* All experimental methods are cited from the reference, please refer to the original source for details. We do not guarantee the accuracy of the content in the reference.
Reference：
[1] Journal of Physical Chemistry, 1986, vol. 90, # 19, p. 4648 - 4650
2
[ 288-32-4 ]
[ 100-19-6 ]
[ 2301-25-9 ]
Reference：
[1] European Journal of Organic Chemistry, 2011, # 14, p. 2692 - 2696
3
[ 100-19-6 ]
[ 99-81-0 ]
Yield
Reaction Conditions
Operation in experiment
99%
With copper(ll) bromide In ethyl acetate at 60 - 65℃; for 8 h;
2-1-1: Preparation of α-bromo-4-nitroacetophenone 5 g (30.3 mmol) of 4-nitroacetophenone was dissolved in 150 ml of ethyl acetate and 13.5 g (60.6 mmol) of copper (II) bromide was added thereto, followed by stirring at a temperature of 60 to 65° for 8 hours. After the reaction was complete, the reaction liquid was cooled to room temperature and the salt formed during the reaction was filtered off The filtrate was washed three times with a sodium bicarbonate saturated solution. This solution was dried over anhydrous magnesium sulfate, filtered under reduced pressure, distilled under reduced pressure and then dried under vacuum at about 40° to afford 7.3 g (yield: 99percent) of the desired compound which was then directly subjected to the subsequent reaction. Mass (M+): 245.1
99%
With copper(ll) bromide In ethyl acetate at 60 - 65℃; for 8 h;
Example 2-1-1 Preparation of a-bromo-4-nitroacetophenone 5g (30.3mmol) of 4-nitroacetophenone was dissolved in 150ml of ethyl acetate and 13.5g (60.6mmol) of copper (II) bromide was added thereto, followed by stirring at a temperature of 60 to 65°C for 8 hours. After the reaction was complete, the reaction liquid was cooled to room temperature and the salt formed during the reaction was filtered off. The filtrate was washed three times with a sodium bicarbonate saturated solution. This solution was dried over anhydrous magnesium sulfate, filtered under reduced pressure, distilled under reduced pressure and then dried under vacuum at about 40°C to afford 7.3g (yield: 99percent) of the desired compound which was then directly subjected to the subsequent reaction. Mass (M+): 245.1
95%
With aluminum (III) chloride; bromine In diethyl ether at 0 - 20℃; for 3 h;
To a solution of 4-nitroacetophenone (30 g, 0.18 mol) in dry ether(500 mL) stirred at 0 oC, was added AlCl3 (cat), followed by Br2(10.3 mL, 0.20 mol). The reaction mixture was stirred at rt fot 3h. Then the reaction was quenched with Na2S2O3-NaHCO3 (aq),extracted with DCM (400 mL*2), the combined organic phase waswashed with brine, dried over Na2SO4, filtered and concentratedto give the title compound as yellow solid (42 g, 95percent); 1H-NMR(300 MHz, CDCl3): δ 8.36–8.33 (m, 2H), 8.17–8.14 (m, 2H), 4.46 (s,2H); LRMS (ESI) m/z 244 [M+H]+; mp 76–79 oC.
94%
With bromine In diethyl ether at 20℃; for 2 h; Cooling with ice
To a solution of 1 (1.65 g, 10 mmol) in dry ethylether (150 mL) was added Br2 (1.60 g, 10 mmol) dropwise in an ice bath. The reaction mixture was stirred at room temperature for 2 h. Evaporation of the solvent afforded 2.29 g of 2 as a white crystal (94percent). 1H NMR (400 MHz, CDCL3) δ 8.35 (d, J = 9.1 Hz, 2H), 8.15 (d, J = 9.1 Hz, 2H), 4.47 (s, 2H).
89%
With N-Bromosuccinimide; tetrachlorosilane In acetonitrile at 20℃; for 7 h;
General procedure: To a mixture of NXS and substrate (1 or 6) in CH3CN at room temperature was added SiCl4 and the mixture left to stir until TLC showed the disappearance of the starting material. The reaction was then poured onto H2O and the mixture extracted with CH2Cl2. The extracts were combined, dried over MgSO4 and evaporated. The residue was purified by recrystallization (pet. ether-Et2O, 3:1) to give pure 2b-2g, 3b, or by silica gel column chromatography (hexane-EtOAc 10:1 or 30:1) to give pure 2a,h,i, 3a-5 or 7-9, respectively
88%
With N-Bromosuccinimide; toluene-4-sulfonic acid In acetonitrile at 50℃; for 24 h;
In a 500 ml single-port the bottle, the nitro-acetophenone (63.74g, 386mmol), N-bromo succinimide (68.77g, 386 . 4mmol), P-toluene sulfonic acid monohydrate (73.33g, 386mmol) and acetonitrile 200 ml, in the 50 °C reaction under 24 hours. TLC shows the reaction is complete, solvent is removed under reduced pressure, the residue add saturated sodium bicarbonate solution and to neutral, extraction with ethyl acetate, the organic phase is dried with anhydrous sodium sulfate, evaporated under reduced pressure, washed with petroleum ether, to obtain yellow solid (82.9g, 88.0percent).
82%
at 670℃; for 6 h; Green chemistry
The representative example of oxidative bromination is described as follows: A mixture of 1.2 g acetophenone 1a (10 mmol) and 0.121 g Cu(NO3)2•3H2O (0.5mmol) was stirred and an oxygen balloon (about 0.5–1 L) was attached to the reaction system. Then 8mol/L aqueous solution of hydrobromic acid (1.5mL, 12mmol) was added dropwise to the mixture. The reaction mixture was then stirred at 70°C and monitored by TLC or GC. After the completion of the reaction, the mixture was extracted with CH2Cl2. The organic extract was first washed with 5percent sodium sulfite, saturated sodium bicarbonate solution, and then water and finally dried over anhydrous magnesium sulfate. The solvent was removed under vacuum and the residue was purified by column chromatography (silica gel, petroleum ether/dichloromethane 3:1) to afford the product, α-bromoacetophenone (2a) in 1.81 g, yield: 91percent.
81.96%
With aluminum (III) chloride; bromine In chloroform at 45℃;
4-Nitroacetophenone (16.5 g, 0.1 mol) was dissolved in 50 ml ofchloroform and to this, 200 mg of anhydrous aluminum trichloride(AlCl3) was added at once. It was then kept for stirring at around45 °C. A bromine solution (0.15 mol), which was previously dilutedin chloroform 20 ml, was added drop-wise for 1 h. The completionof reaction was confirmed by TLC. The solvent was removed underreduced pressure. The residual solid was filtered and crystallizedfrom methanol and afforded 20.0 g (81.96percent yields) of 1.
81%
With bromine In chloroform at 0 - 20℃; for 16 h;
General procedure: A solution of bromine (2.90 g, 18.0 mmol) in chloroform (150 mL) was slowly added to a cooled solution (0 °C) of acetophenone 1b–c (17.0 mmol) in chloroform (150 mL), over a period of 1 h, the mixture stirred at room temperature for 15 h and quenched with ice-cold water. The organic layer was washed with saturated sodium bicarbonate solution, water and brine. The organic phase was dried over anhydrous sodium sulfate, concentrated under vacuum and purified on a silica gel (100–200 mesh) column. Elution with hexane–ethyl acetate (9 : 1) yielded pure compounds 2b and 2c.
80%
With sulfuric acid; bromine; nitric acid; potassium iodide In chlorobenzene at 40 - 60℃; for 3.5 h;
p-Nitroacetophenone (10.0g, 60.6mmol), H2SO4 (10mL, 6M), HNO3 (7.0mL, 3M), KI (0.50g,3.0 mmol) chlorobenzene (100 mL) was added to a three-necked flask, stirred and dissolved, and Br2 (1.60 mL, 31 mmol) was added dropwise at 40 ° C.After 0.5h,The mixture was heated to 60 ° C with heating and stirring, and after 3 hours of reaction, the reaction was stopped, and the mixture was allowed to stand and then layered.The upper aqueous phase is poured into the reaction bottle for recycling, and the lower organic phase is washed with sodium hydrogen sulfite solution, washed with sodium hydrogen carbonate solution, dried, and analyzed by HPLC, p-nitroacetophenone: α-bromo-p-nitrophenyl Ketone: The molar ratio of α,α-dibromo-p-nitroacetophenone is 5:88.2:6.8.The organic phase was desolvated under reduced pressure and recrystallized to give α-bromo-p-nitroacetophenone, 11.85 g, yield 80percent.
79.6%
at 0 - 20℃; for 2 h;
General procedure: To a solution of 4-substitutedacetophenone (0.3 mol) and acetic acid (75 mL), added drop-wise bromine (20 mL) in acetic acid (75 mL). The contentswere stirred for 1 h at 0-10 °C and further for 1 h at room tempe-rature. Then the reaction mixture was poured into crushed ice,the solid separated was filtered and washed with water [21,22].The product was recrystallized from methanol. R f was deter-mined in a solvent mixture of n-hexane and ethyl acetate (7:3).
71%
With N-Bromosuccinimide; toluene-4-sulfonic acid In dichloromethaneIrradiation
General procedure: In a dry tube, substituted acetophenone (2 mmol), NBS (2 mmol) and PTSA (0.2 mmol, 10 molpercent) were added. 3-4 ml of anhydrous DCM was added and the tube was then irradiated in ultrasonic both till the completion of reaction (TLC). The reaction mixture was then cooled and extracted with 3 x 10 ml quantities of DCM. Organic layers were separated, dried over anhydrous MgSO4 and finally purified by silica gel chromatography [16].
69%
With bromine In diethyl ether for 0.666667 h;
4-Nitroacetophenone (25 g) in ether (250 ml) was treated with aluminium chloride (catalytic amount) followed by bromine (7.77ml) for 10 minutes and the reaction was stirred for 30 minutes. The reaction was quenched with aqueous NaHCC>3, the ether layer was separated, dried using Na2S04 and concentrated. The residue was dissolved in EtOAc, dried using Na2S04, and concentrated to get off white solid which was crystallized in EtOAc/ Pet ether to yield 25.5gm (69percent) of the title compound. ^NMR (CDC13, 300MHz): δ 8.19 (d, 2H), 8.36 (d, 2H), 4.47 (s, 2H).
69%
for 0.666667 h;
Example 1 :2-Bromo-1-(4-nitrophenyl)ethanone4-Nitroacetophenone (25 g) in ether (250 mL) was treated with aluminium chloride (catalytic amount) followed by bromine (7.77 mL) over 10 min and the reaction was stirred for 30 min. The reaction was quenched with aqueous sodium bicarbonate, the ether layer was separated, dried over anhydrous Na2S04 and concentrated to yield a residue. The residue obtained was crystallized using ethyl acetate and petroleum ether to afford the title compound (according to the procedure described in US4812470). Yield: 25.5 g (69 percent); 1 H NMR (CDCI3, 300MHz): δ 8.19 (d, 2H), 8.36 (d, 2H), 4.47 (s, 2H).
69%
With aluminum (III) chloride; bromine In diethyl ether at 20℃; for 0.666667 h;
A solution of 4-nitroacetophenone (25 g, 151 mmol, 1.0 equiv) in ether (250 ml) was treated with catalytic amount of aluminum chloride followed by bromine (7.77 ml, 151 mmol, 1.0 equiv) over 10 min and the reaction was stirred for an additional 30 min. The reaction was then quenched with aqueous sodium bicarbonate, the ether layer separated, dried over sodium sulfate, and evaporated under reduced pressure. The residue was crystallized using ethyl acetate and petroleum ether to afford the title compound (25.5 g, 69percent).1H NMR (CDCl3, 300 MHz) δ 8.39-8.36 (d, J = 8.7 Hz, 2H), 8.19-8.16 (d, J = 8.7 Hz, 2H), 4.48 (s, 2H); MS (ESI-) m/z 243 [M - H]-, MS (ESI+) m/z 245 [M + H]+.
69%
With aluminum (III) chloride; bromine In diethyl ether for 0.666667 h; Inert atmosphere
To a solution of 4-Nitroacetophenone (25.0 g, 151 mmol,1.0 equiv) in ether (250 ml) bromine (7.77 ml, 151 mmol, 1.0 equiv) was added over 10 min. The reaction mixture was stirred for 30 minin the presence of catalytic amount of aluminum chloride (1.0 g,7.5 mmol, 0.05 equiv). Following reaction completion the reaction mixture was quenched with aqueous sodium bicarbonate. The ether layer was separated and dried over sodium sulfate and evaporated under reduced pressure. The off white residue thus obtained was crystallized in EtOAc:Pet ether to afford the title compound (25.5 g, 69percent).
63%
With N-Bromosuccinimide In ethyl acetate at 40℃;
In a 100 mL round bottom flask, 10 mmol of 4-nitroacetophenone and 11 mmol of N-bromosuccinimide (NBS) were added.35mL of ethyl acetate dissolved,1 g of Amberlyst 15 Ion Exchange Resin was added as a catalyst, and the reaction liquid was heated to 40°C.reaction. After TLC tracking reaction, the reaction solution was filtered to remove Amberlyst 15 ion exchange resin, and the filtrate was spin-dried.Separation (eluent: petroleum ether/ethyl acetate) gave a pale yellow solid with a yield of 63percent.
63%
With N-Bromosuccinimide In ethyl acetate at 40℃;
10 mmol 4-nitroacetophenone is added to a 100 mL round bottom flaskAnd 11mmol of N-bromosuccinimide (NBS),35mL of ethyl acetate dissolved,Then add 1g of Amberlyst 15 ion exchange resin as catalyst.The reaction was warmed to 40°C and reacted.After TLC tracking reaction, the reaction solution was filtered to remove Amberlyst 15 ion exchange resin.The filtrate was spin-dried and separated by column chromatography (eluent: petroleum ether/ethyl acetate) to give a pale yellow solid with a yield of 63percent.
62%
With aluminum (III) chloride; bromine In diethyl ether at 20℃; for 1.66667 h;
To a solution of 4-nitroacetophenone (50g, 302mmol, 1.0equiv) in diethyl ether (500ml) was added catalytic amount of aluminum chloride (2g, 15mmol, 0.05equiv) and the reaction mixture was stirred for 10min. To this bromine (15.4ml, 302mmol) was added using an addition funnel over 30min at rt and the resulting mixture was stirred for 1h. Following reaction completion the reaction mixture was quenched using aqueous sodium bicarbonate. The ether layer was separated, dried over sodium sulfate, and evaporated under reduced pressure. The solid thus obtained was recrystallized using ethyl acetate and petroleum ether to afford the title compound (43g, 62percent). (0040) 1H NMR (CDCl3, 300MHz) δ 8.36 (d, J=8.1Hz, 2H), 8.18 (d, J=8.1Hz, 2H), 4.48 (s, 2H); Mass (ESI+) m/z 245.0 [M+H]+.
62%
With tetra-N-butylammonium tribromide In methanol at 220℃; for 4 h;
1-(4-Nitropheny)ethanone (1.0 g, 6.05 mmol) and tetra-nbutylammoniumtribromide (3.82 g, 7.96 mmol) were takenin methanol (100 mL). The reaction was stirred at room temperatureovernight. The solvent was then removed under reducedpressure and the residue was dissolved in AcOEt (60 mL).The mixture was washed twice with water (2 × mL) and oncewith brine. The organic solution was then dried over Na2SO4and the solvent from the filtrate was removed. The crude product was purified using FCC (hexane-CH2Cl2) (1:1 v/v + 2 percentAcOEt), yielding the desired product as a yellow solid (0.970g, 4.47 mmol, 62 percent). δH (400 MHz; DMSO; Me4Si): δ 8.34(2H, d, J = 8.8 Hz, CH), 8.21 (2H, d, J = 8.8 Hz, CH), 5.01(2H, s, CH2Br). δC (100 MHz; DMSO; Me4Si): 191.40 (-CO-),150.61 (C), 139.13 (C), 130.60 (C), 124.38 (C), 34.79 (-CH2Br-).
37%
With bromine In chloroform at 0 - 20℃; for 2 h;
General procedure: To a solution of 8.40 ml (64.70 mmol) 1-(4-chlorophenyl)-ethanone (A, Scheme 2 ) in 40 ml chloroform, 3.33 ml bromine (64.7 mmol) in 10 ml chloroform were added drop wise at 0 °C. The mixture was stirred at room temperature for 2 h and was washed with H2O (3 * 50 ml) and saturated Na2S2O3 solution (2 * 50 ml). The organic phase was dried over Na2SO4, filtered and the solvent was removed in vacuum. The crude product, 2-bromo-1-(4-chlorophenyl)ethanone (B, Scheme 2 ), was recrystallized from petrolether and gave 14.20 g of a white crystalline solid, yield: 92percent.
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4
[ 100-19-6 ]
[ 21566-36-9 ]
[ 99-81-0 ]
Yield
Reaction Conditions
Operation in experiment
47%
With N-Bromosuccinimide; silica gel In methanol for 0.25 h; Reflux
General procedure: The α-bromination reaction was carried out using acetophenone (1200 mg, 10 mmol), N-bromosuccinimide (2136 mg, 12 mmol), 10percent (w/w) silica gel (120mg) in 10 mL of methanol at reflux conditions until the disappearance of the substrate. (Note: 2136mg of N-bromosuccinimide was added portion wise i.e. 356 mg for each time in six portions). The progress of the reaction was monitored by TLC. The reaction mass was filtered after the completion of the reaction as per TLC and the catalyst was collected for reuse. The filtrate was concentrated under vacuum. Double distilled water was added to the reaction mixture and quenched with aqueous sodium thiosulfate and the product extracted with dichloromethane (Caution: Severe burning sensation of eyes was observed during the work-up process). The layers were separated and the organic layer was collected and washed thrice with distilled water (3×50mL). The collected organic layer was dried over anhydrous Na2SO4, filtered and concentrated. The obtained crude product was purified by column chromatography over silica gel (60–120 mesh) using n-hexane–EtOAc (99:1 ratio). With the aim of studying the recycling of the catalyst, the isolated catalyst was washed with ethyl acetate (5mL) after its filtration from the reaction medium, collected and dried in vacuum at 70°C to a constant weight. Subsequently it was reused for the α-bromination of acetophenone and achieved 95percent, 86percent and 83percent yields of product (2a) for first, second and third reuse of catalyst respectively. All products gave spectroscopic data in agreement with the literature [15,21,27–30]. The method is also very practical for scale up in process development. We attempted large scale (100 gram scale) synthesis of 2-bromo-1-phenylethanone 2a and obtained fruitful results with isolated yields ranging from 93percent to 96percent.
Reference：
[1] Chinese Chemical Letters, 2014, vol. 25, # 1, p. 179 - 182
[2] Tetrahedron Letters, 2006, vol. 47, # 3, p. 291 - 293
5
[ 67-56-1 ]
[ 100-19-6 ]
[ 828935-07-5 ]
[ 99-81-0 ]
Yield
Reaction Conditions
Operation in experiment
21%
for 1.5 h; Reflux
General procedure: Oxone (1.352 g, 2.2 mmol) was added to the well stirred solution of substrate (2 mmol) and NH4Br (0.215 g, 2.2 mmol) in methanol (10 ml) and the reaction mixture was allowed to stir at room temperature (or reflux temperature). After completion of the reaction, as monitored by TLC, the reaction mixture was quenched with aqueous sodium thiosulfate, and extracted with ethyl acetate (3.x.25 ml). Finally, the combined organic layer was washed with water, dried over anhydrous sodium sulfate, filtered and removal of solvent in vacuo yielded a crude residue, which was further purified by column chromatography over silica gel (finer than 200 mesh) to afford pure products. All the products were identified on the basis of 1H NMR and mass spectral data.
Reference：
[1] Drug Design, Development and Therapy, 2016, vol. 10, p. 1807 - 1815
8
[ 7402-45-1 ]
[ 100-19-6 ]
[ 99-81-0 ]
Reference：
[1] Chemische Berichte, 1953, vol. 86, p. 1556,1560
9
[ 98-86-2 ]
[ 577-59-3 ]
[ 100-19-6 ]
[ 121-89-1 ]
Reference：
[1] Journal of the Chemical Society - Perkin Transactions 1, 1996, # 19, p. 2385 - 2389
[2] Tetrahedron Letters, 2001, vol. 42, # 38, p. 6767 - 6769
Reference：
[1] Chemistry of Heterocyclic Compounds (New York, NY, United States), 1974, vol. 10, p. 1294 - 1297[2] Khimiya Geterotsiklicheskikh Soedinenii, 1974, vol. 10, p. 1472 - 1476
13
[ 100-19-6 ]
[ 14922-36-2 ]
Yield
Reaction Conditions
Operation in experiment
79.2%
at 110℃; for 1 h; Inert atmosphere
SeO2 (0.167 g, 1.5 mmol), p-nitroacetophenone (0.165 g, 1 mmol) in a 25 mL round bottom flask under nitrogen.Add 10 mL of anhydrous pyridine, heat the oil bath to 110 ° C and stir to reflux.After 1 hour, the progress of the reaction was detected by TLC thin layer chromatography, and after cooling for 4 hours, it was cooled to room temperature.Filtration through a Buchner funnel, filtering off the solution containing SeO2 precipitate, washing the residue with 50 mL of ethyl acetate;The filtrate was combined and treated with 1 mmol/L hydrochloric acid (20 mL).The aqueous layer was extracted three times with ethyl acetate (50 mL) to give aqueous layer 2 and organic layer 2;After the organic layer 1 and the organic layer 2 are combined, extracted three times with 25 ml of water to obtain an organic layer 3 and an aqueous layer 3;The aqueous layer 3 was treated with 1 mmol/L NaOH (50 mL), and the reaction solution was diluted to obtainTo the filtrate 4.After the filtrate 4 was combined with the aqueous layer 2, the pH was adjusted to 1.5 with hydrochloric acid (1 mmol/L).The mixture was extracted with EtOAc (3~50 mL).Drying in a vacuum desiccator overnight gave the product 4-nitrophenylglyoxylic acid.Yield: 0.154 g. The yield was 79.2percent.
Reference：
[1] Synthetic Communications, 2008, vol. 38, # 24, p. 4434 - 4444
[2] Patent: CN108623611, 2018, A, . Location in patent: Paragraph 0041; 0043; 0044; 0045; 0046
[3] Journal of Organic Chemistry, 2018, vol. 83, # 3, p. 1422 - 1430
[4] Journal of the American Chemical Society, 2010, vol. 132, # 34, p. 11898 - 11899
[5] Chemical Communications, 2013, vol. 49, # 35, p. 3640 - 3642
[6] Organic and Biomolecular Chemistry, 2017, vol. 15, # 20, p. 4320 - 4327
[7] Advanced Synthesis and Catalysis, 2017, vol. 359, # 14, p. 2390 - 2395
[8] Organic Letters, 2017, vol. 19, # 17, p. 4556 - 4559
[9] Advanced Synthesis and Catalysis, 2018, vol. 360, # 17, p. 3345 - 3355
14
[ 100-19-6 ]
[ 100-27-6 ]
Reference：
[1] Journal of Organic Chemistry, 1984, vol. 49, # 3, p. 438 - 442
[2] Journal of Organic Chemistry, 1984, vol. 49, # 3, p. 438 - 442
General procedure: A mixture of a substrate (0.6 mmol), vinyl bromide 2a (0.06 mmol) in DMSO (1.1 mL) was heated in an open flask (the temperature of an oil bath and the reaction time are specified in refPreviewPlaceHolderTable 2). After the completion of the reaction (checked by TLC), the reaction mixture was diluted with water (11 mL), saturated with NaCl and extracted with ethyl acetate (5.x.4 mL). Only in the case of the synthesis of arylglyoxals the organic layer was additionally washed with Na2CO3 (0.12 mmol in 2 mL of water), with saturated aq NaCl and dried with anhydrous Na2SO4. Column chromatography (eluent: gradient petrolether/ethyl acetate) of the extract gave the pure products.
Reference：
[1] Tetrahedron Asymmetry, 2010, vol. 21, # 18, p. 2244 - 2248
[2] Tetrahedron, 2011, vol. 67, # 41, p. 8000 - 8008
[3] Journal of Fluorine Chemistry, 2010, vol. 131, # 12, p. 1289 - 1296
[4] Tetrahedron Letters, 2011, vol. 52, # 31, p. 4036 - 4038
[5] Tetrahedron, 2013, vol. 69, # 1, p. 22 - 28
[6] Synlett, 2013, vol. 24, # 8, p. 998 - 1000
[7] Tetrahedron, 2017, vol. 73, # 47, p. 6587 - 6596
[8] Journal of Organometallic Chemistry, 2013, vol. 744, p. 101 - 107
[9] Journal of Sulfur Chemistry, 2013, vol. 34, # 5, p. 464 - 473
[10] Journal of the American Chemical Society, 2013, vol. 135, # 45, p. 16849 - 16852
[11] Journal of Fluorine Chemistry, 2014, vol. 168, p. 151 - 157
[12] Tetrahedron Letters, 2015, vol. 56, # 32, p. 4701 - 4703
[13] Turkish Journal of Chemistry, 2015, vol. 39, # 2, p. 244 - 254
[14] Research on Chemical Intermediates, 2015, vol. 41, # 10, p. 7263 - 7272
[15] Australian Journal of Chemistry, 2015, vol. 68, # 10, p. 1529 - 1534
[16] Journal of Organic Chemistry, 2016, vol. 81, # 15, p. 6402 - 6408
[17] Journal of the Iranian Chemical Society, 2017, vol. 14, # 11, p. 2299 - 2304
[18] Journal of Heterocyclic Chemistry, 2017, vol. 54, # 6, p. 3163 - 3168
[19] Heterocyclic Communications, 2018, vol. 24, # 1, p. 37 - 41
[20] Tetrahedron Letters, 2018, vol. 59, # 31, p. 2970 - 2974
[21] Organic and Biomolecular Chemistry, 2018, vol. 16, # 38, p. 6998 - 7003
[22] Heterocyclic Communications, 2018, vol. 24, # 6, p. 297 - 302
24
[ 100-19-6 ]
[ 90434-58-5 ]
Reference：
[1] Bulletin des Societes Chimiques Belges, 1963, vol. 72, p. 202 - 207
With dimethylsulfide borane complex; 2-hydroxy-N-[(1S,2R)-2-hydroxy-1,2-diphenylethyl]benzamide; In tetrahydrofuran; at 65℃;Inert atmosphere;
General procedure: A 25mL two-necked flask was charged with beta-hydroxyamide 1-7 (0.05mmol, 10%) in dry and fresh THF (3mL), equipped with a magnetic stirrer and a connection to the combined nitrogen/vacuum line and closed with a septum. The air in the flask was replaced by nitrogen. beta-hydroxyamides 1-7 were dissolved in THF (3mL) with stirring and a solution of BH3·SMe2 (0.5mmol, 10M) complex was added at 0C by a syringe. After the mixture was stirred for 1h at 65C, the freshly distilled ketone (0.5mmol) in freshly dried THF (2mL) was added over a period of 1.5h by a syringe at the same temperature. The reaction mixture was kept stirring at the 65C until the ketone was completely consumed. After stirring for a further 30min at rt, the reaction mixture was quenched by the addition of MeOH (2mL) and extracted with CH2Cl2 three times. The combined organic extracts were washed with brine and dried over MgSO4. After evaporating the solvent under reduced pressure, the product was purified by column chromatography on silica gel using petroleum ether/EtOAc (5:1; for 4?-nitroacetophenone: 5/3) as the eluent. The ee value was determined by HPLC with Chiralcel AS-3 or Chiralcel OD-H columns.
With dimethylsulfide borane complex; 2-hydroxy-N-[(1S)-2-hydroxy-1,2,2-triphenylethyl]benzamide; In tetrahydrofuran; at 65℃;Inert atmosphere;
General procedure: A 25mL two-necked flask was charged with beta-hydroxyamide 1-7 (0.05mmol, 10%) in dry and fresh THF (3mL), equipped with a magnetic stirrer and a connection to the combined nitrogen/vacuum line and closed with a septum. The air in the flask was replaced by nitrogen. beta-hydroxyamides 1-7 were dissolved in THF (3mL) with stirring and a solution of BH3·SMe2 (0.5mmol, 10M) complex was added at 0C by a syringe. After the mixture was stirred for 1h at 65C, the freshly distilled ketone (0.5mmol) in freshly dried THF (2mL) was added over a period of 1.5h by a syringe at the same temperature. The reaction mixture was kept stirring at the 65C until the ketone was completely consumed. After stirring for a further 30min at rt, the reaction mixture was quenched by the addition of MeOH (2mL) and extracted with CH2Cl2 three times. The combined organic extracts were washed with brine and dried over MgSO4. After evaporating the solvent under reduced pressure, the product was purified by column chromatography on silica gel using petroleum ether/EtOAc (5:1; for 4?-nitroacetophenone: 5/3) as the eluent. The ee value was determined by HPLC with Chiralcel AS-3 or Chiralcel OD-H columns.
With dichloro(mesitylene)ruthenium(II) dimer; C45H77NO35; sodium formate; In water; N,N-dimethyl-formamide; at 25℃; for 96h;
General procedure: A solution of modified beta-CD (0.02mmol) and [RuCl2(Arene)]2 (0.01mmol) in the mixture of H2O and DMF (1mL) was stirred at 25C for 1.0h, and then HCOONa·2H2O (2.0mmol) was added. After the resultant mixture was stirred at 25C for another 1.0h, aromatic ketone (0.2mmol) was added. After stirring at 25C for 24.0h or 96.0h, the obtained solution was extracted with n-hexane (4×2mL), and the combined organic phase was dried over anhydrous Na2SO4 and analyzed by HPLC to determine the yield and ee value.
With [(2R)-2-(ferrocenylmethylamino)-2-phenylethyldiphenylphosphinito(dichloro(eta6-benzene)ruthenium(II))]; sodium hydroxide; In isopropyl alcohol; at 82℃; for 0.25h;Inert atmosphere; Schlenk technique;Catalytic behavior;
General procedure: 2.2;General procedures for synthesis of ferrocene based Ru(II)-phosphinites complexes (17-24) ;[Ru(eta6-benzene)(mu-Cl)Cl]2 (0.15 mmol) and ferrocene based phosphinite (0.30 mmol) were dissolved in 20 mL of toluene and stirred for 1 h at room temperature.The volume was concentrated to ca.1-2 mL under reduced pressure and addition of petroleum ether (20 mL) gave the desired complex a tile red solid which was collected by filtration and dried in vacuum.
With [(2S)-2-(ferrocenylmethylamino)-3-phenylpropyldiphenylphosphinito(dichloro(eta6-benzene)ruthenium(II))]; sodium hydroxide; In isopropyl alcohol; at 82℃; for 0.33h;Inert atmosphere; Schlenk technique;Catalytic behavior;
General procedure: 2.2;General procedures for synthesis of ferrocene based Ru(II)-phosphinites complexes (17-24) ;[Ru(eta6-benzene)(mu-Cl)Cl]2 (0.15 mmol) and ferrocene based phosphinite (0.30 mmol) were dissolved in 20 mL of toluene and stirred for 1 h at room temperature.The volume was concentrated to ca.1-2 mL under reduced pressure and addition of petroleum ether (20 mL) gave the desired complex a tile red solid which was collected by filtration and dried in vacuum.
With (2R)-2-(ferrocenylmethylamino)-2-phenylethyl diphenylphosphinito(dichloro(eta6-p-cymene)ruthenium(II)); isopropyl alcohol; potassium hydroxide; for 0.25h;Reflux; Inert atmosphere; Schlenk technique;
General procedure: Typical procedure for the catalytic hydrogen-transfer reaction: a solution of ruthenium complexes 9-12 (0.005mmol), KOH (0.025mmol), and the corresponding ketone (0.5mmol) in degassed iso-PrOH (5mL) was refluxed until the reaction was completed. Next a sample of the reaction mixture was taken off, diluted with acetone, and analyzed immediately by GC, conversions obtained are related to the unreacted ketone.
With (2S)-2-(ferrocenylmethylamino)-2-phenylethyl diphenylphosphinito(dichloro(eta6-p-cymene)ruthenium(II)); isopropyl alcohol; potassium hydroxide; for 0.25h;Reflux; Inert atmosphere; Schlenk technique;
General procedure: Typical procedure for the catalytic hydrogen-transfer reaction: a solution of ruthenium complexes 9-12 (0.005mmol), KOH (0.025mmol), and the corresponding ketone (0.5mmol) in degassed iso-PrOH (5mL) was refluxed until the reaction was completed. Next a sample of the reaction mixture was taken off, diluted with acetone, and analyzed immediately by GC, conversions obtained are related to the unreacted ketone.
General procedure: In a schlenk tube, BH3·SMe2(0.55 mmol, 275 L) was added inthe solution of IL 5 (28 mg, 10 mol%) dissolved in THF (1 mL), undernitrogen atmosphere. The homogenous mixture was stirred andheated at 70C for 30 min. Later, a solution of ketone (0.5 mmolin THF (0.5 mL)) was added within 30 min. After the addition wascompleted, the solvent was evaporated under vacuum. An aqueoussolution of 1M HCl (5 mL) was added and the product was extractedwith DCM. The solvent was dried on anhydrous sodium sulfateand evaporated under reduced pressure. Crude residue was furtherpurified by column chromatography on silica gel using hexane-ethyl acetate as eluent. Enantiomeric excesses of all alcohols weredetermined by HPLC analysis using Chiralcel OD-H/AD-H chiralcolumn, isopropanol-n-hexane as mobile phase and HPLC condi-tions are given in SI.
With C21H20BNO2; isopropyl alcohol; sodium hydroxide; at 82℃; for 4h;Schlenk technique; Inert atmosphere;
General procedure: Typical procedure for the catalytic hydrogen-transfer reaction:a solution of boron-complexes (0.01 mmol), NaOH (0.05 mmol)and the corresponding ketone (1 mmol) in degassed iso-PrOH(10 mL) was refluxed until the reaction was completed. Next, asample of the reaction mixture was taken, diluted with acetoneand analyzed immediately by GC; the conversions obtained arerelated to the residual unreacted ketone.
With bis(1,5-cyclooctadiene)iridium(I) tetrafluoroborate; formic acid; sodium formate; (1R,2R)-N1,N-di(naphthalen-1-yl)cyclohexane-1,2-diamine; In methanol; water; at 70℃; for 22h;Inert atmosphere;Catalytic behavior;
General procedure: In a pressure tube, 0.5 mol% of metal precursor [C16H24BF4Ir](2.48 mg, 0.005 mol) and 1 mol% of chiral amine ligand (3.66 mg,0.01 mmol) were dissolved in 2 mL of water and methanol (ratio1:1) and stirred at room temperature for 1 h under argon atmo-sphere. Then formic acid (2.5eq, 0.1 mL), sodium formate (2.5eq,170 mg) and 1eq of ketone substrate (1 mmol) were introduced.The reaction mixture was stirred at 500 rpm and heated at 70C for22 h. After that, the tube was cooled to room temperature; and theorganic compound was extracted with either with ethyl acetate orCH2Cl2, then the solution was dried over Na2SO4, filtrated and con-centrated under reduced pressure. The crude material was purifiedby flash column chromatography on silica gel using cyclohex-ane/ethyl acetate as gradient eluent (90:10-7:3). After evaporation,alcohols were obtained as oil or solid. The products were identifiedby NMR. The conversion and the enantioselectivity were deter-mined by chiral GC or chiral HPLC analysis (Scheme 1).
With (S)-bis[[N-2-diphenylphosphinite propyl]-1,1'-ferrocenylmethyldiamine(dichloro eta5-pentamethylcyclopentadienyl iridium(III))]; isopropyl alcohol; sodium hydroxide; at 82℃; for 0.333333h;Inert atmosphere; Schlenk technique;Catalytic behavior;
General procedure: Typical procedure for the catalytic hydrogen-transfer reaction:a solution of the Ir(III)-complexes 1-8, (0.01 mmol), NaOH(0.05 mmol) and the corresponding ketone (1 mmol) in degassed2-propanol (10 mL) was refluxed until the reaction wascompleted. A sample of the reaction mixture was then takenoff, diluted with acetone and analyzed immediately by GC.The conversions obtained are related to the residual unreactedketone.
With bis[[N-(2-diphenylphosphinite-1,2-diphenyl)ethyl]-1,1'-ferrocenylmethyldiamine(dichloro eta5-pentamethylcyclopentadienyl iridium(III))]; isopropyl alcohol; sodium hydroxide; at 82℃; for 0.333333h;Inert atmosphere; Schlenk technique;Catalytic behavior;
General procedure: Typical procedure for the catalytic hydrogen-transfer reaction:a solution of the Ir(III)-complexes 1-8, (0.01 mmol), NaOH(0.05 mmol) and the corresponding ketone (1 mmol) in degassed2-propanol (10 mL) was refluxed until the reaction wascompleted. A sample of the reaction mixture was then takenoff, diluted with acetone and analyzed immediately by GC.The conversions obtained are related to the residual unreactedketone.
With dimethylsulfide borane complex; 3-hydroxy-N-[(2S)-1-hydroxy-3-methyl-1,1-diphenylbutane-2-yl]naphthalene-2-carboxamide; In tetrahydrofuran; at 65℃;Inert atmosphere;Catalytic behavior;
General procedure: A 25mL two-necked flask was charged with beta-hydroxyamide 1-7 (0.05mmol, 10%) in dry and freshly distilled THF (3mL), equipped with a magnetic stirrer and a connection to a combined nitrogen/vacuum line and closed with a septum. The air in the flask was replaced by nitrogen. beta-Hydroxyamides 1-7 were dissolved in THF (3mL) under stirring after which a solution of BH3.SMe2 (0.5mmol, 10M) complex was added at 0C by a syringe. After the mixture was stirred for 1h at 65C, the freshly distilled ketone (0.5mmol) in dry and freshly distilled THF (2mL) was added over a period of 1.5h by syringe at the same temperature. The reaction mixture was stirred at 65C until the ketone was completely consumed. After stirring for a further 30min at rt, the reaction mixture was quenched by the addition of MeOH (2mL) and extracted with CH2Cl2 (3×3mL). The combined organic extracts were washed with brine and dried over MgSO4. After evaporating the solvent under reduced pressure, the product was purified by column chromatography on silica gel using petroleum ether/EtOAc (5:1; for 4?-nitroacetophenone: 5/3) as eluent. The ee value was determined by HPLC with Chiralcel AS-3 or Chiralcel OD-H columns
With dimethylsulfide borane complex; 3-hydroxy-N-[(1S)-2-hydroxy-1,2,2-triphenylethyl]naphthalene-2-carboxamide; In tetrahydrofuran; at 65℃;Inert atmosphere;Catalytic behavior;
General procedure: A 25mL two-necked flask was charged with beta-hydroxyamide 1-7 (0.05mmol, 10%) in dry and freshly distilled THF (3mL), equipped with a magnetic stirrer and a connection to a combined nitrogen/vacuum line and closed with a septum. The air in the flask was replaced by nitrogen. beta-Hydroxyamides 1-7 were dissolved in THF (3mL) under stirring after which a solution of BH3.SMe2 (0.5mmol, 10M) complex was added at 0C by a syringe. After the mixture was stirred for 1h at 65C, the freshly distilled ketone (0.5mmol) in dry and freshly distilled THF (2mL) was added over a period of 1.5h by syringe at the same temperature. The reaction mixture was stirred at 65C until the ketone was completely consumed. After stirring for a further 30min at rt, the reaction mixture was quenched by the addition of MeOH (2mL) and extracted with CH2Cl2 (3×3mL). The combined organic extracts were washed with brine and dried over MgSO4. After evaporating the solvent under reduced pressure, the product was purified by column chromatography on silica gel using petroleum ether/EtOAc (5:1; for 4?-nitroacetophenone: 5/3) as eluent. The ee value was determined by HPLC with Chiralcel AS-3 or Chiralcel OD-H columns
With (2R)-2-(ferrocenylmethylamino)-2-phenylethyldiphenylphosphinito(dichloro(?5-pentamethylcyclopentadienyl)iridium(III)); isopropyl alcohol; potassium hydroxide; at 82℃; for 0.25h;Inert atmosphere; Schlenk technique;Catalytic behavior;
General procedure: Typical procedure for the catalytic hydrogen transfer reaction: asolution of iridium complexes 17-24 (0.005 mmol), KOH (0.025 mmol) and the corresponding ketone (0.5 mmol) in degassed 2-propanol (5 mL) was refluxed until the reaction completed. Then, a sample of the reaction mixture is taken off, diluted with acetone and analyzed immediately by GC, conversions obtained are related to the residual unreacted ketone.
With C22H32ClN2Ru(1+)*Cl(1-); sodium formate; In water; at 60℃; for 12h;Inert atmosphere; Schlenk technique;
General procedure: To a solution of a ruthenium catalyst (0.0168 mmol)in degassed water (8 mL) was added a ketone (0.168mmol) and sodium formate (0.84 mmol). The reactionmixture was kept in a thermostat at 60C. 1 mL of thesolution from the reaction mixture was withdrawn at 1 h,2 h and 12 h; extracted with 5 mL of ethyl acetate;dried over anhydrous sodium sulphate and analyzedby 1H NMR spectroscopy. Conversion was calculatedfrom the 1H NMR spectrum. Chiral alcohols were purifiedby preparative thin layer chromatography. Enantiomericexcess (ee) was determined using the chiralHPLC technique employing the Chiralcel OD column,except in the case of 1-(4-Chlorophenyl)ethanol, 1-(2-Chlorophenyl)ethanol, 1-(4-Nitrophenyl)ethanol), forwhich it was determined using a Chiralcel OJ-Hcolumn.
With fermented yeast cells; In aq. phosphate buffer; at 30 - 35℃; for 24h;pH 7.5;Enzymatic reaction;
General procedure: The fermentation medium, in a total volume of 1L, consists of 20gL-1 glucose, 20gL-1 peptone and 10gL-1 yeast extract, to this yeast cells were inoculated, followed by incubation at 28-30C for 48h. After optimal growth, the medium was centrifuged to isolate fermented yeast cells, which were then washed with sterile distilled water. These fermented yeast cells were immobilized different alginate matrix i.e. a) Calcium alginate immobilized yeast beads and b) Succinyl modified alginate immobilized beads as described in our earlier studies [14]. The degree of succinylation was determined by the titration method as described by Wurzburg [15]. To the 4% sodium alginate/succinylated alginate solution, 2% (v/v) of fermented S.cerevisiae cells were added and the resultant cell suspension (107cfu/cm3) was extruded through a needle with diameter-0.5mm injector added as droplets into 2% calcium chloride solution under continuous stirring to get the calcium alginate/succinylated alginate-immobilized beads. Beads having a diameter in the range of 1.5-2.5mm were selected for subsequent fermentation experiments. Cell viability was determined by plate counts. The stability of yeast entrapped in the succinyl alginate matrix (beads) was measured as described in [14]. The binding efficiency of yeast cells in the alginate/functionalized alginate matrix has been confirmed by SEM studies (Fig. 1 ). To the above immobilized yeast cells (10gm in 250mL of phosphate buffer, pH 7.5), the pro-chiral ketones 1a-9a or azido ketones 10a-12a, (100mg/mL) each were added and incubated at 30-37C. The progress of the reactions at different time intervals was monitored by TLC and HPLC. After optimal biotransformation of ketones to respective chiral alcohols the immobilized beads containing yeast cells were separated and reused up to 7 cycles without much loss enzyme activity. Thus collected reaction medium containing products was extracted with equal amounts of ethyl acetate and the products obtained were isolated and purified by column chromatography. The spectral data of all the chiral products synthesized has confirmed by literature [9,10,17-23]. Further the chiral azido alcohols 10b-12b obtained were subjected to hydrogenation by using Pd nanoparticles to obtain chiral amino alcohols.
With (2R)-2-[benzyl([6-({benzyl[(1R)-2-[(diphenylphosphanyl)oxy]-1-phenylethyl]amino}methyl)pyridin-2-yl]methyl})amino]-2-phenylethyl diphenylphosphinite bis(dichloro-eta6-p-cymeneruthenium(II)); isopropyl alcohol; potassium hydroxide; at 82℃; for 0.333333h;Inert atmosphere; Schlenk technique;Catalytic behavior;
General procedure: Typical procedure for the catalytic hydrogen-transfer reaction: a solution of the Ru(II)-complexes 17-24 (0.005 mmol), KOH (0.025mmol) and the corresponding ketone (0.5 mmol) in degassed 2-propanol (5 mL) was refluxed until the reaction was completed. Periodically samples taken from the reaction medium were passed through acetone silica gel column and conversion rates were observed in gas chromatography, which were calculated based on unreacted ketone.
With C31H40Cl2NO2PRu; In isopropyl alcohol; for 0.25h;Inert atmosphere; Schlenk technique;
General procedure: Appropriate amount of metal complexes were dissolved in degassed 2-propanol and appropriate volumes of this solution were added to the 20mL test tubes capped with septum under argon atmosphere. Always freshly prepared solutions were used. Then the solution of related ketone in 2-propanol (0.25mM) was added, followed by the addition of base solution in 2-propanol, resulted the starting of the reaction. The total volume was 2.5mL and substrate concentration was 0.1M for all experiments. 0.1mL samples were taken after the related times, diluted with Et2O (1:10) and passed through the silica-gel. Conversions and enantiomeric excess were determined by GC equipped with Supelco BETA DEX 120 (30m×0.25mm×0.25mum) column [35-37].
With [(1S,2S)-N-(p-toluensulfonyl)-1,2-diphenylethanediamine](p-cymene)ruthenium (I); sodium formate; In methanol; water; at 50℃; for 12h;Green chemistry;
Add 0.5 mmol of 1-(4-nitrophenyl)ethanol to the test tube, add 1.5 mmol of dipropylene glycol dimethyl ether to the oxygen balloon, and react at 120 C for 12 hours until the reaction is complete. Add sodium formate to the reaction system. Then, 0.0025 mmol of catalyst B was added, and 4 mL of methanol:water (3:1) was added, and the mixture was replaced with nitrogen for 3 times, and reacted at 50 C for 12 hours. After the reaction was completed, the mixture was washed with water, and the aqueous phase was extracted three times with ethyl acetate. Dry, column chromatography (petroleum ether: ethyl acetate = 10:1) gave (S)-1-(4-nitrophenyl)ethanol (76.6 mg), yield 87%, ee value 81 %. HPLC separation conditions: chiral column competition OJ-H column, mobile phase: n-hexane / isopropanol = 95:5 (volume ratio), flow rate: 1.0 ml / min, wavelength: 254 nm, temperature, 25 C, t1 = 36.74min, t2=41.44min;
With formic acid; hydroxylamine hydrochloride; silica gel; at 80℃; for 4h;
General procedure: A mixture of 10 mmol of ketone 1-10, 30 mmol of hydroxylamine hydrochloride, 1 g of silica gel in 8 mL of formic acid was heated at 80 while stirring (TLC monitoring) for the time indicated in the table. Silica gel was filtered from the reaction mixture, the filtrate was diluted with 150 mL of water and neutralized with 20% solution of NaOH. The separated precipitate of amides 11, 12a, 12b-16a, 16b, and 18a was filtered off, washed with water on the filter, and dried. Amides 17a, 17b, 19a, 19b, and 20 were extracted from the water solution with toluene (3 × 20 mL), the extract was dried with Na2SO4 and evaporated on a rotary evaporator. The prevailing amide isomer obtained from ketones 2-6 was isolated by recrystallization from 2-propanol. Amides 17, 17b and 19, 19b were analyzed as mixtures.
90%
With mesitylenesulfonylhydroxylamine; In acetonitrile; at 20 - 70℃; for 6h;
General procedure: To a round bottom flask, equipped with a magnetic stirring bar, was added ketone 1 (0.5 mmol, 1.0 equiv.) and acetonitrile (2 mL) at room temperature. To this stirred solution, freshly prepared O-(Mesitylsulfonyl)hydroxylamine 2 (2.0 equiv.) was added. The reaction mixture was stirred for the specified duration and temperature. The progress of the reaction was monitored by TLC. After completion, the reaction mixture was diluted with ethyl acetate (10 mL) and washed with a saturated aqueous NaHCO3 solution (3 x 5 mL). The combined organic layer was washed with brine solution and dried over anhydrous Na2SO4. Solvent was removed under reduced pressure to get the crude product. The reaction that required elevated temperature was stirred first at room temperature for 2 hours after addition of MSH and then heated at 70 C for the specified time.
88%
With hydroxylamine hydrochloride; water; Thiamine hydrochloride; In 1,4-dioxane; at 90℃; for 0.5h;
General procedure: A mixture of ketone 1 (2 mM), hydroxylamine hydrochloride (3 mM) and thiamine hydrochloride (0.4 mM) was taken in 10mL dioxane:H2O (9:1) in a round-bottom flask and heated at 90 C for specific time (30-90 min). The progress of the reaction was monitored using thin layer chromatography (tlc). After completion of the reaction, the reaction flask was cooled to room temperature. The residue was taken in ethyl acetate (30 ml), washed with water (2x15 ml), brine (1x15 ml) and the organic layer was dried (anhyd. Na2SO4). The resulting ethyl acetate solution was concentrated and the desired amides 2 (75-95% yield) are obtained by recrystallization from ethanol.
87%
With hydroxylamine hydrochloride; In acetonitrile;Reflux;
General procedure: Ketones (1 mmol) and hydroxylamine hydrochloride (0.0694g,1 mmol) were dissolved in CH3CN (10 mL) and stirred for 10 - 15 min. The complex (CS-SalBr-Zn-L) (10 mol%) were added tothe reaction flask. The reaction mixture was heated under reflux for specific time (3e7 h). After completion, the reaction mixture was cooled to room temperature and the catalyst was removed by filtration. The filtrate was treated with ethyl acetate (3 10 mL).The combined organic layers were treated with saturated brine solution and dried over anhydrous sodium sulphate. The removal of solvent yields crude product, which after purification by column chromatography over Silica gel (100e200 mesh), afforded the desired products.
With D-glucose; In aq. phosphate buffer; at 25℃; for 24h;pH 7.0;
General procedure: For isolation and characterization of the bioreduction product, the reaction was performedon a preparative scale: 300 g resting cells of R. rubra AS 2.2241 were resuspended in 1000 mL of Na2HPO4-KH2PO4 buffer (100 mM, pH 7.0) with 50 g glucose and 10 mM of each substrate (1a-1i,1m and 1n). The reaction mixture was incubated at 25C and shaken at 220 rpm for 24 h. The cellswere removed by centrifugation and the supernatant was saturated with NaCl. The supernatantwas extracted with EtOAc (1000 mL 3). The organic phases were washed with brine, dried overNa2SO4, filtered and concentrated in vacuo. The residue was purified by flash chromatography onsilica gel (eluent: EtOAc/PE 1:20) to give the enantiomerically pure alcohols 2a-2i, 2m, 2n. The isolatedyield and ee of preparative-scale are comparable to those obtained from screening biotransformations.The spectroscopic data (1H and 13 C NMR, and HPLC retention times) of enantiomerically alcohols 2a-2i, 2m and 2n are in agreement with those obtained for racemic forms, as described in theSupplementary Materials.
98%
With tetrahydrofuran; dimethylsulfide borane complex; In toluene; at 0℃;Inert atmosphere;
General procedure: ketonesBH3/SMe2(1.1 ml, 1 M) was added by syringe to a solution ofchiral polyether ligand Poly-6 (0.78 g, 0.1 mmol) in dry THF (5 ml)under nitrogen at 0C. The mixture was stirred for 1 h at 0C andthen a solution of ketone (1 mmol) in dry THF (5 ml) was addeddropwise over a period of 1 h at the same temperature and stirredfor 6 h, the reaction mixture was then quenched by dropwise addi-tion of 10% NH4Cl (5 ml). The alcohol product was isolated byextraction with ethyl acetate (10 ml × 3). The organic phase waswashed with brine, dried over anhydrous sodium sulfate. Afterconcentration by rotatory evaporation, the product was purifiedby column chromatography on silica gel (petroleum ether/ethylacetate 6:1) to afford the corresponding alcohol. The enantiomericexcesses were determined by HPLC with a chiral column (Dai-cel Chiralcel OD-H; eluent, hexane-isopropyl alcohol; UV detector,254 nm).
98%
With borane-THF; at 30℃; for 6.5h;Inert atmosphere;
General procedure: To a 25ml round-bottom flask was added 0.05mmol (0.05equiv) of chiral ligand in 5ml of THF. Under a nitrogen atmosphere and at 0C, BH3·THF (5M) (1.1mmol, 1.1equiv) was added. The mixture was stirred at 0C for 0.5h and then warmed to 30C for a further hour. The ketone (1mmol) in 2ml of THF was added slowly over a period of 0.5h under the same temperature and stirred for 6h. The reaction mixture was cooled to 0C and quenched with a 1M aqueous HCl solution (8ml), then extracted with ethyl acetate (3ml×10ml). The combined organic layer was washed twice with brine and dried with anhydrous MgSO4. The solvent was removed under reduced pressure. The residue was passed through a short silica gel column to afford a pure product before being subjected to HPLC analysis.
95%
Reaction conditions: 100 mg-42 g substrate, substrate concentration = 0.6-1 M toluene, >99% conversion is observed in all cases.
93%
With Kluyveromyces marxianus CBS 6556 growing cells; In ethanol; at 30℃; for 24h;
General procedure: Kluyveromyces marxianus CBS 6556 was stored on agar slants at 4 C. For the inoculum preparation, a 250-mL conical Erlenmeyer flask containing 100 mL of yeast maintenance medium (YMM) (previously autoclaved at 121 C, 1 atm, for 15 min), was inoculated with a single loopful of the microorganisms from the agar slants. The flask was then incubated aerobically at 30 C in a rotary shaker at 200 rpm for 24 h. Next, the growing cultures were inoculated (5% v/v) into a 250 mL conical Erlenmeyer flask containing 100 mL of YMM and incubated for an additional 24 h under the same conditions. These cultures were then used as the final inoculum (1% v/v) into a 1000 mL flask containing 400 mL of YMM. After 24 h incubation at 30 C in the shaker (200 rpm), 100 mg of the ketone 1a-n dissolved in 1 mL of absolute ethanol was added. The reactions were monitored by GC, by collecting suspension of aliquots of 1 mL after 1, 3, 4, and 5 days of reaction from each flask: after extraction with ethyl acetate (2 mL), the organic phase was analyzed by GC. After appropriate conversion, the suspension was centrifuged (3000 rpm, 6 min, 4 C), and the aqueous phase was extracted with ethyl acetate (4 × 150 ml). The yellow organic phase was dried over Na2SO4, filtered, and evaporated under reduced pressure. The residue was purified by silica gel column chromatography using petroleum ether and ethyl acetate (90:10 or 80:20) as eluents to yield the desired alcohols. The absolute configurations of alcohols 2a-n obtained from the bioprocess were determined by comparison of their specific rotations with those previously reported in the literature, from commercially available compounds, or by comparison of retention times with previously published data.
91%
With C19H30B10ClIrN2; hydrogen; In ethanol; at 120℃; for 5h;
Using the ruthenium complex prepared in Example 1 as a catalyst,Catalytic asymmetric reduction of aryl ketones:To 4-nitroacetophenone (10 mmol, 1.65 g), a solution of a trivalent ruthenium complex (0.02 mmol, 26.0 mg) containing an ortho-carbobane structure was added.And reacting with hydrogen as a reducing agent,The reaction temperature is 120 C,The reaction time is 300 minutes.After the end, the concentrated reaction solution is directly separated by silica gel column chromatography and dried to a constant mass.The corresponding chiral alcohol compound C8H9NO3 was obtained (yield 91%).Ee>99%,Elemental analysis: C 57.48, H 5.43, N 8.38 (theory); C 57.52, H 5.38, N 8.32 (actual).
83%
With Daucus carota plant cells; In water; at 23 - 27℃; for 96h;Enzymatic reaction;Kinetics;
General procedure: Ketones 1a-5a (20 mmol) were added to a suspension of freshly cut D. carota or P. crispum (15 g) in distilled water or isooctane (70 mL) under constant stirring in a conical Erlenmeyer flask. The reaction mixture was then placed in an orbital shaker (150 rpm) at room temperature. After achieving the necessary conversions, the suspension was filtered, and D. carota or P. crispum were washed three times with water. The filtrates were extracted with diethyl ether (3 x 125 mL). The organic phase was dried over MgSO4, evaporated and monitored by GLC.
82%
Daucas carota root; extract of; In water; at 37 - 40℃; for 40h;pH 7.0;Enzymatic reaction; Aqueous phosphate buffer;Conversion of starting material;
The General Methodology for the Reduction of the Substituted Acetophenones; 100 mg of each of the compounds in Table 1 entry No. 1-10 and other similarly related compounds were added to a crude extract of 2 gm Daucas carota (protein 1 gm/ml) in 50 ml of 0.1 M sodium phosphate buffer pH 6.5 to 7.5. The reactions were incubated in a shaking incubator for 30 to 50 hours. The product formed was isolated and purified by flash chromatography and the product obtained was confirmed by standard spectral data.
65%
With D-glucose; at 35℃; for 36h;pH 7.5;Tris buffer; Microbiological reaction; Enzymatic reaction;
General procedure: The preparative scale (large scale) production of (S)-1-phenylethanol 1b from acetophenone 1a by immobilized C. laurentii EBK-19 cells was also achieved. The reduction of 1a was carried out in a 1000-mL Erlenmeyer flask using beads prepared as described in Section 4.4. The cells were activated by suspending the beads in 300 mL tris buffer containing 4% glucose. After cell activation (3 h), acetophenone 1a (6 mM) was directly added to the mixture. During the 36 h reaction period, the beads were regularly separated by filtration, resuspended in tris buffer and glucose and reused for the same reaction without washing. At regular time intervals (36 h), the conversion and enantiomeric excess (ee) of the product were determined and the yields calculated. The run time of the beads was optimized for the production of 1b and found to be 27 days.
With sodium formate; In water; at 40℃; for 3h;
General procedure: For asymmetric transfer hydrogenation of ketones, the catalyst 5 (15.0 mg, 4.0 mumol of Ru based on the ICP analysis), HCO2Na (0.27 g, 10.0 mmol), ketone (0.40 mmol), and 2.0 mL of water were added in a 10 mL round bottom flask in turn. The mixture was allowed to react at 40 C for 3.0-9.0 h. [For asymmetric transfer hydrogenation of quinolines, the catalyst 5 (15.0 mg, 4.0 mumol of Ru based on the ICP analysis), HCO2Na (0.27 g, 10.0 mmol), quinolines (0.40 mmol), and 2.0 mL (2.0 M HCOOH/HCOONa buffer solution, pH = 5.0) were added in a 10 mL round bottom flask in turn. The mixture was allowed to react at 40 C for 10.0-24 h.] During that time, the reaction was monitored constantly by TLC. After completion of the reaction, the catalyst was separated via centrifuge (10,000 r/min) for the recycle experiment. The aqueous solution was extracted by Et2O (3 × 3.0 mL). The combined Et2O was washed with brine twice and dehydrated with Na2SO4. After the evaporation of Et2O, the residue was purified by silica gel flash column chromatography to afford the desired product. The conversion could be determined by an external standard method, and the ee value could be determined by chiral GC using a Supelco beta-Dex 120 chiral column (30 m × 0.25 mm (i.d.), 0.25 mum film) or a HPLC analysis with a UV-Vis detector using a Daicel OJ-H/OD-H/OB-H chiralcel column (Phi 0.46 × 25 cm).
With [(2S)-2-(ferrocenylmethylamino)-2-phenylethyldiphenylphosphinito(dichloro(eta6-benzene)ruthenium(II))]; sodium hydroxide; In isopropyl alcohol; at 82℃; for 0.25h;Inert atmosphere; Schlenk technique;Catalytic behavior;
General procedure: 2.2;General procedures for synthesis of ferrocene based Ru(II)-phosphinites complexes (17-24) ;[Ru(eta6-benzene)(mu-Cl)Cl]2 (0.15 mmol) and ferrocene based phosphinite (0.30 mmol) were dissolved in 20 mL of toluene and stirred for 1 h at room temperature.The volume was concentrated to ca.1-2 mL under reduced pressure and addition of petroleum ether (20 mL) gave the desired complex a tile red solid which was collected by filtration and dried in vacuum.
With glucose; glucose dehydrogenase from Bacillus subtilis CGMCC 1.1398; medium-chain dehydrogenase from Kuraishia capsulate CBS1993; NAD; In aq. phosphate buffer; for 16h;pH 7.0;Enzymatic reaction;
General procedure: Substrate scope and enantioselectivity determination The relative activities of 26 substrates were measured using thepreviously described assay protocol with adjusted ratio of enzymeand substrate concentration. The a-chloroacetophenone activitywas assumed 100%.Enantioselectivity was determined by examining the reductionof aromatic ketones using an NADH-regeneration system consist-ing of the puried KcDH and glucose dehydrogenase (GDH) fromBacillus subtilis CGMCC 1.1398. The 1-mL reaction mixture con-tained 0.5 mM NAD+, 10 mM ketone, 1 U KcDH, 50 mg glucoseand 2 U GDH in 50 mM potassium phosphate buffer (pH 7.0). After16 h, the reaction sample was equally separated into two parts,with one terminated by adding an equal volume of methanol, fol-lowed by HPLC analysis to determine the conversion ratio, and theother extracted with ethyl acetate, followed by ee analysis. Meth-ods used for analysing chiral products using HPLC or GC aredescribed in Supplementary Table S1.
With (2S)-2-(ferrocenylmethylamino)-2-phenylethyldiphenylphosphinito(dichloro(?5-pentamethylcyclopentadienyl)iridium(III)); isopropyl alcohol; potassium hydroxide; at 82℃; for 0.25h;Inert atmosphere; Schlenk technique;Catalytic behavior;
General procedure: Typical procedure for the catalytic hydrogen transfer reaction: asolution of iridium complexes 17-24 (0.005 mmol), KOH (0.025 mmol) and the corresponding ketone (0.5 mmol) in degassed 2-propanol (5 mL) was refluxed until the reaction completed. Then, a sample of the reaction mixture is taken off, diluted with acetone and analyzed immediately by GC, conversions obtained are related to the residual unreacted ketone.
With D-glucose; immobilized ketoreductase from Pichiaglucozyma (KRED1-Pglu) and a glucose dehydrogenase from Bacillus megaterium (BmGDH) immobilization on aldehyde agarose; nicotinamide adenine dinucleotide phosphate; In dimethyl sulfoxide; at 30℃;pH 8;Enzymatic reaction;
Reactions were carried in 2 mL volume of 50 mM Tris HCl bufferpH 8.0 containing NADP+ (0.1 mM), substrate (0.5 g/L), glucose(4 eq × eq of substrate) at 30 C. The reaction was started by the additionof KRED1-Pglu and BmGDH, maintained under orbital shaking(180 rpm), and was monitored by HPLC.
99%Chromat.
With sodium tetrahydroborate; In tetrahydrofuran; at 20℃; for 0.416667h;Green chemistry;
General procedure: The magnetic nanocomposite, Fe3O4SiO2/Pr-beta-CD (0.02 g), was suspended in 5 mL dry THF, then NaBH4 (0.06 g, 1.5 mmol) was added and stirred for 0.5 h. To the mixture, ketone (1 mmol) was added drop-wise at room temperature. Progress of the reaction was monitored by TLC, after the completion of the reaction; it was quenched by HCl (2 N). The nanocomposite was magnetically removed from the mixture and washed several times with ethanol for reuse. Then the organic phase was extracted with CH2Cl2.
With hydrogenchloride; phosphorus tribromide; sodium borohydrid; In ethanol; dichloromethane;
(1) Preparation of 1-(4-nitrophenyl)ethyl bromide 6.0 g of p-nitroacetophenone was dissolved in 100 ml of ethanol, and 0.75 g of sodium borohydride was added thereto under ice cooling. Afterward, the reaction solution was stirred at room temperature for 2 hours, and 1 ml of 0.1N hydrochloric acid was added thereto so as to bring the reaction to an end. This reaction mixture was concentrated under reduced pressure, and 100 ml of 0.5N hydrochloric acid was added to the resulting residue and extraction was then carried out twice with 50 ml of ether. The resulting ether layers were joined together, washed with water, and then dried over anhydrous sodium sulfate, and the solvent was distilled off. Afterward, the resulting residue was dissolved in 100 ml of methylene chloride. 7.2 g of phosphorus tribromide was added dropwise to the solution under ice cooling, followed by stirring at room temperature for 10 hours. Next, an aqueous potassium carbonate solution was added to the reaction solution to neutralize the same, and the resulting methylene chloride layer was separated, washed with water, and then dried over anhydrous sodium sulfate. Afterward, the solvent was distilled off under reduced pressure, and the resulting residue was purified through a silica gel column chromatograph (chloroform/hexane=2/1 in volume ratio), thereby obtaining 3.5 g of oily 1-(4-nitrophenyl)ethyl bromide. Analytical results of the obtained bromide derivative NMR (CDCl3) delta ppm: 2.06 (d, 3 H), 5.23 (q. 1 H), 7.60 (d, 2 H), 8.20 (d, 2 H).
3-(3,4-Dihydroxy-5-nitrophenyl)-1-(4-nitrophenyl)prop-2-en-1-one[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
1.25 g (38%)
EXAMPLE 76 3-(3,4-Dihydroxy-5-nitrophenyl)-1-(4-nitrophenyl)prop-2-en-1-one The procedure described in Example 8 was repeated using 1.83 g of <strong>[116313-85-0]3,4-dihydroxy-5-nitrobenzaldehyde</strong> and 1.65 g of 4'-nitroacetophenone. Yield 1.25 g (38%), m.p. 255-256 C.
With pyridine; selenium(IV) oxide; at 110℃; for 1h;Inert atmosphere;
SeO2 (0.167 g, 1.5 mmol), p-nitroacetophenone (0.165 g, 1 mmol) in a 25 mL round bottom flask under nitrogen.Add 10 mL of anhydrous pyridine, heat the oil bath to 110 C and stir to reflux.After 1 hour, the progress of the reaction was detected by TLC thin layer chromatography, and after cooling for 4 hours, it was cooled to room temperature.Filtration through a Buchner funnel, filtering off the solution containing SeO2 precipitate, washing the residue with 50 mL of ethyl acetate;The filtrate was combined and treated with 1 mmol/L hydrochloric acid (20 mL).The aqueous layer was extracted three times with ethyl acetate (50 mL) to give aqueous layer 2 and organic layer 2;After the organic layer 1 and the organic layer 2 are combined, extracted three times with 25 ml of water to obtain an organic layer 3 and an aqueous layer 3;The aqueous layer 3 was treated with 1 mmol/L NaOH (50 mL), and the reaction solution was diluted to obtainTo the filtrate 4.After the filtrate 4 was combined with the aqueous layer 2, the pH was adjusted to 1.5 with hydrochloric acid (1 mmol/L).The mixture was extracted with EtOAc (3~50 mL).Drying in a vacuum desiccator overnight gave the product 4-nitrophenylglyoxylic acid.Yield: 0.154 g. The yield was 79.2%.
With pyridine; selenium(IV) oxide; at 90℃; for 4h;Inert atmosphere;
Specific operation: p-nitroacetophenone (1g) was dissolved in pyridine (10mL), and SeO2 (1g) was added.The mixture was purged with nitrogen and stirred at 90 C for 4 h, wherein the molar ratio of p-nitroacetophenone to SeO 2 was 1:1.5.After the reaction was completed, the mixture was cooled and filtered, and the filter cake was washed three times with ethyl acetate. The organic layer was collected, washed with 2M HCl, and then the organic layer was combined.Dry with anhydrous sodium sulfate,The solvent was distilled off under reduced pressure, and the residue was purified by column chromatography.
With (Z/E)-2-bromo-2-[4-oxothiazolidin-2-ylidene]-N-phenylacetamide; dimethyl sulfoxide; for 36h;Reflux;
General procedure: A mixture of a substrate (0.6 mmol), vinyl bromide 2a (0.06 mmol) in DMSO (1.1 mL) was heated in an open flask (the temperature of an oil bath and the reaction time are specified in refPreviewPlaceHolderTable 2). After the completion of the reaction (checked by TLC), the reaction mixture was diluted with water (11 mL), saturated with NaCl and extracted with ethyl acetate (5×4 mL). Only in the case of the synthesis of arylglyoxals the organic layer was additionally washed with Na2CO3 (0.12 mmol in 2 mL of water), with saturated aq NaCl and dried with anhydrous Na2SO4. Column chromatography (eluent: gradient petrolether/ethyl acetate) of the extract gave the pure products.
With iodine; In dimethyl sulfoxide; at 100℃;
General procedure: A mixture of acetophenone 1a (120 mg, 1.0 mmol), benzylamine 2a (160.7 mg, 1.5 mmol), and iodine (507.6 mg, 2.0 mmol) in DMSO (3 mL) was stirred at 100 C for 5 h. After disappearance of the reactant (monitored by TLC), and added 50 mL water to the mixture, then extracted with EtOAc three times (3 50 mL). The extract was washed with 10% Na2S2O3 solution (w/w), dried over anhydrous Na2SO4 and evaporation. The residue was purified by column chromatography on silica gel (petroleum ether/EtOAc=100:1) to yield the desired product 3aa as a white solid (183.4 mg, 83% yield).
With selenium(IV) oxide; In water; acetic acid; at 115℃; for 3h;
13.46 g (121.4 mmol) of selenium dioxide are added to 60 mL of acetic acid and 9 mL of water. The mixture was stirred at 60 C until solid had dissolved. Then the reaction mixture was heated to 115 C, 20.00 g (121.2 mmol) of 4-nitroacetophenone were added and the heating was continued for further 3 h until the solution became clear and the precipitation of metallic selenium stopped. To remove the selenium precipitate, the solution was filtered while hot.
With selenium(IV) oxide; water; In 1,4-dioxane;Reflux;
General procedure: Melting points were determined with an electrothermal 9100 apparatus. Fourier transform infrared (FT-IR) spectra were recorded on a Unicam/Mattson 8700 spectrometer. 1H and 13C NMR spectrawere recorded on a Bruker 400 spectrometer in CDCl3. The chemicals used in this work were purchased from Fluka and Merck and were used without further purification. Arylglyoxal hydrates were prepared by the oxidation of acetophenones using SeO2 in refluxing dioxane in the presence of water as done in the Riley et al. (47) method.
General procedure: A mixture of <strong>[4113-04-6]6-quinolinecarboxaldehyde</strong> 1 (2 mmol), the respective acetophenone 2a-g (2 mmol) was dissolved in 30 mL ethanol. To this mixture, sodium hydroxide (10percent, 4 mL) was added at 0-5 °C. The reaction mixture was stirred at room temperature for 15 h. The yellow solid thus obtained was filtered, washed with water and EtOH. The compounds were recrystallized from dichloromethane/diisopropyl ether to give analytically pure 6-quinolinyl chalcones 3a-g.
With acetylhydroxamic acid; sulfuric acid; In acetonitrile; at 80℃; under 1292.9 Torr; for 0.25h;Microwave irradiation;
General procedure: Acetophenone 1a (1.0 g, 8.3 mmol), acetohydroxamic acid (0.92 g, 12.5 mmol), acetonitrile (3 ml), and conc. H2SO4 (0.2 ml) were taken into a 10 ml pressure tube and subjected to microwave heating (CEM discover, 360 W, 80 C, 25 psi) for 10 min. The crude product obtained was purified as mentioned above to afford acetanilide 2a (0.94 g, 86%) and it gave spectral data same as above.
With potassium hydroxide; In methanol; at 20℃; for 24h;
General procedure: The novel chalcones (1-8)were prepared by magnetic stirring with acetophenone (1 mmol), methanol (30 ml), KOH 50% w/v (5 ml) and <strong>[130345-50-5]quinoxaline-6-carbaldehyde</strong> (12) (1 mmol), at room temperature for 24 h. Distilled water and chloridric acid 10% were added in the reaction for total precipitation of the compounds. The compounds were then obtained by vacuum filtration and later recrystallized in dichloromethane/hexane. The purified chalcones were obtained with yields between 41% and 93%.
With copper(II) acetate monohydrate; caesium carbonate; In N,N-dimethyl-formamide; at 100℃; for 4h;Inert atmosphere; Schlenk technique;
General procedure: Under N2 atmosphere, a Schlenk tube was charged with nitroarenes 1 (0.5 mmol), phenols 2 (1.0 mmol), Cu(OAc)2·H2O (5 mol %), and Cs2CO3 (1.0 mmol) in DMF (3 mL) at room temperature. After that, the mixture was stirred constantly at 100 C (oil bath temperature) for 4 h. After the completion of the reaction, as monitored by TLC and GC-MS analysis, the reaction mixture was cooled to room temperature, diluted with ethyl acetate, and filtrated. The filtrate was concentrated under vacuum, and the resulting residue was purified by silica gel column chromatography (petroleum ether/ethyl acetate) to afford the desired arylated product 3.
80%
With caesium carbonate; In N,N-dimethyl-formamide; at 100℃; for 5h;Inert atmosphere; Schlenk technique; Green chemistry;
General procedure: Under an argon atmosphere, a Schlenk tube was charged with MCM-41-2N-Cu(OAc)2(46 mg, 0.025 mmol), nitroarene 1 (0.5 mmol), phenol 2 (1.0 mmol), Cs2CO3 (1.0 mmol) and DMF (3 mL). The reaction mixture was stirred at 100 C for 5 h under Ar. After being cooled to room temperature, the mixture was diluted with ethyl acetate (20 mL) and filtered. The MCM-41-2N-Cu(OAc)2 catalyst was washed with distilled water (2 × 5 mL), DMF (2 × 5 mL) and EtOH (2 × 5 mL) and could be reused in the next run. The filtrate was washed with water (2 × 10 mL) and dried over anhydrous MgSO4. After removal of the solvent under reduced pressure, the residue was purified by column chromatography (EtOAc/hexane) on silica gel to afford the desired product 3.
78%
With potassium phosphate; tetrabutylammomium bromide; nickel dichloride; at 100℃; for 4h;
General procedure: A vessel was charged with nitrobenzene (0.5 mmol), phenol/alcohol (1 mmol), NiCl2(0.1 mmol), and K3PO4(2 mmol). To this mixture, was added TBAB (1.5 g) and heated to100 C. Progress of the reaction was monitored by TLC.After completion of the reaction, silica gel (1 g) was addedto the reaction vessel and the mixture was added to a columnchromatography. Petroleum ether/ethylacetate (10:1)was used as the eluent to separate the desired product.
With Oxone; In water; acetonitrile; at 20℃; for 5.5h;
General procedure: To 16 mL of acetonitrile/water (1:1 v/v) mixture was added 0.5-1.2 mmol of the starting compound. The contents were heated at reflux with introduction of oxone (cf. entries for each case) incrementally over the entire duration of the reaction. For secondary benzyl halides, the reactions were run at room temperature. The progress of the reaction in each case was monitored by TLC analysis. After completion of the reaction, the reaction mixture was cooled to room temperature and the organic matter was extracted with ethyl acetate. The combined organic extract was dried over anhyd Na2SO4 and concentrated in vacuo. Short pad silica gel column chromatography of the residue led to isolation of the pure product.
General procedure: solutionof acid hydrazide (0.01 mol) and appropriate benzaldehyde/acetophenone (0.01 mol) in ethanol was refluxed for 5-6 h. The precipitated title compounds were then filtered off, washed with water and recrystallized from ethanol.
(E)-1-(4-nitrophenyl)-3-(2,6-dimethoxyphenyl)prop-2-en-1-one[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
97%
General procedure: A 50 mL flask was charged with substituted acetophenone (5 mmol) and a solution of sodium hydroxide (10 mmol) in a 4:1 (v/v) mixture of ethanol/H2O (25 mL), and the resulting mixture was stirred at room temperature for 5 min. A substituted benzaldehyde (5 mmol) was then added to the reaction, and the resulting mixture was stirred at room temperature. The reaction was then monitored byTLC using ethyl acetate/petroleum ether (1:4 or 1:2 v/v) as the solvent system. Upon completion of the reaction, the crude product was filtered off and recrystallized from a mixture of dichloromethane and ethanol or purified by column chromatography over silica gel eluting with a mixture of petroleum ether and ethyl acetate to give the pure product.
With oxygen; palladium diacetate; toluene-4-sulfonic acid; In tetrahydrofuran; for 12h;Reflux;
General procedure: A mixture of aryl ketones (1.0 mmol), 1,3-diaminopropane (1.3 mmol) and p-toluene sulphonic acid (1.0 mmol) was stirred under oxygen atmosphere in THF. In this Pd (OAc)2 (0.1 mmol) was added and reaction mixture was heated to reflux temperature for 8-12 h. After completion of the reaction (TLC), reaction mixture was cooled to room temperature and concentrated under reduce pressure. The resulting concentrated solution was further diluted with water and then extracted with ethyl acetate. The ethyl acetate layer was washed with Na2S2O3 solution, dried over anhydrous Na2SO4 and concentrated under reduced pressure to get the crude product. The product was then purified by using silica gel column chromatography (Hexane-EtOAc).
With hydrogenchloride; In ethanol; water;Reflux; Inert atmosphere;
To a single-neck 250 ml round-bottom flask was added p-nitroacetophenone (16.5 g), paraformaldehyde (4.5 g), <strong>[6091-44-7]<strong>[6091-44-7]piperidine</strong> hydrochloride</strong> (12.1 g), absolute ethanol (100 mL) and a magnetic stir bar. To the stirred heterogeneous mixture was added hydrochloric acid (37 wt% in water, 1 mL) and the solution was heated to reflux under nitrogen. After a 1-2 h period more paraformaldehyde (3.0 g) was added. The solution was allowed to reflux for approximately 18 h during which time further paraformaldehyde was added (3.0 g). After allowing the reaction solution to cool a crystalline solid settled that would not dissolve upon further refluxing. The solid was isolated by filtration and recrystallised using very hot methanol to afford large yellow crystals (10.9 g). 1H NMR (DMSO-d6) delta 1.34-1.50 (m, 1H), 1.64-1.79 (m, 2H), 1.79-1.94 (m, 4H), 2.89-3.05 (m, 2H), 3.41 (q, 2H), 3.51-3.54 (m, 2H), 3.82 (t, 2H), 8.26 (s, 1H), 8.29 (s, 1H), 8.41 (s, 1H), 8.44 (s, 1H).
ethyl 2-(3,4-dimethoxybenzoyl)-4-(4-nitrophenyl)-4-oxobut-2-enoate[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
With iodine; copper(II) oxide; In dimethyl sulfoxide; at 70℃; for 12h;Sealed tube;
General procedure: A sealed tube was charged with acetophenone 5a (600 mg, 5 mmol), ethyl 3-oxo-3-(3,4,5-trimethoxyphenyl)propanoate 6a (1410 mg, 5.0 mmol), iodine (1396 mg, 5.5 mmol) and CuO (440 mg, 5.5 mmol) at room temperature, and then solvent DMSO (10 mL) was added. The resulting mixture was stirred at 70 C for 12 h, after disappearance of the reactant (monitored by TLC), and added 50 mL water to the mixture, then extracted with EtOAc 3 times (3 × 50 mL). The extract was washed with 10% Na2S2O3 solution, dried over anhydrous Na2SO4 and concentrated under reduced pressure. The residue was purified by column chromatography on silica gel (petroleum ether/EtOAc) to yield the desired product 1a as a yellow solid (yield: 84%).
(2E)-1-(4-nitrophenyl)-3-(quinoxalin-2-yl)prop-2-en-1-one[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
60%
This procedure is based on our previous report27 and vogels procedure36. To a conical flask containing NaOH solution (1.5eq, 10 mL H2O) was added substituted acetophenones (1mmole) in ethanol (10 mL), and the reaction mixture was stirred for 10 minutes to allow enolate formation, to this was added quinoxaline-2- carbaldehyde 1 (1mmole) and the reaction mixture was stirred till completion. After completion of the reaction, as monitored by TLC the reaction mixture was poured in an ice bath and was acidified using conc. HCl. The solid obtained was then filtered, dried and recrystallized using Ethanol. The quinoxalinyl chalcone 2a-n were then characterized using IR, NMR (1H, 13C) and HR-MS spectroscopy. The purity was checked by HPLC measurements using mobile phase consisting methanol and water in the ratio 90:10.
(E)-4-hydroxy-3-ethoxy-5-bromo-4'-nitrochalcone[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
With piperidine; at 160℃; for 0.25h;
In a 50 ml reaction flask, 0.8 g of <strong>[3111-37-3]4-hydroxy-3-ethoxy-5-bromobenzaldehyde</strong>, 0.6 g of p-nitroacetophenone,1ml piperidine, 160 reaction, stirring under reflux 15min, dark red viscous liquid. After cooling to room temperature, concentrated hydrochloric acid was addedSodium solution, adjust the pH to 12 or more, ice bath, add concentrated hydrochloric acid to pH 1-2, filtered to obtain a gray solid, anhydrous ethanol plusRecrystallization of a small amount of acetone gave a yellow crystal, i.e., (E) -4-hydroxy-3-ethoxy-5-bromo-4'-nitrochalcone.
With carbon tetrabromide; caesium carbonate; In acetonitrile; at 80℃; for 6h;Inert atmosphere;
In an oven dried 100 mL round bottomed flask 1-nitrosonaphthalene-2-ol 4a or 2-nitrosophenol 4b (1.0 mmol), acetophenones 5a-k (1.0 mmol), CBr4 (0.5 mmol, 165 mg),Cs2CO3 (2.1 mmol, 682 mg) and 10 mL CH3CN were added successively and the reactionmixture was heated for 6h at 80 C under nitrogen atmosphere. After completion of thereaction (progress was monitored by TLC; SiO2, Hexane/EtOAc = 9:1), the reaction mixturewas allowed to cool at room temperature and then solvent was removed under vacuum. Thecrude product was purified by using column chromatography over silica gel using hexane /ethyl acetate = 9:1 as an eluent to obtain the desired products (3a-f, 3h-3i, 3k, 3m, 3w, 3x) inhigh yields..
General procedure: To a solution of the appropriate acetophenone (0.04 mol) in 20 mLethanol, 4-methanesulfonyl phenyl hydrazine hydrochloride (6a,0.04 mol) was added. The resulting solution was heated under reflux for12 h. The precipitated hydrazones was filtered and washed with sufficientamount of ethanol and recrystallized from ethanol to afford hydrazones8a, 8b and 8f. Physical and spectral data are listed below:
(2E)-3-(quinolin-5-yl)-1-(4-nitrophenyl)prop-2-en-1-on[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
With ammonium acetate; In tetrahydrofuran; ethanol; at 70℃; for 72h;
2E)-3-(Quinolin-5-yl)-1-(4-nitrophenyl)prop-2-en-1-on To 1-(4-nitrophenyl)ethanone (CAS 100-19-6, 3.00 g, 18.2 mmol) in THF (49 mL) and ethanol (240 mL) were added chinolin-5-carbaldehyde (CAS 22934-41-4, 3.43 g, 21.8 mmol) and ammonium acetate (1.34 g, 17.4 mmol). The mixture was heated to 70 C for 3 days. Then the mixture was cooled down and formic acid (69 mL, 1.8 mol) was added at 60 C. The mixture was stirred for 1 h until r.t. was reached. The formed precipitate was filtered off, washed with ethanol to give a first batch. The filtrate was concentrated under reduced pressure and ethanol (80 mL) and THF (12 mL) were added. The resulting mixture was stirred overnight, the formed precipitate was filtered off, washed with ethanol to give a second batch. The resulting filtrate was concentrated under reduced pressure and was purified by flash chromatography (SiO2, hexane/ethyl acetate gradient 0%-45%-70%) to give a third batch. All batches were combined to give 3.15 g (85% purity, 50% yield) of the title compound. (0669) LC-MS (Method 1): Rt = 1.12 min; MS (ESIpos): m/z = 305 [M+H]+ (0670) 1H-NMR (400MHz, DMSO-d6) delta [ppm]: 7.66 (dd, 1H), 7.89 (t, 1H), 8.09 (d, 1H), 8.17 (d, 1H), 8.38 - 8.47 (m, 5H), 8.58 (d, 1H), 8.80 (d, 1H), 8.99 (dd, 1H).
3-(6-methoxynaphthalen-2-yl)-3-(5-methylisoxazol-3-ylamino)-1-(4-nitro-phenyl)propan-1-one[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
86.6%
General procedure: 5-Methyl-3-aminoisoxazole (2 mmol) and aromatic aldehyde (2 mmol) were added to absolute ethanol (4~6 mL) with electromagnetic stirring for about 1 h, followed by adding p-nitroacetophenone (2 mmol) and concentrated HCl (0.1~0.2 mL) with continuous stirring. TLC monitored the reaction progress. Upon completion, the suspension was cooled overnight in a refrigerator (4C). The resulting solid was subsequently collected by filtration. The filter cake was washed successively with water (2x3 mL) and absolute ethanol (2x3 mL), dried to afford the corresponding crude product. The crude product was recrystallized in toluene or a mixed solvent of ethyl acetate and cyclohexane, dried in vacuum to give the pure product with 57.1% ~ 94.9% yields. All compounds were identified by 1H NMR, 13C NMR, ESI-MS and HR MS.
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