific reaction; | ||
With cinchonidine; hydrogen In toluene at 20℃; for 4h; optical yield given as %ee; enantioselective reaction; | ||
With [ruthenium(II)(η6-1-methyl-4-isopropyl-benzene)(chloride)(μ-chloride)]2; lithium chloride; sodium t-butanolate; Boc-L-alanine(2S)-hydroxypropylamide In tetrahydrofuran; ethanol; water at 40℃; for 1h; Inert atmosphere; optical yield given as %ee; enantioselective reaction; | General procedure for the ATH of aryl alkyl ketones General procedure: To a 10 ml vial equipped with a septum and stirring bar, [Ru(p-cymene)Cl2)2 (0.0024 g, 0.004 mmol), ligand 1 (0.0028 g, 0.0088 mmol), and LiCl (0.0034 g, 0.08 mmol) were added. The vial was sealed and the atmosphere exchanged via 3 × vacuum/N2 cycles. The vial was placed in an oil bath at 40 °C and dry THF (0.8 ml), 99% EtOH (0.4 ml) and the substrate (0.8 mmol) were added. The mixture was allowed to stir for 20 min, after which NaOtBu (0.0046 g, 0.048 mmol) dissolved in 99% EtOH (0.4 ml) was added. Aliquots were removed and filtered through a small plug of silica before analysis on chiral GC. Solid substrates were added to the vial at the same time as the metal precursor and the ligand. | |
With [ruthenium(II)(η6-1-methyl-4-isopropyl-benzene)(chloride)(μ-chloride)]2; C27H42N2O8; sodium isopropylate; isopropyl alcohol; lithium chloride In tetrahydrofuran at 20℃; for 3h; Inert atmosphere; optical yield given as %ee; enantioselective reaction; | ||
With C10H22N2*C44H32Cl2P2Ru; hydrogen; potassium hydroxide In isopropyl alcohol at 20℃; for 12h; enantioselective reaction; | ||
With phenylsilane; copper diacetate; (S)-2,2',6,6'-tetramethoxy-4,4'-bis(di(3,5-xylyl)phosphino)-3,3'-bipyridine In toluene at -20℃; for 12h; stereoselective reaction; | ||
With dichloro(pentamethylcyclopentadienyl)rhodium (III) dimer; C25H36N2O7S; sodium isopropylate; lithium chloride In tetrahydrofuran; isopropyl alcohol at 20℃; for 3h; Inert atmosphere; optical yield given as %ee; enantioselective reaction; | ||
With RuCl2P(C6H5)3C5H5FeC5H3CHP(C6H5)2CH3COCH2CHCH(CH3)2N; hydrogen; potassium carbonate In water; toluene at 20℃; for 16h; optical yield given as %ee; enantioselective reaction; | ||
95 % ee | With sodium formate In water at 40℃; for 3h; | 2.3 General procedure for asymmetric transfer hydrogenation General procedure: For asymmetric transfer hydrogenation of ketones, the catalyst 5 (15.0 mg, 4.0 μmol of Ru based on the ICP analysis), HCO2Na (0.27 g, 10.0 mmol), ketone (0.40 mmol), and 2.0 mL of water were added in a 10 mL round bottom flask in turn. The mixture was allowed to react at 40 °C for 3.0-9.0 h. [For asymmetric transfer hydrogenation of quinolines, the catalyst 5 (15.0 mg, 4.0 μmol of Ru based on the ICP analysis), HCO2Na (0.27 g, 10.0 mmol), quinolines (0.40 mmol), and 2.0 mL (2.0 M HCOOH/HCOONa buffer solution, pH = 5.0) were added in a 10 mL round bottom flask in turn. The mixture was allowed to react at 40 °C for 10.0-24 h.] During that time, the reaction was monitored constantly by TLC. After completion of the reaction, the catalyst was separated via centrifuge (10,000 r/min) for the recycle experiment. The aqueous solution was extracted by Et2O (3 × 3.0 mL). The combined Et2O was washed with brine twice and dehydrated with Na2SO4. After the evaporation of Et2O, the residue was purified by silica gel flash column chromatography to afford the desired product. The conversion could be determined by an external standard method, and the ee value could be determined by chiral GC using a Supelco β-Dex 120 chiral column (30 m × 0.25 mm (i.d.), 0.25 μm film) or a HPLC analysis with a UV-Vis detector using a Daicel OJ-H/OD-H/OB-H chiralcel column (Φ 0.46 × 25 cm). |
97 % ee | With water; sodium formate at 40℃; enantioselective reaction; | |
92 % ee | With dichloro(pentamethylcyclopentadienyl)rhodium (III) dimer; C33H44N2O8S; sodium isopropylate; lithium chloride In tetrahydrofuran; isopropyl alcohol at 20℃; for 80h; Inert atmosphere; Schlenk technique; enantioselective reaction; | |
92 % ee | With trans-1,2-(1S,2S)-1,2-diaminocyclohexane-N,N’-bis(2’-diphenylphosphinobenzoyl); rhodium(III) chloride hydrate; hydrogen; sodium carbonate In methanol at 20℃; for 22h; Autoclave; enantioselective reaction; | |
49 %Chromat. | With (S)-selective alcohol dehydrogenase whole-cell lyophilisate In aq. buffer enantioselective reaction; | |
97 % ee | With bis(1,5-cyclooctadiene)diiridium(I) dichloride; C49H67FeN2O2PS; hydrogen; lithium tert-butoxide In isopropyl alcohol at 20℃; for 12h; Inert atmosphere; Autoclave; | 14 Preparation of 1-p-Trifluoromethyl Benzyl Alcohol from p-Trifluoromethyl Acetophenone (S/C=10000) In a high-purity argon atmosphere, [Ir(COD)Cl]2 (3.4 mg, 0.005 mmol)The chiral ligand L6 (9.2 mg, 0.011 mmol) was dissolved in isopropanol (1 mL).Stirring for 3 hours at room temperature gives an orange clear solution.20 μL (0.001 mol%) of the orange solution was taken with a micro-injector and added to a mixed system of p-bromoacetophenone (2 mmol), isopropyl alcohol (2 mL) and lithium tert-butoxide (1 mol%). Place the reaction system in an autoclaveStir at room temperature under H2 (20 atm) for 12 hours. Remove the solvent under reduced pressureColumn chromatography (silica gel, eluent: ethyl acetate),The pure 1-p-trifluoromethyl phenyl ethanol was obtained and the product was analyzed by HPLC. The ee value was found to be 97%. |
97 % ee | With bis(1,5-cyclooctadiene)diiridium(I) dichloride; C49H67FeN2O2PS; hydrogen; lithium tert-butoxide In isopropyl alcohol at 25 - 30℃; for 12h; Autoclave; enantioselective reaction; | |
99 %Chromat. | With tris-(dibenzylideneacetone)dipalladium(0); copper(I) thiophene-2-carboxylate; triethyl phosphite In isopropyl alcohol at 30℃; for 24h; | |
95 % ee | With hydrogen; C32H12BF24(1-)*C39H43IrN2P(1+) In isopropyl alcohol at 20℃; for 0.5h; enantioselective reaction; | |
Multi-step reaction with 3 steps 1: sodium tetrahydroborate; methanol / 0.67 h / 0 - 20 °C / Inert atmosphere 2: (OC-6-23)-[2-[6-[(amino-κN)methyl]-2-pyridinyl-κN]-5-methylphenyl-κC][1,1'-(1,4-butanediyl)bis[1,1-diphenylphosphine-κP]]chlororuthenium(II); copper(l) chloride; sodium t-butanolate; (R,R)-1,2-bis(2,5-diphenylphospholanyl)ethane / toluene / 14 h / 20 °C / Glovebox; Inert atmosphere 3: tetrabutyl ammonium fluoride / tetrahydrofuran / 0.5 h / 20 °C / Inert atmosphere | ||
86 %Chromat. | With NADPH In isopropyl alcohol at 37℃; for 10h; enantioselective reaction; | |
> 99 % ee | With pyridoxal-5-phosphate; tris hydrochloride; diisopropylamine at 30℃; for 24h; Enzymatic reaction; enantioselective reaction; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
89% | With [(C5Me5)Rh(vinyltrimethylsilane)2] In cyclohexane at 120℃; for 72h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
97% | With p-toluenesulfonic acid monohydrate; acetic acid; In 1,2-dichloro-ethane; at 110℃; for 10h;Sealed tube; | General procedure: The corresponding alkyne (1 mmol) was added to a solution of p-toluenesulfonic acidmonohydrate (1 mmol, 0.190 g), acetic acid (0.5 mL) in CH2Cl2 (1.0 mL). Thereaction was then sealed and stirred at the indicated temperature (oC) and for theindicated amount of times (h) in Table 2. After completion, saturated aqueousNaHCO3 (10 mL) was added to quench the reaction and then extracted with CH2Cl2(10 mL×3). The organic layer was dried over Na2SO4 and concentrated in vacuo. Theresidue was purified by column chromatography to give the pure product. Forsubstrates 1j. 1l, 1n, 1p and 1q, DCE was used as solvent in consideration ofoperation convenience. |
91% | With chloro(1,3-bis(2,6-di-i-propylphenyl)imidazol-2-ylidene)gold(I); water; In methanol; at 120℃; for 6h; | The catalyst [(IPr) AuCl] (6.2mg, 1mol%), 4- trifluoromethyl-phenylacetylene (1mmol), in methanol (1ml) and water (0.5ml) was added successively 25ml reactor.After the reaction mixture was reacted for 6 hours at 120 , 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: 91% |
81% | With Perfluorooctanesulfonic acid; C8AgF17O3S*H2O; In water; at 100℃; for 8h;Darkness; | General procedure: To the mixture of phenylacetylene (1 mmol), water (3.0 mL),silver perfluorooctanesulfonate (5 mol%) and perfluorooctane sulfonateacid (2 mol%) was added. The mixture was stirred at 100 Cfor 8 h. The solution was extracted with n-hexane (diethyl ether)(3 5 mL), the combined extract was dried with anhydrous MgSO4. The rest of the solution was used for the next cycle of reaction. Theextraction solvent was removed and the crude product was separatedby column chromatography to give the pure sample. |
75% | With silver tetrafluoroborate; water; In acetic acid; at 110℃; for 10h; | General procedure: To the mixture of terminal alkyne (1mmol), water (2.0 equiv), and acetic acid (2 mL), silver tetrafluoroborate (5 mol%) was added. The mixture was stirred at 110C for 10 h. Water (10 mL) was added and the solution was extracted with ethyl acetate (3×8 mL), the combined extract was dried with anhydrous MgSO4. The solvent was removed and the crude product was separated by column chromatography to give the pure sample. 4.2.15. 1-(4-(Trifluoromethyl)phenyl)ethanone (2o). 1H NMR (400 MHz, CDCl3): delta=8.06 (d, J=8.0 Hz, 2H), 7.73 (d, J=8.0 Hz, 2H), 2.65 (s, 3H). 13C NMR (100 MHz, CDCl3): delta=196.9, 139.6, 134.2, 134.2, 128.6, 125.7, 125.7, 125.6, 125.6, 124.9, 26.7. MS (EI) m/z: 188, 173, 145, 125, 95, 75, 50. |
28% | With iron(III) sulfate hydrate; acetic acid; at 120℃; for 168h;Schlenk technique; | General procedure: Ferric sulfate hydrate (I, 8 mol%), glacial acetic acid (5 mL) and the alkyne (1 - 2 mmol) were introducedinto a 50 mL Schlenk tube, equipped with an air condenser, and the mixture kept under stirring at 95 C or120 C, until consumption of the substrate or no further conversion, as evidenced by TLC or GC. Uponcooling, the supernatant solution was poored into water and the residue washed twice with diethyl ether.After extraction with diethyl ether ( 2), the combined organic layers were washed with a saturated aqueoussolution of sodium bicarbonate and then water until neutrality. Alternatively, the crude from the reactions ofsubstrates featuring hydroxyl or carbonyl groups, as for 12, 15, 20 and 22, was obtained by removing aceticacid under vacuum, in order to reduce loss of material during biphasic extraction. The products were purified |
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 4-ethynyl-A, A, A-trifluorotoluene(170 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: 81% |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With palladium diacetate; oxygen; (-)-sparteine In 1,2-dichloro-ethane at 60℃; Title compound not separated from byproducts.; | ||
With [bis(acetoxy)iodo]benzene; potassium bromide In dichloromethane; water at 20℃; for 1h; Title compound not separated from byproducts.; | ||
30 % ee | With [(2S,2’S)-1,1’-bis((3-methyl-4-(2,2,2-trifluoroethoxy)pyridin-2-yl)methyl)-2,2’-bipyrrolidineMnII(OTf)2]; dihydrogen peroxide In acetonitrile at -10℃; Resolution of racemate; enantioselective reaction; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With sodium hydride; at 20℃;Cooling with ice; | A 100 ml round bottom flask was charged with a magnet, and sodium hydride (0.88 g, 22 mmol, purity 60%, 1.1 eq) was added thereto. Further 50 ml of ethyl acetate was added under ice bath, and p-trifluoromethylacetophenone (2.76 g, 20 mmol, 1.0 eq) was slowly added. After 30 min in ice bath, react at room temperature for more than 10 h, and monitored by TLC plate. After the reaction was completed, it was quenched with 10% ammonium chloride and extracted with ethyl acetate. The solvent was dried to give 1-p-trifluoromethylphenylbutane-1,3-dione. | |
2.24 g | 1-[4-(Trifluoromethyl)phenyl]ethan-1 -one (2 g; 10.63 mmol) is dissolved in 50 ml_ tetrahydrofurane and cooled to 0C. Sodium hydride dispersion (60 %; 1.275 g; 31.89 mmol) is added and reaction mixture is stirred for 30 minutes. At 0C ethyl acetate (waterfree 10.38 ml106.3 mmol) is added and the reaction mixture is stirred over night. The reaction is concentrated and then quenched with water, acidified with HCI (1 M aqueous solution) and extracted three times with ethyl acetate.The organic layer is dried over sodium sulfate, filtrated and concentrated under reduced pressure. The residue is purified by silica gel chromatography (eluent: cyclohexane /ethyl acetate 0 -> 30%).Yield: 2.24 g (92 % of theory)Mass spectrometry (ESI-): m/z = 229 [M-H]HPLC (Method 1 ): Retention time = 0.679 min. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
86% | Diethyl oxalate (266 mmol, 36.1 ml_, 38.8 g) was slowly added to a solution of sodium ethanolate (266 mmol, 99 ml_, 86 g) in (dry) toluene (415 ml.) at <;10 C under nitrogen. Once added the resulting orange solution was removed from the ice bath and stirred for 30 min. Then 1-(4-(trifluoromethyl)phenyl)ethanone (266 mmol, 50 g) was added portionwise. A very thick orange/brown suspension formed which was stirred overnight (mechanical stirring required) (NB -50 ml. toluene added to aid stirring). The suspension was filtered and the resulting solid washed with toluene to yield a yellow solid. This was partitioned between 1000 ml. of water containing 200 ml. of 2N HCI and diethyl ether. Once dissolved the organic layer was separated and washed with brine, dried over Na2SO4 and taken to dryness to give a yellow oil which solidified on cooling to give the title compound as a low melting yellow/orange solid (66 g, 86 %). MS (ESI) m/z (M+H+): 289.5. | |
80% | With sodium hydride; In DMF (N,N-dimethyl-formamide); at 0 - 45℃; for 0.75h; | Step 1.Preparation of 5-(4-Trifluoromethyl-phenyl)-isoxazole-3-carboxylic Acid Ethyl Ester (Compound 42A) sodium hydride (1.6 g, 63.7 mmol, 95%) was added to a solution of 1-(4-trifluoromethyl-phenyl)-ethanone (10.0 g, 53.1 mmol) and oxalic acid diethyl ester (8.7 ML, 63.7 mmol) in 75 ML dry DMF at 0 C. The reaction was allowed to come to room temperature and then heated to 45 C. for 45 minutes.The reaction was then cooled, concentrated in vacuo, and the residue taken up in EtOAc. The organic layer was then washed with 2 M HCl (1*100 ML), dried (Na2SO4) and the solvent removed in vacuo.Purification by flash column chromatography (gradient elution: 5% EtOAc/hexane to 55% EtOAc/hexane) gave the intermediate 2,4-dioxo-4-(4-trifluoromethyl-phenyl)-butyric acid ethyl ester (12.2 g, 80%) which was then taken up in EtOH and refluxed in the presence of hydroxyl amine hydrochloride (10.2 g, 132.3 mmol) for 3H. The reaction was then cooled, diluted with EtOAc, washed with dilute NaHCO3, brine, dried (Na2SO4), and concentrated in vacuo.Recrystallization from EtOAc/hexane gave 5.2 g of the title compound. MS m/z 286 (M+1). |
With sodium ethanolate; In tetrahydrofuran; ethanol; at 0 - 20℃; for 0.333333h; | Sodium ethoxide (35 mL, 191 mmol), a 21wt.% solution in ethanol, was diluted with tetrahydrofuran (15 mL) and cooled to 0 0C. A solution of 4-(trifluoromethyl)- acetophenone (4.5 g, 23.9 mmol) and diethyl oxalate (6.5 mL, 95.6 mmol) in tetrahydrofuran (20 mL) was added dropwise by addition funnel over 10 minutes. After stirring an additional 10 minutes at room temperature, the reaction mixture was diluted with diethyl ether, and IM HCl (80 mL) was added. The layers were separated and the aqueous layer was extracted with two additional portions of diethyl ether. The combined ether extracts were washed with brine, dried over MgSO4, and reduced in vacuo to obtain the title compound (6.89 g, 23.9 mmol). |
Example 62 Ethyl 2,4-dioxo-4-{4-(trifluoromethyl)phenyl}butanoate To a solution of sodium metal (239 mg, 10.4 mmol) in ethanol (17 mL) were slowly added drops of 1-{4-(trifluoromethyl)phenyl}ethanone (949 mg, 4.94 mmol) at 0 C. Thirty minutes later, drops of diethyl oxalate (0.70 mL, 5.19 mmol) were slowly added at the same temperature. Stirring was conducted overnight at room temperature, and when the reaction was completed as measured by TLC (Hexane:EtOAc=1:1), the reaction mixture was concentrated in vacuo. At 0 C., 3M HCl was added to the concentrate, followed by extraction with dichloromethane and water. The organic layer thus formed was dried over anhydrous magnesium sulfate, filtered, and concentrated to afford the title compound without further purification (1.30 g, 91%, crude yellow solid). 1H NMR (300 MHz, CDCl3) delta 8.14 (d, J=8.2 Hz, 2H), 7.84-7.79 (m, 2H), 7.13 (s, 1H), 4.46 (q, J=7.2 Hz, 2H), 1.47 (t, J=7.2 Hz, 3H) |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Stage #1: 4-isopropyl-1-(trifluoromethyl)benzene With triethylsilane; [Bu4N]4W10O32; oxygen In acetonitrile at 5 - 10℃; for 4h; Irradiation; Stage #2: With triphenylphosphine Further stages.; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
95.5% | With pyridine; hydroxylamine hydrochloride; In water; isopropyl alcohol; at 80℃; for 1h; | Add 4-trifluoromethylacetophenone (10.0g, 53.1mmol) to a 250mL reaction flask. hydroxylamine hydrochloride (5.5g, 79.7mmol),80mL of isopropanol, 20mL of water and 10mL of pyridine, the reaction was refluxed at 80 C for 1 hour. After the reaction, the solvent was distilled off under reduced pressure.Water was added, washed with suction, and dried to obtain 10.3 g of 4-trifluoromethylacetophenone oxime as a white solid with a yield of 95.5%. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
84% | With 4 A molecular sieve In toluene Heating; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 2 steps 1: NaH / tetrahydrofuran / 0 - 20 °C 2: hydrazine / methanol | ||
127 Production Example 127 3-(4-Trifluoromethylphenyl)-1H-pyrazole 5.82 g of the title compound was obtained as pale reddish brown crystals from 5.12 g 4'-(trifluoromethyl)acetophenone by the same method as in Production Example 3.1H-NMR (CDCl3) δ: 6.69(d, J=2.4Hz, 1H), 7.66(m, 3H), 7.90(d, J=8.8Hz, 2H) |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
91% | With hydrogenchloride; sodium methylate; In tetrahydrofuran; | Step 1: Preparation of 4,4-difluoro-1-[4-(trifluoromethyl)phenyl]-butane-1,3-dione Ethyl difluoroacetate (2.78 g, 22.4 mmol) was placed in a 100 mL round bottom flask and dissolved in ether (10 mL). To the stirred solution was added 25 weight % sodium methoxide (6.02 g, 27.8 mmol) followed by 4'-(trifluoromethyl)acetophenone (3.80 g, 20.2 mmol) and THF (20 mL). The reaction was stirred air room temperature overnight (15.6 hours), then treated with 3N HCl (20 mL). The organic layer was collected and washed with brine, dried over MgSO4, concentrated in vacuo to give a brown oil (4.88 g, 91%). 1 H NMR (acetone d6) 300 MHz 15.10 (br s, 1H), 8.03 (d, J=8.7 Hz, 2H), 7.77 (d, J=8.5 Hz, 2H), 6.59 (s, 1H), 6.02 (t, J=54.2 Hz, 1H); 19 F NMR (acetone d6) 300 MHz: - 63.70 (s), -127.10 (d); M+266. |
91% | With hydrogenchloride; sodium methylate; In tetrahydrofuran; | Step 1 Preparation Of 4,4-difluoro-1-[4-(trifluoromethyl)phenyl]-butane-1,3-dione Ethyl difluoroacetate (2.78 g, 22.4 mmol) was placed in a 100 mL round bottom flask and dissolved in ether (10 mL). To the stirred solution was added 25 weight % sodium methoxide (6.02 g, 27.8 mmol) followed by 4'-(trifluoromethyl)acetophenone (3.80 g, 20.2 mmol) and THF (20 mL). The reaction was stirred at room temperature overnight (15.6 hours), then treated with 3N HCl (20 mL). The organic layer was collected and washed with brine, dried over MgSO4, concentrated in vacuo to give a brown oil (4.88 g, 91%). 1 H NMR (acetone d6) 300 MHz 15.10 (br s, 1H), 8.03 (d, J=8.7 Hz, 2H), 7.77 (d, J=8.5 Hz, 2H), 6.59 (s, 1H), 6.02 (t, J=54.2 Hz, 1H); 19 F NMR (acetone d6) 300 MHz: - 63.70 (s), -127.10 (d); M+ 266. |
With sodium methylate; In methanol; tert-butyl methyl ether; at 20℃; for 19h; | a) To a stirred solution of <strong>[454-31-9]ethyl difluoroacetate</strong> (5.0 ml, 21 mmol) in tert-butyl-methyl-ether (30 ml) was added at room temperature a 5.4M solution of sodium methanolate in methanol (4.65 ml, 25 mmol) followed by a solution of commercially available 4-trifluoromethyl-acetophenone (4.0 g, 21 mmol) in tert-butyl-methyl-ether (10 ml). The reaction mixture was stirred at room temperature for 19 h, poured into ice/water (50 ml), acidified with 2N HCl (40 ml) and extracted with diethyl ether (2*100 ml). The combined organic layers were washed with brine (2*50 ml), dried (MgSO4) and evaporated to give crude 4,4-difluoro-1-(4-trifluoromethyl-phenyl)-butane-1,3-dione (5.87 g) as a yellow liquid, which was used without further purification. |
With sodium methylate; In methanol; tert-butyl methyl ether; at 20℃; for 19h; | Example C.1 7-Difluoromethyl-5-(4-trifluoromethyl-phenyl)-pyrazolo[1,5-a]pyrimidine-3-carboxylic acid; a) To a stirred solution of <strong>[454-31-9]ethyl difluoroacetate</strong> (5.0 ml, 21 mmol) in tert-butyl-methyl-ether (30 ml) was added at room temperature a 5.4M solution of sodium methanolate in methanol (4.65 ml, 25 mmol) followed by a solution of commercially available 4-trifluoromethyl-acetophenone (4.0 g, 21 mmol) in tert-butyl-methyl-ether (10 ml). The reaction mixture was stirred at room temperature for 19 h, poured into ice/water (50 ml), acidified with 2N HCl (40 ml) and extracted with diethyl ether (2×100 ml). The combined organic layers were washed with brine (2×50 ml), dried (MgSO4) and evaporated to give crude 4,4-difluoro-1-(4-trifluoromethyl-phenyl)-butane-1,3-dione (5.87 g) as a yellow liquid, which was used without further purification. | |
With sodium methylate; In methanol; tert-butyl methyl ether; at 20℃; for 19h; | To a stirred solution of <strong>[454-31-9]ethyl difluoroacetate</strong> (5.0 ml, 21 mmol) in tert-butyl-methyl- ether (30 ml) was added at room temperature a 5.4M solution of sodium methanolate in methanol (4.65 ml, 25 mmol) followed by a solution of commercially available 4- trifluoromethyl-acetophenone (4.0 g, 21 mmol) in tert-butyl-methyl-ether (10 ml). The reaction mixture was stirred at room temperature for 19 h, poured into ice/water (50 ml), acidified with 2N HCI (40 ml) and extracted with diethyl ether (2 x 100 ml). The combined organic layers were washed with brine (2 x 50 ml), dried (MgS04) and evaporated to give crude 4,4-difluoro-1-(4-trifluoromethyl-phenyl)-butane-1,3-dione (5.87 g) as a yellow liquid, which was used without further purification. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
3.54 g (77%) | In tetrahydrofuran; ethanol; water; ethyl acetate; | a] 1-(4-Trifluoromethyl-phenyl)-butane-1,3-dione To a stirred suspension of 1.70 g (39 mmol) sodium hydride in 20 ml THF kept under argon were added at room temperature 3.94 ml (40 mmol) ethyl acetate, followed by 0.1 ml of ethanol. Then, a solution of 3.76 g (20 mmol) 4-trifluoromethyl-acetophenone in 20 ml THF was added below 25 C., finally 0.12 g (0.32 mmol) dibenzo-18-crown-6 were added and the reaction mixture heated at reflux for 90 minutes. After cooling to approximately 0 C., the reaction mixture was acidified with 20 ml sulfuric acid (10% solution in water) and the reaction product was isolated by extraction with ether. The combined organic phases were dried over MgSO4 and evaporated. The residue formed was finally purified by flash-chromatography (silica gel, eluent: gradient of hexane and ethyl acetate) to give 3.54 g (77%) of 1-(4-trifluoromethyl-phenyl)-butane-1,3-dione as yellow crystals. MS: 230.1 (M), 215.0, 173.0. NMR: (CDCl3, 1H, delta, TMS, 300 MHz) 2.24 (s, 3H), 6.20 (s, 1H), 7.69-7.72 (d, J=7, 2H), 7.96-7.99 (d, J=7, 2H), 15.99 (s, 1H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
4.4 g (93%) | With bromine; In diethyl ether; N,N-dimethyl-formamide; | EXAMPLE 121 5-Chloro-3-[2-oxo-2-[4-(trifluoromethyl)phenyl]ethyl]-2(3H)-benzoxazolone (XXIV121) STR81 Bromine (0.67 ml, 13 mmol) was added dropwise to a solution of 4'-(trifluoromethyl)acetophenone (2.5 g, 13 mmol) in diethylether (20 ml) and 1,4-dioxane (10 ml) at room temperature. <strong>[95-25-0]Chlorzoxazone</strong> (2.19 g, 13 mmol) was treated with sodium hydride (400 mg, 13 mmol) in DMF for 15 min. under N2 and transferred by cannulation into the freshly prepared solution of bromide. The reaction mixture was stirred at 60 C. for 3 h, and poured into water (1 vol). The product was extracted with ethyl acetate, and the organic layer washed with water and brine and dried. Concentration gave a solid 4.4 g (93%) which was recrystallized from acetonitrile. mp 188-189 C.; IR(KBr, nu=cm-1) 1776, 1704, 1330, 1226, 1122; 1 H NMR (300 MHz, DMSO-d6) delta5.64 (2H, s), 7.20 (1H, dd, J=8.6 Hz, 2.1 Hz), 7.44 (1H, d, J=8.5 Hz), 7.57 (1H, d, J=2.1 Hz), 7.99 (2H, d, J=8.3 Hz), 8.27 (2H, d, J=8.1 Hz); MS(DCl)m/z: 356 (MH+) Anal. calcd. for C16 H9 ClF3 NO3: C, 54.03; H, 2.55; N, 3.94. Found: C, 53.73; H, 2.43; N, 3.88. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With potassium tert-butylate;18-crown-6 ether; In tetrahydrofuran; 1-Cyclopentyl-3-(4-trifluoromethylphenyl)-propane-1,3-dione; | EXAMPLE XIV 1-Cyclopentyl-3-(4-trifluoromethylphenyl)-propane-1,3-dione STR52 1.97 kg of potassium tert-butoxide, 2.26 kg of <strong>[4630-80-2]methyl cyclopentanecarboxylate</strong>, 1.66 kg of p-trifluoromethylacetophenone and 36 g of 18-crown-6 ether were refluxed in 18 litres of tetrahydrofuran for 4 hours. Quenching of the reaction was carried out using 16 litres of 10percent strength hydrochloric acid at room temperature. The aqueous phase was extracted with ethyl acetate and the combined organic phases were washed with saturated sodium chloride solution. After distilling off the solvent, the residue was distilled in an oil-pump vacuum at 1.5 mbar. 1.664 kg of 1-cyclopentyl-3-(4-trifluoromethylphenyl)propane-1,3-dione resulted as an oil, which crystallized completely on allowing to stand. Boiling point: 138-145° C./1.5 mbar. | |
With potassium tert-butylate;18-crown-6 ether; In tetrahydrofuran; 1-Cyclopentyl-3-(4-trifluoromethylphenyl)-propane-1,3-dione; | EXAMPLE XIV 1-Cyclopentyl-3-(4-trifluoromethylphenyl)-propane- 1,3-dione 1.97 kg of potassium tert-butoxide, 2.26 kg of <strong>[4630-80-2]methyl cyclopentanecarboxylate</strong>, 1.66 kg of p-trifluoromethylacetophenone and 36 g of 18-crown-6 ether were refluxed in 18 liters of tetrahydrofuran for 4 hours. Quenching of the reaction was carried out using 16 liters of 10percent strength hydrochloric acid at room temperature. The aqueous phase was extracted with ethyl acetate and the combined organic phases were washed with saturated sodium chloride solution. After distilling off the solvent, the residue was distilled in an oil-pump vacuum at 1.5 mbar. 1.664 kg of 1-cyclopentyl-3-(4-trifluoromethylphenyl)propane-1,3-dione resulted as an oil, which crystallized completely on allowing to stand. Boiling point: 138-145° C./1.5 mbar. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
51% | [00277] To a solution of 4'-(trifluoromethyl)acetophenone (8.0 g, 43 mmol) in toluene (15 mL) was added NaH (2.5 g, 64 mmol, 60% in mineral oil) and stirred for 30 min at 0 C. Diethyl carbonate (10 g, 85 mmol) was added, and the reaction mixture was stirred at 15 C for 3h. The reaction mixture was diluted with H20 (30 mL) and extracted with EtOAc (50 mL x 3). The combined organic layers were dried over anhydrous Na2S04, filtered, and concentrated under reduced pressure. The crude residue was purified by silica gel column chromatography (0 - 10% EtOAc in petroleum ether) to give ethyl 3-oxo-3-(4-(trifluoromethyl)phenyl)propanoate as a yellow oil (5.7 g, 51% yield); LCMS (ESI+): m/z 261 (M+H)+. | |
In water; | Reference Example 3 A mixture of 4'-trifluoromethylacetophenone (10.0 g), sodium hydride (60%, oil, 2.13 g) and diethyl carbonate (80 ml) was stirred at 80ØC for 90 min. Water was added to the reaction mixture, and the mixture was neutralized with dilute hydrochloric acid and extracted with ethyl acetate. The ethyl acetate layer was washed with saturated brine, dried (MgSO4) and concentrated. The residue was subjected to silica gel column chromatography, and ethyl 3-oxo-3-(4-trifluoromethylphenyl)propionate was obtained as an oil from a fraction eluted with ethyl acetate-hexane (1:9, volume ratio). | |
Sodium hydride (2.55 g, 106.4 mmmol) was taken in dry THF (40 mL) in a 250 mL round bottom flask under N2 and cooled it down to 0 C. To it was added a solution of 1-(4-(trifluoromethyl)phenyl)ethan-1-one (10 g, 53.2 mmol) in THF (10 mL). The reaction mixture was stirred at rt for 30 min followed by the addition of diethyl carbonate (25.8 mL, 212.8 mmol). The reaction mixture was then stirred at rt for 14 h. Ice-cooled water was added dropwise to quench the reaction. It was extracted with EtOAc (3 * 50 mL). The combined organic layer was dried over anhydrous Na2SO4 and concentrated under reduced pressure. The crude was triturated with Et2O afford 2j as a brown solid (10.0 g, 72%). LCMS(ESI) m/z 259.14 [M-H+]; 61% (purity). |
With sodium hydride; In toluene; mineral oil; for 1h;Inert atmosphere; Reflux; | General procedure: Compounds 2 were prepared according to the previous literature(Scheme 4) [16]. A mixture of compound 7 (66 mmol), toluene(20 mL) and NaH (3.7 g, 60% in mineral oil, 92 mmol)was added to adried 250 mL RBF under N2 atmosphere. The mixturewas heated toreflux and a solution of compound 6 (33 mmol) in toluene (20 mL) was added into the mixture dropwise. After 1 h, the mixture wascooled to room temperature. Glacial acetic acid (10 mL) was addeddropwise and a heavy pasty solid separated. Ice-cold water(150 mL) was slowly added until the solid was dissolvedcompletely. Then, the reaction system was diluted with 200 mL ofEtOAc. The organic layer was separated,washed withwater (20 mL)and brine (20 mL) and dried over Na2SO4. And the combined extractswere concentrated under reduced pressure and purified bycolumn chromatography to afford the pure product b-keto esters 2. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 2 steps 1: copper(ll) bromide / ethanol; chloroform; ethyl acetate / 0.5 h / 65 °C 2: ethanol / 2 h / Reflux | ||
Multi-step reaction with 2 steps 1: copper(ll) bromide / ethyl acetate; chloroform / 0.5 h / 65 °C 2: copper(ll) bromide / ethanol / 2 h / Reflux | ||
Multi-step reaction with 2 steps 1: copper(ll) bromide / ethyl acetate / 3 h / Reflux 2: ethanol / 2 h / Reflux |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
99% | With ethyl acetohydroximate; scandium tris(trifluoromethanesulfonate); In ethanol; at 40℃; for 24h;Inert atmosphere; | In a test tube (containing a stirring bar) at room temperature under an argon atmosphere, 2-naphthacetophenone (57.9 mg, 0.346 mmol, 1.0 eq.), Scandium trifluoromethanesulfonate (III) (8.4 mg, 0.0170 mmol, 5 mol%), Ethanol (0.34 ml, 1.0 M), Ethyl acetohydroxamate (52.6 muL, 0.510 mol, 1.5 eq.) And the mixture was stirred at room temperature for 24 hours. Thereafter, 20 ml of ethyl acetate was added, The reaction solution was filtered through a pad of silica gel under reduced pressure, the solvent was distilled off, and the NMR was measured. Silica gel column chromatography (manufactured by Kanto Chemical Co., Ltd., silica gel 60 (40 to 50 mum), Hexane / methylene chloride = 2/8 to methylene chloride / diethyl ether = 95/5) To obtain white (E) -2-naphthacetophenoxime (compound 3a) (Yield 99%) of the title compound. In Example 1,Using various ketone compounds instead of 2-naphthacetophenone,A ketoxime compound was synthesized as shown by the following chemical formula.The obtained ketoxime compound, yield, E / Z are shown below. |
98% | With hydroxylamine hydrochloride; sodium hydroxide; In ethanol; water; at 20℃; for 24h;pH 9.0;Cooling with ice; | General procedure: To a 50 mL round bottom flask, ketone (10.0 mmol) and hydroxylamine hydrochloride (15.0mmol) were added in 25 mL ethanol/ water (4:1). A quantity of NaOH solution was added topH=9 in ice bath, stirred at room temperature for 24 hours. The mixture was then extracted withethyl acetate (3 × 20 mL). The combined organic extracts were dried over Mg2SO4andconcentrated under reduced pressure. The ketoxime products were obtained by recrystallization ofS4ethyl acetate or petroleum ether. |
98% | With hydroxylamine hydrochloride; sodium hydroxide; In ethanol; water; at 0 - 20℃; for 24h;pH 9.0; | General procedure: To a 50 mL round bottom flask, ketone (10.0 mmol) and hydroxylamine hydrochloride (15.0mmol) were added in 25 mL ethanol/ water (4:1). A quantity of NaOH solution was added top H=9 in ice bath, stirred at room temperature for 24 hours. The mixture was then extracted with ethyl acetate (3 × 20 mL). The combined organic extracts were dried over Mg2SO4 and concentrated under reduced pressure. The ketoxime products were obtained by recrystallization of ethyl acetate or petroleum ether. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Stage #1: 1-(4-trifluoromethylphenyl)ethanone; trimethoxy(phenylethynyl)silane With dilithium (R)-3,3'-diphenylbinaphtholate In tetrahydrofuran; hexane at 0℃; for 4h; Inert atmosphere; Stage #2: With tetrabutyl ammonium fluoride In tetrahydrofuran; hexane for 0.5h; enantioselective reaction; | ||
Stage #1: 1-(4-trifluoromethylphenyl)ethanone; trimethoxy(phenylethynyl)silane With dilithium (R)-3,3'-diphenylbinaphtholate In tetrahydrofuran; hexane at 0℃; for 4h; Inert atmosphere; Stage #2: With tetrabutyl ammonium fluoride In tetrahydrofuran; hexane for 0.5h; Inert atmosphere; optical yield given as %ee; enantioselective reaction; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With (S,S)-(+)-N,N’-bis(3,5-di-tert-butylsalicylidene)-1,2-cyclohexanediaminomanganese(III) chloride; [bis(acetoxy)iodo]benzene; potassium bromide In dichloromethane; water at 23℃; for 0.5h; Inert atmosphere; optical yield given as %ee; enantioselective reaction; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
72% | Stage #1: cyclopropylphenylsulfide With n-butyllithium In tetrahydrofuran; hexane at 0℃; for 1h; Inert atmosphere; Stage #2: 1-(4-trifluoromethylphenyl)ethanone In tetrahydrofuran; hexane at 0℃; for 4h; Inert atmosphere; Stage #3: With water In tetrahydrofuran; hexane Inert atmosphere; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
96% | With sodium hydride at 25℃; for 0.0833333h; | 67.1 Step 1. Methyl 3-oxo-3-(4-(trifluoromethyl)phenyl)propanoate Into a 500-mL 3-necked round-bottom flask, was placed 1-(4-(trifluoromethyl)phenyl)ethanone (15.27 g, 81.22 mmol, 1.00 equiv), dimethyl carbonate (50 mL), sodium hydride (5.53 g, 138.25 mmol, 1.70 equiv, 60%). The resulting solution was stirred for 5 mins at 25° C. The mixture was concentrated by evaporation. The solids were collected by filtration and washed with 3*50 ml of H2O. This resulted in 19.28 g (96%) of methyl 3-oxo-3-(4-(trifluoromethyl)phenyl)propanoate as a yellow solid. |
95% | With sodium hydride In toluene Inert atmosphere; Schlenk technique; Reflux; | |
92% | Stage #1: carbonic acid dimethyl ester With sodium hydride In tetrahydrofuran Stage #2: 1-(4-trifluoromethylphenyl)ethanone In tetrahydrofuran Reflux; |
Stage #1: carbonic acid dimethyl ester With sodium hydride In toluene Reflux; Inert atmosphere; Stage #2: 1-(4-trifluoromethylphenyl)ethanone In toluene Reflux; Inert atmosphere; | ||
Stage #1: carbonic acid dimethyl ester With sodium hydride In toluene Inert atmosphere; Reflux; Stage #2: 1-(4-trifluoromethylphenyl)ethanone In toluene at 20℃; Inert atmosphere; Reflux; | ||
With sodium hydride In toluene Reflux; Inert atmosphere; | ||
With sodium hydride at 100℃; for 4h; | ||
With sodium hydride In toluene Inert atmosphere; Reflux; | ||
With sodium hydride at 100℃; for 4h; Inert atmosphere; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
83% | With Y[N(SiMe3)2](kappa2-C6H5C(O)NC6H3(iPr)2)2(THF); In neat (no solvent); at 25℃; for 0.666667h;Schlenk technique; Inert atmosphere; Glovebox; Green chemistry; | General procedure: A 30 mL Schlenk flask, equipped with a magnetic stirring bar, was charged with the bis(amidate)ytterbium amide 1 (10.1 mg,0.01 mmol for aldehydes and 20.2 mg, 0.02 mmol for ketones), diethyl phosphite (12.0 mmol) and aldehyde or ketone(10.0 mmol). The resulting mixture was allowed to stir at 25 C for the given time. After the reaction was quenched by water (3.0 mL), the mixture was extracted with ethyl acetate (3 x 10.0 mL). The combined organic layer was dried over anhydrous Na2SO4 and filtered, concentrated under reduced pressure and purified by chromatography on silica gel [ratio of eluent:ethylacetate/petroleum ether (60-90 C) from 1:10 to 1:5] to afford the desired products. Except for 7s, all alpha-hydroxy phosphonates reported here are known [23d,h,g], and their 1H NMR spectra are consistent with reported data. 7s has been characterized by 1H, 13C, and 31P NMR spectroscopies. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
33.2% | With acetyl chloride In ethanol at 0 - 20℃; for 36h; Inert atmosphere; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
75% | General procedure: A solution of (EtO)2P(O)CH2P(O)(OEt)2 (1.44 g, 5 mmol) in THF (2 mL) was slowly added at 0 C to a slurry of NaH (0.19 g, 5.5 mmol, 70% in oil) in THF (10 mL). After the addition, the mixture was stirred at room temperature for 0.5 h. To the mixture, a solution of ketone (4.25 mmol) in THF (3 mL) was added. The reaction mixture was stirred at room temperature until the ketone disappeared when monitored by TLC. The mixture was then diluted with ether and washed with an aqueous solution of saturated NH4Cl (25 mL × 1) and brine (25 mL × 1). The organic layer was separated, and dried over anhydrous NaSO4. After removal of the volatiles, the residue was purified by column chromatography (silica gel, AcOEt/hexane 1:1). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
82% | With C28H35PRuS(1+)*C33H15BF23(1-) In hexane at 20℃; for 0.0833333h; Inert atmosphere; chemoselective reaction; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
90% | With sodium hydroxide In ethanol; water at 20℃; for 1h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
1: 78% 2: 77% | With iodine In neat (no solvent) at 85℃; for 2h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
5%; 11%; 6% | With sodium ethanolate; copper; for 16h;Reflux; | Compound 1034 (2.5g, 10mmol) and Cu powder (220mg, 3.5mmol) were added to 11a40 (3.5g, 15mol) and NaOEt (1.6g, 23mmol) in EtOH (35mL). The mixture was boiled under reflux for 16h, then poured into H2O and acidified with aq HCl (2M). Extraction (Et2O), evaporation and chromatography (hexane/EtOAc 4:1) gave 12a (160mg, 5%) as yellow crystals, with data as below. Further elution gave 13 (210mg, 11%) as a colourless oil (lit.41 oil): 1H NMR (CDCl3) delta 2.56 (3H, s, Me), 7.55 (2H, d, J=8.2Hz, Ph 3,5-H2), 8.14 (2H, d, J=8.2Hz, Ph 2,6-H2). Further elution gave 14 (130mg, 6%) as a colourless oil (lit.42 oil): 1H NMR (CDCl3) delta 1.41 (3H, t, J=7.2Hz, Me), 4.41 (2H, q, J=7.2Hz, CH2), 7.75 (2H, d, J=8.2Hz, 3,5-H2), 8.16 (2H, d, J=8.2Hz, 2,6-H2). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
9.1 g | With caesium carbonate; 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene; bis(dibenzylideneacetone)-palladium(0) In 1,4-dioxane at 150℃; for 0.5h; Inert atmosphere; Microwave irradiation; | 1.i (i) 2-(2,4-Dichloro-phenyl)-1 -(4-trifluoromethyl-phenyl)-ethanone A solution of 6 g of 2,4-Dichloro-1 -iodo-benzene, 15.7 g of CS2CO3, 63 mg of Pd(dba)2 (Bis(dibenzylidenacetonpalladium), 127 mg of Xantphos (9,9-Dimethyl-4,5- bis(diphenylphosphino)xanthene) and 8.3 g of 1 -(4-Trifluoromethyl-phenyl)-ethanone in 45 ml of dioxane was heated under argon for 30 min at 150°C by microwave irradiation. After cooling to room temperature and dilution with saturated aqueous sodium hydrogen carbonate solution, the reaction mixture was filtered through a chem elut cartridge by eluting with ethyl acetate. The solvents were removed under reduced pressure and the crude product was purified by chromatography on silica gel eluting with a gradient of n-heptane/ethyl acetate. The fractions containing the product were combined and the solvent evaporated under reduced pressure. Yield: 9.1 g. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
95% | With copper(l) iodide; 1,10-Phenanthroline; sodium t-butanolate In toluene at 20℃; for 4.5h; Inert atmosphere; Sealed tube; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
72 % ee | Stage #1: isopropyl alcohol With dichloro(1,5-cyclooctadiene)ruthenium(II); (R)-(6-methoxyquinolin-4-yl)((1S,2R,4S,5R)-5-vinylquinuclidin-2-yl)methanamine at 20℃; for 0.5h; Inert atmosphere; Stage #2: With potassium hydroxide for 0.5h; Inert atmosphere; Stage #3: 1-(4-trifluoromethylphenyl)ethanone at 0℃; for 96h; Inert atmosphere; enantioselective reaction; | Asymmetric transfer hydrogenation reaction; general procedure Cinchona alkaloid was added to [Ru(COD)Cl2]n in dry degassedi-PrOH (10 mL) and stirred at room temperature for 30 min under argon. The base was added and the reaction mixture was stirred for another 30 min. The aromatic ketone was then added in one portion(0.1 M) and the reduction was conducted at the given temperature for the time indicated. After completion of the reaction, the resulting solution was neutralised, and then extracted with Et2O. The organic phase was dried over MgSO4 and the conversion and enantiomeric excess were determined by GC analysis according to the literature.4,16-18(S)-(-)-1-Phenylethanol: Table 4, entry 1; 83% yield, 90% ee (S),[α]25D = -45.0 (c 1.0, CH2Cl2) [lit.4, [α]23D = -50.0 (c 1.0, CH2Cl2)]. 1H NMR(400 M, CDCl3), δ 1.40-1.55 (m, 3H), 1.90 (s, 1H), 4.95 (d, J = 6.3 Hz,1H), 7.20-7.65 (m, 5H). GC β-DEX120 capillary column, column temperature: 115 °C, t (R) = 12.7 min, t (S) = 13.5 min.(S)-(-)-1-Phenyl-1-propanol: Table 4, entry 2; 98% yield, 86% ee (S),[α]25D = -30.5 (c 5.0, EtOH) [lit.4, [α]23D = -34.0 (c 5.03, EtOH)]. 1H NMR(400 M, CDCl3),δ 1.15-1.25 (m, 3H), 1.69 (s, 1H), 1.72-1.92 (m, 2H), 4.61(d, J = 4.5 Hz, 1H), 7.20-7.56 (m, 5H). GC β-DEX120 capillary column, column temperature: 115 °C, t (R) = 14.5 min, t (S) = 15.9 min. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
66% | With iodine at 100℃; for 8h; | General procedure for synthesis of 2-amino-4-(substituted-phenyl)-1,3-thiazoles General procedure: A mixture of thiourea (7, 50 mmol), the corresponding acetophenone (6, 25 mmol) and iodine(25 mmol) is stirred at 100 °C for 8 h. Then the reaction mixture is cooled, extracted with diethylether to remove excess of acetophenone, and then washed with aqueous sodium thiosulfate to remove excess iodine and later with cold water. The crude product is dissolved in hot water, filtered to remove sulphone, and the filtrate is basified with aqueous Na2CO3 to yield the corresponding 2-amino-4-(substituted-phenyl)-1,3-thiazole (5). The crude product is purified by recrystallization from alcohol. The synthesis and spectral data of compounds 5a-i have been reported by us earlier [2]. The data in respect of compounds 5j-l is described here. |
18% | With iodine for 4h; Heating; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
60% | With oxygen; copper(II) bis(trifluoromethanesulfonate); toluene-4-sulfonic acid In hexan-1-ol at 110℃; for 24h; Sealed tube; Schlenk technique; | |
45% | With oxygen; lithium chloride In N,N-dimethyl acetamide at 160℃; for 12h; Schlenk technique; Sealed tube; | |
14% | With tris(2,2'-bipyridyl)ruthenium dichloride; oxygen; toluene-4-sulfonic acid In acetonitrile at 82℃; for 48h; Irradiation; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
87% | With [(η5-C5Me5)Ir(6,6'-dihydroxy-2,2'-bipyridine)(H2O)]OTf2; potassium hydroxide In water monomer at 100℃; for 12h; | |
87% | With [(η5-C5Me5)Ir(6,6'-dihydroxy-2,2'-bipyridine)(H2O)]OTf2; potassium hydroxide In water monomer for 12h; Reflux; Green chemistry; | 8 2- (4- (trifluoromethyl) phenyl) quinoline Trifluoroacetophenone (226 mg, 1.2 mmol),[Cp * Ir (6,6 '- (OH) 2bpy) (H2O)] [OTf] 2 (8.3 mg,0.01 mmol, 1 mol%), potassium hydroxide (56 mg, 1.0 mmol, 1.0 equiv.), O-aminobenzyl alcohol (123 mg, 1.0 mmol) and water (1 mL) were sequentially added to a 5 mL round bottom flask.The reaction mixture was refluxed in air for 12 hours and then cooled to room temperature.Extraction with ethyl acetate, removal of the solvent by rotary evaporation followed by column chromatography (developing solvent: petroleum ether / ethyl acetate) gave the pure target compound in 87% yield |
86% | With dimanganese decacarbonyl; sodium hydroxide In toluene at 110℃; for 2h; Inert atmosphere; Glovebox; Sealed tube; |
83% | With potassium hydroxide; 1,3-diisopropyl-1H-benzo[d]imidazol-3-ium bromide In toluene at 60℃; for 1h; | |
82% | With (1,3-bis(2,6-diisopropylphenyl)-2,3-dihydro-1H-imidazol-2-yl)copper(I) chloride; dimethyl sulfoxide; potassium hydroxide In toluene at 20℃; for 6h; | |
80% | With 1,3,5-trimethyl-benzene at 170℃; for 24h; Inert atmosphere; | |
80% | With [(p-cymene)Ru(BiBzImH2)Cl][Cl]; Cs2CO3 In tert-Amyl alcohol at 125℃; for 12h; | 4.4. Procedure for acceptorless dehydrogenative coupling of ketoneswith o-aminobenzyl alcohols to quinolines catalyzed by [(p-cymene)Ru(BiBzImH2)Cl][Cl] General procedure: In a round-bottomed flask with a condenser tube were added oaminobenzylalcohols 1 (1 mmol) and ketones 2 (1.2 mmol, 1.2equiv), cat. 1 (6 mg, 0.01 mmol, 1 mol %), Cs2CO3 (163 mg,0.5 mmol, 0.5 equiv) and tert-amyl alcohol (1 mL). The reactionmixture was heated at 125 C in an oil bath for 12 h and thencooled to ambient temperature, concentrated in vacuo and purifiedby flash column chromatography with hexane/ethyl acetate (10:1,v/v) to afford corresponding products. |
69% | With potassium-t-butoxide; Zn(2-((4-chlorophenyl)diazenyl)-1,10-phenanthroline)Cl<SUB>2</SUB>; zinc powder In toluene at 90℃; for 10h; | |
68% | With potassium-t-butoxide; oxygen; [Fe(2-((4-chlorophenyl)diazenyl)-1,10-phenanthroline)Cl2] In toluene at 100℃; for 16h; | 4.3. Procedure for substituted quinoline synthesis General procedure: To an oven-dried 20.0 mL round bottom flask containing a magnetic stir bar, a mixture of catalyst 1 (3.0 mol%), tBuOK (0.5equiv.), acetophenone (1.1 mmol), and 2-aminobenzyl alcohol(1.0 mmol) were added under air. To it, 5.0 mL dry toluene was added by a syringe. The reaction vessel was then fitted with a water condenser and allowed to stir at 100 °C for 16 h, under air. The reaction was monitored by TLC. After the reaction was complete, the resulting mixture was concentrated under vacuum using a rotary vacuum evaporator and purified by silica gel column chromatography using petroleum ether/ethyl acetate (18: 1). |
66% | With C18H11Cl3CuN4; sodium hydroxide In toluene at 85℃; for 18h; | |
66% | With samarium diiodide; potassium-t-butoxide In tetrahydrofuran; toluene at 140℃; for 1h; Microwave irradiation; Inert atmosphere; | |
55% | With C24H22N6Ni; potassium-t-butoxide In toluene at 80℃; for 10h; | |
55% | With C27H24Cl3F6IrN2; potassium hydroxide In toluene at 135℃; for 16h; | |
54% | With sodium hydroxide In toluene at 135℃; for 24h; Green chemistry; | |
51% | With nickel(II) dibenzotetramethyltetraaza[14]annulene; potassium-t-butoxide In toluene at 90℃; Inert atmosphere; Schlenk technique; Sealed tube; Green chemistry; | |
40% | With caesium hydroxide monohydrate In 1,4-dioxane at 120℃; for 24h; Schlenk technique; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
59% | With methanesulfonic acid; tetrabutylammoniun azide In 1,2-dimethoxyethane at 80℃; for 0.0833333h; Flow reactor; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
72% | Stage #1: methyl 4-(trifluoromethyl)benzoate With sodium hydride In dimethyl sulfoxide at 20℃; for 0.666667h; Inert atmosphere; Stage #2: 1-(4-trifluoromethylphenyl)ethanone In dimethyl sulfoxide at 60℃; for 4h; | 3 Synthesis of intermediate (65-a): A dry 250ml bottle was repeatedly evacuated and filled with nitrogen three times, placed sodium hydride (5eq) followed by dimethyl sulfoxide (150mL), followed by methyl 4-(trifluoromethyl)benzoate (1eq), After stirring at room temperature for 40 minutes, 4'-trifluoromethylacetophenone (0.7eq) was slowly added, and the reaction was completed by heating to 60°C for 4 hours.Then slowly add ice water (1000mL) to quench the remaining sodium hydride, then add petroleum ether (1000mL x 3) for extraction, concentrate to obtain a reddish-brown liquid, after distillation, a clear liquid intermediate (65-a) is obtained, the yield is 72 %. |
57% | With sodium hydride In tetrahydrofuran at 0℃; for 16h; Inert atmosphere; Reflux; | 1,3-Bis(4-methylphenyl)propane-1,3-dione(37b). General procedure: NaH (2.00 g, 50 mmol, 60% in oil) was washed free from oil with dryhexane (10 mL) at 0C under Ar. Dry THF (30 mL) was added, followed by methyl4-methylbenzoate (3.30 g, 22 mmol) in dry THF (10 mL) and 4-methyl-1-acetylbenzene (2.66 g, 20 mmol) in dry THF (10mL) at 0C under Ar. The suspension was stirred under reflux for 16 h. The mixturewas cooled and filtered (Celite). The solid was washed with EtOH(20 mL). The combined filtrates were poured into Et2O (20 mL) andaq. HCl (1 M, 20 mL). The aq. layer was extracted (Et2O, 2 ). The combinedextracts were washed (brine, 3 ) and dried. Evaporation and recrystallisation (EtOH) gave 37b(2.50 g, 50%) as yellow needles. |
48% | With sodium hydride In tetrahydrofuran; mineral oil at 20℃; |
45% | With 18-crown-6 ether; sodium hydride In tetrahydrofuran; ethanol; mineral oil at 70℃; for 6.5h; Inert atmosphere; | |
18% | With sodium hydride In toluene Inert atmosphere; Reflux; | |
Stage #1: 1-(4-trifluoromethylphenyl)ethanone With sodium hydride In tetrahydrofuran at 0℃; for 1h; Stage #2: methyl 4-(trifluoromethyl)benzoate In tetrahydrofuran at 0 - 20℃; | ||
With sodium hydride In tetrahydrofuran at 0 - 20℃; for 4h; Inert atmosphere; | ||
With sodium hydride In tetrahydrofuran; mineral oil at 0℃; Inert atmosphere; Reflux; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
88% | With iodine; 4-aminobenzene sulfonic acid In dimethyl sulfoxide at 100℃; for 5h; | Typical Procedure for the Preparation of 2,5-Diphenyloxazole General procedure: A test tube was charged with 1a (0.32 mmol), 2a (0.38 mmol), I2 (2.0 equiv.) and PABS (0.5equiv.). Then 2 mL DMSO was added to the reaction system. The reaction was stirred at 100 oCfor 5 h. After cooling to room temperature, the solvent diluted with 10 mL ethyl acetate andwashed with 5 mL brine and dried over anhydrous Na2SO4. After the solvent was evaporated invacuo, the residues were purified by column chromatography, eluting with petroleum ether/EtOAc to afford pure 3aa. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
64% | General procedure: An over-dried 50 mL Schlenk tube equipped with a magnetic stir bar was charged with CuTC (95.3 mg, 0.5 mmol, 1.0 eq) and TBAT (809.8 mg, 1.5 mmol, 3.0 eq). The seal tube was evacuated and backfilled with N2. Then HCF2OTf (233 μL, 2.0 mmol, 4.0 eq) and DMF (10.0 mL) were added by syringes. The mixture was stirred at room temperature for 5 min and diaryliodonium salt (0.5 mmol, 1.0 eq) was added under N2. After stirring for 5 min, the reaction was quenched by H2O and the aqueous layer was extracted with Et2O. The combined organic layers were washed with brine, dried over Na2SO4 and concentrated under reduced vacuum. The resulting residue was purified by column chromatography or HPLC to provide the desired product. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
49% | With caesium carbonate; In dimethyl amine; at 20℃;Glovebox; | In the glove box,Cs2CO3 (0.6 mmol) and 4-trifluoromethylacetophenone (0.2 mmol) were weighed into a 25 mL reaction tube,Measure the amount of DMA (1 mL) into the reaction tube.A bromodifluoromethylphosphonium salt (0.6 mmol) was weighed,With DMA (2mL) dissolved, inhaled into the syringe.Stirred at room temperature,A DMA solution of bromodifluoromethylphosphonium salt was injected into the reaction tube at a rate of 0.5 mL / h with a syringe pump.After the injection, the reaction is over. The solution in the reaction tube was transferred to a separatory funnel, 15 mL of water was added, extracted three times with dichloromethane (10 mL x 3), and the organic phases were combined and washed three times with water (10 mL x 3). The final obtained organic phase was dried over anhydrous sodium sulfate, and the solid was filtered off, the solvent removed by rotary evaporation, on a silica gel column with n-pentane and ethyl acetate as eluent, to give the final isolated product difluoromethyl, yield 49%, purity> 99.9% (nuclear magnetic purity). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
95% | With potassium acetate; In ethanol; at 20℃; | To a solution of <strong>[21938-47-6]2,3-dichlorophenylhydrazine hydrochloride</strong> (1.07 g, 5.00 mmol), and 4-acetylbenzotrifluoride (941 mg, 5.00 mmol) in ethanol (20 mL), potassium acetate (981 mg, 10.00 mmol) was added, and the resulting mixture was stirred overnight at room temperature. After completion of the reaction, the solvent was evaporated, then water was added to the residue, and the resulting mixture was extracted with ethyl acetate. The extract was dried over anhydrous magnesium sulfate, and the solvent was evaporated to obtain the title compound. (1.65 g, yield 95%). 1H-NMR (CDCl3) delta: 2.34 (3H, s), 7.00 (1H, dd, J=1.3 Hz, 8.2 Hz), 7.20 (1H, t, J=8.2 Hz), 7.59 (1H, dd, J=1.3 Hz, 8.2 Hz), 7.64 (2H, d, J=8.6 Hz), 7.91 (2H, d, J=8.6 Hz), 8.01 (1H, br) |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
41 %Spectr. | With 3-methylpyridin-2-ylamine; chlorobis(ethylene)rhodium(I) dimer; ethyl crotonate; 1,3-bis(2,4,6-trimethylphenyl)4,5-dimethyl-1,3-dihydro-2H-imidazol-2-ylidene; water; toluene-4-sulfonic acid In 2-methyltetrahydrofuran at 150℃; for 120h; Inert atmosphere; Glovebox; Sealed tube; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
77% | With potassium carbonate; at 120℃; for 48h; | (0568) 1-[4-(Trifluoromethyl)phenyl]ethanone (50 g, 0.266 mol) and diethyl oxomalonate (50.9 g, 0.292 mol) were stirred at 120 C for 48 h. The reaction mixture was cooled to rt and the solid was filtered and washed with petrol ether (300 ml.) affording 70 g (77%) of the title compound. 1H-NMR (400MHz, DMSO-de): d [ppm] = 1.19 (t, 6H), 3.76 (s, 2H), 4.18 (q, 4H), 6.47 (s, 1 H), 7.91 (d, 2H), 8.15 (d, 2H). |
73% | at 120℃; for 48h; | 1-[4-(Trifluoromethyl)phenyl]ethanone (50 g, 0.266 mol) and diethyl oxomalonate (66.0 g,0.379 mol) were stirred at 120C for 48 h. The reaction mixture was cooled to rt and the solid was filtered and washed with petrol ether (300 mL) affording 70 g (73%) of the title compound.1H-NMR (400MHz, DMSO-d6): 6 [ppm] = 1.19 (t, 6H), 3.76 (s, 2H), 4.18 (q, 4H), 6.47 (s, 1H),7.91 (d, 2H), 8.15 (d, 2H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
79% | With bismuth(lll) trifluoromethanesulfonate; dipotassium peroxodisulfate; silver nitrate In water at 30℃; for 24h; Inert atmosphere; Green chemistry; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
1: 59% 2: 14% | With iron(III) chloride; palladium diacetate; copper(II) acetate monohydrate; DavePhos In dimethyl sulfoxide; N,N-dimethyl-formamide at 120℃; for 40h; Inert atmosphere; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
38 % ee | With ruthenium; (R,R)-1,2-diphenylethylenediamine; hydrogen; cinchonidine In ethanol at 40℃; for 10h; Autoclave; Ionic liquid; enantioselective reaction; | 4.3 General Procedure for the Heterogeneous Enantioselective Hydrogenation General procedure: In stainless steel autoclave, previously prepared Rh(0) catalyst was charged with the appropriate modifier, co-solvent and substrate, and then the autoclave was sealed and purged with pure hydrogen several times. After the reactants were heated to predetermined temperature, the reaction timing began. After completion of the reaction and cooling to ambient temperature, the products were isolated by high speed centrifugation or liquid-liquid extraction and analyzed by gas chromatography. Isolation of the Rh NPs for TEM analysis after catalytic cycles was achieved by dissolving the reaction mixture in acetone(5mL), centrifuging (5000 rpm for 10min), washing with acetone (3 × 5mL) and drying under vacuum. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
56.1% | With sodium hydroxide In ethanol Cooling with ice; | 2.2.2. Synthesis of 3-(2H-chromen-3-yl)-1-phenylpropen-1-one derivatives (2a-2s) General procedure: Benzopyran-3-carbaldehyde (0.64 g, 4.0 mmol) and theappropriately substituted acetophenone (5.2 mmol) wereadded to 20 mL absolute ethanol and 8 mL NaOH solution(3.5 M) in a round-bottom flask, which was placed in an icewaterbath and stirred overnight. TLC was used to monitorthe reaction. The product was recrystallized from ethyl acetateto acquire crystals of the chromen-chalcone derivatives2a-2s. (Scheme 1). |
With sodium hydroxide In ethanol at 20℃; | The synthesis of 3-(2H-chromen-3-yl)-1-(2,4-dichloro)phenyl-prop-2-en-1-one 3g and nineteen 3-(3H-benzo[f]chromen-2-yl)-1-(2,4-dichloro)phenylprop-2-en-1-one 4g General procedure: To a solution of 2H-chromene-3-carbaldehyde 1 or 3H-benzo[f]chromene-2-carbaldehyde 2 (1mmol) and 2,4-dichloroacetophenone (1mmol) in absolute ethanol (20mL), NaOH solution (3.5M, 8mL) was added and stirred overnight at room temperature. The reaction mixture was diluted with water and the precipitate was filtered and crystallized from ethanol to give the target compounds. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
General procedure: A mixture of compound 8 (0.3 mmol) and corresponding ketones (0.4 mmol) in Ti(OPr)4 was stirred at 70 C for 8 h and cooled to room temperature. MeOH (5 mL) and NaCNBH3 (1.6 mmol) wasadded to the mixture, and stirred for 5 h at 40 C. The mixture was quenched by 1 N NaOH (10 mL), filtered by Celite, and washed by MeOH. The MeOH was evaporated under vacuo. The residue wasdiluted by H2O, and extracted by Et2O. The combined organic layer was washed by brine, dried over anhydrous MgSO4, filtered, andconcentrated. The residue was purified over silica gel column(DCM: MeOH = 30 : 1) to yield oils 11c-g (yield, 40-70%). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
95% | With piperidine In ethanol at 70℃; | 2.2. Synthesis of indole chalcone derivatives General procedure: In an RB flask, 1H-indole-3-carboxaldehyde (1 mmol) andappropriate acetophenones (1.2 mmol) were taken and 5 ml ofethanol and 5 drops of piperidine were added. The resulting solutionwas then refluxed at 70 °C and TLC was used to track the reactionprogress. Upon accomplishement of the reaction, thereaction mixture was transferred into cold water and furtherneutralized utilizing 1 N hydrochloric acid. The crude precipitateformed was filtered out, dried and recrystallized from chloroform.All the indole chalcones (1 to 25) were characterized using spectraltechniques and the spectral data are listed in the supplementarydata. |
50% | With sodium hydroxide In ethanol; water at 20℃; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
78% | With sodium hydroxide In ethanol at 0℃; for 3h; | 4.3.1. General procedure for the synthesis of 2-benzylidene-1-indanone derivates General procedure: We placed NaOH (2.4 eq.) in 30 mL of ethanol at 0 C in a round flask equipped with a magnetic stirring bar. We added o-phthalaldehyde(1.0 eq.) and acetophenone (1.0 eq.) to this suspension and the resulting mixture was stirred at this temperature until the reaction was completed (monitored by TLC). After approximately 3 h, the reaction mixture was poured into a mixture of ice-water and acidified with concentrated hydrochloric acid. The resulting solid was filtered and purified by column chromatography using hexane/ethyl acetate as eluent.The characterization of 2-benzylidene-1-indanones derivatives 3a-d has been previously described in Refs. [33,34] |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
66% | With 1,8-diazabicyclo[5.4.0]undec-7-ene; scandium tris(trifluoromethanesulfonate) In tetrahydrofuran at 25℃; for 4h; Inert atmosphere; Glovebox; Sealed tube; | 4.2. General procedure of the synthesis of 4-difluoromethylated andperfluoroalkylated pyrazoles General procedure: In a glove box filled with nitrogen, to an oven-dried 5 mL pressure tube equipped with a stir bar was added aryl ketone 2 (0.20 mmol, 1.0 equiv), 1a, 1b or 1c (0.60 mmol, 3.0 equiv), Sc(OTf)3 (1.0 mg, 0.0020 mmol, 1 mol%), and THF (1.5 mL). Then, DBU (92.4 mg, 0.60 mmol, 3.0 equiv) was added dropwise over 0.5 min using a microsyringe. The tube was sealed with Teflon screw cap and the solution was stirred at 25 °C for 4 h. The crude mixture was diluted with ethyl acetate (4 mL) and a saturated ammonium chloride solution (4 mL). The organic phase was extracted and dried over anhydrous sodium sulfate, filtered, and the solvent was removed by rotary evaporation. The resulting 3-5 was purified by column chromatography on silica gel with petroleum ether/ethyl acetate. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
88.6% | With sodium hydroxide In ethanol for 2h; | 4.1 1. Synthesis of 1-(4-trifluoromethylphenyl)-3-(4-hydroxymethylphenyl)-2-en-1-one Using 4-trifluoromethyl acetophenone and 4-hydroxymethyl benzaldehyde to react in sodium hydroxide and absolute ethanol, the yield was 88.6%. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
20% | Stage #1: 1-(4-trifluoromethylphenyl)ethanone With iodine In dimethyl sulfoxide at 110℃; for 1h; Schlenk technique; Stage #2: 4-phenyl-semicarbazide With potassium carbonate In dimethyl sulfoxide for 15h; Schlenk technique; | 1,3,4-Oxadiazoles 3aa-ka; General Procedure General procedure: A 25 mL Schlenk-flask equipped with a magnetic stirrer bar wascharged with the appropriate methyl ketone 1 (0.2 mmol, 1.0equiv.), I2 (0.5 mmol), and DMSO (1.0 mL), and the mixture washeated at 110 °C for 1 h. 4-Phenylsemicarbazide (2; 0.24 mmol),K2CO3 (0.6 mmol), and DMSO (1.0 mL) were added, and theresulting mixture was stirred at 110 °C for 15 h. The reactionwas then quenched with 5% aq Na2S2O3 (20 mL), and themixture was extracted with CH2Cl2 (3 × 20 mL). The organiclayer was dried (Na2SO4) and concentrated, and the residue waspurified by chromatography (silica gel) |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With sodium tetrahydridoborate Inert atmosphere; Schlenk technique; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
60% | With sulphur In lithium hydroxide monohydrate; dimethyl sulfoxide at 95℃; for 6h; Green chemistry; | General procedure for 2-amino-4-arylthiazoles synthesis General procedure: A mixture of aromatic methyl keones (1 mmol), 50 wt% aqueous cyanamide solution (1275 mg, 15 mmol) and sulfur powder (64 mg, 2 mmol) in DMSO (1 mL) was stirred at 95 °C for 6 h. After the completion of reaction, it was cooled to room temperature and was treated with H2O (20 mL) and extracted with EtOAc (20 mL × 3). The combined organic layer was dried over anhydrous Na2SO4, concentrated, and purified through silica gel column chromatography to afford the substrates 3a-q. |
Tags: 709-63-7 synthesis path| 709-63-7 SDS| 709-63-7 COA| 709-63-7 purity| 709-63-7 application| 709-63-7 NMR| 709-63-7 COA| 709-63-7 structure
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