* 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 aluminum (III) chloride In neat (no solvent) at 140 - 150℃;
p-Chlorophenyl acetate 2c (10 gm, 0.091mol) was in 500 mL round bottom flask containing aluminium chloride (14.56 gm, 0.11 mol). It was heated on an oil bath at 140-150 °C for 5-6 hr. The progress of the reaction was monitored by TLC using ethyl acetate:hexane as a solvent system. The reaction mixture was quenched with crushed ice and obtained solid product was extracted with ethyl acetate (2×50 mL). The organic extracts were washed with brine solution (2×15 mL) and dried over anhydrous sodium sulphate. The solvent was evaporated under reduced pressure to afford the corresponding crude compound. The obtained crude compound 3c was recrystallized using aq. ethanol. Yield 90percent. M.p. 54-56 °C.
87%
at 0 - 20℃; for 16 h;
General procedure: O-Acyloxy benzenes (0.28 mmol) were dissolved in TfOH (3 ml) at 0 °C. The reaction mixture was warmed to room temperature for appropriate time in Table 3, then poured into cold water and ethyl acetate. The organic layer was washed with 1 M HCl, saturated NaHCO3, and saturated NaCl, and dried over MgSO4, then filtrated. The filtrate was concentrated and the residue was subjected silica column chromatography to afford acylated products. All spectral data were identical with the literatures.26
60%
at 120 - 160℃;
4-chlorophenyl acetate (2) (0.1 mole) and anhydrous aluminum trichloride (0.11 mole) were mixed thoroughly in a round bottom flask. The reaction mixture was heated gradually at 120°C till HCl gas was completely exhausted. The heating was extended for 2 hours at 160°C. The progress and completion of the reaction was monitored by TLC. At the end of the reaction the resulting aluminum complex was decomposed from crushed ice containing little amount of hydrochloric acid. The crude product was filtered dried and crystallized from methanol. Yield 60percent, m. p. 53-55 °C (Reported m.p. 53°C).
Reference：
[1] Chinese Chemical Letters, 2016, vol. 27, # 7, p. 1058 - 1063
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[3] Tetrahedron, 2011, vol. 67, # 3, p. 641 - 649
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[11] Chemische Berichte, 1924, vol. 57, p. 92[12] Justus Liebigs Annalen der Chemie, 1926, vol. 446, p. 157 Anm. 2, 177
[13] Chemische Berichte, 1924, vol. 57, p. 1273
[14] Journal of the Indian Chemical Society, 1949, vol. 26, p. 366,367
[15] Chemische Berichte, 1954, vol. 87, p. 194,201
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[17] Journal of Medicinal Chemistry, 1971, vol. 14, p. 758 - 766
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2
[ 876-27-7 ]
[ 1450-74-4 ]
Reference：
[1] Patent: US2003/176482, 2003, A1,
3
[ 7446-70-0 ]
[ 876-27-7 ]
[ 1450-74-4 ]
Reference：
[1] Chemische Berichte, 1924, vol. 57, p. 92[2] Justus Liebigs Annalen der Chemie, 1926, vol. 446, p. 157 Anm. 2, 177
[3] W., vol. 57, p. 1275
4
[ 7446-70-0 ]
[ 876-27-7 ]
[ 108-88-3 ]
[ 1450-74-4 ]
[ 122-00-9 ]
Reference：
[1] Rikagaku Kenkyusho Iho, 1943, vol. 22, p. 828,830, 831[2] Chem.Abstr., 1949, p. 7924
[3] Scientific Papers of the Institute of Physical and Chemical Research (Japan), 1943, vol. 41, p. 182,188[4] Rikagaku Kenkyusho Iho, 1942, vol. 21, p. 247,249, 251
5
[ 876-27-7 ]
[ 54731-75-8 ]
[ 4202-14-6 ]
Reference：
[1] Journal of Organic Chemistry, 2003, vol. 68, # 12, p. 4815 - 4818
With hydrogen fluoride supported on silica gel In neat (no solvent) at 55℃; for 4h; Green chemistry;
3.4. General Procedure for Synthesis of Hydroxyaryl Ketones
General procedure: A mixture of aryl ester (25 mmol), HFSiO2 (2 g), and EtOAc (5 mL) was charged in a 50 ml flask and stirred for 5min. EtOAc was used for homogenization of the reactionmixture in this step. The solvent was evaporated under vacuumand the residue was heated with the classical method for 4 h at 55°C for aryl acetates and at 75°C for aryl benzoates(Table 1). After cooling, the reaction mixture was extractedwith EtOAc (3 × 10 mL) and the solvent was removed under vacuum. The residue was subjected to short column chromatography (EtOAc/hexane; 1:5) on silica gel to obtain pureproducts. All the isolated hydroxyaryl ketones successfullygave the related spectral data of IR, 1H NMR, 13C NMR andMS spectrometers (see the Supporting Information, Fig. 12S-39S) and comparison with authentic samples prepared byreported methods [33-36].
90%
With aluminum (III) chloride In neat (no solvent) at 140 - 150℃;
Synthesis of 2-hydroxy-5-chloroacetophenone 3c
p-Chlorophenyl acetate 2c (10 gm, 0.091mol) was in 500 mL round bottom flask containing aluminium chloride (14.56 gm, 0.11 mol). It was heated on an oil bath at 140-150 °C for 5-6 hr. The progress of the reaction was monitored by TLC using ethyl acetate:hexane as a solvent system. The reaction mixture was quenched with crushed ice and obtained solid product was extracted with ethyl acetate (2×50 mL). The organic extracts were washed with brine solution (2×15 mL) and dried over anhydrous sodium sulphate. The solvent was evaporated under reduced pressure to afford the corresponding crude compound. The obtained crude compound 3c was recrystallized using aq. ethanol. Yield 90%. M.p. 54-56 °C.
88%
With potassium carbonate In hexane at 25℃; for 12h; Irradiation;
87%
With trifluorormethanesulfonic acid at 0 - 20℃; for 16h; regiospecific reaction;
4.4. General procedure of Fries rearrangement for O-acyloxy benzenes in TfOH
General procedure: O-Acyloxy benzenes (0.28 mmol) were dissolved in TfOH (3 ml) at 0 °C. The reaction mixture was warmed to room temperature for appropriate time in Table 3, then poured into cold water and ethyl acetate. The organic layer was washed with 1 M HCl, saturated NaHCO3, and saturated NaCl, and dried over MgSO4, then filtrated. The filtrate was concentrated and the residue was subjected silica column chromatography to afford acylated products. All spectral data were identical with the literatures.26
85%
With aluminium trichloride In chlorobenzene for 0.0333333h; Irradiation;
82%
With aluminum (III) chloride at 120 - 160℃; for 30h;
79%
With N,N-dimethyl-formamide; zinc at 68℃; for 18h; microwave irradiation;
74.14%
With aluminium trichloride at 140℃; for 2h;
62%
With aluminium trichloride at 160℃; for 1h;
60%
With aluminum (III) chloride at 120 - 160℃;
5'-chloro-2'-hydroxyacetophenone (3):
4-chlorophenyl acetate (2) (0.1 mole) and anhydrous aluminum trichloride (0.11 mole) were mixed thoroughly in a round bottom flask. The reaction mixture was heated gradually at 120°C till HCl gas was completely exhausted. The heating was extended for 2 hours at 160°C. The progress and completion of the reaction was monitored by TLC. At the end of the reaction the resulting aluminum complex was decomposed from crushed ice containing little amount of hydrochloric acid. The crude product was filtered dried and crystallized from methanol. Yield 60%, m. p. 53-55 °C (Reported m.p. 53°C).
55%
With aluminium trichloride at 120℃;
With aluminium trichloride at 120℃;
With aluminium trichloride at 130℃;
With boron trifluoride at 125℃; unter Druck;
With aluminium trichloride at 175 - 185℃;
With aluminium trichloride
With Lewis acid In nitrobenzene Heating;
72 g
With aluminium trichloride at 160℃; for 2h;
With aluminium trichloride Heating;
With aluminium trichloride Heating;
With aluminium trichloride at 120℃;
With aluminum (III) chloride; sodium chloride Neat (no solvent);
With titanium tetrachloride; 1-n-butyl-3-methylimidazolim bromide at 120℃; for 3h; Inert atmosphere;
With aluminum (III) chloride
With aluminum (III) chloride
Stage #1: 4-chlorophenyl acetate With aluminum (III) chloride at 120℃; for 6h;
Stage #2: With water Cooling;
2 Synthesis of substituted o-hydroxyacetophenone
General procedure: Powdered anhydrous AlCl3 (186 g, 1.4 mol) was added little by little to acetic acid phenyl ester b1 (95.3 g, 0.7 mol) in a round-bottomed flask in an ice-water bath. The resultant mixture was heated to 120 °C for 6 h in an oil bath. Then the reaction mixture was added a lot of crushed ice for hydrolysis. The new formed organic layer in the reaction mixture was extracted by EtOAc, dried over anhydrous Na2SO4, and filtered off by suction filtration. The solvent was removed under reduced pressure to give the crude product, which was then purified by chromatography on silica using petroleum ether/ethyl acetate as the eluent. o-hydroxyacetophenone c1 (20.1 g, 21%) was obtained
With aluminum (III) chloride
With aluminum (III) chloride Heating;
With Fluoro Flash In neat (no solvent) at 80℃; for 4h; Green chemistry;
4.2 General procedure for Fries rearrangement and catalyst preparation
General procedure: Catalyst (FSG) was purchased from Fluorous Technologies Inc. and used without further purification. Its synthesis procedure is reported by Curran et al. [24]. General procedure for Fries rearrangement was done by adding FSG to aryl ester at the ambient temperatures. Before adding FSG to reaction mixture, aryl esters were obtained by in situ formation through the reaction of acyl chloride derivatives and phenol derivatives. Thus, to a 100ml round bottom flask stirring by a magnetic bar 10mmol of phenols was added and then, 10mmol of acyl chloride derivatives (for catechols 20mmol) was added dropwise and allowed to react at room temperature. After 30min, temperature was raised to remove HCl from reaction mixture. Then 1g of FSG was added to reaction mixture at ambient temperature. After 4h heating at appropriate temperature in oil bath, the reaction mixture was cooled to room temperature and washed with dichloromethane. The catalyst was separated by filtration. The solvent was removed by rotary evaporator and resulting mixture was separated by column chromatography (stationary phase: silica-gel, eluent:hexane:ethyl acetate) and purified by recrystallization. All isolated products successfully gave related spectral data of IR, NMR, and mass spectrometers.
With aluminum (III) chloride at 120℃;
With aluminum (III) chloride at 120 - 130℃; Dean-Stark;
With aluminum (III) chloride at 120 - 130℃;
With aluminum (III) chloride at 150℃;
With aluminum (III) chloride
With aluminum (III) chloride at 80 - 150℃; for 3h; Enzymatic reaction;
4.1.2. Synthesis of 1-(5-chloro-2-hydroxyphenyl)propan-1-one(11a)
General procedure: A mixture of 10a (6.5 g, 35.20 mmol) and AlCl3 (14.07 g,105.60 mmol) was heated at 80 C for 1 h then at 150 °C for 2 h theresulting residuewas decomposed with 3 N HCl and extracted withEtOAc. The organic layer was washed with brine, dried over MgSO4,and evaporated under reduced pressure to give crude productwhich was purified by flash chromatography on silica gel using amixture of EtOAc, hexanes (1:30) as eluent to yield 11a (5 g, 77%) aswhite solid
With aluminum (III) chloride at 120℃; for 5h;
2.1.2.2. Fries Rearrangement of Ester Derivatives
General procedure: The above reaction mixture was treated with anhydrousAluminum Chloride (AlCl3) (28.03 g, 0.2100 moles) at120oC for 5 hours. The reaction was monitored by TLC(Ethylacetate:hexane::30:70). The reaction was cooled downand neutralized by ammonium chloride. The mixture wasextracted with ethyl acetate (3 x 250 ml). All the ethyl acetatefractions were combined and concentrated after treatingwith sodium sulfate (100 g) to obtain the crude product(Scheme 1).
With anhydrous magnesium perchlorate at 80℃; for 0.25h;
99%
With sodium hydroxide for 0.0125h; microwave irradiation;
99%
With aluminum triflate at 20℃; for 0.00277778h;
99%
at 20℃; for 0.25h;
99%
With SiO2-supported Co(II) Salen complex catalyst at 50℃; for 0.833333h;
99%
With Cp2Ti(OSO2C8F17)2 at 20℃; for 1h; Neat (no solvent);
99%
With Zn(N4,N4'-di(pyridin-4-yl)biphenyl-4,4'-dicarboxamide)(5-aminoisophthalate) In dichloromethane at 20℃; for 12h;
99%
With Sodium thiosulfate In N,N-dimethyl-formamide at 70℃; for 16h; Inert atmosphere;
98%
With mesoporous silica for 0.0333333h; Microwave irradiation; neat (no solvent);
98%
With 2,3-dihydro-5,7-dimethyl-1,4-diazepinium perchlorate In neat (no solvent) at 40℃; for 3.5h;
97%
With H3[P(Mo3O10)4]*nH2O at 20℃; for 0.166667h;
97%
With polyvinylpolypyrrolidone supported triflic acid In neat (no solvent) at 20℃; for 0.266667h; Green chemistry;
General experimental procedure
General procedure: To a mixture of substrate (1.0 mmol) and acetic anhydride (1.0 mmol), 0.008 g PVPP.OTf (3.4 mol%) was added. The mixture was stirred at room temperature for the time indicated in Tables 2, 3 and 4. The progress of the reaction was followed by TLC or GC for aliphatic alcohols. After completion of the reaction, ethyl acetate (2 9 10 cm3) was added, and the catalyst was separated by filtration. The filtrate was washed with an aqueous solution of NaHCO3 (10%, 2 9 10 cm3) and water (2 9 10 cm3) and dried with Na2SO4. The solvent was evaporated under reduced pressure to afford the expected product.
96%
With trifluoromethane sulfonic acid silver salt at 60℃; for 0.0333333h; neat (no solvent);
95%
With oxidovanadium(IV) sulfate trihydrate at 20℃; for 1h;
95%
With triethylamine
4.5. Synthesis of 4-chlorophenyl acetate
155.57 mmol de para-chlorophenol (20 g), 1.1 equiv of Et3N and 1.5 equiv of anhydride acetic. After the standard work up, the acetate is obtained as an uncolored oil, in a 95% yield. IR (film, cm-1): ν = 682.75; 717.47; 798.47; 840.91; 906.48; 941.2; 1010.63; 1087.78; 1164.92; 1485.09; 1758.96. 1H NMR (300 MHz, CDCl3): δ (ppm) = 2.28 (s, 3H, H3C-CO); 7.02-7.05 (d, J = 8.7Hz, 3H aromatic); 7.32-7.35 (d, J = 8.7Hz, 3H aromatic). 13C NMR (75 MHz, CDCl3): δ (ppm) = 8.64; 21.03; 46.17; 116.85; 123.00; 129.20; 129.46; 131.14; 149.15; 169.24. MS (CI; m/z): 170.1 ([M]+, 100%).
95%
With [SnIV(TNH2PP)(OTf)2]*CMP In acetonitrile at 20℃; for 0.133333h;
95%
With N,N'-dimethyl-N,N'-di(pyridin-4-yl)ferrocene-1,1'-dicarboxamide at 20℃; for 0.333333h;
94%
With silica gel-supported phosphotungstic acid In dichloromethane at 20℃; for 0.0166667h;
94%
With silica sulfate In dichloromethane at 20℃; for 0.0166667h;
94%
With silica-sulfuric acid nanoparticles In neat (no solvent) at 20℃; for 0.25h;
94%
With 1,8-diazabicyclo[5.4.0]undec-7-en-8-ium acetate In neat (no solvent) at 50℃; for 0.75h; Green chemistry;
94%
With iron oxide nanoparticles supported on porous silicates SBA-15 In neat (no solvent) at 40℃; for 0.333333h;
2.3 General procedure for the acetylation of alcohols and phenols
General procedure: To a solution of substrate (1 mmol) and acetic anhydride (1.5 mmol) was added supported iron catalyst (Fe/SBA-15) (0.005 mmol, 0.085 g) and the mixture was stirred at 40 °C. After completion of the reaction (TLC), the reaction mixture was filtered and the catalyst rinsed with ethyl acetate and heated at 70 °C prior to its reuse in the next reaction. The organic layer was washed with saturated NaHCO3 and water, and dried over anhydrous sodium sulfate. The product was obtained after removal of the solvent.
94%
With pyridine Cooling with ice;
Synthesis of p-chlorophenylacetate 2c
A mixture of p-chloro phenol (1c) (8 gm, 0.1mol) and dry pyridine (5mL) was placed in a 500 mL beaker. It was kept in ice bath and acetic anhydride (12.75 mL, 0.125 mol) was added slowly with constant stirring. It was poured on a mixture of ice and concentrated hydrochloric acid (10 mL) and extracted with ethylacetate (2×50 mL). The extract was washed successively with water, 10% NaOH solution and brine solution (2×20 mL). It was dried over anhydrous sodium sulphate. The solvent was removed by distillation and p-chloro phenyl acetate was collected at 175 to 182 °C, Yield 94%.
93%
With 1-butyl-3-methylimidazolium tetrachloroferrate(III) at 20℃; for 0.333333h; Ionic liquid;
92%
at 20℃; for 0.0666667h;
92%
With decamolybdodivanadogermanic acid nanoparticles at 24.84℃; for 0.3h; Neat (no solvent);
92%
With silica-coated ferrite nanoparticles supported with montmorillonite-K10 at 20℃; for 0.166667h;
91%
With SBA-15-Ph-Pr-SO3H at 20℃; for 0.666667h;
90%
With Sm{N<SO2OCH(CF3)2>2}3 In dichloromethane at 30℃; for 1.5h;
90%
With tin(IV) tetraphenylporphyrin perchlorate at 20℃; for 0.166667h;
90%
90%
With sulfuric acid for 2h; Reflux;
General Procedure for the synthesis of 4-chlorophenyl acetate (2):
A mixture of 4-Chlorophenol (1) (0.1 mole) and acetic anhydride (0.11 mole) along with catalytic amount of concentrated sulfuric acid was refluxed for 2 hours on boiling water bath. The progress and completion of the reaction was monitored by TLC. After completion of reaction, the reaction mass was poured into crushed ice. The reaction mass was extracted with dichloromethane. The organic layer was dried over anhydrous sodium sulphate and concentrated under vacuum distillation to yield 4-chlorophenyl acetate as colorless oil. Yield 90%, b.p. >300°C (Reported b.p. 305-307°C).
90%
With polydopamine sulfamic acid-functionalized silica gel nanocatalyst In neat (no solvent) at 20℃; for 3h;
2.2 General Procedure for Acylation Reaction
General procedure: A 25 mL ballon containing a magnetic stir bar was chargedwith phenol/alcohol/amine (1 mmol) and acetic anhydride(2 mmol), SiO2/PDA-SO3H (30 mg, 1 mol% H+)as catalyst.The reaction mixture was stirred at room temperature and thereaction progress was monitored on thin-layer chromatography(TLC). After completion of the reaction, the reaction mixturewas diluted with ethyl acetate and catalyst was separatedfrom reaction mixture by centrifugation. The reaction mixturewas washed with sat. NaHCO3solution (1 × 15 mL) and theproduct was extracted with ethyl acetate (3 × 10 mL) and driedover Na2SO4and evaporated under vacuum. All the obtainedproducts are well known in the literature.
90%
With Fe3O4-polyethylene glycol composite magnetic nanoparticles In neat (no solvent) at 20℃; for 0.666667h; Sonication; Green chemistry;
General procedure for acylation reaction under ultrasonic conditions
General procedure: A 10-mL balloon was charged with phenol/alcohol/amine (1mmol) and acetic anhy-dride (3mmol), with Fe 3 O 4 PEG (10mg) as catalyst. The reaction balloon was taken in the ultrasonic bath, where the level of the reaction mixture is lower than the surface of the water. Then, the mixture was sonicated under 60W of power of the ultrasonic bath at room temperature for the appropriate time, as shown in Table2. After completion of the reaction (monitored by thin-layer chromatography), the reaction mixture was diluted with ethyl acetate and the catalyst was separated from reaction mixture by an external magnet. The separated catalyst was washed with DI water and absolute ethanol several times then dried in oven and reused for further reaction. The reaction mixture was washed with sat. NaHCO 3 solution (1 × 15mL) and the product was extracted with ethyl acetate (3 × 10mL) and dried over Na 2 SO 4 and evaporated under vacuum. All the obtained products are well known in the liter-ature and were confirmed by nuclear magnetic resonance (NMR) analysis and com -parison with literature data.
89%
With magnesium bis(trifluoromethylsulfonyl)imide at 20℃; for 0.25h;
88%
at 20℃; for 0.5h;
87%
With ruthenium(III) 2,4-pentanedionate at 25℃; for 4h;
87%
With zirconium phosphate In neat (no solvent) at 60℃; for 2h; Green chemistry;
87%
With polystyrene-nanoencapsulated FeCl3 catalyst In acetonitrile at 20℃; for 1h;
2.3. A typical experimental procedure for the acetylation of alcohols, phenols, amines, and thiols with Ac 2 O catalyzed by PS-NC/ FeCl 3
General procedure: In a single-round bottomed flask (25 mL) containing a mixture of alcohol or phenol (1 mmol) and acetic anhydride (2 mmol) in CH 3 CN (4 mL) was added PS-NC/FeCl 3 (60 mg, 3.55 mol%, with respect to iron(III) content and the resulting heterogeneous mix- ture was stirred at room temperature for the time indicated in the Table ( 2 ). Upon completion of the reaction as monitored by TLC, the reaction mixture was filtered and the nanocapsules rinsed with CH 3 CN and methanol. The filtrate was washed with distilled water after quenching with a saturated solution of NaHCO 3 , dried over anhydrous MgSO 4 , and concentrated under reduced pressure us- ing a rotary evaporator to obtain the almost pure acetate products. It should be pointed out that the filtrate was analyzed at each run by ICP and atomic absorption spectroscopy to determine the leach- ing of the Fe(III) component. All products were characterized by a comparison of their spectral data (IR and 1 HNMR) and compared with the literature data. Nanoencapsulated catalyst recovery / reuse experiment, and determination of Fe in PS-NC / FeCl 3 by ICP analysis are given in ESI.
85%
In benzene for 4h; Heating;
85%
With polyvinylpolypyrrolidone-bound boron trifluoride In acetonitrile at 20℃; for 1h;
85%
With pentafluoroanilinium trifluoromethanesulfonate In neat (no solvent) at 20℃; for 0.833333h;
83%
With ZnCl2/SiO2 In acetonitrile at 80℃; for 4h;
83%
With Copper Zirconium Phosphate at 80℃; for 1.5h;
2.3. General experimental procedure for the acetylation of substrates under solvent-free conditions
General procedure: ZPCu (2 mol%) was added to a mixture of phenol (1 mmol)and AA (2 mmol), and the resulting mixture was stirred at 60 °C for the specified time (Scheme 2). Upon completion of the reaction(as determined by GC), the catalyst was separated from the reaction mixture by centrifuge, then the supernatant was collected and diluted with 10% NaHCO3 solution (10 ml) before being extracted with Et2O (2 . 10 ml). The combined organic extracts were washed and then dried over anhydrous CaCl2 before being evaporated to dryness under vacuum to give the desired product. In some cases, it was necessary for the product to be purified by column chromatography over silica gel eluting with a mixture of cyclohexane and ethyl acetate.
83%
With nickel zirconium phosphate In neat (no solvent) at 60℃; for 0.75h;
General experimental procedure for the acetylation of substrates under solvent-free conditions
General procedure: ZPNi (1 mol %) was added to a mixture of alcohol(1 mmol) and AA (2 mmol), and the resulting mixture was stirred at 40 °C for the specified time (Scheme 2). Upon completion of the reaction (as determined by GC), the catalyst was separated from the reaction mixture by centrifuge,then the supernatant was collected and diluted with 10 %NaHCO3 solution (10 ml) before being extracted with Et2O(2 × 10 ml). The combined organic extracts were washed and then dried over anhydrous CaCl2 before being evaporated to dryness under vacuum to give the desired product. In some cases, it was necessary for the product to be purified by column chromatography over silica gel eluting witha mixture of cyclohexane and ethyl acetate.
82%
With multi-walled carbonnanotubes functionalized with phosphonic acid In neat (no solvent) at 20℃; for 1h;
82%
With iron zirconium phosphate In neat (no solvent) at 60℃; for 0.75h; Green chemistry;
General experimental procedure for the acetylation of substrates under solvent-free conditions
General procedure: ZPFe (1 mol%) was added to a mixture of alcohol (1 mmol) and AA (2 mmol), and the resulting mixture was stirred at 40 °C for a specified time (Scheme 2). Upon completion of the reaction (as determined by gas chromatography), the catalyst was separated from the reaction mixture by centrifuge, after which the supernatant was collected and diluted with a 10% NaHCO3 solution (10 mL) before being extracted with Et2O (2 × 10 mL).The combined organic extracts were washed and then dried over anhydrous CaCl2 before being evaporated to dryness under vacuum to give the desired product. In some cases, it was necessary to purify the product by column chromatography ona silica gel column with elution by a mixture of cyclohexane and ethyl acetate.
80%
With anhydrous Sodium acetate for 1h; Heating;
79%
With 4-methylbenzene-1-sulfonyl chloride at 20℃; for 1.11667h; neat (no solvent);
With sodium hydroxide; sulfuric acid; acetic anhydride In ice-water
R.5 Synthesis of 4-Chlorophenyl Acetate [Compound (7-1)]
Referential Example 5 Synthesis of 4-Chlorophenyl Acetate [Compound (7-1)] Acetic anhydride (80.1 g, 0.78 mol) and one drop of concentrated sulfuric acid were added to 4-chlorophenol [compound (6-1)] (100 g, 0.78 mol) at room temperature, and the mixture was stirred for 17 hours. The resultant mixture was added to ice-water, and converted to alkaline by the addition of sodium hydroxide (20% aqueous solution), followed by extraction with diethyl ether. The organic layer was washed with water, dried over magnesium sulfate. Subsequently, the solvent was removed under reduced pressure, and then the residue was subjected to distillation under reduced pressure (81° C./1.5 mmHg), to thereby yield 4-chlorophenyl acetate as a colorless oily product (130 g, yield: 98.0%). 1H-NMR (CDCl3) δ: 2.25 (3H, s), 6.97 (2H, d, J=8 Hz), 7.30 (2H, d, J=8 Hz).
With pyridine; acetic anhydride
2.C Preparation of p-Chlorophenyl Acetate
Part C Preparation of p-Chlorophenyl Acetate Into a reaction flask equipped with a magnetic stirrer and thermometer was charged 257.2 grams (2.0 moles) of p-chlorophenol, 245 grams (2.4 moles) of acetic anhydride and 200 milliliters of pyridine and the resulting reaction mixture was then heated to a temperature of 23° C.-47° C. After completion of the reaction, work-up and distillation at reduced pressure, p-chlorophenyl acetate was obtained (93 percent of theoretical). The nuclear magnetic resonance (NMR) spectrum was consistent with the chemical structure.
Multi-step reaction with 2 steps
1: toluene / 12 h / Inert atmosphere; Reflux
2: triethylamine / toluene / 12 h / Inert atmosphere; Reflux
With hydrogenchloride In chloroform at 20℃; for 12h;
90%
With dihydrogen peroxide; iodine; glacial acetic acid at 20℃; for 0.25h;
85%
With oxygen; benzyl aldehyde In 1,2-dichloro-ethane at 20℃; for 11h;
70%
With 3-chloro-benzenecarboperoxoic acid In lithium hydroxide monohydrate at 80℃; for 1h;
With o-Nitroperoxybenzoesaeure In chloroform at 30℃;
With dihydrogen peroxide In neat (no solvent) at 20℃; for 4h; Green chemistry;
2.3 Typical Procedure for Oxidation of Ketone
General procedure: Ketone (2 mmol), H2O2(2.2 ml approx 20 mmol) and 25 mgAg-NPsmont were taken in 10 ml round bottom flask andthe reaction mixture was stirred at room temperature for 4 h.After completion of the reaction, the solid catalyst was recoveredby filtration. The product obtained contains water as abyproduct was removed by using anhydrous sodium sulphate.The conversion of the reaction was determined using GC.
With oxygen; Pseudomonas fluorescens FW300-N2E2 4-hydroxyacetophenone monooxygenase; NADPH In methanol at 30℃; Enzymatic reaction;
General procedure: Acetophenones with hydroxy group at ortho, meta, para-positions ofthe phenyl ring and six different para-substituted-acetophenones substrates(F-, Cl-, NH2-, CH3-, CH3O-, NO2-) were tested for determining thesubstrate specificity. Additionally, conversion and enantioselectivity ofHAPMOpf toward methyl phenyl sulfide (S17) and methyl phenyl sulfidederivatives bearing electron-donating groups (σ 0; Cl, Br) at ortho, meta, para-positionsof the phenyl ring were determined. Finally, some aliphatic ketoneswere measured, including cyclic ketones and open-chain ketones. Theassays were carried out in standard conditions (100 mM Tris-HCl, pH9.0, 30 C). At different time intervals, samples were withdrawn andprocessed as above mentioned for chiral GC and HPLC analysis. All themeasurements were performed in triplicate.
With 50wtpercent Cs2.5H0.5PW12O40 supported on MCM-41 In acetonitrile at 50℃; for 0.5h;
77%
With phosphoric acid; trifluoroacetic anhydride at 50℃; for 0.0833333h;
59%
With nano-silica melamine trisulfonic acid at 20℃; for 2h;
General procedure for the acetylation of alcoholsin acetic acid
General procedure: In a typical experiment, acetic acid (5 mL), benzyl alcohol(5 mmol, 0.52 mL), and the NSMTSA (0.2 g) were stirred atroom temperature for 5 h. Upon completion of the reaction,monitored by TLC (n-hexane/EtOAc, 4:1, V/V), the reactionvessel was cooled to room temperature. Then, the reactionmixture was stirred with NaHCO3(aq) (20%) to eliminatethe excess of acid. The product was extracted by CH2Cl2(3 × 50 mL) and washed with brine (2 × 50 mL). The solventwas dried by anhydrous CaCl2and evaporated by vacuorotary.The desired benzyl acetate was obtained in 92% yield,exclusively (Table 4, entry 1).
13%
With tungstophosphoric acid-modified zirconia In toluene at 110℃; for 14h;
Catalytic test
General procedure: testIn all the reactions, a 25 cm3round-bottomed flask, at thereaction temperature and connected with a water jacketed con-denser, was used. In a typical experience, the reactor was loadedwith a mixture of 1 mmol of 2-phenylethanol (122 mg), 5 mmolof acetic acid (300 mg), 5 cm3of toluene and 100 mg of the cata-lyst. The mixture was stirred at 700 rpm. Samples were withdrawnfrom the organic phase at different intervals (1, 3, 5, 7, 10 and14 h). Each sample volume was approximately 10 mm3and wasdiluted with 2 cm3of acetonitrile. The concentration of substrateswas calculated with the corresponding areas, using a ShimadzuHP2010 gas chromatography instrument (Chromopack CP Sil 8 CB,30 m × 0.32 mm ID). A similar procedure was followed with theother studied alcohols and phenols.After 14 h of reaction, the solution was concentrated undervacuum, and the residue was purified by column chromatogra-phy employing silica gel as the stationary phase and a mixtureof hexane-ethyl acetate as the elution solvent. The reaction prod-ucts were identified by chromatographic comparison with standardsamples. The conversion was expressed as the ratio of moles ofproducts to moles of initial alcohol.
10%
With S4B15W12.5 borated zirconia modified with ammonium metatungstate In toluene at 110℃; for 14h;
With ZnAl2O4 nanoparticles at 20℃; for 0.583333h; Neat (no solvent);
95%
With trifluorormethanesulfonic acid In acetonitrile at 20℃; for 1h;
4.2. General procedure for O-acylation of phenols in TfOH
General procedure: Phenol (0.28 mmol) and acyl chloride (0.84 mmol, 3 equiv) were dissolved in 1% TfOH/CH3CN (1 ml) at room temperature. The reaction mixture was stirred at same temperature for an hour, then poured into cold water and ethyl acetate. The organic layer was washed with 1 M HCl, saturated NaHCO3, and saturated NaCl, and dried over MgSO4, then filtered. The filtrate was concentrated to afford O-acylated products. All spectral data were identical with the literatures.[27], 27(a), 27(b), 27(c), 27(d), 27(e), 27(f), 27(g) and 27(h)
92%
With dmap; triethylamine In dichloromethane at 20℃; for 6h; Reflux;
90%
With zinc(II) oxide at 20℃; for 0.25h;
86%
With dmap; triethylamine In dichloromethane for 16h; Ambient temperature;
86.87%
With pyridine In dichloromethane at 5℃;
85%
With titanium(IV) oxide at 25℃; for 0.0833333h;
74%
With dmap; triethylamine In toluene at 50℃; for 16h; Inert atmosphere; Sealed tube;
63%
With tetrabutyl-ammonium chloride; sodium hydroxide In dichloromethane; water at 0℃; for 0.0833333h;
In benzene Heating;
With sodium hydroxide; tetrabutyl-ammonium chloride In dichloromethane at 0℃; for 0.0833333h;
Heating;
With dmap; triethylamine In dichloromethane at 20℃;
With dmap; triethylamine In dichloromethane at 20℃;
Stage #1: 4-chloro-phenol With triethylamine In 1,2-dichloro-ethane at 20℃; for 0.0833333h;
Stage #2: acetyl chloride In 1,2-dichloro-ethane
for 1h; Heating;
In neat (no solvent) at 20℃; for 0.5h;
4.2 General procedure for Fries rearrangement and catalyst preparation
General procedure: Catalyst (FSG) was purchased from Fluorous Technologies Inc. and used without further purification. Its synthesis procedure is reported by Curran et al. [24]. General procedure for Fries rearrangement was done by adding FSG to aryl ester at the ambient temperatures. Before adding FSG to reaction mixture, aryl esters were obtained by in situ formation through the reaction of acyl chloride derivatives and phenol derivatives. Thus, to a 100ml round bottom flask stirring by a magnetic bar 10mmol of phenols was added and then, 10mmol of acyl chloride derivatives (for catechols 20mmol) was added dropwise and allowed to react at room temperature. After 30min, temperature was raised to remove HCl from reaction mixture. Then 1g of FSG was added to reaction mixture at ambient temperature. After 4h heating at appropriate temperature in oil bath, the reaction mixture was cooled to room temperature and washed with dichloromethane. The catalyst was separated by filtration. The solvent was removed by rotary evaporator and resulting mixture was separated by column chromatography (stationary phase: silica-gel, eluent:hexane:ethyl acetate) and purified by recrystallization. All isolated products successfully gave related spectral data of IR, NMR, and mass spectrometers.
With triethylamine In dichloromethane at 0 - 5℃;
In toluene for 5h; Reflux;
4.1.1. Synthesis of p-chlorophenyl propionate (10a)
General procedure: mixture of p-chlorophenol 9 (5 g, 38.89 mmol) and propionylchloride (3.74 mL, 42.78 mmol) in dry toluene (30 mL) was refluxedfor 5 h. The toluenewas evaporated in vacuo to give p-chlorophenylpropionate 10a (6.9 g, 96%) as an oil whichwas used for further stepwithout purification.
at 90℃;
2.1.2.1. Acetylation of 6/7/8-Substituted Phenol
General procedure: The reaction was carried out by refluxing 6/7/8-substituted phenol (10 g, 0.077 moles) with acetyl chloride(15 ml, 0.1167 moles) in RBF at 90oC in the anhydrous reactionconditions, to obtain corresponding ester derivatives.The reaction was monitored by TLC (Ethylacetate:hexane::30:70) till the disappearance of the spot of thereactant (Scheme 1).
With pyridine In dichloromethane at 0 - 20℃; for 5h;
With potassium <i>tert</i>-butylate; sodium carbonate In toluene at 20℃; for 42h;
1
Comparative Example 1; The procedure of Example 1 was repeated except that 3 molar equivalents of p-chlorophenyl acetate (a conventional acylating agent) was used in place of isopropenyl acetate in the presence of three times the amount of the enzyme catalyst used in Example 1 over a reaction period of 42 hours, to obtain (R)-1-phenylethyl acetate having an optical purity of higher than 99%, at a yield of 95%. The results of Examples 1 to 5 with Comparative Example 1 show that even when an alkenyl acetate is used as an acylating agent in accordance with the present invention, a desired enantiomer can be effectively resolved from its racemate at a yield comparable to that obtained using an aryl acetate that gives an aryl alcohol by-product which is difficult to separate from the reaction product.
92%
With acetophenone In <i>tert</i>-butyl alcohol at 70℃; for 87h;
81%
Stage #1: 1-Phenylethanol With dicarbonylhydro[2,5-di(trimethylsilyl)-3,4-butylene-1-hydroxy(η5-cyclopentadienyl)]iron; lipase from Candida antarctica In toluene for 0.0833333h; Schlenk technique; Inert atmosphere; Resolution of racemate; Enzymatic reaction;
Stage #2: 4-chlorophenyl acetate In toluene at 60℃; for 24h; Schlenk technique; Inert atmosphere; enantioselective reaction;
With Novozym 435; <Ru2(CO)4(μ-H)(C4Ph4COHOCC4Ph4)> In toluene at 70℃; for 46h;
95 % Chromat.
With Novozym 435; (isopropylamino)(tetraphenyl)cyclopentadienyl Ru(CO)2Cl; potassium <i>tert</i>-butylate In toluene at 25℃; for 42h;
With Candida antarctica B lipase; [RuCl2(p-cymene)]2; (E)-2-((1-hydroxy-2-methylpropan-2-ylimino)methyl)phenol; potassium hydroxide In toluene at 70℃; for 72h; Enzymatic reaction; optical yield given as %ee; enantioselective reaction;
96 %Spectr.
With potassium <i>tert</i>-butylate; sodium carbonate In toluene at 60℃; for 48h; Schlenk technique; Inert atmosphere; Enzymatic reaction; enantioselective reaction;
Stage #1: 1-Indanol With dicarbonylhydro[2,5-di(trimethylsilyl)-3,4-butylene-1-hydroxy(η5-cyclopentadienyl)]iron; lipase from Candida antarctica In toluene for 0.0833333h; Schlenk technique; Inert atmosphere; Resolution of racemate; Enzymatic reaction;
Stage #2: 4-chlorophenyl acetate In toluene at 60℃; for 24h; Schlenk technique; Inert atmosphere; enantioselective reaction;
In <i>tert</i>-butyl alcohol at 70℃; for 69h; Yield given;
With Novozym 435; <Ru2(CO)4(μ-H)(C4Ph4COHOCC4Ph4)> In toluene at 70℃; for 48h;
Stage #1: rac-octan-2-ol With dicarbonylhydro[2,5-di(trimethylsilyl)-3,4-butylene-1-hydroxy(η5-cyclopentadienyl)]iron; lipase from Candida antarctica In toluene for 0.0833333h; Schlenk technique; Inert atmosphere; Resolution of racemate; Enzymatic reaction;
Stage #2: 4-chlorophenyl acetate In toluene at 60℃; for 24h; Schlenk technique; Inert atmosphere; enantioselective reaction;
80%
With Novozym 435; <Ru2(CO)4(μ-H)(C4Ph4COHOCC4Ph4)> In toluene at 70℃; for 24h;
Stage #1: 2-(2-naphthyl)ethanol With dicarbonylhydro[2,5-di(trimethylsilyl)-3,4-butylene-1-hydroxy(η5-cyclopentadienyl)]iron; lipase from Candida antarctica In toluene for 0.0833333h; Schlenk technique; Inert atmosphere; Resolution of racemate; Enzymatic reaction;
Stage #2: 4-chlorophenyl acetate In toluene at 60℃; for 24h; Schlenk technique; Inert atmosphere; enantioselective reaction;
79%
With Novozym 435; <Ru2(CO)4(μ-H)(C4Ph4COHOCC4Ph4)> In toluene at 70℃; for 48h;
95 %Spectr.
With potassium <i>tert</i>-butylate; sodium carbonate In toluene at 60℃; for 48h; Schlenk technique; Inert atmosphere; Enzymatic reaction; enantioselective reaction;
With Novozym 435; <Ru2(CO)4(μ-H)(C4Ph4COHOCC4Ph4)> In toluene at 70℃; for 48h; Title compound not separated from byproducts;
With 2,2,6,6-Tetramethyl-1-piperidinyloxy free radical; Candida antarctica B lipase; [RuCl2(p-cymene)]2; (E)-2-((1-hydroxy-2-methylpropan-2-ylimino)methyl)phenol In toluene at 70℃; for 72h; Inert atmosphere; Enzymatic reaction; optical yield given as %ee; enantioselective reaction;
4.3. General procedure for the dynamic kinetic resolution of alcohols 1-9
General procedure: The reaction was carried out under an argon atmosphere at 70 °C for 72 h in a dry Schlenk tube with 2.5 mol % of [RuCl2(p-cymene)2]2 (15 mg), 5 mol % of ligand, 150 μmol of TEMPO (23 mg) and 40 mg of CAL-B in 2 mL of toluene. After 5 min, 1 mmol of racemic alcohol was added. The mixture took a red color. After 15 min, 3 mmol of p-chlorophenylacetate were added to the red reaction mixture. The reaction conversion and enantiomeric excess of the alcohol were monitored by taking samples for CG analysis. The samples were diluted with diethyl ether and washed with a saturated solution of NH4Cl, and filtered on silica. After 72 h, the dark reaction mixture was filtered on Celite, washed with a saturated solution of NH4Cl and extracted with ether. The organic layers were dried over Na2SO4, and concentrated in vacuo.
(R)-1,2,3,4-tetrahydro-1-naphthyl acetate[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
68%
Stage #1: 1,2,3,4-Tetrahydro-1-naphthol With dicarbonylhydro[2,5-di(trimethylsilyl)-3,4-butylene-1-hydroxy(η5-cyclopentadienyl)]iron; lipase from Candida antarctica In toluene for 0.0833333h; Schlenk technique; Inert atmosphere; Resolution of racemate; Enzymatic reaction;
Stage #2: 4-chlorophenyl acetate In toluene at 60℃; for 24h; Schlenk technique; Inert atmosphere; enantioselective reaction;
65%
With Novozym 435; <Ru2(CO)4(μ-H)(C4Ph4COHOCC4Ph4)> In toluene at 70℃; for 48h;
89 %Spectr.
With potassium <i>tert</i>-butylate; sodium carbonate In toluene at 60℃; for 72h; Schlenk technique; Inert atmosphere; Enzymatic reaction; enantioselective reaction;
With 2,2,6,6-Tetramethyl-1-piperidinyloxy free radical; Candida antarctica B lipase; [RuCl2(p-cymene)]2; (E)-2-((1-hydroxy-2-methylpropan-2-ylimino)methyl)phenol In toluene at 70℃; for 72h; Inert atmosphere; Enzymatic reaction; optical yield given as %ee; enantioselective reaction;
4.3. General procedure for the dynamic kinetic resolution of alcohols 1-9
General procedure: The reaction was carried out under an argon atmosphere at 70 °C for 72 h in a dry Schlenk tube with 2.5 mol % of [RuCl2(p-cymene)2]2 (15 mg), 5 mol % of ligand, 150 μmol of TEMPO (23 mg) and 40 mg of CAL-B in 2 mL of toluene. After 5 min, 1 mmol of racemic alcohol was added. The mixture took a red color. After 15 min, 3 mmol of p-chlorophenylacetate were added to the red reaction mixture. The reaction conversion and enantiomeric excess of the alcohol were monitored by taking samples for CG analysis. The samples were diluted with diethyl ether and washed with a saturated solution of NH4Cl, and filtered on silica. After 72 h, the dark reaction mixture was filtered on Celite, washed with a saturated solution of NH4Cl and extracted with ether. The organic layers were dried over Na2SO4, and concentrated in vacuo.
With Novozym 435; <Ru2(CO)4(μ-H)(C4Ph4COHOCC4Ph4)> In toluene at 70℃; for 48h;
With (η5-indenyl)ruthenium(bis(triphenylphosphine))chloride; Pseudomonas cepocia lipase; triethylamine at 60℃; for 43h; Enzymatic reaction; Title compound not separated from byproducts;
With (η5-indenyl)ruthenium(bis(triphenylphosphine))chloride; Pseudomonas cepocia lipase; triethylamine at 60℃; for 43h; Enzymatic reaction;
75 %Spectr.
With η-p-cymene dichloro(pyridine)ruthenium(II); potassium <i>tert</i>-butylate; sodium carbonate In toluene at 70℃; for 48h; Inert atmosphere; Schlenk technique; Enzymatic reaction; enantioselective reaction;
General procedure for dynamic kinetic resolution of rac-alcohols
General procedure: To a 25 mL Schlenk tube containing 5 mL toluene, Ru or Ir complex (0.01 mmol, 2.0 mol%) and potassium tert-butoxide (0.04mmol, 5.0mol%) were added and stirred for 10min. Sodium carbonate (0.5mmol), alcohol (0.5mmol), acylating agents (1.5mmol) and Novozym-435 (10mg) were then added. The solvent was then stirred for 24hat 60°C or 70°C. After evaporation to dryness, the mixture was loaded to a 10×3cm silica column. Elution with petroleum ether removed any alcohol. The product was eluted with 3:50 ethyl acetate/petroleum ether, and the solvent removed to give an oily mixture. The yield was directly determined by 1H NMR. Enantiomeric excesses were determined by specific rotation, HPLC or GC.
With (η5-indenyl)ruthenium(bis(triphenylphosphine))chloride; Pseudomonas cepocia lipase; triethylamine at 60℃; for 43h; Enzymatic reaction;
93 %Spectr.
With [ruthenium(II)(η6-1-methyl-4-isopropyl-benzene)(chloride)(μ-chloride)]2; potassium <i>tert</i>-butylate; sodium carbonate In toluene at 60℃; for 48h; Inert atmosphere; Schlenk technique; Enzymatic reaction; enantioselective reaction;
General procedure for dynamic kinetic resolution of rac-alcohols
General procedure: To a 25 mL Schlenk tube containing 5 mL toluene, Ru or Ir complex (0.01 mmol, 2.0 mol%) and potassium tert-butoxide (0.04mmol, 5.0mol%) were added and stirred for 10min. Sodium carbonate (0.5mmol), alcohol (0.5mmol), acylating agents (1.5mmol) and Novozym-435 (10mg) were then added. The solvent was then stirred for 24hat 60°C or 70°C. After evaporation to dryness, the mixture was loaded to a 10×3cm silica column. Elution with petroleum ether removed any alcohol. The product was eluted with 3:50 ethyl acetate/petroleum ether, and the solvent removed to give an oily mixture. The yield was directly determined by 1H NMR. Enantiomeric excesses were determined by specific rotation, HPLC or GC.
With Novozym 435; 2,6-dimethyl-4-heptanol In toluene at 70℃; for 44h; Enzymatic reaction;
96 % ee
With novozyme 435; dicarbonylhydro[2,5-di(trimethylsilyl)-3,4-butylene-1-hydroxy(η5-cyclopentadienyl)]iron; hydrogen In toluene at 90℃; for 18h; Schlenk technique; Enzymatic reaction; enantioselective reaction;
(S)-2-cyano-1-(p-nitrophenyl)ethyl acetate[ No CAS ]
Acetic acid (R)-2-cyano-1-(4-nitro-phenyl)-ethyl ester[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
With 2,4-dimethyl-3-pentanol; Novocym 435 (Candida antarctica lipase B) In toluene at 100℃; for 36h; Enzymatic reaction; Title compound not separated from byproducts.;
With Novozym 435; potassium <i>tert</i>-butylate; sodium carbonate In toluene at 25℃; for 42h;
With [ruthenium(II)(η6-1-methyl-4-isopropyl-benzene)(chloride)(μ-chloride)]2; potassium <i>tert</i>-butylate; sodium carbonate In toluene at 60℃; for 48h; Inert atmosphere; Schlenk technique; Enzymatic reaction; Overall yield = 70 %Spectr.; Optical yield = 40 %ee; enantioselective reaction;
General procedure for dynamic kinetic resolution of rac-alcohols
General procedure: To a 25 mL Schlenk tube containing 5 mL toluene, Ru or Ir complex (0.01 mmol, 2.0 mol%) and potassium tert-butoxide (0.04mmol, 5.0mol%) were added and stirred for 10min. Sodium carbonate (0.5mmol), alcohol (0.5mmol), acylating agents (1.5mmol) and Novozym-435 (10mg) were then added. The solvent was then stirred for 24hat 60°C or 70°C. After evaporation to dryness, the mixture was loaded to a 10×3cm silica column. Elution with petroleum ether removed any alcohol. The product was eluted with 3:50 ethyl acetate/petroleum ether, and the solvent removed to give an oily mixture. The yield was directly determined by 1H NMR. Enantiomeric excesses were determined by specific rotation, HPLC or GC.
With η-p-cymene dichloro(pyridine)ruthenium(II); potassium tert-butylate; sodium carbonate; In toluene; at 70℃; for 48h;Inert atmosphere; Schlenk technique; Enzymatic reaction;
General procedure: To a 25 mL Schlenk tube containing 5 mL toluene, Ru or Ir complex (0.01 mmol, 2.0 mol%) and potassium tert-butoxide (0.04mmol, 5.0mol%) were added and stirred for 10min. Sodium carbonate (0.5mmol), alcohol (0.5mmol), acylating agents (1.5mmol) and Novozym-435 (10mg) were then added. The solvent was then stirred for 24hat 60C or 70C. After evaporation to dryness, the mixture was loaded to a 10×3cm silica column. Elution with petroleum ether removed any alcohol. The product was eluted with 3:50 ethyl acetate/petroleum ether, and the solvent removed to give an oily mixture. The yield was directly determined by 1H NMR. Enantiomeric excesses were determined by specific rotation, HPLC or GC.
With [ruthenium(II)(η6-1-methyl-4-isopropyl-benzene)(chloride)(μ-chloride)]2; potassium tert-butylate; sodium carbonate; In toluene; at 70℃; for 48h;Inert atmosphere; Schlenk technique; Enzymatic reaction;
General procedure: To a 25 mL Schlenk tube containing 5 mL toluene, Ru or Ir complex (0.01 mmol, 2.0 mol%) and potassium tert-butoxide (0.04mmol, 5.0mol%) were added and stirred for 10min. Sodium carbonate (0.5mmol), alcohol (0.5mmol), acylating agents (1.5mmol) and Novozym-435 (10mg) were then added. The solvent was then stirred for 24hat 60C or 70C. After evaporation to dryness, the mixture was loaded to a 10×3cm silica column. Elution with petroleum ether removed any alcohol. The product was eluted with 3:50 ethyl acetate/petroleum ether, and the solvent removed to give an oily mixture. The yield was directly determined by 1H NMR. Enantiomeric excesses were determined by specific rotation, HPLC or GC.
With Lipase PS-C; triethylamine In dichloromethane at 40℃; for 44h;
13 EXAMPLE 13
[00050] A racemic alcohol of formula 4a(0.25 mmol), triethylamine(0.25 mmol), ruthenium complex of formula 10(0.0100 mmol), where X is Cl, 40 mg of lipase PS-C, and p-chlorophenyl acetate(0.75 mmol) were mixed in 1.2 ml of methylene chloride to give a dark redish suspension. [00051] Argon gas was purged into the reaction suspension, after removing oxygen under the vacuum condition and then it was heated at 40° C. for 44 hours.
1: 90%
2: 8%
With Lipase PS-C; triethylamine In dichloromethane at 40℃; for 44h;
7 EXAMPLE 7
[00047] A racemic alcohol of formula 4a(0.25 mmol), triethylamine(0.25 mmol), ruthenium complex of formula 7(0.0130 mmol), where X is Cl, 40 mg of lipase PS-C, and p-chlorophenyl acetate(0.75 mmol) were mixed in 1.2 ml of methylene chloride to give a dark redish suspension. [00048] Argon gas was purged into the reaction suspension, after removing oxygen under the vacuum condition and then it was heated at 40° C. for 44 hours.
1: 80%
2: 20%
With Novozym 435 In toluene at 70℃; for 46h;
1 Comparative Example 1
[00053] A racemic alcohol of formula 4a(2 mmol), ruthenium complex expressed in the following structure below(0.04 mmol), 60 mg of Novozym 435, and p-chlorophenyl acetate(6 mmol) were mixed in 5 ml of toluene to give a dark redish suspension. [00054] The reaction suspension was heated at 70° C. for 46 hours under argon gas.
With Lipase PS-C; oxygen; triethylamine In dichloromethane at 60℃; for 43h;
1 EXAMPLE 1
[00044] A racemic alcohol of formula 4a(0.25 mmol), triethylamine(0.75 mmol), ruthenium complex of formula 6(0.0130 mmol), where X is Cl, 40 mg of lipase PS-C, and p-chlorophenyl acetate (0.75 mmol) were mixed in 2.0 ml of dichloromethane to give a reddish brown suspension. [00045] Argon gas was purged into the reaction suspension, after removing oxygen under the vacuum condition. Oxygen(0.0130 mmol) was injected with syringe in the reaction suspension and then it was heated at 60° C. for 43 hours.
50 %Chromat.
With Novozyme 435 lipase In toluene at 40℃; for 0.5h; Enzymatic reaction; optical yield given as %ee; enantioselective reaction;
4.3. Kinetic resolution of 1-phenylethanol
General procedure: In a typical kinetic resolution, the acyl donor (600 mmol) was added to a stirred solution of rac-1-phenylethanol (24.4 mg, 200 mmol) and lipase Novozyme 435 (20 mg) in toluene (2 ml) at 40 °C.
With potassium phosphate;tris(dibenzylideneacetone)dipalladium(0) chloroform complex; catacxium A; at 120℃; for 15.5h;Product distribution / selectivity;
Example 7 A 10 ml-Schlenk tube equipped with magnetic stirrer was charged with 119 mg (0.7 mmol) 4-acetoxychlorophenol, 200 mg (0.84 mmol, 1.2 eq) 3,5-diacetoxystyrene, 177 mg (0.84 mmol, 1.2 eq) potassium triphosphate, 5 mg diadamantyl-n-butylphosphine (0.014 mmol, 2 MOL%) and 3.7 mg (0.003 mmol, 0.5 mol%) tris (dibenzylideneacetone)-dipalladium chloroform complex. The tube was evacuated and flushed with argon three times and 2 ml de-aerated DMAC were added under inert conditions. The reaction was carried out under stirring for 15.5 hours at 120. Work-up of the reaction mixture following the procedure of Example 5 gave (E)-3, 4', 5-triacetoxystilbene.
With caesium carbonate;tris(dibenzylideneacetone)dipalladium(0) chloroform complex; tri-tert-butyl phosphine; at 120℃; for 19h;Product distribution / selectivity;
Example 8 A 10 ml Schlenk tube equipped with magnetic stirrer was charged with 59 mg (0.7 mmol) 4-ACETOXYCHLOROPHENOL, 100 mg (0.84 mmol, 1.2 eq) 3, 5-DIACETOXYSTYRENE, 125 mg cesium carbonate (0.38 mmol 1. 1 eq), 5 UL P (t-Bu) 3 (0.02 mmol, 6 mol%) and 5.57 mg (0.01 MMOL, 1.5 MOL%) TRIS (DIBENZYLIDENEACETONE) -DIPALLADIUM CHLOROFORM COMPLEX. THE tube was evacuated and flushed with argon three times and 1 ml de-aerated dioxane was added under inert conditions. The reaction was carried out under stirring for 19 hours at 120C. Work-up was conducted following the procedure of Example 5 and gave (E)-3, 4 , 5- triacetoxystilbene.
With 1-hydroxytetraphenylcyclopentadienyl(tetraphenyl-2,4-cyclopentadien-1-one)-μ-hydrotetracarbonyldiruthenium(II); Pseudomonas cepacia; hydrogen In toluene at 70℃; Inert atmosphere; optical yield given as %de; diastereoselective reaction;
With 1-hydroxytetraphenylcyclopentadienyl(tetraphenyl-2,4-cyclopentadien-1-one)-μ-hydrotetracarbonyldiruthenium(II); Pseudomonas cepacia; hydrogen In toluene at 70℃; Inert atmosphere;
With 1-hydroxytetraphenylcyclopentadienyl(tetraphenyl-2,4-cyclopentadien-1-one)-μ-hydrotetracarbonyldiruthenium(II) In toluene at 80℃; for 24h; Inert atmosphere; Enzymatic reaction; optical yield given as %ee; stereoselective reaction;
With Candida antarctica lipase B; C38H24O3Ru; potassium <i>tert</i>-butylate; sodium carbonate In toluene for 20h; Enzymatic reaction;
15.8 %Chromat.
With acidic CD8604 resin In toluene at 40℃; for 12h;
4.2. General procedure for the non-selective transesterification reaction
General procedure: At first, rac-1-phenylethanol (24.4 mg, 200 mmol) and CD8604 (40 mg) were dissolved in toluene (2 mL). The acyl donors (600 mmol) were then added into the mixture system, and the system stirred at 40 °C.
With perchloric acid immobilized on silica gel In dichloromethane for 10h;
4.2. General procedure for direct transformation
General procedure: HClO4-SiO2 (0.5 mmol/g; 50 mg) was added to a stirred solution of substrate (1.0 mmol) and Ac2O (0.45 mL, 5.0 mmol) in CH2Cl2 (5 mL) at rt or heated under reflux. After complete conversion and filtration to remove the catalyst, saturated aqueous solution of NaHCO3 (10 mL) was added and separated. The aqueous solution was extracted with CH2Cl2 (2×10 mL). The organic layer was combined, washed with brine (10 mL), dried (MgSO4), and concentrated under reduced pressure. The residual was isolated through short column chromatography on silica gel, which was eluted with ethyl acetate-petroleum (bp 60-90 °C) to give the target products.All new products were characterized by 1H NMR, 13C NMR and HRMS (ESI) spectra and the NMR data for known compounds matched that reported in literature.
tert-butyl-4-chlorophenoxy-diphenylsilane[ No CAS ]
TBDPSOAc[ No CAS ]
[ 876-27-7 ]
Yield
Reaction Conditions
Operation in experiment
1: 90%
2: 86%
With perchloric acid immobilized on silica gel In dichloromethane at 20℃; for 10h;
4.2. General procedure for direct transformation
General procedure: HClO4-SiO2 (0.5 mmol/g; 50 mg) was added to a stirred solution of substrate (1.0 mmol) and Ac2O (0.45 mL, 5.0 mmol) in CH2Cl2 (5 mL) at rt or heated under reflux. After complete conversion and filtration to remove the catalyst, saturated aqueous solution of NaHCO3 (10 mL) was added and separated. The aqueous solution was extracted with CH2Cl2 (2×10 mL). The organic layer was combined, washed with brine (10 mL), dried (MgSO4), and concentrated under reduced pressure. The residual was isolated through short column chromatography on silica gel, which was eluted with ethyl acetate-petroleum (bp 60-90 °C) to give the target products.All new products were characterized by 1H NMR, 13C NMR and HRMS (ESI) spectra and the NMR data for known compounds matched that reported in literature.
With 2,2,6,6-Tetramethyl-1-piperidinyloxy free radical; Candida antarctica B lipase; [RuCl2(p-cymene)]2; (E)-2-((1-hydroxy-2-methylpropan-2-ylimino)methyl)phenol In toluene at 70℃; for 72h; Inert atmosphere; Enzymatic reaction; optical yield given as %ee; enantioselective reaction;
4.3. General procedure for the dynamic kinetic resolution of alcohols 1-9
General procedure: The reaction was carried out under an argon atmosphere at 70 °C for 72 h in a dry Schlenk tube with 2.5 mol % of [RuCl2(p-cymene)2]2 (15 mg), 5 mol % of ligand, 150 μmol of TEMPO (23 mg) and 40 mg of CAL-B in 2 mL of toluene. After 5 min, 1 mmol of racemic alcohol was added. The mixture took a red color. After 15 min, 3 mmol of p-chlorophenylacetate were added to the red reaction mixture. The reaction conversion and enantiomeric excess of the alcohol were monitored by taking samples for CG analysis. The samples were diluted with diethyl ether and washed with a saturated solution of NH4Cl, and filtered on silica. After 72 h, the dark reaction mixture was filtered on Celite, washed with a saturated solution of NH4Cl and extracted with ether. The organic layers were dried over Na2SO4, and concentrated in vacuo.
With 1-hydroxytetraphenylcyclopentadienyl(tetraphenyl-2,4-cyclopentadien-1-one)-μ-hydrotetracarbonyldiruthenium(II); Novozym 435 In toluene at 80℃; for 82h; Schlenk technique; Enzymatic reaction; stereoselective reaction;
General procedure A for inversion of L-alkyl lactates:
General procedure: A Schlenk tube was charged with Shvo's catalyst 2 (27 mg, 0.045 mmol), alkyl lactate (0.5 mmol), Novozym 435 (10 mg, 100 units), p-chlorophenyl acetate (0.21 mL, 1.5 mmol), and abs. degassed toluene (5 mL) at rt. The mixture was stirred for 82 h at 80 °C. The composition of the reaction mixture was analyzed by gas chromatography.
With [ruthenium(II)(η6-1-methyl-4-isopropyl-benzene)(chloride)(μ-chloride)]2; potassium <i>tert</i>-butylate; sodium carbonate In toluene at 70℃; for 48h; Inert atmosphere; Schlenk technique; Enzymatic reaction; enantioselective reaction;
General procedure for dynamic kinetic resolution of rac-alcohols
General procedure: To a 25 mL Schlenk tube containing 5 mL toluene, Ru or Ir complex (0.01 mmol, 2.0 mol%) and potassium tert-butoxide (0.04mmol, 5.0mol%) were added and stirred for 10min. Sodium carbonate (0.5mmol), alcohol (0.5mmol), acylating agents (1.5mmol) and Novozym-435 (10mg) were then added. The solvent was then stirred for 24hat 60°C or 70°C. After evaporation to dryness, the mixture was loaded to a 10×3cm silica column. Elution with petroleum ether removed any alcohol. The product was eluted with 3:50 ethyl acetate/petroleum ether, and the solvent removed to give an oily mixture. The yield was directly determined by 1H NMR. Enantiomeric excesses were determined by specific rotation, HPLC or GC.
(R)-1,2,3,4-tetrahydro-1-naphthyl acetate[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
88 %Spectr.
With [ruthenium(II)(η6-1-methyl-4-isopropyl-benzene)(chloride)(μ-chloride)]2; potassium <i>tert</i>-butylate; sodium carbonate In toluene at 60℃; for 48h; Inert atmosphere; Schlenk technique; Enzymatic reaction; enantioselective reaction;
General procedure for dynamic kinetic resolution of rac-alcohols
General procedure: To a 25 mL Schlenk tube containing 5 mL toluene, Ru or Ir complex (0.01 mmol, 2.0 mol%) and potassium tert-butoxide (0.04mmol, 5.0mol%) were added and stirred for 10min. Sodium carbonate (0.5mmol), alcohol (0.5mmol), acylating agents (1.5mmol) and Novozym-435 (10mg) were then added. The solvent was then stirred for 24hat 60°C or 70°C. After evaporation to dryness, the mixture was loaded to a 10×3cm silica column. Elution with petroleum ether removed any alcohol. The product was eluted with 3:50 ethyl acetate/petroleum ether, and the solvent removed to give an oily mixture. The yield was directly determined by 1H NMR. Enantiomeric excesses were determined by specific rotation, HPLC or GC.
(R)-1-[4-(trifluoromethyl)phenyl]ethan-1-ol[ No CAS ]
[ 172424-27-0 ]
Yield
Reaction Conditions
Operation in experiment
With [ruthenium(II)(η6-1-methyl-4-isopropyl-benzene)(chloride)(μ-chloride)]2; potassium <i>tert</i>-butylate; sodium carbonate In toluene at 70℃; for 48h; Inert atmosphere; Schlenk technique; Enzymatic reaction; Overall yield = 95 %Spectr.; Optical yield = 86 %ee; enantioselective reaction;
General procedure for dynamic kinetic resolution of rac-alcohols
General procedure: To a 25 mL Schlenk tube containing 5 mL toluene, Ru or Ir complex (0.01 mmol, 2.0 mol%) and potassium tert-butoxide (0.04mmol, 5.0mol%) were added and stirred for 10min. Sodium carbonate (0.5mmol), alcohol (0.5mmol), acylating agents (1.5mmol) and Novozym-435 (10mg) were then added. The solvent was then stirred for 24hat 60°C or 70°C. After evaporation to dryness, the mixture was loaded to a 10×3cm silica column. Elution with petroleum ether removed any alcohol. The product was eluted with 3:50 ethyl acetate/petroleum ether, and the solvent removed to give an oily mixture. The yield was directly determined by 1H NMR. Enantiomeric excesses were determined by specific rotation, HPLC or GC.
With η-p-cymene dichloro(pyridine)ruthenium(II); potassium <i>tert</i>-butylate; sodium carbonate In toluene at 70℃; for 48h; Inert atmosphere; Schlenk technique; Enzymatic reaction; enantioselective reaction;
General procedure for dynamic kinetic resolution of rac-alcohols
General procedure: To a 25 mL Schlenk tube containing 5 mL toluene, Ru or Ir complex (0.01 mmol, 2.0 mol%) and potassium tert-butoxide (0.04mmol, 5.0mol%) were added and stirred for 10min. Sodium carbonate (0.5mmol), alcohol (0.5mmol), acylating agents (1.5mmol) and Novozym-435 (10mg) were then added. The solvent was then stirred for 24hat 60°C or 70°C. After evaporation to dryness, the mixture was loaded to a 10×3cm silica column. Elution with petroleum ether removed any alcohol. The product was eluted with 3:50 ethyl acetate/petroleum ether, and the solvent removed to give an oily mixture. The yield was directly determined by 1H NMR. Enantiomeric excesses were determined by specific rotation, HPLC or GC.
With chlorobis(cyclooctene)-iridium(I) dimer In tetrahydrofuran at 60℃; Inert atmosphere;
With chlorobis(cyclooctene)-iridium(I) dimer In tetrahydrofuran at 60℃; Inert atmosphere;
4.2 General procedure for preparation of arylsilyl triflates from phenyl acetates (5)
General procedure: (i) [Ir(coe)2Cl]2 (0.9 mg, 0.1mol %) and aryl acetates 1 (1 mmol) were added to a flame-dried, nitrogen-purged septum-capped vial. The mixture was dissolved with THF (0.3 mL, 3.3 M), and diethylsilane (0.26 mL, 2 mmol) was added to the mixture. The septum on the vial was replaced by a screw cap with a Teflon liner under a N2 atmosphere [note: diethylsilane (bp 56 °C and density 0.686 g/mL) is volatile]. The reaction mixture was stirred for 3-12 h at 60 °C. Volatiles were removed in vacuo to afford silyl acetals, which were directly used for subsequent reactions without further purification. (ii) [Rh(nbd)Cl]2 (1.8 mg, 0.4 mol %), tris(4-methoxyphenyl)phosphine (8.4 mg, 2.4 mol %), norbornene (188 mg, 2 mmol), and THF (1 mL, 1M) were added to the crude silyl acetals (1 mmol). The septum on the vial was replaced by a screw cap with a Teflon liner, and the mixture was stirred at 120 °C for 15 min. The reaction progress was monitored by GC/MS spectrometry. The resulting benzodioxasilines 3 were directly used for a subsequent reaction without further purification. For hindered substrates 3o-r, the resulting benzodioxasilines 3 were purified for the subsequent reactions; volatiles were removed in vacuo, and the resulting mixture was dissolved with pentane, filtered through a pad of Celite, and concentrated in vacuo. The crude product was purified by MPLC (hexanes/EtOAc=80:1, 5mL/min, retention time 5-15 min). (iii) The crude benzodioxasilines 3 (1 mmol, THF, 1M) were diluted with diethyl ether (3 mL, 0.33 M) and cooled to -78 °C. MeLi (3 mmol, 1.6 M in Et2O) were added into the reaction mixture at -78 °C and stirred for 1 min. (iv) Trifluoromethanesulfonyl anhydride (1.2 mmol, 0.2 mL) was added into the reaction mixture. The reaction mixture was warmed to rt and stirred for 30 min. The reaction mixture was cooled to 0 °C and saturated aqueous ammonium chloride solution was added. The mixture was extracted with diethyl ether three times. The combined organic layer was washed with water and brine, and dried over anhydrous sodium sulfate. Volatiles were removed in vacuo, and the crude mixture was purified by MPLC to afford arylsilyl triflates 5 (hexanes/EtOAc=40:1, 5mL/min, retention time 6-20 min).
1-(3,5-bis(trifluoromethyl)phenyl)ethan-1-ol[ No CAS ]
[ 534613-13-3 ]
Yield
Reaction Conditions
Operation in experiment
99.7%
With Novozym 435 In toluene at 45℃; for 15h;
To a 100 ml Erlenmeyer flask was added 50 ml of toluene as a solvent,Followed by the addition of 5.16 g(20 mmol)3,5-bistrifluoromethylphenethyl alcohol,(22.5 mmol)P-chlorobenzoate acetate,0.5 g Novozym 435,Lg acidic resin 550, after the end of feeding,Bottle seal,Placed in a 45 ° C shaker to carry out the reaction,15 hours after the test,3,5-bistrifluoromethylphenethyl alcohol was completely converted to R-3,5-bistrifluoromethylphenethyl alcohol acetate,And the value of 99.7%.After the completion of the reaction, the solution was filtered and concentrated to give 8.51 g of a pale yellow oily liquid.
3,6-diethyl-2,5-dimethylcyclohex-2-en-1-ol[ No CAS ]
C14H24O2[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
98.1%
With porcine pancreatic lipase In toluene at 45℃; for 6h; Enzymatic reaction;
2.5 Example 2
5) In a constant temperature shaker, with 1000ml blue bottle as the reaction vessel, 700 g of toluene, 91 g of 3,6-diethyl-2,5-dimethylcyclohex-2-en-1-ol, 110 g of p-chlorophenol acetate, 9 g of porcine pancreatic lipase PPL were added. After completion of addition, the temperature was raised to 45 ° C. After 6 hours, the conversion of 3,6-diethyl-2,5-dimethylcyclohex-2-en-1-ol was measured to 50%. The reaction was stopped and the reaction solution was cooled, filtered, concentrated and passed through column to give 44.77 g of S -3,6-diethyl-2,5-dimethylcyclohex-2-en-1-ol. The yield was 98.4%, the product ee was 99.9%, and the yield was 54.94 g of R-3,6-diethyl-2,5-dimethylcyclohex-2-ene-1-ol acetyl compound 98.1%.
With porcine pancreatic lipase PPL at 40℃; for 6h; Enzymatic reaction;
2.5 Example 2
5) 700 ml of toluene, 90 g of 1-piperonyl-2-propanol, 110 g of p-chlorophenol acetate and 9 g of porcine pancreatic lipase PPL were charged in a constant temperature shaker with a 1000 ml blue cap as a reaction vessel , The temperature was raised to 45 ° C, and after 6 hours, the conversion of 1-piperonyl-2-propanol was measured to 50%; the reaction was stopped, the reaction solution was cooled, filtered, concentrated,44.28 g of S -1-piperonyl-2-propanol were obtained in a yield of 98.4% and the product value was 99.8%The yield of the R-1-piperonyl-2-propanol acetyl compound was 54.57 g, the yield was 98.5% and the product value was 99.8%.
With Pseudomonas fluorescens lipase AK In toluene at 45℃; for 6h; Enzymatic reaction;
1.2
A 100 ml toluene, 17.6 g of a-cyclopentyl (phenyl) methanol was added to a reaction vessel in a constant temperature shaker with 200 ml of blue cap as a reaction vessel, 10 g p-Chlorophenol acetate, 1.5 g of Pseudomonas fluorescens lipase Lipase AK, the feed was completed and the temperature was raised to 45 ° C. After 6 hours, the conversion of α-cyclopentyl (phenyl) methanol was 50%, and Ra-cyclopenta (Phenyl) methanol is converted into a Ra-cyclopentyl (phenyl) methanol acetyl compound; the reaction solution is cooled, filtered and concentrated to give a Ra-cyclopentyl (phenyl) methanol acetyl compound and (Phenyl) methanol, 8.66 g of Sa-cyclopentyl (phenyl) methanol and 49.1% of the S configuration were obtained in the presence of a base to give the 10.36 g of a R - alpha - cyclopentyl (phenyl) methanol acetyl compound in a yield of 49.0%.
With Pseudomonas fluorescens lipase AK In toluene at 45℃; for 12h; Enzymatic reaction;
1.3
A 100 ml toluene, 17.6 g of a-cyclopentyl (phenyl) methanol, 19.0 g of p-chlorobenzoic acid acetate, 1.5 g of incineration was charged in a constant temperature shaker with 200 ml of blue cap as a reaction vessel 16g solid superacid S042-_Fe203, feeding is completed, the temperature to 45 ° C for 12 hours after the detection of α-cyclopentyl (phenyl) methanol disappeared, (Phenyl) methanolic acetylated compound (21.02 g), the yield was 96.4%, and the reaction was carried out in the same manner as in Example 1, except that the R-cyclopentyl (phenyl) methanol
With porcine pancreatic lipase In toluene at 40℃; for 12h; Enzymatic reaction;
2.2
2) In a constant temperature shaker, a 1000 ml blue bottle was used as the reaction vessel, 700 ml of toluene was added,85 g of 1-hydroxyacenaphthene, 110 gP-chlorophenol acetate, 9g porcine pancreatic lipase PPL, 18g acidic resin D006, feeding and heating to 40 ° C. After 12 hours, 1-hydroxyacenaphthene was detected and converted to R-1-hydroxyacenaphthene The reaction solution is cooled, filtered,Concentrated, crude product.
With porcine pancreatic lipase In toluene at 40℃; for 6h; Enzymatic reaction; enantioselective reaction;
2.5
5) In a thermostatic shaker, a 1000 ml blue cap was used as the reaction vessel, 700 ml of toluene, 85 g of 1-hydroxyacenaphthene, 110 gP-chlorophenol acetate, 9g porcine pancreatic lipase PPL, feeding, heating to 45 ° C reaction, 6 hours later, the detection of 1-hydroxyThe conversion of the acenaphthene was 50%; the reaction was stopped, the reaction solution was cooled, filtered, concentrated and passed through the column to give S-1-hydroxyAcenaphthene 41.82 g, the yield was 98.4%, the product 66 value was 99.9%; 1? -1-hydroxyacenaphthyleneprin compound 52.218, the yield was98.5%, product 66 value of 99.8%
With porcine pancreatic lipase In toluene at 45℃; for 6h; Enzymatic reaction;
2.5
5) In a thermostatic shaker, with 200ml blue cap bottle as the reaction vessel, add 60ml of toluene, 11g of - (3E, 7E) -3,7-dimethyl-10- (1-methylethylidene) -3,7-cyclodecadien-1-ol, 11 g of p-chlorophenol acetate, 0.6 g of porcine pancreatic fatEnzyme PPL, the feed is completed, the reaction was heated to 40 ° C, 6 hours later, - (3E, 7E) -3,7-dimethyl-10-Ylidene) -3,7-cyclodecadien-1-ol conversion up to 50%; the reaction was stopped, the reaction solution was cooled, filtered, concentrated,After passing through the column, 5.4 g of S - (3E, 7E) -3,7-dimethyl-10- (1-methylethylidene) -3,7-cyclodecene-1-The yield was 98.2% and the ee value of the product was 99.9%. S - (3E, 7E) -3,7-dimethyl-10- (1-methylethylidene)Ene-1-ol B-methine compound 6.4g, yield 97.6%. 5) In a thermostatic shaker, a 1000 ml bottle of blue capped flask was charged with 700 ml of toluene, 110 g of - (3E, 7E) -3,7-dimethyl-10- (1- methylethylidene) Cyclodexadien-1-ol, 110 g of p-chlorophenol acetate and 10 g of porcine pancreatic lipase PPL. After completion of the addition, the mixture was warmed to 45 ° C and reacted for 6 hours. The amount of - (3E, 7E ) -3,7-dimethyl-10- (1-methylethylidene) -3,7-cyclodecanedien-1-ol of 50% conversion;Stop the reaction, the reaction solution was cooled, filtered,Concentrated and passed through a column to give 54.2 g of S - (3E, 7E) -3,7-dimethyl-10- (1-methylethylidene) -3,7-cyclodecene- , The yield was 98.5% and the product ee was 99.9%. S - (3E, 7E) -3,7-dimethyl-10- (1-methylethylidene) Alkene-1-ol B-methine compound was obtained in a yield of 98.3%.
With caesium carbonate In N,N-dimethyl-formamide at 80℃; for 6h; Inert atmosphere;
3.2. General Procedure for the Aryloxyalkyl Esters from Phenolic Esters (3aa-3aq)
General procedure: Phenyl esters 1a-1c (0.5 mmol) were loaded into a flask (10 mL). DMF (2 mL) and Cs2CO3 (488 mg,1.5 mmol, 3.0 equiv) were then added, which was followed by the addition of 3-bromoethanol (2a,0.525 mmol, 1.05 equiv). Then the reaction mixture was stirred at 80 °C for 6 h under an Ar atmosphere. After completion of the reaction, as confirmed by TLC, the reaction mixture was cooled down to roomtemperature and 10 mL of CH2Cl2 (DCM) and 10 mL of water were added. After separation of thedichloromethane layer from the water, the aqueous phase was extracted with CH2Cl2 (2 5 mL) again.The combined organic layers were then dried over anhydrous Na2SO4, filtered, and concentratedunder vacuum to yield the crude product. The crude product was purified by silica gel columnchromatography to obtain the desired pure compound.
5-methyl-2-hexenoic acid p-chlorophenyl ester[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
61.7%
With sodium ethanolate In ethanol at 25℃; for 10h; Green chemistry;
5 Example 1: Preparation of Intermediate 1
General procedure: Under argon protection,1.5L of ethyl acetate,23.7g of sodium ethoxide was added to the dry three-necked bottle.150 g of isovaleraldehyde was added dropwise with stirring at room temperature.The dropping time is 120min.After the reaction at room temperature for 5 h,Gas phase detection of isovaleraldehyde conversion is complete,Stop stirring,Adjust the pH to 6-7 with 1N aqueous HCl solution in an ice bath.Divide the organic phase,The aqueous phase was extracted with ethyl acetate.Combine the organic phase,Wash the organic phase with saturated brine,The organic phase is concentrated,After the concentrate was rectified, 245.1 g of intermediate 1 was obtained.(5-methyl-2-hexenoic acid ethyl ester),The yield was 90.1%.
1-(1-{1-[dimethyl(phenyl)silyl]vinyl}cyclohexyl)ethan-1-one[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
58%
With 1,2-bis(bis(3,5-di-tert-butylphenyl)phosphino)benzene; copper (I) acetate In toluene at 100℃; for 16h; Inert atmosphere; Glovebox; regioselective reaction;
Copper-Catalyzed Sila-acylation of Allenes 3
General procedure: To a screw-cap vial in a glovebox were added CuOAc (1.8 mg, 15 μmol), DTB-dppbz (16 mg, 18 μmol) and ester 2 (0.60 mmol). Toluene (1.0 mL), allene 1 (0.39 mmol), and PhMe2Si-B(pin) (82 μL, 0.30 mmol) [BnMe2Si-B(pin) (80 μL, 0.30 mmol) in the case of 3g] were sequentially added to the vial. The system was closed, and the mixture was stirred at 100 °C for 16 h. After cooling to room temperature, DMSO (2.0 mL) and 1.0 M NaOH (2.0 mL) were added and the mixture was stirred at 60 °C overnight. After cooling, the mixture was extracted with Et2O and the combined organic layers were washed with brine, dried over MgSO4 and then filtered. The filtrate was evaporated to dryness and the residue was purified by MPLC to afford products 3.
With Candida antarctica lipase B In toluene at 20℃; for 16h; Inert atmosphere;
26.1 Step 1: cyclohexyl 3-hydroxyacetate
A solution of 4-chlorophenyl acetate (84.2 g, 495 mmol) in anhydrous toluene (800 ml) was exchanged 3 timeswith N2. Cyclohexane-1,3-diol (38.3 g, 330 mmol) and Candida antarctica lipase B (CALB) (7.6 g) were added, and themixture was further exchanged and stirred at room temperature for 16h. The resulting solution was filtrated to removesolid, and filtrate was vacuum concentrated, and residue was purified with silica gel column (ethyl acetate: petroleumether = 0-100%) to afford 47.2 g, yield 91%.1H NMR (400 MHz, CDCl3) 5.14-4.72 (m, 1H), 4.03-3.67(m, 1H), 2.25-2.20(m, 1H), 2.02(s, 3H), 1.91-1.59(m, 4H),1.44-1.25(m, 3H).
91%
With Candida antarctica lipase B In toluene at 20℃; for 16h; Inert atmosphere;
26.1 Step 1: cyclohexyl 3-hydroxyacetate
A solution of 4-chlorophenyl acetate (84.2 g, 495 mmol) in anhydrous toluene (800 ml) was exchanged 3 timeswith N2. Cyclohexane-1,3-diol (38.3 g, 330 mmol) and Candida antarctica lipase B (CALB) (7.6 g) were added, and themixture was further exchanged and stirred at room temperature for 16h. The resulting solution was filtrated to removesolid, and filtrate was vacuum concentrated, and residue was purified with silica gel column (ethyl acetate: petroleumether = 0-100%) to afford 47.2 g, yield 91%.1H NMR (400 MHz, CDCl3) 5.14-4.72 (m, 1H), 4.03-3.67(m, 1H), 2.25-2.20(m, 1H), 2.02(s, 3H), 1.91-1.59(m, 4H),1.44-1.25(m, 3H).
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