* 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.
With oxone; sodium ortho-iodobenzenesulfonate In acetonitrile at 90℃; for 18 h;
General procedure: Method A: a mixture of 2,2,2-trifluoro-1-(4-methoxyphenyl)ethanol (2c) (0.206 g, 1.0 mmol) and sodium 2-iodobenzenesulfonate (8) (as monohydrate, 0.016 g, 0.05 mmol, 5 molpercent), powdered Oxone.(R). (0.554 g, 0.9 mmol) in CH3CN (5 mL) was stirred at 90 °C under the atmosphere of air. After stirring for 18 h, the reaction mixture was allowed to cool to room temperature. The reaction mixture was filtered, being successively washed with ethyl acetate. The combined filtrates were washed with water (3.x. 10 mL), dried over anhydrous Na2SO4, and concentrated in vacuo. The residue was purified by silica gel column chromatography (eluent: hexane/EtOAc = 10/1) to give 2,2,2-trifluoro-1-(4-methoxyphenyl)-1-ethanone (1c) (0.165 g, 0.81 mmol, 81percent yield).
Reference：
[1] Tetrahedron Letters, 2013, vol. 54, # 33, p. 4483 - 4486
[2] Journal of Fluorine Chemistry, 2012, vol. 137, p. 99 - 104
[3] Chemical Communications, 2018, vol. 54, # 78, p. 11017 - 11020
2
[ 108-37-2 ]
[ 383-63-1 ]
[ 321-31-3 ]
Yield
Reaction Conditions
Operation in experiment
97.3%
Stage #1: With n-butyllithium In tetrahydrofuran at -78 - -50℃; for 1 h; Stage #2: at -78 - 20℃;
Accurate weighing of m-chlorobromobenzene (3-chlorobromobenzene) (19.15 g, 0.1 mol) was dissolved in 100 ml of tetrahydrofuran and the ethanol-dry ice bath cooled the solution temperature to a negative 78 to negative 50 ° C. A solution of butyllithium (0.12 mol) was added dropwise and incubated for 1 hour at a negative 78 to negative temperature of 50 ° C. Then, ethyl trifluoroacetate (18.4 g, 0.13 mol) was added dropwise at this temperature. After completion of the dropwise addition, the mixture was withdrawn and the mixture was spontaneously stirred at room temperature. Then, hydrochloric acid (30 ml, 0.3 mol) was added dropwise, the layers were stirred, the organic layer was depressurized to remove the solvent. 20.7 g of crude 2,2,2-trifluoro-(3'-chlorophenyl)ethanone was obtained and distilled to give 20.3 g of a colorless transparent liquid, content of 95percent, yield 97.3percent.
Stage #1: With isopropylmagnesium chloride In tert-butyl methyl ether at -20 - -10℃; for 1 h; Stage #2: at -20 - 20℃;
Accurate weighing of m-chloroiodobenzene (3-chloroiodobenzene) (23.85 g, 0.1 mol) was dissolved in 120 ml of methyl tert-butyl ether and the ethanol cooled ice bath cooled to a negative temperature of 20 to minus 10 ° C. A solution of isopropylmagnesium chloride (0.13 mol) was added dropwise and incubated for 1 hour at a negative 20 to minus 10 ° C after completion of the dropwise addition. Then, trifluoroacetate (18.4 g, 0.13 mol) was added dropwise at this temperature. After completion of the dropwise addition, the mixture was stirred and cooled to room temperature, and then hydrochloric acid (30 ml, 0.3 mol) was added dropwise. The organic layer was removed under reduced pressure to give 20.5 g of crude 2,2,2-trifluoro-(3'-chlorophenyl)ethanone and distilled to give 18.3 g of a colorless transparent liquid, content of 95.9.7percent, the yield of 88percent.
Reference：
[1] Patent: CN106518636, 2017, A, . Location in patent: Paragraph 0117; 0118; 0119; 0120
4
[ 360-92-9 ]
[ 541-73-1 ]
[ 321-31-3 ]
Yield
Reaction Conditions
Operation in experiment
83.4%
Stage #1: With magnesium; ethylene dibromide In tetrahydrofuran at 40 - 50℃; for 2 h; Stage #2: at 10 - 30℃; for 0.5 h;
The flask was added with magnesium powder (3 g, 0.125 mol), 20 ml of tetrahydrofuran, stirred. Accurately weighed m-dichlorobenzene (14.7 g, 0.1 mol) was dissolved in an additional 30 ml of tetrahydrofuran and added to a constant pressure dropping funnel, and 10percent of the m-dichlorobenzene solution was added to the flask. The flask was heated to 40-45 ° C and then 0.3 ml of 1,2-dibromoethane was added to initiate the reaction. Then, the m-dichlorobenzene solution was slowly added dropwise at this temperature. After completion of the dropwise addition, the mixture was stirred at 40 to 50 ° C for 2 hours, and then the inside of the flask was cooled to 10 to 30 ° C, and trifluoroacetyl diethylamine was added dropwise, and the mixture was stirred for 30 minutes. Then, hydrochloric acid (30 ml, 0.3 mol) was added and the layers were separated and the organic layer was removed under reduced pressure to give 20.8 g of crude product. After distillation, 17.4 g of colorless transparent 2,2,2-trifluoro-(3'-chlorophenyl)ethanone was obtained, the content was 99.3percent and the yield was 83.4percent.
Reference：
[1] Patent: CN106518636, 2017, A, . Location in patent: Paragraph 0125; 0126; 0127; 0128
5
[ 340-07-8 ]
[ 108-37-2 ]
[ 321-31-3 ]
Reference：
[1] Bioorganic and Medicinal Chemistry, 2004, vol. 12, # 5, p. 979 - 993
6
[ 434-45-7 ]
[ 321-31-3 ]
Reference：
[1] Journal of the American Chemical Society, 1951, vol. 73, p. 709
7
[ 76-05-1 ]
[ 36229-42-2 ]
[ 321-31-3 ]
Reference：
[1] Journal of the American Chemical Society, 1980, vol. 102, # 12, p. 4167 - 4172
8
[ 108-37-2 ]
[ 407-25-0 ]
[ 321-31-3 ]
Reference：
[1] Bulletin of the Chemical Society of Japan, 1997, vol. 70, # 12, p. 3081 - 3090
9
[ 587-04-2 ]
[ 321-31-3 ]
Reference：
[1] Tetrahedron Letters, 2013, vol. 54, # 33, p. 4483 - 4486
[2] Chemical Communications, 2018, vol. 54, # 78, p. 11017 - 11020
10
[ 36229-42-2 ]
[ 407-25-0 ]
[ 321-31-3 ]
Reference：
[1] Bulletin of the Chemical Society of Japan, 1990, vol. 63, # 4, p. 1129 - 1137
11
[ 625-99-0 ]
[ 76-05-1 ]
[ 321-31-3 ]
Reference：
[1] Canadian Journal of Chemistry, 1980, vol. 58, p. 2497 - 2503
12
[ 108-37-2 ]
[ 353-85-5 ]
[ 321-31-3 ]
Reference：
[1] Journal of medicinal chemistry, 1966, vol. 9, # 2, p. 176 - 178
13
[ 108-37-2 ]
[ 360-92-9 ]
[ 321-31-3 ]
Reference：
[1] Journal of Organic Chemistry USSR (English Translation), 1982, vol. 18, p. 317 - 324[2] Zhurnal Organicheskoi Khimii, 1982, vol. 18, # 2, p. 365 - 373
With oxone; sodium ortho-iodobenzenesulfonate; In acetonitrile; at 90℃; for 18h;
General procedure: Method A: a mixture of 2,2,2-trifluoro-1-(4-methoxyphenyl)ethanol (2c) (0.206 g, 1.0 mmol) and sodium 2-iodobenzenesulfonate (8) (as monohydrate, 0.016 g, 0.05 mmol, 5 mol%), powdered Oxone (0.554 g, 0.9 mmol) in CH3CN (5 mL) was stirred at 90 C under the atmosphere of air. After stirring for 18 h, the reaction mixture was allowed to cool to room temperature. The reaction mixture was filtered, being successively washed with ethyl acetate. The combined filtrates were washed with water (3× 10 mL), dried over anhydrous Na2SO4, and concentrated in vacuo. The residue was purified by silica gel column chromatography (eluent: hexane/EtOAc = 10/1) to give 2,2,2-trifluoro-1-(4-methoxyphenyl)-1-ethanone (1c) (0.165 g, 0.81 mmol, 81% yield).
With Almag CRED A131; NADP; glucose dehydrogenase; In water; dimethyl sulfoxide; isopropyl alcohol; at 20℃;pH 7.0;Enzymatic reaction;
General procedure: Almac CRED (200 mg) and NADP or NAD (10 mg)were charged into a 100 mL round bottomed flask and dissolvedin 0.1 M potassium phosphate buffer (pH 7, ca. 50 mL). Next, IPA(7 mL) was added, followed by a solution of ketone (900-1700 mg) in DMSO (2.5-5 mL, depending on solubility). This was shaken at room temperature overnight and the reaction progresswas checked by 1H NMR. If not complete, additional CRED (100-200 mg) and NADP or NAD (10 mg) were added and shaking wascontinued. This was repeated until the reaction reached completion.If the reaction appeared to stall or proceed very slowly, experimentalmethod C was used.
With Almag CRED A131; NADP; glucose dehydrogenase; In water; dimethyl sulfoxide; isopropyl alcohol; at 35℃; under 375.038 Torr;pH 7.0;Enzymatic reaction;
General procedure: Method C: Almac CRED (200 mg) andNADP or NAD (10 mg) were measured into a 250 mL roundbottomedflask then dissolved in 0.1 M potassium phosphate buffer(pH 7, ca. 50 mL). IPA (7 mL) was added, followed by a solutionof ketone (900-1700 mg) in DMSO (2.5-5 mL, depending on solubility).This was stirred at 35 C under 500 mbar reduced pressureto aid removal of acetone formed by IPA oxidation. Standardwork-up procedure: The pH of the reaction mixture was adjustedif necessary (basic or acidic depending on estimated pKa of alcoholproduct) with either 1 M NaOH or 1 M HCl. The reaction mixturewas then extracted with MTBE (3 100 mL).
(-)-(S,E)-5-(3-chlorophenyl)-6,6,6-trifluoro-5-hydroxy-1-phenylhex-2-en-1-one[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
94%
General procedure: Jones reagent (0.25 mL) was added dropwise to a solution of homoallic alcohols 1 (0.4 mmol,4.0 equiv.) in tert-butylbenzene (1.0 mL) at 0 C over a period of 3.5-7 h. When the reactionwas completed (monitored by TLC), the sample was stewed for a moment until a clear separationbetween the organic and aqueous phase was formed, and the aqueous phase was released. Thenthe trifluoromethyl ketone 2 (0.1 mmol, 1.0 equiv.) was added, the reaction mixture was stirred at10 C for 10 min. Sodium phosphate (0.2 mmol, 2.0 equiv.) and catalyst 4 (0.01 mmol, 0.1 equiv.)were added sequentially (10 min interval). The reaction mixture was stirred at 10 C and monitoredby TLC. Upon complete consumption of trifluoromethyl ketone 2, the reaction mixture was directlyloaded onto a short silica column, followed by gradient elution with PE/EA mixture (20/1-5/1 ratio).Removing the solvent in vacuum afforded products 5a-y.
Accurate weighing of m-chlorobromobenzene (3-chlorobromobenzene) (19.15 g, 0.1 mol) was dissolved in 100 ml of tetrahydrofuran and the ethanol-dry ice bath cooled the solution temperature to a negative 78 to negative 50 C. A solution of butyllithium (0.12 mol) was added dropwise and incubated for 1 hour at a negative 78 to negative temperature of 50 C. Then, ethyl trifluoroacetate (18.4 g, 0.13 mol) was added dropwise at this temperature. After completion of the dropwise addition, the mixture was withdrawn and the mixture was spontaneously stirred at room temperature. Then, hydrochloric acid (30 ml, 0.3 mol) was added dropwise, the layers were stirred, the organic layer was depressurized to remove the solvent. 20.7 g of crude 2,2,2-trifluoro-(3'-chlorophenyl)ethanone was obtained and distilled to give 20.3 g of a colorless transparent liquid, content of 95%, yield 97.3%.
The flask was added with magnesium powder (3 g, 0.125 mol), 20 ml of tetrahydrofuran, stirred. Accurately weighed m-dichlorobenzene (14.7 g, 0.1 mol) was dissolved in an additional 30 ml of tetrahydrofuran and added to a constant pressure dropping funnel, and 10% of the m-dichlorobenzene solution was added to the flask. The flask was heated to 40-45 C and then 0.3 ml of 1,2-dibromoethane was added to initiate the reaction. Then, the m-dichlorobenzene solution was slowly added dropwise at this temperature. After completion of the dropwise addition, the mixture was stirred at 40 to 50 C for 2 hours, and then the inside of the flask was cooled to 10 to 30 C, and trifluoroacetyl diethylamine was added dropwise, and the mixture was stirred for 30 minutes. Then, hydrochloric acid (30 ml, 0.3 mol) was added and the layers were separated and the organic layer was removed under reduced pressure to give 20.8 g of crude product. After distillation, 17.4 g of colorless transparent 2,2,2-trifluoro-(3'-chlorophenyl)ethanone was obtained, the content was 99.3% and the yield was 83.4%.
Accurate weighing of m-chloroiodobenzene (3-chloroiodobenzene) (23.85 g, 0.1 mol) was dissolved in 120 ml of methyl tert-butyl ether and the ethanol cooled ice bath cooled to a negative temperature of 20 to minus 10 C. A solution of isopropylmagnesium chloride (0.13 mol) was added dropwise and incubated for 1 hour at a negative 20 to minus 10 C after completion of the dropwise addition. Then, trifluoroacetate (18.4 g, 0.13 mol) was added dropwise at this temperature. After completion of the dropwise addition, the mixture was stirred and cooled to room temperature, and then hydrochloric acid (30 ml, 0.3 mol) was added dropwise. The organic layer was removed under reduced pressure to give 20.5 g of crude 2,2,2-trifluoro-(3'-chlorophenyl)ethanone and distilled to give 18.3 g of a colorless transparent liquid, content of 95.9.7%, the yield of 88%.
1-(5-chloro-2-nitrophenyl)-2,2,2-trifluoroethanone[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
84%
With sulfuric acid; nitric acid; In dichloromethane; at 20 - 40℃; for 2h;
<strong>[321-31-3]2,2,2-trifluoro-(3'-chlorophenyl)ethanone</strong> (20.8 g, 0.1 mol) was mixed with 20% fuming sulfuric acid (50 g, 0.5 mol) in a flask, 100 ml of methylene chloride was added, stirred, and then fuming nitric acid (7.7 g, 0.12 mol) was added dropwise between 20 and 40 C. After completion of the dropwise addition, the mixture was stirred for 2 hours, and then the reaction solution was slowly added to 200 g of ice water and stirred for 30 minutes. Then, the dichloromethane layer was washed with 10% aqueous sodium carbonate solution (100 ml). The dichloromethane layer was washed with water (100 ml). The dichloromethane layer was removed under reduced pressure to give 24.2 g of crude 2,2,2-trifluoro- (2'-nitro-5'-chlorophenyl) ethanone. Then, 25 g of toluene was added to a temperature of 50 C to dissolve and clarify, and the mixture was allowed to stand for 5 hours at a negative temperature of 30 C and filtered to give 2,2,2-trifluoro-(2'-nitro-5'-chlorophenyl)ethanone as a pale yellow solid, 21.3 g, content of 98.5%, yield 84%.
Sequentially 1- (3'-chlorophenyl) -2,2,2-trifluoro-ethanone (1.0mmol), ethyl propiolate (0.5 mmol) of Ag2SO. 3F.. 3(0.05 mmol), Cs2CO3(0.1 mmol) and dimethyl carbonate (1 mL) were added to Xu Linke bottles and the reaction was stirred at room temperature for24 h. The reaction was followed by TLC.After the reaction was completed, the reaction was quenched by adding 15 mL of saturated brine and the reaction mixture was extracted withdichloromethane (15 mL × 3). The combined organic phases were concentrated using a rotary evaporator to give the crude product, which was purified by column chromatography to give thetitle product. The eluant for column chromatography was petroleum ether: ethyl acetate (100: 1) and the product structure was identified by NMR and high resolution massspectrometry.1q isolated yield of 49%, 2q isolated yield of 47%.
N-(2-(3-chlorophenyl)-4-methylene-5-oxo-2-(trifluoromethyl)pyrrolidin-1-yl)benzamide[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
70%
General procedure: Trifluoromethyl ketones (1; 0.30 mmol, 1 equiv), acylhydrazines (2; 0.45 mmol, 1.5 equiv) and TsOH (20 mol%) were added to a dried round-bottom flask (50 mL) fitted with a magnetic bar. 1,4-Dioxane 4 mL) was then added and the mixture was stirred and heated to reflux. After the formation of acylhydrazones (monitored by TLC), tin powder (1.35 mmol, 4.5 equiv) and ethyl 2-(bromomethyl)acrylate (3; 1.20 mmol, 4 equiv) were added to the flask. When acylhydrazones had essentially disappeared (monitored by TLC), the reaction mixture was cooled to r.t., then 1,4-dioxane was removed under vacuum. Saturated NH4Cl solution (10 mL) was added and the mixture was stirred for 10 min. The mixture was extracted with EtOAc (3 × 10 mL) and the combined organic phases were dried (MgSO4) and concentrated. Purification of the residue by silica gel column chromatography (petroleum ether-EtOAc, 4:1) furnished the pure products 4.
(R)-3-(2-(3-chlorophenyl)-3,3,3-trifluoro-2-hydroxypropyl)cyclohex-2-en-1-one[ No CAS ]
3-(2-(3-chlorophenyl)-3,3,3-trifluoro-2-hydroxypropyl)cyclohex-2-en-1-one[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
With C24H22N2O2S; benzoic acid; In diethyl ether; at 20℃;
General procedure: To a stirred solution of trifluoromethyl ketone 2 (0.3 mmol, 3.0 equiv.), 3-methyl2-cyclohexen-1-one 1a (0.1 mmol, 1.0 equiv.) and benzoic acid (0.05 mmol, 0.5 equiv.) in ether(1 mL), catalyst 12 was added (0.02 mmol, 20 mol %), then the resulting mixture was stirred atroom temperature until the disappearance of the starting material (monitored by TLC). Themixture was directly purified by column chromatography on silica gel (hexane/EtOAc = 15:1 to10:1) to afford the desired product 3.
3-(2-(3-chlorophenyl)-3,3,3-trifluoro-2-hydroxypropyl)cyclohex-2-en-1-one[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
With 1,8-diazabicyclo[5.4.0]undec-7-ene; benzoic acid; In diethyl ether; at 20℃;
General procedure: To a stirred solution of trifluoromethyl ketone 2 (0.3 mmol, 3.0 equiv.), 3-methyl2-cyclohexen-1-one 1a (0.1 mmol, 1.0 equiv.) and benzoic acid (0.05 mmol, 0.5 equiv.) in ether(1 mL), catalyst 12 was added (0.02 mmol, 20 mol %), then the resulting mixture was stirred atroom temperature until the disappearance of the starting material (monitored by TLC). Themixture was directly purified by column chromatography on silica gel (hexane/EtOAc = 15:1 to10:1) to afford the desired product 3.
2-(3-chlorophenyl)-2-(trifluoromethyl)-5-vinyldihydrofuran-3,3(2H)-dicarbonitrile[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
87%Spectr.
With palladium diacetate; 2,2'-bis-(diphenylphosphino)-1,1'-binaphthyl; In tetrahydrofuran; at 20℃; for 72h;Inert atmosphere; Sealed tube;
General procedure: To a flame dried sealing tube were added Pd(OAc)2 (2.25 mg, 0.01 mmol),(rac)-BINAP (12.45 mg, 0.02 mmol), freshly distilled anhydrous tetrahydrofuran (1.0mL). The resulting mixture was allowed to stir for 30 mins. The ketone 2 (0.2 mmol) and vinyl cyclopropane 1 (0.5 mmol) were added subsequently. The resulting reaction mixture was stirred at room temperature for 72 h. After the volatile was removed in vacuo, the ratio of two diastereoisomers was determined by crude 1H NMR. The yieldwas determined by NMR using mesitylene as the internal standard. Then the resulting residue was purified by preparative TLC to afford pure sample for characterization.
With potassium carbonate; In methanol; at 50℃; for 18h;
General procedure: To a solution of aminoester hydrochloride 1-4 (2.21 mmol) in drymethanol (5 mL), under an argon atmosphere, potassium carbonate(4.42 mmol) and the appropriate trifluoroacetophenone (2.43 mmol)were added. The mixture was stirred at 50 C for 18 h and then, thereaction was cooled to r.t., filtered and the solvent was removed undervacuum. The collected oil was used in the next step without furtherpurification.
ethyl (E)-3-(3-chlorophenyl)-4,4,4-trifluorobut-2-enoate[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
41%
Stage #1: diethoxyphosphoryl-acetic acid ethyl ester With sodium hydride In tetrahydrofuran at 0 - 20℃; for 2h; Inert atmosphere;
Stage #2: 1-(3-chlorophenyl)-2,2,2-trifluoroethanone In tetrahydrofuran at 20℃; for 10h; Inert atmosphere;
Stage #1: 1-(3-chlorophenyl)-2,2,2-trifluoroethanone With sulfuric acid; nitric acid at 60℃; for 1.66667h;
Stage #2: With 5%-palladium/activated carbon; hydrogen In ethanol at 50℃; for 1.5h; Further stages;
1.S1-1; 1.S1-2; 1.S2-1; 1.S2-2; 1.S3-1; 1.S3-2; 1.S4-1; 1.S4-2; 1.S4-3; 1.S4-4; 2-25
Step S1 specifically includes the following sub-steps: S1-1. Take 104.5g (0.5mol) of compound I and stir and mix with 200g of 98% concentrated sulfuric acid (acid I). The temperature is raised to 60°C, and after the temperature is completed, 35.3g fuming nitric acid (0.55mol) is uniformly added dropwise within 10 minutes, and the reaction is kept for 1.5 hours to obtain intermediate reaction solution I; S1-2. Cool the intermediate reaction solution I after the reaction to 0°C, and add the reaction solution dropwise to the ice-water mixture at 0°C. Then add 1000 mL of dichloromethane as extractant I, and after fully stirring for 30 minutes, stand still and separate liquids to obtain organic phase I; S1-3. Add 500 mL of 10% sodium bicarbonate solution to the organic phase I for washing, separate the liquids again and remove the extractant I by vacuum distillation to obtain a composition of compound II and compound III. Step S2 specifically includes the following sub-steps: S2-1. Take 122.8 g (0.484 mol) of the composition of compound II and compound III obtained in step S1-3, and add 300 mL of absolute ethanol as solvent I. Add 5.0 g of 5% platinum carbon catalyst as catalyst I, replace it with nitrogen three times to remove air, and replace it with hydrogen three times to remove nitrogen. Introduce hydrogen to start stirring and react. During the reaction, the hydrogen pressure is between 0.1 MPa and the temperature is controlled at 50±10°C. After 1.5 hours of reaction, the intermediate reaction solution II is obtained; S2-2. Cool the intermediate reaction liquid II to room temperature, filter to remove the platinum carbon catalyst, and distill the ethanol out, After steaming, add 150mL of toluene, raise the temperature to 40°C and stir to dissolve and clarify, then cool to -20°C, Let it stand overnight, filter, and dry to obtain a composition of compound IV and compound V. Step S3 specifically includes the following sub-steps: S3-1. Take 44.7 g of the composition of compound IV and compound V obtained in step S2-2, add 200 mL of toluene (solvent II) and raise the temperature to 50° C., after fully dissolving, 33.7g (0.25mol) of sulfonyl chloride was uniformly added dropwise within 90 minutes as a chlorinating reagent, and then the reaction was incubated for 8 hours to obtain intermediate reaction solution III; S3-2. Lower the intermediate reaction solution III to room temperature, add 200 mL of water for rinsing, and stand still for layering after rinsing to obtain organic phase II. Step S4 specifically includes the following sub-steps: S4-1. The organic phase II obtained in S3-2 (contains 49.3g of compound VI and compound VII, total moles of 0.191 mol) is cooled to -10°C, 80 g of sulfuric acid (acid II) with a mass fraction of 92.5% was added dropwise within 30 minutes, and after the addition was completed, the mixture was kept and stirred for 1 hour to obtain an intermediate reaction solution IV; S4-2. Add 33% sodium nitrite solution (containing 0.41 mol of sodium nitrite) as the nitrite reagent solution to the intermediate reaction solution IV in 1 hour. And keep the temperature below 0°C, continue to keep the temperature and react for 2h after the addition is completed, to obtain the intermediate reaction solution V; S4-3. The intermediate reaction solution V is heated to 20°C, and 83 g of 50% hypophosphorous acid solution is added, Add 0.5 g of cuprous oxide as catalyst II, and react with stirring for 2 hours to obtain intermediate reaction solution VI; S4-4. Separate the intermediate reaction solution VI into static layers, and wash the organic layer with 5% sodium bicarbonate solution. After drying with sewage magnesium sulfate, the solvent was distilled under reduced pressure, and the clear and transparent liquid obtained was 41.2g of 3',5'-dichloro-2,2,2-trifluoroacetophenone with a purity of 99.3% and a yield of 89.1% .
1-(2-amino-3,5-dichlorophenyl)-2,2,2-trifluoroethanone[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
Stage #1: 1-(3-chlorophenyl)-2,2,2-trifluoroethan-1-one With sulfuric acid; HNO3 at 60℃; for 1.66667h;
Stage #2: With 5%-palladium/activated carbon; hydrogen In ethanol at 50℃; for 1.5h;
Stage #3: With sulfuryl dichloride In toluene at 50℃; for 8h;
1.S1-1; 1.S1-2; 1.S2-1; 1.S2-2; 1.S3-1; 1.S3-2; 2-25
Step S1 specifically includes the following sub-steps: S1-1. Take 104.5g (0.5mol) of compound I and stir and mix with 200g of 98% concentrated sulfuric acid (acid I). The temperature is raised to 60°C, and after the temperature is completed, 35.3g fuming nitric acid (0.55mol) is uniformly added dropwise within 10 minutes, and the reaction is kept for 1.5 hours to obtain intermediate reaction solution I; S1-2. Cool the intermediate reaction solution I after the reaction to 0°C, and add the reaction solution dropwise to the ice-water mixture at 0°C. Then add 1000 mL of dichloromethane as extractant I, and after fully stirring for 30 minutes, stand still and separate liquids to obtain organic phase I; S1-3. Add 500 mL of 10% sodium bicarbonate solution to the organic phase I for washing, separate the liquids again and remove the extractant I by vacuum distillation to obtain a composition of compound II and compound III. Step S2 specifically includes the following sub-steps: S2-1. Take 122.8 g (0.484 mol) of the composition of compound II and compound III obtained in step S1-3, and add 300 mL of absolute ethanol as solvent I. Add 5.0 g of 5% platinum carbon catalyst as catalyst I, replace it with nitrogen three times to remove air, and replace it with hydrogen three times to remove nitrogen. Introduce hydrogen to start stirring and react. During the reaction, the hydrogen pressure is between 0.1 MPa and the temperature is controlled at 50±10°C. After 1.5 hours of reaction, the intermediate reaction solution II is obtained; S2-2. Cool the intermediate reaction liquid II to room temperature, filter to remove the platinum carbon catalyst, and distill the ethanol out, After steaming, add 150mL of toluene, raise the temperature to 40°C and stir to dissolve and clarify, then cool to -20°C, Let it stand overnight, filter, and dry to obtain a composition of compound IV and compound V. Step S3 specifically includes the following sub-steps: S3-1. Take 44.7 g of the composition of compound IV and compound V obtained in step S2-2, add 200 mL of toluene (solvent II) and raise the temperature to 50° C., after fully dissolving, 33.7g (0.25mol) of sulfonyl chloride was uniformly added dropwise within 90 minutes as a chlorinating reagent, and then the reaction was incubated for 8 hours to obtain intermediate reaction solution III; S3-2. Lower the intermediate reaction solution III to room temperature, add 200 mL of water for rinsing, and stand still for layering after rinsing to obtain organic phase II.
Stage #1: 1-(3-chlorophenyl)-2,2,2-trifluoroethan-1-one With sulfuric acid; HNO3 at 60℃; for 1.5h;
Stage #2: With platinum on carbon; hydrogen In ethanol at 40 - 60℃; for 1.5h;
Stage #3: With sulfuryl dichloride In toluene at 50℃; for 1.5h;
1.3-1; 1.3-2; 18; 19.3-1'; 19.3-2'
S3-1, take 44.7 g of the composition of compound IV and compound V obtained in step S2-2,200 mL of toluene (solvent II) was added and the temperature was raised to 50°C,After fully dissolving, 33.7g (0.25mol) Sulfuryl chloride was added dropwise as a chlorination reagent evenly within 90min.Subsequently, the reaction was incubated for 8 h.to obtain intermediate reaction solution III; S3-2. Lower the intermediate reaction solution III to room temperature,Add 200mL of water to rinse, after rinsing, let stand for stratification,An organic phase II is obtained.
Stage #1: 1-(3-chlorophenyl)-2,2,2-trifluoroethan-1-one With sulfuric acid; HNO3 at 60℃; for 1.66667h;
Stage #2: With 5%-palladium/activated carbon; hydrogen In ethanol at 50℃; for 1.5h;
1.S1-1; 1.S1-2; 1.S2-1; 1.S2-2; 2-25
Step S1 specifically includes the following sub-steps: S1-1. Take 104.5g (0.5mol) of compound I and stir and mix with 200g of 98% concentrated sulfuric acid (acid I). The temperature is raised to 60°C, and after the temperature is completed, 35.3g fuming nitric acid (0.55mol) is uniformly added dropwise within 10 minutes, and the reaction is kept for 1.5 hours to obtain intermediate reaction solution I; S1-2. Cool the intermediate reaction solution I after the reaction to 0°C, and add the reaction solution dropwise to the ice-water mixture at 0°C. Then add 1000 mL of dichloromethane as extractant I, and after fully stirring for 30 minutes, stand still and separate liquids to obtain organic phase I; S1-3. Add 500 mL of 10% sodium bicarbonate solution to the organic phase I for washing, separate the liquids again and remove the extractant I by vacuum distillation to obtain a composition of compound II and compound III. Step S2 specifically includes the following sub-steps: S2-1. Take 122.8 g (0.484 mol) of the composition of compound II and compound III obtained in step S1-3, and add 300 mL of absolute ethanol as solvent I. Add 5.0 g of 5% platinum carbon catalyst as catalyst I, replace it with nitrogen three times to remove air, and replace it with hydrogen three times to remove nitrogen. Introduce hydrogen to start stirring and react. During the reaction, the hydrogen pressure is between 0.1 MPa and the temperature is controlled at 50±10°C. After 1.5 hours of reaction, the intermediate reaction solution II is obtained; S2-2. Cool the intermediate reaction liquid II to room temperature, filter to remove the platinum carbon catalyst, and distill the ethanol out, After steaming, add 150mL of toluene, raise the temperature to 40°C and stir to dissolve and clarify, then cool to -20°C, Let it stand overnight, filter, and dry to obtain a composition of compound IV and compound V.
Stage #1: 1-(3-chlorophenyl)-2,2,2-trifluoroethan-1-one With sulfuric acid; HNO3 at 60℃; for 1.5h;
Stage #2: With platinum on carbon; hydrogen In ethanol at 40 - 60℃; for 1.5h;
1.2-1; 1.2-2; 14-17
S2-1. Take 122.8 g (0.484 mol) of the composition of compound II and compound III obtained in step S1-3,And add anhydrous ethanol 300mL as solvent I,5.0g of 5% platinum carbon catalyst was added as catalyst I,Replaced with nitrogen three times to remove air,Replaced with hydrogen three times to remove nitrogen,Introduce hydrogen to start stirring and react,During the reaction, the hydrogen pressure was between 0.1 MPa,The temperature is controlled at 50±10,After 1.5h of reaction, intermediate reaction solution II was obtained; S2-2, cooling the intermediate reaction solution II to room temperature,and filtered to remove the platinum-carbon catalyst, and the ethanol was distilled off,After steaming, 150 mL of toluene was added,After warming up to 40°C and stirring to dissolve and clarify,Cool down to -20°C, let stand overnight, filter, dry,A composition of compound IV and compound V is obtained.
1-(5-chloro-2-nitrophenyl)-2,2,2-trifluoroethanone[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
With sulfuric acid; HNO3 at 60℃; for 1.66667h;
1.S1-1; 1.S1-2; 2-25
Step S1 specifically includes the following sub-steps: S1-1. Take 104.5g (0.5mol) of compound I and stir and mix with 200g of 98% concentrated sulfuric acid (acid I). The temperature is raised to 60°C, and after the temperature is finished, 35.3g of fuming nitric acid (0.55mol) is uniformly added dropwise within 10 minutes, and the reaction is kept for 1.5 hours to obtain intermediate reaction solution I; S1-2. Cool the intermediate reaction solution I after the reaction to 0°C, and add the reaction solution dropwise to the ice-water mixture at 0°C. Then add 1000 mL of dichloromethane as extractant I, and after fully stirring for 30 minutes, stand still and separate liquids to obtain organic phase I; S1-3. Add 500 mL of 10% sodium bicarbonate solution to the organic phase I for washing, separate the liquids again and remove the extractant I by vacuum distillation to obtain a composition of compound II and compound III.
With sulfuric acid; HNO3 at 60℃; for 1.5h;
1.1-1; 1.1-2; 1.1-3; 2-12
S1-1, take 104.5 g (0.5 mol) of compound I,Stir and mix with 200g of concentrated sulfuric acid (acid I) with a mass fraction of 98%.The temperature was raised to 60°C, and after the heating was completed, 35.3 g of fuming nitric acid was added dropwise as a nitration reagent (0.55 mol) within 10 min, and the reaction was kept for 1.5 h to obtain the intermediate reaction solution I; S1-2, cooling the intermediate reaction solution I after the reaction to 0°C,The reaction was added dropwise to an ice-water mixture at 0°C.Then add 1000mL dichloromethane as extractant I,After fully stirring for 30min, stand still and separate liquid to obtain organic phase I; S1-3, add 500 mL of 10% sodium bicarbonate solution to the organic phase I for washing,After separating the liquid again, the extractant I was removed by distillation under reduced pressure.A composition of compound II and compound III is obtained.
The procedure to prepare α-trifluoromethylated nitroalkenes: (2a, 2n - 2x and 2z) [5, 6]
General procedure: To a solution of the corresponding trifluoromethyl ketone (1 equiv.) in CH3NO2 (0.5 M) was added Et3N (1.5 equiv.). After the reaction mixture was stirred for 24 h at room temperature, the mixture was poured into ethyl acetate and washed with aq. HCl (1N) and brine. The organic layer was dried over anhydrous Na2SO4 and concentrated in vacuo. The residue was used in next reaction step without further purification.
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