* 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] Patent: WO2012/48181, 2012, A1,
[2] Patent: WO2012/83165, 2012, A1,
[3] Heterocycles, 2015, vol. 91, # 7, p. 1445 - 1454
[4] European Journal of Organic Chemistry, 2016, vol. 2016, # 8, p. 1606 - 1611
3
[ 5263-87-6 ]
[ 3373-00-0 ]
Reference：
[1] Bioorganic and Medicinal Chemistry Letters, 2006, vol. 16, # 13, p. 3415 - 3418
[2] Journal of the Chemical Society, Perkin Transactions 1: Organic and Bio-Organic Chemistry (1972-1999), 1980, p. 1933 - 1939
[3] Patent: EP3293177, 2018, A1,
4
[ 5263-87-6 ]
[ 120-15-0 ]
Yield
Reaction Conditions
Operation in experiment
92%
With tetrahydroxydiboron; copper diacetate In acetonitrile at 40℃; for 8 h; Schlenk technique
General procedure: A 20 mL Schlenk tube was charged with quinoline (1a; 65 mg,0.5 mmol), Cu(OAc)2 (4.5 mg, 0.025 mmol), B2(OH)4 (135 mg,1.5 mmol), and MeCN (2.0 mL). The mixture was stirred at 40 °C for 8 h until the reaction was completed (TLC), then cooled to room temperature and concentrated under reduced pressure. Water (10 mL) was added and the mixture was extracted with EtOAc (3 x 10 mL). The organic phases were combined, dried over anhydrous Na2SO4, filtered, and concentrated under reduced pressure. The residue was purified by column chromatography with petroleum ether/ethyl acetate (8:1) as an eluent to give a brown liquid (2a: 65 mg, 98percent yield).
90%
With tetrahydroxydiboron; copper diacetate In acetonitrile at 40℃; for 12 h;
6-methoxyquinoline (0.3 mmol, 48 mg),Tetrahydroxy diboron (0.9mmol, 81mg),Cu (OAc) 2 (0.015 mmol, 2.5 mg) was added to 1 mL of acetonitrile,40 ° C for 12 hours,The residue was purified by thin layer chromatography to give 44.0 mg of 6-methoxytetrahydroquinoline in 90percent yield, 98percent purity,
90%
With iron(II) triflate; C13H21N3O2 In chloroform at 40℃; for 2 h; Schlenk technique
General procedure: In a 10 mL Schlenk tube, Fe(OTf)2 (0.005 mmol, 1.8 mg), quinoline (0.5 mmol, 72 mg), Hantzsch ester A(1.25 mmol, 318 mg), and 1.0 mL CHCl3were added. The mixture was stirred at 40oCfor 2 h. The solution was concentrated under reduced pressure. The crude product was purified by silica gel column chromatography to afford the pure 1,2,3,4-tetrahydroquinoline (63.8 mg, 96percent yield).
87%
Stage #1: With nickel-aluminum alloy In ethanol at 0 - 4℃; for 0.5 h; Stage #2: With sodium hydroxide In ethanol; water at 20℃; for 6 h;
To the stirred solution of 6-methoxyquinoline 1 (5 g,31.44 mmol) in ethanol, Ni-Al alloy (2.5 g) was added and stirringwas continued for 30 min. Further, reaction mass was cooled to 0–4 C and then aqueous sodium hydroxide solution (10percent w/v, 50 ml)was added slowly. After the complete addition, reaction mixturewas further stirred at room temperature for 6 h. After completionof reaction as per TLC, reaction mass was passed through a tightcelite bed, further ethanol (2 75 ml) was passed through thecelite bed. Combined filtrate was evaporated on rotary evaporatortill its volume remained one-fourth to its original volume. Further,reaction mass was acidified with 2 N HCl, until its pH became neutral.Further, reaction mass was taken in separating funnel andextracted twice with ethyl acetate (2 150 ml). Combined ethylacetate layer was first washed with water (300 ml) and then withbrine (300 ml). Ethyl acetate layer was dried over anhydroussodium sulphate and finally evaporated on rotary evaporator toafford the compound 2 as crude oil. Crude 2 was purified by columnchromatography using 5percent ethyl acetate in hexane as mobilephase and silica (mesh size 100–200) as stationary phase, whichafforded the pure compound 2, as light yellow oil with 87percent yield[33].
85%
With iodine; 4,4,5,5-tetramethyl-[1,3,2]-dioxaboralane In dichloromethane at 20℃; for 24 h;
The elemental iodine (0.05 mmol) and 6-methoxy-quinoline (0.25 mmol) were added to the reaction flask to displace the air.Dichloromethane (1 mL) and pinacol borane (1 mmol) were added separately;After stirring at room temperature for 24 hours,The reaction mixture was diluted with dichloromethane (5 mL).The combined organic layers were dried over anhydrous sodium sulfate, filtered and evaporated.The crude product was separated by column chromatography (ethyl acetate: petroleum ether 1percent to 10percent).6-methoxy-tetrahydroquinoline, colorless oil,The yield was 85percent.
39%
With platinum(IV) oxide; hydrogen In methanol at 45℃; for 24 h;
6-Methoxyquinoline (3.0 g, 18.85 mmol) and PtO2 (0.2 g 0.8 mmol) were dissolved in methanol (20 mL) andheated to 45 °C and stirred for 24 hours. The reaction was detected by TLC. After the reaction was cooled to roomtemperature, the residue was isolated by silica gel column chromatography (petroleum ether/ethyl acetate = 10: 1) toobtain a compound 26A (pale yellow oil, 1.2 g, the yield was 39percent) after spin-drying the solvent.1H NMR (400 MHz, CHLOROFORM-d) d 6.51-6.66 (m, 2H), 6.45 (d, J = 8.5 Hz, 1H), 3.73 (s, 3H), 3.20-3.30 (m, 2H),2.76 (t, J = 6.5 Hz, 2H), 1.86-1.98 (m, 2H).
Reference：
[1] Bioorganic and Medicinal Chemistry Letters, 2006, vol. 16, # 13, p. 3415 - 3418
[2] Advanced Synthesis and Catalysis, 2017, vol. 359, # 4, p. 677 - 686
[3] Advanced Synthesis and Catalysis, 2017, vol. 359, # 6, p. 933 - 940
[4] Chemistry - A European Journal, 2016, vol. 22, # 48, p. 17151 - 17155
[5] ChemCatChem, 2017, vol. 9, # 13, p. 2496 - 2505
[6] Chemical Science, 2018, vol. 9, # 42, p. 8134 - 8141
[7] Tetrahedron Letters, 1987, vol. 28, # 1, p. 77 - 80
[8] Bulletin of the Chemical Society of Japan, 1989, vol. 62, # 9, p. 2968 - 2976
[9] Tetrahedron Letters, 2016, vol. 57, # 3, p. 329 - 332
[10] Tetrahedron, 2018, vol. 74, # 17, p. 2121 - 2129
[11] Angewandte Chemie - International Edition, 2017, vol. 56, # 12, p. 3216 - 3220[12] Angew. Chem., 2017, vol. 129, # 12, p. 3264 - 3268,5
[13] Patent: CN106831565, 2017, A, . Location in patent: Paragraph 0095; 0096; 0097; 0098
[14] Tetrahedron Letters, 2017, vol. 58, # 36, p. 3571 - 3573
[15] ACS Catalysis, 2018, vol. 8, # 5, p. 4545 - 4557
[16] Chemistry - A European Journal, 2018,
[17] Tetrahedron, 1996, vol. 52, # 5, p. 1631 - 1636
[18] Chemistry Letters, 2010, vol. 39, # 8, p. 832 - 834
[19] Bioorganic Chemistry, 2016, vol. 67, p. 75 - 83
[20] Journal of the American Chemical Society, 2015, vol. 137, # 36, p. 11718 - 11724
[21] Journal of Medicinal Chemistry, 2010, vol. 53, # 17, p. 6490 - 6505
[22] Chemical Communications, 2018, vol. 54, # 62, p. 8622 - 8625
[23] Patent: CN108822030, 2018, A, . Location in patent: Paragraph 0031; 0032; 0033; 0034
[24] Advanced Synthesis and Catalysis, 2015, vol. 357, # 4, p. 753 - 760
[25] Advanced Synthesis and Catalysis, 2016, vol. 358, # 19, p. 3039 - 3045
[26] ChemCatChem, 2013, vol. 5, # 8, p. 2183 - 2186
[27] Catalysis Science and Technology, 2017, vol. 7, # 10, p. 1981 - 1985
[28] Synthetic Communications, 1998, vol. 28, # 3, p. 485 - 492
[29] Chemical Communications, 2017, vol. 53, # 66, p. 9262 - 9264
[30] Catalysis Science and Technology, 2018, vol. 8, # 10, p. 2648 - 2653
[31] Synthetic Communications, 1990, vol. 20, # 22, p. 3553 - 3562
[32] Chemistry - A European Journal, 2012, vol. 18, # 2, p. 574 - 585
[33] Bioorganic and Medicinal Chemistry, 2009, vol. 17, # 2, p. 830 - 847
[34] Synlett, 1998, # 9, p. 1029 - 1030
[35] Journal of the Chemical Society. Perkin Transactions 1, 2001, # 9, p. 955 - 977
[36] Patent: EP3293177, 2018, A1, . Location in patent: Paragraph 0222; 0223
[37] Monatshefte fuer Chemie, 1885, vol. 6, p. 767
[38] Fortschr. Teerfarbenfabr. Verw. Industriezweige, vol. 1, p. 180
[39] Journal of the American Chemical Society, 1944, vol. 66, p. 401
[40] Journal of Organic Chemistry, 1946, vol. 11, p. 175
[41] Journal of the Chemical Society, Perkin Transactions 1: Organic and Bio-Organic Chemistry (1972-1999), 1980, p. 1933 - 1939
[42] Helvetica Chimica Acta, 1985, vol. 68, p. 1952 - 1960
[43] Journal of the American Chemical Society, [44] Journal of the American Chemical Society, 2009, vol. 131, p. 8410 - 8412
[45] Patent: US2006/58361, 2006, A1, . Location in patent: Page/Page column 35-36
[46] Bioorganic and Medicinal Chemistry, 2012, vol. 20, # 21, p. 6313 - 6320
[47] Journal of the American Chemical Society, 2012, vol. 134, # 42, p. 17592 - 17598,7
[48] Organic and Biomolecular Chemistry, 2013, vol. 11, # 7, p. 1209 - 1215
[49] Catalysis Science and Technology, 2015, vol. 5, # 10, p. 4746 - 4749
[50] Journal of Materials Chemistry A, 2017, vol. 5, # 7, p. 3260 - 3266
[51] Chemical Science, 2017, vol. 8, # 12, p. 8164 - 8169
[52] Tetrahedron Letters, 2018, vol. 59, # 10, p. 949 - 953
[53] Organic Letters, 2018, vol. 20, # 4, p. 1171 - 1174
[54] Molecular Catalysis, 2018, vol. 452, p. 145 - 153
[55] Applied Catalysis A: General, 2018, vol. 560, p. 37 - 41
[56] Angewandte Chemie - International Edition, 2018, vol. 57, # 31, p. 9950 - 9954[57] Angew. Chem., 2018, vol. 130, p. 10098 - 10102,5
5
[ 5263-87-6 ]
[ 120-15-0 ]
Reference：
[1] Green Chemistry, 2017, vol. 19, # 3, p. 749 - 756
Reference：
[1] Journal of the American Chemical Society, 2016, vol. 138, # 37, p. 12234 - 12242
8
[ 5263-87-6 ]
[ 120-15-0 ]
Reference：
[1] Chemical Communications, 2015, vol. 51, # 35, p. 7558 - 7561
9
[ 5263-87-6 ]
[ 10500-57-9 ]
[ 120-15-0 ]
[ 75414-06-1 ]
Reference：
[1] Journal of the Chemical Society, Perkin Transactions 1: Organic and Bio-Organic Chemistry (1972-1999), 1980, p. 1933 - 1939
10
[ 5263-87-6 ]
[ 64-18-6 ]
[ 120-15-0 ]
[ 1013-36-1 ]
Reference：
[1] Advanced Synthesis and Catalysis, 2017, vol. 359, # 4, p. 677 - 686
11
[ 5263-87-6 ]
[ 105532-25-0 ]
Reference：
[1] Monatshefte fuer Chemie, 1885, vol. 6, p. 767
12
[ 5263-87-6 ]
[ 14036-96-5 ]
Reference：
[1] Journal of the American Chemical Society, 2015, vol. 137, # 2, p. 592 - 595
[2] Bioorganic and Medicinal Chemistry Letters, 2018, vol. 28, # 14, p. 2358 - 2363
13
[ 5263-87-6 ]
[ 187679-62-5 ]
Reference：
[1] Journal of the Chemical Society - Perkin Transactions 1, 1997, # 7, p. 1017 - 1024
14
[ 5263-87-6 ]
[ 327044-56-4 ]
Reference：
[1] Bioorganic and Medicinal Chemistry Letters, 2006, vol. 16, # 13, p. 3415 - 3418
With methylamine hydrochloride; ammonium chloride In N,N-dimethyl-formamide at 200℃; for 20h;
92%
With pyridine hydrochloride at 200℃; for 0.75h; Microwave irradiation; Ionic liquid;
68%
With hydrogen bromide In water Reflux;
66%
With water; hydrogen bromide; 1-butylpyridinium bromide at 100℃; Microwave irradiation; Neat (no solvent);
With hydrogen bromide
With hydrogen bromide for 24h;
With trimethylammonium heptachlorodialuminate In dichloromethane Heating;
With D-glucose; GDH; cytochrome P450 monooxygenase CYP116B4 from Labrenzia aggregata; nicotinamide adenine dinucleotide phosphate In aq. buffer at 30℃; for 5h; Enzymatic reaction;
With nicotinamide adenine dinucleotide phosphate; cytochrome P450 monooxygenase from Labrenzia aggregata In aq. buffer at 30℃; for 5h; Enzymatic reaction;
With aluminum (III) chloride In dichloromethane at 20℃; for 24h;
With tetrahydroxydiboron; copper diacetate; In acetonitrile; at 40℃; for 8h;Schlenk technique;
General procedure: A 20 mL Schlenk tube was charged with quinoline (1a; 65 mg,0.5 mmol), Cu(OAc)2 (4.5 mg, 0.025 mmol), B2(OH)4 (135 mg,1.5 mmol), and MeCN (2.0 mL). The mixture was stirred at 40 C for 8 h until the reaction was completed (TLC), then cooled to room temperature and concentrated under reduced pressure. Water (10 mL) was added and the mixture was extracted with EtOAc (3 x 10 mL). The organic phases were combined, dried over anhydrous Na2SO4, filtered, and concentrated under reduced pressure. The residue was purified by column chromatography with petroleum ether/ethyl acetate (8:1) as an eluent to give a brown liquid (2a: 65 mg, 98% yield).
90%
With tetrahydroxydiboron; copper diacetate; In acetonitrile; at 40℃; for 12h;
6-methoxyquinoline (0.3 mmol, 48 mg),Tetrahydroxy diboron (0.9mmol, 81mg),Cu (OAc) 2 (0.015 mmol, 2.5 mg) was added to 1 mL of acetonitrile,40 C for 12 hours,The residue was purified by thin layer chromatography to give 44.0 mg of 6-methoxytetrahydroquinoline in 90% yield, 98% purity,
90%
With iron(II) triflate; C13H21N3O2; In chloroform; at 40℃; for 2h;Schlenk technique;
General procedure: In a 10 mL Schlenk tube, Fe(OTf)2 (0.005 mmol, 1.8 mg), quinoline (0.5 mmol, 72 mg), Hantzsch ester A(1.25 mmol, 318 mg), and 1.0 mL CHCl3were added. The mixture was stirred at 40oCfor 2 h. The solution was concentrated under reduced pressure. The crude product was purified by silica gel column chromatography to afford the pure 1,2,3,4-tetrahydroquinoline (63.8 mg, 96% yield).
87%
To the stirred solution of 6-methoxyquinoline 1 (5 g,31.44 mmol) in ethanol, Ni-Al alloy (2.5 g) was added and stirringwas continued for 30 min. Further, reaction mass was cooled to 0-4 C and then aqueous sodium hydroxide solution (10% w/v, 50 ml)was added slowly. After the complete addition, reaction mixturewas further stirred at room temperature for 6 h. After completionof reaction as per TLC, reaction mass was passed through a tightcelite bed, further ethanol (2 75 ml) was passed through thecelite bed. Combined filtrate was evaporated on rotary evaporatortill its volume remained one-fourth to its original volume. Further,reaction mass was acidified with 2 N HCl, until its pH became neutral.Further, reaction mass was taken in separating funnel andextracted twice with ethyl acetate (2 150 ml). Combined ethylacetate layer was first washed with water (300 ml) and then withbrine (300 ml). Ethyl acetate layer was dried over anhydroussodium sulphate and finally evaporated on rotary evaporator toafford the compound 2 as crude oil. Crude 2 was purified by columnchromatography using 5% ethyl acetate in hexane as mobilephase and silica (mesh size 100-200) as stationary phase, whichafforded the pure compound 2, as light yellow oil with 87% yield[33].
85%
With iodine; 4,4,5,5-tetramethyl-[1,3,2]-dioxaboralane; In dichloromethane; at 20℃; for 24h;
The elemental iodine (0.05 mmol) and 6-methoxy-quinoline (0.25 mmol) were added to the reaction flask to displace the air.Dichloromethane (1 mL) and pinacol borane (1 mmol) were added separately;After stirring at room temperature for 24 hours,The reaction mixture was diluted with dichloromethane (5 mL).The combined organic layers were dried over anhydrous sodium sulfate, filtered and evaporated.The crude product was separated by column chromatography (ethyl acetate: petroleum ether 1% to 10%).6-methoxy-tetrahydroquinoline, colorless oil,The yield was 85%.
39%
With platinum(IV) oxide; hydrogen; In methanol; at 45℃; for 24h;
6-Methoxyquinoline (3.0 g, 18.85 mmol) and PtO2 (0.2 g 0.8 mmol) were dissolved in methanol (20 mL) andheated to 45 C and stirred for 24 hours. The reaction was detected by TLC. After the reaction was cooled to roomtemperature, the residue was isolated by silica gel column chromatography (petroleum ether/ethyl acetate = 10: 1) toobtain a compound 26A (pale yellow oil, 1.2 g, the yield was 39%) after spin-drying the solvent.1H NMR (400 MHz, CHLOROFORM-d) d 6.51-6.66 (m, 2H), 6.45 (d, J = 8.5 Hz, 1H), 3.73 (s, 3H), 3.20-3.30 (m, 2H),2.76 (t, J = 6.5 Hz, 2H), 1.86-1.98 (m, 2H).
With hydrogen;palladium 10% on activated carbon; In ethanol; at 20℃; under 2327.23 Torr; for 144h;
Preparation 28 1-Methyl-1,2,3,4-tetrahydro-quinolin-6-ol 10% Pd/C (600 mg) was added to a solution of 6-methoxy-quinoline (6.0 g, 38 mmol) in ethanol (100 mL). The resulting mixture was shaken under an atmosphere of hydrogen at 45 psi at rt for 6 days. The mixture was filtered through a pad of Celite to remove the catalyst and concentrated to afford 6-methoxy-1,2,3,4-tetrahydro-quinoline (6.0 g).
With hydrogen; In methanol; at 80℃; under 750.075 Torr; for 4h;Autoclave;
General procedure: Typically, 1.0 mmol of quinoline compounds, 6 mL of solvent and acertain amount of PdCIL-T catalyst were added into a 50 mL PTFEreaction vessel or thick walled pressure vessel. The mixture was stirredfor 2 min to ensure complete dispersion of the catalyst and then placedin a 50 mL stainless-steel autoclave. After being flushed three timeswith H2, the pressure was elevated to 1-10 atm at room temperature.The autoclave was then heated to 30-120 C with a magnetic stir for acertain time. Subsequently, the catalyst was removed from the mixtureby centrifugation, and the liquid sample was analyzed by GC or GC-MS.The calculations of conversion and selectivity were based on the followingformula: Conversion=[consumed substrate]/[initial substrate]×100%, Selectivity=[py-THQs]/[all hydrogenated products]×100%.
With hydrogen; In pentan-1-ol; water; at 130℃; under 22502.3 Torr; for 2h;Autoclave;Catalytic behavior;
General procedure: In a typical experiment, the above-prepared thermoregulated phasetransferPt nanocatalyst, n-decane (100 mg) and a certain amount ofsubstrates were added in the autoclave. Then the reactor was replacedthree times with 2 MPa H2 and stirred under hydrogen pressure at adesignated temperature for an appointed time. After reaction, the reactorwas cooled to room temperature and depressurized. The upperproduct phase was easily separated from the lower catalyst phase anddirectly analysed by GC and GC-MS.
> 99%Chromat.
With Co3CuO(x); hydrogen; In tetrahydrofuran; at 80℃; under 7500.75 - 30003 Torr; for 15h;Autoclave; Sealed tube;
General procedure: The hydrogenation reactions of quinolines were carried out in16 mL stainless steel autoclaves with a Teflon inner container in a batch mode of operation [33,34]. In a typical reaction, quinoline (0.129 g,1 mmol), catalyst 20 mg and THF (1 mL) were added into the inner container, which was transferred into the autoclave. The reactor was sealed and charged with 1 MPa of H2 to remove the air for three times. After that, it was charged with 4 MPa of H2 and heated to 60 C andstirred for 15 h. Upon completion of reaction, the solid catalyst was separated using an extra magnet, and the liquid was analysed on a gas chromatograph (GC9720, Zhejiang Fuli Analytical Instruments Co.,Ltd., China) equipped with a flame ionization detector and a HP-5 capillary column (30m×0.32mm×0.25 mum) with toluene as an internal standard and GC-MS (Agilent 6890N-5975) with a HP-5 capillarycolumn (30m×0.32mm×0.25 mum).
With dihydrogen peroxide; In water; for 0.25h;Sonication;
In a 50 mL round-bottom flask, 1.59 g of 6-methoxyquinoline and then 1.1 g of hydrogen peroxide (35% by mass) were successively added.5% mass fraction of perfluorosulfonic acid resin, 10 ml of water as a solvent, and the resulting mixture in an ultrasonic reaction apparatus at 60 W/The reaction was performed for 15 minutes under 20 KHz ultrasound. The resin catalyst in the reaction system was removed by filtration, and the reaction solvent was removed under reduced pressureWater, finally recrystallized to give 1.69 g of 6-methoxyquinoline nitrous oxide in 97% yield.
90%
With 3-chloro-benzenecarboperoxoic acid; In dichloromethane; at 0 - 20℃; for 24h;
General procedure: To a solution of the corresponding quinoline substrate (5 mmol) in CH2Cl2 (30 mL), m-CPBA (7.5 mmol, 1.5 equiv) was added at 0 C. The reaction mixture was allowed to stir at room temperature for 24 h. Next, saturated aq NaHCO3 solution (100 mL) was added to the reaction mixture. Then, the mixture was extracted with CH2Cl2 (3 × 50 mL) and the organic extracts were dried over anhydrous Na2SO4, filtered, and concentrated under reduced pressure. The crude product was purified by column chromatography on silica gel to obtain the pure quinoline N-oxide (70-90% yield).
82%
With dihydrogen peroxide; In acetic acid; at 100℃; for 2h;
6-Methoxy quinoline (15 g, 0.094 mol) was dissolved in acetic acid (97 ml) and treated with hydrogen peroxide (37 ml). The mixture was stirred to 100 C. for 2 hours. After evaporation to dryness 100 ml of water was added to the residue until a precipitate appears. Filtration and washing with water gives a yellow precipitate that is dried under vacuum to yield 13.5 g of the title compound as a light yellow solid (82%). MS (m/e): 176.3 (M+H)+.
55%
To a solution of 6- methoxyquinoline (2.00 g, 12.6 mmol) in AcOH (10 mL) was added Η202 (30% in water, 1.9 mL, 18.9 mmol), the mixture was heated to 70 C for 21 hours. The mixture was basified with 2M NaOH to pH 8-9 and extracted with CH2C12 (200 mL), the combined organic layer was washed with brine (50 mL), dried over Na2S04, filtered and concentrated to give the crude product, which was purified by silica gel column (EtOAc / MeOH=10 / 1) to give 6- methoxyquinoline 1-oxide (1.20 g, 55%) as a solid.
55%
To a solution of 6- methoxyquinoline (2.00 g, 12.6 mmol) in AcOH (10 mL) was added H202 (30% in water, 1.9 mL, 18.9 mmol), the mixture was heated to 70 C for 21 hours. The mixture was basified with 2M NaOH to pH 8-9 and extracted with CH2C12 (200 mL), the combined organic layer was washed with brine (50 mL), dried over Na2S04, filtered and concentrated to give the crude product, which was purified by silica gel column (EtOAc / MeOH=10 / 1) to give 6- methoxyquinoline 1-oxide (1.20 g, 55%) as a solid.
With dihydrogen peroxide; In acetic acid; at 82℃; for 19h;
A solution of 6-methoxyquinoline (11.21 g, 70 [MMOL)] in glacial acetic acid is treated dropwise with 30% hydrogen peroxide (15 mL) and then heated at [82C] for 19 hours. The reaction mixture is cooled, poured onto ice and carefully basified with concentrated ammonium hydroxide. The precipitate is collected, washed with hexane and dried in vacuo to provide the title compound (quantitative yield), which is used as such in the next step. MS [ (+) ES, m/z]: 176.1 [M+H] +
With 3-chloro-benzenecarboperoxoic acid; In dichloromethane; at 0 - 20℃; for 12h;
General procedure: To a solution of the corresponding N-heterocycles (10.0 mmol) in CH2Cl2 (20 mL), m-chloroperoxybenzoic acid (m-CPBA, 20.0 mmol, 2.0 equiv) was added at 0 C. The reaction mixture was allowed to stir at room temperature for 12 h. Then saturated aqueous NaHCO3 (20 mL) was added. The aqueous was extracted with CH2Cl2 (10 mL x 3) and the combined organic extracts were dried over anhydrous Na2SO4, filtered, and concentrated under reduced pressure. The residue was purified by column chromatography on silica gel with EtOAc/n-hexene or EtOAc/MeOH to afford desired N-oxides.
With 3-chloro-benzenecarboperoxoic acid; In dichloromethane; at 0 - 20℃;Inert atmosphere;
General procedure: To a solution of 6-methylquinoline (270 µL, 2.0 mmol, 1.0 eq) in dry dichloromethane (4.0 mL), m-chloroperbenzoic acid (690 mg, 4.0 mmol, 2.0 eq) was added at 0 C under argon. The mixture was stirred overnight at room temperature, then diluted with dichloromethane and washed with potassium hydroxide (6 M). The organic layers were dried over magnesium sulfate, filtered and evaporated to dryness under reduced pressure. A mixture of the residue, molecular sieve (4 Å) and tetrabutylammonium bromide (967 mg, 3.0 mmol, 1.5 eq) in dry dichloromethane (200 mL) was stirred for 10 min at room temperature. p-Toluenesulfonic anhydride (979 mg, 3.0 mmol, 1.5 eq) was added and stirring was continued at room temperature overnight. The reaction mixture was filtered and the solvent was evaporated to dryness under reduced pressure. The crude product was purified by column chromatography (cyclohexane/chloroforme 10:15:11:1) to give 297 mg (1.34 mmol, 67%) of the analytically pure compound. C10H8BrN; MW: 222; 1H NMR (CDCl3, 400 MHz): δ 7.99-7.87 (m, 2H), 7.62-7.53 (m, 2H), 7.46 (d, J = 8.5 Hz, 1H), 2.52 (s, 3H); 13C NMR (CDCl3, 100 MHz): δ 147.3, 140,9, 137.9, 137.3, 132.9, 128.4, 127.1, 126.7, 125.8, 21.7.; MS (ESI): 223 (M+H)+.
With 3-chloro-benzenecarboperoxoic acid; In dichloromethane; at 0 - 20℃;
General procedure: 77% 3-chloroperbenzoic acid (m-CPBA) (3 mmol) in CH2Cl2 (5 mL) was dropped into a solutionof quinoline derivatives (2 mmol) in CH2Cl2 (5 mL) cooled to 0 under vigorous magnetic stirringfor overnight. After the completion of this course, the reaction mixture was allowed up to roomtemperature and stirred overnight. An aqueous solution of saturated NaHCO3 was added to themixture to neutralize residual m-CPBA. The resulting mixture was extracted with CH2Cl2 (3 × 10mL). The organic phase was combined and washed with saturated NaCl solution (3 × 5 mL). The organiclayer was dried over anhydrous Na2SO4, filtered, and evaporated under reduced pressure to givecrude products, which were purified by column chromatography (silica gel 200-300 mesh, AcOEt:MeOH (95:05) as eluent). The products were identified by 1H NMR and MS spectra and comparedto the previous literature.
With 2,2,6,6-Tetramethyl-1-piperidinyloxy free radical; 3,6‐di‐tert‐butyl‐9‐mesityl‐10‐phenylacridin‐10‐ium tetrafluoroborate; oxygen; ammonium carbamate In water; 1,2-dichloro-ethane at 23℃; for 24h; Irradiation; regioselective reaction;
Multi-step reaction with 2 steps
1: 85 percent / fuming nitric acid / 0.5 h
2: tin; HCl / ethanol / 1 h / Heating
1 5-Amino-6-methoxyquinoline
EXAMPLE 1 5-Amino-6-methoxyquinoline Commercially available 6-methoxyquinoline (13.80 g) was nitrated according to the procedure of Campbell, et. al. (J. Am. Chemo Soc., 1946, 68, 1559) to give 5-nitro-6-methoxyquinoline (17.51 g). This crude product was directly reduced according to the procedure of Jacobs, et. al. (J. Am. Chem. Soc., 1920, 42, 2278) to give 5-amino-6-methoxyquinoline (6.25 g). M.p. 152.5°-154.5° C.
Multi-step reaction with 2 steps
1: ammonium peroxydisulfate; tris(1,10-phenathrolinyl)ruthenium(II) hexafluorophosphate / acetonitrile; water / 24 h / 23 °C / Irradiation; Schlenk technique; Inert atmosphere
2: pyrrolidine / 12 h / 70 °C
8 Methoxylation of 6-Bromo-1-Acetyl-1,2,3,4-Tetrahydroquinoline with subsequent hydrolysis to yield 6-Methoxy-1,2,3,4-Tetrahydroquinoline
Its infra-red spectrum was identical to that of authentic material obtained by the hydrogenation of 6-methoxyquinoline. Overall yield=67%.
With diethylazodicarboxylate; In chloroform; toluene; at 20℃; for 12h;
General procedure: To a 10 mL round bottom flask equipped with a magnetic stir bar, 1,2,3,4-tetrahydroquinoline (0.5 mmol), DEAD solution 40 wt% in toluene (2.2 eq, 1.1 mmol, 0.5 mL), and CHCl3 (1.0 mL) was added. The reaction mixture was stirred at room temperature for 12 h. The mixture was concentrated on rotary evaporator. The residue was purified by column chromatography with EtOAc:hexane (1:5) to give quinolines. In case of 2f and 2m, the product spot was close to the spot of the remained DEAD. To eliminate the remained DEAD, 1 equivalent of PPh3 was added after the reaction and the reaction mixture was stirred.[19] After 10 min, the reaction mixture was concentrated on rotary evaporator. The residue was purified by column chromatography with CHCl3:hexane (1:1) to give quinolines.
90%
With oxygen; at 100℃; for 12h;
Carbon material preparation As described in Example 1,To a Schlenk flask was added 0.5 mmol of <strong>[120-15-0]6-methoxy-1,2,3,4-tetrahydroquinoline</strong>,20 mg of catalyst,Oxygen balloon as oxygen source,The reaction was stirred at 100 C for 12 h,Get the corresponding target product,The yield was 90%.
60%
With cobalt(II) 5,10,15,20-tetraphenylporphyrin; oxygen; In N,N-dimethyl-formamide; for 10h;
General procedure: N-Heterocyclic amine (0.50 mmol), CoTPP (10 mg) and DMF (2 mL) were mixed in a carousel reaction tube. The reaction mixture was stirred at 120 C under oxygen atmosphere, the reaction was sampled periodically and monitored by TLC (petroleum ether/ethyl acetate (10:1 v/v)). After the reaction, the reaction mixture was then cooled to room temperature and purified using flash chromatography to give the corresponding product. All the dehydrogenation products are known, and their NMR spectra were consistent with the literature. NMR spectra were recorded at 25 C on an Bruker AVANCE III 400-NMR spectrometer at 400 MHz for 1H and 100 MHz for 13C, using CDCl3 as solvent with TMS as the internal standard. Thin-layer chromatography was performed on silica gel 60 F254 (Sinopharm) thin-layer chromatography plates using petroleum ether/ethyl acetate (10:1 v/v) as the mobile phase.
General procedure: beta-Trifluoroacetyl vinyl ethyl ether 1 (0.168 g, 1 mmol) and quinoline 3a (0.129 g, 1 mmol) were solved in DMSO 5 ml. A solution of DMAD 2a (0.142 g, 1 mmol) in DMSO 2 ml was added into the mixture dropwise. Monitored by TLC, when the reaction completed, the mixture was poured into water 20 ml and extracted by ethyl ether (30 ml × 4). The organic layer was dried over Na2SO4 anhydrous. After removing the solvent by a rotary evaporator, the product was isolate on silica gel (n-hexane/ethyl ether V/V = 5:1). The product was further purified by recrystallization from ethyl ether and hexane. An orange crystal was obtained in a yield of 63%.
With pyridine; bromine; In tetrachloromethane; for 2.0h;Reflux;
General procedure: To a solution of 6-substituted or 7-substituted quinoline (14 mmol) in 20 mL of CCl4 was added Br2 (14 mmol) dropwise at room temperature. The mixture was heated to reflux and pyridine was added (14 mmol). The reaction solution was refluxed for another 2 h. The mixture was allowed to cool to room temperature, diluted with 50 mL of DCM, washed with 50 mL of water and brine, dried with Na2SO4, concentrated in vacuo. The residue was purified by column chromatography on silica gel (PE: EA = 40: 1) to give 17-23, as an offwhite solid.
With 1-methyl-1H-imidazole In neat (no solvent) at 100℃; for 0.1h; Microwave irradiation; Green chemistry;
Typical procedure for the synthesis of alkoxycoumarin (4)
General procedure: In a 10-mL reaction vial, a mixture of N-methylimidazole (3, 0.26 g, 2.0 mmol) and dimethyl acetylenedicarboxylate (2a, 0.24 mL, 2.0 mmol) under solvent-free condition was stirred for 1 min. Subsequently, 4-hydroxycoumarin (1a, 0.32 g, 2.0 mmol) was added to the reaction mixture, and the reaction vial was capped and pre-stirred for 20 s. The mixture was subjected to microwave irradiation at a power of 600 W for 6 min at 100 °C. Upon completion, monitored by TLC, the reaction mixture was cooled to room temperature. The resulting precipitate was separated by filtration and recrystallized from diethyl ether (Et2O) to afford the pure compound 4a.
With bis(1,5-cyclooctadiene)nickel (0); cesium fluoride; 1,3-dicyclohexyl-1H-imidazol-3-ium chloride; sodium t-butanolate In toluene at 120℃; for 12h; Glovebox; Inert atmosphere; Sealed tube;
With dipotassium peroxodisulfate; TEMPO; 3,6‐di‐tert‐butyl‐9‐mesityl‐10‐phenylacridin‐10‐ium tetrafluoroborate In 1,2-dichloro-ethane at 37℃; for 40h; Sealed tube; Irradiation; Inert atmosphere; regioselective reaction;
General Procedure B (Stoichiometric Oxidant)
General procedure: To a microwave vial equipped with a stir bar were added thesubstrate (1.0 equiv, 0.6-0.9 mmol), sulfoximine (2.0 equiv),photocatalyst (0.05 equiv), TEMPO (0.2 equiv), and peroxodisulfatesalt (1.1 equiv), then the vial was closed with a septum cap.DCE or MeCN (0.1 M) was added, and the mixture was spargedwith argon. The reaction mixture was subsequently irradiatedin a Hepatochem PhotoRedOx Duo photoreactor and two KessilLED lamps (each 40 W, A160WE) or a PennOC photoreactor m1(450 nm). For the reaction workup, the mixture was eitherdirectly evaporated or half-saturated aqueous NaHCO3 solutionwas added followed by extraction (5 × EtOAc, Na2SO4). Purificationwas performed using an automated Isolera SpektraSystem or preparative HPLC as described in the SupportingInformation.
Chemistry
Pharmaceutical Intermediates
Inhibitors/Agonists
Material Science
For Research Only
110K+ Compounds
Competitive Price
1-2 Day Shipping
