* 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] Bulletin de la Societe Chimique de France, 1959, p. 1398,1400
7
[ 100-06-1 ]
[ 27069-16-5 ]
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[1] Bioorganic and Medicinal Chemistry Letters, 2013, vol. 23, # 1, p. 273 - 280
[2] Bioorganic and Medicinal Chemistry, 2015, vol. 23, # 15, p. 4649 - 4659
[3] Bioorganic and Medicinal Chemistry Letters, 2016, vol. 26, # 17, p. 4372 - 4376
8
[ 100-06-1 ]
[ 105-58-8 ]
[ 2881-83-6 ]
Yield
Reaction Conditions
Operation in experiment
95%
Stage #1: With sodium hydride In tetrahydrofuranReflux Stage #2: With acetic acid In tetrahydrofuran
General procedure: To a stirred mixture of sodium hydride (3 mol equiv) washed with hexane (3 .x. 15 ml), and diethyl carbonate (4 mol equiv) in 50 mL of tetrahydrofuran (THF) was added drop wise appropriately substituted acetophenone (1 mol equiv) over 30 min. Reaction mixture was refluxed for 3-4 h till color changed to dark brown and monitored by TLC (10percent ethyl acetate/hexanes). The reaction mixture was cooled and acidified with 5 mL glacial acetic acid followed by addition 100 mL of ice cold dilute HCl solution. The aqueous layer was extracted with ethyl acetate (3 .x. 75 ml); combined organic phase was washed with saturated sodium bicarbonate, brine and water, dried over anhydrous Na2SO4 and evaporated in vacuo, yielded the desired product as viscous mass in excellent yield. The compounds were characterized on the basis of their 1H NMR and 13C NMR spectra as reported in the literature.
87%
With sodium hydride In toluene; mineral oil
General procedure: The substrate b-ketoesters 10 a–n were either purchased or synthesized following published procedures. Some benzoylacetates were commercially available. Ethyl 3-oxo-3-phenyl propanoate (10a) was purchased. The reaction of benzoylacetates 10 b–n was prepared as described in previous reports. 25–27 A solution of a substituted acetophenone 8 a–n (0.05 mol) dissolved in toluene (50 mL) was added dropwise to a solution containing diethyl carbonate (9) (0.10 mol) and sodium hydride (0.15 mol 60percent dispersion in mineral oil). The mixture was stirred at room temperature, and then refluxed for 30 min. The mixture was poured into ice water,acidified with glacial acetic acid, and extracted with EtOAc (3x100 mL). The EtOAc extract was then dried over anhydrous MgSO4. After removal of the solvent in vacuo, the crude products were purified by silica gel column chromatography eluting with dichloromethane to afford benzoylacetates 10 b–n. All synthetic compounds were in agreement with 1H NMR, 13C NMR, IR and mass spectroscopic data.
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[9] European Journal of Organic Chemistry, 2014, vol. 2014, # 25, p. 5591 - 5597
[10] Beilstein Journal of Organic Chemistry, 2017, vol. 13, p. 1950 - 1956
[11] Journal of the American Chemical Society, 1941, vol. 63, p. 2252
[12] Helvetica Chimica Acta, 1974, vol. 57, # 7, p. 2201 - 2209
[13] Journal of the American Chemical Society, 1961, vol. 83, p. 1951 - 1955
[14] Bulletin of the Chemical Society of Japan, 1988, vol. 61, # 6, p. 2277 - 2280
[15] Journal of Medicinal Chemistry, 1997, vol. 40, # 3, p. 322 - 330
[16] Journal of Medicinal Chemistry, 1997, vol. 40, # 20, p. 3217 - 3227
[17] Journal of Medicinal Chemistry, 1997, vol. 40, # 14, p. 2266 - 2275
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[19] Patent: WO2006/34094, 2006, A1, . Location in patent: Page/Page column 22-23
[20] Patent: WO2006/34234, 2006, A1, . Location in patent: Page/Page column 16
[21] Patent: US2008/132710, 2008, A1, . Location in patent: Page/Page column 8
[22] Chemistry - A European Journal, 2008, vol. 14, # 27, p. 8082 - 8085
[23] Patent: WO2006/34085, 2006, A1, . Location in patent: Page/Page column 13
[24] Patent: US6348618, 2002, B1, . Location in patent: Page column 10
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[26] Journal of the American Chemical Society, 2013, vol. 135, # 32, p. 11692 - 11695
[27] Tetrahedron Letters, 2014, vol. 55, # 48, p. 6534 - 6537
[28] Bioorganic and Medicinal Chemistry Letters, 2015, vol. 25, # 6, p. 1177 - 1181
[29] European Journal of Organic Chemistry, 2015, vol. 2015, # 17, p. 3656 - 3660
[30] Advanced Synthesis and Catalysis, 2015, vol. 357, # 14-15, p. 3076 - 3080
[31] Tetrahedron Letters, 2016, vol. 57, # 27-28, p. 3024 - 3028
[32] Organic Letters, 2016, vol. 18, # 20, p. 5408 - 5411
[33] Chemical Communications, 2017, vol. 53, # 58, p. 8136 - 8139
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[37] Russian Journal of General Chemistry, 2017, vol. 87, # 12, p. 2951 - 2960[38] Zh. Obshch. Khim., 2017, vol. 87, # 12, p. 2951 - 2960
[39] Organic and Biomolecular Chemistry, 2018, vol. 16, # 25, p. 4683 - 4687
[40] Organic Letters, 2018, vol. 20, # 20, p. 6349 - 6353
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[ 41233-93-6 ]
[ 100-06-1 ]
[ 105-58-8 ]
[ 2881-83-6 ]
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[1] Patent: US6124341, 2000, A,
[2] Patent: US2006/63825, 2006, A1, . Location in patent: Page/Page column 9
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[ 100-06-1 ]
[ 2881-83-6 ]
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[1] Journal of the American Chemical Society, 1948, vol. 70, p. 2755,2757
[2] Patent: US5342845, 1994, A,
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[ 623-53-0 ]
[ 100-06-1 ]
[ 2881-83-6 ]
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[1] Chemical Communications, 2011, vol. 47, # 39, p. 11143 - 11145
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[ 95-92-1 ]
[ 100-06-1 ]
[ 2881-83-6 ]
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[1] European Journal of Medicinal Chemistry, 2013, vol. 59, p. 176 - 182
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[ 33868-76-7 ]
[ 100-06-1 ]
[ 81874-58-0 ]
[ 2881-83-6 ]
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[1] Journal of Organic Chemistry, 1982, vol. 47, # 16, p. 3027 - 3038
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[1] Chemistry - An Asian Journal, 2016, vol. 11, # 3, p. 395 - 400
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[ 100-06-1 ]
[ 41068-36-4 ]
[ 157487-30-4 ]
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[1] Indian Journal of Chemistry - Section B Organic and Medicinal Chemistry, 2004, vol. 43, # 6, p. 1335 - 1338
17
[ 104-92-7 ]
[ 108-24-7 ]
[ 16740-73-1 ]
[ 100-06-1 ]
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[1] Comptes Rendus Hebdomadaires des Seances de l'Academie des Sciences, 1946, vol. 223, p. 159
18
[ 7446-70-0 ]
[ 104-92-7 ]
[ 108-24-7 ]
[ 16740-73-1 ]
[ 100-06-1 ]
Reference：
[1] Comptes Rendus Hebdomadaires des Seances de l'Academie des Sciences, 1946, vol. 223, p. 159
19
[ 100-06-1 ]
[ 35310-75-9 ]
Yield
Reaction Conditions
Operation in experiment
98%
With N-Bromosuccinimide; sulfuric acid In water at 60℃; for 5 h;
Ketone 7a (5.0 g, 33.3 mmol) and N-bromosuccinimide (NBS, 5.9 g, 33.3 mmol) were added to 100 mL water and heated to 60°C, followed by slow drop-wise addition of 40percent H2SO4 (66.7 mmol, 8.9 mL). The resulting mixture was continuously stirred for 5 h. When the mixture was cooled to room temperature, isolation was performed using AcOEt (60 mL × 3) extraction. The combined organic extracts were washed with saturated NaHCO3, dried over MgSO4 and evaporated to yield a crude product 7b (7.5 g, 98percent) as a white solid. Rf 0.85 (PE/AcOEt, 3:1). 1H NMR (400 MHz, DMSO–d6) δ: 3.09 (3H, s), 3.93 (3H, s), 3.95 (6H, s), 7.92 (1H, d, J = 8.9 Hz), 7.97 (1H, dd, J = 2.1 Hz, 8.9 Hz), 8.10 (2H, d, J = 2.1 Hz); LC–MS m/z: 230.9 [M+H]+.
97%
With N-Bromosuccinimide; iodine In acetonitrile for 12 h; Darkness
General procedure: To a reaction tube charged with NBS (1.5 equiv, 0.3 mmol), catalyst (10 molpercent, 0.02 mmol) and CH3CN (1.0 mL),was added para-chloroanisole 1a (0.2 mmol). After being stirred at room temperature for 12 h in dark, the reaction was quenched by saturated aq. solution of Na2S2O3 (2 mL). The resulting mixture was extracted by ethyl acetate (3 5 mL). The combined organic extracts were washed by brine (10 mL), dried over Na2SO4 and filtered through a pad of Celite. The filtrate was concentrated under reduced pressure and the residuewas purified by flash chromatography on a silica gel column with petroleum ether/dichloromethane (5:1) as the eluent to give 4.3.1. 2-Bromo-4-chloroanisole (2a)
96%
With iodine pentoxide; potassium bromide In water at 20℃; for 10 h;
General procedure: A mixture of arene (0.5 mmol), I2O5 (334 mg, 1.0 mmol), and KBr (148 mg, 1.25 mmol) was dissolved in 2mL of H2O. The reaction was complete after stirring for the indicated time at room temperature. The mixture was extracted by ethyl acetate and concentrated under reduced pressure, and the mixture was purified by flash column chromatography (silica gel) to afford the desired product.
88%
at 20℃; for 1.16667 h; Inert atmosphere
Bromine (0.54 mL, 10.5 mmol) in acetic acid (1.7 mL) was added dropwise to a mixture of 4-methoxyacetophenone (758 mg,5 mmol) and sodium acetate (1.28 g, 15.5 mmol) in acid acetic (10 mL) at room temperature over 10 min. The reaction mixture was stirred for 1 h at room temperature. H2O (30 mL) was added and the solid was filtered, washed with H2O and dried under high vacuum to afford 3-bromo-4-methoxyacetophenone 11b as a white solid in 88percent yield (1.01 g, 4.4 mmol).
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[1] Bioorganic and Medicinal Chemistry Letters, 2016, vol. 26, # 17, p. 4372 - 4376
[2] Tetrahedron, 2017, vol. 73, # 50, p. 7105 - 7114
[3] Synthetic Communications, 2014, vol. 44, # 2, p. 181 - 187
[4] Bioorganic and Medicinal Chemistry, 2015, vol. 23, # 13, p. 3618 - 3628
[5] Organic Letters, 2013, vol. 15, # 9, p. 2108 - 2111
[6] Tetrahedron Letters, 2006, vol. 47, # 49, p. 8693 - 8697
[7] Organic Letters, 2009, vol. 11, # 2, p. 365 - 368
[8] Tetrahedron Letters, 2006, vol. 47, # 27, p. 4707 - 4710
[9] New Journal of Chemistry, 2016, vol. 40, # 10, p. 8198 - 8201
[10] Huaxue Xuebao, 1959, vol. 25, p. 277,285[11] Chem.Abstr., 1960, p. 17306
[12] Chemische Berichte, 1953, vol. 86, p. 1556,1560
[13] Chemische Berichte, 1957, vol. 90, p. 1922,1926
[14] Journal of the American Chemical Society, 1984, vol. 106, # 5, p. 1361 - 1372
[15] Synlett, 2014, vol. 25, # 12, p. 1769 - 1775
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[1] Tetrahedron Letters, 2005, vol. 46, # 52, p. 8975 - 8979
[2] Bulletin of the Chemical Society of Japan, 2005, vol. 78, # 9, p. 1677 - 1684
22
[ 3319-15-1 ]
[ 104-92-7 ]
[ 35310-75-9 ]
[ 100-06-1 ]
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[1] Synlett, 2003, # 7, p. 951 - 954
23
[ 100-06-1 ]
[ 104-92-7 ]
[ 35310-75-9 ]
[ 21702-84-1 ]
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[1] Journal of Organic Chemistry, 2002, vol. 67, # 13, p. 4487 - 4493
24
[ 100-06-1 ]
[ 2657-25-2 ]
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[1] European Journal of Medicinal Chemistry, 2015, vol. 101, p. 627 - 639
25
[ 100-06-1 ]
[ 455-91-4 ]
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[1] Tetrahedron Letters, 1996, vol. 37, # 20, p. 3591 - 3594
[2] Chemical Communications, 2000, # 14, p. 1323 - 1324
[3] Molecules, 2009, vol. 14, # 7, p. 2394 - 2409
26
[ 100-06-1 ]
[ 6343-93-7 ]
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[1] Organic Preparations and Procedures International, 1995, vol. 27, # 5, p. 552 - 555
27
[ 616-38-6 ]
[ 100-06-1 ]
[ 22027-50-5 ]
Yield
Reaction Conditions
Operation in experiment
98%
With sodium hydride In toluene for 4 h; Inert atmosphere; Reflux
General procedure: To a dried three-necked flask equipped with a dropping funnel, a condenser, and a magnetic stirrer, dimethyl carbonate 5 (2 eq), NaH 60percent (2.8 eq) and dry toluene (2 M) were added. The mixture was heated to reflux under nitrogen. A solution of the corresponding aryl-methyl-ketone (4a–h) (1 eq) in dry toluene (2 M) was added dropwise over 1 h. The resulting reaction mixture was refluxed for 3 h, and then was cooled to 0 °C and glacial acetic acid was added dropwise until pH 4. The solid obtained was filtered and subsequently dissolved in hot water. The aqueous phase was extracted with EtOAc(×3). The combined organic layers were washed with brine, dried over sodium sulphate, and concentrated in vacuo to give the desired Aryl β-Keto ester, which was pure enough to be used for the next step without purification.
98%
With sodium hydride In toluene; mineral oil for 0.5 h; Reflux
General procedure: In a dry two neck flask equipped with a reflux condenser and rubber septum and a stir bar, NaH (60percent wt in mineral oil, 4.0 g, 100 mmol) was suspended in toluene (8 mL) and dimethylcarbonate (9.1 g, 100 mmol, 2.5 eq) was added. The mixture was heated to reflux and acetophenone (4.8 g, 40 mmol, 1.0 eq) in toluene (20 mL) was added dropwise. The reaction mixture was stir for 0.5 h when hydrogen evolution had ceased.The suspension was cooled to 0 °C, diluted with EtOAc (150 mL) and carefully quenched with MeOH (10 mL), followed by H2O, and then acidified to pH < 5 using 1N HCl. The organic layer is separated and then washed with H2O (200 mL) then brine (100 mL), and dried over MgSO4, and concentrated in vacuo. The resulting biphasic liquid was partitioned between MeCN (20 mL) and hexanes (10 mL) and then washed with hexanes (25 mL x 2) and concentrated in vacuo to give the β-ketoesters. Dicarbonyl compound (6mmol) was dissolved in MeOH (6 mL) and then cooled in a brine-ice bath. Then, 30percent KOH in MeOH (6 mL) solution was added dropwise an the mixture was allowed to stir for 2 minutes after which a solution of iodobenzene diacetate (6 mmol) was added dropwise and the resulting mixture was allowed to stir for 1 hr and then poured onto icewater (100 mL). The suspension is then extracted with CH2Cl2 (50 mL x 3). The combined extracts were dried over MgSO4, filtered through Buchner funnel, then concentrated in vacuo to approximately one third of the original volume. The ylide was slowly precipitated using Et2O and/or hexanes, and cooled to 0 °C and isolated by filtration.
87%
for 0.166667 h; Reflux
Step 1. Methyl 3-(4-methoxyphenyl)-3-oxopropanoate Into a 500-mL 3-necked round-bottom flask, was placed a solution of 1-(4-methoxyphenyl)ethanone (30 g, 200 mmol, 1.00 equiv) in dimethyl carbonate (50 mL). To the above was added NaH (13.6 g, 340 mmol, 1.70 equiv, 60percent) in several batches. The resulting solution was allowed to react, with stirring, for 10 min while the temperature was maintained at reflux. It was poured into 400 mL of ice-water to get a solution, then washed with ether (50 mL*2), acidified with AcOH, extracted with ethyl acetate (200 mL*3), and the ethyl acetate layers were washed with saturated NaHCO3 and dried over Na2SO4. The solution was concentrated to provide 37 g (87percent) of methyl 3-(4-methoxyphenyl)-3-oxopropanoate as yellow oil.
61%
With sodium hydride In toluene; mineral oil at 20 - 110℃; for 7 h; Inert atmosphere
General procedure: In a three-necked round bottomed flask equipped with a reflux condenser and a magnetic stirrer, NaH (4equiv, 60percent mineral oil dispersion), was placed under nitrogen and washed with toluene (3×10mL). Next the solution of dimethyl carbonate (3equiv) in toluene (50mL) was added. The appropriate derivative of acetophenone (10g) in toluene (50mL) was added dropwise over 1h to the resultant suspension, with stirring at rt. The reaction mixture was subsequently diluted with toluene (250mL) and stirred vigorously at 105–110°C for the time given in Table 1. The resulting mixture was cooled to rt, and glacial acetic acid (8mL) was added dropwise until a heavy, pasty solid appeared. This was treated with a solution of conc. HCl (30mL) in ice water (200mL). The separated aqueous solution was extracted with AcOEt (3×200mL). The organic layers were neutralized by extraction with saturated NaHCO3 (2×200mL) and dried over anhydrous Na2SO4. The volatiles were then removed under reduced pressure and the resultant crude oil was purified by vacuum distillation to give the appropriate β-keto ester as a keto-enol tautomer.
13.18 g
Stage #1: With sodium hydride In tetrahydrofuran for 2 h; Stage #2: With potassium hydride In tetrahydrofuran for 1.5 h;
To an NaH (10.4 g, used after washing with dry hexane) suspension(50 mL, THF), (MeO)2CO (15.9 g) and p-methoxyacetophenon(13 g) were added dropwise over 2 h. Next, KH (ca. 0.5 g) wasadded and the resulting mixture was stirred for 1.5 h and thenquenched with AcOH (1000 mL). Extraction, distillation(423 K/1 mmHg), and subsequent purification via column chromatographygave 2 (13.18 g) as a yellow oily product (1H NMR:(keto-form) d 7.91 (d, J = 8.9 Hz, 2H), 6.93 (d, J = 6.9 Hz, 2H), 3.94(s, 2H), 3.86 (s, 3H), 3.73 (s, 3H), (enol-form) d 7.72 (d, J = 6.0 Hz,2H), 6.9 (d, J = 6.9 Hz, 2H), 5.57 (s, 1H), 3.86 (s, 1H), 3.83 (s, 3H),3.73 (s, 3H)).
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[1] Chemistry - A European Journal, 2017, vol. 23, # 41, p. 9716 - 9720
[2] Chemistry - A European Journal, 2018, vol. 24, # 32, p. 8092 - 8097
[3] Molecules, 2015, vol. 20, # 9, p. 17275 - 17287
[4] Synthesis (Germany), 2016, vol. 48, # 5, p. 772 - 782
[5] Angewandte Chemie - International Edition, 2017, vol. 56, # 43, p. 13319 - 13323[6] Angew. Chem., 2017, vol. 129, p. 13504 - 13508,5
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[9] Synthesis, 2003, # 15, p. 2405 - 2409
[10] Patent: US2012/277224, 2012, A1, . Location in patent: Page/Page column 72
[11] Advanced Synthesis and Catalysis, 2003, vol. 345, # 1-2, p. 261 - 274
[12] Molecules, 2004, vol. 9, # 3, p. 135 - 157
[13] Chemical Communications (Cambridge, United Kingdom), 2018, vol. 54, # 82, p. 11602 - 11605
[14] Tetrahedron Asymmetry, 2013, vol. 24, # 15-16, p. 925 - 936
[15] Bioorganic and Medicinal Chemistry Letters, 2005, vol. 15, # 20, p. 4520 - 4525
[16] Journal of the American Chemical Society, 2007, vol. 129, # 37, p. 11583 - 11592
[17] Organic Letters, 2009, vol. 11, # 18, p. 4176 - 4179
[18] Patent: EP2168959, 2010, A1, . Location in patent: Page/Page column 159
[19] Patent: EP2168960, 2010, A1, . Location in patent: Page/Page column 109
[20] Patent: US6348618, 2002, B1, . Location in patent: Page column 10
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[23] Chemistry - A European Journal, 2008, vol. 14, # 32, p. 9864 - 9867
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[30] Journal of the American Chemical Society, 2014, vol. 136, # 46, p. 16120 - 16123
[31] Tetrahedron, 2014, vol. 70, # 44, p. 8405 - 8412
[32] Journal of Medicinal Chemistry, 2016, vol. 59, # 7, p. 3272 - 3302
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[34] Tetrahedron Asymmetry, 2016, vol. 27, # 14-15, p. 657 - 662
[35] Angewandte Chemie - International Edition, 2017, vol. 56, # 32, p. 9577 - 9581[36] Angew. Chem., 2017, vol. 129, # 32, p. 9705 - 9709,5
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28
[ 246140-20-5 ]
[ 100-06-1 ]
[ 22027-50-5 ]
Yield
Reaction Conditions
Operation in experiment
77%
With sodium hydride In tetrahydrofuranReflux
General procedure: Substrates 1g-j and 1l were prepared adaptedfrom a previously reported procedure with some modications: toa solution of ketone (20 mmol) in THF (80 mL) was added methyldicarbonate (60 mmol) and NaH (40 mmol, 60percent). The reactionmixture was reuxed until TLC indicated complete consumption ofthe ketone. After cooling, the reaction mixture was poured into ice-water (100 mL), acidied with aqueous HCl (3 M) to pH 2e3 andextracted with EA (100 mL 3). The combined organic layer wasdried over Na2SO4 and evaporated under reduced pressure. Thedesired pure product was obtained by silica gel chromatographyusing a mixture of EA/PE (v/v 1/9) as eluent.
Reference：
[1] Green Chemistry, 2011, vol. 13, # 2, p. 376 - 383
31
[ 100-06-1 ]
[ 6298-96-0 ]
[ 6298-96-0 ]
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[1] Angewandte Chemie - International Edition, 2003, vol. 42, # 44, p. 5472 - 5474
[2] Journal of the Chemical Society. Perkin Transactions 2, 2000, # 7, p. 1339 - 1347
[3] Chemical Communications, 2010, vol. 46, # 30, p. 5500 - 5502
[4] Journal of the American Chemical Society, 2018, vol. 140, # 6, p. 2024 - 2027
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[ 100-06-1 ]
[ 6298-96-0 ]
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[2] Tetrahedron, 1994, vol. 50, # 15, p. 4399 - 4428
[3] Advanced Synthesis and Catalysis, 2015, vol. 357, # 8, p. 1732 - 1740
33
[ 100-06-1 ]
[ 6298-96-0 ]
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[1] European Journal of Organic Chemistry, 2015, vol. 2015, # 24, p. 5393 - 5401
34
[ 70249-37-5 ]
[ 100-06-1 ]
[ 6298-96-0 ]
[ 99-06-9 ]
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[1] Chemical Communications, 2013, vol. 49, # 2, p. 161 - 163
35
[ 100-06-1 ]
[ 75172-66-6 ]
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[1] Advanced Synthesis and Catalysis, 2017, vol. 359, # 20, p. 3665 - 3673
36
[ 100-06-1 ]
[ 74457-86-6 ]
Reference：
[1] Patent: CN103922904, 2016, B,
37
[ 100-06-1 ]
[ 3883-94-1 ]
Yield
Reaction Conditions
Operation in experiment
62.1%
Stage #1: With N-Bromosuccinimide In ethanol at 40℃; for 3 h; Large scale Stage #2: With hexamethylenetetramine In ethanol at 25℃; for 3 h; Large scale Stage #3: With hydrogenchloride In ethanol at 25℃; for 12 h; Large scale
The starting material for this synthesis is 1-(4-methoxyphenyl)-ethanone: [0089] The first step is allylic bromination. Anhydrous ethanol (400 kg) and 1-(4-methoxyphenyl)ethanone (42 kg) were added to a 1000 L vessel and stirred at 25° C. Then N-bromosuccinimide (56 kg) was added potionwise. This mixture was stirred at 40° C. for 3 hours, after which the mixture was cooled to 25° C. Next, hexamethylenetetramine (38 kg) was added potionwise. This mixture was stirred at 25° C. for 3 hours and then filtered. Anhydrous ethanol (560 kg) was added to the precipitated solid in a 1000 L vessel, and the mixture was stirred at 25° C. Concentrated hydrogen chloride (HCl, 35 kg) was then added for acid hydrolysis, and stirring continued at 25° C. for 12 hours. After this time, the volume was concentrated to , and the temperature was reduced to 5° C. for crystallization. The product was filtered and dried. This product is intermediate 2-amino-1-(4-methoxyphenyl)ethanone hydrochloride (35 kg): The yield of 2-amino-1-(4-methoxyphenyl)ethanone hydrochloride, based on starting product 1-(4-methoxyphenyl)ethanone, was 62.1percent.
Reference：
[1] Patent: US2014/134283, 2014, A1, . Location in patent: Paragraph 0088-0089
[2] Journal of Pharmaceutical Sciences, 2014, vol. 103, # 9, p. 2797 - 2808
[3] Bioorganic and Medicinal Chemistry Letters, 2016, vol. 26, # 3, p. 849 - 853
[4] Journal of Medicinal Chemistry, 2017, vol. 60, # 22, p. 9275 - 9289
38
[ 100-06-1 ]
[ 82640-04-8 ]
Reference：
[1] Patent: WO2011/132194, 2011, A1,
39
[ 100-06-1 ]
[ 148990-17-4 ]
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[1] Chemical Biology and Drug Design, 2017, vol. 90, # 5, p. 936 - 942
40
[ 26537-19-9 ]
[ 100-06-1 ]
[ 70356-09-1 ]
Yield
Reaction Conditions
Operation in experiment
95%
With potassium methanolate In toluene at 110℃; for 2 h;
condensation with various bases In a reaction flask with a 30 ml toluene and the base were provided under a blanket of inert gas. 20 mmole 4-tert-Butyl benzoic acid methyl ester (TBBM) and 20 mmole p-methoxy acetophenone (pMAc) was added. The mixture was stirred at about 110°C/ 1 bar while alcohol and toluene was slowly distilled off (toluene was occasionally replenished to maintain 20 ml volume). After complete conversion of TBBM and pMAc the reaction mixture was cooled and acidified with 2M acetic acid. An aliquot was analyzed by HPLC for the chemical yield of 4-te/f-Butyl-4'-methoxydibenzoylmethane. The results are given in table 1. Table 1 : ResultsAs can be seen from the results in table 1 the use of a potassium alcoholate results in higher yields and shorter reaction times compared to the use of other alkali or earth alkali alcoholates.Furthermore, the potassium salt did not crystallize and remained homogeneously dissolved in toluene whereas the sodium, magnesium and the lithium salt formed a crystalline inhomogeneous mixture
78%
With sodium amide In 5,5-dimethyl-1,3-cyclohexadiene at 95 - 100℃; for 5 h;
5), the condensation reaction with p-tert-butyl benzoate and p-methoxy acetophenone as raw materials,With sodium amide as catalyst,Xylene as solvent,The molar ratio of p-methoxyacetophenone to methyl p-tert-butylbenzoate was 1: 1.4,The reaction temperature was 100 ° C,Reaction time is 5h,Eventually get Avobenzone.The reaction temperature was 95 ° C,The molar ratio of p-methoxyacetophenone to methyl p-tert-butylbenzoate was 1: 1.4.The final yield of avobenzone was 78percentThe purity is 99percent.
Reference：
[1] Patent: WO2012/84770, 2012, A1, . Location in patent: Page/Page column 8-9
[2] Patent: CN104876814, 2017, B, . Location in patent: Paragraph 0021; 0028; 0035
[3] Research on Chemical Intermediates, 2013, vol. 39, # 6, p. 2311 - 2320
[4] Journal of the American Chemical Society, 2010, vol. 132, # 7, p. 2160 - 2162
41
[ 92279-83-9 ]
[ 100-06-1 ]
[ 70356-09-1 ]
Yield
Reaction Conditions
Operation in experiment
91%
With potassium methanolate In toluene for 1.75 h; Heating
In a reaction flask with a stirrer was provided at ambient temperature under a blanket of inert gas: 16 ml toluene, 24 mmole base and 20.4 mmole 4-tert. butyl benzoic acid methylester (TBBM), respectively 20.4 mmole 4-tert. butyl benzoic acid fe/f.-butyl ester (TBBT) as indicated in table 3. The resulting reaction mixture was heated to boiling. Afterwards a 3 molar solution of p-methoxy acetophenone (pMAc) in toluene was added within 1 h under slow distillation of a mixture of methanol and/ or te/t-butanol and toluene at 1 bar. The mixture was stirred for x additional hours as indicated in table 3. The reaction mixture was occasionally replenished to 20 ml volume by addition of toluene. The reaction mixture was cooled and acidified with 2M acetic acid. An aliquot was analyzed by HPLC for the chemical yield of 4-te/f-butyl-4'-methoxydibenzoylmethane. The results are presented in table 3.Table 3Base Ester Appearance of reaction mixture time [h] Yield [molepercent]KOMe TBBT homogeneous 1.75 91KOtBu TBBT homogeneous 2 85KOtBu TBBM homogeneous 3 92NaOtBu TBBT inhomogeneous 1.75 63NaOMe TBBT inhomogeneous 4 80NaOtBu TBBM inhomogeneous 3 85TBBT = 4-(1 ,1-dime1 hylethyl)-benzoic acid te/f-butyl est er TBBM = 4-(1 , 1-dimethylethyl)-benzoic acid methyl esterAs can be retrieved from table 3 highest yields of butyl methoxydibenzoylmethane were achieved with either the te/f-butylester TBBT and potassium methylate or the methylester TBBM with potassium te/f-butylate, whereas the combination of the te/f-butylester TBBT with potassium te/f-butylate resulted in lower yields.Furthermore, as can be retrieved from table 3, the use of the respective sodium alcoholate resulted in significant lower yields compared to the use of the respective potassium alcoholate. Furthermore, the use of sodium alcoholate resulted in inhomogeneous badly stirrable reaction mixtures.
Reference：
[1] Patent: EP2308838, 2011, A1,
[2] Organic and Biomolecular Chemistry, 2015, vol. 13, # 11, p. 3416 - 3431
[3] Organic and Biomolecular Chemistry, 2015, vol. 13, # 40, p. 10162 - 10178
[4] Chemical Biology and Drug Design, 2017, vol. 89, # 4, p. 634 - 638
43
[ 100-06-1 ]
[ 925006-96-8 ]
Reference：
[1] European Journal of Pharmaceutical Sciences, 2011, vol. 42, # 3, p. 180 - 191
[2] European Journal of Medicinal Chemistry, 2013, vol. 64, p. 42 - 53
[3] Letters in Drug Design and Discovery, 2018, vol. 15, # 6, p. 576 - 582
[4] European Journal of Medicinal Chemistry, 2018, vol. 159, p. 90 - 103
[5] Journal of Enzyme Inhibition and Medicinal Chemistry, 2018, vol. 33, # 1, p. 1352 - 1361
With N-Bromosuccinimide; sulfuric acid; In water; at 60℃; for 5h;
Ketone 7a (5.0 g, 33.3 mmol) and N-bromosuccinimide (NBS, 5.9 g, 33.3 mmol) were added to 100 mL water and heated to 60C, followed by slow drop-wise addition of 40% H2SO4 (66.7 mmol, 8.9 mL). The resulting mixture was continuously stirred for 5 h. When the mixture was cooled to room temperature, isolation was performed using AcOEt (60 mL × 3) extraction. The combined organic extracts were washed with saturated NaHCO3, dried over MgSO4 and evaporated to yield a crude product 7b (7.5 g, 98%) as a white solid. Rf 0.85 (PE/AcOEt, 3:1). 1H NMR (400 MHz, DMSO-d6) delta: 3.09 (3H, s), 3.93 (3H, s), 3.95 (6H, s), 7.92 (1H, d, J = 8.9 Hz), 7.97 (1H, dd, J = 2.1 Hz, 8.9 Hz), 8.10 (2H, d, J = 2.1 Hz); LC-MS m/z: 230.9 [M+H]+.
97%
With N-Bromosuccinimide; iodine; In acetonitrile; for 12h;Darkness;
General procedure: To a reaction tube charged with NBS (1.5 equiv, 0.3 mmol), catalyst (10 mol%, 0.02 mmol) and CH3CN (1.0 mL),was added para-chloroanisole 1a (0.2 mmol). After being stirred at room temperature for 12 h in dark, the reaction was quenched by saturated aq. solution of Na2S2O3 (2 mL). The resulting mixture was extracted by ethyl acetate (3 5 mL). The combined organic extracts were washed by brine (10 mL), dried over Na2SO4 and filtered through a pad of Celite. The filtrate was concentrated under reduced pressure and the residuewas purified by flash chromatography on a silica gel column with petroleum ether/dichloromethane (5:1) as the eluent to give 4.3.1. 2-Bromo-4-chloroanisole (2a)
96%
With iodine pentoxide; potassium bromide; In water; at 20℃; for 10h;
General procedure: A mixture of arene (0.5 mmol), I2O5 (334 mg, 1.0 mmol), and KBr (148 mg, 1.25 mmol) was dissolved in 2mL of H2O. The reaction was complete after stirring for the indicated time at room temperature. The mixture was extracted by ethyl acetate and concentrated under reduced pressure, and the mixture was purified by flash column chromatography (silica gel) to afford the desired product.
88%
With bromine; sodium acetate; acetic acid; at 20℃; for 1.16667h;Inert atmosphere;
Bromine (0.54 mL, 10.5 mmol) in acetic acid (1.7 mL) was added dropwise to a mixture of 4-methoxyacetophenone (758 mg,5 mmol) and sodium acetate (1.28 g, 15.5 mmol) in acid acetic (10 mL) at room temperature over 10 min. The reaction mixture was stirred for 1 h at room temperature. H2O (30 mL) was added and the solid was filtered, washed with H2O and dried under high vacuum to afford 3-bromo-4-methoxyacetophenone 11b as a white solid in 88% yield (1.01 g, 4.4 mmol).
86%
40.05 g (0.24 mol) of potassium bromate and 100 ml of water were placed in a 500 ml four-necked flask, and a mixed solution of 30.05 g (0.2 mol) of p-methoxyacetophenone and 90 g of methanol was placed in a 500 ml four-necked flask, and stirred. 312 g of a 20% by mass sodium hydrogen sulfite solution was added dropwise.The dropping temperature was controlled not to exceed 50 C, the dropping time was about 3 hours, and the reaction was kept for 2 hours after the completion of the dropwise addition.The mixture was cooled to room temperature, suction filtered, washed with water, and then recrystallized from ethanol to give 39.4 g of light gray solid, yield 86%, melting point (m.p.) = 84-86 C.
45%
With N-Bromosuccinimide; sulfuric acid; In water; at 60℃; for 5h;Inert atmosphere;
l-(4-methoxyphenyl)ethan-l-one (0.98 g, 6.5 mmol) and NBS (1.16 g, 6.5 mmol) were added to 20 mL of water. The mixture was stirred at 60 C and 96 % H2SO4 (0.7 mL, 13 mmol) was added dropwise. The resulting mixture was stirred at 60 C for 5 h, then cooled to 25 C, and extracted with EtOAc (3 x 15 ml). The combined organic extracts were washed with a saturated aqueous solution of Nal ICO-, (50 mL), dried over MgSCb, filtered, and the solvent was evaporated in vacuo. The product (670 mg, 45 %) was obtained as a white solid. (0112) NMR (500 MHz, CDCl3) d (ppm) 8.18 (d, / = 2.2 Hz, 1H), 7.93 (dd, / = 8.6, 2.2 Hz, 1H), 6.95 (d, J = 8.6 Hz, 1H), 3.98 (s, 3H), 2.57 (s, 3H); (0113) 13C NMR (126 MHz, CDCl3) d (ppm) 195.8, 159.8, 134.1, 131.6, 129.7, 112.1, 111.3, 56.7, 26.5; (0114) HRMS calcd for C9Hi0BrO2 [M+H]+ 228.9859, found 228.9858.
With N-Bromosuccinimide; chloro-trimethyl-silane; In acetonitrile; at 20℃; for 1h;
General procedure: To a solution of 4-bromoanisole (200.8 mg, 1.09 mmol, 1.0 equiv) in acetonitrile (2 mL) was added N-chlorosuccinimide(NCS) (158.3 mg, 1.19 mmol, 1.1 equiv) at rt to give a slightly cloudy mixture. Chlorotrimethylsilane (TMSCl) (14 muL, 0.11 mmol, 0.1 equiv) was then added drop-wise to the reaction mixture. Within a few minutes, the reaction mixture became clear pale yellow solution. The mixture continued to stir at rt for 1 h and was diluted with hexane. The biphasic mixture was concentrated on a rotary evaporator to a crude white solid-oil mixture. This mixture was taken up in hexane and filtered through a short plug of SiO2 and eluted with 5-10% EtOAc-hexane solution. The clear filtrate was concentrated to obtain a mixture of 4-bromo-2-chloro-1-methoxybenzene (2a-Cl) and 2,4-dichloro-1-methoxybenzene (2a-diCl) 237.0 mg (88% of 2a-Cl and 11% of 2a-diCl,based on NMR ratio 2a-Cl: 2a-diCl = 7.1: 1.0; as a pale yellow solid).
With tert.-butylhydroperoxide; 2.9-dimethyl-1,10-phenanthroline; copper(II) choride dihydrate; In water; at 20℃; for 7h;
General procedure: A stock solution of CuCl2·2H2O in water (0.0171 g/mL) was prepared (by dissolving 0.171 g in 10 mL H2O). To a Teflon screw cap glass tube, catalyst A (100 muL of a stock solution, 0.01 mmol of CuCl2, 2.1mg, 0.01 mmol of neocuproine) was added. Then 0.7 mL of H2O, 0.2 mmol of arylalkanes, and 70 % aq tert-butyl hydroperoxide (200 muL, 1.4 mmol) were added in each case. The mixture was stirred vigorously at room temperature till to its reaction time specified in the Tables 2 and 3. The reaction mixture was then diluted with ethyl acetate and the products dissolved in ethyl acetate layer were analyzed by GC using internal standard 1,4-di-tert-butylbenzene (19.4 mg, 0.1 mol). For product separation, the aqueous phase was extracted with ethyl acetate (3×10 mL). The combined extracts were dried over anhydrous MgSO4 and filtered. The filtrate was concentrated and product isolation was carried out by TLC. The pure products of benzophenone, 9-fluorenone (Table 2, entries 2 and 3) and 4-methoxyacetophenone (Table 3 entry 2) were obtained from drying their ethyl acetate extract without chromatographic workup. Filtration of the reaction mixture afforded pure 9-xanthenone (Table 2, entry 4).
83%
With tert.-butylnitrite; N-hydroxyphthalimide; In acetonitrile; at 80℃; for 24h;Schlenk technique;
into a 25mL Schlenk reaction tube added NHPI 0.5equivalent, dried in vacuum for 15 minutes, put on an oxygen sphere, under the oxygen atmosphere followed by adding acetonitrile 1mL, tert-butyl nitrite 1.0 equiv., P-ethyl anisole 0.5mmol, on the reaction tube add Poly tetra-fluoroethylene plug into the oil bath after the pot, and carry on reaction at 80 C for 24 h. After completion of the reaction, the solvent acetonitrile has been removed by concentration under reduced pressure, column chromatography, the eluent is petroleum ether / ethyl acetate (nu: nu = 20: 1), and then obtained p-methoxyacetophenone. Yield 83%, light yellow solid;
78%
With aluminum(III) nitrate nonahydrate; In acetonitrile; at 0 - 23℃;
General procedure: In a 25 ml dry round-bottom flask was suspended polymeric PhIO (0.25 equivalent) indry acetonitrile at 23C. Then, Al(NO 3 ) 3 (0.35 equivalent) was added and stirred for10 min, afterward, it was cooled to 0C. The benzylic aryl derivative (1 equivalent) wasincorporated in one portion. The reaction was warmed to 23C for a period of 2-4 huntil the starting material was fully consumed judging its advance by TLC. The reactionmixture was quenched by the addition of NH 4 Cl saturated solution (25 mL) and thenextracted with EtOAc (3 10 mL). The organic extracts were collected, dried overanhydrous sodium sulfate, filtered, and concentrated in vacuo to remove the solventand yield the crude of the reaction. The product was purified by flash column chroma-tography on silica gel (100-200 mesh) with EtOAc/hexane system.
72%
With pyridine; dipotassium peroxodisulfate; oxygen; In acetonitrile; at 80℃; under 760.051 Torr; for 16h;Green chemistry;
General procedure: Ethylbenzene (3a) (0.0531 g, 0.5 mmol), K2S2O8 (0.2703 g, 1.0 mmol), pyridine (0.0158 g, 0.2 mmol) and CH3CN (1.0 mL) were added to an oven-dried pressure vessel with a magnetic stir bar. Then the pressure vessel was filled with dioxygen and the reaction mixture was stirred at 80 C for 16 hours (oil bath). After the completion of the reaction, the solvent was evaporated and the reaction mixture was purified with column chromatography (eluenet: ethyl acetate/PE = 1/10) to give acetophenone (4a) (0.0535 g yield 89%).
61%
With [bis(acetoxy)iodo]benzene; acetic acid; trifluoroacetic acid; In tetrahydrofuran; at 20℃; for 24h;
General procedure: To a solvent of (bisacetoxyliodo)benzene (DAIB) (4.75g, 14.75mmol) in dry THF (20-30mL) was added trifluoroacetic acid (1.12g, 9.83mmol) and acetic acid (0.29g, 4.92mmol). The mixture stirred for 30 min, after which the compound added for benzylic C-H oxidation (2.46mmol) and further reacted for 24h. The progress of the chemical reaction was monitored using thin-layer chromatography with precoated silica gel 60 (0.25mm thickness) plates. The reaction was quenched with 1mL of sat. NaHCO3 (aq), and the solvent removed in vacuo on a rotatory evaporator. The residue was extracted with ethyl acetate (30mL×2) and water (20mL). The combined organic extracts were washed with brine, dried over anhydrous MgSO4, filtered, and concentrated in vacuo.
53%
With tert.-butylhydroperoxide; copper(l) chloride; In decane; tert-butyl alcohol; at 50℃; for 12h;
General procedure: To a test tube charged with CuCl (2.0 mg, 0.02 mmol) andisochroman (1a; 251 muL, 2.0 mmol) in t-BuOH (20 mL) wasadded TBHP (5.0-6.0 M in decane, 10.9 muL, 0.6 mmol) and themixture was stirred and heated at 50 C for 12 h under open air.After cooling to room temperature, the reaction was quenchedwith 25% aqueous ammonia solution and water then themixture was extracted with EtOAc. The separated organic layerwas dried over Na2SO4 and products were concentrated after filtration.The residue was purified by silica gel column chromatography(EtOAc/hexane, 1:10) to give isochromanone (2a) as acolorless oil in 83% yield.
With calcined praseodymium incorporated AlPO-5 molecular sieves ((Al+P)/Pr = 25); air; In neat liquid; at 120℃; for 6h;Green chemistry;
General procedure: PrAlPO-5 (200 mg) and ethylbenzene (50 mmol) were taken in a two necked round bottom flask fitted with acondenser and a magnetic pellet for stirring. To this heterogeneous reaction mixture, air was purged through balloon for 6 h. After the completion of reaction, the reaction mixture was filtered and washed the catalyst with ether for 5 to 6 times. The filtrate was poured into ice cold waterand extracted with ether. The ether layer and washings were combined and dried over anhydrous sodium sulphate.The ether layer was evaporated to obtain the product. The products were analyzed by gas chromatograph (ShimadzouGC-17A model) and also identified by gas chromatograph coupled with mass spectrometer (Perkin Elmer Clarus 500)using helium as the carrier gas at a flow rate of 1 ml min-1.
With pyridine; tert.-butylhydroperoxide; In acetonitrile; at 80℃; for 24h;
General procedure: A mixture of 4,4-diuorodiphenylmethane (178.4 L,1.0 mmol) and P4VPDVB2.5-40%-Fe(III) catalyst (2.0 mol%), pyridine (8.0 L,0.1 mmol), TBHP (5.0-6.0 M in decane, 545.0 L, 3.0 mmol) and 1.0 mL acetonitrile was dissolved in a 25 mL single-necked flask fitted with a reflux condenser. The mixture was heated at 80C for 24 h under air atmosphere in an oil bath. Then the mixture was cooled to 25C and centrifuged to get a catalyst and supernatant solution. Then the solution was analyzed by Agilent 7890/5975C-GC/MSD using nitrobenzene as an internal standard. A calibration curve for each reactant and product has been built, which is included in the ESI?. The in situ 1H NMR monitoring of the reaction conversion and yield was performed in the DMSO-d6 solvent, the crude sample of entry 11 in Table 3 was filtered for direct 1H NMR analysis (see ESI?). Furthermore, the products of entries 1 and 7 in Table 2 were isolated through column chromatography and the isolated yields were provided.
75%Chromat.
With tert.-butylhydroperoxide; C66H60Fe2N12O4(4+)*4BF4(1-)*4H2O; In water; acetonitrile; at 20℃; for 6h;
A Schlenk tube was charged with the substrate (0.3 mmol) andthe catalyst (4.5 lmol) dissolved in ACN (0.5 mL). The oxidanttBuOOH (0.32 mL, 70 wt% in H2O, 2.4 mmol) was slowly addedwithin 30 min, and then solution was shaken for 6 h at room temperature.0.2 mL of the solution were dissolved in 1 mL of DCM andthe yield was determined by GC
With tert.-butylhydroperoxide; In acetonitrile; at 80℃; for 24h;Green chemistry;
General procedure: In a typical procedure, to a mixture of catalyst (0.5 mmol), acetonitrile (10 mL) and alkyl aromatics (5 mmol) were added tert-butyl hydroperoxide (15 mmol) in turn. Samples were withdrawn periodically. After required hours, the reaction mixture was cooled to room temperature.
General procedure: A ketone compound, paraformaldehyde and suitable amine were taken in 1:1.2:1 mol ratios and heated in 10 ml of glacial acetic acid at 120 C for several times. The reactions were monitored by TLC using CHCl3: MeOH (9:1 or 8:2) as a solvent system. Compounds were purified by crystallisation. Chemical structures of the compounds were confirmed by 1H NMR (See Supplementary File) and their reported melting points. Amine part was changed as morpholine in Fig. ((1) Series A (1-9)) and <strong>[6091-44-7]piperidine</strong> in Series B (10-18). Physical data of the compounds obtained by the conventional heating method are reported in Table 1 (See Supplementary File).
51%
With hydrogenchloride; In ethanol; water;Reflux;
General procedure: Synthesis Procedure A. Compounds were synthesized as described before [27]. A suspension of substrate (1 mmol), amine hydrochloride (1.1 mmol), formalin (1.1 mmol) and 2 gtt concd. hydrochloric acid in ethanol was refluxed (Scheme 2). The reaction mixture was monitored with TLC. Removal of the solvent in vacuum produced the crude residue, which was recrystallized from appropriate solvents to yield the desired Mannich bases.
In 100 mL round-bottom flask fitted with magnetic stirrer were placed the NaH (1.62 g of 60% suspension in mineral oil, 40 mmol) and the solution of t<strong>[24059-83-4]3-methoxypyridine-2-carboxylic acid methyl ester</strong> (3.5 g, 20 mmol) in anhydrous DMF (20 mL). The mixture was stirred for 15 min at it under N2, then the solution of 4-methoxyacetophenone (3.3 g, 22 mmol) was added via syringe. The reaction mixture was stirred overnight at rt, then 10% aqueous solution of NaHSO4 was used to adjust pH to 7. The organic layer was separated and aqueous layer was extracted with EtOAc. The combined organic extracts were dried over Na2SO4 and concentrated to give the crude product. The crude product was purified by column chromatography using 30% EtOAc in hexane to give 4.68 g of 1-(4-methoxyphenyl)-3-(3-methoxypyridin-2-yl) propane-1,3-dione (80%).
With potassium methanolate; In toluene; at 110℃; under 750.075 Torr; for 2h;Product distribution / selectivity;
condensation with various bases In a reaction flask with a 30 ml toluene and the base were provided under a blanket of inert gas. 20 mmole 4-tert-Butyl benzoic acid methyl ester (TBBM) and 20 mmole p-methoxy acetophenone (pMAc) was added. The mixture was stirred at about 110C/ 1 bar while alcohol and toluene was slowly distilled off (toluene was occasionally replenished to maintain 20 ml volume). After complete conversion of TBBM and pMAc the reaction mixture was cooled and acidified with 2M acetic acid. An aliquot was analyzed by HPLC for the chemical yield of 4-te/f-Butyl-4'-methoxydibenzoylmethane. The results are given in table 1. Table 1 : ResultsAs can be seen from the results in table 1 the use of a potassium alcoholate results in higher yields and shorter reaction times compared to the use of other alkali or earth alkali alcoholates.Furthermore, the potassium salt did not crystallize and remained homogeneously dissolved in toluene whereas the sodium, magnesium and the lithium salt formed a crystalline inhomogeneous mixture
92.8%
With potassium methanolate; sodium methylate; In methanol; toluene; at 105 - 108℃; for 3.5h;
In a reaction vessel with a rectification column (stacked theta-ring stainless steel filler, theoretical plate number 20), 800 g of toluene, 12 g of sodium methoxide, 80 g of methyl p-tert-butylbenzoate were added, and methanol was distilled off while heating, to the kettle temperature. Up to 105 ~ 108 C; Start to add 60g of a mixed solution of p-methoxyacetophenone and 80g of toluene, and simultaneously distill off the by-product methanol from the top of the rectification column to maintain the kettle temperature at 105-108 C. The dropping time is controlled. 1.5h, after adding 0.5h, add 6g of 32% liquid potassium methoxide solution. After the completion of the dropwise addition, 12 g of sodium methoxide was added again, and the reaction was kept for 2 hours. During the heat preservation, the methanol produced by the reaction was continuously distilled from the top of the distillation column to maintain the temperature of the kettle at 105 to 108 C. After completion of the reaction, 120 g of a 10% by weight aqueous solution of dilute sulfuric acid was added, and the mixture was stirred and washed, and the aqueous layer was separated. The organic layer was washed three times with 300 g of water. Distillation of the solvent toluene was carried out by distillation, 300 g of methanol was added to the bottom, and the mixture was filtered, and the cake was recrystallized to obtain a white needle-like crystal avobenzone. The purity of the avobenzone GC prepared by the above method (area normalization method) was 98.7461%, the weight content was 99.4%, and the yield was 92.8%
78%
With sodium amide; In 5,5-dimethyl-1,3-cyclohexadiene; at 95 - 100℃; for 5h;
5), the condensation reaction with p-tert-butyl benzoate and p-methoxy acetophenone as raw materials,With sodium amide as catalyst,Xylene as solvent,The molar ratio of p-methoxyacetophenone to methyl p-tert-butylbenzoate was 1: 1.4,The reaction temperature was 100 C,Reaction time is 5h,Eventually get Avobenzone.The reaction temperature was 95 C,The molar ratio of p-methoxyacetophenone to methyl p-tert-butylbenzoate was 1: 1.4.The final yield of avobenzone was 78%The purity is 99%.
With potassium hydroxide; In ethanol; water; for 24h;
The commercially available 4-methoxyacetophenone and <strong>[56961-75-2]2,3,5-trichlorobenzaldehyde</strong> were purchased from Sigma Aldrich Chemicals Pvt. Ltd., Bangalore. (E)-1-(4-methoxyphenyl)-3-(2,3,5-trichlorophenyl)prop-2-en-1-one [MPTCPP] was synthesized by adopting Claisen-Schmidt condensation reaction method [20]. Here, 0.01 mol solution of 4-methoxyacetophenone was mixed with 0.01 mol of <strong>[56961-75-2]2,3,5-trichlorobenzaldehyde</strong> in ethanol (20 ml) and the mixture was treated with an aqueous solution of potassium hydroxide (2 ml, 30%). This mixture was stirred well and kept aside for 24 h. The resulting solid mass was collected by filtration and dried. The obtained compound was purified three to four times by re-crystallizing in ethanol. The molecular formula of MPTCPP compound is C16H11Cl3O2 and its molecular weight is 341.60. In order to confirm the newly synthesized compound the 1H NMR spectra were recorded on a Bruker AV3-400 FT NMR spectrometer operating at 400 MHz.
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 potassium methanolate; In toluene; under 750.075 Torr; for 1.75h;Heating;Product distribution / selectivity;
In a reaction flask with a stirrer was provided at ambient temperature under a blanket of inert gas: 16 ml toluene, 24 mmole base and 20.4 mmole 4-tert. butyl benzoic acid methylester (TBBM), respectively 20.4 mmole 4-tert. butyl benzoic acid fe/f.-butyl ester (TBBT) as indicated in table 3. The resulting reaction mixture was heated to boiling. Afterwards a 3 molar solution of p-methoxy acetophenone (pMAc) in toluene was added within 1 h under slow distillation of a mixture of methanol and/ or te/t-butanol and toluene at 1 bar. The mixture was stirred for x additional hours as indicated in table 3. The reaction mixture was occasionally replenished to 20 ml volume by addition of toluene. The reaction mixture was cooled and acidified with 2M acetic acid. An aliquot was analyzed by HPLC for the chemical yield of 4-te/f-butyl-4'-methoxydibenzoylmethane. The results are presented in table 3.Table 3Base Ester Appearance of reaction mixture time [h] Yield [mole%]KOMe TBBT homogeneous 1.75 91KOtBu TBBT homogeneous 2 85KOtBu TBBM homogeneous 3 92NaOtBu TBBT inhomogeneous 1.75 63NaOMe TBBT inhomogeneous 4 80NaOtBu TBBM inhomogeneous 3 85TBBT = 4-(1 ,1-dime1 hylethyl)-benzoic acid te/f-butyl est er TBBM = 4-(1 , 1-dimethylethyl)-benzoic acid methyl esterAs can be retrieved from table 3 highest yields of butyl methoxydibenzoylmethane were achieved with either the te/f-butylester TBBT and potassium methylate or the methylester TBBM with potassium te/f-butylate, whereas the combination of the te/f-butylester TBBT with potassium te/f-butylate resulted in lower yields.Furthermore, as can be retrieved from table 3, the use of the respective sodium alcoholate resulted in significant lower yields compared to the use of the respective potassium alcoholate. Furthermore, the use of sodium alcoholate resulted in inhomogeneous badly stirrable reaction mixtures.
With sodium hydride; In tetrahydrofuran; dimethyl sulfoxide; at 95.0℃; for 6.0h;
To a solution of <strong>[71777-70-3]ethyl 4-ethoxypicolinate</strong> (3.44 g, 17.43 mmol) and 4-methoxy acetophenone (2.62 g, 17.43 mmol) in THF (100 mL) and DMSO (50 mL) was added NaH (1.4 g, 34.80 mmol). The resulting mixture was stirred at 95 C. for 6 h. The reaction mixture was cooled to rt and quenched with water (100 mL). The mixture was extract with EtOAc (3×150 mL) and concentration to a yellow solid. The solid was washed with hexanes to afford the diketone (3.6 g, 69%).
ethyl 8-methoxy-2,5-dimethylpyrazolo[1,5-a]quinoline-3-carboxylate[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
55%
With caesium carbonate; In N,N-dimethyl-formamide; at 120℃; for 16h;
4.2.1 Ethyl 2,5-dimethylpyrazolo[1,5-a]quinoline-3-carboxylate (5a) Condition A: A mixture of 2-fluoroacetophenone 3a (138 mg, 1.00 mmol), 1H-pyrazole 2a (202 mg, 1.20 mmol) and K2CO3 (420 mg, 3.00 mmol) in DMF (5.0 mL) was stirred at 120 C for 16 h. After monitoring the end of the reaction on TLC, the mixture was cooled to room temperature and diluted with water. The resulting mixture was extracted with ethyl acetate twice. The combined organic layers were washed with water twice, dried over MgSO4 and the solvent was removed in vacuo to afford a residue. The residue was purified by flash column chromatography (hexane:EtOAc=5:1) on silica gel to afford 5a (92.0 mg, 34% yield). Condition B: The reaction was carried out with Cs2CO3 instead of K2CO3 under the same conditions as that of Condition A to afford 5a (210 mg, 78% yield).
4-(2-(4-methoxyphenyl)-2-oxoethyl)-3-phenyl-1,2,4-oxadiazol-5(4H)-one[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
93%
To a solution of 4?-methoxyacetophenone (300 mg, 2.00 mmol) in CH2Cl2 (4 mL) was added bromine (0.102 mL, 2.00 mmol) dropwise at room temperature, and the mixture wasstirred at this temperature for 8 h. Then <strong>[1456-22-0]3-phenyl-1,2,4-oxadiazol-5(4H)-one</strong> (584 mg, 3.60mmol) and K2CO3 (498 mg, 3.60 mmol), acetone (5 mL) was added to the reaction mixture.After stirring at 50 C for 12 h, the reaction mixture was quenched with H2O and extractedwith EtOAc three times. The combined organic layer was dried over MgSO4, filtered, andconcentrated under vacuum. The residue was subjected to column chromatography on silicagel (CH2Cl2/EtOAc = 4/1) to give 578 mg of compound 3j as a pale yellow oil (1.86 mmol,93% yield). 1H NMR (CDCl3): delta 3.87 (s, 3H), 5.02 (s, 2H), 6.94 (d, J = 8.8 Hz, 2H), 7.46 (t,J = 7.3 Hz, 2H), 7.49-7.58 (m, 3H), 7.87 (d, J = 8.8 Hz, 2H). 13C NMR (CDCl3): delta 47.7,55.1, 113.8, 122.6, 125.9, 127.6, 128.9, 30.0, 131.6, 158.9, 159.0, 164.2, 188.3. HRMS(FAB) calcd for C17H15N2O4 (M+H)+ 311.1032, found 311.1035.
(E)-1-(4-methoxyphenyl)-3-(4-bromo-2-chlorophenyl)prop-2-en-1-one[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
86%
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.
(Z)-1-(1,5-dimethyl-1H-pyrazol-3-yl)-3-hydroxy-3-(4-methoxyphenyl)prop-2-en-1-one[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
31%
General procedure: To a suspension of sodium (15.21 mmol) in 20 mL of toluene, the appropriate heterocyclic carboxylate (12.01 mmol) in 25 mL of toluene was slowly added; then acetone or aryl methyl ketones (12.01 mmol) in 10 mL of toluene was added at 0 C. The resulting mixture was stirred at room temperature for two days. The precipitate formed was filtered, washed with toluene, dissolved in water, and neutralized with acetic acid to pH 5. After extraction with CH2Cl2, the organic layer was dried over anhydrous sodium sulfate and concentrated in vacuo. The obtained residue was filtered through silica using CH2Cl2/MeOH as eluant to give the desired products 1-10 as a white solid in 35%-48% yield. beta-keto-enol forms were recrystallized from methanol (95%) to obtain target compounds 1-10 which were confirmed by FT-IR, 1H-NMR, 13C-NMR, elemental analysis, and mass spectroscopy.
In these schemes, ketone (4.0 equiv.) and a catalytic amount of diethylamine (10 drops) are added to a solution of substituted isatin (1.0 equiv.) in methanol (5 mL). The mixture is stirred at room temperature until starting material (substituted isatin) disappears completely. The resulting solution is concentrated and applied to flash chromatography eluting with hexane / ethyl acetate to afford pure product in quantitative yield. Further purification is done by recrystallization with hexane / ethyl acetate. An example compound synthesized by the above scheme includes: 4,7-Dichloro-3- hydroxy-3-[2-(4-methoxyphenyl-2-oxoethyl)]-l,3-dihydroindol-2-one: white solid; mp 149- 151 °C; 1H NMR (DMSO, 400 MH 1 z) delta 10.93 (s, 1H), 7.86 (d, 2H, J = 9.2 Hz), 7.26 (d, 1H, J = 8.8 Hz), 6.98 (d, 2H, J= 8.8 Hz), 6.86 (d, 1H, J = 8.4 Hz), 6.39 (s, 1H), 4.31 (d, 1H, J= 18.0 Hz), 3.80 (s, 3H), 3.61 (d, 1H, J= 18.0 Hz).
With C32H25Cl2N6O2Rh2(1+)*Cl(1-); sodium hydroxide; In water; at 110℃; for 18.0h;Inert atmosphere;
The 152 mg type g shown in lignin of beta - O - 4 model compound, 8 mg double rhodium catalyst, 80 mg NaOH added 1 ml distilled water, under protection of argon 110 C reaction 18 hours, to complete the lignin complete degradation, wherein the degradation product to the methoxy acetophenone of yield is 24%, P-acetone to yield 34%, O-methoxyphenol of yield is 62%.
With sodium hydroxide; In ethanol; at 20℃; for 48h;
General procedure: To a stirred solution of 4-methoxyacetophenone (5) (250 mg, 2.08 mmol) and the appropriate benzaldehydes (6a-w; 2.29 mmol) in EtOH (2.5 mL) was added saturated ethanolic NaOH (20 mL). The mixture was stirred for 48 h at room temperature. After reaction time, the reaction mixture was neutralized with HCl 5% solution until pH ? 7 and extracted with ethyl acetate (3 x 50 mL). Later, the organic phase was dried, concentrated and purified by flash column chromatography using EtOAc: Hexane mix (0:1-1:1) as eluent, obtaining the corresponding chalcones (7a-w).
7-chloro-2-(4-methoxybenzoyl)quinazolin-4(3H)-one[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
68%
With iodine; In dimethyl sulfoxide; at 110℃; for 12h;
General procedure: DMSO (3 mL) was added to a mixture of acetophenone (1.0equiv.) and I2 (1.1 equiv.). The solutionwas stirred at 110 °C, then 2-aminobenzamide (1.0 equiv.) in 2mL DMSO was added dropwise tothe mixture during 1-2 h. After a complete disappearance of thestarting material, 50 mL water and 30 mL saturated brine wereadded to the mixture. The solution was extracted with CH2Cl2(50 mLx3). The organic layer was washed with 10percent Na2S2O3 solution, dried over anhydrous Na2SO4 and concentrated underreduced pressure. The residue was purified by silica gel chromatography(petroleum ether/EtOAc 5:1) to yield the desiredproducts 9a-9d.
(E)-1-(1-(4-methoxyphenyl)ethylidene)-2-(4-(methylsulfonyl)phenyl)hydrazine[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
81%
In ethanol; for 12h;Reflux;
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:
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